Siamak Moghadam-Kia

Anti-Melanoma Differentiation-Associated Gene 5 Is Associated With Rapidly Progressive Lung Disease and Poor Survival in US Patients With Amyopathic and Myopathic Dermatomyositis.

Clinically amyopathic dermatomyositis (CADM) is a subset of dermatomyositis (DM) presenting with the characteristic rash of DM without objective muscle weakness. Asian studies report that anti–melanoma differentiation–associated gene 5 (anti–MDA‐5) autoantibody in CADM is associated with interstitial lung disease (ILD), particularly rapidly progressive ILD (RPILD). These associations have not been established in US myositis patients. The goal of our study was to determine the association of anti–MDA‐5 autoantibody with ILD, RPILD, and survival in US patients with CADM and classic DM.

Anti‐MDA5 is associated with rapidly progressive lung disease and poor survival in U.S. patients with amyopathic and myopathic dermatomyositis

Clinically amyopathic dermatomyositis (CADM) is a subset of dermatomyositis (DM) presenting with the characteristic rash of DM without objective muscle weakness. Asian studies report that anti–melanoma differentiation–associated gene 5 (anti–MDA‐5) autoantibody in CADM is associated with interstitial lung disease (ILD), particularly rapidly progressive ILD (RPILD). These associations have not been established in US myositis patients. The goal of our study was to determine the association of anti–MDA‐5 autoantibody with ILD, RPILD, and survival in US patients with CADM and classic DM.

Autoimmune Disease and Hair Loss

Once systemic disease is in remission, it is prudent to recognize the importance of alopecia in the patients overall sense of well-being and quality-of-life clinical outcome. Scarring alopecia (scalp discoid lupus erythematosus) can be the presenting manifestation of lupus in more than half of affected individuals. Diffuse nonscarring alopecia in lupus is usually responsive to treatment of the systemic disease. Severe, often intractable burning pruritus of the scalp is a frequent complaint in dermatomyositis. Lichen planopilaris may mimic other autoimmune forms of scarring alopecia. Alopecia can also be caused by medications used to treat systemic autoimmune disease and fibromyalgia.

Treatment of inflammatory myopathy: emerging therapies and therapeutic targets

Despite the lack of placebo-controlled trials, glucocorticoids are considered the mainstay of initial treatment for idiopathic inflammatory myopathy and myositis-associated interstitial lung disease. Glucocorticoid-sparing agents are often given concomitantly with other immunosuppressive agents, particularly in patients with moderate or severe disease. First-line conventional immunosuppressive drugs include either methotrexate or azathioprine, and when they fail, more aggressive therapy includes mycophenolate mofetil, tacrolimus or cyclosporine, intravenous immunoglobulin, rituximab, or cyclophosphamide, used alone or in various combinations. Further investigations are required to assess the role of more novel therapies in the treatment of myositis and myositis-associated interstitial lung disease.

Approach to asymptomatic creatine kinase elevation

How to manage a patient who has an elevated serum creatine kinase (CK) level but no or insignificant muscle-related signs and symptoms is a clinical conundrum. The authors provide a systematic approach, including repeat testing after a period of rest, defining higher thresholds over which pursuing a diagnosis is worthwhile, and evaluating for a variety of nonneuromuscular causes. They also outline a workup for neuromuscular causes. Standard cutoffs may be too low. First, repeat the test after 7 days without exercise.

Antimelanoma Differentiation-associated Gene 5 Antibody: Expanding the Clinical Spectrum in North American Patients with Dermatomyositis

Objective. To determine the clinical features associated with the antimelanoma differentiation-associated gene 5 antibody (anti-MDA5) in US patients with clinically amyopathic dermatomyositis (CADM) and classic DM. Methods. Patients with CADM were consecutively selected from the University of Pittsburgh Myositis Database from 1985 to 2013. CADM was defined by a typical DM rash without objective muscle weakness and no or minimal abnormalities of muscle enzymes, electromyography, or muscle biopsy. DM was defined by Bohan and Peter criteria and was 1:1 matched (sex and age ± 5 yrs) to patients with CADM. Anti-MDA5 autoAb levels were determined using ELISA. Clinical features were compared between CADM and DM and between MDA5-positive and MDA5-negative subjects, using chi-squared and/or Mann-Whitney U tests as appropriate. Results. We identified 61 patients with CADM who were matched to 61 DM controls (female 62% vs 64%; mean age 44.8 yrs vs 48.2, p < 0.5). Anti-MDA5 frequency was the same in both cohorts (13.1%), and anti-MDA5 was significantly associated with a higher likelihood of cutaneous ulcers, digital tip ulcerations, and puffy fingers as well as interstitial lung disease (ILD). Most patients with ILD had rapidly progressive ILD (RPILD) leading to early death. Patients with CADM were more likely to have dysphagia, but there were no other clinical differences seen associated with CADM as compared to classic DM. Conclusion. Anti-MDA5 positivity had a similar frequency in US patients with CADM and DM and is associated with ILD, RPILD, cutaneous ulcers, digital tip ulceration, and poor survival.

Modern Therapies for Idiopathic Inflammatory Myopathies (IIMs): Role of Biologics

Despite the lack of placebo-controlled trials, glucocorticoids are considered the mainstay of initial treatment for idiopathic inflammatory myopathy (IIMs) and myositis-associated ILD (MA-ILD). Glucocorticoid-sparing agents are often given concomitantly with other immunosuppressive agents, particularly in patients with moderate or severe disease. As treatment of refractory cases of idiopathic inflammatory myopathies has been challenging, there is growing interest in evaluating newer therapies including biologics that target various pathways involved in the pathogenesis of IIMs. In a large clinical trial of rituximab in adult and juvenile myositis, the primary outcome was not met, but the definition of improvement was met by most of this refractory group of myositis patients. Rituximab use was also associated with a significant glucocorticoid-sparing effect. Intravenous immune globulin (IVIg) can be used for refractory IIMs or those with severe dysphagia or concomitant infections. Anti-tumor necrosis factor (anti-TNF) utility in IIMs is generally limited by previous negative studies along with recent reports suggesting their potential for inducing myositis. Further research is required to assess the role of new therapies such as tocilizumab (anti-IL6), ACTH gel, sifalimumab (anti-IFNα), and abatacept (inhibition of T cell co-stimulation) given their biological plausibility and encouraging small case series results. Other potential novel therapies include alemtuzumab (a humanized monoclonal antibody which binds CD52 on B and T lymphocytes), fingolimod (a sphingosine 1-phosphate receptor modulator that traps T lymphocytes in the lymphoid organs), eculizumab, and basiliximab. The future investigations in IIMs will depend on well-designed controlled clinical trials using validated consensus core set measures and improvements in myositis classification schemes based on serologic and histopathologic features.

A diagnostic and therapeutic approach to primary burning mouth syndrome

Primary burning mouth syndrome (BMS) is an oral mucosal disorder that is characterized by a chronic and often debilitating intraoral burning sensation for which no localized or systemic cause can be found. BMS most commonly affects postmenopausal women. The pathophysiology of primary BMS is not well understood. Diagnosing BMS can prove to be challenging. BMS patients can also pose a therapeutic challenge to clinicians who are consulted to evaluate these patients. Most commonly used therapies include tricyclic antidepressants, α-lipoic acid, clonazepam, and cognitive-behavioral therapy. Clinical judgment, patient counseling, and monitoring of pain are important. Further research is required to assess the effectiveness of serotonin and newer serotonin-noradrenalin reuptake inhibitors.

Biologics for idiopathic inflammatory myopathies.

Purpose of review As treatment of refractory cases of idiopathic inflammatory myopathies (IIMs) has been challenging, there is growing interest in assessing novel biologics that target various pathways implicated in the pathogenesis of IIM. Recent findings In the largest clinical trial in adult and juvenile IIM assessing the effectiveness of rituximab, the primary outcome was not met but 83% of this refractory group of IIM patients met a predefined definition of improvement and rituximab demonstrated a significant glucocorticoid-sparing effect. Antitumor necrosis factor utility in IIM is generally limited by uncertain efficacy data along with recent reports suggesting their potential for inducing systemic autoimmune disease including IIM. Summary Further research is required to evaluate the role of newer therapies such as tocilizumab (anti-interleukin-6), abatacept (inhibition of T-cell costimulation), sifalimumab (anti-interferon&agr;) and ruxolitinib, (Janus kinase inhibitor) given their biological plausibility and encouraging recent small case series results. Future clinical trials should consider the targeting of biomarkers implicated in the etiopathogenesis of IIM, predictive factors of treatment response, recent revisions in IIM classification criteria, as well as newly developed data-driven response criteria which employ validated core set measures.

FRI0251 Anti-MDA5 Auto-Antibody: Expanding The Clinical Spectrum in Patients with Dermatomyositis in North america

Background Clinically amyopathic dermatomyositis (CADM) is a subset of dermatomyositis (DM) presenting with the characteristic DM rash (es) without objective proximal muscle weakness. Asian studies report that anti-MDA5 auto-antibody (autoAb) in CADM is associated with a unique clinical phenotype, which has not been well established in US. Objectives The goals of our study were to determine the clinical features associated with anti-MDA5 autoAb in CADM as compared to classic DM in US. Methods CADM patients were selected consecutively from the patients enrolled in the University of Pittsburgh Myositis Database from January 1985 to July 2013 (n=450). CADM was defined a typical DM rash without objective muscle weakness for at least 6 months after rash onset and no or minimal abnormalities of serum muscle enzymes [<3 x ULN], electromyography or muscle biopsy. The classic DM was defined as per probable and definite criteria of Bohan and Peter. DM patients were selected similarly and 1:1 matched (gender and age ±5 years) to CADM patients. The clinical features were assessed using our prospective myositis database, along with electronic medical record review when necessary. Results We identified 61 CADM patients and 61 matching DM controls. Demographics were similar in both groups. Anti-MDA5 frequency was similar in two cohorts (13.1% [8/61] vs. 13.1% [8/61]). Anti-MDA5 positivity was associated with a higher likelihood of abnormal capillary microscopy, vasculitic rash and digital tip ulceration (18.7% vs. 2.8%) and a lower frequency of Raynauds as compared to anti-MDA5 negativity. The frequency of DM rashes (Gottron sign or papule, heliotrope, mechanics hands, etc were similar in both groups. However, puffy finger frequency was higher in the anti-MDA5+ patients as compared to anti-MDA5- patients (20% vs. 4.7%). Anti-MDA5 positivity was significantly associated with ILD (p=0.043), RPILD (p<0.001), and poor survival (p=0.007). Multivariate analysis suggested that anti-MDA5 positivity was predictive of survival even after controlling for diagnosis, age at diagnosis, gender, ethnicity, smoking, and ILD (p=0.001). ILD frequency was similar in CADM and DM (31.1% vs. 26.2%) as was RPILD (8.2% vs. 5%). CADM patients were more likely to have puffy fingers (9.8% vs. 4.9%) but less likely to have mechanics hands (3.2% 9.8%) and heliotrope rash (36.1 vs. 19.7%) than DM patients. Rest of the clinical features were similar for both CADM and DM cohorts.Table 1 Clinical features MDA5+ MDA-5− P value CADM Classic DM P value (N=16) (N=106) (N=61) (N=61) ILD 50% 25.5% 0.04 31% 26% 0.46 RPILD 44% 1% <0.001 8% 5% 0.55 Raynauds 12.5% 26.4% 0.35 22.9% 26.2% 0.67 Vasculitic rash 18.7% 1.8% 0.01 3.2% 4.9% 1 Abnormal capillary microscopy 43.7% 26.4% 0.15 29.5% 27.8% 0.8 Digital tip ulceration 18.7% 2.8% 0.02 4.9% 4.9% 1 Heliotrope rash 18.7% 29.2% 0.55 36% 19.6% 0.04 Dysphagia 31.2% 10.3% 0.03 24.5% 1.6% <0.001 Conclusions Anti-MDA-5 autoAb is seen in similar frequency in CADM and DM patients in US. Anti-MDA-5 autoAb is associated with a unique clinical phenotype consisting of ILD, RPILD, abnormal nailfold capillary, vasculitic rash, and digital tip ulceration in U.S. patients. CADM patients were similar to DM apart from obvious disease defining features of muscle weakness and muscle enzyme. In addition there was more puffy fingers, less mechanics hands and heliotrope rash in CADM. Disclosure of Interest None declared