A patient of infantile polymyositis triggered by respiratory syncytium virus infection

An 11-month-old boy developed acute polymyositis about 1 week after respiratory syncytium virus (RSV) pneumonia. He was admitted to our hospital because of interstitial pneumonia. RSV infection was confirmed by the presence of its antigen in his nasal discharge. Two weeks later, his chest X-ray findings improved and RSV antigen became negative, but severe generalized muscle weakness developed, causing respiratory failure. Muscle biopsy demonstrated inflammatory cellular infiltration with occasional fiber necrosis. Intravenous steroid pulse therapy was remarkably effective resulting in complete recovery of his muscle power. In this patient polymyositis was preceded with RSV infection, suggesting a close relationship between polymyositis and RSV infection. Although many patients of viral myositis have been reported to be associated with coxsackie B, HCV and HTLV-1 viruses, our patient is the first infantile polymyositis secondary to RSV infection.     

Completion of chronic hepatitis C virus treatment in interferon-induced major depressive disorder with psychotic features

Interferon (IFN)-associated psychiatric disorders can be managed without interruption to hepatitis C virus (HCV) treatment. The limited number of cases in the literature reporting psychotic depression as an adverse drug reaction to IFN resulted in discontinuation of HCV therapy. The author reports a case of a 49 year-old man with chronic HCV genotype 1a treated with pegylated interferon-alpha and ribavirin developing major depressive disorder with psychotic features. The patient was successfully treated with both an antidepressant and antipsychotic for this suspected IFN-associated adverse drug effect while continuing 12 months of uninterrupted HCV treatment and subsequently achieving sustained hepatitis C virological response. Although IFN can cause distressing psychiatric disturbances, appropriate treatment with psychotropic agents and careful monitoring allows patients to be maintained on a full course of HCV treatment.     

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.     

A patient of chronic graft-versus-host disease presenting simultaneously with polymyositis and myasthenia gravis]

We report a patient of polymyositis and myasthenia gravis as manifestations of chronic graft-versus-hot disease (GVHD). A 48-year-old man was diagnosed as having chronic myelogenous leukemia at the age of 42 years, and had bone marrow transplantation (BMT) two years after the onset of the disease. Since he suffered from mild liver dysfunction and cutaneous involvement manifesting chronic GVHD, he was placed on prednisolone and cyclophosphamide. As his condition improved, the prednisolone was gradually tapered. Forty-one months after the BMT, the patient developed muscle pain and muscle weakness. A diagnosis of polymyositis was made from muscle biopsy and laboratory findings. An increase in the prednisolone dose was effective but a few weeks later the patient noticed ptosis and recurrence of muscle weakness. A tensilon test and anti-acetylcholine receptor antibody produced positive results, leading to a diagnosis of myasthenia gravis. Only one case of polymyositis and myasthenia gravis as manifestations of chronic GVHD has been reported, and in our patient both symptoms appeared almost at the same time. Although neuromuscular symptoms as a manifestation of chronic GVHD are rare, all patients receiving BMT should be carefully followed up neurologically to detect neuromuscular complications.     

In situ identification of hepatitis C virus RNA in muscle

The authors examined skeletal muscle specimens from four patients with myositis and hepatitis C virus (HCV) infection. PCR analysis identified HCV RNA in muscle homogenates from two patients. In situ hybridization signals for HCV RNA were detected within muscle fibers as well as in infiltrating lymphocytes from the same patients. The results may relate to the pathomechanism of myositis in patients with HCV infection.     

Restless legs syndrome due to interferon-alpha.

A patient developed restless legs symptoms paralleling the course of interferon-alpha (IFN alpha) therapy for chronic hepatitis C. Symptoms began during a course of IFN alpha, resolved with its suspension, and recurred on rechallenge. Restless legs syndrome may thus be an adverse effect of IFN alpha treatment.     

A case with myositis as a manifestation of chronic graft-versus-host-disease (GVHD) with severe muscle swelling developed after aggressive muscular exercise]

We report a 21-year-old-man, with myositis as a manifestation of chronic graft-versus-host-disease (GVHD). He was diagnosed as having acute myelogenous leukemia at the age of 18 years, and had bone marrow transplantation (BMT) two years after the onset of the disease. Cutaneous manifestation of acute GVHD appeared on the twelfth day following BMT, which responded to prednisolone. Thereafter, GVHD has been well-controlled except for mild liver dysfunction which was thought to be a sign of chronic GVHD. Eleven months after BMT, he enjoyed snowboarding for two days from morning till night. Two days later, he experienced muscle swelling with pain and fever, which gradually worsened for which he was admitted to our hospital. Neurological examination revealed severe proximal and distal muscle swelling with fever and tenderness in all extremities. Mild, symmetrical, proximal weakness was observed in all four limbs. Severity of muscle swelling and its generalized nature restricted the movements of shoulder-, elbow- and ankle-joints and he was unable to walk. Laboratory investigations revealed creatine kinase (CK) of 7,860 IU/L, C-reactive protein (CRP) of 21.5 mg/dL and raised biliary enzymes. MRI generated high intensity signals from the swollen muscles. Muscle biopsy examination of involved areas showed severe interstitial edema and mononuclear cells infiltration. Macrophages were scattered through out the perimysium and endomysium. On the other hand, T cells and B cells were localized to the endomysium. Although a lot of CD8 positive T cells were seen adjacent to non-necrotic fibers, none of them was obviously invading the non-necrotic fibers. Perifascicular atrophy was not seen. Symptoms gradually worsened over two weeks or so when prednisolone was started to which he responded rapidly. While tapering steroids, the symptoms relapsed on resuming aggressive exercise. Resumption of the treatment regime promptly controlled the symptoms. The cause of myositis as a manifestation of chronic GVHD is unclear. T-cell or B-cell dysfunction, collagen-vascular-like processes, viral infection and direct damage by radiation or chemotherapy have been supposed to involve in the disease process. Our case suggests that aggressive muscular exercise could play as a initiator of myositis as a manifestation of chronic GVHD.     

Hypothyroid myopathy caused by interferon-alpha therapy for chronic hepatitis C]

We reported a rare case with hypothyroid myopathy after interferon-alpha (IFN-alpha) therapy. A 59-year-old man complained of his weakness in proximal part of upper and lower extremities which started at 1 month and progressed during 6 months after IFN-alpha therapy for chronic hepatitis C, but he did not complain of any other symptoms. Blood chemistry showed an elevated level of CK (1,843 IU/l; normal range 43-170 IU/l) and increased myoglobin (250 ng/ml; normal range < 60 ng/ml). Thyroid function tests revealed an elevated level of TSH (148.7 microIU/ml; normal range, 0.4-4.1 microIU/ml), and decreased levels of free T3 (0.56 pg/ml; normal range, 2.27-3.90 pg/ml) and free T4 (0.24 ng/ml; normal range, 0.95-1.74 ng/ml). Blocking type TSH receptor antibody titer was elevated (75.4%; normal range < 15%) while other types of antithyroid antibody were not detected in his serum. Muscle biopsy from his quadriceps femoris muscle showed non-specific mild myopathic changes. His weakness was completely ameliorated and serum CK levels were normalized by thyroid hormone administration alone, confirming the diagnosis of hypothyroid myopathy. However, even after total amelioration of his hypothyroidism, blocking type TSH receptor antibody titer remained elevated. These findings may suggest that IFN-alpha fostered an autoreactivity arising from HCV infection to cause the autoimmune thyroid disease.     

Peripheral neuropathy associated with essential mixed cryoglobulinaemia: a role for hepatitis C virus infection?

BACKGROUND--The prevalence of hepatitis C virus (HCV) infection has been estimated at 43 to 84% in patients with essential mixed cryoglobulinaemia in recent large series. Some of these cases have been successfully treated with interferon-alpha. The objective was to evaluate the prevalence and the possible role of HCV infection in essential mixed cryoglobulinaemia. METHODS--Fifteen patients (eight men and seven women; mean age: 61.2 (SD 16.5) years) with peripheral neuropathy (10 polyneuropathies and five multifocal mononeuropathies) and essential mixed cryoglobulinaemia were tested for serum anti-HCV antibodies. RESULTS--Antibodies were found in 10 of 15 patients involving either polyneuropathies (seven patients) or multifocal mononeuropathies (three patients). Electrophysiological studies and teased nerve fibre studies (in seven patients) allowed neuropathies to be classified as predominantly sensory axonopathies. Compared with HCV-negative (HCV -) patients, HCV-positive (HCV +) patients had a more pronounced and more widespread motor deficit; motor nerve conduction velocities in peroneal and median nerves were more impaired in HCV + patients, although significance was not reached except for the mean value of the amplitude of the compound muscle action potentials of the median nerves (P < 0.05); necrotising vasculitis was found in two of nine nerve biopsies from the HCV + patients studied and in none of the three HCV - patients. In addition, HCV + patients had more frequent cryoglobulin related cutaneous signs, higher aminotransferase and serum cryoglobulin concentrations, lower total haemolytic complement concentrations, and more frequent presence of rheumatoid factor. A liver biopsy performed in eight HCV + patients disclosed a range of lesions, from chronic active hepatitis (six patients) to persistent hepatitis (two patients). Lastly, treatment with interferon-alpha conducted over six months in two patients seemed to improve the peripheral neuropathy. CONCLUSIONS--Patients with peripheral neuropathy and essential mixed cryoglobulinaemia should be tested for anti-HCV antibodies to determine the appropriate treatment.     

Eosinophilic myositis as presenting symptom in γ-sarcoglycanopathy

The patient reported here presented with first symptoms at the age of 10 showing an abnormal gait, calf hypertrophy and winged scapulae. She was diagnosed with eosinophilic myositis after muscle biopsy. A second muscle biopsy at the age of 20 and subsequent genetic testing, however, revealed the underlying condition of a primary γ-sarcoglycanopathy, or LGMD2C. To our knowledge, this is the first LGMD2C patient reported who initially presented with eosinophilic myositis. Eosinophilia has been reported previously in patients with Calpainopathy and Becker Muscular Dystrophy and might be an early, but transient feature of a wider range of muscular dystrophies.     

Hyaline inclusion myopathy: Unmasked by statin therapy

We report a case of a patient with history of alcohol abuse, treatment for hepatitis C and repeated strenuous physical activity who developed severe muscle pain and weakness during statin therapy. The symptoms persisted after discontinuation of the drug. The diagnosis of myopathy was made clinically and by electromyography. As his symptoms persisted a muscle biopsy was performed which showed inclusions consistent with hyaline inclusions. Hyaline inclusion myopathy is discussed in the context of this case with review of the literature. Muscle Nerve, 2009     

Lower activities of serum peptidases predict higher depressive and anxiety levels following interferon-alpha-based immunotherapy in patients with hepatitis C

OBJECTIVE: There is evidence that in patients with chronic hepatitis C, immunotherapy with interferon-alpha (IFN alpha) may induce depression. A lowered activity of peptidases, such as prolylendopeptidase (PEP) and dipeptidyl peptidase IV (DPP IV), occurs in depression. This study examines whether lowered serum PEP or DPP IV activity before starting IFN alpha-based immunotherapy predicts the increase in depressive symptoms during immunotherapy. METHOD: Serum PEP and DPP IV activities are measured in patients with hepatitis C before and 2, 4 and 16 weeks after starting IFN alpha-based immunotherapy. The Montgomery Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A) are completed. RESULTS: Patients with lower baseline PEP or DPP IV had significantly higher MADRS and HAM-A scores both at baseline and during immunotherapy. Patients with lower baseline DPP IV had significantly higher increases in the MADRS following IFN alpha treatment. CONCLUSION: Lower baseline PEP and DPP IV predict higher depressive and anxiety ratings during IFN alpha-based immunotherapy.     

Inclusion body myositis and paraproteinemia: Incidence and immunopathologic correlations

Serum from 70 patients with sporadic inclusion body myositis (IBM) was subjected to agarose gel immunofixation electrophoresis. The IgG extracted from 9 patients with monoclonal proteins, 3 without, and 2 control subjects and was purified, biotinylated, and applied to muscle biopsy sections for immunocytochemistry and to purified muscle protein fractions for immunoblots. Sixteen of 70 (22.8%) patients with IBM, compared with 2% of agematched controls, had a monoclonal gammopathy characterized as IgGλ in 9 patients, IgGk in 4, IgMk in 2, and IgAλ in 1. The mean age of IBM patients with gammopathy was 60.6 years (range, 35–77 years), compared with 66.1 years (range, 42–80 years) of the IBM patients without gammopathy. The IgG of the patients, more often than that of the control subjects, immunostained myonuclei and recognized various muscle proteins of 35 to 145 kd. We conclude that IBM, regardless of age, is frequently associated with monoclonal gammopathies, which often recognize various muscle components, especially myonuclei, suggesting disturbed immunoregulation.     

Glucocorticoid-sensitive hereditary inclusion body myositis

We report a hereditary muscle disorder with features of inclusion body myositis (IBM) in two adult sisters with slowly progressive asymmetrical muscle weakness. The findings of light microscopic and ultrastructural investigations of muscle biopsy specimens were consistent with a diagnosis of IBM. Both patients improved and stabilized on immunosuppressive treatment with corticosteroids and azathioprine. This differentiates our patients from other sporadic and familial cases of IBM. Clinical and histological features are described and compared with those of other previously reported families with IBM.     

A case of HTLV-1 associated myelopathy and adult T-cell leukemia, presenting unique muscle pathology including rimmed vacuole]

A 63-year-old man developed muscular atrophy and weakness in his four extremities since 1983, and was pointed out to have smoldering ATL by elevated HTLV-1 antibody titers in the serum (x 2,500) and CSF (x 32) in 1985. Neurological examinations revealed proximal muscular weakness and atrophy of four extremities, and mild spasticity of both legs. Deep tendon reflexes were hypoactive in both arms and hyperactive in both lower extremities with ankle clonus and bilateral positive Babinski and Chaddock reflexes. These findings were compatible with HAM. His gait, however, was markedly waddling, requiring support. Muscle biopsy at left biceps muscle revealed inflammatory change with rimmed vacuoles, small group atrophy, and marked type 1 fiber predominance. These findings on muscle biopsy are different from those of previously reported cases with HAM, showing some similarities to inclusion body myositis or distal myopathy with rimmed vacuole.     

Severe exacerbation of hepatitis C-associated vasculitic neuropathy following treatment with interferon alpha: a case report and literature review

Vasculitic neuropathy may occur in association with chronic hepatitis C infection. Interferon alpha (IFN(alpha)), an effective treatment for chronic hepatitis C, can precipitate or worsen autoimmune diseases. We report a patient with chronic hepatitis C and mild indolent vasculitic sensorimotor peripheral polyneuropathy, who developed severe mononeuropathy multiplex soon after IFN(alpha) was initiated, and review the literature on worsening vasculitic neuropathy after IFN(alpha) treatment for chronic hepatitis C. Care should be taken after starting patient with chronic hepatitis C-associated vasculitic neuropathy on IFN(alpha), as there is evidence that IFN(alpha) may exacerbate the neuropathy.     

Lewis-Sumner syndrome presenting unilateral quadriceps amyotrophy as an initial symptom]

We report a 55-year-old man with a chief complaint of wasting and weakness of the left quadriceps muscle. At age 54, he noticed difficulty in running and weakness in the left thigh, which gradually progressed. On the first admission to our hospital, based on the nerve conduction studies (NCS), the muscle biopsy findings showing neurologenic changes, and no abnormality of spinal MRI, we diagnosed as unilateral quadriceps amyotrophy, which resulted from an atypical form of spinal progressive muscular atrophy. One year later, he showed the bilateral hand weakness, conduction blocks on the right median and ulnar nerves by NCS, and the presence of serum anti-GM 1 antibody. From these findings, Lewis-Sumner syndrome was diagnosed. The therapy of high-dose intravenous immunoglobulin moderately improved his symptoms. The clinical symptoms of quadriceps amyotrophy is produced by various disorders including spinal progressive muscular atrophy, spinal extradural arachnoid cyst, rimmed vacuole myopathy, Becker dystrophy, limb-girdle dystrophy, and focal myositis. However, there have been no reports of a case of Lewis-Sumner syndrome. It is important to consider Lewis-Sumner syndrome in the differential diagnosis of quadriceps amyotrophy.     

Eosinophilc polymyositis

A case of eosinophilic polymyositis is reported. Tender muscle swelling was followed by proximal weakness, creatinine kinase elevation, and electromyographic features typical of polymyositis. Severe myocarditis, pericarditis and heart failure were present. Muscle biopsy specimen showed active myositis with eosinophil infiltrate. Unlike previous cases, blood eosinophils count was normal. The clinical response to corticosteroids was excellent, and a relapse occurring as steroid dose was lowered responded rapidly to an increased dose of prednisolone. Eosinophilic polymyositis may be a component of a general systemic illness with prominent cardiac involvement.     

Inclusion body myositis with cricopharyngeus muscle involvement and severe dysphagia.

A patient with inclusion body myositis (IBM) is presented. Unusual aspects of this case include a myopathy of 36 years duration, severe dysphagia due to cricopharyngeus muscle dysfunction, improvement with cricopharyngeus myotomy, and a diagnostic cricopharyngeus muscle biopsy.