Calcinosis in dermatomyositis: Origins and possible therapeutic avenues.

Calcinosis, insoluble calcium compounds deposited in skin and other tissues, is a crippling sequela of dermatomyositis. Prolonged disease associated with ongoing inflammation, ischemia, repetitive trauma, and certain autoantibodies are associated with calcinosis. Herein, we describe potential pathogenic mechanisms including the role of mitochondrial calcification. There are no widely effective treatments for calcinosis. We review available pharmacologic therapies for calcinosis including those targeting calcium and phosphorus metabolism; immunosuppressive/anti-inflammatory therapies; and vasodilators. Mounting evidence supports the use of various formulations of sodium thiosulfate in the treatment of calcinosis. Although the early institution of aggressive immunosuppression may prevent calcinosis in juvenile dermatomyositis, only limited data support improvement once it has developed. Minocycline can be useful particularly for lesions associated with surrounding inflammation. Powerful vasodilators, such as prostacyclin analogs, may have promise in the treatment of calcinosis, but further studies are necessary. Surgical removal of lesions when amenable is our treatment of choice.

Interstitial Lung Disease in Anti-MDA5 Positive Dermatomyositis.

Anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5+ DM) is a rare autoimmune disease predominantly reported in East Asia. MDA5+ DM is an intractable disease with impressively high mortality due to rapid-progressive interstitial lung disease (RPILD). Other typical clinical manifestations comprise DM-specific rash (Gottron's papules, heliotrope rash) and amyopathic/hypomyopathic muscle involvement. Multiple prognostic factors have been identified. Baseline forced vital capacity (FVC) %-based staging could serve as a simplified risk stratification system. Serum biomarkers including MDA5 Ab titers, ferritin, KL-6 levels, and CD4+CXCR4+ T cell percentage could provide additional surrogate value of ILD severity and treatment response, as well as potential predictive value for survival. Spontaneous pneumomediastinum (PNM), ground-glass opacity (GGO), and consolidation were demonstrated to be the most significant features in pulmonary high-resolution computed tomography (HRCT) findings of MDA5+ DM-ILD. The semi-quantitative assessment of lesions in HRCT has also been demonstrated relevant to the outcome. The current treatment of this disease is still largely empirical. Immunosuppressive treatments, i.e., "triple therapy" (combination of high-dose glucocorticoids, tacrolimus, and intravenous cyclophosphamide) and JAK inhibitor-based therapy, are the mainstream regimens for MDA5+ DM-ILD, supported by the recently published trials. However, more efficacious regimen with favorable safety profile and high-level evidence is still urgently demanded for patients with MDA5+ DM-ILD, especially those at advanced-stage. We will summarize the terminology, etiology and pathogenesis, clinical features and outcome, prognostic factors, and treatment of MDA5+ DM-ILD in this review.

Increased risk of coronary heart disease among patients with idiopathic inflammatory myositis: a nationwide population study in Taiwan.

OBJECTIVE: To evaluate the risk of incident coronary heart disease (CHD) among patients with DM and PM in a general population context. METHODS: We conducted a retrospective cohort study using the Taiwan National Health Insurance Research Database containing records covering the years from 2000 to 2010. DM and PM were confined for the purposes of this study to those aged ⩾18 years who were eligible for the Taiwan catastrophic illness certificate. The diagnoses, CHD outcomes and cardiovascular risk factors were identified from electronic claims data. We conducted two cohort analyses: CHD and DM, and CHD and PM, excluding for each analysis individuals with CHD already identified at baseline. Data for the comparison group was obtained from the Longitudinal Health Insurance database, comprising 1 million persons randomly sampled from the total beneficiaries during 2000. We estimated hazard ratios comparing myositis with comparison cohorts, adjusting for potential cardiovascular risk factors. RESULTS: A total of 1145 patients with idiopathic myositis were identified, along with 732 723 control patients aged ⩾18 years. The incidence rates of CHD were 15.1 in DM and 30.1 in PM per 1000 person-years, vs 8.4 and 10.5 per 1000 person-years in the comparison cohort. The adjusted hazard ratios for CHD in patients with idiopathic myositis were 2.21 (95% CI 1.64, 2.99) for DM and 3.73 (95% CI 2.83, 4.90) for PM. CONCLUSION: Results of this general population-based cohort study suggest that DM and PM are associated with an increased risk of CHD.

Breast Cancer with Paraneoplastic Syndrome in a 72 Year Old Male Patient.

Breast cancer in male is rare which accounts about 1% of all malignant breast neoplasm cases. Since paraneoplastic syndrome is unusual with male breast cancer, very few reported cases are found. A72- year-old gentleman presented with proximal myopathy in all four limbs was referred to Dr. Sirajul Islam Medical College and Hospital in April 2017. He had generalized wasting with reduced tone and reflexes. Planter responses were normal with intact sensory. There were typical Heliotrope rash bilaterally. In background, he had history of radical mastectomy due to stage IIA ductal carcinoma of left breast 7 years back. Three years later, he was found to have multiple metastases in lung and liver, however, deliberately discontinued chemotherapy after first dose. Currently he is on Tamoxifen. Two months back, he was diagnosed to have brain metastasis. Also his serum sodium level was low with low urine osmolality. Considering his background, we diagnosed him dermatomyositis with peripheal neuropathy & SIADH as paraneoplastic presentation of breast malignancy. Despite of normal CPK and NCV, we treated him with steroid as dermatomyositis can present with normal CPK. His myopathy improved after 2 weeks of steroid treatment. Fluid restriction increased his serum sodium level. The aim of reporting this case is to aware physicians about the aggressive nature of male breast cancer, its orthodox paraneoplastic presentation and to differentiate neuropathy from myopathy so that early treatment can improve the outcome.

Topical sodium thiosulfate for calcinosis cutis associated with autoimmune connective tissue diseases: the Mayo Clinic experience, 2012-2017.

In this case series, we retrospectively identified all patients treated with topical sodium thiosulfate (TST) for calcinosis cutis (CC) associated with underlying autoimmune connective tissue diseases at Mayo Clinic (Rochester, MN, USA) during the period 1 January 2012 to 27 June 2017. Of 28 patients identified (mean age 57.0 years; 96% female), 19 (68%) had clinical improvement of their CC with TST, 7 (25%) had no response and 2 (7%) had unknown response. There were adverse events in three patients: two had skin irritation and the third, who had a zinc allergy, experienced pain with application. Overall, our findings support those of previous case reports that TST appears to be a relatively well-tolerated adjuvant treatment for CC, although future studies with a control group are warranted to assess the true efficacy of TST for the indication of CC.

Hemophagocytic Syndrome Complicated with Dermatomyositis Controlled Successfully with Infliximab and Conventional Therapies.

A 57-year-old woman was admitted to our hospital because of a high fever, anemia, and hyperferritinemia. Since a bone marrow examination revealed hemophagocytosis, she was diagnosed with hemophagocytic syndrome (HPS). During treatment of HPS, a heliotrope rash and Gottron's sign appeared with elevated levels of serum aldolase. She also developed heart failure. She was diagnosed with dermatomyositis (DM) and associated myocarditis. Although the administration of glucocorticoids, calcineurin inhibitors, intravenous immunoglobulins, and etoposide ameliorated the clinical findings of DM and cytopenia, the fever and hyperferritinemia remained. The addition of infliximab to glucocorticoids and tacrolimus improved the fever and hyperferritinemia and enabled a reduction in the dose of prednisolone without relapse of the diseases.

The long-term outcome of interstitial lung disease with anti-aminoacyl-tRNA synthetase antibodies.

RATIONALE: Anti-aminoacyl transfer RNA synthetase antibodies (anti-ARS) are a group of myositis-specific autoantibodies that are detected in the sera of patients with polymyositis and dermatomyositis (PM/DM) and also in those of patients with idiopathic interstitial pneumonias without any connective tissue disease (CTD), including PM/DM. Although we reported the clinical characteristics of interstitial lung disease with anti-ARS antibodies (ARS-ILD) with and without PM/DM, the long-term prognosis of ARS-ILD remains undetermined. As our previous studies revealed that ARS-ILD without PM/DM was similar to CTD-associated ILD, and that ARS-ILD with PM/DM was radiologically suggestive of a nonspecific interstitial pneumonia (NSIP) pathological pattern, we hypothesized that the prognosis of ARS-ILD might be distinct from that of idiopathic pulmonary fibrosis (IPF) without anti-ARS. OBJECTIVES: To elucidate the long-term outcome of ARS-ILD with and without PM/DM and compare it to that of IPF. METHODS: A two-center retrospective study was conducted. The study population comprised 36 patients with ARS-ILD (8 with PM, 12 with DM, and 16 without myositis throughout the course), 100 patients with IPF without anti-ARS, and 7 patients with NSIP without anti-ARS. The presence of anti-ARS was determined by RNA immunoprecipitation using the sera obtained at the time of diagnosis before specific treatment. MEASUREMENTS AND MAIN RESULTS: During the observational period (median 49 months; range, 1-114 months), 7 patients with ARS-ILD (19%; 3 with PM, 1 with DM, and 3 without PM/DM) and 51 patients with IPF (51%) died. Patients with ARS-ILD had better overall survival than those with IPF (log-rank test, P < 0.001) and similar survival compared to those with NSIP (log-rank test, P = 0.59). The prognosis for patients with ARS-ILD was similar between those with and without myositis (log-rank test, P = 0.91). At the median follow-up time of 76.5 months, 14 of the 36 patients with ARS-ILD had deteriorated. Both a decline in forced vital capacity or an initiation of long-term oxygen therapy during the course (odds ratio [OR], 5.34) and acute exacerbation (OR, 28.4) significantly increased the mortality risk. CONCLUSIONS: The long-term outcome of ARS-ILD was significantly better than that of IPF regardless of the presence or absence of myositis.

Predictive factors for long-term outcome in polymyositis/dermatomyositis-associated interstitial lung diseases.

BACKGROUND: Interstitial lung disease (ILD) is strongly associated with polymyositis (PM), dermatomyositis (DM), and clinically amyopathic dermatomyositis (CADM). It is also related to mortality. Previous studies have highlighted that the acute form of PM/DM/CADM-associated ILD (PM/DM/CADM-ILD) has a poor short-term prognosis. However, little is known about the long-term clinical features of patients with PM/DM/CADM-ILD. The aim of the present study is to clarify the clinical characteristics and the predictive factors for long-term outcomes in patients with PM/DM/CADM-ILD. METHODS: Thirty-four patients with PM/DM/CADM-ILD who were followed up for more than 12 months were analyzed retrospectively. The patients were classified as "stable" or "deterioration" according to respiratory symptoms, serial changes in forced vital capacity (FVC) or arterial oxygen pressure, and radiologic findings during the follow-up period. RESULTS: Twenty-six patients (76%) were in the stable group and eight patients (24%) were in the deterioration group. Home oxygen therapy was performed in six cases in the deterioration group because of chronic respiratory failure due to progression of ILD. The deterioration group, in comparison to the stable group, had a significantly lower %FVC and a higher positive rate for the anti-PL-7 antibody. Multivariate logistic regression analysis revealed that a positive anti-PL-7 antibody test and a lower %FVC were independently associated with deterioration during long-term follow-up. CONCLUSIONS: Patients with PM/DM/CADM-ILD are at risk for chronic respiratory failure due to the deterioration of ILD during long-term follow-up. The presence of anti-PL-7 antibody and a lower %FVC at initial diagnosis may predict long-term deterioration in patients with PM/DM/CADM-ILD.

[A woman with skin abnormalities and muscle weakness]. / Een vrouw met huidafwijkingen en spierzwakte.

A 54-year-old woman presented to the emergency department with progressive proximal muscle weakness and a symmetric skin rash. Physical examination demonstrated a heliotrope rash, Gottron lesions, mechanic's hands and symmetrical erythema of the face, neck and upper legs. The diagnosis 'dermatomyositis' was established. Subsequently, the patient was successfully treated with prednisolone 1 mg/kg.

Clinical analysis of 50 children with juvenile dermatomyositis.

OBJECTIVE: We performed a retrospective review of medical records to assess the clinical characteristics of 50 Japanese children with juvenile dermatomyositis (JDM). METHODS: Fourteen boys and 36 girls who visited Yokohama City University Hospital between 1983 and 2008 were enrolled. Gender, age at disease onset and diagnosis, presenting clinical features, laboratory data at onset, complications, treatment, and outcome were reviewed. RESULTS: Mean age at disease onset was 6.9 years. Clinical manifestations at the first visit were muscle pain and/or weakness (90 %), malar rash (90 %), Gottron's papules (86 %), and heliotrope rash (80.0 %). Elevated serum levels of creatine kinase were found in 57.0 % of patients and aldolase in 95 %. T2-weighted magnetic resonance (MR) images with fat suppression demonstrated positive findings in 89.5 % of patients. Initial treatment was prednisolone (PSL) orally or pulsed methylprednisolone (mPSL) i.v. Pulsed mPSL therapy showed efficacy superior to PSL [flare in 8 of 19 (42 %) vs. 18 of 25 (72 %)]. Children refractory to initial treatment were given additional pulsed mPSL and/or cyclophosphamide (IVCY; n = 19) i.v.. Four patients with interstitial pneumonia responded well to IVCY. CONCLUSIONS: Our findings support the notion that JDM might be considered as both a systemic inflammatory and noninflammatory vasculopathy best treated by IVCY, as shown in previous literature.

A comparative study of clinical characteristics, work-up, treatment, and association to malignancy in dermatomyositis between two tertiary skin centers in the USA and Singapore.

BACKGROUND: To date, no study has compared the clinical characteristics, malignancy associations, and treatment of dermatomyositis in predominantly Caucasian vs. Asian populations. MATERIALS AND METHODS: This prospective study was conducted to compare clinical characteristics of dermatomyositis, its relationship to malignancy, and treatment between two tertiary medical centers in the USA and Singapore. A total of 19 newly-diagnosed patients in the USA and 15 patients in Singapore were enrolled. Dermatomyositis or amyopathic dermatomyositis were diagnosed based on clinical assessment, skin and muscle biopsies, and muscle testing. RESULTS: Ninety-five percent of patients in the USA group were of Caucasian descent, while 93% of patients in the Singapore group were of Chinese descent. Both groups were predominantly female. Pruritus was the most common initial symptom reported in both groups, while periungual erythema and Gottron's papules were the most common skin presentations. Heliotrope eruption was more common in the Singapore group, occurring in 80% of patients vs. 32% of patients in the USA group (P = 0.007). Three patients in the Singapore group developed a malignancy, with two of these patients having nasopharyngeal carcinoma. None of the USA patients developed malignancies in a follow- up period of 2-5 years. Immunosuppressive steroid sparing therapy with hydroxychloroquine was more frequently used in Singapore, while topical tacrolimus was more frequently used in the USA. CONCLUSION: The clinical presentations of dermatomyositis vary among different ethnic populations. Chinese patients with dermatomyositis have a significant risk for nasopharyngeal carcinoma.

Successful treatment for conventional treatment-resistant dermatomyositis-associated interstitial lung disease with adalimumab.

Dermatomyositis (DM) is a systemic autoimmune disorder characterized by the inflammation of skeletal muscles and pathognomonic skin rashes, namely heliotrope rash and Gottron's papules and involvement of other organs. Interstitial lung disease (ILD) seems to be one of the most characteristic manifestations of the lung and associated with increased morbidity and mortality in patients with DM. Despite DM-associated ILD requires aggressive therapy with cytotoxic agents, the efficacy is questionable in some cases, and more effective and less toxic therapies are needed. Recently, although there have been several reports of successful treatment of refractory case of PM and DM with the TNF-α antagonists, including infliximab and etanercept, there was no enough evidence for DM-associated ILD. We described herein a patient with DM-associated ILD who had poor response to conventional therapies and successfully treated with adalimumab.

Three cases of pneumatosis intestinalis presenting in autoimmune diseases.

Pneumatosis intestinalis (PI) is a comparatively rare disease characterized by the presence of intramural gas in the gastrointestinal tract. PI is known to be associated with several clinical conditions, such as pulmonary diseases, gastrointestinal diseases, and traumatic injury, as well as autoimmune disorders. In particular, PI is commonly seen in systemic sclerosis (SSc) but rarely in systemic lupus erythematosus and dermatomyositis (DM). In this report, we present three cases of PI presenting in autoimmune diseases, including DM, Sjögren's syndrome, and limited SSc, and further discuss its background characteristics.

Double trouble: therapeutic challenges in patients with both juvenile dermatomyositis and psoriasis.

BACKGROUND: Juvenile dermatomyositis (JDM) and psoriasis are inflammatory disorders that share interferon-α induced responses and dysregulation of cytokines, including tumor necrosis factor alpha. Although 13% of patients with JDM have a family history of psoriasis there is little information concerning children with JDM and psoriasis. OBSERVATIONS: We identified 3 children with both JDM and psoriasis. In 2 cases, psoriatic lesions occurred after the child's JDM symptoms had diminished following effective immunosuppressive therapy (high-dose intermittent intravenous methylprednisolone, methotrexate, and low dose oral corticosteroids). Patient 2, initially diagnosed as having psoriasis, was treated with prednisone and methotrexate but then developed classic JDM, which worsened following use of tumor necrosis factor alpha inhibitor and reduction of prednisone and methotrexate dosage. For each child, their history of JDM complicated the choice of therapy for psoriasis. CONCLUSIONS: Two therapies commonly used to treat psoriasis-phototherapy and tumor necrosis factor-alpha antagonists-must be used with caution in patients with both JDM and psoriasis owing to their potential to exacerbate clinical manifestations of JDM. We discuss the implications affecting treatment of children with these dual diagnoses and consider the pathophysiology linking these 2 conditions.

Dermatomiositis de comienzo precoz: a propósito de un caso / Early-onset juvenile dermatomyositis

Introducción. La dermatomiositis es una vasculopatía sistémica, de origen autoinmune, que afecta sobre todo a músculo y piel. Su incidencia es de 0,2/100.000. El síntoma más frecuente es la debilidad de la musculatura proximal y la aparición del exantema típico de esta enfermedad. El diagnóstico se basa en el cumplimiento de los criterios de Bohan y Peter (1975). El tratamiento de primera línea son los corticoides. El pronóstico en las formas agudas y tratadas suele ser favorable en el 80% de los casos, con remisión de la sintomatología a los 2 años. Puede haber recidivas. Caso clínico. Presentamos un paciente varón de 2 años y medio de edad con pérdida de fuerza muscular progresiva y dolor en el área Dermatomiositis juvenil d’inici precoç Alicia Mainou-Pintó 1, Carlos Mainou-Cid 1, Fernando Plaza-Martín 1, Joan Ros-Viladons 2, Jordi Antón-López 2 1 Unitat de Pediatria. EAP Sarrià/Vallvidrera/Les Planes. Barcelona. 2 Unitat de Reumatologia Pediàtrica. Servei de Pediatria. Hospital Sant Joan de Déu. Universitat de Barcelona. Esplugues de Llobregat (Barcelona) proximal de las extremidades inferiores, de 3 semanas de evolución. En los últimos 15 días le aparece una erupción en cara y manos. Como pruebas complementarias destacan: analítica sanguínea con elevación de ALT, AST, LDH, CPK y aldolasa, electromiograma mostrando un patrón miopático, resonancia nuclear magnética de cintura escapular con edema muscular, y biopsia muscular normal. Tras el tratamiento con prednisona, cloroquina, omeprazol y suplementos de calcio y vitamina D su evolución es favorable, y recupera paulatinamente todas las habilidades musculares perdidas. Comentarios. Se presenta un caso clínico que, aunque es típico en cuanto a la forma de presentación y la sintomatología, no lo es tanto por la edad de su comienzo. La dermatomiositis suele ser una enfermedad de diagnóstico hospitalario, aunque, conociendo bien las peculiaridades de su sintomatología, su sospecha y confirmación puede llegar del pediatra de atención primaria, como en el caso publicado(AU)

Introduction. Dermatomyositis is a systemic vasculopathy of autoimmune origin that affects especially muscle and skin. Its incidence is 0.2/100,000. The most frequent symptom is a progressive proximal muscle weakness and a typical skin rash. The diagnosis is based on the Bohan and Peter criteria (1975). The first line of treatment is with steroids. The prognosis of the acute and treated forms is favourable in 80% of patients with remission in 2 years, although there is risk of recurrence. Clinical observation. A 2.5 year-old boy presented with a 3-week history of progressive loss of muscle strength and pain in the proximal the lower limbs. Two weeks prior to presentation, a rash developed on his hands and face. Diagnostic work-up showed elevated ALT, AST, LDH, CPK and aldolase, abnormal electromyography with myopathic pattern, magnetic resonance of scapular area with muscle edema, and normal muscle biopsy. He was treated with prednisone, chloroquine, omeprazole, calcium supplements and vitamin D, with good evolution and progressive recovery of muscular strength. Commentary. Although this case presented with typical symptoms, of dermatomyositis, the young age of the patient is unusual. Dermatomyositis is usually diagnosed in the hospital setting; however, as highlighted by this case, awareness of the disease and its clinical presentation may facilitate its diagnosis and treatment by the primary care pediatrician(AU)

[Effective treatment of interstitial pneumonia with tacrolimus in a patient with dermatomyositis who was intolerant to cyclosporin-A].

A 67-year-old woman was admitted to our hospital because of erythema in the eyelids and fingers of both hands. Slight muscle weakness in the proximal limbs, a heliotrope rash, Gottron's sign, and mechanic's hand were observed. Creatine kinase serum levels were slightly elevated (376U/l), and the patient tested negative for all autoantibodies except for the antinuclear antibody. Chest computed tomography showed interstitial pneumonia (IP). Based on these findings, the patient was given a diagnosis of dermatomyositis (DM) associated with IP. Combined prednisolone (1 mg/kg/day) and cyclosporin-A (Cy-A 4 mg/kg/day) therapy was initiated; the patient showed marked improvement, but the Cy-A caused liver damage. Therefore, Cy-A was tapered off, and tacrolimus was simultaneously started, initially at a dose of 1 mg/day, building up to a sustained dose of 4 mg/day. The patient's IP and liver condition improved. Tacrolimus is a useful drug for the treatment of DM-IP in cases where Cy-A causes intolerable adverse reactions.