Association of autoimmune disorders with chronic rhinosinusitis in adults.

INTRODUCTION: Increasing evidence suggests that autoimmune disorders and their immunomodulating medications may increase the risk of rhinosinusitis compared to rhinitis. GOAL: To investigate the association between autoimmune disorders and rhinosinusitis. METHODS: We performed a case-control study of patients referred to West Virginia University from August 2020 to October 2022 for rhinologic complaints. Rhinosinusitis patients were diagnosed with either chronic rhinosinusitis (CRS) or recurrent acute rhinosinusitis (RARS). These patients were compared to non-rhinosinusitis patients. Patients' characteristics, comorbidities, and type of treatment of autoimmune disorders were reviewed. RESULTS: The sample consisted of 527 rhinosinusitis [184 CRS without nasal polyps (CRSsNP), 263 CRS with nasal polyps (CRSwNP) and 80 RARS patients] patients and 564 non-rhinosinusitis patients. Patients with rhinosinusitis were more likely to be older, males, have asthma, and have current and past smoking history (all with p-value < 0.05). Autoimmune disorders, primary antibody deficiency, and immunomodulator agents were more common in rhinosinusitis patients (16.5 % vs 9.4 %, OR = 1.9, p < 0.001; 5.1 % vs 0.5 %, OR = 10.1, p < 0.001; and 3.8 % vs 1.1 %, OR = 3.7, p = 0.003 respectively). Multivariate logistic regression adjusting for confounders showed that autoimmune disorders were strongly associated with rhinosinusitis [OR = 1.6, 95 % CI = 1.10-2.48], whereas the immunomodulators did not reach statistical significance [OR = 2.4, 95 % CI = 0.87-6.47]. Subgroup analysis showed the autoimmune disorders did not significantly differ between CRS and RARS groups [OR = 1.0, 95 % CI = 0.5-2.1], or between the CRSsNP and CRSwNP groups [OR = 0.9, 95 % CI = 0.5-1.7]. CONCLUSION: Autoimmune disorders are associated with rhinosinusitis, both CRS and RARS, independently of other risk factors.

Interplay of Anti-Viral Vaccines with Biologic Agents and Immunomodulators in Individuals with Autoimmune and Autoinflammatory Diseases.

Vaccines are an essential part of a preventative healthcare strategy. However, response to vaccines may be less predictable in immunocompromised people. While outcomes for individuals with autoimmune and autoinflammatory diseases have dramatically improved with treatment using immunomodulating and biologic agents, infections have caused significant morbidity in these people today often more than due to their underlying diseases. Immune-based biologic therapies contribute to these infectious complications. This review addresses anti-viral vaccines, their effectiveness and safety in patients treated with approved biologic agents and immune targeted therapy with a focus on vaccines against influenza, human papillomavirus, hepatitis B virus and varicella zoster virus. Preliminary information regarding SARS-CoV-2 anti-viral vaccines is addressed. Additionally, we present recommendations regarding the safe use of vaccines in immunocompromised individuals with the goal to enhance awareness of the safety and efficacy of these anti-viral vaccines in these high-risk populations.

Subconjunctival bone marrow-derived mesenchymal stem cell therapy as a novel treatment alternative for equine immune-mediated keratitis: A case series.

Equine immune-mediated keratitis (IMMK) leads to increased corneal opacity and inflammation secondary to an alteration of the local immune system. Bone marrow-derived mesenchymal stem cells (BM-MSC) have been shown to modulate the immune system by downregulating inflammation. Four horses with unilateral IMMK poorly responsive to traditional medical treatments underwent novel, autologous subconjunctival BM-MSC therapy. Bone marrow was harvested and processed as previously described for equine orthopedic disease. Horses received autologous subconjunctival BM-MSC injections approximately every 3-4 weeks for 1-5 treatments total. Horses were maintained on their current medical treatment regimen throughout the BM-MSC treatment period. Three horses had a positive response to therapy as demonstrated by an increase in corneal clarity, a decrease in neovascularization and a reduction in surface irregularity. One horse was nonresponsive to therapy. These experimental results demonstrate the safety and potential efficacy of an innovative solution for IMMK.

Early versus later treatment start in multiple sclerosis: a register-based cohort study.

BACKGROUND AND PURPOSE: To assess long-term treatment effectiveness of disease-modifying therapy (DMT) initiated early in disease course versus later treatment start. METHODS: We included all Danish patients with multiple sclerosis (MS) treated with DMT through two nationwide population-based MS registries. Patients were categorized as early treated if treatment started within 2 years after the first MS symptom (n = 2316) and later treated if treatment started between 2 and 8 years after clinical onset (n = 1479). We compared time from treatment start to progression to an Expanded Disability Status Scale (EDSS) score of 6 and mortality between cohorts as hazard ratio (HR) using a Cox proportional hazards model with adjustment for stabilized inverse probability of treatment weights. Several sensitivity analyses were conducted. RESULTS: The median follow-up time of 3795 patients was 7.0 (range 0.6-19.5) years for the EDSS score of 6 outcome and 10.4 (range 1.2-20.1) years for the mortality outcome. Patients with later treatment start showed a 42% increased hazard rate of reaching an EDSS score of 6 compared with the early-treated patients [HR, 1.42; 95% confidence interval (CI), 1.18-1.70; P < 0.001]. When stratified by sex, the increased hazard among later-treated women persisted (HR, 1.53; 95% CI, 1.22-1.93; P < 0.001), whereas the HR was lower in men (1.25; 95% CI, 0.93-1.69; P = 0.15). Mortality was increased by 38% in later starters (HR, 1.38; 95% CI, 0.96-1.99; P = 0.08). CONCLUSIONS: Patients who started treatment with DMT later reached an EDSS score of 6 more quickly compared with patients who started early and the delay showed a tendency to shorten time to death. Our results support the use of early treatment.

Biologicals for pediatric patients with atopic dermatitis: practical challenges and knowledge gaps.

Biologicals are becoming increasingly important in the therapeutic landscape of pediatric patients with moderate-to-severe atopic dermatitis (AD). Currently, dupilumab and tralokinumab are registered for the treatment of moderate-to-severe AD, and novel biologicals are expected to follow. Dupilumab was the first biological registered for AD in pediatric patients and was recently approved for patients aged six months to five years. Current and emerging biologicals may address the unmet need for effective and safe treatment options for pediatric AD patients, however, little is known about the practical implementation of biologicals in infants and preschoolers (aged <6 years), including the timing of treatment initiation, discontinuation, and long-term administration of the subcutaneous injections. Currently, only a small number of biologicals are approved for the treatment of infants and preschoolers for other inflammatory diseases. Consequently, data on the practical implementation of biological treatment remain scarce. In addition, long-term effects, impact on co-morbidities, and impact on live-accentuated vaccination are still unknown. With the introduction of biologicals for AD from the age of six months, potential challenges within the implementation of biologicals may arise. Therefore, we aim to discuss current practical challenges and knowledge gaps of the treatment with biologicals in infants and preschoolers with AD.

Muscle MRI in immune-mediated necrotizing myopathy (IMNM): implications for clinical management and treatment strategies.

OBJECTIVES: Immune-mediated necrotizing myopathy (IMNM) is the most severe idiopathic inflammatory myopathy (IIM) and early aggressive poly-immunotherapy is often required to reduce long-term disability. The aim of this study is to investigate muscle MRI in IMNM as outcome measure for disease activity, severity, progression, response to treatment, and to better characterize the pattern of muscle involvement. METHODS: This is a retrospective, observational, cross-sectional, and longitudinal study including 22 IMNM patients, divided into three groups based on timing of first MRI and if performed before or under treatment. T1 score and percentage of STIR positive muscles (STIR%) were considered and analyzed also in relation to demographic, clinical and laboratory characteristics. RESULTS: STIR% was higher in untreated patients and in those who performed MRI earlier (p = 0.001). Pelvic girdle and thighs were in general more affected than legs. T1 score was higher in patients with MRI performed later in disease course (p = 0.004) with a prevalent involvement of the lumbar paraspinal muscles, gluteus medius and minimus, adductor magnus and hamstrings. 22% of STIR positive muscles showed fat replacement progression at second MRI. Higher STIR% at baseline correlated with higher risk of fat replacement at follow-up (p = 0.003); higher T1 score correlated with clinical disability at follow-up, with late treatment start and delayed treatment with IVIG (p = 0.03). INTERPRETATION: Muscle MRI is a sensitive biomarker for monitoring disease activity and therapy response, especially when performed early in disease course and before treatment start, and could represent a supportive outcome measure and early prognostic index in IMNM.

Molluscum contagiosum eruption during therapy with methotrexate and abatacept: A clinical and dermoscopic case study.

The use of multiple drugs acting as modulators of the immune system are common among patients with severe autoimmune diseases. In these clinical scenarios, great attention should be placed on diagnosing infective cutaneous disorders that can underly iatrogenic immunosuppression. Here within, we report a rare case of molluscum contagiosum eruption on the face and the scalp during an immunomodulating treatment for rheumatoid arthritis, with clinical and dermatoscopic characterization.

Change of the microvascularization in systemic sclerosis, a matter of air.

Systemic sclerosis (SSc) is a rare complex disease, characterized by microvascular damage, auto-immunity, and fibrosis. Nailfold capillary microscopy (NCM), a safe and noninvasive imaging technique, can be used to visualize specific microvascular alterations in SSc. In this review, we discuss an interesting case of a patient with changes in microvascular pattern on NCM after pulmonary transplantation. We provide an overview of microvascular alterations in systemic sclerosis and the evidence in the literature about the effect of vasoactive and immunomodulation therapy on these vascular changes. We also outline the influence of pulmonal pathology, such as interstitial lung disease and pulmonary arterial hypertension, on the capillaroscopic pattern, and finally, we discuss how NCM could possibly serve as a biomarker of treatment.

[Effect of different groups of first line DMT on endothelial damage in multiple sclerosis]. / Vliyanie razlichnykh grupp PITRS pervoi linii na povrezhdenie endoteliya pri rasseyannom skleroze.

INTRODUCTION: Vascular changes, including destabilization of the blood-brain barrier, are common pathological signs in multiple sclerosis (MS). There are prerequisites, which indicate the direct effects of disease modifying therapy (DMT) on the state of the vascular wall and reduce the damage to the endothelium in MS. AIM OF THIS STUDY: Was to identify and evaluate the relationship of endothelial dysfunction in patients with multiple sclerosis with used DMT. MATERIALS AND METHODS: The study included 85 patients with a reliable diagnosis of MS according to the McDonald criteria of 2010 (56 women, 29 men) aged from 17 to 62 years (average age 36.3±1.2 years). All patients underwent a comprehensive clinical and neurological examination, laboratory tests (blood serum analysis for the content of adhesion molecules sICAM-1, sPECAM-1, sE-selectin, sP-selectin, for the content of homocysteine and matrix metalloproteinase 9 (MMR-9) by ELISA; blood plasma analysis for Von Willebrand factor antigen (vWf) by ELISA).The results of the study indicate a decrease of endothelial damage in MS during interferon therapy. Its also allow the use of indicators such as von Willebrand factor antigen, sPECAM-1, sE-selectin levels as potential markers of the effectiveness of DMT.

Adverse Effects of Immune Checkpoint Inhibitors (Programmed Death-1 Inhibitors and Cytotoxic T-Lymphocyte-Associated Protein-4 Inhibitors): Results of a Retrospective Study.

In recent years the use of immunomodulating therapy to treat various cancers has been on the rise. Three checkpoint inhibitors have been approved by the Food and Drug Administration (ipilimumab, pembrolizumab and nivolumab). The use of these drugs comes with serious adverse events related to excessive immune activation, collectively known as immune-related adverse events (irAEs). We conducted a system-based review of 139 case reports/case series that have described these adverse events between January 2016 and April 2018, found in the PubMed database. There was a broad spectrum of presentations, doses and checkpoint inhibitors used. The most common check point inhibitor observed in our literature review was nivolumab. The most common adverse effects encountered were colitis (14/139), hepatitis (11/139), adrenocorticotropic hormone insufficiency (12/139), hypothyroidism (7/139), type 1 diabetes (22/139), acute kidney injury (16/139) and myocarditis (10/139). The treatment most commonly consisted of cessation of the immune checkpoint inhibitor, initiation of steroids and supportive therapy. This approach provided a complete resolution in a majority of cases; however, there were many that developed long-term adverse events with deaths reported in a few cases. The endocrine system was the mostly commonly affected with the development of type 1 diabetes mellitus or diabetic ketoacidosis being the most frequently reported adverse events. While immunomodulating therapy is a significant advance in the management of various malignancies, it is capable of serious adverse effects. Because the majority of the cases developed pancreatic dysfunction within five cycles of therapy, in addition to the evaluation of other systems, pancreatic function should be closely monitored to minimize adverse impact on patients.

bFGF Polymorphism Is Associated with Disease Progression and Response to Chemotherapy in Multiple Myeloma Patients.

BACKGROUND/AIM: Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) play an important role in the initiation of angiogenesis. We aimed to assess whether polymorphisms within the genes coding for these angiogenic activators (VEGF (rs3025039;C>T) and bFGF (rs308395;G>C)) contribute to susceptibility and/or progression in multiple myeloma patients (MM) and to chemotherapy. PATIENTS AND METHODS: One hundred and thirty-two patients with MM and 122 controls were genotyped for the VEGF and bFGF alleles by the PCR-RFLP technique. Genotyping results were compared regarding progression, risk of disease and response to treatment. RESULTS: Patients in stage I-II disease (Durie-Salmon criteria) more frequently carried the bFGF -921G allele compared to patients in stage III (p=0.053) and healthy controls (OR=2.010, p=0.040). Progression after first-line chemotherapy was more frequent among patients carrying this variant (p=0.022). CONCLUSION: Our results imply that the course of disease in MM patients is associated with a polymorphism within the bFGF gene.

Polymorphisms within beta-catenin encoding gene affect multiple myeloma development and treatment.

Recent studies have suggested that cereblon (CRBN) is essential for the anti-myeloma (MM) activity of immunomodulatory drugs (IMiDs), such as thalidomide and lenalidomide, and that dysregulation of Wnt/ß-catenin pathway may be one of possible reasons of lenalidomide resistance. This prompted us to analyze the effect of polymorphisms within the genes coding for cereblon (CRBN (rs121918368 C>T)) and ß-catenin (CTNNB1 (rs4135385 A>G; rs4533622 A>C)). MM patients (n=142) and healthy individuals (n=123) were genotyped using the Light SNiP assays. The presence of the CTNNB1 (rs4533622) A allele was more frequently detected in patients presented with stage II-III disease according to International Staging System (63/82 vs. 26/44, p=0.043) and Durie-Salmon criteria (75/99 vs. 14/26, p=0.049). The CTNNB1 (rs4135385) AA homozygosity was more frequent among patients with better response to CTD, i.e., cyclophosphamide-thalidomide-dexamethasone (18/23 vs. 32/60, p=0.047). Patients carrying the CTNNB1 (rs4533622) AA genotype were better responders to the first line therapy with thalidomide containing regimens (p<0.05). No significant association was observed between the effect of lenalidomide therapy and polymorphisms studied. However, the occurrence of neutropenia during lenalidomide therapy was more frequent among the CTNNB1 (rs4135385) AA carriers (p=0.019), while the CTNNB1 (rs4533622) AA homozygosity characterized patients with high grade (3-4) neutropenia (p=0.044). No association was found for the CRBN polymorphism. These results suggest that the CTNNB1 polymorphisms may affect the clinical course and response to chemotherapy in patients with multiple myeloma.

Guillain-barré syndrome in pregnancy: an unusual case.

Guillain-Barré syndrome (GBS) is rare in pregnancy with an estimated incidence between 1.2 and 1.9 cases per 100,000 people annually, and it carries a high maternal risk. We report a 29-year-old primigravida who had pain and progressive heaviness of both lower limbs in her third trimester of pregnancy. The attending gynecologist ascribed these symptoms to ongoing pregnancy. The intrapartum period (lower segment caesarian section) passed uneventfully. On third postpartum day, the patient developed weakness of all the four limbs. A detailed history and physical examination pointed toward GBS although there was no antecedent infective episode. Subsequent nerve conduction velocity studies and cerebrospinal fluid analysis confirmed GBS. All other investigations including electrolytes were normal. The patient improved without the introduction of immunomodulating therapy.

Assessment of ovarian reserve and Doppler characteristics in patients with multiple sclerosis using immunomodulating drugs.

OBJECTIVE: There is limited data about fertility in multiple sclerosis (MS) patients using immunomodulating drugs and no data exists regarding the ovarian reserve of these patients. Therefore, we aimed to evaluate, the ovarian reserve and doppler characteristics of MS patients using immunomodulating drugs. MATERIAL AND METHODS: MS patients using immunomodulating drugs (interferon (IFN) ß and glatiramer acetate) and age-matched healthy controls were included in the study. Subjects were examined in the early follicular phase of the menstrual cycle with transvaginal ultrasound to evaluate ovarian volume, antral follicle count (AFC) and ovarian stromal artery Doppler. On the same day, blood was taken for determining serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) levels. A subgroup analysis was also carried out between MS patients using only IFN ß and controls to compare the same parameters. RESULTS: Mean ovarian volume and total AFC were lower in MS patients using immunomodulating drugs than in the controls. FSH and E2 levels did not show any differences between the groups, but LH levels were significantly higher in MS patients. All the Doppler parameters of the ovarian stromal artery were higher in MS patients but not significantly. In the subgroup analysis, the same significant differences were found for ovarian volume, AFC and LH levels. In addition, MS patients showed significantly higher mean pulsatility index measurement than the controls. CONCLUSION: The findings of this study demonstrated diminished ovarian volume and follicular reserve in MS patients using immunomodulating drugs compared to age matched healthy controls. However, further studies are required to elucidate whether compromised ovarian reserve in MS patients is due to drugs or the disease itself.

Beta interferons in clinically isolated syndromes: a meta-analysis

Beta-interferon use in definite multiple sclerosis (MS) has been proven to modify clinical and magnetic resonance imaging outcome. We review and summarize the data of published double-blind, randomized clinical trials to assess, with a meta-analysis the safety and efficacy of beta-interferon on the occurrence of relapses in patients with a first clinical event suggestive of MS. After two years of follow-up, interferon beta decreased the risk of conversion to clinically definite MS 0.51[0.39-0.65], and delayed the time to diagnosis up to 367 days. Side-effects were mild and self limited. Our findings support the efficacy of early treatment with beta-interferon in reducing conversion to clinically defined MS in patients with clinically isolated syndromes.

Já é suficientemente conhecido que a utilização de interferon beta modifica o prognóstico clínico e de ressonância magnética em pacientes com esclerose múltipla (EM). Revisamos e sumarizamos os dados dos ensaios clínicos, duplo-cegos, randomizados e controlados com placebos para analisar, através de meta-análise, a segurança e eficácia dos interferons-beta sobre a ocorrência de recidivas em pacientes com um primeiro evento clínico sugestivo de EM. Após dois anos de seguimento, os interferons-beta diminuíram o risco de conversão para EM clinicamente definida 0,51[0,39-0,65] e retardaram o tempo para diagnóstico em 367 dias. Os efeitos colaterais foram leves e auto limitados. Nossos dados comprovam a eficácia e segurança do interferon-beta em reduzir a conversão para EM clinicamente definida de pacientes com síndromes clínicas isoladas.