Propensity-Matched Analysis of the Risk of Age-Related Macular Degeneration with Systemic Immune-Mediated Inflammatory Disease.

PURPOSE: The pathogenesis of age-related macular degeneration (AMD) involves aberrant complement activation and is a leading cause of vision loss worldwide. Complement aberrations are also implicated in many systemic immune-mediated inflammatory diseases (IMIDs), but the relationship between AMD and these conditions remains undescribed. The aim of this study is to first assess the association between AMD and IMIDs, and then assess the risk of AMD in patients with specific IMIDs associated with AMD. DESIGN: Cross-sectional study and cohort study. SUBJECTS AND CONTROLS: Patients with AMD were compared with control patients with cataracts and no AMD to ensure evaluation by an ophthalmologist. Patients with IMIDs were compared with patients without IMIDs but with cataracts. METHODS: This study used deidentified data from a national database (2006-2023), using International Classification of Diseases 10 codes to select for IMIDs. Propensity score matching was based on patients on age, sex, race, ethnicity, and smoking. Odds ratios were generated for IMIDs and compared between AMD and control patients. For IMIDs associated with AMD, the risk of AMD in patients with the IMID versus patients without IMIDs was determined utilizing a cohort study design. MAIN OUTCOME MEASURES: Odds ratio of IMID, risk ratios (RRs), and 95% confidence intervals (CIs) of AMD diagnosis, given an IMID. RESULTS: After propensity score matching, AMD and control cohorts (n = 217 197 each) had a mean ± standard deviation age of 74.7 ± 10.4 years, were 56% female, and 9% of patients smoked. Age-related macular degeneration showed associations with systemic lupus erythematosus (SLE), Crohn's disease, ulcerative colitis, rheumatoid arthritis (RA), psoriasis, sarcoidosis, scleroderma, giant cell arteritis, and vasculitis. Cohorts for each positively associated IMID were created and matched to control cohorts with no IMID history. Patients with RA (RR, 1.40; 95% CI, 1.30-1.49), SLE (RR, 1.73; 95% CI, 1.37-2.18), Crohn's disease (RR, 1.42; 95% CI, 1.20-1.71), ulcerative colitis (RR, 1.45; 95% CI, 1.29-1.63), psoriasis (RR, 1.48; 95% CI, 1.37-1.60), vasculitis (RR, 1.48; 95% CI, 1.33-1.64), scleroderma (RR, 1.65; 95% CI, 1.35-2.02), and sarcoidosis (RR, 1.42; 95% CI, 1.24-1.62) showed a higher risk of developing AMD compared with controls. CONCLUSIONS: The results suggest that there is an increased risk of developing AMD in patients with RA, SLE, Crohn's disease, ulcerative colitis, psoriasis, vasculitis, scleroderma, and sarcoidosis compared with patients with no IMIDs. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Current and future advances in practice: a practical approach to the diagnosis and management of primary central nervous system vasculitis.

Primary CNS vasculitis (CNSV) is a rare, idiopathic autoimmune disease that, if untreated, can cause significant morbidity and mortality. It is a challenging diagnosis due to multiple mimics that can be difficult to differentiate, given that the CNS is an immunologically privileged and structurally isolated space. As such, diagnosis requires comprehensive multimodal investigations. Usually, a brain biopsy is required to confirm the diagnosis. Treatment of CNSV involves aggressive immunosuppression, but relapses and morbidity remain common. This expert review provides the reader with a deeper understanding of presentations of CNSV and the multiple parallel diagnostic pathways that are required to diagnose CNSV (and recognize its mimics), highlights the important knowledge gaps that exist in the disease and also highlights how we might be able to care for these patients better in the future.

The prevalence of radiological cerebral amyloid angiopathy-related inflammation in patients with cerebral amyloid angiopathy.

OBJECTIVES: Cerebral amyloid angiopathy (CAA) related inflammation (CAA-RI) is an autoimmune inflammatory condition occurring in patients with CAA. We aimed to determine the prevalence of radiological CAA-RI amongst patients with CAA and to describe their presenting clinical features. METHODS: We performed a retrospective review of electronic medical records across multiple centers within a single healthcare network. Patients who met radiological modified Boston 2.0 criteria for CAA and had white matter hyperintensity (WMH) were included. Scans were analyzed by a vascular neurologist and confirmed by a neuroradiologist blinded to clinical information for meeting criteria for possible or probable radiographic CAA-RI. RESULTS: Out of 1100 patients reviewed, 511 patients met radiological modified Boston criteria for CAA and 193 patients had WMH on MRI. A total of 55 (28.5 % of those with CAA and WMH, and 10.8 % of all CAA with or without WMH) patients had MRI brain imaging suggestive of possible or probable radiographic CAA-RI. The diagnosis of CAA-RI was reported in only 10 (18.2 %) patients initially while 20 (36.4 %) were diagnosed up to 74 months later (median 0, IQR 0-9 months). At the time of earliest probable CAA-RI findings on imaging, the most common concurrent findings were cognitive impairment (74.5 %), macro-hemorrhages (52.7 %), headache (30.9 %), seizures (14.5 %), and ischemic infarcts (14.5 %). Only 18 (32.7 %) patients were treated with immunosuppression. CONCLUSIONS: The prevalence of radiographic CAA-RI was high, and most cases were unrecognized and untreated. Further studies are needed to assess if earlier detection and treatment of radiologic CAA-RI may halt disease progression and prevent cognitive decline in these patients.

Central Nervous System Vasculitis: Primary Angiitis of the Central Nervous System and Central Nervous System Manifestations of Systemic Vasculitis.

Central nervous system vasculitis (CNSV) is a group of disorders leading to inflammatory vasculopathy within the brain, spinal cord, and leptomeninges. CNSV is divided into primary angiitis of the central nervous system (PACNS) and secondary CNSV based on the underlying etiology. PACNS is a rare inflammatory disorder with poorly understood pathophysiology and heterogeneous and highly variable clinical features. The diagnosis depends on a combination of clinical and laboratory variables, multimodal imaging, and histopathological examination as well as exclusion of mimics. Several systemic vasculitides, infectious etiologies and connective tissue disorders have been shown to cause secondary CNSV and require prompt recognition.

Clinical characteristics, brain magnetic resonance imaging findings and diagnostic approach of the primary central nervous system vasculitis according to angiographic classification.

OBJECTIVES: To determine the diagnostic accuracy for high-resolution vessel wall image (HR-VWI) and brain biopsy according to angiographical classification in patients with primary central nervous system vasculitis (PCNSV). METHODS: We extracted the patients with PCNSV who underwent the complete brain MRI protocol and cerebral vascular image from Cleveland Clinic prospective CNS vasculopathy Bioregistry. The large-medium vessel variant (LMVV) was defined as patients with cerebral vasculature indicating vasculitis in proximal or middle arterial segments, whereas vessel involvements in smaller distal branches or normal angiography were considered as the small vessel variant (SVV). We compared clinical demographics, magnetic resonance imaging (MRI) findings, and diagnostic approaches between two variants. RESULTS: In this case-control study that included 34 PCNSV patients, the LMVV group comprised a total of 11 patients (32.4%), and 23 patients (67.6%) were classified as the SVV group. The LMVV had more strong/concentric vessel wall enhancement on HR-VWI (LMVV: 90% (9/10) vs. SVV: 7.1% (1/14), p<0.001). By contrast, meningeal/parenchymal contrast enhancement lesion was more frequently observed in the SVV group (p=0.006). The majority of SVV was diagnosed by brain biopsy (SVV: 78.3% vs. LMVV: 30.8%, p=0.022). The diagnostic accuracy of the brain biopsy was 100% (18/18) in SVV and 57.1% (4/7) in LMVV, respectively (p=0.015). CONCLUSIONS: Diagnostic approach for PCNSV differs concerning the affected vessel size. HR-VWI is a useful imaging modality for the diagnosis of LMVV. Brain biopsy remains the gold standard for proving PCNSV with SVV but is still positive in almost one-third of LMVV.

Outcomes Following Acute Coronary Syndrome in Patients With and Without Rheumatic Immune-Mediated Inflammatory Diseases.

Background Rheumatic immune mediated inflammatory diseases (IMIDs) are associated with high risk of acute coronary syndrome. The long-term prognosis of acute coronary syndrome in patients with rheumatic IMIDs is not well studied. Methods and Results We identified Medicare beneficiaries admitted with a primary diagnosis of myocardial infarction (MI) from 2014 to 2019. Outcomes of patients with MI and concomitant rheumatic IMIDs including systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, dermatomyositis, or psoriasis were compared with propensity matched control patients without rheumatic IMIDs. One-to-three propensity-score matching was done for exact age, sex, race, ST-segment-elevation MI, and non-ST-segment-elevation MI variables and greedy approach on other comorbidities. The study primary outcome was all-cause mortality. The study cohort included 1 654 862 patients with 3.6% prevalence of rheumatic IMIDs, the most common of which was rheumatoid arthritis, followed by systemic lupus erythematosus. Patients with rheumatic IMIDs were younger, more likely to be women, and more likely to present with non-ST-segment-elevation MI. Patients with rheumatic IMIDs were less likely to undergo coronary angiography, percutaneous coronary intervention or coronary artery bypass grafting. After propensity-score matching, at median follow up of 24 months (interquartile range 9-45), the risk of mortality (adjusted hazard ratio [HR], 1.15 [95% CI, 1.14-1.17]), heart failure (HR, 1.12 [95% CI 1.09-1.14]), recurrent MI (HR, 1.08 [95% CI 1.06-1.11]), and coronary reintervention (HR, 1.06 [95% CI, 1.01-1.13]) (P<0.05 for all) was higher in patients with versus without rheumatic IMIDs. Conclusions Patients with MI and rheumatic IMIDs have higher risk of mortality, heart failure, recurrent MI, and need for coronary reintervention during follow-up compared with patients without rheumatic IMIDs.

Serial vessel wall enhancement pattern on high-resolution vessel wall magnetic resonance imaging and clinical implications in patients with central nervous system vasculitis.

OBJECTIVES: High-resolution vessel wall imaging (HR-VWI) often demonstrates strong and concentric vessel wall enhancement (VWE) in patients with central nervous system vasculitis (CNS-V). However, little is known about follow-up VWE characteristics and monitoring the response to treatments. The aim of this study was to investigate serial VWE patterns and its clinical practice through the management of CNS-V. METHODS: We extracted 9 patients with diagnosed of CNS-V who underwent serial HR-VWI (baseline, 1st follow-up, and 2nd follow-up) from Cleveland Clinic CNS vasculopathy registry. VWE were analysed in 17 intracranial artery segments. VWE was graded on a 3-point scale (0; none, 1; mild/eccentric, and 2; strong/concentric). VWE grade for each arterial segment was summed to create a total VWE score. We investigated the relationship between serial VWE patterns and clinical course. RESULTS: In unique 153 intracranial arterial segments, 39 arteries (25.5%) had strong/concentric VWE on baseline HR-VWI. The positive rates of concentric VWE have decreased to 12.4% (19/153) at 1st follow-up and (10/153) 6.5% at 2nd follow-up, respectively (p<0.001). Mean total VWE scores have significantly decreased over time courses (p=0.034). Two patients had relapse at 1st follow-up image. In relapse cases, mean total VWE scores have worsened at 1st follow-up (baseline:2.0 to 1st follow-up: 6.0). After intensive immunosuppressive treatment, mean VWE scores have improved at 2nd follow-up (1st follow-up: 6.0 to 2nd follow-up: 2.0). CONCLUSIONS: Decreasing contrast VWE at follow-up images may indicate good response to treatment in CNS-V. By contrast, relapse patients might have temporal VWE worsening during the clinical course.

Retinal Vasculitis Associated With Dermatomyositis Treated With Intravenous Steroids.

Purpose: This work aims to present treatment and long-term follow-up of a 31-year-old woman with dermatomyositis who presented with hemorrhagic retinal vasculitis and macular edema. Methods: A retrospective case report is presented. Results: A 31-year-old woman with dermatomyositis treated with systemic immunosuppression was evaluated for acute, reduced vision. Best-corrected visual acuity was hand motion in the right eye and 20/200 in the left eye. Fundus examination revealed diffuse intraretinal hemorrhages, cotton-wool spots, and vascular sheathing with a frosted branch angiitis-like appearance. Optical coherence tomography revealed significant macular edema and subretinal fluid that quickly resolved after admission and treatment with intravenous steroids. Multimodal imaging at 7-year follow-up disclosed long-term sequelae including peripheral nonperfusion and retinal neovascularization. Conclusions: When vasculitis associated with dermatomyositis is treated aggressively with intravenous steroids at initial presentation, good visual acuity outcomes can be achieved, but long-term consequences of retinal nonperfusion and neovascularization persist.

Novel de novo TREX1 mutation in a patient with retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations mimicking demyelinating disease.

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare fatal autosomal dominant vasculopathy associated with mutations in the TREX1 gene. Only one de novo case has been reported in the literature. We report the long-term clinical, radiological, and pathological presentation of a patient with a de novo and novel mutation in this gene. Description of the clinical, genetic, imaging and pathologic characteristics is important to better characterize RVCL-S and prevent unnecessary interventions. RVCL-S should be considered in patients with tumefactive brain lesions unresponsive to immunotherapy.

Safety of recombinant zoster vaccine: a retrospective study of 622 rheumatology patients.

OBJECTIVES: To provide insight into the safety of recombinant zoster vaccine (RZV) in patients with immune-mediated inflammatory diseases (IMID). METHODS: Patients who received RZV in a single-centre rheumatology department were retrospectively included. An IMID flare was defined as (i) a documentation of flare in the office notes or patient portal communication or (ii) new prednisone prescription, in the 12 weeks after each dose. RESULTS: Six-hundred and twenty-two patients were included (67% female, median age 67 years), 8.5% of them experienced adverse events (AEs) and herpes zoster (HZ) incidence was 0.6% after median follow-up of 36 weeks. Of 359 IMID patients: 88 had RA (25%), 50 vasculitis (14%) and 29 PMR (8%). At vaccination, 35% were on glucocorticoids (GC). Fifty-nine patients (16%) experienced a flare, 18 flares occurred in temporal relation to a treatment change (31%). RA patients had the highest flare rate (n = 21, 24%), 25% of patients who flared required adjustment of immunosuppression. In a multivariate analysis, use of GC at time of vaccination was associated with flare after vaccination [odds ratio (OR) 2.31 (1.3-4.1), P =0.004]. A time-to-flare survival analysis (Cox-model) showed that GC was a significant predictor of IMID flare after first RZV dose [hazard ratio (HR) 2.4 (1.3-4.5), P =0.0039] and that a flare after the first dose was associated with flaring after the second RZV dose [HR 3.9 (1.7-9), P =0.0015]. CONCLUSION: RZV administration in patients with IMIDs was generally well-tolerated, though mild flares were not uncommon in the first 12 weeks after vaccination. These data may provide useful information for patient education when considering RZV administration.

Recurrent Nephritis and/or Pulmonary Hemorrhage in Patients with Anti-Glomerular Basement Membrane Disease with and without ANCA Positivity.

Introduction: Anti-glomerular basement membrane (anti-GBM) disease is characterized by rapidly progressive glomerular nephritis with or without pulmonary hemorrhage with disease severity correlating with antibody titer. Following treatment, relapse is rare but has been reported in the literature. The objective of this study was to assess for clinical, serologic, and histologic differences associated with disease relapse in patients with anti-GBM disease. Methods: Patients seen at our facility between 1997 and 2017 were screened for anti-GBM disease by ICD 9/10 codes. They were included if the diagnosis was confirmed by a board-certified rheumatologist or nephrologist and had positive antibodies and/or biopsy results consistent with anti-GBM disease. Relapsing disease was defined as recurrence of pulmonary or renal manifestations after achieving remission following the initial presentation. All charts were reviewed for baseline demographics, clinical manifestations, and antibody positivity and compared between groups. Results: 40 patients were confirmed as having anti-GBM disease. Mean follow-up from disease onset to the date of last follow-up was 56.2 months. 8 patients had relapsing disease and 32 patients had nonrelapsing disease. Baseline characteristics and clinical manifestations were similar between groups. Patients with relapsing disease had a high incidence of anti-neutrophilic cytoplasmic antibody (ANCA) co-positivity as compared to nonrelapsing patients (50 vs. 15.6%, respectively, p = 0.059), but this did not reach statistical significance. In patients with relapsing disease, only one had positive anti-GBM antibodies at time of relapse. Conclusions: In this study, patients with relapsing disease had a high incidence of ANCA co-positivity (50%). In patients with newly diagnosed anti-GBM disease, ANCAs should be obtained to assess for the risk of relapse and to help guide long-term follow-up and treatment.

Recurrence Rates of Inflammation after Switching from the Originator Infliximab to Biosimilar Infliximab-abda for Noninfectious Uveitis.

PURPOSE: To describe the frequency of ocular flares in patients with noninfectious uveitis who were switched from the originator infliximab to a biosimilar infliximab. DESIGN: Retrospective case series. METHODS: All patients with noninfectious uveitis who were switched from the originator infliximab to biosimilar infliximab-abda for nonmedical reasons were reviewed. Patients were excluded if they had less than 3 months of follow-up on either drug. Data included patient demographics, infliximab dosage information, additional immunosuppression medications, and numbers of and times to flares. The main study outcome was frequency of flares, defined as new or worsening inflammatory activity on examination or imaging. RESULTS: A total of 17 patients met the inclusion criteria. There were no statistical differences between the duration of follow-up while on the originator and the duration while on the biosimilar infliximab (12.0 vs. 10.1 months, respectively; P = .307). Patients experienced more flares per person-years after switching to infliximab-abda (.92), than on the originator infliximab (0.19; P = .028). Four of the 6 patients (66.7%) who experienced flare after switching to infliximab-abda did so within 90 days. Only 1 patient had flares while on originator infliximab went on to develop a single flare on infliximab-abda. The final normalized dosage for patients who flared and remained on infliximab-abda (1.301 mg/kg/week) was higher than that for those who did not flare (1.186 mg/kg/week) but was not statistically significant (P = .417). CONCLUSIONS: Patients who were switched to biosimilar infliximab-abda experience more flares than when previously treated with the originator infliximab. Providers should closely observe patients who switch to biosimilar infliximab, especially within the first 90 days. Patients who do have flares after switching may achieve quiescence with increased biosimilar dosage.

Noninfectious Autoimmune Scleritis: Recognition, Systemic Associations, and Therapy.

PURPOSE OF REVIEW: The aim of this review is to provide the information necessary for recognizing scleritis in rheumatology patients, recognize associated systemic diseases in scleritis patients referred to rheumatology, and choose the best conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biologic therapy, based on the most recent data. RECENT FINDINGS: Scleritis is most often associated with systemic conditions, particularly autoimmune conditions. Rheumatologists should be most vigilant about rheumatoid arthritis and ANCA-associated vasculitis. A recent systemic association has been found with IgG4-related disease as well. Most of the therapeutic decisions are based on observational data. Most recently, there is increasing evidence of the role of rituximab for refractory disease. Scleritis is a severe inflammatory ocular condition that leads to complications including vision loss. It can precede a systemic autoimmune disease diagnosis, especially in the case of vasculitis. Prompt recognition and adequate therapy are needed in order to avoid serious ocular complications. There is an unmet need for (1) head-to-heat trials on csDMARDs and biologic drugs for the treatment of idiopathic scleritis and (2) randomized controlled trials on the treatment of refractory cases.

Differentiation between neurosarcoidosis and primary central nervous system vasculitis based on demographic, cerebrospinal and imaging features.

OBJECTIVES: Neurosarcoidosis (NS) and primary angiitis of central nervous system (PACNS) are inflammatory diseases affecting central nervous system, with overlapping clinical and pathological characteristics. Distinguishing these diseases is important given distinct therapeutic implications. In this study, we aimed to compare demographic, CSF and MRI characteristics between these two conditions. METHODS: All the clinical, CSF and laboratory characteristics at the time of presentation were retrieved from electronic medical records. Brain and/or spinal cord MRI performed near the time of presentation were blindly evaluated by two neuroradiologists. Data regarding involvement of pachy- and leptomeninges, basal meninges, cranial nerves, cerebral grey and white matter, and spinal cord were recorded for each patient. RESULTS: 78 patients with PACNS and 25 patients with NS were included in the study. Mean age of patients was 43.7 (±16.7) and 43.6 (±12.5) in PACNS and NS, respectively. African-American race was found to be associated with the diagnosis of NS rather than PACNS. Patients with PACNS had higher frequency of cerebral involvement, while patients with NS demonstrated more frequent spinal cord, basal meningeal and cranial nerve involvements. CONCLUSIONS: These findings suggest that MRI can be an efficient tool in distinguishing PACNS from NS. A follow-up study with a larger sample size would be required to validate our results.

Central nervous system vasculitis: advances in diagnosis.

PURPOSE OF REVIEW: The main purpose of this review is to present advances in diagnostics of central nervous system vasculitis (CNS-V). RECENT FINDINGS: Progress in molecular technologies and neuroimaging have added formidably to our knowledge of CNS-V. Next-generation sequencing has the promise to enhance our ability to diagnose, interrogate, and track infectious diseases, making this test attractive and capable of avoiding brain biopsy in cases where CNS infections are suspected. Further the continuum of neuroimaging progress has advanced our ability to diagnose CNS-V. Our capability to visualize the vessel wall have added a great value in differentiating inflammatory from noninflammatory vasculopathies. New genetic variations are being exposed with exome and genome sequences which will aid future diagnosis. SUMMARY: We have witnessed tremendous advances in CNS-V mainly by our ability to rule out mimics. Progress in molecular technologies, neuroimaging and genetic studies will continue to enhance the field further.

Exploratory proteomic analysis implicates the alternative complement cascade in primary CNS vasculitis.

OBJECTIVE: To identify molecular correlates of primary angiitis of the CNS (PACNS) through proteomic analysis of CSF from a biopsy-proven patient cohort. METHODS: Using mass spectrometry, we quantitatively compared the CSF proteome of patients with biopsy-proven PACNS (n = 8) to CSF from individuals with noninflammatory conditions (n = 11). Significantly enriched molecular pathways were identified with a gene ontology workflow, and high confidence hits within enriched pathways (fold change >1.5 and concordant Benjamini-Hochberg-adjusted p < 0.05 on DeSeq and t test) were identified as differentially regulated proteins. RESULTS: Compared to noninflammatory controls, 283 proteins were differentially expressed in the CSF of patients with PACNS, with significant enrichment of the complement cascade pathway (C4-binding protein, CD55, CD59, properdin, complement C5, complement C8, and complement C9) and neural cell adhesion molecules. A subset of clinically relevant findings were validated by Western blot and commercial ELISA. CONCLUSIONS: In this exploratory study, we found evidence of deregulation of the alternative complement cascade in CSF from biopsy-proven PACNS compared to noninflammatory controls. More specifically, several regulators of the C3 and C5 convertases and components of the terminal cascade were significantly altered. These preliminary findings shed light on a previously unappreciated similarity between PACNS and systemic vasculitides, especially anti-neutrophil cytoplasmic antibody-associated vasculitis. The therapeutic implications of this common biology and the diagnostic and therapeutic utility of individual proteomic findings warrant validation in larger cohorts.

Long-term outcomes of patients with primary angiitis of the central nervous system.

OBJECTIVES: Primary angiitis of the central nervous system (PACNS) is a vasculitis confined to the brain and spinal cord, which often presents with severe cognitive and functional deficits. Despite progress in diagnosis, little is still known about long-term outcomes. Our aim was to evaluate long-term functional capabilities, quality of life, and depression, and to determine the effect of treatment duration on patient outcomes. METHODS: We identified patients by ICD-9 codes for cerebral angiitis, and included them if they met two of the three following criteria: inflammatory cerebrospinal fluid (CSF), cerebral angiogram typical of vasculitis, or findings of vasculitis on pathologic examination of brain tissue. Disability was assessed by the Barthel Index, quality of life was assessed by EuroQol, and depression was assessed with Patient Health Questionnaire. RESULTS: Seventy-eight patients met the inclusion criteria, of which 27 responded to the questionnaire (34.6%). Mean follow-up of those who responded was 5.5 years (± 4.7). Nineteen of 27 patients (70.4%) had mild disability; meanwhile, 5 (18.5%) had severe disability. Fourteen of 27 patients (51.9%) had no mobility problem, 18 (66.7%) had no problems with self-care, 15 (55.6%) had no problems with usual activities, 14 (51.9%) had no pain, and 8 (29.6%) had no anxiety. Approximately 70% of patients had minimal or no depression. CONCLUSIONS: This is the longest reported follow-up of patients with PACNS described in the literature to date. Most patients had mild long-term disability and minimal to no depression, which may be reflective of treatment advances.

Characteristics of inflammatory eye disease associated with hidradenitis suppurativa.

OBJECTIVE: Hidradenitis suppurativa (HS) is an inflammatory skin condition that can cause profound morbidity. Patients can present with recurrent nodules, sinus tract formation, abscesses, and/or scarring, mainly affecting the intertriginous areas. Case reports have documented the coexistence of HS and inflammatory eye disease (IED). Herein, we aimed to assess the types of IED associated with HS and the outcomes of IED treatment in patients with HS. METHODS: All the cases with a diagnosis of HS and any IED were identified. Patients with episcleritis and sicca were excluded, and only those with chronic IED were included. An independent ophthalmologist reviewed notes to ensure accuracy of IED diagnosis. Demographics, IED patterns, comorbidities, treatments, and outcomes were retrieved from patient charts. RESULTS: Twenty patients [16 females (80%); 12 African Americans (60%)] were included in this study after the exclusion of 436 cases due to lack of data. The mean age at the diagnosis of HS and IED was 42.1 and 43.6 years, respectively. Thirteen patients had uveitis (65%), six had scleritis (30%), and one had peripheral ulcerative keratitis. Thirteen out of 20 patients (65%) had multiple autoimmune and/or inflammatory comorbidities, including inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, and lupus. Seven patients (35%) did not have any comorbid inflammatory/autoimmune conditions. CONCLUSION: One-third of the patients with HS and IED did not have any autoimmune or inflammatory comorbidity that could explain the eye involvement. The potential association between HS and IED might be a manifestation of a common immune dysregulation phenomenon. Furthermore, the management of IED required an escalation of therapy to systemic immunosuppressive agents in 70% of patients with HS.

TREX1 is expressed by microglia in normal human brain and increases in regions affected by ischemia.

BACKGROUND: Mutations in the three-prime repair exonuclease 1 (TREX1) gene have been associated with neurological diseases, including Retinal Vasculopathy with Cerebral Leukoencephalopathy (RVCL). However, the endogenous expression of TREX1 in human brain has not been studied. METHODS: We produced a rabbit polyclonal antibody (pAb) to TREX1 to characterize TREX1 by Western blotting (WB) of cell lysates from normal controls and subjects carrying an RVCL frame-shift mutation. Dual staining was performed to determine cell types expressing TREX1 in human brain tissue. TREX1 distribution in human brain was further evaluated by immunohistochemical analyses of formalin-fixed, paraffin-embedded samples from normal controls and patients with RVCL and ischemic stroke. RESULTS: After validating the specificity of our anti-TREX1 rabbit pAb, WB analysis was utilized to detect the endogenous wild-type and frame-shift mutant of TREX1 in cell lysates. Dual staining in human brain tissues from patients with RVCL and normal controls localized TREX1 to a subset of microglia and macrophages. Quantification of immunohistochemical staining of the cerebral cortex revealed that TREX1+ microglia were primarily in the gray matter of normal controls (22.7 ± 5.1% and 5.5 ± 1.9% of Iba1+ microglia in gray and white matter, respectively) and commonly in association with the microvasculature. In contrast, in subjects with RVCL, the TREX1+ microglia were predominantly located in the white matter of normal appearing cerebral cortex (11.8 ± 3.1% and 38.9 ± 5.8% of Iba1+ microglia in gray and white matter, respectively). The number of TREX1+ microglia was increased in ischemic brain lesions in central nervous system of RVCL and stroke patients. CONCLUSIONS: TREX1 is expressed by a subset of microglia in normal human brain, often in close proximity to the microvasculature, and increases in the setting of ischemic lesions. These findings suggest a role for TREX1+ microglia in vessel homeostasis and response to ischemic injury.