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We report a case of myositis that resulted from disseminated cryptococcosis in a patient with hepatitis C cirrhosis. One year after cessation of treatment, the patient remains symptom free with negative results of serum cryptococcal antigen tests and negative culture results.
We describe a patient with a history of allogeneic hematopoietic stem cell transplantation complicated by chronic graft-versus-host disease who developed painful meningoradiculitis and myositis due to Lyme borreliosis. To our knowledge, this is the first report of such an infection occurring after allogeneic hematopoietic stem cell transplantation in the United States.
BACKGROUND: Cryptococcus neoformans var. neoformans is an opportunistic yeast that typically infects immunocompromised patients. METHODS: A case report and review of the pertinent English-language literature are presented. RESULTS: Necrotizing vasculitis associated with cryptococcal invasion was identified in 1986. Until now, only 24 cases of cryptococcal cellulitis have been reported, including one case of cryptococcal necrotizing fasciitis and one case of necrotizing vasculitis. We report an unusual case of occult disseminated cryptococcosis presenting as necrotizing cellulitis, fasciitis, and myositis. CONCLUSIONS: Cryptococcal soft tissue infection serves as a marker of disseminated cryptococcosis in immunocompromised hosts. Owing to its rarity as a cause of soft tissue infections, diagnosis is difficult and mortality is high.
Inclusion body myositis (IBM), a condition characterised by progressive muscle weakness and inclusion bodies visible on muscle biopsy, is the most common type of myopathy in patients over 50 years of age. However, it is not only under diagnosed but frequently misdiagnosed as polymyositis and hence wrongly treated with steroids. In the evaluation of progressive weakness in older Caucasian males, IBM should be an important diagnostic consideration. Treatment-resistant 'polymyositis' in patients over 50 years of age is often IBM. If there is no histological confirmation, the diagnostic criteria allow for a category of 'possible IBM'. Sometimes, the diagnosis is missed because of the slow progression of the disease and a lack of suspicion on the part of physicians. The following case report and literature review will explore many of these issues.
Five of 6 male siblings were affected by a progressive myopathy beginning in early childhood. Muscle biopsies in all patients showed the characteristic changes of inclusion body myositis. Computerized tomography and magnetic resonance imaging revealed a markedly abnormal appearance of cerebral white matter in the 4 affected patients tested, but clinical and other laboratory examinations failed to demonstrate evidence of central white matter dysfunction. Muscle biopsies and brain imaging were normal in all clinically unaffected family members. On the basis of the genetics, muscle biopsy findings and cerebral white matter changes, we conclude that this constellation represents a hitherto undescribed syndrome.
Inclusion body myositis (IBM) was suspected on light microscopic grounds in 48 of 170 consecutive patients with inflammatory myopathies. One or more vacuoles containing membranous material, groups of atrophic fibres, and an autoaggressive endomysial inflammatory exudate occurred in 100, 96 and 92% of the muscle specimens. All three of these features were present in 88% of the specimens. Electron microscopy confirmed the presence of filamentous inclusions in 40 of 43 patients. The inclusions are typically near vacuoles and a minimum of three vacuolated fibres must be scrutinized to detect them with confidence. There is no electromyographic pattern that can reliably distinguish IBM from other inflammatory myopathies. The typical clinical features in the patients diagnosed by histological criteria as IBM were: insidious onset after age 50 yrs with painless, proximal lower extremity weakness; slow but relentless progression with selectively severe involvement of quadriceps, iliopsoas, tibialis anterior, biceps and triceps muscles; relatively early depression of the knee reflexes; and a normal or mildly elevated serum creatine kinase level. The male: female ratio was 3:1. Distal weakness occurred in about 50%, but only in 35% was it as great or greater than proximal weakness. Significant associated illnesses include other autoimmune disorders (15%), diabetes mellitus (20%), and diffuse peripheral neuropathy (18%). Prednisone treatment at dose levels frequently effective in polymyositis failed to prevent disease progression in those patients observed for 2 or more years. Our findings support the notion that IBM is a distinct entity in which a set of pathological features is associated with a constellation of clinical findings.
Sporadic inclusion body myositis (IBM) is the most common inflammatory myopathy affecting patients over the age of 50 years. Dysimmune and degenerative aetiologies have been postulated, but viral infections have not been associated with the disease. Two HIV-I (human immunodeficiency virus type 1) infected men and one woman infected with HTLV-1 (human T cell leukaemia virus type 1) developed progressive proximal muscle weakness unrelated to antiretroviral therapy. Their muscle biopsies were studied by light and electron microscopy, by immunocytochemistry to determine the expression of major histocompatibility complex (MHC) molecules and identify the type of infiltrating cells and T cell receptor (TCR) subunits, and by reverse transcription-polymerase chain reaction (RT-PCR) and single or double immunocytochemistry to search for retrovirally infected endomysial cells. The clinical features were consistent with sporadic IBM. The muscle biopsies showed primary endomysial inflammation, red-rimmed vacuoles, amyloid deposits, eosinophilic inclusions, and small round fibres in groups, all diagnostic of IBM. The muscle fibres expressed MHC class-1 antigens and were invaded primarily by CD8+ T-lymphocytes preferentially bearing TCR V beta 5.1 and V beta 13 chains. The HIV-1 or HTLV-1 antigens were detected only on endomysial macrophages on or around muscle fibres, but not within the muscle fibres. We conclude that IBM occurs in HIV-1 and HTLV-1 infected individuals and has a clinical, histological and immunological pattern identical to sporadic IBM in the non-retrovirally infected patients. Retroviruses do not directly infect the muscle, but persistent retroviral infections may provide superantigenic stimulation and trigger an endomysial inflammatory response identical to that occurring in sporadic IBM.
Sporadic inclusion body myositis (s-IBM) is a chronic inflammatory myopathy of unknown pathogenesis. The common findings of ragged red fibres, cytochrome c oxidase-negative fibres and multiple mitochondrial DNA deletions in the muscle of patients with s-IBM have suggested that a deficit of energy metabolism may be of pathogenic relevance. To test this hypothesis we used 31P magnetic resonance spectroscopy to assess in vivo skeletal muscle mitochondrial function in the calf muscles of 12 patients with definite s-IBM. Eleven patients showed multiple mitochondrial DNA deletions in skeletal muscle and 67% showed ragged red fibres and/or cytochrome c oxidase-negative fibres. T1-weighted MR images showed increased signal intensity in the calf muscle of all patients except one. The involvement of calf muscle was confirmed by 31P magnetic resonance spectroscopy of resting muscle, which disclosed abnormalities in metabolite ratios in all patients. However, muscle oxidative metabolism assessed during recovery from exercise was normal in patients with s-IBM, as maximum rates of mitochondrial ATP production and post-exercise ADP recovery rates were within the normal range in all cases. We conclude that muscle mitochondrial abnormalities are a secondary process and unlikely to play a significant role in the pathogenesis of s-IBM.
Inclusion body myositis (IBM) is an inflammatory myopathy characterized immunohistologically by prominent invasion of the non-necrotic, MHC-I class antigen-expressing muscle fibres by CD8+ cytotoxic T cells. If the autoinvasive CD8+ T cells are recruited specifically to the muscle and play a primary pathogenetic role in the disease, a clonal restriction persisting over time should be anticipated. In this study, we analysed the T-cell receptor (TCR) gene usage by endomysial T lymphocytes in three sequential muscle biopsies from three different IBM patients over a 19-22 month period using immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and sequence analysis of the complementarity determining region (CDR3) of the amplified TCRs. We found that CD8+ T lymphocytes persist in the endomysial infiltrates in all biopsies during a 19-22 month period. The most frequently detected TCRs were the V beta 3, V beta 5.1, V beta 6.7 and V beta 13 gene families, and several of the autoinvasive CD8+ T cells expressed the TCRs V beta 6.7 and V beta 5.1. A restricted usage of the examined V beta 6 gene family was found to persist in the complementarity CDR3 determining region of the autoinvasive T cells over the 22 month period. Identical V beta 6 CDR3 gene arrangements were also found in the multiple muscle biopsies from two of the three IBM patients. The results indicate that in IBM there is a restricted expression of the TCR gene families among the autoinvasive T lymphocytes with homologies in the CDR3 region that persist over the course of the disease. A continuous, antigen-driven T-cell response is prominent in the muscle of patients with IBM.
Interactions between inducible co-stimulatory molecule (ICOS) and ICOS-ligand (ICOS-L) are crucial for T-cell co-stimulation, effector cell differentiation and memory CD8+ T-cell activation. Because in the muscle of patients with sporadic inclusion body myositis (sIBM) clonally expanded CD8+ T cells invade major histocompatibility complex (MHC) class I-expressing muscle fibres, we investigated ICOS.ICOS-L interactions and correlated their expression with perforin, a marker for cytotoxic effector function by autoinvasive CD8+ T cells. The mRNA from 20 muscle biopsies of sIBM, 20 non-inflammatory or dystrophic controls, two dermatomyositis (DM) and two polymyositis (PM) patients was reverse transcribed and reamplified by semi-quantitative and quantitative reverse transcription-polymerase chain reaction (RT-PCR), using primers for ICOS, ICOS-L and perforin. The glyceraldehyde 3-phosphate dehydrogenase (GAPDH)-normalized ratio of ICOS, ICOS-L and perforin expression was compared with the degree of endomysial inflammation. Protein expression of ICOS, ICOS-L and perforin was confirmed by immunohistochemistry. We demonstrate that ICOS-L mRNA was upregulated in sIBM (arbitrary units, median +/- SEM: 48.6 +/- 14.9) compared with controls (6.2 +/- 17.8, P < 0.05) and significantly correlated with the expression of ICOS (53.9 +/- 16.6 versus 6.7 +/- 8.9 in controls, P < 0.001). By triple labelling immunohistochemistry, the CD8+ T cells in sIBM and PM were found to invade ICOS-L- and MHC class I-co-expressing muscle fibres. Among the autoinvasive CD8+ T cells, however, only a subset of approximately 5-10% were ICOS positive, and thereby perceptive for ICOS.ICOS-L signalling at the immunological synapse. In contrast, in Duchenne muscular dystrophy and DM, although ICOS and ICOS-L mRNA expression was also increased, the majority of ICOS-L- and ICOS-positive cells were in the perimysial regions and connective tissue. The mRNA for perforin was increased in sIBM (28.1 +/- 8.7) compared with controls (4.3 +/- 11.2, P = 0.18), and significantly correlated with mRNA of ICOS, ICOS-L and the degree of endomysial inflammation as assessed in coded haematoxylin/eosin tissue sections. By triple immunohistochemical staining and cell counting, perforin granules were found in 71% of the autoinvasive CD8+ T cells that were also ICOS positive. Our data indicate that in sIBM there is upregulation of ICOS.ICOS-L co-stimulatory signalling in association with enhanced perforin expression by the autoinvasive CD8+ T cells. The findings support previous suggestions that in IBM, the muscle fibres have the capacity for antigen presentation, thereby activating a specific subset among the autoinvasive CD8+ T cells to exert a cytotoxic effect. The observations strengthen the immunopathogenesis of sIBM, and offer the basis for future therapeutic interventions targeting ICOS.ICOS-L co-stimulatory interactions.
Inclusion body myositis (IBM) is the most frequent inflammatory myopathy over the age of fifty. Pathological findings suggest that two processes may contribute to IBM pathogenesis: a primary degenerative process affecting muscle fibre and/or an autoimmune process mediated by major histocompatibility complex (MHC) class-I-restricted cytotoxic CD8+ T cells. Previous studies have demonstrated that muscle-infiltrating CD8+ T cells in IBM display restricted expression of T-cell receptor (TCR)-BV families or evidenced oligoclonal T-cell expansions. This study was performed to investigate whether blood T cells similarly exhibit clonal expansions due to the recirculation of muscle-infiltrating T cells in the periphery. For this, we studied the T-cell repertoire of 17 IBM patients by complementarity-determining-region (CDR) 3 length distribution (immunoscope) analysis of TCR-B transcripts. Mean age was 68 years (range 53-88) and mean duration of the disease was 6.5 years (2-20). Oligoclonal T-cell expansions were observed in the blood of IBM patients. The quantitative average perturbation D index was significantly increased in IBM patients [D = 13.7% +/- 1.2%, mean +/- standard error of measurement (SEM)] as compared with 17 age-matched controls suffering from connective tissue diseases not associated with T-cell repertoire perturbation, that is, dermatomyositis (DM) and systemic sclerosis (9.3 +/- 0.6%, P < 0.005). Nevertheless, there was no correlation between the level of blood perturbation and muscle inflammation. Sorting experiments showed that these perturbations were due to oligoclonal expansions of CD8+ T cells. In the three IBM patients analysed, we could relate the blood expansions to T-cell clones also found in muscle. The clonally expanded blood T cells dramatically responded to interleukin-2 (IL-2) in vitro, suggesting that they had been primed in vivo, presumably in response to yet unknown muscle auto-antigens. Together, our results indicate that clonally expanded muscle-infiltrating CD8+ T cells re-circulate in the blood and support the concept of a CD8+ T-cell-mediated autoimmune component in IBM, similarly to what is observed in polymyositis (PM).
A man with AIDS presented with a deep soft-tissue mass involving the right thigh. Biopsy of a skin lesion on the back and culture of a specimen from this lesion showed bacillary angiomatosis due to Bartonella (formerly Rochalimaea) quintana. Magnetic resonance imaging revealed a large heterogeneous mass involving the vastus medialis and intermedius muscles. Therapy with erythromycin caused rapid resolution of both the cutaneous lesion and the muscle lesion. Bartonella infection is proposed as an additional cause of bacterial myositis and expands the spectrum of presentation of bacillary angiomatosis.
Hantaviruses are etiologic agents of hemorrhagic fever with renal syndrome, an acute illness characterized by acute renal insufficiency, proteinuria, and hemodynamic instability. Recently, a New World form of hantavirus disease, hantavirus pulmonary syndrome (HPS), was recognized; in this form, pulmonary edema is prominent, but renal insufficiency is generally lacking. HPS cases from the southeastern United States may be exceptional in that they have exhibited both pulmonary and renal manifestations. One case in Louisiana and one case in Florida were linked to infection by the distinct but closely related Bayou and Black Creek Canal hantaviruses, respectively. We report a nonfatal case of HPS caused by Bayou hantavirus that occurred in eastern Texas. Clinical manifestations included pulmonary and renal insufficiency and myositis, which had previously been observed in the patient from Florida. The occurrence of distinctive clinical abnormalities in HPS cases from the southeastern United States supports the concept that there are clinically significant differences between western and southeastern forms of HPS.
The group G streptococcus (GGS) is a rare cause of deep soft-tissue infection. We report that we believe is the first case of acute diffuse GGS myositis in association with toxic shock. Although the causative organism did not contain the genes for group A streptococcal pyrogenic exotoxins (SPEs) or make SPEs, the organism produced at least one new toxin that shared the biologic properties of the SPEs.
A 54-year-old man presented with gangrenous myositis caused by Streptococcus pyogenes. A review of the literature disclosed 10 similar cases. Their presenting manifestations were spontaneously occurring, localized, excruciating pain; mottling suggestive of ischemic changes; and signs of sepsis. The duration of illness ranged from two to six days, and the outcome was uniformly fatal. This rare but distinct entity resembles clostridial myonecrosis except that it lasts slightly longer and does not involve gaseous crepitus. A definitive diagnosis of myonecrosi scan be established by surgical exploration; early, radical debridement plus penicillin therapy should be undertaken after diagnosis in an attempt to alter the usual devastating outcome.
We investigated the relative efficacies of penicillin, clindamycin, and erythromycin in a mouse model of myositis due to Streptococcus pyogenes. Penicillin was ineffective unless given at the time of bacterial injection, and treatment delays of 2 h reduced its efficacy such that survival was no better than that of untreated control animals (P less than .05). Survival of erythromycin-treated mice was greater than that of both penicillin-treated mice and untreated controls, but only if treatment was begun within 2 h. Mice receiving clindamycin, however, had survival rates of 100%, 100%, 80%, and 70% even if treatment was delayed 0, 2, 6, and 16.5 h, respectively. Thus, clindamycin demonstrated superior efficacy to penicillin among all the various treatment groups (P less than .05). Our results corroborate the failure of penicillin in this model of streptococcal infection and suggest that, unlike penicillin, the efficacy of clindamycin is not adversely altered by the "Eagle effect."
Alpha-synuclein (alpha-syn) is an important component of neuronal and glial inclusions in brains of patients with several neurodegenerative disorders. Sporadic inclusion-body myositis (s-IBM) is the most common progressive muscle disease of older patients. Its muscle phenotype shows several similarities with Alzheimer disease brain. A distinct feature of s-IBM pathology is specific vacuolar degeneration of muscle fibers characterized by intracellular amyloid inclusions formed by both amyloid-beta (Abeta) and paired-helical filaments composed of phosphorylated tau. We immunostained alpha-syn in muscle biopsies of s-IBM, disease-control, and normal patients. Approximately 60% of Abeta-positive vacuolated muscle fibers (VMF) contained well-defined inclusions immunoreactive with antibodies against alpha-syn. In those fibers. alpha-syn co-localized with Abeta, both by light microscopy, and ultrastructurally. Paired-helical filaments did not contain alpha-syn immunoreactivity. In all muscle biopsies, alpha-syn was strongly immunoreactive at the postsynaptic region of the neuromuscular junctions. alpha-syn immunoreactivity also occurred diffusely in regenerating and necrotic muscle fibers. In cultured human muscle fibers, alpha-syn and its mRNA were expressed by immunocytochemistry, immunoblots, and Northern blots. Our study provides the first demonstration that alpha-syn participates in normal and pathologic processes of human muscle. Therefore. its function is not exclusive to the brain and neurodegenerative diseases.
We review the newest advances related to seeking the pathogenic mechanism(s) of sporadic inclusion-body myositis (s-IBM) and present the pathologic diagnostic criteria of s-IBM. We discuss the possible pathogenic role of several themes, such as 1) increased amyloid-beta precursor protein (AbetaPP) and of its fragment Abeta; 2) phosphorylation of tau protein; 3) oxidative stress; 4) abnormal a) signal-transduction, b) transcription, and c) RNA accumulation; 5) "junctionalization" and myogenous" denervation; and 6) lymphocytic inflammation. Evidence is provided supporting our hypothesis that overexpression of AbetaPP within the aging muscle fibers is an early upstream event causing the subsequent pathogenic cascade. The remarkable pathologic similarities between s-IBM muscle and Alzheimer disease (AD) brain are discussed, and the possible cause and significance are addressed.