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Targeted inhibition of tumour necrosis factor-α (TNF-α) is an effective therapy in rheumatoid arthritis and Crohn's disease (CD). Infliximab, a monoclonal murine-human chimeric antibody to TNF-α, and etanercept, a fusion protein of two p75 chains of the TNF receptor II and the Fc portion of IgG1, are generally well tolerated. Rarely does clinically significant autoimmunity, including drug-induced lupus and vasculitis occur. Immunologic mechanisms underlying the development of autoimmunity in the presence of such powerful immunosuppressants are unknown. We describe a patient with CD, who developed cutaneous vasculitis on etanercept, which worsened significantly with switch to infliximab. Investigation of the associated systemic and local immune response demonstrated the absence of human antichimera antibodies, but mRNA for T-helper 1 cytokines, chemokines and defensins in the skin and elevated angiogenesis factors in the serum, as determined by reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. Histopathology revealed a lymphocytic vasculitis composed of T cells. A permanent B-cell line (MD-B) producing extremely high amounts of chemokines and interleukin-6 was established from this patient's peripheral blood. Lesions progressed despite discontinuation of the drugs and (40 mg/day) prednisone but almost completely resolved with single dose of (0.1 mg/kg) intravenous dexamethasone, which may be therapy of choice for this reaction. A few lesions (<10) have recurred intermittently over 4 years of follow-up, suggesting possible persistence of this TNF-inhibitor-triggered autoimmune disease. [ABSTRACT FROM AUTHOR]

A 70-year-old patient with a chronic cutaneous ulcer treated by minocycline hydrochloride developed hyperpigmentation of the forearms. Biopsy material was studied by light microscopy, electron microscopy and X-ray energy spectroscopy. Granular gold-brown pigment was found in dermal histiocytes and eccrine myoepithelial cells, which gave positive reaction with Prussian blue and Fontana-Masson stains. Electron microscopy revealed intracytoplasmic granules of dark, homogeneous material and small line particles. X-ray energy spectroscopy showed iron and other elements in smaller amounts. The different types of minocycline-related hyperpigmentation and the possible patho-mechanism are discussed with special regard to the importance of the diagnostic methods. [ABSTRACT FROM AUTHOR]