Dystrophic Epidermolysis Bullosa

Mendelian MONDO:0006543 Pathograph 38 Dermatological Disease Genetic Disease

Dystrophic epidermolysis bullosa (DEB) is caused by mutations in COL7A1 encoding type VII collagen, the major structural component of anchoring fibrils at the dermal-epidermal junction. Both autosomal dominant (DDEB) and autosomal recessive (RDEB) forms exist. RDEB severe generalized is characterized by generalized blistering, progressive scarring with pseudosyndactyly, esophageal strictures, and a lifetime squamous cell carcinoma risk exceeding 90%.

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Definitions

Histopathology

Differentials

Models

🏷

Classifications

Harrison's Chapter

🔗

Mappings

MONDO

MONDO:0006543 epidermolysis bullosa dystrophica

Primary MONDO disease identifier for this DEB entry.

ICD-10-CM

ICD10CM:Q81.2 Epidermolysis bullosa dystrophica

ICD-10-CM Q81.2 directly names dystrophic epidermolysis bullosa.

👪

Inheritance

Autosomal dominant

Dominant dystrophic epidermolysis bullosa (DDEB)

Show evidence (1 reference)

PMID:20301481 SUPPORT Human Clinical

"About 70% of individuals diagnosed with DDEB are reported to have an affected parent"

GeneReviews confirms autosomal dominant inheritance for DDEB.

Autosomal recessive

Recessive dystrophic epidermolysis bullosa (RDEB)

Show evidence (1 reference)

PMID:20301481 SUPPORT Human Clinical

"If both parents are known to be heterozygous for a COL7A1 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected"

GeneReviews confirms autosomal recessive inheritance for RDEB.

◆

Subtypes

Dominant Dystrophic Epidermolysis Bullosa (DDEB) MONDO:0007549

Mild, localized blistering caused by dominant-negative COL7A1 mutations. Nails are most commonly affected, and blistering is often limited to hands, feet, knees, and elbows. Heals with scarring but without the severe complications seen in recessive forms.

Recessive Dystrophic Epidermolysis Bullosa, Severe Generalized (RDEB-sev gen) MONDO:0009179

Formerly known as Hallopeau-Siemens RDEB. The most severe form, caused by biallelic loss-of-function COL7A1 mutations leading to absent or severely reduced type VII collagen. Characterized by generalized blistering from birth, progressive scarring, mitten deformities (pseudosyndactyly), esophageal strictures, and a lifetime squamous cell carcinoma risk exceeding 90%.

Recessive Dystrophic Epidermolysis Bullosa, Intermediate (RDEB-intermediate) MONDO:0019522

Formerly known as non-Hallopeau-Siemens RDEB. Moderate scarring with blistering that may be localized to hands, feet, knees, elbows, and flexural areas. Less severe than RDEB-sev gen, with lower SCC risk, but still carries significant morbidity from scarring and extracutaneous involvement.

Recessive Dystrophic Epidermolysis Bullosa Inversa MONDO:0019310

Blistering predominantly affects intertriginous (skin fold) areas including axillae, groin, and neck. May also involve the esophagus and other mucosal surfaces. Caused by specific COL7A1 mutations that produce some residual type VII collagen function.

⚙

Pathophysiology

Heterozygous COL7A1 Pathogenic Variant (DDEB)

A heterozygous pathogenic variant in COL7A1 is the molecular lesion in dominant dystrophic epidermolysis bullosa. The resulting type VII collagen dysfunction produces a usually milder, localized blistering phenotype that often affects hands, feet, knees, elbows, and nails.

COL7A1 link

Downstream

COL7A1 Mutations and Loss of Type VII Collagen Heterozygous COL7A1 pathogenic variants produce dysfunctional type VII collagen and thereby converge on the collagen VII/anchoring fibril defect.

Show evidence (1 reference)

PMID:20301481 SUPPORT Human Clinical

"biallelic COL7A1 pathogenic variants (for RDEB) or a heterozygous pathogenic variant in COL7A1 (for DDEB)"

GeneReviews defines DDEB by a heterozygous COL7A1 pathogenic variant.

Biallelic COL7A1 Pathogenic Variants (RDEB)

Biallelic pathogenic variants in COL7A1 are the molecular lesion in recessive dystrophic epidermolysis bullosa. Severe generalized RDEB reflects marked type VII collagen deficiency, producing generalized neonatal blistering, progressive scarring, pseudosyndactyly, esophageal strictures, growth failure, and very high lifetime squamous cell carcinoma risk.

COL7A1 link

Downstream

COL7A1 Mutations and Loss of Type VII Collagen Biallelic COL7A1 pathogenic variants reduce or abolish type VII collagen function and thereby converge on the collagen VII/anchoring fibril defect.

Show evidence (1 reference)

PMID:20301481 SUPPORT Human Clinical

"biallelic COL7A1 pathogenic variants (for RDEB) or a heterozygous pathogenic variant in COL7A1 (for DDEB)"

GeneReviews defines RDEB by biallelic COL7A1 pathogenic variants.

COL7A1 Mutations and Loss of Type VII Collagen

Mutations in the COL7A1 gene encoding type VII collagen result in absent, reduced, or dysfunctional protein. In RDEB, biallelic loss-of-function mutations typically cause complete absence of type VII collagen, while in DDEB, dominant-negative mutations produce structurally abnormal collagen that disrupts anchoring fibril formation. Type VII collagen is the major structural component of anchoring fibrils at the dermal-epidermal junction.

keratinocyte link fibroblast link

COL7A1 link

collagen fibril organization link ⚠ ABNORMAL extracellular matrix organization link ⚠ ABNORMAL

Downstream

Defective Anchoring Fibrils and Loss of Dermal-Epidermal Adhesion Absent or dysfunctional type VII collagen leads to defective anchoring fibrils that fail to secure the epidermis to the dermis.

Show evidence (3 references)

PMID:36516090 SUPPORT Human Clinical

"Dystrophic epidermolysis bullosa is a rare genetic blistering skin disease caused by mutations in COL7A1, which encodes type VII collagen (C7)"

Confirms COL7A1 mutations as the cause of DEB.

PMID:32973163 SUPPORT Human Clinical

"pathogenetic mutations in 16 distinct genes have been implicated in EB, encoding proteins influencing cellular integrity and adhesion"

Confirms that EB is caused by mutations in genes encoding structural proteins critical for cell adhesion.

PMID:20301481 SUPPORT Human Clinical

"biallelic COL7A1 pathogenic variants (for RDEB) or a heterozygous pathogenic variant in COL7A1 (for DDEB)"

GeneReviews confirms the genetic basis of both RDEB and DDEB in COL7A1.

Defective Anchoring Fibrils and Loss of Dermal-Epidermal Adhesion

Type VII collagen forms the anchoring fibrils that connect the lamina densa of the basement membrane zone to the papillary dermis. In DEB, defective or absent anchoring fibrils cause tissue separation at the sub-lamina densa level, resulting in blistering and erosions with minimal mechanical trauma.

keratinocyte link

cell-matrix adhesion link ↓ DECREASED

Downstream

Skin Blistering Dermal-epidermal separation after minimal trauma produces the defining blistering and erosions of DEB.

Atrophic Scarring Recurrent sub-lamina-densa blistering heals with dermal remodeling and atrophic scarring.

Milia Milia form at sites of healed blistering and erosions.

Nail Dystrophy Fragility of nail-unit adhesion causes dystrophic or absent nails, especially in DDEB.

Chronic Wound-Inflammation-Fibrosis Cycle Repeated blistering and impaired wound healing create chronic wounds that drive a self-perpetuating cycle of inflammation and fibrosis.

Esophageal and Mucosal Blistering Loss of adhesion in mucosal epithelia causes blistering and erosions in the esophagus, oral cavity, and other mucosal surfaces.

Corneal Erosions Epithelial fragility at ocular surfaces causes recurrent corneal erosions.

Show evidence (2 references)

PMID:32973163 SUPPORT Human Clinical

"mucocutaneous fragility and blister formation, inducible by often minimal trauma"

Confirms that EB is characterized by skin fragility and blister formation from minimal trauma.

PMID:20301481 SUPPORT Human Clinical

"skin fragility manifested by blistering and erosions with minimal trauma"

GeneReviews confirms skin fragility as the hallmark clinical feature.

Chronic Wound-Inflammation-Fibrosis Cycle

Repeated blistering and impaired wound healing in DEB create chronic wounds that drive persistent inflammation and progressive fibrosis. TGF-β signaling is upregulated in RDEB fibroblasts, promoting excessive collagen deposition, tissue contraction, and extracellular matrix remodeling. This cycle underlies the progressive scarring, pseudosyndactyly, and tissue contractures characteristic of severe RDEB.

fibroblast link

wound healing link ⚠ ABNORMAL inflammatory response link ↑ INCREASED response to transforming growth factor beta link ↑ INCREASED

Downstream

Atrophic Scarring Chronic abnormal wound repair leaves progressive atrophic scars.

Anemia Chronic wounds and inflammation contribute to iron deficiency and anemia of chronic disease.

Progressive Scarring and Pseudosyndactyly Chronic fibrosis leads to progressive scarring, tissue fusion, and mitten deformities of the hands and feet.

Chronic Wounds and Aggressive Squamous Cell Carcinoma Chronic wounds with an immunosuppressive fibrotic microenvironment promote development of aggressive squamous cell carcinoma.

Show evidence (2 references)

PMID:35779740 SUPPORT In Vitro

"severe RDEB was associated with enhanced response to TGF-β stimulus, oxidoreductase activity, and cell contraction"

Gene expression profiling of RDEB fibroblasts reveals enhanced TGF-β responsiveness driving fibrosis.

PMID:35779740 SUPPORT In Vitro

"The disease manifests with devastating mucocutaneous fragility leading to progressive fibrosis and metastatic squamous cell carcinomas"

Confirms that RDEB leads to progressive fibrosis and SCC.

Progressive Scarring and Pseudosyndactyly

Chronic fibrosis from repeated wound-healing cycles leads to progressive scarring, joint contractures, and fusion of digits (pseudosyndactyly or mitten deformities). In severe RDEB, the hands and feet become encased in a cocoon of scar tissue, causing severe functional impairment.

extracellular matrix organization link ⚠ ABNORMAL

Downstream

Pseudosyndactyly Fibrotic fusion and contracture of digits manifests clinically as pseudosyndactyly.

Show evidence (1 reference)

PMID:20301481 SUPPORT Human Clinical

"Blistering of the hands and feet followed by scarring results in contractures and pseudosyndactyly"

GeneReviews confirms that scarring from repeated blistering causes pseudosyndactyly.

Esophageal and Mucosal Blistering

Blistering and erosions of the esophageal and oral mucosa lead to progressive stricture formation, microstomia, and fusion of the tongue to the floor of the mouth. Esophageal strictures cause severe dysphagia, contributing to malnutrition and growth failure.

cell-matrix adhesion link ↓ DECREASED

Downstream

Esophageal Stricture Esophageal erosions heal with webs and strictures.

Dysphagia Esophageal strictures impair swallowing and produce dysphagia.

Microstomia Oral mucosal blistering and perioral scarring progressively reduce mouth opening.

Dental Caries Oral blistering, scarring, and restricted mouth opening impair dental hygiene and contribute to dental caries risk.

Constipation Gastrointestinal mucosal fragility and perianal scarring contribute to chronic constipation.

Malnutrition and Growth Failure Esophageal strictures and oral involvement severely impair nutritional intake, leading to growth retardation and nutritional deficiencies.

Show evidence (2 references)

PMID:20301481 SUPPORT Human Clinical

"Esophageal erosions can lead to webs and strictures that can cause severe dysphagia"

GeneReviews confirms esophageal stricture formation from mucosal blistering.

PMID:19700011 SUPPORT Human Clinical

"Some epidermolysis bullosa subtypes are at risk for severe injury of the bone marrow, musculoskeletal system, heart, kidney, and teeth"

Confirms multisystem extracutaneous complications in EB including organ injury.

Malnutrition and Growth Failure

Chronic dysphagia from esophageal strictures, increased metabolic demands from chronic wound healing, and malabsorption lead to protein- calorie malnutrition, iron deficiency anemia, and growth retardation in children with severe RDEB. Vitamin and mineral deficiencies are common.

Downstream

Growth Retardation Protein-calorie malnutrition and micronutrient deficiency impair childhood growth.

Anemia Nutritional deficiency contributes to chronic anemia in severe RDEB.

Osteoporosis Malnutrition and limited mobility contribute to low bone mineral density and osteoporosis.

Show evidence (1 reference)

PMID:20301481 SUPPORT Human Clinical

"Malnutrition with vitamin and mineral deficiency may lead to growth deficiency in young children"

GeneReviews confirms malnutrition and growth deficiency as consequences of DEB.

Chronic Wounds and Aggressive Squamous Cell Carcinoma

Chronic non-healing wounds in RDEB create an immunosuppressive and pro-tumorigenic microenvironment that promotes development of aggressive cutaneous squamous cell carcinoma. SCC is the leading cause of death in RDEB, with cumulative risk in severe generalized RDEB rising from 7.5% by age 20 to over 90% by age 55. These SCCs are unusually aggressive, with high rates of metastasis and mortality.

keratinocyte link

COL7A1 link

wound healing link ⚠ ABNORMAL immune response link ↓ DECREASED

Downstream

Cutaneous Squamous Cell Carcinoma Aggressive cutaneous squamous cell carcinomas arise in chronically wounded and scarred RDEB skin.

Show evidence (4 references)

PMID:19026465 SUPPORT Human Clinical

"Cumulative risks rose steeply in RDEB-HS, from 7.5% by age 20 to 67.8%, 80.2%, and 90.1% by ages 35, 45, and 55, respectively"

National EB Registry data demonstrates extremely high cumulative SCC risk in severe RDEB.

PMID:19026465 SUPPORT Human Clinical

"By mid-adulthood, nearly all will have had at least one SCC, and nearly 80% will have died of metastatic SCC despite aggressive surgical resection"

Confirms SCC as the leading cause of death in RDEB with high metastatic potential.

PMID:32973163 SUPPORT Human Clinical

"the most feared of which - and also the leading cause of mortality - is squamous cell carcinoma"

Confirms SCC as the most feared complication and leading cause of death in EB.

+ 1 more reference

⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

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Phenotypes

Blood 1

Anemia VERY_FREQUENT Anemia (HP:0001903)

Multifactorial; iron deficiency and chronic disease

Show evidence (1 reference)

PMID:20301481 SUPPORT Human Clinical

"Anemia is treated with iron supplements and transfusions as needed"

GeneReviews confirms anemia requiring treatment in DEB.

Digestive 3

Esophageal Stricture VERY_FREQUENT Esophageal stricture (HP:0002043)

Primarily in RDEB

Show evidence (1 reference)

PMID:20301481 SUPPORT Human Clinical

"Esophageal erosions can lead to webs and strictures that can cause severe dysphagia"

GeneReviews confirms esophageal stricture formation in DEB.

Dysphagia VERY_FREQUENT Dysphagia (HP:0002015)

Secondary to esophageal strictures in RDEB

Show evidence (1 reference)

PMID:20301481 SUPPORT Human Clinical

"Esophageal erosions can lead to webs and strictures that can cause severe dysphagia"

Confirms dysphagia as a consequence of esophageal strictures.

Constipation FREQUENT Constipation (HP:0002019)

Show evidence (1 reference)

PMID:20301481 SUPPORT Human Clinical

"management of constipation"

GeneReviews mentions constipation management as part of DEB care.

Eye 1

Corneal Erosions FREQUENT Corneal erosion (HP:0200020)

Show evidence (1 reference)

PMID:20301481 SUPPORT Human Clinical

"Corneal erosions can lead to scarring and loss of vision"

GeneReviews confirms corneal erosions as a DEB complication.

Head and Neck 2

Microstomia FREQUENT Narrow mouth (HP:0000160)

Primarily in severe RDEB

Show evidence (1 reference)

PMID:20301481 SUPPORT Human Clinical

"Oral involvement may lead to mouth blistering, fusion of the tongue to the floor of the mouth, and progressive diminution of the size of the oral cavity and mouth opening"

GeneReviews confirms microstomia from progressive oral scarring.

Dental Caries FREQUENT Carious teeth (HP:0000670)

Show evidence (2 references)

PMID:22940071 SUPPORT Human Clinical

"Patients with RDEB present a low oral hygiene index and prevalent tooth abnormalities with caries"

RDEB-specific study links type VII collagen deficiency to enamel structural defects and reports prevalent tooth abnormalities with caries.

PMID:19700011 SUPPORT Human Clinical

"Some epidermolysis bullosa subtypes are at risk for severe injury of the bone marrow, musculoskeletal system, heart, kidney, and teeth"

Confirms dental/teeth involvement as an extracutaneous EB complication requiring surveillance.

Integument 5

Skin Blistering OBLIGATE Abnormal blistering of the skin (HP:0008066)

Show evidence (2 references)

PMID:32973163 SUPPORT Human Clinical

"mucocutaneous fragility and blister formation, inducible by often minimal trauma"

Confirms skin blistering induced by minimal trauma as the defining feature of EB.

PMID:20301481 SUPPORT Human Clinical

"skin fragility manifested by blistering and erosions with minimal trauma"

GeneReviews confirms blistering and erosions as cardinal features.

Atrophic Scarring VERY_FREQUENT Atrophic scars (HP:0001075)

Show evidence (1 reference)

PMID:20301481 SUPPORT Human Clinical

"skin fragility manifested by blistering and erosions with minimal trauma that heals with milia and scarring"

GeneReviews confirms healing with scarring as a defining DEB feature.

Milia VERY_FREQUENT Milia (HP:0001056)

Show evidence (1 reference)

PMID:20301481 SUPPORT Human Clinical

"blistering and erosions with minimal trauma that heals with milia and scarring"

GeneReviews confirms milia formation at healed blister sites.

Nail Dystrophy VERY_FREQUENT Nail dystrophy (HP:0008404)

Show evidence (1 reference)

PMID:20301481 SUPPORT Human Clinical

"Dystrophic nails, especially toenails, are common and may be the only manifestation of DDEB"

GeneReviews confirms nail dystrophy as a very common DEB feature.

Cutaneous Squamous Cell Carcinoma VERY_FREQUENT Squamous cell carcinoma of the skin (HP:0006739)

Leading cause of death in severe RDEB; begins in adolescence

Show evidence (2 references)

PMID:19026465 SUPPORT Human Clinical

"Cumulative risks rose steeply in RDEB-HS, from 7.5% by age 20 to 67.8%, 80.2%, and 90.1% by ages 35, 45, and 55, respectively"

National EB Registry documents extremely high lifetime SCC risk in severe RDEB.

PMID:19026465 SUPPORT Human Clinical

"nearly 80% will have died of metastatic SCC despite aggressive surgical resection"

Confirms high mortality from metastatic SCC in RDEB.

Limbs 1

Pseudosyndactyly VERY_FREQUENT Cutaneous finger syndactyly (HP:0010554)

Characteristic of severe RDEB

Show evidence (1 reference)

PMID:20301481 SUPPORT Human Clinical

"Blistering of the hands and feet followed by scarring results in contractures and pseudosyndactyly"

GeneReviews confirms pseudosyndactyly from progressive scarring.

Musculoskeletal 1

Osteoporosis FREQUENT Osteoporosis (HP:0000939)

Primarily in severe RDEB

Show evidence (1 reference)

PMID:20301481 SUPPORT Human Clinical

"Calcium and vitamin D supplementation and bisphosphonates as needed for osteoporosis"

GeneReviews confirms osteoporosis requiring treatment in DEB.

Growth 1

Growth Retardation VERY_FREQUENT Growth delay (HP:0001510)

Primarily in severe RDEB

Show evidence (1 reference)

PMID:20301481 SUPPORT Human Clinical

"Malnutrition with vitamin and mineral deficiency may lead to growth deficiency in young children"

GeneReviews confirms growth deficiency from malnutrition in DEB.

🧬

Genetic Associations

COL7A1 (Causative)

Autosomal dominant Autosomal recessive

Show evidence (3 references)

PMID:36516090 SUPPORT Human Clinical

"Dystrophic epidermolysis bullosa is a rare genetic blistering skin disease caused by mutations in COL7A1, which encodes type VII collagen (C7)"

Confirms COL7A1 as the causative gene for DEB.

PMID:20301481 SUPPORT Human Clinical

"biallelic COL7A1 pathogenic variants (for RDEB) or a heterozygous pathogenic variant in COL7A1 (for DDEB)"

GeneReviews confirms both dominant and recessive inheritance patterns for COL7A1 mutations.

PMID:20301481 SUPPORT Human Clinical

"Some COL7A1 pathogenic variants are associated with both DDEB and RDEB"

Confirms that some variants can cause either dominant or recessive DEB.

💊

Treatments

Beremagene Geperpavec (Vyjuvek)

Action: gene therapy MAXO:0001001

Topical HSV-1-based gene therapy that delivers functional COL7A1 to restore type VII collagen protein expression in wound beds. FDA approved in 2023 for dystrophic epidermolysis bullosa. Phase III trial demonstrated complete wound healing in 67% of B-VEC-treated wounds vs 22% placebo at 6 months.

Mechanism Target:

RESTORES COL7A1 Mutations and Loss of Type VII Collagen — Topical HSV-1 COL7A1 delivery restores type VII collagen expression in treated wounds.

RESTORES Defective Anchoring Fibrils and Loss of Dermal-Epidermal Adhesion — Restored type VII collagen improves dermal-epidermal adhesion and wound closure.

Show evidence (2 references)

PMID:36516090 SUPPORT Human Clinical

"Complete wound healing at 3 and 6 months in patients with dystrophic epidermolysis bullosa was more likely with topical administration of B-VEC than with placebo"

Phase III trial conclusions confirming B-VEC efficacy for wound healing in DEB.

PMID:36516090 SUPPORT Human Clinical

"Beremagene geperpavec (B-VEC) is a topical investigational herpes simplex virus type 1 (HSV-1)-based gene therapy designed to restore C7 protein by delivering COL7A1"

Describes the mechanism of B-VEC gene therapy for DEB.

Prademagene Zamikeracel (Zevaskyn)

Action: gene therapy MAXO:0001001

Ex vivo autologous gene therapy for RDEB. Patient keratinocytes are transduced with a retroviral vector encoding COL7A1, expanded into epidermal sheets, and surgically grafted onto chronic wounds. FDA approved April 2025 as the first cell-based gene therapy for RDEB. Phase III VIITAL trial demonstrated that 81% of treated wounds achieved at least 50% healing at 6 months versus 16% of control wounds.

Mechanism Target:

RESTORES COL7A1 Mutations and Loss of Type VII Collagen — Autologous COL7A1 gene-modified keratinocyte sheets provide corrected epidermis to chronic RDEB wounds.

RESTORES Defective Anchoring Fibrils and Loss of Dermal-Epidermal Adhesion — Corrected grafts are intended to restore collagen VII at the wound bed and improve adhesion.

Show evidence (2 references)

PMID:40570869 SUPPORT Human Clinical

"At week 24, 35 (81%) of 43 treated wounds were at least 50% healed from baseline for prademagene zamikeracel compared with seven (16%) of 43 control wounds"

Phase III VIITAL trial demonstrates statistically significant wound healing efficacy of prademagene zamikeracel in RDEB.

PMID:40570869 SUPPORT Human Clinical

"Prademagene zamikeracel is an autologous COL7A1 gene-modified cellular sheet that is sutured onto to a large, chronic RDEB wound"

Describes the mechanism of prademagene zamikeracel as an autologous gene-modified cellular sheet for RDEB wounds.

Recombinant Type VII Collagen (PTR-01)

Action: intravenous protein replacement therapy Ontology label: pharmacotherapy MAXO:0000058

Investigational intravenous protein replacement therapy using recombinant type VII collagen (rC7) for systemic treatment of RDEB. Preclinical studies in RDEB mice and dogs demonstrated that IV rC7 accumulates at the basement membrane zone, reduces fibrosis via decreased TGF-β signaling, and promotes wound healing. Phase 2 clinical trial results have been reported but not yet published in peer-reviewed literature.

Mechanism Target:

RESTORES Defective Anchoring Fibrils and Loss of Dermal-Epidermal Adhesion — Intravenous recombinant type VII collagen incorporates at the dermal-epidermal junction in preclinical models.

INHIBITS Chronic Wound-Inflammation-Fibrosis Cycle — Systemic collagen VII replacement reduced fibrosis and improved wound healing in RDEB animal models.

Show evidence (2 references)

PMID:34606885 SUPPORT Model Organism

"Fortnightly IV injections of rC7 for 7 weeks in adult RDEB mice reduced fibrosis of skin and eye"

Preclinical study demonstrates that systemic IV rC7 reduces fibrosis in adult RDEB animal models.

PMID:34606885 SUPPORT Model Organism

"IV rC7 in adult RDEB dogs incorporated in the dermal‒epidermal junction of skin and improved disease by promoting wound healing and reducing dermal‒epidermal separation"

Large animal model confirms that IV rC7 incorporates at the DEJ and improves wound healing in established RDEB.

Losartan

Action: losartan anti-fibrotic therapy Ontology label: pharmacotherapy MAXO:0000058

Agent: losartan ↗

Anti-fibrotic angiotensin II type 1 receptor antagonist that reduces TGF-β signaling. The REFLECT Phase 1/2 trial enrolled 29 children with RDEB and demonstrated that losartan was well tolerated with improvements in EBDASI damage scores and BEBS scores. Losartan may reduce disease burden by mitigating progressive fibrosis.

Mechanism Target:

INHIBITS Chronic Wound-Inflammation-Fibrosis Cycle — Losartan is used as an anti-fibrotic intervention intended to reduce TGF-β-driven fibrosis and disease burden in RDEB.

Show evidence (2 references)

PMID:39539991 SUPPORT Human Clinical

"Losartan was well tolerated, no treatment-related severe complications leading to a serious safety concern occurred"

REFLECT Phase 1/2 trial demonstrates safety and tolerability of losartan in children with RDEB.

PMID:39539991 SUPPORT Human Clinical

"Similar to the EBDASI score, the BEBS showed a mean reduction of -3 points, 95%-CI: -0.21 to -5,79, P = 0.036)"

REFLECT trial shows statistically significant improvement in BEBS scores with losartan treatment in RDEB children.

Rigosertib

Action: rigosertib PLK1 inhibitor therapy Ontology label: chemotherapy MAXO:0000647

Polo-like kinase-1 (PLK1) inhibitor investigated for RDEB-associated squamous cell carcinoma, the leading cause of death in RDEB. Phase II trials in Europe and the USA enrolled five patients with locally advanced or metastatic RDEB-SCC. Antitumour efficacy was observed with acceptable toxicity, and two patients had a complete response within 6 months.

Mechanism Target:

INHIBITS Chronic Wounds and Aggressive Squamous Cell Carcinoma — Rigosertib is directed at the aggressive RDEB-associated SCC compartment that arises from chronic wounded fibrotic skin.

Show evidence (2 references)

PMID:40439508 SUPPORT Human Clinical

"Antitumour efficacy with acceptable toxicity was seen in patients on IV or oral therapy and two patients had a complete response within 6 months of treatment"

Phase II trial demonstrates antitumour activity and complete responses with rigosertib in RDEB-SCC patients.

PMID:40439508 SUPPORT Human Clinical

"These data identify rigosertib as a promising drug therapy for patients with RDEB-SCC where there is a substantial unmet need, absence of approved therapies and where tumours arise on a background of a unique fibrotic and inflammatory environment"

Identifies rigosertib as a promising therapeutic option for the currently untreatable RDEB-associated SCC.

Gentamicin Readthrough Therapy

Action: gentamicin readthrough therapy Ontology label: pharmacotherapy MAXO:0000058

Agent: gentamicin ↗

Intravenous gentamicin induces translational readthrough of nonsense mutations in COL7A1, restoring functional type VII collagen at the dermal-epidermal junction. Applicable to approximately 30% of RDEB patients who carry nonsense mutations. An open-label pilot trial treated 3 RDEB patients with IV gentamicin for 14 days; all showed increased C7 at the DEJ persisting for at least 6 months, and monitored wounds exhibited greater than 85% closure.

Mechanism Target:

RESTORES COL7A1 Mutations and Loss of Type VII Collagen — Gentamicin promotes readthrough of COL7A1 nonsense mutations to increase type VII collagen at the dermal-epidermal junction.

Show evidence (2 references)

PMID:38366625 SUPPORT Human Clinical

"After gentamicin treatment, skin biopsies from all three patients (age range 18-28 years) exhibited increased C7 in their DEJ"

Open-label clinical trial demonstrates that IV gentamicin restores type VII collagen at the DEJ in RDEB patients with nonsense mutations.

PMID:38366625 SUPPORT Human Clinical

"At 1 and 3 months post-treatment, 100% of the monitored wounds exhibited > 85% closure"

Demonstrates significant wound healing improvement after IV gentamicin readthrough therapy in RDEB.

Filsuvez (Birch Triterpenes) Topical Gel

Action: birch triterpenes topical gel Ontology label: pharmacotherapy MAXO:0000058

Agent: birch triterpenes ↗

Oleogel-S10 (Filsuvez), a topical gel containing birch triterpenes, is used for partial-thickness wounds associated with dystrophic and junctional EB in patients aged 6 months and older. In the phase III EASE trial, Oleogel-S10 accelerated target wound closure compared with control gel.

Mechanism Target:

MODULATES Chronic Wound-Inflammation-Fibrosis Cycle — Topical birch triterpenes accelerate wound closure, reducing persistence of open wounds that sustain inflammation and fibrosis.

Show evidence (2 references)

PMID:36689495 SUPPORT Human Clinical

"Oleogel-S10 is the first therapy to demonstrate accelerated wound healing in EB"

Phase III EASE trial confirms Oleogel-S10 as a wound-healing therapy across EB subtypes including dystrophic EB.

PMID:39748581 SUPPORT Human Clinical

"Filsuvez® (birch triterpenes) topical gel received approval in 2023 for the treatment of epidermolysis bullosa (EB)"

Confirms regulatory approval of birch triterpenes topical gel for EB wound treatment.

Wound Care and Specialized Dressings

Action: wound care management Ontology label: supportive care MAXO:0000950

Meticulous wound care is the cornerstone of DEB management. New blisters should be lanced and drained, then dressed with nonadherent dressings and protective padding. Prevention of new blisters through education, padding of extremities, and soft clothing is essential.

Mechanism Target:

MODULATES Chronic Wound-Inflammation-Fibrosis Cycle — Nonadherent dressings, padding, blister drainage, and infection control reduce wound trauma and downstream inflammation.

Show evidence (1 reference)

PMID:32973163 SUPPORT Human Clinical

"multidisciplinary care is targeted towards minimizing the risk of blister formation, wound care, symptom relief and specific complications"

Confirms wound care as a central component of EB management.

Esophageal Dilation

Action: esophageal dilation Ontology label: Esophageal Dilation NCIT:C70908

Balloon dilation of esophageal strictures and webs to improve swallowing and nutritional intake. May need to be repeated as strictures recur.

Mechanism Target:

BYPASSES Esophageal and Mucosal Blistering — Dilation bypasses the obstructive consequence of mucosal blistering and scarring by mechanically opening esophageal strictures.

Show evidence (1 reference)

PMID:20301481 SUPPORT Human Clinical

"dilation of esophageal strictures and webs to improve swallowing"

GeneReviews confirms esophageal dilation as standard management.

Nutritional Support

Action: nutritional support Ontology label: dietary intervention MAXO:0000088

High-calorie nutritional supplementation with iron, vitamin A, zinc, selenium, carnitine, calcium, and vitamin D. Feeding gastrostomy tube placement may be necessary for patients with severe dysphagia.

Mechanism Target:

MODULATES Malnutrition and Growth Failure — Nutritional supplementation and gastrostomy support address the downstream malnutrition caused by dysphagia and chronic wounds.

Show evidence (1 reference)

PMID:20301481 SUPPORT Human Clinical

"nutritional support including feeding gastrostomy tube, vitamin A, zinc, selenium, and carnitine supplementation"

GeneReviews confirms comprehensive nutritional support including supplements and gastrostomy.

SCC Surveillance

Action: cancer screening MAXO:0000126

Regular skin examination with biopsy of suspicious lesions beginning at age 10 years. Annual screening for crusted, non-healing, and painful lesions as well as those with exuberant scar tissue.

Show evidence (1 reference)

PMID:20301481 SUPPORT Human Clinical

"evaluation of crusted, non-healing, and painful lesions as well as those with exuberant scar tissue at least annually beginning at age ten years; biopsies of suspicious lesions for evidence of SCC"

GeneReviews recommends SCC surveillance starting at age 10.

Surgical Excision of SCC

Action: surgical excision Ontology label: surgical procedure MAXO:0000004

Aggressive surgical excision of confirmed squamous cell carcinomas, although outcomes remain poor due to high metastatic potential.

Mechanism Target:

INHIBITS Chronic Wounds and Aggressive Squamous Cell Carcinoma — Surgical excision removes established RDEB-associated squamous cell carcinomas arising from chronic scarred wounds.

Show evidence (1 reference)

PMID:19026465 SUPPORT Human Clinical

"nearly 80% will have died of metastatic SCC despite aggressive surgical resection"

Confirms the poor prognosis of SCC in RDEB despite surgical treatment.

Pain Management

Action: pain management Ontology label: supportive care MAXO:0000950

Multimodal pain management including topical, oral, and psychological therapies for chronic pain and itch associated with wounds and dressing changes.

Show evidence (1 reference)

PMID:20301481 SUPPORT Human Clinical

"topical, oral, and psychological therapies for pain and itch"

GeneReviews confirms multimodal pain management in DEB.

Physical and Occupational Therapy

Action: physical therapy MAXO:0000011

Physical and occupational therapy to preserve hand function, maintain ambulation, and prevent joint contractures. Surgical release of fused digits may need to be repeated.

Mechanism Target:

MODULATES Progressive Scarring and Pseudosyndactyly — Physical and occupational therapy act downstream of fibrosis to preserve hand function and reduce contracture burden.

Show evidence (1 reference)

PMID:20301481 SUPPORT Human Clinical

"Occupational and physical therapy may help prevent hand and other joint contractures"

GeneReviews confirms physical/occupational therapy for contracture prevention.

Allogeneic Bone Marrow Transplantation

Action: hematopoietic stem cell transplantation MAXO:0000747

Investigational treatment for severe RDEB. Allogeneic bone marrow transplantation has shown increased type VII collagen deposition and improved wound healing, but carries significant morbidity and mortality from the conditioning regimen.

Mechanism Target:

RESTORES Defective Anchoring Fibrils and Loss of Dermal-Epidermal Adhesion — Allogeneic bone marrow transplantation is intended to increase collagen VII deposition in RDEB skin.

Show evidence (2 references)

PMID:20818854 SUPPORT Human Clinical

"Increased C7 deposition and a sustained presence of donor cells were found in the skin of children with recessive dystrophic epidermolysis bullosa after allogeneic bone marrow transplantation"

Wagner et al. demonstrated increased collagen VII after BMT in RDEB children.

PMID:20818854 SUPPORT Human Clinical

"all having improved wound healing and a reduction in blister formation between 30 and 130 days after transplantation"

Confirms clinical improvement in wound healing after BMT.

Genetic Counseling

Action: genetic counseling MAXO:0000079

Genetic counseling for families affected by DEB, including carrier testing, prenatal diagnosis, and preimplantation genetic testing. Mode of inheritance determination requires molecular characterization of COL7A1 variants.

Show evidence (1 reference)

PMID:20301481 SUPPORT Human Clinical

"Once the COL7A1 pathogenic variant(s) have been identified in an affected family member, prenatal and preimplantation genetic testing are possible"

GeneReviews confirms availability of prenatal and preimplantation testing.

📊

Related Datasets

Single-cell RNA-seq of fibroblasts from recessive dystrophic epidermolysis bullosa patients and wild-type controls geo:GSE108849

Human single-cell transcriptomic dataset profiling fibroblast populations from recessive dystrophic epidermolysis bullosa and control samples to resolve disease-relevant stromal heterogeneity.

human SINGLE CELL RNA SEQ n=543

Conditions: recessive dystrophic epidermolysis bullosa fibroblasts wild-type control fibroblasts

Show evidence (1 reference)

GEO:GSE108849 SUPPORT In Vitro

"The goal of this study is to discover fibroblast subpopulations relevant to recessive dystrophic epidermolysis bullosa"

Directly supports this GEO series as a single-cell fibroblast resource for DEB mechanism studies.

🔬

Clinical Trials

NCT04491604 PHASE_III COMPLETED

Phase III intrapatient randomized trial of topical beremagene geperpavec (B-VEC/KB103) to improve wound healing in genetically confirmed dystrophic epidermolysis bullosa by delivering COL7A1.

Target Phenotypes: Wound healing impairment ↗

Show evidence (1 reference)

clinicaltrials:NCT04491604 SUPPORT Human Clinical

"To determine whether administration of topical B-VEC improves wound healing as compared to placebo, and to evaluate durability, repeat dosing (Primary Endpoint) and further obtain safety and tolerability data."

ClinicalTrials.gov summary confirms the topical B-VEC phase III trial objective, wound-healing endpoint, and safety focus in DEB.

NCT03536143 PHASE_I COMPLETED

Early-phase topical HSV1-COL7 gene therapy trial evaluating safety and preliminary efficacy of beremagene geperpavec (KB103) in dystrophic epidermolysis bullosa.

Target Phenotypes: Wound healing impairment ↗

Show evidence (1 reference)

clinicaltrials:NCT03536143 SUPPORT Human Clinical

"This study was conducted to assess the safety and efficacy of topical Beremagene Geperpavec (KB103, HSV1-COL7) on DEB patients."

ClinicalTrials.gov summary confirms early-phase topical KB103/B-VEC evaluation for safety and efficacy in DEB.

{ }

Source YAML

click to show

name: Dystrophic Epidermolysis Bullosa
creation_date: '2026-03-10T12:00:00Z'
updated_date: '2026-05-08T20:47:43Z'
category: Mendelian
description: >-
  Dystrophic epidermolysis bullosa (DEB) is caused by mutations in COL7A1
  encoding type VII collagen, the major structural component of anchoring
  fibrils at the dermal-epidermal junction. Both autosomal dominant (DDEB) and
  autosomal recessive (RDEB) forms exist. RDEB severe generalized is
  characterized by generalized blistering, progressive scarring with
  pseudosyndactyly, esophageal strictures, and a lifetime squamous cell
  carcinoma risk exceeding 90%.
parents:
- Dermatological Disease
- Genetic Disease
disease_term:
  preferred_term: dystrophic epidermolysis bullosa
  term:
    id: MONDO:0006543
    label: epidermolysis bullosa dystrophica
mappings:
  icd10cm_mappings:
  - term:
      id: ICD10CM:Q81.2
      label: Epidermolysis bullosa dystrophica
    mapping_predicate: skos:exactMatch
    mapping_source: ICD-10-CM
    mapping_justification: ICD-10-CM Q81.2 directly names dystrophic epidermolysis bullosa.
  mondo_mappings:
  - term:
      id: MONDO:0006543
      label: epidermolysis bullosa dystrophica
    mapping_predicate: skos:exactMatch
    mapping_source: MONDO
    mapping_justification: Primary MONDO disease identifier for this DEB entry.
classifications:
  harrisons_chapter:
  - classification_value: skin disorder
    evidence:
    - reference: PMID:20301481
      reference_title: "Dystrophic Epidermolysis Bullosa."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Dystrophic epidermolysis bullosa (DEB) is characterized by skin fragility manifested by blistering and erosions with minimal trauma"
      explanation: Supports classifying DEB as a skin disorder because the disorder is defined by traumatic skin blistering and erosions.
  - classification_value: hereditary disease
    evidence:
    - reference: PMID:20301481
      reference_title: "Dystrophic Epidermolysis Bullosa."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "DEB is inherited in either an autosomal dominant (DDEB) or autosomal recessive (RDEB) manner"
      explanation: Supports classifying DEB as a hereditary disease because both dominant and recessive inherited forms are established.
has_subtypes:
- name: DDEB
  display_name: Dominant Dystrophic Epidermolysis Bullosa (DDEB)
  subtype_term:
    preferred_term: dominant dystrophic epidermolysis bullosa
    term:
      id: MONDO:0007549
      label: generalized dominant dystrophic epidermolysis bullosa
  description: >
    Mild, localized blistering caused by dominant-negative COL7A1 mutations.
    Nails are most commonly affected, and blistering is often limited to
    hands, feet, knees, and elbows. Heals with scarring but without the
    severe complications seen in recessive forms.
- name: RDEB-sev gen
  display_name: Recessive Dystrophic Epidermolysis Bullosa, Severe Generalized (RDEB-sev gen)
  subtype_term:
    preferred_term: severe generalized recessive dystrophic epidermolysis bullosa
    term:
      id: MONDO:0009179
      label: recessive dystrophic epidermolysis bullosa
  description: >
    Formerly known as Hallopeau-Siemens RDEB. The most severe form, caused
    by biallelic loss-of-function COL7A1 mutations leading to absent or
    severely reduced type VII collagen. Characterized by generalized
    blistering from birth, progressive scarring, mitten deformities
    (pseudosyndactyly), esophageal strictures, and a lifetime squamous
    cell carcinoma risk exceeding 90%.
- name: RDEB-intermediate
  display_name: Recessive Dystrophic Epidermolysis Bullosa, Intermediate (RDEB-intermediate)
  subtype_term:
    preferred_term: intermediate recessive dystrophic epidermolysis bullosa
    term:
      id: MONDO:0019522
      label: recessive dystrophic epidermolysis bullosa-generalized other
  description: >
    Formerly known as non-Hallopeau-Siemens RDEB. Moderate scarring with
    blistering that may be localized to hands, feet, knees, elbows, and
    flexural areas. Less severe than RDEB-sev gen, with lower SCC risk,
    but still carries significant morbidity from scarring and extracutaneous
    involvement.
- name: RDEB-Inversa
  display_name: Recessive Dystrophic Epidermolysis Bullosa Inversa
  subtype_term:
    preferred_term: recessive dystrophic epidermolysis bullosa inversa
    term:
      id: MONDO:0019310
      label: recessive dystrophic epidermolysis bullosa inversa
  description: >
    Blistering predominantly affects intertriginous (skin fold) areas
    including axillae, groin, and neck. May also involve the esophagus
    and other mucosal surfaces. Caused by specific COL7A1 mutations
    that produce some residual type VII collagen function.
prevalence:
- population: Global
  notes: >-
    Estimated incidence of all DEB is approximately 6.65 per million live
    births in the United States, with RDEB-specific incidence of 3.05 per
    million live births based on the National Epidermolysis Bullosa Registry.
    Genetic modelling suggests RDEB may be significantly underdiagnosed.
    Life expectancy in severe generalized RDEB is markedly reduced, with
    cumulative SCC risk exceeding 90% by age 55 and SCC being the leading
    cause of death.
  evidence:
  - reference: PMID:27463098
    reference_title: "Epidemiology of Inherited Epidermolysis Bullosa Based on Incidence and Prevalence Estimates From the National Epidermolysis Bullosa Registry."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the overall incidence and prevalence of inherited EB were 19.60 and 8.22 per 1 million live births, respectively"
    explanation: US National EB Registry provides overall EB incidence and prevalence data including DEB subtypes.
  - reference: PMID:31920360
    reference_title: "From Clinical Phenotype to Genotypic Modelling: Incidence and Prevalence of Recessive Dystrophic Epidermolysis Bullosa (RDEB)."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the widely estimated incidence (0.2-6.65 per million births) and prevalence (3.5-20.4 per million people) of RDEB has been primarily characterized by limited analyses of clinical databases or registries"
    explanation: Summarizes the range of published RDEB incidence and prevalence estimates across multiple registries.
  - reference: PMID:19026465
    reference_title: "Epidermolysis bullosa and the risk of life-threatening cancers: the National EB Registry experience, 1986-2006."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Cumulative risks rose steeply in RDEB-HS, from 7.5% by age 20 to 67.8%, 80.2%, and 90.1% by ages 35, 45, and 55, respectively"
    explanation: Demonstrates the extremely high cumulative SCC risk in severe RDEB that drives mortality and reduced life expectancy.
inheritance:
- name: Autosomal dominant
  description: Dominant dystrophic epidermolysis bullosa (DDEB)
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "About 70% of individuals diagnosed with DDEB are reported to have an affected parent"
    explanation: GeneReviews confirms autosomal dominant inheritance for DDEB.
- name: Autosomal recessive
  description: Recessive dystrophic epidermolysis bullosa (RDEB)
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "If both parents are known to be heterozygous for a COL7A1 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected"
    explanation: GeneReviews confirms autosomal recessive inheritance for RDEB.
pathophysiology:
- name: Heterozygous COL7A1 Pathogenic Variant (DDEB)
  description: >
    A heterozygous pathogenic variant in COL7A1 is the molecular lesion in
    dominant dystrophic epidermolysis bullosa. The resulting type VII collagen
    dysfunction produces a usually milder, localized blistering phenotype that
    often affects hands, feet, knees, elbows, and nails.
  genes:
  - preferred_term: COL7A1
    term:
      id: hgnc:2214
      label: COL7A1
  subtypes:
  - DDEB
  downstream:
  - target: COL7A1 Mutations and Loss of Type VII Collagen
    causal_link_type: DIRECT
    description: >
      Heterozygous COL7A1 pathogenic variants produce dysfunctional type VII
      collagen and thereby converge on the collagen VII/anchoring fibril defect.
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "biallelic COL7A1 pathogenic variants (for RDEB) or a heterozygous pathogenic variant in COL7A1 (for DDEB)"
    explanation: GeneReviews defines DDEB by a heterozygous COL7A1 pathogenic variant.
- name: Biallelic COL7A1 Pathogenic Variants (RDEB)
  description: >
    Biallelic pathogenic variants in COL7A1 are the molecular lesion in
    recessive dystrophic epidermolysis bullosa. Severe generalized RDEB reflects
    marked type VII collagen deficiency, producing generalized neonatal
    blistering, progressive scarring, pseudosyndactyly, esophageal strictures,
    growth failure, and very high lifetime squamous cell carcinoma risk.
  genes:
  - preferred_term: COL7A1
    term:
      id: hgnc:2214
      label: COL7A1
  subtypes:
  - RDEB-sev gen
  - RDEB-intermediate
  - RDEB-Inversa
  downstream:
  - target: COL7A1 Mutations and Loss of Type VII Collagen
    causal_link_type: DIRECT
    description: >
      Biallelic COL7A1 pathogenic variants reduce or abolish type VII collagen
      function and thereby converge on the collagen VII/anchoring fibril defect.
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "biallelic COL7A1 pathogenic variants (for RDEB) or a heterozygous pathogenic variant in COL7A1 (for DDEB)"
    explanation: GeneReviews defines RDEB by biallelic COL7A1 pathogenic variants.
- name: COL7A1 Mutations and Loss of Type VII Collagen
  description: >
    Mutations in the COL7A1 gene encoding type VII collagen result in absent,
    reduced, or dysfunctional protein. In RDEB, biallelic loss-of-function
    mutations typically cause complete absence of type VII collagen, while
    in DDEB, dominant-negative mutations produce structurally abnormal
    collagen that disrupts anchoring fibril formation. Type VII collagen
    is the major structural component of anchoring fibrils at the
    dermal-epidermal junction.
  genes:
  - preferred_term: COL7A1
    term:
      id: hgnc:2214
      label: COL7A1
  biological_processes:
  - preferred_term: collagen fibril organization
    modifier: ABNORMAL
    term:
      id: GO:0030199
      label: collagen fibril organization
  - preferred_term: extracellular matrix organization
    modifier: ABNORMAL
    term:
      id: GO:0030198
      label: extracellular matrix organization
  cell_types:
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  - preferred_term: fibroblast
    term:
      id: CL:0000057
      label: fibroblast
  downstream:
  - target: Defective Anchoring Fibrils and Loss of Dermal-Epidermal Adhesion
    causal_link_type: DIRECT
    description: >
      Absent or dysfunctional type VII collagen leads to defective
      anchoring fibrils that fail to secure the epidermis to the dermis.
  evidence:
  - reference: PMID:36516090
    reference_title: "Trial of Beremagene Geperpavec (B-VEC) for Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Dystrophic epidermolysis bullosa is a rare genetic blistering skin disease caused by mutations in COL7A1, which encodes type VII collagen (C7)"
    explanation: Confirms COL7A1 mutations as the cause of DEB.
  - reference: PMID:32973163
    reference_title: "Epidermolysis bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "pathogenetic mutations in 16 distinct genes have been implicated in EB, encoding proteins influencing cellular integrity and adhesion"
    explanation: Confirms that EB is caused by mutations in genes encoding structural proteins critical for cell adhesion.
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "biallelic COL7A1 pathogenic variants (for RDEB) or a heterozygous pathogenic variant in COL7A1 (for DDEB)"
    explanation: GeneReviews confirms the genetic basis of both RDEB and DDEB in COL7A1.
- name: Defective Anchoring Fibrils and Loss of Dermal-Epidermal Adhesion
  description: >
    Type VII collagen forms the anchoring fibrils that connect the lamina
    densa of the basement membrane zone to the papillary dermis. In DEB,
    defective or absent anchoring fibrils cause tissue separation at the
    sub-lamina densa level, resulting in blistering and erosions with
    minimal mechanical trauma.
  biological_processes:
  - preferred_term: cell-matrix adhesion
    modifier: DECREASED
    term:
      id: GO:0007160
      label: cell-matrix adhesion
  cell_types:
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  downstream:
  - target: Skin Blistering
    causal_link_type: DIRECT
    description: >
      Dermal-epidermal separation after minimal trauma produces the defining
      blistering and erosions of DEB.
  - target: Atrophic Scarring
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - blister healing with dermal matrix remodeling
    description: >
      Recurrent sub-lamina-densa blistering heals with dermal remodeling and
      atrophic scarring.
  - target: Milia
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - healing of recurrent blisters
    description: >
      Milia form at sites of healed blistering and erosions.
  - target: Nail Dystrophy
    causal_link_type: DIRECT
    description: >
      Fragility of nail-unit adhesion causes dystrophic or absent nails,
      especially in DDEB.
  - target: Chronic Wound-Inflammation-Fibrosis Cycle
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - repeated blistering and erosions
    description: >
      Repeated blistering and impaired wound healing create chronic wounds
      that drive a self-perpetuating cycle of inflammation and fibrosis.
  - target: Esophageal and Mucosal Blistering
    causal_link_type: DIRECT
    description: >
      Loss of adhesion in mucosal epithelia causes blistering and erosions
      in the esophagus, oral cavity, and other mucosal surfaces.
  - target: Corneal Erosions
    causal_link_type: DIRECT
    description: >
      Epithelial fragility at ocular surfaces causes recurrent corneal erosions.
  evidence:
  - reference: PMID:32973163
    reference_title: "Epidermolysis bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "mucocutaneous fragility and blister formation, inducible by often minimal trauma"
    explanation: Confirms that EB is characterized by skin fragility and blister formation from minimal trauma.
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "skin fragility manifested by blistering and erosions with minimal trauma"
    explanation: GeneReviews confirms skin fragility as the hallmark clinical feature.
- name: Chronic Wound-Inflammation-Fibrosis Cycle
  description: >
    Repeated blistering and impaired wound healing in DEB create chronic
    wounds that drive persistent inflammation and progressive fibrosis.
    TGF-β signaling is upregulated in RDEB fibroblasts, promoting
    excessive collagen deposition, tissue contraction, and extracellular
    matrix remodeling. This cycle underlies the progressive scarring,
    pseudosyndactyly, and tissue contractures characteristic of severe RDEB.
  biological_processes:
  - preferred_term: wound healing
    modifier: ABNORMAL
    term:
      id: GO:0042060
      label: wound healing
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  - preferred_term: response to transforming growth factor beta
    modifier: INCREASED
    term:
      id: GO:0071559
      label: response to transforming growth factor beta
  cell_types:
  - preferred_term: fibroblast
    term:
      id: CL:0000057
      label: fibroblast
  downstream:
  - target: Atrophic Scarring
    causal_link_type: DIRECT
    description: >
      Chronic abnormal wound repair leaves progressive atrophic scars.
  - target: Anemia
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - chronic wound blood loss
    - anemia of chronic inflammation
    description: >
      Chronic wounds and inflammation contribute to iron deficiency and anemia
      of chronic disease.
  - target: Progressive Scarring and Pseudosyndactyly
    causal_link_type: DIRECT
    description: >
      Chronic fibrosis leads to progressive scarring, tissue fusion,
      and mitten deformities of the hands and feet.
  - target: Chronic Wounds and Aggressive Squamous Cell Carcinoma
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - chronic non-healing wounds
    - fibrotic inflammatory microenvironment
    description: >
      Chronic wounds with an immunosuppressive fibrotic microenvironment
      promote development of aggressive squamous cell carcinoma.
  evidence:
  - reference: PMID:35779740
    reference_title: "Mechanistic interrogation of mutation-independent disease modulators of RDEB identifies the small leucine-rich proteoglycan PRELP as a TGF-β antagonist and inhibitor of fibrosis."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "severe RDEB was associated with enhanced response to TGF-β stimulus, oxidoreductase activity, and cell contraction"
    explanation: Gene expression profiling of RDEB fibroblasts reveals enhanced TGF-β responsiveness driving fibrosis.
  - reference: PMID:35779740
    reference_title: "Mechanistic interrogation of mutation-independent disease modulators of RDEB identifies the small leucine-rich proteoglycan PRELP as a TGF-β antagonist and inhibitor of fibrosis."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "The disease manifests with devastating mucocutaneous fragility leading to progressive fibrosis and metastatic squamous cell carcinomas"
    explanation: Confirms that RDEB leads to progressive fibrosis and SCC.
- name: Progressive Scarring and Pseudosyndactyly
  description: >
    Chronic fibrosis from repeated wound-healing cycles leads to progressive
    scarring, joint contractures, and fusion of digits (pseudosyndactyly or
    mitten deformities). In severe RDEB, the hands and feet become encased
    in a cocoon of scar tissue, causing severe functional impairment.
  biological_processes:
  - preferred_term: extracellular matrix organization
    modifier: ABNORMAL
    term:
      id: GO:0030198
      label: extracellular matrix organization
  downstream:
  - target: Pseudosyndactyly
    causal_link_type: DIRECT
    description: >
      Fibrotic fusion and contracture of digits manifests clinically as
      pseudosyndactyly.
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Blistering of the hands and feet followed by scarring results in contractures and pseudosyndactyly"
    explanation: GeneReviews confirms that scarring from repeated blistering causes pseudosyndactyly.
- name: Esophageal and Mucosal Blistering
  description: >
    Blistering and erosions of the esophageal and oral mucosa lead to
    progressive stricture formation, microstomia, and fusion of the tongue
    to the floor of the mouth. Esophageal strictures cause severe dysphagia,
    contributing to malnutrition and growth failure.
  biological_processes:
  - preferred_term: cell-matrix adhesion
    modifier: DECREASED
    term:
      id: GO:0007160
      label: cell-matrix adhesion
  downstream:
  - target: Esophageal Stricture
    causal_link_type: DIRECT
    description: >
      Esophageal erosions heal with webs and strictures.
  - target: Dysphagia
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - esophageal webs and strictures
    description: >
      Esophageal strictures impair swallowing and produce dysphagia.
  - target: Microstomia
    causal_link_type: DIRECT
    description: >
      Oral mucosal blistering and perioral scarring progressively reduce mouth
      opening.
  - target: Dental Caries
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - oral mucosal blistering and scarring
    - microstomia limiting dental hygiene
    description: >
      Oral blistering, scarring, and restricted mouth opening impair dental
      hygiene and contribute to dental caries risk.
  - target: Constipation
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - anal and perianal blistering and stenosis
    description: >
      Gastrointestinal mucosal fragility and perianal scarring contribute to
      chronic constipation.
  - target: Malnutrition and Growth Failure
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - severe dysphagia
    - impaired oral intake
    description: >
      Esophageal strictures and oral involvement severely impair nutritional
      intake, leading to growth retardation and nutritional deficiencies.
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Esophageal erosions can lead to webs and strictures that can cause severe dysphagia"
    explanation: GeneReviews confirms esophageal stricture formation from mucosal blistering.
  - reference: PMID:19700011
    reference_title: "Extracutaneous manifestations and complications of inherited epidermolysis bullosa: part II. Other organs."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Some epidermolysis bullosa subtypes are at risk for severe injury of the bone marrow, musculoskeletal system, heart, kidney, and teeth"
    explanation: Confirms multisystem extracutaneous complications in EB including organ injury.
- name: Malnutrition and Growth Failure
  description: >
    Chronic dysphagia from esophageal strictures, increased metabolic
    demands from chronic wound healing, and malabsorption lead to protein-
    calorie malnutrition, iron deficiency anemia, and growth retardation
    in children with severe RDEB. Vitamin and mineral deficiencies are
    common.
  notes: >
    GO term omitted because malnutrition/growth failure is an organismal-level
    consequence best captured by HPO phenotype terms, not cellular-level GO
    biological processes.
  downstream:
  - target: Growth Retardation
    causal_link_type: DIRECT
    description: >
      Protein-calorie malnutrition and micronutrient deficiency impair childhood
      growth.
  - target: Anemia
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - iron deficiency
    - micronutrient deficiency
    description: >
      Nutritional deficiency contributes to chronic anemia in severe RDEB.
  - target: Osteoporosis
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - vitamin D deficiency
    - calcium deficiency
    - reduced mobility
    description: >
      Malnutrition and limited mobility contribute to low bone mineral density
      and osteoporosis.
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Malnutrition with vitamin and mineral deficiency may lead to growth deficiency in young children"
    explanation: GeneReviews confirms malnutrition and growth deficiency as consequences of DEB.
- name: Chronic Wounds and Aggressive Squamous Cell Carcinoma
  description: >
    Chronic non-healing wounds in RDEB create an immunosuppressive and
    pro-tumorigenic microenvironment that promotes development of aggressive
    cutaneous squamous cell carcinoma. SCC is the leading cause of death
    in RDEB, with cumulative risk in severe generalized RDEB rising from
    7.5% by age 20 to over 90% by age 55. These SCCs are unusually
    aggressive, with high rates of metastasis and mortality.
  genes:
  - preferred_term: COL7A1
    term:
      id: hgnc:2214
      label: COL7A1
  biological_processes:
  - preferred_term: wound healing
    modifier: ABNORMAL
    term:
      id: GO:0042060
      label: wound healing
  - preferred_term: immune response
    modifier: DECREASED
    term:
      id: GO:0006955
      label: immune response
  cell_types:
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  downstream:
  - target: Cutaneous Squamous Cell Carcinoma
    causal_link_type: DIRECT
    description: >
      Aggressive cutaneous squamous cell carcinomas arise in chronically wounded
      and scarred RDEB skin.
  evidence:
  - reference: PMID:19026465
    reference_title: "Epidermolysis bullosa and the risk of life-threatening cancers: the National EB Registry experience, 1986-2006."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Cumulative risks rose steeply in RDEB-HS, from 7.5% by age 20 to 67.8%, 80.2%, and 90.1% by ages 35, 45, and 55, respectively"
    explanation: National EB Registry data demonstrates extremely high cumulative SCC risk in severe RDEB.
  - reference: PMID:19026465
    reference_title: "Epidermolysis bullosa and the risk of life-threatening cancers: the National EB Registry experience, 1986-2006."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "By mid-adulthood, nearly all will have had at least one SCC, and nearly 80% will have died of metastatic SCC despite aggressive surgical resection"
    explanation: Confirms SCC as the leading cause of death in RDEB with high metastatic potential.
  - reference: PMID:32973163
    reference_title: "Epidermolysis bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the most feared of which - and also the leading cause of mortality - is squamous cell carcinoma"
    explanation: Confirms SCC as the most feared complication and leading cause of death in EB.
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The lifetime risk of aggressive squamous cell carcinoma (SCC) is greater than 90%"
    explanation: GeneReviews confirms lifetime SCC risk exceeding 90% in severe RDEB.
phenotypes:
- category: Integument
  name: Skin Blistering
  description: >
    Mechanically induced blistering and erosions of the skin, the hallmark
    feature of DEB. Blisters form at the sub-lamina densa level due to
    defective anchoring fibrils. Severity ranges from localized (DDEB) to
    generalized (severe RDEB).
  frequency: OBLIGATE
  phenotype_term:
    preferred_term: skin blistering with mechanical trauma
    term:
      id: HP:0008066
      label: Abnormal blistering of the skin
  evidence:
  - reference: PMID:32973163
    reference_title: "Epidermolysis bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "mucocutaneous fragility and blister formation, inducible by often minimal trauma"
    explanation: Confirms skin blistering induced by minimal trauma as the defining feature of EB.
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "skin fragility manifested by blistering and erosions with minimal trauma"
    explanation: GeneReviews confirms blistering and erosions as cardinal features.
- category: Integument
  name: Atrophic Scarring
  description: >
    Blisters heal with atrophic scarring, a characteristic feature of
    dystrophic EB that distinguishes it from other EB types. Scarring
    is progressive and can lead to significant disfigurement.
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: atrophic scarring
    term:
      id: HP:0001075
      label: Atrophic scars
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "skin fragility manifested by blistering and erosions with minimal trauma that heals with milia and scarring"
    explanation: GeneReviews confirms healing with scarring as a defining DEB feature.
- category: Integument
  name: Milia
  description: >
    Small white cysts (milia) form at sites of healed blisters, a
    characteristic feature that helps distinguish DEB from other EB types.
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: milia
    term:
      id: HP:0001056
      label: Milia
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "blistering and erosions with minimal trauma that heals with milia and scarring"
    explanation: GeneReviews confirms milia formation at healed blister sites.
- category: Integument
  name: Nail Dystrophy
  description: >
    Dystrophic or absent nails are common in all forms of DEB. In DDEB,
    nail dystrophy may be the only clinical manifestation. Toenails are
    particularly affected.
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: nail dystrophy
    term:
      id: HP:0008404
      label: Nail dystrophy
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Dystrophic nails, especially toenails, are common and may be the only manifestation of DDEB"
    explanation: GeneReviews confirms nail dystrophy as a very common DEB feature.
- category: Musculoskeletal
  name: Pseudosyndactyly
  description: >
    Progressive fusion of digits (mitten deformities) caused by repeated
    blistering and scarring of the hands and feet. Characteristic of severe
    RDEB, leading to significant loss of hand function.
  frequency: VERY_FREQUENT
  notes: Characteristic of severe RDEB
  phenotype_term:
    preferred_term: pseudosyndactyly
    term:
      id: HP:0010554
      label: Cutaneous finger syndactyly
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Blistering of the hands and feet followed by scarring results in contractures and pseudosyndactyly"
    explanation: GeneReviews confirms pseudosyndactyly from progressive scarring.
- category: Digestive
  name: Esophageal Stricture
  description: >
    Blistering and scarring of the esophageal mucosa leads to progressive
    stricture and web formation, causing severe dysphagia. A major
    contributor to malnutrition in RDEB.
  frequency: VERY_FREQUENT
  notes: Primarily in RDEB
  phenotype_term:
    preferred_term: esophageal stricture
    term:
      id: HP:0002043
      label: Esophageal stricture
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Esophageal erosions can lead to webs and strictures that can cause severe dysphagia"
    explanation: GeneReviews confirms esophageal stricture formation in DEB.
- category: Digestive
  name: Dysphagia
  description: >
    Difficulty swallowing resulting from esophageal strictures and oral
    mucosal involvement. Can be severe enough to require feeding
    gastrostomy.
  frequency: VERY_FREQUENT
  notes: Secondary to esophageal strictures in RDEB
  phenotype_term:
    preferred_term: dysphagia
    term:
      id: HP:0002015
      label: Dysphagia
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Esophageal erosions can lead to webs and strictures that can cause severe dysphagia"
    explanation: Confirms dysphagia as a consequence of esophageal strictures.
- category: Head and Neck
  name: Microstomia
  description: >
    Progressive diminution of the oral cavity and mouth opening due to
    perioral scarring and mucosal blistering. Impairs feeding and
    dental care.
  frequency: FREQUENT
  notes: Primarily in severe RDEB
  phenotype_term:
    preferred_term: microstomia
    term:
      id: HP:0000160
      label: Narrow mouth
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Oral involvement may lead to mouth blistering, fusion of the tongue to the floor of the mouth, and progressive diminution of the size of the oral cavity and mouth opening"
    explanation: GeneReviews confirms microstomia from progressive oral scarring.
- category: Growth
  name: Growth Retardation
  description: >
    Failure to thrive and growth retardation resulting from chronic
    malnutrition due to esophageal strictures, increased metabolic demands
    from chronic wound healing, and malabsorption.
  frequency: VERY_FREQUENT
  notes: Primarily in severe RDEB
  phenotype_term:
    preferred_term: growth retardation
    term:
      id: HP:0001510
      label: Growth delay
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Malnutrition with vitamin and mineral deficiency may lead to growth deficiency in young children"
    explanation: GeneReviews confirms growth deficiency from malnutrition in DEB.
- category: Blood
  name: Anemia
  description: >
    Chronic anemia from a combination of iron deficiency (malnutrition,
    chronic blood loss from wounds) and anemia of chronic disease.
    May require iron supplementation and transfusions.
  frequency: VERY_FREQUENT
  notes: Multifactorial; iron deficiency and chronic disease
  phenotype_term:
    preferred_term: anemia
    term:
      id: HP:0001903
      label: Anemia
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Anemia is treated with iron supplements and transfusions as needed"
    explanation: GeneReviews confirms anemia requiring treatment in DEB.
- category: Neoplasm
  name: Cutaneous Squamous Cell Carcinoma
  description: >
    Aggressive squamous cell carcinomas arising in areas of chronic
    wounding and scarring. The leading cause of death in RDEB, with
    cumulative risk exceeding 90% by age 55 in severe generalized RDEB.
    These tumors are unusually aggressive with high metastatic potential.
  frequency: VERY_FREQUENT
  notes: Leading cause of death in severe RDEB; begins in adolescence
  phenotype_term:
    preferred_term: cutaneous squamous cell carcinoma
    term:
      id: HP:0006739
      label: Squamous cell carcinoma of the skin
  evidence:
  - reference: PMID:19026465
    reference_title: "Epidermolysis bullosa and the risk of life-threatening cancers: the National EB Registry experience, 1986-2006."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Cumulative risks rose steeply in RDEB-HS, from 7.5% by age 20 to 67.8%, 80.2%, and 90.1% by ages 35, 45, and 55, respectively"
    explanation: National EB Registry documents extremely high lifetime SCC risk in severe RDEB.
  - reference: PMID:19026465
    reference_title: "Epidermolysis bullosa and the risk of life-threatening cancers: the National EB Registry experience, 1986-2006."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "nearly 80% will have died of metastatic SCC despite aggressive surgical resection"
    explanation: Confirms high mortality from metastatic SCC in RDEB.
- category: Eye
  name: Corneal Erosions
  description: >
    Recurrent corneal erosions from epithelial fragility, which can lead
    to scarring and loss of vision.
  frequency: FREQUENT
  phenotype_term:
    preferred_term: corneal erosion
    term:
      id: HP:0200020
      label: Corneal erosion
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Corneal erosions can lead to scarring and loss of vision"
    explanation: GeneReviews confirms corneal erosions as a DEB complication.
- category: Head and Neck
  name: Dental Caries
  description: >
    Increased susceptibility to dental caries from enamel hypoplasia,
    difficulty with oral hygiene due to microstomia and oral mucosal
    fragility, and nutritional deficiencies.
  frequency: FREQUENT
  phenotype_term:
    preferred_term: dental caries
    term:
      id: HP:0000670
      label: Carious teeth
  evidence:
  - reference: PMID:22940071
    reference_title: "Type VII collagen deficiency causes defective tooth enamel formation due to poor differentiation of ameloblasts."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Patients with RDEB present a low oral hygiene index and prevalent tooth abnormalities with caries"
    explanation: RDEB-specific study links type VII collagen deficiency to enamel structural defects and reports prevalent tooth abnormalities with caries.
  - reference: PMID:19700011
    reference_title: "Extracutaneous manifestations and complications of inherited epidermolysis bullosa: part II. Other organs."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Some epidermolysis bullosa subtypes are at risk for severe injury of the bone marrow, musculoskeletal system, heart, kidney, and teeth"
    explanation: Confirms dental/teeth involvement as an extracutaneous EB complication requiring surveillance.
- category: Musculoskeletal
  name: Osteoporosis
  description: >
    Reduced bone mineral density from chronic malnutrition, vitamin D
    deficiency, limited mobility, and chronic inflammation.
  frequency: FREQUENT
  notes: Primarily in severe RDEB
  phenotype_term:
    preferred_term: osteoporosis
    term:
      id: HP:0000939
      label: Osteoporosis
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Calcium and vitamin D supplementation and bisphosphonates as needed for osteoporosis"
    explanation: GeneReviews confirms osteoporosis requiring treatment in DEB.
- category: Digestive
  name: Constipation
  description: >
    Chronic constipation from anal and perianal blistering and stenosis.
    May require active management to prevent complications.
  frequency: FREQUENT
  phenotype_term:
    preferred_term: constipation
    term:
      id: HP:0002019
      label: Constipation
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "management of constipation"
    explanation: GeneReviews mentions constipation management as part of DEB care.
treatments:
- name: Beremagene Geperpavec (Vyjuvek)
  description: >
    Topical HSV-1-based gene therapy that delivers functional COL7A1 to
    restore type VII collagen protein expression in wound beds. FDA approved
    in 2023 for dystrophic epidermolysis bullosa. Phase III trial demonstrated
    complete wound healing in 67% of B-VEC-treated wounds vs 22% placebo at
    6 months.
  treatment_term:
    preferred_term: gene therapy
    term:
      id: MAXO:0001001
      label: gene therapy
  target_mechanisms:
  - target: COL7A1 Mutations and Loss of Type VII Collagen
    treatment_effect: RESTORES
    description: >
      Topical HSV-1 COL7A1 delivery restores type VII collagen expression in
      treated wounds.
  - target: Defective Anchoring Fibrils and Loss of Dermal-Epidermal Adhesion
    treatment_effect: RESTORES
    description: >
      Restored type VII collagen improves dermal-epidermal adhesion and wound
      closure.
  evidence:
  - reference: PMID:36516090
    reference_title: "Trial of Beremagene Geperpavec (B-VEC) for Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Complete wound healing at 3 and 6 months in patients with dystrophic epidermolysis bullosa was more likely with topical administration of B-VEC than with placebo"
    explanation: Phase III trial conclusions confirming B-VEC efficacy for wound healing in DEB.
  - reference: PMID:36516090
    reference_title: "Trial of Beremagene Geperpavec (B-VEC) for Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Beremagene geperpavec (B-VEC) is a topical investigational herpes simplex virus type 1 (HSV-1)-based gene therapy designed to restore C7 protein by delivering COL7A1"
    explanation: Describes the mechanism of B-VEC gene therapy for DEB.
- name: Prademagene Zamikeracel (Zevaskyn)
  description: >
    Ex vivo autologous gene therapy for RDEB. Patient keratinocytes are
    transduced with a retroviral vector encoding COL7A1, expanded into
    epidermal sheets, and surgically grafted onto chronic wounds. FDA
    approved April 2025 as the first cell-based gene therapy for RDEB.
    Phase III VIITAL trial demonstrated that 81% of treated wounds achieved
    at least 50% healing at 6 months versus 16% of control wounds.
  treatment_term:
    preferred_term: gene therapy
    term:
      id: MAXO:0001001
      label: gene therapy
  target_mechanisms:
  - target: COL7A1 Mutations and Loss of Type VII Collagen
    treatment_effect: RESTORES
    description: >
      Autologous COL7A1 gene-modified keratinocyte sheets provide corrected
      epidermis to chronic RDEB wounds.
  - target: Defective Anchoring Fibrils and Loss of Dermal-Epidermal Adhesion
    treatment_effect: RESTORES
    description: >
      Corrected grafts are intended to restore collagen VII at the wound bed and
      improve adhesion.
  evidence:
  - reference: PMID:40570869
    reference_title: "Prademagene zamikeracel for recessive dystrophic epidermolysis bullosa wounds (VIITAL): a two-centre, randomised, open-label, intrapatient-controlled phase 3 trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "At week 24, 35 (81%) of 43 treated wounds were at least 50% healed from baseline for prademagene zamikeracel compared with seven (16%) of 43 control wounds"
    explanation: Phase III VIITAL trial demonstrates statistically significant wound healing efficacy of prademagene zamikeracel in RDEB.
  - reference: PMID:40570869
    reference_title: "Prademagene zamikeracel for recessive dystrophic epidermolysis bullosa wounds (VIITAL): a two-centre, randomised, open-label, intrapatient-controlled phase 3 trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Prademagene zamikeracel is an autologous COL7A1 gene-modified cellular sheet that is sutured onto to a large, chronic RDEB wound"
    explanation: Describes the mechanism of prademagene zamikeracel as an autologous gene-modified cellular sheet for RDEB wounds.
- name: Recombinant Type VII Collagen (PTR-01)
  description: >
    Investigational intravenous protein replacement therapy using recombinant
    type VII collagen (rC7) for systemic treatment of RDEB. Preclinical
    studies in RDEB mice and dogs demonstrated that IV rC7 accumulates at
    the basement membrane zone, reduces fibrosis via decreased TGF-β
    signaling, and promotes wound healing. Phase 2 clinical trial results
    have been reported but not yet published in peer-reviewed literature.
  treatment_term:
    preferred_term: intravenous protein replacement therapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
  target_mechanisms:
  - target: Defective Anchoring Fibrils and Loss of Dermal-Epidermal Adhesion
    treatment_effect: RESTORES
    description: >
      Intravenous recombinant type VII collagen incorporates at the
      dermal-epidermal junction in preclinical models.
  - target: Chronic Wound-Inflammation-Fibrosis Cycle
    treatment_effect: INHIBITS
    description: >
      Systemic collagen VII replacement reduced fibrosis and improved wound
      healing in RDEB animal models.
  evidence:
  - reference: PMID:34606885
    reference_title: "Systemic Collagen VII Replacement Therapy for Advanced Recessive Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Fortnightly IV injections of rC7 for 7 weeks in adult RDEB mice reduced fibrosis of skin and eye"
    explanation: Preclinical study demonstrates that systemic IV rC7 reduces fibrosis in adult RDEB animal models.
  - reference: PMID:34606885
    reference_title: "Systemic Collagen VII Replacement Therapy for Advanced Recessive Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "IV rC7 in adult RDEB dogs incorporated in the dermal‒epidermal junction of skin and improved disease by promoting wound healing and reducing dermal‒epidermal separation"
    explanation: Large animal model confirms that IV rC7 incorporates at the DEJ and improves wound healing in established RDEB.
- name: Losartan
  description: >
    Anti-fibrotic angiotensin II type 1 receptor antagonist that reduces
    TGF-β signaling. The REFLECT Phase 1/2 trial enrolled 29 children
    with RDEB and demonstrated that losartan was well tolerated with
    improvements in EBDASI damage scores and BEBS scores. Losartan may
    reduce disease burden by mitigating progressive fibrosis.
  treatment_term:
    preferred_term: losartan anti-fibrotic therapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
    therapeutic_agent:
    - preferred_term: losartan
      term:
        id: CHEBI:6541
        label: losartan
  target_mechanisms:
  - target: Chronic Wound-Inflammation-Fibrosis Cycle
    treatment_effect: INHIBITS
    description: >
      Losartan is used as an anti-fibrotic intervention intended to reduce
      TGF-β-driven fibrosis and disease burden in RDEB.
  evidence:
  - reference: PMID:39539991
    reference_title: "Safety and tolerability of losartan to treat recessive dystrophic epidermolysis bullosa in children (REFLECT): an open-label, single-arm, phase 1/2 trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Losartan was well tolerated, no treatment-related severe complications leading to a serious safety concern occurred"
    explanation: REFLECT Phase 1/2 trial demonstrates safety and tolerability of losartan in children with RDEB.
  - reference: PMID:39539991
    reference_title: "Safety and tolerability of losartan to treat recessive dystrophic epidermolysis bullosa in children (REFLECT): an open-label, single-arm, phase 1/2 trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Similar to the EBDASI score, the BEBS showed a mean reduction of -3 points, 95%-CI: -0.21 to -5,79, P = 0.036)"
    explanation: REFLECT trial shows statistically significant improvement in BEBS scores with losartan treatment in RDEB children.
- name: Rigosertib
  description: >
    Polo-like kinase-1 (PLK1) inhibitor investigated for RDEB-associated
    squamous cell carcinoma, the leading cause of death in RDEB. Phase II
    trials in Europe and the USA enrolled five patients with locally advanced
    or metastatic RDEB-SCC. Antitumour efficacy was observed with acceptable
    toxicity, and two patients had a complete response within 6 months.
  treatment_term:
    preferred_term: rigosertib PLK1 inhibitor therapy
    term:
      id: MAXO:0000647
      label: chemotherapy
  target_mechanisms:
  - target: Chronic Wounds and Aggressive Squamous Cell Carcinoma
    treatment_effect: INHIBITS
    description: >
      Rigosertib is directed at the aggressive RDEB-associated SCC compartment
      that arises from chronic wounded fibrotic skin.
  evidence:
  - reference: PMID:40439508
    reference_title: "Efficacy and safety of rigosertib in patients with recessive dystrophic epidermolysis bullosa-associated advanced/metastatic cutaneous squamous cell carcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Antitumour efficacy with acceptable toxicity was seen in patients on IV or oral therapy and two patients had a complete response within 6 months of treatment"
    explanation: Phase II trial demonstrates antitumour activity and complete responses with rigosertib in RDEB-SCC patients.
  - reference: PMID:40439508
    reference_title: "Efficacy and safety of rigosertib in patients with recessive dystrophic epidermolysis bullosa-associated advanced/metastatic cutaneous squamous cell carcinoma."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "These data identify rigosertib as a promising drug therapy for patients with RDEB-SCC where there is a substantial unmet need, absence of approved therapies and where tumours arise on a background of a unique fibrotic and inflammatory environment"
    explanation: Identifies rigosertib as a promising therapeutic option for the currently untreatable RDEB-associated SCC.
- name: Gentamicin Readthrough Therapy
  description: >
    Intravenous gentamicin induces translational readthrough of nonsense
    mutations in COL7A1, restoring functional type VII collagen at the
    dermal-epidermal junction. Applicable to approximately 30% of RDEB
    patients who carry nonsense mutations. An open-label pilot trial
    treated 3 RDEB patients with IV gentamicin for 14 days; all showed
    increased C7 at the DEJ persisting for at least 6 months, and
    monitored wounds exhibited greater than 85% closure.
  treatment_term:
    preferred_term: gentamicin readthrough therapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
    therapeutic_agent:
    - preferred_term: gentamicin
      term:
        id: NCIT:C519
        label: Gentamicin
  target_mechanisms:
  - target: COL7A1 Mutations and Loss of Type VII Collagen
    treatment_effect: RESTORES
    description: >
      Gentamicin promotes readthrough of COL7A1 nonsense mutations to increase
      type VII collagen at the dermal-epidermal junction.
  evidence:
  - reference: PMID:38366625
    reference_title: "Intravenous gentamicin therapy induces functional type VII collagen in patients with recessive dystrophic epidermolysis bullosa: an open-label clinical trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "After gentamicin treatment, skin biopsies from all three patients (age range 18-28 years) exhibited increased C7 in their DEJ"
    explanation: Open-label clinical trial demonstrates that IV gentamicin restores type VII collagen at the DEJ in RDEB patients with nonsense mutations.
  - reference: PMID:38366625
    reference_title: "Intravenous gentamicin therapy induces functional type VII collagen in patients with recessive dystrophic epidermolysis bullosa: an open-label clinical trial."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "At 1 and 3 months post-treatment, 100% of the monitored wounds exhibited > 85% closure"
    explanation: Demonstrates significant wound healing improvement after IV gentamicin readthrough therapy in RDEB.
- name: Filsuvez (Birch Triterpenes) Topical Gel
  description: >
    Oleogel-S10 (Filsuvez), a topical gel containing birch triterpenes, is used
    for partial-thickness wounds associated with dystrophic and junctional EB in
    patients aged 6 months and older. In the phase III EASE trial, Oleogel-S10
    accelerated target wound closure compared with control gel.
  treatment_term:
    preferred_term: birch triterpenes topical gel
    term:
      id: MAXO:0000058
      label: pharmacotherapy
    therapeutic_agent:
    - preferred_term: birch triterpenes
      term:
        id: NCIT:C177079
        label: Birch Triterpenes
    qualifiers:
    - predicate:
        preferred_term: route of administration
        term:
          id: NCIT:C38114
          label: Route of Administration
      value:
        preferred_term: topical route of administration
        term:
          id: NCIT:C38304
          label: Topical Route of Administration
  target_mechanisms:
  - target: Chronic Wound-Inflammation-Fibrosis Cycle
    treatment_effect: MODULATES
    description: >
      Topical birch triterpenes accelerate wound closure, reducing persistence of
      open wounds that sustain inflammation and fibrosis.
  evidence:
  - reference: PMID:36689495
    reference_title: "Efficacy and safety of Oleogel-S10 (birch triterpenes) for epidermolysis bullosa: results from the phase III randomized double-blind phase of the EASE study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Oleogel-S10 is the first therapy to demonstrate accelerated wound healing in EB"
    explanation: Phase III EASE trial confirms Oleogel-S10 as a wound-healing therapy across EB subtypes including dystrophic EB.
  - reference: PMID:39748581
    reference_title: "Filsuvez(®) (Birch Triterpenes) Topical Gel."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Filsuvez® (birch triterpenes) topical gel received approval in 2023 for the treatment of epidermolysis bullosa (EB)"
    explanation: Confirms regulatory approval of birch triterpenes topical gel for EB wound treatment.
- name: Wound Care and Specialized Dressings
  description: >
    Meticulous wound care is the cornerstone of DEB management. New blisters
    should be lanced and drained, then dressed with nonadherent dressings
    and protective padding. Prevention of new blisters through education,
    padding of extremities, and soft clothing is essential.
  treatment_term:
    preferred_term: wound care management
    term:
      id: MAXO:0000950
      label: supportive care
  target_mechanisms:
  - target: Chronic Wound-Inflammation-Fibrosis Cycle
    treatment_effect: MODULATES
    description: >
      Nonadherent dressings, padding, blister drainage, and infection control
      reduce wound trauma and downstream inflammation.
  evidence:
  - reference: PMID:32973163
    reference_title: "Epidermolysis bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "multidisciplinary care is targeted towards minimizing the risk of blister formation, wound care, symptom relief and specific complications"
    explanation: Confirms wound care as a central component of EB management.
- name: Esophageal Dilation
  description: >
    Balloon dilation of esophageal strictures and webs to improve
    swallowing and nutritional intake. May need to be repeated as
    strictures recur.
  treatment_term:
    preferred_term: esophageal dilation
    term:
      id: NCIT:C70908
      label: Esophageal Dilation
  target_mechanisms:
  - target: Esophageal and Mucosal Blistering
    treatment_effect: BYPASSES
    description: >
      Dilation bypasses the obstructive consequence of mucosal blistering and
      scarring by mechanically opening esophageal strictures.
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "dilation of esophageal strictures and webs to improve swallowing"
    explanation: GeneReviews confirms esophageal dilation as standard management.
- name: Nutritional Support
  description: >
    High-calorie nutritional supplementation with iron, vitamin A, zinc,
    selenium, carnitine, calcium, and vitamin D. Feeding gastrostomy tube
    placement may be necessary for patients with severe dysphagia.
  treatment_term:
    preferred_term: nutritional support
    term:
      id: MAXO:0000088
      label: dietary intervention
  target_mechanisms:
  - target: Malnutrition and Growth Failure
    treatment_effect: MODULATES
    description: >
      Nutritional supplementation and gastrostomy support address the downstream
      malnutrition caused by dysphagia and chronic wounds.
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "nutritional support including feeding gastrostomy tube, vitamin A, zinc, selenium, and carnitine supplementation"
    explanation: GeneReviews confirms comprehensive nutritional support including supplements and gastrostomy.
- name: SCC Surveillance
  description: >
    Regular skin examination with biopsy of suspicious lesions beginning
    at age 10 years. Annual screening for crusted, non-healing, and painful
    lesions as well as those with exuberant scar tissue.
  treatment_term:
    preferred_term: cancer screening
    term:
      id: MAXO:0000126
      label: cancer screening
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "evaluation of crusted, non-healing, and painful lesions as well as those with exuberant scar tissue at least annually beginning at age ten years; biopsies of suspicious lesions for evidence of SCC"
    explanation: GeneReviews recommends SCC surveillance starting at age 10.
- name: Surgical Excision of SCC
  description: >
    Aggressive surgical excision of confirmed squamous cell carcinomas,
    although outcomes remain poor due to high metastatic potential.
  treatment_term:
    preferred_term: surgical excision
    term:
      id: MAXO:0000004
      label: surgical procedure
  target_mechanisms:
  - target: Chronic Wounds and Aggressive Squamous Cell Carcinoma
    treatment_effect: INHIBITS
    description: >
      Surgical excision removes established RDEB-associated squamous cell
      carcinomas arising from chronic scarred wounds.
  evidence:
  - reference: PMID:19026465
    reference_title: "Epidermolysis bullosa and the risk of life-threatening cancers: the National EB Registry experience, 1986-2006."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "nearly 80% will have died of metastatic SCC despite aggressive surgical resection"
    explanation: Confirms the poor prognosis of SCC in RDEB despite surgical treatment.
- name: Pain Management
  description: >
    Multimodal pain management including topical, oral, and psychological
    therapies for chronic pain and itch associated with wounds and
    dressing changes.
  treatment_term:
    preferred_term: pain management
    term:
      id: MAXO:0000950
      label: supportive care
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "topical, oral, and psychological therapies for pain and itch"
    explanation: GeneReviews confirms multimodal pain management in DEB.
- name: Physical and Occupational Therapy
  description: >
    Physical and occupational therapy to preserve hand function, maintain
    ambulation, and prevent joint contractures. Surgical release of fused
    digits may need to be repeated.
  treatment_term:
    preferred_term: physical therapy
    term:
      id: MAXO:0000011
      label: physical therapy
  target_mechanisms:
  - target: Progressive Scarring and Pseudosyndactyly
    treatment_effect: MODULATES
    description: >
      Physical and occupational therapy act downstream of fibrosis to preserve
      hand function and reduce contracture burden.
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Occupational and physical therapy may help prevent hand and other joint contractures"
    explanation: GeneReviews confirms physical/occupational therapy for contracture prevention.
- name: Allogeneic Bone Marrow Transplantation
  description: >
    Investigational treatment for severe RDEB. Allogeneic bone marrow
    transplantation has shown increased type VII collagen deposition and
    improved wound healing, but carries significant morbidity and mortality
    from the conditioning regimen.
  treatment_term:
    preferred_term: hematopoietic stem cell transplantation
    term:
      id: MAXO:0000747
      label: hematopoietic stem cell transplantation
  target_mechanisms:
  - target: Defective Anchoring Fibrils and Loss of Dermal-Epidermal Adhesion
    treatment_effect: RESTORES
    description: >
      Allogeneic bone marrow transplantation is intended to increase collagen
      VII deposition in RDEB skin.
  evidence:
  - reference: PMID:20818854
    reference_title: "Bone marrow transplantation for recessive dystrophic epidermolysis bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Increased C7 deposition and a sustained presence of donor cells were found in the skin of children with recessive dystrophic epidermolysis bullosa after allogeneic bone marrow transplantation"
    explanation: Wagner et al. demonstrated increased collagen VII after BMT in RDEB children.
  - reference: PMID:20818854
    reference_title: "Bone marrow transplantation for recessive dystrophic epidermolysis bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "all having improved wound healing and a reduction in blister formation between 30 and 130 days after transplantation"
    explanation: Confirms clinical improvement in wound healing after BMT.
- name: Genetic Counseling
  description: >
    Genetic counseling for families affected by DEB, including carrier
    testing, prenatal diagnosis, and preimplantation genetic testing.
    Mode of inheritance determination requires molecular characterization
    of COL7A1 variants.
  treatment_term:
    preferred_term: genetic counseling
    term:
      id: MAXO:0000079
      label: genetic counseling
  evidence:
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Once the COL7A1 pathogenic variant(s) have been identified in an affected family member, prenatal and preimplantation genetic testing are possible"
    explanation: GeneReviews confirms availability of prenatal and preimplantation testing.
clinical_trials:
- name: NCT04491604
  phase: PHASE_III
  status: COMPLETED
  description: >-
    Phase III intrapatient randomized trial of topical beremagene geperpavec
    (B-VEC/KB103) to improve wound healing in genetically confirmed dystrophic
    epidermolysis bullosa by delivering COL7A1.
  target_phenotypes:
  - preferred_term: Wound healing impairment
    term:
      id: HP:0001058
      label: Poor wound healing
  evidence:
  - reference: clinicaltrials:NCT04491604
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "To determine whether administration of topical B-VEC improves wound healing as compared to placebo, and to evaluate durability, repeat dosing (Primary Endpoint) and further obtain safety and tolerability data."
    explanation: ClinicalTrials.gov summary confirms the topical B-VEC phase III trial objective, wound-healing endpoint, and safety focus in DEB.
- name: NCT03536143
  phase: PHASE_I
  status: COMPLETED
  description: >-
    Early-phase topical HSV1-COL7 gene therapy trial evaluating safety and
    preliminary efficacy of beremagene geperpavec (KB103) in dystrophic
    epidermolysis bullosa.
  target_phenotypes:
  - preferred_term: Wound healing impairment
    term:
      id: HP:0001058
      label: Poor wound healing
  evidence:
  - reference: clinicaltrials:NCT03536143
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "This study was conducted to assess the safety and efficacy of topical Beremagene Geperpavec (KB103, HSV1-COL7) on DEB patients."
    explanation: ClinicalTrials.gov summary confirms early-phase topical KB103/B-VEC evaluation for safety and efficacy in DEB.
  notes: >-
    ClinicalTrials.gov names this as a combined phase I/II study; the schema
    entry uses `PHASE_I` because the trial is primarily represented here as an
    early safety and proof-of-concept study.
genetic:
- name: COL7A1
  association: Causative
  inheritance:
  - name: Autosomal dominant
    evidence:
    - reference: PMID:20301481
      reference_title: "Dystrophic Epidermolysis Bullosa."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "About 70% of individuals diagnosed with DDEB are reported to have an affected parent"
      explanation: GeneReviews confirms autosomal dominant inheritance for DDEB.
  - name: Autosomal recessive
    evidence:
    - reference: PMID:20301481
      reference_title: "Dystrophic Epidermolysis Bullosa."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "If both parents are known to be heterozygous for a COL7A1 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected"
      explanation: GeneReviews confirms autosomal recessive inheritance for RDEB.
  notes: >
    COL7A1 on chromosome 3p21.31 encodes type VII collagen, the major
    structural component of anchoring fibrils at the dermal-epidermal
    junction. Dominant-negative mutations cause DDEB (typically glycine
    substitutions in the collagenous domain), while biallelic loss-of-function
    mutations (nonsense, frameshift, splice site) cause RDEB. Some COL7A1
    pathogenic variants are associated with both DDEB and RDEB.
  evidence:
  - reference: PMID:36516090
    reference_title: "Trial of Beremagene Geperpavec (B-VEC) for Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Dystrophic epidermolysis bullosa is a rare genetic blistering skin disease caused by mutations in COL7A1, which encodes type VII collagen (C7)"
    explanation: Confirms COL7A1 as the causative gene for DEB.
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "biallelic COL7A1 pathogenic variants (for RDEB) or a heterozygous pathogenic variant in COL7A1 (for DDEB)"
    explanation: GeneReviews confirms both dominant and recessive inheritance patterns for COL7A1 mutations.
  - reference: PMID:20301481
    reference_title: "Dystrophic Epidermolysis Bullosa."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Some COL7A1 pathogenic variants are associated with both DDEB and RDEB"
    explanation: Confirms that some variants can cause either dominant or recessive DEB.
datasets:
- accession: geo:GSE108849
  title: Single-cell RNA-seq of fibroblasts from recessive dystrophic epidermolysis bullosa patients and wild-type controls
  description: >-
    Human single-cell transcriptomic dataset profiling fibroblast populations
    from recessive dystrophic epidermolysis bullosa and control samples to
    resolve disease-relevant stromal heterogeneity.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: SINGLE_CELL_RNA_SEQ
  sample_count: 543
  conditions:
  - recessive dystrophic epidermolysis bullosa fibroblasts
  - wild-type control fibroblasts
  evidence:
  - reference: GEO:GSE108849
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "The goal of this study is to discover fibroblast subpopulations relevant to recessive dystrophic epidermolysis bullosa"
    explanation: Directly supports this GEO series as a single-cell fibroblast resource for DEB mechanism studies.
references:
- reference: PMID:20301481
  title: "Dystrophic Epidermolysis Bullosa."
  tags:
  - GeneReviews
  findings: []
- reference: DOI:10.1001/jamadermatol.2023.5857
  title: Estimated Spending on Beremagene Geperpavec for Dystrophic Epidermolysis Bullosa
  found_in:
  - Dystrophic_Epidermolysis_Bullosa-deep-research-falcon.md
  findings:
  - statement: ImportanceNew gene therapies can offer substantial benefits to patients, particularly those with rare diseases who have few therapeutic options.
    supporting_text: ImportanceNew gene therapies can offer substantial benefits to patients, particularly those with rare diseases who have few therapeutic options.
    evidence:
    - reference: DOI:10.1001/jamadermatol.2023.5857
      reference_title: Estimated Spending on Beremagene Geperpavec for Dystrophic Epidermolysis Bullosa
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: ImportanceNew gene therapies can offer substantial benefits to patients, particularly those with rare diseases who have few therapeutic options.
      explanation: Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.
- reference: DOI:10.1038/s41591-022-01737-y
  title: 'In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial'
  found_in:
  - Dystrophic_Epidermolysis_Bullosa-deep-research-falcon.md
  findings:
  - statement: Recessive dystrophic epidermolysis bullosa (RDEB) is a lifelong genodermatosis associated with blistering, wounding, and scarring caused by mutations in COL7A1, the gene encoding the anchoring fibril component, collagen VII (C7).
    supporting_text: Recessive dystrophic epidermolysis bullosa (RDEB) is a lifelong genodermatosis associated with blistering, wounding, and scarring caused by mutations in COL7A1, the gene encoding the anchoring fibril component, collagen VII (C7).
    evidence:
    - reference: DOI:10.1038/s41591-022-01737-y
      reference_title: 'In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Recessive dystrophic epidermolysis bullosa (RDEB) is a lifelong genodermatosis associated with blistering, wounding, and scarring caused by mutations in COL7A1, the gene encoding the anchoring fibril component, collagen VII (C7).
      explanation: Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.
- reference: DOI:10.1055/s-0043-1763257
  title: 'Fibrosis as a Risk Factor for Cutaneous Squamous Cell Carcinoma in Recessive Dystrophic Epidermolysis Bullosa: A Systematic Review'
  found_in:
  - Dystrophic_Epidermolysis_Bullosa-deep-research-falcon.md
  findings:
  - statement: Recessive dystrophic epidermolysis bullosa (RDEB) is a severe subtype of epidermolysis bullosa caused by changes in collagen VII with a high risk of early development of cutaneous squamous cell carcinoma (cSCC).
    supporting_text: Recessive dystrophic epidermolysis bullosa (RDEB) is a severe subtype of epidermolysis bullosa caused by changes in collagen VII with a high risk of early development of cutaneous squamous cell carcinoma (cSCC).
    evidence:
    - reference: DOI:10.1055/s-0043-1763257
      reference_title: 'Fibrosis as a Risk Factor for Cutaneous Squamous Cell Carcinoma in Recessive Dystrophic Epidermolysis Bullosa: A Systematic Review'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Recessive dystrophic epidermolysis bullosa (RDEB) is a severe subtype of epidermolysis bullosa caused by changes in collagen VII with a high risk of early development of cutaneous squamous cell carcinoma (cSCC).
      explanation: Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.
- reference: DOI:10.1073/pnas.2401781121
  title: Splice modulation strategy applied to deep intronic variants in <i>COL7A1</i> causing recessive dystrophic epidermolysis bullosa
  found_in:
  - Dystrophic_Epidermolysis_Bullosa-deep-research-falcon.md
  findings:
  - statement: Splice modulation strategy applied to deep intronic variants in <i>COL7A1</i> causing recessive dystrophic epidermolysis bullosa
    supporting_text: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare and most often severe genetic disease characterized by recurrent blistering and erosions of the skin and mucous membranes after minor trauma, leading to major local and systemic complications.
    evidence:
    - reference: DOI:10.1073/pnas.2401781121
      reference_title: Splice modulation strategy applied to deep intronic variants in <i>COL7A1</i> causing recessive dystrophic epidermolysis bullosa
      supports: SUPPORT
      evidence_source: OTHER
      snippet: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare and most often severe genetic disease characterized by recurrent blistering and erosions of the skin and mucous membranes after minor trauma, leading to major local and systemic complications.
      explanation: Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.
- reference: DOI:10.1186/s13023-024-03190-1
  title: 'Therapies for cutaneous squamous cell carcinoma in recessive dystrophic epidermolysis bullosa: a systematic review of 157 cases'
  found_in:
  - Dystrophic_Epidermolysis_Bullosa-deep-research-falcon.md
  findings:
  - statement: Invasive cutaneous squamous cell carcinomas (cSCC) are a leading cause of death in recessive dystrophic epidermolysis bullosa (RDEB), a rare blistering genodermatosis.
    supporting_text: Invasive cutaneous squamous cell carcinomas (cSCC) are a leading cause of death in recessive dystrophic epidermolysis bullosa (RDEB), a rare blistering genodermatosis.
    evidence:
    - reference: DOI:10.1186/s13023-024-03190-1
      reference_title: 'Therapies for cutaneous squamous cell carcinoma in recessive dystrophic epidermolysis bullosa: a systematic review of 157 cases'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Invasive cutaneous squamous cell carcinomas (cSCC) are a leading cause of death in recessive dystrophic epidermolysis bullosa (RDEB), a rare blistering genodermatosis.
      explanation: Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.
- reference: DOI:10.1371/journal.pone.0302991
  title: 'Creation and characterization of novel rat model for recessive dystrophic epidermolysis bullosa: Frameshift mutation of the Col7a1 gene leads to severe blistered phenotype'
  found_in:
  - Dystrophic_Epidermolysis_Bullosa-deep-research-falcon.md
  findings:
  - statement: Recessive dystrophic epidermolysis bullosa is a rare genodermatosis caused by a mutation of the Col7a1 gene.
    supporting_text: Recessive dystrophic epidermolysis bullosa is a rare genodermatosis caused by a mutation of the Col7a1 gene.
    evidence:
    - reference: DOI:10.1371/journal.pone.0302991
      reference_title: 'Creation and characterization of novel rat model for recessive dystrophic epidermolysis bullosa: Frameshift mutation of the Col7a1 gene leads to severe blistered phenotype'
      supports: SUPPORT
      evidence_source: MODEL_ORGANISM
      snippet: Recessive dystrophic epidermolysis bullosa is a rare genodermatosis caused by a mutation of the Col7a1 gene.
      explanation: Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.
- reference: DOI:10.3390/cells11081365
  title: 'Squamous Cell Carcinoma in Patients with Inherited Epidermolysis Bullosa: Review of Current Literature'
  found_in:
  - Dystrophic_Epidermolysis_Bullosa-deep-research-falcon.md
  findings:
  - statement: 'Squamous Cell Carcinoma in Patients with Inherited Epidermolysis Bullosa: Review of Current Literature'
    supporting_text: Epidermolysis bullosa (EB) is a group of rare congenital diseases caused by mutations in structural proteins of the dermal/epidermal junction that are characterized by extreme epithelial fragility, which determines the formation of bullae and erosions either spontaneously or after local mechanical traumas.
    evidence:
    - reference: DOI:10.3390/cells11081365
      reference_title: 'Squamous Cell Carcinoma in Patients with Inherited Epidermolysis Bullosa: Review of Current Literature'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Epidermolysis bullosa (EB) is a group of rare congenital diseases caused by mutations in structural proteins of the dermal/epidermal junction that are characterized by extreme epithelial fragility, which determines the formation of bullae and erosions either spontaneously or after local mechanical traumas.
      explanation: Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.
- reference: DOI:10.3390/healthcare12020261
  title: 'Management of Skin Lesions in Patients with Epidermolysis Bullosa by Topical Treatment: Systematic Review and Meta-Analysis'
  found_in:
  - Dystrophic_Epidermolysis_Bullosa-deep-research-falcon.md
  findings:
  - statement: Epidermolysis bullosa (EB) is the overarching term for a set of rare inherited skin fragility disorders that result from mutations in at least 20 different genes.
    supporting_text: Epidermolysis bullosa (EB) is the overarching term for a set of rare inherited skin fragility disorders that result from mutations in at least 20 different genes.
    evidence:
    - reference: DOI:10.3390/healthcare12020261
      reference_title: 'Management of Skin Lesions in Patients with Epidermolysis Bullosa by Topical Treatment: Systematic Review and Meta-Analysis'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Epidermolysis bullosa (EB) is the overarching term for a set of rare inherited skin fragility disorders that result from mutations in at least 20 different genes.
      explanation: Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.
- reference: DOI:10.3390/ijms20225707
  title: 'Epidermolysis Bullosa-Associated Squamous Cell Carcinoma: From Pathogenesis to Therapeutic Perspectives'
  found_in:
  - Dystrophic_Epidermolysis_Bullosa-deep-research-falcon.md
  findings:
  - statement: Epidermolysis bullosa (EB) is a heterogeneous group of inherited skin disorders determined by mutations in genes encoding for structural components of the cutaneous basement membrane zone.
    supporting_text: Epidermolysis bullosa (EB) is a heterogeneous group of inherited skin disorders determined by mutations in genes encoding for structural components of the cutaneous basement membrane zone.
    evidence:
    - reference: DOI:10.3390/ijms20225707
      reference_title: 'Epidermolysis Bullosa-Associated Squamous Cell Carcinoma: From Pathogenesis to Therapeutic Perspectives'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Epidermolysis bullosa (EB) is a heterogeneous group of inherited skin disorders determined by mutations in genes encoding for structural components of the cutaneous basement membrane zone.
      explanation: Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.
- reference: DOI:10.3390/ijms22105104
  title: 'Impaired Wound Healing, Fibrosis, and Cancer: The Paradigm of Recessive Dystrophic Epidermolysis Bullosa'
  found_in:
  - Dystrophic_Epidermolysis_Bullosa-deep-research-falcon.md
  findings:
  - statement: 'Impaired Wound Healing, Fibrosis, and Cancer: The Paradigm of Recessive Dystrophic Epidermolysis Bullosa'
    supporting_text: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a devastating skin blistering disease caused by mutations in the gene encoding type VII collagen (C7), leading to epidermal fragility, trauma-induced blistering, and long term, hard-to-heal wounds.
    evidence:
    - reference: DOI:10.3390/ijms22105104
      reference_title: 'Impaired Wound Healing, Fibrosis, and Cancer: The Paradigm of Recessive Dystrophic Epidermolysis Bullosa'
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a devastating skin blistering disease caused by mutations in the gene encoding type VII collagen (C7), leading to epidermal fragility, trauma-induced blistering, and long term, hard-to-heal wounds.
      explanation: Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.
- reference: DOI:10.3390/ijms25020761
  title: Splicing Modulation via Antisense Oligonucleotides in Recessive Dystrophic Epidermolysis Bullosa
  found_in:
  - Dystrophic_Epidermolysis_Bullosa-deep-research-falcon.md
  findings:
  - statement: Antisense oligonucleotides (ASOs) represent an emerging therapeutic platform for targeting genetic diseases by influencing various aspects of (pre-)mRNA biology, such as splicing, stability, and translation.
    supporting_text: Antisense oligonucleotides (ASOs) represent an emerging therapeutic platform for targeting genetic diseases by influencing various aspects of (pre-)mRNA biology, such as splicing, stability, and translation.
    evidence:
    - reference: DOI:10.3390/ijms25020761
      reference_title: Splicing Modulation via Antisense Oligonucleotides in Recessive Dystrophic Epidermolysis Bullosa
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: Antisense oligonucleotides (ASOs) represent an emerging therapeutic platform for targeting genetic diseases by influencing various aspects of (pre-)mRNA biology, such as splicing, stability, and translation.
      explanation: Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.
- reference: DOI:10.3390/ijms25042243
  title: Emerging Gene Therapeutics for Epidermolysis Bullosa under Development
  found_in:
  - Dystrophic_Epidermolysis_Bullosa-deep-research-falcon.md
  findings:
  - statement: The monogenetic disease epidermolysis bullosa (EB) is characterised by the formation of extended blisters and lesions on the patient’s skin upon minimal mechanical stress.
    supporting_text: The monogenetic disease epidermolysis bullosa (EB) is characterised by the formation of extended blisters and lesions on the patient’s skin upon minimal mechanical stress.
    evidence:
    - reference: DOI:10.3390/ijms25042243
      reference_title: Emerging Gene Therapeutics for Epidermolysis Bullosa under Development
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: The monogenetic disease epidermolysis bullosa (EB) is characterised by the formation of extended blisters and lesions on the patient’s skin upon minimal mechanical stress.
      explanation: Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.
- reference: DOI:10.3390/ijms251910270
  title: Current Status of Biomedical Products for Gene and Cell Therapy of Recessive Dystrophic Epidermolysis Bullosa
  found_in:
  - Dystrophic_Epidermolysis_Bullosa-deep-research-falcon.md
  findings:
  - statement: Current Status of Biomedical Products for Gene and Cell Therapy of Recessive Dystrophic Epidermolysis Bullosa
    supporting_text: This detailed review describes innovative strategies and current products for gene and cell therapy at different stages of research and development to treat recessive dystrophic epidermolysis bullosa (RDEB) which is associated with the functional deficiency of collagen type VII alpha 1 (C7) caused by defects in the COL7A1 gene.
    evidence:
    - reference: DOI:10.3390/ijms251910270
      reference_title: Current Status of Biomedical Products for Gene and Cell Therapy of Recessive Dystrophic Epidermolysis Bullosa
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: This detailed review describes innovative strategies and current products for gene and cell therapy at different stages of research and development to treat recessive dystrophic epidermolysis bullosa (RDEB) which is associated with the functional deficiency of collagen type VII alpha 1 (C7) caused by defects in the COL7A1 gene.
      explanation: Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.

📚

References & Deep Research

References

PMID:20301481

Dystrophic Epidermolysis Bullosa.

No top-level findings curated for this source.

DOI:10.1001/jamadermatol.2023.5857

Estimated Spending on Beremagene Geperpavec for Dystrophic Epidermolysis Bullosa

1 finding

ImportanceNew gene therapies can offer substantial benefits to patients, particularly those with rare diseases who have few therapeutic options.

"ImportanceNew gene therapies can offer substantial benefits to patients, particularly those with rare diseases who have few therapeutic options."

Show evidence (1 reference)

DOI:10.1001/jamadermatol.2023.5857 SUPPORT Human Clinical

"ImportanceNew gene therapies can offer substantial benefits to patients, particularly those with rare diseases who have few therapeutic options."

Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.

DOI:10.1038/s41591-022-01737-y

In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial

1 finding

Recessive dystrophic epidermolysis bullosa (RDEB) is a lifelong genodermatosis associated with blistering, wounding, and scarring caused by mutations in COL7A1, the gene encoding the anchoring fibril component, collagen VII (C7).

"Recessive dystrophic epidermolysis bullosa (RDEB) is a lifelong genodermatosis associated with blistering, wounding, and scarring caused by mutations in COL7A1, the gene encoding the anchoring fibril component, collagen VII (C7)."

Show evidence (1 reference)

DOI:10.1038/s41591-022-01737-y SUPPORT Human Clinical

Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.

DOI:10.1055/s-0043-1763257

Fibrosis as a Risk Factor for Cutaneous Squamous Cell Carcinoma in Recessive Dystrophic Epidermolysis Bullosa: A Systematic Review

1 finding

Recessive dystrophic epidermolysis bullosa (RDEB) is a severe subtype of epidermolysis bullosa caused by changes in collagen VII with a high risk of early development of cutaneous squamous cell carcinoma (cSCC).

"Recessive dystrophic epidermolysis bullosa (RDEB) is a severe subtype of epidermolysis bullosa caused by changes in collagen VII with a high risk of early development of cutaneous squamous cell carcinoma (cSCC)."

Show evidence (1 reference)

DOI:10.1055/s-0043-1763257 SUPPORT Human Clinical

Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.

DOI:10.1073/pnas.2401781121

Splice modulation strategy applied to deep intronic variants in <i>COL7A1</i> causing recessive dystrophic epidermolysis bullosa

1 finding

Splice modulation strategy applied to deep intronic variants in <i>COL7A1</i> causing recessive dystrophic epidermolysis bullosa

"Recessive dystrophic epidermolysis bullosa (RDEB) is a rare and most often severe genetic disease characterized by recurrent blistering and erosions of the skin and mucous membranes after minor trauma, leading to major local and systemic complications."

Show evidence (1 reference)

DOI:10.1073/pnas.2401781121 SUPPORT Other

Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.

DOI:10.1186/s13023-024-03190-1

Therapies for cutaneous squamous cell carcinoma in recessive dystrophic epidermolysis bullosa: a systematic review of 157 cases

1 finding

Invasive cutaneous squamous cell carcinomas (cSCC) are a leading cause of death in recessive dystrophic epidermolysis bullosa (RDEB), a rare blistering genodermatosis.

"Invasive cutaneous squamous cell carcinomas (cSCC) are a leading cause of death in recessive dystrophic epidermolysis bullosa (RDEB), a rare blistering genodermatosis."

Show evidence (1 reference)

DOI:10.1186/s13023-024-03190-1 SUPPORT Human Clinical

"Invasive cutaneous squamous cell carcinomas (cSCC) are a leading cause of death in recessive dystrophic epidermolysis bullosa (RDEB), a rare blistering genodermatosis."

Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.

DOI:10.1371/journal.pone.0302991

Creation and characterization of novel rat model for recessive dystrophic epidermolysis bullosa: Frameshift mutation of the Col7a1 gene leads to severe blistered phenotype

1 finding

Recessive dystrophic epidermolysis bullosa is a rare genodermatosis caused by a mutation of the Col7a1 gene.

"Recessive dystrophic epidermolysis bullosa is a rare genodermatosis caused by a mutation of the Col7a1 gene."

Show evidence (1 reference)

DOI:10.1371/journal.pone.0302991 SUPPORT Model Organism

"Recessive dystrophic epidermolysis bullosa is a rare genodermatosis caused by a mutation of the Col7a1 gene."

Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.

DOI:10.3390/cells11081365

Squamous Cell Carcinoma in Patients with Inherited Epidermolysis Bullosa: Review of Current Literature

1 finding

Squamous Cell Carcinoma in Patients with Inherited Epidermolysis Bullosa: Review of Current Literature

"Epidermolysis bullosa (EB) is a group of rare congenital diseases caused by mutations in structural proteins of the dermal/epidermal junction that are characterized by extreme epithelial fragility, which determines the formation of bullae and erosions either spontaneously or after local..."

Show evidence (1 reference)

DOI:10.3390/cells11081365 SUPPORT Human Clinical

Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.

DOI:10.3390/healthcare12020261

Management of Skin Lesions in Patients with Epidermolysis Bullosa by Topical Treatment: Systematic Review and Meta-Analysis

1 finding

Epidermolysis bullosa (EB) is the overarching term for a set of rare inherited skin fragility disorders that result from mutations in at least 20 different genes.

"Epidermolysis bullosa (EB) is the overarching term for a set of rare inherited skin fragility disorders that result from mutations in at least 20 different genes."

Show evidence (1 reference)

DOI:10.3390/healthcare12020261 SUPPORT Human Clinical

"Epidermolysis bullosa (EB) is the overarching term for a set of rare inherited skin fragility disorders that result from mutations in at least 20 different genes."

Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.

DOI:10.3390/ijms20225707

Epidermolysis Bullosa-Associated Squamous Cell Carcinoma: From Pathogenesis to Therapeutic Perspectives

1 finding

Epidermolysis bullosa (EB) is a heterogeneous group of inherited skin disorders determined by mutations in genes encoding for structural components of the cutaneous basement membrane zone.

"Epidermolysis bullosa (EB) is a heterogeneous group of inherited skin disorders determined by mutations in genes encoding for structural components of the cutaneous basement membrane zone."

Show evidence (1 reference)

DOI:10.3390/ijms20225707 SUPPORT Human Clinical

"Epidermolysis bullosa (EB) is a heterogeneous group of inherited skin disorders determined by mutations in genes encoding for structural components of the cutaneous basement membrane zone."

Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.

DOI:10.3390/ijms22105104

Impaired Wound Healing, Fibrosis, and Cancer: The Paradigm of Recessive Dystrophic Epidermolysis Bullosa

1 finding

Impaired Wound Healing, Fibrosis, and Cancer: The Paradigm of Recessive Dystrophic Epidermolysis Bullosa

"Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a devastating skin blistering disease caused by mutations in the gene encoding type VII collagen (C7), leading to epidermal fragility, trauma-induced blistering, and long term, hard-to-heal wounds."

Show evidence (1 reference)

DOI:10.3390/ijms22105104 SUPPORT Human Clinical

Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.

DOI:10.3390/ijms25020761

Splicing Modulation via Antisense Oligonucleotides in Recessive Dystrophic Epidermolysis Bullosa

1 finding

Antisense oligonucleotides (ASOs) represent an emerging therapeutic platform for targeting genetic diseases by influencing various aspects of (pre-)mRNA biology, such as splicing, stability, and translation.

"Antisense oligonucleotides (ASOs) represent an emerging therapeutic platform for targeting genetic diseases by influencing various aspects of (pre-)mRNA biology, such as splicing, stability, and translation."

Show evidence (1 reference)

DOI:10.3390/ijms25020761 SUPPORT Human Clinical

Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.

DOI:10.3390/ijms25042243

Emerging Gene Therapeutics for Epidermolysis Bullosa under Development

1 finding

The monogenetic disease epidermolysis bullosa (EB) is characterised by the formation of extended blisters and lesions on the patient’s skin upon minimal mechanical stress.

"The monogenetic disease epidermolysis bullosa (EB) is characterised by the formation of extended blisters and lesions on the patient’s skin upon minimal mechanical stress."

Show evidence (1 reference)

DOI:10.3390/ijms25042243 SUPPORT Human Clinical

"The monogenetic disease epidermolysis bullosa (EB) is characterised by the formation of extended blisters and lesions on the patient’s skin upon minimal mechanical stress."

Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.

DOI:10.3390/ijms251910270

Current Status of Biomedical Products for Gene and Cell Therapy of Recessive Dystrophic Epidermolysis Bullosa

1 finding

Current Status of Biomedical Products for Gene and Cell Therapy of Recessive Dystrophic Epidermolysis Bullosa

"This detailed review describes innovative strategies and current products for gene and cell therapy at different stages of research and development to treat recessive dystrophic epidermolysis bullosa (RDEB) which is associated with the functional deficiency of collagen type VII alpha 1 (C7)..."

Show evidence (1 reference)

DOI:10.3390/ijms251910270 SUPPORT In Vitro

Deep research cited this publication as relevant literature for Dystrophic Epidermolysis Bullosa.

Deep Research

Falcon ▸

Disease Characteristics Research Template

Edison Scientific Literature 88 citations 2026-05-08T13:43:36.197959

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Characteristics Research Template

Target Disease

Disease Name: Dystrophic Epidermolysis Bullosa
MONDO ID: (if available)
Category: Mendelian

Research Objectives

Please provide a comprehensive research report on Dystrophic Epidermolysis Bullosa covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.

For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.

1. Disease Information

Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed

What is the disease? Provide a concise overview.
What are the key identifiers? (OMIM, Orphanet, ICD-10/ICD-11, MeSH, Mondo)
What are the common synonyms and alternative names?
Is the information derived from individual patients (e.g., EHR) or aggregated disease-level resources?

2. Etiology

Disease Causal Factors: What are the primary causes? (genetic, environmental, infectious, mechanistic)
Risk Factors:

Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases
Genetic risk factors (causal variants, susceptibility loci, modifier genes)
Environmental risk factors (toxins, lifestyle, occupational exposures, age, sex, family history)
Protective Factors:

Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases
Genetic protective factors (protective variants, modifier alleles)
Environmental protective factors (diet, lifestyle, exposures that reduce risk)
Gene-Environment Interactions: How do genetic and environmental factors interact to influence disease?

Search first: CTD, PubMed, PheGenI, GxE databases

3. Phenotypes

Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC

For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities

For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype

4. Genetic/Molecular Information

Causal Genes: Gene mutations or chromosomal abnormalities responsible for disease (gene symbols, OMIM IDs)

Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene
Pathogenic Variants:
Affected genes (gene symbols, HGNC IDs) > Search first: OMIM, NCBI Gene, Ensembl, HGNC, UniProt, GeneCards
Variant classification (pathogenic, likely pathogenic, VUS per ACMG/AMP guidelines) > Search first: ClinVar, ClinGen, ACMG/AMP guidelines, VarSome
Variant type/class (missense, frameshift, nonsense, splice-site, structural)
Allele frequency in population databases > Search first: gnomAD, 1000 Genomes, ExAC, TOPMed, dbSNP
Somatic vs germline origin > Search first: COSMIC (somatic), ClinVar, ICGC, TCGA
Functional consequences (loss of function, gain of function, dominant negative)
Modifier Genes: Genes that modify disease severity or expression
Epigenetic Information: DNA methylation, histone modifications, chromatin changes affecting disease

Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
Chromosomal Abnormalities: Large-scale genetic changes (aneuploidy, translocations, inversions)

Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser

5. Environmental Information

Environmental Factors: Non-genetic contributing factors (toxins, radiation, pollution, occupational exposure)

Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases
Lifestyle Factors: Behavioral factors (smoking, diet, exercise, alcohol consumption)

Search first: CDC databases, WHO, PubMed, NHANES
Infectious Agents: If applicable, pathogens causing or triggering disease (bacteria, viruses, fungi, parasites)

Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON

6. Mechanism / Pathophysiology

Molecular Pathways: Specific signaling cascades or biochemical pathways involved (Wnt, MAPK, mTOR, PI3K-AKT, etc.)

Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc
Cellular Processes: Cell-level mechanisms (apoptosis, autophagy, cell cycle dysregulation, inflammation, etc.)

Search first: Gene Ontology (GO), Reactome, KEGG, PubMed
Protein Dysfunction: How protein structure or function is altered (misfolding, aggregation, loss of function, gain of function)

Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold
Metabolic Changes: Alterations in metabolic processes (energy metabolism, lipid metabolism, amino acid metabolism)

Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA
Immune System Involvement: Role of immune response (autoimmunity, immunodeficiency, chronic inflammation)

Search first: ImmPort, Immunome Database, IEDB, Gene Ontology
Tissue Damage Mechanisms: How tissues/ are injured (oxidative stress, ischemia, fibrosis, necrosis)

Search first: PubMed, Gene Ontology, Reactome
Biochemical Abnormalities: Specific molecular defects (enzyme deficiencies, receptor dysfunction, ion channel defects)

Search first: BRENDA, UniProt, KEGG, OMIM, PubMed
Epigenetic Changes: DNA methylation, histone modifications affecting gene expression in disease

Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth
Molecular Profiling (if available):
Transcriptomics/gene expression changes > Search first: GEO (Gene Expression Omnibus), ArrayExpress, GTEx, Human Cell Atlas, SRA
Proteomics findings > Search first: PRIDE, ProteomeXchange, Human Protein Atlas, STRING, BioGRID
Metabolomics signatures > Search first: MetaboLights, Metabolomics Workbench, HMDB, METLIN
Lipidomics alterations > Search first: LIPID MAPS, SwissLipids, LipidHome, Metabolomics Workbench
Genomic structural features > Search first: UCSC Genome Browser, Ensembl, NCBI, dbVar, DGV
Advanced Technologies (if applicable):
Single-cell analysis findings (cell-type specific mechanisms, cellular heterogeneity) > Search first: Human Cell Atlas, Single Cell Portal, GEO, CELLxGENE
Spatial transcriptomics findings > Search first: GEO, Spatial Research, Vizgen, 10x Genomics data
Multi-omics integration results > Search first: TCGA, ICGC, cBioPortal, LinkedOmics, PubMed
Functional genomics screens (CRISPR, RNAi) > Search first: DepMap, GenomeRNAi, PubMed, BioGRID ORCS

For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types

7. Anatomical Structures Affected

Organ Level:
Primary organs directly affected
Secondary organ involvement (complications, secondary effects)
Body systems involved (cardiovascular, nervous, digestive, respiratory, endocrine, etc.)

Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT
Tissue and Cell Level:
Specific tissue types affected (epithelial, connective, muscle, nervous)
Specific cell populations targeted (with Cell Ontology terms)

Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB
Subcellular Level:
Cellular compartments involved (mitochondria, nucleus, ER, lysosomes) (with GO Cellular Component terms)

Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas
Localization:
Specific anatomical sites (with UBERON terms) > Search first: FMA, Uberon, NeuroNames (for brain), SNOMED CT
Lateralization (unilateral, bilateral, asymmetric) > Search first: HPO, clinical literature, imaging databases

8. Temporal Development

Onset:
Typical age of onset (congenital, pediatric, adult, geriatric)
Onset pattern (acute, subacute, chronic, insidious)

Search first: OMIM, Orphanet, HPO, PubMed
Progression:
Disease stages (early, intermediate, advanced, end-stage) > Search first: Cancer Staging Manual (AJCC), WHO classifications, PubMed
Progression rate (rapid, slow, variable)
Disease course pattern (episodic, relapsing-remitting, progressive, stable)
Disease duration (self-limited, chronic lifelong)

Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM
Patterns:
Remission patterns (spontaneous, treatment-induced) > Search first: Clinical trial databases, disease registries, PubMed
Critical periods (time windows of vulnerability or opportunity for intervention) > Search first: PubMed, developmental biology databases, clinical guidelines

9. Inheritance and Population

Epidemiology:
Prevalence (cases per 100,000 at given time)
Incidence (new cases per 100,000 per year)

Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries
For Genetic Etiology:
Inheritance pattern (AD, AR, X-linked, mitochondrial, multifactorial, polygenic) > Search first: OMIM, Orphanet, ClinVar, GTR (Genetic Testing Registry)
Penetrance (complete, incomplete, age-dependent) > Search first: ClinVar, OMIM, PubMed, ClinGen
Expressivity (variable, consistent) > Search first: OMIM, ClinVar, PubMed
Genetic anticipation (increasing severity in successive generations) > Search first: OMIM, PubMed (especially for repeat expansion disorders)
Germline mosaicism > Search first: ClinVar, OMIM, genetic counseling literature, PubMed
Founder effects (population-specific mutations) > Search first: gnomAD, population genetics databases, PubMed
Consanguinity role > Search first: OMIM, population studies, genetic counseling resources
Carrier frequency > Search first: gnomAD, carrier screening databases, GeneReviews, GTR
Population Demographics:
Affected populations (ethnic or demographic groups with higher prevalence) > Search first: gnomAD, 1000 Genomes, PAGE Study, PubMed, population registries
Geographic distribution (endemic areas, regional variation) > Search first: WHO, CDC, GBD, Orphanet, geographic epidemiology databases
Geographic distribution of specific variants
Sex ratio (male:female) > Search first: Disease registries, OMIM, PubMed, epidemiological databases
Age distribution of affected individuals > Search first: CDC, disease registries, SEER, Orphanet

10. Diagnostics

Clinical Tests:
Laboratory tests (blood, urine, tissue chemistry, specific enzyme assays) > Search first: LOINC, LabTests Online, PubMed
Biomarkers (proteins, metabolites, genetic markers, circulating biomarkers) > Search first: FDA Biomarker List, BEST (Biomarkers, EndpointS, and other Tools), PubMed
Imaging studies (X-ray, CT, MRI, PET, ultrasound) > Search first: RadLex, DICOM, Radiopaedia, imaging databases
Functional tests (pulmonary function, cardiac stress tests) > Search first: LOINC, clinical guidelines, PubMed
Electrophysiology (EEG, EMG, ECG, nerve conduction studies) > Search first: LOINC, clinical neurophysiology databases, PubMed
Biopsy findings (histopathology, immunohistochemistry) > Search first: SNOMED CT, College of American Pathologists resources, PubMed
Pathology findings (microscopic examination) > Search first: SNOMED CT, Digital Pathology databases, PubMed
Genetic Testing:

Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen
Overview of recommended genetic testing approach
Whole genome sequencing (WGS) utility > Search first: GTR, ClinVar, GEL (Genomics England), gnomAD
Whole exome sequencing (WES) utility > Search first: GTR, ClinVar, OMIM, GeneMatcher
Gene panels (which panels, which genes) > Search first: GTR, ClinVar, laboratory-specific databases
Single gene testing > Search first: GTR, ClinVar, OMIM, GeneReviews
Chromosomal microarray (CMA) > Search first: DECIPHER, ClinVar, dbVar, ECARUCA
Karyotyping > Search first: Chromosome Abnormality Database, ClinVar, cytogenetics resources
FISH > Search first: ClinVar, cytogenetics databases, PubMed
Mitochondrial DNA testing > Search first: MITOMAP, MSeqDR, ClinVar, GTR
Repeat expansion testing > Search first: GTR, ClinVar, repeat expansion databases, PubMed
Omics-Based Diagnostics (if applicable):
RNA sequencing / transcriptomics > Search first: GEO, ArrayExpress, GTEx, RNA-seq databases
Proteomics > Search first: PRIDE, ProteomeXchange, FDA Biomarker database
Metabolomics > Search first: MetaboLights, Metabolomics Workbench, HMDB
Epigenomics > Search first: GEO, ENCODE, Roadmap Epigenomics, MethBase
Liquid biopsy > Search first: COSMIC, ClinVar, liquid biopsy databases, PubMed
Clinical Criteria:
Standardized diagnostic criteria (DSM, ICD, society guidelines) > Search first: DSM-5, ICD-11, clinical society guidelines, UpToDate
Differential diagnosis (other conditions to rule out, with distinguishing features) > Search first: DynaMed, UpToDate, clinical decision support systems
Screening:
Screening methods for asymptomatic individuals (newborn screening, carrier screening, cascade screening) > Search first: ACMG recommendations, CDC newborn screening, GTR

11. Outcome/Prognosis

Survival and Mortality:
Survival rate (5-year, 10-year, overall) > Search first: SEER, cancer registries, disease-specific registries, PubMed
Life expectancy (with and without treatment if applicable) > Search first: Orphanet, disease registries, actuarial databases, PubMed
Mortality rate > Search first: CDC, WHO, GBD, national mortality databases
Disease-specific mortality (deaths directly attributable to disease) > Search first: Disease registries, CDC Wonder, GBD, PubMed
Morbidity and Function:
Morbidity (disease-related disability and health impacts) > Search first: GBD, WHO, disability databases, PubMed
Disability outcomes (long-term functional impairments) > Search first: ICF (International Classification of Functioning), disability registries
Quality of life measures (EQ-5D, SF-36, PROMIS, disease-specific tools) > Search first: EQ-5D database, SF-36, PROMIS, PubMed
Disease Course:
Complications (secondary problems: infections, organ failure, etc.) > Search first: ICD codes, disease registries, clinical databases, PubMed
Recovery potential (likelihood and extent of recovery, with vs without treatment) > Search first: Natural history studies, rehabilitation databases, PubMed
Prediction:
Prognostic factors (age, disease severity, biomarkers, treatment response) > Search first: Prognostic models databases, clinical calculators, PubMed
Prognostic biomarkers (molecular markers predicting disease course) > Search first: FDA Biomarker database, PubMed, cancer prognostic databases

12. Treatment

Pharmacotherapy:
Pharmacological treatments (drug names, drug classes, mechanisms of action) > Search first: DrugBank, RxNorm, ATC classification, DailyMed, FDA databases
Pharmacogenomics (how genetic variants affect drug metabolism, efficacy, toxicity) > Search first: PharmGKB, CPIC (Clinical Pharmacogenetics), FDA Table of PGx Biomarkers
Advanced Therapeutics:
Gene therapy (viral vectors, CRISPR, gene replacement, gene editing) > Search first: ClinicalTrials.gov, FDA gene therapy database, ASGCT resources
Cell therapy (stem cell transplant, CAR-T, cellular therapeutics) > Search first: ClinicalTrials.gov, FDA cell therapy database, FACT standards
RNA-based therapies (ASOs, siRNA, mRNA therapies) > Search first: ClinicalTrials.gov, FDA approvals, PubMed
Targeted therapies (treatments directed at specific molecular targets) > Search first: My Cancer Genome, OncoKB, ClinicalTrials.gov, FDA approvals
Immunotherapies (checkpoint inhibitors, monoclonal antibodies) > Search first: Cancer Immunotherapy Database, FDA approvals, ClinicalTrials.gov
Surgical and Interventional:
Surgical interventions (types of surgery, timing, outcomes) > Search first: CPT codes, surgical registries, clinical guidelines, PubMed
Supportive and Rehabilitative:
Supportive care (symptom management, pain control, nutrition) > Search first: Clinical guidelines, Cochrane Library, PubMed
Rehabilitation (physical therapy, occupational therapy, speech therapy) > Search first: Rehabilitation medicine databases, clinical guidelines, PubMed
Experimental:
Experimental treatments in clinical trials (with NCT identifiers if available) > Search first: ClinicalTrials.gov, EU Clinical Trials Register, WHO ICTRP
Treatment Outcomes:
Treatment response rates > Search first: Clinical trial databases, FDA reviews, systematic reviews, PubMed
Side effects and adverse events > Search first: FDA Adverse Event Reporting System (FAERS), MedWatch, PubMed
Treatment Strategy:
Treatment algorithms (clinical pathways, decision trees) > Search first: Clinical practice guidelines, NCCN Guidelines, UpToDate
Combination therapies > Search first: ClinicalTrials.gov, treatment guidelines, PubMed
Personalized medicine approaches (genotype-guided treatment) > Search first: My Cancer Genome, CIViC, PharmGKB, precision medicine databases

For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.

13. Prevention

Prevention Levels:
Primary prevention (preventing disease occurrence: vaccination, risk factor modification) > Search first: CDC, WHO, USPSTF recommendations, Cochrane Library
Secondary prevention (early detection and treatment: screening programs, early intervention) > Search first: USPSTF, CDC screening guidelines, WHO
Tertiary prevention (preventing complications in those with disease) > Search first: Clinical guidelines, disease management protocols, PubMed
Immunization: Vaccine strategies (if applicable)

Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database
Screening and Early Detection:
Screening programs (population-based: newborn screening, cancer screening) > Search first: CDC screening programs, USPSTF, cancer screening databases
Genetic screening (carrier screening, preimplantation genetic diagnosis, prenatal testing) > Search first: ACMG recommendations, ACOG guidelines, GTR
Risk stratification (identifying high-risk individuals for targeted prevention) > Search first: Risk prediction models, clinical calculators, PubMed
Behavioral Interventions: Lifestyle modifications to reduce risk

Search first: CDC, WHO, behavioral intervention databases, Cochrane Library
Counseling: Genetic counseling (risk assessment, family planning guidance)

Search first: NSGC resources, ACMG guidelines, GeneReviews
Public Health:
Public health interventions (sanitation, vector control, health education) > Search first: CDC, WHO, public health databases, PubMed
Environmental interventions (reducing environmental risk factors) > Search first: EPA databases, WHO environmental health, PubMed
Prophylaxis: Preventive medications or procedures

Search first: Clinical guidelines, FDA approvals, PubMed

14. Other Species / Natural Disease

Taxonomy: Species affected (with NCBI Taxon identifiers)

Search first: NCBI Taxonomy
Breed: Specific breeds affected (with VBO identifiers if applicable)

Search first: VBO (Vertebrate Breed Ontology)
Gene: Orthologous genes in other species (with NCBI Gene IDs)

Search first: NCBI Gene
Natural Disease:
Naturally occurring disease in other species (companion animals, wildlife) > Search first: OMIA (Online Mendelian Inheritance in Animals), VetCompass, PubMed
Veterinary relevance and importance in animal health > Search first: OMIA, veterinary databases, PubMed
Comparative Biology:
Comparative pathology (similarities and differences across species) > Search first: OMIA, comparative pathology databases, PubMed
Evolutionary conservation of disease mechanisms > Search first: HomoloGene, OrthoMCL, Alliance of Genome Resources
Transmission (if applicable):
Zoonotic potential > Search first: CDC zoonotic diseases, WHO zoonoses, GIDEON
Cross-species susceptibility > Search first: NCBI Taxonomy, veterinary databases, PubMed

15. Model Organisms

Model Types:
Model organism type (mammalian, invertebrate, cellular, in vitro) > Search first: Alliance of Genome Resources, model organism databases
Specific model systems (mouse, rat, zebrafish, Drosophila, C. elegans, yeast, cell lines, organoids, iPSCs) > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, SGD, ATCC, Cellosaurus
Induced models (drug treatment, surgical intervention, environmental manipulation) > Search first: MGI, model organism databases, PubMed
Genetic Models:
Types available (knockout, knock-in, transgenic, conditional, humanized) > Search first: MGI, IMPC, KOMP, EuMMCR, IMSR
Model Characteristics:
Phenotype recapitulation (how well model reproduces human disease features) > Search first: Model organism databases, comparative studies, PubMed
Model limitations (aspects of human disease not captured) > Search first: Model organism databases, PubMed, review articles
Applications:
Research applications (what aspects of disease can be studied) > Search first: Model organism databases, PubMed
Resources:
Model databases > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, IMSR, EMMA, MMRRC

Citation Requirements

Cite primary literature (PMID preferred) for all mechanistic and clinical claims
Prioritize recent reviews and landmark papers
Include direct quotes from abstracts where possible to support key statements
Distinguish evidence source types: human clinical, model organism, in vitro, computational

Output Format

Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease

This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details

Dystrophic Epidermolysis Bullosa (DEB) — Disease Characteristics Research Report (2026-05-08)

Target disease

Disease: Dystrophic epidermolysis bullosa (DEB) (Mendelian mechanobullous genodermatosis).

Note on identifiers (OMIM/Orphanet/ICD/MeSH/MONDO): In this tool run, curated database identifier pages were not retrieved directly. The report therefore focuses on evidence-backed clinical/genetic characterization from the peer‑reviewed literature and ClinicalTrials.gov records; identifier fields are flagged as not captured in retrieved evidence.

1. Disease information

Overview and definition

DEB is a major subtype of epidermolysis bullosa (EB), a group of inherited disorders with skin and mucosal membrane blistering induced by mechanical trauma. In DEB, pathogenic variants in COL7A1 impair type VII collagen (C7) and thereby anchoring fibrils at the dermal–epidermal junction, causing separation below the lamina densa (upper dermis/sub‑lamina densa) (hou2023innovationsinthe pages 1-2, bischof2024emerginggenetherapeutics pages 1-2, zorina2024currentstatusof pages 1-2).

Recent review language defining the core concept: DEB is “caused by inherited pathogenic variants in the COL7A1 gene, which encodes type VII collagen, the major component of anchoring fibrils which maintain adhesion between the outer epidermis and underlying dermis.” (Hou et al., 2023-06; URL: https://doi.org/10.2147/TCRM.S386923) (hou2023innovationsinthe pages 1-2).

Subtypes / classification

DEB is subclassified by inheritance into: - Dominant DEB (DDEB) (often milder). - Recessive DEB (RDEB) (often severe with extensive blistering, chronic wounds, fibrosis/scarring and high cancer risk). (hou2023innovationsinthe pages 1-2)

Synonyms / alternative names (from literature usage)

Dystrophic epidermolysis bullosa (DEB)
Dominant dystrophic epidermolysis bullosa (DDEB)
Recessive dystrophic epidermolysis bullosa (RDEB)
RDEB generalized severe / generalized intermediate (terminology used in registry cohorts) (kim2018epidemiologyandoutcome pages 3-4, kim2018epidemiologyandoutcome pages 1-2)

Evidence source type

The information above is derived primarily from aggregated disease-level resources in peer‑reviewed reviews, and registry/cohort studies for outcomes (hou2023innovationsinthe pages 1-2, bischof2024emerginggenetherapeutics pages 1-2, robertson2021cutaneoussquamouscell pages 3-3, kim2018epidemiologyandoutcome pages 1-2).

2. Etiology

Disease causal factors

Primary cause: germline pathogenic variants in COL7A1 causing reduced/absent functional type VII collagen (C7), leading to loss/dysfunction of anchoring fibrils and mechanical fragility with sub‑lamina densa blistering (hou2023innovationsinthe pages 1-2, zorina2024currentstatusof pages 1-2).

Dominant vs recessive molecular patterns (current understanding): Reviews emphasize that DDEB commonly involves glycine substitutions in the C7 triple helix, while RDEB is frequently driven by loss-of-function variants (nonsense/frameshift/splice) that reduce/abolish C7 (hou2023innovationsinthe pages 2-5, zorina2024currentstatusof pages 1-2).

Risk factors

Because DEB is monogenic, “risk factors” are predominantly genetic: - Family history / carrier status (autosomal dominant or autosomal recessive inheritance, depending on subtype). (hou2023innovationsinthe pages 1-2, shehata2024geneticimplicationsand pages 7-8) - Consanguinity can increase the frequency of autosomal recessive EB/DEB in some populations (reported in a Saudi cohort). (Shehata et al., 2024-08; https://doi.org/10.7759/cureus.66678) (shehata2024geneticimplicationsand pages 7-7)

Protective factors

No validated protective genetic variants or environmental protective factors were identified in the retrieved evidence.

Gene–environment interactions

DEB blistering is mechanically provoked; environmental friction/trauma triggers lesions on a genetically fragile dermal–epidermal junction, but formal GxE interaction studies were not identified in this run.

3. Phenotypes

Core clinical phenotype spectrum

Across reviews and cohorts, DEB/RDEB is characterized by: - Trauma-induced blistering and erosions of skin and mucosae (hou2023innovationsinthe pages 1-2, azevedo2023fibrosisasa pages 1-2) - Chronic nonhealing wounds with recurrent breakdown (hou2023innovationsinthe pages 1-2, tartaglia2021impairedwoundhealing pages 1-2) - Scarring and fibrosis (including progressive deformity such as “mitten” deformities in severe RDEB due to scarring) (zorina2024currentstatusof pages 1-2) - Systemic complications (commonly cited in reviews): anemia, malnutrition, osteoporosis, failure to thrive, strictures (danescu2024treatmentofepidermolysis pages 1-4, hou2023innovationsinthe pages 1-2) - Pain and pruritus are prominent symptoms; supportive management remains central (stone2024creationandcharacterization pages 1-2) - Cutaneous squamous cell carcinoma (cSCC): high-risk complication particularly in severe generalized RDEB (hou2023innovationsinthe pages 1-2, robertson2021cutaneoussquamouscell pages 3-3)

A mechanistic systematic review frames the wound-to-fibrosis-to-cancer phenotype chain: “The alteration in col VII expression leads to the formation of recurrent bullae… subsequent events are deficient healing associated with an intense inflammatory process resulting in the development of chronic wounds… creating a vicious cycle… [that] contribute[s] to a microenvironment favorable to epithelial carcinogenesis.” (de Azevedo et al., 2023-02; https://doi.org/10.1055/s-0043-1763257) (azevedo2023fibrosisasa pages 4-5).

Age of onset and progression (typical)

DEB is generally congenital/early onset, with lifelong mechanobullous disease. Disease course is typically chronic and progressive in severe RDEB with cumulative scarring/fibrosis and increasing risk of cSCC in early adulthood (hou2023innovationsinthe pages 1-2, robertson2021cutaneoussquamouscell pages 3-3).

Quality-of-life impact

Retrieved evidence emphasizes substantial daily burden and “extremely poor quality of life” in RDEB (e.g., systemic involvement and early death described in preclinical therapeutic work), but this run did not retrieve quantitative QOLEB/EBDASI/QoL instrument summary statistics (hou2023innovationsinthe pages 1-2, paboncarrasco2024managementofskin pages 6-7). This is a gap for knowledge-base fields requiring numeric QoL values.

Suggested HPO terms (examples; non-exhaustive)

Skin blistering: HP:0032123 (Blistering of the skin)
Skin erosions: HP:0001058 (Skin erosion)
Skin fragility: HP:0001035 (Fragile skin)
Abnormal scarring: HP:0100699 (Abnormal scar)
Cutaneous squamous cell carcinoma: HP:0006732 (Squamous cell carcinoma)
Nail dystrophy: HP:0008404 (Nail dystrophy)
Pruritus: HP:0000989 (Pruritus)
Pain: HP:0012531 (Pain)
Anemia: HP:0001903 (Anemia)
Failure to thrive: HP:0001508 (Failure to thrive)
Esophageal stricture: HP:0002043 (Esophageal stricture)

4. Genetic / molecular information

Causal gene(s)

COL7A1 (type VII collagen α1 chain) is the causal gene for DEB, encoding C7 that forms anchoring fibrils at the dermal–epidermal junction/basement membrane zone (hou2023innovationsinthe pages 1-2, zorina2024currentstatusof pages 1-2).

Pathogenic variant classes and consequences

Loss-of-function (RDEB): reduced/absent C7 leading to absent/insufficient anchoring fibrils; sub‑lamina densa cleavage and severe blistering and chronic wounds (zorina2024currentstatusof pages 1-2, azevedo2023fibrosisasa pages 1-2).
Dominant-negative / structural (DDEB): glycine substitutions in the triple helix domain are highlighted as common dominant patterns in reviews (hou2023innovationsinthe pages 2-5).
Splice variants and deep intronic variants: 2024 work demonstrates deep intronic loss‑of‑function variants causing aberrant splicing can be corrected in patient keratinocytes/fibroblasts via antisense oligonucleotides (ASOs), restoring normal splicing to >94% and C7 protein up to ~56% of normal (Pironon et al., 2024-08; https://doi.org/10.1073/pnas.2401781121) (pironon2024splicemodulationstrategy pages 1-2, pironon2024splicemodulationstrategy pages 4-6).

Recent developments (2023–2024) in variant-targeted correction

Splice modulation / ASO splicing enhancement: Hainzl et al. (2024-01; https://doi.org/10.3390/ijms25020761) screened 2′‑MOE ASOs in RDEB cells with c.425A>G and identified candidates increasing correctly spliced COL7A1 transcripts (ddPCR ~3.8–4.2-fold for leading ASOs), with increased full‑length C7 in RDEB skin equivalents (hainzl2024splicingmodulationvia pages 7-10, hainzl2024splicingmodulationvia pages 1-2).
Exon skipping: A DEB treatment review describes exon-skipping logic (“Of the 118 exons in COL7A1, 80 of these could be skipped in frame”) and notes topical exon‑73 ASO trial NCT03605069 had low uptake/limited efficacy; follow-on PTW‑002 is in clinical testing (NCT05529134) (hou2023innovationsinthe pages 6-8).

Modifier genes / epigenetics / chromosomal abnormalities

Evidence for specific modifier genes and epigenetic signatures was not directly retrieved in this run (although some cohort papers mention modifiers in passing). This should be filled from curated genetics resources or dedicated modifier studies.

5. Environmental information

DEB is primarily genetic. Environmental contributors are mainly mechanical trauma/friction triggering blistering. No toxin/pollution/infectious etiology was identified in retrieved evidence.

6. Mechanism / pathophysiology

Causal chain (from trigger to clinical manifestations)

Germline COL7A1 variants → reduced/abnormal C7 (hou2023innovationsinthe pages 1-2, zorina2024currentstatusof pages 1-2).
C7 deficiency → impaired anchoring fibrils → skin cleavage below lamina densa causing mechanical fragility and blistering (azevedo2023fibrosisasa pages 1-2, condorelli2019epidermolysisbullosaassociatedsquamous pages 8-10).
Recurrent wounding with chronic nonhealing ulcers, often with bacterial colonization that perpetuates inflammation (condorelli2019epidermolysisbullosaassociatedsquamous pages 8-10, azevedo2023fibrosisasa pages 4-5).
Fibrosis amplification loop: inflammatory infiltrates and myofibroblasts produce TGF‑β1, sustaining a self‑renewing fibrotic process and ECM stiffening; fibroblasts can acquire CAF‑like transcriptional features (condorelli2019epidermolysisbullosaassociatedsquamous pages 8-10, condorelli2019epidermolysisbullosaassociatedsquamous pages 6-8).
Carcinogenesis: chronic wounds + inflammation + fibrosis create a permissive tumor microenvironment; RDEB cSCC often arises in chronic wound/scar sites rather than UV-driven pathways (azevedo2023fibrosisasa pages 4-5, robertson2021cutaneoussquamouscell pages 1-2).

Mechanistic quote emphasizing signaling beyond structural failure: “absent expression of wild-type C7 in RDEB dermal fibroblasts… leads to increased TGFβ signaling and a disruption to ECM protein organization and composition that is tumor-promoting.” (Tartaglia et al., 2021-05; https://doi.org/10.3390/ijms22105104) (tartaglia2021impairedwoundhealing pages 2-4).

Upstream vs downstream

Upstream: COL7A1 loss/dysfunction; anchoring fibril failure (hou2023innovationsinthe pages 1-2, zorina2024currentstatusof pages 1-2)
Downstream: chronic inflammation, TGF‑β signaling, myofibroblast differentiation, ECM remodeling and stiffness, impaired re‑epithelialization, tumor microenvironment and cSCC (condorelli2019epidermolysisbullosaassociatedsquamous pages 6-8, tartaglia2021impairedwoundhealing pages 2-4).

Cell types involved (suggested CL terms)

Basal keratinocyte (CL:0000312; keratinocyte)
Dermal fibroblast (CL:0000057; fibroblast)
Myofibroblast (CL:0000186; myofibroblast)
Macrophage (CL:0000235) and neutrophil/granulocyte (CL:0000775) in chronic wound inflammation (tartaglia2021impairedwoundhealing pages 2-4)

Molecular pathways / GO term suggestions

TGF‑β signaling pathway (GO:0007179)
Extracellular matrix organization (GO:0030198)
Wound healing (GO:0042060)
Inflammatory response (GO:0006954)
Epithelial to mesenchymal transition (GO:0001837) (discussed in RDEB-SCC context) (condorelli2019epidermolysisbullosaassociatedsquamous pages 8-10)

7. Anatomical structures affected

Organ/tissue level

Skin (primary) and mucous membranes (hou2023innovationsinthe pages 1-2, azevedo2023fibrosisasa pages 1-2)
Basement membrane zone / dermal–epidermal junction (structural locus of failure) (zorina2024currentstatusof pages 1-2)

Suggested UBERON terms - Skin: UBERON:0002097 - Epidermis: UBERON:0001003 - Dermis: UBERON:0002067 - Basement membrane: UBERON:0003725

Subcellular / molecular localization (suggested GO CC) - Extracellular matrix: GO:0031012 - Basement membrane: GO:0005604

8. Temporal development

Onset: typically congenital/early life, given monogenic structural defect (hou2023innovationsinthe pages 1-2, zorina2024currentstatusof pages 1-2).
Course: chronic lifelong; severe RDEB is progressive with cumulative scarring/fibrosis and increasing cSCC risk in early adulthood (hou2023innovationsinthe pages 1-2, robertson2021cutaneoussquamouscell pages 3-3).
Critical period: adolescence/early adulthood for rising cSCC risk, motivating early surveillance (kim2018epidemiologyandoutcome pages 5-6, bonamonte2022squamouscellcarcinoma pages 6-8).

9. Inheritance and population

Inheritance patterns

Autosomal dominant (DDEB) and autosomal recessive (RDEB) (hou2023innovationsinthe pages 1-2, nikolova2024autosomalrecessivetype pages 2-4).

Epidemiology (recent summarized estimates)

EB incidence ~40–60 per 1,000,000 live births; prevalence ~20–30 per 1,000,000 in some countries (England/Wales, Netherlands) (Bischof et al., 2024-02; https://doi.org/10.3390/ijms25042243) (bischof2024emerginggenetherapeutics pages 1-2).
DEB may represent ~30% of EB cases (Hou et al., 2023-06; https://doi.org/10.2147/TCRM.S386923) (hou2023innovationsinthe pages 1-2).

High-impact complication epidemiology: RDEB-associated cSCC

RDEB carries extremely high age-dependent cSCC risk and poor survival: - In the US National EB Registry estimates summarized in a London cohort paper: cumulative risk of ≥1 SCC in severe RDEB ~7.5% by age 20, 67.8% by 35, 90.1% by 55, with SCC-related death risk ~38.7% by 35 and ~70% by 45 (robertson2021cutaneoussquamouscell pages 3-3). - Australasian registry: cumulative risk of SCC by age 35 was 76.1% in RDEB generalized severe vs 10% in generalized intermediate; median survival after first SCC 4 years (severe) and 5 years (intermediate) (Kim et al., 2018-01; https://doi.org/10.2340/00015555-2781) (kim2018epidemiologyandoutcome pages 3-4, kim2018epidemiologyandoutcome pages 1-2).

10. Diagnostics

Recommended diagnostic approach (evidence-backed components)

EB/DEB classification is anchored to the level of skin cleavage and confirmation by a combination of: - Immunofluorescence antigen mapping (IFM) on skin biopsy - Transmission electron microscopy (TEM/EM) to localize cleavage plane and anchoring fibril defects - Molecular testing (NGS gene panels/WES) for COL7A1 variants interpreted under ACMG criteria (montaudie2016inheritedepidermolysisbullosa pages 1-2, nikolova2024autosomalrecessivetype pages 1-2, nikolova2024autosomalrecessivetype pages 2-4).

A case-based diagnostic statement: the “most effective diagnostic approach… combines TEM and immunofluorescence antigen mapping… together with DNA mutational analysis,” and NGS is described as preferable for cost-effective multi-variant screening (Nikolova et al., 2024-09; https://doi.org/10.3892/br.2024.1855) (nikolova2024autosomalrecessivetype pages 1-2).

Real-world implementation example (referral center workflow): In a Romanian ERN-Skin affiliated center, patients received clinical assessment with IFM/TEM and molecular testing when available (molecular testing performed in 29/56; IFM in 5; TEM in 10), illustrating staged diagnosis constrained by access/logistics (Suru et al., 2024-05; https://doi.org/10.7759/cureus.61160) (suru2024descriptivestudyof pages 2-4).

Genetic testing approaches

NGS panels (multi-gene EB panels) (shehata2024geneticimplicationsand pages 7-7, nikolova2024autosomalrecessivetype pages 1-2)
WES (noted in pediatric case literature) (ali2024epidermolysisbullosatwo pages 12-13)

Differential diagnosis

Not comprehensively captured in the retrieved evidence; would typically include other EB subtypes (EBS, JEB, Kindler EB) and other blistering disorders, but specific evidence-backed differential criteria were not retrieved here.

11. Outcomes / prognosis

Prognosis dominated by severe RDEB complications, especially cSCC

A 28-year London retrospective study reported for severe RDEB: metastatic disease in 16/31 (52%), SCC-associated mortality 64.5%, and median survival after first SCC 2.4 years (Robertson et al., 2021-07; https://doi.org/10.2340/00015555-3875) (robertson2021cutaneoussquamouscell pages 1-2, robertson2021cutaneoussquamouscell pages 3-3).

Systematic review synthesis (2024): in 157 RDEB-cSCC cases, median age at diagnosis was 30 years (range 6–68.4), and among cases with survival data, median survival after first cSCC varied with treatments (e.g., surgery only ~2 years; immunotherapy ~4.6 years; anti‑EGFR therapy ~4.0 years), noting small sample sizes (Hwang et al., 2024-05; https://doi.org/10.1186/s13023-024-03190-1) (hwang2024therapiesforcutaneous pages 1-3).

12. Treatment

Current applications / real-world implementations (supportive and multidisciplinary)

Current best practice remains multidisciplinary supportive care, prioritizing wound care, infection prevention/management, pain and itch control, nutrition, and treatment of complications (danescu2024treatmentofepidermolysis pages 1-4, shehata2024geneticimplicationsand pages 7-8).

FDA-approved causal/molecular therapy (major 2023 milestone)

Beremagene geperpavec (B‑VEC; VYJUVEK) is an in vivo topical gene therapy using a non‑replicating HSV‑1 vector delivering COL7A1 to promote C7 expression and anchoring fibril assembly.

Evidence from the phase 1/2 trial report emphasizes safety and molecular correction: in a randomized, placebo-controlled phase 1/2 trial (NCT03536143), “No grade 2 or above B‑VEC-related adverse events or vector shedding… were noted,” and primary/secondary objectives including “C7 expression” and “anchoring fibril assembly” and wound-closure outcomes were met (Gurevich et al., 2022-03; https://doi.org/10.1038/s41591-022-01737-y) (gurevich2022invivotopical pages 1-2).

Quantitative efficacy (from 2024 therapy review summarizing trials): - Phase 1/2 (NCT03536143): 10/12 (83%) B‑VEC wounds closed vs 1/7 (14%) placebo at 12 weeks (koutsoukos2024highlightsofgene pages 5-7). - Phase 3: complete wound healing reported as 67% B‑VEC vs 22% placebo, and 71% vs 20% at 3 months in summary sources (koutsoukos2024highlightsofgene pages 5-7, paboncarrasco2024managementofskin pages 6-7).

Mechanistic tissue restoration evidence from figures/tables: Gurevich et al. include tabulated wound closure endpoints and images showing restored C7 at the dermal–epidermal junction and mature anchoring fibrils after therapy (gurevich2022invivotopical media 3ae5ad4d, gurevich2022invivotopical media 80fb8fb9).

Other advanced therapeutics (2023–2024 research emphasis)

Ex vivo gene-corrected epidermal grafts (EB‑101): Review synthesis reports durable wound closure at multi-year follow-up for gene-corrected autologous keratinocyte grafts (hou2023innovationsinthe pages 2-5).
Splice modulation / exon skipping (ASOs): active 2024 preclinical work (Hainzl 2024; Pironon 2024) demonstrating restoration of correct COL7A1 splicing and partial C7 rescue, including deep intronic variant targeting (pironon2024splicemodulationstrategy pages 1-2, hainzl2024splicingmodulationvia pages 1-2).
Readthrough therapy: IV gentamicin open-label pilot in nonsense-variant RDEB increased C7 at the DEJ and reported >85% closure of monitored wounds at 1 and 3 months in three participants (Woodley et al., 2024-02; https://doi.org/10.1093/bjd/ljae063) (danescu2024treatmentofepidermolysis pages 1-4).

Clinical trials (examples; not exhaustive)

B‑VEC phase 1/2: NCT03536143 (NCT03536143 chunk 1)
Exon 73 ASO programs: NCT03605069 (terminated) and NCT05529134 (PTW‑002) (pironon2024splicemodulationstrategy pages 6-7, hou2023innovationsinthe pages 6-8)
EB‑101 phase 3 (ex vivo gene therapy): NCT04227106 (retrieved in trials list)

MAXO suggestions (selected)

Topical gene therapy: MAXO:0000123 (Gene therapy; general)
Skin wound care: MAXO:0000756 (Wound care)
Pain management: MAXO:0000747 (Pain management)
Genetic counseling: MAXO:0000079 (Genetic counseling)

13. Prevention

Primary prevention (disease occurrence)

Because DEB is genetic, primary prevention is via reproductive risk management: - After identifying a causal variant in an affected individual, “biological parents and siblings should undergo carrier status testing… following genetic counseling guidelines.” (Shehata et al., 2024-08; https://doi.org/10.7759/cureus.66678) (shehata2024geneticimplicationsand pages 7-8).

Secondary prevention (early detection)

cSCC surveillance is a critical prevention strategy in severe RDEB. - Review guidance: full skin exam every 3–6 months from age 10 for the highest-risk RDEB patients, with shorter intervals for those with prior cSCC (Bonamonte et al., 2022-04; https://doi.org/10.3390/cells11081365) (bonamonte2022squamouscellcarcinoma pages 6-8). - Registry guidance: “Regular skin checks at least every 3 months are… vital,” with biopsy triggers for persistent ulcers/hyperkeratosis and a goal of rapid excision of biopsy-proven SCC (Kim et al., 2018-01; https://doi.org/10.2340/00015555-2781) (kim2018epidemiologyandoutcome pages 5-6).

Tertiary prevention (complication prevention)

Multidisciplinary specialized EB centers integrating dermatology, genetics, pain management, nutrition, and wound care are advocated to reduce complication burden (shehata2024geneticimplicationsand pages 7-8).

14. Other species / natural disease

Naturally occurring DEB/RDEB-like disease has been reported in multiple species including dogs, cats, cattle, sheep, goats, and ostriches, with limited utility of some animal cases for therapy testing (Stone et al., 2024-05; https://doi.org/10.1371/journal.pone.0302991) (stone2024creationandcharacterization pages 1-2).

15. Model organisms

In vivo genetic models

Mouse models: Col7a1 knockout mice show severe blistering and early death; hypomorphic mice (~10% Col7a1 expression) recapitulate blistering, nail dystrophy, mitten deformities but do not capture patient-specific compound heterozygosity well (takaki2022generationofa pages 1-2).
Patient-mutation compound heterozygous mouse models: CRISPR/i‑GONAD enabled creation of a mouse model carrying patient-derived compound heterozygous mutations, supporting genotype-relevant studies and including single-cell transcriptomics readouts (Takaki et al., 2022-06; https://doi.org/10.1038/s41374-022-00735-5) (takaki2022generationofa pages 1-2).
New rat model (2024): a Lewis rat Col7a1del8/del8 model (8-bp deletion causing a premature stop) shows severe postnatal blistering with absent anchoring fibrils, offering larger surface area for topical/transfusion therapy testing but limited survival (median ~3 days) (stone2024creationandcharacterization pages 7-9, stone2024creationandcharacterization pages 9-10).

Human cell and xenograft models

iPSC-derived skin equivalents / xenografts: gene-corrected iPS-derived skin constructs grafted onto immunodeficient mice restored collagen VII expression and anchoring fibrils (koutsoukos2024highlightsofgene pages 5-7).

Recent quantitative statistics (quick reference)

The following table consolidates key epidemiology, cSCC outcomes, and B‑VEC efficacy endpoints with URLs and publication dates.

Finding/Metric	Population/Subtype	Value	Study type	Source (authors/year)	Publication date/month	URL/DOI	Evidence citation id
EB incidence	EB overall	~19.6 per 1,000,000 live-born infants	Review	Shehata et al. 2024	2024-08	https://doi.org/10.7759/cureus.66678	(shehata2024geneticimplicationsand pages 1-4)
EB incidence	EB overall	~40–60 per 1,000,000 live births	Review	Bischof et al. 2024	2024-02	https://doi.org/10.3390/ijms25042243	(bischof2024emerginggenetherapeutics pages 1-2)
EB prevalence	EB overall	~20–30 per 1,000,000 people (England/Wales, Netherlands)	Review	Bischof et al. 2024	2024-02	https://doi.org/10.3390/ijms25042243	(bischof2024emerginggenetherapeutics pages 1-2)
EB prevalence	EB overall (USA)	8.22 per 1,000,000	Review	Bonamonte et al. 2022	2022-04	https://doi.org/10.3390/cells11081365	(bonamonte2022squamouscellcarcinoma pages 1-2)
DEB prevalence	DEB overall	~6 per 1,000,000 in USA/Spain; up to 20 per 1,000,000 in Scotland	Review	Bonamonte et al. 2022	2022-04	https://doi.org/10.3390/cells11081365	(bonamonte2022squamouscellcarcinoma pages 1-2)
DEB proportion among EB	DEB among all EB cases	~30%	Review	Hou et al. 2023	2023-06	https://doi.org/10.2147/TCRM.S386923	(hou2023innovationsinthe pages 1-2)
DEB proportion among EB	Saudi cohort of EB patients	42.9% (12/28)	Retrospective cohort	Shehata et al. 2024	2024-08	https://doi.org/10.7759/cureus.66678	(shehata2024geneticimplicationsand pages 7-7)
DEB proportion among EB	Romanian referral-center cohort	55.4% (31/56)	Retrospective cohort	Suru et al. 2024	2024-05	https://doi.org/10.7759/cureus.61160	(suru2024descriptivestudyof pages 2-4)
cSCC cumulative risk by age	RDEB-severe / RDEB-HS	7.5% by age 20; 67.8% by 35; 80.2% by 45; 90.1% by 55	Registry/cohort data summarized in retrospective study	Robertson et al. 2021	2021-07	https://doi.org/10.2340/00015555-3875	(robertson2021cutaneoussquamouscell pages 3-3)
cSCC cumulative risk by age	RDEB-severe / RDEB-HS	7.5% by age 20; 52% by 30; 80% by 45	Systematic review citing cohort/registry estimates	Hwang et al. 2024	2024-05	https://doi.org/10.1186/s13023-024-03190-1	(hwang2024therapiesforcutaneous pages 1-3)
cSCC cumulative risk by age	RDEB-generalized severe	26.3% by age 20; 76.1% by 35	Registry cohort	Kim et al. 2018	2018-01	https://doi.org/10.2340/00015555-2781	(kim2018epidemiologyandoutcome pages 3-4, kim2018epidemiologyandoutcome pages 1-2)
cSCC cumulative risk by age	RDEB-generalized intermediate	10% by age 35; 66.7% by 65	Registry cohort	Kim et al. 2018	2018-01	https://doi.org/10.2340/00015555-2781	(kim2018epidemiologyandoutcome pages 3-4)
cSCC-related death cumulative risk by age	RDEB-severe / RDEB-HS	38.7% by age 35; 70.0% by 45; 78.7% by 55	Registry/cohort data summarized in retrospective study	Robertson et al. 2021	2021-07	https://doi.org/10.2340/00015555-3875	(robertson2021cutaneoussquamouscell pages 3-3)
cSCC-related death cumulative risk by age	RDEB-generalized severe	30% by age 25; 84.4% by age 34	Registry cohort	Kim et al. 2018	2018-01	https://doi.org/10.2340/00015555-2781	(kim2018epidemiologyandoutcome pages 3-4)
Median age at first cSCC	EB overall in London cohort	32.8 years	Retrospective cohort	Robertson et al. 2021	2021-07	https://doi.org/10.2340/00015555-3875	(robertson2021cutaneoussquamouscell pages 3-3)
Median age at first cSCC	RDEB-severe	29.5 years (range 13–52)	Retrospective cohort	Robertson et al. 2021	2021-07	https://doi.org/10.2340/00015555-3875	(robertson2021cutaneoussquamouscell pages 3-3, robertson2021cutaneoussquamouscell pages 1-2)
Median age at cSCC diagnosis	RDEB cSCC cases	30 years (range 6–68.4)	Systematic review	Hwang et al. 2024	2024-05	https://doi.org/10.1186/s13023-024-03190-1	(hwang2024therapiesforcutaneous pages 1-3)
Median age at first cSCC	Australasian RDEB cohort	30 years (earliest 16, latest 62)	Registry cohort	Kim et al. 2018	2018-01	https://doi.org/10.2340/00015555-2781	(kim2018epidemiologyandoutcome pages 1-2)
Metastatic rate	EB patients with cSCC overall (London cohort)	17/44 (39%)	Retrospective cohort	Robertson et al. 2021	2021-07	https://doi.org/10.2340/00015555-3875	(robertson2021cutaneoussquamouscell pages 3-3)
Metastatic rate	RDEB-severe with cSCC (London cohort)	16/31 (52%)	Retrospective cohort	Robertson et al. 2021	2021-07	https://doi.org/10.2340/00015555-3875	(robertson2021cutaneoussquamouscell pages 3-3)
Metastatic rate	EB-cSCC patients (Dutch registry)	11/22 (50%) developed metastases; all 11 died	Registry cohort	Harrs et al. 2022	2022-11	https://doi.org/10.1111/bjd.21769	(harrs2022theaggressivebehaviour pages 1-1)
SCC-associated mortality	EB patients with cSCC overall (London cohort)	25/44 (57%) died	Retrospective cohort	Robertson et al. 2021	2021-07	https://doi.org/10.2340/00015555-3875	(robertson2021cutaneoussquamouscell pages 3-3)
SCC-associated mortality	RDEB-severe with cSCC (London cohort)	21/31 (68%) died; 20/21 deaths SCC-related	Retrospective cohort	Robertson et al. 2021	2021-07	https://doi.org/10.2340/00015555-3875	(robertson2021cutaneoussquamouscell pages 3-3)
Median survival after first cSCC	EB overall (London cohort)	2.1 years	Retrospective cohort	Robertson et al. 2021	2021-07	https://doi.org/10.2340/00015555-3875	(robertson2021cutaneoussquamouscell pages 3-3)
Median survival after first cSCC	RDEB-severe (London cohort)	2.4 years (range 0.5–12.6)	Retrospective cohort	Robertson et al. 2021	2021-07	https://doi.org/10.2340/00015555-3875	(robertson2021cutaneoussquamouscell pages 1-2)
Median survival after first cSCC	RDEB-generalized severe	4 years	Registry cohort	Kim et al. 2018	2018-01	https://doi.org/10.2340/00015555-2781	(kim2018epidemiologyandoutcome pages 3-4, kim2018epidemiologyandoutcome pages 1-2)
Median survival after first cSCC	RDEB-generalized intermediate	5 years	Registry cohort	Kim et al. 2018	2018-01	https://doi.org/10.2340/00015555-2781	(kim2018epidemiologyandoutcome pages 3-4)
Median survival after first cSCC	RDEB-severe (Dutch registry)	41 months	Registry cohort	Harrs et al. 2022	2022-11	https://doi.org/10.1111/bjd.21769	(harrs2022theaggressivebehaviour pages 1-1)
B-VEC phase 1/2 wound closure at 12 weeks	RDEB wounds treated in NCT03536143	10/12 (83%) wounds closed with B-VEC vs 1/7 (14%) placebo	Randomized placebo-controlled phase 1/2 trial	Gurevich et al. 2022 / summarized by Koutsoukos et al. 2024	2022-03 / 2024-08	https://doi.org/10.1038/s41591-022-01737-y ; https://doi.org/10.1007/s13555-024-01239-4	(koutsoukos2024highlightsofgene pages 5-7, gurevich2022invivotopical pages 1-2, gurevich2022invivotopical media 3ae5ad4d)
B-VEC phase 1/2 median time to closure	RDEB wounds treated in NCT03536143	13.5 days vs 22.5 days placebo	Randomized placebo-controlled phase 1/2 trial	Koutsoukos et al. 2024	2024-08	https://doi.org/10.1007/s13555-024-01239-4	(koutsoukos2024highlightsofgene pages 5-7)
B-VEC phase 1/2 median duration of closure	RDEB wounds treated in NCT03536143	103.0 days vs 16.5 days placebo	Randomized placebo-controlled phase 1/2 trial	Koutsoukos et al. 2024	2024-08	https://doi.org/10.1007/s13555-024-01239-4	(koutsoukos2024highlightsofgene pages 5-7)
B-VEC phase 1/2 responder analysis	RDEB wounds treated in NCT03536143	79% B-VEC responders vs 0% placebo; P=0.0026	Randomized placebo-controlled phase 1/2 trial	Gurevich et al. 2022	2022-03	https://doi.org/10.1038/s41591-022-01737-y	(gurevich2022invivotopical media 3ae5ad4d)
B-VEC phase 3 complete wound healing	DEB patients aged ≥6 months	67% of B-VEC-treated wounds healed vs 22% placebo	Phase 3 double-blind intrapatient randomized placebo-controlled trial	Koutsoukos et al. 2024	2024-08	https://doi.org/10.1007/s13555-024-01239-4	(koutsoukos2024highlightsofgene pages 5-7)
B-VEC phase 3 complete wound healing at 3 months	DEB patients aged ≥6 months	71% with B-VEC vs 20% placebo	Phase 3 double-blind intrapatient randomized placebo-controlled trial	Koutsoukos et al. 2024 / Pabón-Carrasco et al. 2024	2024-08 / 2024-01	https://doi.org/10.1007/s13555-024-01239-4 ; https://doi.org/10.3390/healthcare12020261	(koutsoukos2024highlightsofgene pages 5-7, paboncarrasco2024managementofskin pages 6-7)
B-VEC phase 3 pain during dressing changes	DEB patients in phase 3 trial	Mean change to week 22: −0.88 with B-VEC vs −0.71 placebo	Phase 3 double-blind intrapatient randomized placebo-controlled trial	Pabón-Carrasco et al. 2024	2024-01	https://doi.org/10.3390/healthcare12020261	(paboncarrasco2024managementofskin pages 6-7)
B-VEC regulatory milestone	DDEB and RDEB / DEB wounds	FDA approval May 2023; first topical gene therapy approved for DEB wounds	Regulatory summary/review	Koutsoukos et al. 2024; Raymakers et al. 2024	2024-08 / 2024-03	https://doi.org/10.1007/s13555-024-01239-4 ; https://doi.org/10.1001/jamadermatol.2023.5857	(koutsoukos2024highlightsofgene pages 5-7)

Table: This table compiles key quantitative epidemiology, cSCC outcome data, and B-VEC trial efficacy metrics for dystrophic epidermolysis bullosa from recent reviews, cohort studies, and trials. It is useful as a quick-reference evidence summary for disease burden, prognosis, and emerging therapy performance.

Key figures/tables supporting B‑VEC molecular correction (visual evidence)

Wound closure endpoint table and longitudinal wound area reduction plots: (gurevich2022invivotopical media 3ae5ad4d)
Restored collagen VII immunofluorescence at the dermal–epidermal junction: (gurevich2022invivotopical media 80fb8fb9)
Anchoring fibril assembly by immunoelectron microscopy: (gurevich2022invivotopical media 2ab3990c)

Limitations of this report (evidence not retrieved in this run)

Curated identifier mappings (OMIM, Orphanet, ICD‑10/ICD‑11, MeSH, MONDO) were not retrieved via the available tools in this session.
Quantitative, instrument-based quality-of-life statistics (QOLEB, SF‑36, EQ‑5D) were not retrieved.
Differential diagnosis criteria were not comprehensively retrieved.

These gaps should be filled by targeted retrieval from GeneReviews/OMIM/Orphanet/HPO/MeSH and EB consensus guideline documents.

References

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(ali2024epidermolysisbullosatwo pages 12-13): Fatma Mabrouk Ali, Jieyu Zhou, Mingyan Wang, Qiuxia Wang, Lulu Sun, Mansour Maulid Mshenga, and Hongyan Lu. Epidermolysis bullosa: two rare case reports of col7a1 and ebs-gen sev krt14 variants with review of literature. BMC Pediatrics, Apr 2024. URL: https://doi.org/10.1186/s12887-024-04715-0, doi:10.1186/s12887-024-04715-0. This article has 3 citations and is from a peer-reviewed journal.
(hwang2024therapiesforcutaneous pages 1-3): Austin Hwang, Andie Kwon, Corinne H. Miller, Antonia Reimer-Taschenbrecker, and Amy S. Paller. Therapies for cutaneous squamous cell carcinoma in recessive dystrophic epidermolysis bullosa: a systematic review of 157 cases. Orphanet Journal of Rare Diseases, May 2024. URL: https://doi.org/10.1186/s13023-024-03190-1, doi:10.1186/s13023-024-03190-1. This article has 13 citations and is from a peer-reviewed journal.
(gurevich2022invivotopical pages 1-2): Irina Gurevich, Pooja Agarwal, PeiPei Zhang, John A. Dolorito, Stacie Oliver, Henry Liu, Nicholas Reitze, Nikhil Sarma, Isin Sinem Bagci, Kunju Sridhar, Visesha Kakarla, Vamsi K. Yenamandra, Mark O’Malley, Marco Prisco, Sara F. Tufa, Douglas R. Keene, Andrew P. South, Suma M. Krishnan, and M. Peter Marinkovich. In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial. Nature Medicine, 28:780-788, Mar 2022. URL: https://doi.org/10.1038/s41591-022-01737-y, doi:10.1038/s41591-022-01737-y. This article has 181 citations and is from a highest quality peer-reviewed journal.
(koutsoukos2024highlightsofgene pages 5-7): Stefanos A. Koutsoukos and Ganna Bilousova. Highlights of gene and cell therapy for epidermolysis bullosa and ichthyosis. Dermatology and Therapy, 14:2379-2392, Aug 2024. URL: https://doi.org/10.1007/s13555-024-01239-4, doi:10.1007/s13555-024-01239-4. This article has 5 citations.
(gurevich2022invivotopical media 3ae5ad4d): Irina Gurevich, Pooja Agarwal, PeiPei Zhang, John A. Dolorito, Stacie Oliver, Henry Liu, Nicholas Reitze, Nikhil Sarma, Isin Sinem Bagci, Kunju Sridhar, Visesha Kakarla, Vamsi K. Yenamandra, Mark O’Malley, Marco Prisco, Sara F. Tufa, Douglas R. Keene, Andrew P. South, Suma M. Krishnan, and M. Peter Marinkovich. In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial. Nature Medicine, 28:780-788, Mar 2022. URL: https://doi.org/10.1038/s41591-022-01737-y, doi:10.1038/s41591-022-01737-y. This article has 181 citations and is from a highest quality peer-reviewed journal.
(gurevich2022invivotopical media 80fb8fb9): Irina Gurevich, Pooja Agarwal, PeiPei Zhang, John A. Dolorito, Stacie Oliver, Henry Liu, Nicholas Reitze, Nikhil Sarma, Isin Sinem Bagci, Kunju Sridhar, Visesha Kakarla, Vamsi K. Yenamandra, Mark O’Malley, Marco Prisco, Sara F. Tufa, Douglas R. Keene, Andrew P. South, Suma M. Krishnan, and M. Peter Marinkovich. In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial. Nature Medicine, 28:780-788, Mar 2022. URL: https://doi.org/10.1038/s41591-022-01737-y, doi:10.1038/s41591-022-01737-y. This article has 181 citations and is from a highest quality peer-reviewed journal.
(NCT03536143 chunk 1): A Phase I/II Study of KB103, a Topical HSV1-COL7, on DEB Patients. Krystal Biotech, Inc.. 2018. ClinicalTrials.gov Identifier: NCT03536143
(pironon2024splicemodulationstrategy pages 6-7): Nathalie Pironon, Emmanuelle Bourrat, Catherine Prost, Mei Chen, David T. Woodley, Matthias Titeux, and Alain Hovnanian. Splice modulation strategy applied to deep intronic variants in col7a1 causing recessive dystrophic epidermolysis bullosa. Proceedings of the National Academy of Sciences of the United States of America, Aug 2024. URL: https://doi.org/10.1073/pnas.2401781121, doi:10.1073/pnas.2401781121. This article has 7 citations and is from a highest quality peer-reviewed journal.
(takaki2022generationofa pages 1-2): Satoshi Takaki, Takashi Shimbo, Kentaro Ikegami, Tomomi Kitayama, Yukari Yamamoto, Sho Yamazaki, Shiho Mori, and Katsuto Tamai. Generation of a recessive dystrophic epidermolysis bullosa mouse model with patient-derived compound heterozygous mutations. Laboratory Investigation, 102:574-580, Jun 2022. URL: https://doi.org/10.1038/s41374-022-00735-5, doi:10.1038/s41374-022-00735-5. This article has 10 citations and is from a peer-reviewed journal.
(stone2024creationandcharacterization pages 7-9): William Stone, Chloe Strege, William Miller, Aron M. Geurts, Michael Grzybowski, Megan Riddle, Christopher Lees, Cindy Eide, Douglas R. Keene, Sara F. Tufa, Davis Seelig, John McGrath, and Jakub Tolar. Creation and characterization of novel rat model for recessive dystrophic epidermolysis bullosa: frameshift mutation of the col7a1 gene leads to severe blistered phenotype. PLOS ONE, 19:e0302991, May 2024. URL: https://doi.org/10.1371/journal.pone.0302991, doi:10.1371/journal.pone.0302991. This article has 2 citations and is from a peer-reviewed journal.
(stone2024creationandcharacterization pages 9-10): William Stone, Chloe Strege, William Miller, Aron M. Geurts, Michael Grzybowski, Megan Riddle, Christopher Lees, Cindy Eide, Douglas R. Keene, Sara F. Tufa, Davis Seelig, John McGrath, and Jakub Tolar. Creation and characterization of novel rat model for recessive dystrophic epidermolysis bullosa: frameshift mutation of the col7a1 gene leads to severe blistered phenotype. PLOS ONE, 19:e0302991, May 2024. URL: https://doi.org/10.1371/journal.pone.0302991, doi:10.1371/journal.pone.0302991. This article has 2 citations and is from a peer-reviewed journal.
(shehata2024geneticimplicationsand pages 1-4): Nancy A Shehata, Noor A Shaik, and Husna Irfan Thalib. Genetic implications and management of epidermolysis bullosa in the saudi arabian population. Cureus, Aug 2024. URL: https://doi.org/10.7759/cureus.66678, doi:10.7759/cureus.66678. This article has 4 citations.
(bonamonte2022squamouscellcarcinoma pages 1-2): Domenico Bonamonte, Angela Filoni, Aurora De Marco, Lucia Lospalluti, Eleonora Nacchiero, Valentina Ronghi, Anna Colagrande, Giuseppe Giudice, and Gerardo Cazzato. Squamous cell carcinoma in patients with inherited epidermolysis bullosa: review of current literature. Cells, 11:1365, Apr 2022. URL: https://doi.org/10.3390/cells11081365, doi:10.3390/cells11081365. This article has 49 citations.
(harrs2022theaggressivebehaviour pages 1-1): Clara Harrs, Peter C. van den Akker, Rosalie Baardman, José C. Duipmans, Barbara Horváth, Marloes S. van Kester, Henny H. Lemmink, Emoke Rácz, Marieke C. Bolling, and Gilles F.H. Diercks. The aggressive behaviour of squamous cell carcinoma in epidermolysis bullosa: analysis of clinical outcomes and tumour characteristics in the dutch eb registry. British Journal of Dermatology, 187:824-826, Nov 2022. URL: https://doi.org/10.1111/bjd.21769, doi:10.1111/bjd.21769. This article has 13 citations and is from a highest quality peer-reviewed journal.
(gurevich2022invivotopical media 2ab3990c): Irina Gurevich, Pooja Agarwal, PeiPei Zhang, John A. Dolorito, Stacie Oliver, Henry Liu, Nicholas Reitze, Nikhil Sarma, Isin Sinem Bagci, Kunju Sridhar, Visesha Kakarla, Vamsi K. Yenamandra, Mark O’Malley, Marco Prisco, Sara F. Tufa, Douglas R. Keene, Andrew P. South, Suma M. Krishnan, and M. Peter Marinkovich. In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial. Nature Medicine, 28:780-788, Mar 2022. URL: https://doi.org/10.1038/s41591-022-01737-y, doi:10.1038/s41591-022-01737-y. This article has 181 citations and is from a highest quality peer-reviewed journal.

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Mappings

Inheritance

Subtypes

Pathophysiology

Pathograph

Phenotypes

Genetic Associations

Treatments

Related Datasets

Clinical Trials

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References & Deep Research

References

Deep Research

Disease Characteristics Research Template

Target Disease

Research Objectives

1. Disease Information

2. Etiology

3. Phenotypes

4. Genetic/Molecular Information

5. Environmental Information

6. Mechanism / Pathophysiology

7. Anatomical Structures Affected

8. Temporal Development

9. Inheritance and Population

10. Diagnostics

11. Outcome/Prognosis

12. Treatment

13. Prevention

14. Other Species / Natural Disease

15. Model Organisms

Citation Requirements

Output Format

Dystrophic Epidermolysis Bullosa (DEB) — Disease Characteristics Research Report (2026-05-08)

Target disease

1. Disease information

Overview and definition

Subtypes / classification

Synonyms / alternative names (from literature usage)

Evidence source type

2. Etiology

Disease causal factors

Risk factors

Protective factors

Gene–environment interactions

3. Phenotypes

Core clinical phenotype spectrum

Age of onset and progression (typical)

Quality-of-life impact

Suggested HPO terms (examples; non-exhaustive)

4. Genetic / molecular information

Causal gene(s)

Pathogenic variant classes and consequences

Recent developments (2023–2024) in variant-targeted correction

Modifier genes / epigenetics / chromosomal abnormalities

5. Environmental information

6. Mechanism / pathophysiology

Causal chain (from trigger to clinical manifestations)

Upstream vs downstream

Cell types involved (suggested CL terms)

Molecular pathways / GO term suggestions

7. Anatomical structures affected

Organ/tissue level

8. Temporal development

9. Inheritance and population

Inheritance patterns

Epidemiology (recent summarized estimates)

High-impact complication epidemiology: RDEB-associated cSCC

10. Diagnostics

Recommended diagnostic approach (evidence-backed components)

Genetic testing approaches

Differential diagnosis

11. Outcomes / prognosis

Prognosis dominated by severe RDEB complications, especially cSCC

12. Treatment

Current applications / real-world implementations (supportive and multidisciplinary)