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British Journal of Haematology May 2024Idiopathic hypereosinophilic syndrome (iHES) is a condition wherein persistent hypereosinophilia associated with end-organ damage occurs without any known causes. Due to...
Idiopathic hypereosinophilic syndrome (iHES) is a condition wherein persistent hypereosinophilia associated with end-organ damage occurs without any known causes. Due to the rarity of the disease, insufficient knowledge has been accumulated. We therefore conducted a retrospective, multicentre, nationwide survey on iHES in Japan. A total of 57 patients were identified. For 43 patients who received any treatment, all cases were first treated with corticosteroids. An eosinophil percentage of less than 30% in the bone marrow and the absence of oedema were identified as factors associated with steroid dependency. The 5-year overall survival was 88.2%, and five patients died during follow-up; factors associated with worse overall survival were age >50, haemoglobin <12 g/dL, activated partial thromboplastin time >34 s, the presence of dyspnoea, the presence of thrombotic tendency and the presence of renal failure. Given the rarity of fatalities in our cohort, time-to-next-treatment (TTNT) was further analysed; the presence of renal failure, splenomegaly and lung abnormalities were associated with worse TTNT. Our nationwide study not only demonstrated clinical characteristics and the outcome of patients with iHES but also for the first time revealed clinical factors associated with steroid dependency and duration of first-line corticosteroid efficacy.
PubMed: 38797527
DOI: 10.1111/bjh.19527 -
Cureus Apr 2024Infectious mononucleosis (IM) is a clinical disease caused by the Epstein-Barr virus (EBV). Common presenting symptoms include sore throat, lymph node enlargement,...
Infectious mononucleosis (IM) is a clinical disease caused by the Epstein-Barr virus (EBV). Common presenting symptoms include sore throat, lymph node enlargement, fever, and malaise. Although severe upper airway obstruction is uncommon, it is a potentially fatal complication that requires immediate intervention. We describe the case of an 18-year-old Hispanic man who presented with a progressive sore throat and difficulty speaking, requiring endotracheal intubation for airway protection. CT images showed diffuse swelling of Waldeyer's tonsillar ring, multiple enlarged lymphadenopathies, and splenomegaly. Acute EBV infection was confirmed considering clinical presentation and using the heterophile antibody, anti-nuclear and anti-viral capsid antigens, and quantitative PCR. The patient was managed with ventilatory support, empirical antibiotic therapy, and systemic corticosteroids, achieving a positive outcome. Our case illustrates the use of corticosteroids in managing severe upper airway obstruction complicating IM.
PubMed: 38779228
DOI: 10.7759/cureus.58735 -
Disease Models & Mechanisms May 2024Hyperinflammatory disease is associated with an aberrant immune response resulting in cytokine storm. One such instance of hyperinflammatory disease is known as...
Hyperinflammatory disease is associated with an aberrant immune response resulting in cytokine storm. One such instance of hyperinflammatory disease is known as macrophage activation syndrome (MAS). The pathology of MAS can be characterised by significantly elevated serum levels of interleukin (IL)-18 and interferon (IFN)-γ. Given the role for IL-18 in MAS, we sought to establish the role of inflammasomes in the disease process. Using a murine model of CpG-DNA induced MAS, we discovered that the expression of the NLRP3 inflammasome was increased and correlated with IL-18 production. Inhibition of the NLRP3 inflammasome, or downstream caspase-1, prevented MAS-mediated upregulation of plasma IL-18 but interestingly did not alleviate key features of hyperinflammatory disease including hyperferritinaemia and splenomegaly. Furthermore IL-1 receptor blockade with IL-1Ra did not prevent the development of CpG-induced MAS, despite being clinically effective in the treatment of MAS. These data demonstrate that in the development of MAS, the NLRP3 inflammasome was essential for the elevation in plasma IL-18, a key cytokine in clinical cases of MAS, but was not a driving factor in the pathogenesis of CpG-induced MAS.
PubMed: 38775430
DOI: 10.1242/dmm.050762 -
Real-life use of ropeg-interferon α2b in polycythemia vera: patient selection and clinical outcomes.Annals of Hematology May 2024Ropeginterferon-alfa2b (ropegIFNα2b) is a long-acting IFN formulation with broad FDA/EMA approval as a therapy of polycythemia vera (PV) with no symptomatic...
Ropeginterferon-alfa2b (ropegIFNα2b) is a long-acting IFN formulation with broad FDA/EMA approval as a therapy of polycythemia vera (PV) with no symptomatic splenomegaly. There is currently lack of information on the real-world patient selection, including the impact of local reimbursement policies, and drug management, particularly: type/timing of screening and follow-up tests; absolute/relative contraindications to therapy; ropegIFNα2b dose and combinations with hydroxyurea. As a sub-analysis of the PV-ARC retrospective study (NCT06134102), we here report our monocenter experience with ropegIFNα2b in the period from January 2021, corresponding to drug availability outside clinical trial, and December 2023. Among the 149 patients with EMA/FDA indication, only 55 (36.9%) met the local reimbursement criteria and 18 (12.1%) received ropegIFNα2b. Thanks to appropriate screening, relative/absolute contraindications to ropegIFNα2b were detected and managed in a multidisciplinary manner. Efficacy and safety of ropegIFNα2b was confirmed, with 3 cases of early molecular response. General use of low ropegIFNα2b dose, with frequent need for hydroxyurea combinations, was noted. This real-world experience suggests a significant impact of local regulations on drug prescription and the need for greater real-world data collection on ropegIFNα2b in PV patients. Also, it describes appropriate multidisciplinary screening and monitoring procedures during ropegIFNα2b therapy.
PubMed: 38771499
DOI: 10.1007/s00277-024-05809-6 -
Vascular and Endovascular Surgery May 2024Venous stasis ulcers are nonhealing lesions due to venous hypertension secondary to valvular dysfunction or deep venous outflow obstruction. We describe a case of a...
Venous stasis ulcers are nonhealing lesions due to venous hypertension secondary to valvular dysfunction or deep venous outflow obstruction. We describe a case of a 71-year-old male with a history of polycythemia vera, secondary myelofibrosis, and massive splenomegaly up to 38 cm who presented with chronic, perimalleolar venous stasis ulcers and pain on the left lower extremity. CT showed significant compression of the left common iliac vein due to mass effect from the spleen. He was managed medically while being evaluated for partial splenic artery embolization but expired due to other chronic conditions before any intervention could be performed. Partial splenic artery embolization may be considered as a treatment option for patients with symptomatic iliac vein compression due to massive splenomegaly secondary to myelofibrosis, as long as extramedullary hematopoiesis is not compromised.
PubMed: 38770560
DOI: 10.1177/15385744241256318 -
Therapeutics and Clinical Risk... 2024Lymphoproliferation is defined by lymphadenopathy, splenomegaly, hepatomegaly, or lymphocytic organ and tissue infiltration. The most common etiologies of... (Review)
Review
The Etiologic Landscape of Lymphoproliferation in Childhood: Proposal for a Diagnostic Approach Exploring from Infections to Inborn Errors of Immunity and Metabolic Diseases.
Lymphoproliferation is defined by lymphadenopathy, splenomegaly, hepatomegaly, or lymphocytic organ and tissue infiltration. The most common etiologies of lymphoproliferation are represented by infectious diseases and lymphoid malignancies. However, it is increasingly recognized that lymphoproliferative features can be the presenting sign of rare conditions, including inborn errors of immunity (IEI) and inborn errors of metabolism (IEM). Among IEI, lymphoproliferation is frequently observed in autoimmune lymphoproliferative syndrome (ALPS) and related disorders, common variable immunodeficiency (CVID), activated phosphoinositide 3-kinase δ syndrome, and Epstein-Barr virus (EBV)-related disorders. Gaucher disease and Niemann-Pick disease are the most common IEMs that can present with isolated lymphoproliferative features. Notably, other rare conditions, such as sarcoidosis, Castleman disease, systemic autoimmune diseases, and autoinflammatory disorders, should be considered in the differential diagnosis of patients with persistent lymphoproliferation when infectious and malignant diseases have been reasonably ruled out. The clinical features of lymphoproliferative diseases, as well as the associated clinical findings and data deriving from imaging and first-level laboratory investigations, could significantly help in providing the correct diagnostic suspicion for the underlying etiology. This paper reviews the most relevant diseases associated with lymphoproliferation, including infectious diseases, hematological malignancies, IEI, and IEM. Moreover, some practical indications to orient the initial diagnostic process are provided, and two diagnostic algorithms are proposed for the first-level assessment and the approach to persistent lymphoproliferation, respectively.
PubMed: 38770035
DOI: 10.2147/TCRM.S462996 -
Cureus Apr 2024Congenital dyserythropoietic anemias (CDAs) are rare hereditary disorders, of which type II CDA is the most common. Mutations in the gene located on chromosome 20...
Congenital dyserythropoietic anemias (CDAs) are rare hereditary disorders, of which type II CDA is the most common. Mutations in the gene located on chromosome 20 result in this autosomal recessive disorder. In this case report, we present a case of CDA II with unique biopsy findings being detected via genetic testing. A female aged 30 years presented with major complaints of pallor weakness and easy fatiguability since childhood. The patient gave a history of 25 units of blood transfusion, the majority of which were transfused during pregnancy, followed by regular transfusions thereafter. On examination, all her vitals were in the normal range. Pallor, frontal bossing, and malocclusion of teeth were noted. Her laboratory workup showed the following: hemoglobin (Hb): 3.7 g/dl; mean corpuscular volume: 83 fl; mean corpuscular Hb: 29 g/dl; mean corpuscular Hb concentration: 34.9 g/dl; red cell distribution width: 30.4%; reticulocyte count (RC): 6.2%; corrected RC: 1.3%; lactate dehydrogenase: 441 IU/L; direct Coombs test/indirect Coombs test: negative; serum iron: 242 microgram/dl; transferrin saturation: 96.08%; ferritin: 1,880 ng/ml; and normal high-performance liquid chromatography and eosin-5'-maleimide binding test. The peripheral blood film showed normocytic normochromic anemia with anisopoikilocytosis in the form of a few spherocytes. No immature cells were seen. After obtaining the patient's consent, we performed a hereditary hemolytic anemia gene analysis test, which showed homozygous missense variation in exon 12 of the gene. The bone marrow examination showed hyperplasia in the erythroid series with dyserythropoiesis, and surprisingly, myelofibrosis grade I-II (WHO 2017) was also observed on biopsy. Patients with CDA type II generally present with variable degrees of anemia along with pallor, icterus, splenomegaly, gallstones, and iron overload. In our case, the diagnosis of CDA type II was made at an adult age. Also, evidence of myelofibrosis was noted in our case, making it worth reporting. The use of a hereditary hemolytic anemia gene analysis panel test came as a rescue for its exact diagnosis. This case report emphasizes the role of molecular genetic testing for early and accurate diagnosis, which, in turn, could help in appropriate treatment planning and proper genetic counseling. The prevalence of CDA type II is still vaguely known; hence, extensive workup of persistent anemias and proper follow-up would be beneficial.
PubMed: 38765414
DOI: 10.7759/cureus.58515 -
Transplantation Proceedings May 2024A 21-year-old woman diagnosed with cystic fibrosis developed cirrhosis, exocrine pancreatic insufficiency, and insulin-dependent diabetes mellitus. The patient qualified...
BACKGROUND
A 21-year-old woman diagnosed with cystic fibrosis developed cirrhosis, exocrine pancreatic insufficiency, and insulin-dependent diabetes mellitus. The patient qualified for double organ liver-pancreas transplantation beyond typical indications. The respiratory symptoms of cystic fibrosis were moderate and well-treated. The patient was endangered mainly by liver insufficiency and recurrent hypoglycemia, which was due to the treatment of diabetes with high doses of insulin. Computed tomography showed mild bronchiectasis, cirrhotic liver, splenomegaly, and atrophy of the pancreas. Pseudomonas aeruginosa colonized the upper respiratory tract. Gastrointestinal complications were sufficient for the patient to be qualified for combined liver-pancreas transplantation.
METHODS
First, a standard hepatectomy was performed. The liver was transplanted orthotopically. Subsequently, the team performed pancreas transplantation through a separate incision. The donor's duodenum was anastomosed to the recipient's jejunum, close to the ligament of Treitz.
RESULTS
No serious complications were noted during the postoperative period. Transplanted organs started functioning without delay. The patient was discharged after 6 weeks in general good condition. Twenty months later, the patient felt well, and the grafts kept functioning properly.
CONCLUSION
Combined liver-pancreas transplantation in patients with CF restores exocrine and endocrine pancreatic function and minimizes the risk of life-threatening complications associated with liver insufficiency. Improvement of life quality coincides with the possibility of discontinuing insulin and pancreatic enzyme supplementation. The combination of liver and pancreas transplantation may prevent advanced pulmonary complications, extend the prognosis of survival, and improve the long-term life quality.
Topics: Humans; Cystic Fibrosis; Pancreas Transplantation; Female; Liver Transplantation; Young Adult; Diabetes Mellitus, Type 1; Exocrine Pancreatic Insufficiency; Treatment Outcome
PubMed: 38749862
DOI: 10.1016/j.transproceed.2024.03.034 -
Journal of Fish Diseases May 2024This study aimed to identify and characterize isolates of Francisella salimarina associated with an outbreak on a marine fish farm in Brazil and to analyse their genetic...
This study aimed to identify and characterize isolates of Francisella salimarina associated with an outbreak on a marine fish farm in Brazil and to analyse their genetic variability and antimicrobial susceptibility. In 2021, diseased cobias (Rachycentron canadum, n = 10) and dusky groupers (Epinephelus marginatus, n = 10) were sampled and subjected to bacteriological and pathological examinations. The isolates obtained were morphologically and biochemically characterized and identified by matrix-assisted laser desorption/ionization-time of flight (MALDI-ToF) and 16S rRNA gene sequencing. The genetic diversity of these isolates was analysed using repetitive extragenic palindromic-polymerase chain reaction (REP-PCR). Antimicrobial susceptibility was assessed using the disk diffusion technique. Macroscopically, the fish presented skin ulcerations, ocular lesions, hepatomegaly and splenomegaly. A pleomorphic, gram-negative, catalase- and oxidase-positive bacterium was isolated from seven cobias and two groupers. The 16S rRNA gene sequences showed >99% coverage and identity with other deposited sequences of F. salimarina. The results of the biochemical analysis corresponded to these bacterial species. Histologically, granulomas were observed in the spleen, liver and heart of the cobias (n = 6), and necrotizing and fibrinous dermatitis and myositis were identified in some groupers (n = 2). The isolates exhibited the same banding pattern when REP-PCR was performed, indicating that they were clonally related. Finally, the antibiogram test, no inhibition halo was observed for amoxicillin and trimethoprim-sulfamethoxazole. To our knowledge, this is the first report of F. salimarina infection in cobias and dusky groupers.
PubMed: 38747073
DOI: 10.1111/jfd.13962