Acne fulminans – Pathophysiology, Clinical, Diagnosis and Treatment
Acne fulminans (AF) is a severe, ulcerative form of acne with an acute onset and systemic symptoms. AF was originally described in 1959 by Burns and Colville (1), who described a 16-year-old student with acute fever and acne conglobata. In 1975, Plewig renamed the syndrome AF to characterize the fast onset, severity, and systemic symptoms. A more common acne fulminans-like syndrome mainly on the trunk may be precipitated by isotretinoin with dramatic ulcerating and granulating lesions and no systemic symptoms.
The pathophysiology of AF is unknown. The combination of fever, arthritis, and leukocytosis point to a primarily immune etiology. The syndrome is mostly seen in those with severe inflammatory acne, that is, those with the greatest anti-Propionibacterium acnes immunity, and the disease may be triggered by the response to an antigen from P. acnes (2). Additionally, other factors may be involved. Elevated blood levels of testosterone may play an important role in the pathogenesis of AF (3). The mechanism by which isotretinoin precipitates AF is unknown but is associated with high starting doses of the drug in those with the severest acne (4). Identical twins who developed AF have been documented, suggesting a genetic component (5).
AF is a rare systemic disease that usually affects men aged 13 to 22 years who have a history of acne. The mean duration of acne before the onset of AF is two years (range 0.5 5) (6). There are approximately 100 patients with AF in the literature.
Prior to developing AF, most patients have papulopustular or mild nodular acne. Patients experience a sudden onset of severe, ulcerating acne, accompanied by fever and other systemic symptoms. On exam, patients have numerous, highly inflammatory tender nodules with hemorrhagic crusts, distributed more on the upper chest, back, and shoulders than on the face (7). The lesions often ulcerate with gelatinous, necrotic debris, and the healing is slow, leaving severe scars. The systemic symptoms include fatigue, malaise, axial arthralgia, joint swelling, myalgia, and fever.
AF if often associated with a leukemoid reaction (8). Patients may also have increased erythrocyte sedimentation rate (ESR) or C-reactive protein. Patients with lytic bone lesions may have elevated serum alkaline phosphatase levels (9). Microscopic hematuria, proteinuria, and other kidney abnormalities are some-times found. Laboratory studies are not helpful in establishing the diagnosis, but may be predictive of therapeutic response (10).
Aseptic osteolytic bone lesions have been reported at the clavicle, sternum, and long bones. Approximately 50% of patients have lytic bone lesions demonstrated on radiographs, and 70% of patients show increased uptake using technetium scintig-raphy (“hot spots”) (11). Destructive lesions resembling osteomyelitis are demon-strated on radiographs in 25% of patients. These frequencies may be elevated, since large studies are lacking and most cases of AF do not have imaging performed.
The differential diagnosis of AF includes acne vulgaris, rosacea fulminans/ pyoderma faciale, other acneiform eruptions, folliculitis, pyoderma gangrenosum, and acne conglobata.
Recurrence of AF occurs rarely. Severe scarring and keloid formation is com-mon. Bone lesions usually resolve with treatment but radiographic changes including hyperostosis may remain.
As with many uncommon dermatoses, there are no large randomized trials to consult for therapy, and we rely on the collective experience of small series and case reports. Topical, high-potency corticosteroids, applied on all ulcerated nodules as well as intralesional corticosteroids, may be beneficial in limited forms of the disease. Systemic steroids are a typically required treatment for AF. Systemic corticosteroids (0.5 1.0 mg/kg of prednisone) are indicated in AF, because they effectively control the skin lesions, reduce fever, and also have a favorable effect on the musculoskeletal symptoms. Symptoms tend to recur when the steroid dose is lowered or discontinued too quickly. Oral steroids should be started and gradually reduced over six weeks to avoid adverse effects of a prolonged course of systemic steroids. The required duration of steroid therapy is determined by symptoms and in rare instances may be as long as three to five months to avoid relapses (10). The relapse usually occurs two to eight weeks after the acute attack when the corticosteroids dosage is reduced or stopped (12). Typically, patients are simultaneously treated with minocycline or doxycycline as a steroid-sparing agent.
The combination of oral steroids and isotretinoin is beneficial. Isotretinoin is started after four weeks of corticosteroid treatment. The delay in starting isotretinoin therapy is necessary not to aggravate the AF (13 16). Isotretinoin should be started at four weeks, initially at 0.25 mg/kg daily and gradually increased to achieve complete clearance. Isotretinoin with a minimum total dose of 120 mg/kg is recommended. If required, a repeat course of isotretinoin (150 mg/kg) may be used. Duration of treatment depends on individual response and usually should not be less than three to five months (17).
Isotretinoin-induced AF typically but infrequently occurs in patients with moderate to severe trunk acne who are treated initially with higher dosages of the drug, for example, >40 mg/day. Acne appears to worsen and then develops ulcerative draining lesions. The isotretinoin should be discontinued or lowered radically, for example, to 10 mg/day and prednisone begun at least 1 mg/kg. Typically, several months of gradually decreasing prednisone and slowly increasing isotretinoin are required before the reaction resolves.
Other options have been reported including azathioprine (18), dapsone (19), methotrexate (20), sulfasalazine (20), cyclosporine A (21), bisphosphonates, and infliximab (22) with varying results. Dapsone has been shown to be effective treatment in patients with AF and erythema nodosum. Dapsone may be substituted for the retinoid if need be. The initial dose is 50 mg/day, which can be increased to 100 or 150 mg/day, rarely 200 mg/day (19,23 25). Pulsed dye laser may be an effective adjuvant treatment for AF associated granulation tissue (26).
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