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CASE REPORT
Year : 2014  |  Volume : 41  |  Issue : 3  |  Page : 211-214

Celiac disease manifesting as isolated cobalamin deficiency megaloblastic anemia: Case series and review


1 Department of Paediatrics, Subbaiah Institute of Medical Sciences, Shimoga, Karnataka, India
2 Department of Surgery, Subbaiah Institute of Medical Sciences, Shimoga, Karnataka, India

Date of Web Publication19-Sep-2014

Correspondence Address:
Suresh Birur Parmeshwarappa
Department of Surgery, Subbaiah Institute of Medical Sciences, Shimoga - 577 222, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0974-5009.141246

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  Abstract 

Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. It has been identified as one of the most common lifelong disorders on a worldwide basis. Enteropathy in CD is thought to be the final consequence of an abnormal immune reaction, showing features of both an innate and adaptive response to gluten prolamins. The clinical spectrum is wide, including cases with either typical intestinal or atypical extra intestinal features, or silent forms. Anemia has frequently been reported as the only manifestation or the most frequent extra-intestinal symptom of CD. The only available treatment consists in dietary exclusion of grains containing gluten.

Keywords: Celiac disease, cobalamin deficiency, megaloblastic anemia


How to cite this article:
Kumar VS, Parmeshwarappa SB, Vadde AR. Celiac disease manifesting as isolated cobalamin deficiency megaloblastic anemia: Case series and review. J Sci Soc 2014;41:211-4

How to cite this URL:
Kumar VS, Parmeshwarappa SB, Vadde AR. Celiac disease manifesting as isolated cobalamin deficiency megaloblastic anemia: Case series and review. J Sci Soc [serial online] 2014 [cited 2020 Sep 22];41:211-4. Available from: http://www.jscisociety.com/text.asp?2014/41/3/211/141246


  Introduction Top


Celiac disease (CD) is an immune-mediated enteropathy caused by permanent sensitivity to gluten in genetically susceptible individuals. Genetic, environmental, and immunological factors play a role in the pathogenesis. The disease presents different clinical pictures. Atypical features occur in patients with later onset of the disease. Some patients may be asymptomatic. It is well-known that CD is associated with a number of autoimmune and inflammatory diseases, implicating a common genetic background. CD may be considered as an archetypal malabsorption syndrome, and it is a frequent cause of anemia without associated intestinal symptoms. Anemia has frequently been reported as the only manifestation or the most frequent extra-intestinal symptom of CD. [1],[2] We report a case series of children presenting with isolated cobalamin deficiency anemia due to CD, which is to the best of our knowledge not yet reported in Indian medical literature.


  Case reports Top


0Case 1

A 15-year-old boy was referred to the outpatient department (OPD) with anemia. His main complaints were easy fatigability and listlessness. His history was not significant. He had an elder sister who was doing well. Of late, his appetite was decreased, and the calorie and protein intake were on the lower side of recommended dietary allowance for his age and weight. He was adequately vaccinated and developmentally normal. He belonged to a lower middle-class social status. On examination, weight: 48 kg, height: 157 cm, significant pallor with knuckle hyperpigmentation were present. Rest of the examination findings was unremarkable. His investigations revealed Vitamin B12 deficient megaloblastic anemia with normal serum iron indices. Initially, his anemia was diagnosed as purely nutritional Vitamin B12 deficient anemia and was given Vitamin B12, folate and iron supplements, with dietary advice and was sent home. Initially, parenteral Vitamin B12 with folate was given followed by oral supplementation. He did well for about 3-4 months and again came back with severe anemia. This time, an endoscopic biopsy of the duodenum with celiac antibody profile was done which came positive. He is on regular follow-up and is doing well on gluten-free diet.

Case 2

A 14-year-old girl was referred to the OPD for evaluation of anemia and not yet attained menarche. Her main complaints were easy fatigability, listlessness, constipation, and repeated episodes of headaches. She was the only child with no significant family history. She was adequately vaccinated and developmentally normal. She belonged to a middle-class social status. On examination, weight: 32 kg, height: 140 cm, SMR 2 (for both breast and pubic hair) significant pallor with knuckle hyperpigmentation were present. Rest of the examination findings was unremarkable. Her investigations revealed Vitamin B12 deficient megaloblastic anemia with normal serum iron indices. She was diagnosed as nutritional Vitamin B12 deficient anemia with migraine and constitutionally delayed puberty and was given Vitamin B12, folate and iron supplements, anti-migraine treatment, with dietary advice and was sent home. On follow-up, it was noticed that her anemia was not improving. Hence, an endoscopic biopsy of the duodenum with celiac antibody profile was done which came positive. She is on regular follow-up and is doing well on gluten-free diet. Her problems of constipation and headache are also better. After the above cases, a protocol of duodenoscopy and biopsy for all children in adolescent age group presenting with anemia was adapted in our institution.

Case 3

A 13-year-old boy was referred to the OPD with not improving anemia. His main complaints were also easy fatigability and listlessness. He was on various types of hematinics for almost 6 months. All his previous peripheral smear reports were significant for macrocytic anemia.

He had an elder brother who was apparently doing well. He was adequately vaccinated and developmentally normal. He belonged to a lower class social status. On examination, weight: 34 kg, height: 140 cm, significant pallor with knuckle hyperpigmentation were present. Rest of the examination findings was unremarkable. This time, an endoscopic biopsy of the duodenum was done which was consistent with coeliac disease. After the biopsy report, celiac antibody profile was done, which came positive. He is on regular follow-up and is doing well on gluten-free diet.

Case 4

This boy 15-year-old is the sibling of case 3, on screening was found to be having macrocytic anemia, and duodenal biopsy was consistent with CD. On examination, he had mild pallor and otherwise everything else was unremarkable.

The duodenal biopsies showed partial villous atrophy, increased lymphotheliocytes, and mononuclear infiltration in all cases [Figure 1] and [Figure 2]. Co-morbid conditions like systemic lupus erythematosus and inflammatory bowel disease were excluded by serological tests.
Figure 1: Blunting of villi, crypt hyperplasia with intraepithelial lymphocytes (H and E, ×100)

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Figure 2: Intraepithelial Lymphocytes (H and E, ×400)

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All the cases were investigated for red blood cell (RBC) indices, serum iron studies, serum ferritin, serum Vitamin B12 level, RBC folate level, bone marrow examination, and celiac antibody profile with IgA level. Other tests done as part of CD screening were normal at the time of diagnosis.


  Discussion Top


The link between CD and anemia is well-documented. The majority of prior studies have focused on micronutrient deficiencies, especially iron as the cause of anemia in individuals with CD. Our findings suggest that this hypothesis is inadequate, and that the etiology of anemia in CD is multifactorial. The overall number of CD cases is the size of the iceberg [Figure 3], which is influenced not only by the frequency of the predisposing genotypes in the population, but also by the pattern of gluten consumption.
Figure 3: The celiac iceberg model

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Currently, the best approach to improve the diagnostic rate is the process of case finding focused on at-risk groups, a procedure that minimizes costs and is ethically appropriate. [3],[4],[5],[6],[7],[8],[9],[10],[11],[ 12] An increased awareness of the many clinical faces of CD, coupled with a higher inclination for using blood tests, could efficiently uncover a large portion of the submerged CD iceberg. Clinical features at presentation are very variable. While some develop CD very early in life, others may eat gluten for many years before the disease becomes apparent. [9],[10],[11],[12] In India, unlike in western countries, the majority of patients are diagnosed late in the disease due to various reasons. [13],[14],[15],[16]

The clinical picture of CD is very heterogeneous and has been classified by various authors [Table 1]. [5],[6],[9],[17],[18],[19],[20] A large number of silent cases of CD has been reported in at-risk groups (such as first-degree relatives and patients with insulin-dependent diabetes) and general population samples enrolled in screening programs. Case 4 had silent CD in the present case series. He was diagnosed by family screening.

In the present series, the mean age at diagnosis was 8.3 years, suggesting delayed recognition of the disease. Similar delay has been reported from both developing and developed countries (mean age at diagnosis 8.4 years' vs. 2.4 years, respectively). One possible reason for the delayed diagnosis could be lack of awareness, nonavailability of diagnostic tools, and cost. [13],[14],[15],[16]
Table 1: Various types and diff erence between each CD

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The cause of the Vitamin B12 deficiency in CD is not known but may include decreased gastric acid, bacterial overgrowth, autoimmune gastritis, decreased efficiency of mixing with transfer factors in the intestine, or perhaps subtle dysfunction of the distal small intestine. [3] Recent studies suggested that 8-41% of previously untreated subjects with CD were deficient in Vitamin B12. [2],[17],[21],[22],[23]

The other issue is, the unexpectedly high prevalence of anemia not due solely to iron deficiency, has not been addressed in the celiac literature adequately. We do know that CD is associated with inflammation that is not only intestinal but also systemic. Thus, the hematologic manifestations of the disease likely reflect the interplay between local and systemic factors. [24],[25],[26],[27],[28] Future studies addressing the role of malabsorption versus degree of inflammation in contributing to the anemia associated with CD are necessary.


  Conclusion Top


The clinical picture of CD is very heterogeneous; therefore, high index of suspicion for CD should be maintained in patients especially adolescents presenting with anemia. Our case series demonstrate that the pathophysiologic mechanisms of hematologic abnormalities occurring in CD patients are complex. The mechanisms by which patients with CD develop anemia need to be further explored. CD-already an under-recognized disorder in India-should be considered not only in the differential diagnosis of iron-deficiency anemia, but also in anemia of chronic disease. It seems reasonable to obtain a small-bowel biopsy in all patients with nutritional anemia undergoing an upper endoscopy, regardless of the endoscopic findings.

 
  References Top

1.Bottaro G, Cataldo F, Rotolo N, Spina M, Corazza GR. The clinical pattern of subclinical/silent celiac disease: An analysis on 1026 consecutive cases. Am J Gastroenterol 1999;94:691-6.  Back to cited text no. 1
    
2.Halfdanarson TR, Litzow MR, Murray JA. Hematologic manifestations of celiac disease. Blood 2007;109:412-21.  Back to cited text no. 2
    
3.Stevens D. Nutritional anaemia in childhood coeliac disease. Proc Nutr Soc 1979;38:102A.  Back to cited text no. 3
[PUBMED]    
4.Stene-Larsen G, Mosvold J, Ly B. Selective vitamin B12 malabsorption in adult coeliac disease. Report on three cases with associated autoimmune diseases. Scand J Gastroenterol 1988;23:1105-8.  Back to cited text no. 4
    
5.Croese J, Harris O, Bain B. Coeliac disease. Haematological features, and delay in diagnosis. Med J Aust 1979;2:335-8.  Back to cited text no. 5
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6.Collin P, Reunala T, Pukkala E, Laippala P, Keyriläinen O, Pasternack A. Coeliac disease - associated disorders and survival. Gut 1994;35:1215-8.  Back to cited text no. 6
    
7.Hallert C, Svensson M, Tholstrup J, Hultberg B. Clinical trial: B vitamins improve health in patients with coeliac disease living on a gluten-free diet. Aliment Pharmacol Ther 2009;29:811-6.  Back to cited text no. 7
    
8.Hadithi M, Stam F, Azizi F, Smulders YM, Mulder CJ. Vitamin levels and homocysteine in coeliac disease. In: Green P, Jabri B, Koshla C, Murray JA, Beckman C, editors. XII International Celiac Symposium. New York: Columbia University Medical Center; 2006. p. 134.  Back to cited text no. 8
    
9.Lionetti E, Catassi C. New clues in celiac disease epidemiology, pathogenesis, clinical manifestations, and treatment. Int Rev Immunol 2011;30:219-31.  Back to cited text no. 9
    
10.Kuloglu Z, Kirsaçlioglu CT, Kansu A, Ensari A, Girgin N. Celiac disease: Presentation of 109 children. Yonsei Med J 2009;50:617-23.  Back to cited text no. 10
    
11.Fasano A, Catassi C. Coeliac disease in children. Best Pract Res Clin Gastroenterol 2005;19:467-78.  Back to cited text no. 11
    
12.Catassi C, Fasano A. New developments in childhood celiac disease. Curr Gastroenterol Rep 2002;4:238-43.  Back to cited text no. 12
    
13.Mohindra S, Yachha SK, Srivastava A, Krishnani N, Aggarwal R, Ghoshal UC, et al. Coeliac disease in Indian children: Assessment of clinical, nutritional and pathologic characteristics. J Health Popul Nutr 2001;19:204-8.  Back to cited text no. 13
    
14.Walia BN, Sidhu JK, Tandon BN, Ghai OP, Bhargava S. Coeliac disease in North Indian children. Br Med J 1966;2:1233-4.  Back to cited text no. 14
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15.Mandal AK, Mehdi I, Munshi SK, Lo TC. Value of routine duodenal biopsy in diagnosing coeliac disease in patients with iron deficiency anaemia. Postgrad Med J 2004;80:475-7.  Back to cited text no. 15
    
16.Pawson R, Mehta A. Review article: The diagnosis and treatment of haematinic deficiency in gastrointestinal disease. Aliment Pharmacol Ther 1998;12:687-98.  Back to cited text no. 16
    
17.Bodé S, Gudmand-Høyer E. Symptoms and haematologic features in consecutive adult coeliac patients. Scand J Gastroenterol 1996;31:54-60.  Back to cited text no. 17
    
18.Mearin ML. Celiac disease among children and adolescents. Curr Probl Pediatr Adolesc Health Care 2007;37:86-105.  Back to cited text no. 18
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19.Ward PC. Modern approaches to the investigation of vitamin B12 deficiency. Clin Lab Med 2002;22:435-45.  Back to cited text no. 19
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20.Fisgin T, Yarali N, Duru F, Usta B, Kara A. Hematologic manifestation of childhood celiac disease. Acta Haematol 2004;111:211-4.  Back to cited text no. 20
    
21.Hin H, Bird G, Fisher P, Mahy N, Jewell D. Coeliac disease in primary care: Case finding study. BMJ 1999;318:164-7.  Back to cited text no. 21
    
22.Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med 2005;352:1011-23.  Back to cited text no. 22
    
23.Pittschieler K. Folic acid concentration in the serum and erythrocytes of patients with celiac disease. Padiatr Padol 1986;21:363-6.  Back to cited text no. 23
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24.Dahele A, Ghosh S. Vitamin B12 deficiency in untreated celiac disease. Am J Gastroenterol 2001;96:745-50.  Back to cited text no. 24
    
25.Dickey W. Low serum vitamin B12 is common in coeliac disease and is not due to autoimmune gastritis. Eur J Gastroenterol Hepatol 2002;14:425-7.  Back to cited text no. 25
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26.Kastrup W, Mobacken H, Stockbrügger R, Swolin B, Westin J. Malabsorption of vitamin B12 in dermatitis herpetiformis and its association with pernicious anaemia. Acta Med Scand 1986;220:261-8.  Back to cited text no. 26
    
27.Shamir R, Levine A, Yalon-Hacohen M, Shapiro R, Zahavi I, Rosenbach Y, et al. Faecal occult blood in children with coeliac disease. Eur J Pediatr 2000;159:832-4.  Back to cited text no. 27
    
28.Jason W. Harper, Stephen F. Holleran. Anemia in celiac disease is multifactorial in etiology. Am. J. Hematol 2007;82:996-1000.  Back to cited text no. 28
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1]



 

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