RESUMO
OBJECTIVES: To efficiently detect somatic UBA1 variants and establish a clinical scoring system predicting patients with pathogenic variants in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. METHODS: Eighty-nine Japanese patients with clinically suspected VEXAS syndrome were recruited [81 males and 8 females; median onset age (IQR) 69.3 years (62.1-77.6)]. Peptide nucleic acid-clamping PCR (PNA-PCR), regular PCR targeting exon 3 clustering UBA1 variants, and subsequent Sanger sequencing were conducted for variant screening. Partitioning digital PCR (pdPCR) or targeted amplicon deep sequencing (TAS) was also performed to evaluate the variant allele frequency (VAF). We developed our clinical scoring system to predict UBA1 variant-positive and negative patients and assessed the diagnostic value of our system using receiver operating characteristic (ROC) curve analysis. RESULTS: Forty patients with reported pathogenic UBA1 variants (40/89, 44.9%) were identified, including a case having a variant with VAF of 1.7%, using a highly sensitive method. Our clinical scoring system considering >50 years of age, cutaneous lesions, lung involvement, chondritis, and macrocytic anaemia efficiently predicted patients with UBA1 variants (the area under the curve for the scoring total was 0.908). CONCLUSIONS: Genetic screening with the combination of regular PCR and PNA-PCR detected somatic UBA1 variants with high sensitivity and specificity. Our scoring system could efficiently predict patients with UBA1 variants.
RESUMO
Background: Polymyositis/dermatomyositis (PM/DM) patients often develop interstitial lung disease (ILD), which can lead to relapse despite anti-inflammatory treatments. This study aims to elucidate the clinical characteristics of relapses in PM/DM-associated ILD patients. Methods: We gathered clinical data, including laboratory results, pulmonary function tests, chest high-resolution computed tomography findings from patients treated at Okinawa Chubu Hospital between January 1, 2010 and December 31, 2018. Results: We identified a total of 74 patients, comprising 21 men and 53 women. Among them, 38 patients remained relapse-free with maintenance therapy, while 36 experienced relapses despite immunosuppressive management. We followed these patients until June 30, 2023, and 13 patients died. The median survival period was 51.4 months (range, 0.3-214 months). When comparing clinical variables, relapsed patients tended to be younger (49.9 vs. 64.1 years), reported myalgia and rash more frequently (63.9% vs. 28.9% and 61.15% vs. 21.1%, respectively). In terms of laboratory findings, lactate dehydrogenase (LDH) levels were higher in relapsed patients (613±464 vs. 381±203 U/L). Radiological findings showed that ground glass opacity (GGO) was more prevalent in relapsed patients (58.3% vs. 16.7%). A Cox-proportional hazards model for relapse demonstrated that serum LDH [hazard ratio (HR) 1.005, 95% confidence interval (CI): 1.000-1.009, P=0.02] and GGO (HR 1.863, 95% CI: 1.103-3.147, P=0.02) were valuable predictors of relapse. Receiver operating characteristic curve analysis of serum LDH indicated that a threshold of 450 correctly classified relapse in PM/DM-associated ILD patients. Conclusions: Serum LDH and GGO may serve as predictors of relapse in PM/DM-associated ILD patients.
RESUMO
Myopathy and peritoneal involvement are rare complications of sarcoidosis, and the latter can mimic malignancy with peritoneal dissemination. In this case, a patient with a history of polyarthritis and positive rheumatoid factor presented with proximal muscle weakness and abdominal pain. Biopsies of muscle and peritoneum revealed non-caseating granuloma suggesting sarcoidosis. Ocular and pulmonary involvement later developed and confirmed the diagnosis of sarcoidosis.
Assuntos
Doenças Musculares , Miosite , Sarcoidose , Granuloma , Humanos , Doenças Musculares/diagnóstico , Doenças Musculares/etiologia , Peritônio , Sarcoidose/complicações , Sarcoidose/diagnósticoRESUMO
A postpartum patient with acute-onset dyspnoea and hypotention, associated with reduced left ventricular function requiring intensive blood pressure control, was initially misdiagnosed as having peripartum cardiomyopathy. Her clinical symptoms rapidly resolved. Echocardiography revealed reversible left ventricular dysfunction with apical ballooning and coronary angiography was normal. Based on these findings, we diagnosed takotsubo syndrome. Over the next two months, the patient experienced repeated bouts of elevated sympathetic activity. On workup, we found an adrenal mass and elevated urine metanephrines. After adrenalectomy, histology confirmed pheochromocytoma. Our patient had the rare diagnosis of postpartum pheochromocytoma-induced takotsubo syndrome.
Assuntos
Neoplasias das Glândulas Suprarrenais , Feocromocitoma , Cardiomiopatia de Takotsubo , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia , Feminino , Humanos , Feocromocitoma/complicações , Feocromocitoma/diagnóstico , Feocromocitoma/cirurgia , Período Pós-Parto , Cardiomiopatia de Takotsubo/diagnóstico , Cardiomiopatia de Takotsubo/etiologiaRESUMO
BACKGROUND Patients with late-onset systemic lupus erythematosus (SLE) do not present with typical SLE symptoms or serology, and this can lead to a major delay in diagnosis. We report a complex case of an older woman who developed autoimmune hemolytic anemia and sixth cranial nerve palsy that posed considerable challenges in diagnosing late-onset SLE. CASE REPORT A 78-year-old Japanese woman presented with polyarthritis associated with generalized fatigue for 2 months, who later developed diplopia. Physical examination revealed conjunctival pallor, polyarthritis, and subsequent development of sixth cranial nerve palsy. Laboratory data revealed a decreased white blood cell count; macrocytic anemia; elevated levels of lactate dehydrogenase, indirect bilirubin, and erythrocyte sedimentation rate; hypocomplementemia; positive Coombs test; antinuclear antibodies (ANAs, 1: 40); and positive anti-double-strand DNA antibodies. Lymphoma, cerebral venous sinus thrombosis, and varicella-zoster virus infection were unlikely based on head computed tomography, brain magnetic resonance imaging, and cerebrospinal fluid analysis. She was diagnosed with late-onset SLE associated with autoimmune hemolytic anemia and sixth cranial nerve palsy. The patient was successfully treated with prednisone and hydroxychloroquine. CONCLUSIONS The difficulty in diagnosing late-onset SLE with atypical presentations and uncommon complications must be recognized. SLE cannot be excluded based on a low titer of ANA in a particular subgroup such as the elderly, and the prozone effect should be considered responsible for low ANA titers. In this case, late-onset SLE was diagnosed by considering multisystem pathologies despite low ANA titers.
Assuntos
Doenças do Nervo Abducente , Anemia Hemolítica Autoimune , Lúpus Eritematoso Sistêmico , Idoso , Anemia Hemolítica Autoimune/complicações , Anemia Hemolítica Autoimune/diagnóstico , Anticorpos Antinucleares , Feminino , Humanos , Hidroxicloroquina , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnósticoRESUMO
Ureteral calcification is a rare complication of systemic vasculitis. Bilateral ureteral calcification in a patient with eosinophilic granulomatosis with polyangitis led to obstructive uropathy. A combination of immunosuppressive therapy and ureteral reconstruction successfully restored kidney function.