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Key Clinical Updates in Relapsing Polychondritis

A newly described genetic syndrome, VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic), is caused by somatic mutations in UBA1 in hematopoietic progenitor cells. Clinical features include hematologic manifestations (cytopenias, bone marrow failure) and a spectrum of inflammatory features such as chondritis, vasculitis, fever, and arthritis. This rare syndrome (predominately in males because it is X-linked) should be considered in the differential diagnosis of chondritis especially in the presence of an unexplained macrocytosis and evidence of systemic inflammation (ie, high ESR/CRP).

Ferrada MA et al. Arthritis Rheumatol. [PMID: 33779074]

This disease is characterized by inflammatory destructive lesions of cartilaginous structures, principally the ears, nose, trachea, and larynx. Nearly 40% of cases are associated with another disease, especially other immunologic disorders (ANCA vasculitis, SLE, rheumatoid arthritis, or Hashimoto thyroiditis), cancers (plasma cell myeloma), or hematologic disorders (myelodysplastic syndrome). Relapsing polychondritis is episodic and affects men and women equally. The cartilage is painful, swollen, and tender during an attack and subsequently becomes atrophic, resulting in permanent deformity. Biopsy of the involved cartilage shows inflammation and chondrolysis. Laryngotracheal and bronchial chondritis can lead to life-threatening airway narrowing and collapse. Noncartilaginous manifestations of the disease include fever, episcleritis, uveitis, deafness, aortic regurgitation, inflammatory arthritis, and rarely, glomerulonephritis. In 85% of patients, a migratory, asymmetric, and seronegative arthropathy occurs, affecting both large and small joints and the costochondral junctions. Large vessel vasculitis is a frequently overlooked but potentially catastrophic complication. Diagnosing this uncommon disease is especially difficult since the signs of cartilage inflammation (such as red ears or nasal pain) may be more subtle than the fever, arthritis, rash, or other systemic manifestations and there are no serologic markers for the disease.

Prednisone, 0.5–1 mg/kg/day orally, is often effective. Dapsone (100–200 mg/day orally) or methotrexate (7.5–20 mg orally per week) may also have efficacy, sparing the need for long-term high-dose corticosteroid treatment. Involvement of the tracheobronchial tree may respond to inhibitors of TNF.

A newly described genetic syndrome, VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic), is caused by somatic mutations in UBA1 in hematopoietic progenitor cells. Clinical features include hematologic manifestations (cytopenias, bone marrow failure) and a spectrum of inflammatory features such as chondritis, vasculitis, fever, and arthritis. This rare syndrome (predominately in males because it is X-linked) should be considered in the differential diagnosis of chondritis especially in the presence of an unexplained macrocytosis and evidence of systemic inflammation (ie, high ESR/CRP).

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Beck  DB  et al. Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease. N Engl J Med. 2020;383:2628.
[PubMed: 33108101]  
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Ferrada  M  et al. Defining clinical subgroups in relapsing polychondritis: a prospective observational cohort study. Arthritis Rheumatol. 2020;72:1396.
[PubMed: 32249511]  
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Ferrada  MA  et al. Somatic mutations in UBA1 define a distinct subset of relapsing polychondritis patients with VEXAS. Arthritis Rheumatol. 2021;73:1886.
[PubMed: 33779074]  
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Tomelleri  A ...

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