Autoimmune Rheumatologic Diseases Research Articles

Association between atopic dermatitis and autoimmune diseases: a population-based case-control study.

SummaryBackgroundAtopic dermatitis (AD) is a common chronic skin disorder and is well known to be associated with other atopic conditions. There is increasing evidence for an association also with nonatopic conditions, including autoimmune diseases, but data are limited about several autoimmune diagnoses.ObjectivesTo investigate the association between AD and autoimmune diseases.MethodsThis case–control study used Swedish national healthcare registers. The source population comprised the entire Swedish population aged ≥ 15 years from 1968 to 2016. Cases, including all those with an inpatient diagnosis of AD (from 1968) and/or a specialist outpatient diagnosis of AD (from 2001), were matched by sex and age to healthy controls (104 832 cases of AD, 1 022 435 controls).ResultsAD was significantly associated with one or more autoimmune diseases compared with controls – adjusted odds ratio (aOR) 1·97, 95% confidence interval (CI) 1·93–2·01 – and this association was significantly stronger in the presence of multiple autoimmune diseases compared with only one. The association was strongest for autoimmune disorders involving the skin (aOR 3·10, 95% CI 3·02–3·18), the gastrointestinal tract (aOR 1·75, 95% CI 1·69–1·82) or connective tissue (aOR 1·50, 95% CI 1·42–1·58). In the overall analysis, men with AD had a stronger association with rheumatoid arthritis and coeliac disease than did women with AD. In subanalyses, the findings remained stable in multivariable analyses after adjustment for smoking and parental autoimmune disease.ConclusionsThis large population‐based study indicates significant autoimmune comorbidity of adults with AD, especially between AD and autoimmune dermatological, gastrointestinal and rheumatological diseases. Having multiple autoimmune diseases resulted in a stronger association with AD than having only one autoimmune disease.

Acute Myocardial Infarction in Autoimmune Rheumatologic Disease: A Nationwide Analysis of Clinical Outcomes and Predictors of Management Strategy

ObjectivesTo examine national-level differences in management strategies and outcomes in patients with autoimmune rheumatic disease (AIRD) with acute myocardial infarction (AMI) from 2004 through 2014. MethodsAll AMI hospitalizations were analyzed from the National Inpatient Sample, stratified according to AIRD diagnosis into 4 groups: no AIRD, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSC). The associations between AIRD subtypes and (1) receipt of coronary angiography and percutaneous coronary intervention (PCI) and (2) clinical outcomes were examined compared with patients without AIRD. ResultsOf 6,747,797 AMI hospitalizations, 109,983 patients (1.6%) had an AIRD diagnosis (RA: 1.3%, SLE: 0.3%, and SSC: 0.1%). The prevalence of RA rose from 1.0% (2004) to 1.5% (2014), and SLE and SSC remained stable. Patients with SLE were less likely to receive invasive management (odds ratio [OR] [95% CI]: coronary angiography—0.87; 0.84 to 0.91; PCI—0.93; 0.90 to 0.96), whereas no statistically significant differences were found in the RA and SSC groups. Subsequently, the ORs (95% CIs) of mortality (1.15; 1.07 to 1.23) and bleeding (1.24; 1.16 to 1.31) were increased in patients with SLE; SSC was associated with increased ORs (95% CIs) of major adverse cardiovascular and cerebrovascular events (1.52; 1.38 to 1.68) and mortality (1.81; 1.62 to 2.02) but not bleeding or stroke; the RA group was at no increased risk for any complication. ConclusionIn a nationwide cohort of AMI hospitalizations we found lower use of invasive management in patients with SLE and worse outcomes after AMI in patients with SLE and SSC compared with those without AIRD.

Cardiogenic shock in autoimmune rheumatologic diseases: an insight on etiologies, management, and treatment outcomes.

Autoimmune rheumatological disorders are known to have an increased risk for cardiovascular diseases including coronary artery disease (CAD), myocarditis, pericarditis, valvulopathy, and in consequence cardiogenic shock. Data on cardiogenic shock in rheumatological diseases are scarce; however, several reports have highlighted this specific entity. We sought to review the available literature and highlight major outcomes and the management approaches in each disease. Systematic literature search, including PubMed, Ovid/Medline, Cochrane Library, and Web of Science, was conducted between January 2000 and December 2009. We reviewed all cases reporting cardiogenic shock with rheumatologic conditions, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Takayasu's arteritis (TA), granulomatosis with polyangiitis (GPA), giant cell arteritis (GCA), and antiphospholipid syndrome (APS). We selected 45 papers reporting a total of 48 cases. Mean age was 39 ± 7.3years and 68.8% were females. Most common rheumatologic conditions associated with cardiogenic shock were SLE (31%), GPA (23%), TA (14.6%), APA (10.4%), and RA (8.3%). Cardiogenic shock was found to be caused by eosinophilic myocarditis in 58% of cases, CAD in 19% of cases, and valvulopathy in 6% of cases. Most patient required high-dose steroids and second immunosuppressant therapy. Mechanical circulatory supported was required in 23 cases, IABP in 16 cases, and ECMO in 12 cases. Complete recovery occurred in 37 patients while 9 patients died and 2 required heart transplant. Responsible for two-thirds of cases, eosinophilic myocarditis should be suspected in young cardiogenic shock patients with underlying rheumatologic conditions. Lupus and GPA are the two most common conditions.

SUN-304 Hypophisitis in Patients with and Without Autoimmune Rheumatological Disease

Background: Hypophysitis is an inflammatory process of the pituitary gland with different origins. Infundibulum may be also involved, called infundibulum-hypophysitis. Sometimes, enlargement of pituitary gland causes mass effect and anterior or posterior hormonal dysfunction, including hypopituitarism, and diabetes insipidus (DI), respectively. Hypophysitis is a rare autoimmune disease, however, the number of cases have been recently increasing due to higher detection related with more magnetic resonance imaging (MRI) studies. In addition, hypophysitis may be related with autoimmune rheumatologic disease (ARD) such as generalized lupus erythematosus (GLE), granulomatosis with polyangeitis (GPA), IgG4-related disease, and rheumatoid arthritis (RA). Aim: to compare the clinical and biochemical findings among patients with hypophysitis grouped depending on the presence of coexistent ARD activity. Methodology: it is a comparative and cross-sectional study. We registered all data from cases followed-up in Neuroendocrinology and Rheumatology units, from January 1987 to July 2019. Results: 24 patients showed confirmed diagnosis of hypophysitis. Majority of them (n=17, 71%) do not have coexistent diagnosis of ARD. However, 7 cases (29%) presented pituitary involvement with coexistent activity of GPA (n=4, 17%), GLE (n=1, 4%), RA (n=1, 4%) and IgG4-related disease (n=1, 4%). Female gender predominate in hypophysitis cases with and without ARD (p=0.9). Interestingly, age of hypophysitis diagnosis was significantly younger in cases without (38±14) vs. with (49±5) ARD (p=0.01). MRI results showed similar and typical findings related with hypophysitis independently of the presence of ARD. Hypopituitarism was present in the majority of cases, however, none of cases with hypophysitis and ARD showed hypogonadism (p=0.02). DI was present in 15 patients (63%), three of them with ARD (all with GPA). All cases received only medical therapy (i.e., glucocorticoids, rituximab, or azathioprine). Surgery or radiotherapy was not necessary in any case. Conclusions: Almost a 30% of cases with hypophysitis may have coexistent ARD. Pituitary function should be evaluated in cases with previous ARD diagnosis. However, hypogonadism was not present in cases with ARD and hypophysitis. Patients with ARD presented hypophysitis at older age. The remaining clinical and radiological data were similar between groups.

Oxidative Stress in Rheumatoid Arthritis: What the Future Might Hold regarding Novel Biomarkers and Add-On Therapies.

Numerous rheumatologic autoimmune diseases, among which rheumatoid arthritis, are chronic inflammatory diseases capable of inducing multiple cumulative articular and extra-articular damage, if not properly treated. Nevertheless, benign conditions may, similarly, exhibit arthritis as their major clinical finding, but with short-term duration instead, and evolve to spontaneous resolution in a few days to weeks, without permanent articular damage. Such distinction—self-limited arthritis with no need of immunosuppressive treatment or chronic arthritis at early stages?—represents one of the greatest challenges in clinical practice, once many metabolic, endocrine, neoplastic, granulomatous, infectious diseases and other autoimmune conditions may mimic rheumatoid arthritis. Indeed, the diagnosis of rheumatoid arthritis at early stages is a crucial step to a more effective mitigation of the disease-related damage. As a prototype of chronic inflammatory autoimmune disease, rheumatoid arthritis has been linked to oxidative stress, a condition in which the pool of reactive oxygen species increases over time, either by their augmented production, the reduction in antioxidant defenses, or the combination of both, ultimately implying compromise in the redox signaling. The exact mechanisms through which oxidative stress may contribute to the initiation and perpetuation of local (in the articular milieu) and systemic inflammation in rheumatoid arthritis, particularly at early stages, still remain to be determined. Furthermore, the role of antioxidants as therapeutic adjuvants in the control of disease activity seems to be overlooked, as a little number of short studies addressing this issue is currently found. Thus, the present review focuses on the binomial rheumatoid arthritis-oxidative stress, bringing insights into their pathophysiological relationships, as well as the implications of potential diagnostic oxidative stress biomarkers and therapeutic interventions directed to the oxidative status in patients with rheumatoid arthritis.

Biologics in rheumatology

Monoclonal antibodies and fusion proteins were introduced into clinical rheumatology 20 years ago. Nowadays they are an established component of modern internal medical practice. This article gives an overview of the breadth of biologics currently in clinical use. Evaluation of published approval studies and guideline recommendations, discussion of the immunological principles and targets in the treatment with biologics. Monoclonal antibodies and fusion proteins for influencing cytokine signals, T‑cell costimulation and B‑cell function are the most important innovations in the treatment of rheumatological diseases. Nowadays they are indispensible for the treatment of moderate and severe disease courses of rheumatoid arthritis, spondylarthropathies and vasculitides. Although a cure or permanent freedom from symptoms in rheumatological autoimmune diseases is still not possible, much more favorable disease courses with less long-term limitations can be achieved by the early administration of biologics.

Rheumatic complications in cancer patients treated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have revolutionized anticancer therapy due to their long-term clinical benefits and immune boosting mechanisms. However, despite their consistent therapeutic effects, the use of ICIs is associated with a spectrum of adverse events due to their autoimmune and auto-inflammatory actions. These adverse events can affect any organ system, including the endocrine, neurologic, gastrointestinal, cardiac, skin, pulmonary, and musculoskeletal systems. Of the immune-related adverse events (irAEs), rheumatic complications are common and appear to be distinct from irAEs in other organs in terms of variability of onset time, capacity for persistence, and relationship with pre-existing autoimmune rheumatologic diseases. In this article, we review the mechanisms of the anti-cancer effects of ICIs, the irAEs of immuno-oncology drugs, and the general recommendations for managing irAEs. In particular, we focus on rheumatologic irAEs and discuss their prevalence, clinical characteristics, and management.

Checking in with immune checkpoint inhibitors: Results of a needs assessment survey of Canadian rheumatologists

Objectives: Immune checkpoint inhibitors (ICI) are associated with immune-related adverse events (irAE), including autoimmune rheumatologic diseases. The Canadian Research Group of Rheumatology in Immuno-Oncology (CanRIO) undertook a survey to understand the needs of Canadian rheumatologists. Methods: A 25-item survey was developed. It was distributed via electronic mail to 574 members of the Canadian Rheumatology Association (CRA). Results were summarized using descriptive statistics. Results: Over 25% of the respondents were not familiar with irAE. 48.7% reported being ‘slightly or not confident’ in providing advice regarding irAE. Conclusion: The survey highlighted the strong rationale to develop clinical practice guidelines for managing irAE.

Clinical Characteristics and Associated Systemic Diseases in Patients With Esophageal "Absent Contractility"-A Clinical Algorithm.

This study was carried out to assess the clinical characteristics and associated systemic diseases seen in patients diagnosed with absent contractility as per the Chicago Classification version 3.0, allowing us to propose a diagnostic algorithm for their etiologic testing. The Chicago Classification version 3.0 has redefined major and minor esophageal motility disorders using high-resolution esophageal manometry. There is a dearth of publications based on research on absent contractility, which historically has been associated with myopathic processes such as systemic sclerosis (SSc). We conducted a retrospective, multicenter study. Data of patients diagnosed with absent contractility were pooled from Cleveland Clinic, Cleveland, OH (January 2006 to July 2016) and Metrohealth Medical Center, Cleveland, OH (July 2014 to July 2016) and included: age, gender, associated medical conditions, surgical history, medications, and specific antibody testing. A total of 207 patients, including 57 male individuals and 150 female individuals, with mean age of 56.1 and 60.0 years, respectively, were included. Disease distribution was as follows: SSc (diffuse or limited cutaneous) 132, overlap syndromes 7, systemic lupus erythematosus17, Sjögren syndrome 4, polymyositis 3, and dermatomyositis 3. Various other etiologies including gastroesophageal reflux disease, postradiation esophagitis, neuromuscular disorders, and surgical complications were seen in the remaining cohort. Most practitioners use the term "absent contractility" interchangeably with "scleroderma esophagus"; however, only 63% of patients with absent contractility had SSc. Overall, 20% had another systemic autoimmune rheumatologic disease and 16% had a nonrheumatologic etiology for absent contractility. Therefore, alternate diagnosis must be sought in these patients. We propose an algorithm for their etiologic evaluation.

Systemic Sclerosis Pathogenesis and Emerging Therapies, beyond the Fibroblast.

Systemic sclerosis (SSc) is a complex rheumatologic autoimmune disease in which inflammation, fibrosis, and vasculopathy share several pathogenic pathways that lead to skin and internal organ damage. Recent findings regarding the participation and interaction of the innate and acquired immune system have led to a better understanding of the pathogenesis of the disease and to the identification of new therapeutic targets, many of which have been tested in preclinical and clinical trials with varying results. In this manuscript, we review the state of the art of the pathogenesis of this disease and discuss the main therapeutic targets related to each pathogenic mechanism that have been discovered so far.

Prescribing patterns and safety of biologics in immune-mediated rheumatic diseases: Karnataka biologics cohort study group experience

Introduction: Biologics are widely used in Autoimmune rheumatologic diseases (AIRDs), however the need to capture real life data which monitors indications, adverse reactions cannot be over emphasized. Methods: This is a cross-sectional ambidirectional multi-center study conducted over 8 months from January 2016 to August 2016, across 12 tertiary care rheumatology centers in Karnataka, India conducted by members of the Karnataka Rheumatology Association. Results: The most common biologic prescribed is tumour necrosis factor antagonist etanercept. Commonest indication for biologics being Spondyloarthropathy group of disorders. The most common cause for stopping biologics is clinical improvement. Only 4.8% of patents discontinued biologics due to ADRs. Conclusion: The prescribing patterns, mode of use, prebiologics screening methods, and adverse event profile are similar across centres. Pre-screening for latent tuberculosis (TB) is consistent across centres, and TB prophylaxis appears to be effective in preventing its reactivation.

The Mutation Profile of Myelodysplastic Syndrome Associated with Auto-Immune Rheumatological Disorders

Introduction: A subset of patients with MDS and related myeloid disorders present with concomitant autoimmune rheumatological diseases (AIRD); however the prevalence ranges from 10-48% based on limited literature. Further, use of immunosuppressive agents in AIRD patients could confound the secondary diagnosis of MDS and in some cases cause it (therapy-related myeloid neoplasm; t-MN). The prevalence of cytopenia in AIRD patients is unknown and the genetic characteristics of MDS patients with concomitant AIRD have not been described. Hence, we interrogated two large multi-institutional databases -Royal Adelaide Hospital Rheumatology Database (RAH-RD) and South-Australian MDS (SA-MDS) registry in this study.Methods: Demographic, clinical, laboratory and treatment data of 2663 AIRD and 1157 MDS patients were analysed. In AIRD patients (autoimmune inflammatory arthritis, spondyloarthritis, vasculitis and connective tissue diseases), cytopenia (persisting >6 months) were defined as follows: hemoglobin <100g/dL, absolute neutrophil <1800/mm3 and platelet <100,000/mm3. Targeted massively parallel sequencing of a custom panel of 43 myeloid neoplasms associated genes and 20 Fanconi (FA) DNA repair pathway genes (all coding regions) was performed on diagnosis bone marrow samples (n=237). An in-house well established filtering pipeline was used for identification of somatic mutations. Matched germline material was available for 62/194 (32%) patients. Only variants with Genome Aggregation Database minor allele frequency of ≤0.01% and variant allele frequency of ≥35% were selected for further analysis of germline variants.Results: During follow up of 2663 AIRD patients, 36 (1.3%) patients satisfied the criteria for at least one cytopenia. Anemia (19/36, 53%) was most common followed by neutropenia (8/36, 22%), thrombocytopenia (4/36, 11%) and bi-cytopenia (5/36, 14%). Twenty-two patients had bone marrow examination which was non-diagnostic in 16 patients, while 7/2663 (0.3%) patients were diagnosed with MDS. Importantly, 5 patients with MDS and 11 patients with cytopenia did not receive any cytotoxic agents.In the MDS database, 69(5.4%) were diagnosed with AIRD, with rheumatoid arthritis (n=20, 29%) being the most common AIRD. Among these 69 patients, 24 (34.8%) had low risk MDS and 15 (21.7%) had higher risk MDS. The remaining 30 patients had t-MN (n=19, 27.5%), MDS/MPN (n=8, 11.6%) and AML (n=3, 4.3%). Overall, in a combined population of 2663 RAH-RD and 1157 SA-MDS, 76(2%) had concomitant MDS and AIRD.Genetic profile of patients with MDS and AIRD: The cytogenetic and mutational profile of MDS patients with (n=20) or without (n=217) AIRD were compared. No significant difference was seen in the cytogenetic profile (normal, complex or monosomal karyotype, chr. 5 or 7 abnormalities) between the two groups but in mutational analysis, 56 mutations were seen in 20 MDS patients with AIRD (Fig1). In these patients, mutations in epigenetic pathways were most common (23/56, 41%) followed by transcription pathway (10/56, 18%). Splicing mutations were seen in 5 patients, with SRSF2 mutations being more common than SF3B1. Mutations in TP53 were present in 4 (24%) patients; 3/4 patients developed MDS following therapy for AIRD (t-MDS). IDH1 mutations were found in significantly higher frequency in MDS patients with AIRD compared to MDS without AIRD (30% vs 3%, p=0.04). There was no significant difference in the frequency of other mutations or overall mutation frequency between the two groups.Interestingly, 2 (10%) patients with MDS and AIRD also had rare, deleterious germline mutations in FA pathway genes (BRCA2 V2601M and L2512F) which could suggest either genetic predisposition to both these conditions or compromised DNA repair capability increasing susceptibility to t-MN.Conclusions: In a large multi-institutional cohort of autoimmune rheumatological disorders, 1.3% patients developed persistent cytopenia with 0.3% diagnosed with MDS. This is significantly higher than incidence of MDS in the general population (30-50/100,000). Similarly, 5% MDS patients had AIRD. The mutation profile of MDS patients with AIRD shows higher frequency of IDH1 and SRSF2 mutations. A small proportion of cases also had deleterious rare germline mutations in the DNA repair pathway. Our findings warrant further study and have potential implications for selection of immunosupressive agents for AIRD. [Display omitted] DisclosuresHiwase:Novartis: Research Funding; Celgene: Research Funding.

Histopathology of the skin in rheumatic diseases.

Rheumatological systemic autoimmune diseases, such as connective tissue diseases, rheumatoid arthritis or spondyloarthritis, are characterized by the presence of joint involvement associated with extra-articular manifestations. Among them, cutaneous diseases are often the most relevant and representative clinical manifestation, as in psoriatic arthritis, scleroderma or systemic lupus erythematosus. In this context, it is useful for rheumatologists to understand better skin diseases and their histopathological features. Evaluation of skin biopsy specimens can be helpful not only to confirm the diagnosis in both classic and clinically atypical variants, but also to improve further our knowledge of the pathogenetic mechanisms and the close link between skin and articular diseases. In this review, we discuss the clinical features, diagnostic evaluation and the histopathological features of skin manifestation of the most relevant rheumatological autoimmune diseases.

Impact of an Exercise Training Program in a Patient with Relapsing Polychondritis: A Case Report

Background: Exercise training has demonstrating to be safe and promote benefits for several rheumatologic autoimmune diseases. However, no study has evaluated the safety and benefits of exercise in relapsing polychondritis. Aim: To evaluate the effectiveness of an exercise training program in a patient with relapsing polychondritis. Case presentation: A 67-year-old female patient with relapsing polychondritis in remission was submitted to a 12-week, twice weekly, aerobic and resistance training program. Aerobic capacity, muscle strength and function capacity, as well as body composition, were evaluated at baseline and after 12-weeks. Conclusions: Exercise training program demonstrated to be effective for increasing aerobic capacity, muscle strength and function, and for improving body composition in the patient. Further studies are necessary to confirm these findings.

AUTOIMMUNOLOGY: NEW BRANCH OF MEDICINE

The article written by the co-chairmen of the First St. Petersburg Congress on Autoimmunity "Bridge between East and West", held in St. Petersburg State University June 30-July 2, 2017 describes this event and gives an overview of the main lectures and discussions during the Congress. The latest data on the role of diet, adjuvants, vaccines, viruses and microbiome, on genetic factors, stress, smoking, lifestyle, drugs - in etiology, as well as the role of lymphocytes, macrophages, various autoantibodies, complement and cytokines - in the pathogenesis and diagnosis of autoimmune diseases were discussed. The congress discussed their comorbidity, ways of treatment and prevention, markers, methodology and contribution of serological tests in the diagnosis and classification of autoimmune diseases. Current data on physiological autoimmunity, as well as the early predictive role of autoantibodies were described. The participants performed philosophical discussions about immunological concepts, and organizational discussions of the standardization of diagnostics and the principles of working with large databases, as applied to this field. The programme included Clinical Pathophysiology все of various autoimmune rheumatologic, psycho-neurological, endocrine, cardiovascular, obstetric-gynecological and many other diseases. The authors conclude that the rapid formation of Autoimmunology as a new integral medical branch happens nowadays (9 figs, bibliography: 69 refs).

Functional dyspepsia and duodenal eosinophilia: A new model

Functional dyspepsia (FD) is a highly prevalent disorder that affects more than 10% of the population. In the past decade, the theoretical underpinning of the concept of FD has begun to change, in light of new data on the underlying pathophysiological mechanisms of this disorder, with a focus on the duodenum. The Rome IV criteria, published in 2016, note that gastroesophageal reflux disease and irritable bowel syndrome overlap with FD more than expected by chance, suggesting that they may be part of the same disease spectrum. Infection by Helicobacter pylori (H. pylori) may explain a minority of cases of FD and in the Rome IV criteria H. pylori-associated dyspepsia (defined as symptom relief after eradication therapy) is considered a separate entity. Duodenal inflammation characterized by increased eosinophils and in some cases mast cells, may impair the intestinal barrier. Post-infectious gastroenteritis is now an established risk factor for FD. Other risk factors may include atopy, owning herbivore pets and exposure to antibiotics, together with gastroduodenal microbiome disturbances. Small bowel homing T cells and increased cytokines in the circulation occur in FD, correlating with slow gastric emptying, and a possible association with autoimmune rheumatological disease supports background immune system activation. A genetic predisposition is possible. FD has been linked to psychological disorders, but in some cases psychological distress may be driven by gut mechanisms. Therapeutic options are limited and, aside from responders to H. pylori eradication, provide only modest and temporary relief. Advances in understanding FD may alter clinical practice, and the treatment of duodenal inflammation or microbiome alterations may lead to a cure for a subset of these patients in the future.

Association between demyelinating disease and autoimmune rheumatic disease in a pediatric population

IntroductionMultiple sclerosis (MS) and neuromyelitis optica (NMO) are demyelinating diseases of the central nervous system. Autoimmunity in patients with demyelinating disease and in their families has been broadly investigated and discussed. Recent studies show a higher incidence of rheumatic autoimmune diseases among adult patients with MS or NMO and their families, but there are no studies in the pediatric population. ObjectiveTo evaluate an association of MS and NMO with autoimmune rheumatic diseases in pediatric patients. Method22 patients younger than 21 years old with MS or NMO diagnosed before the age of 18 years were evaluated regarding epidemiological data, clinical presentation, association with autoimmune diseases, family history of autoimmune diseases, laboratory findings, imaging studies and presence of auto-antibodies. ResultsAmong the patients studied, there was a prevalence of females (68.1%). The mean age of symptoms onset was 8 years and 9 months and the mean current age was 16 years and 4 months. Two patients (9%) had a history of associated autoimmune rheumatic disease: one case of juvenile dermatomyositis in a patient with NMO and another of systemic lupus erythematosus in a patient with MS. Three patients (13%) had a family history of autoimmunity in first-degree relatives. Antinuclear antibody was found positive in 80% of patients with NMO and 52% of patients with MS. About 15% of antinuclear antibody-positive patients were diagnosed with rheumatologic autoimmune diseases. ConclusionAmong patients with demyelinating diseases diagnosed in childhood included in this study there was a high frequency of antinuclear antibody positivity but a lower association with rheumatologic autoimmune diseases than that observed in studies conducted in adults.

Associação entre doença desmielinizante e doença reumática autoimune em uma população pediátrica

IntroductionMultiple sclerosis (MS) and neuromyelitis optica (NMO) are demyelinating diseases of the central nervous system. Autoimmunity in patients with demyelinating disease and in their families has been broadly investigated and discussed. Recent studies show a higher incidence of rheumatic autoimmune diseases among adult patients with MS or NMO and their families, but there are no studies in the pediatric population. ObjectiveTo evaluate an association of MS and NMO with autoimmune rheumatic diseases in pediatric patients. Method22 patients younger than 21 years old with MS or NMO diagnosed before the age of 18 years were evaluated regarding epidemiological data, clinical presentation, association with autoimmune diseases, family history of autoimmune diseases, laboratory findings, imaging studies and presence of auto‐antibodies. ResultsAmong the patients studied, there was a prevalence of females (68.1%). The mean age of symptoms onset was 8 years and 9 months and the mean current age was 16 years and 4 months. Two patients (9%) had a history of associated autoimmune rheumatic disease: one case of juvenile dermatomyositis in a patient with NMO and another of systemic lupus erythematosus in a patient with MS. Three patients (13%) had a family history of autoimmunity in first‐degree relatives. ANA was found positive in 80% of patients with NMO and 52% of patients with MS. About 15% of ANA‐positive patients were diagnosed with rheumatologic autoimmune disieses. ConclusionAmong patients with demyelinating diseases diagnosed in childhood included in this study there was a high frequency of ANA positivity but a lower association with rheumatologic autoimmune diseases than that observed in studies conducted in adults.

Periodic Acid-Schiff Staining Parallels the Immunoreactivity Seen By Direct Immunofluorescence in Autoimmune Skin Diseases.

Background:In many countries and laboratories, techniques such as direct immunofluorescence (DIF) are not available for the diagnosis of skin diseases. Thus, these laboratories are limited in the full diagnoses of autoimmune skin diseases, vasculitis, and rheumatologic diseases. In our experience with these diseases and the patient's skin biopsies, we have noted a positive correlation between periodic acid-Schiff (PAS) staining and immunofluorescence patterns; however, these were just empiric observations. In the current study, we aim to confirm these observations, given the concept that the majority of autoantibodies are glycoproteins and should thus be recognized by PAS staining.Aims:To compare direct immunofluorescent and PAS staining, in multiple autoimmune diseases that are known to exhibit specific direct immunofluorescent patterns.Materials and Methods:We studied multiple autoimmune skin diseases: Five cases of bullous pemphigoid, five cases of pemphigus vulgaris, ten cases of cutaneous lupus, ten cases of autoimmune vasculitis, ten cases of lichen planus (LP), and five cases of cutaneous drug reactions (including one case of erythema multiforme). In addition, we utilized 45 normal skin control specimens from plastic surgery reductions.Results:We found a 98% positive correlation between DIF and PAS staining patterns over all the disease samples.Conclusion:We recommend that laboratories without access to DIF always perform PAS staining in addition to hematoxylin and eosin (H&E) staining, for a review of the reactivity pattern.

Primary complement and antibody deficiencies in autoimmune rheumatologic diseases with juvenile onset: a prospective study at two centers.

BackgroundOur aim was to investigate the prevalence and clinical relevance of inherited complement and antibody deficiency states in a large series of patients with various autoimmune rheumatologic diseases (ARD) with juvenile onset.MethodsA total number of 117 consecutive patients from 2 tertiary referral hospitals were included in the study. All patients underwent genetic screening for type I C2 deficiency and C4 allotyping. Serum levels of immunoglobulin classes measured systematically throughout their regular medical care were recorded retrospectively.ResultsOur cohort of patients included 84 with juvenile idiopathic arthritis (JIA), 21 with systemic lupus erythematosus (SLE), 6 with systemic vasculitis, 2 with juvenile scleroderma, 2 with idiopathic uveitis, 1 with mixed connective tissue disease and 1 with SLE/scleroderma overlap syndrome. We have found 16 patients with evidence of primary immunodeficiency in our series (13.7 %), including 7 with C4 deficiency, 5 with selective IgA deficiency, 3 with C2 deficiency and 2 with unclassified hypogammaglobulinemia (one also presented C4D). Of the 84 patients with JIA, 4 (4.8 %) had a complement deficiency, which was less prevalent than in the SLE cohort (23.8 %), but all of them have exhibited an aggressive disease. Most of our patients with primary antibody deficiencies showed a more complicated and severe disease course and even the co-occurrence of two associated autoimmune diseases (SLE/scleroderma overlap syndrome and SLE/autoimmune hepatitis type 1 overlap).ConclusionsOur findings among others demonstrate that complement and immunoglobulin immunodeficiencies need careful consideration in patients with ARD, as they are common and might contribute to a more severe clinical course of the disease.