Relapsing Polychondritis

Article Author:
Krati Chauhan
Article Editor:
Andrew Hanna
Updated:
8/30/2019 1:23:01 PM
PubMed Link:
Relapsing Polychondritis

Introduction

Relapsing polychondritis (RP) is a rare autoimmune condition which presents as recurrent episodes of cartilaginous inflammation of the auricular, nasal and tracheal cartilage. Jaksh-Wartenhorst described the first case in 1923. A 32-year-old patient presented with fever, pain, and swelling of the ears and later developed stenosis of external auditory canal and saddle nose deformity. A biopsy of the nasal cartilage showed the absence of cartilage. The term relapsing polychondritis was coined by Pearson and his coworkers in 1960. They recognized it as an inflammatory condition of the and noncartilaginous structures.[1][2][3]

Etiology

The etiology of relapsing polychondritis is not known. It is suggested to result in a genetically predisposed individual on exposure to a triggering factor. The triggering factor may be an infectious agent, chemical, toxic exposure, or direct trauma. Relapsing polychondritis cases have been reported after trauma to pinna. A possible explanation includes cryptogenic antigenic release after trauma and recognition antigen by the immune system. Genetic studies have shown an association between HLA-DR4 antigen and relapsing polychondritis.[4][5]

Epidemiology

It is a rare disease, more common in Caucasians; prevalence is 4.5 cases/million. The peak age at onset is between 40 years to 50 years, though it can occur at any age. It occurs with equal frequency in both sexes and all racial groups. Over 30% of cases are associated with existing autoimmune condition or hematologic condition. [6][7]

Pathophysiology

Relapsing polychondritis primarily involves cartilaginous structures, suggesting immune mechanism are acting against proteoglycan the main constituent of cartilage. Circulating and tissue-specific antibodies against collagen type II, IX and XI are shown in patients with relapsing polychondritis. In addition to humoral immunity, cellular immunity helps in maintaining cartilage inflammation. CD4+ cell secretes cytokines like interelukin-8, macrophage inflammatory protein 1β, monocyte chemoattractant protein one which leads to recruitment of monocyte and macrophages. Macrophage release proteolytic enzymes, metalloproteinase (MMP-3), cathepsin L and K which leads to the destruction of cartilage. In early stages of the disease there is polymorphic inflammatory cell infiltration, later there is chondrocyte apoptosis, focal calcification, and fibrosis of the cartilage.[8]

History and Physical

Clinical spectrum of relapsing polychondritis is variable and varies with duration of the disease and disease severity. Auricular involvement is present in 90% of the cases, and inflammation is restricted to the cartilaginous portion of the ear with sparing of the ear lobes. Patients most frequently present with discoloration of the ear and pain. Articular involvement is the second most common manifestation present in 50% to 75% of patients. Wrist, metacarpophalangeal, proximal interphalangeal joints are commonly involved. Ocular manifestation occurs in 20% to 60% of relapsing polychondritis patients and involves episcleritis, scleritis, keratitis, and uveitis. Nasal chondritis occurs in about 25% of cases. Inflammation of the cartilaginous rings around trachea and bronchi results in the collapse of these airways (tracheobronchomalacia). Patient presents with a cough, hoarseness of voice, wheezing. Respiratory compromise is the most frequent cause of death in these patients.

Evaluation

Diagnosis of relapsing polychondritis is primarily based on a combination of clinical features, radiology, and biopsy of a cartilaginous site. It is guided by a set of clinical criteria suggested by McAdams et al. [9]  [10]Three of out of six criteria are required to make the diagnosis. These include:

  1. Recurrent chondritis of both auricles
  2. Nonerosive inflammatory arthritis
  3. Chondritis of nasal cartilages
  4. Inflammation of ocular structures: conjunctivitis/keratitis/scleritis/uveitis
  5. Chondritis of respiratory tract: Laryngeal, tracheal cartilage
  6. Cochlear or vestibular damage: Neurosensory hearing loss/tinnitus/vertigo

Any patient suspecting of having relapsing polychondritis should have a dynamic exploratory CT scan to evaluate for airway involvement. CT scans show functional airway abnormalities such as air trapping and collapse. It can also show thickening of the airway wall and luminal narrowing. Pulmonary function testing is done to evaluate for airway trapping. Pulmonary function test should be done to evaluate for lung volumes. PET-CT is a new diagnostic modality which helps in early disease recognition and provides a site for targeted biopsy.

Biopsy of auricular cartilage is performed to confirm the diagnosis of polychondritis. When relapsing polychondritis is associated with other Rheumatic diseases, positive serologic tests for rheumatoid factor, the anti-nuclear antibody may be seen. Complement levels are usually normal in patients with relapsing polychondritis. A non-erosive process of juxta-articular osteopenia and uniform, joint space narrowing characterizes arthropathy of relapsing polychondritis. Anti-type II collagen antibody tests are not routinely available, and hen these tests are done, these antibodies are not present in all the cases. There are no lab markers to assess for ongoing cartilage damage.

Treatment / Management

Due to the rarity of the disease, there are no there is no standardized treatment approach, and the treatment is guided by the clinical presentation and the severity of the disease.[2][11]

For patients presenting with auricular, nasal or articular involvement but no systemic involvement, anti-inflammatory medications, colchicine or dapsone is recommended. Low-dose glucocorticoid therapy is often required.

For patients with large airway involvement (laryngeal or tracheobronchial chondritis), abrupt onset of sensorineural hearing loss, ocular involvement IV methylprednisolone 1 gram for three days followed by oral prednisone 1 mg/kg along with immunosuppressive therapy is indicated. Most commonly used immunosuppressive agents include cyclophosphamide, methotrexate, azathioprine and cyclosporine. Cyclophosphamide is commonly used as the initial medication (1 mg/kg to 2 mg/kg) after remission is achieved it is switched to other less toxic immunosuppressive agents like azathioprine or methotrexate.

Biologics have been used in the treatment of relapsing polychondritis, most commonly used biologic is TNF inhibitor-Infliximab. Other biologics which have been tried with variable results include Adalimumab, etanercept, abatacept, tocilizumab. Data on Rituximab did not show success, and this agent is not recommended as the first line biologic agent.

Surgical intervention such as stenting, airway dilation, tracheostomy and laryngotracheal reconstruction are needed in case of airway collapse.

Differential Diagnosis

There is a presentation where the diagnosis of RP may be challenging. Nasal damage may occur as a result of drug abuse (cocaine), infections from fungi, tuberculosis, syphilis, granulomatous conditions like ANCA-associated vasculitis and lymphomatoid granulomatosis. Eye involvement similar to relapsing polychondritis may occur with rheumatoid arthritis, ANCA-associated vasculitis, polyarteritis nodosa, Behcet syndrome or Cogan syndrome.

Prognosis

The outcome of patients with relapsing polychondritis has improved in the recent years; survival has increased from 70% at five years to 91% at ten years. The more common clinical presentation is a relatively benign disease with respiratory failure due to airway collapse being the most common cause of death.

Enhancing Healthcare Team Outcomes

RP is a very rare disorder that typically causes inflammation in cartilage bearing tissues like the ear, nose, larynx and the airways. The inflammatory episodes are recurrent and unpredictable. A concomitant autoimmune disease also occurs in more than 30% of patients. The diagnosis is not always easy because there are no specific tests. Even when diagnosed, the treatment is not standardized. The drug treatment is tailored to each patient and the cornerstone of therapy is the use of glucocorticoids. For patients with severe disease, other immunosuppressive are used including methotrexate and cyclophosphamide.[12][13] (level III)

Because these drugs have potent adverse effects, the role of the pharmacist and nurses are critical. Both these professionals play a role in educating the patient on the signs and symptoms of the adverse effects and also ensuring compliance with the medications. Recently newer biological agents have also been used to manage RP patients with varying results. However, prior to initiating treatment with these novel agents, the patient needs a thorough work up to ensure that he or she is fit to receive the therapy. Any patient with worsening of symptoms should be referred to the specialist. [14] (level III)

Outcomes

Patients with RP have frequent relapses and the quality of life is poor. The mortality rate of RP patients is twice that of the general population. Until randomized controlled studies are available, the treatment of RP will remain empirical and based on personal experience. For healthcare workers who have never treated such a patient, referral to a tertiary care center is recommended.[15] (level III)


References

[1] Borgia F,Giuffrida R,Guarneri F,Cannavò SP, Relapsing Polychondritis: An Updated Review. Biomedicines. 2018 Aug 2     [PubMed PMID: 30072598]
[2] Zheutlin A,Schiopu E, Relapsing Polychondritis following Treatment with Secukinumab for Ankylosing Spondylitis: Case Report and Review of the Literature. Case reports in rheumatology. 2018     [PubMed PMID: 30057845]
[3] Masuda N,Nishikawa R,Ueda T,Ogata N, Severe panuveitis with relapsing polychondritis. American journal of ophthalmology case reports. 2018 Sep     [PubMed PMID: 30050999]
[4] Paravar T, Less common rheumatologic disorders: Current concepts of skin and systemic manifestations. Clinics in dermatology. 2018 Jul - Aug     [PubMed PMID: 30047435]
[5] Krishnan Y,Grodzinsky AJ, Cartilage diseases. Matrix biology : journal of the International Society for Matrix Biology. 2018 May 24     [PubMed PMID: 29803938]
[6] Leung KK,Edani S, Red-eared zebra diagnosis: Case of relapsing polychondritis. Canadian family physician Medecin de famille canadien. 2018 May     [PubMed PMID: 29760256]
[7] Haslag-Minoff J,Regunath H, Relapsing Polychondritis. The New England journal of medicine. 2018 May 3     [PubMed PMID: 29719184]
[8] Zampeli E,Moutsopoulos HM, Relapsing polychondritis: a diagnosis not to be missed. Rheumatology (Oxford, England). 2018 Apr 30     [PubMed PMID: 29718381]
[9] Rose T,Schneider U,Bertolo M,Klotsche J,Casteleyn V,Biesen R,Burmester GR,Hiepe F, Observational study and brief analysis of diagnostic criteria in relapsing polychondritis. Rheumatology international. 2018 Aug 6     [PubMed PMID: 30084004]
[10] Behar JV,Choi YW,Hartman TA,Allen NB,McAdams HP, Relapsing polychondritis affecting the lower respiratory tract. AJR. American journal of roentgenology. 2002 Jan     [PubMed PMID: 11756115]
[11] Lekpa FK,Chevalier X, Refractory relapsing polychondritis: challenges and solutions. Open access rheumatology : research and reviews. 2018     [PubMed PMID: 29391837]
[12] Dion J,Leroux G,Mouthon L,Piette JC,Costedoat-Chalumeau N, [Relapsing polychondritis: What's new in 2017?] La Revue de medecine interne. 2018 Jun     [PubMed PMID: 28890262]
[13] Meshkov AD,Novikov PI,Zhilyaev EV,Ilevsky IDJ,Moiseev SV, Tofacitinib in steroid-dependent relapsing polychondritis. Annals of the rheumatic diseases. 2018 May 3     [PubMed PMID: 29724732]
[14] Moulis G,Pugnet G,Costedoat-Chalumeau N,Mathian A,Leroux G,Boutémy J,Espitia O,Bouillet L,Berthier S,Gaultier JB,Jeandel PY,Konaté A,Mékinian A,Solau-Gervais E,Terrier B,Wendling D,Andry F,Garnier C,Cathébras P,Arnaud L,Palmaro A,Cacoub P,Amoura Z,Piette JC,Arlet P,Lapeyre-Mestre M,Sailler L, Efficacy and safety of biologics in relapsing polychondritis: a French national multicentre study. Annals of the rheumatic diseases. 2018 Aug     [PubMed PMID: 29535124]
[15] Sharma A,Law AD,Bambery P,Sagar V,Wanchu A,Dhir V,Vijayvergiya R,Sharma K,Gupta A,Panda NK,Singh S, Relapsing polychondritis: clinical presentations, disease activity and outcomes. Orphanet journal of rare diseases. 2014 Dec 20     [PubMed PMID: 25527201]