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Complement levels were normal

Complement levels were normal. Differential?diagnosis Our patient had classical signs and symptoms of PMR; however, clinical challenges exist in distinguishing PMR from other disease mimics, including GCA, infection, malignancy, endocrine disorders and elderly?onset rheumatoid arthritis. clinical and the R-BC154 pathogenesis remains unknown. It is typically treated with 12.5C25?mg oral prednisolone.2 There is a clinical overlap with the related condition giant cell arteritis (GCA)1; both conditions are associated with elevated circulating interleukin?(IL)-6 levels. Here, we report a case of chronic lymphocytic leukaemia?(CLL) that developed PMR following therapy with idelalisib, a PI3K inhibitor, and rituximab. Case?presentation An 85-year-old Caucasian woman received idelalisib (Zydelig, Gilead Sciences) together with rituximab as part of a clinical trial for patients with previously untreated CLL with chromosome 17p deletion. The patient had been diagnosed with CLL in January 2013, initially presenting with anaemia, recurrent disseminated herpes zoster and a severe chest infection, without B?symptoms. At first, she was managed conservatively. However, over the next 2?years, her CLL progressed, with anaemia, thrombocytopaenia, lymphocytosis, widespread lymphadenopathy and palpable hepatosplenomegaly. In 2015, she commenced a clinical trial (Gilead GS-US-312C0133; EudraCT no: 2013-003314-41) in which rituximab 375?mg was administered intravenously once weekly for 8 weeks with oral idelalisib 150? mg given twice daily continuously throughout the study. Prior to treatment, her haemoglobin (Hb) was 7.5?g/dL, white cell?count (WCC) 163109/L, lymphocytes 160109/L, platelets 54109/L and lactate dehydrogenase (LDH) 777 IU/L (normal range 70C250 IU/L) and her C reactive protein?(CRP) was 15.5?mg/L. Antinuclear antibody was negative, plasma viscosity of 1 1.85 mPa-s, IgM 0.66?g/L, IgA 0.18?g/L and IgG 8.8?g/ L. Serum Rabbit polyclonal to Osteocalcin protein electrophoresis revealed an IgG kappa paraprotein. After 10 weeks of treatment within the clinical trial, she complained of bone pains that she managed with simple analgesia. After 18 weeks of therapy with idelalisib, she presented with increasing pain in her neck, shoulders and thigh muscles, early morning stiffness lasting greater than 1?hour and difficulty getting out of bed. Examination revealed limitation of movement of upper and lower limbs and clinical features suggestive of bilateral subacromial bursitis. There was no clinical evidence of synovitis, myositis or neurological disease. Investigations Blood R-BC154 tests revealed normal creatine kinase and an elevated CRP at 45?mg/L. Autoantibodies including antinuclear antibody?(ANA), antineutrophil cytoplasmic antibody?(ANCA) and rheumatoid factor were negative. Immunoglobulin levels had remained low since commencing the trial. Complement levels were normal. Differential?diagnosis Our patient had classical signs and symptoms of PMR; however, clinical challenges exist in distinguishing PMR from other disease mimics, including GCA, infection, malignancy, endocrine disorders and elderly?onset rheumatoid arthritis. The most commonly misdiagnosed diseases include malignancy and rheumatoid arthritis.3 Relevant tests that help to exclude PMR disease mimics include a negative rheumatoid factor, anticyclic citrullinated peptide antibody, ANA, together with normal levels of thyroid-stimulating hormone, creatine kinase, serum protein electrophoresis and vitamin D. Treatment She was initially treated with 2?weeks of 10?mg prednisolone with no symptomatic response and a rise in her CRP to 74?mg/L. The dose of oral prednisolone was therefore increased to 15?mg daily, together with injection of 40?mg methylprednisolone (Depo-Medrone) to the subacromial bursa on each side. This resulted in complete resolution of her pain within 3?weeks and a fall in CRP to 5.7?mg/L. This pattern of response R-BC154 to the said dose of glucocorticoid is very characteristic of PMR. Outcome and follow-up She followed a prednisolone taper following American College of Rheumatology/European League Against Rheumatism guidelines. Three months from her original presentation, after reducing the prednisolone dose from 10 to 9?mg, she had a relapse of symptoms in association with a rise in CRP to 39?mg/L. This responded well to an increase in prednisolone dose to 10?mg daily. Throughout the above, the patient continued to take idelalisib 150?mg twice a day. Her underlying haematological disease responded extremely well with improvement in her blood indices (Hb 9.8?g/dL, WCC of 5.17109/L, lymphocytes 2.05109/L, platelets 136109/L, LDH 559 IU/L) and CT scans showing significant reduction in nodal disease. Discussion Idelalisib is a first-in-class inhibitor of phosphatidylinositol-3-kinase (PI3K) p110 isoform .4 PI3K is highly active in B?cell malignancies and plays an essential role in the B?cell receptor pathway signalling and regulates cell proliferation, increased cellular metabolism and resistance to apoptosis.4 5 Idelalisib is used in combination with rituximab as a treatment option for patients with.