**9. Morphea-like reactions**

Morphea, also called localised scleroderma, is manifested by thickening of the skin and subcutaneous tissue due to the deposition of excessive amounts of collagen. There are only a few cases of morphea induced by TNF-alpha reported in the literature. Morphea may be induced by mechanical effects or by medications. The exact etiopathogenesis of TNF-alpha-induced morphea is not known, although there are several theories of possible etiopathogenesis. TNF inhibitors can act on tumour growth factor beta (TGF beta 1), a profibrotic cytokine that effects the growth and accumulation of extracellular matrix by the action of fibroblasts and endothelial cells. An increase in Th1 and Th17 proinflammatory cytokines has been demonstrated in the early stage of localised scleroderma. Th2 lymphocytes correlate with the severity of the disease and the extent of fibrosis. Inhibition of Th1 response induced by TNF-alpha inhibitors may lead to the prevalence of Th2 lymphocytes, which may be the cause of morphea [48].
