Comorbid Autoimmune Diseases Research Articles

Large-scale global retrospective study on the interaction between ancestry and risk of comorbid autoimmune diseases in patients with pemphigus

The pemphigus family of skin blistering diseases represents a rare yet potentially life-threatening condition characterized by multiple known genetic loci associated with other autoimmune disorders. While several studies have empirically indicated an increased risk of developing additional autoimmune diseases in individuals with pemphigus, the scarcity of data and the rarity of pemphigus have hindered efforts to establish and generalize these associations across diverse populations. In this study, we analyzed a dataset comprising 126 million patients, including 18,000 with pemphigus, to assess the likelihood of developing any of 74 autoimmune diseases following a diagnosis of pemphigus. For a subset of 26 diseases from this list with adequate patient numbers, we conducted further case-control retrospective analyses to quantify the odds and hazard ratios of developing comorbid conditions across various ethnicities. Our findings reveal highly significant and generalizable associations between pemphigus and pemphigoid diseases, discoid lupus erythematosus, lichen planus, and undifferentiated connective tissue disease, among others.

Prevalence of comorbid autoimmune diseases and antibodies in newly diagnosed multiple sclerosis patients

BackgroundDiagnosing multiple sclerosis (MS) is challenging due to diverse symptoms and the absence of specific biomarkers. Concurrent autoimmune diseases (AID) or non-specific antibodies further complicate diagnosis, progression monitoring, and management. Data on AID prevalence in MS patients are sparse. This study aims to identify concurrent AIDs alongside MS.MethodsIn this retrospective single-center study, we analyzed patient records at our university hospital from 2010 to 2017, focusing on cases suspected of inflammatory demyelinating disease. The 2017 McDonald criteria were applied. Additionally, we measured neurofilament light (NfL) levels from available CSF samples in our biobank.ResultsWe identified a total of 315 patients, of whom 66% were women. In total, 13.7% of all patients had concurrent AID, while 20.3% had isolated antibody findings without AID. The most common AID was autoimmune thyroiditis (8.9%), followed by chronic inflammatory skin diseases (1.6%), arthritis (1%), type 1 diabetes (1%), Sjögren’s syndrome (0.6%), and inflammatory bowel diseases (0.6%). Cardiolipin antibodies were the most frequent isolated antibody finding (8.6%). Our data showed that, from the perspective of the initial demyelinating event, neither comorbid AID nor isolated antibodies significantly influenced relapses or MS progression over a median follow-up of 9 months. Standard CSF parameters and NfL levels were similar between the groups at the time of MS diagnosis.ConclusionOur study shows that AIDs, particularly autoimmune thyroiditis, frequently occur at the onset of MS. The proportion of AIDs commonly treated with immunomodulatory therapy in our cohort was similar to that observed in the general population. Comorbid AID did not affect NfL levels, indicating similar disease activity. Future research should explore new AID emergence during the course of MS, especially considering the increased incidence of rheumatic diseases later in life.

Screening for comorbid autoimmune disease should be considered in children with ANA positive juvenile idiopathic arthritis – results from the south-Swedish juvenile idiopathic arthritis cohort

BackgroundThere is no consensus or clinical guidelines for screening routines of autoimmune disease in individuals with juvenile idiopathic arthritis (JIA), since results are conflicting whether the risk for such conditions is increased or not among individuals with JIA. The aim of this study was to investigate if the frequency of comorbid autoimmune conditions is increased after JIA diagnosis in a validated population-based JIA cohort in southern Sweden.MethodsAutoimmune comorbidities were evaluated in a pre-existing population-based JIA cohort of 302 participants, constituting of individuals diagnosed with a validated JIA diagnosis 2000–2010 in southern Sweden. The comorbidities were determined through analysis of diagnosis codes registered after the JIA diagnosis and until 2019. With the use of a reference population of 1510 age- and sex matched individuals, hazard ratios (HR) were calculated with Cox proportional models.ResultsDuring the study period, 7.7% of the JIA cohort received an autoimmune diagnosis after their JIA diagnosis. Individuals with JIA had an increased risk of autoimmune diseases in general (HR 4.11, 95% CI 2.13–7.91) within the first 7 years of disease, as well as separately for coeliac disease (HR 5.24, 95% CI 1.76–15.65) and hypothyroidism (HR 3.74, 95% CI 1.14–12.30) compared to the reference population. Antinuclear antibody (ANA) positivity was associated with a significantly increased risk of comorbid autoimmune disease in the JIA cohort, with HR 6.21 (95% CI 1.64–23.55) for ANA positive individuals.ConclusionsIndividuals with JIA have a significantly increased risk of being diagnosed with an autoimmune condition after receiving their JIA diagnosis compared to matched references. ANA positivity is associated with a further increased risk. Our results emphasize awareness in physicians of additional autoimmune disorders in individuals with JIA and advocate serological screening of autoimmune conditions during follow-up.

Aquaporin4-IgG seropositivity significantly increases the risk of comorbid autoimmune diseases in NMOSD patients: population-based registry data.

The aim of our study was to estimate the frequency of autoimmune comorbidities, in NMOSD patients from the national Serbian NMOSD Registry. Our study comprises 136 patients with NMOSD, diagnosed according to the NMOSD criteria 2015. At the time of the study, in the Registry were collected demographic and clinical data, including those related to the coexisting comorbidities and pathogenic autoantibodies. Not all patients were tested for all autoimmune antibodies. None of the seronegative aquaporin4-IgG (AQP4-IgG) NMOSD patients, included in the Registry, were positive for the myelin oligodendrocyte glycoprotein IgG. Among 136 NMOSD patients, 50 (36.8%) had at least one associated autoimmune disorder. AQP4-IgG was present in the sera from 106 patients (77.9%), the proportion of NMOSD patients with autoimmune comorbidities being significantly higher in the AQP4-IgG positive subgroup in comparison to the AQP4-IgG negative (p = 0.002). AQP4-IgG seropositive NMOSD patients had 5.2-fold higher risk of comorbid autoimmune diseases (OR = 5.2, 95% CI 1.4-18.5, p = 0.012). The most frequently reported diseases were autoimmune thyroid disease (15.4%), Sjogren's syndrome (11.0%), systemic lupus erythematosus (5.1%), myasthenia gravis (4.4%), and primary antiphospholipid antibody syndrome (2.9%). Antinuclear antibodies (ANAs) were frequently detected in the subgroup of NMOSD patients tested for this antibody (50/92; 54.3%). The higher frequency of ANAs and anti-extractable nuclear antigen autoantibodies, in the subgroups of AQP4-IgG-positive patients compared to the AQP4-IgG negative, tested for these antibodies, was statistically significant (p = 0.009, and p = 0.015, respectively). In conclusion, based on our results, in a defined cohort with European ethnical background, a wide spectrum of autoimmune diseases is frequently associated with AQP4-IgG seropositive NMOSD patients.

Long-Term Effects and Prognosis Following Suction Blister Epidermal Grafting in Vitiligo Patients.

Suction blister epidermal grafting (SBEG) is currently one of the most prevalent surgical methods for stable vitiligo. To investigate the long-term outcomes of vitiligo patients who underwent SBEG and to explore risk factors associated with postoperative relapse. A retrospective cohort study was conducted in patients who underwent SBEG in our department between January 2016 and December 2022. Treatment outcomes, including repigmentation rate, adverse events, and postoperative relapse, were surveyed via telephone interview or out-=patient visit. Multivariate logistic regression models were used to assess the potential risk factors for postoperative relapse. Statistical significance was assumed at P < .05. A total of 253 patients were included with a repigmentation rate of 96% (243/253) after grafting. Common adverse events included cobblestone-like appearance (73.1%, 185/253) in the donor site, perigraft halo (46.2%, 117/253), and cobblestone-like appearance (26.1%, 66/253) in the recipient site. Postoperative relapse occurred in 20.1% of patients over a mean time of 29.7 months after grafting. Nonsegmental type of vitiligo and coexistence of autoimmune diseases were risk factors for postoperative relapse. SBEG is an effective surgical treatment for vitiligo with high repigmentation rate and good safety profile. Nonsegmental vitiligo and comorbid autoimmune diseases may increase the risk of postoperative relapse.

Glomerulonephritis as a renal manifestation in a patient with systemic sclerosis overlapped with anti-neutrophil cytoplasmic antibody-associated vasculitis

Introduction and Importance: Systemic sclerosis (SSc) is a systemic immune disorder that may overlap with other rheumatologic disease; however, overlapping with antineutrophil cytoplasmic antibody-associated vasculitis is rare. Case Presentation: A 28-year-old Syrian male patient with SSc diagnosed according to the American College of Rheumatology/European League against Rheumatism 2013 criteria with a disease duration of 4 years, was admitted to the hospital complaining of palpable purpura in the lower limbs and hemoptysis and later, a rise in creatinine level. Laboratory tests showed high levels of perinuclear antineutrophil cytoplasmic antibodies (p-ANCA). The renal biopsy results were consistent with the diagnosis of glomerulonephritis. He was treated with methylprednisolone, cyclophosphamide, and rituximab, as he was diagnosed with SSc overlapping antineutrophil cytoplasmic antibody-associated vasculitis. Clinical Discussion: SSc most commonly renal manifestations are proliferative vasculopathy leading to scleroderma renal crisis. However, other types of renal involvement were also reported in SSc patients with comorbid autoimmune diseases such as glomerulonephritis and signs of concurrent vasculitis. SSc may overlap with rheumatoid arthritis, systemic lupus erythromatosus, polymyositis/dermatomyositis (PM/DM), and Sjogren Syndrome. Overlapping with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is mentioned in rare cases. The authors reported a rare case of overlapping SSc with antineutrophil cytoplasmic antibody-associated vasculitis with renal involvement. Conclusion: The authors revealed a rare case of overlapping SSc with antineutrophil cytoplasmic antibody-associated vasculitis with renal involvement. In SSc, renal involvement as glomerulonephritis is infrequent and should be detect in other rheumatologic disease such as systemic lupus erythematosus or antineutrophil cytoplasmic antibody-associated vasculitis.

A223 DEMOGRAPHIC AND CLINICAL CHARACTERISTICS OF PATIENTS WITH INFLAMMATORY BOWEL DISEASE AND PRIMARY SCLEROSING CHOLANGITIS AT THE OTTAWA HOSPITAL

Abstract Background Primary sclerosing cholangitis (PSC) is present in up to 8% of individuals with inflammatory bowel disease (IBD). Characteristics of this population are unique and data are limited. Aims To describe the demographic and clinical characteristics of all individuals with PSC-IBD managed at The Ottawa Hospital (TOH). Methods A chart review was performed for 132 patients with PSC-IBD followed at TOH between January 1998 and July 2023. Results Of 132 individuals with PSC-IBD identified at TOH, 26.5% had Crohn’s disease (CD), 68.2% had ulcerative colitis (UC) and 5.3% had IBD-unclassified. Median age at diagnosis were 25.3 (IQR 20.94) for IBD and 33.84 (IQR 23.98) for PSC, and 66.7% of all patients were male. More than 17% had a co-morbid autoimmune disease other than IBD or PSC. Of those with CD, roughly 15% had fibrostenotic or penetrating complications and 17% had perianal disease at the time of IBD diagnosis. Only 28% ever had a liver biopsy, whereas the majority were diagnosed with PSC by cholangiography. PSC distribution was isolated intrahepatic in 47%, isolated extra-hepatic in 5.1% and mixed intra/extra-hepatic in 38.5%. Clinically significant portal hypertension was present in 11.5% at PSC diagnosis, while 27.3% and 16.7% developed cirrhosis and liver decompensation, respectively by last follow-up. 17.4% underwent liver transplant, of which 30.4% developed PSC recurrence post-transplant. Conclusions Our study showed that the majority of PSC-IBD patients are young males with UC. Co-morbid autoimmune diseases are common while isolated extra-hepatic PSC is uncommon. Cirrhosis, liver decompensation and liver transplant are frequent occurrences in this population. PSC recurrence post-transplant is observed in more than 30% of patients. Funding Agencies None

Clinical characterization of Co-morbid autoimmune disease and eating disorders: a retrospective chart review

ABSTRACT Research suggests a link between autoimmune illnesses (AI) and eating disorders (ED). We retrospectively reviewed charts of adolescent patients presenting for eating disorder treatment. We compared the presentation and treatment course for those with an ED and comorbid AI [with (GI-AI, N = 59) or without (non-GI, N = 21) gastrointestinal inflammation] with matched ED-only cases. The sample was overwhelmingly female, with an average age of 15.40. Weight gain trajectories differed across groups, with similar rates of weight gain between controls and non GI-AI cases and with a lower rate of weight gain for individuals with comorbid GI-AI. Over half (56%) of patients reported an AI diagnosis prior to ED; 38% reported an AI diagnosis following ED, and 6% reported ED and AI simultaneous diagnosis. On presentation, ED-only controls had higher rates of comorbid anxiety than cases in either AI group, while those with non-GI AI were more likely to report depression. Mean total GI symptoms, % goal weight at presentation, vital sign instability, and markers of refeeding syndrome did not differ across groups. Health care professionals treating patients with either condition should have a low threshold for asking additional questions to identify the presence of the other condition.

Trends in Thymic Epithelial Tumor Patients with Comorbid Autoimmune Disease

Thymic epithelial tumors (TETs) are rare malignancies originating from the thymus in the anterior mediastinum. TETs include thymic carcinoma and thymoma. Approximately 30-40% of thymomas have associated autoimmune paraneoplastic disorders, the most common being myasthenia gravis. A broad range of other paraneoplastic syndromes have also been reported. Currently, little is known about demographic or histological trends in thymoma patients with comorbid autoimmune disease. In this single institution retrospective chart review, we assessed the distribution of thymoma-associated paraneoplastic syndromes at the IU Simon Cancer Center (IUSCC) to identify trends within demographic and histological features. We created a database of IUSCC patients seen from 2000-2023 and identified 170 subjects with biopsy-proven malignant TET and associated autoimmune disease. Data was exported to excel and R for analysis. Factors analyzed included: age at diagnosis, sex assigned at birth, BMI, WHO (World Health Organization) classification, and Masaoka staging. Overall survival was also compared to matched controls without paraneoplastic syndrome. A total of 37 different paraneoplastic syndromes were identified in association with thymoma in IUSCC patients. The most prevalent was Myasthenia Gravis (110 patients), followed by Hypothyroidism (21 patients, 5 confirmed as Hashimoto’s thyroiditis), Good Syndrome (19 patients), and Pure Red Cell Aplasia (15 patients). Significant findings included: 36.4% of patients with paraneoplastic comorbidity had &gt;1 paraneoplastic syndrome, 51.8% presented with Stage IV disease, and 40.4% had WHO Type B2 tumor pathology, with Type B3 being second most common (25%). No significant demographic associations were identified. 10-year survival of TET patients with paraneoplastic syndromes was not significantly different from those without (p= 0.721). These results indicate potential associations between thymoma staging and grading and development of paraneoplastic disease. Further analysis with a larger data set is warranted. Serum and blood test analysis may also elucidate reasons behind the development of paraneoplastic disease in thymoma patients.

Clinical features of myasthenia gravis with neurological and systemic autoimmune diseases.

Multiple reports on the co-existence of autoimmune diseases and myasthenia gravis (MG) have raised considerable concern. Therefore, we reviewed autoimmune diseases in MG to explore their clinical presentations and determine whether the presence of autoimmune diseases affects the disease severity and treatment strategies for MG. We reviewed all the major immune-mediated coexisting autoimmune conditions associated with MG. PubMed, Embase and Web of Science were searched for relevant studies from their inception to January 2023. There is a higher frequency of concomitant autoimmune diseases in patients with MG than in the general population with a marked risk in women. Most autoimmune comorbidities are linked to AChR-MG; however, there are few reports of MuSK-MG. Thyroid disorders, systemic lupus erythematosus, and vitiligo are the most common system autoimmune diseases associated with MG. In addition, MG can coexist with neurological autoimmune diseases, such as neuromyelitis optica (NMO), inflammatory myopathy (IM), multiple sclerosis (MS), and autoimmune encephalitis (AE), with NMO being the most common. Autoimmune diseases appear to develop more often in early-onset MG (EOMG). MS coexists more commonly with EOMG, while IM coexists with LOMG. In addition, MG complicated by autoimmune diseases tends to have mild clinical manifestations, and the coexistence of autoimmune diseases does not influence the clinical course of MG. The clinical course of neurological autoimmune diseases is typically severe. Autoimmune diseases occur most often after MG or as a combined abnormality; therefore, timely thymectomy followed by immunotherapy could be effective. In addition, thymoma-associated AChR MG is associated with an increased risk of AE and IM, whereas NMO and MS are associated with thymic hyperplasia. The co-occurrence of MG and autoimmune diseases could be attributed to similar immunological mechanisms with different targets and common genetic factor predisposition. This review provides evidence of the association between MG and several comorbid autoimmune diseases.

Risk of comorbid autoimmune diseases in patients with immunobullous disorders: A global large-scale cohort study

Risk of comorbid autoimmune diseases in patients with immunobullous disorders: A global large-scale cohort study

Repeated Traumatic Brain Injury is Associated with Neurotoxic Plasma Autoantibodies Directed against the Serotonin 2A and Alpha 1 Adrenergic Receptors.

Traumatic brain injury (TBI) was associated with increased plasma agonist autoantibodies targeting the serotonin 2A receptor. Repeated TBI exposure is associated with high risk for neurodegenerative and neuropsychiatric complications. Here we tested a hypothesis that repeated TBI is associated with plasma agonist autoantibodies targeting more than one kind of catecholamine G-protein coupled receptor. Protein-A affinity chromatography was used to isolate the IgG fraction of plasma in forty-two middle-aged and older adults who had experienced one or more TBI exposures. The Ig (1/40th dilution=7.5 ug/mL) were tested for neurotoxicity in mouse neuroblastoma cells using an acute neurite retraction assay indicative of Gq11/IP3/Ca2+ and RhoA/Rho kinase signaling pathways' activation. Three different linear synthetic peptides corresponding to the second extracellular loop of the alpha 1A, alpha 2A or serotonin 2A receptors were used as target antigen in different enzyme-linked immunoassays. The second extracellular loop receptor peptides themselves (alpha 1A, alpha 2A) or a fragment (serotonin 2A) were tested for ability to prevent Ig-induced neurite retraction. Patients who had experienced either repeated TBI (N=10) or a single TBI with a co-morbid autoimmune disease (N=5) were significantly more likely to harbor neurotoxic plasma autoantibodies targeting both alpha 1 adrenergic and serotonin 2A receptors vs. patients having only a single TBI. Ig-induced neurotoxicity was significantly prevented by co-incubation with either 850 nM prazosin (alpha 1 adrenergic receptor) and/or 500 nM M100907 (serotonin 2A receptor) antagonists. Alpha 1 adrenergic receptor and serotonin 2A receptor Ig immunoreactive level and titer were significantly increased in repeated TBI and single TBI/autoimmune patients (N=7-8) compared to age-matched TBI patients without neurotoxic plasma Ig (N=4). SN.8, a linear synthetic peptide corresponding to a conserved region of the second extracellular loop (ECL) of the serotonin 2A receptor completely prevented neurite retraction induced by repeated TBI plasma Ig. A repeated TBI patient harboring alpha adrenergic receptor AAB alone experienced prospective steep decline in cognitive function over two years. Repeated TBI and TBI with associated autoimmunity harbored more than one kind of neurotoxic catecholaminergic agonist GPCR autoantibody each associated with high risk for steep rate of cognitive decline. Specific immunoassays using the second extracellular receptor loop as target antigen are needed to detect each specific different GPCR autoantibody. A fragment of the second ECL of the serotonin 2A receptor (SN.8) neutralized Ig-induced neurotoxicity in repeated TBI or TBI with associated systemic autoimmunity.

Shifting levels of peripheral inflammatory profiles as an indicator for comorbid multiple autoimmune diseases and bipolar disorder: a case report

Autoimmune diseases (AID) cause inflammatory changes in the peripheral blood, which might be a predisposing factor for the development of comorbid bipolar disorder (BD). The levels of peripheral inflammatory indicators and cytokines may also serve as potential biomarkers for predicting BD susceptibility and the efficacy of antipsychotics in patients with AID. Herein, we present the case of a 43-year-old female who has suffered from AID for over 16 years and was recently diagnosed with “bipolar and related disorder due to another medical condition”.

Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK

A rise in the incidence of some autoimmune disorders has been described. However, contemporary estimates of the overall incidence of autoimmune diseases and trends over time are scarce and inconsistent. We aimed to investigate the incidence and prevalence of 19 of the most common autoimmune diseases in the UK, assess trends over time, and by sex, age, socioeconomic status, season, and region, and we examine rates of co-occurrence among autoimmune diseases. In this UK population-based study, we used linked primary and secondary electronic health records from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex and ethnicity. Eligible participants were men and women (no age restriction) with acceptable records, approved for Hospital Episodes Statistics and Office of National Statistics linkage, and registered with their general practice for at least 12 months during the study period. We calculated age and sex standardised incidence and prevalence of 19 autoimmune disorders from 2000 to 2019 and used negative binomial regression models to investigate temporal trends and variation by age, sex, socioeconomic status, season of onset, and geographical region in England. To characterise co-occurrence of autoimmune diseases, we calculated incidence rate ratios (IRRs), comparing incidence rates of comorbid autoimmune disease among individuals with a first (index) autoimmune disease with incidence rates in the general population, using negative binomial regression models, adjusted for age and sex. Among the 22 009 375 individuals included in the study, 978 872 had a new diagnosis of at least one autoimmune disease between Jan 1, 2000, and June 30, 2019 (mean age 54·0 years [SD 21·4]). 625 879 (63·9%) of these diagnosed individuals were female and 352 993 (36·1%) were male. Over the study period, age and sex standardised incidence rates of any autoimmune diseases increased (IRR 2017-19 vs 2000-02 1·04 [95% CI 1·00-1·09]). The largest increases were seen in coeliac disease (2·19 [2·05-2·35]), Sjogren's syndrome (2·09 [1·84-2·37]), and Graves' disease (2·07 [1·92-2·22]); pernicious anaemia (0·79 [0·72-0·86]) and Hashimoto's thyroiditis (0·81 [0·75-0·86]) significantly decreased in incidence. Together, the 19 autoimmune disorders examined affected 10·2% of the population over the study period (1 912 200 [13·1%] women and 668 264 [7·4%] men). A socioeconomic gradient was evident across several diseases, including pernicious anaemia (most vs least deprived area IRR 1·72 [1·64-1·81]), rheumatoid arthritis (1·52 [1·45-1·59]), Graves' disease (1·36 [1·30-1·43]), and systemic lupus erythematosus (1·35 [1·25-1·46]). Seasonal variations were observed for childhood-onset type 1 diabetes (more commonly diagnosed in winter) and vitiligo (more commonly diagnosed in summer), and regional variations were observed for a range of conditions. Autoimmune disorders were commonly associated with each other, particularly Sjögren's syndrome, systemic lupus erythematosus, and systemic sclerosis. Individuals with childhood-onset type 1 diabetes also had significantly higher rates of Addison's disease (IRR 26·5 [95% CI 17·3-40·7]), coeliac disease (28·4 [25·2-32·0]), and thyroid disease (Hashimoto's thyroiditis 13·3 [11·8-14·9] and Graves' disease 6·7 [5·1-8·5]), and multiple sclerosis had a particularly low rate of co-occurrence with other autoimmune diseases. Autoimmune diseases affect approximately one in ten individuals, and their burden continues to increase over time at varying rates across individual diseases. The socioeconomic, seasonal, and regional disparities observed among several autoimmune disorders in our study suggest environmental factors in disease pathogenesis. The inter-relations between autoimmune diseases are commensurate with shared pathogenetic mechanisms or predisposing factors, particularly among connective tissue diseases and among endocrine diseases. Research Foundation Flanders.

The effect of comorbid autoimmune gastrointestinal diseases on time to resolution of pyoderma gangrenosum: A retrospective review

The effect of comorbid autoimmune gastrointestinal diseases on time to resolution of pyoderma gangrenosum: A retrospective review

Sex differences in autoimmune inner ear disease treatment and audiological outcomes

ObjectiveThe primary objective of this study was to assess possible sex-related differences in AIED treatment. The secondary aim was to assess the long-term outcomes of treatment using pre- and post-treatment audiometry and speech discrimination scores. MethodsAdult patients with a diagnosis of AIED who were treated for their condition at the senior author's (RTS) practice from 2010 to 2022 were included in this study. Patients were grouped as males or females for further analysis and comparison. Data included past medical history, medication use, surgical history and social history. Air-conduction thresholds (500 to 8000 Hz) were collected and averaged into discrete variables for pre- and post-treatment. The change (∆) and percent change (%∆) of these variables following therapy were analyzed. Speech discrimination score (SDS) testing results were taken at the same time points as pure tone averages, and patients were sub-stratified based on evidence of improvement in SDS and compared accordingly. ResultsOne hundred eighty-four patients (78 male/106 female) were included in this study. The mean age of the male participants was 57.18 ± 15.92 years, and the mean age of the female participants was 53.49 ± 16.04 years (p = 0.220). Comorbid autoimmune disease (AD) was more prevalent in females than in males (38.7 % vs. 16.7 %, p = 0.001). Of the patients treated with oral steroids, females received significantly more courses than males (2.554 ± 2.078 vs. 1.946 ± 1.301, p = 0.020). However, the average duration of oral steroids used per trial did not differ significantly between males and females (21.02 ± 18.05 vs. 20.62 ± 7.49, p = 0.135). Audiological results demonstrated that the change (∆) in pure tone average (PTA) at 0.5, 1, 2, and 3 kHz (−4.21 ± 6.394 vs. -3.91 ± 6.105) and high-frequency pure tone average (HFPTA) at 4, 6, and 8 kHz (−4.55 ± 6.544 vs. -2.19 ± 6.842) was not significantly different between the sexes following treatment (p = 0.376 and p = 0.101, respectively). Similarly, the percentage change (%∆) in PTA (−13.17 % vs. -15.01 %) and HFPTA (−8.50 % vs. -6.76 %) also did not differ significantly between males and females (p = 0.900 and p = 0.367, respectively). One hundred-five (57.1 %) patients qualified for the SDS improvement subgroup for analysis, with 50 (47.6 %) being male and 55 (51.9 %) being female (p = 0.159). The change (∆) in SDS (15.12 ± 21.159 vs. 10.62 ± 19.206) and the percentage change (%∆) in SDS (16.71 % vs. 12.40 %) also showed no significant difference between male and female patients (p = 0.312 and p = 0.313, respectively). ConclusionAIED is not a uniform condition regarding clinical presentation, audiological findings or progression, nor is its treatment straightforward. The utilization and duration of cytotoxic medications, as well as PTA and SDS findings, did not differ between the sexes. However, significantly more courses of oral steroids were prescribed to females than males. Sex as a biological variable and its implications in the pathogenesis and treatment of AIED warrant further study.

Comorbidities in Patients with Vitiligo: A Systematic Review and Meta-Analysis

Vitiligo has been reported to be associated with a variety of diseases, but it has not been systematically reviewed. Therefore, we aimed to identify prevalent diseases in patients with vitiligo and quantify their associations compared with healthy controls. A comprehensive search of the MEDLINE and EMBASE from the inception to June, 2022 was conducted. Observational studies on prevalent diseases in vitiligo patients compared to healthy controls were included, whereas studies limited to pediatrics or providing only laboratory results were excluded. A total of 78 studies were eligible for analyses. Patients with vitiligo showed higher risks of having comorbid autoimmune and connective tissue diseases, including alopecia areata (odds ratio [OR], 2.63; 95% confidence interval [CI], 2.50-2.78), discoid lupus erythematosus (OR, 2.54; 95% CI, 1.74-3.72), Sjogren's syndrome (OR, 2.50; 95% CI, 1.98-3.16), myasthenia gravis (OR, 2.30; 95% CI, 1.74-3.02), systemic lupus erythematosus (OR, 1.96; 95% CI, 1.52-2.52), and rheumatoid arthritis (OR, 1.82; 95% CI, 1.55-2.15). Thyroid diseases, diabetes mellitus, metabolic syndrome, sensorineural hypoacusis and ophthalmic abnormalities were also more prevalent in patients with vitiligo. In conclusion, vitiligo is associated with various systemic diseases. Physicians should evaluate and manage potential comorbid conditions in patients with vitiligo.

Skin Biopsy and Quantitative Sudomotor Axon Reflex Testing in Patients With Postural Orthostatic Tachycardia Syndrome.

No formal diagnostic criteria exist for the neuropathic subtype of postural orthostatic tachycardia syndrome (POTS). Skin biopsy and quantitative sudomotor axon reflex testing (QSORT) are preferred methods of assessment for autonomic small fiber neuropathy (SFN). This study characterizes the utility of these testing methods at a tertiary center and identifies clinical features associated with abnormal testing. Medical records of 2658 patients undergoing tilt table testing at a single institution between June 2018 and December 2020 were reviewed. Patients with postural orthostatic tachycardia syndrome were included for analysis of intraepidermal nerve fiber density (IENFD), sweat output, comorbidities, symptoms, measures of cardiovascular autonomic function, and serum antibody levels. 356 patients (90% female, mean age 31 ± 10) met the diagnostic criteria for postural orthostatic tachycardia syndrome. Of 211 patients who underwent quantitative sudomotor axon reflex testing, 70 (33%) demonstrated reduced sweat output. These patients were more likely to demonstrate sympathetic impairment during the Valsalva maneuver. Of 80 patients who underwent skin biopsies, 19 (24%) demonstrated reduced intraepidermal nerve fiber density. These patients tended to be older and have reduced heart rate variability during deep breathing. Neither test was associated with specific serum antibodies, symptoms, or comorbidities, though there was a trend toward higher rates of comorbid autoimmune disease in patients with abnormal testing. A subset of patients with postural orthostatic tachycardia syndrome have evidence of small fiber neuropathy. These patients tend to have impaired cardiovascular autonomic function but are otherwise similar to patients with no evidence of small fiber neuropathy.

AUTOIMMUNE DISEASE BURDEN IN CHILDREN WITH EOSINOPHILIC ESOPHAGITIS: A NATIONWIDE LONGITUDINAL STUDY.

<h3>Introduction</h3> Eosinophilic Esophagitis (EoE) is a chronic immune mediated disorder involving eosinophils leading to esophageal dysfunction. In this retrospective multi-center study, we investigated the incidence and risk factors for comorbid autoimmune diseases (AiD) in children using Cerner Health Facts, a national longitudinal database representing approximately 69 million patients. <h3>Methods</h3> All patients under 18 years of age with EoE were included in our analysis. Patient characteristics were evaluated as potential risk factors for comorbid AiD using multivariable regression built using all variables with p<0.05 on univariable analysis. <h3>Results</h3> We identified 6,285 patients with EoE. Mean age was 9.41±5.04 years, 32.04% (2,014) were female. In terms of race, 75.27% (4,731) were white and 11.81% (742) were African American. Overall, 7.0% (440/6,285) of children with EoE had at least one comorbid AiD. The most common AiD in those with EoE was ulcerative-colitis (143) followed by celiac (116) and autoimmune-thyroid disease (89). On multivariable regression, the factors associated with a higher risk of AiD included type-2 diabetes (odds-ratio (OR) 4.46), steroid use (OR 3.51), long-term medication use (OR 2.42), and digestive disorders (OR 1.85). African American race decreased the risk of AiD (OR 0.64). <h3>Conclusion</h3> We utilized a national database of patients with diag nosed EoE to identify the incidence and risk factors for AiD. Ulcerative colitis, celiac, and autoimmune thyroid disease were the most common AiD comorbid with EoE. The greatest risk factor for AiD was type-2 diabetes. Given that nearly 7% of identified EoE patients had comorbid AiD, careful evaluation for AiD in EoE setting may be warranted. We compared patient characteristics and variables of interest between the cohorts of patients with and without comorbid AiD using the chi-squared test for categorical variables, the t-test for normally distributed continuous variables, and the Mann-Whitney U test for non-normally distributed continuous variables. Factors with p<0.05 on univariable analysis were included in multivariable regression model. Statistical significance was defined as p<0.05. Independent risk factors for comorbid AiD were presented as adjusted Odds Ratios with 95% Confidence Intervals. All analyses were performed using SAS version 9.4 (SAS Institute, Cary, North Carolina).

Investigation of comorbid autoimmune diseases in women with autoimmune bullous diseases: An interplay of autoimmunity and practical implications.

Autoimmune bullous diseases are a group of skin disorders resulting from an autoimmune reaction against intercellular adhesion molecules or components of the basement membrane of skin and mucosa. Autoimmune disorders often occur in patients with a history of another autoimmune disease and most autoimmune diseases have a striking female predominance. In this review, we aim to analyze the different associations of autoimmune bullous diseases with other autoimmune diseases and highlight the distinctiveness of the female gender in these associations.