Idiopathic eosinophilic myositis: a systematic literature review

Eosinophilic myositis belong to the idiopathic inflammatory myopathies and are defined by an inflammatory infiltrate composed of eosinophils within the muscle. To date, no consensus exists for diagnosis and care of such patients. The aim of this review was to describe clinical and histological presentation, treatment, and outcome of eosinophilic myositis based on a systematic review of all published histologically proven cases of eosinophilic myositis. A total of 453 records were identified in MEDLINE until November 2020. A total of 69 published cases were identified. The analysis of these allowed the distinction of the 3 previously described pathological subtypes: focal eosinophilic myositis (n = 17); diffuse eosinophilic myositis (n = 36); and eosinophilic perimyositis (n = 16). We propose a simple algorithm for diagnosis and treatment strategy for the care of patient with muscular symptoms and blood eosinophilia. This work also highlights eosinophilic myositis pathogenesis and the need for careful investigations in order to rule out differential diagnoses.     

Myositis caused by Borrelia burgdorferi: report of four cases

Myositis was proven histopathologically in 4 patients (age range 36-66 years) who suffered from early or late stages of Borrelia burgdorferi infection. Muscle weakness was present in 3 patients, 1 complaining of additional myalgias. One man came to medical attention because of skin discoloration and swelling of one leg. Deep biopsy from skin, fascia and muscle revealed acrodermatitis chronica atrophicans, panniculitis, fasciitis, and myositis, respectively. Creatine kinase was slightly elevated in 3 cases and normal in one. Infiltrates were found in the perimysium and within the muscle bundles, mainly around small vessels. The infiltrates consisted of many B cells and T4 lymphocytes with fewer cytotoxic T cells, suggesting that Borrelia myositis might be due to a local immune response to unknown Borrelia antigens. Cultivation of Borrelia from muscle was not successful. Antibiotic therapy cured the myositis.     

Case of the month. Disseminated histoplasmosis presenting as myositis and fasciitis in a patient with dermatomyositis

A 54-year-old man with dermatomyositis initially responsive to corticosteroids and methotrexate developed severe myalgias, increasing weakness, and fevers. Laboratory studies were suggestive of disseminated histoplasmosis, and muscle biopsy revealed myositis, fasciitis, and yeast in the perimysial connective tissue. Histoplasma capsulatum was cultured from skeletal muscle. Despite antifungal therapy, necrotizing fasciitis progressed to gluteal abscess formation. Disseminated histoplasmosis may present atypically in immunocompromised hosts as fasciitis and myositis. Patients with dermatomyositis could be particularly vulnerable to soft tissue invasion by fungi due to their underlying microangiopathy. © 1995 John Wiley & Sons, Inc.     

Inflammatory myopathies: Part 1

The inflammatory myopathies have diverse clinical and pathological features and multiple etiologies. Some are confined to a single muscle or group of muscles (e.g., orbital myositis and localized nodular myositis) while others are diffuse. Infective forms may be due to viral, bacterial, fungal, protozoal, or parasitic organisms. Viruses may cause acute self-limited forms of myositis and have been isolated from muscle in some cases of acute rhabdomyolysis and inclusion body myositis. They have also been implicated in some cases of congenital myopathy and in polymyositis and dermatomyositis, but there is no evidence of viral invasion of muscle in these conditions. In polymyositis and dermatomyositis there are derangements in humoral and cellular immune function, and recent evidence suggests an underlying disturbance of immunoregulation. The roles of genetic factors, drugs, and Toxoplasma infection have been under scrutiny. There is increasing recognition of immunological and pathological differences in polymyositis and juvenile and adult dermatomyositis, and in cases with associated connective tissue diseases, suggesting different underlying pathogenetic mechanisms. Inclusion body myositis, eosinophilic myositis, and granulomatous myositis can be separated from the other idiopathic inflammatory myopathies because of distinctive clinical and pathological features and this may also reflect different mechanisms of muscle injury. Recent developments in the treatment of the idiopathic inflammatory myopathies include the use of plasmapheresis and total-body irradiation in cases that are resistant to corticosteroids and immunosuppressive drugs.     

Adalimumab and myositis: A case report and review of the French and international Pharmacovigilance Databases

TNFα inhibitors, including adalimumab, are widely used in inflammatory rheumatologic and bowel diseases. Well-known adverse effects include: opportunistic infections, immunogenicity and new inflammatory manifestations. Myositis is an inflammatory disease, which manifests with muscle symptoms and can be life-threatening. Little is known about drug-induced myositis. We aimed to describe a case of myositis induced by adalimumab and reviewed national and international pharmacovigilance databases for other cases until 01/02/2019. This was a 63 years old woman with Crohn's disease, who developed muscle weakness, and rhabdomyolysis 3 months after starting adalimumab. Diagnosis of myositis was suspected and confirmed with electromyography and muscle biopsy. Improvement in muscle symptoms was observed after stopping adalimumab and starting corticosteroids. Muscular adverse effects are well-known and usually benign with adalimumab. However, five cases of myositis during treatment with adalimumab were registered in French PharmacoVigilance Database (FPVD) with muscle symptoms observed 3 months to 7 years after starting adalimumab. In VigiBase^Ⓡ, 90 cases of myositis associated with adalimumab with some similar characteristics were registered. When a patient treated with adalimumab complains of muscular symptoms, inflammatory myopathies should be considered. This adverse effect should be mentioned in a ‘Summary of Product Characteristics’ to alert healthcare professionals.     

Eosinophilia-myalgia syndrome (L-tryptophan-associated neuromyopathy)

Histopathologic study of skeletal muscle biopsy in a patient with eosinophilia-myalgia syndrome following L-tryptophan use showed prominent lymphocytic perineuritis, neuritis, and perimysial fasciitis. The presence of perineuritis and neuritis provides a histopathologic basis for clinical features of neuropathy in eosinophilia-myalgia syndrome and occurred in conjunction with a fasciitis or interstitial myositis that was predominantly perimysial and focally endomysial.     

Microsporidial polymyositis in human immunodeficiency virus−infected patients,a rare life‐threatening opportunistic infection: Clinical suspicion,diagnosis, and management in resource‐limited settings

Introduction: Microsporidial myositis is a rare opportunistic infection that has been reported in HIV‐infected and HIV‐uninfected immunocompromised patients. Methods: In this study we present a retrospective analysis of 5 cases of microsporidial myositis in HIV‐infected patients, including the clinical, laboratory, and histologic features, and a review of the literature. Results: Five young men with HIV infection [median CD4 count of 20 cells (range 14?144)/mm³] who presented with signs and symptoms suggestive of myositis underwent EMG‐NCV and muscle biopsy, which revealed signs compatible with microsporidial myositis. Early and aggressive treatment led to improvement in 3 patients. Two of the 5 patients died due to a delay in diagnosis, because the spores were mistaken for Candida without confirmatory stains or a high index of suspicion. Conclusions: Myositis in HIV‐infected patients with low CD4 counts should be evaluated using muscle biopsy. A high index of suspicion is required for early diagnosis of microsporidial myositis in HIV‐infected patients. Early diagnosis and immediate, aggressive treatment are the keys to favorable outcomes in these patients. Muscle Nerve 51 :775–780, 2015     

The association of sporadic inclusion body myositis and Sjögren's syndrome in carriers of HLA-DR3 and the 8.1 MHC ancestral haplotype

Sporadic inclusion body myositis (sIBM) usually occurs as an isolated condition, but it may occur in association with another autoimmune disorder such as Sjögren's syndrome. We reviewed sIBM cases with Sjögren's syndrome (sIBM/SS) from the Perth Inflammatory Myopathies Database to determine whether they are distinguishable from other sIBM cases. Six such cases were identified, representing 12% of all sIBM cases. Muscle biopsies confirmed the presence of an inflammatory myopathy with rimmed vacuoles and the characteristic muscle fibre inclusions of sIBM. Five of the six were females, contrasting with a 2:1 male preponderance in the rest of the sIBM cohort. The mean age-at-onset and the pattern of muscle weakness were similar in the two groups. Four out of five sIBM/SS patients treated with immune therapies had improvement in muscle strength lasting for 6-24 months, whereas only 27% of other sIBM patients improved. All 6 patients with sIBM/SS carried the HLA-DRB1*0301 allele, or its equivalent HLA-DR3 serological specificity, compared with 83% of other sIBM cases and all carried some or all of the major markers of the 8.1 MHC ancestral haplotype which is also associated with Sjögren's syndrome. Patients with sIBM/SS represent a subgroup of sIBM cases who are more likely to be female and carriers of HLA-DR3 and the 8.1 MHC ancestral haplotype, and are more likely to respond to treatment. The association of sIBM and Sjögren's syndrome is likely to be due to a common genetic predisposition linked to the MHC and supports the notion that sIBM has an autoimmune basis.     

Granulomatous myositis associated with brucellosis: a case report and literature review

Brucellosis, a multisystem infectious disorder, continues to be a serious public health problem in some parts of the world. Neurobrucellosis constitutes about 4% of all brucellosis cases. Brucellosis-associated myositis is extremely rare, and there is only 1 reported case in the English literature. We report a 16-year-old boy with subacute, fluctuating, progressive muscle pain, with tenderness, swelling, and diffuse, asymmetric weakness. He also had significantly elevated serum Brucella titers and a muscle biopsy showed inflammatory granulomatous myositis. We review the literature on myositis associated with brucellosis.     

Canine masticatory muscle disorders: a study of 29 cases

The histopathologic features in temporalis muscle biopsies from 29 dogs with masticatory muscle disorders were characterized and used for their subgrouping: 2 without lesions, 3 with nonspecific changes, 7 with neurogenic atrophy, and 16 with myositis. The immunocytochemical and immunochemical features of the muscle biopsies and sera from those dogs were compared among the histopathologic subgroupings and compared with biopsies and sera from healthy dogs and dogs with polymyositis. Of the 14 biopsies from dogs with masticatory muscle myositis, 12 had immune complexes limited to type 2M fibers, whereas 13 of 16 sera samples had detectable antibodies against type 2M fibers. The immune complex deposition was found only in biopsies of dogs with masticatory muscle myositis, and the antibodies were detected in the sera of only one dog that did not have masticatory muscle myositis. Immunoblot assays revealed that the antibodies were most often directed against a 185 K protein, myosin heavy chain, and a band that appeared to be LC2-M (myosin light chain 2-masticatory).     

Case of eosinophilic myositis in continuum from localized nodular myositis]

We report a 72-year-old man with eosinophilic myositis (EM). At age 71 he noticed a painful nodule in his left calf. A biopsy (first biopsy) showed marked infiltration of mononucleated cells and necrotic muscle fibers. Several phagocytosed fibers were also seen. He was diagnosed as having myositis. The painful nodule disappeared spontaneously. At age 72, he again had a painful nodule, but this time in his right calf; again, this disappeared spontaneously on the first admission. Just after discharge, he noted painful nodules in the left thigh and right anterior tibial muscles and was again admitted (second admission). Neurological examination revealed mild proximal-dominant weakness in all four extremities but no other abnormalities. Laboratory studies showed elevated creatine kinase (CK) level (38,803 U/l; normal 62-287) and positive Jo-1 antibody, but no eosinophilia. Needle electromyography of the limb muscles showed myogenic patterns. Magnetic resonance imaging of the lower limbs demonstrated several T2-high and gadolinium (Gd)-enhanced lesions. Muscle biopsy (second biopsy) from the left quadriceps femoris showed marked infiltration of eosinophils; he was diagnosed as having EM. Administration of prednisolone was initiated at 60 mg/day and then gradually tapered. After starting treatment with steroids, his muscle weakness gradually ameliorated, CK level dramatically decreased, and the nodules disappeared. Clinically, the patient had developed localized nodular myositis (LNM), but pathologically it was EM without peripheral blood eosinophilia and positive Jo-1 antibody that is occasionally found in polymyositis (PM). Thus, this patient demonstrated overlapping characteristics of EM, LNM, and possibly PM, suggesting that a common mechanism underlay these conditions. As discussed, the involvement of eosinophils in three inflammatory myopathies was indicated.     

Inclusion body myositis in Alzheimer's disease

Roos PM, Vesterberg O, Nordberg M. Inclusion body myositis in Alzheimer’s disease.
Acta Neurol Scand: 2011: 124: 215–217.
© 2010 John Wiley & Sons A/S. Background – The prevalence of Alzheimer’s disease is increasing. Could findings of similar deposits in brain and muscle tissue explain this increase? The purpose of this report is to illustrate that Alzheimer’s disease and inclusion body myositis may share a common aetiology. Results – We present a case where Alzheimer’s disease and inclusion body myositis coexist in the same patient. Amyloid‐beta deposition and the presence of phosphorylated tau protein have been noted in brain tissue and in muscle biopsy from patients with these disorders. Methods – Electrophysiological methods are needed for proper diagnosis of this brain and muscle disorder. Recent data on deposit structures in both conditions may indicate an environmental aetiology for Alzheimer’s disease and inclusion body myositis. Conclusion – By combining electrophysiological methods with muscle biopsy in cases of Alzheimer’s disease, the possible aetiological connection between simultaneous affection of both muscle and brain in this condition can be established.     

A child case of atypical chronic fasciitis--diagnostic usefulness of muscle CT scan

Eosinophilic fasciitis is an uncommon disorder characterized by peripheral blood eosinophilia, hypergamma-globulinemia, and inflammation of fascia and skin. Its typical symptom in the acute stage includes muscle pain and swelling, followed by slowly progressive joint contractures. We report an 11-year-old girl with pathological diagnosis of chronic fasciitis, probable eosinophillic fasciitis. Her first symptom was chronic symmetrical joint contractures, which developed when she was 4 years old. She had atypical course as compared with patients described in literature, lack of acute symptom and very early onset of the disease. Her muscle CT scan revealed very fibrotic fascia, which might be responsible for joint contractures. Muscle and fascia biopsies were performed to confirm the diagnosis. The fascia was very fibrotic containing mononuclear cell infiltration, compatible with a chronic stage of eosinophilic fasciitis. In conclusion muscle CT scan is useful for differential diagnosis of this disorder in patients presenting with chronic symmetrical joint contractures, but without acute inflammatory symptom.     

Inclusion body myositis: current pathogenetic concepts and diagnostic and therapeutic approaches

Inclusion body myositis is the most common acquired muscle disease in older individuals, and its prevalence varies among countries and ethnic groups. The aetiology and pathogenesis of sporadic inclusion body myositis are still poorly understood; however genetic factors, ageing, and environmental triggers might all have a role. Unlike other inflammatory myopathies, sporadic inclusion body myositis causes slowly progressing muscular weakness and atrophy, it has a distinctive pattern of muscle involvement, and is unresponsive to conventional forms of immunotherapy. This review covers the clinical presentation, diagnosis, treatment, and the latest information on genetic susceptibility and pathogenesis of sporadic inclusion body myositis.     

Sodium and chloride channelopathies with myositis: Coincidence or connection?

Introduction: A proximal myopathy develops in some patients with muscle channelopathies, but the causative molecular mechanisms are unknown. Methods: We reviewed retrospectively all clinical and muscle biopsy findings of 3 patients with channelopathy and additional myositis. Direct DNA sequencing was performed. Results: Pathogenic mutations were identified in each case. Biopsies demonstrated inflammatory infiltrates. Conclusions: Clinicians should consider muscle biopsy in channelopathy patients with severe myalgia and/or subacute weakness and accompanying elevated creatine kinase. Chance association of myositis and channelopathy is statistically unlikely. An alternative hypothesis suggests that inflammatory insults could contribute to myopathy in some patients. Muscle Nerve, 2011     

Inclusion body myositis

The clinical features of inclusion body myositis (IBM) were of minor importance in the design of consensus diagnostic criteria, mainly because of controversial views on the specificity of signs and symptoms, although some authors reported "typical" signs. To re–assess the clinical spectrum of IBM, a single investigator using a standard protocol studied a cohort of 64 patients cross–sectionally. Symptom onset was before the age of 50 years in 20% of cases. Only a few patients (14 %) started with weakness other than that of quadriceps, finger flexor or pharyngeal muscles. The sequence of power loss was erratic, but onset of symptoms with quadriceps weakness predicted an earlier onset of dysphagia in older patients (≥ 56 years) compared with younger ones (< 56 years) (p = 0.02). Despite widespread weakness patients had favourable scores on three commonly used function scales and they kept their employment. Complete wheel–chair dependency was rare (3 %). A dominant characteristic was the anatomical distribution of afflicted muscles: ventral extremity muscle groups were more affected than dorsal muscle groups and girdle muscles were least affected, the latter preserving postural stability. Ankylosis, especially in extension of the fingers,was frequently present. Together with the sparing of intrinsic hand muscles it was helpful in the preservation of many skilful movements. IBM has a unique distribution of muscle weakness. Ankylotic contractures are common. We feel that their joint impact on daily functioning is characteristic for the disease.     

Concurrence of myasthenia gravis, polymyositis, thyroiditis and eosinophilia in a patient with type B1 thymoma]

We presented a 43-year-old Japanese woman who acutely developed weakness of all extremities and difficulty in swallowing and drooping of eyelids, characterized by easy fatigability at the end of December, 2005. On general physical examination, she had moderate goiter. No cervical lymphadenopathy, cardiac murmur, or skin rash was noted. Neurologically, she had blepharoptosis, more on the right, only in the upright position with easy fatigability and marked weakness in the neck flexor, trunk, and all limb muscles much more proximally than distally. She had neither muscular atrophy nor upper motor neuron sign. Laboratory data showed slight leukocytosis with eosinophilia (up to 31%), and serum creatine kinase was markedly increased to over 2,000 IU/l. TSH receptor antibody (11.9%) and anti-acetylcholine receptor antibody (46.6 nmol/L) were also increased. Edrophonium test was positive. Electrophysiologically, muscle evoked potentials by repetitive motor nerve stimulation showed 13% and 50% waning in abductor pollicis brevis and deltoid muscle, respectively, at low frequency and no waxing at high frequency. Needle EMG showed fibrillation potentials and positive sharp waves in proximal muscles. Polymyositis was diagnosed by muscle biopsy which showed infiltration of lymphocytes in the endomysium and around non-necrotic muscle fibers. Upper arm muscle MRI showed multifocal high signal intensity lesions on T2-weighted images which were likely related to myositis. This finding is atypical for polymyositis. X-ray and CT of chest showed a mass lesion in the left pulmonary hilum, which was histologically diagnosed as type B1 thymoma. Thus, the present case had myasthenia gravis, polymyositis, thyroidititis and eosinophilia associated with type B1 thymoma. After the thymectomy, corticosteroid administration and immunoadsorption therapy, clinical symptoms and all laboratory abnormalities markedly improved.     

Apolipoprotein E and apolipoprotein E messenger RNA in muscle of inclusion body myositis and myopathies

Sporadic inclusion body myositis and the hereditary inclusion body myopathies are severe, progressive muscle diseases, characterized pathologically by vacuolated muscle fibers containing paired helical filaments. We immunostained muscle biopsy specimens from sporadic inclusion body myositis, hereditary inclusion body myopathy, disease control, and normal patients with several antibodies against apolipoprotein E (ApoE). Approximately 80 to 90% of the vacuolated muscle fibers of sporadic inclusion body myositis contained well-defined, strongly immunoreactive ApoE inclusions, In hereditary inclusion body myopathy, only rare vacuolated fibers had immunoreactive inclusions, whereas most had diffuse cytoplasmic ApoE immunoreactivity. Ultrastructurally, ApoE immunoreactivity in sporadic myositis was localized mainly to the paired helical filaments. By contrast, in the hereditary form, ApoE immunoreactivity occurred on material in close proximity to the paired helical filaments, but never was on the paired helical filaments. In both muscle diseases, ApoE was also on the 6-to 10-nm filaments and amorphous material. In the sporadic form, ApoE-immunoreactive deposits colocalized with Congo red-positive deposits; however, in muscle fibers from patients with hereditary disease there was no congophilia. ApoE messenger RNA was not detectable in muscle fibers from patients with hereditary or sporadic disease but was expressed abundantly in muscle macrophages. In all control and inclusion body myositis or myopathy biopsy specimens, ApoE immunoreactivity was strong at the postsynaptic domain of neuromuscular junctions; nonjunctional regions of normal fibers were negative for ApoE. ApoE immunoreactivity occurred diffusely in regenerating muscle fibers, a subset of which had detectable ApoE messenger RNA.     

Muscular complications of human immunodeficiency virus (HIV) infection in the era of effective anti-retroviral therapy

Introduction of highly active antiretroviral therapy (HAART) has dramatically modified the natural history of HIV disease, but lengthening the survival of HIV-infected individuals has been associated with an increasing prevalence of iatrogenic conditions. Muscular complications of HIV infection are classified as follows: (1) HIV-associated myopathies and related conditions including polymyositis, inclusion-body myositis, nemaline myopathy, diffuse infiltrative lymphocytosis syndrome (DILS), HIV-wasting syndrome, vasculitis, myasthenic syndromes, and chronic fatigue; (2) iatrogenic conditions including mitochondrial myopathies, HIV-associated lipodystrophy syndrome, and immune restoration syndrome; (3) opportunistic infections and tumor infiltrations of skeletal muscle; and (4) rhabdomyolysis. These features are described in the present review.