CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy for Systemic Autoimmune Diseases.

A small number of drugs have been the sole stay of conventional treatment for autoimmune illnesses for the past 10 years. These medications have a number of side effects that restrict their usage and necessitate continuous administration to keep a patient in a state of remission. While many new treatments are being researched to address this problem, chimeric antigen receptor (CAR) T-cell therapy currently shows the greatest potential. Current medical guidelines do not currently advocate the use of this medicine because it is still in its early stages of development due to continuing clinical research. Therefore, the aim of this systematic review was to determine what new findings have been reported in recent studies about the safety and efficacy of CAR T-cells. From the nine studies collected in total, it was found that systemic lupus erythematosus (SLE) was the most often researched autoimmune disease. The CAR T-cell therapy had noticeable results after one to two months on average. The most frequent adverse effect was cytokine release syndrome (CRS), which was treated cautiously and infrequently necessitated extensive intervention. All serological tests showed improvement, and clinical remission was always achieved. This review concludes that, due to the one-time infusion and low adverse reaction rate, the therapy not only outperforms conventional drugs but is also more practical. There is even more cause to look forward to the full deployment of this innovative therapeutic alternative, as variations of the therapy are currently being explored.

[Messages from the estates general on French internal medicine]. / Que retenir des états généraux de la médecine interne française ?

Internal medicine is a medical specialty that is often poorly understood by the general public and sometimes misidentified. In an era of increasing subspecialization and high technicality, it is characterized by a comprehensive approach centered on clinical evaluation. Unlike what is observed in most developed countries, where systemic autoimmune diseases are managed by organ specialists based on their mode of presentation, French internists are at the forefront for diagnosing and managing these diseases. Their multidisciplinary training gives them legitimacy to justify this role. Internists also play a crucial role in the management of patients requiring unplanned hospitalizations downstream from emergency departments and in connection with primary care. Internists primarily practice in a hospital setting, with a specific position in the French healthcare system aligned with the training frameworks of all medical specialties. To better define internal medicine, its role in care activities, as well as in education and research, internists organized a General Assembly of internal medicine that took place on September 28, 2023, in Paris. Structured around think tanks focusing on care, education, and research activities, the general assembly aimed to improve visibility on internal medicine and internists. This article recounts the discussions that animated this meeting and highlights the main ideas that emerged. These general assemblies constitute a foundational step and will be followed by a Consultation Conference in order to better identify and promote internal medicine and internists, regardless of their types and places of practice.

A Case of Eosinophilic Granulomatosis With Polyangiitis (EGPA) Peripheral Neuropathy With Positive Anti-Myelin Oligodendrocyte (MOG) Antibodies.

Peripheral neuropathy is a common manifestation of Eosinophilic Granulomatosis with Polyangiitis (EGPA), a rare autoimmune disorder caused by eosinophilic infiltration of multiple organs including the nervous system. Recent research has shown an association between myelin oligodendrocyte glycoprotein (MOG) antibodies and various neurologic conditions. We present a unique case of EGPA with positive MOG antibodies in the cerebrospinal fluid (CSF) in a patient presenting with peripheral neuropathy. We also highlight a few diagnostic dilemmas with EGPA and the importance of early diagnosis and appropriate treatment. Clinical, laboratory, radiological, and electrophysiologic findings are discussed.

New Onset Autoimmune Diseases after the Sputnik Vaccine.

The vertiginous advance for identifying the genomic sequence of SARS-CoV-2 allowed the development of a vaccine including mRNA-based vaccines, inactivated viruses, protein subunits, and adenoviral vaccines such as Sputnik. This study aims to report on autoimmune disease manifestations that occurred following COVID-19 Sputnik vaccination. Patients and Methods: A retrospective study was conducted on patients with new-onset autoimmune diseases induced by a post-COVID-19 vaccine between March 2021 and December 2022, in two referral hospitals in Mexico City and Argentina. The study evaluated patients who received the Sputnik vaccine and developed recent-onset autoimmune diseases. Results: Twenty-eight patients developed recent-onset autoimmune diseases after Sputnik vaccine. The median age was 56.9 ± 21.7 years, with 14 females and 14 males. The autoimmune diseases observed were neurological in 13 patients (46%), hematological autoimmune manifestations occurred in 12 patients (42%), with thrombotic disease observed in 10 patients (28%), and autoimmune hemolytic anemia in two patients (7.1%). Rheumatological disorders were present in two patients (7.1%), and endocrine disorders in one patient (3.5%). Principio del formulario Conclusion: Although the COVID-19 Sputnik vaccine is generally safe, it can lead to adverse effects. Thrombosis and Guillain-Barre were the most frequent manifestations observed in our group of patients.

Biologic therapy in large and small vessels vasculitis, and Behçet's disease: Evidence- and practice-based guidance.

OBJECTIVE: Vasculitis are a very heterogenous group of systemic autoimmune diseases, affecting large vessels (LVV), small vessels or presenting as a multisystemic variable vessel vasculitis. We aimed to define evidence and practice-based recommendations for the use of biologics in large and small vessels vasculitis, and Behçet's disease (BD). METHODS: Recommendations were made by an independent expert panel, following a comprehensive literature review and two consensus rounds. The panel included 17 internal medicine experts with recognized practice on autoimmune diseases management. The literature review was systematic from 2014 until 2019 and later updated by cross-reference checking and experts' input until 2022. Preliminary recommendations were drafted by working groups for each disease and voted in two rounds, in June and September 2021. Recommendations with at least 75% agreement were approved. RESULTS: A total of 32 final recommendations (10 for LVV treatment, 7 for small vessels vasculitis and 15 for BD) were approved by the experts and several biologic drugs were considered with different supporting evidence. Among LVV treatment options, tocilizumab presents the higher level of supporting evidence. Rituximab is recommended for treatment of severe/refractory cryoglobulinemic vasculitis. Infliximab and adalimumab are most recommended in treatment of severe/refractory BD manifestations. Other biologic drugs can be considered is specific presentations. CONCLUSION: These evidence and practice-based recommendations are a contribute to treatment decision and may, ultimately, improve the outcome of patients living with these conditions.

Biological therapy in systemic lupus erythematosus, antiphospholipid syndrome, and Sjögren's syndrome: evidence- and practice-based guidance.

Systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and Sjögren's syndrome (SS) are heterogeneous autoimmune diseases. Severe manifestations and refractory/intolerance to conventional immunosuppressants demand other options, namely biological drugs, and small molecules. We aimed to define evidence and practice-based guidance for the off-label use of biologics in SLE, APS, and SS. Recommendations were made by an independent expert panel, following a comprehensive literature review and two consensus rounds. The panel included 17 internal medicine experts with recognized practice in autoimmune disease management. The literature review was systematic from 2014 until 2019 and later updated by cross-reference checking and experts' input until 2021. Preliminary recommendations were drafted by working groups for each disease. A revision meeting with all experts anticipated the consensus meeting held in June 2021. All experts voted (agree, disagree, neither agree nor disagree) during two rounds, and recommendations with at least 75% agreement were approved. A total of 32 final recommendations (20 for SLE treatment, 5 for APS, and 7 for SS) were approved by the experts. These recommendations consider organ involvement, manifestations, severity, and response to previous treatments. In these three autoimmune diseases, most recommendations refer to rituximab, which aligns with the higher number of studies and clinical experience with this biological agent. Belimumab sequential treatment after rituximab may also be used in severe cases of SLE and SS. Second-line therapy with baricitinib, bortezomib, eculizumab, secukinumab, or tocilizumab can be considered in SLE-specific manifestations. These evidence and practice-based recommendations may support treatment decision and, ultimately, improve the outcome of patients living with SLE, APS, or SS.

Rheumatic Diseases Development in Patients Treated by Anti-PD1 Immune Checkpoint Inhibitors: A Single-Centre Descriptive Study.

The introduction of the so-called immune checkpoint inhibitors (ICIs) substantially changed the history of cancer therapy. On the other hand, they can induce the development of rheumatic immune-related adverse events (Rh-irAEs). In the scenario of a joint oncology/rheumatology outpatient clinic, we conducted a single-centre descriptive study to define from a laboratory, clinical and therapeutic point of view, rheumatic conditions developed during anti-PD1 treatment. The study included 32 patients (M/F 16/16, median age 69, IQR 16.5). According to the international classification criteria, eight patients could be classified as affected by Rheumatoid Arthritis, one by Psoriatic Arthritis, six by Polymyalgia Rheumatica, five by systemic connective tissue diseases (two systemic lupus erythematosus, two Sjögren's syndrome, one undifferentiated connective tissue disease). The remaining patients were diagnosed as having undifferentiated arthritis or inflammatory arthralgia. The median interval between ICIs starting and the onset of symptoms was 14 weeks (IQR 19.75). Moving to treatment, the longitudinal observation revealed that all RA, PsA and CTD patients required the introduction of treatment with DMARDs. In conclusion, the growing use of ICIs in a real-life setting confirmed the possible development of different rheumatological conditions, further emphasising the need for shared oncology/rheumatology management.

[Autoimmune hearing loss and a chance of its development in children: literature review and own observations]. / Autoimmunnaya tugoukhost' i veroyatnost' ee formirovaniya v detskom vozraste: obzor literatury i sobstvennye nablyudeniya.

Autoimmune sensorineural hearing loss (AiSNHL) is an uncommon auditory disorder characterized by rapidly progressive bilateral hearing loss and a positive clinical response to treatment with corticosteroids and cytostatics. The prevalence of the disease in the adult population is less than 1% among all cases of subacute and permanent sensorineural hearing loss (precise data are unknown), it is even rarer in children. AiSNHL can be primary (isolated, organ-specific) or secondary (manifestation of another systemic autoimmune disease). The pathogenesis of AiSNHL is based on the proliferation of autoaggressive T cells and the pathological production of autoantibodies to the protein structures of the inner ear, which leads to damage to various parts of the cochlea (possibly also to the retrocochlear parts of the auditory system), less frequently to the vestibular labyrinth. Pathologically, the disease is most often represented by cochlear vasculitis with degeneration of the vascular stria, damage to hair cells and spiral ganglion cells, and endolymphatic hydrops. In 50% of cases, the result of autoimmune inflammation may be fibrosis and/or ossification of the cochlea. The most characteristic symptoms of AiSNHL at any age are episodes of sudden progression of hearing loss, fluctuations of hearing thresholds, and bilateral, often asymmetric impairments. The article presents contemporary ideas of the clinical and audiological manifestations of AiSNHL, the possibilities of diagnosing and treating the disease, and highlights the current approaches to (re)habilitation. Along with literature data, two own clinical cases of an extremely rare pediatric AiSNHL are given.

ANA-specific antibodies, ANA patterns, anti-ds-DNA results, and clinical diagnosis: a laboratory and clinical audit.

The diagnosis of systemic autoimmune diseases (SAID) is challenging, due to overlapping features with other non-immune disorders. Anti-nuclear antibodies (ANA)/anti-cellular antibodies are the sensitive screening tests but anti-double-stranded-deoxyribonucleic acid-antibody (anti-ds-DNA) and ANA-specific antibodies are specific for SAID. We aimed to look at ANA-specific antibodies in our patients and correlated them with ANA patterns, anti-ds-DNA, and clinical diagnosis for proper interpretation and better patient management cost-effectively. A retrospective data analysis of 641 patients was done (1st of February 2019 to 31st of July 2021) who were tested for ANA-specific antibodies at the Immunology Department of Indus Hospital and Health Network. ANA and anti-ds-DNA results and clinical diagnosis were also analyzed for ANA-specific antibody-positive patients. Descriptive data were presented in mean ± standard deviation and frequency percentages whereas inferential data were analyzed with a chi-square test for association between ANA-specific antibodies status, ANA, anti-ds-DNA, and clinical features. ANA-specific antibodies test revealed positivity for at least one autoantibody in 245 (38.2%) patients. Of these, ANA was tested in 206 patients reactive for ANA-specific antibodies and found positive in 195 (95%) as compared to negative (< 0.001). Speckled and homogenous were predominant ANA patterns in ANA-specific antibody-positives (56% and 42% respectively). Multiple ANA patterns were found in 18 patients most commonly with systemic lupus erythematosus (SLE) and mixed connective tissue disorder (MCTD). Anti-SSA were the most common ANA-specific antibodies (50%) and were mostly found in sera with speckled (61/97) and homogenous (38/97) patterns and associated mostly with SLE (48%) and Sjogren's syndrome (86%). Among ANA-negative patients, anti-SSA were the most common antibodies (n = 5). Anti-ds-DNA was found in 66% of SLE patients along with another ANA-specific antibody. This study showed that testing for ANA-specific antibodies cannot be gated on ANA patterns. Also, there is a redundancy of these antibodies with various clinical diagnoses. Moreover, they are useful in making a diagnosis in ANA-negative patients as well with clinical suspicion.

Active vaccination campaign to increase seasonal influenza vaccination coverage: a monocenter experience in a cohort of Italian patients with systemic autoimmune diseases.

Seasonal influenza is a frequent cause of hospitalization and mortality among patients with systemic autoimmune diseases. Despite this evidence, vaccination coverage is generally much lower than the minimum 75% target proposed by the WHO. Therefore, an active campaign was implemented in the years 2019/2020 and 2020/2021 within the Rheumatology Department of the Niguarda Hospital (Milan, Italy) to improve the vaccination coverage in patients with inflammatory arthritis. This study aims to evaluate the vaccination coverage in the 2019/2020 and 2020/2021 (active campaigns) seasons and to compare these results with the 2018/2019 season. A monocenter observational study was conducted among adult patients with rheumatoid arthritis, spondylarthritis, or psoriatic arthropathy, who were referred to the Rheumatology Department of the Niguarda Hospital. Patients were given a questionnaire to investigate previous years' vaccination coverage and to propose an influenza vaccine for the 2020/2021 season. Compared with 2018/2019, a trend for increase in vaccination coverage was reported in 2019/2020 season (+ 10.7%, p = 0.055; 45.5% of coverage) and a statistically significant increase was reported in 2020/2021 (+ 31.2%, p < 0.001; 65.9% of coverage). The increase was also significant when comparing the 2020/2021 and 2019/2020 seasons (+ 20.5%, p < 0.001). The greatest increase in vaccination coverage was observed among under-65-year-old patients. Obtained results support the implementation of active vaccination campaigns to increase vaccination coverage among patients with systemic autoimmune diseases and highlight the importance of external factors (such as the COVID-19 pandemic) in directing the patient to adopt preventive measures to avoid infections and related complications.

Research progress of single-cell transcriptome sequencing in autoimmune diseases and autoinflammatory disease: A review.

Autoimmunity refers to the phenomenon that the body's immune system produces antibodies or sensitized lymphocytes to its own tissues to cause an immune response. Immune disorders caused by autoimmunity can mediate autoimmune diseases. Autoimmune diseases have complicated pathogenesis due to the many types of cells involved, and the mechanism is still unclear. The emergence of single-cell research technology can solve the problem that ordinary transcriptome technology cannot be accurate to cell type. It provides unbiased results through independent analysis of cells in tissues and provides more mRNA information for identifying cell subpopulations, which provides a novel approach to study disruption of immune tolerance and disturbance of pro-inflammatory pathways on a cellular basis. It may fundamentally change the understanding of molecular pathways in the pathogenesis of autoimmune diseases and develop targeted drugs. Single-cell transcriptome sequencing (scRNA-seq) has been widely applied in autoimmune diseases, which provides a powerful tool for demonstrating the cellular heterogeneity of tissues involved in various immune inflammations, identifying pathogenic cell populations, and revealing the mechanism of disease occurrence and development. This review describes the principles of scRNA-seq, introduces common sequencing platforms and practical procedures, and focuses on the progress of scRNA-seq in 41 autoimmune diseases, which include 9 systemic autoimmune diseases and autoinflammatory diseases (rheumatoid arthritis, systemic lupus erythematosus, etc.) and 32 organ-specific autoimmune diseases (5 Skin diseases, 3 Nervous system diseases, 4 Eye diseases, 2 Respiratory system diseases, 2 Circulatory system diseases, 6 Liver, Gallbladder and Pancreas diseases, 2 Gastrointestinal system diseases, 3 Muscle, Bones and joint diseases, 3 Urinary system diseases, 2 Reproductive system diseases). This review also prospects the molecular mechanism targets of autoimmune diseases from the multi-molecular level and multi-dimensional analysis combined with single-cell multi-omics sequencing technology (such as scRNA-seq, Single cell ATAC-seq and single cell immune group library sequencing), which provides a reference for further exploring the pathogenesis and marker screening of autoimmune diseases and autoimmune inflammatory diseases in the future.

Systemic Autoimmune Diseases in Patients Hospitalized with COVID-19 in Spain: A Nation-Wide Registry Study.

We aimed to evaluate the clinical outcome of Systemic Autoimmune Diseases (SADs) patients hospitalized with COVID-19 in Spain, before the introduction of SARS-CoV-2 vaccines. A nationwide, retrospective and observational analysis of the patients admitted during 2020, based on the ICD10 codes in the National Registry of Hospital Discharges, was performed. Among 117,694 patients, only 892 (0.8%) presented any type of SAD before COVID-19-related admission: Sjogren's Syndrome constituted 25%, Systemic Vasculitides 21%, Systemic Lupus Erythematosus 19%, Sarcoidosis 17%, Systemic Sclerosis 11%, Mixed and Undifferentiated Connective Tissue Disease 4%, Behçet's Disease 4% and Inflammatory Myopathies 2%. The in-hospital mortality rate was higher in SAD individuals (20% vs. 16%, p < 0.001). After adjustment by baseline conditions, SADs were not associated with a higher mortality risk (OR = 0.93, 95% CI 0.78−1.11). Mortality in the SADs patients was determined by age (OR = 1.05, 95% CI 1.04−1.07), heart failure (OR = 1.67, 95% CI 1.10−2.49), chronic kidney disease (OR = 1.29, 95% CI 1.05−1.59) and liver disease (OR = 1.97, 95% CI 1.13−3.44). In conclusion, the higher COVID-19 mortality rate seen in SADs patients hospitalized in Spain in 2020 was related to the higher burden of comorbidities, secondary to direct organ damage and sequelae of their condition. Whilst further studies should evaluate the impact of baseline immunosuppression on COVID-19 outcomes in this population, efforts should be focused on the optimal management of SAD to minimize the impact of the organ damage that has been shown to determine COVID-19 prognosis.

Alarmins in autoimmune diseases.

Alarmins are endogenous, constitutively expressed, chemotacting and immune activating proteins or peptides released because of non-programmed cell death (i.e. infections, trauma, etc). They are considered endogenous damage-associated molecular patterns (DAMPs), able to induce a sterile inflammation. In the last years, several studies highlighted a possible role of different alarmins in the pathogenesis of various autoimmune and immune-mediated diseases. We reviewed the relevant literature about this topic, for about 160 articles. Particularly, we focused on systemic autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, idiopathic inflammatory myopathies, ANCA-associated vasculitides, Behçet's disease) and cutaneous organ-specific autoimmune diseases (vitiligo, psoriasis, alopecia, pemphigo). Finally, we discussed about future perspectives and potential therapeutic implications of alarmins in autoimmune diseases. In fact, identification of receptors and downstream signal transducers of alarmins may lead to the identification of antagonistic inhibitors and agonists, with the capacity to modulate alarmins-related pathways and potential therapeutic applicability.

Crioglobulinemia / Cryoglobulinemia

Las crioglobulinas son inmunoglobulinas que precipitan in vitro a temperaturas inferiores a 37°C, cuya precipitación reversible tras la exposición a bajas temperaturas permite su detección en el laboratorio. Esta característica tan especial tiene también implicaciones patógenas, aunque los mecanismos moleculares involucrados no están totalmente dilucidados. La enfermedad asociada a las crioglobulinas es heterogénea, ya que no todos los pacientes la presentan, incluye diversas presentaciones sindrómicas (la vasculitis es la más frecuente, el síndrome de hiperviscosidad es excepcional), y puede asociarse a cuadros clínicos agudos de una elevada mortalidad. Hasta la aparición de los tratamientos específicos antivirales, la principal etiología ha sido la infección crónica por el virus hepatitis C (VHC), y en la actualidad se asocia principalmente a enfermedades autoinmunes sistémicas, neoplasias malignas y casos sin etiología identificada (crioglobulinemia esencial). El tratamiento debe ser modulado según la etiopatogenia predominante (vasculitis o hiperviscosidad), la gravedad de la afectación de órganos internos y, especialmente, la enfermedad subyacente asociada (viral, autoinmune o hematológica). Debido al complejo escenario etiológico, clínico y patológico de la crioglobulinemia, resulta esencial el reconocimiento temprano de las presentaciones clínicas más frecuentes, una evaluación clínica integral de los diferentes órganos que pueden verse afectados, y el trabajo multidisciplinar liderado desde una unidad especializada en enfermedades autoinmunes sistémicas. (AU)

Cryoglobulins are immunoglobulins that precipitate in vitro at temperatures below 37 ̊C. Cryoglobulin-associated disease is heterogeneous, as not all patients present with it, includes various syndromic presentations (vasculitis is the most common, hyperviscosity syndrome is more exceptional), and can be associated with acute clinical pictures with high mortality. Until the appearance of specific antiviral treatments, the main aetiology has been chronic HCV infection, and currently it is mainly associated with systemic autoimmune diseases, malignant neoplasms and cases with no identified aetiology (essential cryoglobulinemia). Treatment should be modulated according to the predominant etiopathogenesis (vasculitis or hyperviscosity), the severity of internal organ involvement and, especially, the associated underlying disease. Due to the complex aetiological, clinical and pathological scenario of cryoglobulinaemia, early recognition of the most common clinical presentations, a comprehensive clinical assessment of the different organs that may be affected, and multidisciplinary work led by a unit specialised in systemic autoimmune diseases is essential. (AU)

The Relationship Between Health Literacy and Quality of Life, Attitudes and Perceptions of Covid-19 and Vaccination Among Patients with Systemic Autoimmune Diseases.

This study aimed to evaluate health literacy in patients (n=395) with systemic autoimmune diseases (SAD) and analyze their relationships with health-related quality of life (HRQoL), attitudes and beliefs about Covid-19 and vaccination, and perceptions of changes in medical care during the pandemic. This study was cross-sectional and the majority (81%) of particpants resided in Spain. An anonymous online survey was distributed to an online SAD association. Health literacy was measured using the European Health Literacy Survey Questionnaire (HLS-EU-Q16) and the SF-36 tool was used to assess HRQoL. More than half of patients (57.7%) have inadequate health literacy and the mean health literacy level was 9.63(5.66). Patients with inadequate health literacy levels presented the lowest HRQoL scores in all SF-36 domains (p < .001). Health literacy scores were positively correlated with all SF-36 domains (p < .001). The reservations to get vaccinated against Covid-19 were linked to health literacy level (p = 0.024). There are high levels of inadequate health literacy among patients with SAD and it is associated with worse HRQoL and risk attitudes about Covid-19 vaccination and medical care during the pandemic.

The Interplay between Autonomic Nervous System and Inflammation across Systemic Autoimmune Diseases.

The autonomic nervous system (ANS) and the immune system are deeply interrelated. The ANS regulates both innate and adaptive immunity through the sympathetic and parasympathetic branches, and an imbalance in this system can determine an altered inflammatory response as typically observed in chronic conditions such as systemic autoimmune diseases. Rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis all show a dysfunction of the ANS that is mutually related to the increase in inflammation and cardiovascular risk. Moreover, an interaction between ANS and the gut microbiota has direct effects on inflammation homeostasis. Recently vagal stimulation techniques have emerged as an unprecedented possibility to reduce ANS dysfunction, especially in chronic diseases characterized by pain and a decreased quality of life as well as in chronic inflammation.

Immunomodulatory effects of curcumin in systemic autoimmune diseases.

Systemic autoimmune diseases like rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus represent various autoimmune conditions identified by immune system dysregulation. The activation of immune cells, auto-antigen outbreak, inflammation, and multi-organ impairment is observed in these disorders. The immune system is an essential complex network of cells and chemical mediators which defends the organism's integrity against foreign microorganisms, and its precise operation and stability are compulsory to avoid a wide range of medical complications. Curcumin is a phenolic ingredient extracted from turmeric and belongs to the Zingiberaceae, or ginger family. Curcumin has multiple functions, such as inhibiting inflammation, oxidative stress, tumor cell proliferation, cell death, and infection. Nevertheless, the immunomodulatory influence of curcumin on immunological reactions/processes remains mostly unknown. In the present narrative review, we sought to provide current information concerning the preclinical and clinical uses of curcumin in systemic autoimmune diseases.

Dry eye disease, a prominent manifestation of systemic autoimmune disorders.

OBJECTIVES: Dry eye disease (DED) is arguably the most frequent ocular disease encountered in ophthalmic clinical practice. DED is frequently an underestimated condition causing a significant impact on visual function and quality of life. Many systemic autoimmune diseases (SAIDs) are related to moderate to severe DED. The main objective of this review is to enhance the awareness among ophthalmologists of the potential association of an underlying SAID in a high-risk patient with DED. METHODS: An exhaustive literature search was performed in the National Library of Medicine's Pubmed, Scopus, Web of Science, and Google Scholar databases for all English language articles published until November 2021. The main keywords included "dry eye disease" associated with autoimmune, connective tissue, endocrine, gastrointestinal, hematopoietic, vascular, and pulmonary diseases. Case reports, series, letters to the editor, reviews, and original articles were included. RESULTS: Although DED is frequently associated with SAIDs, its diagnosis is commonly delayed or missed, producing significant complications, including corneal ulceration, melting, scleritis, uveitis, and optic neuritis resulting in severe complications detrimental to visual function and quality of life. SAID should be suspected in a woman, 30 to 60 years old with a family history of autoimmunity, presenting with DED symptoms and extraocular manifestations including arthralgias, dry mouth, unexplained weight and hair loss, chronic fatigue, heat or cold intolerance, insomnia, and mood disorders. CONCLUSIONS: Establishing the correct diagnosis and treatment of DED associated with SAIDs is crucial to avoid its significant burden and severe ocular complications.

[Cryoglobulinemia]. / Crioglobulinemia.

Cryoglobulins are immunoglobulins that precipitate in vitro at temperatures below 37 ̊C. Cryoglobulin-associated disease is heterogeneous, as not all patients present with it, includes various syndromic presentations (vasculitis is the most common, hyperviscosity syndrome is more exceptional), and can be associated with acute clinical pictures with high mortality. Until the appearance of specific antiviral treatments, the main aetiology has been chronic HCV infection, and currently it is mainly associated with systemic autoimmune diseases, malignant neoplasms and cases with no identified aetiology (essential cryoglobulinemia). Treatment should be modulated according to the predominant etiopathogenesis (vasculitis or hyperviscosity), the severity of internal organ involvement and, especially, the associated underlying disease. Due to the complex aetiological, clinical and pathological scenario of cryoglobulinaemia, early recognition of the most common clinical presentations, a comprehensive clinical assessment of the different organs that may be affected, and multidisciplinary work led by a unit specialised in systemic autoimmune diseases is essential.

Pesticide use and risk of systemic autoimmune diseases in the Agricultural Health Study.

BACKGROUND: Systemic lupus erythematosus (SLE) risk has been associated with pesticide use, but evidence on specific pesticides or other agricultural exposures is lacking. We investigated history of pesticide use and risk of SLE and a related disease, Sjögren's syndrome (SS), in the Agricultural Health Study. METHODS: The study sample (N = 54,419, 52% male, enrolled in 1993-1997) included licensed pesticide applicators from North Carolina and Iowa and spouses who completed any of the follow-up questionnaires (1999-2003, 2005-2010, 2013-2015). Self-reported cases were confirmed by medical records or medication use (total: 107 incident SLE or SS, 79% female). We examined ever use of 31 pesticides and farm tasks and exposures reported at enrollment in association with SLE/SS, using Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI), with age as the timescale and adjusting for gender, state, and correlated pesticides. RESULTS: In older participants (>62 years), SLE/SS was associated with ever use of the herbicide metribuzin (HR 5.33; 95%CI 2.19, 12.96) and applying pesticides 20+ days per year (2.97; 1.20, 7.33). Inverse associations were seen for petroleum oil/distillates (0.39; 0.18, 0.87) and the insecticide carbaryl (0.56; 0.36, 0.87). SLE/SS was inversely associated with having a childhood farm residence (0.59; 0.39, 0.91), but was not associated with other farm tasks/exposures (except welding, HR 2.65; 95%CI 0.96, 7.35). CONCLUSIONS: These findings suggest that some agricultural pesticides may be associated with higher or lower risk of SLE/SS. However, the overall risk associated with farming appears complex, involving other factors and childhood exposures.