Search

We hereby present the case of a 25-year-old man who presented at the emergency department of Civil Hospital Karachi, Pakistan with signs and symptoms of acute viral hepatitis. Serology tests revealed that the patient was suffering from hepatitis E viral (HEV) infection. Concurrently, the patient was also found to have thrombocytopaenia (TCP). His TCP became better after the resolution of his jaundice, with the patient requiring a transfusion of one mega unit of platelets. After ruling out other common causes of TCP and after a thorough literature search, we concluded that an immune-mediated mechanism secondary to HEV infection might have been the cause behind his low platelet counts. Hence, we propose considering the possibility of HEV infection in patients presenting with acute liver failure and TCP, irrespective of age, gender, and geographical location of the patient. [ABSTRACT FROM AUTHOR]

Crohn's disease (CD) is an immune-mediated condition characterized by the transmural inflammation of the gut tissue, associated with progressive bowel damage often leading to surgical intervention. As operative resection of the damaged segment is not curative, a majority of patients undergoing intestinal resections for complicated CD present disease recurrence within 3 years after the intervention. Postoperative recurrence can be defined as endoscopic, clinical, radiological or surgical. Endoscopic recurrence rates within 1 year exceed 60% and the severity, according to the Rutgeerts' score, is associated with worse prognosis and can predict clinical recurrence (in up to 1/3 of the patients). Most importantly, about 50% of patients will undergo a reoperation after 10 years of their first intestinal resection. Therefore, the prevention of postoperative recurrence in CD remains a challenge in clinical practice and should be properly managed. We aim to summarize the most recent data on the definition, risk factors, assessment and treatment of postoperative CD recurrence., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Canine perianal fistulas are painful sinus tracts and ulcers that spontaneously develop in the skin around the anus. Middle-aged German shepherd dogs are most commonly affected and may have a genetic susceptibility. Although the disease was once believed related to conformational factors and primarily managed surgically, an immune-mediated pathogenesis is now recognized. Long-term medical management with immunomodulatory agents has become standard of care for canine perianal fistulas. Perianal fistulas can be debilitating and have a negative impact on quality of life of dogs and owners. Accurate diagnosis and aggressive medical therapy are key to successful management of canine perianal fistulas., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Severe delayed drug hypersensitivity reactions comprise different clinical entities and can involve different immune-mediated mechanisms. Common examples are severe cutaneous adverse reactions and druginduced internal organ injuries. The incidence of such reactions is overall low but seems to be on the rise reaching numbers as high as 9 per million individuals-years in the case of SJS/TEN and DRESS. Such conditions carry an important associated morbidity, and mortality can attain 40% in SJS/TEN patients, making these hypersensitivity reactions important targets when implementing preventive measures. Several risk factors have been identified for reaction severity; some are transverse, such as older age and underlying chronic diseases. The recent advances in pharmacogenetics allowed the identification of specific populations with higher risk and permitted strategic avoidance of certain drugs being HLA-B*57:01 screening in patients initiating abacavir the best successful example. In this work, we reviewed the epidemiology of SCARs and liver/kidney/lung drug-induced immune-mediated reactions. We focus on particular aspects such as prevalence and incidence, drugs involved, mortality and risk factors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: An E321G mutation in MYH1 was recently identified in Quarter Horses (QH) with immune-mediated myositis (IMM) defined by a phenotype of gross muscle atrophy and myofiber lymphocytic infiltrates., Hypothesis/objectives: We hypothesized that the MYH1 mutation also was associated with a phenotype of nonexertional rhabdomyolysis. The objective of this study was to determine the prevalence of the MYH1 mutation in QH with exertional (ER) and nonexertional (nonER) rhabdomyolysis., Animals: Quarter Horses: 72 healthy controls, 85 ER-no atrophy, 56 ER-atrophy, 167 nonER horses selected regardless of muscle atrophy., Methods: Clinical and histopathologic information and DNA was obtained from a database for (1) ER > 2 years of age, with or without atrophy and (2) nonER creatine kinase (CK) ≥ 5000 U/L, <5 years of age. Horses were genotyped for E321G MYH1 by pyrosequencing., Results: The MYH1 mutation was present in a similar proportion of ER-no atrophy (1/56; 2%) and in a higher proportion of ER-atrophy (25/85; 29%) versus controls (4/72; 5%). The MYH1 mutation was present in a significantly higher proportion of nonER (113/165; 68%) than controls either in the presence (39/42; 93%) or in absence (72/123; 59%) of gross atrophy. Lymphocytes were present in <18% of muscle samples with the MYH1 mutation., Conclusions and Clinical Importance: Although not associated with ER, the MYH1 mutation is associated with atrophy after ER. The MYH1 mutation is highly associated with nonER regardless of whether muscle atrophy or lymphocytic infiltrates are present. Genetic testing will enhance the ability to diagnose MYH1 myopathies (MYHM) in QH., (© 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Abstract: Although there are reports of narcolepsy type 1 caused by lesions of the central nervous system, there are far fewer reports of narcolepsy type 2 (NT2) caused by discrete brain lesions. We report a case of a patient in whom NT2 was diagnosed after a viral illness, and inflammatory lesions in the right thalamus and amygdala were found. In addition, symptoms of autonomic impairment developed and postural tachycardia syndrome was subsequently diagnosed in this patient. To our knowledge this is the first reported case of NT2 resulting from central nervous system lesions in these discrete locations, as well as the first reported case of postural tachycardia syndrome associated with narcolepsy., (© 2018 American Academy of Sleep Medicine.)

Immune suppressive therapies target exaggerated and deleterious responses of the immune system. Triggered by exogenous or endogenous factors, these improper responses can lead to immune or inflammatory manifestations, such as urticaria, equine asthma, or autoimmune and immune-mediated diseases. Glucocorticoids are the most commonly used immune suppressive drugs and the only ones supported by robust evidence of clinical efficacy in equine medicine. In some conditions, combining glucocorticoids with other pharmacologic and nonpharmacologic treatments, such as azathioprine, antihistamine, bronchodilators, environmental management, or desensitization, can help to decrease dosages and associated side effects., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Immune mediated inflammatory anterior segment diseases are variable and their management requires intense immunosuppression. Treatment with topical steroids is associated with serious ocular side effects. In order to overcome the potentially blinding complications of topical steroids, immunomodulatory drugs are being used more frequently. Tacrolimus is a calcineurin inhibitor that induces suppression of T lymphocytes activity and reduction of ocular inflammation. Tacrolimus was recently investigated for application in various anterior segment inflammatory disorders. In this review, we will discuss the therapeutic application of topical tacrolimus as a steroid-sparing agent in treating T cell mediated anterior segment inflammation.

Introduction: Infectious and immune-mediated encephalitides are important but under-recognised causes of morbidity and mortality in childhood, with a 7% death rate and up to 50% morbidity after prolonged follow-up. There is a theoretical basis for ameliorating the immune response with intravenous immunoglobulin (IVIG), which is supported by empirical evidence of a beneficial response following its use in the treatment of viral and autoimmune encephalitis. In immune-mediated encephalitis, IVIG is often used after a delay (by weeks in some cases), while diagnosis is confirmed. Wider use of IVIG in infectious encephalitis and earlier use in immune-mediated encephalitis could improve outcomes for these conditions. We describe the protocol for the first ever randomised control trial of IVIG treatment for children with all-cause encephalitis., Methods and Analysis: 308 children (6 months to 16 years) with a diagnosis of acute/subacute encephalitis will be recruited in ∼30 UK hospitals and randomised to receive 2 doses (1 g/kg/dose) of either IVIG or matching placebo, in addition to standard treatment. Recruitment will be over a 42-month period and follow-up of each participant will be for 12 months post randomisation. The primary outcome is 'good recovery' (score of 2 or lower on the Glasgow Outcome Score Extended-paediatric version), at 12 months after randomisation. Additional secondary neurological measures will be collected at 4-6 weeks after discharge from acute care and at 6 and 12 months after randomisation. Safety, radiological, other autoimmune and tertiary outcomes will also be assessed., Ethics and Dissemination: This trial has been approved by the UK National Research Ethics committee (South Central-Oxford A; REC 14/SC/1416). Current protocol: V4.0 (10/03/2016). The findings will be presented at national and international meetings and conferences and published in peer-reviewed journals., Trial Registration Numbers: NCT02308982, EudraCT201400299735 and ISRCTN15791925; Pre-results., Competing Interests: CSL Behring have provided the study IMP (IVIG) and funded manufacture of placebo and the supply and distribution of IMP and placebo. AJP reports grants from NIHR EME programme, during the conduct of the study. The University of Oxford and AV hold patents for VGKC-complex antibody tests, licensed to Euroimmun AG, and receive royalties. The neuroimmunology work in the described trial is funded through the MRC/NIHR grant. MA serves on the data safety monitoring board for a study sponsored by Neurim Pharmaceuticals and is on the editorial advisory board for the International Journal of Language and Communication Disorders. MAI and LW report salary from the NIHR EME grant. ML has received consultation fees from CSL Behring, travel grants from Merck Serono and been awarded educational grants to organise meetings by Novartis, Biogen Idec, Merck Serono and Bayer. MS reports grants from Pfizer, outside the submitted work. TS is supported by the National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections at Liverpool. AE, LW, L-MY, MP, MS, RK and WKC have nothing to disclose., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: The aim of this retrospective study was to evaluate frequency, prognostic factors, and differences for various etiologies of neutropenia in dogs., Material and Methods: A total of 391 dogs with neutrophil counts < 2.78 x 10 9 /l (January 2008 to December 2012) were included and, depending on the etiology of neutropenia, assigned to seven diagnostic groups: nonbacterial infectious disease, increased demand due to marked inflammation, drug-associated, bone-marrow diseases, immune-mediated, physiologic, miscellaneous. Absolute neutrophil counts, evidence of neutrophil toxicity or left shift, case history, rectal temperature, hospitalization, and survival were compared among groups., Results: Increased demand due to marked inflammation (90/391, 23%) and nonbacterial infectious disease (70/391, 18%) were the most common causes for neutropenia, followed by drug-associated neutropenia (43/391, 11%) and bone-marrow disease (32/391, 8%). Immune-mediated and physiologic neutropenia (both 16/391, 4%) were uncommon. Almost one third (124/391, 32%) of dogs were assigned to the miscellaneous group. Absolute neutrophil counts were significantly higher (p < 0.01) in dogs of the physiologic and miscellaneous groups than in the other groups. Dogs with immune-mediated neutropenia or nonbacterial infectious disease displayed significantly lower absolute neutrophil counts than dogs with neutropenia due to an increased demand (p < 0.001) and were most commonly referred with a history of fever (11/16, 69%) or gastrointestinal signs (52/70, 74%), respectively. Neutrophil toxicity and left shift were most commonly associated with an increased demand due to marked inflammation (60/90 and 25/90, 67% and 28%, respectively) and the mortality rate was highest in this group (32/90, 36%)., Conclusion: Neutrophil toxicity and left shift are associated with an increased demand due to marked inflammation and may indicate a poor prognosis. The lower the absolute neutrophil count, the greater the probability of an immune-mediated neutropenia., Clinical Relevance: Neutropenia should be assessed in context with case history, clinical examination, and neutrophil morphology.

Ipilimumab is a human monoclonal IgG1 antibody against CTLA-4 that has been shown to prolong the overall survival of advanced melanoma. The most common adverse events associated with ipilimumab are immune-related. Severe hematological toxicity is rare. We report a case of severe neutropenia following ipilimumab therapy that fully resolved after the administration of prednisone, cyclosporine, and anti-thymocyte globulin therapies.

Autoimmune neurologic diseases are of major clinical importance in children. Antibody-mediated diseases of the central nervous system are now increasingly recognized in childhood, where the antibodies bind to cell surface epitopes on neuronal or glial proteins, and the patients demonstrate either focal or more generalized clinical signs depending on the extent of brain regions targeted by the antibodies. The antibodies are directed towards ion channels, receptors, and membrane proteins; and the diseases include limbic encephalitis and N-methyl-d-aspartate receptor-antibody encephalitis, among many others. Additionally there are conditions where the wider immune system is implicated. Neurologic features like seizures, movement disorders, autonomic dysfunction, and sleep disorders, with neuroimaging and electrophysiologic features, may indicate a specific antibody-mediated or immune disorder. Often, phenotypic overlap is observed between these conditions, and phenotypic variation seen in children with the same condition. Nevertheless, many patients benefit from immunotherapy with substantial improvement, although huge efforts are still required to optimize the outcome for many patients. In many patients no antibodies have yet been identified, even though they respond to immunotherapies. Here we describe the known antibodies and associated diseases, discuss conditions that are thought to be immune-mediated but have no known immunologic biomarker, and provide guidelines for the investigation and classification of these disorders., (© 2016 Elsevier B.V. All rights reserved.)

Antibody-mediated diseases of the central nervous system are a relatively new and challenging field in autoimmune neurologic disease and of major clinical importance in children and adults. The antibodies bind to cell-surface epitopes on neuronal or glial proteins, and the patients demonstrate either focal or more generalized clinical signs depending on the extent of brain regions targeted by the antibodies. The presence of seizures, movement disorders, autonomic dysfunction and sleep disorders, alongside neuroimaging and electrophysiological features may indicate a specific antibody-mediated disorder. However, phenotypic variation may be observed in children with the same antibody. Regardless, many patients benefit from immunotherapy with substantial improvement., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Meningoencephalomyelitis of unknown origin (MUO) is a heterogeneous group of overlapping central nervous system inflammatory diseases of unknown cause. This article highlights the current understanding of MUO and its phenotypic variants encountered in clinical practice. Diagnostic evaluation of presumptive MUO includes lesion distribution on magnetic resonance imaging and ruling out other acquired diseases. Recent evidence provides further knowledge of immune-mediated processes that underlie the pathogenesis of MUO. Current empiric treatment options include corticosteroids and other adjunctive immunomodulating therapies. As the understanding of neuroimmunology and genetic influences on these disorders evolves, a more targeted treatment approach is becoming attainable., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Thrombocytopenia is commonly seen in laboratory findings, especially in critically ill patients. Although the incidence is rare, drug-induced immune thrombocytopenia (DITP) is a serious complication that is often overlooked as a cause of thrombocytopenia. Over the last century, extensive research and data collection have been done in an attempt to better characterize DITP. Heparin-induced thrombocytopenia is the most common DITP and has distinct pathogenesis, diagnosis, and treatment options. However, other offending medications are less well known and have triggered many questions and constant search for answers. This review will discuss both drug-induced immune-mediated and nonimmune-mediated thrombocytopenias, with a focus on immune-mediated processes. Thrombocytopenia caused by chemotherapy will not be discussed in this article., (© The Author(s) 2014.)

Background: Inpatient providers have varying levels of knowledge in managing patients with drug and/or penicillin (PCN) allergy., Objectives: Our objectives were (1) to survey inpatient providers to ascertain their baseline drug allergy knowledge and preparedness in caring for patients with PCN allergy, and (2) to assess the impact of an educational program paired with the implementation of a hospital-based clinical guideline., Methods: We electronically surveyed 521 inpatient providers at a tertiary care medical center at baseline and again 6 weeks after an educational initiative paired with clinical guideline implementation. The guideline informed providers on drug allergy history taking and antibiotic prescribing for inpatients with PCN or cephalosporin allergy., Results: Of 323 unique responders, 42% (95% CI, 37-48%) reported no prior education in drug allergy. When considering those who responded to both surveys (n = 213), we observed a significant increase in knowledge about PCN skin testing (35% vs 54%; P < .001) and loss of PCN allergy over time (54% vs 80%; P < .0001). Among those who reported attending an educational session (n = 62), preparedness to determine if an allergy was severe significantly improved (77% vs 92%; P = .03). Other areas, including understanding absolute contraindications to receiving a drug again and PCN cross-reactivity with other antimicrobials, did not improve significantly., Conclusions: Inpatient providers have drug allergy knowledge deficits but are interested in tools to help them care for inpatients with drug allergies. Our educational initiative and hospital guideline implementation were associated with increased PCN allergy knowledge in several crucial areas. To improve care of inpatients with drug allergy, more research is needed to evaluate hospital policies and sustainable educational tools., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Abstract- Mast cells were found in the surface epidermis and outer root sheath epithelium in 37 of 338 cats (11.6 per cent) with non-neoplastic skin disorders. Epidermal mast cells were most commonly found in the eosinophilic plaque and the eosinophilic granuloma. Thevast majority of dermatoses wherein epidermal mast cells were found were characterised by: (1) a presumed immune-mediated pathogenesis, and (2) tissue eosinophilias. Résumé- Des mastocytes ont été observés dans l'épiderme superficiel ainsi que dans l'épithélium folliculaire chez 37 chats parmi 338 (11,6%) atteints de dermatoses non néoplasiques. Les mastocytes épidermiques ont été le plus souvent trouvés dans la plaque éosinophilique et le granulome éosinophilique. La grande majorité des dermatoses présentant des mastocytes épidermiques était caractérisée par: (1) la présomption d'une pathogénie immunodépendante et (2) une éosinophilie tissulaire. Zusammenfassung- Mastzellen konnten in der oberflächlichen Epidermis und in den Epithelien der äußeren Wurzelscheide bei 37 von 338 untersuchten Katzen (11.6%) mit nicht-neoplastischen Plaques oder eosinophilem Granulom gefunden werden. Die überwiegende Zahl der Dermatosen, bei denen epidermale Mastzellen auftraten, war durch die beiden Kriterien 1) vermutlich immunvermittelte Pathogenese und 2) Gewebs-Eosionophilie charakterisiert. Resumen  En el presente trabajo se describe la presencia de mastocitos en la epidermis superficial y en la vaina folicular externa de 37 gatos de 338 examinados (11,6%) ninguno de los gatos examinados padecia enfermedades neoplásicas. Los mastocitos epidérmicos fueron más frecuentes en animates que padecian placas eosinofilicas y granulomas eosinofilicos. La gran mayoría de las dermatosis en las cuales se detectan mastocitos epidérmicos cuales se se caracterizan por: 1. Una posible patogenia inmunomediada y 2. eosinofilia tisular.