Occurrence and risk factors of uveitis in juvenile psoriatic arthritis: Data from a population-based nationwide study in Germany

Objective Data on uveitis in juvenile psoriatic arthritis (JPsA), a category of juvenile idiopathic arthritis (JIA), are scarce. We describe prevalence and risk factors for JPsA-associated uveitis (JPsA-U). Methods Cross-sectional data from the National Pediatric Rheumatological Database (from 2002 to 2014) were used to characterize JPsA-U and assess risk factors for uveitis development. Results Uveitis developed in 6.6% of 1862 JPsA patients. JPsA-U patients were more frequently female (73.0 vs 62.9%, p=0.031), ANA positive (60.3 vs 37.0%, p<0.001), younger at JPsA onset (5.3 ± 4.1 vs 9.3 ± 4.4 years, p<0.001), and received DMARD (disease modifying antirheumatic drug) treatment significantly more frequently than JPsA patients without uveitis. On multivariable analysis of a subgroup of 655 patients, mean cJADAS during study documentation was significantly associated with uveitis development. Children with early onset of JPsA were significantly more frequently ANA positive (48.4% vs 35.7% for those younger than 5 years at JPsA onset versus those aged 5 years and older, p<0.001), less often affected by skin disease (55.3% vs 61.0%, p=0.032), but more frequently by uveitis (17.3% vs 3.8%, p<0.001), and required DMARD treatment more frequently (52.9% vs 43.8%, p<0.001). Conclusion The characteristics of JPsA patients developing uveitis are similar to those of patients with uveitis in other JIA categories, such as oligoarticular JIA. Especially those children with early onset of JPsA seem to be at a higher risk for ocular involvement. Our data support the notion of a major clinical difference between those patients with early versus late onset of JPsA.

Plasma Homocysteine in Behcet's Disease: A Systematic Review and Meta-Analysis

Aim To evaluate the relevance of plasma homocysteine (HC) in Behcet's disease (BD) and its clinical manifestations. Methods Systematic review of EMBASE and PubMed databases according to PRISMA guidelines from inception to July 2021; random-effects meta-analyses for continuous outcomes. Results The search strategy retrieved 48 case–control (2,669 BD and 2,245 control participants) and 5 cohort studies (708 BD participants). Plasma HC was higher in BD than in controls (p < 0.0001) with wide heterogeneity (I2 = 89.7%) that remained unchanged after sensitivity analysis according to year of article publication, age of BD participants, study size, study quality, method of HC determination, and male/female ratio >1.5; some pooled ethnicities explained a small part of the heterogeneity (I2 = 16.3%). Active BD participants had higher HC than inactive ones (p < 0.0001), with moderate heterogeneity (I2 = 49.2%) that disappeared after removal of an outlier study with very high disease activity. BD participants with any vascular involvement had higher HC than those without (p < 0.0001) with wide heterogeneity (I2 = 89.7%); subgroup analysis on venous thrombosis only changed neither effect size (p < 0.0001) nor heterogeneity (I2 = 72.7%). BD participants with ocular involvement had higher HC than those without (p < 0.0001) with moderate heterogeneity (I2 = 40.3%). Conclusion Although causality cannot be inferred, the consistency of the elevation of plasma HC in BD, particularly in patients with active disease, with vascular and ocular involvement suggests an intrinsic involvement of HC in these clinical manifestations.

Conjunctival lymphangiectasia and retinal angiopathy in hereditary transthyretin amyloidosis

Background Hereditary transthyretin amyloidosis (ATTR amyloidosis) is a rare condition where a mutation in the transthyretin gene leads to systemic deposition of amyloid. The manifestations and prognosis of ATTR amyloidosis depends on the specific ATTR mutation, with over 100 mutations reported in the literature. The manifestations of many rare forms of ATTR amyloidosis have not been well described, particularly the late-onset ophthalmic findings. Case presentation We present the case of a 43-year-old Caucasian male with a diagnosis of ATTRD18E amyloidosis confirmed by fat pad biopsy. He had diffuse systemic involvement, including cardiovascular, pulmonary, and gastrointestinal symptoms. He also had significant ocular involvement including vitreous opacities, retinal angiopathy, and conjunctival lymphangiectasia. These ocular findings modestly progressed at 2-year follow-up. Discussion The ATTRD18E mutation is a rare variant, with few described cases. To our knowledge, this is the first documented case of ATTRD18E amyloidosis with significant ocular involvement. These ocular findings may serve as a relevant biomarker for severe disease prognosis in ATTRD18E amyloidosis. With improving treatments addressing the systemic symptoms of ATTR amyloidosis, a better understanding of the late-onset ocular symptoms is becoming increasingly relevant.

Bilateral intraocular and lung involvements associated with Nasal NK/T-cell lymphoma

Background To report a rare case of nasal natural killer/T (NK/T) cell lymphoma with bilateral intraocular and lung metastasis and to further describe the clinical features of intraocular manifestations. Case presentation A 54-year-old man presented with a 3-month history of left nasal congestion, and bilateral vision impairment of one week duration. Subsequent maxillary computed tomography (CT) and multiple biopsies confirmed the diagnosis of nasal NK/T-cell lymphoma. EBV-encoded small RNA (EBER) in situ hybridization revealed EBV infection. A comprehensive ophthalmic examination found lymphoma-associated retinopathy and choroidopathy, which presented as bilateral diverse patterns and retinal detachment. In addition, the chest CT showed multiple scattered nodules in both lungs, and soft-tissue mass in the left hilum with mediastinal and axillary lymphadenopathy. The condition of this patient deteriorated rapidly and he died shortly after diagnosis. Conclusions The rarity of secondary ocular NK/T-cell lymphoma makes it challenging to identify these tumors early. Both otolaryngologist and ophthalmologists should be aware of ocular involvement and other secondary manifestations of NK/T-cell lymphoma.

Clinical characteristics and disease patterns of patients with relapsing polychondritis: a retrospective cohort

Background Relapsing polychondritis (RP) is a rare autoimmune disease affected various cartilage, Patients with tracheal cartilage involvement are different from other patients. The objectives of this study were to allocated RP patients into two subgroups by chest computed tomography (CT) and compare the clinical features and disease patterns of each group.Methods A retrospective cohort study collected RP patients hospitalized at the Beijing Chao-Yang Hospital between January 2012 - August 2021. Patients were divided into two groups: respiratory involvement group and non-respiratory involvement group according to chest CT.Results In our study, respiratory involvement found in 59.7% (n=43) patients, which had higher rate of costochondritis, fewer rate of Inflammatory eye disease and auricular chondritis than those in non-respiratory involvement. Compared with non-respiratory involvement subgroup, The incidence of pulmonary infection marginally increased and those inflammatory indexes except for CAR were significantly higher in respiratory involvement subgroup, further subgroup analysis found that there was no significant relationship between inflammatory indexes and pulmonary infection. Finally, 5 patients died during the follow-up in this cohort with a median follow-up time of 6 years (range 3-8 years).Conclusion 59.7% of patients had respiratory involvement according to chest CT findings in our cohort, which had a strong inverse relationship between respiratory and auricular, ocular involvement. Increase inflammatory indexes were not correlated with pulmonary infection, suggesting that patients with respiratory involvement had a higher disease activity index of RP. The probability of survival was not found significant in two subgroups.

Findings and Graduation of Sarcoidosis-Related Uveitis: A Single-Center Study

Ocular involvement is present in up to 79% of sarcoid patients. Uveitis is the main ocular manifestation and presents as a chronic intraocular inflammatory condition with potentially detrimental effects on visual acuity and quality of life. This retrospective study was conducted to explore the incidence and characteristics of ocular sarcoidosis in a single tertiary ophthalmology center. Medical records of 84 patients presenting between June 2007 and March 2021 were analyzed. Based on the “International Workshop on Ocular Sarcoidosis” (IWOS) criteria, ocular sarcoidosis was determined as: definite (n = 24; 28.6%), presumed (n = 33; 39.3%), probable (n = 10; 11.9%), and indefinite (n = 17; 20.2%) in our study population. In 43.9% of the definite and presumed cases, the eye was primarily affected. In addition to specific ocular findings, the diagnosis was supported by biopsy (28.6%) and chest x-ray or computer tomography (66.7%). Moreover, an increased soluble interleukin-2 receptor (sIL-2R) expression (76.2%), elevated angiotensin-converting enzyme (ACE) levels (34.8%), and lymphocytopenia (35.1%) were valuable laboratory findings. Co-affected organs were lungs (60.7%), skin (15.5%), and central nervous system (8.3%). Our findings support the prominent role of the eye in the early detection of sarcoidosis. In addition to the IWOS criteria, sIL-2R, in particular, was shown to be relevant in establishing the diagnosis.

Analyses and Correlation of Pathologic and Ocular Cutaneous Changes in Murine Graft versus Host Disease

Graft versus host disease (GVHD) is initiated by donor allo-reactive T cells activated against recipient antigens. Chronic GVHD (cGVHD) is characterized by immune responses that may resemble autoimmune features present in the scleroderma and Sjogren’s syndrome. Unfortunately, ocular involvement occurs in approximately 60–90% of patients with cGVHD following allo-hematopoietic stem cell transplants (aHSCT). Ocular GVHD (oGVHD) may affect vision due to ocular adnexa damage leading to dry eye and keratopathy. Several other compartments including the skin are major targets of GVHD effector pathways. Using mouse aHSCT models, the objective was to characterize cGVHD associated alterations in the eye and skin to assess for correlations between these two organs. The examination of multiple models of MHC-matched and MHC-mismatched aHSCT identified a correlation between ocular and cutaneous involvement accompanying cGVHD. Studies detected a “positive” correlation, i.e., when cGVHD-induced ocular alterations were observed, cutaneous compartment alterations were also observed. When no or minimal ocular signs were detected, no or minimal skin changes were observed. In total, these findings suggest underlying cGVHD-inducing pathological immune mechanisms may be shared between the eye and skin. Based on the present observations, we posit that when skin involvement is present in aHSCT patients with cGVHD, the evaluation of the ocular surface by an ophthalmologist could potentially be of value.

Multi-state model for predicting ocular progression in acute Stevens-Johnson syndrome/toxic epidermal necrolysis

This study aimed to clarify the etiologic factors predicting acute ocular progression in SJS/TEN, and identify patients who require immediate and intensive ophthalmological treatment. We previously conducted two Japanese Surveys of SJS/TEN (i.e., cases arising between 2005–2007 and between 2008–2010), and obtained the medical records, including detailed dermatological and ophthalmological findings, of 230 patients. Acute ocular severity was evaluated as none, mild, severe, and very severe. A multi-state model assuming the Markov process based on the Cox proportional hazards model was used to elucidate the specific factors affecting the acute ocular progression. Our findings revealed that of the total 230 patients, 23 (24%) of 97 cases that were mild at initial presentation worsened to severe/very severe. Acute ocular progression developed within 3 weeks from disease onset. Exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) and younger patient age were found to be statistically significant for the progression of ocular severity from mild to severe/very severe [hazard ratio (HR) 3.83; 95% confidence interval (CI) 1.48 to 9.91] and none to severe/very severe [HR 0.98; 95% CI 0.97 to 0.99], respectively. The acute ocular severity score at worst-condition was found to be significantly correlated with ocular sequelae. Thus, our detailed findings on acute ocular progression revealed that in 24% of SJS/TEN cases with ocular involvement, ocular severity progresses even after initiating intensive treatment, and that in younger-age patients with a history of exposure to NSAIDs, very strict attention must be given to their ophthalmological appearances.

Sensorineural Hearing Loss of Suspected Autoimmune Etiology: Two Cases of Cogan’s Syndrome

Cogan’s syndrome is a rare inflammatory disease characterized by non-syphilitic keratitis and vestibulo-auditory symptoms including hearing loss, tinnitus, and vertigo. Although its precise pathogenesis is not known, Cogan’s syndrome is generally considered an autoimmune disease. This hypothesis is supported by the frequently successful remission of hearing loss after steroid administration and the association with other autoimmune disorders such as rheumatoid arthritis. Medical treatment of Cogan’s syndrome depends on disease severity and on how extensive the disease is. The involvement of inner ear pathology requires systemic corticosteroid therapy. In cases of treatment failure or the need for a corticosteroid-sparing effect, other immunosuppressive drugs can be used. We experienced two patients with typical Cogan’s syndrome, presenting bilateral progressive sensorineural hearing loss and dizziness with ocular involvement, which we have successfully treated with systemic steroid administration and immunosuppressive therapy.