[Tracheobronchial involvement in relapsing polychondritis and differential diagnoses]. / Atteinte trachéo-bronchique de la polychondrite atrophiante et diagnostics différentiels.

Relapsing polychondritis is a systemic auto-immune disease that mainly affects cartilage structures, progressing through inflammatory flare-ups between phases of remission and ultimately leading to deformation of the cartilages involved. In addition to characteristic damage of auricular or nasal cartilage, tracheobronchial and cardiac involvement are particularly severe, and can seriously alter the prognosis. Tracheobronchial lesions are assessed by means of a multimodal approach, including dynamic thoracic imaging, measurement of pulmonary function (with recent emphasis on pulse oscillometry), and mapping of tracheal lesions through flexible bronchoscopy. Diagnosis can be difficult in the absence of specific diagnostic tools, especially as there may exist a large number of differential diagnoses, particularly as regards inflammatory diseases. The prognosis has improved, due largely to upgraded interventional bronchoscopy techniques and the development of immunosuppressant drugs and targeted therapies, offering patients a number of treatment options.

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.

Orbital/ocular inflammatory involvement in VEXAS syndrome: Data from the international AIDA network VEXAS registry.

VEXAS syndrome is a recently described monogenic autoinflammatory disease capable of manifesting itself with a wide array of organs and tissues involvement. Orbital/ocular inflammatory manifestations are frequently described in VEXAS patients. The objective of this study is to further describe orbital/ocular conditions in VEXAS syndrome while investigating potential associations with other disease manifestations. In the present study, twenty-seven out of 59 (45.8 %) VEXAS patients showed an inflammatory orbital/ocular involvement during their clinical history. The most frequent orbital/ocular affections were represented by periorbital edema in 8 (13.6 %) cases, episcleritis in 5 (8.5 %) patients, scleritis in 5 (8.5 %) cases, uveitis in 4 (6.8 %) cases, conjunctivitis in 4 (6.8 %) cases, blepharitis in 3 (5.1 %) cases, orbital myositis in 2 (3.4 %) cases. A diagnosis of systemic immune-mediated disease was observed in 15 (55.6 %) cases, with relapsing polychondritis diagnosed in 12 patients. A significant association was observed between relapsing polychondritis and orbital/ocular involvement in VEXAS syndrome (Relative Risk: 2.37, 95 % C.I. 1.03-5.46, p = 0.048). Six deaths were observed in the whole cohort of patients after a median disease duration of 1.2 (IQR=5.35) years, 5 (83.3 %) of which showed orbital/ocular inflammatory involvement. In conclusion, this study confirms that orbital/ocular inflammatory involvement is a common finding in VEXAS patients, especially when relapsing polychondritis is diagnosed. This makes ophthalmologists a key figure in the diagnostic process of VEXAS syndrome. The high frequency of deaths observed in this study seems to suggest that patients with orbital/ocular involvement may require increased attention and more careful follow-up.

Autoimmunity and Autoinflammation: Relapsing Polychondritis and VEXAS Syndrome Challenge.

Relapsing polychondritis is a chronic autoimmune inflammatory condition characterized by recurrent episodes of inflammation at the level of cartilaginous structures and tissues rich in proteoglycans. The pathogenesis of the disease is complex and still incompletely elucidated. The data support the important role of a particular genetic predisposition, with HLA-DR4 being considered an allele that confers a major risk of disease occurrence. Environmental factors, mechanical, chemical or infectious, act as triggers in the development of clinical manifestations, causing the degradation of proteins and the release of cryptic cartilage antigens. Both humoral and cellular immunity play essential roles in the occurrence and perpetuation of autoimmunity and inflammation. Autoantibodies anti-type II, IX and XI collagens, anti-matrilin-1 and anti-COMPs (cartilage oligomeric matrix proteins) have been highlighted in increased titers, being correlated with disease activity and considered prognostic factors. Innate immunity cells, neutrophils, monocytes, macrophages, natural killer lymphocytes and eosinophils have been found in the perichondrium and cartilage, together with activated antigen-presenting cells, C3 deposits and immunoglobulins. Also, T cells play a decisive role in the pathogenesis of the disease, with relapsing polychondritis being considered a TH1-mediated condition. Thus, increased secretions of interferon γ, interleukin (IL)-12 and IL-2 have been highlighted. The "inflammatory storm" formed by a complex network of pro-inflammatory cytokines and chemokines actively modulates the recruitment and infiltration of various cells, with cartilage being a source of antigens. Along with RP, VEXAS syndrome, another systemic autoimmune disease with genetic determinism, has an etiopathogenesis that is still incompletely known, and it involves the activation of the innate immune system through different pathways and the appearance of the cytokine storm. The clinical manifestations of VEXAS syndrome include an inflammatory phenotype often similar to that of RP, which raises diagnostic problems. The management of RP and VEXAS syndrome includes common immunosuppressive therapies whose main goal is to control systemic inflammatory manifestations. The objective of this paper is to detail the main etiopathogenetic mechanisms of a rare disease, summarizing the latest data and presenting the distinct features of these mechanisms.

Risk factors associated with severe adverse events in patients with relapsing polychondritis undergoing flexible bronchoscopy.

BACKGROUND: Patients with relapsing polychondritis (RP) sometimes experience upper airway collapse or lower airway stenosis, and bronchoscopy may provide a valuable typical image to confirm the diagnosis. This study aimed to identify potential risk factors associated with severe adverse effects during bronchoscopy. METHODS: We performed a retrospective cohort study of 82 consecutive patients with RP hospitalized at Peking Union Medical College Hospital between January 1, 2012 and December 31, 2022. Clinical features and disease patterns were compared among patients with RP undergoing bronchoscopy with or without severe adverse effects. Binary logistic regression analysis was performed to identify the associated risk factors. RESULTS: For patients with RP undergoing bronchoscopy with severe adverse effects, the forced vital capacity (FVC), forced vital capacity percent predicted values (FVC%), and peak expiratory flow were significantly lower (P = 0.001, P = 0.001, and P = 0.021, respectively) than those in the non-severe adverse effect subgroup. Binary logistic regression analysis revealed that low FVC% (odds ratio, 0.930; 95% confidence interval, 0.880-0.982; P = 0.009) was an independent risk factor for severe adverse events in patients undergoing bronchoscopy. CONCLUSIONS: Low FVC or FVC% suggests a high risk of severe adverse effects in patients with RP undergoing bronchoscopy. Patients with such risk factors should be carefully evaluated before bronchoscopy and adequately prepared for emergency tracheal intubation or tracheostomy.

Relapsing polychondritis presenting with sero-negative limbic encephalitis.

The presented case highlights a rare instance of relapsing polychondritis (RP) manifesting as seronegative limbic encephalitis, an uncommon neurological complication. A 70-year-old female patient with a history of RP-related inflammation, along with neuropsychiatric symptoms, was diagnosed through multidisciplinary collaboration. Swift administration of steroid therapy, followed by azathioprine, led to remarkable physical and cognitive recovery. This case emphasises the importance of a multidisciplinary approach in diagnosing and treating complex autoimmune disorders with neurological manifestations.

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.

French practical guidelines for the diagnosis and management of relapsing polychondritis.

Relapsing polychondritis is a rare systemic disease. It usually begins in middle-aged individuals. This diagnosis is mainly suggested in the presence of chondritis, i.e. inflammatory flares on the cartilage, in particular of the ears, nose or respiratory tract, and more rarely in the presence of other manifestations. The formal diagnosis of relapsing polychondritis cannot be established with certainty before the onset of chondritis, which can sometimes occur several years after the first signs. No laboratory test is specific of relapsing polychondritis, the diagnosis is usually based on clinical evidence and the elimination of differential diagnoses. Relapsing polychondritis is a long-lasting and often unpredictable disease, evolving in the form of relapses interspersed with periods of remission that can be very prolonged. Its management is not codified and depends on the nature of the patient's symptoms and association or not with myelodysplasia/vacuoles, E1 enzyme, X linked, autoinflammatory, somatic (VEXAS). Some minor forms can be treated with non-steroidal anti-inflammatory drugs, or a short course of corticosteroids with possibly a background treatment of colchicine. However, the treatment strategy is often based on the lowest possible dosage of corticosteroids combined with background treatment with conventional immunosuppressants (e.g. methotrexate, azathioprine, mycophenolate mofetil, rarely cyclophosphamide) or targeted therapies. Specific strategies are required if relapsing polychondritis is associated with myelodysplasia/VEXAS. Forms limited to the cartilage of the nose or ears have a good prognosis. Involvement of the cartilage of the respiratory tract, cardiovascular involvement, and association with myelodysplasia/VEXAS (more frequent in men over 50years of age) are detrimental to the prognosis of the disease.

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.

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.

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.

Lung Cancer Complicated by Relapsing Polychondritis.

A 77-year-old man presented with a 1-month history of cough, pharyngeal discomfort, and weight loss. Chest radiography revealed a mass shadow in the right upper lung field. Bronchoscopy showed multiple white nodules along the tracheal cartilage ring. Although adenocarcinoma cells were detected in the mass, several biopsy specimens of the tracheal lesions exhibited no malignancy. 18F-fluorodeoxyglucose positron emission tomography revealed an intense accumulation in the mass, nasal septum, and tracheal cartilage. Furthermore, anti-type II collagen antibody levels were elevated. We finally diagnosed him with lung cancer complicated by relapsing polychondritis. Treatment with oral prednisolone was initiated, followed by sequential chemoradiotherapy for lung cancer.

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.

Clinical analysis of relapsing polychondritis with airway involvement.

OBJECTIVE: To identify the clinical characteristics, treatment, and prognosis of relapsing polychondritis patients with airway involvement. METHODS: Twenty-eight patients with relapsing polychondritis, hospitalised in the First Hospital of Shanxi Medical University between April 2011 and April 2021, were retrospectively analysed. RESULTS: Fifty per cent of relapsing polychondritis patients with airway involvement had a lower risk of ear and ocular involvement. Relapsing polychondritis patients with airway involvement had a longer time-to-diagnosis (p < 0.001), a poorer outcome following glucocorticoid combined with immunosuppressant treatment (p = 0.004), and a higher recurrence rate than those without airway involvement (p = 0.004). The rates of positive findings on chest computed tomography and bronchoscopy in relapsing polychondritis patients with airway involvement were 88.9 per cent and 85.7 per cent, respectively. Laryngoscopy analysis showed that 66.7 per cent of relapsing polychondritis patients had varying degrees of mucosal lesions. CONCLUSION: For relapsing polychondritis patients with airway involvement, drug treatment should be combined with local airway management.

Coexistence of relapsing polychondritis and eosinophilic granulomatous with polyangiitis: A rare entity.

Abstract: Relapsing polychondritis (RP) is a a rare multisystemic disease and it affects cartilaginous tissue and proteoglycan rich organs. The spectrum of clinical features are intermittent inflammation involving especially the auricular and nasal regions. In some patients with RP, systemic vasculitis, autoimmune diseases or malignancy may accompany. Although rare, any of the ANCA-associated vasculitis have been reported in patients with RP. Eosinophilic granulomatous with polyangiitis (EGPA) is a multisystem small vessel vasculitis associated with asthma and eosinophilia. Here we present a case of coexistence of RP and EGPA.

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome (VEXAS syndrome) with prominent supraglottic larynx involvement: a case-based review.

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome (VEXAS syndrome) is a recently described genetic disorder that gathers autoinflammatory symptoms and myeloid dysplasia. The first description was reported in 2020, and subsequently, a growing number of cases have been described worldwide. Herein, we describe a case of a 72-year-old male patient with VEXAS syndrome with p.Met41Val mutation of the UBA1 gene, prominent supraglottic larynx involvement, and costochondritis. To our knowledge, this is the first report of VEXAS syndrome in Colombia and South America. This disease could present features of relapsing polychondritis, polyarteritis nodosa, giant cell arteritis, and Sweet syndrome, associated with hematologic involvement, including cytopenias, myelodysplastic syndrome, or thromboembolic disease. Supraglottic larynx chondritis and costochondritis are atypical manifestations. These features were proposed previously to differentiate relapsing polychondritis from VEXAS syndrome but are not entirely reliable like in the case described. A diagnosis of VEXAS should be considered in male patients with incomplete or complete features of the previously described conditions, refractory to treatment, requiring high-dose glucocorticoids, and associated progressive hematologic abnormalities. Key Points • VEXAS syndrome is a recently described genetic (somatic mutations in UBA1 gene) disorder that gathers autoinflammatory and hematologic manifestations. • VEXAS syndrome should be considered in male patients with incomplete or complete features of relapsing polychondritis, polyarteritis nodosa, giant cell arteritis, and Sweet syndrome, refractory to treatment, associated with hematologic involvement, including cytopenias, myelodysplastic syndrome, or thromboembolic disease. • Glucocorticoids ameliorate symptoms effectively. However, other treatment options are limited due to a lack of evidence. Traditional immunosuppressants and biological therapy have been used empirically with limited efficacy and a transient effect. Bone marrow transplant offers a curative approach, but it has high morbidity and mortality.

Small cell lung cancer with relapsing polychondritis: A report of one case and the review of literature.

The present study reports the clinical data of a patient with small cell lung cancer who developed relapsing polychondritis. We report a case of a 57-year-old female presented with cough, expectoration, and fever. A Computed Tomography (CT) scan performed at the hospital revealed diffuse thickening of bronchial walls in both lungs. Bronchoscopy revealed that the tracheal mucosa was thickened, narrowed, and collapsed, and the bronchoscope could pass through. The bronchial mucosa on both sides was thickened and edematous, the surface was rough, each bronchus was narrow, and the intervertebral ridges were widened. Needle biopsy: considering small cell carcinoma in combination with immunohistochemical results. Her symptom was not improved after anti-infective therapy. The left auricle was red and swollen, the auricle collapsed, and the left eye had subconjunctival hemorrhage during her hospitalization without obvious cause. After multidisciplinary consultation, pulmonary small cell lung cancer cT0N2Mx rumen lymph node metastasis and RP were considered. Treatment: Prednisone, orally for RP. Chemotherapy combined with radiotherapy was given for small cell lung cancer. The chemotherapy regimen was carboplatin combined with etoposide. The patient has already been followed for 1 year after receiving chemoradiotherapy; the condition of the patient is stable at present. Based on the case of our patient, for cases of RP with symptoms such as auricle chondritis, ocular inflammatory disease, and nasal chondritis, we should pay great attention to whether the case is caused by lung cancer with relapsing polychondritis. Because of the rarity of the disease, the clinician should improve the recognition of the disease in order to strive for early diagnosis and therapy.

Comparison between idiopathic and VEXAS-relapsing polychondritis: analysis of a French case series of 95 patients.

OBJECTIVE: A new adult-onset autoinflammatory syndrome has been described, named VEXAS (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic). We aimed to compare the clinical characteristics, the laboratory features and the outcomes between idiopathic-relapsing polychondritis (I-RP) and VEXAS-relapsing polychondritis (VEXAS-RP). METHODS: Patients from French retrospective multicentre cohort of RP were separated into two groups: a VEXAS-RP and an I-RP. RESULTS: Compared with patients with I-RP (n=40), patients with VEXAS-RP (n=55) were men (96% vs 30%, p<0.001) and were older at diagnosis (66 vs 44 years, p<0.001). They had a greater prevalence of fever (60% vs 10%, p<0.001), of skin lesions (82% vs 20%, p<0.001), of ocular involvement (57% vs 28%, p=0.01), of pulmonary infiltrates (46% vs 0%, p<0.001), of heart involvement (11% vs 0%, p=0.0336) and with higher median C-reactive protein levels (64 mg/L vs 10 mg/L, p<0.001). Seventy-five per cent of the patients with VEXAS-RP had myelodysplastic syndrome (MDS) versus none in I-RP group. The glucocorticoids use, and the number of steroid sparing agents were similar in both groups, but patients with VEXAS-RP had more frequent refractory disease (remission obtained in 27% vs 90%, p<0001). VEXAS-RP was associated with higher risk of death: six patients (11%) died in the VEXAS-RP group after a median follow-up of 37 months and none in the I-RP group after a median follow-up of 92 months (p<0.05). CONCLUSION: We report the largest cohort of VEXAS-RP, characterised by high prevalence of male sex, fever, skin lesion, ocular involvement, pulmonary infiltration, heart involvement, older age and MDS association.

Case Report: Tocilizumab Treatment for VEXAS Syndrome With Relapsing Polychondritis: A Single-Center, 1-Year Longitudinal Observational Study In Japan.

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an autoinflammatory disease caused by somatic variants in the UBA1 gene that lead to severe systemic inflammation and myelodysplastic syndrome. Although no standard therapy has been established yet, azacitidine and bone marrow transplantation have been reported to be promising possibilities; however, the indications for these treatments are problematic and not necessarily applicable to all patients. We previously reported the results of short-term treatment with tocilizumab (TCZ) and glucocorticoids in three patients with VEXAS syndrome. In this paper, we report that the combination of TCZ and glucocorticoids allowed the patients to continue treatment for at least one year without significant disease progression. Glucocorticoids were able to be reduced from the start of TCZ. Adverse events were herpes zoster, skin ulceration after cellulitis, and decreased blood counts. The results suggest the significance of this treatment as a bridge therapy for the development of future therapies.