LAUSR

Polymyalgia rheumatica (PMR) is a common, rheumatic inflammatory disease causing debilitating pain and stiffness of the shoulder and hip girdle. Inflammation of bursae and tendon sheaths is a key finding in PMR. Glucocorticoids have remained the mainstay of treatment for 60 years. Alternative treatments for PMR are highly needed, since half of patients require prolonged treatment, which is associated with substantial toxicity. 2 A recent phase 2/3 trial has shown promising efficacy of antiinterleukin (IL)−6 receptor (antilIL6R) therapy for newonset PMR: 63% of patients treated with antiIL6R therapy reached glucocorticoidfree remission at week 16, whereas 12% of placebotreated patients reached this primary end point. The biological rationale for targeting the IL6 pathway stems from the observation that serum levels of IL6 are increased in PMR. 4 However, it is unclear whether IL6 is also expressed in the tissues affected by PMR. We investigated the expression of IL6 in synovial tissue obtained from six patients with newonset, treatmentnaïve PMR (four women; median age 72 years, range 58–79) showing subacromialsubdeltoid (SASD) bursitis on ultrasonography. The median erythrocyte sedimentation rate at the time of the biopsy collection was 67 mm/hour (range 39–89) and serum C reactive protein was 67 mg/L (range 3–118). All patients fulfilled the Chuang criteria for PMR. Their diagnosis was confirmed after 6 months of followup and concomitant largevessel giant cell arteritis was ruled out by vascular ultrasonography and/or FDGPET/CT. Synovial tissue was obtained at diagnosis from the SASD bursa by ultrasoundguided biopsy with a 16G core needle (Argon Medical Devices). All bursae showed some level of synovial hypertrophy with power Doppler signal on ultrasound examination (online supplemental figure S1). The number of biopsies available from each patient was five (n=5 patients) or three (n=1 patient). More details are provided in online supplemental methods. First, synovitis scores according to Krenn et al were determined on H&Estained slides. The median synovitis score was 2.5 (range 1–5.5), suggestive of lowgrade synovitis. Next, immunohistochemistry was performed for IL6 (figure 1A,B). A large number of IL6 cells was observed throughout the synovial tissue, as indicated by semiquantitative scoring (figure 1C). A semiquantitative score of 4 was obtained for IL6 expression in the patient in which three biopsies were obtained. Subsequently, immunofluorescence was applied on biopsies of all patients to identify potential cellular sources of IL6. This cytokine was detected in substantial portions of CD34 endothelial cells, CD34 fibroblasts/stromal cells, CD90 fibroblasts and CD68 macrophages (figure 1D–F and online supplemental figure S24). Bearing in mind the limited number of patients, no correlation was found between semiquantitative IL6 scores in the tissue and Letter