Disclaimer: The information contained within the Grand Rounds Archive is intended for use by doctors and other health care professionals. These documents were prepared by resident physicians for presentation and discussion at a conference held at Baylor College of Medicine in Houston, Texas. No guarantees are made with respect to accuracy or timeliness of this material. This material should not be used as a basis for treatment decisions, and is not a substitute for professional consultation and/or peer-reviewed medical literature. Relapsing Polychondritis I will be talking about relapsing polychondritis. Briefly, we will go over an introduction of the disease, its clinical features, diagnosis, pathology and pathogenesis as well as associated diseases, the prognosis of the disease and its medical and surgical management. Jackson and Wortenhorse, in 1923, were the first to describe this disease. They termed it polychrondropathia. Marburg, in 1936, described it chondromalacia after an autopsy result on a 14-year-old boy who had destruction of the larynx, ears, nose, ribs, and multiple joints. Pearson, in 1960, was finally responsible for coining the term "relapsing polychondritis". It is an uncommon multisystem disease, known mostly because of its inflammation of cartilaginous tissues. It is recurrent, potentially severe, and debilitating. It can be life threatening as well as very difficult to diagnose. All types of cartilage are involved: the elastic cartilage of the ears and nose, hyaline cartilage of the peripheral joints, tracheobronchial cartilage, and less commonly, fibrocartilage in axial sites. There is also inflammation of proteoglycan enriched structures in the eyes, heart, blood vessels and the inner ear. There is a marked propensity for Caucasians and although most of the earlier papers said there is no sex predominance, one of the more recent literature reviews showed a female predominance of 3:1. The peek onset is in the 4th and 5th decade, the average age being 47 years, although it can occur at all extremes. There is a big issue with delay in diagnosis due to the difficulty in diagnosing the disease. In a study by Trentham and Lee in 1998, they reviewed 66 patients who had been seen by their primary care physicians, otolaryngologists, rheumatologists, and ophthalmologists. The mean delay in symptoms onset to diagnosis was 2.9 years. Sixty-eight percent occurred longer than one year and five or more physicians had been seen prior to diagnosis in one-third of the patients. The clinical features include auricular chondritis, arthritis, laryngotracheal symptoms, nasal chondritis, ocular inflammation, audiovestibular symptoms and cardiovascular symptoms. Auricular chondritis is the most common presenting symptom. It will be the isolated symptom in 91% of patients when they present. There is extreme pain and swelling in the cartilaginous ear, the external auditory canal may be narrowed and there may be serous drainage due to edema. The auricle is nodular and eventually becomes floppy and deformed. Typically, this is classic for the disease. The lobule is spared obviously because there is no cartilage. Eventually there will be bilateral ear involvement in the majority of patients. It is frequently misdiagnosed as infectious polychondritis, trauma, insect bite, or overexposure to temperature extremes. Arthritis is the second most common early presenting symptom, present in 80% of the patients and can affect large or small joints and there may or may not be swelling. It is a nondeforming polyarthritis or oligoarthritis. It most commonly affects the joints in the metacarpophalangeal and proximal interphalangeal joints, followed by the knees, wrists, metatarsal joints and the elbow. All synovial joints can be involved including the temporomandibular, the costochondral junction, pubic symphysis, sternoclavicular and sternomanubrial joints. The arthritis can be migratory or transient and it is also misdiagnosed frequently as rheumatoid arthritis, septic arthritis, or gout. Eighteen percent of patients will present with airway symptoms. However, throughout the disease, up to 50% of patients will have symptoms involving this region. It can range from hoarseness to complete aphonia. There is usually tenderness and swelling over the thyroid cartilage and trachea. Other symptoms include cough, dyspnea, wheezing, and choking. The involvement can be localized or diffuse, most commonly located in the upper extrathoracic segment of the larynx and trachea. Intrathoracic trachea and bronchi can be involved. This is generally later in the disease process. Complications are very common in this area, the worst being acute airway obstruction. This occurs due to subglottic edema, laryngeal and tracheal ring collapse, or tracheomalacia. It can also be iatrogenic after instrumentation in the operating room. Recurrent lower respiratory tract infections, including tracheitis, pneumonia, and bronchitis, may occur as well. This is due to a disruption in mucocilliary clearance as well as diminished effectiveness of the cough. Airway complications are actually responsible for 50% of related deaths. Nasal chondritis is also common. It is sudden in onset and targets the cartilaginous septum. Patients have severe pain and complain of fullness in the nose and adjacent tissues. It is also evident on exam. This finding is more common in women. They are generally younger than 50-years of age. A late complication is a saddle-nose deformity. Ocular inflammation is also seen and it is actually one of the most consistent symptoms over the span of the disease. It can affect almost any part of the eye. Episcleritis, scleritis, iritis, keratoconjunctivitis, keratitis, coroiditis and cataracts may occur. All patients should undergo an ophthalmologic exam. Audiovestibular symptoms also exist. Hearing loss can be conductive or sensorineural. Conductive loss is due to edema or collapse of the external auditory canal, or secondary to auricular collapse. There may also be Eustachian tube chondritis which will cause an effusion. The sensorineural loss is thought to be due to a vasculitis of the cochlear branch of the internal auditory artery. There are three patterns: sudden, rapidly progressive, and gradually progressive. There is also cardiovascular deterioration. It is rare, but it is the second most common cause of death. The manifestations include valve regurgitation, often in the aortic valve. There can be thoracic or abdominal aortic aneurysms, silent myocardial infarctions, abnormal electrocardiogram changes, paroxysmal atrial tachycardia, heart block and thrombosis. Vasculitis is also present in the skin and kidney. Seventeen to forty percent of patients will develop skin lesions presenting as macules, papules, or vesicles. Renal involvement is rare and it does indicate a worse prognosis. There is mesangial proliferation and it ranges to focal segmental glomerulonephritis. McAdam first proposed the criteria for diagnosis in 1976 and then Damiani modified this in 1979. There need to be either three or more clinical signs, one or more clinical signs with histologic confirmation, or involvement of two or more anatomic regions with a positive response to therapy. Unfortunately, there are not any laboratory findings that are diagnostic. Seventy to eighty-five percent of patients will have an elevated erythrocyte sedimentation rate, sixty percent will have a normochromic, normocytic anemia, thrombocytosis, and ANA and rheumatoid factor will be negative if lupus or rheumatoid arthritis does not exist prior to the presentation of relaxing polychondritis. Thin section CT as well as MRI are helpful in further evaluating the airway. They enhance on CT and T1 with gadolinium and T2 images on MRI. It is also helpful to get any one of these studies early on to evaluate the airway distally because frequently airway findings will exist without symptoms. Pulmonary function studies are also equally mandatory. Lesions can be fixed or dynamic. If the lesion is dynamic, there is interest in whether it is extrathoracic or intrathoracic. Extrathoracic will show a drop in their inspiratory flow and this is because the intraluminal pressure is negative on inspiration relative to extraluminal pressure, which is about atmospheric, and this will cause narrowing of the airway. Airflow turbulence and acceleration of airflow due to Bernoulli effect also worsen this. If the lesion is intrathoracic and dynamic you will see a decrease in expiratory flow. This is because extraluminal pressure is positive during expiration, which causes collapse in the airway, and this, in turn, is exaggerated by cough. So, it is very important to get a baseline exam in order to monitor change over time. Bronchoscopy is obviously very informative but extremely risky. It exacerbates already existing inflammation and patients are at great risk during intubation. There is a narrow margin of safety in patients who are chronically oxygen deprived. They can be very difficult to intubate due to their disease and the possibility of inciting localized disease in an otherwise stable airway just by trauma. Biopsy is not pathognomonic but it is helpful. Generally it shows nonspecific granulation tissue. In the acute phase, cartilage may show loss of basophilic staining of the matrix; perichondral inflammation vacuolated in the necrotic chondrocytes and they are eventually replaced by fibrous tissue. In the inflammatory phase, there can be perichondral edema and inflammation and the chondrocytes may differentiate into fibroblasts. This is very nonspecific. Then there is a quiescent phase that is marked mainly just by fibrosis. It is helpful to exclude other disease such as Wegner's and lethal midline granuloma. Nose and tracheobronchial tree biopsies are rarely useful, so they recommend biopsy in the auricular cartilage. Unfortunately, the cause and the pathogenesis of the disease are unknown. An autoimmune response is suspected. The humoral arm demonstrated antibodies to Type II collagen in patients as well as immune complex deposition of IgG, IgA, and IgM. There is also thought to be a cell-mediated arm. Relapsing polychondritis can be induced in rats who have been immunized with Type II collagen, and there has been shown to be an increase HLA-DR4 as well in humans. The effectiveness of high-dose steroids also points to an autoimmune phenomenon. Relapsing polychondritis can be associated with other diseases; specifically, other vasculitides although it is rare. It is most commonly seen with lupus and rheumatoid arthritis. It may be also associated with Sjorgren's, Wegner's, polyarteritis nodosa, the MAGIC syndrome, which is mouth and genital ulcers, myelodysplastic syndromes, and hyperthyroidism. The five-year survival rate used to be 70%. Fortunately, more recent literature is citing 84%. The average disease duration is eight years. The most common cause of death is pneumonia due to airway structure and complications from long-term steroid use. Medical therapy can include NSAIDs in very mild disease; however, frequently this does not provide relief. Corticosteroids are the main line of therapy. They are indicated when respiratory tract involvement is present, especially acute airway obstruction. Renal involvement is also an indication for steroids and it is especially effective with interstitial nephritis. A suppressive dose of 0.75 to 1.0 milligram per kilogram per day is used and the goal is to find a maintenance dose where symptoms are under control. They do have the effect of accelerating the resolution of an attack and, hopefully, decreasing the frequency and severity of attacks. When steroids are not effective or side effects are seen, immunosuppressive agents can be added. Frequently used agents are methotrexate, AZT, cyclophosphamide and cyclosporine. These agents allow tapering of the steroid dose. Dapsone and minocycline have been used in mild disease with minimal effect. Surgical therapy options are tracheostomy, laser, endotracheal prostheses, external airway splinting, and laryngotracheal reconstruction. Tracheostomy is only recommended for patients with localized subglottic disease and should be performed early in the course of the disease. One must always keep in mind that tracheostomy can result in fatal airway obstruction. It is not always the answer to the patient who is not able to breathe, especially if there is a distal lesion that is dynamic and more likely to be tracheomalacia. Endotracheal prostheses have been used, although rarely. The Montgomery tube has been attempted. It allows retaining voice in those requiring tracheostomy, but there are respiratory complications. There can be displacement of the stent, mucosal erosion, and aspiration pneumonia. External airway splinting is the treatment of choice in the thoracic literature for extensive tracheobronchial relapsing polychondritis. It prevents the prolapse of the posterior membranous tracheal wall and is performed via right-sided thoracotomy. The trachea is suspended to the vascular adventitia of the aorta and then percutaneous sutures are placed. Other materials have been attached to the trachea for suspension: pericardium, dura, skin grafts, and tissue adhesive to avoid sutures. Overall, the thought is that any surgical intervention on patients with inflammatory airway disease is not very successful. Endotracheal reconstruction is an option as well, although the reported results are poor, again with no large series. This is an option for isolated lesions of the subglottis and trachea. An interesting reconstructive option that has been published is the sternohyoid myocutaneous rotary door flap. The patient was extubated and decannulated without difficulty. Case Presentation The patient is a 45-year old female with a long history of acupuncture practice involving her ear, who presents with the acute onset of unilateral auricle pain and swelling. She had recently undergone acupuncture therapy. She denied previous history of ear disease and had no other muscular skeletal complaints. She denied dysphasia, odynophagia, hoarseness, difficulties breathing, hearing loss, nasal congestion and pain, and hemoptysis. Past medical history, medication for allergies and surgical history were unremarkable. She denied tobacco, alcohol and drug use. Review of systems was negative for pulmonary, cardiovascular and neurological symptoms. Physical exam was remarkable for left auricular erythremia and edema sparing the lobule. The external auditory canal and tympanic membrane were clear bilaterally. The right auricle was within normal limits. The nose, nasal pharynx, oral cavity, oropharynx, larynx, hypopharynx and neck were within normal limits. The patient was admitted for intravenous antibiotics for auricular chondritis. She slowly improved over five days and was discharged home. A few months later, she developed right-sighted chondritis. She was still practicing acupuncture. This was successfully treated with oral antibiotics. She subsequently developed a progressive sensorineural hearing loss. The erythrocyte sedimentation rate was significantly elevated. 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Ann Intern Med 1998;129:114-122. Grand Rounds Archive | Department Home page BCM Public | BCM Intranet | Privacy Notices | Contact BCM | BCM Site Map | ©2001-2006 Baylor College of Medicine
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