Rheumatoid arthritis, gold therapy, contact allergy and blood cytokines

OBJECTIVE: To study the clinical and biochemical effects of a low starting dose for gold therapy in rheumatoid arthritis patients with a contact allergy to gold. METHODS: Serum cytokines were assayed before and 24 h after the first injection of gold sodium thiomalate (GSTM). RESULTS: Contact allergy to gold was found in 4 of 19 patients. Compared to gold-negative patients (starting dose: 10 mg GSTM), there was a larger increase in serum TNFalpha (p < 0.05), sTNF-R1 (NS), and IL-1 ra (p < 0.05) in gold-allergic patients. CONCLUSIONS: Cytokines are released in blood by GSTM in RA patients with gold allergy. To minimize the risk of acute adverse reactions the starting dose of GSTM should be lowered to 5 mg. Alternatively, patients should be patch-tested before gold therapy; in test-positive cases, 5 mg is recommended as the first dose

Pemphigus autoimmunity: Hypotheses and realities

The goal of contemporary research in pemphigus vulgaris and pemphigus foliaceus is to achieve and maintain clinical remission without corticosteroids. Recent advances of knowledge on pemphigus autoimmunity scrutinize old dogmas, resolve controversies, and open novel perspectives for treatment. Elucidation of intimate mechanisms of keratinocyte detachment and death in pemphigus has challenged the monopathogenic explanation of disease immunopathology. Over 50 organ-specific and non-organ-specific antigens can be targeted by pemphigus autoimmunity, including desmosomal cadherins and other adhesion molecules, PERP cholinergic and other cell membrane (CM) receptors, and mitochondrial proteins. The initial insult is sustained by the autoantibodies to the cell membrane receptor antigens triggering the intracellular signaling by Src, epidermal growth factor receptor kinase, protein kinases A and C, phospholipase C, mTOR, p38 MAPK, JNK, other tyrosine kinases, and calmodulin that cause basal cell shrinkage and ripping desmosomes off the CM. Autoantibodies synergize with effectors of apoptotic and oncotic pathways, serine proteases, and inflammatory cytokines to overcome the natural resistance and activate the cell death program in keratinocytes. The process of keratinocyte shrinkage/detachment and death via apoptosis/oncosis has been termed apoptolysis to emphasize that it is triggered by the same signal effectors and mediated by the same cell death enzymes. The natural course of pemphigus has improved due to a substantial progress in developing of the steroid-sparing therapies combining the immunosuppressive and direct anti-acantholytic effects. Further elucidation of the molecular mechanisms mediating immune dysregulation and apoptolysis in pemphigus should improve our understanding of disease pathogenesis and facilitate development of steroid-free treatment of patients

Aplicação da dermatoscopia no auxílio diagnóstico da ocronose exógena Use of dermoscopy for diagnosis of exogenous ochronosis

A ocronose exógena consiste em hiperpigmentação crônica de áreas previamente tratadas com agentes tópicos como: a hidroquinona, a resorcina, os antimaláricos e o fenol. O diagnóstico precoce permite suspender prontamente o agente causador, uma vez que as opções terapêuticas disponíveis são escassas e com resultados insatisfatórios. Reportam-se três casos de ocronose exógena na face, diagnosticados pela dermatoscopia. O estudo dermatoscópico evidenciou estruturas amorfas de coloração cinza-enegrecido, algumas obliterando as aberturas foliculares. O exame histopatológico corroborou o diagnóstico<br>Exogenous ochronosis consists of chronic hyperpigmentation of areas previously treated with topical agents such as hydroquinone, resorcinol, antimalarials and phenol. Early diagnosis allows to promptly suspend the causative agent and it is imperative since the available therapeutic options are scarce and have presented so far unsatisfactory results. Three cases of exogenous ochronosis on the face which were diagnosed with the use of dermoscopy are presented. Dermatoscopy showed blackish-gray amorphous structures, some obliterating the follicular openings. Histopathological examination confirmed the diagnosi