- Email: [email protected]
Clinical characteristics of coeliac disease (CD) in the Maltese islands
Correspondence / Digestive and Liver Disease 38 (2006) 781–785
[2] [3]
[4]
[5]
1aL is a partial agonist for outer surface protein A-reaticve T cells. J Immunol 2001;166:5286–91. Guerau-de-Arellano M, Huber BT. Development of autoimmunity in Lyme arthritis. Curr Opin Theumatol 2002;14:388–93. Benvenga S, Guarnieri F, Vaccaro M, Santarpia L, Trimarchi F. Homologies between proteins of Borrelia Burgdorferi and thyroid autoantigens. Thyroid 2004;14:964–6. Benvenga S, Santarpia L, Trimarchi F, Guarnieri F. Human thyroid autoantigens and proteins of Yersinia and Borrelia share amino acid sequence homology that includes binding motifs to HLA-DR molecules and T-cell receptor. Thyroid 2006;16:225–36. Invernizzi P, Selmi C, Poli F, Bianchi I, Rosina F, Floreani A, et al. HLA-DRB1 polymorphisms in 676 Italian patients with primary biliary cirrhosis and 2028 matched healthy controls. A nation-wide populationbased case-control study. Hepatology 2005;42(Suppl. 1):462A (Abs).
A. Floreani ∗ F. Ferrara Department of Surgical and Gastroenterological Sciences, University of Padova, Padua, Italy Available online 27 June 2006
∗ Correspondence to: Divisione Gastroenterologia, Via Giustiniani, 2, Padova 35128, Italy. Tel.: +39 049 8212894; fax: +39 049 8760820. E-mail address: [email protected] (A. Floreani)
doi: 10.1016/j.dld.2006.05.017
Clinical characteristics of coeliac disease (CD) in the Maltese islands Sir/Madam, In 2005 we performed a study to determine the clinical characteristics of adult coeliac disease (CD) in the Maltese Islands. A questionnaire was distributed to: (a) 70 successive patients attending our gastroenterology out-patients clinic (OPC), (b) 70 randomly selected patients that were not being followed at any medical OPC. (In Malta all CD patients are registered for gluten-free (GF) food. This register was consulted to select these patients). Our questionnaire was distributed to about 25% of known CD patients. We consulted their medical notes to verify the diagnosis and other present conditions. Sixty-two patients from the first group and 68 patients from the second group answered the questionnaire (97.1%). The mean age was 42 years (14–79 years), 31 were males and 99 females. In 115 patients, an oesophago-gastroduodenoscopy with biopsy confirmation of the diagnosis was done, 11 patients had a Crosby Capsule biopsy. Four patients were diagnosed on blood testing and clinical improvement on a GF diet. Most patients were diagnosed between 31 and 50 years of age (50.8%) and 47% of patients were diagnosed over 15 years ago.
783
One hundred and seven patients (82.3%) were symptomatic. The most common symptom was diarrhoea (69.2%). Other presenting symptoms were abdominal pain, abdominal bloating, dyspepsia, weight loss and failure to thrive. In the asymptomatic group, CD was diagnosed in the investigation of anaemia in 86.9% of cases (2 males and 18 females). The rest were diagnosed in (a) the investigation for osteoporosis (2 males) and (b) family screening (1 female). Seventy patients (53.8%) were diagnosed since serological studies were introduced. Seventy-seven percent were symptomatic (compared to 82.3% of total patients), and 71.7% of them had diarrhoea (compared to 69.2% of total). Twenty-seven patients (20.7%) had a first-degree relative with CD. With regards to dietary compliance, 69% claimed that they were always compliant, 27.7% were very often compliant, two patients answered sometimes and one was never compliant. 97.2% of the symptomatic patients reported a marked clinical improvement or resolution of their symptoms. Three patients were still symptomatic: two were non-compliant and one had lactose intolerance. Autoimmune thyroid disease was found in 9.23%, type 1 diabetes mellitus (DM) in 3.85%, recurrent aphthae in 15.4% and dermatitis herpetiformis in 5.4% of patients. One female patient had primary biliary cirrhosis, another had chronic persistent active hepatitis. No patients ever had any malignancy. The prevalence of CD in most European countries is about 0.5% [1]. The prevalence of classical presentation of CD in the Maltese Islands is higher than that from other similar studies and has not changed since the introduction of serological assays [2]. In our study 96.9% of patients had an intestinal biopsy, which is the gold standard diagnostic method for CD [3]. The female to male ratio (3:1) and the prevalence of the associated disorders were similar to the other studies [4–6]. This similarity supports the validity of our sample population. No malignancies were reported in our study. A possible explanation could be that we did not study CD patients who had died. Possibly, also, since 96.7% of our CD patients were either always or very often compliant to the diet, this prevented the development of any malignancy. To our knowledge, in Malta, serological screening is routinely done in anaemic patients but has only been recently introduced for first-degree relatives. This may explain the excess of symptomatic patients as serological assays have been introduced. In conclusion, we suggest that all at high-risk patient groups should be screened and a study in the general Maltese population should be done to estimate the true prevalence of CD in these Mediterranean islands.
References [1] Volta U, Bellentani S, Bianchi FB, et al. High prevalence of celiac disease in the Italian general population. Dig Dis Sci 2001;46:1500–5.
784
Correspondence / Digestive and Liver Disease 38 (2006) 781–785
[2] Dickey W, McMillan SA. Increasing numbers at a specialist coeliac clinic: contribution of serological testing in primary care. Dig Liver Dis 2005;37:928–33. [3] Trier JS. Diagnosis of celiac sprue. Gastroenterology 1998;115:211–6. [4] Collin P, Reunala T, Pukkala E, et al. Celiac disease-associated disorders and survival. Gut 1994;35:1215–8. [5] Kumar V, Rajadhyaksha M, Wortsman J. Celiac diseaseassociated autoimmune endocrinopathies. Clin Diagn Lab Immunol 2001;8:678–85. [6] Collin P, Kaukinen K, V¨alim¨aki M, Salmi J. Endocrinological disorders and celiac disease. Endocr Rev 2002;23:464–83.
Pierre Ellul∗ St. Luke‘s Hospital, Malta Mario Vassallo St. Luke‘s Hospital, Malta Christiane Ellul Primary Health Care Department, Harper Lane, Floriana, Malta (EU) Available online 3 July 2006
∗ E-mail
address: pierre [email protected] (P. Ellul)
doi: 10.1016/j.dld.2006.04.019
Multiple food intolerance or refractory celiac sprue? Sir, Celiac Disease (CD) is a gluten-triggered enteropathy in genetically susceptible individuals [1]. The atypical onset of CD occurs always more often in older children, classic forms being present under 2 years of age [2]. Refractory Sprue (RS) is a clinical condition presenting with severe malabsorption and histological finding of villous atrophy without improvement in spite of gluten-free diet (GFD) [3–5]. Food intolerance may be defined like several adverse reactions to food ingestion including metabolic, toxic and allergic ones. Clinical features may be gut related or may involve skin or respiratory tract system [6]. A 16-year-old girl was admitted for tiredness and recurrent loss of conscience episodes. She weighed 48 kg with a satisfactory nutritional status (BMI: 19); a systolic murmur was heard to mitralic region. After meal and during fast glucose blood concentration, blood pressure, ammonium plasmatic level, electrocardiographical pattern and cardiac US were normal. Also, CT of the brain did not show anything of relevance. The total blood cell count showed a reduced number of RBC (3,800,000/mm3 ), a MCV of 60 fl and also, the haemoglobin plasmatic concentration was reduced to 6.8 g/dl. Parents refused an upper endoscopy. The total iron-binding capacity was increased, whilst ferritin was also reduced. What was the reason responsible for this iron-deficiency anaemia? Elisa serological test-
ing of anti-gliadin (AGA) and anti-transglutaminase (␣-tTG) antibodies gave positive results (AGA IgA: 54 mg/ml and ␣tTG IgA: 22.9 UA/ml, respectively). Immunofluorescence of anti-endomisium antibodies also proved this finding (+++). Genetical predisposition to CD was confirmed by the presence of DQ2 HLA heterodimer. Serological screening tests for IBD (ASCA and P-ANCA), ESR, Crp and stool samples for detecting Giardia antigens were negative. Histological examination with Haematoxylin–Eosin staining, after duodeno-jejunal biopsy, showed absolute villous atrophy, glandular crypts hypertrophy and a severe intra-epithelial lymphocyte infiltration. So GFD was started. During followup, patient anaemia improved and the serological autoantibodies titres decreased but malabsorption, abdominal pain, diarrhoea, bloating and other symptoms resembling a classic form of CD occurred. This unusual clinical course gave doubt on real patient’s compliance to GFD (Secondary RS). In fact, the clinical and symptomatologic improvement is the first goal during GFD, followed by decrease of autoantibody titre and progressive histological recovery. In order to diagnose a Primary RS, we need lymphocyte typification, which gives us a proof of the monoclonal origin of IEL infiltration associated to typical markers (CD 103+ , CD 4− and CD 8− ) with monoclonal ␥ chain re-arrangement of T-cell receptor. But before this, we wanted to exclude all other possible associated conditions that may mimic a Primary RS: first of all, a multiple food intolerance and pancreatic failure. So we tested serological amylases and lipases, total IgE count and specific cutaneous prick tests with negative results. On the other side, the double blind challenge test with rice cream versus maize provided evidence for maize intolerance. Indeed, maize starch is the most common component of all gluten-free “foodstuffs”. The occurrence of abdominal pain, and sudden diarrhoea after ingestion of maize cream forced to stop the challenge test. So, the patient started a gluten-maize-free diet with clinical improvement and 5 kg weight gain during the 10-month follow-up. At the same time, serological tests and haemoglobin plasmatic concentration came back to normal values. A second duodenal biopsy performed 3 months later after starting the double exclusion diet, revealed histological improvement and a decreased intra-epithelial lymphocyte number. Our young girl complained tiredness up to loss of conscience due to iron-deficiency anaemia refractory to oral supplementation; iron absorption, indeed, occurs in the distal duodenal tract, i.e. the gut region most frequently impaired in celiac disease. The clinical manifestations of food allergies may involve only the gastro-intestinal tract but in other cases clinical presentation can change from cutaneous manifestations to respiratory ones or in the worst case, systemic anaphylaxis with life-threatening shock. Histological findings are non-specific and can vary from mild inflammation to duodenal villous atrophy; highly suggestive is an increased number of eosinophils in the colonic mucosa. The peculiarity of the immunologic system of gastro-intestinal tract consists in IgA production and induction of oral tolerance.
[2] [3]
[4]
[5]
1aL is a partial agonist for outer surface protein A-reaticve T cells. J Immunol 2001;166:5286–91. Guerau-de-Arellano M, Huber BT. Development of autoimmunity in Lyme arthritis. Curr Opin Theumatol 2002;14:388–93. Benvenga S, Guarnieri F, Vaccaro M, Santarpia L, Trimarchi F. Homologies between proteins of Borrelia Burgdorferi and thyroid autoantigens. Thyroid 2004;14:964–6. Benvenga S, Santarpia L, Trimarchi F, Guarnieri F. Human thyroid autoantigens and proteins of Yersinia and Borrelia share amino acid sequence homology that includes binding motifs to HLA-DR molecules and T-cell receptor. Thyroid 2006;16:225–36. Invernizzi P, Selmi C, Poli F, Bianchi I, Rosina F, Floreani A, et al. HLA-DRB1 polymorphisms in 676 Italian patients with primary biliary cirrhosis and 2028 matched healthy controls. A nation-wide populationbased case-control study. Hepatology 2005;42(Suppl. 1):462A (Abs).
A. Floreani ∗ F. Ferrara Department of Surgical and Gastroenterological Sciences, University of Padova, Padua, Italy Available online 27 June 2006
∗ Correspondence to: Divisione Gastroenterologia, Via Giustiniani, 2, Padova 35128, Italy. Tel.: +39 049 8212894; fax: +39 049 8760820. E-mail address: [email protected] (A. Floreani)
doi: 10.1016/j.dld.2006.05.017
Clinical characteristics of coeliac disease (CD) in the Maltese islands Sir/Madam, In 2005 we performed a study to determine the clinical characteristics of adult coeliac disease (CD) in the Maltese Islands. A questionnaire was distributed to: (a) 70 successive patients attending our gastroenterology out-patients clinic (OPC), (b) 70 randomly selected patients that were not being followed at any medical OPC. (In Malta all CD patients are registered for gluten-free (GF) food. This register was consulted to select these patients). Our questionnaire was distributed to about 25% of known CD patients. We consulted their medical notes to verify the diagnosis and other present conditions. Sixty-two patients from the first group and 68 patients from the second group answered the questionnaire (97.1%). The mean age was 42 years (14–79 years), 31 were males and 99 females. In 115 patients, an oesophago-gastroduodenoscopy with biopsy confirmation of the diagnosis was done, 11 patients had a Crosby Capsule biopsy. Four patients were diagnosed on blood testing and clinical improvement on a GF diet. Most patients were diagnosed between 31 and 50 years of age (50.8%) and 47% of patients were diagnosed over 15 years ago.
783
One hundred and seven patients (82.3%) were symptomatic. The most common symptom was diarrhoea (69.2%). Other presenting symptoms were abdominal pain, abdominal bloating, dyspepsia, weight loss and failure to thrive. In the asymptomatic group, CD was diagnosed in the investigation of anaemia in 86.9% of cases (2 males and 18 females). The rest were diagnosed in (a) the investigation for osteoporosis (2 males) and (b) family screening (1 female). Seventy patients (53.8%) were diagnosed since serological studies were introduced. Seventy-seven percent were symptomatic (compared to 82.3% of total patients), and 71.7% of them had diarrhoea (compared to 69.2% of total). Twenty-seven patients (20.7%) had a first-degree relative with CD. With regards to dietary compliance, 69% claimed that they were always compliant, 27.7% were very often compliant, two patients answered sometimes and one was never compliant. 97.2% of the symptomatic patients reported a marked clinical improvement or resolution of their symptoms. Three patients were still symptomatic: two were non-compliant and one had lactose intolerance. Autoimmune thyroid disease was found in 9.23%, type 1 diabetes mellitus (DM) in 3.85%, recurrent aphthae in 15.4% and dermatitis herpetiformis in 5.4% of patients. One female patient had primary biliary cirrhosis, another had chronic persistent active hepatitis. No patients ever had any malignancy. The prevalence of CD in most European countries is about 0.5% [1]. The prevalence of classical presentation of CD in the Maltese Islands is higher than that from other similar studies and has not changed since the introduction of serological assays [2]. In our study 96.9% of patients had an intestinal biopsy, which is the gold standard diagnostic method for CD [3]. The female to male ratio (3:1) and the prevalence of the associated disorders were similar to the other studies [4–6]. This similarity supports the validity of our sample population. No malignancies were reported in our study. A possible explanation could be that we did not study CD patients who had died. Possibly, also, since 96.7% of our CD patients were either always or very often compliant to the diet, this prevented the development of any malignancy. To our knowledge, in Malta, serological screening is routinely done in anaemic patients but has only been recently introduced for first-degree relatives. This may explain the excess of symptomatic patients as serological assays have been introduced. In conclusion, we suggest that all at high-risk patient groups should be screened and a study in the general Maltese population should be done to estimate the true prevalence of CD in these Mediterranean islands.
References [1] Volta U, Bellentani S, Bianchi FB, et al. High prevalence of celiac disease in the Italian general population. Dig Dis Sci 2001;46:1500–5.
784
Correspondence / Digestive and Liver Disease 38 (2006) 781–785
[2] Dickey W, McMillan SA. Increasing numbers at a specialist coeliac clinic: contribution of serological testing in primary care. Dig Liver Dis 2005;37:928–33. [3] Trier JS. Diagnosis of celiac sprue. Gastroenterology 1998;115:211–6. [4] Collin P, Reunala T, Pukkala E, et al. Celiac disease-associated disorders and survival. Gut 1994;35:1215–8. [5] Kumar V, Rajadhyaksha M, Wortsman J. Celiac diseaseassociated autoimmune endocrinopathies. Clin Diagn Lab Immunol 2001;8:678–85. [6] Collin P, Kaukinen K, V¨alim¨aki M, Salmi J. Endocrinological disorders and celiac disease. Endocr Rev 2002;23:464–83.
Pierre Ellul∗ St. Luke‘s Hospital, Malta Mario Vassallo St. Luke‘s Hospital, Malta Christiane Ellul Primary Health Care Department, Harper Lane, Floriana, Malta (EU) Available online 3 July 2006
address: pierre [email protected] (P. Ellul)
doi: 10.1016/j.dld.2006.04.019
Multiple food intolerance or refractory celiac sprue? Sir, Celiac Disease (CD) is a gluten-triggered enteropathy in genetically susceptible individuals [1]. The atypical onset of CD occurs always more often in older children, classic forms being present under 2 years of age [2]. Refractory Sprue (RS) is a clinical condition presenting with severe malabsorption and histological finding of villous atrophy without improvement in spite of gluten-free diet (GFD) [3–5]. Food intolerance may be defined like several adverse reactions to food ingestion including metabolic, toxic and allergic ones. Clinical features may be gut related or may involve skin or respiratory tract system [6]. A 16-year-old girl was admitted for tiredness and recurrent loss of conscience episodes. She weighed 48 kg with a satisfactory nutritional status (BMI: 19); a systolic murmur was heard to mitralic region. After meal and during fast glucose blood concentration, blood pressure, ammonium plasmatic level, electrocardiographical pattern and cardiac US were normal. Also, CT of the brain did not show anything of relevance. The total blood cell count showed a reduced number of RBC (3,800,000/mm3 ), a MCV of 60 fl and also, the haemoglobin plasmatic concentration was reduced to 6.8 g/dl. Parents refused an upper endoscopy. The total iron-binding capacity was increased, whilst ferritin was also reduced. What was the reason responsible for this iron-deficiency anaemia? Elisa serological test-
ing of anti-gliadin (AGA) and anti-transglutaminase (␣-tTG) antibodies gave positive results (AGA IgA: 54 mg/ml and ␣tTG IgA: 22.9 UA/ml, respectively). Immunofluorescence of anti-endomisium antibodies also proved this finding (+++). Genetical predisposition to CD was confirmed by the presence of DQ2 HLA heterodimer. Serological screening tests for IBD (ASCA and P-ANCA), ESR, Crp and stool samples for detecting Giardia antigens were negative. Histological examination with Haematoxylin–Eosin staining, after duodeno-jejunal biopsy, showed absolute villous atrophy, glandular crypts hypertrophy and a severe intra-epithelial lymphocyte infiltration. So GFD was started. During followup, patient anaemia improved and the serological autoantibodies titres decreased but malabsorption, abdominal pain, diarrhoea, bloating and other symptoms resembling a classic form of CD occurred. This unusual clinical course gave doubt on real patient’s compliance to GFD (Secondary RS). In fact, the clinical and symptomatologic improvement is the first goal during GFD, followed by decrease of autoantibody titre and progressive histological recovery. In order to diagnose a Primary RS, we need lymphocyte typification, which gives us a proof of the monoclonal origin of IEL infiltration associated to typical markers (CD 103+ , CD 4− and CD 8− ) with monoclonal ␥ chain re-arrangement of T-cell receptor. But before this, we wanted to exclude all other possible associated conditions that may mimic a Primary RS: first of all, a multiple food intolerance and pancreatic failure. So we tested serological amylases and lipases, total IgE count and specific cutaneous prick tests with negative results. On the other side, the double blind challenge test with rice cream versus maize provided evidence for maize intolerance. Indeed, maize starch is the most common component of all gluten-free “foodstuffs”. The occurrence of abdominal pain, and sudden diarrhoea after ingestion of maize cream forced to stop the challenge test. So, the patient started a gluten-maize-free diet with clinical improvement and 5 kg weight gain during the 10-month follow-up. At the same time, serological tests and haemoglobin plasmatic concentration came back to normal values. A second duodenal biopsy performed 3 months later after starting the double exclusion diet, revealed histological improvement and a decreased intra-epithelial lymphocyte number. Our young girl complained tiredness up to loss of conscience due to iron-deficiency anaemia refractory to oral supplementation; iron absorption, indeed, occurs in the distal duodenal tract, i.e. the gut region most frequently impaired in celiac disease. The clinical manifestations of food allergies may involve only the gastro-intestinal tract but in other cases clinical presentation can change from cutaneous manifestations to respiratory ones or in the worst case, systemic anaphylaxis with life-threatening shock. Histological findings are non-specific and can vary from mild inflammation to duodenal villous atrophy; highly suggestive is an increased number of eosinophils in the colonic mucosa. The peculiarity of the immunologic system of gastro-intestinal tract consists in IgA production and induction of oral tolerance.