Reactions Weekly | 2021
Multiple drugs
Abstract
Lack of efficacy: case report A woman in her 60s’ [exact age not stated] exhibited a lack of efficacy during treatment with leflunomide, methylprednisolone, cyclophosphamide, immune globulin and methotrexate for granulomatosis with polyangiitis (GPA) [not all routes and dosages stated]. The woman (at the age of 59 years) was referred to the rheumatology unit in 2003 following the development of symmetric polyarthritis of the small and large joints and a pulmonary nodule. She had a history of spontaneous abortion in the first trimester of pregnancy. On examination, a presumptive diagnosis of seronegative rheumatoid arthritis was made. Subsequently, she was treated with hydroxychloroquine and prednisone. After 2 months, she developed digital ischaemic lesions on her hands with necrosis in the first phalange of the third left finger, which led to autoamputation. She tested positive for lupus anticoagulant and anticardiolipin antibodies IgG and IgM. Anticoagulation treatment with acenocoumarol was initiated. In the next 3 years, she progressively developed left ptosis related to third cranial nerve palsy, distal sensory-motor polyneuropathy, sinusitis, bloody rhinorrhoea and livedo reticularis in her lower limbs with petechiae progressing to small necrotic ulcerations. Hence, treatment with leflunomide was included. Laboratory examination showed positive results for antineutrophil cytoplasmic antibody (c-ANCA), anti-proteinase 3 antibodies (anti-PR3) and a negative result for anti-CCP antibodies. Therefore, a diagnosis of GPA was made. Subsequently, she was treated with IV methylprednisolone 1 g/day for 3 days, followed by oral prednisone in tapering doses and IV cyclophosphamide 1 g/m2 monthly for 12 consecutive months. However, in May 2007, she developed painful ulcers in the right leg with the consequent formation of a large necrotic eschar. Hence, the woman underwent escharotomy, and anatomopathological findings revealed leucocytoclastic vasculitis and thrombosis. Between June and July 2007, her treatment with anticoagulation was discontinued after lower GI bleeding and pulmonary haemorrhage. Subsequently, she started receiving IV immune globulin [gammaglobulin; IVIG]. Treatment with cyclophosphamide was also re-started for 6 months, along with tapering doses of prednisone. In view of the severity of arthritis and no renal involvement, treatment with leflunomide 20 mg/day and methotrexate 15 mg/week was added to her treatment regimen. She also started receiving anticoagulation with acenocoumarol. In February 2009, she had extended skin lesions and necrosis. Therefore, two possible pathogenic mechanisms as thrombosis and vasculitis due to antiphospholipid antibody (APL) were considered. Therefore, she started receiving rituximab with a successful response. In November 2009, new skin lesions appeared with exophthalmia due to a right-sided retroorbital pseudotumor. Hence, she received another infusion of rituximab, which resulted in cutaneous and neurological improvement. Afterwards, she was continued on maintenance treatment with azathioprine, prednisone and rituximab till September 2013. Later, she was lost to follow-up. After discontinuing all types of therapies (in December 2013), she presented with severe renal failure. Eventually, she died due to complications of renal failure.