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Medical Ultrasonography May 2024VEXAS syndrome is a recently described condition characterized by systemic inflammation, predisposition to hematologic malignancy and a high rate of venous thrombosis....
VEXAS syndrome is a recently described condition characterized by systemic inflammation, predisposition to hematologic malignancy and a high rate of venous thrombosis. Here we report the case of an elderly male with erythema nodosumlike lesions, ankle arthralgia, and general symptoms. B-mode and Doppler ultrasound of the subcutis diagnosed superficial thrombophlebitis of the lower limbs, which turned out to be the manifestation of a paucisymptomatic VEXAS syndrome. VEXAS should be considered in any patient who presents with unexplained superficial thrombophlebitis, macrocytic anemia and unexplained systemic inflammation.
PubMed: 38805617
DOI: 10.11152/mu-4384 -
Clinical Neurology and Neurosurgery Jul 2024VEXAS (Vacuoles, E1 Enzyme, X-linked, autoinflammatory, Somatic) syndrome is a recently described severe adult-onset autoinflammatory disorder mediated by X-linked gene...
INTRODUCTION
VEXAS (Vacuoles, E1 Enzyme, X-linked, autoinflammatory, Somatic) syndrome is a recently described severe adult-onset autoinflammatory disorder mediated by X-linked gene UBA1 somatic mutations, responsible of recurrent fever, skin involvement, chondritis, macrocytic anemia and inflammatory syndrome. Neurological manifestations are rarely described, and predominantly involve peripheral nervous system (PNS) impairment.
RESULTS
We report the first central nervous system (CNS) vasculitis in VEXAS syndrome, characterized by headache, cognitive dysfunction and focal signs (cerebellar ataxia). Magnetic resonance imaging (MRI) revealed multifocal white-matter lesions corresponding to recent ischemic strokes, combined with cortical hemorrhagic lesions and gadolinium enhancement of the distal wall vessels. Treatment with methylprednisone, ruxolitinib and tocilizumab led to clinical improvement and a decrease of the inflammatory syndrome. The patient died few months after due to infectious complications.
CONCLUSION
CNS vasculitis, occurring as a manifestation of the systemic auto-inflammatory state of VEXAS syndrome, might be a rare but severe complication. We suggest that it be added to the list of inflammatory vasculopathies. More prospective studies are needed to optimize the treatment.
Topics: Humans; Vasculitis, Central Nervous System; Male; Middle Aged; Magnetic Resonance Imaging; Fatal Outcome; Adult; Genetic Diseases, X-Linked; Ubiquitin-Activating Enzymes
PubMed: 38801808
DOI: 10.1016/j.clineuro.2024.108351 -
Veterinary Sciences May 2024Anemia is a well-known complication in CKD dogs, but its frequency in AKI dogs has been poorly investigated. The aim of the present study was to retrospectively evaluate...
Anemia is a well-known complication in CKD dogs, but its frequency in AKI dogs has been poorly investigated. The aim of the present study was to retrospectively evaluate frequency, degree of severity, and regeneration rate of anemia in relation to IRIS grade, etiology, therapy, and outcome. Medical records of dogs (2017-2023) with historical, laboratory, and ultrasound findings consistent with AKI were retrospectively reviewed. According to etiology, AKI was classified as ischemic/inflammatory (IS), infectious (INF), nephrotoxic (NEP), obstructive (OBS), and unknown (UK). AKI dogs were also classified according to therapeutical management (medical vs. hemodialysis), survival to discharge (survivors vs. non-survivors). Anemia was defined as HCT < 37% and classified as mild (HCT 30-37%), moderate (HCT 20-29%), severe (13-19%), or very severe (<13%). Anemia was classified as microcytic (MCV < 61 fL), normocytic (61 and 73 fL), and macrocytic (>73 fL). Anemia was considered hypochromic (MCHC< 32 g/dL), normochromic (32 and 38 g/dL), and hyperchromic (>38 g/dL). Regeneration rate was considered absent (RET ≤ 60,000/μL), mild 61,000-150,000/μL), and moderate (>150,000/μL). A total of 120 AKI dogs were included in the study, and anemia was found in 86/120 dogs (72%). The severity of anemia was mild in 32/86 dogs (37%), moderate in 40/86 dogs (47%), severe in 11/86 dogs (13%), and very severe in 3/86 (3%). Anemia was normochromic in 71/86 dogs (83%), hyperchromic in 12/86 dogs (14%), and hypochromic in 3/86 dogs (3%). Normocytic anemia was present in 56/86 dogs (65%), microcytic anemia in 27/86 dogs (31%), and macrocytic anemia in 3/86 dogs (4%). Non-regenerative anemia was found in 76/86 dogs (88%). The frequency of anemia increased significantly ( < 0.0001) with the progression of IRIS grade, although no significant difference in the severity of anemia was found among the IRIS grades. The frequency of non-regenerative forms of anemia was significantly higher than regenerative forms ( < 0.0001) in all IRIS grades. In our population of AKI dogs, anemia was a very frequent finding, in agreement with current findings in human nephrology.
PubMed: 38787184
DOI: 10.3390/vetsci11050212 -
The Gulf Journal of Oncology May 2024Polycythemia vera (PV) is a chronic myeloproliferative disorder characterized by uncontrolled red blood cell production. Megaloblastic anemia is caused by deficiency of...
Polycythemia vera (PV) is a chronic myeloproliferative disorder characterized by uncontrolled red blood cell production. Megaloblastic anemia is caused by deficiency of cobalamin (vitamin B12) and/or folate (vitamin B9). While B12 deficiency may be caused by insufficient dietary intake or impairment of its utilization, its association with PV is described without exact knowledge of the physiopathology. We herein report the occurrence of megaloblastic anemia due to Vitamin B12 deficiency in an 85-year-old North African woman patient with PV. This case highlights this atypical presentation of PV and challenges that comes with it causing the delay of diagnosis and the complexity of its diagnosis and treatment. Keywords: megaloblastic anemia, polycythemia vera, association, case report.
Topics: Humans; Anemia, Megaloblastic; Female; Polycythemia Vera; Aged, 80 and over; Vitamin B 12 Deficiency
PubMed: 38774937
DOI: No ID Found -
Cureus Apr 2024Biermer's disease (BD) or pernicious anemia (PA) is an autoimmune atrophic gastritis characterized by the absence of intrinsic factor (IF) secretion, leading to...
Biermer's disease (BD) or pernicious anemia (PA) is an autoimmune atrophic gastritis characterized by the absence of intrinsic factor (IF) secretion, leading to malabsorption of vitamin B12 in the ileum. Its clinical manifestations are primarily hematological, with neuropsychiatric and cardiovascular manifestations being less common. We present the case of a patient with PA diagnosed based on neurological and cardiovascular complications. The patient, a 56-year-old man with no specific medical history, presented with an episode of melena without other associated digestive symptoms. He also complained of memory and gait disturbances. Clinical examination revealed a cerebellar ataxia with impaired proprioceptive and vibratory sensitivity, and a swollen and red right lower limb with a positive Homan sign. The blood count showed macrocytic anemia. Gastroscopy revealed flattened fundic folds resembling a fundus appearance, and histopathological examination confirmed fundic atrophic gastritis with pseudopyloric metaplasia and lymphoplasmacytic infiltration. Anti-intrinsic factor antibodies were positive, while anti-parietal cell antibodies were negative. Vitamin B12 levels were severely low, and vitamin B9 levels were normal. TSH and HbA1c levels were within normal ranges. The abdominal CT scan showed no abnormalities. Lower limb Doppler ultrasound confirmed the diagnosis of deep vein thrombosis (DVT). Cardiac evaluation revealed sinus bradycardia suggestive of secondary dysautonomia. Therapeutically, the patient was started on vitamin B12 supplementation and anticoagulant therapy for DVT, resulting in a good clinical and biological outcome.
PubMed: 38765343
DOI: 10.7759/cureus.58601 -
The National Medical Journal of India 2023We report a 26-year-old girl who was diagnosed with diabetes mellitus in her childhood and was treated with insulin. With a history of visual disturbances during her...
We report a 26-year-old girl who was diagnosed with diabetes mellitus in her childhood and was treated with insulin. With a history of visual disturbances during her childhood and anaemia, which was partially evaluated; the possibility of syndromic diabetes was considered. Genetic analysis was done and revealed a mutation in the SLC19A2 gene, confirming the diagnosis of thiamine-responsive megaloblastic anaemia. She was supplemented with thiamine, which dramatically improved her haemoglobin levels and glucose control. However, her vision could not be salvaged as the rod-cone dystrophy is a permanent damage.
Topics: Humans; Female; Anemia, Megaloblastic; Adult; Thiamine; Thiamine Deficiency; Membrane Transport Proteins; Mutation; Vitamin B Complex; Diabetes Mellitus; Hearing Loss, Sensorineural
PubMed: 38759983
DOI: 10.25259/NMJI_20_21 -
BMC Cancer May 2024Observational study investigated the association between pernicious anemia (PA) and cancers. However, with the exception of gastric cancer, the results are mostly...
BACKGROUND
Observational study investigated the association between pernicious anemia (PA) and cancers. However, with the exception of gastric cancer, the results are mostly contradictory. The purpose of this study was to investigate the potential causal relationship between PA and cancers through bidirectional two-sample Mendelian randomized (MR) analysis.
METHODS
The European sample FinnGen project provided the genetic summary data for PA and 20 site-specific cancers. This bidirectional two-sample MR design mainly used the inverse variance weighting (IVW) method to evaluate the causal relationship between PA and cancer risk. Benjamini-Hochberg correction was performed to reduce the bias caused by multiple tests.
RESULTS
Our study shows that there was a causal relationship between PA and gastric cancer, prostate cancer, testicular cancer and malignant melanoma of skin, and there was a reverse causal relationship between prostate cancer or gastric cancer and PA (P < 0.05). After Benjamini-Hochberg correction test, there was still a causal correlation between PA and gastric or prostate cancer (P' < 0.05), while there was only an implied causal association between PA and testicular cancer and malignant melanoma of skin (P'> 0.05). There was still a reverse causal relationship between gastric cancer and PA (P'< 0.05), while prostate cancer shows an implied reverse causal relationship(P'> 0.05). In addition, MR-Egger and MR-PRESSO tests showed no significant horizontal pleiotropy.
CONCLUSIONS
PA may be genetically associated with testicular cancer, prostate cancer, gastric cancer, and malignant melanoma of skin.
Topics: Humans; Mendelian Randomization Analysis; Anemia, Pernicious; Male; Stomach Neoplasms; Neoplasms; Testicular Neoplasms; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Prostatic Neoplasms; Female
PubMed: 38741062
DOI: 10.1186/s12885-024-12354-y -
Clinical Nutrition (Edinburgh, Scotland) Jun 2024
Topics: Humans; Anemia, Pernicious; Dietary Supplements; Anemia, Iron-Deficiency; Iron; Iron Deficiencies; Female; Male
PubMed: 38677043
DOI: 10.1016/j.clnu.2024.04.025 -
American Journal of Hematology Apr 2024Congenital Dyserythropoietic Anemia type I (CDA I) is a rare hereditary condition characterized by macrocytic/normocytic anemia, splenomegaly, iron overload, and...
Congenital Dyserythropoietic Anemia type I (CDA I) is a rare hereditary condition characterized by macrocytic/normocytic anemia, splenomegaly, iron overload, and distinct abnormalities during late erythropoiesis, particularly internuclear bridges between erythroblasts. Diagnosis of CDA I remains challenging due to its rarity, clinical heterogeneity, and overlapping phenotype with other rare hereditary anemias. In this case series, we present 36 patients with suspected CDA I. A molecular diagnosis was successfully established in 89% of cases, identifying 16 patients with CDA I through the presence of 18 causative variants in the CDAN1 or CDIN1 genes. Transcriptomic analysis of CDIN1 variants revealed impaired erythroid differentiation and disruptions in transcription, cell proliferation, and histone regulation. Conversely, 16 individuals received a different diagnosis, primarily pyruvate kinase deficiency. Comparisons between CDA I and non-CDA I patients revealed no significant differences in erythroblast morphological features. However, hemoglobin levels and red blood cell count differed between the two groups, with non-CDA I subjects being more severely affected. Notably, most patients with severe anemia belonged to the non-CDA I group (82% non-CDA I vs. 18% CDA I), with a subsequent absolute prevalence of transfusion dependency among non-CDA I patients (100% vs. 41.7%). All patients exhibited reduced bone marrow responsiveness to anemia, with a more pronounced effect observed in non-CDA I patients. Erythropoietin levels were significantly higher in non-CDA I patients compared to CDA I patients. However, evaluations of erythroferrone, soluble transferrin receptor, and hepcidin revealed no significant differences in plasma concentration between the two groups.
PubMed: 38666530
DOI: 10.1002/ajh.27350 -
EMBO Reports May 2024Microcephaly is a common feature in inherited bone marrow failure syndromes, prompting investigations into shared pathways between neurogenesis and hematopoiesis. To...
Microcephaly is a common feature in inherited bone marrow failure syndromes, prompting investigations into shared pathways between neurogenesis and hematopoiesis. To understand this association, we studied the role of the microcephaly gene Mcph1 in hematological development. Our research revealed that Mcph1-knockout mice exhibited congenital macrocytic anemia due to impaired terminal erythroid differentiation during fetal development. Anemia's cause is a failure to complete cell division, evident from tetraploid erythroid progenitors with DNA content exceeding 4n. Gene expression profiling demonstrated activation of the p53 pathway in Mcph1-deficient erythroid precursors, leading to overexpression of Cdkn1a/p21, a major mediator of p53-dependent cell cycle arrest. Surprisingly, fetal brain analysis revealed hypertrophied binucleated neuroprogenitors overexpressing p21 in Mcph1-knockout mice, indicating a shared pathophysiological mechanism underlying both erythroid and neurological defects. However, inactivating p53 in Mcph1 mice failed to reverse anemia and microcephaly, suggesting that p53 activation in Mcph1-deficient cells resulted from their proliferation defect rather than causing it. These findings shed new light on Mcph1's function in fetal hematopoietic development, emphasizing the impact of disrupted cell division on neurogenesis and erythropoiesis - a common limiting pathway.
Topics: Animals; Erythropoiesis; Microcephaly; Mice; Mice, Knockout; Cell Cycle Proteins; Tumor Suppressor Protein p53; Cyclin-Dependent Kinase Inhibitor p21; Cytoskeletal Proteins; Mutation; Anemia, Macrocytic; Cell Differentiation; Erythroid Precursor Cells
PubMed: 38605277
DOI: 10.1038/s44319-024-00123-8