Vexas autoinflammatory syndrome, cutaneous and systemic manifestations – case study

Abstract

Autoinflammatory syndromes are rare diseases characterized by chronic and recurrent inflammation of various tissues and organs. VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) is a recently described condition characterized by genetic mutations in the UBA1 gene and varied cutaneous and systemic manifestations [1,2]. This article aims to emphasize the importance of recognizing VEXAS syndrome in patients presenting with recurrent and undiagnosed cutaneous and systemic symptoms, highlighting the need for early genetic diagnosis and appropriate management to improve the prognosis and quality of life of patients affected by this rare and complex condition. Case Presentation The patient, a 65-year-old male, presents with a wide range of symptoms, including painful erythematous nodular eruptions of varying sizes in the facial region, lip and facial swelling, xerostomia, dysphagia to  liquids, arthralgia in the radiocarpal and metatarsophalangeal areas, myalgia, and paresthesia. The disease history extends over 5 years, with exacerbations and complications, including persistent fever. Dermatological status shows chronic inflammatory lesions exacerbating symmetrically on the face, head, and neck, represented by painful nodules, erythematous angioedema of the lips and periorbital region, as well as vasculitis on the lower limbs. Paraclinical findings include a skin biopsy showing mild hyperkeratosis, leukocytoclastic vasculitis of small vessels in the dermis, histiocytic infiltration, necrotic areas, and extension of the infiltrate around the adnexa and subcutaneous tissue. Genetic analysis using EDTA/NGS methods revealed a pathogenic variant in the UBA1 gene associated with VEXAS syndrome, with a Met41 mutation. The Met41Leu variant is associated with VEXAS syndrome and carries a high risk for developing Sweet syndrome. Based on anamnesis data, clinical examination, and paraclinical findings, a diagnosis of VEXAS Autoinflammatory Syndrome with cutaneous and systemic manifestations was made. Treatment consisted of Methylprednisolone 4mg, 5 tablets/day for 10 days, with subsequent dose reduction by 1/4 tablet every 10 days to 4 tablets/day, Sol. Methotrexate 10mg-1ml i/m, 1 injection/week, with monthly hepatic toxicity monitoring, and Folic Acid 5mg/day. Discussion The clinical case demonstrates the importance of genetic diagnosis, as VEXAS syndrome presents symptoms overlapping with other autoimmune and inflammatory diseases, making diagnosis based solely on clinical symptoms very difficult. Genetic testing can confirm the presence of specific mutations in the UBA1 gene, thus providing a definitive diagnosis, allowing for an effective, patient-centered approach, personalized disease management, avoidance of inappropriate treatments, and genetic counseling for the patient’s family. Conclusion The peculiarities of the presented case underscore the importance of recognizing VEXAS syndrome in the context of patients with recurrent and undiagnosed cutaneous and systemic symptoms. Genetic diagnosis and appropriate management are essential for improving the prognosis and quality of life of patients with this rare and complex condition. Further studies are needed to better understand the pathogenesis and treatment of this disease to provide more effective and personalized care for patients with VEXAS syndrome.