Recommendations for the treatment of anti-melanoma differentiation-associated gene 5-positive dermatomyositis-associated rapidly progressive interstitial lung disease.

OBJECTIVES: The study aimed to develop evidence-based recommendations for the treatment of rapidly progressive interstitial lung disease (RPILD) associated with the anti-Melanoma Differentiation-Associated Gene 5-positive dermatomyositis (DM) syndrome. METHODS: The task force comprised an expert panel of specialists in rheumatology, intensive care medicine, pulmonology, immunology, and internal medicine. The study was carried out in two phases: identifying key areas in the management of DM-RPILD syndrome and developing a set of recommendations based on a review of the available scientific evidence. Four specific questions focused on different treatment options were identified. Relevant publications in English, Spanish or French up to April 2018 were searched systematically for each topic using PubMed (MEDLINE), EMBASE, and Cochrane Library (Wiley Online). The experts used evidence obtained from these studies to develop recommendations. RESULTS: A total of 134 studies met eligibility criteria and formed the evidentiary basis for the recommendations regarding immunosuppressive therapy and complementary treatments. Overall, there was general agreement on the initial use of combined immunosuppressive therapy. Combination of high-dose glucocorticoids and calcineurin antagonists with or without cyclophosphamide is the first choice. In the case of calcineurin antagonist contraindication or treatment failure, switching or adding other immunosuppressants may be individualized. Plasmapheresis, polymyxin B hemoperfusion and/or intravenous immunoglobulins may be used as rescue options. ECMO should be considered in life-threatening situations while waiting for a clinical response or as a bridge to lung transplant. CONCLUSIONS: Thirteen recommendations regarding the treatment of the anti-MDA5 positive DM-RPILD were developed using research-based evidence and expert opinion.

Validation of the Japanese version of the Systemic Lupus Activity Questionnaire that includes physician-based assessments in a large observational cohort.

The Systemic Lupus Activity Questionnaire (SLAQ) is a patient-reported outcome for systemic lupus erythematosus (SLE). We aimed to translate it into Japanese and further investigate its validity and reliability. The English version of the SLAQ was translated into Japanese and administered to Japanese SLE patients at our university clinic. Physicians assessed disease activity using the SLE Disease Activity Index 2000 (SLEDAI-2K). The patients were prospectively followed for repeat assessment a year later. Ultimately, 255 patients participated. The patients' 10-point ratings of disease activity and SLAQ scores were significantly correlated (Spearman's ρ = 0.53). The SLAQ score was weakly correlated with the SLE Disease Activity Index 2000 (SLEDAI-2K)-nolab (omitting laboratory items; ρ = 0.18) but not with the SLEDAI-2K (ρ = 0.02). These results suggested its convergent and discriminant validity. The SLAQ demonstrated acceptable internal consistency (Cronbach's α = 0.80), and good test-retest reliability (intraclass correlation coefficient = 0.85). The effect sizes and the standardized response means of the SLAQ were as follows: clinical worsening, 0.26 and 0.31, and improvement, -0.39 and -0.41, respectively, which indicated a small but significant responsiveness. The Japanese version of the SLAQ demonstrated acceptable reliability and validity; its performance was comparable to that of the original version.

Peripheral nerve involvement in primary systemic AL amyloidosis: a clinical and electrophysiological study.

BACKGROUND: Involvement of visceral organs usually dominates the clinical picture of primary systemic AL amyloidosis, but some patients suffer from serious peripheral neuropathy. The aim of this study is to clinically and electrophysiologically investigate peripheral nerve involvement in AL amyloidosis patients. PATIENTS AND METHODS: We reviewed clinical manifestations, electrophysiological findings including nerve conduction velocities and treatments in 43 consecutive patients. Twenty age-matched healthy subjects were employed as controls. RESULTS: Fifteen patients (34.9%) showed apparent neuropathic symptoms, which consisted of polyneuropathy in 11 (25.6%), bilateral carpal tunnel syndrome in 4 (9.3%), and autonomic dysfunction in 8 (18.6%). Polyneuropathy in this disease was characterized by symmetrical and sensory-dominant impairment, early involvement of the lower limbs, loss of all sensations, rarity of motor weakness, and painful paresthesia in the legs predominant at an early stage. Autonomic dysfunction including orthostatic hypotension was frequently associated with polyneuropathy at an advanced stage. On electrophysiological studies, motor conduction velocity and compound muscle action potential of both median and tibial nerves were significantly decreased in the patients with polyneuropathy but also in those without any signs of neuropathy. Only four of 15 patients with neuropathy were able to receive intensive but promising chemotherapy with a large dose of melphalan for plasma cell dyscrasia. CONCLUSIONS: Peripheral nerves in primary systemic AL amyloidosis patients seem to be involved more extensively than clinical manifestations might suggest. The clinical picture of polyneuropathy in this disease closely resembles that in transthyretin-type familial amyloid polyneuropathy patients with a late age at onset, particularly those originating from sporadic kindreds.

Selective expression of MHC class I in the affected muscle of a patient with idiopathic inflammatory myopathy.

The dominant clinical feature of polymyositis/dermatomyositis is weakness in proximal, rather than distal, musculature. Although rare, cases of focal/localized myositis in which polymyositis-like muscle inflammation is present in only one muscle or extremity have also been reported. The underlying mechanisms dictating involvement of specific muscle groups in polymyositis/dermatomyositis and focal/localized myositis have not been identified. Here, we describe a rare case of dropped-head syndrome due to localized idiopathic inflammatory myopathy (IIM) in the splenius capitis (neck extensor) muscle where major histocompatibility complex (MHC) class I expression was up-regulated in involved muscle fibers. Interestingly, the adjacent trapezius muscle was not affected, corresponding to muscle biopsy findings that did not show any sign of inflammation or MHC class I expression. Our case report therefore suggests that selection of affected muscle in IIM might be influenced by the MHC class I expression of the muscle.

Analysis of peripheral blood lymphocytes using flow cytometry in polymyalgia rheumatica, RS3PE and early rheumatoid arthritis.

OBJECTIVE: Clinical pictures of poly-myalgia rheumatica (PMR) and remitting seronegative symmetrical synovitis with pitting edema (RS3PE) are often indistinguishable from those of early rheumatoid arthritis (RA). To investigate whether there is a difference in immunological aspects among these 3 disorders, we performed a phenotypic analysis of peripheral blood lymphocytes. PATIENTS AND METHODS: Eleven patients with early RA, 14 with PMR and 11 with RS3PE were enrolled in this study. After separation of mononuclear cells from peripheral blood using the Ficoll-Hypaque method, surface markers and intracellular cytokines of lymphocytes were analyzed by 2- or 3-color flow cytometry. RESULTS: Both PMR and RS3PE showed a significant decrease in CD8+CD25+ cells (p<0.05), and significant increases in CD4+IFN-gamma+IL-4- (p<0.05), CD8+IFN-gamma+IL-4- (p<0.05 and p<0.01, respectively) and CD4+TNF-alpha+ cells (p<0.05) compared with early RA. CD3+CD4+ cells were higher in PMR than in RS3PE (p<0.01), but there were no significant differences in any other phenotypes between these disorders. CONCLUSION: A decrease in activated cytotoxic/suppressor T cells and increases in circulating Th1 and Tc1 cells may be common characteristics of PMR and RS3PE in comparison with early RA. Both disorders are clearly different from early RA, and probably belong to the same disease entity with regard to phenotypes of peripheral blood lymphocytes.