Relapsing polychondritis

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Relapsing polychondritis is a clinical syndrome rather than a positive-test disease. Establish repeated episodes, anatomical cartilage involvement and objective damage. Examine both pinnae including the lobule, nasal bridge, oral and laryngeal structures, costochondral junctions and peripheral joints; assess eye inflammation, hearing, vestibular function, skin, pulses, blood pressure in both arms, murmurs and features of associated autoimmune or marrow disease.

Auricular chondritis produces abrupt pain, warmth and swelling of the helix, antihelix or tragus while the fatty lobule remains relatively normal. Repeated episodes deform and soften the ear. Infection can also spare or involve cartilage and is especially important after piercing or trauma; obtain microbiology and look for abscess before giving high-dose steroid. Nasal bridge pain and tenderness can precede visible collapse.

Airway symptoms must be separated into upper-airway, fixed central stenosis and dynamic collapse. Hoarseness and stridor suggest laryngeal or subglottic disease. A monophonic wheeze, cough, secretion retention and recurrent infections can reflect tracheobronchial narrowing. Expiratory breathlessness or positional symptoms suggest malacia. Ordinary inhalers will not correct a mechanically collapsing trachea.

Obtain inspiratory and dynamic expiratory CT of neck and chest with thin airway reconstruction. Spirometry may show fixed or variable upper-airway flow-volume limitation but can be normal early. Flexible nasendoscopy assesses vocal cords and subglottis. Bronchoscopy defines collapse and stenosis and enables intervention, but an unstable airway requires rigid-bronchoscopy, anaesthetic and surgical capability before sedation.

Ocular disease includes episcleritis, scleritis, uveitis, keratitis, retinal vasculitis and orbital inflammation. Pain and photophobia are not simply another cartilage flare. Audiovestibular disease causes sudden or progressive sensorineural hearing loss, tinnitus and vertigo; prompt audiology and ENT treatment may preserve function. Non-erosive inflammatory arthritis often affects large or small peripheral joints and may occur independently of chondritis.

Cardiovascular screening uses examination, ECG and echocardiography at baseline, followed by CT or MR angiography when symptoms, murmurs, pulse discrepancy or inflammation suggests aortitis. Aortic root inflammation can cause regurgitation; disease also affects mitral valve, coronaries and medium or large arteries. Repeat imaging follows initial risk because clinically silent progression can occur.

Routine tests include FBC with indices, blood film, CRP or ESR, renal and liver profiles and urinalysis. ANA, ANCA, complements and infection testing answer phenotype-driven questions and are not diagnostic screens. Persistent macrocytosis, anaemia, thrombocytopenia or monocytopenia needs haematology review; marrow vacuoles are a clue to VEXAS but somatic UBA1 testing establishes the molecular diagnosis.

Classification criteria can support recognition. McAdam uses bilateral auricular, non-erosive polyarthritis, nasal, ocular, respiratory-tract and audiovestibular features; three are required. Damiani permits one McAdam feature plus histology or response to corticosteroid or dapsone. Michet requires proven inflammation in two of auricular, nasal or laryngotracheal cartilage, or one plus two other features. None is a gold-standard diagnostic test.

Cartilage biopsy is reserved for diagnostic uncertainty, suspected infection or malignancy, or when tissue can enable UBA1 and marrow assessment through another site. Histology can show perichondrial inflammation, loss of basophilic matrix, chondrocyte death and fibrosis but is not specific. Sampling the active edge is more informative than an entirely calcified deformed ear and adds a permanent scar.

Mild limited disease can use a brief NSAID where safe, colchicine 500 micrograms once or twice daily or dapsone 50–100 mg daily after G6PD and blood assessment. These regimens are off-label and evidence comes from observational practice. Recurrent or organ-significant disease generally needs prednisolone 0.5–1 mg/kg/day, with dose and taper determined by response and structural threat.

For airway, severe ocular, sudden hearing, cardiovascular or vasculitic disease, give IV methylprednisolone 500–1000 mg daily for three days when the specialist team judges delay dangerous, then oral treatment and an early steroid-sparing drug. Methotrexate 15–25 mg once weekly is common. Azathioprine, mycophenolate or cyclophosphamide is selected according to organ and associated vasculitis; none has a dedicated relapsing-polychondritis licence.

Biologic evidence is uncontrolled. TNF inhibition, tocilizumab, abatacept and rituximab have produced variable responses; the target should match airway, vascular, joint or associated disease and infection risk. VEXAS may need azacitidine, JAK inhibition or allogeneic transplantation through haematology rather than serial rheumatology biologics. Objective reassessment prevents steroid response from being mistaken for structural recovery.

Mechanical airway disease needs mechanical care. Non-invasive positive pressure can splint selected malacia; fixed critical stenosis may need dilation or tracheostomy, and focal severe malacia may require silicone stent or reconstruction in an experienced centre. Stents migrate, obstruct with secretion, granulate and infect, so they are not a substitute for inflammatory control or longitudinal bronchoscopy.

Key points

Relapsing polychondritis is recurrent immune inflammation of cartilage and proteoglycan-rich structures; the classic hot tender pinna spares the non-cartilaginous lobule.
Ask about hoarseness, cough, stridor, positional or exertional breathlessness and wheeze that does not behave like asthma at every encounter because airway disease determines mortality.
Nasal chondritis causes bridge pain before saddle-nose collapse; audiovestibular, ocular, non-erosive joint, skin, aortic and valvular disease complete the multisystem pattern.
Diagnosis is clinical and no blood test confirms it. McAdam, Damiani or Michet criteria organise evidence but do not replace exclusion of infection, GPA and VEXAS.
First-line airway assessment combines inspiratory and expiratory CT, flow-volume loops and ENT laryngoscopy; bronchoscopy requires an expert plan because sedation and instrumentation can precipitate collapse.
Biopsy is not routine in a classic presentation. Sample an active accessible cartilage edge when malignancy, infection, VEXAS or another diagnosis remains materially possible.
Mild auricular, nasal or joint disease may use an NSAID, colchicine or dapsone, but systemic prednisolone is usual first-line treatment for important inflammation.
Airway, ocular, audiovestibular, cardiac or vascular threat requires high-dose glucocorticoid plus early steroid-sparing therapy and the relevant surgical or device team.
Methotrexate is a common steroid-sparing choice; azathioprine, mycophenolate, cyclophosphamide and biologics are off-label and selected from organ severity and associated disease.
Screen older men with macrocytosis, cytopenia, thrombosis or neutrophilic dermatosis for VEXAS because treating it as ordinary cartilage-limited disease misses marrow ownership.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Idiopathic immune-mediated disease

Most cases have no single cause; adaptive and innate responses to type II collagen, matrilin and other cartilage matrix proteins are implicated without one diagnostic antibody.

Associated autoimmune or clonal disease

Systemic vasculitis, rheumatoid disease, inflammatory bowel disease, myelodysplasia and haematological malignancy coexist often enough that atypical blood or organ findings need explanation.

UBA1-associated VEXAS

Somatic UBA1 variants in haematopoietic cells cause late-onset autoinflammation, chondritis, neutrophilic skin disease, thrombosis and macrocytic marrow failure, predominantly in men.

Triggering tissue injury

Trauma, infection and procedures can focus cartilage inflammation but do not alone establish relapsing polychondritis; external-ear infection remains a dangerous alternative.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Perichondrial immune attack
Antibodies, T cells, neutrophils and cytokines injure avascular cartilage through its vascular perichondrium, causing pain and swelling before structural matrix loss.
2
Proteoglycan and collagen destruction
Enzymatic degradation removes cartilage resilience, leaving floppy pinnae, saddle-nose collapse, subglottic narrowing and tracheobronchomalacia after inflammation subsides.
3
Dynamic airway failure
Weak central-airway cartilage permits excessive expiratory collapse, while scar and mucosal oedema produce fixed stenosis; both mechanisms can coexist and require different procedures.
4
Ocular and vascular inflammation
Scleritis, uveitis, retinal vasculitis, aortitis and valvulitis show that the disease extends beyond cartilage and can threaten sight, perfusion and valve integrity.
5
Relapse with cumulative damage
Repeated inflammatory episodes may be reversible early, but each attack can add permanent deformity, hearing loss and airway or cardiac damage that no later immunosuppression restores.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Auricular chondritis

Painful erythematous swelling involves the cartilaginous helix, antihelix or tragus and characteristically leaves the soft lobule relatively unaffected.

Nasal and costochondral disease

Bridge tenderness, recurrent epistaxis, progressive saddle nose and inflamed rib cartilage support broader cartilage involvement beyond one ear.

Laryngotracheobronchial diseaseRed flag

Hoarseness, stridor, fixed wheeze, exertional or positional dyspnoea and recurrent lower-respiratory infection can indicate stenosis or dynamic collapse.

Ocular and audiovestibular diseaseRed flag

Scleritis, uveitis, keratitis, sudden hearing loss, tinnitus or vertigo is function threatening and needs organ-specialist treatment alongside systemic control.

Cardiovascular involvementRed flag

A new regurgitant murmur, pulse asymmetry, aneurysmal pain, conduction change or heart failure raises aortitis, valvulitis and coronary or arterial disease.

VEXAS-associated phenotype

Late male onset with fever, chondritis, macrocytosis, cytopenia, thrombosis and neutrophilic skin or lung inflammation strongly supports a myeloid autoinflammatory process.

Red flags requiring action

Stridor, new voice change, refractory monophonic wheeze, inability to lie flat or exertional desaturation requires same-day upper and central airway assessment.
Sudden visual loss, severe ocular pain, proptosis or corneal change may indicate scleritis, retinal vasculitis, keratitis or orbital inflammation and needs urgent ophthalmology.
Syncope, pulse deficit, new murmur, chest or back pain, heart failure or unequal pressures raises aortitis, aneurysm, dissection, coronary ostial or valvular disease.
Fever with a hot swollen pinna after piercing, surgery or trauma requires infection assessment; immunosuppression for presumed relapse can accelerate Pseudomonas perichondritis.
Macrocytic anaemia, thrombocytopenia, neutrophilic skin disease, venous thrombosis or steroid-dependent chondritis in an older man raises VEXAS and marrow failure.
Haematuria, rapidly falling eGFR, pulmonary haemorrhage or destructive ENT disease is atypical for isolated relapsing polychondritis and requires vasculitis or associated-disease assessment.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line dynamic inspiratory and expiratory CTFirst stepFirst line
Why
Define subglottic and central-airway thickening, fixed stenosis, calcification and expiratory collapse.
Interpretation and limitations
Interpret with symptoms and respiratory expertise; standard inspiratory CT can miss malacia, while extensive collapse changes anaesthetic and procedural safety.
02
Flow-volume loops and full lung function
Why
Detect upper-airway obstruction and provide a non-invasive trajectory measure.
Interpretation and limitations
Plateau patterns can support fixed or variable obstruction, but normal spirometry does not exclude focal or dynamic disease and low flows require anatomical correlation.
03
ENT nasendoscopy and expert bronchoscopy
Why
Inspect laryngeal movement, subglottis, stenosis and malacia and enable sampling or intervention.
Interpretation and limitations
Nasendoscopy is often safer initially. Bronchoscopy in a critical collapsible airway is performed only where rigid rescue, anaesthesia and airway surgery are available.
04
FBC with indices, film and inflammatory profile
Why
Find systemic inflammation, medicine safety and a clonal or VEXAS signal.
Interpretation and limitations
Macrocytic anaemia, thrombocytopenia, monocytopenia or dysplasia prompts haematology and marrow assessment; CRP may track activity but normality does not exclude structural airway risk.
05
Somatic UBA1 testing
Why
Confirm VEXAS in a compatible late-onset inflammatory and haematological phenotype.
Interpretation and limitations
Test peripheral blood or marrow through the genomic and haematology pathway; variant allele fraction and lineage context matter, and germline panels are not equivalent.
06
ECG, echocardiogram and aortic imaging
Why
Detect valvular, myocardial, conduction and arterial involvement.
Interpretation and limitations
A new murmur or pulse discrepancy prompts CT or MR angiography; serial interval depends on baseline abnormality and systemic activity rather than one universal schedule.
07
Audiogram and urgent ophthalmic examination
Why
Quantify hearing loss and classify sight-threatening inflammation.
Interpretation and limitations
Sensorineural change can become permanent; slit-lamp, retinal and optic assessment distinguishes scleritis, uveitis, keratitis and posterior disease.
08
Targeted cartilage or alternative tissue biopsy
Why
Resolve infection, malignancy, vasculitis or uncertain clinical criteria.
Interpretation and limitations
Perichondrial inflammation and matrix loss are supportive but nonspecific. Culture suspected infection and prefer marrow or skin when it better answers VEXAS or clonal disease.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Infectious auricular perichondritis

Recent piercing, trauma, discharge, abscess and systemic infection favour bacterial disease; culture and drainage precede immunosuppression when infection is plausible.

Granulomatosis with polyangiitis

Destructive sinus disease, pulmonary nodules or haemorrhage, glomerulonephritis and compatible PR3-ANCA or biopsy favour GPA; both diseases can cause saddle nose and airway stenosis.

VEXAS syndrome

Older male onset with macrocytosis, cytopenia, vacuolated marrow precursors, thrombosis and neutrophilic dermatosis prompts somatic UBA1 testing rather than idiopathic classification.

Cogan, Behçet and sarcoidosis

Inflammatory eye and audiovestibular disease, oral or genital ulcers, thrombosis, granulomas, nodes and calcium disturbance define competing multisystem patterns.

Trauma, neoplasm and degenerative airway disease

Repeated pressure, frostbite, chondral tumour, amyloid, post-intubation stenosis and COPD can reproduce one anatomical feature but not the relapsing cartilage constellation.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01First diagnostic sequenceProve the pattern and test dangerous alternativesFirst stepRecurrent ear, nose, airway or costochondral inflammation raises relapsing polychondritis.

1Document lobule sparing and at least one additional cartilage, ocular, hearing, joint or cardiovascular feature and apply criteria as support rather than proof.
2Exclude bacterial perichondritis, GPA and focal trauma or tumour and obtain FBC indices, urine and organ-directed autoimmune or infection tests.
3In an older man with macrocytosis, cytopenia, thrombosis or neutrophilic skin disease, refer for marrow and somatic UBA1 assessment before final classification.

02Airway first-line escalationStabilise before sedating or scopingFirst lineEscalationStridor, progressive hoarseness, central wheeze or positional respiratory compromise is present.

1Admit, monitor oxygenation and ventilation and involve anaesthesia, ENT, respiratory, interventional bronchoscopy and critical care before airway manipulation.
2Obtain dynamic CT and nasendoscopy if stable, preserving spontaneous ventilation; perform bronchoscopy only with a planned rigid, surgical and tracheostomy rescue.
3Give specialist glucocorticoid for active inflammation and use positive pressure, dilation, tracheostomy, stent or reconstruction according to fixed versus dynamic failure.

03Mild inflammatory diseaseUse the least toxic effective optionAuricular, nasal, costochondral or joint symptoms are limited and no airway, eye, hearing or vascular threat exists.

1Confirm infection is unlikely, document photographs and functional baseline and offer a short NSAID when organ and pregnancy risks permit.
2Consider off-label colchicine or dapsone for recurrent limited disease with appropriate blood, renal, liver and G6PD safety.
3EscalationEscalate promptly if attacks recur, damage accumulates or systemic features appear rather than repeating unmonitored rescue courses.

04Organ-threatening inductionSuppress inflammation and protect structureAirway, sight, hearing, cardiovascular, neurological or severe vasculitic disease is active.

1Use high-dose oral or IV glucocorticoid according to speed and severity while treating infection and arranging the required device or surgical protection.
2Start methotrexate or another organ-appropriate steroid-sparing agent early; use cyclophosphamide for selected life-threatening vasculitic or airway disease.
3Review objective airway, eye, hearing and cardiovascular measures and change mechanism when inflammation remains active or steroid cannot taper.

Key medicines and prescribing safety5 treatments · regimens, roles and cautions

Usual first-line systemic suppression because uncontrolled cartilage and vascular inflammation can cause irreversible structural damage.

Prednisolone

For important systemic disease, give 0.5–1 mg/kg orally each morning, then taper against organ response; minor disease may require a lower, shorter course and airway or vascular disease often needs early steroid-sparing therapy.

Exclude infection, monitor glucose, pressure, mood, bone, eye and adrenal risks and avoid allowing partial symptom response to postpone airway or vascular procedures.

Rapid induction where hours to days of delay could permit cartilage collapse or permanent organ loss.

Methylprednisolone intravenous pulse

For selected life-, sight-, hearing- or airway-threatening inflammation, give 500–1000 mg intravenously once daily for three days, followed by oral taper and steroid-sparing treatment.

Coordinate cultures, airway stability, cardiac rhythm, glucose, mental state and infection prophylaxis; this off-label syndrome regimen requires multidisciplinary supervision.

Common off-label first steroid-sparing option for recurrent cartilage, joint and systemic inflammation.

Methotrexate with folic acid

Start 15 mg orally or subcutaneously once weekly and titrate to 20–25 mg weekly as response and safety allow; give folic acid at least 5 mg on a separate day.

Never dose daily; monitor FBC, liver and renal function, lung symptoms, infection and pregnancy and avoid trimethoprim or co-trimoxazole.

Off-label option for auricular, nasal or skin-predominant inflammation when glucocorticoid reduction is needed.

Dapsone

For selected limited disease, start 50 mg orally daily and increase cautiously toward 100 mg daily when response and blood monitoring justify it.

Check G6PD, FBC, reticulocytes and liver function and monitor methaemoglobinaemia, haemolysis, agranulocytosis, neuropathy and severe hypersensitivity.

Selected rescue for life-threatening airway, aortic or systemic vasculitic disease when safer steroid-sparing treatment is inadequate.

Cyclophosphamide

Use only within a named specialist IV pulse or oral protocol adjusted for age, kidney function, counts and cumulative exposure; no regimen is specifically licensed for relapsing polychondritis.

Address infection, fertility preservation, pregnancy, bladder protection, marrow monitoring, malignancy and cumulative-dose risk and transition promptly to safer maintenance.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Irreversible airway obstruction

Subglottic scar, tracheobronchomalacia, secretion retention and recurrent infection can lead to respiratory failure, emergency tracheostomy and complex stent complications.

Permanent sensory loss

Cochlear or vestibular inflammation causes sensorineural deafness and imbalance, while severe ocular inflammation can scar cornea, retina or optic structures.

Aortic and valvular catastrophe

Aortitis can produce aneurysm, regurgitation or dissection, and inflammation of valve roots causes progressive heart failure requiring surgery.

Structural facial and chest deformity

Repeated nasal and auricular injury causes saddle nose and floppy or calcified pinnae; costochondral disease can contribute pain and restrictive mechanics.

Treatment and associated-disease harm

Infection and cumulative glucocorticoid or cytotoxic toxicity compound mortality, while missed marrow or vasculitic disease follows a different prognosis and treatment path.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Ask about voice, stridor, wheeze, positional or exertional dyspnoea, secretion clearance and infection at every visit and repeat dynamic CT or physiology when trajectory changes.
Photograph ears and nose with consent, document chondritis frequency and examine eyes, hearing, joints, skin, pulses and murmurs rather than relying on CRP alone.
Repeat audiometry, ophthalmic examination, echocardiography and aortic imaging at intervals determined by initial involvement and new symptoms.
Track FBC indices and urine as disease tests as well as medicine safety, escalating new macrocytosis or cytopenia to haematology rather than attributing it automatically to methotrexate.
After airway intervention monitor stent migration, granulation, mucus plugging, infection and recurrent collapse through the expert centre.
Record cumulative glucocorticoid, DMARD tests, vaccines, infection and reproductive plan and distinguish active inflammation from fixed damage before dose escalation.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

The lobule has no cartilage

Relative sparing of the soft ear lobe helps identify chondritis, although it cannot alone distinguish sterile inflammation from every infection.

Wheeze can be a central tube

A fixed monophonic sound, abnormal flow-volume loop and poor bronchodilator response should prompt tracheal imaging rather than repeated asthma escalation.

Malacia can hide on inspiratory CT

Airway calibre may appear acceptable during inspiration and collapse only on expiration, cough or sedation, making dynamic assessment essential.

VEXAS changes clinical ownership

Cartilage inflammation with macrocytic marrow failure is a somatic myeloid disease requiring haematology strategy, not simply stronger conventional DMARD treatment.

Inflammation and mechanics coexist

Steroid can reduce airway wall oedema while fixed scar or cartilage collapse still requires dilation, pressure support or reconstruction.

Criteria organise, not confirm

McAdam, Damiani and Michet definitions improve consistency but no set is sufficiently sensitive, specific or validated to replace clinical judgement.

11Common pitfallsFrequent interpretation and management errors.

01
Diagnosing an ear flare without asking about piercing, trauma, discharge and abscess or obtaining culture when infection is plausible.
02
Treating stridor or monophonic wheeze as asthma and arranging routine sedated bronchoscopy without a rescue airway plan.
03
Using a normal CRP to dismiss severe fixed stenosis or tracheobronchomalacia.
04
Failing to screen an older man with macrocytic anaemia and thrombosis for VEXAS and myelodysplasia.
05
Escalating immunosuppression for saddle nose without urine, chest and ANCA assessment for GPA.
06
Assuming reduced pain means cartilage, hearing or cardiovascular damage has reversed and stopping objective surveillance.