Tocilizumab for treatment of cutaneous and systemic manifestations of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome without myelodysplastic syndrome

Goyal, Amrita; Narayanan, Damodaran; Wong, Waihay; Laga, Alvaro C.; Connell, Nathan T.; Ritter, Susan; Cobos, Gabriela

doi:10.1016/j.jdcr.2022.02.022

Cited by 37 publications

(21 citation statements)

References 8 publications

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“…Treatment of VEXAS syndrome involves suppression of the initial in ammation with steroids, followed by disease-modifying antirheumatic drugs (DMARDs) and immunosuppressive drugs to reduce the steroid dose [15][16][17]. Bone marrow transplantation is also considered a radical treatment [18].…”

Section: Discussionmentioning

confidence: 99%

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome presenting as recurrent aseptic peritonitis in a patient receiving peritoneal dialysis: a case report

Fukuda

Kanai

Hoshino

et al. 2023

Preprint

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Background Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is caused by mutations in the ubiquitin-activating enzyme 1 (UBA1) gene and is characterised by the overlap of multiple autoinflammatory and haematologic disorders. It is a rare disease first described in December 2020. Case presentation: We report the case of a 67-year-old Japanese man undergoing peritoneal dialysis (PD) for recurrent aseptic peritonitis caused by VEXAS syndrome. He presented with an unexplained fever, headache, abdominal pain, conjunctival hyperaemia, ocular pain, auricular pain, arthralgia, and inflammatory skin lesions. Laboratory investigations showed a high serum C-reactive protein concentration and an increased white blood cell count in the PD effluent. He was treated with antibiotics for PD-related peritonitis but to no avail. Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography demonstrated intense FDG uptake in the left superficial temporal artery, nasal septum, and bilateral auricles. The working diagnosis was giant cell arteritis, and the patient was treated with oral prednisolone (PSL) 15 mg daily, with a good response. However, the PSL dose could not be tapered to less than 10 mg daily because of auricular pain, skin lesions, and PD effluent turbidity. Tocilizumab was administered every two weeks as a steroid-sparing agent; hence, the PSL dose could be tapered to 2 mg daily without any symptoms. Sanger sequencing of his peripheral blood sample revealed a mutation affecting methionine-41 (c.122 T > C; p.Met41Thr) of the UBA1 gene. We made the final diagnosis of VEXAS syndrome. He had a flare of VEXAS syndrome at a PSL of 1 mg daily with cloudy PD effluent, conjunctival hyperaemia, arthralgia, auricular chondritis, and inflammatory skin lesions, such as Sweet's syndrome, on his upper limbs and neck. Increasing the PSL dose to 11 mg daily relieved the symptoms within a few days. Conclusions VEXAS syndrome causes turbid PD effluent without infection. When peritonitis is observed in patients on PD, nephrologists and general physicians should consider the possibility of aseptic peritonitis due to autoimmune diseases, including VEXAS syndrome, and pay attention to their systemic findings.

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Section: Discussionmentioning

confidence: 99%

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome presenting as recurrent aseptic peritonitis in a patient receiving peritoneal dialysis: a case report

Fukuda

Kanai

Hoshino

et al. 2023

Preprint

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“…High serum IL-6 levels have been reported in patients with VEXAS syndrome [ 1 ]. In this regard, tocilizumab has been described to induce both modest effect and a good disease control [ 26 , 37 ]. A study on three patients suggested that tocilizumab associated to low-dosage glucocorticoids may be an effective option in patients without severe hematologic abnormalities.…”

Section: Therapy Evidencementioning

confidence: 99%

“…Regarding patients with gastrointestinal involvement, tocilizumab treatment seems to be a risk factor for perforation of the jejunum or ileum in the site of diverticulitis. Consequently, despite the tocilizumab effectiveness reported in VEXAS syndrome [ 37 , 40 ], a particular attention should be given to this subgroup of patients.…”

Section: Therapy Evidencementioning

confidence: 99%

VEXAS syndrome: a new paradigm for adult-onset monogenic autoinflammatory diseases

et al. 2023

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VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a recently described pathological entity. It is an acquired monogenic autoinflammatory disease caused by somatic mutations of the UBA1 gene in blood cells precursors; the gene encodes one of the two E1 enzyme isoforms that initiates ubiquitylation in cell’s cytoplasm. VEXAS syndrome leads to systemic inflammation, with all organs and tissues potentially involved. The clinical picture may be extremely heterogenous, mimicking different other systemic rheumatologic entities coexisting with haematological disorders, especially myelodysplastic syndrome. This new disease represents a very intriguing clinical condition in several respects: it accounts for the paradigm of adult-onset monogenic autoinflammatory diseases determined by a genetic mosaicism resulting in the development of a challenging multiorgan inflammatory condition. Moreover, VEXAS syndrome is perhaps not an exceptionally rare condition and represents an example of a systemic genetic autoinflammatory disease drawing its origin in bone marrow disorders. VEXAS syndrome should be strongly considered in each adult patient with an unexplained systemic inflammatory condition, especially when recurrent fevers, neutrophilic dermatosis, relapsing polychondritis, ocular inflammation and other systemic inflammatory symptoms accompanying myelodysplastic syndrome or other haematological disorders. The syndrome deserves a multidisciplinary approach to reach the diagnosis and ensure the best management of a potentially very challenging condition. To quickly describe the clinical course, long-term outcomes, and the optimal management of this new syndrome it is essential to join forces internationally. To this end, the international AutoInflammatory Disease Alliance (AIDA) registry dedicated to VEXAS syndrome has been developed and is already active.

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“…Treatment of VEXAS is an evolving area of research and it is beyond the scope of this article to be able to comment on potential therapeutic options from the evidence presented here. Treatment strategies used in the included cases varied markedly, and included high-dose corticosteroids (most commonly reported), conventional synthetic disease-modifying antirheumatic drugs (DMARDs) including methotrexate and mycophenolate, and biologic DMARDS, including cyclophosphamide, IL-1 antagonists, IL-6 inhibitors, TNF inhibitors, rituximab and JAK inhibitors [1,8,24,26,29,32,35,42]. There was one reported case of the use of ruxolitinib followed by allogeneic stem cell transplant [39].…”

Section: Points To Consider In Treatmentmentioning

confidence: 99%

Pulmonary manifestations in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome: a systematic review

et al. 2023

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Background VEXAS (vacuoles, E1 enzyme, X-linked, auto-inflammatory, somatic) syndrome is a newly described auto-inflammatory disease. Many cases feature pulmonary infiltrates or respiratory failure. This systematic review aimed to summarize respiratory manifestations in VEXAS syndrome described to date. Methods Databases were searched for articles discussing VEXAS syndrome until May 2022. The research question was: What are the pulmonary manifestations in patients with VEXAS syndrome? The search was restricted to English language and those discussing clinical presentation of disease. Information on basic demographics, type and prevalence of pulmonary manifestations, co-existing disease associations and author conclusions on pulmonary involvement were extracted. The protocol was registered on the PROSPERO register of systematic reviews. Results Initially, 219 articles were retrieved with 36 ultimately included (all case reports or series). A total of 269 patients with VEXAS were included, 98.6% male, mean age 66.8 years at disease onset. The most frequently described pulmonary manifestation was infiltrates (43.1%; n = 116), followed by pleural effusion (7.4%; n = 20) and idiopathic interstitial pneumonia (3.3%; n = 9). Other pulmonary manifestations were: nonspecific interstitial pneumonia (n = 1), bronchiolitis obliterans (n = 3), pulmonary vasculitis (n = 6), bronchiectasis (n = 1), alveolar haemorrhage (n = 1), pulmonary embolism (n = 4), bronchial stenosis (n = 1), and alveolitis (n = 1). Several patients had one or more co-existing autoimmune/inflammatory condition. It was not reported which patients had particular pulmonary manifestations. Conclusion This is the first systematic review undertaken in VEXAS patients. Our results demonstrate that pulmonary involvement is common in this patient group. It is unclear if respiratory manifestations are part of the primary disease or a co-existing condition. Larger epidemiological analyses will aid further characterisation of pulmonary involvement and disease management.

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Tocilizumab for treatment of cutaneous and systemic manifestations of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome without myelodysplastic syndrome

Cited by 37 publications

References 8 publications

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome presenting as recurrent aseptic peritonitis in a patient receiving peritoneal dialysis: a case report

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome presenting as recurrent aseptic peritonitis in a patient receiving peritoneal dialysis: a case report

VEXAS syndrome: a new paradigm for adult-onset monogenic autoinflammatory diseases

Pulmonary manifestations in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome: a systematic review

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