Worsening Acne After Isotretinoin Treatment in Adolescent Girls

Case

A healthy 17-year-old girl with inflammatory acne did not respond to topical tretinoin, benzoyl peroxide, and oral minocycline. She was then treated with 0.5 mg/kg/d oral isotretinoin. . Two days later, she developed fever, joint pain, and progressive severe inflammatory lesions on her back, chest, shoulders, and sides of her face, many of which were ulcerated. (Figure 1-3). Isotretinoin was discontinued and she was started on oral prednisone at 1 mg/kg/d and tapered over 4 months. She relapsed 1 week after her and required oral steroids at 0.5 mg/kg/d, then tapered over 2 months. She was also concurrently treated with oral doxycycline, continued for several months after her steroids were discontinued.

What is the diagnosis?

Diagnosis: fulminant acne

clinical findings

Acne fulcrum (AF) is a rare and serious variant of inflammatory acne. It presents as sudden eruptions of multiple large, painful, hemorrhagic, crusted nodulocystic lesions that rapidly become necrotic and ulcerative and heal with scarring.¹ Areas commonly involved include the face, upper chest, back, and shoulders. Rarely, lesions extend into the thighs. The spectrum of disease ranges from skin-limited disease to systemic manifestations such as fever, malaise, joint and bone pain, erythema nodosum, and painful splenomegaly.² Laboratory anomalies may also be noted.

Epidemiology/Pathogenesis

The incidence of AF is unknown, with approximately 200 cases reported overall in the medical literature. It usually affects Caucasian adolescent boys with a history of acne, but there have been reports of the condition in adolescent females as well.³

Common triggers for AF include the use of moderate to high doses of 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 is thought to be the result of an inflammatory cytokine response to the massive immune response triggered by the inflammation of inflammatory acne alone or the initiation of isotretinoin. Acne bacteria.³ A classification system is used to refer to the absence (AF-WOSS) or presence (AF-SS) of systemic symptoms.

Differential diagnosis

Differential diagnosis of AF may include Conglobata acnes. rosacea fulminans; and synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome.³ Acne conglobatae presents the slow evolution of numerous inflammatory nodules into burrowing abscesses, painful nodules, and multiple porous comedones without systemic involvement. Rosacea fulminans is a severe, female-dominant variant of rosacea that presents with sudden onset of painful coalesced nodules with facial papules, pustules, cysts, and red cyanotic central facial erythema.

SAPHO syndrome is a chronic disease, commonly described in women with a long lag time between cutaneous manifestations (besides acne, including palmoplantar pustulosis) and the onset of systemic symptoms, including fever and weight loss. It is believed that SAPHO syndrome and atrial fibrillation fall within the same spectrum of illness and are probably caused by the same underlying processes.⁷

evaluation

As associated with systemic symptoms, the workup should include:^1,2:

1. A complete blood count may reveal an elevated white blood cell count with neutrophilia, anemia, and/or leukemia-type reaction.
2. Inflammatory markers such as erythrocyte sedimentation rate and C-reactive protein levels may be elevated.
3. Liver function tests may show transaminitis.
4. Elevated serum alkaline phosphatase may suggest underlying bone lesions.
5. Imaging studies, such as x-rays of the extremities, may reveal the presence of sterile osteolytic lesions resembling osteomyelitis, but have been shown to be culture-negative.
6. Urinary or serum human chorionic gonadotropin may be elevated in female patients.

treatment and management

There are no standardized guidelines for managing AF. However, we do have evidence-based recommendations and recommend seeing a dermatologist early on for optimal results.¹

The mainstay of initial treatment is early administration of systemic corticosteroids (prednisone or prednisolone) because of their potent anti-inflammatory and immunosuppressive effects. Corticosteroids can rapidly control systemic AF symptoms, including fever and/or musculoskeletal symptoms. Recommended management includes prednisone at 0.5–1 mg/kg/day for up to 4 weeks or longer until lesions heal, before adding low-dose isotretinoin at 0.1 mg/kg/day. will be You can slowly taper off the former and gradually increase the latter. This may take him 3-4 months and may be prolonged if the patient experiences redness with increasing doses of isotretinoin. Case reports in the literature show that patients are effectively treated with a combination of corticosteroids and retinoids until the maximum tolerated isotretinoin dose is reached without flare.

One week after discontinuing prednisone, the patient experienced a recurrence of atrial fibrillation. Her condition responded to her second low-dose course of corticosteroids for 2 months and remained in remission without systemic medication. Some hypertrophic scars subsequently improved dramatically with topical steroids. Notably, her isotretinoin was not restarted.

Alternative treatments to the above regimens are being used in treatment-resistant patients. These agents include dapsone, immunosuppressants such as methotrexate and azathioprine, or biologic agents such as infliximab and etanercept. However, no large-scale clinical trials are available to recommend general use of these agents. Antibiotic therapy is generally not recommended for AF.¹

A pulsed dye laser (585-595 nm) can be used to remove excess granulation tissue and reduce scarring.² Because the lesion is large, multiple treatments are required. Scarring and depigmentation remain common complications.

References

1. Greywal T, Zaenglein AL, Baldwin HE, et al. Evidence-based recommendations for the management of fulminant acne and its variants. J am Akad Dermatol2017;77(1):109-117. doi:10.1016/j.jaad.2016.11.028
2. Zito PM, Badri T. Acne fulminance. In: Stat Pearls. StatPearls Publishing; 2022. Accessed 7 November 2022. http://www.ncbi.nlm.nih.gov/books/NBK459326/
3. Dall’oglio F, Puglisi DF, Nasca MR, Micali G. Acne fulminance. G Ital Dermatol Benereol2020;155(6):711-718.doi:10.23736/S0392-0488.20.06711-5
4. Fakih A, Goens J, Grozdev I, Dangoisse C, Richert B. Fulminant acne induced by low-dose isotretinoin: a case report and review of the literature. Dermatol Online J2020;26(12):13030/qt14h2419w
5. Gualtieri B, Tonini A, Panduri S, Chiricozzi A, Romanelli M. Fulminant acne associated with leimecycline intake: a case report. Clin Cosmetic Investig Dermatol2018; 11:403-405. doi:10.2147/CCID.S158925
6. Lee G, Ferri-Huerta R, Greenberg KB, Somers KE. Fulminant acne in a transgender boy after increasing testosterone dose. JAAD Case Representative2022;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 Difficult Diagnosis That Can’t Be Missed. J infection2016;72(suppl):S106-S114.doi:10.1016/j.jinf.2016.04.030