Systemic Corticosteroids Effective for Acne Fulminans Regardless of Phenotype

TEM of Cutibacterium acnes
TEM of propionibacterium acnes
Results from a novel study suggest that there is no specific Cutibacterium acnes phylotype associated with acne fulminans, raising the possibility that the mechanism involved in acne fulminans could be more related to abnormal activation of the cutaneous innate immunity.

There is no specific Cutibacterium acnes phylotype associated with acne fulminans, which may indicate that the acute inflammation associated with the disease may be more related to an abnormal cutaneous innate immunity activation, according to study results published in the Journal of the European Academy of Dermatology and Venereology. Regardless of strain, systemic corticosteroids and adjunctive isotretinoin were found to be the most effective treatment for acute acne fulminans.

Investigators conducted a retrospective observational study of all patients with acne fulminans seen in the department of dermatology at the Centre Hospitalier Universitaire, Nantes, France, between 2008 and 2018. For the study, 15 patients with a median age of 15 years, 80% of whom were men, were identified. A family history of acne was found in 86.7% of patients. Of the patients, 9 (60%) had isotretinoin-induced acne fulminans. Bacteriologic samples were taken from each patient to analyze C acnes phylotype distribution and the therapeutic response was assessed using the Echelle de Cotation des Lésions d’Acné and Global Acne Severity scales.

Cultivable skin microbiota was assessed and the bacteriologic culture was positive in all patients. While C acnes was identified in 12 patients (80%), the Cutibacterium species alone was identified in 10 (C acnes, 9; C avidum, 1). Staphylococcus aureus was identified in association with C acnes in 2 patients and alone in 2 other patients. A single patient had a positive culture for both C acnes and C granulosum.

When assessing the face and back, C acnes phylotypes IA1 was predominant, occurring in 9 patients (60%), followed by phylotype II (3 patients), phylotype IB (2 patients), and phylotype IA2 (1 patients).

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Investigators also evaluated the treatment regimens the study patients followed.  Systemic corticosteroids were given as first-line treatment in patients with (n=9) and without (n=6) isotretinoin-induced acne fulminans. The median initial dose for patients with isotretinoin-induced acne fulminans was 0.47 mg/kg/day, and the median total treatment duration was 12.75 months. Isotretinoin was discontinued in all patients. Complete remission was achieved in 3 patients after a median of 5 months using systemic corticosteroids with either minocycline or in combination with spironolactone and zinc. The non-isotretinoin-induced patients received a median initial dose of 0.5 mg/kg/day with a median taper of 5 months. Low-dose isotretinoin was added for 4 patients; the remaining 2 patients were given conjunctive oral antibiotics. Only 2 patients in this group achieved a partial response or complete remission within a median of 4.5 months; in 1 case, in conjunction with minocycline and in the other, with isotretinoin.

Antibiotic resistance was studied for all strains of C acnes. No strain was resistant to tetracyclines. Erythromycin resistance was seen in 4 of the 12 strains in facial samples, one of which was also resistant to clindamycin. Of the resistant patients, 3 had been previously treated with a topical antibiotic.

In the cohort, 7 patients resistant to several therapeutic lines were treated with biologics. Partial response (n=3) and complete remission (n=2) were seen with secukinumab, an anti-IL-17. Partial remission was seen in the patient given ustekinumab, an anti-IL12/23. No effect was seen in the 2 patients given anakinra, an anti-IL-1; 1 patient subsequently received secukinumab.

“Our study raises the hypothesis that [acne fulminans] is not associated with a specific phylotype of C. acnes, nor with a loss of phylotypic diversity. S. aureus could play a role in the development of the acute inflammatory response in association with C. acnes but this remains to be confirmed,” the investigators wrote. They recommended systemic corticosteroids from the onset of acne fulminans for rapid inflammation control. “A low dose of isotretinoin may then be combined (0.1 mg/kg/day), while continuing oral corticosteroids for at least 4 weeks. Isotretinoin doses may then be progressively increased concomitantly with the decrease in oral corticosteroids.”

Future studies are needed to assess the use of biologics and preventive strategies, as well as the effect of combined treatments in acne fulminans, the researchers concluded.

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Bocquet-Trémoureux S, Corvec S, Khammari A, Dagnelie MA, Boisrobert A, Dreno B. Acne fulminans and Cutibacterium acnes phylotypes [published online November 12, 2019]. J Eur Acad Dermatol Venereol. doi:10.1111/jdv.16064