RESUMEN

INTRODUCTION: Pompe disease is a lysosomal storage disorder. This study aimed to validate and compare 2 fluorimetric methods for measuring α-glucosidase acid activity in dried blood spot sample (DBS), with potential applications in neonatal screening, and disease follow-up of Pompe patients among the Iranian population for the first time. MATERIALS AND METHODS: The evaluation involved 3 enzyme levels and 7 parameters. The analysis included 141 Healthy individuals, 8 Pompe patients, and 10 obligate heterozygotes using reference and modified methods. RESULTS: Both methods exhibited highly linear calibration curves. The limit of detection (LOD) and limit of quantification (LOQ) were obtained in the micromolar concentration range in 2 methods. Inter-day and intra-day precision, expressed as relative standard deviations (RSD%) were calculated. The normal ranges were determined in healthy individuals. Receiver operating characteristic (ROC) curves were analyzed, and 2 parameters, total neutral α-glucosidase (NAG)/acid α-glucosidase (GAA) and pH ratio, were identified as cut-off values with excellent accuracy, sensitivity, and specificity for evaluating Pompe disease in both methods. CONCLUSIONS: Establishing and implementing these 2 methods for the Iranian population effectively differentiated between healthy and patient individuals. Method II, with its shorter incubation time, demonstrated practicality in the clinical setting.

Asunto(s)

Enfermedad del Almacenamiento de Glucógeno Tipo II , Recién Nacido , Humanos , Enfermedad del Almacenamiento de Glucógeno Tipo II/diagnóstico , alfa-Glucosidasas , Irán , Tamizaje Neonatal , Fluorometría

RESUMEN

Checkpoint inhibitors induce a plethora of immune-related adverse events (irAEs) including autoimmune colitis, hepatitis, endocrinopathies, and rarer side effects like neuritis. Here, a case of autoimmune cardiomyopathy (grade 3 CTCAE) and myocarditis under combination therapy with nivolumab plus ipilimumab in a 72-year-old melanoma patient is reported. Treatment induced a partial response for 14 months. However, after 10 infusions the patient developed dyspnea, edema of the legs, ascites and a weight gain of 10 kg because of a decompensated heart insufficiency with a reduced ejection fraction from formerly 48%-50% to 15%. Ischemia and viral infections were ruled out. Histopathology showed hypertrophic myocarditis with interstitial lymphocytes. Prednisolone improved the patient's condition within 3 days, leading to a 25% and 30% ejection fraction after 2 and 8 weeks, respectively, and clinical symptoms subsided completely. Importantly, reinduction of anti-PD1 therapy resulted in a flare of myocarditis. Awareness for potentially life-threatening irAE of checkpoint inhibitors like autoimmune cardiomyopathy and myocarditis is crucial to rapidly initiate adequate treatment.

Asunto(s)

Anticuerpos Monoclonales/uso terapéutico , Brazo/patología , Inmunoterapia/métodos , Ipilimumab/uso terapéutico , Melanoma/tratamiento farmacológico , Miocarditis/diagnóstico , Neoplasias Cutáneas/tratamiento farmacológico , Anciano , Antígeno CTLA-4/inmunología , Resultado Fatal , Paro Cardíaco , Humanos , Inmunoterapia/efectos adversos , Masculino , Melanoma/diagnóstico , Miocarditis/tratamiento farmacológico , Miocarditis/etiología , Nivolumab , Prednisolona/uso terapéutico , Receptor de Muerte Celular Programada 1/inmunología , Neoplasias Cutáneas/diagnóstico

RESUMEN

Antibiotics are known to cause severe cutaneous adverse reactions, such as the rare acute generalized exanthematous pustulosis (AGEP). Unlike Stevens-Johnson syndrome or toxic epidermal necrolysis, AGEP is rarely life-threatening. Systemic involvement is not typical, and if present usually coincides with a mild elevation of the hepatic enzymes and a decrease in renal function. Hence, AGEP is known to have a good prognosis and to be life-threatening only in elderly patients or patients with chronic diseases. Herein, we report a case of AGEP in a young healthy male leading to systemic inflammatory response syndrome and to treatment in an intensive care unit after being treated with 5 different antibiotics. Initial symptoms were not indicative for AGEP and the patient's course of disease led promptly to critical cardiorespiratory symptoms and systemic inflammatory response syndrome. We assume that the administration of the 5 different antibiotics resulted in type IV allergy as well as secondary infection with Enterococcus faecium and Staphylococcus aureus, while the underlying periodontitis also contributed to the severity of this case.

Asunto(s)

Pustulosis Exantematosa Generalizada Aguda/diagnóstico , Pustulosis Exantematosa Generalizada Aguda/patología , Antibacterianos/efectos adversos , Antibacterianos/inmunología , Síndrome de Respuesta Inflamatoria Sistémica/patología , Adulto , Amoxicilina/efectos adversos , Amoxicilina/inmunología , Amoxicilina/uso terapéutico , Ampicilina/efectos adversos , Ampicilina/inmunología , Ampicilina/uso terapéutico , Antibacterianos/uso terapéutico , Ciprofloxacina/efectos adversos , Ciprofloxacina/inmunología , Ciprofloxacina/uso terapéutico , Enterococcus faecium/aislamiento & purificación , Humanos , Masculino , Penicilina G/efectos adversos , Penicilina G/inmunología , Penicilina G/uso terapéutico , Periodontitis/tratamiento farmacológico , Periodontitis/microbiología , Infecciones Estafilocócicas/complicaciones , Staphylococcus aureus/aislamiento & purificación , Sulbactam/efectos adversos , Sulbactam/inmunología , Sulbactam/uso terapéutico

RESUMEN

Immune-checkpoint blocking antibodies have demonstrated objective antitumor responses in multiple tumor types including melanoma, non-small cell lung cancer (NSCLC), and renal cell cancer (RCC). In melanoma, an increase in overall survival has been demonstrated with anti-CTLA-4 and PD-1 inhibition. However, a plethora of immune-mediated adverse events has been reported with these agents. Immune-mediated cardiotoxicity induced by checkpoint inhibitors has been reported in single cases with variable presentation, including myocarditis and pericarditis. Among six clinical cancer centers with substantial experience in the administration of immune-checkpoint blocking antibodies, eight cases of immune-related cardiotoxicity after ipilimumab and/or nivolumab/pembrolizumab were identified. Diagnostic findings, treatment and follow-up are reported. A large variety of cardiotoxic events with manifestations such as heart failure, cardiomyopathy, heart block, myocardial fibrosis and myocarditis was documented. This is the largest case series to date describing cardiotoxicity of immune-checkpoint blocking antibodies. Awareness, monitoring of patients with pre-existing cardiac disorders and prompt evaluation by the treatment team is essential. Treatment including application of steroids is critical for patient safety.

RESUMEN

Immune-related adverse events (irAEs) induced by checkpoint inhibitors are well known. Since fatal outcomes have been reported early detection and adequate management are crucial. In particular, colitis is frequently observed and can result in intestinal perforation. This is the first report of an autoimmune colitis that was treated according to algorithms but became resistant due to a CMV reactivation. The 32-y-old male patient with metastatic melanoma treated within an anti-PD-1/ipilimumab combination study developed severe immune-mediated colitis (CTCAE grade 3) with up to 18 watery stools per day starting 2 weeks after treatment initiation. After improving upon therapy with immunosuppressive treatment (high dose steroids and infliximab) combined with parenteral nutrition diarrhea again exacerbated. Additionally, the patient had asymptomatic grade 3 CTCAE amylase and lipase elevation. Colitis was monitored by weekly endoscopies and colon biopsies were analyzed histologically with CMV staining, multi-epitope ligand cartography (MELC) and qRT-PCR for inflammatory genes. In the course, CMV reactivation was detected in the colon and treated with antiviral medication in parallel to a reduction of corticosteroids. Subsequently, symptoms improved. The patient showed a complete response for 2 y now including regression of bone metastases. CMV reactivation under checkpoint inhibitor therapy in combination with immunosuppressive treatment for autoimmune side effects has to be considered in these patients and if present treated. Potentially, CMV reactivation is underdiagnosed. Treatment algorithms should include CMV diagnostics.