Hemi‐Orolingual Angioedema in a Patient With VEXAS Syndrome

Since the original description of VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome, several atypical manifestations of this unusual disease have been reported, providing further insight into the condition [1]. A 66-year-old male patient presented with multiple episodes of ear chondritis and panniculitis over the past 2 years (Figure 1: Panel A and B). Laboratory tests revealed mild macrocytic anemia, and biopsy of the skin lesions (Figure 1: Panel B) showed neutrophilic panniculitis. A bone marrow biopsy was performed, revealing dysplastic features in the myeloid and erythroid series. He was diagnosed with VEXAS syndrome (UBA1 [Met41Thr] mutation using the Sanger method). Concurrently, the presence of low-level biclonal IgG lambda and IgM lambda components, a low-proportion lymphoplasmacytic infiltrate as determined by flow cytometry, and mutated MYD88 was identified. In addition, in next-generation sequencing, DNMT3A mutated with a variant allele frequency of 28%, and normal cytogenetics was observed. The patient was diagnosed with Waldenström macroglobulinemia (smoldering) and low-risk myelodysplastic syndrome. He was treated with 5-azacitidine, and on Day 29 of the first cycle, he reported experiencing dysesthesia in the left hemilingual area, with no other notable findings on physical examination. A second cycle of 5-azacitidine was initiated, and on Day 3, the lingual symptoms persisted, accompanied by significant swelling of the left side of the tongue (Figure 1: Panel C). This condition improved after brief treatment with corticosteroids, and the patient had no further symptoms. He was re-administered 5-azacitidine until the cycle was completed, with no further angioedema observed. Conventional laboratory tests for angioedema revealed no discernible cause. Following the fourth cycle of hypomethylating therapy, the patient continues to show a clinical response, with an improvement in all symptoms and a disappearance of the UBA1 mutation in the bone marrow, as determined using the same technique. Drug reaction to 5-azacitidine. Nevertheless, the Naranjo scale (a method of assessing the causality of drug reactions) has indicated a degree of uncertainty [2, 3]. This is due to the inclusion of re-exposure to the potentially causative agent and the absence of a reaction within the scale's assessment parameters. The underlying mechanism could be non-inflammatory neurovascular compromise, as reported in some patients with stroke; however, most of these cases occur after intravenous thrombolysis with recombinant tissue plasminogen activator in patients taking angiotensin-converting enzyme inhibitors. [4] The VEXAS syndrome itself. A review of the literature reveals that otorhinolaryngological manifestations, periorbital angioedema, and hemifacial edema have been reported in cases of VEXAS syndrome [5]. However, hemi-orolingual angioedema has not been observed, suggesting the possibility of an as-yet undescribed etiology. A deliberative exchange with the medical community was deemed essential to establish a comprehensive understanding framework in the event of the emergence of additional cases involving this entity. All authors participated in the preparation of every component of the article. The authors have nothing to report. Informed consent has been obtained. All authors had access to the data and a role in writing this manuscript. The authors declare no conflicts of interest. The data that support the findings of this study are available on request from the corresponding author.