[VEXAS gene variants explain previously unrecognized clinical syndrome].

This review aims to make clinicians aware of the newly described syndrome, VEXAS. VEXAS should become an obvious differential diagnosis in cases of unexplained inflammation, anemia, and rheumatological and/or hematological manifestations. Patients with VEXAS are typically male aged > 60, with inflammation, and macrocytic anaemia. On suspicion of cancer or infections patients have frequently been exposed to extensive diagnostic procedures and hospital admissions. In this review, we summarise the current knowledge of VEXAS regarding pathogenesis, symptoms, diagnosis, and treatment.

Hyperregenerative macrocytic anaemia: the role of copper and zinc.

In a patient with a history of bariatric surgery, severe copper deficiency presenting with macrocytic hyperregenerative anaemia was diagnosed. Besides the impaired intestinal absorption due to a short bowel syndrome, the enteral zinc supplementation competitively decreased the intestinal copper uptake. Once the zinc supplementation was stopped, enteral copper replacement ensued and normalised haemoglobin levels with decreasing median corpuscular volume were observed during follow-up visits.

Cecal Malakoplakia - an Unusual Cause of Anemia in Liver Cirrhosis.

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Macrocytic anemia in Lesch-Nyhan disease and its variants.

PURPOSE: Lesch-Nyhan disease is an inherited metabolic disorder characterized by overproduction of uric acid and neurobehavioral abnormalities. The purpose of this study was  to describe macrocytic erythrocytes as another common aspect of the phenotype. METHODS: The results of 257 complete blood counts from 65 patients over a 23-year period were collected from 2 reference centers where many patients are seen regularly. RESULTS: Macrocytic erythrocytes occurred in 81-92% of subjects with Lesch-Nyhan disease or its neurological variants. After excluding cases with iron deficiency because it might pseudonormalize erythrocyte volumes, macrocytosis occurred in 97% of subjects. Macrocytic erythrocytes were sometimes accompanied by mild anemia, and rarely by severe anemia. CONCLUSION: These results establish macrocytic erythrocytes as a very common aspect of the clinical phenotype of Lesch-Nyhan disease and its neurological variants. Macrocytosis is so characteristic that its absence should prompt suspicion of a secondary process, such as iron deficiency. Because macrocytosis is uncommon in unaffected children, it can also be used as a clue for early diagnosis in children with neurodevelopmental delay. Better recognition of this characteristic feature of the disorder will also help to prevent unnecessary diagnostic testing and unnecessary attempts to treat it with folate or B12 supplements.

Psychomotor regression due to vitamin B12 deficiency.

A vitamin B12 deficiency in infants is rare, but may sometimes be seen in breastfed babies of strict vegetarian mothers. Vitamin B12, also known as cobalamin, is only found in meat and other animal products. Most babies have a sufficient supply as long as the mother was not deficient herself. Symptoms and signs of vitamin B12 deficiency appear between the ages of 2 to 12 months and include vomiting, lethargy, failure to thrive, hypotonia, and arrest or regression of developmental skills. Urinary concentrations of methylmalonic acid and homocystine are characteristically elevated in vitamin B12 deficiency. Early treatment for a vitamin B12 deficiency in an infant involves immediate administration of vitamin B12 to the baby and the breastfeeding mother. The infant and mother will each receive an injection of vitamin B12 containing 1,000 mcg or more of the vitamin, and the mother will continue to receive injections every month to raise her own stores. After the initial injection, the baby will often receive future vitamin B12 through food sources. We present a case of vitamin B12 deficiency in a 9-month-old girl presented with psychomotor regression, hypotonia and lethargy. The child was exclusively breast-fed from birth by a mother who was on strict vegetarian diet and belong to a low socio-economic status. Laboratory data revealed bicytopenia with macrocytic anemia and methylmalonic acid in the urine, consistent with vitamin B12 deficient anemia. The Brain CT revealed a cerebral atrophy and delayed myelination. Vitamin B12 supply was effective on anaemia and psychomotor delay. This case figures out the importance of an early diagnosis in front of psychomoteur regression and hypotonia, given the risk of incomplete neurologic recovery due to vitamin B12 deficiency mainly in the setting of maternal nutritional deficiency.

Foot-strike haemolysis in an ultramarathon runner.

This case report describes mild anaemia and intravascular haemolysis in an otherwise healthy 41-year-old ultramarathon runner. In long-distance endurance athletes, trace gastrointestinal bleeding and plasma volume expansion are recognised sources of mild anaemia, often found incidentally. However, repetitive forceful foot striking can lead to blood cell lysis in the feet, resulting in a mild macrocytic anaemia and intravascular haemolysis, as was demonstrated in the patient described herein. Mild anaemia in runners, often called 'runner's pseudoanaemia', is typically clinically insignificant and does not require intervention. However, an unexplained anaemia can cause undue worry for otherwise healthy patients and lead to costly further testing, providing an argument against routine testing with complete blood counts in healthy, asymptomatic patients.

Copper deficiency caused by excessive alcohol consumption.

Copper deficiency is a disease that causes cytopaenia and neuropathy and can be treated by copper supplementation. Long-term tube feeding, long-term total parenteral nutrition, intestinal resection and ingestion of zinc are known copper deficiency risk factors; however, alcohol abuse is not. In this case, a 71-year-old man had difficulty waking. He had a history of drinking more than five glasses of spirits daily. He was well until 3 months ago. A month before his visit to our hospital, he could not eat meals but continued drinking. He had macrocytic anaemia on admission. Copper and ceruloplasmin levels were markedly low, and we diagnosed copper deficiency. There were no other known risk factors for copper deficiency. After he began drinking cocoa as a copper supplement, the anaemia ameliorated and he was able to walk. This is the first report showing alcohol abuse as a risk factor for copper deficiency.

[Macrocytosis of red blood cells and early arthritis positive for rheumatoid factor such as initial manifestations of a neuroendocrine gastrin-secreting gastric tumor.] / Macrocitosi emaziale ed early arthritis positiva per fattore reumatoide quali manifestazioni di presentazione di un tumore neuroendocrino gastrico gastrina-secernente.

Neuroendocrine tumors (NETs) represent uncommon tumors arising from the excessive proliferation of enterochromaffin-like (ECL) cells (so-called Kulchitsky cell). Gastric NETs (GNET) represent less than 2% of all NETs and less than 1% of all stomach neoplasms. In particular, gastric NETs type 1 (associated to chronic atrophic gastritis and hypergastrinaemia) is the more frequent one, accounting for 70-80% of all GNET. A macrocytic anemia is a frequent manifestation of GNET type 1. The possibility that macrocytic anemia appear during therapy with methotrexate (MTX) is widely documented. Similarly, MTX can determine gastric atrophy. We describe the case of a patient with rheumatoid factor-positive early arthritis (EA) in which the appearance of macrocytic anemia during treatment with MTX led to the recognition of a GNET type 1, until then asymptomatic. The endoscopic eradication of polypoid formations forming the GNET, the immediate suspension of MTX and therapy with octreotide long-action determined the complete remission of arthritis. This remission is maintained until today. According to our knowledge, the possibility that an EA may represent a paraneoplastic manifestation of GNET has never been described.

Clinically distinct presentations of copper deficiency myeloneuropathy and cytopenias in a patient using excessive zinc-containing denture adhesive.

OBJECTIVES: While copper deficiency has long been known to cause cytopenias, copper deficiency myeloneuropathy is a more recently described entity. Here, we present the case of two clinically distinct presentations of acquired copper deficiency syndromes secondary to excessive use of zinc-containing denture adhesive over five years: myeloneuropathy and severe macrocytic anemia and neutropenia. METHODS: Extensive laboratory testing and histologic evaluation of the liver and bone marrow, were necessary to rule out other disease processes and establish the diagnosis of copper deficiency. RESULTS: The initial presentation consisted of a myelopathy involving the posterior columns. Serum and urine copper were significantly decreased, and serum zinc was elevated. On second presentation (five years later), multiple hematological abnormalities were detected. Serum copper was again decreased, while serum zinc was elevated. CONCLUSIONS: Zinc overload is a preventable cause of copper deficiency syndromes. This rare entity presented herein highlights the importance of patient, as well as provider, education.

5q- syndrome-like features as the first manifestation of myelodysplastic syndrome in a patient with an unbalanced whole-arm translocation der(5;19)(p10;q10).

Derivative (5;19)(p10;q10) [der(5;19)(p10;q10)] is a rare chromosomal abnormality in myelodysplastic syndrome (MDS), and is genetically similar to deletion 5q [del(5q)]. However, MDS with der(5;19)(p10;q10) and 5q- syndrome are generally characterized as distinct subtypes. Here, we report a case of a patient with 5q- syndrome-like features as the first manifestation of MDS with der(5; 19)(p10;q10). A 59-year-old woman was admitted to our hospital for anemia without leukopenia and thrombocytopenia. She had received chemotherapy comprising carboplatin and docetaxel for endometrial cancer eight years before. Bone marrow aspirate (BM) revealed low blast counts with trilineage dysplastic cells, and fluorescent in situ hybridization revealed the loss of colony-stimulating factor 1 receptor (CSF1R) signals at 5q33-34. Although the initial manifestation was 5q- syndrome, G-banded metaphase analysis and spectral karyotyping analysis revealed der(5;19)(p10;q10). Consequently, a diagnosis of therapy-related MDS (t-MDS) was made. She failed to respond to azacitidine and lenalidomide therapy. Consequently, transfusion-dependent anemia and thrombocytopenia developed with increasing myeloblasts. Cytarabine, aclarubicin, and granulocyte colony-stimulating factor therapy also failed, and unfortunately the patient died. Thus, MDS with der(5;19)(p10;q10) may represent a platinum agent-related t-MDS that is highly resistant to chemotherapy.

Prevalence of potential underlying aetiology of macrocytic anaemia in Dutch general practice.

BACKGROUND: Macrocytic anaemia (MCV ≥ 100 fL) is a relatively common finding in general practice. However, literature on the prevalence of the different causes in this population is limited. The prevalence of macrocytic anaemia and its underlying aetiology were analysed in a general practice population. The potential effect of the different aetiology on survival was also evaluated. METHODS: Between the 1st of February 2007 and the 1st of February 2015, patients aged 50 years or older and presenting to their general practitioner with a newly diagnosed anaemia, were included in the study. Anaemia was defined as haemoglobin level below 13.7 g/dL in men and below 12.1 g/dL in women. A broad range of laboratory tests was performed for each patient. The causes of anaemia were consequently determined by two independent observers based on the laboratory results. RESULTS: Of the 3324 included patients, 249 (7.5 %) displayed a macrocytic anaemia and were subsequently analysed. An underlying explanation could be established in 204 patients (81.9 %) with 27 patients (13.2 %) displaying multiple causes. Classic aetiology (i.e. alcohol abuse, vitamin B12/folic acid deficiency, haemolysis and possible bone marrow disease) was found in 115 patients. Alternative causes (i.e. anaemia of chronic disease, iron deficiency, renal anaemia and other causes) were encountered in 101 patients. In addition, a notable finding was the median gamma GT of 277 U/L in patients diagnosed with alcohol abuse (N = 24, IQR 118.0-925.5) and 23 U/L in the remaining cohort (N = 138, IQR 14.0-61.0). The distribution of gamma GT values was statistically different (P < 0.001). Five year survival rates were determined for six categories of causes, ranging from 39.9 % (95 % CI 12.9-66.9) for renal anaemia to 76.2 % (95 % CI 49.4-103.0) for the category multiple causes. CONCLUSION: In addition to classic explanations for macrocytosis, alternative causes are frequently encountered in patients with macrocytic anaemia in general practice.

Causes of macrocytic anemia among 628 patients: mean corpuscular volumes of 114 and 130 fL as critical markers for categorization.

There have been no studies on the distribution of causes of macrocytic anemia with respect to mean corpuscular volume (MCV) cutoff values. We retrospectively investigated the causes of macrocytic anemia (MCV ≥100 fL) among 628 patients who visited the outpatient hematology clinic in Tohoku University Hospital. To ensure data validity, we also analyzed data from 307 patients in eight other hospitals in the Tohoku district. The leading causes of macrocytic anemia (number of patients, %) were myelodysplastic syndromes (121, 19.3 %), suspected bone marrow failure syndromes (BMF; 74, 11.8 %), aplastic anemia (51, 8.1 %), plasma cell dyscrasia (45, 7.2 %), and vitamin B12 deficiency (40, 6.4 %) in Tohoku University Hospital. We made three primary findings as follows. First, the most common cause of macrocytic anemia is BMF. Second, lymphoid and solid malignancies are also common causes of macrocytosis. Third, macrocytic anemia may be classified into three groups: Group 1 (megaloblastic anemia and medications), which can exceed MCV 130 fL; Group 2 (alcoholism/liver disease, BMF, myeloid malignancy, and hemolytic anemia), which can exceed MCV 114 fL; and Group 3 (lymphoid malignancy, chronic renal failure, hypothyroidism, and solid tumors), which does not exceed MCV 114 fL. These conclusions were supported by the results from eight other hospitals.