Antibody negative coeliac disease presenting in elderly people—an easily missed diagnosis

Antonio TURSI,M.D.

Consultant Gastroenterologist

Digestive Endoscopy Unit, “Lorenzo Bonomo” Hospital, Andria (BA) - Italy

Sir,

I read with extreme interest the recent case report by David Sanders and
collegues about the uncommon case of a 79-year old man in whom celiac
disease was diagnosed despite antibodies negativity (1). This case
confirms several other recent reports, which showed that in some celiac
patients antibodies may be negative. In particular, seronegative celiac
disease seems to be quite frequent in patients with Marsh I-IIIa lesions
(2-6). This is a very important challenge in clinical practice, since most
of general pratictioners (and most of gastroenterologists) advice and
carry out gastroscopy in suspected coeliac disease only after a positive
antibodies assessment. On the other hand, it is not easy to obtain
patients’ consent to gastroscopy in presence of mild gastrointestinal
symptoms (as dyspepsia) or in absence of them but suspected for celiac
disease (as patients complaining for iron-deficiency anaemia or
osteoporosis), and negative for serological searching. How we can overcome
this problem? In their recent excellent review, Armin Alaedini and Peter
Green underline the concept of intestinal biopsy in high clinical
suspicion of celiac disease and irrespective of serological results (7).

However, I think that other non-invasive methods should be carried out to
select patients to undergo gastroscopy. In particular, I think that tests
evaluating small bowel absorption should be performed in every case of
suspicious celiac disease and irrespective of serological searching, since
they may supply more information about small bowel function. In fact we
cannot forget that coeliac disease is a malapsorptive syndrome, and that
it affect always small bowel function.

We performed a sorbitol H2 breath test in every patient suspected for
celiac disease as adjunctive non invasive method assessing small bowel
function. Sorbitol, a hexahydroxy alcohol used as a sugar substitute in
many dietetic foods and as a drug vehicle, has been recently used to
diagnose celiac patients, since its supply at low dose and concentration
to patients with celiac disease resulted in an increased excretion of H2
with respect to healthy controls (8). At the same time, it has been showed
that this test may be useful as a screening tool in patients with celiac
disease (9), as well as we demonstrate more recently its effectiveness
both in detecting histological lesions in patients affected by
subclinical/silent form of celiac disease (10) and in detecting
histological damage in first-degree seronegative relatives (11). Sorbitol
H2 breath test is useful even in borderline gluten-sensitive enteropathy,
in whom histology is often confounding or misleading or inconsistent for
coeliac disease but clinical features are consistency for celiac disease
(as iron deficiency anaemia not responding to oral iron supplementation):
in these cases sorbitol H2 breath test- positivity before gluten-free
diet and sorbitol H2 breath test- negativity after gluten-free diet
showed a small bowel restoration after gluten withdrawal and permitted to
made a definitive diagnosis of celiac disease (12).

Unfortunately, this test shows high sensitivity but low specificity in
detecting small bowel histological damage, since also diseases involving
small bowel (as Crohn’s disease) may show abnormal sorbitol H2 breath test
(13). So, I don’t think that sorbitol H2 breath test may replace
serological tests nor intestinal biopsy. However, Sorbitol H2 breath test
is a cheap, easy and non-invasive method to assess small bowel function,
and I think that it may supply a valid contribution in detecting
intestinal damage even in seronegative patients and in selecting patients
to undergo small intestinal biopsy.

REFERENCES

1) Sanders DS; Hurlstone DP, McAlindon ME, Hadjuvassiliou M, Cross SS,
Wild G, Atkins CJ. Antibody negative celiac disease presenting in elderly
people – an easily missed diagnosis. BMJ 2005;330: 775-6

2) Rostami K, Kerckhaert J, Tiemessen R, von Blomberg ME, Meijer JWR,
Mulder CJJ. Sensitivity of antiendomysium and antigliadin antibodies in
untreated celiac disease: disappointing in clinical practice. Am J
Gastroenterol 1999;94: 888-94

3) Dickey W, Hughes DF, McMillan SA. Reliance on serum endomysial antibody
testing underestimates the true prevalence of coeliac disease by one
fifth. Scand J Gastroenterol 2000;35: 181-3

4) Tursi A, Brandimarte G, Giorgetti G, Gigliobianco A, Lombardi D,
Gasbarrini G. Low prevalence of antigliadin and anti-endomysium antibodies
in subclinical/silent coeliac disease. Am J Gastroenterol 2001; 96: 1507-
10

5) Tursi A, Brandimarte G, Giorgetti G. Prevalence of anti-tissue
transglutaminase antibodies in different degrees of intestinal damage in
celiac disease. J Clin Gastroenterol 2003; 36: 219-221

6) Abrams JA, Diamone B, Rotterdam H, Green PHR. Seronegative celiac
disease: increased prevalence with lesser degrees of villous atrophy. Dig
Dis Sci 2004;49: 546-50

7) Alaedini A, Green PHR. Narrative review. Celiac disease: understanding
a complex autoimmune disordes. Ann Intern Med 2005;142: 289-98

8) Corazza GR, Strocchi A, Rossi R, Sirola D , Gasbarrini G. Sorbitol
malabsorption in normal volunteers and in patients with coeliac disease.
Gut 1988;29: 44-8

9) Pelli MA, Capodicasa E, De Angelis V, Morelli A, Bassotti G. Sorbitol
H2-breath test in celiac disease. Importance of early positivity.
Gastroenterol Int 1998;11: 65-8

10) Tursi A, Brandimarte G, Giorgetti GM. Sorbitol H2-Breath test versus
anti-endomysium (EMA) antibodies for the diagnosis of subclinical/silent
coeliac disese. Scand J Gastroenterol 2001;36: 1170-2

11) Tursi A, Brandimarte G, Giorgetti GM, Inchingolo CD. Effectiveness of
sorbitol H2 breath test in detecting histological damage among relatives
of coeliacs. Scand J Gastroenterol 2003;38: 727-731

12) Tursi A, Brandimarte G. The symptomatic and histological response to a
gluten-free diet in patients with borderline enteropathy. J Clin
Gastroenterol 2003;36(1): 13-17

13) Tursi A, Giorgetti GM, Brandimarte G, Elisei W. High prevalence of
celiac disease among patients affected by Crohn’s disease. Inflamm Bowel
Dis 2005; (in press)

Competing interests:
None declared