Worsening acne after isotretinoin treatment in an adolescent girl

Contemporary PEDS JournalNovember/December 2022

A healthy 17-year-old girl with inflammatory acne had failed to respond to topical tretinoin, benzoyl peroxide, and oral minocycline. What's the diagnosis?

The Case

A healthy 17-year-old girl with inflammatory acne had failed to respond to topical tretinoin, benzoyl peroxide, and oral minocycline. She was subsequently treated with oral isotretinoin at 0.5 mg/kg/d. Two days later, she developed fever, arthralgias, and progressive severe inflammatory lesions on the back, chest, shoulders, and sides of her face, many of which were ulcerated (Figures 1-3). The isotretinoin was discontinued, and she was started on oral prednisone at 1 mg/kg/d which was tapered over 4 months. She had a recurrence a week later and required 0.5 mg/kg/d of oral steroids which were tapered over the subsequent 2 months. She was also treated concurrently with oral doxycycline, which was continued for several months after the steroids were discontinued.

Figure 1. Note hemorrhagic, crusted nodulocystic lesions that have undergone extensive ulceration. (Image provided by author)

Figure 1. Note hemorrhagic, crusted nodulocystic lesions that have undergone extensive ulceration. (Image provided by author)

Figure 2. Ulcerated lesions with some necrosis present. (Image provided by author)

Figure 2. Ulcerated lesions with some necrosis present. (Image provided by author)

Figure 3. Solitary ulcerated lesion on the right cheek. (Image provided by author)

Figure 3. Solitary ulcerated lesion on the right cheek. (Image provided by author)

What’s the diagnosis?

Diagnosis: Acne fulminans

Clinical findings

Acne fulminans (AF) is a rare and severe variant of inflammatory acne. It presents as an abrupt eruption of multiple large, painful, hemorrhagic, crusted nodulocystic lesions that rapidly undergo necrosis and ulceration and heal with scarring.1 Commonly involved areas include the face, upper chest, back, and shoulders. In rare cases, lesions may extend down to the thighs. The spectrum of disease ranges from skin-limited disease to systemic symptoms such as fever, malaise, arthralgias, bone pain, erythema nodosum, and painful splenomegaly.2 Laboratory abnormalities may also be noted.


The incidence of AF is unclear, with about 200 reported cases overall in the medical literature. It typically affects White adolescent boys with a prior history of acne, but there are also reports of this condition in adolescent females.3

Common triggers for AF include the use of moderate- to high-dose isotretinoin to manage severe acne, anabolic steroids in bodybuilders, exogenous hormone administration, certain antibiotics, or spontaneous occurrence.4-6 The underlying etiologic mechanism is currently unknown, but it is posited to be the result of an inflammatory cytokine response to the massive immune reaction triggered by flaring inflammatory acne alone or the initiation of isotretinoin against Cutibacterium acnes.3 Classification systems are used to refer to the absence (AF-WOSS) or presence (AF-SS) of systemic symptoms.

Differential diagnosis

The differential diagnosis of AF may include acne conglobata; rosacea fulminans; and synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome.3 Acne conglobata presents with slow evolution of numerous inflammatory nodules into burrowing abscesses, painful nodules, and multiple polyporous comedones without systemic involvement. Rosacea fulminans is a severe, female-predominant variant of rosacea presenting with sudden onset of facial papules, pustules, cysts, and painful coalescing nodules with red-cyanotic centrofacial erythema.

SAPHO syndrome is a chronic disease often reported in women with a long lag time between cutaneous manifestations (besides acne, these include palmoplantar pustulosis) and the development of systemic manifestations, which may also include fever and weight loss. There is some thought that SAPHO syndrome and AF are on the same disease spectrum, possibly triggered by the same underlying process.7


Because of the association with systemic symptoms, the workup should include the following1,2:

  1. Complete blood count may reveal elevated white blood cell count with neutrophilia, anemia, and/or leukemic-type reaction.
  2. Inflammatory markers including erythrocyte sedimentation rate and C-reactive protein level may be elevated.
  3. Liver function tests may show transaminitis.
  4. Elevated serum alkaline phosphatase may suggest underlying bone lesions.
  5. Imaging such as x-rays of the extremities may reveal the presence of aseptic osteolytic lesions that can mimic osteomyelitis but have been shown to be culture negative.
  6. Urine or serum human chorionic gonadotropin may be elevated in female patients.

Treatment and management

There are no standardized guidelines for the management of AF. However, there are evidence-based recommendations, and it is best to involve a dermatologist early on to ensure an optimal outcome.1

The mainstay of initial therapy is the early administration of systemic corticosteroids (prednisone or prednisolone) because of their strong anti-inflammatory and immunosuppressive properties. Corticosteroids can rapidly bring systemic AF symptoms under control, including fever and/or musculoskeletal manifestations. Recommended management includes prednisone at 0.5 to 1 mg/kg/d for up to 4 weeks or longer until lesions have healed before adding low-dose isotretinoin at 0.1 mg/kg/d.1 Subsequently, there should be overlap between corticosteroid therapy and isotretinoin to allow for slow tapering of the former with gradual increase in the latter. This may take 3 to 4 months and may be prolonged if the patient experiences flares with an increase in the isotretinoin dose. Case reports in the literature show patients are treated effectively with combination corticosteroid and retinoid therapy until they reach the maximum tolerated isotretinoin dose without flares.

A week after stopping prednisone, the patient experienced a relapse of AF. Her condition responded to a second, lower-dose course of corticosteroids for 2 months and remained in remission without systemic medications. Several hypertrophic scars subsequently improved dramatically with topical steroids. Notably, her isotretinoin was not restarted.

Alternative treatments to the above regimen have been used in treatment-resistant patients. These agents include dapsone, immunosuppressants such as methotrexate or azathioprine, or biologic agents such as infliximab or etanercept. However, larger clinical trials that recommend the general use of these agents are unavailable. Antibiotic therapy is generally not recommended for AF.1

The use of pulsed dye laser (585-595 nm) may be used to remove excess granulation tissue and reduce scarring.2 Because of the large lesions, multiple treatments are required. Scarring and hypopigmentation remain common complications.


  1. 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;77(1):109-117. doi:10.1016/j.jaad.2016.11.028
  2. Zito PM, Badri T. Acne fulminans. In: StatPearls. StatPearls Publishing; 2022. Accessed November 7, 2022. http://www.ncbi.nlm.nih.gov/books/NBK459326/
  3. Dall’oglio F, Puglisi DF, Nasca MR, Micali G. Acne fulminans. G Ital Dermatol Venereol. 2020;155(6):711-718. doi:10.23736/S0392-0488.20.06711-5
  4. Fakih A, Goens J, Grozdev I, Dangoisse C, Richert B. Acne fulminans induced by a low dose isotretinoin: case report and review of the literature. Dermatol Online J. 2020;26(12):13030/qt14h2419w
  5. Gualtieri B, Tonini A, Panduri S, Chiricozzi A, Romanelli M. Acne fulminans associated with lymecycline intake: a case report. Clin Cosmet Investig Dermatol. 2018;11:403-405. doi:10.2147/CCID.S158925
  6. Lee G, Ferri-Huerta R, Greenberg KB, Somers KE. Acne fulminans in a transgender boy after an increase in testosterone dosage. JAAD Case Rep. 2022;21:32-34. doi:10.1016/j.jdcr.2021.11.029
  7. Zimmermann P, Curtis N. Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome - a challenging diagnosis not to be missed. J Infect. 2016;72(suppl):S106-S114. doi:10.1016/j.jinf.2016.04.030
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