Case Letter

Severe Acne Fulminans Following Low-Dose Isotretinoin and Testosterone Use

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Marked improvement was noted after 24 hours (Figure 2) as well as on the third day of treatment (Figure 3A). After 6 weeks, only disfiguring scars were visible (Figure 3B). Oral isotretinoin was reincorporated after 8 weeks and was subsequently discontinued after 5 months of therapy with a cumulative dose of 150 mg/kg.

Figure 2. Marked improvement of acne fulminans was noted after 24 hours of treatment with prednisone, clindamycin, and doxycycline.

Figure 3. A, Acne fulminans lesions on the trunk showed clearance after 3 days of treatment. B, After 6 weeks, only disfiguring scars were visible.

It is important to differentiate AF from exacerbation of acne vulgaris because patients typically have mild or moderate acne vulgaris before the onset of acute symptoms.1 Acne fulminans is characterized by systemic symptoms such as myalgia, polyarthralgia, fatigue, and osteolytic bone lesions.1,7 Additionally, hematologic symptoms such as fever, leukocytosis, anemia, splenomegaly, and hepatomegaly may be present.1,5,7 Our patient demonstrated the polysymptomatic form of AF. The patient had severe acne with a tendency to scar. There also were some systemic manifestations such as polyarthralgia, weight loss, leukocytosis, an elevated erythrocyte sedimentation rate, and an elevated C-reactive protein level.

The clinical diagnosis in our patient also was supported by the hypothesis that heredity, overactive immune reactions, bacterial infections, and use of some drugs (eg, isotretinoin, tetracycline, testosterone) can trigger AF.8 The most well-known theory is that low doses of isotretinoin induce AF.6 The majority of cases are caused by doses of less than 20 mg/kg once daily, but there have been reports of patients using full doses and developing this condition.9 The fact that the use of low- and high-dose isotretinoin can provoke AF suggests an idiosyncratic reaction that is not clearly dose related. The most dangerous triggering factor of AF is concomitant usage of testosterone and isotretinoin.10 Our patient used testosterone injections to increase muscle mass and underwent treatment with isotretinoin for acne.

Treatment of AF is controversial, as there is no standard therapy. Currently, steroids and isotretinoin are the treatments of choice. Antibiotic use is controversial because of a lack of randomized trials.11

In the first stage of treatment, prednisone 0.5 to 1 mg/kg once daily is recommended as an initial anti-inflammatory therapy, with gradual dose reduction. According to evidence-based recommendations, a low dose of isotretinoin can be introduced after crusted lesions have healed. The overlapping therapy with steroids and isotretinoin should be provided for at least 4 weeks. High-potency topical corticosteroids can be used on granulation tissue, which can shorten the systemic treatment with prednisone or can be an alternative treatment for patients with contraindications to systemic corticosteroids.11

Additionally, local care of the lesions including compresses and topical emollients is crucial. There are some case reports in which there is introduction of high doses of isotretinoin, subsequently with systemic steroids.7,8,12 Seukeran and Cunliffe5 proved that it is beneficial to give acne prophylaxis to prevent further episodes. Our patient was similarly treated with systemic steroids and isotretinoin. Treatment guidelines for AF do not recommend oral antibiotics,11 but data are limited in the case of isotretinoin-induced AF. Our patient was given doxycycline concomitant with systemic steroids, which was necessary due to signs of secondary infection from a lesion culture. Doxycycline was stopped when isotretinoin treatment was initiated to prevent pseudotumor cerebri. The patient achieved good clinical improvement with no relapse.

Using isotretinoin to treat acne vulgaris has many benefits, despite the possibility of developing AF as an extremely rare complication. Clinicians should be aware of the risk of this complication to make the diagnosis and provide appropriate care, especially in young men. It is particularly important to consider the possibility of concomitant testosterone and isotretinoin when documenting the patient’s medical history.

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