Relapsing Polychondritis: Symptoms, Types, Causes and Treatment

Relapsing polychondritis (RP) is a rare, chronic autoimmune disease that targets the body’s cartilage and proteoglycan-rich tissues. It can cause life-altering symptoms and, in some cases, be life-threatening. Despite its rarity, understanding RP is crucial for early detection and effective management. In this comprehensive overview, we’ll explore its symptoms, recognized types, underlying causes, and available treatment strategies, all synthesized from the latest research.

Symptoms of Relapsing Polychondritis

Relapsing polychondritis presents with a wide variety of symptoms, often making diagnosis challenging. People with RP commonly experience recurrent episodes of inflammation affecting multiple organs and cartilaginous structures. Early recognition of these symptoms is essential for timely intervention and to avoid serious complications.

Main Symptom	Description	Prevalence/Note	Source(s)
Auricular pain	Painful, swollen ear cartilage	Seen in 80% at diagnosis, often first	1 4 7 11
Nasal chondritis	Redness, pain, swelling of nose	In 10–30%; may lead to saddle nose	1 4 7 11
Respiratory issues	Hoarseness, cough, airway narrowing	Up to 50%; can be life-threatening	1 4 7 9 11
Polyarthritis	Joint pain/swelling, non-erosive	Present in 50–80%	1 4 7 11
Ocular inflammation	Red eyes, pain, scleritis, uveitis	Up to 50%; can be first manifestation	1 5 11
Hearing loss	Sudden/gradual, conductive or sensorineural	Up to 46% of patients	1 11
Systemic symptoms	Fever, fatigue, weight loss	Common, especially during flares	1 2 11

Table 1: Key Symptoms

Overview of Symptom Presentation

RP’s symptoms are highly variable, both in type and severity, and can involve almost any tissue with cartilage or rich in proteoglycans.

Auricular, Nasal, and Airway Involvement

• Auricular Chondritis: The most common and often initial symptom is painful, red, and swollen ear cartilage, usually sparing the earlobe (which lacks cartilage). Repeated attacks may cause deformity or “cauliflower” ear 1 4 7.
• Nasal Chondritis: Less frequent but significant, presents as redness, pain, and swelling of the nose, sometimes progressing to collapse of the nasal bridge (“saddle nose”) 1 4.
• Respiratory Tract: Inflammation in the larynx, trachea, or bronchi can cause hoarseness, cough, stridor, and even airway obstruction. Tracheobronchomalacia is particularly dangerous and may be misdiagnosed as asthma 1 9.

Joint and Systemic Manifestations

• Polyarthritis: Many patients experience migratory, non-erosive joint pain or swelling that may mimic rheumatoid arthritis. The knees, hands, and ankles are frequently affected 1 4.
• Systemic Symptoms: Fatigue, fever, and weight loss often accompany flares, contributing to diagnostic confusion 1 2.

Ocular and Audiovestibular Features

• Ocular Involvement: Includes scleritis, episcleritis, uveitis, and conjunctivitis. In some cases, ocular inflammation is the first sign of RP 5.
• Hearing and Balance: Hearing loss, dizziness, and vertigo may occur due to inflammation or vasculitis affecting the inner ear 1 5.

Other Manifestations

• Cardiovascular: Rare but serious, may include aortic or valvular involvement 1 7.
• Skin and Other Organs: Vasculitis affecting the skin or internal organs can occur 1 7.

Types of Relapsing Polychondritis

RP does not manifest the same way in every patient. Recent research indicates there are distinct clinical types, each with its own pattern of symptoms, severity, and progression. Understanding these types helps tailor monitoring and treatment plans.

Type/Cluster	Key Characteristics	Prognosis/Notes	Source(s)
Classic/Multisystemic	Involvement of multiple organs/cartilage	Variable, often progressive	1 6 10
Respiratory-dominant	Severe airway/tracheal involvement	Higher risk of morbidity	6 9 10
Mild/Extremely mild	Limited to few flares, less organ damage	Good prognosis	6 8 10

Table 2: Types of Relapsing Polychondritis

Classic (Multisystemic) RP

This is the most widely recognized form, where patients experience recurrent flares involving several organs—ears, nose, joints, eyes, respiratory tract, and sometimes the cardiovascular system. The course is typically relapsing and remitting, but many cases progress over time, leading to structural damage 1 6.

Respiratory-Dominant Subtype

• Features: Marked by predominant involvement of the larynx, trachea, and bronchi. Tracheobronchomalacia—collapse and weakness of the airways—is a hallmark and can be mistaken for severe asthma 6 9 10.
• Risks: This form carries the highest risk for life-threatening complications due to airway obstruction. Emergency interventions, such as tracheostomy or airway stenting, may be required 9.

Mild or Limited Disease

A subset of patients experiences infrequent flares with mild symptoms, often limited to one or two organs (e.g., isolated ear chondritis or mild joint involvement). These patients generally have a better prognosis and may only need intermittent treatment 6 8.

Other Proposed Types

• Ocular-dominant: Rare, but some patients present mainly with eye inflammation 5 6.
• Overlap Syndromes: RP can overlap with other autoimmune or hematologic disorders, leading to atypical presentations and added complexity 8 15.

Causes of Relapsing Polychondritis

The precise cause of RP remains unknown, but significant advances have been made in understanding its mechanisms. RP is now recognized as an autoimmune disease, with both genetic and environmental components likely contributing.

Factor	Role/Association	Key Insight	Source(s)
Autoimmunity	Self-directed immune attack on cartilage	Central to pathogenesis	1 2 7 11 13
Genetic factors	HLA-DR4, possible genetic predisposition	Increased risk in carriers	1 2 12 13
Environmental	Sunlight, arsenic exposure (suggested)	Possible triggers	8 12
Microbiome	Gut bacteria and immune modulation	May influence disease course	12
Associated diseases	Overlap with other autoimmune/hematologic	Up to 30–56% association	1 8 13 15

Table 3: Causes and Risk Factors

Autoimmune Basis

RP is widely regarded as an autoimmune disease. The immune system mistakenly recognizes cartilage proteins as foreign, leading to recurrent inflammation and destruction of cartilage in multiple organs 1 2 7 11 13. The presence of autoantibodies against type II collagen and other cartilage components has been reported in some patients.

Genetic Influences

• HLA-DR4 Association: There is a strong link between RP and the HLA-DR4 gene, suggesting a genetic predisposition 1 2 12. However, not all patients have this marker, and RP can occur in people without a family history.
• Other Genetic/Monogenic Disorders: Emerging research points to rare genetic syndromes (e.g., VEXAS) that can mimic RP, highlighting the growing complexity of its genetic landscape 10.

Environmental and Microbial Factors

• Environmental Triggers: Epidemiological data suggest that exposure to sunlight and possibly arsenic in drinking water could trigger RP in genetically susceptible individuals, though evidence is not definitive 8.
• Gut Microbiome: Recent studies point to alterations in gut bacteria affecting immune regulation, possibly contributing to disease onset or flares. Changes in regulatory T-cell responses and short-chain fatty acid (propionate) production have been noted in RP patients 12.

Overlap with Other Diseases

A significant proportion of RP patients (up to 30–56%) also have other autoimmune or hematologic disorders, such as systemic vasculitis, myelodysplastic syndromes, or Sjögren’s syndrome, suggesting shared pathogenic mechanisms or predispositions 1 8 13 15.

Treatment of Relapsing Polychondritis

There is no single “cure” for RP, and treatment is highly individualized. The goal is to control inflammation, alleviate symptoms, and prevent irreversible damage. The choice of therapy depends on disease severity, organ involvement, and patient response.

Therapy	Indication/Use	Notes on Effectiveness & Risks	Source(s)
NSAIDs	Mild disease, pain relief	For mild symptoms only	2 11 13 15
Corticosteroids	Mainstay for moderate/severe disease	Rapid response; long-term side effects	1 2 11 13
Immunosuppressants	Severe/refractory cases (e.g. azathioprine, methotrexate, cyclophosphamide, mycophenolate)	Used as steroid-sparing agents; variable efficacy	1 11 13 15
Dapsone	Alternative for mild/moderate disease	Some success in small studies	1 17
Biologics	Targeted therapy in refractory/advanced cases	TNF inhibitors, rituximab, etc.; variable results	14 15 18
Airway support	Tracheostomy, stenting, CPAP in airway collapse	Critical in respiratory cases	9 11

Table 4: Treatment Approaches

General Principles

Treatment must be tailored to each patient’s disease activity and organ involvement. The absence of standardized protocols means that most therapies are based on expert consensus, small studies, or case reports 15 16.

First-Line: NSAIDs and Corticosteroids

• NSAIDs: Used for patients with mild symptoms, such as joint pain, but generally insufficient for controlling active flares 2 11.
• Corticosteroids: The mainstay for moderate to severe disease. Oral prednisone or high-dose intravenous methylprednisolone is used for acute flares, airway involvement, or systemic symptoms 1 2.

Steroid-Sparing and Immunosuppressive Agents

• Methotrexate, Azathioprine, Cyclophosphamide, Mycophenolate: These are often added for severe or relapsing cases, or when patients cannot taper steroids without recurrence 1 11 13 15.
• Dapsone: Can be effective in some patients, especially with milder disease or when other immunosuppressants are not tolerated 1 17.

Biologic Therapies

• TNF inhibitors, Rituximab, Anakinra, Tocilizumab: Used for refractory disease or when conventional agents fail. Results are mixed, and no biologic has been universally effective 14 15 18.
• Rituximab: May deplete B cells but has not shown consistent benefit in small studies 18.

Management of Airway and Organ Complications

• Airway Support: In cases of tracheobronchomalacia or airway collapse, interventions such as tracheostomy, stenting, or non-invasive ventilation (e.g., CPAP) are life-saving 9 11.
• Ophthalmologic and Cardiac Care: Targeted treatment for eye or heart involvement is critical to prevent vision loss or cardiac complications 5 13.

Monitoring and Multidisciplinary Care

• Regular Assessment: Frequent evaluation for new organ involvement or complications is vital.
• Multidisciplinary Teams: Optimal care involves rheumatologists, pulmonologists, ENT specialists, ophthalmologists, and, when needed, cardiologists 1 10 11.

Conclusion

Relapsing polychondritis is a rare but serious autoimmune disease with diverse symptoms, presentation types, and significant management challenges. Ongoing research into its causes and new therapies offers hope for improved outcomes.

Key Points to Remember:

• RP is an autoimmune disease marked by recurrent inflammation of cartilage and proteoglycan-rich tissues, most often affecting the ears, nose, joints, eyes, and respiratory tract 1 2 7 11 13.
• Classic, respiratory-dominant, and mild/limited types are now recognized, each with distinct features and risks 6 8 9 10.
• Diagnosis relies on clinical criteria due to lack of specific tests and is frequently delayed due to protean symptoms 1 4 7 11.
• The causes include autoimmune mechanisms, genetic predisposition (notably HLA-DR4), possible environmental triggers, and gut microbiome influences 1 2 8 12 13.
• Treatment is individualized, ranging from NSAIDs for mild disease to corticosteroids and immunosuppressants for moderate/severe disease, with biologics reserved for refractory cases 1 2 11 13 14 15 18.
• Airway involvement is potentially life-threatening and requires rapid intervention and multidisciplinary care 9 11.
• Early recognition and coordinated, flexible management are crucial for improving patient quality of life and prognosis.

Understanding RP requires vigilance and teamwork among patients and healthcare providers. With new research and increased awareness, earlier diagnosis and better therapies are on the horizon.