BackgroundInterstitial lung disease (ILD) is the most common internal organ manifestation of idiopathic inflammatory myopathies (IIM) that can severely affect the course of the disease. IIM patients with ILD often show resistance to conventional treatment with glucocorticoids (GC) and cytotoxic drugs so addition of biologic agents is an interesting possibility.ObjectivesTo assess efficacy and tolerability of rituximab (RTM) in IIM patients with ILD.MethodsIIM patients fulfilling Bohan and Peter criteria and having ILD were followed up in the Nasonova Research Institute of Rheumatology from 2009 to 2015. RTM was administered in case of intolerance or inadequate response to GC and other immunosuppressive drugs. Manual muscle testing (MMT), dyspnea assessment according to NYHA, creatinkinase (CK) and anti-Jo-1 antibodies (anti-Jo-1) assay; forced vital capacity (FVC) and carbon monoxide diffusion capacity (DLCO) evaluation as well as high-resolution computed tomography (HRCT) scanning of the chest were performed at baseline, 6–12 and 18–24 months after inclusion.Results41 patients (34 females, 7 males) with median age 50 [44;56], median disease duration 24 months [7;108] were included. 28 from them had decreased MMT value and class 1–2 NYHA dyspnea was present in 19. 18 patients were positive for anti-Jo-1 and 15 had elevated CK level. HRCT showed ILD signs including ground glass opacities (GGO) in all cases. FVC<80% was revealed in 16 and DLCO<80% - in 32 cases. All patients received GC 10–90 mg/day equivalent to prednisolone, 28 were treated with immunosuppressive agents (cyclophosphamide or mycophenolate mofetil). Patients received RTM courses consisted from 2 infusions of RTM 1000 or 500 mg at days 0 and 14. 1 RTM course was provided in 13, 2 – in 10, 3 – in 11, 4 – in 2, 5 – in 2, and 8 – in 3 patients. The follow up lasted for at least 12 months in 33, and for at least 24 months – in 15 patients. Dyspnea subsided and CK level decreased to normal values in all patients within 6–12 months after the first RTM infusion. 16 patients improved FVC by >10%, and 7 demonstrated DLCO increase by >10%. Worsening of pulmonary function tests was documented in 2 cases, while in the rest they were stable. After 18–24 months of follow up FVC remained +10% better vs baseline value in 10, DLCO – in 8 patients. In the rest patients these parameters remained stable. ILD was not progressing in 27 patients based on HRCT images in 6–12 months, moreover GGO lesions count was reduced in 10 patients, but there were cases of ILD worsening documented in 6 patients. Although, HRCT monitoring in 18–24 months showed ILD improvement in 7 patients and worsening – in 2, in remaining patients ILD was stable. Comorbid infections were documented in 18 patients, commonly manifesting in 2–3 months after the first RTM infusion.ConclusionsRTM treatment allows to achieve stable disease without typical for this condition further progression of pulmonary lesions in the majority of IIM patients with ILD.Disclosure of InterestNone declared

The article presents a review of the literature and a clinical observation of a patient with long-term anamnesis of primary Sjцgren's syndrome (SS) in combination with sporadic inclusion body myositis (sIBM). The diagnosis of SS was confirmed in accordance with the Russian diagnostic criteria for SS 2001, as well as with the ACR 2012 and ACR/EULAR 2016 criteria. The diagnosis of sIBM was established on the basis of a characteristic clinical picture: the development of the disease in a woman after 50 years of age with slowly progressive asymmetric muscle weakness and a typical distribution, a moderate increase in the level of creatine phosphokinase (<10 norms for the entire observation period), the presence of a generalized primary muscle process according to needle electromyography, a typical picture of muscle involvement according to magnetic resonance imaging, and the ineffectiveness of high doses of glucocorticoids. The absence of histological confirmation does not contradict the diagnosis, since morphological examination of muscles in patients with a typical course of the disease fails to detect characteristic signs of sIBM in 20% of cases.Currently, there is no effective pathogenetic therapy for sIBM. Understanding the mechanisms of sIBM development will allow to develop effective methods of its treatment.

BackgroundB-cell depletion therapy (BCDT) may improve the efficacy of conventional idiopathic inflammatory myopathies (IIM) treatment. However, administration of such drugs is associated with increased risk of adverse events, first of all – infections.ObjectivesTo assess the risk of infections in IIM patients receiving rituximab (RTM).MethodsThe study included IIM patients who required RTM therapy because of interstitial lung disease (ILD) or active myositis when administration of effective glucocorticoid (GC) dose was not possible. All patients continued treatment with GC and cytostatic drugs (CSD). RTM was administered at 1000 mg or 2000 mg doses (2 infusions of 500 mg or 1000 mg with 2 week interval). All patients were thoroughly examined at baseline and thereafter each 3 months after RTM infusion. Follow up period varied from 3 months to 4 years.Results38 IIM patients were enrolled (5 males and 33 females aged 22- 79 years, with 3-313 months duration of the disease). 22 patients received one RTM course, the rest 16 patients received 2 – 7 RTM courses. In the first course 17 patients received 2000 mg, 21 – 1000 mg of RTM, in each subsequent course 1000 mg were administered. At initiation of RTM all patients were on conventional therapy with GC in the dose varied from 10 to 90 mg/day prednisone equivalent (14 patients were taking 5 - 20 mg/day, 24 – more than 20 mg/day); 25 were taking CSD: 18– cyclophosphamide 600-2000 mg/month, 2– mycophenolate mofetil 1,5-2 g/day, 2- methotrexate 20 mg/week, 1- azathioprine 150 mg/day. Among patients taking GC at a dose ≤20 mg/day urinary tract infection was registered in 4 cases (3 – asymptomatic bacteriuria, 1- pyelonephritis), as well as one case of each - sinusitis and bronchitis. Among patients taking GC at a dose ≥20 mg/day there were 5 cases of pneumonia, 1 case of oropharyngeal candidiasis, 1- urogenic sepsis, 1- hepatitis B virus reactivation, 3 – herpes virus (HSV) infection, 1- immunosuppressive Kaposi sarcoma associated with HSV type 8 infection, and latent mycobacterial infection in 1 patient was diagnosed in 6 months after first RTM infusion. Infections usually occurred in 2-3 months after the first RTM infusion. All patients with upper and lower respiratory tract infections had ILD at baseline. There were 2 deaths in the cohort due to pneumonia and urogenic sepsis in patients with severe course of the disease. In remaining patients infection was eventually successfully controlled with no relapses (except for the only patient with bronchiectases and ILD, who had recurrent pneumonias). Tumor reduction was documented in Kaposi sarcoma patient.ConclusionsHigh activity of IIM in association with high or moderates GC doses and severe IDL at initiation of RTM therapy are the predictors of serious infectious adverse events. The highest risk emerges in 2-3 months after the first RTM infusion. Raising RTM dose up to 2000 mg was not associated with increased rate or severity of co-morbid infections. It remains unclear to what degree high doses of GC themselves would incre...

Background Similarity of muscle and skin symptoms during idiopathic polymyositis/dermatomyositis (DM/PM) and paraneoplasic myositis (PNM) makes clear the clinical tendencies of PNM. Objectives To determine the clinical tendencies of PNM. Methods We investigated 139 patients with PM/DM and 22 patients with PNM (4 males, 18 females). Laboratory investigation included definition of liver ferments, erythrocyte sedimentation rate (ESR), antibodies to Jo-1, creatinkinase (CK). The manual muscle testing (MMT) was performed according to IMACS recommendations. Results Duration of PNM was 8,68±11,6 months at the moment of investigation. Duration of investigation was 36,5±21,2 months. The mean age of patients with debut of PNM was 55,9 years. The tumor was diagnosed in 10 patients before the clinical manifestations of myositis, and in 12 (54,5%) patients after manifestation. Tumor localization was in ovaries (10 patients (45%)), breast (4 patients (18%)), lungs (4 patients (18%)), uterus (2 patients (10%)), colon (1 patient (4,5%)), and stomach (1 patient (4,5%)). Clinical presentation in debut of PNM included skin erythema (8 patients (81%)), ulcer vasculitis (3 patients (13,6%)), muscle syndrome (3 patients (13,6%)), and fever (1 patient (4,5%)). Dysphagia was determined in 19 patients (86,4%). MMT in patients with PNM before and the year after steroid therapy was similar to the patients with DM/PM. All patients with PNM were Jo-1 antibodies and interstitial lung disease negative. CK level in patients with PNM was lower to compare with patients with DM/PM (1893±1846 vs 3704±3916, p≤0,027); opposite, ESR level in patients with PNM was higher to compare with patients with DM/PM (31,65±15,16 vs 17,35+10,9, p≤0,0001). Levels of CK and ESR were the same after 12 months of steroid therapy. During the period of investigation 9 patients died, 9 patients survived. 4 patients had 5 years survival rate. The fate of 4 patients is unknown. 16 (72,7%) patients had skin erythema and 2 (9,09%) patients had ulcer vasculitis in period of normalized muscle power. The aggravation of PNM in 50% of patients was related to metastasis. Conclusions PNM occurs in 9,9% patients with DM/PM. Most of the patients are older 50 years. PNM has clinical features of DM. The main features are Jo-1 antibodies and interstitial lung disease negative, the high level of dysphagia, increasing of muscle power during steroid therapy, and not sufficient effect of steroid concerning skin syndrome. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3641

Differential diagnosis of inflammatory myopathies with hereditary muscular dystrophies accompanied by a secondary inflammatory process is a time‑consuming clinical and pathomorphological task. In particular, false diagnosis of polymyositis in patients with dysferlinopathy reaches 25 % of cases.A 40‑year‑old female patient with a limb‑girdle phenotype of dysferlinopathy, initially diagnosed as polymyositis, is presented. The reasons that led to the erroneous diagnosis were: sporadic case; subacute onset; proximal muscle weakness; myalgia, which stopped on the glucocorticosteroid therapy; high levels of creatine phosphokinase (up to 17 times); the presence of lymphocytic‑macrophage infiltrate in the muscle biopsy and the absence of magnetic resonance imaging data in primary examination of the patient.The refractoriness of clinical and laboratory signs to complex immunosuppressive therapy was the reason for revising the muscle biopsy with typing of the inflammatory infiltrate. The predominantly unexpressed perivascular infiltrate was characterized by the predominance of macrophages and, to a lesser extent, CD4+, which indicated the secondary nature of the inflammation in the muscle observed in some hereditary muscular dystrophies. When conducting an immunohistochemical reaction, the absence of the dysferlin protein in the sarcoplasmic membrane was revealed.Whole‑exome sequencing (NGS) revealed a mutation in exon 39 of the DYSF gene (p.Gln1428Ter) in the heterozygous state, which leads to the appearance of a stop codon and premature termination of protein translation. MLPA method registered 3 copies of exons 18, 19, 20, 22, 24 of the DYSF gene.Thus, this clinical example reflects the main methodological errors and possible effects of immunosuppressive therapy in patients with dysferlinopathy.