Explore the vast range of titles available.

•Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease targeting myelin in the central nervous system (CNS).•Fingolimod was introduced in 2010 as the first oral disease modifying therapy (DMT) to treat relapsing multiple sclerosis.•We report the first case of fingolimod-induced immune thrombocytopenic purpura in North America.•This case highlights the importance of early consideration of a drug-induced adverse event, and its prompt discontinuation.

A 45-year-old Italian woman, affected by relapsing–remitting multiple sclerosis (RR-MS) starting from 2011, started treatment with alemtuzumab in July 2016. Nine months after the second infusion, she had an immune thrombocytopenic purpura (ITP) with complete recovery after steroid treatment. Three months after the ITP, the patient presented with transient aphasia, cognitive deficits, and focal epilepsy. Serial brain magnetic resonance imaging showed a pattern compatible with encephalitis. Autoantibodies to glutamate receptor 3 peptide A and B were detected in cerebrospinal fluid and serum, in the absence of any other diagnostic cues. After three courses of intravenous immunoglobulin (0.4 mg/kg/day for 5 days, 1 month apart), followed by boosters (0.4 mg/kg/day) every 4–6 weeks, her neurological status improved and is currently comparable with that preceding the encephalitis. Autoimmune complications of the central nervous system during alemtuzumab therapy are relatively rare: only one previous case of autoimmune encephalitis following alemtuzumab treatment has been reported to date.

Abstract Background A method of quantifying clinical bleeding in dogs with immune thrombocytopenia (ITP) is needed because ITP patients have variable bleeding tendencies that inconsistently correlate with platelet count. A scoring system will facilitate patient comparisons and allow stratification based on bleeding severity in clinical trials. Hypothesis/Objectives To develop and evaluate a bleeding assessment tool for dogs, and a training course for improving its consistent implementation. Animals Client-owned dogs (n = 61) with platelet counts <50,000/μL; 34 classified as primary ITP, 17 as secondary ITP, and 10 as non-ITP. Methods A novel bleeding assessment tool, DOGiBAT, comprising bleeding grades from 0 (none) to 2 (severe) at 9 anatomic sites, was developed. Clinicians and technicians completed a training course and quiz before scoring thrombocytopenic patients. The training course was assessed by randomizing student volunteers to take the quiz with or without prior training. A logistic regression model assessed the association between training and quiz performance. The correlation of DOGiBAT score with platelet count and outcome measures was assessed in the thrombocytopenic dogs. Results Clinicians and technicians consistently applied the DOGiBAT, correctly scoring all quiz cases. The odds of trained students answering correctly were higher than those of untrained students (P < .0001). In clinical cases, DOGiBAT score and platelet count were inversely correlated (rs = −0.527, P < .0001), and DOGiBAT directly correlated with transfusion requirements (rs = 0.512, P < .0001) and hospitalization duration (rs = 0.35, P = .006). Conclusions and Clinical Importance The DOGiBAT and assessment quiz are simple tools to standardize evaluation of bleeding severity. With further validation, the DOGiBAT may provide a clinically relevant metric to characterize ITP severity and monitor response in treatment trials.

Immune thrombocytopenia (ITP) is an autoimmune disease defined by low platelet counts which presents with an increased bleeding risk. Several genetic risk factors (e.g., polymorphisms in immunity-related genes) predispose to ITP. Autoantibodies and cytotoxic CD8 T cells (Tc) mediate the anti-platelet response leading to thrombocytopenia. Both effector arms enhance platelet clearance through phagocytosis by splenic macrophages or dendritic cells and by induction of apoptosis. Meanwhile, platelet production is inhibited by CD8 Tc targeting megakaryocytes in the bone marrow. CD4 T helper cells are important for B cell differentiation into autoantibody secreting plasma cells. Regulatory Tc are essential to secure immune tolerance, and reduced levels have been implicated in the development of ITP. Both Fcγ-receptor-dependent and -independent pathways are involved in the etiology of ITP. In this review, we present a simplified model for the pathogenesis of ITP, in which exposure of platelet surface antigens and a loss of tolerance are required for development of chronic anti-platelet responses. We also suggest that infections may comprise an important trigger for the development of auto-immunity against platelets in ITP. Post-translational modification of autoantigens has been firmly implicated in the development of autoimmune disorders like rheumatoid arthritis and type 1 diabetes. Based on these findings, we propose that post-translational modifications of platelet antigens may also contribute to the pathogenesis of ITP.

BackgroundChronic Granulomatous Disease (CGD) is a rare immunodeficiency disorder characterized by impaired phagocytic function, leading to recurrent infections and granuloma formation. Genetic mutations in NADPH oxidase complex components, such as CYBB, NCF1, NCF2, and CYBA genes, contribute to the pathogenesis. This case report explores the possible ocular and hematologic complications associated with CGD.Case PresentationA 6-year-old girl with a history of vitrectomy, membranotomy, and laser therapy due to congenital blindness (diagnosed with chorioretinopathy) was referred to the hospital with generalized ecchymosis and thrombocytopenia. Diagnostic workup initially suggested chronic immune thrombocytopenic purpura (ITP). Subsequent admissions revealed necrotic wounds, urinary tract infections, and recurrent thrombocytopenia. Suspecting immunodeficiency, tests for CGD, Nitroblue tetrazolium (NBT) and dihydrorhodamine (DHR) were performed. She had a low DHR (6.7), and her NBT test was negative (0.0%). Her whole exome sequencing results confirmed autosomal recessive CGD with a homozygous NCF1 mutation.ConclusionThis case underscores the diverse clinical manifestations of CGD, including recurrent thrombocytopenia and possible early-onset ocular involvement. The diagnostic challenges highlight the importance of a multidisciplinary approach involving hematologists, immunologists, and ophthalmologists for accurate diagnosis and management. The rare coexistence of ITP in CGD emphasizes the intricate link between immunodeficiency and autoimmunity, requiring tailored therapeutic strategies.

BackgroundImmune thrombocytopenic purpura (ITP) is a challenging disease in its presentation and management as it may cause life-threatening hemorrhaging in vital organs and may resist several lines of treatment. This systematic review and meta-analysis aimed to evaluate the safety and efficacy of mycophenolate mofetil (MMF) in treating patients with ITP.MethodsWe systematically searched four electronic databases (PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials) from inception until 10 October 2022. We included all clinical trials, either controlled or single arm, and prospective and retrospective observational studies that evaluate the efficacy and safety of MMF in patients with ITP. We assessed the risk of bias using three tools (ROBINS-I, Cochrane ROB-2, and NIH), each for eligible study design.ResultsNine studies were included in this meta-analysis, with a total of 411 patients with ITP. We found that MMF demonstrated an overall response rate of (62.09%; 95% CI = [43.29 to 77.84]) and the complete response rate was (46.75%; 95% CI = [24.84 to 69.99]). The overall proportion of adverse events was (12%; 95% CI = [6 to 24]). After the sensitivity analysis, the overall response rate became 50%; 95% CI = [38 to 63]) and the complete response rate became (32%; 95% CI = [24 to 42]). However, MMF did not appear to affect white blood cell counts or hemoglobin levels significantly.ConclusionThis systematic review and meta-analysis demonstrate that MMF appears to be an effective and relatively safe treatment option for patients with ITP when combined with steroids and even in those who have not responded to standard therapies (steroid-resistant cases). Further research with well-designed studies is warranted to better understand the factors influencing treatment response and to refine the use of MMF in the management of ITP. An interactive version of our analysis can be accessed from here: https://databoard.shinyapps.io/mycophenolate_meta/

A 33-year-old Chinese woman with a history of immune thrombocytopenic purpura presented with heavy menstrual bleeding. She was found to have thrombocytopenia, plasma ADAMTS13 activity of 0%, and positivity for the plasma ADAMTS13 inhibitor. She was diagnosed with the coexistence of thrombotic thrombocytopenic purpura and immune thrombocytopenic purpura. The patient was treated by plasmapheresis, a glucocorticoid, and rituximab. Her platelet level returned to normal, and she was discharged 28 days after admission. The number of plasmapheresis sessions and the timing of rituximab administration may be the key aspects of management of patients with thrombotic thrombocytopenic purpura who have underlying immune dysfunction caused by diseases such as immune thrombocytopenic purpura.

Epidermolysis bullosa acquisita (EBA) is a rare autoimmune blistering disease caused by autoantibodies to type VII collagen. While dipeptidyl peptidase-4 (DPP-4) inhibitors are established triggers for bullous pemphigoid (BP), their association with EBA has not been reported. A 68-year-old Japanese man with type 2 diabetes and chronic renal dysfunction, treated with linagliptin, developed widespread tense blisters with mucosal involvement. Histopathology and immunological studies confirmed EBA. Despite corticosteroids, cyclosporine, pulse therapy, and intravenous immunoglobulin, the disease remained refractory. Eighty days after onset, he developed pneumonia, renal failure requiring dialysis, and severe thrombocytopenia. After exclusion of other causes, immune thrombocytopenic purpura (ITP) was clinically diagnosed. Although treatment yielded transient platelet recovery, the patient ultimately died. This is the first reported case of EBA following DPP-4 inhibitor therapy complicated by ITP. It highlights the therapeutic challenges of EBA and the potential for systemic autoimmune manifestations beyond the skin in patients receiving DPP-4 inhibitors.

A prospective, single-arm, open-label Phase III clinical trial was conducted across multiple centers in China from April 27, 2020, to June 15, 2021, to assess the efficacy and safety of 10% intravenous immunoglobulin (IVIg) in treating adult immune thrombocytopenic purpura (ITP). Within 7 days of treatment initiation, the 10% IVIg group exhibited an overall response rate of 87.0%, with 32 patients (46.4%) achieving complete response and 28 patients (40.6%) demonstrating partial response, comparable to the 5% IVIg group. Notably, the median time to achieve a platelet count (PLT) of 50 × 10 9 /L was significantly shorter for the 10% IVIg group at 2 days (IQR: 2–3) versus 3 days (IQR: 3–5) for the 5% IVIg group. Additionally, the 10% IVIg group reached a PLT of 100 × 10 9 /L in 3 days (IQR: 3–4), compared to 5 days (IQR: 4–6) for the 5% IVIg group. Post-treatment bleeding scores significantly decreased, and no significant adverse reactions were reported. This inaugural study highlights the efficacy and safety of 10% IVIg in the urgent management of adult ITP, positioning it as a rapid therapeutic option.