Original article
Evidence-based recommendations for the management of acne fulminans and its variants

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Background

Acne fulminans (AF) is a severe variant of inflammatory acne. It typically manifests as an explosive worsening and ulceration of skin lesions, and can be associated with systemic symptoms. However, there is a paucity of evidence-based information and no clear guidelines concerning the classification and treatment of AF.

Objective

To better define the spectrum of AF and its variants, devise optimal therapeutic approaches, and identify areas of future research.

Methods

A panel of physicians with expertise in severe acne vulgaris was convened after a comprehensive literature review of severe acne variants. Priority topics were reviewed and presented by each panelist at a 5-hour conference. Following review of the audiotape and scribed notes from the conference, surveys were utilized to address points of controversy and to clarify consensus recommendations.

Results

Appropriate clinical case presentations and consensus survey questions were utilized to create final recommendations based on both the literature and the expert consensus.

Limitations

Limited evidenced-based data and prospective studies in the literature concerning the treatment of AF is available.

Conclusion

These guidelines better characterize AF and provide health care practitioners approaches to the classification, treatment, and prevention of AF and its variants.

Section snippets

Methods

Twelve physicians with extensive academic knowledge base and clinical expertise in severe acne vulgaris were selected by the chairs (Sheila Fallon Friedlander, MD, and Andrea L. Zaenglein, MD) to take part in developing a consensus of the pathogenesis, prevention, treatment, and future research directions of AF and its variants. The ultimate goal was to develop evidence and experience-based recommendations of care for these disorders.

Prior to convening, a comprehensive literature review was

Definitions

AF was initially labeled acne maligna or acute febrile ulcerative acne conglobota. However, in 1975 Plewig and Kligman coined the term AF, emphasizing its distinctive characteristics. The spectrum of severity ranges from skin-limited disease (acne fulminans without systemic symptoms, AF-WOSS) to acne fulminans with systemic symptoms (AF-SS) (Fig 1, A and B). The common feature of all forms of AF consists of ulcerative lesions that preferentially occur on the trunk with hemorrhagic erosions and

Incidence and demographics

AF is rarely reported, with <200 cases documented in the literature.1, 2, 3 The incidence of reports has decreased over the last decade, supporting the belief that severe disease with systemic findings might be decreasing.2 Some have postulated that recognition of disease and treatment are now occurring earlier, and acne is therefore less likely to progress to a truly fulminant form.2 The panel agreed that the de novo form of AF is quite uncommon. In contrast, IIAF-WOSS appears to be increasing

Associated disorders: SAPHO, PAPA, PASH, and PAPASH

SAPHO, PAPA, PASH, and PAPASH are syndromes that share the manifestations of joint disease and severe acne. SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) is a musculoskeletal disorder with variable skin findings.12 Its most common skin manifestation is palmoplantar pustulosis. Acne, including acne conglobata, AF, and hidradenitis suppurativa, are less frequently associated with SAPHO. High fever and weight loss are also often present. The largest case series of SAPHO

Pathogenesis

The sequence of events leading to the explosive cutaneous inflammation in patients with AF is unknown. Alterations in innate immunity, autoimmunity, adaptive immunity, and autoinflammation have been proposed; however, the evidence is inconclusive.17 An immunological deficiency or a generalized hypersensitivity state was suspected but no specific clues could be found in qualitative or quantitative immunoglobulin assays, skin tests, biopsies, or other studies.17 The autoinflammatory syndromes are

Corticosteroids and isotretinoin

Unfortunately, there is an absence of large-scale randomized controlled trials evaluating treatment for AF. Nonetheless, a review of case series, individual reports, and case analyses supports the use of systemic corticosteroids in combination with isotretinoin when treating all forms of AF.1, 4, 11, 24, 25, 26, 27

Systemic corticosteroids are recommended at the immediate onset of AF to quickly control the severity of inflammation.1 The panel recommends initiating prednisone 0.5 mg/kg/day to

Special consideration regarding severe adverse treatment effects: Pseudotumor cerebri syndrome

Tetracycline, isotretinoin, and corticosteroids have been associated with the development of pseudotumor cerebri syndrome (PTCS). PTCS encompasses primary and secondary disorders of elevated intracranial pressure (ICP) caused by increased resistance in cerebrospinal fluid outflow.47, 48, 49 PTCS usually causes headache and blurry vision and can result in permanent vision loss if unrecognized. The signs most suggestive of PTCS are postural headache, tinnitus, transient visual disturbance, and

Future directions

The consensus panel acknowledges that there is a paucity of strong evidence addressing the pathogenesis and treatment of AF and its variants. AF with and without systemic symptoms is rare, but several case series exist that provide some guidance regarding management. Unfortunately, isotretinoin-induced disease is more common and appears to be increasing, but evidence-based data is similarly lacking for this disorder. Using a uniform classification system should simplify and optimize future

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    Funding sources: None.

    Conflicts of interest: None declared.

    Previously presented at the American Acne and Rosacea Society Acne Fulminans Consensus Conference, San Francisco, California, March 19, 2015.

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