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Revista Espanola de Enfermedades... Nov 2023A 49-year-old man presented with a three-week history of abdominal pain, bloody diarrhoea and fever. Reported oral ulcers, weight loss and asthenia, as well as...
A 49-year-old man presented with a three-week history of abdominal pain, bloody diarrhoea and fever. Reported oral ulcers, weight loss and asthenia, as well as papulo-pustular lesions on his limbs and a recurrent ulcer in the lip (Fig.1) in the previous year. During hospitalization, he developed pathergy at venipuncture sites and painful scrotum ulcers. Laboratory showed pancytopenia and elevated CRP. Viral and autoimmune tests were negative. Abdominal CT revealed thickening of the ileocecal region with adenopathies. Blood smear and myelogram were compatible with Chronic Myeloid Leukemia (CML). Bone marrow culture and BK were negative. Karyotype revealed no changes, namely, no trisomy of the 8th. Ileocolonoscopy revealed aphthoid erosions of the ileocecal mucosa and ovoid punched-out cecal ulcers. Biopsies showed intense chronic inflammation in the lamina propria and submucosa with erosions and ulcers. Thus, presenting 5 points in the International Criteria for Behçet's Disease, this diagnosis was assumed as a paraneoplastic manifestation of CML. Corticosteroids improved symptoms, but the patient died three weeks later due to a blastic crisis. BS has been reported in association with CML, some concurrent with, or following treatment with interferon-a or hydroxyurea. Although the pathogenesis remains unclear, there is increasing awareness of its link to hematological malignancies, and trisomy of the 8th.
PubMed: 37929953
DOI: 10.17235/reed.2023.10015/2023 -
International Journal of Molecular... Sep 2023We previously reported that granulocytic myeloid-derived suppressor cells (G-MDSCs) suppressed T-cell activation and attenuated bone marrow failure (BMF) in a minor...
We previously reported that granulocytic myeloid-derived suppressor cells (G-MDSCs) suppressed T-cell activation and attenuated bone marrow failure (BMF) in a minor histocompatibility (minor-H) antigen mismatched murine aplastic anemia (AA) model. In the current study, we tested the hypothesis that exosomes, a subset of extracellular vesicles, are responsible at least partially for G-MDSCs' therapeutic efficacy. Indeed, exosomes isolated from GMDSCs (G-MDSC-exos) suppressed CD4 and CD8 T-cell proliferation in vitro and mildly attenuated immune BMF in the minor-H mismatched AA model. G-MDSC-exos treatment significantly increased red blood cells, hemoglobin, and total bone marrow (BM) cells, and moderately reduced BM CD8 T cells. G-MDSC-exos' effects were associated with upregulations in an array of lymphocyte-suppression-related miRNAs such as hsa-miR-142-5p, miR-19a-3p, and miR-19b-3p in both BM CD4 and CD8 T cells. We concluded that G-MDSC-exos attenuate immune BMF via modulating the delivery of immunosuppressive miRNAs into activated T lymphocytes.
Topics: Mice; Animals; Myeloid-Derived Suppressor Cells; CD8-Positive T-Lymphocytes; Disease Models, Animal; Exosomes; Granulocytes; Immunosuppressive Agents; MicroRNAs; Pancytopenia; Bone Marrow Failure Disorders
PubMed: 37834110
DOI: 10.3390/ijms241914661 -
Hepatology Communications Oct 2023Graft-versus-host disease following liver transplantation is a serious and usually fatal complication. Data identifying the risk factors and specifying the diagnosis and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Graft-versus-host disease following liver transplantation is a serious and usually fatal complication. Data identifying the risk factors and specifying the diagnosis and treatment options of the disease are scarce and contentious. Moreover, recommendations for therapeutic approaches are similarly sparse.
METHODS
A systematic review of the literature from 1988 to 2020 on graft-versus-host disease following liver transplantation was performed using the PubMed and MEDLINE databases. Medical subject headings, such as graft-versus-host disease and GvHD were used in combination with solid organ transplant, transplantation, or liver transplant. Following duplicate removal, 9298 articles were screened for suitability. A total of 238 full-text articles were analyzed for eligibility, resulting in 130 eligible articles for meta-analysis. Two hundred twenty-five patients developing graft-versus-host disease following liver transplantation reported herein were mainly published in case reports and case series.
RESULTS
Graft-versus-host disease occurred with an incidence of 1.2%. 85% developed following deceased donor liver transplant and 15% following living-related donor liver transplantation. The median follow-up period following liver transplantation was 84 days (interquartile range, 45-180). The median time from liver transplantation to graft-versus-host disease onset was 30 days (interquartile range, 21-42). The main clinical features included skin rash (59%), fever (43%), diarrhea (36%), and pancytopenia (30%). The overall mortality rate was 71%. Neither univariate (HR = 0.999; 95% CI, 0.493-2.023; p = 1.0) nor multivariate Cox regression analysis revealed a significant correlation between adaptation of immunosuppression and survival probability (HR = 1.475; 95% CI, 0.659-3.303; p = 0.3).
CONCLUSIONS
This systematic review suggests that an increase in immunosuppressive regimen does not yield any survival benefit in patients suffering from graft-versus-host disease following liver transplantation.
Topics: Humans; Liver Transplantation; Living Donors; Graft vs Host Disease; Immunosuppressive Agents; Risk Factors
PubMed: 37755878
DOI: 10.1097/HC9.0000000000000260 -
Journal of Medical Case Reports Jul 2023Vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome is a newly discovered inflammatory disease affecting male subjects, for which few data exist in the...
BACKGROUND
Vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome is a newly discovered inflammatory disease affecting male subjects, for which few data exist in the literature. Here, we describe the case of a patient with known Sweet's syndrome admitted to the intensive care unit and for whom a vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome was diagnosed, allowing for appropriate treatment and the patient's discharge and recovery.
CASE PRESENTATION
A 70-year-old male White patient was hospitalized in the intensive care unit following an intrahospital cardiac arrest. History started a year before with repeated deep vein thrombosis and episodes of skin eruption compatible with Sweet's syndrome. After a course of oral steroids, fever and inflammatory syndrome relapsed with onset of polychondritis, episcleritis along with neurological symptoms and pulmonary infiltrates. Intrahospital hypoxic cardiac arrest happened during patient's new investigations, and he was admitted in a critical state. During the intensive care unit stay, he presented with livedoid skin lesions on both feet. Vasculitis was not proven; however, cryoglobulinemia screening came back positive. Onset of pancytopenia was explored with a myelogram aspirate. It showed signs of dysmyelopoiesis and vacuoles in erythroid and myeloid precursors. Of note, new deep vein thrombosis developed, despite being treated with heparin leading to the diagnosis of heparin-induced thrombocytopenia. The course of symptoms were overlapping multiple entities, and so a multidisciplinary team discussion was implemented. Screening for UBA1-mutation in the blood came back positive, confirming the vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome. Corticosteroids and anti-IL1 infusion were started with satisfactory results supporting patient's discharge from intensive care unit to the internal medicine ward.
CONCLUSIONS
Vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome should be suspected in male patients presenting with inflammatory symptoms, such as fever, skin eruption, chondritis, venous thromboembolism, and vacuoles in bone marrow precursors. Patients with undiagnosed vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic syndrome may present with organ failure requiring hospitalization in intensive care unit, where screening for UBA1 mutation should be performed when medical history is evocative. Multidisciplinary team involvement is highly recommended for patient management, notably to start appropriate immunosuppressive treatments.
Topics: Humans; Male; Aged; Sweet Syndrome; Vacuoles; Hospitalization; Exanthema; Fever; Heart Arrest; Venous Thrombosis
PubMed: 37480098
DOI: 10.1186/s13256-023-04034-5 -
Cureus Nov 2023We present a 29-year-old man admitted to our hospital with fatigue for two months of duration and recent palpitations, lightheadedness, blurred vision and nausea. Workup...
We present a 29-year-old man admitted to our hospital with fatigue for two months of duration and recent palpitations, lightheadedness, blurred vision and nausea. Workup showed pancytopenia with severe macrocytic anemia, laboratory and blood smear features of hemolysis, low reticulocyte percentage and a negative direct Coombs test. B12 and folate levels were normal. As bone marrow aspirate was suggestive of megaloblastic anemia and upper endoscopy showed atrophic gastritis, we ordered homocysteine (elevated) and intrinsic factor (IF) antibodies (positive). The workup led to the diagnosis of pernicious anemia with spuriously normal B12 levels. Replacement therapy allowed a rapid recovery. We highlight that the presence of IF antibodies can interfere with the competitive binding assays commonly used to measure B12 levels.
PubMed: 38106734
DOI: 10.7759/cureus.48937 -
Cureus Dec 2023Massive splenomegaly complicating pregnancy is a rare clinical entity that poses special difficulties, such as anemia, thrombocytopenia, ascites, and jaundice. This case...
Massive splenomegaly complicating pregnancy is a rare clinical entity that poses special difficulties, such as anemia, thrombocytopenia, ascites, and jaundice. This case report of a pregnant woman with large splenomegaly and pancytopenia highlights the value of prompt diagnosis and effective treatment. Splenomegaly can have a number of causes, including viral infections, hematological problems, portal hypertension, and metabolic abnormalities. A 29-year-old gravida 3 woman at 37 weeks of gestation who had massive splenomegaly was admitted and underwent a cesarean section to avoid complications of splenomegaly. The case report discusses the difficulties in obstetric management caused by enormous splenomegaly during pregnancy, including the choice of delivery method. Significant complications include splenic rupture and bleeding, particularly when pancytopenia is present. The need for several transfusions, the potential side effects of transfusion therapy, and factors related to the origin of splenomegaly when assessing maternal-fetal outcomes are discussed in this case report. The study concludes that in cases with pancytopenia splenomegaly during pregnancy, vigilant monitoring, prompt intervention, and a multidisciplinary approach are crucial to achieve positive outcomes for both the mother and the fetus.
PubMed: 38229813
DOI: 10.7759/cureus.50656 -
Cureus Aug 2023Background This multicentric cross-sectional study aimed to examine the prevalence of thrombocytopenia (TCP) and investigate the various causes of chronic liver disease...
Background This multicentric cross-sectional study aimed to examine the prevalence of thrombocytopenia (TCP) and investigate the various causes of chronic liver disease (CLD) across 15 Southeast Asian (India, Pakistan, and Bangladesh) tertiary care centers over a three-month period. The study focused on assessing the fibrosis index (FI) and Model for End-Stage Liver Disease (MELD)-sodium (Na) score's capacity to grade and predict the progression and outcomes of patients with already diagnosed CLD. Methods The cross-sectional study enrolled 377 CLD patients. The study utilized admission registries from 15 tertiary care hospitals in Southeast Asia, spanning from April 2023 to June 2023. Various descriptive variables were collected, including gender, tobacco use (specifically, chewed tobacco), underlying etiology, presence of anemia, leukopenia, pancytopenia, infectious state, and liver cirrhosis diagnosed via traditional ultrasonography. This study examined liver failure indicators, including alanine transaminase levels, compensation status, TCP, and liver transplant (LT) listing. The MELD-Na score was the focus of frequency and percentage analysis. MELD-Na and FI medians and standard deviations were provided. Results The study of 377 patients with CLD found that TCP was present in 4% of patients and leukopenia was present in 12% of patients. The risk of TCP was significantly higher in leukopenic patients (89.5%) than in non-leukopenic patients (52.5%) (p = 0.003). The most common CLD cause was undiagnosable (31%), followed by autoimmune (26%), hepatitis C virus (21%), hepatitis B virus (14%), and schistosomiasis (8%). The majority of patients (98%) had decompensated liver disease. Of the patients, 64% had TCP, while 36% did not. The illness severity indicators MELD score and FI had mean ± SD values of 16.89 ± 6.42 and 4.1 ± 1.06, respectively. Similarly, the prevalence of LT needs among traditional ultrasonography-diagnosed cirrhotic patients was 83.1%, compared to 59.6% among non-cirrhotic patients (p = 0.001). Conclusion Leukopenia and TCP may be linked, which may affect CLD treatment and prognosis in this population. Non-invasive indicators like the FI and MELD-Na score can detect liver fibrosis and severity without invasive procedures, enhancing patient management. These findings highlight the need to improve early diagnosis methods for CLD in Southeast Asia and raise awareness among clinicians about effective diagnostic strategies for non-infectious causes of CLD.
PubMed: 37700968
DOI: 10.7759/cureus.43356 -
Cureus Jul 2023Immune checkpoint inhibitors (ICIs) as standard of care have revolutionized the treatment of patients with metastatic melanoma. The combination of nivolumab and...
Immune checkpoint inhibitors (ICIs) as standard of care have revolutionized the treatment of patients with metastatic melanoma. The combination of nivolumab and ipilimumab improves treatment efficacy and prolongs survival compared to monotherapy alone. However, combination therapy is also associated with an increased incidence of adverse events. We report an uncommon yet important case of multi-organ failure in a patient following a single dose of nivolumab plus ipilimumab. A 60-year-old male with a history of ulcerative colitis in remission and metastatic melanoma was admitted on February 25, 2021, for presumed sepsis, after presenting with neutropenic fever. His brain metastases were previously resected on January 14, 2021, and he was started on dexamethasone 4 mg BID for six weeks. On February 11, 2021, he received one dose of nivolumab plus ipilimumab, per the CheckMate-067 protocol. He presented 14 days later with fever, diarrhea, pancytopenia, renal failure, drug-induced hepatitis, and myocarditis. The infectious workup was negative. His neutropenia responded to growth factors. He was diagnosed with interstitial nephritis due to immunotherapy and treated with corticosteroids. His symptoms resolved with concomitant improvement of his renal, hepatic, and cardiac function. He was discharged home in a stable condition. Although these specific immune-related adverse events (irAEs) are uncommon and rarely occur simultaneously, ICIs can trigger non-specific immune system activation, resulting in widespread inflammatory effects. Since irAEs can lead to multi-organ failure, as evidenced in this case, early recognition and institution of high-dose steroids are critical to preventing rapid deterioration. Given that ICI therapy is the standard of care for several cancers and is often studied in clinical trials, increased education on irAE toxicity and updated algorithms on the management of febrile cancer patients are warranted.
PubMed: 37575835
DOI: 10.7759/cureus.41781 -
Cureus Nov 2023Hematological disorders pose a diagnostic challenge due to overlapping clinical features, as demonstrated by the difficulty in differentiating between aplastic anemia...
Hematological disorders pose a diagnostic challenge due to overlapping clinical features, as demonstrated by the difficulty in differentiating between aplastic anemia (AA) and primary myelofibrosis (PM). Myeloproliferative disorders, characterized by aberrant proliferation of bone marrow stem cells, present complexities in diagnosis, often requiring a comprehensive evaluation to distinguish between disorders with similar manifestations. The distinctions between myelofibrosis and AA lie not only in clinical presentations but also in genetic and molecular markers, necessitating a nuanced diagnostic approach. We present a case of a 37-year-old male initially diagnosed with myelofibrosis based on a history of pancytopenia, warm submandibular and submental swelling, and negative BCR-ABL and JAK2 mutations. Further examination revealed empty fragmented cells, hypoplastic bone marrow, and suppressed erythropoiesis and myelopoiesis. Subsequent core biopsy showed increased megakaryocytes, prompting a revised diagnosis of AA. This case underscores the importance of a meticulous diagnostic journey, incorporating physical examination, genetic testing, and advanced imaging to unravel the complexities of hematological disorders. The intricacies of this case prompt a reevaluation of diagnostic paradigms, highlighting the limitations of relying solely on specific mutations for diagnosis. The absence of BCR-ABL and JAK2 mutations in AA raises questions about its genetic landscape, necessitating further exploration. Immunological considerations, given the immune-mediated nature of AA, provide a foundation for future research into immune dysregulation and potential therapeutic interventions. The clinical management challenges posed by AA underscore the need for personalized treatment strategies, guided by a deeper understanding of its underlying pathophysiology. Advanced imaging techniques, in conjunction with traditional diagnostic methods, emerge as crucial tools for enhancing diagnostic accuracy in hematological disorders. This case serves as a paradigm for ongoing medical education, multidisciplinary collaboration, and innovative approaches in the evolving landscape of hematology, emphasizing the imperative for continuous refinement in diagnostic strategies and patient care.
PubMed: 38149134
DOI: 10.7759/cureus.49445 -
Pathogens (Basel, Switzerland) Sep 2023Leishmaniasis is a vector-borne disease caused by protozoan parasites of the genus Leishmania and is transmitted through the bite of infected female sandflies. In the...
Leishmaniasis is a vector-borne disease caused by protozoan parasites of the genus Leishmania and is transmitted through the bite of infected female sandflies. In the Mediterranean region, visceral leishmaniasis is caused by and it is usually responsible for symptoms such as fever, pancytopenia and enlargement of the liver and spleen. Relapse is rare in immunocompetent patients as much as the mucous involvement. We present a rare case of mucosal relapse of visceral leishmaniasis in a child with SARS-CoV-2 infection and perform an extensive review of the literature about leishmaniasis relapses in children. Atypical mucosal involvement during Leishmaniasis relapse is an eventuality in pediatric patients. Clinical follow-up and periodic PCR tests must be considered essential for the early recognition and treatment of an eventual relapse.
PubMed: 37764934
DOI: 10.3390/pathogens12091127