Toxic epidermal necrolysis and Stevens-Johnson syndrome

Toxic epidermal necrolysis (TEN) and Stevens Johnson Syndrome (SJS) are severe adverse cutaneous drug reactions that predominantly involve the skin and mucous membranes. Both are rare, with TEN and SJS affecting approximately 1or 2/1,000,000 annually, and are considered medical emergencies as they are potentially fatal. They are characterized by mucocutaneous tenderness and typically hemorrhagic erosions, erythema and more or less severe epidermal detachment presenting as blisters and areas of denuded skin. Currently, TEN and SJS are considered to be two ends of a spectrum of severe epidermolytic adverse cutaneous drug reactions, differing only by their extent of skin detachment. Drugs are assumed or identified as the main cause of SJS/TEN in most cases, but Mycoplasma pneumoniae and Herpes simplex virus infections are well documented causes alongside rare cases in which the aetiology remains unknown. Several drugs are at "high" risk of inducing TEN/SJS including: Allopurinol, Trimethoprim-sulfamethoxazole and other sulfonamide-antibiotics, aminopenicillins, cephalosporins, quinolones, carbamazepine, phenytoin, phenobarbital and NSAID's of the oxicam-type. Genetic susceptibility to SJS and TEN is likely as exemplified by the strong association observed in Han Chinese between a genetic marker, the human leukocyte antigen HLA-B*1502, and SJS induced by carbamazepine. Diagnosis relies mainly on clinical signs together with the histological analysis of a skin biopsy showing typical full-thickness epidermal necrolysis due to extensive keratinocyte apoptosis. Differential diagnosis includes linear IgA dermatosis and paraneoplastic pemphigus, pemphigus vulgaris and bullous pemphigoid, acute generalized exanthematous pustulosis (AGEP), disseminated fixed bullous drug eruption and staphyloccocal scalded skin syndrome (SSSS). Due to the high risk of mortality, management of patients with SJS/TEN requires rapid diagnosis, evaluation of the prognosis using SCORTEN, identification and interruption of the culprit drug, specialized supportive care ideally in an intensive care unit, and consideration of immunomodulating agents such as high-dose intravenous immunoglobulin therapy. SJS and TEN are severe and life-threatening. The average reported mortality rate of SJS is 1-5%, and of TEN is 25-35%; it can be even higher in elderly patients and those with a large surface area of epidermal detachment. More than 50% of patients surviving TEN suffer from long-term sequelae of the disease

Severe cutaneous adverse reactions due to inappropriate medication use

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[Severe tularaemia mimicking glandular tuberculosis during adalimumab therapy].

International audienceBACKGROUND: Tularaemia is an anthropozoonosis, transmitted by small mammals (hares) and arthropods (ticks, horseflies). The causative agent is Francisella tularensis, a facultatively intracellular Gram-negative bacillus. We report a case of tularaemia in its ulceroglandular form occurring during methotrexate and adalimumab treatment (Humira) for rheumatoid arthritis. PATIENTS AND METHODS: A 58-year-old man with a history of primary tuberculosis receiving adalimumab in combination with methotrexate for rheumatoid arthritis for almost 1 year consulted for a febrile inflammatory plaque on the left leg with a small central necrotic area. An enlarged left inguinal lymph node was present. Doxycycline has previously been prescribed for a tick bite. The lymphadenopathy gradually became enlarged resulting in skin fistulisation. After surgical excision, histopathology revealed epithelioid granulomas accompanied by giant cells and central necrosis. Mycobacterial cultures were negative. Positive tularaemia serology at significant titres suggested a diagnosis of tularaemia, with probable transmission via a tick bite. The diagnosis was confirmed by F. tularensis DNA amplification using PCR on a lymph node biopsy. Doxycycline was continued for a further 6 weeks. One year later, no relapse had occurred. DISCUSSION: A febrile adenopathy presenting the histological features of necrotic granulomas in a patient receiving anti-TNF alpha treatment initially suggested reactivation of tuberculosis. However, the history of tick bite and failure to isolate mycobacteria from different tissue specimens prompted screening for a tick-borne disease, finally leading to a diagnosis of tularaemia. We discuss the possible relationship between immunosuppression and the clinical course of this rare infection