Relapsing polychondritis complicated by cognitive dysfunction: two distinct clinical phenotypes?

Relapsing polychondritis (RPC) is a rare, immune-mediated condition affecting approximately 3.5 per million population per year. Neurological involvement in RPC is still rarer and is presumed to be the result of a vasculitic process, although this is seldom confirmed in the literature. We present two cases of RPC complicated by cognitive dysfunction with contrasting clinical trajectories. Our findings suggest that there are two clinical phenotypes of cognitive dysfunction in RPC. The first is a fulminant, multisystem presentation with sub-acute cognitive decline mimicking central nervous system vasculitis, and we provide histopathological evidence of this process occurring. The other is an insidious cognitive decline without associated constitutional or systemic symptoms.

Relapsing Polychondritis: an Update on Pathogenesis, Clinical Features, Diagnostic Tools, and Therapeutic Perspectives.

Relapsing polychondritis is a rare multisystemic disease widely accepted as a complex autoimmune disorder affecting proteoglycan-rich structures and cartilaginous tissues, especially the auricular pinna, cartilage of the nose, tracheobronchial tree, eyes, and heart's connective components. The clinical spectrum may vary from intermittent inflammatory episodes leading to unesthetic structural deformities to life-threatening cardiopulmonary manifestations, such as airway collapse and valvular regurgitation. The frequent association with other rheumatologic and hematologic disorders has been extensively reported over time, contributing to define its complexity at a diagnostic and also therapeutic level. Diagnosis of relapsing polychondritis is mainly based on clinical clues, while laboratory data have only a supportive contribution. Conversely, radiology is showing a relevant role in estimating the rate of systemic involvement as well as disease activity. The present review is aimed at providing an update on scientific data reported during the last 3 years about relapsing polychondritis in terms of pathogenesis, clinical features, diagnosis, and new treatment options.

Diagnosis and classification of relapsing polychondritis.

Relapsing polychondritis is a rare and potentially fatal autoimmune disease of unknown etiology, characterized by inflammation and destruction of different cartilaginous structures, including the ear, nose, larynx, trachea, bronchi, peripheral joints, eye, heart and skin, with high risk of misdiagnosis. The spectrum of clinical presentations is protean and may vary from intermittent episodes of painful and disfiguring auricular and nasal chondritis or polyarthritis to severe progressive multi-organ damage. A laryngotracheobronchial involvement appears in nearly half of patients and is complicated by local obstructions, which may be life-threatening. A highly medical specialized approach is required for diagnosis of relapsing polychondritis. This review comprehensively examines the literature related to the clinical sceneries of the disease and focuses on both diagnostic tools used in clinical studies and recent findings related to its etiopathogenesis.

[Relapsing polychondritis].

Relapsing polychondritis (RP) is a systemic inflammatory condition leading to irreversible structural changes in cartilaginous tissue as a result of generalized proteoglycane decomposition. Auricular and nasal cartilage is usually the first to be affected at the onset of the disease which leads to episcleritis. At the later stages, the larynx and trachea become involved, vasculitis develops affecting the organs of hearing, coronary arteries, kidneys, meninges, and other organs. The disease has an intermittent, recurrent character. The clinical course of RP is irregular. The disease is a rare occurrence and difficult to diagnose. The present review is based on the publications by domestic and foreign authors. It is intended to enhance awareness of the clinical picture and peculiarities of RP among clinicians with a view to improving its diagnostics.

Relapsing polychondritis: state-of-the-art review with three case presentations.

BACKGROUND: Relapsing polychondritis (RPC) is a complex immune-mediated systemic disease affecting cartilaginous tissue and proteoglycan-rich organs. The most common and earliest clinical features are intermittent inflammation involving the auricular and nasal regions, although all cartilage types can be potentially affected. The life-threatening effects of rpc involve the tracheobronchial tree and cardiac connective components. Rpc is difficult to identify among other autoimmune comorbidities; diagnosis is usually delayed and based on nonspecific clinical symptoms with limited laboratory aid and investigations. Medications can vary, from steroids, immunosuppressants, and biologics, including anti-tnf alpha antagonist drugs. METHOD: Information on updated etiology, clinical symptoms, diagnosis, and treatment of rpc has been obtained via extensive research of electronic literature published between 1976 and 2019 using PubMed and medline databases. English was the language of use. Search inputs included 'relapsing polychondritis,' 'polychondritis,' 'relapsing polychondritis symptoms,' and 'treatment of relapsing polychondritis.' Published articles in English that outlined and reported rpc's clinical manifestations and treatment ultimately met the inclusion criteria. Articles that failed to report the above and reported on other cartilaginous diseases met the exclusion criteria. RESULT: Utilizing an extensive overview of work undertaken in critical areas of RPC research, this review intends to further explore and educate the approach to this disease in all dimensions from pathophysiology, diagnosis, and management. CONCLUSION: RPC is a rare multi-systemic autoimmune disease and possibly fatal. The management remains empiric and is identified based on the severity of the disease per case. The optimal way to advance is to continue sharing data on RPC from reference centers; furthermore, clinical trials in randomized control groups must provide evidence-based treatment and management. Acquiring such information will refine the current knowledge of RPC, which will improve not only treatment but also diagnostic methods, including imaging and biological markers.

Relapsing Polychondritis with a Cobble-stone Appearance of the Tracheal Mucosa, Preceded by Posterior Reversible Encephalopathy Syndrome.

A 25-year-old woman had convulsions and disturbance of consciousness. Head magnetic resonance imaging (MRI) showed punctate areas in the occipital lobes with increased signals on T2-weighted imaging. The MRI abnormalities responded well to steroid pulse therapy, so we made a diagnosis of posterior reversible encephalopathy syndrome (PRES). Three months later, she developed a fever and dyspnea. Chest computed tomography revealed marked thickness of the tracheal and bronchial wall, and bronchoscopy showed a cobble-stone appearance of the tracheal mucosa, indicative of relapsing polychondritis (RPC). We consider that PRES had developed due to autoimmune vasculitis in the brain with RPC.

Relapsing polychondritis and malignant lymphoma: is polychondritis paraneoplastic?

BACKGROUND: Relapsing polychondritis (RP) is associated with other rheumatic or autoimmune disease in about 30% of cases; however, an association with malignancy is rare with the exception of myelodysplastic syndrome (MDS). Observation Herein we report the first case, to our knowledge, of RP following splenic non-Hodgkin lymphoma (NHL), and we have reviewed all the previous well-documented reports that described the cases of RP associated with malignant lymphoma (ML). CONCLUSIONS: Our case and the review of reported cases showed that RP preceded ML in 2 cases, RP occurred after diagnosis and treatment of ML in 2 cases, and RP and ML occurred simultaneously in 1 case. The types of ML encountered were Hodgkin lymphoma, orbital mucosa associated lymphoid tissue type lymphoma, nodal NHL, and splenic NHL. From the frequent association of RP with MDS and, less frequently, with ML, we speculate that some RP cases may occur as a paraneoplastic condition of the concurrent hematological malignancies.

Relapsing polychondritis in a liver transplant recipient: A case report.

RATIONALE: Relapsing polychondritis (RP) is a multisystemic, progressive disease of unknown etiology characterized by recurrent inflammation and progressive cartilage destruction. It can involve all types of cartilage including ears and nose, tracheobronchial tree, joints, and any other tissue rich in proteoglycans such as heart, eyes, and blood vessels. Recurrent chondritis can be life-threatening if the respiratory tract, heart valves, or blood vessels are affected. To date there is no data in the literature on the post solid organ transplantation RP. PATIENT CONCERNS: We present a 59-year-old male liver transplant recipient with primary sclerosing cholangitis who developed RP of the earlobes and nose despite post-transplant immunosuppression. DIAGNOSES: Based on the clinical criteria, scintigraphy and biopsy from the left auricle his condition was diagnosed as RP. INTERVENTIONS: Pulses of methylprednisolone followed by high-dose oral steroids along with azathioprine were administered. OUTCOMES: Such therapy diminished local cartilage inflammation, improved patient's general condition and the laboratory results. Significant loss of ear cartilage and characteristic "saddlenose" were observed after remission of acute symptoms. The control scintigraphy proved very good treatment response. LESSONS: To the best of our knowledge this is the first report on the RP in liver transplant recipient. Based on our patient presentation, we suggest that RP should be suspected in any transplant recipient with cartilage inflammation, and that the Michet's clinical criteria and scintigraphy seem to be the best diagnostic tools for solid organ transplant recipients suspected of RP.

Meningeal plasma cell granuloma in the early stage of relapsing polychondritis.

A 77-year-old man showed an asymptomatic meningeal lesion beneath the dura matter in the left fronto-parietal region on MRI during an examination for recurrent hoarsness. The lesion showed no gadolinium enhancement, and extended to neither the sulci nor skull. Neurological examinations revealed hoarseness, cochlear and vestibular dysfunction of the right ear, and mildly decreased Achilles tendon reflexes bilaterally. Laboratory findings showed marked inflammatory responses, but no abnormalities for LDH, IgG4, angiotensin-converting enzyme, or soluble IL-2 receptor. There was no serum monoclonal protein. Autoantibody panels in the serum were unremarkable except for an elevation of anti-type II collagen antibodies to a borderline value. Cerebrospinal fluid analysis disclosed an elevated protein concentration (152 mg/dl) and IgG index (1.41) with normal cell counts, negative results for bacterial/tubercular infection, and a normal cytology. 18F-fluorodeoxyglucose positron emission tomography showed increased uptake in the left frontal region (Max SUV: 7.54). Swelling of the vocal cord, arytenoid cartilage, false vocal cord, and vocal cord palsy on the right side were seen on laryngoscopy, all of which were ameliorated by dexamethasone administration. A meningeal biopsy contained the dura matter and arachnoid, in which a granulation composed of massive mature plasma cells with many Russel bodies, accompanied by occasional lymphocytes and histiocytes were observed. Three months after the biopsy, he developed bilateral auricular chondritis and conjunctivitis. Based on these findings, we diagnosed him with relapsing polychondritis (RP). Prednisolone administration (40 mg/day) improved the chondritis and meningeal lesion. Central nervous system involvement is rare in patients with RP, and meningeal complications, such as aseptic meningitis or pachymeningitis, are mostly observed after the diagnosis of RP. However, due to its rarity, it still remains to be clarified whether a similar pathogenesis of meningeal complications underlies RP. The present case is indicative in that predominant meningeal granuloma arose during chondritis of several portions that had gradually developed, which suggests that meningeal complications could be derived from RP.

Meningeal plasma cell granuloma with relapsing polychondritis. Case report.

Relapsing polychondritis (RP) is a rare systemic disease characterized by recurrent inflammation of the cartilaginous structures and connective tissue. Central nervous system lesions in association with RP have occasionally been reported, but intracranial mass lesions have not been described. The authors report the first such case, in which a 51-year-old man presented with parasagittal meningeal plasma cell granuloma with RP. The mass was subtotally resected and adjuvant radiotherapy was administered. The patient did not experience any recurrence of the lesion during an 8-year follow-up period. In this case, the exact diagnosis of RP was made based on symptoms of respiratory tract chondritis, which was successfully treated by the placement of tracheobronchial stents.

Endolymphatic hydrops as a cause of audio-vestibular manifestations in relapsing polychondritis.

Relapsing polychondritis (RP) is characterized by inflammation and subsequent degeneration of cartilage. We report a 61-year-old woman who had RP with audio-vestibular manifestations. She was also diagnosed as having a myelofibrosis with myeloid metaplasia (MMM). Bilateral endolymphatic hydrops (EH) was confirmed by dominant -SP/AP of the electrocochleogram (ECochG). When thalidomide and prednisolone were prescribed for the treatment of MMM, symptoms of RP -- including the inner ear dysfunction -- were ameliorated. Isosorbide, one of the osmotic diuretics commonly used for the treatment of Meniere's disease (MD) in Japan, was also effective in keeping her free from inner ear dysfunction. This is the first report to confirm the existence of EH in a patient with RP with audio-vestibular manifestations. We suppose that an immunological imbalance due to MMM, in conjunction with a specific immunogenetic background, may have played a role in the pathogenesis of RP and the formation of EH in this patient.

[Relapsing polychondritis: a possible cause of difficult extubation]. / Polychondrite atrophiante: une cause possible d'extubation difficile.

We report the case of a 54-year-old woman suspected of relapsing polychondritis who underwent a nasal septum biopsy under general anaesthesia. Tracheal intubation was unremarkable, but extubation attempts failed because of upper airway inspiratory collapse induced ventilatory distress. Definitive tracheostomy placement was mandatory. Cartilage biopsy confirmed severely developed relapsing polychondritis. Even though relapsing polychondritis is rare, anaesthesiologists should be aware of this pathology and preanaesthetic evaluation may focus on particular risks associated with upper airway cartilaginous structure anatomical and histological modifications.

The cartilage collagens: a review of their structure, organization, and role in the pathogenesis of experimental arthritis in animals and in human rheumatic disease.

This contribution reviews the structure and organization of collagen molecules found in cartilage and the roles that they may play in rheumatic diseases. Cartilage is unique in its physical properties and molecular composition, and contains sufficient amounts of types II, IX, X, and XI collagen to deem these molecules as "cartilage-specific." The vitreous body of the eye, a "cartilage-like" tissue is also rich in the same collagens but is type X deficient. Types VI and XII collagen are present in cartilage as well as noncartilaginous tissues. Types II, IX, and XI collagen are organized into matrix fibrils, where type II constitutes the bulk of the fibril, type XI regulates fibril size, and type IX facilitates fibril interaction with proteoglycan macromolecules. Genetic defects in these collagens can produce mild to severe developmental abnormalities, including spondyloepiphyseal dysplasia often accompanied by an accelerated form of osteoarthritis. Sensitization with collagen can produce experimental rheumatic diseases. Type II collagen induces an erosive polyarthritis in certain strains of rats, mice, and higher primates which can resemble rheumatoid arthritis and relapsing polychondritis. Type XI collagen is arthritogenic in rats but not mice; type IX induces autoimmunity in both species but not arthritis. Arthritis is initiated by complement fixing antibodies that bind to type II collagen in autologous cartilage, and the production of these antibodies is MHC restricted and T cell dependent. It is unclear whether T cells alone can induce arthritis, although they probably help sustain it. Mapping and characterizing the of T cell epitopes on type II collagen has resulted in the synthesis of small homolog and substituted peptides of type II collagen which suppress arthritis in an antigen-specific manner by a variety of routes, including mucosal. Moreover, collagen-induced arthritis has proven a valuable model to study the contribution of cytokines and other biological agents in the pathogenesis of joint injury and how they might be used to develop new therapies. Collagen autoimmunity has been implicated in the pathogenesis rheumatoid arthritis and polychondritis. Circulating antibodies to type II collagen are found in both diseases. Antibodies to types IX and XI collagen are also present in rheumatoid sera but are less prevalent. Rheumatoid cartilage and synovium contain antibodies to type II collagen at a prevalence far greater than serum, suggesting an intra-articular antigen-driven immune process. Although effective in animal models, attempts to treat rheumatoid arthritis with orally administered type II collagen have proven elusive. Different approaches using newer formulations and selected or modified oligopeptides remain to be tested and could prove effective in the treatment of the human rheumatic diseases.

[Manifestations mimicking relapsing polychondritis in a patient with microscopic polyangiitis].

Microscopic polyangiitis (MPA) is a systemic disorder characterized by inflammation of small vessels mainly affecting the kidneys and lungs. We describe a 72-year-old woman who developed multiple cartilage involvements as well as major manifestations of MPA. The left ear biopsy demonstrated cartilaginous inflammation and small vessel vasculitis. She also had conjunctivitis, hearing impairment, interstitial lung disease, glomerulonephritis with vasculitis and mononeuritis multiplex. Serological examinations revealed a positive antineutrophil cytoplasmic antibody (PR-3 ANCA). Cyclophosphamide and oral corticosteroid therapy was instituted and remission achieved. Due to lacks of nasal and bronchial involvements, as well as the evidence of auricular vasculitis, we concluded that her findings mimicking relapsing polychondritis developed as systemic manifestations of MPA.

Hypocomplementemic ear effusion in relapsing polychondritis.

In a case of relapsing polychondritis it was possible to aspirate a collection of subcutaneous fluid from the patient's involved ear. A determination of total hemolytic complement activity of this fluid was low, suggesting that activation of the complement system may have occurred in the course of the patient's disease and might be related to the pathogenesis of this disorder.