RESUMO
OBJECTIVE: Methotrexate (MTX) is a disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis (RA). Genetic polymorphisms of reduced folate carrier (RFC1 A80G), P-glycoprotein (MDR1 G2677T>A/C and C3435T), 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), thymidylate synthase (TS 2R-->3R), methionine synthase (MS A2756G) and methionine synthase reductase (MTRR A66G) modify MTX transport and metabolic effects and may influence the treatment response. METHODS: A genotyping approach was used to determine the studied polymorphisms in 213 RA patients. RESULTS: We observed that 56 (26.3%) patients discontinued MTX treatment due to poor response and/or toxicity. RFC1 A80G and MDR1 C3435T polymorphisms increased the risk for overall MTX toxicity (P = 0.039, OR = 3.574, 95% CI = 1.065-11.993 and P = 0.032, OR = 7.801, 95% CI = 1.194-50.960 respectively), while MTHFR A1298C polymorphism had a protective effect on overall MTX toxicity (P = 0.027, OR = 0.170, 95% CI = 0.035-0.820). CONCLUSION: Our results suggest that genetic polymorphisms in the folate metabolic pathway and MTX transporters modify the toxicity but not the efficacy of MTX treatment.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Ácido Fólico/metabolismo , Metotrexato/metabolismo , Metotrexato/toxicidade , Polimorfismo Genético , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Idoso , Transporte Biológico , Feminino , Ferredoxina-NADP Redutase/genética , Humanos , Masculino , Proteínas de Membrana Transportadoras/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pessoa de Meia-Idade , Timidilato Sintase/genéticaRESUMO
This report illustrates a case of peripheral nerve vasculitis associated with elevated anticardiolipin antibodies. A 49-year-old female with a history of seven spontaneous abortions initially complained of pain and numbness in her right calf that later spread to the left foot and ankle. Over the next few months, she developed a Raynaud phenomenon and livedo reticularis. Clinical examination revealed signs of multiple mononeuropathy. Right sural nerve biopsy performed two months after the beginning of the disease revealed active necrotizing arteritis of the epineural arteries with transmural inflammatory infiltrate and thrombosis. Vasculitis is a rare finding in sural nerve biopsies, usually in patients with systemic vasculitis or autoimmune connective tissue diseases. However, vasculitis restricted to the peripheral nerves has also been described. Our patient had no clinical or laboratory features of any autoimmune disorder and also no signs of systemic vasculitis. We discuss the potential role of anticardiolipin antibodies in the pathogenesis of vasculitis.
Assuntos
Anticorpos Anticardiolipina/sangue , Mononeuropatias/etiologia , Vasculite/complicações , Aborto Espontâneo , Síndrome Antifosfolipídica/complicações , Exantema/etiologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Mononeuropatias/sangue , Mononeuropatias/patologia , Dor/etiologia , Gravidez , Doença de Raynaud/etiologia , Dermatopatias Vasculares/etiologia , Nervo Sural/irrigação sanguínea , Nervo Sural/patologia , Vasculite/sangue , Vasculite/patologiaRESUMO
Amyloid A (AA) (secondary) amyloidosis represents a severe complication of chronic inflammatory diseases. Since pathogenic mechanisms point to the central role of interleukin 6 (IL-6) in the process of amyloid AA generation, IL-6 blockade seems an attractive therapeutic option. We report a case of a patient with polyarteritis nodosa complicated by AA amyloidosis treated with tocilizumab.