Relapsing polychondritis is a rare immune-mediated disease that is characterized by recurrent episodes of inflammation that primarily affects the cartilage of the ear and nose but also potentially involves the eyes, tracheobronchial tree, heart valves, kidneys, joints, skin, and blood vessels. Diagnosis is based on a combination of clinical, laboratory, imaging, and rarely biopsy findings. Treatment is based on severity and usually requires anti-inflammatory medications, corticosteroids, and sometimes other immunosuppressants.
Relapsing polychondritis affects men and women equally; onset typically is in middle age (1).
An association with rheumatoid arthritis, systemic vasculitis, systemic lupus erythematosus (SLE), and other systemic rheumatic diseases suggests an autoimmune etiology.
Reference
1. Hazra N, Dregan A, Charlton J, Gulliford MC, D'Cruz DP. Incidence and mortality of relapsing polychondritis in the UK: a population-based cohort study. Rheumatology (Oxford). 2015;54(12):2181-2187. doi:10.1093/rheumatology/kev240
Symptoms and Signs of Relapsing Polychondritis
Acute pain, erythema, and swelling most commonly affect the pinna cartilage and surrounding tissues, which may lead eventually to deformities of ear cartilage described as cauliflower ear and floppy ear.
Nasal cartilage inflammation is the next most common manifestation, occasionally leading to saddle nose deformity, followed by arthritis that varies from arthralgias to symmetric or asymmetric nondeforming arthritis involving large and small joints, with a predilection for the costochondral joints and knees (1).
Other manifestations include inflammation of the
Eye (eg, keratitis, episcleritis, scleritis, iritis)
Cartilaginous tissue of the larynx, trachea, or bronchi (causing hoarseness, cough, tenderness over the laryngeal cartilage, and, if cartilage involvement is severe, dyspnea)
Middle and inner ears, leading to conductive, sensorineural, or mixed hearing loss
Cardiovascular system (eg, aortic regurgitation, mitral regurgitation, pericarditis, myocarditis, aortic aneurysms, aortitis)
Rarely kidney
Rarely skin (eg, cutaneous manifestations of acute febrile neutrophilic dermatosis, leukocytoclastic vasculitis)
Bouts of acute inflammation heal over days to months, with recurrences over several years.
The cartilaginous portion (pinna) of the ear is erythematous and inflamed.
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This photo shows recurrent inflammation causing destruction of the ear cartilage and forming floppy ear in a patient with relapsing polychondritis patient.
Photo courtesy of Kinanah Yaseen, MD.
A punch biopsy of the small erythematous papules seen in this photo showed spongiotic epidermis surfaced by pustulosis filled with robust neutrophilic infiltrate with perivascular infiltration. These findings are consistent with acute febrile neutrophilic dermatosis.
Photo courtesy of Kinanah Yaseen, MD.
The cartilaginous portion (pinna) of the ear is erythematous and inflamed.
© Springer Science+Business Media
This photo shows recurrent inflammation causing destruction of the ear cartilage and forming floppy ear in a patient with relapsing polychondritis patient.
Photo courtesy of Kinanah Yaseen, MD.
A punch biopsy of the small erythematous papules seen in this photo showed spongiotic epidermis surfaced by pustulosis filled with robust neutrophilic infiltrate with perivascular infiltration. These findings are consistent with acute febrile neutrophilic dermatosis.
Photo courtesy of Kinanah Yaseen, MD.
Advanced disease can lead to destruction of supporting cartilage, causing floppy ears, saddle nose, pectus excavatum, and visual, auditory, and vestibular abnormalities. Tracheal involvement can lead to dyspnea, pneumonia, or even tracheal collapse.
Relapsing polychondritis may overlap with other autoimmune disorders, such as inflammatory bowel disease, spondyloarthropathy, systemic vasculitides (eg, Behcet disease, large-vessel vasculitis) (2), and mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome (3), and lastly with cancers, including myelodysplastic syndrome. A subset of patients with relapsing polychondritis have VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, which was recognized in 2020 as a rare disorder caused by a mutation in the UBA1 gene that encodes the E1-activating enzyme involved in intracellular destruction of defective proteins (4). VEXAS syndrome is reported mainly in older males with a history of relapsing polychondritis, Sweet syndrome, macrocytosis, and recurrent fever.
Symptoms and signs references
1. Ferrada M, Rimland CA, Quinn K, et al. Defining Clinical Subgroups in Relapsing Polychondritis: A Prospective Observational Cohort Study. Arthritis Rheumatol. 2020;72(8):1396-1402. doi:10.1002/art.41270
2. Tomelleri A, Campochiaro C, Sartorelli S, et al. Large-vessel Vasculitis Affecting the Aorta and its Branches in Relapsing Polychondritis: Case Series and Systematic Review of the Literature. J Rheumatol. 2020;47(12):1780-1784. doi:10.3899/jrheum.190862
3. Luo Y, Bolek EC, Quinn KA, et al. A prospective observational cohort study and systematic review of 40 patients with mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome. Semin Arthritis Rheum. 2022;52:151924. doi:10.1016/j.semarthrit.2021.10.007
4. Beck DB, Ferrada MA, Sikora KA, et al. Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease. N Engl J Med. 2020;383(27):2628-2638. doi:10.1056/NEJMoa2026834
Diagnosis of Relapsing Polychondritis
Clinical features
Rarely biopsy
Relapsing polychondritis is mainly a clinical diagnosis after excluding other potential mimickers such as infections and granulomatosis with polyangiitis.
Laboratory tests are not specific but are done to help exclude other disorders. Synovial fluid analysis reveals no or mild inflammatory changes. Blood tests may show anemia (normocytic or macrocytic), leukocytosis, elevated erythrocyte sedimentation rate (ESR) or gamma-globulin levels, and occasionally positive rheumatoid factor or antinuclear antibodies (ANA) in up to 25% of patients. Abnormal renal function may indicate an associated glomerulonephritis. Positive antineutrophil cytoplasmic antibodies (ANCA) that are reactive mainly to proteinase-3 may suggest granulomatosis with polyangiitis, which can cause chondritis. Collagen II antibodies are neither sensitive nor specific for relapsing polychondritis.
The upper and lower airways should be evaluated, including by direct laryngoscopy, complete spirometric testing, expiratory chest CT, and bronchoscopy if airway involvement is suspected. A baseline echocardiogram might be considered to evaluate the aortic root and ascending aorta.
A biopsy of the inflamed cartilage is rarely required to confirm the diagnosis.
Diagnosis of VEXAS syndrome is suggested by bone marrow examination showing cytoplasmic vacuoles in myeloid and erythroid precursor cells and is confirmed by the presence of the UBA1 gene mutation on genetic testing.
Image courtesy of Kinanah Yaseen, MD.
Treatment of Relapsing Polychondritis
Nonsteroidal anti-inflammatory drugs (NSAIDs), dapsone, or colchicine for mild nose or ear disease
Corticosteroids
Sometimes methotrexate or other immunosuppressants (eg, cyclosporine, cyclophosphamide, tumor necrosis factor inhibitors, abatacept, interleukin-6 inhibitors)
Mild recurrent nose or ear disease without organ or life-threatening manifestations may respond to nonsteroidal anti-inflammatory drugs in anti-inflammatory doses, colchicine (0.6 mg twice a day), or oral dapsone (50 to 100 mg once a day). Patients who do not respond adequately to NSAIDs or dapsone may require corticosteroids. For patients with moderate disease, low-dose methotrexate (eg, 15 to 25 mg once a week) might be considered in those with disease refractory to corticosteroids.
Severe cases may require other immunosuppressants, such as cyclosporine, cyclophosphamide, tumor necrosis factor inhibitors, abatacept, or interleukin (IL)-6 inhibitors (1).
None of these therapies has been studied in randomized trials or has been shown to decrease mortality.
If combination immunosuppressive therapy is used, patients should be given prophylaxis for opportunistic infections, such as Pneumocystis jirovecii (see prevention of Pneumocystis jirovecii pneumonia), and vaccines against common infections (eg, streptococcal pneumonia, influenza, COVID-19). Patients on long-term corticosteroid therapy should receive osteoporosis prophylaxis.
If tracheal narrowing causes stridor, a tracheostomy or stent may be needed. Endotracheal intubation can be technically difficult because of tracheal involvement and narrowing; also, intratracheal manipulation can lead to life-threatening postanesthetic deterioration by causing further glottic or subglottic inflammation. Thus, endotracheal intubation should be avoided whenever possible (eg, instead using local and regional anesthesia). When endotracheal intubation is unavoidable, the need for emergency cricothyrotomy should be considered.
More extensive tracheobronchial collapse may require tracheal reconstruction.
Eye disease may sometimes be recalcitrant to treatment, especially when involving the sclera, and has a poor prognosis.
Treatment reference
1. Moulis G, Pugnet G, Costedoat-Chalumeau N, et al. Efficacy and safety of biologics in relapsing polychondritis: a French national multicentre study. Ann Rheum Dis. 2018;77(8):1172-1178. doi:10.1136/annrheumdis-2017-212705
Prognosis for Relapsing Polychondritis
Mortality rates have decreased with newer therapies. Death typically resulting from collapse of laryngeal and tracheal structures or from cardiovascular complications such as large-vessel aneurysm, cardiac valvular insufficiency, or systemic vasculitis.
Patients with VEXAS syndrome may develop hematologic neoplasms such as myelodysplastic syndrome and multiple myeloma. Prognosis is guarded.
Key Points
Consider relapsing polychondritis if patients develop inflammation of the pinna or nasal cartilage, particularly with symptoms and signs compatible with respiratory tract chondritis or unexplained arthritis, ocular inflammation, or auditory or vestibular dysfunction.
Biopsy the affected cartilage only if necessary to confirm the diagnosis.
Treat mild nose or ear disease with nonsteroidal anti-inflammatory drugs, colchicine, or dapsone.
Treat more severe disease with corticosteroids and sometimes methotrexate or other immunosuppressants.
Anticipate the need for possible emergency cricothyrotomy if endotracheal intubation is required.
