Anti-HMGCR immune-mediated necrotizing myopathy: A case report / 北京大学学报(医学版)

The patient was a 55-year-old man who was admitted to hospital with "progressive myalgia and weakness for 4 months, and exacerbated for 1 month". Four months ago, he presented with persistent shoulder girdle myalgia and elevated creatine kinase (CK) at routine physical examination, which fluctuated from 1 271 to 2 963 U/L after discontinuation of statin treatment. Progressive myalgia and weakness worsened seriously to breath-holding and profuse sweating 1 month ago. The patient was post-operative for renal cancer, had previous diabetes mellitus and coronary artery disease medical history, had a stent implanted by percutaneous coronary intervention and was on long-term medication with aspirin, atorvastatin and metoprolol. Neurological examination showed pressure pain in the scapularis and pelvic girdle muscles, and V- grade muscle strength in the proximal extremities. Strongly positive of anti-HMGCR antibody was detected. Muscle magnetic resonance imaging (MRI) T2-weighted image and short time inversion recovery sequences (STIR) showed high signals in the right vastus lateralis and semimembranosus muscles. There was a small amount of myofibrillar degeneration and necrosis, CD4 positive inflammatory cells around the vessels and among myofibrils, MHC-Ⅰ infiltration, and multifocal lamellar deposition of C5b9 in non-necrotic myofibrils of the right quadriceps muscle pathological manifestation. According to the clinical manifestation, imageological change, increased CK, blood specific anti-HMGCR antibody and biopsy pathological immune-mediated evidence, the diagnosis of anti-HMGCR immune-mediated necrotizing myopathy was unequivocal. Methylprednisolone was administrated as 48 mg daily orally, and was reduced to medication discontinuation gradually. The patient's complaint of myalgia and breathlessness completely disappeared after 2 weeks, the weakness relief with no residual clinical symptoms 2 months later. Follow-up to date, there was no myalgia or weakness with slightly increasing CK rechecked. The case was a classical anti-HMGCR-IMNM without swallowing difficulties, joint symptoms, rash, lung symptoms, gastrointestinal symptoms, heart failure and Raynaud's phenomenon. The other clinical characters of the disease included CK as mean levels >10 times of upper limit of normal, active myogenic damage in electromyography, predominant edema and steatosis of gluteus and external rotator groups in T2WI and/or STIR at advanced disease phase except axial muscles. The symptoms may occasionally improve with discontinuation of statins, but glucocorticoids are usually required, and other treatments include a variety of immunosuppressive therapies such as methotrexate, rituximab and intravenous gammaglobulin.

Guidelines of the Brazilian Society of Rheumatology for the treatment of systemic autoimmune myopathies

Abstract Background: Recommendations of the Myopathy Committee of the Brazilian Society of Rheumatology for the management and therapy of systemic autoimmune myopathies (SAM). Main body: The review of the literature was done in the search for the Medline (PubMed), Embase and Cochrane databases including studies published until June 2018. The Prisma was used for the systematic review and the articles were evaluated according to the levels of Oxford evidence. Ten recommendations were developed addressing the management and therapy of systemic autoimmune myopathies. Conclusions: Robust data to guide the therapeutic process are scarce. Although not proven effective in controlled clinical trials, glucocorticoid represents first-line drugs in the treatment of SAM. Intravenous immunoglobulin is considered in induction for refractory cases of SAM or when immunosuppressive drugs are contra-indicated. Consideration should be given to the early introduction of immunosuppressive drugs. There is no specific period determined for the suspension of glucocorticoid and immunosuppressive drugs when individually evaluating patients with SAM. A key component for treatment in an early rehabilitation program is the inclusion of strengthbuilding and aerobic exercises, in addition to a rigorous evaluation of these activities for remission of disease and the education of the patient and his/her caregivers.

¿Podemos mejorar la cicatrización de un desgarro muscular masivo? / Can we improve the healing of a massive muscle tear?

OBJETIVOS: Evaluar macroscópica e histológicamente la cicatrización muscular utilizando Dexametasona (DEX) o Traumeel (TRM), en un modelo experimental animal. MATERIAL Y MÉTODOS: Estudio experimental en 45 ratones BKS. Se seccionó transversal y completamente el cuádriceps derecho en todos los animales. Se definieron 3 grupos de estudio de 15 ratones cada uno, un grupo control, un grupo tratado con Dexametasona y uno con Traumeel. Los animales fueron sacrificados a las 1,2 y 4 semanas después del procedimiento y se les extrajo ambos cuádriceps (derecho como intervención e izquierdo como control) y luego fueron analizados macroscópica e histológicamente por un patólogo calificado, de manera ciega. Los datos se analizaron estadísticamente con el test de Kruskal - Wallis (p < 0,05), utilizando el programa Stata V12.1. RESULTADOS: Macroscopía: A la semana, en todos los grupos se evidenció ausencia de cicatrización con gap persistente. A la segunda semana, se evidencia cicatrización inicial sin gap en todos los grupos. A las 4 semanas todas las muestras estaban cicatrizadas. HISTOLOGÍA: La administración de Dexametasona disminuye el infiltrado inflamatorio y aumenta las fibras regenerativas, pero induce mayor fibrosis y pérdida de masa muscular. La adición de Traumeel aumenta la cantidad de fibras regenerativas, pero incrementa el infiltrado inflamatorio. CONCLUSIONES: A las 4 semanas ninguno de los grupos de estudio presentó regeneración muscular completa, con resultados macroscópicos e histológicos variables.

OBJETIVES: To macroscopically and histologically evaluate a muscle strain healing model, using Dexamethasone and Traumeel. MATERIALS AND METHODS: Experimental study in 45 BKS mice. 3 groups of 15 mice were defined: control group, Dexamethasone treated group and Traumeel treated group. The animals were sacrificed at the 1st, 2nd and 4th week, both quadriceps were resected (right as intervention and left as control) and then analyzed macroscopically and histologically by a qualified and blinded pathologist. Results were analyzed statistically using Kruskal - Wallis test (p<0.05). RESULTS: Macroscopy: the first week, all groups showed absence of healing with persistent gap. At the 2nd week, evidence of initial healing without gap in all groups. By week 4, all samples were healed. HISTOLOGY: Dexamethasone decreased the inflammatory infiltration and increased the regenerative fibers, but induced a higher fibrosis and loss of muscle mass. Traumeel increased the amount of regenerative fibers and the inflammatory infiltration. DISCUSSION: The results of our study fail to define a definitive posture. We observed that Traumeel actually increases the amount of regenerative fibers and contrary to the literature, it increases the inflammatory infiltrate. On the other hand, Dexamethasone showed similar results in both regenerative fibers, fatty infiltration and muscle mass, but with increased necrosis. CONCLUSIONS By the 4th week none of the groups showed complete muscle regeneration with macroscopic and histological variable results.

McArdle's disease: an underestimated or underdiagnosed myopathy in rheumatologic practice? Cases series and literature review / Doença de mcardle: uma miopatias subestimada e subdiagnosticada na pratica reumatológica? série clínica e revisão de literatura

OBJECTIVE: McArdle's disease is a metabolic myopathy that manifests with varied clinical conditions and is often confounded with other diagnoses. Herein, the authors report a case series and carry out a literature review. METHODS: A cross-sectional single-center study evaluating 12 patients with McArdle's disease was conducted. RESULTS: Mean age at onset of symptoms was 28.0±17.4 years, while age at disease diagnosis was 39.0±14.8 years. History of intolerance to physical exercises was observed in 10 cases; muscle weakness in 9, second wind phenomenon in only 1 case. The presence of cramps, fatigue and myalgia was observed in 12, 11 and 9 of the cases respectively. Median creatine phosphokinase level was 5951U/L. Most of the patients (83.3%) were initially diagnosed with another condition (polymyositis, inclusion body myositis, fibromyalgia and/or muscular dystrophy), and approximately half had received glucocorticoids and/or immunosuppressants prior to definitive diagnosis. All patients underwent muscular biopsy, which revealed the presence of subsarcolemmal vacuoles characterized by glycogen deposits, and negative histochemical reaction for the myophosphorylase enzyme. CONCLUSION: The present study reinforces the presence of clinical variability among patients and shows that McArdle's disease should be considered one of the differential diagnoses of inflammatory myopathies and other rheumatic diseases.

OBJETIVO: A doença de McArdle é uma miopatia metabólica que se manifesta com condições clínicas variadas e muitas vezes é confundida com outros diagnósticos. Os autores relatam uma série de casos e realizam uma revisão de literatura. MÉTODOS: Estudo transversal de um único centro em que foram avaliados 12 pacientes com doença de McArdle. RESULTADOS: A média de idade no início dos sintomas foi de 28,0±17,4 anos, enquanto a idade no diagnóstico da doença foi de 39,0±14,8 anos. História de intolerância ao exercício físico foi observada em 10 dos casos; fraqueza muscular em 9; fenômeno do "second wind" em apenas 1 caso. A presença de câimbras, fadiga e mialgia foi observada, respectivamente, em 12, 11 e 9 dos casos. O nível mediano de creatinafosfoquinase foi de 5951U/L. Oito pacientes foram inicialmente diagnosticados com outra condição (polimiosite, miosite de corpos de inclusão, fibromialgia e/ou distrofia muscular), e aproximadamente metade havia recebido glicocorticoides e/ou imunossupressores antes do diagnóstico definitivo. Todos os pacientes foram submetidos à biópsia muscular, que revelou a presença de vacúolos subsarcolêmicos caracterizados por depósitos de glicogênio e reação histoquímica negativa para a enzima miofosforilase. CONCLUSÕES: O presente estudo reforça a presença de variabilidade clínica entre pacientes e mostra que a doença de McArdle deve ser considerada um dos diagnósticos diferenciais de miopatias inflamatórias e outras doenças reumáticas.

Miopatía necrotizante autoinmune (NAM): a propósito de un caso clínico / Necrotizing autoimmune myopathy (NAM): a propos of a clinical case

La miopatía inducida por estatinas es una reacción adversa que limita el uso de estos fármacos. Si bien su incidencia es baja, puede asociarse a cuadros severos e invalidantes. Habitualmente la miopatía es autolimitada y mejora con la suspensión del hipolipemiante, pero se han descrito casos en que el daño es persistente. en muchos de estos casos, la biopsia ha permitido demostrar una nueva entidad, denominada Miopatía Necrotizante Autoinmune (NAM) por estatinas, la cual se relaciona a una sobreexpresión del complejo mayor de histocompatibilidad tipo I y a la presencia de anticuerpos anti-HMGCoA reductasa. La NAM inducida por estatinas es una condición que responde al tratamiento esteroidal e inmunosupresor, pero puede dejar importantes secuelas. Por tal razón, su detección precoz y adecuado tratamiento resultan fundamentales. Presentamos el caso clínico de una mujer con esta entidad que refleja la dificultad diagnóstica y terapéutica.

Statins induced myotoxicity, constitutes sometimes a major barries to the use of these drugs. Although a low incidece, may be associated with severe disease and disability. Usually this myopathy is self-limited and improves with the removal of lipid-lowering agent, but has been reported patients with persistent disease. In many of this cases, the muscle biopsy has demonstrated a new entity called autoimmune necrotizing myopathy (NAM) for statins, which is characterized by an up-regulation of major histocompatibility complex type I (MHC I) and the presence of anti-HMGCoA reductase antibodies. NAM caused by statins in difficult to manage and can cause important damage. by this reason, early detection and treatment is crucial. We report a case of a woman with this condition, which reflects the difficulty in diagnosis and therapy.

Critical illness myopathy

Critical illness myopathy [CIM] is a syndrome of widespread muscle weakness and neurological dysfunction which can develop in critically ill patients receiving intensive care. CIM are often distinguished largely on the basis of specialized electrophysiologic testing or muscle and nerve biopsy and its causes are unknown, though they are thought to be a possible neurological manifestation of systemic inflammatory response syndrome usually developing in patients after a brief period of stay in the Intensive Care Unit [ICU]. This case report aims to analyze the Clinical feature, diagnosis and treatment of CIM of 60 years old male case with Chronic Obstructive Lung disease [COPD] admitted to the intensive care. Health professionals working at critical care unit should be aware that any ICU patient may develop CIM

Symptomatic muscle involvement in neurosarcoidosis: a clinicopathological study of 5 cases

We report on the clinical course and histopathologic muscle alterations of five patients diagnosed with neurosarcoidosis, who underwent biopsy due to their muscle manifestations. The five patients were females and only one was less than 40 years of age. Proximal muscle weakness was presented by all and only two patients complained of myalgia. Only normal values of serum muscle enzymes were detected. Electromyography revealed diverse findings such as normal, myopathic and neuropathic patterns. Granuloma was not present in one muscle biopsy. Two patients thoroughly recovered by taking only prednisone and one patient required a methotrexate addition for 3 months before becoming asymptomatic. The other two patients received azathioprine, one due to steroid side effects but without a satisfactory evolution, and the other to strengthen the prednisone régime, with excellent results

Avaliaçäo comparativa do maleato de flupirtina versus diclofenaco potássico em afecçöes músculo-esqueléticas / Comparative study of maleate of flupirtine versus diclofenac potassium in musculoskeletal diseases

A eficácia terapêutica e a tolerabilidade do maleato de flupirtina foram avaliados comparativamente com o diclofenaco potássico em 61 pacientes portadores de afecçöes músculo-esqueléticas. A flupirtina foi administrada na posologia de uma cápsula de 100mg t.i.d., enquanto que o diclofenaco foi administrado na dose de 1 frágea (50mg) t.i.d. Para análise da eficácia foram avaliados os seguintes parâmetros: dor em repouso, dor à movimentaçäo, sensibilidade local, limitaçäo à movimentaçäo e interferência com o sono. A auto-avaliaçäo da dor pelos pacientes também foi analisada. Uma melhora estatisticamente significante (p < 0,001) foi encontrada em todos os parâmetros avaliados nos dois grupos de tratamento. A tolerabilidade foi excelente ou boa em 100% dos pacientes que fizeram uso da flupirtina, e em 50% dos pacientes que usaram o diclofenaco, diferença esta estatisticamente significante (p < 0,01)

AIDS e miopatia: relato de um caso e revisäo da literatura / AIDS and myopathy: report of a case and review of the literature

É relatado o caso de um paciente com miopatia de apresentaçäo clínica incomum como manifestaçäo inicial da infecçäo por HIV. O paciente apresentava aumento de volume dos membros acompanhado de sinais flogísticos e elevaçäo dos níveis séricos de enzimas musculares. A alteraçäo histopatológica predominante consistia em necrose segmentar de fibrocélulas musculares esqueléticas. Evoluiu com pneumonia por Pneumocytis carini, tratada satisfatoriamente com sulfametaxazol e trimetropim. Apesar do uso sucessivo de indometacina, predinisona e dexametasona, a miopatia continuava a progredir. Após administraçäo de methotrexate, houve regressäo do quadro neurológico

Naproxeno sódico 550 mg no tratamento de enfermidades inflamatórias agudas näo-articulares: traumatismos e afecçöes músculo-esqueléticas / Naproxen sodium 550 mg in the treatment of non articular acute inflammatory conditions: trauma and musculoskeletal affections

Os autores realizaram um estudo aberto com o emprego de naproxeno sódico no tratamento de enfermidades agudas näo-articulares (traumatismos e afecçöes músculo-esqueléticas), em 40 pacientes adultos. O fármaco foi administrado em comprimidos de 550 mg, de duas vezes ao dia, a intervalos de 12 horas (1.100 mg diárias), por via oral, por um período de até 15 dias, objetivando observar seus efeitos analgésicos e antiinflamatório. As patologias estudadas foram as mais variadas, destacando-se, entre as mais numerosas, 12 casos de fraturas (30,00%), 8 bursites (20,00%), 5 sinovites (12,50%), 4 entorses (10,00), etc. Os resultados finais obtidos pelos investigadores mostram 24 pacientes (60,00%) com resultados excelentes, 5 pacientes (12,50%) com resultados muito bons, 3 (7,50%) com resultados bons, 5 (12,50%) pacientes com resultados regulares, 1 (2,50%) com resultados insatisfatórios e 2 (5,00%) pacientes näo foram avaliados. Os resultados finais, sob o ponto de vista dos pacientes, mostram os seguintes resultados: 27(67,50%) excelentes, 4(10,00%) muito bons, 1(2,50%) bom, 3(7,50%) regulares e 3(7,50%) insatisfatórios. Igualmente, 2(5,00%) dos pacientes näo foram avaliados, por exclusäo do ensaio. Com relaçäo a tolerabilidade, os efeitos colaterais ocorreram em 4 pacientes (10,00%), todos na esfera do trato gastrintestinal, sendo 1 leve, 1 moderado e 2 com náuseas intensas (5,00%), que obrigaram a suspensäo do tratamento. Os autores concluem ser o naproxeno sódico 550 mg duas vezes ao dia uma droga eficaz e bem tolerada no tratamento de processos inflamatórios agudos näo articulares

Triquinosis esporádica / Sporadic trichnosis

En el presente trabajo se analizan retrospectivamente las características clínicas y de laboratorio detectadas en 13 casos de triquinosis aguda esporádica, estudiados en el Instituto Nacional de Nutrición "Salvador Zubirán" (INNSZ) de 1977 a 1986. El número de casos por año fue de uno a dos con aumento a cinco en 1986; ningún paciente mostró correlación entre el tipo de dieta o sitio específico en la ciudad. La sintomatología fue similar a la descrita para la forma epidémica; en 69.1 por ciento de los casos se sospechó el diagnóstico en base clínicas y el 84.6 por ciento mostró eosinofilia. El motivo de la biópsia muscular fueron los síntomas musculares (92.3%) y corroboró la parasitosis en el 100 por ciento de los pacientes. El tratamiento fue tiabendazol y/o prednisona con mejoría en la mayoría de los pacientes durante su seguimiento (x: 7 meses). Se discute la utilidad de la biopsia muscular, las posibilidades de tratamiento y se enfatiza en los síntomas, signos y hallazgos de laboratorio de la triquinosis esporádica para sospechar dicha zoonosis ante un cuadro clínico de enfermedad inflamatoria multisistémica con síntomas musculares predominantes