Project details

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The missing link? The novel auto-inflammatory VEXAS syndrome as a potential underlying disorder in patients with Sweet syndrome (acute febrile neutrophilic dermatosis).
Keywords: immunology dermatology Inflammatory rheumatic disease
Researchers: Dr. K. de Leeuw Joost Meijer
Type of project: Pilot project (year 2 or 3)
Nature of the research: This is an exciting project on the newly identified auto-inflammatory VEXAS syndrome with a variable clinical presentation of systemic inflammatory symptoms and frequent cutaneous lesions, especially neutrophilic dermatosis. It is very likely that some of patients who now have the diagnosis of Sweet syndrome, actually have this recent discovered VEXAS syndrome. The aim of this project is to characterize an established patient cohort with Sweet syndrome and to investigate whether some of these patients actually have VEXAS .
Fields of study: dermatology immunology reumatology

Background / introduction

A newly discovered adult auto-inflammatory syndrome entitled VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) was described in 2020. [Beck NEJM 2020] VEXAS is a prototype for a new class of haemato-inflammatory diseases and connects previously unrelated inflammatory syndromes. Cutaneous lesions are one of the most frequent symptoms and have been reported in a broad spectrum of clinical presentations. [Sterling JAAD 2022] Approximately 150 cases have been published, of which the majority of patients were originally diagnosed with hematologic, rheumatologic of dermatologic diseases such as myelodysplastic syndrome, relapsing polychondritis, polyarteritis nodosa or Sweet syndrome.[vd Made JACI 2021] Therefore, a number of the patients now diagnosed with these diseases may actually have VEXAS syndrome.

Research question / problem definition
To characterize clinical, histopathological and immunological features of patients with a diagnosis of Sweet syndrome in an established patient cohort, and to investigate whether these patients may actually have VEXAS syndrome.

Workplan
1. Extract clinical, histopathological, immunological and laboratory data from a patient cohort (approximately 20-25 patients) 2. Build a dataset with established variables 3. Assess parameters indicative for VEXAS syndrome and identify potential patients 4. Genetic analysis to analyse whether VEXAS syndrome is present.

References

1. Beck DB, Ferrada MA, Sikora KA, Ombrello AK, Collins JC, Pei W, et al. Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease . New England Journal of Medicine. 2020 Dec 31;383(27):2628–38.

2. Sterling D, Duncan ME, Philippidou M, Salisbury JR, Kulasekararaj AG, Basu TN. VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) for the dermatologist. Journal of the American Academy of Dermatology. Elsevier Inc.; 2022.

3. van der Made CI, Potjewijd J, Hoogstins A, Willems HPJ, Kwakernaak AJ, de Sevaux RGL, et al. Adult-onset autoinflammation caused by somatic mutations in UBA1: A Dutch case series of patients with VEXAS. Journal of Allergy and Clinical Immunology. 2022 Jan 1;149(1):432-439.e4.

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