Acquired Epidermolysis Bullosa

1. Disease Information

• Overview. EBA is a rare, chronic, acquired autoimmune subepidermal blistering disease. IgG autoantibodies (occasionally IgA) target type VII collagen (COL7A1 product). Type VII collagen is the main component of the anchoring fibrils that tether the epidermal basement membrane to the papillary dermis. Antibody binding causes dermal-epidermal separation below the lamina densa.
• Identifiers.
• MONDO:0018747, as in the existing KB entry.
• ICD-10: L12.3 (acquired epidermolysis bullosa).
• MeSH: Epidermolysis Bullosa Acquisita.
• Orphanet and OMIM codes were not checked. Look them up with just fetch-reference ORPHA:<code>.
• Synonyms. EBA; acquired epidermolysis bullosa; anti-type VII collagen disease.
• Data level. The sources are aggregated, disease-level literature (reviews and case series). No EHR-derived data were used.

2. Etiology

• Primary cause. Loss of tolerance to the NC1 (non-collagenous 1) and other domains of type VII collagen, producing pathogenic autoantibodies.
• Genetic risk.
• HLA-DR2 association; the Perković 2023 review (PMID:36769788) notes that "people of African descent carry the HLA-DRB1 risk allele." The specific allele (reported elsewhere as HLA-DRB1*15:03) is not verified here.
• No Mendelian cause. This is not the inherited dystrophic EB caused by COL7A1 variants.
• Associations (risk contexts).
• Inflammatory bowel disease, especially Crohn's disease. The review mentions the correlation, but the frequency was not verified.
• Lymphoma. Perković 2023 reports an association "in 8% of patients."
• Drug-associated cases, for example after a DPP-4 inhibitor (case report PMC12812923, not read).
• Protective factors and gene-environment interactions. None established. No data found.

3. Phenotypes

Phenotype frequencies were not extracted from the sources I could read. Mark each frequency as "unspecified" in the KB unless it is curated from a primary source.

• Clinical types. Two main types are distinguished: mechanobullous and inflammatory (search-result summary of the literature).
• Onset. Mostly adult, but not quantified here.
• Course. Chronic.
• Quality of life. No data retrieved.

4. Genetic/Molecular Information

• Autoantigen. COL7A1 (HGNC ID not looked up; use lowercase hgnc: and resolve it with runoak).
• Pathogenic variants. None. The disease is autoimmune.
• Modifier genes. HLA class II, as above.
• Epigenetic and chromosomal findings. Not available.

5. Environmental Information

• Drug triggers. Case reports exist, for example DPP-4 inhibitors (unverified beyond the title).
• Lifestyle and infectious agents. None established.
• Mechanical trauma. It determines where lesions form in the mechanobullous type.

6. Mechanism / Pathophysiology

Causal chain (steps marked inferred are not demonstrated in the sources I read):

1. Genetic susceptibility, including HLA class II (HLA-DR2), plus unknown triggers, leads to loss of tolerance to type VII collagen (the trigger is inferred).
2. Autoreactive B and T cells produce IgG anti-COL7 autoantibodies, mainly against the NC1 domain.
3. The autoantibodies bind COL7 in the anchoring fibrils at the dermal-epidermal junction.
4. Binding has two consequences. It can directly impair COL7 function and its interaction with other basement membrane components. It can also recruit complement and Fcγ-receptor-bearing cells.
5. In the inflammatory pathway, neutrophils and other myeloid cells are activated and release proteases and reactive oxygen species. In experimental EBA this involves IFN-γ (PMC11116581, title only).
6. The result is damage to the lamina densa and sublamina densa and dermal-epidermal separation.

7. Clinically, this produces tense subepidermal blisters, with scarring and milia when healing follows trauma.

8. Branching. The mechanobullous type is driven by skin fragility. The inflammatory type is driven by immune-cell infiltration.

9. Suggested terms.
10. GO: adaptive immune response; complement activation; neutrophil activation involved in immune response.
11. CL: B cell (CL:0000236), neutrophil (CL:0000775), plasma cell (CL:0000786).

7. Anatomical Structures Affected

• Primary. Skin, at the dermal-epidermal junction (the sublamina densa, where anchoring fibrils lie).
• Secondary. Oral, ocular and esophageal mucosa.
• Suggested UBERON (verify before binding): skin of body, basement membrane of epithelium, epidermis, dermis.
• Subcellular. Extracellular matrix and anchoring fibrils.
• Lateralization. Typically bilateral and symmetric at trauma-prone sites.

8. Temporal Development

• Onset. Adult.
• Pattern. Chronic, with relapses.
• Remission. Perković 2023 states that "complete remission off-treatment in EBA is impossible since maintenance therapy is needed." Treat this as a review-level claim, not an absolute.

9. Inheritance and Population

• Incidence. Perković 2023 gives "between 0.08 and 0.5 per million," with Germany the highest at 2.8 per million. A search-result summary states an incidence of 0.2 new cases per million per year.
• Inheritance. Not inherited (acquired). The HLA association is a susceptibility factor only.
• Population. HLA-DRB1 risk allele in people of African descent.
• Sex ratio and age distribution. Not verified.

10. Diagnostics

• Direct immunofluorescence (DIF). Linear IgG, and sometimes C3, deposits along the basement membrane zone.
• Salt-split skin immunofluorescence. The deposits localize to the dermal (floor) side, and a u-serrated pattern is a key differentiating feature.
• ELISA. Detects serum anti-COL7 (NC1) autoantibodies.
• Combined criteria. Perković 2023: "Positive DIF test, and ELISA showing patients' serum autoantibodies targeting Col7" constitute ideal diagnostic criteria.
• Histology. Subepidermal split. Infiltrate type was not verified.
• Differential diagnosis.
• Bullous pemphigoid.
• Mucous membrane pemphigoid.
• Dystrophic EB.
• Bullous SLE.
• Porphyria cutanea tarda.
• The KB already has entries for several of these.
• Genetic testing and screening. Not applicable.

11. Outcome/Prognosis

• Chronic course that needs maintenance therapy (Perković 2023).
• Complications: scarring, mucosal strictures, and risk related to immunosuppression. Specific figures were not retrieved.
• Survival and mortality data were not found. This is a gap.

12. Treatment

All details are from Perković 2023 (PMID:36769788) unless stated.

• First line (search-result summary). Systemic corticosteroids with dapsone. Colchicine and dapsone are listed as steroid-sparing agents.
• Rituximab. "Complete disease remission was achieved in 10 cases using the lymphoma protocol."
• IVIG. "After 16 to 31 IVIG infusion therapies...clinical remission was observed."
• Emerging.
• Anti-FcRn therapy.
• Anakinra (anti-IL-1).
• Anti-GM-CSF antibodies.
• Biologic case series: PMC10371012, title only.
• Suggested NCIT terms (look up each CURIE first): Pharmacotherapy (NCIT:C15986, listed in CLAUDE.md), with therapeutic_agent for dapsone, colchicine, rituximab and immunoglobulin; therapeutic_modality MONOCLONAL_ANTIBODY for rituximab and anti-FcRn agents.
• Not covered. Clinical trials (NCT IDs), pharmacogenomics and adverse-event data were not retrieved. Run just fetch-reference on any NCT ID before citing it.

13. Prevention

No primary prevention is known. Secondary and tertiary prevention rely on early diagnosis and trauma avoidance in the mechanobullous type. This is an inference and was not sourced.

14. Other Species / Natural Disease

No naturally occurring animal disease was found in the sources read. OMIA was not queried.

15. Model Organisms

• Mouse. The experimental EBA models are:
• Passive transfer of anti-COL7 antibodies.
• Active immunization with COL7 fragments.
• Recapitulation. Subepidermal blistering with neutrophilic involvement. IFN-γ inhibition impairs induction of experimental EBA (title-level only: PMC11116581).
• Limitations and resources. Not retrieved. In the KB these models belong in animal_models: with modeled_mechanisms.

Gaps for curation follow-up

1. Fetch and cache PMID:36769788 and PMID:23956869 with just fetch-reference, then curate exact snippets.
2. Phenotype frequencies, mortality and survival, HLA allele-level data and drug-trigger evidence are unsourced.
3. Resolve the ontology IDs (COL7A1 HGNC, HP, UBERON, NCIT) by lookup before binding.
4. Add a history/ record for any KB edit.

Sources: - Perković et al. 2023, EBA Current and Emerging Treatments (PMC9917799) - Kim et al., EBA review (PMC3727188) - PubMed 23956869 - StatPearls EBA (NBK554512) - Experimental EBA, IFN-γ (PMC11116581) - Biologic treatment case series (PMC10371012) - DPP-4 inhibitor case report (PMC12812923)

Reference Validation

Checked with linkml-reference-validator 0.3.0rc3.

All extracted references resolved successfully.

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Terms whose name is worth a second look

The report's name for these is recognisably related to the term's own name without being one of them. A loose paraphrase reads the same way as a citation of the wrong sibling term - and so does a related synonym, which the ontology records precisely because it names something adjacent rather than the same thing - so these are listed rather than judged:

• CL:0000236 (1 mention) - the report calls it "CL: B cell"; CL calls it B cell

Every term resolved, and every label the report gave matched.