Polychondritis Research Articles

Physician Global Assessment as a Disease Activity Measure for Relapsing Polychondritis.

Relapsing polychondritis (RP) is a systemic inflammatory disorder of cartilage that lacks validated disease activity measures. Our objective was to test physician global assessment (PhGA), a measure of disease activity commonly used in rheumatic diseases, in a cohort of patients with RP, which has not been done before. Adult patients in an observational cohort of RP underwent standardized, comprehensive evaluation at approximately 6-month intervals. PhGA was scored by 3 physicians from the evaluating institution on a scale of 0-10 for each visit. A random subset of 20 visits was scored by 3 independent physicians not affiliated with the evaluating institution. Treatment change between consecutive visits was categorized as increased, decreased, or unchanged. In total, 78 patients were evaluated over 164 visits. The intraclass correlation coefficient (ICC2,1 ) for the 3 raters from the evaluating institution was excellent (0.79 [95% confidence interval (95% CI) 0.73, 0.84]) but was poor in the subset of cases scored by the additional raters (ICC2,1 0.27 [95% CI -0.01, 0.53]). Median PhGA was 3 (range 0-7). PhGA weakly correlated with C-reactive protein level (rs = 0.30, P < 0.01). In response to increased treatment, median PhGA decreased from 3 (interquartile range [IQR] 2, 4) to 2 (IQR 2, 3) (P < 0.01) but rarely went to 0. Within a single center, PhGA can be used to quantify disease activity and monitor disease response in RP. Persistent disease activity despite treatment, rather than a relapsing-remitting pattern, is observed for most patients with RP. Reliability of PhGA may not generalize across different institutions. A validated disease-specific activity index is needed in RP.

P037 A patient with systemic inflammation, relapsing polychondritis and pancytopaenia: VEXAS

Abstract Background/Aims We report a patient presenting with an inflammatory illness consistent with relapsing polychondritis (RP) and a pancytopaenia. Testing of his bone marrow revealed confirmation of the somatic mutation for the newly recognised condition VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. VEXAS is an acquired, adult-onset autoinflammatory syndrome which is progressive and frequently fatal. First reported in October 2020 by Beck et al, it results from somatic mutations at methionine-41 (p.Met41) of UBA1 gene, the major E1 enzyme that initiates ubiquitylation. Clinical features of VEXAS include periodic fevers, neutrophilic dermatoses, pulmonary infiltrates, chondritis and venous thromboembolic events. Bone marrow biopsy (BMB) shows vacuoles in myeloid precursor cells, and these cause hematologic abnormalities like myelodysplastic syndrome, multiple myeloma, or monoclonal gammopathy of unknown significance. Methods Clinical details were collected retrospectively. UBA1 sequencing: UBA1 exon 3 (NM_153280) was amplified from using High-Fidelity Phusion Polymerase (Life Tech) and primers UBA1-3F and UBA1-3R. PCR products were sequenced using the BigDye v3.1 terminator sequencing kit on an ABI3130xl (Life Tech). Electropherograms were analysed using 4Peaks software. Results A previously fit 63-year-old gentleman presented with a three-month history of recurrent fevers, night sweats and intermittent cough. At presentation he also had left testicular pain. Bloods showed neutropenia (1.9x10^9/L), normocytic anaemia (128g/L) and raised CRP (98mg/L). However, his symptoms progressed with headaches, myalgia, conjunctivitis, nasal chondritis and sinusitis. His CRP rose to 149mg/L and ferritin was 886ng/mL. He had a negative PET scan, autoimmune screen, myeloma screen and normal levels of complement, CK and ACE. Furthermore, multiple blood cultures and infectious disease screening tests were negative. He subsequently developed a left auricular chondritis. Within a week of commencing prednisolone 40mg and methotrexate 15mg his symptoms improved by 80% and his CRP was 10mg/L. At 15mg of prednisolone his CRP rose (134mg/L) and his fevers, night sweats and arthralgia returned. His prednisolone was then increased to 20mg. Over the next nine months his disease progressed despite prednisolone and methotrexate. He developed worsening cytopenias (Hb86/L, plts105x109/L, MCV117fL), bilateral sclerouveitis, inflammatory joint pains, vasculitic rash, chest pain and dyspnoea on exertion. CTPA and HRCT showed no significant abnormalities. VEXAS syndrome was diagnosed after BMB testing identified the UBA1 mutation c.122T&amp;gt;c, p.Met41Thr. His treatment now encompasses prednisolone and Tocilizumab. His cytopenias are transfusion dependent, he has been under review to consider BMT although is currently stable clinically. Conclusion VEXAS syndrome should be considered in men over 50 with treatment-refractory giant cell arteritis, RP, polyarteritis nodosa and Sweet’s syndrome. VEXAS has a significant mortality and developing effective treatments is a priority. Given there is an available confirmatory test early recognition and subsequent testing for the UBA1 mutation will help physicians to identify appropriate treatment options and avoid unnecessary investigations. Disclosure S. Sajawal: None. M. Green: None. S. Savic: Consultancies; Novartis, SOBI, TAKEDA. Member of speakers’ bureau; Novartis, SOBI. Grants/research support; SOBI.

자가면역질환과 동반된 후두기관협착 2예

Autoimmune disease-associated laryngotracheal stenosis (AD-LTS) is very rare but can pose a life-threatening risk. Pathogenesis of AD-LTS is still uncertain and standard treatment protocol has not been proposed. In this study, we reported two rare cases of AD-LTS in patients with relapsing polychondritis and rheumatoid arthritis, respectively. Two middle-aged female patients visited our clinic due to progressive dyspnea, and stenosis of subglottis and upper trachea was identified. Under general anesthesia, stenotic area was dilated with balloon gradually following steroid injection. As both patients had developed dyspnea after several months postoperatively, they underwent revision surgery. After two times of surgery, dyspnea was relieved and patients are maintaining systemic immunosuppressive therapy with regular rheumatology clinic follow up. AD-LTS should be carefully diagnosed and proper intervention with multidisciplinary team approach is required.

A review of VEXAS syndrome in 116 French patients

British Journal of DermatologyVolume 186, Issue 3 p. e115-e115 Plain Language SummaryFree Access A review of VEXAS syndrome in 116 French patients First published: 07 March 2022 https://doi.org/10.1111/bjd.20989AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Linked Article: Georgin-Lavialle et al. Br J Dermatol 2022; 186:564–574. Autoinflammatory syndromes are conditions in which fever and signs of inflammation occur without an infectious cause. Some of these, mostly rare, syndromes are linked to mutations (faults in genetic code) in a specific gene. VEXAS syndrome (Vacuoles, E1 Enzyme, X chromosome, Autoinflammatory, Somatic) has recently been described and linked to a mutation in the UBA1 gene, located on the X chromosome; it is therefore much commoner in men. A major feature of the condition is relapsing polychondritis (an inflammation of the cartilage particularly affecting the respiratory tract). Other features include a tendency to spontaneous blood clotting, lung inflammation, joint pains and skin lesions including vasculitis and neutrophilic dermatosis. VEXAS is often associated with myelodysplasia (premalignant changes in blood cells), and often has a poor prognosis. Treatment includes glucocorticoids and anti-inflammatory disease modifying drugs (DMARDs). In this paper from France, the authors from multiple centres of expertise in autoinflammatory diseases worked with laboratories performing UBA1 gene analysis to collect data on their patients with VEXAS syndrome over a 6-month period. The authors added lymph node enlargement and erosive arthritis to the clinical features. They identified three clusters of disease in their patients. The first had mild to moderate disease with less fever; this group was strongly linked to a mutation in UBA1, and had a relatively good outcome. The second cluster had more severe disease, including relapsing polychondritis, and myelodysplasia was common; this group had a higher mortality rate. The third group comprised older patients who presented with inflammatory features such as skin vasculitis and weight loss. The authors found that increased mortality in VEXAS syndrome was linked to involvement of lung tissue and the gastrointestinal tract (e.g. perforation of the gut). Volume186, Issue3March 2022Pages e115-e115 RelatedInformation

Mechanical model of steady-state and inflammatory conditions in patients with relapsing polychondritis: A review.

Relapsing polychondritis (RP) is a multisystem inflammatory disorder, considered to associate with immune aberration.Increased T helper type-1 cell-related cytokines were reported in RP patients. mRNA expressions of a regulatory T cell cytokine interleukin (IL)-10 increased, whereas pro-inflammatory cytokines IL1β and IL6 mRNA expressions decreased in freshly isolated peripheral blood mononuclear cells of RP patients compared with those in healthy individuals. Upon in vitro stimulation with mitogen, IL10 mRNA expressions decreased, and IL1β and IL6 mRNA expressions increased in RP patients.This short-time dynamic change of gene expressions from anti-inflammatory to pro-inflammatory features of immune cells may be associated with the “relapsing” disease course of patients with RP. IL1β mRNA expressions of peripheral blood mononuclear cells exhibited positive correlations with serum matrix metalloproteinase (MMP)-3 concentrations in patients with respiratory involvement. Such positive correlation was not found in those without respiratory involvement.In a metagenomic analysis, an altered composition of gut microbes was found, suggesting that microbe metabolites such as short-chain fatty acids may affect T cell responses of the patients.In this review, the relationships among RP-related inflammatory molecules were summarized. The data support a hypothesis that the immune conditions are different between steady-state and inflammation in RP patients.

Curcumin ameliorates H2O2-induced inflammatory response in chondrocytes by inducing autophagy activation.

Relapsing polychondritis (RP) is a clinical disease characterized by inflammation of cartilage tissue and chondrocytes. The principal curcuminoid curcumin is the most active component in turmeric and has been reported to have a chondroprotective effect, including anti-inflammatory activity, which is vitally important for mitigating RP symptoms and prognosis. However, the mechanisms underlying these actions have remained to be fully elucidated. In the present study, the chondroprotective mechanisms of curcumin on hydrogen peroxide (H2O2)-treated primary chondrocytes were examined in vitro. The viability of chondrocytes treated with H2O2 was significantly reduced in a dose- and time-dependent manner. Cotreatment of curcumin with H2O2 significantly decreased growth inhibition. It was observed that curcumin inhibited the expression levels of the inflammatory mediators interleukin (IL)-1β, IL-6 and inducible nitric oxide synthase and induced autophagy activation. Curcumin increased the protein levels of the autophagy marker beclin-1 and light chain 3-II and decreased the expression levels of P62 in H2O2-treated chondrocytes. The curcumin-induced anti-inflammatory effects were markedly abrogated by the autophagy inhibitor 3-methyladenine. In conclusion, the present study suggested that curcumin regulates inflammatory factors by activating autophagy in chondrocytes. The protective role of curcumin in chondrocytes was demonstrated, suggesting that it should be explored for the prophylactic treatment of RP in the clinic in the future.

Clinical analysis of relapsing polychondritis with airway involvement.

To identify the clinical characteristics, treatment, and prognosis of relapsing polychondritis patients with airway involvement. Twenty-eight patients with relapsing polychondritis, hospitalised in the First Hospital of Shanxi Medical University between April 2011 and April 2021, were retrospectively analysed. 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. For relapsing polychondritis patients with airway involvement, drug treatment should be combined with local airway management.

Eustachian tube involvement in a patient with relapsing polychondritis detected by magnetic resonance imaging: A case report

BACKGROUNDRelapsing polychondritis (RP) is a rare inflammatory disease involving the systemic cartilage, such as the auricle, trachea, and bronchiole, among others. A patient with RP shows variable symptoms based on the involved cartilage.CASE SUMMARYA 72-year-old Japanese woman with a history of redness of the bilateral auricles for 3 d was referred to a clinician. The clinician prescribed antibiotics to the patient; however, the symptoms worsened; thus, she was referred to our hospital. Head and neck magnetic resonance imaging (MRI) showed edematous auricle with remarkable contrast, fluid collection in the bilateral mastoid cells, suggesting otitis media. The eustachian tube (ET) on the right side was also edematous with contrast enhancement. The patient was suspected of RP according to the diagnostic criteria. A biopsy of the auricular cartilage was performed by an otorhinolaryngologist, confirming pathological proof of RP. Treatments with steroids were immediately administered thereafter.CONCLUSIONWe highlight a rare case of RP with radiologically confirmed involvement of ET in the MRI.

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.

Nationwide cross-sectional survey of patients with relapsing polychondritis in 2019 demonstrates reduction of airway involvement compared with that in 2009

We conducted retrospective cohort studies of patients with relapsing polychondritis (RP) twice in 2009 and 2019, using a physician questionnaire. We compared the patients’ clinical statuses between the years. Age and gender were comparable between the two surveys. Mean disease duration was longer in 2019 survey (8.3 years) than that in 2009 survey (4.8 years, P < 0.001). The mortality rate declined in 2019 survey compared with those in 2009 survey (from 9.2 to 1.6%, P < 0.001). Incidence of airway involvement decreased in 2019 survey compared with that in 2009 survey (from 49 to 37%, P = 0.012). In 2019 survey, we found more frequent use of biological agents and immunosuppressants in patients with airway involvement. When we focused on RP patients with airway involvement, physicians in 2019 chose methotrexate and calcineurin inhibitors preferentially, compared with azathioprine and cyclophosphamide. Of note is that increased use of infliximab was observed in RP patients with airway involvement, but not in those without. Reduction of airway involvement and mortality in patients with RP was observed in 2019 survey. The reduction may associate with the frequent use of biologics including infliximab in RP patients with airway involvement.

Differentiating tracheobronchial involvement in granulomatosis with polyangiitis and relapsing polychondritis on chest CT: a cohort study

BackgroundIn patients with tracheobronchial involvement, the differential diagnosis between granulomatosis with polyangiitis (GPA) and relapsing polychondritis (RP) can be challenging. The aim of this study was to describe the characteristics of airway abnormalities on chest computed tomography (CT) in patients with GPA or RP and to determine whether specific imaging criteria could be used to differentiate them.MethodsGPA and RP patients with tracheobronchial involvement referred to a national referral center from 2008 to 2020 were evaluated. Their chest CT images were reviewed by two radiologists who were blinded to the final diagnosis in order to analyze the characteristics of airway involvement. The association between imaging features and a diagnosis of GPA rather than RP was analyzed using a generalized linear regression model.ResultsChest CTs from 26 GPA and 19 RP patients were analyzed. Involvement of the subglottic trachea (odds ratio for GPA=28.56 [95% CI: 3.17; 847.63]; P=0.001) and extensive airway involvement (odds ratio for GPA=0.02 [95% CI: 0.00; 0.43]; P=0.008) were the two independent CT features that differentiated GPA from RP in multivariate analysis. Tracheal thickening sparing the posterior membrane was significantly associated to RP (odds ratio for GPA=0.09 [95% CI: 0.02; 0.39]; P=0.003) but only in the univariate analysis and suffered from only moderate interobserver agreement (kappa=0.55). Tracheal calcifications were also associated with RP only in the univariate analysis (odds ratio for GPA=0.21 [95% CI: 0.05; 0.78]; P=0.045).ConclusionThe presence of subglottic involvement and diffuse airway involvement are the two most relevant criteria in differentiating between GPA and RP on chest CT. Although generally considered to be a highly suggestive sign of RP, posterior tracheal membrane sparing is a nonspecific and an overly subjective sign.

Ultrasonography of auricular cartilage is a potential tool for diagnosing relapsing polychondritis and monitoring disease activity.

AimTo assess the clinical utility of ultrasonography in the diagnosis and monitoring of disease activity in relapsing polychondritis (RP).MethodsAuricular and nasal chondritis of 6 patients with RP were assessed by ultrasonography before treatment initiation. Changes in the ultrasonographic and clinical findings and serum inflammatory markers were longitudinally assessed. Ultrasonography was also performed in 6 patients with repeat ear trauma, 6 patients with auricular cellulitis and 6 healthy controls for comparison among groups.ResultsIn all cases of RP, ultrasonographic findings before treatment revealed low‐echoic swollen auricular and nasal cartilage and perichondral soft‐tissue with increased power Doppler signals (PDS) corresponding to biopsy findings. After 2‐month treatment with prednisolone (PSL) combined with methotrexate, clinical and serum inflammatory markers were completely resolved. Although swollen perichondral soft‐tissue, cartilage and PDS on auricular ultrasonography were also significantly improved, PDS remained in 2 of 6 cases, which showed flare early after tapering PSL. Finally, ultrasonographic findings of RP were substantially differentiated between patients with repeat trauma and cellulitis and healthy controls based on the thickness of soft tissue around the cartilage, PDS and subperichondral serous effusion.ConclusionAssessment of RP lesions by ultrasonography is useful for the evaluation of cartilaginous lesions and monitoring of disease activity, especially when considering the treatment response and the timing of drug tapering.

Teaching NeuroImage: Seizures as the Initial Symptom of Relapsing Polychondritis.

A 41-year-old man presented with generalized tonic-clonic seizures. MRI revealed left subinsular and right frontal cortex lesions (Figure 1). CSF analysis showed 17 white cells/mm3 (lymphocytes 92%), normal protein, and glucose. The infection and autoimmune screening were negative. On day 3, bilateral auricles swelling and episcleritis emerged (Figure 2). Biopsy of left auricle revealed perivascular lymphocytic infiltration (Figure 2), consistent with relapsing polychondritis (RP). The patient's symptoms improved after oral prednisolone.

이충만감을 초기증상으로 시작된 재발성 다발연골염 1예

Relapsing polychondritis is a rare multisystemic disease which affects cartilaginous tissues of auricles, nose, larynx, trachea and joints as well as proteoglycan-rich structures. The disease is characterized by repetitive inflammatory and destructive episodes. Chondritis most frequently involves external ear, but the spectrum of clinical presentations may vary from intermittent episodes of painful chondritis and ocular inflammation, to organ or even life-threatening manifestations like cardiovascular complications and airway collapse. Its pathogenesis in not determined completely. In the treatment, main medication is a corticosteroid and immunosuppressive drugs represent a second-choice treatment. Authors have recently experienced a case of relapsing polychondritis in a 42 year old man who had ear fullness as an initial manifestation. We report this case with a review of the literature. (J Clinical Otolaryngol 2021;32:245-250)

Extracorporeal high-frequency combined with contrast-enhanced ultrasound: a novel imaging method for detection and treatment evaluation of patients with cervical trachea-associated relapsing polychondritis.

BackgroundThis study aims to evaluate the clinical utility of extracorporeal high-frequency ultrasound (EHFU) combined with contrast-enhanced ultrasound (CEUS) for the diagnosis and treatment of cervical trachea-associated relapsing polychondritis (CT-RP).MethodsFrom January 2013 to January 2020, 24 patients with CT-RP diagnosed clinically and pathologically were retrospectively reviewed. We used EHFU to measure the thickness of trachea cartilage and the minimum internal transverse diameter of trachea and compared it with CT. The EHFU and CEUS imaging features were compared before and after treatment and used to evaluate the effects of therapy.ResultsEHFU revealed the entire cervical tracheal cartilage (136 rings, of which 124 were abnormal). The average thickness of the 124 tracheal cartilage rings was 3.657±0.52 mm on EHFU and 3.32±0.76 mm on CT (t=1.482, P>0.05), while the diameter of the tracheal segment was 11.98±3.22 mm on EHFU and 10.8±2.92 mm on CT (t=1.005, P>0.05). After treatment, most patients (75%) showed no recurrence, and ultrasound revealed that the tracheal ring thickness was restored and the transverse diameter of the tracheal cavity was widened. Differences in EHFU measurements before and after treatment were statistically significant (both P<0.01). CEUS revealed that the tracheal cartilage layer was damaged in six cases (25%) and included structural destruction, deformation, and thinning. Follow-up evaluation revealed that the treatment outcomes of these cases were poor. The mean ultrasound examination time per patient was 10.0±2.3 min.ConclusionsEHFU combined with CEUS clearly and quickly revealed the CT-RP cervical tracheal wall, diameter of the trachea, and microstructural changes in tracheal cartilage. The effects of treatment can be reliably assessed by measuring reductions in tracheal cartilage thickening and echo changes before and after treatment. Dynamic monitoring of the condition provides timely and detailed information on cervical tracheal wall lesions and is valuable for clinical evaluation.

Rare within rare. Necrotising scleritis and peripheral ulcerative keratitis: eye-threatening complications of relapsing polychondritis.

Relapsing polychondritis (RP) evolves with variable and intermittent involvement of cartilage and proteoglycan-rich structures. Ocular manifestations are present in up to two-thirds of RP patients. Necrotising scleritis (NS) and peripheral ulcerative keratitis (PUK) may be inaugural and may lead to eye perforation and vision loss. We aimed to review NS and PUK in RP, in order to characterise them, to identify successful treatment options and unmet needs. A systematic review of the currently available evidence in PubMed, EMBASE and Scopus was performed according to PRISMA, including observational studies, single case reports and case series of NS/PUK in RP. Study design, number of patients, age, gender, treatment and outcome, were extracted. Two RP patients also provided their opinion. Five case reports and two case series were eligible for inclusion. We identified 10 RP patients with eye-threatening complications (NS and/or PUK), 9 adults (2 males, 7 females, aged 35-72, median age 57.6 years) and one paediatric patient (F, 11 years). Apart from glucocorticoids, cyclophosphamide was effective in 4 patients; infliximab, high-dose immunoglobulins, dapsone, or cyclosporine were also successfully employed in a case each. Surgical repair was reported in 2 cases. Ocular inflammation is often bilateral and recurring in RP; NS/PUK are rare complications. All patients who develop NS/PUK should be specifically questioned for RP signs and symptoms. Early institution of immunosuppressive therapies is mandatory. Increasing awareness, physicians' and patients' education and a multidisciplinary approach may help improve the prognosis of these serious complications of RP.

Coexistence of Relapsing Polychondritis and Sickle Cell Disease in a Child

Relapsing polychondritis (RP) is a rare, severe connective tissue disease of unknown etiology affecting cartilaginous and proteoglycan-rich structures in an episodic and inflammatory manner. Approximately a third of RP cases occur in conjunction with another disease usually systemic autoimmune rheumatic disease, or myelodysplastic syndrome. Sickle cell disease (SCD) is a common inherited hematologic condition characterized by the inheritance of two abnormal hemoglobins, of which one is a hemoglobin S, presenting with severe acute and chronic complications from vaso-occlusive phenomena, which can be difficult to differentiate from RP. The pathogenesis of RP is poorly understood but suggests an autoimmune mechanism with a link to sickle cell disease yet to be established. Treatment is empiric with steroids, anti-inflammatory, and disease-modifying antirheumatic drugs being the mainstay of therapy. Severe complications occur despite treatment, with respiratory involvement being the most catastrophic. This case report reviews a complex case of RP in an 11-year-old girl with sickle cell disease (SF genotype) presenting with bilateral red painful eyes, a painful swollen left ear, and knee pain. Laboratory findings revealed elevated inflammatory markers with negative immune serology. A diagnosis of RP was made based on the patient's symptomatology, presentation, and fulfillment of 5 out of the 6 clinical features using McAdam's criteria. Management was instituted with a myriad of conventional and biologic DMARDs and other anti-inflammatory medications with no significant improvement and the development of complications of airway obstruction from disease activity and osteoporotic fracture from steroid therapy and underlying hemoglobinopathy. In children, the diagnosis of RP is delayed or overlooked due to its low incidence, variability in clinical symptoms, or sharing similar clinical features with other coexisting disease entities. This article reports its occurrence in the pediatric population and highlights the difficulty in managing such cases as there are no defined standard treatment protocols.

Bronchoscopy-Guided Intervention Therapy With Extracorporeal Membrane Oxygenation Support for Relapsing Polychondritis With Severe Tracheobronchomalacia: A Case Report and Literature Review

Relapsing polychondritis is an immune disorder of unknown etiology involving multiple systems that is characterized by persistent inflammation and destruction of cartilage, including the ears, nose, costal, joint, and airways. Airway involvement caused by relapsing polychondritis is common, and tracheobronchomalacia is the most serious complication, which is life-threatening. Currently, the exact mechanism of relapsing polychondritis with tracheobronchomalacia is unknown. Although glucocorticoids and immunosuppressive agents are administered, failures often occur. Currently, bronchoscopy-guided intervention therapy used in tracheobronchomalacia caused by chronic obstructive pulmonary disease or other etiology has gradually increased, but bronchoscopy-guided intervention therapy with extracorporeal membrane oxygenation assist used in tracheobronchomalacia caused by relapsing polychondritis has not been reported. Here, we report a case of relapsing polychondritis with severe tracheobronchomalacia. Although drug therapy was provided and airway stent implantation was performed, the tracheal stenosis was further aggravated. Because conventional anesthesia and mechanical ventilation cannot meet the needs of bronchoscopy-guided intervention therapy or guarantee sufficient safety. The intervention treatment was performed with the support of extracorporeal membrane oxygenation, which was successfully completed without obvious complications. The symptoms were significantly improved, and the patient was discharged uneventfully.

Remitting Seronegative Symmetrical Synovitis with Pitting Edema (RS3PE) Syndrome: A Single-Center Experience

Objective: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare disorder characterized by pitting edema, the onset of acute polyarthritis, and negative rheumatoid factor. The absence of joint erosion and good long-term response to low-dose steroids are its other characteristics. The present study aimed to evaluate the characteristics and accompanying conditions of RS3PE for contributing to the literature on the issue. Material and method: This is cross-sectional descriptive study was carried out in a rheumatology clinic between January 2019- October 2020. Fifteen patients over 18 diagnosed with RS3PE were included in the study. Results: Of 15 patients diagnosed with RS3PE, seven were female, and eight male. The following comorbid disorders were present: relapsing polychondritis, scleroderma, seropositive rheumatoid arthritis, gout, monoclonal gammopathy of unknown significance, and primary myelofibrosis. Most patients other than the ones who have hematological malignities and those diagnosed with relapsing polychondritis responded rapidly to steroids, and no recurrence occurred. Conclusion: RS3PE may be associated with neoplasia, drugs, and various rheumatismal conditions, suggesting that it may be heterogeneous and considered a paraneoplastic rheumatic disease. The rare occurrence of this syndrome leads clinicians to miss it commonly. It is essential to increase awareness of this entity among clinicians.

A prospective observational cohort study and systematic review of 40 patients with mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome

ObjectiveMouth and genital ulcers with inflamed cartilage (MAGIC) syndrome is characterized by overlapping features of relapsing polychondritis (RP) and Behcet's disease (BD). To date, no studies have defined the clinical spectrum of disease in a cohort of patients with MAGIC syndrome. MethodsAdult patients within an ongoing prospective, observational cohort study in RP were clinically assessed for MAGIC syndrome. A systematic review was conducted to identify additional cases of MAGIC syndrome by searching four databases: PubMed (US National Library of Medicine), Embase (Elsevier), Scopus (Elsevier) and Web of Science: Core Collection (Clarivate Analytics). The inclusion criteria used were: [1] patients of any age or gender who were diagnosed with MAGIC syndrome, or both RP and BD; [2] case report or case series study; [3] published from 1985 – July 2020; and [4] in English language. Risk of bias was assessed using a checklist developed by the authors and based on the Consensus-based Clinical Case Reporting (CARE) Guidelines. Search results screening, article inclusion, data extraction and risk of bais assessment was performed independently by two investigators. Clinical characteristics, particularly BD-related features, were compared between patients with MAGIC syndrome and cases of non-MAGIC RP. The performance characteristics of different criteria to classify MAGIC syndrome were also evaluated. ResultsOut of 96 patients with RP, 13 (14%) patients were diagnosed with MAGIC syndrome. For the systematic review, 380 articles were retrieved of which 90 were screened at title and abstract levels. Of these screened, 60 were excluded and 30 proceeded to full text review where an additional 8 were excluded. Twenty-two articles were included in our review and from which 27 additional cases of MAGIC syndrome were identified. Pooling all 40 cases together and comparing them with non-MAGIC RP, there was a significantly higher prevalence of ocular involvement (28% vs 4%, p<0.01), cutaneous involvement (35% vs 1%, p<0.01), GI involvement (23% vs 4%, p<0.01), and CNS involvement (8% vs 0, p = 0.04) in MAGIC syndrome. A higher prevalence of aortitis (23% vs 1%, p<0.01), Raynaud's phenomenon (54% vs 11%, p<0.01), and elevated anti-collagen II antibodies (50% vs 9%, p = 0.04) were observed in MAGIC syndrome. Fulfillment of either McAdam's or Damiani's Criteria for RP plus the International Criteria for Behçet's Disease had excellent sensitivity (98%) to classify cases of MAGIC syndrome. ConclusionA substantial proportion of patients with RP can be clinically diagnosed with MAGIC syndrome. These patients have features of RP, BD, and other unique features including aortitis, Raynaud's phenomenon and elevated anti-collagen II antibodies.