Polymyositis in a child with thalassemia after hematopoietic stem cell transplantation: A case report.

RATIONALE: Polymyositis (PM) is a rare neuromuscular phenotype of chronic graft-versus-host disease (cGVHD). Although glucocorticoids have been shown to be effective in the treatment of PM, most people experience poor treatment response and poor prognosis. PATIENT CONCERNS: A six-year-old boy with thalassemia received allogeneic hematopoietic stem cell transplantation (HSCT) and consequently developed sudden myasthenia of limbs 17 months after the transplant. DIAGNOSES: Medical history, current symptoms, laboratory examinations, and imaging findings of the patient indicated cGVHD complicated with PM. INTERVENTIONS: He was then given high-dose corticosteroid therapy, including tacrolimus, ruxolitinib, and rituximab. OUTCOMES: Twenty-three months after transplantation, creatine kinase levels returned to normal range, and the MRI showed that the original muscle edema signal was significantly improved. The patient's muscle weakness continued to improve, and his overall condition was good. LESSONS: This report suggests that glucocorticoids combined with immunosuppressants may be effective against polymyositis. Rituximab and ruxolitinib may be a good choice in treating polymyositis.

Reappraisal of the incidence, various types and risk factors of malignancies in patients with dermatomyositis and polymyositis in Taiwan.

Our study aimed to investigate the incidence, risk factors and time to occurrence of malignancy in patients with dermatomyositis (DM) and polymyositis (PM). The electronic medical records of 1100 patients with DM and 1164 patients with PM were studied between January 2001 and May 2019. Malignancies after myositis were diagnosed in 61 (5.55%) patients with DM and 38 (3.26%) patients with PM. The cumulative incidence of malignancies in patients with DM were significantly higher than patients with PM (hazard ratio = 1.78, log-rank p = 0.004). Patients with DM had a greater risk of developing malignancy than those with PM at 40-59 years old (p = 0.01). Most malignancies occurred within 1 year after the initial diagnosis of DM (n = 35; 57.38%). Nasopharyngeal cancer (NPC) was the most common type of malignancy in patients with DM (22.95%), followed by lung, and breast cancers. In patients with PM, colorectal, lung and hepatic malignancies were the top three types of malignancy. The risk factors for malignancy included old age (≥ 45 years old) and low serum levels of creatine phosphokinase (CPK) for patients with DM and male sex and low serum levels of CPK for patients with PM. Low serum levels of CPK in patients with myositis with malignancy represented a low degree of muscle destruction/inflammation, which might be attributed to activation of the PD-L1 pathway by tumor cells, thus inducing T-cell dysfunction mediating immune responses in myofibers. A treatment and follow-up algorithm should explore the occurrence of malignancy in different tissues and organs and suggested annual follow-ups for at least 5.5 years to cover the 80% cumulative incidence of malignancy in patients with DM and PM.

Replacement and Immunomodulatory Activities of 20% Subcutaneous Immunoglobulin Treatment: A Single-Center Retrospective Study in Autoimmune Myositis and CVID Patients.

Background: Immunoglobulin (Ig) replacement therapy represents a life-saving treatment in primary antibody deficiencies. The introduction of subcutaneous Ig (SCIg) administration brings a major improvement in quality of life for patients, compared to the traditional intravenous administration. In recent years, an additional role has been proposed for Ig therapy for various inflammatory and immune-mediated diseases. Consequently, the use of SCIg has expanded from immunodeficiencies to immune-mediated diseases, such as polymyositis (PM) and dermatomyositis (DM). Given the rarity of these conditions, it is still difficult to evaluate the real impact of SCIg treatment on PM and DM, and additional data are constantly required on this topic, particularly for long-term treatments in real-life settings. Aim: This study aimed to increase the knowledge about the anti-inflammatory and immunomodulatory effects of SCIg treatment for myositis. To this aim, a long-term evaluation of the effectiveness of 20% human SCIg treatment (20% SCIg, Hizentra®, CSL Behring) was carried out in patients with PM/DM in care at our Center. In addition, an evaluation of the 20% SCIg therapy in CVID patients was provided. This analysis, beside adding knowledge about the use of SCIg therapy in this real-life setting, was intended as a term of comparison, regarding the safety profile. Results: Results support the beneficial effect and tolerability of long-term 20% SCIg therapy in PM/DM patients, reporting a significant improvement in creatine kinase levels, muscle strength, skin conditions, dysphagia, disease activity (MITAX score) and disability (HAQ-DI score). None of the patients reported systemic reactions. The duration of the reported local reactions was a few hours in 80% of the patients, and all resolved spontaneously. CVID patients reported an improvement in all the considered effectiveness parameters at the end of 20% SCIg therapy. The frequency of the adverse events reported by PM/DM patients was not different from what reported in CVID patients, where the use of SCIg therapy is more consolidated. Conclusions: This study suggests that 20% SCIg treatment represents a viable and safe treatment for PM/DM patients and a valid therapeutic alternative to IVIg, with important advantages for patients' quality of life.

Association of Ultraviolet Radiation Exposure With Dermatomyositis in a National Myositis Patient Registry.

OBJECTIVE: Dermatomyositis (DM) has been associated with geospatial differences in ultraviolet (UV) radiation, but the role of individual determinants of UV exposure prior to diagnosis is unknown. The objective was to examine the role of those individual determinants. METHODS: We analyzed questionnaire data from 1,350 adults in a US national myositis registry (638 with DM, 422 with polymyositis [PM], and 290 with inclusion body myositis [IBM] diagnosed at ages 18-65 years), examining the likelihood of DM compared with PM and IBM diagnosis, in relation to self-reported sunburn history and job- and hobby-related sun exposures in the year prior to diagnosis. We estimated odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression adjusted for age, skin tone, and sex, to determine the association of individual UV exposures with DM diagnosis. We also evaluated the proportion of DM by maximum daily ambient UV exposure, based on UVB erythemal irradiances for participant residence in the year prior to diagnosis. RESULTS: DM was associated with sunburn in the year before diagnosis (2 or more sunburns OR 1.77 [95% CI 1.28-2.43] versus PM/IBM; 1 sunburn OR 1.44 [95% CI 1.06-1.95]) and with having elevated job- or hobby-related sun exposure (high exposure OR 1.64 [95% CI 1.08-2.49] or moderate exposure OR 1.35 [95% CI 1.02-1.78] versus low or no exposure). Ambient UV intensity was associated with DM in females (ß = 3.97, P = 0.046), but not overall. CONCLUSION: Our findings suggest that high or moderate personal exposure to intense sunlight is associated with developing DM compared with other types of myositis. Prospective research on UV exposure as a modifiable risk factor for DM is warranted.

18F-FDG PET/CT in Graft Versus Host Disease-Associated Polymyositis.

Graft versus host disease (GVHD) is the most frequent and serious complication of allogenic hematopoietic stem cell transplant. Polymyositis is a rare neuromuscular manifestation of GVHD, which often responds well to corticosteroid and immunosuppression therapy. We present a case of a 38-year-old man with a known case of mixed-phenotype acute leukemia after hematopoietic stem cell transplant presenting with GVHD-associated polymyositis. F-FDG PET/CT done in this case not only helped in the detection of the muscle involvement but also helped in obtaining precise muscle sample for histopathological diagnosis using PET-guided biopsy.

Interstitial Lung Disease in Polymyositis and Dermatomyositis.

The idiopathic inflammatory myopathies (IIMs), including polymyositis (PM) and dermatomyositis (DM), are autoimmune connective tissue diseases with variable degrees of muscle inflammation and systemic involvement. Interstitial lung disease (ILD) is a common complication of the IIMs and is associated with increased mortality. Many patients with PM/DM have myositis-specific and myositis-associated antibodies (MSA/MAAs) that result in distinct clinical phenotypes. Among these MSAs, anti-aminoacyl-tRNA antibodies and anti-melanoma differentiation factor 5 antibodies have high rates of ILD. Corticosteroids are the mainstay of treatment, although the addition of other immunosuppressive therapy is typically necessary to achieve disease control.

Risk of autoimmune rheumatic diseases in patients with palindromic rheumatism: A nationwide, population-based, cohort study.

OBJECTIVE: To estimate the relative risk of autoimmune rheumatic diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjogren's syndrome (SS), dermatomyositis (DM) and polymyositis (PM), among patients with palindromic rheumatism (PR) compared with non-PR individuals. METHODS: The study utilized 2003-2013 claims data from the Taiwanese National Health Insurance Research Database. We identified 4,421 cases of PR from 2007 to 2012 and randomly chose 44,210 non-PR individuals who matched (1:10) for age, sex and the year of index date without prior history of RA, SLE, SSc, SS, DM, or PM. After adjusting for age, sex, and the Charlson comorbidity index, we calculated the hazard ratios (HRs) with 95% confidence intervals (CIs) using the Cox proportional hazard model to quantify the risk of RA, SLE, SS, DM and PM in PR patients compared with that in matched non-PR individuals. RESULTS: Among the 4,421 patients with PR, 569 (12.87%) developed RA, 269 (6.08%) developed SS, 113 (2.56%) developed SLE, 5 (0.11%) developed SSc, 8 (0.18%) developed PM, and 1 (0.02%) developed DM. After adjusting for potential confounders, the patients with PR had an increased risk of RA (HR, 118.76; 95% CI, 89.81-157.04), SS (HR, 59.57; 95% CI, 43.87-80.88), SLE (HR, 51.56; 95% CI, 32.96-80.66) PM (HR, 57.38; 95% CI, 6.90-476.83), and SSc (HR, 13.42; 95% CI, 3.79-47.55) but not of DM (HR, 3.44; 95% CI, 0.34-34.59). CONCLUSION: Patients with PR had an increased risk of developing RA, SS, SLE, PM, and SSc.

Current diagnosis and treatment of polymyositis and dermatomyositis.

Idiopathic inflammatory myopathies (IIMs) are heterogeneous disorders that affect the skeletal muscles. Polymyositis, dermatomyositis, and inclusion body myositis are major IIM subsets. Immune-mediated necrotizing myopathy became recognized as a potentially new IIM subset. Since the new classification criteria published by the International Myositis Classification Criteria Project have higher sensitivity and specificity for IIM classification and subclassification than the previous criteria, they should help precise diagnosis. It should be noted that several tests available in current clinical practice, such as electromyography, magnetic resonance imaging, and other myositis-specific autoantibodies than anti-Jo-1 antibodies, were not included in the new criteria. As for treatment, glucocorticoids are used empirically as the first-line treatment despite their various adverse effects. Concomitant treatment with steroid-sparing immunosuppressive agents, including methotrexate, azathioprine, calcineurin inhibitors, mycophenolate mofetil, and cyclophosphamide, reduces successfully initial glucocorticoid doses for the remission induction, the relapse risk during glucocorticoid tapering, and adverse effects of glucocorticoids. Treatment with biologics, including rituximab and abatacept, seems promising in some IIM patients. Multi-target treatment with glucocorticoids and several steroid-sparing immunosuppressive agents is effective in refractory IIM patients. Considering proven steroid-sparing efficacy and tolerability of multi-target treatment in patients with other autoimmune diseases, it should be a good therapeutic option for IIMs.

Overlapping features of polymyositis and inclusion body myositis in HIV-infected patients.

OBJECTIVE: To characterize patients with myositis with HIV infection. METHODS: All HIV-positive patients with myositis seen at the Johns Hopkins Myositis Center from 2003 to 2013 were included in this case series. Muscle biopsy features, weakness pattern, serum creatine kinase (CK) level, and anti-nucleotidase 1A (NT5C1A) status of HIV-positive patients with myositis were assessed. RESULTS: Eleven of 1,562 (0.7%) patients with myositis were HIV-positive. Myositis was the presenting feature of HIV infection in 3 patients. Eight of 11 patients had weakness onset at age 45 years or less. The mean time from the onset of weakness to the diagnosis of myositis was 3.6 years (SD 3.2 years). The mean of the highest measured CK levels was 2,796 IU/L (SD 1,592 IU/L). On muscle biopsy, 9 of 10 (90%) had endomysial inflammation, 7 of 10 (70%) had rimmed vacuoles, and none had perifascicular atrophy. Seven of 11 (64%) patients were anti-NT5C1A-positive. Upon presentation, all had proximal and distal weakness. Five of 6 (83%) patients followed 1 year or longer on immunosuppressive therapy had improved proximal muscle strength. However, each eventually developed weakness primarily affecting wrist flexors, finger flexors, knee extensors, or ankle dorsiflexors. CONCLUSIONS: HIV-positive patients with myositis may present with some characteristic polymyositis features including young age at onset, very high CK levels, or proximal weakness that improves with treatment. However, all HIV-positive patients with myositis eventually develop features most consistent with inclusion body myositis, including finger and wrist flexor weakness, rimmed vacuoles on biopsy, or anti-NT5C1A autoantibodies.

[Polymyositis secondary to a non-Hodgkin's lymphoma]. / Polimiositis secundaria a un linfoma no Hodgkin.

TITLE: Polimiositis secundaria a un linfoma no Hodgkin.

Febuxostat-associated eosinophilic polymyositis in marginal zone lymphoma.

Febuxostat is an orally administered selective inhibitor of xanthine oxidase approved for the treatment of gout and prevention of tumor lysis syndrome. It is a relatively safe medication. Hypersensitivity reactions associated with the use of febuxostat are quite rare with only one reported case of DRESS syndrome. Recently, two case reports of rhabdomyolysis following the initiation of febuxostat were published. We hereby present the first case of rhabdomyolysis with hypereosinophilia following the administration of febuxostat to a 50-year-old patient newly diagnosed with marginal zone lymphoma. Three weeks after the initiation of febuxostat for tumor lysis syndrome prophylaxis, the patient presented with generalized weakness, diffuse myalgia and low-grade fever. Initial studies showed creatinine kinase level of 4471, hypereosinophilia of 1900/mm3, and LDH of 2691. All infectious and autoimmune diseases were ruled out. TSH level was normal. Muscle biopsy showed myonecrosis in addition to an eosinophilic inflammatory infiltrate in the endomysium and perimysium. Discontinuation of febuxostat led to prompt symptom resolution and normalization of blood tests eight days later.

The host defense peptide LL-37 a possible inducer of the type I interferon system in patients with polymyositis and dermatomyositis.

The type I interferon (IFN) system has recently been suggested to play important and essential roles in the pathogenesis of myositis. However, a clarification of how type I IFNs could function as triggering factor(s) in the pathogenesis of myositis has yet failed. Through activation of the type I IFN system, the host defense peptide LL-37 carries numerous immunomodulatory properties and is implicated in the pathogenesis of several other autoimmune diseases, including systemic lupus erythematosus (SLE). The expression of LL-37 can be regulated by various endogenous factors including the active form of vitamin D (25(OH)D3). The aim of this study was to explore a potential role of LL-37 in relation to the type I IFN system in patients with polymyositis (PM) and dermatomyositis (DM) and to compare these with SLE patients and healthy controls. We investigated muscle (3 PM, 5 DM) and symptomatic (5 DM) and non-symptomatic (3 PM, 3 DM) skin biopsies from patients with short disease duration and muscle biopsies (3 PM, 1 DM) from patients with long disease duration. Six SLE patients with symptomatic and non-symptomatic skin and five muscle and six skin biopsies from healthy individuals served as controls. Tissue specimens were immunohistochemically stained for LL-37, neutrophils (CD66b), plasmacytoid dendritic cells (BDCA-2), myxovirus resistance protein A (MxA), and macrophages (CD68, CD163). In addition, LL-37 and CD66b double staining was also performed. Serum levels of 25(OH)D3 were investigated in PM and DM patients with short disease duration (3 PM, 5 DM) and in 40 healthy controls. We found that the expression of LL-37, BDCA-2 (the major producer of type I IFNs), MxA (an interferon-inducible protein), and macrophages were higher in muscle tissue of PM and DM patients compared to healthy controls. The LL-37 expression was mainly derived from neutrophils. Neutrophils were increased in both symptomatic and non-symptomatic skin of myositis and SLE patients and BDCA-2 was increased in symptomatic DM skin when compared to healthy controls. Moreover, the expression of MxA in symptomatic and non-symptomatic skin of SLE patients was higher when compared to both myositis patients and healthy controls. There was no difference in the expression of LL-37 in skin of myositis and SLE patients compared to healthy controls. All PM and DM patients with a short disease duration had low 25(OH)D3 levels compared to healthy controls. In conclusion, the present study supports our hypothesis that LL-37 may activate type I IFNs, which could initiate and perpetuate an inflammatory process. The prolonged exposure of the immune system to type I IFNs may eventually break tolerance and lead to autoimmune myositis.

[Paraneoplastic myasthenia gravis and polymyositis secondary to a thymoma in a young woman].

We present the case of a 33-year-old woman who within weeks developed severe swallowing difficulties and weakness in her limbs to an extent requiring hospitalization. Workup confirmed clinically suspected diagnoses of polymyositis and autoimmune myasthenia. A suspicion of malignant thymoma based on chest computed tomography was histologically verified. Patient treatment and response are presented. The case emphasizes the importance of recognizing that thymomas, in rare instances, may present with a combination of neuromuscular disorders in the same patient.