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Annals of the Rheumatic Diseases Dec 2023The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic variants.
BACKGROUND
The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic variants.
OBJECTIVES
To investigate the presence of VEXAS syndrome among patients with adult-onset undiagnosed AID. Additional studies evaluated the mosaicism distribution and the circulating cytokines.
METHODS
Gene analyses were performed by both Sanger and amplicon-based deep sequencing. Patients' data were collected from their medical charts. Cytokines were quantified by Luminex.
RESULTS
Genetic analyses of enrolled patients (n=42) identified 30 patients carrying pathogenic variants, with frequencies compatible for postzygotic variants. All patients were male individuals who presented with a late-onset disease (mean 67.5 years; median 67.0 years) characterised by cutaneous lesions (90%), fever (66.7%), pulmonary manifestations (66.7%) and arthritis (53.3%). Macrocytic anaemia and increased erythrocyte sedimentation rate and ferritin were the most relevant analytical abnormalities. Glucocorticoids ameliorated the inflammatory manifestations, but most patients became glucocorticoid-dependent. Positive responses were obtained when targeting the haematopoietic component of the disease with either decitabine or allogeneic haematopoietic stem cell transplantation. Additional analyses detected the variants in both haematopoietic and non-haematopoietic tissues. Finally, analysis of circulating cytokines did not identify inflammatory mediators of the disease.
CONCLUSION
Thirty patients with adult-onset AID were definitively diagnosed with VEXAS syndrome through genetic analyses. Despite minor interindividual differences, their main characteristics were in concordance with previous reports. We detected for the first time the mosaicism in non-haematopoietic tissue, which questions the previous concept of myeloid-restricted mosaicism and may have conceptual consequences for the disease mechanisms.
Topics: Adult; Humans; Male; Female; Mosaicism; Arthritis; Cytokines; Ferritins; Glucocorticoids; Mutation
PubMed: 37666646
DOI: 10.1136/ard-2023-224460 -
Cureus Aug 2023While macrocytic anemia is common in vitamin B12 deficiency, rarely, pancytopenia and hemolytic anemia can occur. Homocysteine levels are elevated in severe B12...
While macrocytic anemia is common in vitamin B12 deficiency, rarely, pancytopenia and hemolytic anemia can occur. Homocysteine levels are elevated in severe B12 deficiency, and this is linked to thrombus formation with potentially life-threatening complications. We present a patient with severe vitamin B12 deficiency complicated by hyperhomocysteinemia and obstructive shock from pulmonary embolism. A 56-year-old male with no medical history presented to the hospital with altered mentation. The patient's family stated he was experiencing bilateral paresthesias of his lower extremities, progressive depression, anxiety, and insomnia. Initial vitals were blood pressure of 76/36, heart rate of 70 beats per minute, respiratory rate of 14, and temperature of 36.3 degrees Celsius. He was intubated due to severe encephalopathy. Relevant labs indicated severe macrocytic anemia, thrombocytopenia, decreased B12 levels, elevated methylmalonic acid, and elevated homocysteine. Imaging demonstrated a right common femoral vein thrombosis and subsegmental pulmonary emboli. Peripheral blood smear revealed schistocytes, anisopoikilocytosis, and decreased platelet count. The patient required fluid resuscitation, antibiotics, and multiple blood products. Vitamin B12 was administered intramuscularly, which improved the anemia. Esophagogastroduodenoscopy (EGD) demonstrated gastritis. Gastric and duodenal biopsies were negative for and celiac disease. He was negative for intrinsic factor (IF) antibodies but had elevated gastrin levels. An intravenous unfractionated heparin infusion was started when the platelet count was above 50000. The patient was extubated after seven days. Heparin was transitioned to apixaban and an inferior vena cava (IVC) filter was placed. Hyperhomocysteinemia is a known pro-thrombotic factor that can lead to the development of venous thromboembolism. B12 malabsorption can stem from inflammatory bowel disease, celiac disease, gastritis, pancreatic insufficiency, gastrectomy, gastric bypass surgery, or antibodies to IF. While this case showed gastritis and negative IF antibodies, gastrin levels were elevated, indicating a mixed picture. This highlights the challenge of definitively diagnosing pernicious anemia as the cause of vitamin B12 deficiency. Vitamin B12 deficiency may lead to critical illness in which thromboembolism develops secondary to hyperhomocysteinemia.
PubMed: 37664295
DOI: 10.7759/cureus.42908 -
The Pan African Medical Journal 2023pernicious anemia is an autoimmune disease characterized by atrophic gastritis due to malabsorption of vitamin B12. Certain oral manifestations, such as Hunter´s...
INTRODUCTION
pernicious anemia is an autoimmune disease characterized by atrophic gastritis due to malabsorption of vitamin B12. Certain oral manifestations, such as Hunter´s glossitis and burning mouth syndrome, may precede the onset of this anemia. The aim of this study is to describe the clinical presentation, para-clinical aspects, the treatment, and the evolution of the pernicious anemia (PA) after treatment.
METHODS
retrospective study conducted at the Department of Haematology and Internal Medicine B of the Mohammed V Military Training Hospital in Rabat between January 2009 and December 2018. Thirty-four patients were enrolled with vitamin B12 deficiency, non-regenerative macrocytic anemia, a positive anti-intrinsic factor antibody and anti-parietal cell antibody and a histological diagnosis of atrophic gastritis in the presence or not of Helicobacter pylori. The qualitative variables were expressed in numbers and percentages, and the quantitative variables in mean and standard deviation. Multivariate analysis used the Fischer test; it was considered significant for a p < 0.05 value.
RESULTS
thirty-four cases were studied; the population study consists of 56% (n=19) of men and 44% (n=15) of women. The average age was 54.88± 9.14. The clinical manifestations of pernicious anemia are dominated by megaloblastic anemia 85.3% (n=29), followed by digestive 58.8%(n=20) and oral 55.9% (n=19) signs. Neurological manifestations were rarely found in 41% (n=14). Hunter´s glossitis 37% (n=7), stomatodynia 11% (n=2) were the most common oral manifestations accompanying pernicious anemia. The evolution was favorable in 79.4% (n=27) patients under substitution therapy with vitamin B12.
CONCLUSION
dentists´ involvement in the diagnosis of pernicious anemia is based on changes in oral mucous membranes, which have been reported in 55.9% of all patients. These oral changes may occur in the absence of symptomatic anemia.
Topics: Male; Humans; Female; Middle Aged; Anemia, Pernicious; Retrospective Studies; Cross-Sectional Studies; Morocco; Gastritis, Atrophic; Military Personnel; Vitamin B 12; Autoantibodies; Glossitis; Hospitals
PubMed: 37663641
DOI: 10.11604/pamj.2023.45.79.34204 -
Colombia Medica (Cali, Colombia) 2023Megaloblastic anemias secondary to Vitamin B12 deficiency are a group of pathologies produced by defective nuclear DNA synthesis.
INTRODUCTION
Megaloblastic anemias secondary to Vitamin B12 deficiency are a group of pathologies produced by defective nuclear DNA synthesis.
OBJECTIVE
To describe the maturation alterations found in hematopoietic precursors of the bone marrow in a series of patients with megaloblastic anemia.
METHODS
Were included patients attended at the Regional Hospital of Concepción with bone marrow samples sent for the study of cytopenia by flow cytometry whose final diagnosis was megaloblastic anemia. The immunophenotype was performed with CD45, CD34, CD117, HLA-DR, markers of neutrophil (CD13, CD11b, CD10, CD16) and/or erythroblast (CD105, CD71, CD36) maturation.
RESULTS
From the flow cytometry laboratory database, 8 patients with megaloblastic anemia were identified, and myelodysplastic syndromes (n=9) and normal or reactive bone marrow (n=10) were used as controls. 44% were men, with a median age of 58 years. Megaloblastic anemia was associated with a higher proportion of size and complexity of erythroid and myeloid progenitors compared to lymphocytes compared to controls. The total percentage of erythroblasts and the proportion of CD34+ myeloid cells associated with erythroid lineage was higher in megaloblastic anemia, associated with a maturation arrest in the CD105+ precursor stage (69% vs 19% and 23%, <0.001). The heterogeneity of CD36 and CD71 in megaloblastic anemia was similar to myelodysplastic syndromes.
CONCLUSIONS
Megaloblastic anemia produces a heterogeneous involvement of hematopoiesis, characterized by a greater size and cellular complexity of precursors of the neutrophil and erythroid series and a maturation arrest of the erythroblasts.
Topics: Male; Humans; Middle Aged; Female; Flow Cytometry; Anemia, Megaloblastic; Vitamin B 12 Deficiency; Vitamin B 12
PubMed: 37649984
DOI: 10.25100/cm.v54i2.5494 -
Gastroenterology Dec 2023
Topics: Humans; Stomach; Anemia; Upper Gastrointestinal Tract; Abdomen; Anemia, Pernicious; Stomach Neoplasms
PubMed: 37640254
DOI: 10.1053/j.gastro.2023.08.032 -
Leukemia Research Reports 2023Transient abnormal myelopoiesis (TAM) is a transient, clonal myeloproliferative disorder unique to Down Syndrome (DS) babies. It is characterized by increased peripheral...
INTRODUCTION
Transient abnormal myelopoiesis (TAM) is a transient, clonal myeloproliferative disorder unique to Down Syndrome (DS) babies. It is characterized by increased peripheral blasts and presence of mutation. The clinical spectrum ranges from jaundice and hepatosplenomegaly to multi-organ failure and death. Here we present a case of a premature baby with DS diagnosed to have TAM with extramedullary involvement at birth who had a fatal outcome.
CASE REPORT
A 30.3-week-old female fetus with DS had leukocytosis (WBC: 187.82 K/uL) with neutrophilia (ANC 27.65 K/uL), macrocytic anemia (RBC: 2.41 m/uL, Hb 8.8 g/dL, MCV 108.3, MCH 36.5, MCHC 33.7) and thrombocytosis (platelet count 361 K/uL) at birth. Liver panels demonstrated normal bilirubin levels with elevated liver enzymes (AST = 239 U/L, ALT = 216 U/L).
RESULTS
Peripheral smear showed marked leukocytosis with increased blasts (70%), nucleated RBCs, giant platelets, and megakaryocytic elements. Flow cytometry demonstrated two populations of cells: 20% myeloblasts and 26% dim CD45 CD34- cells. mutation was present. Based on these findings a diagnosis of TAM with extramedullary hematopoiesis was made. She received two cycles of cytarabine chemotherapy. Though her WBC levels reached a low of 18.93 K/uL, she developed multi-organ failure, eventually leading to death on day 45.
DISCUSSION
TAM is a transient condition resulting in disease resolution in around 80% of cases. Death is reported in 10% of cases. Risk factors associated with early death include prematurity, hyperleukocytosis, elevated bilirubin levels. Management of high-risk babies with chemotherapy is recommended to improve survival.
PubMed: 37560406
DOI: 10.1016/j.lrr.2023.100381 -
Cureus Jul 2023A 62-year-old male patient presented with malaise and severe macrocytic anemia. Computed tomography revealed an osteolytic lesion in the left iliac bone. Bone marrow...
A 62-year-old male patient presented with malaise and severe macrocytic anemia. Computed tomography revealed an osteolytic lesion in the left iliac bone. Bone marrow examination revealed that 90% of erythroblasts were large with periodic acid-Schiff (PAS)-positive staining while flow cytometry and immunostaining revealed CD71 (+), GP-A (+), p53 (+), CD117 (+), and CD34 (-) results, indicating pure erythroid leukemia (PEL) diagnosis. A needle biopsy of the osteolytic lesion revealed the same characteristics as PEL. Azacitidine therapy was administered as the first-line treatment, and his general condition temporarily improved. However, PEL quickly deteriorated, and he died 42 days of hospitalization after initial admission. PEL is an extremely rare form of acute myeloid leukemia (AML) and has presented cytogenetic characteristics in addition to the TP53 mutation. Other AML treatment is used because a standard treatment method is unavailable. However, the prognosis is extremely poor. Furthermore, few cases of concurrent bone lesions are reported globally, and more cases must be accumulated and analyzed.
PubMed: 37559863
DOI: 10.7759/cureus.41581 -
Journal of Medical Case Reports Jul 2023Type 1 diabetes mellitus (T1DM) is a lifelong diagnosis that involves immune-mediated damage of pancreatic beta cells and subsequent hyperglycemia, manifesting as:...
BACKGROUND
Type 1 diabetes mellitus (T1DM) is a lifelong diagnosis that involves immune-mediated damage of pancreatic beta cells and subsequent hyperglycemia, manifesting as: polyuria, polydipsia, polyphagia, and weight loss. Treatment of type 1 diabetes centers on insulin administration to replace or supplement the body's own insulin with the goal of achieving euglycemia and preventing or minimizing complications. Patients with T1DM are at risk for developing other autoimmune conditions, most commonly thyroid or celiac disease.
CASE PRESENTATION
A 20-year-old African American female with T1DM was referred by her endocrinologist to pediatric gastroenterology for 2 months of nocturnal, non-bloody diarrhea, left lower quadrant pain, and nausea; she was also being followed by neurology for complaints of lower extremity paresthesias and pain. The patient's initial lab-workup was remarkable for a low total Immunoglobulin A (IgA) level of < 6.7 mg/dL. As IgA deficiency is associated with an increased risk of celiac disease, the patient underwent upper and lower endoscopy, which was grossly unremarkable; however, histology revealed a pattern consistent with autoimmune gastritis. Subsequent serum evaluation was remarkable for an elevated fasting gastrin level and an elevated parietal cell antibody level without macrocytic anemia, iron deficiency, or vitamin B12 depletion. The patient was diagnosed with autoimmune gastritis (AIG) and subsequently initiated on parenteral B12 supplementation therapy with improvement in her neurologic and gastrointestinal symptoms.
CONCLUSION
This case illustrates the importance of recognition of red flag findings in a patient with known autoimmune disease. Following well-established health maintenance recommendations for individuals with T1DM ensures that common comorbidities will be detected. Autoimmune gastritis, while a rarer pathology in the pediatric population, deserves consideration in patients with pre-existing autoimmune conditions and new gastrointestinal or neurologic symptoms, as AIG can be associated with poor outcomes and risk of malignancy. Initial lab findings associated with an eventual diagnosis of AIG typically include anemia, iron deficiency, or Vitamin B12 deficiency. However, as demonstrated in this case, symptoms of AIG can rarely present before anemia or Vitamin B12 deficiency develops. To prevent permanent neurological damage, parenteral Vitamin B12 therapy must be considered even in the absence of Vitamin B12 deficiency, especially in those patients already experiencing neurological symptoms.
Topics: Humans; Child; Female; Young Adult; Adult; Diabetes Mellitus, Type 1; Anemia, Iron-Deficiency; Celiac Disease; Gastritis; Autoimmune Diseases; Vitamin B 12 Deficiency; Vitamin B 12; Diarrhea; Pain; Insulins
PubMed: 37507704
DOI: 10.1186/s13256-023-04039-0 -
Medicine Jul 2023Anemia is the most common dose-limiting toxicity of olaparib. However, few studies have analyzed the clinical features of olaparib-induced anemia. This study...
Anemia is the most common dose-limiting toxicity of olaparib. However, few studies have analyzed the clinical features of olaparib-induced anemia. This study investigated the clinical features of olaparib-induced anemia. Additionally, the role of folate or vitamin B12 in olaparib-induced anemia was examined. This retrospective case-control study included patients who received olaparib at Mie University Hospital between January 2018 and December 2020. Data were collected between initiation of olaparib and discontinuation of olaparib or till December 2021. We investigated the development of grade ≥ 3 anemia during olaparib administration for at least 1 year. We examined patients with grade ≥ 3 anemia considering the mean corpuscular volume (MCV), its association with gastrointestinal events and cumulative dose of carboplatin. For the sub-study analysis, data on patients treated with olaparib for ovarian or endometrial cancer were collected to evaluate the Common Terminology Criteria for Adverse Events (CTCAE) or monthly changes in folate or vitamin B12 levels from baseline to 3 months after olaparib initiation. These data were collected between initiation of olaparib and discontinuation of olaparib or till November 2022. Patients with no data on folic acid or vitamin B12 levels were excluded from the sub-study. In the main study, 40 patients were included. Eighteen patients (45%) developed grade ≥ 3 anemia, and all patients discontinued treatment (94%) or reduced olaparib dose (67%) after developing anemia. Among the patients with grade ≥ 3 anemia, 9 (50%) exhibited macrocytic anemia and 15 (83%) had previously received carboplatin. The incidence of grade ≥ 2 dysgeusia was significantly higher in patients with grade ≥ 3 anemia (P = .034). Moreover, the cumulative dose of previously administered carboplatin was higher in patients who had 3 episodes of anemia (P = .102). In sub-study, 12 had data on folic acid and vitamin B12 levels. Sub-study analysis showed that none fulfilled the criteria for deficiency of folate or vitamin B12, while 3 developed grade 3 anemia. This study revealed that olaparib-induced anemia frequently occurs as macrocytic and normocytic erythroblastic anemia without folate or vitamin B12 deficiencies. A high cumulative dose of previously administered carboplatin and dysgeusia may be associated with olaparib-induced anemia.
Topics: Humans; Case-Control Studies; Retrospective Studies; Carboplatin; Dysgeusia; Hemoglobins; Folic Acid Deficiency; Anemia; Folic Acid; Vitamin B 12; Vitamin B 12 Deficiency
PubMed: 37505180
DOI: 10.1097/MD.0000000000034123