PO:10:141 | A Case Study: Navigating the VEXAS Syndrome Mimickers

Erika Montabone¹, Richard Borrelli¹, Nicolò Rashidy¹, Fabiana Giannoccaro², Giuseppe Guida², Federico Itri³, Renato Carignola⁴, Simone Negrini¹, Stefania Nicola¹, Luca Lo Sardo¹, Iuliana Badiu¹, Federica Corradi¹, Ambra Bonvicino⁵, Maurizio Balbi⁶, Luisa Brussino¹ | ¹SCDU Immunologia e Allergologia, AO Mauriziano, Dipartimento di Scienze Mediche, Università degli Studi di Torino Torino, Italy; ²SSD Asma grave, malattie rare del polmone e fisiopatologia respiratoria, AOU San Luigi Gonzaga Orbassano, Italy; ³SCDU Medicina Interna ad indirizzo Ematologico, AOU San Luigi Gonzaga Orbassano, Italy; ⁴SCDU Medicina Interna, Scleroderma Unit, AOU San Luigi Gonzaga Orbassano, Italy; ⁵SCDU Dermatologia, Città della Salute e della Scienza di Torino Torino, Italy; ⁶SCDU Radiodiagnostica, AOU San Luigi Gonzaga, Dipartimento di Oncologia Orbassano, Italy

Background. The recent identification of VEXAS syndrome has expanded the spectrum of late-onset autoinflammatory disorders associated with somatic mutations in UBA1 gene. However, clinical similarities of VEXAS with autoimmune diseases and the presence of clonal haematopoiesis present diagnostic challenges in patients with negative UBA1 results.

Materials and Methods. We present the case of a 65-year-old man initially diagnosed with psoriatic arthritis and demonstrated ANA positivity. He showed a poor response to methotrexate, TNF-alpha, and IL-17 inhibitors. Later development of biopsy confirmed panniculitic prompted a re-evaluation of the diagnosis, leading to the consideration of systemic lupus erythematosus and subsequent treatment with hydroxychloroquine and dapsone. Over time, he developed unexplained macrocytic anaemia.

Results. Initial investigations excluded emolysis, folate or B12 deficiency and dapsone-related toxicity. Bone marrow analysis revealed mild dyserythropoiesis without overt dysplasia. Due to the onset of a dry cough, a chest HRCT scan was performed, revealing lower-lobe predominant ground-glass opacity with traction bronchiectasis, consistent with non-specific interstitial pneumonia (NSIP). The clinical presentation met the criteria for interstitial pneumonia with autoimmune features. A second bone marrow analysis using NGS identified pathogenic somatic mutations in TET2 and ZRSR2, while sequencing of the UBA1 gene was negative. MMF was introduced, partially controlling joint, skin, and pulmonary symptoms.

Conclusions. This case highlights a diagnostic dilemma involving the coexistence of autoimmune and autoinflammatory features with clonal haematopoiesis. TET2 and ZRSR2 mutations suggested a link with age-related clonal haematopoiesis or an evolving myeloid neoplasm; however, the criteria for myelodysplastic syndrome (MDS) were not met. Although UBA1 sequencing was negative, the clinical overlap with VEXAS syndrome warrants consideration of broader VEXAS-like. This case emphasizes the importance of considering immunological and genetic factors in patients with clonal hematopoiesis of indeterminate potential. This reinforces the importance of considering mutations in genes like TET2 and ZRSR2 within the context of autoimmune and inflammatory disorders, highlighting the complexities discussed in the interplay between clonal hematopoiesis and autoimmune diseases.