Myopathic Dermatomyositis Research Articles

Treatment Utilization in Dermatomyositis: An Analysis of Electronic Medical Records in the United States (P9-5.032)

Treatment Utilization in Dermatomyositis: An Analysis of Electronic Medical Records in the United States (P9-5.032)

Incidence, Prevalence, and Mortality of Dermatomyositis: A Population-Based Cohort Study.

We aimed to determine the population-based incidence, prevalence, and mortality of dermatomyositis (DM) using European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) criteria. This population-based cohort study included incident DM from January 1, 1995 to December 31, 2019. We manually reviewed all individuals with at least 1 code for DM or polymyositis to determine if they met EULAR/ACR criteria, subspecialty physician diagnosis, and/or Bohan and Peter criteria. We age- and sex-adjusted incidence and prevalence estimates to the US non-Hispanic White year 2000 population and estimated prevalence on January 1, 2015. Standardized mortality ratios (SMRs) with 95% confidence intervals (95% CIs) compared observed to expected mortality adjusting for age, sex, and year. We identified 40 cases of verified DM, with 29 cases incident in Olmsted County from 1995 to 2019. The mean age was 57 years, 26 (90%) were female, and 12 (41%) had clinically amyopathic DM (CADM). The median follow-up time was 8.2 years. The overall adjusted incidence of DM was 1.1 (95% CI 0.7-1.5) per 100,000 person-years, and prevalence was 13 (95% CI 6-19) per 100,000. The SMR was significantly elevated among the myopathic DM cases (3.1 [95% CI 1.1-6.8]) but not CADM cases (1.1 [95% CI 0.2-3.3]). The positive predictive value of ≥2 DM codes was only 40 of 82 (49%). This population-based study found that DM incidence and prevalence were higher than previously reported. Mortality was significantly elevated for myopathic DM but not for CADM.

A CASE SERIES OF RAPIDLY-PROGRESSIVE INTERSTITIAL LUNG DISEASE

SESSION TITLE: Medical Student/Resident Diffuse Lung Disease SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Rapidly progressing interstitial lung disease (RP-ILD) is a rare entity associated with poor outcomes. Anti-melanoma differentiation-associated protein 5 antibody (anti-MDA5 Ab) is strongly associated with RP-ILD. We report three cases with varying clinical features, treatment modalities, and outcomes. CASE PRESENTATION: Patient A was a 45-year-old man diagnosed with anti-MDA5 RP-ILD 8 months prior to admission. CT chest demonstrated diffuse peripheral reticulations and groundglass infiltrates without honeycombing in a non-specific interstitial pneumonia pattern. His disease progressed despite outpatient treatment with prednisone and mycophenolate, resulting in respiratory failure. Despite treatment with empiric antibiotics, high dose corticosteroids, IVIG, and rituximab his hypoxemia rapidly progressed to requiring mechanical ventilation and death. Patient B was a 32-year-old female diagnosed with RP-ILD after a 4-month history of arthralgias, facial rash, dyspnea, and recurrent pneumonias that did not improve with antibiotics. Chest CT demonstrated bilateral, multifocal consolidations in an organizing pneumonia pattern. Skin biopsy demonstrated dermatomyositis and surgical lung biopsy demonstrated a parenchymal inflammatory infiltrate of lymphocytes and plasma cells without fibrosis. Despite incremental treatment with high dose corticosteroids, IVIG, cyclophosphamide, and tacrolimus, she developed respiratory failure that quickly progressed to requiring mechanical ventilation and death. Patient C is a 38-year-old female who presented with several months of arthralgias, rash, and dyspnea. Chest CT demonstrated bilateral patchy groundglass and consolidative opacities with peripheral predominance in an organizing pneumonia pattern. Bronchoscopy with transbronchial biopsies demonstrated organizing pneumonia. Anti-MDA5 Ab titers were positive. Prednisone and mycophenolate mofetil for anti-MDA5 RP-ILD demonstrated clinical and radiographic improvement. She was switched to azathioprine and monthly IVIG due to hepatic toxicity but re-developed respiratory and liver failure due to hemophagocytic lymphohistiocytosis. She required mechanical ventilation and eventual tracheostomy. Treatment with anakinra and high dose steroids improved her respiratory failure and she was discharged. DISCUSSION: RP-ILD portends a poor prognosis with a 41% 6-month survival. Management is largely guided by case reports and expert opinion. Only 40% of patients will respond to corticosteroids alone. If mild and diagnosed early, mycophenolate or azathioprine, in addition to steroids, are first-line options. If severe or progressive, treatment with cyclophosphamide, rituximab, or a calcineurin inhibitor are recommended. Despite aggressive treatment, the disease still often progresses, as illustrated in patients A and B. CONCLUSIONS: Additional studies, including observational data, are needed to help guide management. Reference #1: Aoyama J, Hayashi H, Yajima C, et al. Anti-MDA5 antibody-positive rapidly progressive interstitial pneumonia without cutaneous manifestations. Respir Med Case Rep. 2019;26:193-196. Reference #2: Moghadam-kia S, Oddis CV, Sato S, Kuwana M, Aggarwal R. Anti-Melanoma Differentiation-Associated Gene 5 Is Associated With Rapidly Progressive Lung Disease and Poor Survival in US Patients With Amyopathic and Myopathic Dermatomyositis. Arthritis Care Res (Hoboken). 2016;68(5):689-94. Reference #3: Sakamoto N, Ishimoto H, Nakashima S, et al. Clinical Features of Anti-MDA5 Antibody-positive Rapidly Progressive Interstitial Lung Disease without Signs of Dermatomyositis. Intern Med. 2019;58(6):837-841. DISCLOSURES: No relevant relationships by Kelsey Black, source=Web Response No relevant relationships by Derrick Herman, source=Web Response No relevant relationships by Sai Krishna Korada, source=Web Response

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. CADM patients were identified in the University of Pittsburgh Myositis Center Database and matched 1:1 (sex and age) to classic DM controls. Anti-MDA-5 was measured by serum enzyme-linked immunosorbent assay. Kaplan-Meier, log rank, and chi-square tests were used for analysis. We identified 61 CADM patients (62% women, mean age 48.2 years) and 61 classic DM controls (64% women, mean age 44.8 years). The frequencies of anti-MDA-5 positivity, ILD, and RPILD were similar in the 2 cohorts (MDA-5 positive: CADM 13.1% [8 of 61] and DM 13.1% [8 of 61], ILD positive: CADM 31.1% [19 of 61] and DM 26.2% [16 of 61], and RPILD positive: CADM 8.2% [5 of 61] and DM 5% [3 of 61]; P = 1, 0.55, and 0.46, respectively). Anti-MDA-5 positivity was significantly associated with ILD, since 50% of MDA-5-positive subjects (8 of 16) had ILD versus 25.5% of MDA-5-negative subjects (27 of 106; P = 0.04). Anti-MDA-5 was strongly associated with RPILD (P < 0.001). Anti-MDA-5-positive patients with ILD had worse baseline pulmonary function testing variables compared to anti-MDA-5-negative patients. Anti-MDA-5 positivity was significantly associated with poor survival (P = 0.007). Anti-MDA-5 antibody is significantly associated with ILD, RPILD, worse pulmonary outcome, and survival in US classic DM and CADM patients.

The cutaneous manifestations of humanparvovirus B19 infection

The prototypical cutaneous manifestations of human parvovirus B19 (B19) infection include a petechial eruption in a glove and stocking distribution, reticular truncal erythema, and the “slapped cheek” sign. An association with connective tissue disease (CTD) stigmata has recently been made. The clinical and dermatopathologic findings in 14 patients whose skin lesions were accompanied by serological evidence of B19 infection or documentation of B19 genome in lesional skin are presented. The authors encountered skin biopsy specimens from 14 patients who presented with skin eruptions accompanied by clinical signs or serology suggestive of antecedent B19 infection. Clinical findings were correlated to the light microscopic appearance of the lesions and the presence of B19 genome in lesional skin. The study group comprised 9 women, 3 men, and 2 boys. Eruptions characteristic of fifth disease, including the slapped cheek sign, reticulated truncal erythema, and acral petechiae, were present in 3 patients, 1 of whom later developed granuloma annulare. The other patients had atypical clinical presentations comprising an asymptomatic papular eruption (2), an eruption clinically resembling Sweet's syndrome (3), myopathic dermatomyositis (DM) (2), lupus erythematosus (LE)-like syndromes (2), and lower-extremity palpable purpura (2). Skin biopsy specimens in 12 cases showed interstitial histiocytic infiltrates with piecemeal fragmentation of collagen and a mononuclear cell-predominant vascular injury pattern. Other features included an interface dermatitis, eczematous alterations, and papillary dermal edema. Lesions with features of DM or LE also showed mesenchymal mucinosis, whereas a biopsied lesion of palpable purpura showed leukocytoclastic vasculitis (LCV). lmmunofluo-rescent testing showed a positive lupus band test (LBT) with epidermal IgG and C 5b-9 decoration in 1 patient with a systemic LE-like illness, whereas the DM patients had negative LBTs and vascular C 5b-9 deposition typical for DM. Skin biopsy specimens from 11 patients, including those whose presentations resembled LE and DM, were positive for B19 genome. The dermatopathology of B19 infection suggests tissue injury mediated by delayed-type hypersensitivity, by antibody-dependent cellular immunity directed at microbial antigenic targets in the epidermis and endothelium, and by circulating immune complexes in the setting of LCV. These mechanisms appear to generate a clinical and histopathological picture that recapitulates that of CTD. Presented in part at the US-Canadian Academy of Pathologymeeting, Boston, MA, March 1998.

The role of microvascular injury in the pathogenesis of cutaneous lesions of dermatomyositis

Although microvascular injury has been postulated as the pathogenetic basis of skeletal muscle injury in dermatomyositis (DM), its role in the genesis of the skin lesions, which are said to be difficult to distinguish light microscopically from systemic lupus erythematosus (SLE) and subacute lupus erythematosus (SCLE), has not been analyzed. The authors' intention was to assess the role of microvascular injury in the pathogenesis of skin lesions in DM, SLE, and SCLE. Light microscopic features of biopsies of lesional skin from 20 patients with myopathic DM and 11 with amyopathic DM were compared to eight lesional skin biopsies from eight patients with SLE and 12 lesional skin biopsies from 12 patients with SCLE. Vascular density was compared in the three groups using an inmmunohistochemical preparation with an antibody to factor VIII. In 12 biopsies from the DM group, and in 19 of 20 lupus erythematosus (LE) specimens, frozen tissue was available. An indirect immunofluorescence methodology was used to detect C 5b-9 deposition, and direct immunofluorescence studies for other immunoreactants were performed in standard fashion. Compared with LE, lesions of DM showed a greater degree of endothelial injury, vascular ectasia, and vascular fibrin deposition; there were no differences between myopathic versus amyopathic DM. C 5b-9 deposition in vessels was significantly greater in DM than in LE. The superficial vascular plexus density was reduced in lesions of DM versus LE control groups with the greatest reduction observed in myopathic DM. Epithelial injury and mucin was greatest in myopathic DM. Microvascular injury is the apparent pathophysiological basis of skin lesions in DM. Careful attention to microvascular pathology enables distinction of DM from SLE and SCLE. Indirect immunofluorescence testing using a monoclonal antibody to C 5b-9 is a valuable tool to distinguish DM from LE in biopsies of lesional skin.

Use of magnetic resonance imaging and P-31 magnetic resonance spectroscopy to detect and quantify muscle dysfunction in the amyopathic and myopathic variants of dermatomyositis.

To investigate the use of magnetic resonance imaging (MRI) and P-31 magnetic resonance spectroscopy (MRS) in characterizing the metabolic and functional status of muscles in patients with amyopathic dermatomyositis (DM) and to compare the findings with those in patients with classic myopathic DM. Nine patients with amyopathic DM, 11 patients with myopathic DM, and 11 normal individuals were studied. MRI images of thigh muscles were obtained, and T1 and T2 relaxation times were calculated. Biochemical status was quantitated with P-31 MRS, by determining concentrations of phosphate metabolites during rest and exercise. Patients with amyopathic DM showed no muscle inflammation, and MRS data obtained during rest were normal. During exercise at 25% and 50% maximum voluntary contractile force, the MRS data revealed significant differences between amyopathic DM patients and control subjects indicating inefficient metabolism. In contrast, muscles of patients with myopathic DM showed inflammation and metabolic abnormalities even during rest. Metabolic deficiencies in patients with amyopathic DM were unmasked by exercise, suggesting that the 2 DM syndromes may share muscle abnormalities. MRI/MRS may be useful in diagnosis and optimization of treatment.