S4484 A Case of Cyclic Vomiting-Like Syndrome Secondary to a Cryopyrin Gene Mutation Causing Interleukin-1 (Il-1) Overproduction: Durable Symptom Resolution With Anti Il-1β Therapy

Introduction: Muckle-Well syndrome (MWS) and familial cold auto-inflammatory syndrome (FCAS) are cryopyrin-associated periodic syndromes (CAPS) due to mutations in NLRP3, causing defective inflammasomes and subsequent, periodic overproduction of Interleukin-1 (IL-1), resulting in an inflammatory response causing neurologic, cutaneous, ophthalmologic, articular, and gastrointestinal (GI) manifestations. We present a unique case of a patient referred to GI clinic for cyclical vomiting who was ultimately diagnosed with MWS and FCAS. Case Description: A 40-year-old man presented to GI clinic for evaluation of severe, episodic nausea and vomiting. Episodes occurred every 2 weeks since childhood, associated with migraines, visual changes and rash, triggers included heat exposure. He was diagnosed with cyclic vomiting syndrome. Symptoms progressed to fatigue, tremors, abdominal pain, vertigo, memory impairment, and vision loss. No cannabis use was reported. Endoscopic evaluation was only notable for Helicobacter pylori on gastric biopsy which was successfully treated. A colonoscopy was normal. C-reactive protein, antinuclear antibody, serum protein electrophoresis, cytokine panel, and glutamic acid decarboxylase 65 antibody were normal and there was no evidence of porphyria or heavy metal toxicity. Immunoglobulin levels revealed minimally low immunoglobulin M. Biopsy of a skin lesion revealed subacute spongiotic dermatitis with a normal immunofluorescence. A multidisciplinary evaluation failed to reveal a unifying diagnosis. Ultimately, genetic testing revealed heterozygosity in NLRP12 and NLRP3, consistent with CAP (MWS and FCAS). Canakinumab (anti-IL-1β) was initiated with complete resolution of his GI symptoms and drastic improvement in his systemic symptoms. Discussion: CAPS are a family of syndromes related to autosomal dominant and de novo mutations in NLRP3, resulting in periodic inflammatory responses due to overproduction of IL-1 with a prevalence of 1-3 per million persons. Manifestations are systemic, and patients may present with GI symptoms such as episodic abdominal pain and, in this case, also with episodic nausea and vomiting. These syndromes should be considered in patients presenting with episodic GI symptoms in addition to episodic systemic manifestations, as an adequate diagnosis is essential to provide targeted anti-IL-1 treatment, which can provide sustained relief and prevent further complications.