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0
Mappings
0
Definitions
0
Inheritance
7
Pathophysiology
0
Histopathology
6
Phenotypes
4
Genes
18
Treatments
0
Subtypes
3
Differentials
3
Datasets
2
Trials

Pathophysiology

7
Follicular keratinization
Dysregulated keratinocyte differentiation and desquamation within the follicular epithelium promotes retention hyperkeratosis.
keratinocyte link
pilosebaceous unit link
Show evidence (1 reference)
PMID:32748305 SUPPORT
"Acne pathogenesis is attributed to four key factors: excess sebum production, hyperproliferation of Cutibacterium acnes (C. acnes, formerly called Propionibacterium acnes) bacteria, hyperkeratinization of the pilosebaceous follicles, and inflammatory mechanisms"
This review explicitly identifies hyperkeratinization of the pilosebaceous follicles as a key factor in acne pathogenesis.
Microcomedone formation
Follicular obstruction from retained keratin and sebum leads to early microcomedone development that seeds later visible comedones.
keratinocyte link
pilosebaceous unit link
Show evidence (1 reference)
PMID:32748305 SUPPORT
"Acne pathogenesis is attributed to four key factors: excess sebum production, hyperproliferation of Cutibacterium acnes (C. acnes, formerly called Propionibacterium acnes) bacteria, hyperkeratinization of the pilosebaceous follicles, and inflammatory mechanisms"
Follicular hyperkeratinization is the initiating event that drives microcomedone formation in acne.
Sebum overproduction
Androgen and IGF-1 signaling increase sebocyte activity, elevating sebum output and creating a lipid-rich follicular environment.
sebocyte link
lipid metabolism link
Show evidence (1 reference)
PMID:32748305 SUPPORT
"In acne, mTORC1 mediates sebaceous gland hyperproliferation, lipid synthesis, and hyperplasia of keratinocytes"
This review links sebaceous gland hyperproliferation and lipid synthesis to acne pathogenesis.
Sebum compositional change
Altered fatty acid ratios and oxidation products within sebum contribute to comedogenesis and inflammatory signaling.
sebocyte link
lipid metabolism link
Show evidence (1 reference)
PMID:20871834 SUPPORT
"Altered ratio between saturated and unsaturated fatty acids has been indicated as an important feature to be considered in addition to the altered amount of specific fatty acids such as linoleic acid"
This review highlights altered sebum fatty acid composition as a pathophysiologic feature of acne.
C. acnes follicular colonization
Cutibacterium acnes expands within occluded follicles and contributes to lesion progression from noninflammatory comedones to inflamed papules.
sebocyte link
pilosebaceous unit link
Show evidence (1 reference)
PMID:24062871 SUPPORT
"Propionibacterium acnes colonizes the duct of the sebaceous follicle, causing an innate immune response and the progression from a so-called noninflammatory comedo to an inflammatory papule, pustule, or nodule."
This review describes C. acnes colonization and its role in lesion progression.
Inflammasome activation
Innate immune sensing activates inflammasome pathways that amplify inflammatory signaling in acne lesions.
macrophage link
inflammatory response link
Show evidence (1 reference)
"The inflammasomes are intracellular multimeric protein complexes consisting of an innate immune sensor, the adapter protein ASC and the inflammatory caspases-1 and/or -11 and are important for the host defense against pathogens."
This review explains inflammasome activation, a key mechanism implicated in acne inflammation.
Cytokine-driven inflammation
Inflammasome and innate immune activation drive cytokine release that recruits neutrophils and sustains inflammatory lesion formation.
neutrophil link
inflammatory response link
Show evidence (1 reference)
"The inflammasomes are intracellular multimeric protein complexes consisting of an innate immune sensor, the adapter protein ASC and the inflammatory caspases-1 and/or -11 and are important for the host defense against pathogens."
Inflammasome activation supports downstream cytokine-mediated inflammation in acne lesions.

Phenotypes

6
Immune 3
Comedones Comedonal acne (HP:0040137)
Show evidence (1 reference)
PMID:24062871 SUPPORT
"evidence has emerged supporting a role for inflammation at all stages of acne lesion development, perhaps subclinically even before comedo formation"
This review discusses the role of comedones as a key lesion type in acne pathogenesis.
Pustules Pustule (HP:0200039)
Show evidence (1 reference)
PMID:12113648 SUPPORT
"Localized pustular eruptions are seen on the hands and feet in adults with pustulosis palmaris et plantaris and acrodermatitis continua (both of which may be variants of psoriasis); on the face in patients with acne vulgaris, rosacea, and perioral dermatitis"
This review identifies pustular eruptions on the face as a characteristic feature of acne vulgaris.
Nodules and cysts Cystic acne (HP:0033188)
Show evidence (1 reference)
PMID:21062102 SUPPORT
"Severe nodular acne, defined as grade 4 or 5 acne on the Investigator's Static Global Assessment scale, is a skin condition characterized by intense erythema, inflammation, nodules, cysts, and scarring."
This review defines severe nodular acne as characterized by nodules and cysts with associated inflammation and scarring potential.
Integument 3
Inflammatory papules Erythematous papule (HP:0030350)
Show evidence (1 reference)
PMID:24062871 SUPPORT
"the progression from a so-called noninflammatory comedo to an inflammatory papule, pustule, or nodule"
This review describes the progression from comedones to inflammatory papules in acne lesion development.
Post-inflammatory hyperpigmentation Hyperpigmentation of the skin (HP:0000953)
Show evidence (1 reference)
PMID:34468934 SUPPORT
"the inflammatory processes of acne stimulate excess melanogenesis and abnormal melanin deposition, leading to pigmentary sequelae known as post-inflammatory hyperpigmentation"
This paper specifically describes the pathogenesis of acne-induced post-inflammatory hyperpigmentation through excess melanin production.
Scarring Atrophic scars (HP:0001075)
Show evidence (1 reference)
PMID:29344322 SUPPORT
"This review focuses on atrophic scars, the most common type of acne scar."
This review confirms atrophic scars as the most common type of acne scarring.
🧬

Genetic Associations

4
Polygenic susceptibility (Associated)
Show evidence (2 references)
PMID:32748305 SUPPORT
"It is known that multiple factors impact acne pathophysiology, including genetic, hormonal, inflammatory, and environmental influences."
This review explicitly identifies genetic factors as one of the key influences on acne pathophysiology.
PMID:40689430 SUPPORT
"Both GWAS and single gene disorders unequivocally indicate stem/progenitor cell maintenance and cellular migration as the most important processes in the pathogenesis of acne."
This genetics review connects GWAS and monogenic findings to core biological processes underlying acne susceptibility.
Candidate gene families (Associated)
Show evidence (1 reference)
PMID:37662507 SUPPORT
"some genes (such as IL, TNF, RETN, CYP family, MMPs and TIMPs genes et al) are associated with acne vulgaris and may affect the progression and prognosis of the disease."
This review summarizes multiple gene families repeatedly implicated in acne susceptibility and outcomes.
RETN-420C>G and IL6-572G>C polymorphisms (Associated)
Show evidence (1 reference)
PMID:35279931 SUPPORT
"There is a strong correlation between RETN-420 and IL6-572 polymorphisms and acne susceptibility; the RETN-420G and IL6-572C alleles increase the risk of acne development."
This study reports RETN-420 and IL6-572 risk alleles associated with acne susceptibility.
TNFR2 M196R and TLR2 Arg753Gln polymorphisms (Associated)
Show evidence (1 reference)
PMID:20861605 SUPPORT
"The 196R allele of TNFR2 M196R as well as the 753Gln allele of TLR2 Arg753Gln are risk factors for acne vulgaris in Chinese Han patients, further supporting the contribution of inflammatory cytokines to the pathogenesis of acne."
This study links TNFR2 and TLR2 risk alleles to acne susceptibility in a Chinese Han cohort.
💊

Treatments

18
Topical retinoids MAXO:0000237
First-line treatment that normalizes follicular keratinization, reduces comedone formation, and has anti-inflammatory effects. Examples include tretinoin, adapalene, and tazarotene.
Show evidence (1 reference)
PMID:30674002 SUPPORT
"Topical retinoids are safe and efficacious for the treatment of acne vulgaris."
This systematic review confirms the safety and efficacy of topical retinoids for acne treatment.
Trifarotene MAXO:0000237
Topical retinoid selective for retinoic acid receptor gamma with evidence for reducing comedonal and inflammatory lesions, including truncal acne.
Show evidence (1 reference)
PMID:36927117 SUPPORT
"Large-scale randomized, controlled clinical trials have demonstrated trifarotene to be safe, well tolerated, and efficacious in reducing both comedones and papules/pustules of acne."
This review summarizes randomized trials showing trifarotene efficacy across comedonal and inflammatory acne lesions.
Benzoyl peroxide MAXO:0001021
Antimicrobial agent that kills C. acnes through oxidative damage without promoting antibiotic resistance. Also has mild comedolytic activity.
Show evidence (1 reference)
PMID:19761357 SUPPORT
"BPO-containing combinations do not induce bacterial resistance and are important first-line treatments for mild to moderate acne vulgaris."
This review establishes benzoyl peroxide as an important first-line treatment for acne that does not promote bacterial resistance.
Topical antibiotics MAXO:0000061
Clindamycin and erythromycin reduce C. acnes populations and have anti-inflammatory effects. Should be combined with benzoyl peroxide to prevent resistance.
Show evidence (1 reference)
PMID:16086756 SUPPORT
"topical antibiotics remain one of the cornerstones of acne management"
This systematic review confirms topical antibiotics as a cornerstone treatment for acne.
Clindamycin/adapalene/benzoyl peroxide gel MAXO:0000058
Triple-combination topical therapy for moderate to severe acne, combining clindamycin phosphate, adapalene, and benzoyl peroxide for long-term use.
Show evidence (1 reference)
PMID:41552868 SUPPORT
"At week 24, 67% of participants achieved treatment success, and significant reductions from baseline in inflammatory (88%) and noninflammatory (68%) lesions were observed (p < 0.001, both)."
This pooled analysis supports long-term efficacy of the triple-combination gel.
Oral antibiotics MAXO:0000061
Tetracyclines (doxycycline, minocycline) are used for moderate-to-severe inflammatory acne. Have both antimicrobial and anti-inflammatory effects, but prolonged use contributes to antimicrobial resistance and requires stewardship.
Show evidence (2 references)
PMID:28542914 SUPPORT
"isotretinoin therapy reduced acne lesion counts by a clinically relevant amount, and always by a greater amount than control, which was either placebo (two studies), oral antibiotics (seven studies) or other control"
This systematic review confirms oral antibiotics as an established comparator treatment for acne in clinical trials.
PMID:36568833 SUPPORT
"The overuse of topical and/or systemic antibiotics, the long treatment courses used for acne, and the availability of over-the-counter antibiotic preparations, have led to the worldwide emergence of resistant strains in acne patients."
This review documents antibiotic resistance concerns tied to prolonged acne antibiotic use, supporting stewardship in treatment.
Oral isotretinoin MAXO:0000237
Systemic retinoid reserved for severe, recalcitrant acne. Addresses all four pathogenic factors but requires careful monitoring due to teratogenicity and other adverse effects.
Show evidence (1 reference)
PMID:33085149 SUPPORT
"Oral isotretinoin is the most effective treatment for moderate to severe acne and its side effects are mostly dose-dependent."
This systematic review confirms oral isotretinoin as the most effective treatment for moderate to severe acne.
Hormonal therapy MAXO:0000283
Combined oral contraceptives and spironolactone reduce androgen effects on sebaceous glands. Used in female patients with hormonal acne patterns.
Show evidence (1 reference)
PMID:28492054 SUPPORT
"Hormone-based therapies including combined oral contraceptive medications and spironolactone are considered effective therapies to treat adult acne in women."
This systematic review confirms the efficacy of hormonal therapies including oral contraceptives and spironolactone for treating acne in women.
Chemical peels MAXO:0001417
Organic acid-based peels are used to exfoliate acne-prone skin and reduce lesion counts, with agent selection tailored to patient tolerability.
Show evidence (1 reference)
PMID:37894698 SUPPORT
"The findings of this comprehensive bibliographic review indicate that organic acid-based chemical peels represent effective and safe treatment options for individuals with acne-prone skin."
This review supports organic acid chemical peels as effective and safe adjuncts for acne-prone skin.
Azelaic acid peel MAXO:0001417
Azelaic acid peels reduce sebum and lesion burden as a nonpharmacologic option for facial acne.
Show evidence (1 reference)
PMID:31455112 SUPPORT
"Peels with 30% AZA reduced acne lesions and normalized the activity of the sebaceous glands."
This study reports acne lesion reduction and sebum normalization with 30% azelaic acid peels.
Chemical peels for acne scarring MAXO:0001417
Medium-depth peels such as glycolic acid and trichloroacetic acid are used to improve atrophic acne scars.
Show evidence (1 reference)
PMID:39483653 SUPPORT
"A 30% TCA peel is efficacious and well-tolerated for mild-to-moderate acne scars."
This split-face study supports TCA peels for improving acne scarring.
Ablative fractional CO2 laser MAXO:0001578
Ablative fractional CO2 laser is used for atrophic acne scars but can cause erythema, dyspigmentation, and prolonged recovery.
Show evidence (1 reference)
PMID:41521693 SUPPORT
"Ablative fractional CO2 laser is effective for acne scar treatment but is often associated with side effects such as erythema and dyspigmentation, along with prolonged recovery time."
This trial background notes efficacy of CO2 laser for acne scars with notable side effects.
Post-laser antioxidant serum MAXO:0000058
Topical antioxidant serum with vitamins C and E (with ferulic acid) is used after ablative laser procedures to support skin recovery.
Show evidence (1 reference)
PMID:41521693 SUPPORT
"This study found that CE Ferulic led to enhanced wound healing, reduced erythema and melanin levels, and improved skin hydration following laser treatment, suggesting its beneficial application in combination with laser treatment to accelerate skin recovery."
This split-face trial supports antioxidant serum use after CO2 laser for acne scars.
Blue light therapy MAXO:0000014
Blue light phototherapy is used as an alternative for inflammatory acne, with evidence of clinical improvement.
Show evidence (1 reference)
PMID:34696155 SUPPORT
"Studies have shown significant improvements in the overall picture of acne."
This systematic review reports clinical improvement in acne with blue light phototherapy.
Visible light therapy MAXO:0000014
Visible light devices, including blue light, can reduce acne lesion counts in patients seeking nonpharmacologic treatments.
Show evidence (1 reference)
PMID:39056372 SUPPORT
"Overall, 92% of patients achieved partial remission of their acne lesions using visible light therapy."
This systematic review summarizes lesion improvement across visible light studies in acne.
Photodynamic therapy MAXO:0000014
Photodynamic therapy is used off-label for inflammatory acne with evidence supporting efficacy in dermatologic indications.
Show evidence (1 reference)
PMID:39226531 SUPPORT
"Newer indications, for which no approval has yet been granted, but which nevertheless have sufficient evidence of efficacy according to the study situation, are inflammatory (lichen sclerosus, acne) and infectious dermatoses (viral warts, cutaneous leishmaniasis, atypical mycobacteriosis)."
This review identifies acne as an emerging indication for photodynamic therapy with supportive evidence.
Nd:YAG laser and intralesional PRP MAXO:0001417
Nd:YAG laser and intralesional platelet-rich plasma injections are used for inflammatory acne in split-face comparative protocols.
Show evidence (1 reference)
PMID:35084634 SUPPORT
"The intralesional PRP injection and 1064 nm long-pulsed Nd:YAG laser are safe and effective methods for controlling inflammatory as well as non-inflammatory acne vulgaris in both adolescents and post-adolescent patients."
This randomized split-face study supports Nd:YAG laser and PRP injections for inflammatory acne vulgaris.
1726 nm laser therapy MAXO:0001578
Targeted laser therapy that selectively affects sebaceous glands and is being evaluated for moderate to severe acne.
Show evidence (1 reference)
PMID:38271552 SUPPORT
"New 1726 nm lasers specifically target the sebaceous gland, which is known to be pivotal in acne pathophysiology."
This review highlights 1726 nm lasers as a sebaceous gland-targeted treatment approach for acne.
🌍

Environmental Factors

3
Diet
High glycemic index foods and dairy products have been associated with acne severity, possibly through effects on insulin/IGF-1 signaling and hormonal modulation.
Show evidence (2 references)
PMID:32748305 SUPPORT
"Several studies have evaluated the significance of the glycemic index of various foods and glycemic load in patients with acne, demonstrating individuals with acne who consume diets with a low glycemic load have reduced acne lesions compared with individuals on high glycemic load diets."
This review provides evidence for the association between high glycemic load diets and acne severity.
PMID:32748305 SUPPORT
"Dairy has also been a focus of study regarding dietary influences on acne; whey proteins responsible for the insulinotropic effects of milk may contribute more to acne development than the actual fat or dairy content."
The paper describes the mechanism by which dairy consumption may influence acne through insulinotropic effects.
Stress
Psychological stress can exacerbate acne through effects on the hypothalamic-pituitary-adrenal axis and increased sebum production.
Show evidence (2 references)
PMID:28871928 SUPPORT
"Even though emotional stress has long been suspected to trigger or exacerbate acne, its influence on acne severity has been mostly underestimated until recently when studies have brought new data about the different mechanisms and possible factors involved in this interaction."
This review examines the link between psychological stress and acne exacerbation.
PMID:28871928 SUPPORT
"The basis for the association between emotional stress and the onset or exacerbation of acne is in several cutaneous neurogenic factors which interact with a pathogenic cascade in acne."
The paper describes neurogenic mechanisms linking stress to acne pathogenesis.
Air pollution and climate stressors
Repeated exposure to rising pollutant levels and climate-related environmental changes is associated with acne burden.
Show evidence (1 reference)
PMID:41464454 SUPPORT
"Psoriasis, acne vulgaris, atopic dermatitis, photoaging, melasma, and skin cancers have been associated with repeated exposure to rising levels of pollutants."
This review links acne vulgaris with pollutant exposure among climate-sensitive skin conditions.
🔬

Biochemical Markers

3
Androgens (Elevated)
Show evidence (1 reference)
PMID:32748305 SUPPORT
"Excess sebum production occurs because of increased activity of androgen hormones and IGF-1"
This paper directly links androgen hormones to excess sebum production in acne pathogenesis.
Sebum lipids (Altered)
Show evidence (1 reference)
PMID:20871834 SUPPORT
"Altered ratio between saturated and unsaturated fatty acids has been indicated as an important feature to be considered in addition to the altered amount of specific fatty acids such as linoleic acid"
This review describes alterations in sebum fatty acid composition as a key feature in acne pathogenesis.
IL-17 (Decreased)
Show evidence (1 reference)
PMID:41465543 SUPPORT
"Serum IL-17 levels were significantly higher in the control group compared to both acne groups (p < 0.05), with no gender-related differences."
This study reports decreased serum IL-17 in acne vulgaris compared with controls.
🔀

Differential Diagnoses

3

Conditions with similar clinical presentations that must be differentiated from Acne Vulgaris:

PAPASH syndrome Not Yet Curated MONDO:0958343
Overlapping Features Autoinflammatory syndrome combining acne with pyoderma gangrenosum, hidradenitis suppurativa, and inflammatory arthritis.
Distinguishing Features
  • Syndromic triad with pyoderma gangrenosum and hidradenitis suppurativa alongside acne.
  • Systemic inflammatory arthritis or other autoinflammatory features.
Show evidence (1 reference)
PMID:41499625 SUPPORT
"PAPASH spectrum syndrome is a rare autoinflammatory condition encompassing psoriatic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa."
This case report defines PAPASH syndrome as a syndromic condition including acne and related inflammatory diseases.
Rosacea Not Yet Curated MONDO:0006604
Overlapping Features Chronic inflammatory facial dermatosis with papules and pustules but no comedones. Central facial erythema, flushing, and telangiectasias can mimic inflammatory acne on the face.
Distinguishing Features
  • Absence of comedones with prominent centrofacial erythema and telangiectasias.
  • Burning or stinging with triggers such as heat, alcohol, or spicy foods rather than androgen-driven distribution.
Show evidence (1 reference)
PMID:12113648 SUPPORT
"Localized pustular eruptions are seen on the hands and feet in adults with pustulosis palmaris et plantaris and acrodermatitis continua (both of which may be variants of psoriasis); on the face in patients with acne vulgaris, rosacea, and perioral dermatitis; and on the trunk and/or extremities..."
The abstract lists rosacea alongside acne as a facial pustular eruption, underscoring the need for clinical differentiation.
Bacterial folliculitis Not Yet Curated MONDO:0006552
Overlapping Features Infection or inflammation of hair follicles producing papules and pustules on hair-bearing skin, often the trunk or extremities, that can resemble acne lesions but lacks comedones and is frequently pruritic.
Distinguishing Features
  • Lesions centered on hair follicles without open or closed comedones; often pruritic and may follow shaving or occlusion.
  • Distribution favors trunk, buttocks, and extremities rather than the typical facial and truncal comedones of acne.
Show evidence (1 reference)
PMID:12113648 SUPPORT
"Localized pustular eruptions are seen on the hands and feet in adults with pustulosis palmaris et plantaris and acrodermatitis continua (both of which may be variants of psoriasis); on the face in patients with acne vulgaris, rosacea, and perioral dermatitis; and on the trunk and/or extremities..."
The abstract notes folliculitis presents with pustular eruptions on the trunk or extremities, highlighting its overlap with acneiform lesions.
📊

Related Datasets

3
Microbiome-Derived Indole-3-lactic Acid Attenuates Cutibacterium acnes-Induced Inflammation via the Aryl Hydrocarbon Receptor Pathway geo:GSE315350
Transcriptomic profiling of C. acnes-driven inflammation with microbiome- derived tryptophan metabolites highlighting AHR pathway modulation.
Summary describes human keratinocyte stimulation and a C. acnes mouse model.
Spatial transcriptomics reveals dysfunctional lipid metabolism and abnormal pilosebaceous differentiation in acne vulgaris geo:GSE301280
Spatial transcriptomics of healthy, non-lesional, comedonal, and pustular acne skin using a panel targeting sebaceous differentiation, lipid metabolism, and retinoid signaling.
human SPATIAL TRANSCRIPTOMICS
Conditions: healthy skin non-lesional acne skin comedonal acne skin pustular acne skin
Identifies altered sebogenesis and retinoid signaling across lesion types.
High-Resolution Spatial Map of the Human Facial Sebaceous Gland Reveals Marker Genes and Decodes Sebocyte Differentiation [MERFISH] geo:GSE292394
Spatial transcriptomics and MERFISH profiling of human facial sebaceous glands to map sebocyte differentiation stages.
human SPATIAL TRANSCRIPTOMICS
Integrates spatial transcriptomics with single-cell profiling of sebaceous glands.
🔬

Clinical Trials

2
NCT00421993 PHASE_III COMPLETED
Multicenter, randomized, double-blind trial comparing adapalene/benzoyl peroxide gel with monotherapies and vehicle in acne vulgaris over 12 weeks.
Target Phenotypes: comedonal acne erythematous papule pustule
Show evidence (1 reference)
"This is a multi-center, randomized, double-blind, parallel group study with 12 weeks of treatment of acne vulgaris."
The trial evaluates a combination topical therapy specifically in participants with acne vulgaris.
NCT02249767 PHASE_III COMPLETED
Double-blind, randomized, parallel-group study assessing tretinoin gel bioequivalence in patients with mild acne vulgaris.
Target Phenotypes: comedonal acne erythematous papule
Show evidence (1 reference)
"Normal, healthy male and female children and adults (i.e., ages 12 to 40 years) with at least Grade 2 (i.e., mild severity) acne vulgaris were treated on the full face once daily for 84 days with the Tretinoin Gel 0.05%, Brand (tretinoin) Gel 0.05%, or Gel Vehicle."
This study explicitly enrolls participants with acne vulgaris and evaluates topical tretinoin treatment.
{ }

Source YAML

click to show
name: Acne Vulgaris
creation_date: '2026-01-23T23:13:39Z'
updated_date: '2026-02-16T20:19:38Z'
category: Complex
disease_term:
  preferred_term: acne vulgaris
  term:
    id: MONDO:0011438
    label: acne
parents:
- Inflammatory skin disease
- Pilosebaceous unit disorder
infectious_agent:
- name: Cutibacterium acnes
  infectious_agent_term:
    preferred_term: Cutibacterium acnes
    term:
      id: NCBITaxon:1747
      label: Cutibacterium acnes
  description: Commensal skin bacterium that proliferates in occluded follicles and contributes to inflammatory acne lesions.
  evidence:
  - reference: PMID:24062871
    supports: SUPPORT
    snippet: "Propionibacterium acnes colonizes the duct of the sebaceous follicle, causing an innate immune response and the progression from a so-called noninflammatory comedo to an inflammatory papule, pustule, or nodule."
    explanation: This review links C. acnes colonization to inflammatory progression in acne.
prevalence:
- population: Adolescents and young adults (Europe, ages 15-24 years)
  percentage: 57.8
  evidence:
  - reference: PMID:28707712
    supports: SUPPORT
    snippet: "The overall adjusted prevalence of self-reported acne was 57.8% (95% confidence interval 56.9% to 58.7%)."
    explanation: This European survey reports a high prevalence of acne among adolescents and young adults.
- population: Adolescents and young adults (global, ages 10-24 years, 2021)
  percentage: 9.79
  evidence:
  - reference: PMID:39271178
    supports: SUPPORT
    snippet: |-
      RESULTS: Globally, the age-standardized prevalence rate of acne vulgaris among 
      adolescents and young adults increased from 8563.4 per 100 000 population [95% 
      uncertainty interval (UI) 7343.5-9920.1] in 1990 to 9790.5 (95% UI 8420.9-11 
      287.2) per 100 000 population in 2021, with an AAPC of 0.43 [95% confidence 
      interval (CI) 0.41-0.46].
    explanation: The 2021 age-standardized prevalence of 9790.5 per 100,000 corresponds to about 9.79%.
- population: Young people (moderate-to-severe acne)
  percentage: 20
  evidence:
  - reference: PMID:23210645
    supports: SUPPORT
    snippet: "Moderate-to-severe acne affects around 20% of young people and severity correlates with pubertal maturity."
    explanation: This review summarizes the prevalence of moderate-to-severe acne among young people.
pathophysiology:
- name: Follicular keratinization
  description: >
    Dysregulated keratinocyte differentiation and desquamation within the
    follicular epithelium promotes retention hyperkeratosis.
  cell_types:
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  locations:
  - preferred_term: pilosebaceous unit
    term:
      id: UBERON:0011932
      label: pilosebaceous unit
  evidence:
  - reference: PMID:32748305
    supports: SUPPORT
    snippet: "Acne pathogenesis is attributed to four key factors: excess sebum production, hyperproliferation of Cutibacterium acnes (C. acnes, formerly called Propionibacterium acnes) bacteria, hyperkeratinization of the pilosebaceous follicles, and inflammatory mechanisms"
    explanation: This review explicitly identifies hyperkeratinization of the pilosebaceous follicles as a key factor in acne pathogenesis.
- name: Microcomedone formation
  description: >
    Follicular obstruction from retained keratin and sebum leads to early
    microcomedone development that seeds later visible comedones.
  cell_types:
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  locations:
  - preferred_term: pilosebaceous unit
    term:
      id: UBERON:0011932
      label: pilosebaceous unit
  evidence:
  - reference: PMID:32748305
    supports: SUPPORT
    snippet: "Acne pathogenesis is attributed to four key factors: excess sebum production, hyperproliferation of Cutibacterium acnes (C. acnes, formerly called Propionibacterium acnes) bacteria, hyperkeratinization of the pilosebaceous follicles, and inflammatory mechanisms"
    explanation: Follicular hyperkeratinization is the initiating event that drives microcomedone formation in acne.
- name: Sebum overproduction
  description: >
    Androgen and IGF-1 signaling increase sebocyte activity, elevating sebum
    output and creating a lipid-rich follicular environment.
  cell_types:
  - preferred_term: sebocyte
    term:
      id: CL:0000317
      label: sebocyte
  biological_processes:
  - preferred_term: lipid metabolism
    term:
      id: GO:0006629
      label: lipid metabolic process
  evidence:
  - reference: PMID:32748305
    supports: SUPPORT
    snippet: "In acne, mTORC1 mediates sebaceous gland hyperproliferation, lipid synthesis, and hyperplasia of keratinocytes"
    explanation: This review links sebaceous gland hyperproliferation and lipid synthesis to acne pathogenesis.
- name: Sebum compositional change
  description: >
    Altered fatty acid ratios and oxidation products within sebum contribute
    to comedogenesis and inflammatory signaling.
  cell_types:
  - preferred_term: sebocyte
    term:
      id: CL:0000317
      label: sebocyte
  biological_processes:
  - preferred_term: lipid metabolism
    term:
      id: GO:0006629
      label: lipid metabolic process
  evidence:
  - reference: PMID:20871834
    supports: SUPPORT
    snippet: "Altered ratio between saturated and unsaturated fatty acids has been indicated as an important feature to be considered in addition to the altered amount of specific fatty acids such as linoleic acid"
    explanation: This review highlights altered sebum fatty acid composition as a pathophysiologic feature of acne.
- name: C. acnes follicular colonization
  description: >
    Cutibacterium acnes expands within occluded follicles and contributes to
    lesion progression from noninflammatory comedones to inflamed papules.
  cell_types:
  - preferred_term: sebocyte
    term:
      id: CL:0000317
      label: sebocyte
  locations:
  - preferred_term: pilosebaceous unit
    term:
      id: UBERON:0011932
      label: pilosebaceous unit
  evidence:
  - reference: PMID:24062871
    supports: SUPPORT
    snippet: "Propionibacterium acnes colonizes the duct of the sebaceous follicle, causing an innate immune response and the progression from a so-called noninflammatory comedo to an inflammatory papule, pustule, or nodule."
    explanation: This review describes C. acnes colonization and its role in lesion progression.
- name: Inflammasome activation
  description: >
    Innate immune sensing activates inflammasome pathways that amplify
    inflammatory signaling in acne lesions.
  cell_types:
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
  evidence:
  - reference: DOI:10.3389/fimmu.2023.1075834
    supports: PARTIAL
    snippet: "The inflammasomes are intracellular multimeric protein complexes consisting of an innate immune sensor, the adapter protein ASC and the inflammatory caspases-1 and/or -11 and are important for the host defense against pathogens."
    explanation: This review explains inflammasome activation, a key mechanism implicated in acne inflammation.
- name: Cytokine-driven inflammation
  description: >
    Inflammasome and innate immune activation drive cytokine release that
    recruits neutrophils and sustains inflammatory lesion formation.
  cell_types:
  - preferred_term: neutrophil
    term:
      id: CL:0000775
      label: neutrophil
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
  evidence:
  - reference: DOI:10.3389/fimmu.2023.1075834
    supports: PARTIAL
    snippet: "The inflammasomes are intracellular multimeric protein complexes consisting of an innate immune sensor, the adapter protein ASC and the inflammatory caspases-1 and/or -11 and are important for the host defense against pathogens."
    explanation: Inflammasome activation supports downstream cytokine-mediated inflammation in acne lesions.
phenotypes:
- name: Comedones
  description: >
    Non-inflammatory lesions including open comedones (blackheads) and closed
    comedones (whiteheads) resulting from follicular plugging.
  phenotype_term:
    preferred_term: comedonal acne
    term:
      id: HP:0040137
      label: Comedonal acne
  evidence:
  - reference: PMID:24062871
    supports: SUPPORT
    snippet: "evidence has emerged supporting a role for inflammation at all stages of acne lesion development, perhaps subclinically even before comedo formation"
    explanation: This review discusses the role of comedones as a key lesion type in acne pathogenesis.
- name: Inflammatory papules
  description: >
    Small, raised, erythematous lesions resulting from inflammation around
    occluded follicles.
  phenotype_term:
    preferred_term: erythematous papule
    term:
      id: HP:0030350
      label: Erythematous papule
  evidence:
  - reference: PMID:24062871
    supports: SUPPORT
    snippet: "the progression from a so-called noninflammatory comedo to an inflammatory papule, pustule, or nodule"
    explanation: This review describes the progression from comedones to inflammatory papules in acne lesion development.
- name: Pustules
  description: >
    Inflamed lesions containing purulent material, representing more advanced
    inflammatory response.
  phenotype_term:
    preferred_term: pustule
    term:
      id: HP:0200039
      label: Pustule
  evidence:
  - reference: PMID:12113648
    supports: SUPPORT
    snippet: "Localized pustular eruptions are seen on the hands and feet in adults with pustulosis palmaris et plantaris and acrodermatitis continua (both of which may be variants of psoriasis); on the face in patients with acne vulgaris, rosacea, and perioral dermatitis"
    explanation: This review identifies pustular eruptions on the face as a characteristic feature of acne vulgaris.
- name: Nodules and cysts
  description: >
    Deep, painful lesions representing severe inflammatory acne with potential
    for scarring.
  phenotype_term:
    preferred_term: cystic acne
    term:
      id: HP:0033188
      label: Cystic acne
  evidence:
  - reference: PMID:21062102
    supports: SUPPORT
    snippet: "Severe nodular acne, defined as grade 4 or 5 acne on the Investigator's Static Global Assessment scale, is a skin condition characterized by intense erythema, inflammation, nodules, cysts, and scarring."
    explanation: This review defines severe nodular acne as characterized by nodules and cysts with associated inflammation and scarring potential.
- name: Post-inflammatory hyperpigmentation
  description: >
    Darkening of skin at sites of resolved acne lesions, particularly common
    in individuals with darker skin tones. This sequela results from inflammatory
    damage to melanocytes and is a common concern in patients with skin of color.
  phenotype_term:
    preferred_term: hyperpigmentation of the skin
    term:
      id: HP:0000953
      label: Hyperpigmentation of the skin
  evidence:
  - reference: PMID:34468934
    supports: SUPPORT
    snippet: "the inflammatory processes of acne stimulate excess melanogenesis and abnormal melanin deposition, leading to pigmentary sequelae known as post-inflammatory hyperpigmentation"
    explanation: This paper specifically describes the pathogenesis of acne-induced post-inflammatory hyperpigmentation through excess melanin production.
- name: Scarring
  description: >
    Permanent textural changes including atrophic (ice pick, boxcar, rolling)
    and hypertrophic scars resulting from severe or inadequately treated acne.
  phenotype_term:
    preferred_term: atrophic scars
    term:
      id: HP:0001075
      label: Atrophic scars
  evidence:
  - reference: PMID:29344322
    supports: SUPPORT
    snippet: "This review focuses on atrophic scars, the most common type of acne scar."
    explanation: This review confirms atrophic scars as the most common type of acne scarring.
biochemical:
- name: Androgens
  presence: Elevated
  notes: >
    Androgens (testosterone, DHT) stimulate sebaceous gland activity through
    androgen receptor signaling, explaining the onset of acne at puberty and
    its association with hyperandrogenic states.
  evidence:
  - reference: PMID:32748305
    supports: SUPPORT
    snippet: "Excess sebum production occurs because of increased activity of androgen hormones and IGF-1"
    explanation: This paper directly links androgen hormones to excess sebum production in acne pathogenesis.
- name: Sebum lipids
  presence: Altered
  notes: >
    Changes in sebum composition, including altered fatty acid profiles and
    increased squalene oxidation, contribute to comedogenesis and inflammation.
  evidence:
  - reference: PMID:20871834
    supports: SUPPORT
    snippet: "Altered ratio between saturated and unsaturated fatty acids has been indicated as an important feature to be considered in addition to the altered amount of specific fatty acids such as linoleic acid"
    explanation: This review describes alterations in sebum fatty acid composition as a key feature in acne pathogenesis.
- name: IL-17
  presence: Decreased
  notes: >
    Serum IL-17 levels are lower in acne vulgaris compared with controls in a
    severity-stratified cohort, suggesting altered systemic cytokine signaling.
  evidence:
  - reference: PMID:41465543
    supports: SUPPORT
    snippet: "Serum IL-17 levels were significantly higher in the control group compared to both acne groups (p < 0.05), with no gender-related differences."
    explanation: This study reports decreased serum IL-17 in acne vulgaris compared with controls.
genetic:
- name: Polygenic susceptibility
  association: Associated
  notes: >
    Twin studies demonstrate high heritability. Multiple genetic variants
    affecting androgen metabolism, inflammatory pathways, and sebaceous gland
    function contribute to acne susceptibility.
  evidence:
  - reference: PMID:32748305
    supports: SUPPORT
    snippet: "It is known that multiple factors impact acne pathophysiology, including genetic, hormonal, inflammatory, and environmental influences."
    explanation: This review explicitly identifies genetic factors as one of the key influences on acne pathophysiology.
  - reference: PMID:40689430
    supports: SUPPORT
    snippet: "Both GWAS and single gene disorders unequivocally indicate stem/progenitor cell maintenance and cellular migration as the most important processes in the pathogenesis of acne."
    explanation: This genetics review connects GWAS and monogenic findings to core biological processes underlying acne susceptibility.
- name: Candidate gene families
  association: Associated
  notes: >
    Reviews highlight inflammatory cytokine genes (IL, TNF), RETN, CYP family
    genes, and extracellular matrix regulators (MMPs, TIMPs) as recurrent
    candidates linked to acne susceptibility.
  evidence:
  - reference: PMID:37662507
    supports: SUPPORT
    snippet: "some genes (such as IL, TNF, RETN, CYP family, MMPs and TIMPs genes et al) are associated with acne vulgaris and may affect the progression and prognosis of the disease."
    explanation: This review summarizes multiple gene families repeatedly implicated in acne susceptibility and outcomes.
- name: RETN-420C>G and IL6-572G>C polymorphisms
  association: Associated
  notes: >
    Case-control data in a Chinese cohort link RETN-420G and IL6-572C alleles
    to increased acne susceptibility and severity.
  evidence:
  - reference: PMID:35279931
    supports: SUPPORT
    snippet: "There is a strong correlation between RETN-420 and IL6-572 polymorphisms and acne susceptibility; the RETN-420G and IL6-572C alleles increase the risk of acne development."
    explanation: This study reports RETN-420 and IL6-572 risk alleles associated with acne susceptibility.
- name: TNFR2 M196R and TLR2 Arg753Gln polymorphisms
  association: Associated
  notes: >
    Risk alleles in TNFR2 and TLR2 are enriched in moderate-to-severe acne
    subgroups, supporting an inflammatory genetic contribution.
  evidence:
  - reference: PMID:20861605
    supports: SUPPORT
    snippet: "The 196R allele of TNFR2 M196R as well as the 753Gln allele of TLR2 Arg753Gln are risk factors for acne vulgaris in Chinese Han patients, further supporting the contribution of inflammatory cytokines to the pathogenesis of acne."
    explanation: This study links TNFR2 and TLR2 risk alleles to acne susceptibility in a Chinese Han cohort.
environmental:
- name: Diet
  description: >
    High glycemic index foods and dairy products have been associated with
    acne severity, possibly through effects on insulin/IGF-1 signaling and
    hormonal modulation.
  evidence:
  - reference: PMID:32748305
    supports: SUPPORT
    snippet: "Several studies have evaluated the significance of the glycemic index of various foods and glycemic load in patients with acne, demonstrating individuals with acne who consume diets with a low glycemic load have reduced acne lesions compared with individuals on high glycemic load diets."
    explanation: This review provides evidence for the association between high glycemic load diets and acne severity.
  - reference: PMID:32748305
    supports: SUPPORT
    snippet: "Dairy has also been a focus of study regarding dietary influences on acne; whey proteins responsible for the insulinotropic effects of milk may contribute more to acne development than the actual fat or dairy content."
    explanation: The paper describes the mechanism by which dairy consumption may influence acne through insulinotropic effects.
- name: Stress
  description: >
    Psychological stress can exacerbate acne through effects on the
    hypothalamic-pituitary-adrenal axis and increased sebum production.
  evidence:
  - reference: PMID:28871928
    supports: SUPPORT
    snippet: "Even though emotional stress has long been suspected to trigger or exacerbate acne, its influence on acne severity has been mostly underestimated until recently when studies have brought new data about the different mechanisms and possible factors involved in this interaction."
    explanation: This review examines the link between psychological stress and acne exacerbation.
  - reference: PMID:28871928
    supports: SUPPORT
    snippet: "The basis for the association between emotional stress and the onset or exacerbation of acne is in several cutaneous neurogenic factors which interact with a pathogenic cascade in acne."
    explanation: The paper describes neurogenic mechanisms linking stress to acne pathogenesis.
- name: Air pollution and climate stressors
  description: >
    Repeated exposure to rising pollutant levels and climate-related
    environmental changes is associated with acne burden.
  evidence:
  - reference: PMID:41464454
    supports: SUPPORT
    snippet: "Psoriasis, acne vulgaris, atopic dermatitis, photoaging, melasma, and skin cancers have been associated with repeated exposure to rising levels of pollutants."
    explanation: This review links acne vulgaris with pollutant exposure among climate-sensitive skin conditions.

datasets:
- accession: geo:GSE315350
  title: Microbiome-Derived Indole-3-lactic Acid Attenuates Cutibacterium acnes-Induced Inflammation via the Aryl Hydrocarbon Receptor Pathway
  description: >-
    Transcriptomic profiling of C. acnes-driven inflammation with microbiome-
    derived tryptophan metabolites highlighting AHR pathway modulation.
  notes: Summary describes human keratinocyte stimulation and a C. acnes mouse model.
- accession: geo:GSE301280
  title: Spatial transcriptomics reveals dysfunctional lipid metabolism and abnormal pilosebaceous differentiation in acne vulgaris
  description: >-
    Spatial transcriptomics of healthy, non-lesional, comedonal, and pustular
    acne skin using a panel targeting sebaceous differentiation, lipid
    metabolism, and retinoid signaling.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: SPATIAL_TRANSCRIPTOMICS
  conditions:
  - healthy skin
  - non-lesional acne skin
  - comedonal acne skin
  - pustular acne skin
  notes: Identifies altered sebogenesis and retinoid signaling across lesion types.
- accession: geo:GSE292394
  title: High-Resolution Spatial Map of the Human Facial Sebaceous Gland Reveals Marker Genes and Decodes Sebocyte Differentiation [MERFISH]
  description: >-
    Spatial transcriptomics and MERFISH profiling of human facial sebaceous
    glands to map sebocyte differentiation stages.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: SPATIAL_TRANSCRIPTOMICS
  notes: Integrates spatial transcriptomics with single-cell profiling of sebaceous glands.

treatments:
- name: Topical retinoids
  description: >
    First-line treatment that normalizes follicular keratinization, reduces
    comedone formation, and has anti-inflammatory effects. Examples include
    tretinoin, adapalene, and tazarotene.
  treatment_term:
    preferred_term: retinoid agent therapy
    term:
      id: MAXO:0000237
      label: retinoid agent therapy
    qualifiers:
    - predicate:
        preferred_term: therapeutic agent
        term:
          id: NCIT:C2259
          label: Therapeutic Agent
      value:
        preferred_term: retinoid
        term:
          id: NCIT:C68299
          label: Retinoid
  evidence:
  - reference: PMID:30674002
    supports: SUPPORT
    snippet: "Topical retinoids are safe and efficacious for the treatment of acne vulgaris."
    explanation: This systematic review confirms the safety and efficacy of topical retinoids for acne treatment.
- name: Trifarotene
  description: >
    Topical retinoid selective for retinoic acid receptor gamma with evidence
    for reducing comedonal and inflammatory lesions, including truncal acne.
  treatment_term:
    preferred_term: retinoid agent therapy
    term:
      id: MAXO:0000237
      label: retinoid agent therapy
    qualifiers:
    - predicate:
        preferred_term: therapeutic agent
        term:
          id: NCIT:C2259
          label: Therapeutic Agent
      value:
        preferred_term: trifarotene
        term:
          id: NCIT:C118577
          label: Trifarotene
  evidence:
  - reference: PMID:36927117
    supports: SUPPORT
    snippet: "Large-scale randomized, controlled clinical trials have demonstrated trifarotene to be safe, well tolerated, and efficacious in reducing both comedones and papules/pustules of acne."
    explanation: This review summarizes randomized trials showing trifarotene efficacy across comedonal and inflammatory acne lesions.
- name: Benzoyl peroxide
  description: >
    Antimicrobial agent that kills C. acnes through oxidative damage without
    promoting antibiotic resistance. Also has mild comedolytic activity.
  treatment_term:
    preferred_term: antimicrobial agent therapy
    term:
      id: MAXO:0001021
      label: antimicrobial agent therapy
    qualifiers:
    - predicate:
        preferred_term: therapeutic agent
        term:
          id: NCIT:C2259
          label: Therapeutic Agent
      value:
        preferred_term: benzoyl peroxide
        term:
          id: NCIT:C47411
          label: Benzoyl Peroxide
  evidence:
  - reference: PMID:19761357
    supports: SUPPORT
    snippet: "BPO-containing combinations do not induce bacterial resistance and are important first-line treatments for mild to moderate acne vulgaris."
    explanation: This review establishes benzoyl peroxide as an important first-line treatment for acne that does not promote bacterial resistance.
- name: Topical antibiotics
  description: >
    Clindamycin and erythromycin reduce C. acnes populations and have
    anti-inflammatory effects. Should be combined with benzoyl peroxide to
    prevent resistance.
  treatment_term:
    preferred_term: antibacterial agent therapy
    term:
      id: MAXO:0000061
      label: antibacterial agent therapy
    qualifiers:
    - predicate:
        preferred_term: therapeutic agent
        term:
          id: NCIT:C2259
          label: Therapeutic Agent
      value:
        preferred_term: antibiotic
        term:
          id: NCIT:C258
          label: Antibiotic
  evidence:
  - reference: PMID:16086756
    supports: SUPPORT
    snippet: "topical antibiotics remain one of the cornerstones of acne management"
    explanation: This systematic review confirms topical antibiotics as a cornerstone treatment for acne.
- name: Clindamycin/adapalene/benzoyl peroxide gel
  description: >
    Triple-combination topical therapy for moderate to severe acne, combining
    clindamycin phosphate, adapalene, and benzoyl peroxide for long-term use.
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
    qualifiers:
    - predicate:
        preferred_term: therapeutic agent
        term:
          id: NCIT:C2259
          label: Therapeutic Agent
      value:
        preferred_term: clindamycin phosphate
        term:
          id: NCIT:C47978
          label: Clindamycin Phosphate
    - predicate:
        preferred_term: therapeutic agent
        term:
          id: NCIT:C2259
          label: Therapeutic Agent
      value:
        preferred_term: adapalene
        term:
          id: NCIT:C28989
          label: Adapalene
    - predicate:
        preferred_term: therapeutic agent
        term:
          id: NCIT:C2259
          label: Therapeutic Agent
      value:
        preferred_term: benzoyl peroxide
        term:
          id: NCIT:C47411
          label: Benzoyl Peroxide
  evidence:
  - reference: PMID:41552868
    supports: SUPPORT
    snippet: "At week 24, 67% of participants achieved treatment success, and significant reductions from baseline in inflammatory (88%) and noninflammatory (68%) lesions were observed (p < 0.001, both)."
    explanation: This pooled analysis supports long-term efficacy of the triple-combination gel.
- name: Oral antibiotics
  description: >
    Tetracyclines (doxycycline, minocycline) are used for moderate-to-severe
    inflammatory acne. Have both antimicrobial and anti-inflammatory effects,
    but prolonged use contributes to antimicrobial resistance and requires
    stewardship.
  treatment_term:
    preferred_term: antibacterial agent therapy
    term:
      id: MAXO:0000061
      label: antibacterial agent therapy
    qualifiers:
    - predicate:
        preferred_term: therapeutic agent
        term:
          id: NCIT:C2259
          label: Therapeutic Agent
      value:
        preferred_term: tetracycline antibiotic
        term:
          id: NCIT:C1595
          label: Tetracycline Antibiotic
  evidence:
  - reference: PMID:28542914
    supports: SUPPORT
    snippet: "isotretinoin therapy reduced acne lesion counts by a clinically relevant amount, and always by a greater amount than control, which was either placebo (two studies), oral antibiotics (seven studies) or other control"
    explanation: This systematic review confirms oral antibiotics as an established comparator treatment for acne in clinical trials.
  - reference: PMID:36568833
    supports: SUPPORT
    snippet: "The overuse of topical and/or systemic antibiotics, the long treatment courses used for acne, and the availability of over-the-counter antibiotic preparations, have led to the worldwide emergence of resistant strains in acne patients."
    explanation: This review documents antibiotic resistance concerns tied to prolonged acne antibiotic use, supporting stewardship in treatment.
- name: Oral isotretinoin
  description: >
    Systemic retinoid reserved for severe, recalcitrant acne. Addresses all
    four pathogenic factors but requires careful monitoring due to
    teratogenicity and other adverse effects.
  treatment_term:
    preferred_term: retinoid agent therapy
    term:
      id: MAXO:0000237
      label: retinoid agent therapy
    qualifiers:
    - predicate:
        preferred_term: therapeutic agent
        term:
          id: NCIT:C2259
          label: Therapeutic Agent
      value:
        preferred_term: isotretinoin
        term:
          id: NCIT:C603
          label: Isotretinoin
  evidence:
  - reference: PMID:33085149
    supports: SUPPORT
    snippet: "Oral isotretinoin is the most effective treatment for moderate to severe acne and its side effects are mostly dose-dependent."
    explanation: This systematic review confirms oral isotretinoin as the most effective treatment for moderate to severe acne.
- name: Hormonal therapy
  description: >
    Combined oral contraceptives and spironolactone reduce androgen effects
    on sebaceous glands. Used in female patients with hormonal acne patterns.
  treatment_term:
    preferred_term: hormone modifying therapy
    term:
      id: MAXO:0000283
      label: hormone modifying therapy
    qualifiers:
    - predicate:
        preferred_term: therapeutic agent
        term:
          id: NCIT:C2259
          label: Therapeutic Agent
      value:
        preferred_term: oral contraceptive
        term:
          id: NCIT:C389
          label: Oral Contraceptive
    - predicate:
        preferred_term: therapeutic agent
        term:
          id: NCIT:C2259
          label: Therapeutic Agent
      value:
        preferred_term: spironolactone
        term:
          id: NCIT:C840
          label: Spironolactone
  evidence:
  - reference: PMID:28492054
    supports: SUPPORT
    snippet: "Hormone-based therapies including combined oral contraceptive medications and spironolactone are considered effective therapies to treat adult acne in women."
    explanation: This systematic review confirms the efficacy of hormonal therapies including oral contraceptives and spironolactone for treating acne in women.
- name: Chemical peels
  description: >
    Organic acid-based peels are used to exfoliate acne-prone skin and reduce
    lesion counts, with agent selection tailored to patient tolerability.
  treatment_term:
    preferred_term: therapeutic procedure of skin of body
    term:
      id: MAXO:0001417
      label: therapeutic procedure of skin of body
    qualifiers:
    - predicate:
        preferred_term: therapeutic procedure
        term:
          id: NCIT:C49236
          label: Therapeutic Procedure
      value:
        preferred_term: chemical peel
        term:
          id: NCIT:C93203
          label: Chemical Peel
  evidence:
  - reference: PMID:37894698
    supports: SUPPORT
    snippet: "The findings of this comprehensive bibliographic review indicate that organic acid-based chemical peels represent effective and safe treatment options for individuals with acne-prone skin."
    explanation: This review supports organic acid chemical peels as effective and safe adjuncts for acne-prone skin.
- name: Azelaic acid peel
  description: >
    Azelaic acid peels reduce sebum and lesion burden as a nonpharmacologic
    option for facial acne.
  treatment_term:
    preferred_term: therapeutic procedure of skin of body
    term:
      id: MAXO:0001417
      label: therapeutic procedure of skin of body
    qualifiers:
    - predicate:
        preferred_term: therapeutic procedure
        term:
          id: NCIT:C49236
          label: Therapeutic Procedure
      value:
        preferred_term: chemical peel
        term:
          id: NCIT:C93203
          label: Chemical Peel
    - predicate:
        preferred_term: therapeutic agent
        term:
          id: NCIT:C2259
          label: Therapeutic Agent
      value:
        preferred_term: azelaic acid
        term:
          id: NCIT:C47407
          label: Azelaic Acid
  evidence:
  - reference: PMID:31455112
    supports: SUPPORT
    snippet: "Peels with 30% AZA reduced acne lesions and normalized the activity of the sebaceous glands."
    explanation: This study reports acne lesion reduction and sebum normalization with 30% azelaic acid peels.
- name: Chemical peels for acne scarring
  description: >
    Medium-depth peels such as glycolic acid and trichloroacetic acid are
    used to improve atrophic acne scars.
  treatment_term:
    preferred_term: therapeutic procedure of skin of body
    term:
      id: MAXO:0001417
      label: therapeutic procedure of skin of body
    qualifiers:
    - predicate:
        preferred_term: therapeutic procedure
        term:
          id: NCIT:C49236
          label: Therapeutic Procedure
      value:
        preferred_term: chemical peel
        term:
          id: NCIT:C93203
          label: Chemical Peel
    - predicate:
        preferred_term: therapeutic agent
        term:
          id: NCIT:C2259
          label: Therapeutic Agent
      value:
        preferred_term: glycolic acid
        term:
          id: NCIT:C83737
          label: Glycolic Acid
    - predicate:
        preferred_term: therapeutic agent
        term:
          id: NCIT:C2259
          label: Therapeutic Agent
      value:
        preferred_term: topical trichloroacetic acid
        term:
          id: NCIT:C125002
          label: Topical Trichloroacetic Acid
  evidence:
  - reference: PMID:39483653
    supports: SUPPORT
    snippet: "A 30% TCA peel is efficacious and well-tolerated for mild-to-moderate acne scars."
    explanation: This split-face study supports TCA peels for improving acne scarring.
- name: Ablative fractional CO2 laser
  description: >
    Ablative fractional CO2 laser is used for atrophic acne scars but can
    cause erythema, dyspigmentation, and prolonged recovery.
  treatment_term:
    preferred_term: laser surgical procedure
    term:
      id: MAXO:0001578
      label: laser surgical procedure
    qualifiers:
    - predicate:
        preferred_term: therapeutic procedure
        term:
          id: NCIT:C49236
          label: Therapeutic Procedure
      value:
        preferred_term: laser therapy
        term:
          id: NCIT:C15466
          label: Laser Therapy
  evidence:
  - reference: PMID:41521693
    supports: SUPPORT
    snippet: "Ablative fractional CO2 laser is effective for acne scar treatment but is often associated with side effects such as erythema and dyspigmentation, along with prolonged recovery time."
    explanation: This trial background notes efficacy of CO2 laser for acne scars with notable side effects.
- name: Post-laser antioxidant serum
  description: >
    Topical antioxidant serum with vitamins C and E (with ferulic acid) is
    used after ablative laser procedures to support skin recovery.
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
    qualifiers:
    - predicate:
        preferred_term: therapeutic agent
        term:
          id: NCIT:C2259
          label: Therapeutic Agent
      value:
        preferred_term: vitamin C
        term:
          id: NCIT:C68507
          label: Vitamin C
    - predicate:
        preferred_term: therapeutic agent
        term:
          id: NCIT:C2259
          label: Therapeutic Agent
      value:
        preferred_term: topical vitamin E
        term:
          id: NCIT:C67081
          label: Topical Vitamin E
  evidence:
  - reference: PMID:41521693
    supports: SUPPORT
    snippet: "This study found that CE Ferulic led to enhanced wound healing, reduced erythema and melanin levels, and improved skin hydration following laser treatment, suggesting its beneficial application in combination with laser treatment to accelerate skin recovery."
    explanation: This split-face trial supports antioxidant serum use after CO2 laser for acne scars.
- name: Blue light therapy
  description: >
    Blue light phototherapy is used as an alternative for inflammatory acne,
    with evidence of clinical improvement.
  treatment_term:
    preferred_term: radiation therapy
    term:
      id: MAXO:0000014
      label: radiation therapy
    qualifiers:
    - predicate:
        preferred_term: therapeutic procedure
        term:
          id: NCIT:C49236
          label: Therapeutic Procedure
      value:
        preferred_term: phototherapy
        term:
          id: NCIT:C15301
          label: Phototherapy
  evidence:
  - reference: PMID:34696155
    supports: SUPPORT
    snippet: "Studies have shown significant improvements in the overall picture of acne."
    explanation: This systematic review reports clinical improvement in acne with blue light phototherapy.
- name: Visible light therapy
  description: >
    Visible light devices, including blue light, can reduce acne lesion
    counts in patients seeking nonpharmacologic treatments.
  treatment_term:
    preferred_term: radiation therapy
    term:
      id: MAXO:0000014
      label: radiation therapy
    qualifiers:
    - predicate:
        preferred_term: therapeutic procedure
        term:
          id: NCIT:C49236
          label: Therapeutic Procedure
      value:
        preferred_term: phototherapy
        term:
          id: NCIT:C15301
          label: Phototherapy
  evidence:
  - reference: PMID:39056372
    supports: SUPPORT
    snippet: "Overall, 92% of patients achieved partial remission of their acne lesions using visible light therapy."
    explanation: This systematic review summarizes lesion improvement across visible light studies in acne.
- name: Photodynamic therapy
  description: >
    Photodynamic therapy is used off-label for inflammatory acne with
    evidence supporting efficacy in dermatologic indications.
  treatment_term:
    preferred_term: radiation therapy
    term:
      id: MAXO:0000014
      label: radiation therapy
    qualifiers:
    - predicate:
        preferred_term: therapeutic procedure
        term:
          id: NCIT:C49236
          label: Therapeutic Procedure
      value:
        preferred_term: photodynamic therapy
        term:
          id: NCIT:C15300
          label: Photodynamic Therapy
  evidence:
  - reference: PMID:39226531
    supports: SUPPORT
    snippet: "Newer indications, for which no approval has yet been granted, but which nevertheless have sufficient evidence of efficacy according to the study situation, are inflammatory (lichen sclerosus, acne) and infectious dermatoses (viral warts, cutaneous leishmaniasis, atypical mycobacteriosis)."
    explanation: This review identifies acne as an emerging indication for photodynamic therapy with supportive evidence.
- name: Nd:YAG laser and intralesional PRP
  description: >
    Nd:YAG laser and intralesional platelet-rich plasma injections are used
    for inflammatory acne in split-face comparative protocols.
  treatment_term:
    preferred_term: therapeutic procedure of skin of body
    term:
      id: MAXO:0001417
      label: therapeutic procedure of skin of body
    qualifiers:
    - predicate:
        preferred_term: therapeutic procedure
        term:
          id: NCIT:C49236
          label: Therapeutic Procedure
      value:
        preferred_term: laser therapy
        term:
          id: NCIT:C15466
          label: Laser Therapy
    - predicate:
        preferred_term: therapeutic agent
        term:
          id: NCIT:C2259
          label: Therapeutic Agent
      value:
        preferred_term: platelet-rich plasma
        term:
          id: NCIT:C106557
          label: Platelet-rich Plasma
  evidence:
  - reference: PMID:35084634
    supports: SUPPORT
    snippet: "The intralesional PRP injection and 1064 nm long-pulsed Nd:YAG laser are safe and effective methods for controlling inflammatory as well as non-inflammatory acne vulgaris in both adolescents and post-adolescent patients."
    explanation: This randomized split-face study supports Nd:YAG laser and PRP injections for inflammatory acne vulgaris.
- name: 1726 nm laser therapy
  description: >
    Targeted laser therapy that selectively affects sebaceous glands and is
    being evaluated for moderate to severe acne.
  treatment_term:
    preferred_term: laser surgical procedure
    term:
      id: MAXO:0001578
      label: laser surgical procedure
    qualifiers:
    - predicate:
        preferred_term: therapeutic procedure
        term:
          id: NCIT:C49236
          label: Therapeutic Procedure
      value:
        preferred_term: laser therapy
        term:
          id: NCIT:C15466
          label: Laser Therapy
    - predicate:
        preferred_term: therapeutic procedure
        term:
          id: NCIT:C49236
          label: Therapeutic Procedure
      value:
        preferred_term: infrared laser therapy
        term:
          id: NCIT:C66918
          label: Infrared Laser Therapy
  evidence:
  - reference: PMID:38271552
    supports: SUPPORT
    snippet: "New 1726 nm lasers specifically target the sebaceous gland, which is known to be pivotal in acne pathophysiology."
    explanation: This review highlights 1726 nm lasers as a sebaceous gland-targeted treatment approach for acne.

clinical_trials:
- name: NCT00421993
  phase: PHASE_III
  status: COMPLETED
  description: Multicenter, randomized, double-blind trial comparing adapalene/benzoyl peroxide gel with monotherapies and vehicle in acne vulgaris over 12 weeks.
  target_phenotypes:
  - preferred_term: comedonal acne
    term:
      id: HP:0040137
      label: Comedonal acne
  - preferred_term: erythematous papule
    term:
      id: HP:0030350
      label: Erythematous papule
  - preferred_term: pustule
    term:
      id: HP:0200039
      label: Pustule
  evidence:
  - reference: clinicaltrials:NCT00421993
    supports: SUPPORT
    snippet: "This is a multi-center, randomized, double-blind, parallel group study with 12 weeks of treatment of acne vulgaris."
    explanation: The trial evaluates a combination topical therapy specifically in participants with acne vulgaris.
- name: NCT02249767
  phase: PHASE_III
  status: COMPLETED
  description: Double-blind, randomized, parallel-group study assessing tretinoin gel bioequivalence in patients with mild acne vulgaris.
  target_phenotypes:
  - preferred_term: comedonal acne
    term:
      id: HP:0040137
      label: Comedonal acne
  - preferred_term: erythematous papule
    term:
      id: HP:0030350
      label: Erythematous papule
  evidence:
  - reference: clinicaltrials:NCT02249767
    supports: SUPPORT
    snippet: "Normal, healthy male and female children and adults (i.e., ages 12 to 40 years) with at least Grade 2 (i.e., mild severity) acne vulgaris were treated on the full face once daily for 84 days with the Tretinoin Gel 0.05%, Brand (tretinoin) Gel 0.05%, or Gel Vehicle."
    explanation: This study explicitly enrolls participants with acne vulgaris and evaluates topical tretinoin treatment.

differential_diagnoses:
- name: PAPASH syndrome
  disease_term:
    preferred_term: PAPASH syndrome
    term:
      id: MONDO:0958343
      label: PAPASH syndrome
  description: >
    Autoinflammatory syndrome combining acne with pyoderma gangrenosum,
    hidradenitis suppurativa, and inflammatory arthritis.
  distinguishing_features:
  - Syndromic triad with pyoderma gangrenosum and hidradenitis suppurativa alongside acne.
  - Systemic inflammatory arthritis or other autoinflammatory features.
  evidence:
  - reference: PMID:41499625
    supports: SUPPORT
    snippet: "PAPASH spectrum syndrome is a rare autoinflammatory condition encompassing psoriatic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa."
    explanation: This case report defines PAPASH syndrome as a syndromic condition including acne and related inflammatory diseases.
- name: Rosacea
  disease_term:
    preferred_term: rosacea
    term:
      id: MONDO:0006604
      label: rosacea
  description: >
    Chronic inflammatory facial dermatosis with papules and pustules but no comedones. Central facial erythema, flushing,
    and telangiectasias can mimic inflammatory acne on the face.
  distinguishing_features:
  - Absence of comedones with prominent centrofacial erythema and telangiectasias.
  - Burning or stinging with triggers such as heat, alcohol, or spicy foods rather than androgen-driven distribution.
  evidence:
  - reference: PMID:12113648
    supports: SUPPORT
    snippet: "Localized pustular eruptions are seen on the hands and feet in adults with pustulosis palmaris et plantaris and acrodermatitis continua (both of which may be variants of psoriasis); on the face in patients with acne vulgaris, rosacea, and perioral dermatitis; and on the trunk and/or extremities in patients with folliculitis."
    explanation: The abstract lists rosacea alongside acne as a facial pustular eruption, underscoring the need for clinical differentiation.

- name: Bacterial folliculitis
  disease_term:
    preferred_term: folliculitis
    term:
      id: MONDO:0006552
      label: folliculitis
  description: >
    Infection or inflammation of hair follicles producing papules and pustules on hair-bearing skin, often the trunk or extremities,
    that can resemble acne lesions but lacks comedones and is frequently pruritic.
  distinguishing_features:
  - Lesions centered on hair follicles without open or closed comedones; often pruritic and may follow shaving or occlusion.
  - Distribution favors trunk, buttocks, and extremities rather than the typical facial and truncal comedones of acne.
  evidence:
  - reference: PMID:12113648
    supports: SUPPORT
    snippet: "Localized pustular eruptions are seen on the hands and feet in adults with pustulosis palmaris et plantaris and acrodermatitis continua (both of which may be variants of psoriasis); on the face in patients with acne vulgaris, rosacea, and perioral dermatitis; and on the trunk and/or extremities in patients with folliculitis."
    explanation: The abstract notes folliculitis presents with pustular eruptions on the trunk or extremities, highlighting its overlap with acneiform lesions.