USAID Associated with Myeloid Neoplasm and VEXAS Syndrome: Two Differential Diagnoses of Suspected Adult Onset Still’s Disease in Elderly Patients

Abstract

Background: Patients with solid cancers and hematopoietic malignancy can experience systemic symptoms compatible with adult-onset Still’s disease (AOSD). The newly described VEXAS, associated with somatic UBA1 mutations, exhibits an overlap of clinical and/or biological pictures with auto inflammatory signs and myelodysplastic syndrome (MDS). Objectives: To describe a cohort of patients with signs of undifferentiated systemic autoinflammatory disorder (USAID) concordant with AOSD and MDS/chronic myelomonocytic leukemia (CMML) and the prevalence of VEXAS proposed management and outcome. Methods: A French multicenter retrospective study from the MINHEMON study group also used for other published works with the support of multidisciplinary and complementary networks of physicians and a control group of 104 MDS/CMML. Results: Twenty-six patients were included with a median age at first signs of USAID of 70.5 years with male predominance (4:1). Five patients met the criteria for confirmed AOSD. The most frequent subtypes were MDS with a blast excess (31%) and MDS with multilineage dysplasia (18%). Seven patients presented with acute myeloid leukemia and twelve died during a median follow-up of 2.5 years. Six out of 18 tested patients displayed a somatic UBA1 mutation concordant with VEXAS, including one woman. High-dose corticosteroids led to a response in 13/16 cases and targeted biological therapy alone or in association in 10/12 patients (anakinra, tocilizumab, and infliximab). Azacytidine resulted in complete or partial response in systemic symptoms for 10/12 (83%) patients including 3 VEXAS. Conclusion: Systemic form of VEXAS syndrome can mimic AOSD. The suspicion of USAID or AOSD in older males with atypia should prompt an evaluation of underlying MDS and assessment of somatic UBA1 mutation.

Commentary: ‘Case Report: A Rare Case of Elderly-Onset Adult Onset Still’s Disease in a Patient With Systemic Lupus Erythematous’

“…( 10 , 11 ) about atypical skin rash reported in early-onset AOSD, but these patients did not benefit from screening for VEXAS either. Moreover, the oedema described on both eyelids in the case reported reminds us of the 10 patients with periorbital oedema over the 116 VEXAS syndromes from the French cohort but also the 4 patients identified as undifferentiated systemic autoinflammatory disorder in our recent work ( 8 , 12 ).…”

“…Its phenotype is still extending but mostly characterized by fever, skin lesions, lung infiltrates, arthralgia, lymph node, and biological inflammatory syndrome with haematological abnormalities including macrocytic anaemia and myelodysplastic syndrome ( 7 ). In 2022, VEXAS is considered as a differential diagnosis for AOSD particularly in the elderly ( 8 ) and previous diagnosis of AOSD have been rectified a posteriori with UBA1 screening ( 9 ).…”

Bibliometrics analysis on the research status and trends of adult-onset Still’s disease: 1921-2021

“…MAS is a potentially fatal inflammatory disease that lacks targeted therapy and relies primarily on combination immunosuppressive agents to relieve symptoms ( 91 ). Patients with hematopoietic malignancies, such as leukemia, may present with systemic symptoms consistent with AOSD ( 92 ). Therefore, to exclude hematological malignancies, the researchers suggest bone marrow aspiration and lymph node biopsy ( 93 ).…”

The role of interleukin 1 in the development of human diseases: focus on Anakinra (IL-1 receptor antagonist)

“…К ним можно отнести болезнь Стилла взрослых (БСВ) (пример комплекс ного САВЗ) [297], палиндромный ревматизм [298][299][300], «полимилгический» вариант РА у пожилых людей [301][302][303]. Описаны «перекресты» БСВ с анкилозирующим спондилоартритом и псоратическим артритом [304], семейной средиземноморской лихорадкой [305,306]; ассоциация БСВ c другими ИВЗ, включая болезнь Крона [307][308][309], саркоидоз [310,311], синдром VEXAS (vacuoles, E1 enzyme, X-linked, autoinfl ammatory, somatic) [312][313][314], синдром Шницлера [315,316], нейтрофильный уртикарный дерматоз [317,318], а также неклассифицируемого САВЗ, миелодиспластического синдрома и синдрома VEXAS [319]. У пациентов с серонегативным РА в полости сустава могут выявляться кристаллы мочевой кислоты, которые, активируя NLRP3-инфламмасому, индуци руют синтез ИЛ-1β [320].…”