Five cases of livedo‐like dermatitis (Nicolau’s syndrome) due to bismuth salts and various other non‐steroidal anti‐inflammatory drugs

Abstract

The authors report five cases of Nicolau's syndrome observed over a period of about 25 years. The disease had occurred after intramuscular injections of different drugs (bismuth, diclofenac and ibuprofen). In all the described cases the clinical aspect was characterized by a livedoid pattern followed by a slow necrotizing evolution with scar formation; in some cases surgical debridement and plastic reconstructive surgery were performed. In the past Nicolau's syndrome was described after intramuscular injections of bismuth salts for the treatment of syphilis; now, although still rare, it is described after injections of various aqueous drug solutions. The pathogenesis of Nicolau's dermatitis appears to be more complex than the previous hypothesized embolism caused by oleous drugs.

Freestyle Perforator-Based Fasciocutaneous Flap Reconstruction in Nicolau Syndrome-Related Tissue Necrosis

“…Rapid administration of steroids, anticoagulants, and vasoactive agents has been emphasized for clinical improvement and regression of the livedoid lesions whereas it has been demonstrated that heparin and pentoxifylline are useless in preventing the development of necrosis [1,3,10,22]. Hyperbaric oxygen treatment may be beneficial at the early onset of disease [10].…”

“…However, inappropriate injections of drugs (i.e., inadvertent subcutaneous or intraarterial injections) may cause locoregional tissue damage which is known as Nicolau syndrome (NS), synonymously livedo-like dermatitis or embolia cutis medicamentosa [1]. The actual physiopathology of the NS is yet unknown; it has been proposed that the direct arterial damage and vasoconstrictive effects of various drugs may induce inflammation and subsequently cause skin necrosis [2,3].…”

“…If it is diagnosed during early onset, treatment may be conservative [3]. However, if skin necrosis occurs; surgical intervention including debridement and reconstruction is mandatory [1]. Although clinical features of NS have been reported in many case reports, NS-related skin defects are often underestimated and are not studied in detail.…”

Nicolau Syndrome Due to Diclofenac Injection: Case Report

“…2 Up to date, NS cases have been reported in relation with using antiinflammatory drugs, local anesthetics, corticosteroids, antihistamines, vitamin B complexes, sulfonamides, penicillin, recombinant interferon alpha and beta, vaccines (varicella and diphtheria-tetanus-pertussis), pyrazolone, and etanercept. [3][4][5][6][7][8][9][10] A possible cause is the development of arterial spasm following a tissue necrosis after the drug is injected into a blood vessel by mistake. 1 Actually, diclofenac is a cyclo-oxygenase inhibitor and inhibits synthesis of prostaglandin.…”

“…3 For intramuscular injections, generally thighs are preferred in children and gluteal area in adults. In reported cases up to date, lesions have been compatible with these preferences.…”