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

Abstract

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.

VEXAS syndrome presenting as diffuse alveolar haemorrhage

“…Pulmonary manifestations in the form of pulmonary infiltrates were seen in 72% of patients in the study by Beck et al . Other pulmonary manifestations reported include idiopathic interstitial pneumonia, pulmonary embolism, alveolitis, pleural effusion, non-specific interstitial pneumonia and bronchiectasis 2. Borie et al 3 in the largest published cohort of pulmonary manifestations of VEXAS syndrome did not report any cases of alveolar haemorrhage.…”

“…It was recently described in 2020, and since then, the spectrum of the disease has been expanding. Lung manifestations in the form of ground glass opacities, consolidation, reticulations, nodules and pleural effusion have been described in literature 1 2. Overlap with various connective tissue disorders and vasculitides has also been seen.…”

Case report: VEXAS as an example of autoinflammatory syndrome in pulmonology clinical practice

“…The pulmonological aspects of VEXAS are less precisely characterized, although they are reported as constant clinical features during follow-up and seldom as the main clinical complaint (14). In 2022, the first systematic review aimed to summarize the respiratory manifestations of VEXAS as described in the literature (15). The most commonly described manifestation was pulmonary infiltrates, present in 43% of patients, often coexisting with other lung pathologies, such as nonspecific interstitial pneumonia, pulmonary vasculitis, and pleural effusion.…”

VEXAS syndrome: a new discovered systemic rheumatic disorder

“…Pulmonary manifestations are relatively common [ 32 ]. Almost half of the patients have pulmonary infiltrates.…”

“…Less common are pleural effusion and idiopathic interstitial pneumonia. Single case reports of bronchiolitis obliterans, pulmonary vasculitis, bronchiectasis, and alveolar hemorrhage have been published [ 7 , 32 ].…”