Search

Background: Inflammatory myopathy is generally categorized into generalized inflammatory myopathies (gIM), which affect muscles throughout the body, and focal inflammatory myopathies (fIM), which are localized to specific muscles or muscle groups. This report details a case of immune-mediated polymyositis in a dog, successfully diagnosed using MRI and IHC and managed with immunosuppressive therapy. Case presentation: A 5-year-old castrated male Poodle was admitted to our hospital presenting with lethargy and exercise intolerance. Biochemical analysis revealed significantly elevated serum levels of aspartate aminotransferase (AST) and creatine kinase (CK). Physical examination showed muscle atrophy in the hind legs, but further orthopedic and neurological examinations identified no additional abnormalities. MRI demonstrated hyperintense and heterogeneous signal changes across the muscles, including contrast enhancement, suggesting inflammatory myopathy. This diagnosis was confirmed through histopathological examination, which revealed inflammatory lesions with fibrous tissue proliferation within the muscle tissue. To investigate the presence and type of inflammatory cells and vascular changes, aiding in the differential diagnosis of inflammatory myopathies, immunohistochemistry (IHC) was performed, revealing positive findings for CD8+, CD4+, and VEGF in the evaluated tissue, leading to a diagnosis of polymyositis. Conclusions: The dog was diagnosed with immune-mediated polymyositis and treatment was initiated with prednisolone at 1 mg/kg twice daily and azathioprine at 2 mg/kg once daily. Following the administration of these immunosuppressive agents, CK levels returned to normal, and the dog's exercise intolerance and lethargy resolved. The thickness of the hind legs also increased progressively. The dog has maintained an improved condition under continued immunosuppressive therapy for four months. This case highlights the critical role of MRI and immunohistochemistry in diagnosing immune-mediated polymyositis, demonstrating their alternative capability in cases where conventional electromyography (EMG) is not feasible in this context. [ABSTRACT FROM AUTHOR]

Acute-onset seizures in children pose a diagnostic and therapeutic dilemma. Some epilepsy cases presenting with seizures but without encephalopathy, though treatable with immunotherapy, are often missed due to lack of suspicion of immune mechanism in the context of absent encephalitis. A prospective study was conducted on premorbidly normal children with new-onset seizures occurring in clusters, with normal neuroimaging. Investigations included electroencephalogram (EEG), cerebrospinal fluid examination, and testing for autoantibodies. All cases received methylprednisolone pulse therapy along with antiseizure medications (ASMs), followed by monthly dexamethasone oral pulse therapy. Fifteen cases were enrolled (11 males, four females). Mean age at seizure onset was 4.6 years. Focal seizures were present in 13/15 (86.7%) cases. Magnetic resonance imaging of the brain was normal in all. EEG showed interictal epileptiform discharges in 12 cases (focal in nine) and ictal record in two cases. On monthly oral steroids, number of ASMs could be reduced. Eight cases never had a relapse, while seven did have it. Relapses were more common if more than three ASMs were tried and less if steroids were started within 30 days. Immune-mediated seizures/epilepsy without encephalopathy is a new, important, and treatable entity. Early diagnosis and institution of immunotherapy results in significant improvement in seizure control and also reduces the need for long-term polytherapy. Awareness of this entity is crucial, especially when premorbidly normal children present with new-onset clusters of refractory seizures. [ABSTRACT FROM AUTHOR]

We report the case of an acute cerebellitis following COVID-19 in 32-year-old man who presented with a life-threatening critical cerebellar syndrome contrasting with normal paraclinical findings. Despite this fulminant critical presentation, the patient fully recovered in 37 days after early treatment with high-dose steroids and intravenous immunoglobulins. This case highlights the need for clinicians to be aware of acute cerebellitis following COVID-19, despite normal laboratory, imaging and electroencephalography findings and the importance to start appropriate treatment as soon as possible. [ABSTRACT FROM AUTHOR]

Simple Summary: Canine immune-mediated polyarthritis is a common disease that affects young dogs. This study aims at assessing whether leflunomide as add-on treatment to steroids would reduce the rate of relapse and improve survival in dogs with the disease. However, the results of this study suggest that there was no difference in outcomes between dogs that received or did not receive the drug as an add-on therapy. This could provide another step in understanding the nature of immune-mediated diseases and assist practicing veterinarians in making informed decisions about the most appropriate treatment for these conditions. Immune-mediated polyarthritis (IMPA) has a relatively high relapse rate compared to other immune-mediated diseases. Leflunomide is frequently used to treat dogs with IMPA in conjunction with prednisolone. This retrospective cohort study aimed to evaluate the therapeutic efficacy of leflunomide as an adjunctive therapy to prednisolone in reducing relapse and mortality rates in dogs diagnosed with IMPA in Australia. The medical records of client-owned dogs diagnosed with IMPA at a specialist referral hospital in Southeast Queensland from 2017 to 2024 were reviewed. A total of 93 dogs were included in this study, divided into two groups based on the treatment received: Group PRED, consisting of 53 dogs treated with prednisolone as the sole immunosuppressive agent, and Group L+PRED, consisting of 40 dogs that received leflunomide as adjunctive therapy alongside prednisolone. Data collected included breed, age, weight, sex, serum C-reactive protein concentration, results of synovial fluid analysis and microbial culture, treatment protocol, relapse rates and time to relapse, and mortality rates. There was no difference in relapse or mortality rates, time to relapse, nor time to discontinue prednisolone between the PRED and L+PRED groups. The L+PRED group had higher body weights and lower prednisolone dose rate at discharge compared to those in the PRED group. This study demonstrated that the use of leflunomide as an adjunctive therapy to prednisolone for the treatment of dogs with IMPA had no improved outcomes, reduced relapse rates, or shortening in the duration of prednisolone therapy when compared to dogs receiving prednisolone monotherapy. [ABSTRACT FROM AUTHOR]

Background & aimsGaps remain in understanding the epidemiology of eosinophilic esophagitis (EoE). Our aim was to identify and validate a national cohort of individuals with EoE using Veterans Health Administration (VHA) data.MethodsWe used 2 validation strategies to develop algorithms that identified adults with EoE between 1999 and 2020. The first validation strategy applied International Classification of Diseases (ICD) code algorithms to a base cohort of individuals who underwent esophagogastroduodenoscopy with esophageal biopsy specimens. The second applied ICD code algorithms to a base cohort of all individuals in the VHA. For each ICD algorithm applied, a random sample of candidate EoE cases and non-EoE controls were selected and the charts were reviewed manually by a blinded reviewer. Each algorithm was modified iteratively until the prespecified diagnostic accuracy end point (95% confidence lower bound for a positive predictive value [PPV], >88%) was achieved. We compiled individuals from each strategy's maximum performance algorithm to construct the Veterans Affairs Eosinophilic Esophagitis Cohort.ResultsThe maximum performance algorithm from the first validation strategy included 2 or more ICD code encounters for EoE separated by more than 30 days and achieved a 93.3% PPV (lower bound, 88.1%) for identifying true EoE cases. The maximum performance algorithm from the second validation strategy included 4 or more ICD code encounters for EoE in which 2 codes were separated by at least 30 days, and similarly achieved a 93.3% PPV (lower bound, 88.1%). Combining both strategies yielded 6637 individuals, which comprised the Veterans Affairs Eosinophilic Esophagitis Cohort.ConclusionsWe developed and validated 2 highly accurate coding algorithms for EoE and established a nationwide VHA cohort of adults with EoE for future studies.

Idiopathic generalized tremor syndrome is a disorder characterized by an acute onset of full-body tremors, sometimes accompanied by vestibulo-cerebellar signs, that is responsive to treatment with corticosteroids. Although considered to have an overall good outcome, relapsing and persistent mild clinical signs have been described. So far, little is known about the etiopathology of this syndrome, but it is believed to have an immune-mediated origin. In human medicine, description of numerous autoantibodies involved in certain noninfectious neurologic disorders has revolutionized understanding of their pathophysiology, diagnosis and treatment. In this multicenter retrospective study, we aimed to describe the clinical signs, course, and outcome of dogs with idiopathic generalized tremor syndrome and correlate potential findings with the presence or absence of autoantibodies associated with autoimmune cerebellar syndromes in humans. Information regarding signalment, history, clinical signs, laboratory findings, diagnostic imaging and testing for regional infectious diseases was gathered and the remaining serum and CSF samples were then analyzed for neural antibodies against targets associated with autoimmune encephalitic diseases of humans. Thirty-three dogs were included, and screening for neural antibodies was performed in 30 of those dogs. The analysis showed an increased titer of mGluR1 antibodies in two dogs, GFAP and later in the course of disease mGluR1 antibodies in one dog and an increase in unspecific autoantibodies which could not be further classified in two dogs. Dogs with detectable neural autoantibodies always had cerebrospinal fluid abnormalities in the form of a pleocytosis, with or without increased protein concentration, and tended to present with hyperthermia, potentially indicating a more severe clinical form of idiopathic generalized tremor syndrome in these cases. In conclusion, idiopathic generalized tremor syndrome is proposed to be an immune-mediated disorder potentially mediated by neural autoantibodies in a subgroup of dogs. [ABSTRACT FROM AUTHOR]

In Serbia, Babesia gibsoni in dogs is less common than Babesia canis. Although two clinical cases were reported a decade ago, no additional clinical reports have since been published. Recently, a co-infection of B. gibsoni and B. canis was documented in Austria following a dog's trip to Serbia. The objectives of this study were to present comprehensive clinicopathological results of two clinical cases of B. gibsoni monoinfection in dogs in Serbia. Two male dogs: an 11-year-old Shih Tzu, and a 2-yearold Pit Bull Terrier, presented with clinical signs related to babesiosis with a history of biting by another dog. Both dogs had regenerative anemia, thrombocytopenia, and monocytosis while Shih Tzu had immune-mediated hemolytic anemia (IMHA). B. gibsoni mono-infection was confirmed by PCR testing. Both dogs were treated with a single dose of imidocarb-dipropionate, and a combination of metronidazole, clindamycin, and doxycycline (MCD protocol). The Shih Tzu also received prednisolone for three weeks. Following the MCD protocol, the Pitt Bull recovered, although thrombocytopenia persisted for nine months. In contrast, Shih Tzu's clinical condition worsened. The prednisolone treatment was discontinued, and azithromycin and atovaquone were introduced, leading to recovery after another three weeks of treatment. Long-term clinical and PCR monitoring revealed that the Pit Bull Terrier exhibited a more favorable response and a lower frequency of relapses compared to Shih Tzu. The findings suggest that B. gibsoni has become a clinically significant pathogen in Serbia. The MCD protocol appears effective for treating acute B. gibsoni infection in dogs, but further investigation is required to evaluate its efficacy in eliminating the parasite. [ABSTRACT FROM AUTHOR]

Purpose: To describe the clinical and histopathological features of a sterile granulomatous panuveitis syndrome in 33 dogs that underwent enucleation and ocular histopathology. Methods: Retrospective review of the medical records and ocular histopathology reports of 33 cases. Inclusion criteria were enucleation in conjunction with characteristic clinical and histopathological features. Results: Thirteen breeds were represented (including crossbreeds). Panuveitis was acute and fulminating, and secondary glaucoma was common (n = 27). Interval from initial presentation to enucleation was 99 days (median 33 days, range 5–605 days). The mean age at enucleation was 6.7 years. Ocular signs were initially unilateral (n = 18) or bilateral (n = 15). The disease became bilateral in 18/25 cases that initially underwent unilateral enucleation, resulting in enucleation or euthanasia in 9/18 (mean interval of 168 days). Seven out of 59 eyes had a good outcome following topical anti‐inflammatory and systemic immunosuppressive therapy. None of the dogs had travel history nor relevant systemic signs from presentation to follow‐up (mean 619 days, range 16–3012 days). Histopathology revealed histiocytic and lymphoplasmacytic panuveitis with pigment dispersion, and no infectious agents were identified on light microscopy. Conclusion: To the authors' knowledge, this is the first report of a sterile granulomatous panuveitis syndrome in dogs in the UK. The clinical signs are severe, with rapid progression, and can result in bilateral enucleation or euthanasia in affected dogs. There does not appear to be an age or breed predisposition, however further research is necessary in this regard. Early and aggressive intervention, with both topical and systemic immunosuppressive therapy, is recommended to reduce the risk of blindness, enucleation, and euthanasia. [ABSTRACT FROM AUTHOR]

Arsenic trioxide (ATO) is now part of the standard regimen for the treatment of newly diagnosed and relapsed acute promyelocytic leukemia. The availability of an oral form of ATO has greatly reduced the incidence of cardiotoxicity as compared to intravenous (IV) administration. Increasing evidence suggests that ATO has anti-inflammatory properties that may be useful for the treatment of autoimmune diseases. These include the modulation of Treg cell activation, Th1/Th2 and Th17/Treg balance, depletion of activated T cells and plasmacytoid dendritic cells, and influence of B-cell differentiation, leading to reduced autoantibody and cytokine production. ATO has also been shown to induce apoptosis of activated fibroblast-like synoviocytes through the generation of reactive oxygen species and alter the gut microbiota in collagen-induced arthritis. Despite the emergence of newer treatment modalities, the treatment of systemic lupus erythematosus (SLE), especially refractory manifestations, remains a challenge, owing to the paucity of effective biological and targeted therapies that are devoid of adverse effects. Oral ATO is an attractive option for the treatment of SLE because of the lower cost of production, convenience of administration, and reduced cardiotoxicity. This article summarizes the anti-inflammatory mechanisms of ATO and its potential application in the treatment of SLE and other rheumatic diseases. [ABSTRACT FROM AUTHOR]

Background: Autoimmune neurological syndromes pose diagnostic challenges due to their resemblance to neurodegenerative conditions. Autoimmune spastic ataxia is a rare phenomenon. This case presents a 56‐y‐old woman with subacute‐onset spastic ataxia, highlighting the complexities in diagnosis and the role of autoimmunity in such cases. Case Presentation: A woman in her fifties developed progressive spastic ataxia over a year and presented to our outpatient department for evaluation. The patient exhibited clinical signs including saccadic intrusions, gaze‐evoked nystagmus, mixed dysarthria, spasticity, exaggerated reflexes, and cerebellar dysfunction. Brain magnetic resonance imaging (MRI) displayed the "hot cross bun sign" and cerebral and cerebellar atrophy. Initial tests yielded minimal abnormalities, but a positive antinuclear antibody (ANA) emerged. The patient initially declined immunotherapy. Upon symptom progression, a repeat cerebrospinal fluid (CSF) analysis showed inflammatory changes and a whole‐body positron emission tomography (PET) scan indicated reduced uptake in the cerebellum and brainstem. Subsequent paraneoplastic antibody testing revealed an unspecified neuronal antibody targeting capillaries and arterioles. Treatment with steroids, plasmapheresis, and azathioprine led to sustained improvement, reducing spasticity, and enabling her to walk short distances. Conclusions: This case emphasizes the diagnostic complexity of autoimmune neurological syndromes, particularly spastic ataxia. Autoimmune etiology should be considered even when neurodegenerative conditions seem likely. The presence of neuronal antibodies, inflammatory CSF, and response to immunotherapy underscores the role of autoimmunity in this case. Additionally, the "hot cross bun sign" may not always signify neurodegeneration, but can indicate immune‐mediated neural damage. Recognizing autoimmune involvement early offers therapeutic possibilities and highlights the need for a comprehensive diagnostic approach in such cases. [ABSTRACT FROM AUTHOR]

Abstract Immune thrombocytopenia (ITP) is the most common acquired primary hemostatic disorder in dogs. Immune thrombocytopenia less commonly affects cats but is an important cause of mortality and treatment‐associated morbidity in both species. Immune thrombocytopenia remains a diagnosis of exclusion for which diagnostic guidelines are lacking. Primary, or non‐associative, ITP refers to autoimmune platelet destruction. Secondary, or associative, ITP arises in response to an underlying disease trigger. However, evidence for which comorbidities serve as ITP triggers has not been systematically evaluated. To identify key diagnostic steps for ITP and important comorbidities associated with secondary ITP, we developed 12 Population Evaluation/Exposure Comparison Outcome (PECO) format questions. These questions were addressed by evidence evaluators utilizing a literature pool of 287 articles identified by the panelists using a structured search strategy. Evidence evaluators, using panel‐designed templates and data extraction tools, summarized evidence and created guideline recommendations that then were integrated by diagnosis and comorbidity domain chairs. The revised PECO responses underwent a Delphi survey process to reach consensus on final guidelines. A combination of panel expertise and PECO responses were employed to develop algorithms for diagnosis of ITP in dogs and cats, which also underwent 4 iterations of Delphi review. Comorbidity evidence evaluators employed an integrated measure of evidence (IME) tool to determine evidence quality for each comorbidity; IME values combined with evidence summaries for each comorbidity were integrated to develop ITP screening recommendations, which also were subjected to Delphi review. Commentary was solicited from multiple relevant professional organizations before finalizing the consensus. The final consensus statement provides clinical guidelines for the diagnosis of, and underlying disease screening for, ITP in dogs and cats. The systematic consensus process identified numerous knowledge gaps that should guide future studies. This statement is a companion manuscript to the ACVIM Consensus Statement on the Treatment of Immune Thrombocytopenia.

Abstract Background Romiplostim, a thrombopoietin analog, is commonly used to treat immune‐mediated thrombocytopenia (ITP) in humans, but its use in dogs remains limited. Objectives Evaluate the effects and adverse events of romiplostim administration in dogs with thrombocytopenia caused by various underlying diseases. Animals Forty‐two client‐owned dogs with naturally occurring thrombocytopenia at 2 referral animal hospitals. Methods Retrospective, multi‐institutional analysis to evaluate the outcomes of romiplostim treatment in dogs. Results Among the dogs treated with romiplostim, 27 experienced an increase in platelet count and 26 maintained a platelet count within the reference range. Platelet count improvement was observed in various conditions: primary ITP (90%, n = 18/20), pancytopenia of unknown etiology (42.9%, n = 3/7), chemotherapy‐induced thrombocytopenia (50%, n = 3/6), babesiosis (100%, n = 1/1), radiotherapy‐induced thrombocytopenia (0%, n = 0/1), and disseminated intravascular coagulopathy (33.3%, n = 2/6). The median time for platelet recovery (>50 000/μL) after romiplostim administration was 4 days, and the median time for platelet count normalization was 7 days. Median hospitalization time for the improvement group (I) was 5 days. The survival‐to‐discharge rates were 85%, 40%, and 28.6% for dogs with primary ITP, secondary thrombocytopenia, and thrombocytopenia of unknown etiology, respectively. Conclusions and Clinical Importance Romiplostim is a well‐tolerated and promising treatment for primary ITP in dogs, suggesting its potential as a valuable therapeutic option for dogs with thrombocytopenia caused by various underlying conditions. These findings emphasize the need for further research to optimize romiplostim dosing and understand its role in treating secondary thrombocytopenia and pancytopenia of unknown etiology.

Abstract Background Traditionally, 6‐month courses of prednisolone are used to treat steroid‐responsive meningitis‐arteritis (SRMA), but this medication is associated with adverse effects that can lead to poor quality of life. Hypothesis/Objectives Resolution of clinical signs and rate of relapse of SRMA would not be significantly different between a 6‐month prednisolone protocol and a 6‐week protocol. Animals Forty‐four hospital cases from multiple referral centers in the United Kingdom (2015‐2019). Twenty of 44 were treated with the 6‐month protocol and 24/44 with the 6‐week protocol. Methods Prospective, randomized trial with 12‐month follow‐up. The same prednisolone protocol reinitiated in the event of relapse. Analysis of relapses with binary logistic and Poisson regression modeling. Results All cases responded to their treatment protocol. Relapses occurred in 6/20 (30%) of the 6‐month protocol and 9/24 (38%) of the 6‐week protocol. There was no statistical difference in the incidence risk of at least 1 relapse between the 2 groups (odds ratio = 1.40; 95% confidence interval [CI], 0.40‐4.96, P = 0.60). Among the 15 dogs that relapsed, 10/15 (67%) relapsed once, 3/15 (20%) relapsed twice, and 2/15 (13%) relapsed 3 times. No statistical difference was detected in the incidence rate ratio (IRR) of total relapse events between the 2 groups (IRR = 1.46; 95% CI, 0.61‐3.48; P = 0.40). Conclusions and Clinical Importance “Short” 6‐week prednisolone protocols could be used to treat SRMA, thereby presumably reducing the duration and severity of prednisolone's adverse effects.

Cardiovascular diseases are a leading cause of mortality in the United States. The increasing number of cancer patients experiencing cardiovascular side effects from chemotherapeutic drugs is a cause for concern. Trastuzumab is a highly effective targeted therapy for HER2-positive cancers but its use is limited globally due to its cardiotoxic effects. The most severe adverse effect is cardiomyopathy, which is characterized by contractile dysfunction and reduced left ventricular systolic function. The electrophysiological side effects of trastuzumab are still not fully understood. Due to these life-threatening side effects, trastuzumab is routinely discontinued. This review aims to provide a comprehensive overview of trastuzumab-induced cardiomyopathy, including the mechanisms by which trastuzumab exerts its cardiotoxic effects, the clinical manifestations, diagnostic strategies, and potential interventions to protect the heart. By shedding light on the various aspects of this condition, we hope to emphasize the importance of early detection and effective management, as well as the urgent need for further research to optimize the balance between successful cancer treatment and cardiovascular well-being. Cardiologists, oncologists, and researchers are at the forefront of this critical intersection between oncology and cardiology, working collaboratively to enhance patient outcomes in the era of trastuzumab therapy.

Introduction: The objective of this case report is to describe diagnosis and management of life-threatening immune thrombocytopenia (ITP) secondary to pregnancy in a dog with concurrent dystocia. Case summary: A 1-year 11-month old female intact French bulldog was referred for management of severe thrombocytopenia and spontaneous hemorrhage during whelping. The thrombocytopenia was progressive from approximately 32 days of gestation. In the absence of an identifiable cause for the thrombocytopenia, the patient was treated for ITP with immunosuppressive therapies and blood and plasma transfusions. The patient was also supported through dystocia until the platelet count normalized so a Caesarean section and ovariohysterectomy (OVH) could be performed. Discussion: This is the first report documenting ITP in a whelping canine. Pregnancy is a known trigger and can affect the clinical course of autoimmune diseases in women, including ITP. It is suspected that this patient's pregnancy triggered ITP, paralleling what occurs in women. [ABSTRACT FROM AUTHOR]

Additional immunomodulatory treatment is needed for the management of immune‐mediated disease in horses. Mycophenolate mofetil (MMF) is an immunomodulatory agent used in human and veterinary medicine for the prevention of graft rejection and the management of autoimmune diseases. Few studies exist investigating the pharmacokinetics of MMF in horses. The aim of this study was to evaluate the pharmacokinetics of a single dose of MMF in healthy horses in the fed vs. fasted state. Six healthy Standardbred mares were administered MMF 10 mg/kg by a nasogastric (NG) tube in a fed and fasted state. A six‐day washout period was performed between the two doses. No statistically significant differences in mycophenolic acid (MPA) concentrations were seen at any time point apart from 8 h, when plasma metabolite concentrations were significantly higher in the fasted state compared to the fed state (p =.038). Evidence of enterohepatic recirculation was seen only in the fasted state; this did not yield clinical differences in horses administered a single‐dose administration but may be significant in horses receiving long‐term MMF treatment. [ABSTRACT FROM AUTHOR]

Myasthenia gravis (MG) is the most frequent transmission disease in the neuromuscular junction. Juvenile myasthenia gravis (JMG) is an autoimmune antibody-mediated disease of postsynaptic endplate defined as MG presentation in patients before the age of 18 years old. While many clinical features of JMG are identical to the adults, there are some significant differences between them regarding presentation, clinical course, antibody level, and thymus histopathology. In JMG, ocular symptoms are more frequent, the clinical course is comparably benign, and the outcome is better than adult MG. Antibodies attack the muscle endplate proteins in the postsynaptic membrane and interfere with transmission. These antibodies in most patients are against the acetylcholine receptors, but they may also be directed toward muscle-specific kinase, lipoprotein-related protein 4, and agrin. Findings show racial influences and genetic effects on the occurrence of JMG. The essential clinical symptom is fatigable weakness of muscles that can be in the form of isolated ocular type or more disseminated weakness. The diagnosis of JMG is essentially clinical, with fluctuating patterns of weakness and easy fatigability, but a series of diagnostic evaluations can confirm the diagnosis. Precise diagnostic evaluation and distinction from congenital myasthenic syndromes is critical. The treatment plan is conducted according to the clinical course (ocular or generalized), antibody type, and disease severity. The mainstay of treatment includes symptomatic therapy, long-lasting immunosuppressive treatment and treatment of myasthenic crisis. Novel medications are introduced and conducted to the specific pathophysiologic mechanisms of the disease, and they are used primarily in the refractory MG. [ABSTRACT FROM AUTHOR]

Background: Romiplostim, a thrombopoietin analog, is commonly used to treat immune‐mediated thrombocytopenia (ITP) in humans, but its use in dogs remains limited. Objectives: Evaluate the effects and adverse events of romiplostim administration in dogs with thrombocytopenia caused by various underlying diseases. Animals: Forty‐two client‐owned dogs with naturally occurring thrombocytopenia at 2 referral animal hospitals. Methods: Retrospective, multi‐institutional analysis to evaluate the outcomes of romiplostim treatment in dogs. Results: Among the dogs treated with romiplostim, 27 experienced an increase in platelet count and 26 maintained a platelet count within the reference range. Platelet count improvement was observed in various conditions: primary ITP (90%, n = 18/20), pancytopenia of unknown etiology (42.9%, n = 3/7), chemotherapy‐induced thrombocytopenia (50%, n = 3/6), babesiosis (100%, n = 1/1), radiotherapy‐induced thrombocytopenia (0%, n = 0/1), and disseminated intravascular coagulopathy (33.3%, n = 2/6). The median time for platelet recovery (>50 000/μL) after romiplostim administration was 4 days, and the median time for platelet count normalization was 7 days. Median hospitalization time for the improvement group (I) was 5 days. The survival‐to‐discharge rates were 85%, 40%, and 28.6% for dogs with primary ITP, secondary thrombocytopenia, and thrombocytopenia of unknown etiology, respectively. Conclusions and Clinical Importance: Romiplostim is a well‐tolerated and promising treatment for primary ITP in dogs, suggesting its potential as a valuable therapeutic option for dogs with thrombocytopenia caused by various underlying conditions. These findings emphasize the need for further research to optimize romiplostim dosing and understand its role in treating secondary thrombocytopenia and pancytopenia of unknown etiology. [ABSTRACT FROM AUTHOR]

Background: Traditionally, 6‐month courses of prednisolone are used to treat steroid‐responsive meningitis‐arteritis (SRMA), but this medication is associated with adverse effects that can lead to poor quality of life. Hypothesis/Objectives: Resolution of clinical signs and rate of relapse of SRMA would not be significantly different between a 6‐month prednisolone protocol and a 6‐week protocol. Animals: Forty‐four hospital cases from multiple referral centers in the United Kingdom (2015‐2019). Twenty of 44 were treated with the 6‐month protocol and 24/44 with the 6‐week protocol. Methods: Prospective, randomized trial with 12‐month follow‐up. The same prednisolone protocol reinitiated in the event of relapse. Analysis of relapses with binary logistic and Poisson regression modeling. Results: All cases responded to their treatment protocol. Relapses occurred in 6/20 (30%) of the 6‐month protocol and 9/24 (38%) of the 6‐week protocol. There was no statistical difference in the incidence risk of at least 1 relapse between the 2 groups (odds ratio = 1.40; 95% confidence interval [CI], 0.40‐4.96, P = 0.60). Among the 15 dogs that relapsed, 10/15 (67%) relapsed once, 3/15 (20%) relapsed twice, and 2/15 (13%) relapsed 3 times. No statistical difference was detected in the incidence rate ratio (IRR) of total relapse events between the 2 groups (IRR = 1.46; 95% CI, 0.61‐3.48; P = 0.40). Conclusions and Clinical Importance: "Short" 6‐week prednisolone protocols could be used to treat SRMA, thereby presumably reducing the duration and severity of prednisolone's adverse effects. [ABSTRACT FROM AUTHOR]

Immune thrombocytopenia (ITP) is the most common acquired primary hemostatic disorder in dogs. Immune thrombocytopenia less commonly affects cats but is an important cause of mortality and treatment‐associated morbidity in both species. Immune thrombocytopenia remains a diagnosis of exclusion for which diagnostic guidelines are lacking. Primary, or non‐associative, ITP refers to autoimmune platelet destruction. Secondary, or associative, ITP arises in response to an underlying disease trigger. However, evidence for which comorbidities serve as ITP triggers has not been systematically evaluated. To identify key diagnostic steps for ITP and important comorbidities associated with secondary ITP, we developed 12 Population Evaluation/Exposure Comparison Outcome (PECO) format questions. These questions were addressed by evidence evaluators utilizing a literature pool of 287 articles identified by the panelists using a structured search strategy. Evidence evaluators, using panel‐designed templates and data extraction tools, summarized evidence and created guideline recommendations that then were integrated by diagnosis and comorbidity domain chairs. The revised PECO responses underwent a Delphi survey process to reach consensus on final guidelines. A combination of panel expertise and PECO responses were employed to develop algorithms for diagnosis of ITP in dogs and cats, which also underwent 4 iterations of Delphi review. Comorbidity evidence evaluators employed an integrated measure of evidence (IME) tool to determine evidence quality for each comorbidity; IME values combined with evidence summaries for each comorbidity were integrated to develop ITP screening recommendations, which also were subjected to Delphi review. Commentary was solicited from multiple relevant professional organizations before finalizing the consensus. The final consensus statement provides clinical guidelines for the diagnosis of, and underlying disease screening for, ITP in dogs and cats. The systematic consensus process identified numerous knowledge gaps that should guide future studies. This statement is a companion manuscript to the ACVIM Consensus Statement on the Treatment of Immune Thrombocytopenia. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are a leading cause of mortality in the United States. The increasing number of cancer patients experiencing cardiovascular side effects from chemotherapeutic drugs is a cause for concern. Trastuzumab is a highly effective targeted therapy for HER2-positive cancers but its use is limited globally due to its cardiotoxic effects. The most severe adverse effect is cardiomyopathy, which is characterized by contractile dysfunction and reduced left ventricular systolic function. The electrophysiological side effects of trastuzumab are still not fully understood. Due to these life-threatening side effects, trastuzumab is routinely discontinued. This review aims to provide a comprehensive overview of trastuzumab-induced cardiomyopathy, including the mechanisms by which trastuzumab exerts its cardiotoxic effects, the clinical manifestations, diagnostic strategies, and potential interventions to protect the heart. By shedding light on the various aspects of this condition, we hope to emphasize the importance of early detection and effective management, as well as the urgent need for further research to optimize the balance between successful cancer treatment and cardiovascular well-being. Cardiologists, oncologists, and researchers are at the forefront of this critical intersection between oncology and cardiology, working collaboratively to enhance patient outcomes in the era of trastuzumab therapy. [ABSTRACT FROM AUTHOR]

Key Clinical Message: IgG4‐related disease is a rare and emerging pathology, characterized by the appearance of pseudotumors. Due to the ability to mimic other pathologies, it is essential to consider it as a differential diagnosis in multisystemic processes. The diagnosis is challenging, requiring a multidisciplinary approach, to minimize the associated morbidity and mortality. IgG4‐related disease (IgG4‐RD) is a rare, emerging, systemic and chronic pathology, characterized by the appearance of pseudotumors resulting from tissue infiltration by IgG4‐positive plasma cells that promote eosinophilic inflammation of the tissue with subsequent fibrosis. We present the case of a male, 45‐year‐old patient, with marked weight loss and skin pallor detected by his family doctor during a child health consultation of his daughter. When questioned, the patient referred complaints of postprandial discomfort in the left hypochondrium with a feeling of fullness, weight loss, chronic fatigue and hyperhidrosis that had lasted for a month. On physical examination, he was pale, and had pain at palpation of the left hypochondrium. Laboratory data showed increased inflammation markers, abdominal ultrasound and CT demonstrated numerous enlarged lymph nodes in the upper quadrants, raising concern for a malignant lymphoproliferative process. Serological, imaging, clinical and laparoscopic excisional biopsy revealed features of IgG4‐related disease and excluded malignant lymphoproliferative disease. The immediate response to treatment with oral prednisolone 30 mg/day also contributed for diagnosis confirmation. Due to refractory disease after gradual prednisolone reduction, second‐line therapy with rituximab was initiated. Over the 6 years of follow‐up, the patient presented multiple exacerbations characterized by the emergence of systemic symptoms, being maintained under close clinical and imaging follow‐up by reumathology, infectious diseases, and family medicine specialists. [ABSTRACT FROM AUTHOR]

Idiopathic generalized tremor syndrome is a disorder characterized by an acute onset of full-body tremors, sometimes accompanied by vestibulo-cerebellar signs, that is responsive to treatment with corticosteroids. Although considered to have an overall good outcome, relapsing and persistent mild clinical signs have been described. So far, little is known about the etiopathology of this syndrome, but it is believed to have an immune-mediated origin. In human medicine, description of numerous autoantibodies involved in certain non-infectious neurologic disorders has revolutionized understanding of their pathophysiology, diagnosis and treatment. In this multicenter retrospective study, we aimed to describe the clinical signs, course, and outcome of dogs with idiopathic generalized tremor syndrome and correlate potential findings with the presence or absence of autoantibodies associated with autoimmune cerebellar syndromes in humans. Information regarding signalment, history, clinical signs, laboratory findings, diagnostic imaging and testing for regional infectious diseases was gathered and the remaining serum and CSF samples were then analyzed for neural antibodies against targets associated with autoimmune encephalitic diseases of humans. Thirty-three dogs were included, and screening for neural antibodies was performed in 30 of those dogs. The analysis showed an increased titer of mGluR1 antibodies in two dogs, GFAP and later in the course of disease mGluR1 antibodies in one dog and an increase in unspecific autoantibodies which could not be further classified in two dogs. Dogs with detectable neural autoantibodies always had cerebrospinal fluid abnormalities in the form of a pleocytosis, with or without increased protein concentration, and tended to present with hyperthermia, potentially indicating a more severe clinical form of idiopathic generalized tremor syndrome in these cases. In conclusion, idiopathic generalized tremor syndrome is proposed to be an immune-mediated disorder potentially mediated by neural autoantibodies in a subgroup of dogs.

Immune-mediated polyarthritis (IMPA) has a relatively high relapse rate compared to other immune-mediated diseases. Leflunomide is frequently used to treat dogs with IMPA in conjunction with prednisolone. This retrospective cohort study aimed to evaluate the therapeutic efficacy of leflunomide as an adjunctive therapy to prednisolone in reducing relapse and mortality rates in dogs diagnosed with IMPA in Australia. The medical records of client-owned dogs diagnosed with IMPA at a specialist referral hospital in Southeast Queensland from 2017 to 2024 were reviewed. A total of 93 dogs were included in this study, divided into two groups based on the treatment received: Group PRED, consisting of 53 dogs treated with prednisolone as the sole immunosuppressive agent, and Group L+PRED, consisting of 40 dogs that received leflunomide as adjunctive therapy alongside prednisolone. Data collected included breed, age, weight, sex, serum C-reactive protein concentration, results of synovial fluid analysis and microbial culture, treatment protocol, relapse rates and time to relapse, and mortality rates. There was no difference in relapse or mortality rates, time to relapse, nor time to discontinue prednisolone between the PRED and L+PRED groups. The L+PRED group had higher body weights and lower prednisolone dose rate at discharge compared to those in the PRED group. This study demonstrated that the use of leflunomide as an adjunctive therapy to prednisolone for the treatment of dogs with IMPA had no improved outcomes, reduced relapse rates, or shortening in the duration of prednisolone therapy when compared to dogs receiving prednisolone monotherapy.

Idiosyncratic drug-induced liver injury (iDILI) is a major concern in drug development because its occurrence is unpredictable. Presently, iDILI prediction is a challenge, and cell toxicity is observed only at concentrations that are much higher than the therapeutic doses in preclinical models. Applying a proprietary cell educating technology, we developed a person-dependent spheroid system that contains autologous educated immune cells that can detect iDILI risk at therapeutic concentrations. Integrating this system into a high-throughput screening platform will help pharmaceutical companies accurately detect the iDILI risk of new molecules de-risking drug development. [ABSTRACT FROM AUTHOR]

A 2.5-year-old female entire Pomeranian dog was presented for acute paraparesis progressing within 2 days to paraplegia. General physical examination was unremarkable. Neurological examination showed paraplegia without nociception, a mass reflex upon testing perineal reflexes and withdrawal reflexes in the pelvic limbs and patellar hyperreflexia. Cutaneous trunci reflexes were absent caudal to the level of the 6th thoracic vertebra. Spinal hyperesthesia was present. Neuroanatomical localization was consistent with a T3-L3 myelopathy. Hematological and biochemical blood tests [including C-reactive protein (CRP)] were within reference ranges. MRI of the spinal cord from the level of the 1st thoracic vertebra to the sacrum revealed a patchy, ill-defined, moderate to marked T2W hyperintense, contrast enhancing intramedullary lesion extending from T1 to L4. Medical treatment based on a working diagnosis of meningomyelitis of unknown cause was initiated with corticosteroids and methadone based on pain scores. Prognosis was grave and after 3 days without return of nociception, the dog was euthanized according to the owners' wishes. Post-mortem histopathological examination of the brain and spinal cord yielded a morphological diagnosis of severe, segmental, bilateral and fairly symmetrical, necrotizing lymphohistiocytic leukomyelitis, with a non- suppurative angiocentric leptomeningitis. Some minor, focal, lymphocytic perivascular cuffing was found in the medulla oblongata as well, but otherwise there were no signs of brain involvement. No infectious causes were identified with ancillary tests. This case report underlines the importance of including meningomyelitis in the differential diagnosis list of dogs presented for acute progressive neurological signs referable to a myelopathy. [ABSTRACT FROM AUTHOR]

IntroductionThe objective of this case report is to describe diagnosis and management of life-threatening immune thrombocytopenia (ITP) secondary to pregnancy in a dog with concurrent dystocia.Case summaryA 1-year 11-month old female intact French bulldog was referred for management of severe thrombocytopenia and spontaneous hemorrhage during whelping. The thrombocytopenia was progressive from approximately 32 days of gestation. In the absence of an identifiable cause for the thrombocytopenia, the patient was treated for ITP with immunosuppressive therapies and blood and plasma transfusions. The patient was also supported through dystocia until the platelet count normalized so a Caesarean section and ovariohysterectomy (OVH) could be performed.DiscussionThis is the first report documenting ITP in a whelping canine. Pregnancy is a known trigger and can affect the clinical course of autoimmune diseases in women, including ITP. It is suspected that this patient’s pregnancy triggered ITP, paralleling what occurs in women.

Toxic epidermal necrolysis (TEN) is a rare but serious immune-mediated life-threatening skin and mucous membrane reaction that is mainly caused by drugs, infections, vaccines, and malignant tumors. A 74-year-old woman presented with a moderate fever of unknown cause, which was relieved after 2 days, but with weakness and decreased appetite. Red maculopapules appeared successively on the neck, trunk, and limbs, expanding gradually, forming herpes and fusion, containing a yellow turbidous liquid and rupturing to reveal a bright red erosive surface spreading around the eyes and mouth. The affected body surface area was >90%. The severity of illness score for toxic epidermal necrolysis was 2 points. The drug eruption area and severity index score was 77. She was diagnosed with TEN caused by hepatitis A virus and treated with 160 mg/day methylprednisolone, 300 mg/day cyclosporine, and 20 g/day gammaglobulin. Her skin showed improvements after 3 days of treatment and returned to nearly normal after 1 month, and liver function was completely normal after 2 months.

* The accidental, suicidal, and homicidal toxicities of copper sulfate have been extensively documented. The later stages of the disease demonstrate signs of systemic toxicity, characterized by intravascular hemolysis, oliguric renal failure, convulsions, and circulatory collapse. Despite the extensive description of life-threatening intravascular hemolysis, Hemophagocytic Lymphohistiocytosis (HLH) related to copper sulfate poisoning has not been described. A 45-year-old male presented with accidental consumption of copper sulfate. Laboratory evaluation revealed leukocytosis, intravascular hemolysis, acute liver injury, acute kidney injury, severe metabolic acidosis, and hyperkalemia. The patient was shifted to the Intensive Care Unit and hemodialysis was initiated. On the 9 th day, he developed high-grade fever with chills. With the suspicion of a central line-associated bloodstream infection, empirical antibiotic therapy was initiated, and the lines were revised. On the 19 th day, the high-grade fever recurred. Investigations revealed trilineage cytopenias. With a high degree of suspicion for HLH, further investigations revealed increased ferritin levels. Bone marrow aspiration cytology showed evidence of reactive marrow with haemophagocytic lymphohistiocytosis. The patient was initiated on corticosteroid therapy, after which symptomatic and laboratory recovery was noted. Although copper sulfate poisoning is potentially fatal in large quantities, few studies have examined the possible immune-mediated abnormalities in individuals. Owing to the direct membranolytic effect of copper sulfate, it is not unreasonable to have immune-mediated organ damage. To the best of our knowledge, this is the first report of Hemophagocytic Lymphohistiocytosis attributed to copper sulfate intoxication. The present case demonstrates that the diagnosis of HLH must be considered when treating a case of copper sulfate poisoning; however, the exclusion of the most common complications must be first established.

Abstract Background Additional efficacious immunomodulatory treatment is needed for the management of immune‐mediated disease in horses. Mycophenolate mofetil (MMF) is an immunosuppressive drug that warrants assessment as a viable therapeutic agent for horses. Hypothesis/Objectives To evaluate the pharmacokinetics (PK) of multiple‐day oral dosing of MMF in healthy horses and to determine the tolerability of this dosing regimen. Animals Six healthy Standardbred mares. Methods Horses received MMF 10 mg/kg PO q12h for 7 days in the fed state. Serial sampling was performed over 12 hours on Days 1 and 7 with trough samples collected every 24 hours, immediately before morning drug administration. Noncompartmental PK analyses were performed to determine primary PK parameters, followed by calculation of geometric means and coefficients of variation. A CBC, serum biochemical profile, physical examination, and fecal scoring were used to assess dose tolerability. Results Seven days of treatment resulted in a mycophenolic acid (MPA) area under the curve (AUC0‐12) of 12 594 h × ng/mL (8567‐19 488 h × ng/mL) and terminal half‐life (T1/2) of 11.3 hours (7.5‐15.9 hours), yielding minor metabolite accumulation in all horses treated. Salmonellosis was detected in the feces of 2 horses by Day 7, and all horses developed myelosuppression, hyperbilirubinemia, hyporexia, decreased gastrointestinal motility, and decreased fecal output by the seventh day of treatment. Conclusion and Clinical Importance Administration of MMF at 10 mg/kg PO q12h resulted in hematologic and clinical toxicity within 1 week of treatment. A decreased MMF dose, frequency, or both is needed to avoid colic. Drug monitoring should include frequent hemograms, serum biochemical profiles, and strict biosecurity protocols.

Idiosyncratic drug-induced liver injury (iDILI) is a major concern in drug development because its occurrence is unpredictable. Presently, iDILI prediction is a challenge, and cell toxicity is observed only at concentrations that are much higher than the therapeutic doses in preclinical models. Applying a proprietary cell educating technology, we developed a person-dependent spheroid system that contains autologous educated immune cells that can detect iDILI risk at therapeutic concentrations. Integrating this system into a high-throughput screening platform will help pharmaceutical companies accurately detect the iDILI risk of new molecules de-risking drug development.

Background There are data suggesting that intravenous immunoglobulin treatment has some benefit for certain forms of encephalitis but robust evidence from large randomised controlled trials in children with all-cause encephalitis is lacking. Objective To evaluate whether intravenous immunoglobulin treatment improves neurological outcomes in childhood encephalitis when given early in the illness. Design Phase 3b, investigator-initiated, randomised, double-blind, placebo-controlled trial of intravenous immunoglobulin for the treatment of encephalitis in children. Setting Twenty-one NHS Hospitals in the UK. Participants Children aged 6 months to 16 years with a diagnosis of acute or sub-acute encephalitis. Intervention Two doses (1 g/kg/dose) of either intravenous immunoglobulin or matching placebo, given 24–36 hours apart, in addition to standard treatment. Main outcome measure Participants were followed up for 12 months (+/– 4 weeks) after randomisation. The primary outcome measure was a ‘good recovery’ defined as a score of ≤ 2 on the Paediatric Glasgow Outcome Score Extended at 12 months after randomisation. Secondary outcomes The secondary outcomes were clinical, neurological, neuroimaging and neuropsychological results, identification of the proportion of children with immune-mediated encephalitis, and intravenous immunoglobulin safety data. Results We planned to recruit 308 children over a 42-month period. After enrolment of 18 participants (8 male; 44%) over 21 months (from December 2015 to September 2017), funding was withdrawn due to slow recruitment and the study was terminated. Ten participants were randomised to the intravenous immunoglobulin group, and eight to the placebo group, and all 18 participants were included in the analysis. At 12 months after randomisation, 9 participants [50%; intravenous immunoglobulin n = 5 (50%), placebo n = 4 (50%)] made good recovery and 5 participants [28%; intravenous immunoglobulin n = 3 (30%), placebo n = 2 (25%)] made a poor recovery. Three participants in the placebo group (43%) experienced a total of 10 serious adverse events compared with none in the intravenous immunoglobulin group but none of the adverse events were judged to be related to the study treatment. No deaths occurred during the study period. Conclusion ImmunoglobuliN in the Treatment of Encephalitis (IgNiTE) was halted prematurely due to slow recruitment. Given the small sample size, the study was underpowered to evaluate the effect of intravenous immunoglobulin when compared with placebo in childhood encephalitis. The study findings, albeit from a small sample size, support existing evidence that encephalitis results in poor neurological outcomes for many children. Lessons learned from the ImmunoglobuliN in the Treatment of Encephalitis trial would be valuable for the success of future trials set up to address the efficacy of early treatment with intravenous immunoglobulin in all-cause encephalitis in children. Study limitations and future work The study was underpowered to evaluate the efficacy of intravenous immunoglobulin in the treatment of childhood encephalitis due to the small sample size achieved. Future trials should seek to address this important question. Trial registration This trial is registered as Clinical Trials.gov (NCT02308982) and ISRCTN15791925. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/212/15) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 6. See the NIHR Funding and Awards website for further award information. Plain language summary Encephalitis (inflammation of the brain) is a serious but rare condition affecting approximately 5 in 100,000 children in England. Encephalitis can have a big impact on affected children and their families. Approximately 12 out of 100 affected children will die and half of those that survive experience varying difficulties in the long term; these might include problems with memory, physical disabilities, seizures and changes in how they think and behave. There is some evidence that a treatment called intravenous immunoglobulin may benefit people affected by encephalitis. Intravenous immunoglobulin contains antibodies obtained from blood donations by different people, which is used to treat some types of inflammation. However, there have been no research studies investigating the effect of intravenous immunoglobulin when used in large numbers of children with all types of encephalitis. Furthermore, although intravenous immunoglobulin is sometimes used to treat children with encephalitis, it is often given after other treatments have been unsuccessful. Outcomes from encephalitis are determined largely by the amount of brain inflammation; it would therefore seem logical that giving a treatment early in the illness to limit the inflammation would be beneficial. In the ImmunoglobuliN in the Treatment of Encephalitis study, we aimed to find out whether giving intravenous immunoglobulin to children with encephalitis early in the illness can help them get better more quickly and reduce the difficulties they experience later on. Half of the children in the trial received intravenous immunoglobulin and the other half received an inactive medicine, known as placebo, in addition to the normal care they would receive in a hospital. We aimed to compare the recovery and outcomes between children in these two groups. This trial was stopped early due to withdrawal of funding, as fewer children than expected were enrolled into the study. Too few children were enrolled for us to be sure whether intravenous immunoglobulin benefits children with encephalitis. However, the trial findings highlight the impact of encephalitis on affected children, with around half of children demonstrating ongoing difficulties 1 year after the illness. Scientific summary Background There is significant mortality and morbidity from encephalitis in children despite the current standard of care. Thus, strategies to improve outcomes in patients with encephalitis are urgently required. Theoretical and empirical evidence suggest a beneficial role of intravenous immunoglobulin (IVIG) for viral and auto-immune forms of encephalitis. Therefore, we set up a prospective randomised controlled trial (RCT) to ascertain the efficacy of early IVIG treatment for all-cause encephalitis in children. In the study, children with encephalitis were randomised to receive two doses of either IVIG or placebo within five working days from the suspicion of an encephalitis diagnosis, in addition to normal standard of care. They were then followed up for 12 months after randomisation. We hypothesised that IVIG could have therapeutic benefit for children with encephalitis when administered early in the illness. Objectives The primary objective was to evaluate the efficacy of early IVIG treatment in childhood encephalitis. This was assessed by comparing the proportion of children in the 2 treatment groups who made good recovery, assessed using the paediatric version of the Glasgow outcome score extended, at 12 months after randomisation. The secondary objectives were to: (1) compare clinical, neurological, neuroimaging and neuropsychological outcomes between the treatment groups, (2) evaluate the proportion of participants with autoimmune encephalitis and (3) confirm the safety of IVIG. Methods Trial design This was a phase 3b multicentre, double-blind, randomised, placebo-controlled trial to evaluate the early use IVIG in childhood encephalitis. Setting Participants were recruited from 21 NHS Hospitals in the UK. Participants Inclusion criteria Participants were eligible if they were aged between 6 weeks and 16 years they met the case definition for possible encephalitis based on the International Encephalitis Consensus parents/guardians provided written informed consent, or assent if appropriate. Exclusion criteria The exclusion criteria included: (1) a high clinical suspicion of bacterial meningitis, (2) prior receipt of IVIG during the admission or known contraindication to IVIG, (3) traumatic brain injury, (4) history of metabolic encephalopathy, stroke, toxic or hypertensive encephalopathy, (5) pre-existing demyelinating disorder, (6) significant renal impairment, (7) hypercoagulable state, (8) hyperprolinaemia, (9) participation in another research trial involving an immunomodulatory treatment, (10) known to be pregnant, (11) any significant disease or clinical research that would impact on participation, or interfere with compliance with study requirements. Randomisation Participants were randomly assigned 1 : 1 ratio to receive 2 doses (1 g/kg/dose) of either IVIG or matching placebo, in addition to standard care. Randomisation was stratified by age and receipt of steroid treatment. Interventions Two doses of 1 g/kg/dose of either IVIG or a matching volume of placebo were given 24–36 hours apart, with the first dose administered as soon as possible after enrolment and within five working days from the suspicion of an encephalitis diagnosis. The active treatment (IVIG) used in the study was Privigen (100 mg/ml solution), manufactured and provided by CSL Behring. The placebo was a mixture of 0.9% saline + 0.1% human albumin solution, manufactured at the Royal Broadgreen and Liverpool Aseptic Production Unit, Liverpool, UK, under current good manufacturing practice conditions and its Manufacturer’s Importer’s Authorisation licence. The addition of albumin to saline was necessary to make the placebo visually identical to IVIG. Blinding Participants, treating clinicians, parents/guardians and outcome assessors were blinded to the allocated treatment. Primary outcome The primary outcome was good recovery (i.e. score of ≤2) on the paediatric version of the Glasgow Outcome Score-Extended (GOS-E Peds) at 12 months after randomisation. Secondary outcomes Clinical, neurological and neuropsychological outcomes Multiple clinical and neurological measures were collected during the hospital admission, at 4–8 weeks after discharge from acute care, and at 6 and 12 months after randomisation. A blinded neuropsychologist assessment of cognitive function was carried out at 12 months after randomisation. Radiological outcomes Brain magnetic resonance imaging (MRI) findings at 6 months after randomisation were compared with imaging results obtained during the acute illness. Safety data Safety and adverse events (AEs) data were collected until 12 months after randomisation. Identification of immune-mediated encephalitis Presence of specific auto-antibodies in serum was assessed. Statistical methods The analyses were performed on the intention-to-treat population; this included all participants who were randomised, irrespective of study treatment received. In the analysis of the AEs, all participants who received study treatment were included. Since 20% of participants were recruited before the trial was halted, all analyses are descriptive. Results Recruitment took place between 23 December 2015 and 26 September 2017. Recruitment was paused in September 2017 following withdrawal of funding due to slower than anticipated recruitment. Despite strategies implemented to improve recruitment, funding was not reinstated. Attempts at securing alternative funding were unsuccessful; therefore, the trial was closed on 24 October 2017. Participants and demographics At the time of halting the study, 18 participants had been randomised (IVIG n = 10; placebo n = 8). One participant each from the IVIG and placebo groups were withdrawn from the study before receipt of study treatment and one participant in the placebo arm refused a second dose of study treatment. Therefore 16 participants (IVIG n = 9; placebo n = 7) received at least one dose of the study treatment and 15 participants (IVIG n = 9, placebo n = 6) received two full doses of the study treatment. One participant in the placebo group was lost to follow up after the 6 months visit and 1 participant in the IVIG group withdrew consent prior to the visit 12 months after randomisation. The median age at randomisation was 4.09 years [interquartile range (IQR) = 2.0–11.8], 44% were male and 89% were of white ethnicity. Baseline characteristics were well matched across treatment arms. Primary outcome At 12 months after randomisation, 9 participants [50%; IVIG n = 5 (50%); placebo n = 4 (50%)] made a good recovery (score ≤2 on the GOS-E Peds) and 5 participants [28%; IVIG n = 3 (30%), placebo n = 2 (25%)] made a poor recovery (score > 2). Four participants (22%; IVIG n = 2 (20%), placebo n = 2 (25%)] did not undergo a GOS-E Peds assessment at 12 months after randomisation. Secondary outcomes Inpatient data Ten participants [56%; IVIG n = 5 (50%), placebo = 5 (63%)] were admitted to intensive care, and nine of these [90%; IVIG n = 4 (80%), placebo n = 5(100%)] required invasive ventilation, for a median duration of two days (IQR 2.0–3.0). The median length of stay on intensive care was 4.5 days (3.0–6.8) and the overall median length of hospitalisation for acute care was 11 days (7.8–19.5). Epilepsy diagnosis Three participants [17%; IVIG n = 1 (10%), placebo n = 2 (25%)] had a new diagnosis of epilepsy during the study period. Five participants [28%; IVIG n = 2 (20%), placebo n = 3 (38%)] had incomplete data for this outcome. Glasgow Outcome Score-Extended-Peds at 6 months after randomisation Eight participants [44%; IVIG n = 4 (40%), placebo n = 4 (50%)] made a good recovery at 6 months after randomisation, whereas seven participants [39%; IVIG n = 4 (50%), placebo n = 3 (38%)] made a poor recovery. Three participants [17%; IVIG n = 2 (20%), placebo n = 1 (13%)] did not undergo a GOS-E Peds assessment at 6 months after randomisation. Liverpool outcome score At 4–8 weeks after discharge from acute care, 5 participants [28%; IVIG n = 3 (30%), placebo n = 2 (25%)] made a full recovery [defined as a Liverpool Outcome Score (LOS) of >4], whereas 10 participants [56%; IVIG n = 5 (50%), placebo n = 5 (63%)] had minor to severe sequelae. Three participants [17%; IVIG n = 2 (20%); placebo n = 1 (13%)] did not have LOS data collected at this timepoint. At 12 months after randomisation, six participants [33%; IVIG n = 4 (40%), placebo n = 2 (25%)] made full recovery on the LOS assessment, while 8 participants [44%; IVIG n = 4 (40%), placebo n = 4 (50%)] reported minor to severe sequelae. Four participants [22%; IVIG n = 2 (20%); placebo n = 2 (25%)] did not have LOS data collected at this timepoint. Paediatric quality of life assessment Paediatric quality of life scores were available for seven participants [39%; IVIG n = 5 (50%), placebo n = 2 (25%)] at 4–8 weeks after discharge from acute care and for eight participants [44%; IVIG n = 6 (60%), placebo n = 2 (25%)] at 12 months post randomisation. At 4–8 weeks after discharge from acute care, the mean PedsQL score was 77.9 (standard deviation, SD, 11.10) and 56.5 (SD 7.8) for the IVIG and placebo group, respectively. At 12 months, mean PedsQL scores were 79.9 (SD 21.6) and 63.7 (SD 30.1) for the IVIG and placebo groups, respectively. Gross motor function classification system At 4–8 weeks after discharge from acute care, seven participants [39%; IVIG n = 5 (50%); placebo n = 2 (25%)] had mild impairment of gross motor functioning. These data were not available for 11 participants [61%; IVIG n = 5 (50%), placebo n = 6 (75%)] at this timepoint. At 12 months after randomisation, eight participants [44%; IVIG n = 6 (60%); placebo n = 2 (25%)] experienced mild or severe impairment of gross motor function. These data were not available for ten participants [56%; IVIG n = 4 (40%), placebo n = 6 (75%)] at this timepoint. Strengths and difficulties assessment Strengths and Difficulties Questionnaire (SDQ) results were available for seven participants (IVIG n = 5, placebo n = 2) at 4–8 weeks after discharge from acute care and eight participants (IVIG n = 6, placebo n = 2) at 12 months after randomisation. At 4–8 weeks after discharge from acute care, five participants [28%; IVIG n = 4 (40%); placebo n = 1 (13%)] had a close to average SDQ score, one participant [6%, IVIG n = 1 (10%), placebo n = 0] had a slightly raised SDQ score and one participant [6%, IVIG n = 0, placebo n = 1 (13%)] had a very high SDQ score. At 12 months after randomisation, the same number of participants had a close to average score and slightly raised score, but two participants [11%; IVIG n = 1 (10%), placebo n = 1 (13%)] had a very high SDQ score. Adaptive Behaviors Assessment System – second edition At 4–8 weeks after discharge from acute care, five participants [28%; IVIG n = 4 (40%), placebo n = 1 (13%)] had an Adaptive Behaviors Assessment System-second edition (ABAS-II) score that was either similar or higher than the average score of the normative population. At the same time point, three participants [17%; IVIG n = 2 (20%), placebo n = 1 (13%)] had a score that was lower than the average score. Ten participants [56%; IVIG n = 4 (40%), placebo n = 6 (75%)] did not have ABAS-II assessment at this timepoint. At 12 months after randomisation, the same number of participants had a score that was below the average, but four participants [22%; IVIG n = 3 (30%), placebo n = 1 (13%)] had a score that was either similar or higher than the average score, and 11 participants [61%; IVIG n = 5 (50%), placebo n = 6 (75%)] did not have ABAS-II assessment at this timepoint. Neuropsychology assessment Thirteen participants (72%; IVIG n = 8 (80%); placebo n = 5 (63%)] had blinded neuropsychology assessment at 12 months after randomisation; four [30%; IVIG n = 2 (25%), placebo n = 2 (40%)] of these participants were unable to complete the full battery of assessments due to attention or behavioural needs. Five participants [28%; IVIG n = 2 (20%), placebo n = 3 (38%)] did not undergo neuropsychology assessment. Five participants [28%; IVIG n = 4 (40%), placebo n = 1 (13%)] had a score of ≥85 (indicating normal development) for Full-Scale IQ, six [33%; IVIG n = 4 (40%); placebo n = 2 (25%)] for Verbal Comprehension Index (VCI), five [28%; IVIG n = 4 (40%), placebo n = 1 (13%)] for visual spatial; four [22%; IVIG n = 4 (40%), placebo n = 0 (0%)] for working memory index (WMI); and four [22%; IVIG n = 3 (30%); placebo n = 1 (13%)] for Perceptual Reasoning Index (PRI). Two participants (one in each treatment arm) were assessed using the Bayley scale of infant and toddler development, one participant (IVIG arm) had severe neurodevelopmental impairment while the other (placebo arm) had a normal neurodevelopmental outcome. Neuroimaging Nineteen acute neuroimaging scans were available for 13 participants. Five scans (for five unique participants) had abnormal findings; all of these were MRI scans. Four of the abnormal scans showed bilateral lesions. There were nine follow-up scans for eight unique participants of which six scans (for five unique participants) were normal and unchanged from the acute scan. Three follow-up scans (for three unique participants) had abnormal findings; two of these were unchanged from the acute scans and an acute scan was not available for comparison one participant. Autoantibody testing Twelve participants had autoantibody testing. One participant (placebo n = 1) was positive for LGI1 antibodies, and one participant (placebo n = 1) was positive for myelin oligodendrocyte glycoprotein (MOG) antibodies. Two additional participants (IVIG n = 2) were positive for IgG to live neurons, indicating the presence of IgG antibodies binding to neurons, but negative for antibodies to the specific antigens tested for in the study. Safety reporting One participant in the IVIG group reported an AE of special interest; the participant developed a fever during IVIG infusion; however, this was judged to be unrelated to the study treatment. Ten serious AEs occurred in three participants in the placebo group and none in the IVIG group. None of the serious adverse events (SAEs) were judged to be related to the study treatment. No deaths occurred during the study period. Conclusions ImmunoglobuliN in the Treatment of Encephalitis (IgNiTE) was the first RCT to prospectively evaluate the efficacy of IVIG in childhood encephalitis. It was anticipated that data from IgNiTE would provide definitive evidence on which to base the management of children with encephalitis in the UK and worldwide. However, due to slow recruitment, the trial was terminated early. Therefore, the trial did not reach its pre-determined sample size and was underpowered, making it impossible to reach a conclusion on the role of IVIG in treatment of childhood encephalitis. Nonetheless, IgNiTE has highlighted several key learning points. Firstly, IgNiTE has demonstrated the feasibility of setting up a large multi-centre trial efficacy trial in a cohort of children with a rare condition such as encephalitis. Secondly, data from IgNiTE, albeit derived from a small sample size, suggest the safety of IVIG and provide some insight into the burden that encephalitis places on children and the NHS. Over half of the study participants were admitted to the intensive care unit with 90% of those admitted requiring invasive ventilation, with a prolonged overall length of hospitalisation. In addition, a notable proportion of children experienced some degree of disability at follow-up, highlighting the need to prioritise studies aimed at identifying strategies to alleviate the burden from this rare but debilitating disease. For future studies aimed at addressing the efficacy of early IVIG treatment in childhood encephalitis, consideration should be given to practical challenges with setting up RCTs for rare diseases. These include the necessity to recruit from multiple sites to achieve the sample size, the importance of clinical equipoise amongst treating clinicians, and the trade-off between having a stringent but robust set of entry criteria and the impact of this on recruitment. Trial registration This trial is registered as Clinical Trials.gov (NCT02308982) and ISRCTN15791925. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/212/15) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 6. See the NIHR Funding and Awards website for further award information.

Abstract* The accidental, suicidal, and homicidal toxicities of copper sulfate have been extensively documented. The later stages of the disease demonstrate signs of systemic toxicity, characterized by intravascular hemolysis, oliguric renal failure, convulsions, and circulatory collapse. Despite the extensive description of life-threatening intravascular hemolysis, Hemophagocytic Lymphohistiocytosis (HLH) related to copper sulfate poisoning has not been described. A 45-year-old male presented with accidental consumption of copper sulfate. Laboratory evaluation revealed leukocytosis, intravascular hemolysis, acute liver injury, acute kidney injury, severe metabolic acidosis, and hyperkalemia. The patient was shifted to the Intensive Care Unit and hemodialysis was initiated. On the 9th day, he developed high-grade fever with chills. With the suspicion of a central line-associated bloodstream infection, empirical antibiotic therapy was initiated, and the lines were revised. On the 19th day, the high-grade fever recurred. Investigations revealed trilineage cytopenias. With a high degree of suspicion for HLH, further investigations revealed increased ferritin levels. Bone marrow aspiration cytology showed evidence of reactive marrow with haemophagocytic lymphohistiocytosis. The patient was initiated on corticosteroid therapy, after which symptomatic and laboratory recovery was noted. Although copper sulfate poisoning is potentially fatal in large quantities, few studies have examined the possible immune-mediated abnormalities in individuals. Owing to the direct membranolytic effect of copper sulfate, it is not unreasonable to have immune-mediated organ damage. To the best of our knowledge, this is the first report of Hemophagocytic Lymphohistiocytosis attributed to copper sulfate intoxication. The present case demonstrates that the diagnosis of HLH must be considered when treating a case of copper sulfate poisoning; however, the exclusion of the most common complications must be first established.

A 2.5-year-old female entire Pomeranian dog was presented for acute paraparesis progressing within 2 days to paraplegia. General physical examination was unremarkable. Neurological examination showed paraplegia without nociception, a mass reflex upon testing perineal reflexes and withdrawal reflexes in the pelvic limbs and patellar hyperreflexia. Cutaneous trunci reflexes were absent caudal to the level of the 6th thoracic vertebra. Spinal hyperesthesia was present. Neuroanatomical localization was consistent with a T3-L3 myelopathy. Hematological and biochemical blood tests [including C-reactive protein (CRP)] were within reference ranges. MRI of the spinal cord from the level of the 1st thoracic vertebra to the sacrum revealed a patchy, ill-defined, moderate to marked T2W hyperintense, contrast enhancing intramedullary lesion extending from T1 to L4. Medical treatment based on a working diagnosis of meningomyelitis of unknown cause was initiated with corticosteroids and methadone based on pain scores. Prognosis was grave and after 3 days without return of nociception, the dog was euthanized according to the owners’ wishes. Post-mortem histopathological examination of the brain and spinal cord yielded a morphological diagnosis of severe, segmental, bilateral and fairly symmetrical, necrotizing lymphohistiocytic leukomyelitis, with a non-suppurative angiocentric leptomeningitis. Some minor, focal, lymphocytic perivascular cuffing was found in the medulla oblongata as well, but otherwise there were no signs of brain involvement. No infectious causes were identified with ancillary tests. This case report underlines the importance of including meningomyelitis in the differential diagnosis list of dogs presented for acute progressive neurological signs referable to a myelopathy.

Necrotizing meningoencephalitis (NME) is a fatal neuroinflammatory disease that previously carried a uniformly grave prognosis. Our recent identification of a novel early form of NME in Pugs suggests that disease onset and progression are likely more insidious than previously recognized and provides new hope that early therapeutic intervention may halt disease progression and ultimately prevent or cure NME. This novel perspective also sheds new light on the clinical similarities to multiple sclerosis (MS) in humans and provides a rationale for cross-species translation. The history of recent scientific discoveries in NME and new parallels between MS and NME will be reviewed. [ABSTRACT FROM AUTHOR]

Guillain-Barré syndrome (GBS) is a rare but serious condition that carries with it a high rate of morbidity and mortality. This review highlights the pearls and pitfalls of GBS, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence. GBS is a rare immune-mediated neurologic disorder with peripheral nerve injury. It most commonly presents weeks after a bacterial or viral infection, though there are a variety of associated inciting events. The diagnosis is challenging and often subtle, as only 25–30% of patients are diagnosed on their initial healthcare visit. Clinicians should consider GBS in patients with progressive ascending weakness involving the lower extremities associated with hyporeflexia, but the cranial nerves, respiratory system, and autonomic system may be involved. While the ED diagnosis should be based on clinical assessment, further evaluation includes laboratory testing, cerebrospinal fluid (CSF) analysis, and potentially neuroimaging. Not all patients demonstrate albumino-cytological dissociation on CSF testing. Several criteria exist to assist with diagnosis, including the National Institute of Neurological Disorders and Stroke criteria and the Brighton criteria. Management focuses first on assessment of the patient's hemodynamic and respiratory status, which may require emergent intervention. Significant fluctuations in heart rate and blood pressure may occur, and respiratory muscle weakness may result in the need for airway protection. Neurology consultation is recommended, and definitive treatment includes PLEX or IVIG. An understanding of GBS can assist emergency clinicians in diagnosing and managing this potentially deadly disease. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effect of discontinuing chronic topical immune modulating (IM) treatment on Schirmer tear test (STT) values in dogs with dry eye disease (DED). Methods: Serial measurements of STTs from 14 dogs (16 eyes) previously diagnosed with DED were obtained before and after discontinuation of topical IM agents. Dogs with moderate to severe DED that had been well controlled with a topical IM treatment were included. After initial assessment topical IM treatment was discontinued, but topical lubricant was continued, and STT values were obtained sequentially. A mixed-effects regression model was used to evaluate the effects of age, gender, breed, clinical score, frequency of treatment, baseline STT value, and drug type on final STT values after IM withdrawal. P

Autoimmune hemolytic anemia (IMHA) is one of the leading causes of anemia in dogs and cats. This type of anemia can occur in animals of all ages, but is more common in young and middle-aged adult dogs and cats. In secondary IMHA, a trigger is often suspected because of a temporal association with the administration of certain drugs or a preexisting disease, but establishing a causal link is frequently difficult. While both forms of IMHA affect dogs and cats, the primary form is more common in dogs and the secondary form is more common in cats. [ABSTRACT FROM AUTHOR]

Regression of leukemia in the absence of disease-modifying therapy remains poorly understood, although immunological mechanisms are thought to play a role. Here, we present a unique case of a 17-year-old boy with immune dysregulation and long-lasting regression of a (pre)leukemic clone in the absence of disease-modifying therapy. Using molecular and immunological analyses, we identified bone marrow features associated with disease control and loss thereof. In addition, our case reveals that detection of certain fusion genes with hardly any blasts in the bone marrow may be indicative of an accompanying oncogenic fusion gene, with implications for disease surveillance- and management in future patients. [ABSTRACT FROM AUTHOR]

The predilection for women in systemic autoimmune diseases is well established. However, this sex bias in oral autoimmune diseases has been classically reported from an epidemiological perspective without any elaborate attempts to unveil the underlying mechanisms. The unique nature of the oral environment is likely to impose a combination of systemic and local factors that ultimately result in the sex bias in autoimmune diseases of the oral cavity. Variations of immune responses, target organ vulnerability, endocrine and genetic factors, sex chromosomes and modes of parental inheritance are potential systemic factors, while the oral microbiome, oral tolerance, saliva, and oral epithelial stem cells may account for local contributing factors. This review will discuss the preponderance of women in oral immune‐mediated diseases, the potential systemic and local mechanisms underlying this predominance and highlight the crucial need for further research in this area. [ABSTRACT FROM AUTHOR]

Background: Additional efficacious immunomodulatory treatment is needed for the management of immune‐mediated disease in horses. Mycophenolate mofetil (MMF) is an immunosuppressive drug that warrants assessment as a viable therapeutic agent for horses. Hypothesis/Objectives: To evaluate the pharmacokinetics (PK) of multiple‐day oral dosing of MMF in healthy horses and to determine the tolerability of this dosing regimen. Animals: Six healthy Standardbred mares. Methods: Horses received MMF 10 mg/kg PO q12h for 7 days in the fed state. Serial sampling was performed over 12 hours on Days 1 and 7 with trough samples collected every 24 hours, immediately before morning drug administration. Noncompartmental PK analyses were performed to determine primary PK parameters, followed by calculation of geometric means and coefficients of variation. A CBC, serum biochemical profile, physical examination, and fecal scoring were used to assess dose tolerability. Results: Seven days of treatment resulted in a mycophenolic acid (MPA) area under the curve (AUC0‐12) of 12 594 h × ng/mL (8567‐19 488 h × ng/mL) and terminal half‐life (T1/2) of 11.3 hours (7.5‐15.9 hours), yielding minor metabolite accumulation in all horses treated. Salmonellosis was detected in the feces of 2 horses by Day 7, and all horses developed myelosuppression, hyperbilirubinemia, hyporexia, decreased gastrointestinal motility, and decreased fecal output by the seventh day of treatment. Conclusion and Clinical Importance: Administration of MMF at 10 mg/kg PO q12h resulted in hematologic and clinical toxicity within 1 week of treatment. A decreased MMF dose, frequency, or both is needed to avoid colic. Drug monitoring should include frequent hemograms, serum biochemical profiles, and strict biosecurity protocols. [ABSTRACT FROM AUTHOR]

Abstract Background Endogenous production of carbon monoxide during hemoglobin metabolism leads to the formation of carboxyhemoglobin. Carboxyhemoglobin concentration is abnormally high in humans with hemolytic anemia (HA). Hypothesis Measurement of carboxyhemoglobin concentration can discriminate HA from other forms of anemia. Animals Twenty‐seven dogs with HA (immune‐mediated HA, n = 22; microangiopathic HA, n = 5), 27 dogs with non‐HA (kidney disease, n = 14; immune‐mediated thrombocytopenia, [n = 6]; miscellaneous, n = 7) and 24 nonanemic control dogs. Methods Prospective cohort study. Carboxyhemoglobin quantification, a CBC and biochemistry profile were performed upon admission, and survival to hospital discharge and at 30 days were the measured outcomes. Groups were compared by the Mann‐Whitney and Kruskal‐Wallis tests. Receiver‐operator characteristic (ROC) analyses were used to examine the predictive utility of carboxyhemoglobin for the diagnosis of HA in anemic dogs. Results Carboxyhemoglobin (median [interquartile range]) differed between dogs with HA (7.7% [2.5%]) and non‐HA (3.6% [1.05]; P

Regression of leukemia in the absence of disease-modifying therapy remains poorly understood, although immunological mechanisms are thought to play a role. Here, we present a unique case of a 17-year-old boy with immune dysregulation and long-lasting regression of a (pre)leukemic clone in the absence of disease-modifying therapy. Using molecular and immunological analyses, we identified bone marrow features associated with disease control and loss thereof. In addition, our case reveals that detection of certain fusion genes with hardly any blasts in the bone marrow may be indicative of an accompanying oncogenic fusion gene, with implications for disease surveillance- and management in future patients.

Simple Summary: Babesia gibsoni is rarely reported in cats, and its pathogenic potential in this species is unknown. B. gibsoni DNA was detected using two pan-Babesia PCRs in stored blood from a cat. The cat had died, but retrospective case review identified regenerative anaemia and thrombocytopenia concurrent with B. gibsoni detection. Clinical signs resolved on treatment for a suspected immune-mediated aetiology until the cat suffered fatal haemorrhage 6 months later. Samples stored 4 and 6 months from presentation tested negative for Babesia spp. This is the first report of B. gibsoni detection in a cat to provide clinicopathological information. Tick-borne haemoparasite Babesia gibsoni has been detected rarely in cats, in surveys of apparently healthy animals. In stored blood from a 6-year-old male-neutered domestic shorthair cat in Hong Kong, B. gibsoni DNA was detected retrospectively using PCR for Babesia spp. 18S rRNA and mitochondrial cytochrome B genes, followed by sequencing and basic local alignment search tool (BLAST) analysis. The cat presented with severe haemolytic anaemia and thrombocytopenia. The cat responded to supportive care and glucocorticoids and was clinically normal despite persistent subclinical thrombocytopenia until six months after presentation, when it succumbed to a fatal haemorrhagic episode. Necropsy revealed severe intestinal and pulmonary haemorrhage and hypocellular bone marrow with megakaryocytosis but no other causes of immune-mediated thrombocytopenia (IMTP) or immune-mediated haemolytic anaemia (IMHA). Blood stored on days 158 and 180 tested PCR negative for Babesia spp. This report demonstrates that geographic range of B. gibsoni detection in cats includes Hong Kong. The exclusion of other causes suggests that B. gibsoni might have potentially played a role in triggering immune-mediated disease in this case. [ABSTRACT FROM AUTHOR]

Previously classified as Non Langerhan cell histiocytosis by the Working Group of Histiocytic Society in 1987 Rosai Dorfman Destombes disease was first described by Destombes in 1965 and later in 1969 by Rosai and Dorfman as a rare histiocytic disorder with sinus histiocytosis and massive lymphadenopathy. They exist in both nodal and extranodal forms. Immunohistochemistry is an essential part of diagnosis to differentiate between Langerhans cell histiocytosis and another malignant histiocytosis. Some overlap has also been reported with IgG4-related diseases. We hereby reflect upon a patient who presented to our facility with pyrexia of unknown origin, the challenges faced in order to reach a diagnosis and the management offered. [ABSTRACT FROM AUTHOR]