The Hidden Face of Pernicious Anemia: Age-Related Progression of Autoimmune Gastritis from Iron Deficiency to Cobalamin Depletion.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3603-3603
Author(s):  
Chaim Hershko ◽  
Aharon Ronson ◽  
Moshe Souroujon ◽  
Yzhak Maschler ◽  
Judith Heyd ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Atrophic Gastritis ◽  
Pernicious Anemia ◽  
Serum Gastrin ◽  
Screening Method ◽  
Intrinsic Factor ◽  
Autoimmune Gastritis ◽  
Deficiency Anemia ◽  
Age Cohorts ◽  
H Pylori

Abstract Because gastric acid secretion is critical for food iron absorption, iron deficiency is a known complication of the achlorhydria associated with pernicious anemia at presentation or following cobalamin (Cbl) treatment. In a previous study employing high serum gastrin and strongly positive antiparietal cell antibodies as a screening method for autoimmune atrophic gastritis, we have found a very high (27%) prevalence of atrophic gastritis among young subjects with iron deficiency anemia (IDA). The objectives of the present study were to explore the degree of overlap between patients presenting with atrophic gastritis and microcytic (MVC<80 fl) IDA on one hand, and those presenting with Cbl deficiency and normocytic (MCV 80–100 fl) or macrocytic (MCV>100 fl) anemia typical of pernicious anemia. Of 160 patients diagnosed with autoimmune gastritis presenting with iron, Cbl, or combined deficiency over the years 2001–2005, 83 presented with microcytic IDA, 48 with normocytic and 29 with macrocytic indices. Serum Cbl was abnormal in 100% of macrocytic, 92% of normocytic and 46% of microcytic subjects. IDA patients were 21 y younger (41 ±15 vs 62±15 y), predominantly female (78 vs 41%) and with a higher proportion of active H pylori infection (42 vs 21%). However, there were also marked similarities between all subgroups including a high prevalence of thyroid disease (20%) and diabetes (8%) known for their association with the autoimmune polyendocrine syndrome, and the rate of anti-intrinsic factor positivity was the highest (42% vs 31%) among IDA patients. Stratification by age cohorts from <20 to >60 y showed a very regular correlation, with progressive increase in MCV from 68±9 to 119±8 fl, serum ferritin from 4±2 to 37±41 μg/L, hypergastrinemia from 349±247 to 800±627 u/mL (normal 61±17), and a progressive decrease of Cbl from 392±179 in the youngest, to 108±65 pg/mL in the oldest age cohort. The prevalence of H pylori infection was 87.5% at age <20 y, 47% at 20–40 y, 37.5 % at 41–60 y and 12.5% at age > 60y implying a spontaneous elimination of H pylori by achlorhydria of increasing severity and duration. H pylori eradication by triple therapy in 24 patients resulted in a decrease in serum gastrin from 476±391 to 218±220 u/mL (paired t-test=0.00086) within 19± 12 months and complete remission of pernicious anemia in 2 patients. These findings challenge the common notion that pernicious anemia is a disease of the elderly manifested in megaloblastic anemia, and imply a disease starting many years before the establishment of clinical Cbl deficiency through an autoimmune mechanism directed against gastric parietal cells, likely triggered by H pylori by means of antigenic mimicry. Because of the added strain of young age and fertility on iron requirements, IDA may precede Cbl deficiency by many years until the crucial loss of remaining intrinsic factor in a proportion of patients terminating in typical pernicious anemia.

Resolving the Riddle of Obscure Iron Deficiency Anemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 371-371
Author(s):  
Chaim Hershko ◽  
Julian Patz ◽  
Aharon Ronson
Keyword(s):  
Iron Deficiency ◽  
Atrophic Gastritis ◽  
Iron Deficiency Anemia ◽  
Reproductive Age ◽  
Autoimmune Gastritis ◽  
Deficiency Anemia ◽  
Age Cohorts ◽  
Iron Treatment ◽  
H Pylori ◽  
Autoimmune Atrophic Gastritis

Abstract Conventional endoscopic and radiographic methods fail to identify a source of gastrointestinal blood loss in about one third of males and post-menopausal females and in most women of reproductive age with iron deficiency anemia (IDA). Such patients are often referred for hematologic evaluation. In recent years there is increasing awareness of non-bleeding conditions with abnormal iron absorption as possible causes of unexplained IDA. Both H pylori gastritis and autoimmune atrophic gastritis are associated with impaired gastric acidity interfering with iron absorption. In a prospective study performed in a community hematology clinic, 300 consecutive IDA patients were screened for non-bleeding GI conditions including celiac disease (antiendomysial antibodies), autoimmune atrophic gastritis (hypergastrinemia with strongly positive antiparietal cell antibodies) and H pylori gastritis (IgG antibodies confirmed by urease breath test). Their mean age was 39±18 y, and 251 of 300 (84%) were women. A likely cause of IDA was identified in 93% of patients. As expected in a population of females of reproductive age, only 10% had a source of gastrointestinal bleeding identified. There were 13 new cases of adult celiac disease (4%). A history suggestive of menorrhagia was present in 32%. Autoimmune atrophic gastritis was documented in 77 IDA patients (26%) of whom 39 had coexistent H pylori infection. H pylori infection was the only positive finding in 57 patients (19%). To exclude the compounding effect of menstrual blood loss in evaluating the role of H pylori in the pathogenesis of IDA, we have focused on the 29 male IDA patients with negative gastrointestinal workup, poor initial response to oral iron treatment, and a high prevalence of H pylori infection (25 of 29). Following H pylori eradication, all patients achieved normal hemoglobin levels with follow-up periods ranging from 4 to 69 months (38±15 months mean± 1SD). This was accompanied by a significant decrease in H pylori IgG antibodies and serum gastrin. Sixteen patients discontinued iron treatment, maintaining normal hemoglobin and ferritin and may be considered cured. Remarkably, 4 of the 16 achieved normal hemoglobin without ever having received oral iron after H pylori eradication. To define the relation between IDA-associated autoimmune gastritis, and pernicious anemia, we studied 160 patients with autoimmune gastritis including 83 subjects presenting with IDA, 48 presenting with normocytic indices, and 29 with macrocytic anemia. Stratification by age cohorts of autoimmune gastritis from <20 to >60 y showed coexistent H pylori infection in 87.5% at age <20 y, 47% at 20–40 y, 37.5% at 41–60 y, but only 12.5% at age > 60y. With increasing age cohorts, there was a regular and progressive increase in MCV from 68±9 to 95±16 fl, serum gastrin from 349±247 to 800±627 u/mL, and a decrease in cobalamin from 392±179 to 108±65 pg/mL. Conclusions: The favorable long-term clinical results of H pylori eradication offer strong evidence for a cause-and-effect relation between H pylori and IDA. A proportion of H pylori patients will develop autoimmune gastritis. Our findings in autoimmune gastritis imply a disease presenting as IDA many years before the establishment of clinical cobalamin deficiency. It is likely caused by an autoimmune process triggered by antigenic mimicry between H pylori epitopes and major autoantigens of the gastric mucosa. Recognition of H pylori and autoimmune gastritis as common causes of obscure iron deficiency anemia should have a strong impact on the efficacy of diagnostic workup and management of unexplained, or refractory iron deficiency anemia.

Variable hematologic presentation of autoimmune gastritis: age-related progression from iron deficiency to cobalamin depletion

Blood ◽  
2006 ◽  
Vol 107 (4) ◽  
pp. 1673-1679 ◽  
Author(s):  
Chaim Hershko ◽  
Aaron Ronson ◽  
Moshe Souroujon ◽  
Itzhak Maschler ◽  
Judith Heyd ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Pernicious Anemia ◽  
Macrocytic Anemia ◽  
Gastrin Level ◽  
Autoimmune Gastritis ◽  
Cobalamin Deficiency ◽  
Deficiency Anemia ◽  
Age Cohorts ◽  
Age Related ◽  
Autoimmune Polyendocrine Syndrome

Iron deficiency is a known complication of achlorhydria and may precede the development of pernicious anemia. Among 160 patients with autoimmune gastritis identified by hypergastrinemia and strongly positive antiparietal antibodies, we explored the overlap between 83 subjects presenting with iron deficiency anemia (IDA), 48 with normocytic indices, and 29 with macrocytic anemia. Compared with macrocytic patients, patients with IDA were 21 years younger (41 ± 15 years versus 62 ± 15 years) and mostly women. All groups had a high prevalence of thyroid disease (20%) and diabetes (8%) suggestive of the autoimmune polyendocrine syndrome. Stratification by age cohorts from younger than 20 years to older than 60 years showed a regular and progressive increase in mean corpuscular volume (MCV) from 68 ± 9 to 95 ± 16 fl, serum ferritin levels from 4 ± 2 to 37 ± 41 μg/L, gastrin level from 166 ± 118 to 382 ± 299 pM/L (349 ± 247 to 800 ± 627 pg/mL), and a decrease in cobalamin level from 392 ± 179 to 108 ± 65 pg/mL. The prevalence of Helicobacter pylori infection was 87.5% at age younger than 20 years, 47% at age 20 to 40 years, 37.5% at 41 to 60 years, and 12.5% at age older than 60 years. These findings challenge the common notion that pernicious anemia is a disease of the elderly and imply a disease starting many years before the establishment of clinical cobalamin deficiency, by an autoimmune process likely triggered by H pylori.

How I treat unexplained refractory iron deficiency anemia

Blood ◽  
2014 ◽  
Vol 123 (3) ◽  
pp. 326-333 ◽  
Author(s):  
Chaim Hershko ◽  
Clara Camaschella
Keyword(s):  
Celiac Disease ◽  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Young Patients ◽  
Autoimmune Gastritis ◽  
Cobalamin Deficiency ◽  
Deficiency Anemia ◽  
Strong Impact ◽  
Age Cohorts ◽  
H Pylori

AbstractEndoscopic gastrointestinal workup fails to establish the cause of iron deficiency anemia (IDA) in a substantial proportion of patients. In patients referred for hematologic evaluation with unexplained or refractory IDA, screening for celiac disease, autoimmune gastritis, Helicobacter pylori, and hereditary forms of IDA is recommended. About 4% to 6% of patients with obscure refractory IDA have celiac disease, and autoimmune gastritis is encountered in 20% to 27% of patients. Stratification by age cohorts in autoimmune gastritis implies a disease presenting as IDA many years before the establishment of clinical cobalamin deficiency. Over 50% of patients with unexplained refractory IDA have active H pylori infection and, after excluding all other causes of IDA, 64% to 75% of such patients are permanently cured by H pylori eradication. In young patients with a history suggestive of hereditary iron deficiency with serum ferritin higher than expected for IDA, mutations involving iron trafficking and regulation should be considered. Recognition of the respective roles of H pylori, autoimmune gastritis, celiac disease, and genetic defects in the pathogenesis of iron deficiency should have a strong impact on the current diagnostic workup and management of unexplained, or refractory, IDA.

scholarly journals Chronic Atrophic Gastritis with Negative Intrinsic Factor and Parietal Cell Antibody Presenting as a Severe Hemolytic Anemia

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
G. F. Cittolin-Santos ◽  
S. Khalil ◽  
J. K. Bakos ◽  
K. Baker
Keyword(s):  
Vitamin B12 ◽  
Atrophic Gastritis ◽  
Pernicious Anemia ◽  
Hemolytic Anemia ◽  
Parietal Cell ◽  
Intrinsic Factor ◽  
Peripheral Blood Smear ◽  
Chronic Atrophic Gastritis ◽  
Cell Antibody ◽  
Parietal Cell Antibody

A 28-year-old Caucasian male with Hashimoto’s disease and vitiligo presented with two weeks of dizziness on exertion following pharyngitis which was treated with prednisone 40 mg by mouth once a day for five days. Initial workup revealed anemia, elevated lactate dehydrogenase (LDH), and low haptoglobin. He underwent workup for causes of hemolytic anemia which was remarkable for a peripheral blood smear with hypersegmented neutrophils and low vitamin B12 levels concerning for pernicious anemia. Parietal cell and intrinsic factor antibodies were negative, and he then underwent an esophagogastroduodenoscopy with biopsy. The biopsy was negative for Helicobacter pylori, and the immunohistochemical stains were suggestive of chronic atrophic gastritis. He was started on vitamin B12 1,000 mcg intramuscular injections daily. His hemoglobin, LDH, and haptoglobin normalized. Given the absence of the parietal cell antibody and intrinsic factor antibody, this is a rare case of seronegative pernicious anemia.

Schistocytosis in B12 Deficiency (B12D) Reduces the MCV and Raises the RDW in the Absence of Iron Deficiency: a Cause of Unnecessary Plasmapheresis (PP)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4816-4816
Author(s):  
Maushmi Savjani ◽  
Padma Draksharam ◽  
Albert S Braverman
Keyword(s):  
Iron Deficiency ◽  
Conflicts Of Interest ◽  
Case Reports ◽  
Intrinsic Factor ◽  
Size Variation ◽  
Complete Response ◽  
Initial Therapy ◽  
Deficiency Anemia ◽  
Severe Anemia ◽  
B12 Deficiency

Abstract Background: RBC size variation and microcytes in B12D are often ascribed, but rarely shown, to be due to co-existing Fe deficiency. Schistocytes (aka poikilocytes) were included in early descriptions of pernicious anemia (PA). As it also causes thrombocytopenia, B12D may be confused with thrombotic thrombocytopenic purpura (TTP). Because of the urgency of PP for TTP, it has sometimes been initial therapy for B12D with schistocytes. Purpose: Here we describe 3 PA patients, and review reports of 15 other severely anemic B12D cases, with schistocytes. As they are smaller than mature RBC, they may normalize the MCV, while raising the RDW. We wished to determine whether primary lab studies help to distinguish B12D from TTP. Case Reports: These patients presented with symptoms of severe anemia: Ferritins were normal or high, haptoglobins <30, anti-intrinsic factor and parietal cell antibodies present, and complete response to B12 therapy occurred. Significant numbers of schistocytes were present in all, as was a distinctive population of minute, hypochromic schistocytes (MHS). Review: We found 15 reports of individual B12D patients with schistocytes, published between 2003 and 2015. All but 2 vegans had PA, 6 being anti-IF Ab+. Median & median ages were 52 & 53, [Hb]'s 5.9 & 6.0, MCV's 120 & 117 (3 normal), platelets 97 & 85, WBC 3200 & 3120, LDH's 4050 & 5860; reticulocyte levels were all low for severe anemia. Iron deficiency anemia was not found; ferritin and/or Fe/TIBC were reported normal in 4. Six legible blood smear microphotographs were included, confirming schistocytosis. Five patients had one or more PP before B12 deficiency was discovered. All 15 responded completely to B12. MHS were also observed on 4 of the 6 legible microphotographs, and noted by authors. For comparison, our survey of 36 reported TTP legible blood smears failed to detect MHC. Conclusions: Schistocytes are observed in some severely anemic B12D, may account for as much as 6.7% of RBC, and alter their indices. Schistocytosis and thrombocytopenia suggest TTP, and may lead to unnecessary PP. But such patients' low reticulocyte counts and very high LDH levels are not typical of TTP. Table Table. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Association of H. pylori with Iron Deficiency Anemia: Myth or Reality?

2009 ◽  
Vol 104 ◽  
pp. S40
Author(s):  
Rizwan Kibria ◽  
Khurram Bari ◽  
Qasim Khalil ◽  
Kanan Sharma ◽  
Muhammad Beg ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Deficiency Anemia ◽  
H Pylori
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