RESUMO
Subacute symmetrical proximal muscle weakness and persistent elevated creatine kinase levels are typical of immune-mediated necrotising myopathy (IMNM). These conditions are accompanied by copious myofibre necrosis, degeneration and regeneration with minimal to no inflammation on muscle biopsy. We report two cases (case 1 and case 2) of asymptomatic IMNM from different families with hyperCKaemia associated with positive anti-signal recognition particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies, respectively, and we also reviewed the literature. There are only a few previous descriptions of patients with asymptomatic IMNM.The disease onset could be insidious and lead to delayed diagnosis and treatment. We recommend testing for the anti-HMGCR and anti-SRP antibodies in patients with idiopathic hyperCKaemia because they could show no symptoms of this disorder.
Assuntos
Autoanticorpos/sangue , Creatina Quinase/sangue , Hidroximetilglutaril-CoA Redutases/imunologia , Imunoglobulinas Intravenosas/administração & dosagem , Miosite , Partícula de Reconhecimento de Sinal/imunologia , Doenças Assintomáticas , Biópsia/métodos , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/diagnóstico , Debilidade Muscular/etiologia , Músculo Esquelético/patologia , Miosite/diagnóstico , Miosite/imunologia , Miosite/fisiopatologia , Necrose/patologia , Resultado do TratamentoRESUMO
The therapeutic approach with statins is widely used in the control of dyslipidemias. However, there is no laboratory evaluation to elect patients to make use of this class of therapeutic drugs.We analyzed the prevalence of anti-signal recognition particle (anti-SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibodies in a heterogeneous cohort of 85 patients in order to determine cutoff reference values for these antibodies.Serum samples from 85 patients were screened for the presence of anti-HMGCR and anti-SRP autoantibodies by enzyme-linked immunosorbent assay. The demographic, clinical, and morphological features were also correlated with anti-HMGCR and anti-SRP antibodies. The patients were divided in 2 groups: A, statin-exposed, and B, statin-unexposed.There was no significant association (Pâ>â.05) among anti-HMGCR and anti-SRP titers in relation to age, sex, statin exposure, and CK level. The concentrations of both antibodies were not correlated with symptoms, CK level, or statin exposure. Eleven (12.9%) patients had anti-HMGCR antibodies. We found a tendency (Pâ=â.051) toward greater anti-HMGCR positivity in women with no symptoms. Twelve (14.1%) patients had anti-SRP antibodies. There was no sex predominance, and only 1 patient had muscle complaints. Muscular symptoms were present in 31 (36.5%) patients, 4 (12.9%) were positive for anti-HMGCR antibodies, and 1 (3.2%) was positive for anti-SRP antibodies. A total of 54 (63.5%) patients had no muscle symptoms, 7 (13%) were anti-HMGCR positive, and 11 (20.4%) were anti-SRP positive. We found statistical significance for patients with anti-SRP antibodies when asymptomatic and symptomatic patients were compared (Pâ=â.029). In contrast, there was no statistically significant difference between symptoms and positivity for anti-HMG antibodies.One of the main aims of this study was to define a cutoff point in a heterogeneous population with different diagnoses. We also demonstrated that anti-HMGCR and anti-SRP antibodies are not 100% specific to immune-mediated necrotizing myopathy. We believe that these antibodies must be tested and interpreted within the specific context.
Assuntos
Autoanticorpos/imunologia , Hidroximetilglutaril-CoA Redutases/imunologia , Inibidores de Hidroximetilglutaril-CoA Redutases/imunologia , Músculo Esquelético/imunologia , Partícula de Reconhecimento de Sinal/imunologia , Autoanticorpos/sangue , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miosite/diagnóstico , Miosite/imunologia , Miosite/patologia , Necrose , Valores de Referência , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: Prompted by the few studies available in the literature, we analysed patients with necrotising myopathy associated with anti-signal recognition particle (anti-SRP). METHODS: We conducted a retrospective, single-centre cohort study involving 14 patients with anti-SRP antibody followed between 2001 and 2016. RESULTS: Patients had a mean age at disease onset of 40.7 years and were predominantly female and of white ethnicity. At disease onset, all patients had limb muscle weakness with median serum of creatine phosphokinase level of 8080U/L, 64.3% had constitutional symptoms, 50% dysphagia, 42.9% myalgia, 21.4% and 14.3% pulmonary and articular involvement, respectively. There were no cases of cutaneous, neurological or cardiac involvements. Notably, 21.4% of patients had previous exposure to statins. Moreover, with the exception of one patient, all received methylprednisolone pulse therapy and/or human intravenous immunoglobulin (IVIg), as well as prednisone and different immunosuppressive drugs or rituximab. Relapse occurred in 64.3% of the cases. However, most patients had significant recovery of muscle strength, with half no longer using glucocorticoids and the remainder on a weaning regimen with low dose prednisone. CONCLUSIONS: Unlike the cases described in the literature, there was a high frequency of extra-muscular symptoms in the patients studied. Moreover, one fifth of patients had previous exposure to statin use. There was a high relapse rates, but with good clinical and laboratory recovery, especially with pulse therapy regimen of methylprednisolone and/or IVIg.
Assuntos
Autoanticorpos/sangue , Músculo Esquelético/imunologia , Miosite/imunologia , Partícula de Reconhecimento de Sinal/imunologia , Adolescente , Adulto , Biomarcadores/sangue , Brasil , Creatina Quinase/sangue , Quimioterapia Combinada , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Miosite/sangue , Miosite/diagnóstico , Miosite/tratamento farmacológico , Necrose , Fenótipo , Recidiva , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
This study aimed to investigate the role of anti-SRP19 antibody in muscle tissues of patients with autoimmune necrotizing myopathy. Immunohistochemistry staining was used to determine the expression of anti-SRP19 antibodies in muscle tissues of autoimmune necrotizing myopathy patients. Results demonstrated that anti-SRP19 antibody was expressed in 71.4% (20/28) of muscle tissue specimens from patients with autoimmune necrotizing myopathy. Anti-SRP19 antibody expression was mainly localized in cytoplasm of necrotic muscle fibers surrounding the small blood vessels and interstitial cells. There were no significant differences in the age, course of disease, muscle, and creatine kinase levels between patients with positive or negative expression of anti-SRP19 antibodies. The expression levels of anti-SRP19, serum anti-nuclear antibodies, as well as anti-Ro-52, anti- SSA, anti-Sm, and anti-Jo-1 antibodies were not significantly different among groups. This study demonstrates that anti-SRP19 antibody is highly expressed in muscle tissues of patients with autoimmune necrotizing myopathy, and suggests that this protein may be involved in the origin and progression of the disease.