Irish Journal of Medical Science

, Volume 181, Issue 2, pp 225–229

Adult coeliac disease in Ireland: a case series

Authors

    • Faculty of Health SciencesTrinity College, University of Dublin
    • Department of Gastroenterology and HepatologyCork University Hospital, Wilton
  • H. J. O’. Connor
    • Faculty of Health SciencesTrinity College, University of Dublin
  • P. O’. Regan
    • South Tipperary General Hospital Clonmel
Original Article

DOI: 10.1007/s11845-011-0788-z

Cite this article as:
Saleem, A., Connor, H.J.O. & Regan, P.O. Ir J Med Sci (2012) 181: 225. doi:10.1007/s11845-011-0788-z

Abstract

Background

The clinical spectrum of adult coeliac disease (ACD) is varied with limited Irish data.

Aims and Objectives

The aim of this study was to analyse the presenting symptoms, associated conditions and complications in a consecutive series of patients with ACD.

Methods

Data were obtained from database on patients with ACD between 1988 and 2004.

Results

One hundred and six patients (69F:37M, mean age: 46, range: 23–95 years) were included. The modes of presentation were diarrhoea in 44 patients (45%), weight loss in 41 (42%), anaemia in 37 (38%), abdominal pain in 15 (15%), fatigue in 8 (8%), hypocalcaemia in 4 (4%) and steatorrhoea in 4 (4%). Associated conditions included thyroid disorders in 7 patients (7%), bipolar affective disorder in 4 (4%), major depression in 3 (3%), rheumatoid disease in 3 (3%), inflammatory bowel disease in 4 (4%) and type I diabetes mellitus in 2 (2%). Malignancy emerged as a major complication in 15 patients (15%)

Conclusion

The presenting features of ACD are diverse and associated with high risk of malignancy.

Keywords

Coeliac diseaseAssociated conditionsAutoimmune disease

Introduction

Coeliac disease is an inflammatory disease of the small intestine resulting from sensitivity to ingested gluten in genetically susceptible subjects [1]. Historically it has been considered as an uncommon condition, but recent studies have shown that coeliac disease affects around 1% of the general population [2]. In recent years, ACD is increasingly diagnosed probably due to increased awareness among physicians and the availability of a reliable serological screening test [3].

Patients with ACD may present with minimal symptoms and gastrointestinal manifestations are frequently absent [4, 5]. Manifestations caused by malabsorption such as anaemia or osteoporosis may be the presenting feature, whereas in other patients the predominant features may be of a disorder associated with coeliac disease such as hypothyroidism or inflammatory bowel disease [4]. Patients with coeliac disease may be at increased risk of malignancy, but the magnitude of this risk is unclear because of small patient numbers, lack of systematic cancer assessment and bias from the case series of referral institutions [6]. The aim of this study was to assess the presenting features, associated conditions and complications in a consecutive series of patients with ACD diagnosed at an Irish general hospital.

Methods

This study was carried out at South Tipperary General Hospital in the Republic of Ireland, a 150-bed acute hospital with 10,000 admissions per annum serving a population of approximately 85,000. Clinical data on patients with ACD were entered on a written database including modes of presentation, duration of symptoms, time since diagnosis, associated conditions, serology pre and post gluten-free diet, liver function tests, autoimmune screen, family history, dietary compliance, endoscopy findings and complications. This detailed information was transferred to a Microsoft Excel sheet and a computerised database formed. Dietary compliance was assessed by the dietitian at the outpatient visit. Duodenal biopsies were repeated after 6 months of gluten-free diet (GFD) together with measurement of antiendomysial antibodies and antigliadin IgG and IgA antibodies pre and post GFD to assess compliance and treatment response. Subjective and objective response to the diet was also evaluated at 6 months or annually in a gastroenterology clinic. Routine measurement of bone density using DEXA scanning was carried out in patients diagnosed after 2000. No specific investigations were carried out in order to outrule malignancy at the time of diagnosis. Patients lost to follow-up were sent a postal questionnaire and were also contacted via telephone to update our data.

Statistics

Statistical analysis was performed using Windows SPSS version 14. The Wilcoxon rank sum test was used to identify any statistical difference in the delay in diagnosis. A p value <0.05 was considered significant.

Results

From 1988 to 2004, 106 patients (69F, 37M) with ACD were registered on the coeliac database and complete data were available on 98. The mean age at diagnosis was 46 years (range 23–95). Median duration of symptoms prior to diagnosis for females was 9.5 months compared with 4 months in males (p = 0.655). Median duration of follow-up was 15 years range (4–39).

Presenting complaints

The main presenting complaints of our patients are shown in Fig. 1. Eighty-five patients had more than one presenting symptom. Sixty-three patients presented with gastrointestinal symptoms including diarrhoea (45%), diarrhoea with loss of weight (25%) abdominal pain (15%) and steatorrhoea (4%). Diarrhoea was predominantly associated with loss of weight and iron deficiency anaemia and less often with upper GI symptoms such as dyspepsia, bloating and heartburn and very seldom as a sole symptom. All our patients regardless of the symptoms who underwent upper GI endoscopy had routine duodenal biopsies. One patient presenting with diarrhoea also had concomitant Campylobacter jejuni infection. Lethargy and tiredness were also reported in eight patients presenting with diarrhoea and iron deficiency anaemia. One patient presented with joint pains as a sole symptom. Nausea and vomiting was recorded in seven patients. Abdominal pain in 15 patients was described as mainly epigastric and postprandial in nature associated with dyspepsia. That group of patients presenting with gastroesophageal reflux symptoms and/or abdominal pain were diagnosed as coeliac as an incidental finding on routine duodenal biopsy. Nine patients had a positive family history of ACD. All the patients included in this study were symptomatic.
https://static-content.springer.com/image/art%3A10.1007%2Fs11845-011-0788-z/MediaObjects/11845_2011_788_Fig1_HTML.gif
Fig. 1

Modes of presentation of coeliac disease in %

Associated conditions

Associated diseases were common in our patient group (Fig. 2). The most common associated conditions were autoimmune diseases including thyroid disease (7%), diabetes (2%),inflammatory bowel disease (5%) and rheumatoid arthritis (3%). Hypothyroidism was the predominant endocrine disorder associated with ACD in six patients and three of them had positive antimicrosomal antibodies. These patients showed a good clinical response to thyroid replacement therapy soon after starting on gluten-free diet. One patient with thyrotoxicosis also had Sjogrens syndrome. Patients with insulin-dependent diabetes mellitus were in the advanced stage of the disease with established complications before the diagnosis of coeliac was made. One patient who presented with amenorrhea had low FSH and LH. One patient who had a history of recurrent abortions had B12 and folate deficiency as well as iron deficiency anaemia. Antinuclear antibodies and antismooth muscle antibodies were positive in six patients without any abnormality in liver function tests. Antimitochondrial antibodies were negative in all the patients. One patient had lactose intolerance before the diagnosis of ACD. Six patients had osteoporosis and one patient had osteopenia. Liver function tests were reported as normal in all our patients at presentation. None of our patients had Down’s syndrome. Two patients (2%) had the pathognomonic rash of dermatitis herpetiformis. Associated psychiatric illnesses included bipolar affective disorder in four patients (4%) and major depression in three (3%) patients. The associated conditions in our patients antedated the diagnosis of ACD.
https://static-content.springer.com/image/art%3A10.1007%2Fs11845-011-0788-z/MediaObjects/11845_2011_788_Fig2_HTML.gif
Fig. 2

Clinical conditions associated with adult coeliac disease in %

Malignancy

Of the 98 patients in the study on whom we have full data, 15 (15%) developed malignancy and the details are shown in Table 1. The mean age at diagnosis of malignancy was 54 years and the mean time after diagnosis of ACD was 88 months (range 4–192). Seven patients (7%) developed non Hodgkins lymphoma, 1 small bowel, 1 gastric MALT, 1 spinal and 4 of indeterminate origin. Three patients (3%) developed colon cancer, 1 (1%) vulval squamous cell cancer, one (1%) oesophageal squamous cell carcinoma, one (1%) duodenal adenocarcinoma, one (1%) craniopharyngioma and one (1%) prostate cancer. Two patients (13%) who developed malignancy had a poor response to GFD, two patients (13%) with a simultaneous diagnosis of malignancy and ACD were not on the diet and one patient (6%) was non compliant with GFD. Compliance was also measured in patients without malignancy. Five patients had a poor response to diet and one was non compliant with GFD.
Table 1

Malignancy associated with adult coeliac disease

Malignancy type

Sex

Age at diagnosis (years)

Duration since diagnosis (months)

Survival (months)

Dietary compliance and clinical response post GFD

Gastric MALT

F

42

18

18

EMA/biopsy negative

Spinal

M

43

01

03

EMA/biopsy negative

Small bowel lymphoma

F

58

Simultaneous

04

Not on diet

Disseminated NHL

M

19

13

03

EMA/biopsy negative

Disseminated NHL

M

49

05

05

EMA positive/biopsy negative

Disseminated NHL

M

69

01

02

EMA/biopsy positive

Disseminated NHL

M

34

09

96

Noncompliant/good response on EMA/biopsy

Duodenal adeno

F

50

Simultaneous

02

Not on diet

Vulval

F

67

07

72

Biopsyx2 positive 6 mths apart

Oesophageal

M

52

06

18

EMA positive/biopsy negative

Brain Ca

F

48

15

18

EMA/biopsy negative

Colon

F

75

04

12

EMA/biopsy negative

Colon

F

55

01

60

EMA/biopsy negative

Colon

M

72

04

60

EMA/biopsy negative

Prostate

M

   

EMA/biopsy negative

Discussion

Despite having one of the highest prevalences of coeliac disease in the world, data are sparse on the natural history and outcome of ACD in Ireland. This could be due to community prevalence and non inclusion of asymptomatic patients. The patients in our study represent a consecutive, unselected group of patients from a stable local population with long-term follow-up in a single centre. We found a substantial delay in the diagnosis of ACD, particularly in women of reproductive age. This subgroup of patients mainly presented with iron deficiency anaemia which may have been attributed to menstrual losses. Lombardo et al. [7] found a high prevalence of coeliac disease among 207 women with hypochromic microcytic anaemia. A prospective study of 484 anaemic patients compared with age- and sex-matched non anaemic controls demonstrated one in 44 anaemic patients had coeliac disease compared with one of 498 controls (p < 0.001) [8].

The demographic characteristics of our patient cohort mirror those of other studies [3, 9] with a peak in diagnosis of ACD in the fourth to sixth decade and a female predominance. A study in Italy has also shown that coeliac disease is more frequent and severe in women as compared with men [10]. In contrast, a study of ACD from India showed an equal male:female ratio [11]. Atypical symptoms at presentation such as fatigue and abdominal pain occurred in 30% of our patients highlighting the fact that ACD may not present with an obvious malabsorption syndrome [1, 12, 13]. This finding is in agreement with another study analyzing modes of presentation in 590 patients with ACD where fewer patients presented with diarrhoea over time, with a steady decline from 91.3% of patients diagnosed before 1981 to 37.2% of patients diagnosed after 2000 (p < 0.001) [14]

ACD presents with diarrhoea more commonly in developing countries, whereas in developed countries the percentage of patients presenting with diarrhoea is declining and atypical presentation is more common [8, 15]. Some of our patients presented with non specific dyspeptic symptoms and were diagnosed on routine duodenal biopsies. This was due to the practice of performing duodenal biopsies on every patient undergoing upper GI endoscopy as a routine in our centre. A study from Canada has shown that 56/404 (14%) of patients with ACD were diagnosed by an incidental duodenal biopsy [15]. However, the overall yield and costeffectiveness of routine duodenal biopsies remains controversial [16, 17].

Unexplained hypertransaminasemia with nonspecific changes on liver biopsy is the commonest hepatic presentation of ACD sometimes called coeliac hepatitis [1822]. Liver function tests (LFTs) are known to improve within 6 months of adherence to GFD. ACD is present in about 9% of patients with chronic unexplained hypertransaminasemia [21, 22]. However, LFTs and autoantibodies routinely measured in all our patients at the time of diagnosis were uniformly negative. Autoimmune disorders occur more frequently in patients with coeliac disease than in the general population. 7% of our patients had concomitant thyroid disease. Type I diabetes was already an established diagnosis in 2% of our patients who later were discovered to have coeliac disease. In a study in Olmsted County, 7% of 158 patients with type I diabetes had associated asymptomatic coeliac disease [23]. Some authors suggest routine screening for coeliac disease at the time of diagnosis of Type I diabetes [2426]. Neurological and psychiatric disturbances were reported by Holmes et al. [27] in 86 of 340 patients (25%) with ACD. 4% of our patients had associated bipolar affective disorder and 3% major depression. Epilepsy is the most recognised neurological disorder associated with ACD; however, this association was not seen in our cohort. There is increasing awareness of associated psychiatric illness in patients diagnosed with ACD [28].

The high incidence of malignancy detected in our relatively small cohort of patients with ACD compared with other studies could be a chance finding (see Table 1) In his study from the US, Green reported malignancy in 43 (11%) of 381 coeliac patients [6]. Interestingly poor correlation has been observed between dietary compliance and reduction in the risk of Non Hodgkins lymphoma [6]. A retrospective cohort study of 12,000 subjects with coeliac disease over 38 years of follow-up revealed 249 cancers among those discharged giving a standardized incidence ratio of 1.3 [29]. In our study none of the lymphoma group were enteropathy associated T cell lymphoma (EATL) which is strongly associated with coeliac disease [3032].Two of the patients with simultaneous diagnosis presented with complication of the disease suggestive of spectrum bias. No specific examinations were performed to detect malignancy at the time of diagnosis. Dietary compliance in our subjects seemed adequate but did not protect against the development of malignancy. There were ten malignancy related deaths, six in the lymphoma group, two in the large bowel cancer group, one patient with duodenal adenocarcinoma and one with a brain tumour.

Conclusions

ACD has a varied clinical presentation and the diagnosis is often delayed particularly in women of child bearing age. Associated autoimmune disorders are common with ACD and should prompt investigation from the onset of diagnosis. Affective and neurological disorders are also associated with ACD. Our results suggest that malignancy may occur more frequently in ACD irrespective of compliance with GFD

Conflict of interest

None.

Copyright information

© Royal Academy of Medicine in Ireland 2011