Valproate-acid-induced cutaneous leukocytoclastic vasculitis.

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Vasculitis is an inflammatory disease of blood vessels characterized by the alteration or destruction of the vessel wall. There are three subtypes of vasculitis according to Chapel Hill Consensus Conference defi-nition: Large Vessel Vasculitis, Medium-Sized Vessel Vasculitis and Small Vessel Vasculitis. Drug-induced vasculitis is usually Small Vessel Vasculitis represented as Leukocytoclastic Vasculitis. Leukocytoclastic Vasculitis is relatively common, with an incidence of 20:100 000 yearly. There are no age or sex predictions. The key event is the deposition of immune complexes in the walls of the capillaries and venules. In most cases, the process is a type III immune complex-mediated reaction according to the Gell and Coombs's classi-fication of hypersensitivity reactions. Typical triggers for acute disease include infections and drugs, while recurrent disease is usually associated with hepatitis C infection, collagen-vascular disorders, hematological diseases or malignancy. The cutaneous features of leukocytoclastic vasculitis are highly variable and may change rapidly. Almost all eruptions are symmetric, and the legs are most heavily involved. There is often swelling and pain. Mucosal surfaces are spared. The following clinical patterns can be seen, with wide degrees of overlap: hemorrhagic type, hemorrhagic-necrotic type, papulonecrotic type, polymorphous-nodular type, annular type, pustular type and urticarial type. Leukocytoclastic vasculitis can also occur internally. It may affect certain organs, usually the kidneys or portions of the gastrointestinal tract, though the heart, lungs, and nervous system can also be involved. It can also occur in the joints. There are no significant differences in clinical presentation, serologic abnormalities, and pathologic findings with the idiopathic forms of vasculitis. Skin lesions are characterized by leucocytoclasia and fibrinoid necrosis of the blood vessels. The classic manifestation is destruction of the small blood vessels in the papillary dermis. There is exocytose of erythrocytes, accumulations of neutrophils with nuclear dust, or debris (leukocytoclasia), fibrin deposition in the vessels wall and focal necrosis of the dermis. Early lesions may be dominated by lymphocytes and have little vessel destruction; late lesions may show primarily necrosis. Early lesions almost always have intra- and peri-vascular deposition of C3, IgG and IgM. The outlook varies with the presence of associated disorders or known triggers. Leukocytoclastic vasculitis associated with medications or infections resolves rapidly when the responsible agent is removed. Treatment of leukocytoclastic vasculitis can vary depending on the patient's situation. The most important is to remove possible triggers and to treat any underlying disorder. A patient generally does better with avoidance of standing, resting in bed, elevation of the legs, and compression bandaging of the lower aspects of the legs. Topical therapy revealed application of High-potency corticosteroid creams under occlusion and may be helpful in treating early lesions. For mild recurrent or persistent disease, colchicine and dapsone are first-choice agents. Severe cutaneous and systemic disease requires more potent immunosup-pression (prednisone plus azathioprine, methotrexate, cyclophosphamide, cyclosporine, or mycophenolate mofetil). Valproic acid (VPA) is a chemical compound and an acid that has found clinical use as an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder, and, less commonly, atypical depression with hypersomnia. It is also used to treat migraine headaches and schizophrenia. Dermatological side effects of psychopharma-cological drugs are most common in group of mood stabilizers and antiepileptic drugs, especially related with carbamazepine and lamotrigine. Valproic acid has been associated with stomatitis and cutaneous leukoclastic vasculitis. A case of psoriasiform eruption has been reported in a patient receiving valproic acid. Dermatologic side effects including transient alopecia (2.6-12%), thinning of the hair, hair color changes, hair texture changes, and rare rashes have been reported. Valproic acid has been

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