Abnormal Motility Associated With Tumor Necrosis Factor Receptor-Associated Periodic Fever Syndrome

Abstract

Introduction: Tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS) is a rare autosomal dominant condition with mutations in the TNFRSF1A gene encoding for the tumor necrosis factor receptor 1 (TNFR1) and is commonly associated with gastroenterological related symptoms. An NIH cohort of 53 patients with TRAPS reported that 92% of patients with TRAPS present with abdominal pain. The pathophysiology of TRAPS may be a defective shedding of the mutant TNFR1 receptor. Lack of shedding of this receptor leads to decreased neutralization of serum TNF and to increased proinflammatory signaling. The motility profile of patients with this syndrome has not been delineated. We present a 62-year-old female with a history of acute gastroenteritis 5 years prior to presentation, marking the beginning of persistent GI symptoms including postprandial abdominal pain, constipation, myalgias, nausea, progressive weight loss and fever of unknown origin diagnosed with TRAPS. GI evaluation including colonoscopy showed microscopic colitis and EGD was otherwise negative. Other motility evaluation done such as breath testing showed small bowel overgrowth. Gastric emptying study supported a diagnosis of gastroparesis. As her GI symptoms progressed, a 6-hour antroduodenal manometry was performed showing a disorganized motility pattern in the interdigestive (fasting) state consistent with a visceral neuropathy. Despite treatment with several prokinetics and antibiotics for overgrowth and pseudoobstruction, the patient continued to deteriorate and required TPN for nutritional support. She later developed neurologic symoptoms including tremors and was referred to neurology team for further evaluation. After evaluations for familial mediterranean fever and other neurologic causes of her dysmotility were ruled out, she was worked up for hereditary fever syndrome which prompted genomic studies revealing the patient had a R121Q variant in the TNFRSF1A gene. This variant is also referred to R92Q which is the accurate location in the mature, processed protein. She was then started on immunosupressives. To our knowledge this is the first case that describes a motility disorder in a patient with TRAPS. Our patient’s complicated medical course sheds light into some of the GI symptoms associated with TRAPS and the importance of early diagnosis in these patients before the onset of profound malnutrition.