Unveiling the clinical spectrum of relapsing polychondritis: insights into its pathogenesis, novel monogenic causes, and therapeutic strategies.

Relapsing polychondritis is a rare multisystem disease involving cartilaginous and proteoglycan-rich structures. The diagnosis of this disease is mainly suggested by the presence of flares of inflammation of the cartilage, particularly in the ears, nose or respiratory tract, and more rarely, in the presence of other manifestations. The spectrum of clinical presentations may vary from intermittent episodes of painful and often disfiguring auricular and nasal chondritis to an occasional organ or even life-threatening manifestations such as lower airway collapse. There is a lack of awareness about this disease is mainly due to its rarity. In 2020, VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, a novel autoinflammatory syndrome, was described. VEXAS syndrome is attributed to somatic mutations in methionine-41 of UBA1, the major E1 enzyme that initiates ubiquitylation. This new disease entity connects seemingly unrelated conditions: systemic inflammatory syndromes (relapsing chondritis, Sweet's syndrome, and neutrophilic dermatosis) and hematologic disorders (myelodysplastic syndrome or multiple myeloma). Therefore, this article reviews the current literature on both disease entities.

Ocular Inflammation as the First Sign of Relapsing Polychondritis in Hispanic Patients: Report of Three Cases.

BACKGROUND: Relapsing polychondritis (RP) is a rare inflammatory systemic disease characterized by recurrent inflammatory episodes of cartilaginous and proteoglycan-rich tissues, particularly ears, nose, respiratory tract, eyes, and joints. PURPOSE: To present the clinical features, management, and prognosis of three Hispanic patients presenting with RP and ocular involvement as the first manifestation of the disease. CONCLUSION: This study extends the knowledge regarding ocular disease characteristics in patients with RP. Furthermore, it increases ophthalmologists' awareness of the findings, leading to earlier diagnoses and adequate treatment for improved patients' prognoses.

[Relapsing polychondritis]. / Relapsing Polychondritis.

Relapsing polychondritis (RP) is a rare multisystemic disease predominantly involving the extracellular matrix. Typical manifestations are chondritis of the ears, nose and trachea as well as an asymmetrical oligoarthritis or polyarthritis of small and also larger joints. Various other involvements have also been described. The treatment of RP is individually dependent on a variety of factors, e.g., organ manifestations. Glucocorticoids, immunosuppressants and targeted treatment are implemented. In the case of seronegative rheumatoid arthritis or vasculitis with an atypical course the symptoms of RP should be taken into consideration.

Bilateral, sequential orbital inflammation secondary to relapsing polychondritis.

This report describes a case of a Caucasian man in his 60s with bilateral sequential orbital inflammatory disease associated with relapsing polychondritis (RPC).He first presented with a subclavian vein periphlebitis/thrombosis and swollen left knee. Two weeks later, he developed right orbital inflammation with restricted eye movements. He was treated initially for possible orbital cellulitis. His inflammation failed to respond to antibiotics but rapidly resolved with oral prednisolone. One year later, he presented with left auricular inflammation, a maculopapular rash on his arms and torso and left orbital inflammation. Again, he failed to respond to antibiotics but had rapid resolution of his inflammatory signs following oral prednisolone.Based on his previous inflammatory arthropathy, auricular inflammation, orbital inflammation and response to oral steroids, he was diagnosed with RPC based on the McAdam diagnostic criteria. His steroids were tapered and he was commenced on methotrexate as maintenance therapy.

TNFα inhibitor biosimilar associated with polychondritis. A case-based review.

Relapsing polychondritis (RP) is a rare autoimmune disease characterized by inflammation of the cartilage structures of the body with typical features of auricular chondritis, nasal and ocular inflammation, audio-vestibular damage, as well as respiratory tract manifestations. It is associated with several autoimmune diseases and many other disorders. Tumor necrosis factor alpha (TNFα) inhibitors treat many chronic inflammatory disorders. They have proven effective and relatively safe in many clinical trials and observational studies. However, several autoimmune phenomena and paradoxical inflammation have been described with TNFα inhibitors, among them RP. This report presents a 43-year-old man with psoriatic arthritis treated with ABP-501 (Amgevita), an adalimumab (ADA) biosimilar and who developed RP, 8 months after the initiation of the treatment. This, is the first report of RP development during TNFα inhibitors biosimilar. We concluded that rheumatologists dealing with patients treated with TNFα inhibitors (originators or biosimilars), should be aware of several paradoxical reactions which may emerge and RP, is one of them.

Relapsing polychondritis - A single Centre study in the United Kingdom.

INTRODUCTION AND OBJECTIVES: Relapsing Polychondritis (RP) is a rare immune mediated inflammatory disorder that may result in damage and destruction of cartilaginous tissues. PATIENTS AND METHODS: We retrospectively analysed patients with a clinical diagnosis of RP. Patients were investigated using pulmonary function tests, dynamic high-resolution CT scans, bronchoscopy, laryngoscopy and/or PET-CT scans along with autoimmune serology. Patients had other specialist reviews when indicated. RESULTS: We identified 68 patients with a diagnosis of RP, 55 (81%) were Caucasian, 8 (12%) Afro Caribbean, 4 (6%) Asian and 1 patient had Mixed Ethnicity. Twenty-nine (43%) had pulmonary involvement and in 16, pulmonary involvement was the initial presentation. The mean age at onset was 44 years (range 17-74). There was a mean diagnostic delay of 55 weeks. Sixty-six (97%) patients received a combination of oral Prednisolone and disease modifying anti-rheumatic drugs. Twelve of 19 (63%) received biologics, with an initial good response, and 10 remain on treatment. Eleven patients with respiratory collapse required CPAP to maintain airway patency. Twelve (18%) patients died due to RP and 9 had respiratory complications. Two patients developed myelodysplasia and one had lung carcinoma. In a multivariate regression analysis, the prognostic variables were ethnicity, nasal chondritis, laryngotracheal stricture and elevated serum creatinine. CONCLUSION: RP is a rare autoimmune condition often associated with significant delays in diagnosis and initiation of treatment. Pulmonary involvement in RP may cause significant morbidity and mortality due to organ damage. Disease modifying anti rheumatic drugs and biologics should be considered early in the disease course to minimise adverse effects of long-term corticosteroid therapy and organ damage.

SAPHO syndrome complicated with relapsing polychondritis: A case report.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic inflammatory disease. The main clinical manifestation of SAPHO syndrome is an osteoarthropathy with cutaneous involvement. Relapsing polychondritis (RP) characterized by chronic inflammation and cartilage degeneration is a rare systematic autoimmune disease. Here we report a RP case in a SAPHO syndrome patient, in which auricularitis happened 10 years after the diagnosed as SAPHO syndrome. Tofacitinib treatment can alleviate the symptoms.

Relapsing polychondritis.

This is a case report of a 67-year-old man with the rare autoimmune disease relapsing polychondritis. The patient was initially diagnosed by general practitioners with erysipelas around his left ear, which was found red, swollen, and painful. Due to the lack of effect from antibiotics, the patient was referred to an emergency department. A rheumatologist recognised the patterns of the rare disease, diagnosed the patient and initiated proper treatment. The case clarifies the difficulty in diagnosing relapsing polychondritis, mainly due to the rarity and lack of knowledge of the disease.

Pre-treatment bronchoscopic evaluation in a case of relapsing polychondrits.

BACKGROUND: Relapsing polychondritis (RP) is a chronic and recurrent inflammatory disease of the cartilage tissues in the body. The cause of RP is unknown, and since it is a rare disease with symptoms that affect multiple organs, diagnosis is often delayed. CASE PRESENTATION: A 62-year-old woman with no smoking history visited our institution complaining of fever, cough, and dyspnoea. Chest CT showed a stenosis from the left main bronchus to the left lower lobe branch. Bronchoscopy visualised intense erythema and oedema at the left main bronchus, with airway narrowing. Biopsy of the ear revealed degenerative vitreous cartilage and fibrous connective tissue with a mild inflammatory cell infiltrate. She was subsequently diagnosed with RP and administered systemic corticosteroid therapy. Her symptoms improved rapidly, and post-treatment bronchoscopy revealed that although mild erythema of the airway epithelium remained, oedema markedly improved, and the airway stenosis was resolved. CONCLUSIONS: We report a case where pre-treatment bronchoscopy was able to visually confirm RP at the acute stage. Since RP is difficult to diagnose, severe airway narrowing can occur prior to diagnosis. Therefore, to determine the stage of the disease, it is helpful to perform bronchoscopic observation before treatment. However, bronchoscopic observation before treatment should be performed by experienced bronchoscopists due to the risk of airway obstruction.

Progress and challenges in the use of blood biomarkers in relapsing polychondritis.

Relapsing polychondritis (RP) is a rare inflammatory disease with significant individual heterogeneity that involves systemic organs. The diagnosis of RP mainly depends on the clinical manifestations; currently, there are no molecular biomarkers routinely evaluated in clinical practice. Biomarkers have diagnostic or monitoring values and can predict response to treatment or the disease course. Over the years, many biomarkers have been proposed to facilitate diagnosis and prognosis. Unfortunately, ideal biomarkers to diagnose RP have not yet been discovered. Most of the molecular biomarkers in RP are immunological biomarkers, with autoantibodies and proteins related to cartilage damage in the blood being the most common. Alterations in some genes (HLA typing and UBA1 somatic mutation) were detected in patients with RP, which could serve as a potential biomarker for the diagnosis of RP. Moreover, proinflammatory cytokines and lymphocyte levels, and certain laboratory tests, have certain values of RP diagnosis and disease activity assessment but lack specificity and sensitivity. This review describes the different types of biomarkers and their clinical correlation with respect to the diagnosis of RP and disease activity. Research on biomarkers and disease pathology is ongoing to identify the ideal biomarkers that are sensitive and specific for RP.

A 60-year-old Man Presented with Relapsing Polychondritis with Haemophagocytic Lymphohistiocytosis.

Relapsing polychondritis is a rare autoimmune disorder of unknown etiology, which can affect multiple organs. It usually presents with involvement of elastic cartilage of ear and nose and involvement of other organs like kidney and central nervous system. Here, we report a case of 60-year-old man, who initially presented with fever, polyarthritis, erythema nodosum and painful swelling and redness of both external ears admitted in Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh on 13th December 2019. Two days after hospitalization, he developed sudden onset of proptosis with ophthalmoplegia. After evaluation, he was diagnosed as relapsing polychondritis with haemophagocytic lymphohistiocytosis and was treated with high dose prednisolone. His clinical condition and laboratory parameters significantly improved after treating with prednisolone during follow up.

Relapsing Polychondritis and Aseptic Meningoencephalitis.

We herein report a 49-year-old Japanese man with relapsing polychondritis (RP) and aseptic meningoencephalitis. Four years ago, the patient was diagnosed with RP. Prednisolone (PSL) was started at 30 mg/day, and the symptoms promptly disappeared. However, cognitive impairment gradually appeared from six months before hospitalization. Methylprednisolone pulse therapy was immediately initiated, followed by administration of PSL at 1 mg/kg/day. Intravenous cyclophosphamide was combined with PSL. After treatment, the patient's cognitive impairment clearly improved. In conclusion, RP rarely causes aseptic meningoencephalitis, highlighting the need for prompt and aggressive immunosuppressive therapy.

Tocilizumab in Recalcitrant Bilateral Scleritis in a Case of Relapsing Polychondritis: A 17-year Follow Up.

PURPOSE: To report a challenging case of relapsing polychondritis with bilateral diffuse scleritis, with 17-year follow-up. METHODS: Case report. RESULTS: A 36-year-old female presented 17 years ago with bilateral diffuse scleritis and peripheral corneal infiltrates. Detailed systemic work-up was negative. Fourteen months later, she developed saddle nose deformity, debilitating myalgias, and severe recurrence of scleritis clinching the diagnosis of relapsing polychondritis. Despite high-dose oral corticosteroids, oral immunosuppressants, and cyclophosphamide infusions and adalimumab infusions, the condition showed waxing and waning over the next decade. In 2017, she was started on Tocilizumab injections after which both the systemic and ocular conditions stabilised and has been remained stable for the past 4 years. CONCLUSION: Relapsing polychondritis has a well-known association with scleritis. The ocular disease may precede systemic symptoms in some cases. Newer agent such as tocilizumab appears to be effective in controlling this relentless and recurrent disease.

Successful treatment of relapsing polychondritis with circumferential bronchial wall thickening including the tracheomembranous area with tumor necrosis factor-α inhibitor.

This is a case of a 55-year-old man who presented with cough and anterior chest pain. Tracheal biopsy confirmed the diagnosis of relapsing polychondritis (RP). Although the patient had circumferential bronchial wall thickening extending to the tracheomembranous area and was positive foRPR3-ANCA, he did not meet the diagnostic criteria for granulomatosis with polyangiitis. The patient was refractory to prednisolone + methotrexate + azathioprine and responded to adalimumab, a biologic tumor necrosis factor-α inhibitor effective in RP refractory cases. Herein, we report a rare case of RP with circumferential bronchial wall thickening extending to the tracheomembranous area.