Polychondritis Research Articles

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

BackgroundPatients 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.MethodsWe 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.ResultsFor 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.ConclusionsLow 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.

Dynamic monitoring of UBA1 somatic mutations in patients with relapsing polychondritis

BackgroundCommonly clinically diagnosed with relapsing polychondritis (RP), vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome (VEXAS) is a recently identified autoinflammatory disease caused by UBA1 somatic mutations. The low frequency and dynamic changes challenge the accurate detection of somatic mutations. The present study monitored these mutations in Chinese patients with RP. We included 44 patients with RP. Sanger sequencing of UBA1 was performed using genomic DNA from peripheral blood. Droplet digital polymerase chain reaction (ddPCR) was performed to screen low-prevalence somatic variants.ResultsMultiple ddPCR detections were performed using available blood samples collected at different follow-up time points. Three male patients were UBA1 somatic mutation carriers. Sanger sequencing detected the somatic UBA1 variant c.122T > C (p.Met41Thr) in two male patients. Initial ddPCR confirmed the variant in the two patients, with allele fractions of 73.75% and 88.46%, respectively, while yielding negative results in other patients. Subsequent ddPCR detected the somatic variant (c.122T > C) with low prevalence (1.02%) in another male patient from blood samples collected at a different time point, and confirmed dynamically fractional abundance in one patient with VEXAS, with allele fractions of 73.75%, 61.28%, 65.01%, and 73.75%. Nine patients assessed by ddPCR at different time points remained negative.ConclusionWe report UBA1 variants in patients with RP in the Chinese population for the first time. Multiple ddPCR detections from samples collected at different time points can enhance sensitivity and should be considered for patients with initial negative ddPCR results.

Relapsing polychondritis that developed after piercing (clinical case)

Relapsing polychondritis (RPC) belongs to a group of rare rheumatic diseases with poorly understood etiology and pathogenesis. It is based on progressive systemic inflammatory damage to the cartilage tissue, primarily affecting ears, nose, trachea and bronchi. A standardized approach for the treatment of RPC has not yet been developed, so the treatment tactics are individualized for each patient.We describe a clinical case of a 39-year-old patient, who developed RPC after piercing the cartilaginous part of the ear. The components of the alloy used for the piercing could presumably serve as adjuvants and cause the development of a disease similar to ASIA syndrome (Autoimmune/Inflammatory Syndrome Induced by Adjuvants) with inflammation of the cartilage of the nose and ears. Possible pathogenetic mechanisms are presented, as well as diagnostic criteria for ASIA syndrome.

Bilateral Deafness Due to Relapsing Polychondritis with Semicircular Canal Calcification Treated With Cochlear Implantation: A Case Report.

Relapsing polychondritis (RP) is a rare chronic inflammatory disease characterized by recurrent inflammation of cartilages throughout the body, with treatment-resistant dizziness and hearing loss in 40%-50% of patients with RP. Although rare, severe binaural hearing loss in RP is an indication for cochlear implantation (CI). Therefore, there are only a few reports on CI insertion in cases of RP. This report describes a 68-year-old woman who developed binaural hearing loss due to RP. She was treated with steroids and immunosuppressive drugs; however, her hearing did not improve significantly, and she relied on written communication for conversation. Subsequently, the patient underwent CI in the right ear. The patient showed improvement in speech perception; at 14 months postoperatively, she was able to speak with lipreading, and at 2 years postoperatively, she was able to speak without lipreading. Previous case reports on CI in patients with RP have shown varying degrees of postoperative hearing improvement. Our case demonstrates the effectiveness of CI in improving hearing and speech recognition in patients with RP having semicircular canal calcification. However, previous reports have shown that speech recognition declines 13 years after CI for RP. Therefore, continuous long-term follow-up is necessary.

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.

Cutaneous vasculitis in autoinflammatory diseases.

Autoinflammatory diseases (AIDs) characterized by recurrent episodes of localized or systemic inflammation are disorders of the innate immune system. Skin lesions are commonly found in AIDs and cutaneous vasculitis can coexist with AIDs and even present as the most striking feature. This review aims to focus on the frequent cutaneous vasculitis association in three monogenic AIDs including familial Mediterranean fever (FMF), deficiency of adenosine deaminase type 2 (DADA2), and the recently identified adult-onset VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Cutaneous vasculitis in FMF is characterized by: (1) small-vessel vasculitis similar to IgA vasculitis with palpable purpura but increased intussusception complication and less vascular IgA deposit, and (2) cutaneous arteritis-like vasculitis presenting as subcutaneous nodules most often with higher glomerular involvement. DADA2 has a wide spectrum of clinical presentations ranging from fatal systemic vasculitis with multiple strokes, especially in pediatric patients, to limited cutaneous disease in middle-aged patients. DADA2 shares similar clinical and histopathological features with polyarteritis nodosa (PAN). As a result, DADA2 is commonly initially misdiagnosed as childhood PAN. Livedo racemosa reveals the most common cutaneous manifestation of cutaneous vasculitis in patients with DADA2. VEXAS syndrome is a life-threatening disease. A diagnosis of VEXAS syndrome should be strongly considered or could be made in patients with skin lesions characterized by Sweet syndrome-like eruption, livedo racemosa, concomitant relapsing polychondritis, deep venous thrombosis, pulmonary involvement, and progressive hematologic abnormalities such as myelodysplastic syndrome with a unique finding of cytoplasmic vacuoles in myeloid and erythroid precursor cells from bone marrow aspirate smear. As skin involvement is common in AIDs and may present as the most frequent manifestation, especially in DADA2 (70% to 90%) and VEXAS syndrome (83% to 91%), dermatologists play a crucial role in contributing to the early diagnosis of these AIDs with early initiation of the appropriate therapy to avoid progressing fatal outcomes.

Predictors and prognosis of tracheostomy in relapsing polychondritis.

Airway obstruction can occur in patients with relapsing polychondritis (RP) with laryngeal involvement, occasionally requiring tracheostomy to avoid serious complications. Herein, we assessed the risk factors for tracheostomy and developed a risk prediction model. Clinical characteristics of patients with RP, with and without tracheostomy, were compared using multivariate logistic regression analysis to identify risk factors. A nomogram was developed to predict the population at risk of requiring tracheostomy. In total, 232 patients with RP were reviewed, of whom 146 had laryngeal involvement. Among them, 21 underwent a tracheostomy. Multivariate logistic analysis identified ages ≤ 25 or ≥ 65 (p< 0.001, OR: 24.584, 95% CI: 5.310-113.815), laryngotracheal oedema (p< 0.001, OR: 26.685, 95% CI: 4.208-169.228), and pulmonary infection (p= 0.001, OR: 18.834, 95% CI: 3.172-111.936) as independent risk factors for tracheostomy. A nomogram with a C-index of 0.936 (95% CI: 0.894-0.977) was established based on the multivariate analysis. Internal bootstrap resampling (1000 repetitions) confirmed sufficient discriminatory power with a C-index of 0.926. Decision curve analysis indicated a superior net benefit of the nomogram. Tracheostomy was associated with a significant increase in the in-hospital mortality rate (p= 0.021), but it did not affect the long-term survival rate (p= 0.706). Tracheostomy is associated with an increase in the short-term mortality rate but does not affect the long-term survival rate. The nomogram developed in this study may help identify patients at high risk for tracheostomy and aid in clinical decision-making.

Imaging features and clinical value of 18F-FDG PET/CT for predicting airway involvement in patients with relapsing polychondritis

BackgroundThe clinical value of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in assessing relapsing polychondritis (RP) with airway involvement remains controversial. This study aimed to investigate PET/CT features of RP with airway involvement and explore its clinical value in predicting disease pattern, severity and prognosis.MethodsRP patients with airway involvement who underwent PET/CT from January 2010 to July 2022 were retrospectively reviewed. PET/CT features were analyzed both visually and semiquantitatively with the maximum standardized uptake value (SUVmax) and total lesion glycolysis (TLG). Patterns of airway involvement on PET were summarized. Correlations of SUVmax and TLG of the airway were made with spirometric indicators and serological inflammatory markers (CRP and ESR). In addition, long-term follow-up was conducted through questionnaires in regard to symptom control, subjective feeling, pulmonary function, and quality of life.ResultsFifty-two cases were finally included. 18F-FDG PET showed FDG-avid lesions with increased FDG uptake in the airway among 94.2% of the patients. Three patterns (focal, multifocal and diffuse patterns) were identified. TLG of the whole airway was lower in patients with previous therapy (p = 0.046). Bronchoscopy was more sensitive in detecting tracheal abnormalities (90.7% vs.53.5%, p = 0.039) but less sensitive for peripheral airway lesions (65.1% vs. 79.1%, p = 0.046) compared with PET. SUVmax and TLG of the airway positively correlated with spirometry indicators (FEV1%pred, FEV1/FVC, MEF 50%pred, etc.) and serological inflammatory markers. Five patients died during the follow-up, with two deaths related to airway problems. Higher FDG uptake predicted worse subjective feeling, but not with symptom control or pulmonary function.ConclusionPET/CT is a valuable tool for RP with airway involvement, particularly in assessing peripheral airway lesions, and PET/CT related parameters are significantly associated with disease patterns, severity, and long-term outcomes.

Development and validation of diagnostic and activity-assessing models for relapsing polychondritis based on laboratory parameters.

Relapsing polychondritis (RP) as a rare autoimmune disease is characterized by recurrent inflammation of the organs containing cartilage. Currently, no biomarkers have been integrated into clinical practice. This study aimed to construct and evaluate models based on laboratory parameters to aid in RP diagnosis, assess activity assessment, and explore associations with the pathological process. RP patients and healthy controls (HCs) were recruited at the Peking Union Medical College Hospital from July 2017 to July 2023. Clinical data including Relapsing Polychondritis Disease Activity Index (RPDAI) score and laboratory tests were collected. Differences in laboratory data between RP patients and HCs and active and inactive patients were analyzed. The discovery cohort (cohort 1) consisted of 78 RP patients and 94 HCs. A model based on monocyte counts and neutrophil to lymphocyte ratio (NLR) could effectively distinguish RP patients from HCs with an AUC of 0.845. Active RP patients exhibited increased erythrocyte sedimentation rate, complement 3, platelet to lymphocyte ratio (PLR), NLR, and C-reactive protein to albumin ratio (CAR) compared with stable patients, which were also positively correlated with RPDAI. Notably, CAR emerged as an independent risk factor of disease activity (OR = 4.422) and could identify active patients with an AUC of 0.758. To confirm the reliability and stability of the aforementioned models, a replication cohort (cohort 2) was enrolled, including 79 RP patients and 94 HCs. The monocyte-combined NLR and CAR showed a sensitivity of 0.886 and 0.577 and a specificity of 0.830 and 0.833 in RP diagnosis and activity prediction, respectively. Furthermore, lower natural killer cell levels in RP patients and higher B-cell levels in active patients may contribute to elucidating the pathological mechanisms of disease occurrence and exacerbation. The utilization of laboratory parameters provides cost-effective and valuable markers that can assist in RP diagnosis, identify disease activity, and elucidate pathogenic mechanisms.

The association of relapsing polychondritis and spondylarthritis – three case reports

Background. Relapsing polychondritis (RP) is characterized by recurrent episodes of progressive inflammation that lead to the destruction of cartilaginous structures. The etiopathogenesis is not fully elucidated, but it seems to be an immune-mediated mechanism directed against type 2 collagen. Case reports. We present a series of 3 clinical cases, which associate RP and spondylarthritis – a woman with psoriatic arthritis (PsA) and two men with ankylosing spondylitis (AS). All cases presented with auricular chondritis, which is the emblem of RP. In the PsA case, RP presented typically, with recurrent auricular chondritis, manifested clinically with a cauliflower-like appearance of the ears. In one of the AS cases, a paradoxical immune reaction related to biological therapy was considered in the differential diagnosis of RP. In the other AS case, the patient had a single episode of chondritis, the recurrence of the disease remains to be proved. Conclusions. The diagnosis of RP is usually based on clinical evidence and the elimination of differential diagnoses, since there is no specific laboratory or imaging test. In 20-30% of cases, RP is associated with other conditions, most frequently with vasculitis, but the association of RP with spondylarthritis is rare.

OA13 The skin as a snapshot of systemic inflammation

Abstract Introduction This case focuses on a polymorphic rash of multidisciplinary interest in the setting of seemingly disparate multi-organ inflammatory phenomena. The case highlights the use and shortcomings of skin histopathology in diagnosing systemic conditions, particularly when faced with the dilemma of ordering the differential diagnoses of infection, inflammation and autoimmunity, and the subsequent decision-making around antibiotics or immunosuppression. Case description A 71-year-old man was admitted to a tertiary referral hospital in Adelaide, Australia, with fever (39.4oC), malaise and vomiting following a brief fishing expedition. No sick contacts were noted, although six months prior he had hiked through mountainous Pennsylvania, USA. Shortly after admission, he developed an acute, widespread rash involving his arms, legs, chest and abdomen with relative sparing of the back and face. The rash was erythematous, non-pruritic and polymorphic with papulonodular areas, some coalescing into plaque-like lesions. In areas on the forearms, there were vesicular and pustular components to the rash. Multiple other inflammatory manifestations were subsequently determined: synovitis of the proximal interphalangeal joints, widespread lung nodulosis with associated ground-glass opacities, transverse colon colitis, bilateral epididymo-orchitis, vocal cord ulceration, and bilateral conjunctivitis. Blood tests showed a normocytic anaemia (haemoglobin 82g/L; mean cell volume, MCV 90fL), neutrophilia (11x10^9/L) and elevated C-reactive protein (CRP, 350mg/L). No serological, culture or imaging evidence of infection was found on extensive investigations, including bronchoscopy, colonoscopy and echocardiogram. PET scan revealed no FDG-avid malignancy, vasculitis or infection. A skin biopsy showed both medium vessel and leukocytoclastic vasculitis. Broad spectrum antibiotics appeared to result in partial improvement, with resolution of the rash, defervescence, improvement in ground-glass opacities on chest imaging and stabilisation of the CRP at 200mg/L. The anaemia, however, worsened (nadir haemoglobin 73g/L) and became symptomatic, requiring transfusion, and the patient developed marked hypoalbuminaemia (nadir 12g/L) with associated peripheral and pleural effusions. In the context of the skin biopsy results, a provisional diagnosis of systemic medium-vessel vasculitis was made, and steroid therapy commenced with significant subjective improvement, improvement in anaemia and hypoalbuminaemia, and normalisation of CRP. Two weeks after discharge, genetic testing returned with a somatic variant of the UBA1 gene (Met41Leu), revising the diagnosis to VEXAS (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic Syndrome). Discussion Since VEXAS was first described in 2020, there have been case reports of patients with this diagnosis, typically older males, who present with protean inflammatory manifestations. As a disease entity which exists on a novel continuum of autoinflammation and myelodysplasia, VEXAS can mimic other conditions including vasculitis, inflammatory arthritis, Sweet’s syndrome and relapsing polychondritis. Indeed, there exists a subset of patients previously labelled with these diagnoses who have subsequently been found to have mutation of the UBA1 gene. We report a case of VEXAS initially diagnosed as a medium-vessel vasculitis on the basis of the only definitive finding, namely the result of a skin biopsy, following extensive investigation for infection. Although biopsy remains an important investigation in diagnosing vasculitis, this case demonstrates that there are now instances where genetic testing supersedes histopathology in obtaining a diagnosis. In this case, testing for a UBA1 variant was prompted by widespread inflammatory phenomena and persistent anaemia. Notably, however, VEXAS has almost universally been reported with macrocytosis but the patient in this case had a persistent normocytic anaemia. This case features some distractors: the reported sudden onset of symptoms, recent travel overseas and a partial response to antibiotic therapy with resolution of the patient’s fevers and widespread skin rash. In retrospect, with the diagnosis of VEXAS in mind, it is likely that this improvement represented disease fluctuation rather than response to antibiotics. Outstanding questions from this case include which, if any, of the organs involved in this patient’s initial presentation most suggested VEXAS. Whether a bone marrow biopsy in the work-up of unexplained systemic inflammation would have obtained an earlier diagnosis with the finding of vacuoles (noting that these are not universally present in patients with VEXAS) is also uncertain. Finally, the lack of macrocytosis is unexplained and atypical for VEXAS. Key learning points VEXAS is thought to be underdiagnosed and should be considered as a differential diagnosis, particularly in an older male patient who presents with widespread inflammatory features and haematological abnormalities. VEXAS can cause a variety of rashes and skin histopathology demonstrating vasculitis may reflect systemic inflammation rather than systemic vasculitis. In the frequently encountered quandary of infection versus inflammation/autoimmunity, a seeming response to antibiotics does not necessarily confirm an infectious aetiology and may have other explanations such as the anti-inflammatory effects of antimicrobials (e.g. doxycycline) or natural fluctuations of inflammatory disease activity.

Relapsing polychondritis: focus on cardiac involvement.

Relapsing polychondritis (RP) with cardiac involvement may present with acute cardiovascular events, and may be associated with a negative prognosis. Herein, we analyzed the clinical characteristics of RP patients with cardiac involvement. RP patients, hospitalized from December 2005 to December 2021 at Peking Union Medical College Hospital (PUMCH), were screened. Univariate and multivariate logistic regression analyses were used to statistically analyze the clinical characteristics of these patients. The incidence of cardiac involvement in inpatients with RP was 24.1%. Univariate logistic regression analysis revealed age, central nervous system (CNS) involvement, neutrophil-to-lymphocyte ratio (NLR) > 6.41, and disease duration > 4 years as risk factors for cardiac involvement in RP. Conversely, the incidence of tracheobronchial and chest wall involvement was significantly lower in the group with cardiac involvement. Multivariate logistic regression confirmed that age, CNS involvement, NLR > 6.41, and disease duration > 4 years were independent factors for cardiac involvement. Subsequently, we identified five well-defined clinical patterns of RP, based on the involvement of different organs in our patients, and found that the heart-brain model was significantly mutually exclusive with the airway model. Occurrence of cardiac involvement in RP is associated with age, CNS involvement, NLR, and disease duration. It is mutually exclusive with airway-related involvement. Regular echocardiography and electrocardiography are necessary for patients with RP.

Bibliometric analysis of the global publication activity in the field of relapsing polychondritis during 1960-2023.

Relapsing polychondritis (RP) is an inflammatory disease with significant individual heterogeneity that involves systemic cartilage tissues. This study aimed to perform a bibliometric analysis of RP-related publications to quantitatively assess the scholarly productivity in the field. We extracted the RP-related original research articles and reviews published during 1960-2023 from the Web of Science database by using the keyword "relapsing polychondritis." By using R, CiteSpace, VOSviewer, and SCImago Graphica, the bibliometric analysis was performed on the retrieved publications. A total of 1096 articles, consisting of 909 original research articles and 187 reviews, were identified. A mean annual growth rate of 6.71% was found in the number of RP-related publications during 1960-2022. The United States accounted for the highest number of publications (21.9%), exhibited the highest mean citation number per publication (40.7), and engaged in the most frequent academic collaboration. Three clusters of RP-related journals were identified: 1) otology, rhinology, and laryngology; 2) respiratory and radiology medicine; and 3) rheumatology. Journals with a focus on rheumatology issued the most publications, and most of the RP-related publications were from The Journal of Rheumatology (n = 27). Most of these publications were co-authored by Dr. Jean-Charles Piette (n = 19), who also had the highest H-index (13) among all the authors. The co-citation network analysis revealed 11 highly connected clusters of RP research and indicated the "VEXAS Syndrome" as a hotspot. This overview of the RP research field comprehensively describes the progress in the field. The number of publications on RP has progressively increased but remains insufficient. The United States and European countries are at the forefront of RP-related research, and the journals related to rheumatology have covered the majority of publications. Additionally, several key topics for future investigations, such as "VEXAS Syndrome," have been identified. Key Points •We identified a mean annual growth rate of 6.71% in the number of the RP-related publications during 1960-2022. •The United States accounted for the majority of the publications, exhibited the highest mean citation number per publication, and engaged in the most frequent academic collaborations. •The journals of the publications were categorized into three clusters of research areas: 1) otology, rhinology, and laryngology; 2) respiratory and radiology medicine; and 3) rheumatology. Journals related to rheumatology issued the most publications, and most of the publications were from The Journal of Rheumatology •Most of the publications were co-authored by Dr. Jean-Charles Piette, who also had the highest scientific-research impact among the scholars in the field. •The co-citation network analysis revealed 11 highly connected clusters of RP research and indicated the "VEXAS Syndrome" as a key research area.

Endobronchial obstruction in connective tissue diseases: an uncommon but life threatening complication: two case reports

BackgroundGranulomatosis with polyangiitis and relapsing polychondritis are rare, multisystemic and potentially life-threatening connective tissue diseases. We present two cases of severe endobronchial obstruction in the aforementioned conditions and discuss difficulties with detection and treatment. Despite differing underlying pathophysiologies, endobronchial disease is a less frequently reported but serious complication of both conditions.Case presentationCase 1, a 31-year-old South Asian woman with relapsing polychondritis, required partial tracheal resection and reconstruction in combination with immunosuppressive therapy to achieve respiratory recovery following collapse of her right main bronchus and a stricture in her left main bronchus. Case 2, a 22-year-old Caucasian male with granulomatosis with polyangiitis, underwent surgical resection of an endobronchial growth causing occlusion of his right main bronchus. Although his respiratory status was initially stabilised with increased immunosuppression, he continues to have disease progression in spite of this.ConclusionsOur cases highlight the importance of a multidisciplinary approach combining immunosuppression with supportive care and judicious use of surgical interventions in select cases. A further review of the literature shows endobronchial obstruction is potentially under-reported due to overlap in connective tissue disease symptomatology and there is no consensus on best practice.

Innate immune responses in Behçet disease and relapsing polychondritis.

Behçet disease (BD) and relapsing polychondritis (RP) are chronic multisystem disorders characterized by recurrent flare-ups of tissue inflammation. Major clinical manifestations of BD are oral aphthae, genital aphthous ulcers, skin lesions, arthritis, and uveitis. Patients with BD may develop rare but serious neural, intestinal, and vascular complications, with high relapse rates. Meanwhile, RP is characterized by the inflammation of the cartilaginous tissues of the ears, nose, peripheral joints, and tracheobronchial tree. Additionally, it affects the proteoglycan-rich structures in the eyes, inner ear, heart, blood vessels, and kidneys. The mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome is a common characteristic of BD and RP. The immunopathology of these two diseases may be closely related. It is established that the genetic predisposition to BD is related to the human leukocyte antigen (HLA)-B51 gene. Skin histopathology demonstrates the overactivation of innate immunity, such as neutrophilic dermatitis/panniculitis, in patients with BD. Monocytes and neutrophils frequently infiltrate cartilaginous tissues of patients with RP. Somatic mutations in UBA1, which encodes a ubiquitylation-related enzyme, cause vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome (VEXAS) with severe systemic inflammation and activation of myeloid cells. VEXAS prompts auricular and/or nasal chondritis, with neutrophilic infiltration around the cartilage in 52-60% of patients. Thus, innate immune cells may play an important role in the initiation of inflammatory processes underlying both diseases. This review summarizes the recent advances in our understanding of the innate cell-mediated immunopathology of BD and RP, with a focus on the common and distinct features of these mechanisms.

Relapsing Polychondritis With Palmoplantar Pustulosis.

Palmoplantar pustulosis (PPP) is a very rare cutaneous manifestation observed during relapsing polychondritis (RP),1,2 not found in other conditions associated with saddle nose (eg, granulomatosis with polyangiitis, sarcoidosis, VEXAS [vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic] syndrome, congenital syphilis, leprosy, septal abscess).

Relapsing Polychondritis: The Oto-Rhino-Tracheobronchial Triad on 18 F-FDG PET/CT.

We present a 54-year-old woman with 3-month history of skin rash and bilateral hearing loss. Multiple investigations including biopsy failed to reveal the underlying diagnosis of relapsing polychondritis, until 18 F-FDG PET/CT demonstrated a characteristic FDG activity pattern-the oto-rhino-tracheobronchial triad. The patient was subsequently diagnosed to have relapsing polychondritis and received treatment. The second FDG PET/CT revealed a differential response in different disease sites, which prompted an escalation of treatment.

Evaluation of airway involvement and treatment in patients with relapsing polychondritis

Airway involvement in relapsing polychondritis (RP) can be debilitating and life threatening, often requiring interventional procedures. If standard therapies including systemic corticosteroid and immunosuppressive agents are ineffective, airway stenting is often required. Recently, biologics have been reported to be effective for RP, and the early administration of biologics may avoid airway stenting. To evaluate survival rates and treatment approaches, medical records of RP patients with airway involvement were reviewed. These cases were divided into the following groups: with and without malacia, stenting and non-stenting, and with and without biologics. Kaplan–Meier was used to calculate survival rates and log rank tests were used to analyze biologics groups. A total of 77 patients were enrolled. Airway stenting was performed in 13 patients, all of which developed airway malacia. The stenting group had significantly lower survival rates than the non-stenting group (p < 0.001). Stent-related complications were granulation tissue (85%) and mucostasis (69%). In the non-stenting group, a lower mortality rate was observed. A significantly higher survival rate was seen in patients administered biologics than without (p = 0.014). The early administration of biologics shows promise in preventing severe airway disorders that require airway stenting.

RED EARS, RED EYES AND HEARING LOSS: A DIAGNOSTIC DILEMMA

Relapsing polychondritis (RP) is a disease that confounds clinicians worldwide due to the difficulty in confirming its diagnosis and determining the best treatment plan. We report a case of a 34-year-old lady who presented with bilateral inflamed auricular swelling and red eyes, which turned out to be relapsing polychondritis. The patient was successfully treated with long-term oral steroids and is on regular follow-up. This report highlights how the subtle signs of her condition were picked up, leading to her diagnosis of RP and the treatment regime that successfully reversed her symptoms. The challenge of picking up subtle signs of the disease is best met by working as a team in a multidisciplinary setting. A literature study shows that RP is a rare disease that can present with many symptoms.