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Background/Aims Digital ischaemia is an umbrella term to describe the spectrum of acral vascular phenomena irrespective of aetiology, ranging from temporary (as in Raynaud’s phenomenon) to permanent (necrosis). It can be the presenting feature in multiple cancer types, and can be present with or without other features of connective tissue disease. Methods A 54-year-old woman was referred to Rheumatology with a four-day history of acute pain and ischaemic discolouration of all her fingertips bilaterally. There was no history of Raynaud’s phenomenon and no other clinical features of connective tissue disease. She had never smoked. There was a family history of breast cancer in her maternal aunt. She was admitted under vascular surgery for urgent review. All ten fingertips were ischaemic, with a capillary refill time of greater than five seconds. The history was otherwise significant for abdominal bloating, altered bowel habit and fatigue. Examination revealed normal peripheral pulses with no bruits, normal heart sounds and chest sounds. Her abdomen was soft with a mildly enlarged liver. Results FBC, U&E, and LFTs showed no abnormalities. CRP, ESR, ANA, serum protein electrophoresis and complement levels were all normal. Blood tests for ANCA, rheumatoid factor and anti-CCP were also negative. Lupus anticoagulant, anti-cardiolipin and anti-B2-glycoprotein were all negative. The tumour marker CA125 was markedly elevated at 837kU/L (0.0-35.0kU/L). A CT abdomen & pelvis showed a large right-sided adnexal mass with multiple enhancing peritoneal and omental nodules and moderate ascites. Biopsy of a metastatic deposit in the omentum revealed high grade serous ovarian adenocarcinoma. Partial improvement in digital ischaemia was achieved with iloprost and maintenance apixaban and sildenafil. Four cycles of carboplatin and paclitaxel chemotherapy produced near-complete resolution of digital ischaemia symptoms, corresponding to a fall in her CA125 level and reduction in the size of the ovarian mass and intra-abdominal metastases on CT. Ten cases of digital ischaemia associated with ovarian cancer have been described prior to this. The age of onset ranged from 45 to 71, with a median age of 56. Most patients had digital ischaemia without features of connective tissue disease. Four had no blood test abnormalities other than a raised tumour marker CA125. The time from onset of digital ischaemia to diagnosis of ovarian cancer ranged from less than one week to 2 years, with a median time of four months. Conclusion This case study supports previous findings that patients with digital ischaemia associated with ovarian cancer may have normal markers of inflammatory or rheumatological disease. Marked therapeutic responses can be achieved with systemic anti-cancer therapies. Therefore, underlying cancer should be suspected in patients with new-onset or worsening digital ischaemia over the age of 45. A high index of suspicion is required - rheumatologists beware! Disclosure J.H. Miller: None. P. Merry: None.

Introduction/Background Those working in Rheumatology frequently encounter cytopaenia both as adverse effects of many conventional and biological disease modifying drugs and as manifestations of autoimmune diseases. In cases where cytopaenia progresses, other explanations should be sought. Here we present an unusual cause of cytopaenia, seen in a patient with psoriatic arthritis on immunosuppression. Description/Method An 81-year-old woman with a diagnosis of psoriatic arthritis had been maintained on Infliximab (3mg/kg 8 weekly) and Methotrexate (7.5mg PO weekly) for 12 years. She then developed mild neutropaenia (1.52 x 109/L). Methotrexate was stopped and she continued on Infliximab monotherapy for several months, until ongoing neutropenia resulted in Infliximab being withheld. Sustained mild neutropenia and the development of thrombocytopenia (platelets 95 x 109/L) prompted a referral to Haematology, who suspected autoimmune neutropenia and advised checking haematinics and monitoring the FBC monthly. The neutropenia improved and Infliximab was restarted. Over 6 months she developed gradually worsening and persistent pancytopenia (neutrophils 1.36 x 109/L, platelets 134 x 109/L, Hb 91 g/L). There was no history of fevers, night sweats, bone pain, headaches, recurrent infections, lumps or bumps, chest symptoms, change in bowel habit or urinary symptoms. Examination revealed no pallor, jaundice, clubbing, peripheral lymphadenopathy or sternal tenderness. The chest was clear and the abdomen soft with no organomegaly. Repeat bloods showed microcytic hypochromic anaemia (Hb 86 g/L, MCV 73 fL, MCH 24.6 pg) with target cells on blood film. Iron was low (iron 5.1 umol/L, transferrin 1.52 g/L). Serum protein electrophoresis showed paraprotein bands with abnormal serum free light chain assay possibly consistent with myeloma, lymphoma or MGUS. Haematology suspected myelodysplasia, potentially secondary to previous long term Methotrexate therapy. A bone marrow biopsy was performed; the unexpected result was Leishmaniasis. Our patient was admitted to hospital and, following microbiology review, was treated with liposomal amphotericin (IV) for Visceral Leishmaniasis as an inpatient. Her Infliximab was suspended and her joints have remained quiescent. Discussion/Results Leishmania is an intracellular parasitic protozoan that is transmitted to humans by sandfly bites. It is endemic in Africa, America, Central Asia and the Mediterranean. It usually has an incubation period of 3-8 months. Those who are immunosuppressed, for example due to immunotherapy or HIV, are at increased risk of infection. The patient had only ever travelled to Portugal and Gibraltar. One trip to Gibraltar occurred whilst on dual immunosuppression with Infliximab and Methotrexate and prior to the development of neutropenia. She has no recollection of any insect bites. Visceral leishmaniasis is variable in the severity of symptoms experienced ranging from asymptomatic to a febrile illness with lymphadenopathy, hepatospenomegaly, night sweats, cutaneous pigmentation, appetite loss and weight loss, which can be drastic. Our patient indeed described significant weight loss in the preceding year. This case demonstrated the laboratory abnormalities which are typical of Visceral Leishmaniasis: pancytopenia and hypergammaglobulinaemia. Treatment for visceral Leishmaniasis has classically been with pentavalent antimonials (based on the heavy metal antimony) such as Sodium stibogluconate. Their toxicity profile and growing resistance however has meant amphotericin B is often used first line. This is given intravenously, with the liposomal form preferred as it has lower toxicity. Our patient received 4 mg per kg daily on days 1–5, 10, 17, 24, 31, and 38, following the FDA-approved regimen for immunosuppressed patients. Without treatment Leishmaniasis is usually fatal, with haemmorrhage, infection, cachexia and multiorgan failure as causes of death. Key learning points/Conclusion Whilst patients with Rheumatological conditions may have cytopaenia due to their disease or its treatment, persistent, progressive or unexplained results should be investigated further. In patients with cytopaenia of unclear aetiology, thorough investigation with Haematology involvement is mandatory. You may find an unexpected diagnosis … we did!

[Figure][1] Professor Merry was born on 1 June 1923 in the East End of London, then a depressed, poverty-stricken ghetto. His parents were Jewish e migres from eastern Europe, whose surname was Lustigman, the name Julius carried until expediency obliged him to change it. His father, the

Previous work has established the existence of a pathophysiological environment within the inflamed human joint, capable of sustaining a hypoxic-reperfusion event. Using four different assay systems (two standard and two novel) applied to synovial fluid for the assessment of lipid peroxidation, a series of studies demonstrate that exercise of the inflamed human knee promotes radical-mediated lipid peroxidation within the joint. The implication for novel antioxidant therapeutic approaches to inflammatory joint disease is discussed.

Biological reduction of molecular oxygen in cells is accompanied by the production of dangerously reactive free radical and non-radical oxygen species. Because of the ubiquity of molecular oxygen and its ability to accept electrons, their production is readily associated with cellular damage1.

Revue du role des radicaux libres dans la synovite. Definition. Production de radicaux libres chez le sujet sain; role fondamental dans les reactions d'oxydation. Discussion de leur place exacte dans la genese des lesions tissulaires dans les maladies articulaires inflammatoires (modeles animaux, homme)