Acne fulminans — Viva

Q1: A 15-year-old boy presents with sudden onset of painful ulcerative nodules on his trunk, fever and arthralgia. Discuss the diagnosis. (2 min)

This is acne fulminans — the most severe variant of inflammatory acne, historically called acute febrile ulcerative acne conglobata or acne maligna. The diagnostic triad is: (1) sudden onset of ulcerative, haemorrhagic-crusted inflammatory nodules on the chest, back and shoulders; (2) systemic symptoms — fever (often greater than 39 degrees C), arthralgia, myalgia, malaise, weight loss; and (3) laboratory evidence of systemic inflammation — leukocytosis with neutrophilia, markedly elevated ESR and CRP, mild anaemia of chronic disease. It predominantly affects adolescent males (13 to 17 years), driven by androgen-mediated sebum production. Recognised triggers include testosterone and anabolic-androgenic steroids, initiation of oral isotretinoin, high-protein and bodybuilding supplements (whey protein, BCAAs), and infections. The key discriminator from severe nodulocystic acne and acne conglobata is the presence of systemic symptoms and raised inflammatory markers — these are absent in the purely cutaneous forms.

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Q2: Describe the pathophysiology of acne fulminans and explain why cultures are sterile. (2 min)

Acne fulminans is best understood as an explosive immune-mediated hypersensitivity reaction to Cutibacterium acnes (formerly Propionibacterium acnes) antigens, not as a primary bacterial infection. Three complementary mechanisms operate. First, Type III (immune-complex) hypersensitivity — circulating immune complexes of C. acnes antigen, antibody and complement deposit in tissue (skin, synovium, bone), generating C5a, a potent neutrophil chemoattractant, and accounting for the systemic symptoms. Second, intense neutrophilic infiltration and tissue destruction — C5a and IL-8 recruit massive numbers of neutrophils that degranulate and release lysosomal enzymes (elastase, collagenase), destroying the follicular wall and overlying epidermis to produce the characteristic ulceration with necrotic haemorrhagic crust. Third, the autoinflammatory (IL-1) axis — in a subset, PSTPIP1 mutations drive excess IL-1-beta via inflammasome activation, linking AF to the PAPA/PAPASH/SAPHO family. Cultures are sterile because the inflammation is driven by the host immune response to C. acnes antigen, not by bacterial overgrowth — the organism remains confined to the follicle.

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Q3: State the definitive treatment, including the critical sequence and why isotretinoin must not be started alone. (2 min)

The cardinal principle: systemic corticosteroids FIRST, then low-dose isotretinoin — never isotretinoin alone. The stepwise algorithm is: Step 1 — oral prednisolone 0.5 to 1.0 mg/kg/day for approximately 4 weeks to suppress the immune-complex inflammation, control fever and halt new lesions; fever and arthralgia typically resolve within 24 to 72 hours. Step 2 — once inflammation is controlled (minimum 4 weeks of steroid monotherapy or crusted-lesion resolution), add low-dose isotretinoin at 0.1 mg/kg/day with corticosteroid overlap for at least a further 4 weeks.^[6] Step 3 — taper prednisolone slowly over 2 to 3 months while uptitrating isotretinoin toward 0.5 to 1.0 mg/kg/day. Step 4 — continue isotretinoin to a cumulative dose of 120 to 150 mg/kg over 4 to 6 months. Isotretinoin must not be started alone because it rapidly remodels the pilosebaceous unit and can abruptly release a large bolus of C. acnes antigen into the dermis, triggering or worsening the immune-complex cascade. Isotretinoin-induced acne fulminans is documented even at low starting doses; corticosteroid cover must precede or accompany isotretinoin introduction.

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Q4: Discuss the complications and which you must specifically not miss. (3 min)

The complications fall into three groups. Cutaneous — severe atrophic, keloidal and hypertrophic scarring is inevitable; early treatment limits but does not prevent it; scar revision is deferred 6 to 12 months after disease quiescence; post-inflammatory hyperpigmentation is common, especially in darker skin. Musculoskeletal — osteolytic bone lesions (especially the medial clavicle and sternum), chronic osteitis, sacroiliitis, enthesopathy, and (rarely) pathological fracture; bone lesions usually heal over months once inflammation is controlled. Psychological — depression, anxiety, social isolation, school refusal and suicidal ideation; the sudden disfigurement in an adolescent is devastating; this is mandatory to screen for actively at every visit because both the disease and isotretinoin have been linked to mood disturbance. The two complications I must specifically not miss are: (1) suicidal ideation — the psychological crisis can be life-threatening and must be screened for and managed with urgent adolescent mental-health input; and (2) osteolytic bone lesions — any bone or joint pain warrants X-ray or MRI, as clavicular osteolysis can precede the skin eruption and pathological fracture is a rare but serious consequence. Other pitfalls include: starting isotretinoin alone (the cardinal error); tapering corticosteroids too quickly (rebound flare); missing the anabolic-steroid or supplement history (relapse is guaranteed if the trigger persists); and failing to exclude secondary staphylococcal infection on ulcerated skin.

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Q5 (examiner's probe): How is isotretinoin-induced acne fulminans managed, and what biologic options exist for refractory disease?

Isotretinoin-induced acne fulminans — a patient started on isotretinoin for severe nodulocystic acne who flares with ulcerative lesions, fever, arthralgia and leukocytosis within the first weeks — is managed by: (1) stop or markedly reduce the isotretinoin; (2) start oral prednisolone 0.5 to 1.0 mg/kg/day until inflammation is controlled^[5]; (3) reintroduce isotretinoin cautiously at a low dose with continued corticosteroid cover and gradual uptitration (see the local protocol for the exact restarting dose). For refractory disease — patients unresponsive to or intolerant of the corticosteroid plus isotretinoin regimen, or who relapse on tapering — off-label biologic therapy is supported by case reports and small series (there are no randomised trials). TNF-alpha inhibitors (for example infliximab) have case-report support for refractory disease, including acne fulminans with SAPHO syndrome.^[3][6]

References6ShowHide

1. [1]Ortonne JP. Oral isotretinoin treatment policy. Do we all agree? Dermatology, 1997.PMID 9310744
2. [2]Fakih A, Goens J, Grozdev I, et al. Acne fulminans induced by a low dose isotretinoin: case report and review of the literature Dermatol Online J, 2020.PMID 33423422
3. [3]Iqbal M, Kolodney MS. Acne fulminans with synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome treated with infliximab J Am Acad Dermatol, 2005.PMID 15858507
4. [4]Greywal T, Zaenglein AL, Baldwin HE, et al. Evidence-based recommendations for the management of acne fulminans and its variants J Am Acad Dermatol, 2017.PMID 28619551
5. [5]Seukeran DC, Cunliffe WJ. The treatment of acne fulminans: a review of 25 cases. Br J Dermatol, 1999.PMID 10468806
6. [6]Wozna J, Korecka K, Stepka J, et al. Acne fulminans treatment: case report and literature review. Front Med (Lausanne), 2024.PMID 39139785