Background /Aim: Acne fulminans is a rare form of acne vulgaris with acute clinical deterioration including systemic signs. Etiopathogenesis and management remain largely unknown. Our aim is to assess the efficacy of a combined therapeutic regimen of systemic isotretinoin and prednisolone following the recent concepts of acne pathogenesis and drug kinetics. Methods: A prospective case series was recruited over 15 years. Isotretinoin 0.5 mg/kg bw/d (0.25-0-0.25) and prednisolone 30 mg/d (10-10-10) were administered concomitantly with prednisolone being tapered after that time. The overall efficacy was evaluated at month 1 and every month thereafter. Daily drug doses were split to reduce the risk for adverse effects. Results: 26 patients (20 male, 77%) at a mean age of 19 years and a history of acne vulgaris of 3.2 years presented acutely necrotic and ulcerating skin papules (100%), fever (45%), arthralgia (38.5%), leukocytosis (88.5%) and elevated erythrocyte sedimentation rate (100%). After one month of treatment resolution of systemic signs was achieved in all patients and a >50% skin lesion improvement in 17 patients (65%). Conclusion: The concomitant administration of isotretinoin (0.5 mg/kg bw/d, 0.25-0-0.25) and prednisolone 30 mg/d (10-10-10) is able to resolve systemic signs and markedly improve skin lesions in 65% of the patients at one month.