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Policondritis recidivante
Abstract
La policondritis recidivante se caracteriza por episodios inflamatorios del cartílago de las orejas, la nariz, la laringe y el árbol traqueobronquial cuya repetición puede conducir a la fibrosis y la deformación del cartílago. Las condritis laríngeas y traqueobronquiales son particularmente graves debido al riesgo vital al que dan lugar, y deben sospecharse ante la aparición de una disnea. Esta afección no se limita a la afectación cartilaginosa: también puede ser responsable de numerosas manifestaciones sistémicas: poliartritis aguda intermitente y no erosiva, epiescleritis, insuficiencia aórtica y lesiones de los troncos arteriales, afectación audiovestibular, manifestaciones cutáneas y neurológicas variadas. Los signos biológicos observados, síndrome inflamatorio y leucocitosis, no son específicos, y los anticuerpos anticartílago o anticolágeno de tipo II son inconstantes. El examen histológico del cartílago, no necesario para el diagnóstico, muestra, al inicio de la enfermedad, una infiltración por células linfoplasmocíticas y macrofágicas. La enfermedad evoluciona generalmente por accesos intermitentes. Un síndrome mielodisplásico está presente en más del 40% de los pacientes mayores de 60 años y debe buscarse en presencia de anomalías del hemograma. El tratamiento se basa ante todo en los corticoides y los inmunosupresores en las formas más graves o en caso de dependencia a los corticoides. La experiencia con las bioterapias es controvertida. A veces, es necesaria la cirugía laringotraqueal y cardiovascular en las formas graves de la enfermedad.
... (8,9,10,11,12,13,14) Los síntomas cutáneos en la PR abarcan púrpura, urticaria y angioedema, con menos frecuencia livedo reticularis, tromboflebitis superficial migratoria, eritema nodoso, eritema multiforme y paniculitis. (15,16) Las complicaciones neurológicas en la PR comprenden neuropatía craneal, dolor de cabeza, encefalopatía, hemiplejía y ataxia, a veces también mielitis transversa, mononeuritis múltiple y vasculitis temporal no granulomatosa. Hasta en el 22 % de los pacientes, la PR se acompaña de fiebre bastante alta. ...
Recurrent polychondritis is a rare condition characterized by recurrent inflammation of cartilage and other tissues throughout the body. Ear involvement is the most common feature, but a variety of other areas of the body may be compromised, including costal cartilage, eyes, nose, airways, heart, vascular system, skin, joints, kidneys and nervous system. The signs and symptoms vary from person to person depending on the body parts affected. The exact underlying cause of recurrent polychondritis is unknown; however, scientists suspect it is an autoimmune condition. The main goals of treatment for people with recurrent polychondritis are to alleviate current symptoms and preserve the structure of the affected cartilage.
Objective:
Relapsing polychondritis (RPC) is relatively rare and early diagnosis is difficult. We investigated the utility of fluorodeoxyglucose (FDG)-PET/CT for the diagnosis of RPC and evaluation of disease activity.
Methods:
Five RPC patients undergoing FDG-PET/CT in our hospital between 2006 and 2012 were studied. Eight RPC cases examined by PET reported in the literature were also assessed. Data from a total of 13 patients were analysed.
Results:
Typical FDG accumulation was noted in the tracheobronchial trees of nine patients, the costal cartilage of five, joints of five, larynx of four, nasal cavity/paranasal sinuses of three, auricles of three, lymph nodes of three and the aorta of one. One patient showed nasal chondritis on a PET scan despite the absence of nasal changes on physical examination. Of five patients with costochondritis, four remained asymptomatic. Of nine patients with airway FDG accumulation, eight developed respiratory symptoms and all had CT abnormalities. In the other patient, airway FDG accumulation was evident despite the absence of airway symptoms and a lack of abnormalities in the respiratory function test and CT. PET also revealed bronchial chondritis in asymptomatic patients. The mean maximum standardized uptake values (SUVmax) of the upper and lower airways was 5.79 (s.d. 2.87) and 6.47 (s.d. 4.08), respectively. In five patients with a PET after treatment, FDG accumulation had diminished with symptomatic and inflammatory improvement.
Conclusion:
FDG-PET/CT is a potentially powerful tool for the early diagnosis of RPC, especially in patients without easily biopsied organ involvement. This modality also facilitates evaluation of disease extent and disease activity during treatment.
Objectives:
We aimed to identify a serum biomarker for evaluating the disease activity of relapsing polychondritis (RP).
Methods:
We measured and compared serum levels of 28 biomarkers potentially associated with this disease, including soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), high-sensitivity C-reactive protein (hs-CRP), and cartilage oligomeric matrix protein (COMP), in 15 RP patients and 16 healthy donors (HDs). We divided the 15 RP patients into active RP (n = 8) and inactive RP (n = 7) groups, depending on the extent of the disease, and compared candidate markers between groups. The localization of membrane-bound TREM-1 in the affected tissue was examined by immunohistochemistry.
Results:
Serum levels of sTREM-1, interferon-γ, chemokine (C-C motif) ligand 4, vascular endothelial growth factor, and matrix metalloproteinases-3 were significantly higher in RP patients than HDs. Among these markers, sTREM-1 had the highest sensitivity and specificity (86.7 and 86.7 %, respectively). Furthermore, the serum level of sTREM-1 was significantly higher in active RP patients than inactive RP patients (p = 0.0403), but this was not true for hs-CRP or COMP. TREM-1 was expressed on endothelial cells in RP lesions.
Conclusions:
The serum level of sTREM-1 may be a useful marker of disease activity in RP.
Relapsing polychondritis is an inflammatory disease of unknown cause, affecting the ear, nose, respiratory tract, and joint cartilages. An immune reaction against cartilage antigens resulting in cell damage and consequent cartilage destruction is the most widely accepted hypothesis for the cause. The diagnosis is based on both clinical and pathologic findings. Involvement of the upper respiratory tract causes dyspnea, hoarseness, aphonia and airway obstruction due to edema, and collapse of the tracheal and cricoid rings. Only a few cases of relapsing polychondritis studied by CT have been reported. We describe a patient who had involvement of the arytenoid as well as the other laryngeal cartilages.
Relapsing polychondritis (RPC) is a disorder characterized by inflammation and the destruction of the cartilaginous structures of multiple organs. The typical diagnostic signs are auricular chondritis, nasal chondritis, respiratory tract chondritis and audiovestibular damage, therefore RPC is an important disorder for laryngologists. In particular, tracheal stenosis due to chondritis is the main cause of death.
We present two cases of RPC, comfirmed by diagnostic signs recognized by Damiani's expanded criteria for diagnosing RPC.
This paper presents a case with refractory relapsing polychondritis (RPC), complicated with severe aortic involvement, which is successfully treated with tocilizumab. Previous treatments consisted of methotrexate, corticosteroids, cyclosporine, cyclophosphamide, infliximab, and etanercept. With these treatments, the patient had recurrent episodes of fever, polyarthritis, tenosynovitis, subcutaneous nodules, and progressive cardiac disease. One year after the start of treatment with tocilizumab, there is resolution of all symptoms, normalization of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and the dose of prednisolone is tapered down to 2 mg/day. We have reviewed the English literature for reports of patients with refractory RPC, successfully treated with tocilizumab. We found five additional case reports. In one case report, a patient with refractory RPC complicated with aortitis was successfully treated with tocilizumab. In three case reports, patients with refractory RPC complicated with laryngotracheal involvement were successfully treated with tocilizumab. All cases had, like our patient, failed conventional treatment. We also reviewed the literature for reports of the effect of biologicals on cardiac involvement in RPC. Current literature is presented and discussed.
Relapsing polychondritis is a rare condition characterized by inflammation and subsequent degeneration of cartilages. Deformity of the pinna, nasal saddling and stridor due to involvement of the cartilages of the respiratory tract may lead to patients being referred to the otolaryngologist for initial assessment and further management. Recent observations have suggested that relapsing polychondritis may occur as a paraneoplastic phenomenon in cases of myelodysplasia. The case of a patient with relapsing polychondritis, myelodysplastic syndrome and a monoclonal gammopathy is presented. The authors highlight the apparent existence of this association and encourage otolaryngologists to consider such possible links when cases of relapsing polychondritis present to the outpatients department.
Relapsing polychondritis (RP) is a rare inflammatory disease characterized by diffuse cartilage involvement, especially those of the respiratory tract, leading to potentially life threatening complications. Corticosteroids remain the first-line empirical therapy. Immunosuppressive drugs such as azathioprine, cyclophosphamide and tumor necrosis factor blockers (anti-TNFα) are commonly used as second-line therapy with varying degrees of success.
We report a 40-year-old man with severe RP for whom conventional therapy and immunosuppressive treatments were ineffective. Prolonged clinical remission was obtained after introduction of the anti-interleukin-6 receptor antibody (tocilizumab), which was perfectly tolerated and allowed to taper steroids and methotrexate to a very low dosage.
Our patient is the fifth published one documenting the efficacy of tocilizumab in severe refractory RP, which strengthens the use of anti-IL-6 in that indication.
Relapsing Polychondritis (RP) is a systemic inflammatory disease primarily affecting the cartilaginous structures of the ears, nose and tracheobronchial tree but also the joints, the inner ear, the eyes, and the cardiovascular system. RP is an immune-mediated disease during which target antigens are still unknown, but data from human studies and murine models strongly support a role of both Collagen Type II (CII) and matrilin-1 as potential candidates. RP is likely a Th1-mediated disease as serum levels of interferon(IFN)-γ, interleukin [IL]-12, and IL-2 parallel changes in disease activity, while the levels of Th2 cytokines (IL-4, IL-5, IL-6, and IL-10) do not. Serum levels of sTREM-1, interferon-γ, CCL4, vascular endothelial growth factor, and matrix metalloproteinases-3 are significantly higher in RP patients than in healthy donors, with sTREM-1 correlating with disease activity. Patients with active RP also have significantly higher levels of MCP-1, MIP-1β, MIF, and IL-8 than controls. These pro-inflammatory chemokines are involved in the modulation and recruitement of monocytes and neutrophils. Altogether, these data suggest that a complex cytokine network orchestrates the recruitment of infiltrating cells in RP lesions. Cytokine modulation using TNFα blockers, rituximab, anakinra, tocilizumab, and abatacept has recently been shown effective in some RP cases but further data are needed. Better understanding of the repertoire of infiltrating cells may provide interesting clues to further define the putative RP auto-antigens. Study of circulating mononuclear cells during RP flares may also provide crucial information about the ongoing cellular trafficking and recruitment processes involved in this rare disease.
To describe the effects of biologics in an unbiased series of relapsing polychondritis cases.
We extracted all the cases encoded 'polychondritis' from the computerized medical files of our department. The relapsing polychondritis diagnosis was confirmed using Damiani's criteria. Patients treated with biologics were evaluated for efficacy and adverse drugs reactions until October 2012.
Nine patients were exposed to 22 biologics as corticosteroid-sparing drugs. Biologics were used at the same doses as in rheumatoid arthritis. Mean duration of exposure to biologics was 28 months. A TNF-antagonist was most frequently used as first-line biologic therapy (7/9), leading to partial or complete efficacy in six cases (85.7%). Loss of efficacy occurred in 5 cases. Abatacept (n=3) and tocilizumab (n=2) were effective as second-line biologic therapy while anakinra (n=2) and certolizumab (n=1) were not. Seven serious adverse drug reactions occurred, including 5 infections.
TNF-α antagonists may be proposed earlier in relapsing polychondritis to spare corticosteroids. Switching to another biologic can be proposed in case of loss of efficacy. Tocilizumab or abatacept can be proposed as third-line therapy. The benefit-to-risk ratio of biologics in relapsing polychondritis should be evaluated prospectively.
Les auteurs rapportent une observation de polychondrite atrophiante se manifestant initialement par des thromboses veineuses à répétition, associées à la présence d'anticorps antiphospholipides. De tels anticorps ont été rapportés dans de nombreuses maladies systémiques dont certaines peuvent s'associer à la polychondrite atrophiante;cependant, jamais ils n'ont été mis en évidence au cours de cette maladie.
We report two cases of polychondritis associated with mesenteric panniculitis.
Case 1. In February 1989, a woman born in 1949 presented with 40° C fever accompanied by pain in the abdomen and pelvis. Eight days later, nodular skin lesions appeared on her lower limbs. The abdomen was swollen with gas and undepressible. An abdominal CT scan revealed partitionaed peritoneal collections, and a guided needle aspiration produced a chylous fluid. Direct and indirect bacteriological examinations gave negative results. Histology showed intense inflammatory reaction with giant cells and lipophages, thereby confirming the presence of mesenteric panniculitis. Six months later, the development of chondritic lesions on the nose and the helix of the ear clinched the diagnosis of polychondritis. The patient was put on corticosteroid therapy for a few months, and in January this year (1993) she is durably asymptomatic.
Case 2. In October 1977, a woman born in 1937 presented with polychondritis with prolonged fever, inflammatory syndrome and chondritic lesions of the nose, larynx and helix of the ear. In December 1978, she developed signs of abdominal obstruction. Laparotomy revealed infiltration by multiple nodular formations of the entire posterior line of attachment of the mesentery. Biopsies withdrew a puriform fluid. Histology showed a partly necrotic adipose tissue with giant cells and lipophages. High-dose corticosteroid therapy partially controlled the chondritic and abdominal manifestations.
The occurrence of abdominal pain in patients with polychondritis may result from several disorders, such as iatrogenic complications, digestive tract vasculitis or ulcerative colitis, but also associated mesenteric panniculitis.
To the Editor:
We read with interest the letter from Wallace and Stone1 describing a patient with relapsing polychondritis (RP) refractory to corticosteroids, cyclophosphamide, and tumor necrosis factor (TNF) blockers. The patient’s biological inflammation and clinical symptoms of chondritis responded well after each tocilizumab (TCZ) infusion. We describe a somewhat different experience of TCZ efficacy in a patient with RP.
A 46-year-old woman was diagnosed with RP in 2000 with recurrent episodes of chondritis and mainly synovitis and tenosynovitis. After failure …
Address correspondence to Dr. Wendling; E-mail: dwendling{at}chu-besancon.fr
To the Editor:
Relapsing polychondritis (RPC) can affect the ears, eyes, larynx, trachea, bronchi, joints, audiovestibular system, and heart valves1,2,3. Therapy is difficult in the subset of patients refractory to glucocorticoids and conventional immunosuppressive agents. We describe a 65-year-old woman with RPC refractory to glucocorticoids, cyclophosphamide, and infliximab. Interleukin 6 (IL-6) inhibition led to prompt control of RPC affecting her ears, nose, and trachea, as well as swift normalization of her acute-phase reactants. Re-treatment with tocilizumab on 2 occasions following disease flares again led to prompt disease control without the use of other medications.
The patient presented with 4 months of intermittent but progressive swelling, erythema, and pain of her right ear (Figure 1A). The nasal bridge was swollen and faintly erythematous (Figure 1B), and the trachea was tender. Her left ear appeared normal (Figure 1C). She had thrombocytosis (platelets 767,000/mm3, normal 150,000−400,000/mm3) and elevations of the erythrocyte sedimentation rate (ESR; 103 mm/h, normal < 17 mm/h) and C-reactive protein (CRP; 170 mg/dl, normal < 8 mg/dl). Given her clinical presentation, a diagnosis of RPC was rendered …
Address correspondence to Dr. J.H. Stone, Rheumatology Unit, Massachusetts General Hospital, 55 Fruit St., Yawkey 2, Boston, MA 02114, USA. E-mail: jhstone{at}partners.org
Two cases of relapsing polychondritis are described. Immune reactions against cartilage are discussed, with reference to the protection of chondrocytes from immune reactions by matrix, and antibody- and cell-mediated responses to cartilage matrix components. Cell-mediated responses to proteoglycan are probably more important than antibodies in the pathogenesis of relapsing polychondritis, but are unlikely to initiate the disease process. Cartilage may be injured as an ‘innocent bystander’ in immune reactions, because of its affinity for immune complexes. This, and the cross-reaction between cartilage antigens and streptococcai antigens, could be of importance in the pathogenesis of relapsing polychondritis.
Objective
Relapsing polychondritis (RP) is an inflammatory disease that mainly affects cartilage tissue in the auricle, nose, and lower respiratory tract. When tracheolaryngeal cartilage is involved, the disease is occasionally fatal. Matrilin 1 is a cartilage-specific protein most prominently expressed in tracheal cartilage, but not in joint cartilage. Immunization with the protein in rats and mice induces respiratory distress and nasal destruction, as seen in RP. We investigated the response to matrilin 1 and other cartilage proteins in sera from patients with RP, 4 additional groups of patients with other major connective tissue diseases, and healthy control subjects.Methods
Sera were analyzed by enzyme-linked immunosorbent assay (ELISA) for antibody responses to matrilin 1, types II, IX, and XI collagen, and cartilage oligomeric matrix protein (COMP). Titers above the mean + 3SD of controls were considered positive. Specificity of matrilin 1 recognition was further investigated by the capacity of high-titer sera to block the binding of a matrilin 1–specific monoclonal antibody in inhibition ELISAs. In vivo reactivity and specificity were tested by injecting sera into neonatal mice, and antibody binding was detected by immunohistochemical staining.ResultsSerum antibodies from RP patients bound tracheolaryngeal and nasal cartilage in vivo and inhibited the binding of anti–matrilin 1–specific monoclonal antibodies. Thirteen of the 97 RP patients had increased titers of matrilin 1 antibody. Positive titers correlated with respiratory symptoms in 69% of the cases. Significant responses to type II collagen and COMP were also detected.Conclusion
Antibodies to matrilin 1 bind tracheolaryngeal cartilage in vivo and are correlated with an inflammatory attack on tracheolaryngeal cartilage that is often seen in RP.
There is no standardized therapeutic protocol for relapsing polychondritis (RP). Emergence of biologics holds much hope in the management of this connective tissue disease.
To evaluate the efficacy and safety of biologics in patients with active RP.
A systematic review of the literature using PubMed was performed through December 2010. MeSH terms and keywords were used relating to RP and biologics. All papers reporting the efficacy and/or safety of biologics in RP were selected. Reference lists of included papers were also searched.
All publications relate to case series or isolated case reports. No randomized controlled trial has been performed. Thirty papers that included 62 patients were published. These patients were treated with TNFα blockers (n = 43), rituximab (n = 11), anakinra (n = 5), tocilizumab (n = 2), and abatacept (n = 1). The endpoint of treatment differs from 1 publication to the other and therefore makes the comparison of efficacy among the various biologics difficult. Biologics were effective in 27 patients, partially effective in 5 patients, and not effective in 29 patients. Safety appeared to be good. However, 4 deaths were recorded (2 sepsis, 1 postoperatively after aortic aneurysm surgery, and 1 after accidental dislocation of the tracheostomy device).
The experience with biologics in RP is very limited and their real efficacy and indications need to be better defined. Randomized controlled trials, although difficult to perform because of the rarity of RP, are needed to determine the place of biologics in the treatment strategy of this orphan disease.
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Relapsing polychondritis (RPC) is a rare rheumatic disease characterized by recurrent inflammation of cartilaginous structures, with airway involvement a major cause of morbidity and mortality.
To retrospectively evaluate airway and lung abnormalities in RPC with computed tomography (CT).
From January 2004 to May 2009, 21 patients with RPC (12 men, 9 women; 13-65 years old) underwent chest CT examinations. Two chest radiologists evaluated the CT images retrospectively. Abnormal findings, including airway stenosis, airway malacia, air trapping, and airway wall thickening with or without calcifications, were observed and noted.
Major abnormal CT findings were observed in eight patients (38.1%), which included airway wall thickening (n=7), airway stenosis (n=6), airway malacia (n=6), airway wall calcification (n=8), and air trapping (n=3). Mediastinal lymph nodes were found in 12 patients. Lung infection was identified in four patients and interstitial lung disease in six patients.
The CT findings in patients with RPC consisted mainly of airway wall thickening, airway stenosis, airway malacia, airway wall calcification, and air trapping.
Rituximab, a chimeric monoclonal antibody directed against the CD20 antigen expressed by B cells, is now considered an effective second-line therapy in various systemic diseases. We describe here the effects of rituximab in patients with relapsing polychondritis.
This was a retrospective study of 9 patients with relapsing polychondritis who received different regimens of rituximab in addition to their ongoing therapies. Clinical, laboratory, physiologic, and radiologic indicators were used to assess disease activity. We also examined their corticosteroid doses and any change in immunosuppressive agents. We then compared disease activity in the 6 months preceding rituximab administration and at 6 and 12 months after.
At 6 months, 2 patients showed partial improvement, 4 were stable, and 3 had worsened disease; however, no patient had complete remission. At 12 months (after exclusion of the 3 patients whose disease had worsened at 6 months), 2 patients remained stable and 4 had worsened disease; however, there were no partial or complete remissions. B cells were counted in 8 patients during the first 6 months after treatment, and B cell depletion was observed in all of the patients.
Although we cannot rule out the possibility that rituximab had a small effect, our patients' clinical courses did not improve significantly with this treatment.
This communication has attempted to review the present state of published knowledge on the syndrome of relapsing polychondritis. Basic anatomic, physiologic, and biochemical changes in this disorder are summarized and the role of metabolic and immunologic alterations in the pathogenesis discussed. An additional case of relapsing polychondritis is reported, and the clinical features of this case, plus those of 131 previously reported, are reviewed with discussion of present day therapeutic experience and prognosis.
Relapsing polychondritis is a rare disease of unknown etiology. There are approximately 211 reported cases in the world literature. This is a report of ten cases from the Cleveland Clinic Foundation.
McAdam's diagnostic criteria for R.P. were reviewed and modified. For diagnosis, all patients had to have 1. at least three or more diagnostic criteria, histologic confirmation not necessary; 2. one or more of McAdam's signs with positive histologic confirmation; or 3. chondritis in two or more separate anatomic locations with response to steroids and/or Dapsone.
Chondritis of the auricles (9/10 patients) and arthropathy (8/10 patients) are the most common presenting signs. Chondritis was also seen in the nose (6/10) and the upper respiratory tract involving the larynx and trachea (4/10). Cochlear and vestibular damage and ocular inflammation were each seen in 5/10 patients.
Patients were treated with steroids and/or Dapsone. Both drugs were reliable in abating episodes of activity and in decreasing recurrences. These results further support Dapsone as an alternate form of treatment for RP.
Relapsing polychondritis is rare and its cause is unknown. The tissues affected are those with a high glycosaminoglycan content, such as cartilage, the aorta, the sclera and cornea, and parts of the ear. Symptoms can usually be controlled with oral steroids, but when there is coexistent progressive crescentic glomerulonephritis quadruple chemotherapy may be used. Three cases of the clinical syndrome of relapsing polychondritis were studied in which rapidly progressive cresentic glomerulonephritis developed. In two the patients appeared to respond to aggressive treatment with immunosuppressive agents and anticoagulants. The multisystemic nature of the disease, the renal lesions, and the response to treatment all suggested that the condition might be related to periarteritis nodosa.
Relapsing polychondritis (RP) is not a totally rare rheumatic disease. We have seen 23 patients from 1960-1975, and there are now a total of 159 reported cases, which form the basis of this study. RP occurs equally in both sexes, and has a maximum frequency in the fourth decade. 2) Empirically defined diagnostic criteria are proposed, to include the most common clinical features: a) Bilateral auricular chondritis b) Nonerosive sero-negative inflammatory polyarthritis c) nasal chondritis d) Ocular inflammation e) Respiratory tract chondritis f) Audiovestibular damage The diagnosis is based primarly upon the unique clinical features, and is quite certain if three or more criteria are present together with histologic confirmation. 3) Fifty percent of patients present with either auricular chondritis or the arthropathy of RP; but with prolonged follow-up, a majority of patients develop four or more of the above mentioned criteria. 4) Approximately 30 percent of patients have a preceding or coexistent rheumatic or autoimmune disease, which can lead to initial diagnostic confusion. 5) Laboratory and radiographic investigations help mainly to rule out other diagnostic possibilities, with no characteristic abnormalities being present in a majority of patients. 6) On follow-up, three-fourths of our patients required chronic corticosteroid therapy with an average dose of 25 mg per day of prednisone. Corticosteroids decrease the frequency, duration, and severity of flares, but do not stop disease progression in severe cases. 7) The mortality rate has been 30 percent in our series and 22 percent in the other 136 reported cases. Of the 29 cases where the cause of death was known, 17 were from respiratory tract involvement and 9 from cardiac valvular or vasculitic involvement, emphasizing the need to search for critical involvement of either of these organ systems in each patient. 8) Detailed reports of selected cases are presented to illustrate the clinical diagnosis and differential diagnosis, and to demonstrate the need for careful prolonged follow-up. 9) Although the etiology remains unknown, there is a frequent association with, and clinical similarity to, other rheumatic diseases. 10) Careful clinicopathological study of our 23 patients leads us to postulate an underying systemic vascultis as an important pathologic mechanism in RP.
Review of four cases of relapsing polychondritis (RP) seen at one hospital in the 12-year period 1963 to 1974 revealed that one patient had aortic insufficiency with large artery involvement, two others had involvement of medium and large arteries and the fourth may have had mucocutaneous vasculitis. Valvular disease has occurred in 9% of all cases of RP reported in the literature and, if vasculitis beyong the aortic root is included, 25% of cases of RP manifested inflammatory vascular disease. The frequency of pseudotumour of the orbit and cochlear-labyrinthine dysfunction is also high and may be a manifestation of vasculitis.
Two cases of relapsing polychondritis are described. Immune reactions against cartilage are discussed, with reference to the protection of chondrocytes from immune reactions by matrix, and antibody and cell mediated responses to cartilage matrix components. Cell mediated responses to proteoglycan are probably more important than antibodies in the pathogenesis of relapsing polychondritis, but are unlikely to initiate the disease process. Cartilage may be injured as an 'innocent bystander' in immune reactions, because of its affinity for immune complexes. This, and the cross reaction between cartilage antigens and streptococcal antigens, could be of importance in the pathogenesis of relapsing polychondritis.
We describe a patient with relapsing polychondritis in whom aortic valve inflammation developed 3 years after diagnosis, when the polychondritis had been in apparent remission for an extended period of time. Infection and cardiac involvement can be significant complications of relapsing polychondritis. Recommendations for monitoring and treatment of patients with this disease are discussed.
To analyze the importance of airway involvement in relapsing polychondritis, an illustrative case report is presented and 62 patients reported in the literature with serious airway complications are reviewed. There were 47 female and 17 male patients, with an average age of 40.3 years (range, 2 to 73 years). Patients were seen with hoarseness, breathlessness, cough, stridor, wheezes, and tenderness over laryngotracheal cartilages. Respiratory tract involvement was confirmed by conventional radiography, tomography, computed tomography, dynamic pulmonary function tests, and bronchoscopy. Corticosteroids and antiinflammatory and immunosuppressive agents were used in these patients. Tracheostomy was performed in 18 patients. Death occurred in 13 patients despite tracheostomy or corticosteroid therapy, or both. A detailed analysis of the clinical, radiological, and pulmonary function studies is presented, with emphasis on upper airway mechanics. The medical and surgical management options are reviewed, including the use of endotracheal prosthesis and extraluminal splinting in dynamic airway collapse.
We describe 2 adolescents with relapsing polychondritis who developed acute airway obstruction. Both were successfully treated with intravenous steroids for this complication following failure with oral steroids. Early respiratory tract involvement in younger patients seems predictive of a poor outcome and aggressive therapy with intravenous high dose steroids and/or immunosuppressive drugs appears to be indicated.
The case of a man, 25 years of age and presenting with chronic atrophic polychondritis (CAP), complicated by a complete atrioventricular block, double mitral valve incompetence and aneurysm of the ascending aorta, offered the possibility of investigating the various clinical manifestations and cardiovascular complications of this common disorder. CAP is a connectivitis of unknown etiology, it corresponds to ubiquitous and recurrent cartilage inflammation, leading to characteristic chondritis of the ears and nose, joint disease and laryngo-trachco-bronchial disorders. Other systemic impact is seen at sites containing high levels of proteoglycans, such as the eye, inner ear and cardiovascular system. Respiratory problems are the main cause of death, but cardiovascular effects occur in 25% of cases and constitute the second most frequent cause of mortality. These effects consist mainly of aortic and/or mitral valve incompetence. Annular dilatation, which is often associated with ectasia of the ascending aorta, is the main cause of aortic incompetence. Several cases of isolated AVB or AVB secondary to Al have been reported. Aneurysms develop along the aorta and the large and medium caliber arteries (sub-clavicular, coronary, mesenteric arteries). These are characterized by destruction of the elastic fibers and a reduction in the proteoglycan content of the walls, which is also observed when dystrophy of the cartilage occurs. Other vascular disorders reported include arteritis of the legs, superficial migratory varices and vascularitis, which in some cases gave rise to skin, renal or neurological reactions.
The association of relapsing polychondritis with CSF pleocytosis is reported for the first time. Three cases are described in which infectious etiologies of the pleocytosis were excluded by appropriate cultures and serologic studies. We suggest that the finding of CSF pleocytosis in relapsing polychondritis does not merit empiric antimicrobial therapy in the absence of demonstrated infection.
Three patients with systemic lupus erythematosus (SLE) and relapsing auricular and nasal chondritis are described. Chondritis in SLE is a rare event (less than 1% of our patients), was accompanied by clinical and laboratory evidence of SLE activity and resembled relapsing polychondritis in clinical presentation and pathology. Clinical involvement was limited, cartilage collapse did not occur and response to steroid therapy was prompt. Cartilage inflammation in two ear biopsies was relatively mild, with deposits of IgG and C3 in the chondrofibral junction and adjacent skin vessels. Immune complexes (cryoglobulins) were present in the serum. We postulate an immune complex pathogenesis of this rare manifestation of SLE.
To define the natural history of relapsing polychondritis, the probability of survival and causes of death were determined in 112 patients seen at one institution. By using covariate analysis, early clinical manifestations were identified that predicted mortality. The 5- and 10-year probabilities of survival after diagnosis were 74% and 55%, respectively. The most frequent causes of death were infection, systemic vasculitis, and malignancy. Only 10% of the deaths could be attributed to airway involvement by chondritis. Anemia at diagnosis was a marker for decreased survival in the entire group. There was an interaction between other disease variables and age in determining their impact on outcome. For patients less than 51 years old, saddle-nose deformity and systemic vasculitis were the worst prognostic signs. For older patients, only anemia predicted outcome. The need for corticosteroid therapy did not influence survival.
The ocular and systemic findings in 112 Mayo Clinic patients with relapsing polychondritis were reviewed. The incidence of males and females was equal, with median age at diagnosis of 51 years and the median follow-up of 6 years. Most patients had several organ systems involved at the time of the diagnosis. Twenty-one patients had ocular symptoms at the onset, and 57 developed ocular symptoms during their course. Major ocular complications included proptosis, lid edema, episcleritis/scleritis, corneal infiltrates/thinning, iridocyclitis, retinopathy, and optic neuritis. The major system involvement included otorhinolaryngeal, respiratory, arthritic, renal, cardiovascular, dermatologic, and neurologic diseases. Generally, laboratory studies were not helpful in making the diagnosis but were valuable in monitoring the disease. Based on the experience in these cases, the indications for the various therapeutic modalities are offered.
Twenty-nine of the 129 patients with RP seen at the Mayo Clinic between 1943 and 1984 had renal involvement. These patients were older, had arthritis and extrarenal vasculitis more frequently, and had a significantly worse survival rate than those without renal involvement. Renal biopsies were obtained in 11 of these 29 patients. The predominant lesions were mild mesangial expansion and cell proliferation, and segmental necrotizing glomerulonephritis with crescents. Small amounts of electron-dense deposits, predominantly mesangial, were noted on electron microscopy. Immunofluorescence revealed faint deposition of C3 and/or IgG or IgM, predominantly in the mesangium. Autopsies were obtained in 13 of the 47 patients who had died. Information regarding the renal pathology was available in 10 of these 13 autopsies. At the time of the initial evaluation at the Mayo Clinic, 6 of these 10 patients had evidence of renal involvement. At autopsy, none of these 10 patients had evidence of active renal vasculitis or segmental necrotizing glomerulonephritis, but 8 of the 10 patients exhibited variable degrees of vascular and glomerular sclerosis, segmental mesangial proliferation, tubular loss, and interstitial lymphocytic infiltrates. These observations expand the limited information available in the literature, which is based on 11 previously published case reports of renal involvement in RP. In only a few of our patients and previously reported patients were the manifestations of the disease limited to the systems characteristically involved in pure RP. The frequent coexistence of other autoimmune and connective tissue diseases supports the role of immune mechanisms in the pathogenesis of this syndrome. Deposition of immune complexes is likely to play a role in the pathogenesis of the glomerular lesions associated with RP. Administration of corticosteroids alone is sufficient to induce a complete remission in some cases, while in others the addition of a cytotoxic agent is necessary to control the activity of the disease or to spare corticosteroid side effects and maintain a remission. Immunosuppression-related infectious complications and undetected relapses after discontinuation of immunosuppressive therapy are largely responsible for the morbidity and mortality observed in these patients.
Five patients with features of coexistent relapsing polychondritis and Behçet's disease are described. Review of the literature supports the overlap of the clinical manifestations of these two conditions. A common immunologic abnormality is likely, and elastin is cited as a possible target antigen. The "mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome" is the proposed name for this entity.
Serial studies have been performed on three patients with relapsing polychondritis in an attempt to define a potential immunopathologic role for degradation constituents of cartilage in the causation and/or perpetuation of the inflammation observed. Crude proteoglycan preparations derived by disruptive and differential centrifugation techniques from human costal cartilage, intact chondrocytes grown as monolayers, their homogenates and products of synthesis provided antigenic material for investigation. Circulating antibody to such antigens could not be detected by immunodiffusion, hemagglutination, immunofluorescence or complement mediated chondrocyte cytotoxicity as assessed by (51)Cr release. Similarly, radiolabeled incorporation studies attempting to detect de novo synthesis of such antibody by circulating peripheral blood lymphocytes as assessed by radioimmunodiffusion, immune absorption to neuraminidase treated and untreated chondrocytes and immune coprecipitation were negative. Delayed hypersensitivity to cartilage constituents was studied by peripheral lymphocyte transformation employing [(3)H]thymidine incorporation and the release of macrophage aggregation factor. Positive results were obtained which correlated with periods of overt disease activity. Similar results were observed in patients with classical rheumatoid arthritis manifesting destructive articular changes. This study suggests that cartilage antigenic components may facilitate perpetuation of cartilage inflammation by cellular immune mechanisms.