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.

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

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

Predictors and prognosis of tracheostomy in relapsing polychondritis.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) for the dermatologist.

In 2020, Beck et al1 described a novel adult autoinflammatory syndrome entitled VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic), a newly-discovered disorder that connected previously unrelated inflammatory syndromes and a prototype for a new class of hematoinflammatory diseases.2 Eighty-nine percent of published cases have documented skin involvement, but despite the high incidence and diagnostic accessibility of skin manifestations, there has been little focus on the dermatological features of VEXAS syndrome thus far. A PubMed search of all published case reports of VEXAS syndrome to date was performed, with inclusion of all cases confirmed by genetic sequencing, and this review summarizes the reported dermatological signs. There have already been 141 confirmed published cases since original publication, 126 of which had documented cutaneous signs.1-34 A wide range of skin presentations are reported, including Sweet-like urticated and tender erythematous nodules, cartilaginous involvement with chondritis, cutaneous vasculitis, and periorbital angiodema.1-34 Many patients had been diagnosed with Sweet syndrome, relapsing polychondritis, polyarteritis nodosa, or erythema nodosum.1-34 Hallmarks of skin histopathology are a neutrophilic dermatosis with coexisting or exclusive leukocytoclastic vasculitis.1 The new classification therefore helps link previously disparate inflammatory skin conditions into a unifying pathophysiological pathway.

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.

The ocular manifestations of relapsing polychondritis.

PURPOSE: Relapsing polychondritis (RPC) is a rare, multi-system, inflammatory disorder. Ocular disease is estimated to occur in 14-67% of patients with RPC, and any ocular structure can be affected. Published case reports and series of RPC were analysed to determine the frequency and nature of the ocular manifestations of RPC, including the age and gender distribution. METHODS: A literature search of the MEDLINE database for case reports and series on RPC was conducted in October 2021 using search terms [relapsing polychondritis (MeSH Major Topic)] OR [relapsing polychondritis (Title/Abstract)]. Articles were included if the diagnosis of RPC was confirmed using established diagnostic criteria and if the paper described the clinical features of patients with RPC. RESULTS: 546 articles (454 case reports and 92 case series) described the clinical features in a total of 2414 patients with RPC. 49% of patients with RPC had ocular involvement, and this was a presenting feature in 21%. The most common ocular manifestations were scleritis (32%), episcleritis (31%) and uveitis (23%). CONCLUSION: Many patients with RPC will be seen by an ophthalmologist during the course of their disease. Knowledge and awareness of RPC and its ocular manifestations is therefore essential to enable the ophthalmologist to make the diagnosis.

Focal Pachymeningitis Induced Papilloedema as an Early Manifestation of Relapsing Polychondritis.

A 52-year-old male patient presented with longstanding non-specific symptoms of ocular redness and irritation. Clinical examination not only revealed bilateral anterior scleritis but also bilateral optic disc swelling. Additional history taking revealed headaches and tinnitus, both starting around the same time as the eye redness, as well as a prior episode of swelling and redness of both ears. The lumbar puncture opening pressure was 29 cm of cerebrospinal fluid (CSF). There were 11 white blood cells/µl in the CSF. Subsequent magnetic resonance imaging showed focal thickening of the dura mater over the left cerebral convexity, suggestive of focal pachymeningitis. 18F-fluorodeoxyglucose positron emission tomography demonstrated hypermetabolic abnormalities located at the auricles, the nostrils, the anterior part of the eyes, and the dura mater over the left cerebral convexity, suggestive of relapsing polychondritis (RPC). RPC is a rare systemic immune-mediated condition; diagnosis can sometimes be delayed or missed due to insidious disease onset with non-specific symptoms. Nevertheless, sight-threatening or even life-threatening complications may occur. Given the high prevalence of ocular involvement, one should be suspicious when faced with patients with recurrent ocular inflammation. Optic disc swelling is a more uncommon finding, and while different mechanisms have been reported, it has rarely been associated with raised intracranial pressure. Nevertheless, intracranial hypertension arising from inflammation of the CSF and/or surrounding meninges caused by the newly diagnosed RPC was identified as the most likely underlying mechanism for the bilateral optic disc swelling in our patient.

Discordance in patient and physician global assessment in relapsing polychondritis.

OBJECTIVES: Relapsing polychondritis (RP) is a rare, heterogeneous, systemic inflammatory disease that targets cartilage. Patient-reported outcome measures may differ from physician assessment. This study compared patient global assessment (PtGA) and physician global assessment (PhGA) scores in a prospective cohort of patients with RP. METHODS: Adult patients with RP underwent a standardized comprehensive evaluation at ∼6 month intervals. At each visit, three physicians scored PhGA by consensus. The patient independently completed four patient-reported outcomes: PtGA, 36-item Short Form Health Survey (SF-36), Brief Illness Perception Questionnaire (BIPQ) and Multidimensional Fatigue Inventory (MFI). Patient-physician discordance was defined as a difference between PtGA and PhGA of ≥3 on a 0-10 scale. RESULTS: A total of 76 patients were evaluated over 154 visits. The median PhGA was 3 [interquartile range (IQR) 2-3] and the median PtGA was 5 (IQR 4-7). PtGA and PhGA were concordant in 66 visits (42.9%) and patients scored disease severity ≥3 points higher than physicians scored disease activity (positive discordance) in 84 visits (54.5%). Compared with visits with concordance, visits with positive discordance were associated with significantly worse scores on the MFI, BIPQ, SF-36 physical component score and SF-36 mental component score. CONCLUSION: Patients with RP typically self-report high PtGA that does not align with PhGA. Discordance is likely driven by the high physical and psychological burden of illness experienced by patients. Multifaceted treatment approaches that address the burden of disease in RP from the patient perspective are needed.

Relapsing polychondritis after treatment with PD-1 blockade.

Nivolumab, a programmed death 1 blockade drug, is used in various types of cancers and can cause a unique immune-related adverse event (irAE). Relapsing polychondritis (RP) is a rare autoimmune disease that mainly involves inflammation of the auricle, nose and airway cartilage. A 72-year-old man with mandibular cancer received nivolumab after surgery for the primary lesion and radiation therapy for lung metastases. He then developed radiation pneumonitis, and prednisolone (PSL) was started. During the tapering of PSL, he developed exertional dyspnea and cough. The condition of mandibular cancer and radiation pneumonitis had not deteriorated. Fluorodeoxyglucose (FDG)-PET/CT showed a thickening of and abnormal FDG uptake in the tracheobronchial and nasal septum cartilage. These characteristic findings were not observed before nivolumab was initiated; thus, we clinically diagnosed the patient as having RP induced by nivolumab. Since the symptoms were mild, the patient's condition was carefully managed with inhaled corticosteroids, and the RP has not progressed thus far. Physicians should be aware that RP can occur as an irAE because RP may progress to serious respiratory symptoms.

Comparison of relapsing polychondritis patients with and without respiratory involvement based on chest computed tomography: a retrospective cohort study.

BACKGROUND: Relapsing polychondritis (RP) patients with tracheal cartilage involvement are different from other patients. The objective of this study was to compare the clinical features and disease patterns between a respiratory involvement subgroup and a non-respiratory involvement subgroup according to chest computed tomography. METHOD: We performed a retrospective cohort study collecting RP patients hospitalized at the Beijing Chao-Yang Hospital between January 2012 and August 2021. RESULTS: Respiratory involvement affected 59.7% of patients in our cohort. The incidence of costochondritis was more common in RP patients with respiratory involvement (p = 0.03); the incidence of inflammatory eye disease (p = 0.001) and auricular chondritis (p = 0.001) was less frequent in RP respiratory involvement patients.. Compared with the non-respiratory involvement subgroup the incidence of pulmonary infection marginally increased in the respiratory involvement subgroup (p = 0.06). Inflammatory indexes except for C-reactive protein to albumin ratio (CAR) were significantly higher in the respiratory involvement subgroup; analysis revealed no significant relationship between inflammatory indexes and pulmonary infection. CONCLUSION: RP patients with respiratory involvement had a greater incidence of costochondritis and pulmonary infectionand lesser incidence of inflammatory eye diseases and auricular chondritis compared to non-respiratory involvement. Increasing inflammatory indexes suggests that patients with respiratory involvement had a higher disease activity index of RP. The difference in probability of survival was insignificant between subgroups.

Molecular Mechanisms and Physiological Changes behind Benign Tracheal and Subglottic Stenosis in Adults.

Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different aetiology. Although iatrogenic aetiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent aetiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS.

Respiratory Failure during BIS-Guided Sedation in a Patient with Relapsing Polychondritis: A Case Report.

Relapsing polychondritis (RP) is a rare autoimmune disorder that causes inflammation and deterioration of cartilaginous structures such as the ears, nose, joints and laryngotracheobronchial tree. A 42-year-old man receiving treatment for RP underwent open reduction and internal fixation of a femur fracture under spinal anesthesia and with sedation by propofol and remifentanil. The level of sedation was monitored via a bispectral index (BIS), and maintained at between 60 and 80. At the end of the operation, he lost consciousness and displayed weak respiratory effort. During mask ventilation, the patient was judged to have respiratory failure due to high end-tidal CO2 (EtCO2) concentration and respiratory acidosis in an arterial-blood-gas analysis (ABGA). Ventilation through a properly inserted laryngeal-mask-airway or endotracheal intubation were impossible; instead, a surgical tracheotomy was performed. After recovering from respiratory failure with ventilatory support in the intensive care unit (ICU), he experienced the same symptoms three more times, requiring ventilatory support. He was discharged with bilevel positive-airway-pressure (BiPAP), after successful adaptation.

Correlation between Computed Tomographic Analysis and Pulmonary Function Measurements in Patients with Relapsing Polychondritis.

BACKGROUND: Relapsing polychondritis (RP) is a rare systemic disease of unknown origin, with cartilaginous involvement in multiple organs. Airway involvement is the most important prognostic factor in RP. OBJECTIVES: Spirometric measurements and minimum tracheal cross-sectional area (mtCSA) have been reported as useful to assess the degree of airway stenosis. Because the length and severity of tracheal involvement in RP can vary, mtCSA might not provide enough information to assess tracheal abnormalities. We introduced tracheal volume (TrV) as a new method to evaluate correlations between chest computed tomography (CT) measurements and pulmonary function tests, including impulse oscillometry (IOS). METHOD: We analyzed chest CT images, spirometry, and IOS collected at our institution from April 2004 to March 2019. We calculated correlations between chest CT measurements using software (TrV, TrV/tracheal length [TrV/TL], and mtCSA) and pulmonary function parameters. RESULTS: Twenty-five of 73 clinically diagnosed patients with RP were included. Spirometric findings showed moderate airway obstruction. Peak flow (PEF) was strongly correlated with mtCSA, TrV, and TrV/TL (ρ = 0.74, p < 0.001). FEV1 was significantly correlated with mtCSA (ρ = 0.56, p = 0.004), TrV (ρ = 0.52, p = 0.007), and TrV/TL (ρ = 0.53, p = 0.006). Whereas respiratory resistance at 5 Hz (R5) and 20 Hz (R20) and resonant frequencies (RFs) were significantly correlated with TrV (ρ = -0.46, p = 0.021; ρ = -0.46, p = 0.046; and ρ = -0.42, p = 0.037, respectively), IOS parameters and mtCSA were not. CONCLUSIONS: In patients with RP, TrV and mtCSA were strongly correlated with spirometric measurements. Respiratory resistances assessed by IOS correlated only with TrV. This suggests TrV assessment reflects pulmonary function in patients with RP more appropriately than mtCSA.

Fulminant orbital inflammatory syndrome in a patient with relapsing polychondritis: case report and review of the literature.

We describe a 75-year-old woman with rapid onset orbital inflammatory syndrome as her initial manifestation of relapsing polychondritis. Patient presented after the development of right eyelid swelling, erythema, and proptosis over a 48-hour period. Visual acuity was 20/30 in both eyes. Intraocular pressure was elevated in her right eye along with severe restriction of extraocular motility. Magnetic resonance imaging of the orbits revealed thickened right medial and inferior recti muscles. Serologic laboratory data was unrevealing. Patient demonstrated marked improvement within 12 hours of administration of intravenous corticosteroids. She was symptom-free after 1 week. A diagnosis of relapsing polychondritis was confirmed 3 weeks later after new onset complaints of right ear pain and a rash.

Fluorodeoxyglucose positron emission tomography/computed tomography in the diagnosis, assessment of disease activity and therapeutic response in relapsing polychondritis.

OBJECTIVE: To evaluate 18F-fluorodeoxyglucose (FDG) PET/CT in the assessment of disease activity, extent of the disease and response to therapy in relapsing polychondritis. METHODS: Twenty-five patients (9 men, 16 women) with a mean age of 38.2 years (s.d. 13.7; range 18-62), diagnosed to have relapsing polychondritis according to Damiani and Levine's modification of McAdam's criteria, who underwent PET/CT examination were included. Ten patients underwent a second PET/CT examination after therapy or during follow-up. Clinical symptoms and auxiliary examination findings were recorded. PET/CT findings were reviewed and correlated with the clinical symptoms. RESULTS: The major symptoms were aural pain (n = 21), nasal pain (n = 10), stridor (n = 5), cough (n = 9), fever (n = 8) and laryngeal tenderness (n = 8). The initial PET/CT was positive in 23/25 patients. PET/CT revealed involvement of auricular (n = 14), nasal (n = 8), laryngeal (n = 7), tracheobronchial (n = 6) and Eustachian (n = 3) cartilages with a mean maximum standardized uptake value (SUVmax) of 4.1 (s.d. 2.5; range 1.7-12.7). Fair correlation of aural/nasal pain/stridor with FDG avidity of cartilage involvement on PET/CT was noted. The key finding was detection of asymptomatic large airway involvement in seven patients (28%). Re-examination PET in 10 patients revealed complete therapeutic response (n = 5), partial response (n = 1), stable disease (n = 1), progressive disease (n = 1) and disease recurrence (n = 2). CONCLUSION: FDG PET/CT is a useful tool for the assessment of the disease activity and extent. It identified activity in clinically inaccessible sites that are of clinical significance. It is also useful in assessing treatment response and finding relapse.

Relapsing polychondritis in children: A review.

Relapsing polychondritis (RP) is a rare auto-immune disease that causes progressive destruction of cartilaginous structures. Most cases of pediatric-onset RP were published as a single case report or hand-full case series although the prevalence of RP is unknown. This review aimed to describe the characteristics of pediatric-onset RP in order to provide a comparison between childhood and adulthood features of the disease and to review the experiences of biological agents used in children with RP. In children, the diagnosis of RP is either delayed or overlooked due to low incidence and variability in clinical features. Treatment of RP is challenging due to the recurrent episodic nature of the disease. Different immunosuppressive medications, including steroid and steroid-sparing disease-modifying antirheumatic drugs (DMARDs), such as methotrexate or azathioprine, are used to treat RP. There is no rigorous clinical research to support the use of new therapeutic modalities, including biological agents. It is challenging to protocolize the treatment of pediatric-onset RP due to the rarity of the disease. Corticosteroids are the primary form of therapy. However, DMARDs and biological agents may have a role in treating patients with sustained or refractory disease.

[Clinical Features of Relapsing Polychondritis Patients Presented with Arthropathy].

Objective To explore the clinical characteristics of relapsing polychondritis(RP)patients presented with arthropathy. Methods We retrospectively analyzed the clinical data of 201 RP patients who were hospitalized in our center between December 2005 and February 2019.After 16 patients with co-existing other autoimmune diseases and malignancies were ruled out,185 RP patients entered the final analysis,among whom 16 RP patients were presented with arthropathy and 169 without arthropathy.The demographic data,clinical manifestations,laboratory findings,and prognosis were compared between these two groups. Results Five of the 16 RP patients with arthropathy at presentation were misdiagnosed as rheumatoid arthritis.Compared with RP patients without arthropathy at presentation,RP patients with arthropathy at presentation had a longer disease course[(37.50±66.50)months vs.(9.00±11.00)months,z=-3.186,P =0.001],longer time of diagnostic delay[(24.00±41.25)months vs.(7.00±9.00)months,z=-2.890,P=0.004],and higher incidence of eye(62.50% vs. 36.09%,χ2=4.309,P=0.038)and nervous system involvements(43.75% vs. 15.38%,χ2=6.205,P=0.013). Conclusions RP patients with arthropathy at presentation are most likely to be misdiagnosed as rheumatoid arthritis.These patients are characterized by longer disease course and diagnostic delay and more frequrent eye and nervous system involvements.

[Autoimmunity and autoinflammation in pathogenesis of immunoinflammatory diseases].

Rheumatic diseases relate to the group of the immunoinflammatory diseases (IID), in pathogenesis of which have a value both autoimmune and autoinflammatory processes. AIM: To present the heterogeneous pathogenesis of inflammation in IID. MATERIALS AND METHODS: It is inspected 260 patients (pts) with IID: 242 pts with systemic autoimmune diseases (SAD): 65 systemic lupus erythematosis, 50 systemic sclerosis, 127 systemic vasculitides (SV) and 18 patients with autoinflammatory diseases (AID): 8 Behcets disease, 2 periodic disease, 5 familial cold fever, 2 idiopathic lobular panniculitis and 1 relapsing polychondritis. Is carried out a study of complement, antigen of von Willebrand factor (FW:AG), antinuclear antibodies, antibodies to DNA, anti-endothelial antibodies, antibodies to topoizomeraze I (anti-Scl-70), antineutrophilic cytoplasmic antibodies (ANCA), anticardiolipin antibodies (aCL IgG and aCL IgM), cryoglobulins, VS, CRP. RESULTS: SAD were characterized by the synthesis of wide antibodies spectrum. As the basic serological marker at the screening it follows to consider antinuclear antibodies (75%). Practically in all groups it took place hypcomlemetemia with reduction of C3 and C4 complement. With systemic lupus erythematosis are revealed antibodies to DNA (71%), with ANCA-associated SV-ANCA (94%), aKL (14%); with SSD aScl-70 (17%). At Wegener granulomatosis ANCA are determined in 94% patients in the active stage. It is noted correlation ANCA with the index of the clinical activity of vasculitis. In the remaining SV groups ANCA were separated in the single cases. Cryoglobulins are noted in all patients with cryoglobulinemic vasculitis. aCL IgG and aCL IgM were the markers of antiphospholipid syndrome. Аnti-endothelial antibodies had significant oscillation spectrum. High indices FW:AG are noted with all above nosologic forms indicated, especially with Wegener granulomatosis and vasculitis hemorrhagic. Among the laboratory tests of inflammatory activity should be considered the determination of VS, CRP and FV:AG, which is also considered the marker of vascular wall defeat. Is given clinical characteristic and changes in the laboratory indices at AID: Conclusion.Isolation from the group IID of patients with AID serves as indication for a genetic study of this contingent with the approval of use for their treatment of biological therapy. Isolation from the group SAD patients with AID serves as indication for a genetic study of this contingent with the approval of use for their treatment of biological therapy.

Clinicopathological case: rapid cognitive decline and myoclonus associated with fever, arthropathy and scleritis.

A 65-year-old man presented with transient neurological symptoms, followed by rapid cognitive decline, myoclonus and fevers. He had evidence of scleritis and an arthropathy. This paper reports the clinicopathological conference discussed at the Association of British Neurologists Annual Meeting 2017.

Ocular inflammation associated with relapsing polychondritis in Japanese patients: a review of 11 patients.

PURPOSE: To investigate the clinical features of patients with ocular inflammation associated with relapsing polychondritis in Japan. METHODS: Ocular findings, systemic symptoms, and therapies were analysed retrospectively. RESULTS: Nine of 11 patients had scleritis (diffuse scleritis: six patients, posterior scleritis: two patients, episcleritis: one patient) and two patients had anterior uveitis. All cases were bilateral, and ten patients experienced recurrent episodes. Auricular chondritis was the most common systemic symptom. Ten patients were administered systemic steroids, and five patients were administered other immunosuppressive medications for severe systemic symptoms. At their last visit, none of the patients had decreased visual acuity that resulted from relapsing polychondritis-associated ocular inflammation. CONCLUSIONS: Ocular inflammation is often bilateral and recurring. Patients with ocular inflammation must be questioned regarding systemic symptoms so that the signs of relapsing polychondritis are not overlooked. Early diagnosis and prompt, appropriate treatment are important because relapsing polychondritis is a potentially lethal disease.