Joint Bone Spine 71 (2004) 344–346

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Case report

Systemic lupus erythematosus with celiac disease: a report of five cases

Mondher Zitouni, Wafa Daoud, Maryam Kallel, Sondés Makni *
Immunology Laboratory, la Rabta Hospital, Bab Saadoun, el Jabbari 1007, Tunis, Tunisia
Received 18 March 2003; accepted 5 June 2003

Available online 27 August 2003

Abstract
Systemic lupus erythematosus and celiac disease (CD) are rarely reported in combination. We report five cases seen over a 4–year period.
The two conditions occurred concomitantly in one patient, whereas the CD antedated the lupus in one patient and postdated the lupus in the
remaining three patients. Villous atrophy on duodenal biopsy specimens with a favorable response to a gluten-free diet was noted in all five
patients. Only four patients had positive serological tests for CD and only three had abdominal symptoms.
© 2003 Elsevier SAS. All rights reserved.
Keywords: Systemic lupus erythematosus; Celiac disease

1. Introduction patient 2, who had laboratory evidence of malabsorption,

Although diverse combinations of autoimmune diseases
have been extensively described, few cases of systemic lupus
erythematosus (SLE) with celiac disease (CD) have been
reported.
2. Patients and methods
We retrospectively studied five patients with both SLE
and CD managed in teaching hospitals in Tunis, Tunisia, over
the 4–year period from 1998 to 2002 (Table 1). The two
diseases occurred simultaneously in one patient, whereas the
CD antedated the SLE by several years in one patient and
postdated it by 1–3 years in three patients. Villous atrophy on
duodenal biopsy specimens with a favorable histological
response to a gluten-free diet confirmed the diagnosis of CD
in all five patients. The only patient with CD antedating SLE
was also the only child in the series. CD was suspected based
on abdominal symptoms in three patients (cases 1, 4, and 5),
laboratory evidence of malabsorption (low serum choles-
terol, iron, and albumin) in one patient (case 2), and detection
of anti-reticulin antibodies on rat liver sections during testing
for anti-nuclear antibodies in one patient. Serological mark-
ers for CD were found in four patients, the exception being
* Corresponding author.
E-mail address: sondes.makni@rns.tn (S. Makni).
© 2003 Elsevier SAS. All rights reserved.
doi:10.1016/S1297-319X(03)00159-3
villous atrophy that responded to a gluten-free diet, and
negative investigations for other causes of villous atrophy.
All five patients met SLE criteria developed by the Ameri-
can College of Rheumatology. Tests were positive for anti-
nuclear antibodies and anti-dsDNA antibodies in all five
patients. Two patients had renal involvement with segmental
and focal glomerulonephritis but no evidence of activity on
renal biopsy specimens. The gluten-free diet had no notice-
able influence on the manifestations of SLE.
3. Discussion
A review of articles published between 1965 and 2002
found only seven documented cases of SLE and CD in
combination [1]. Six other cases of SLE with malabsorption
and duodenal biopsy findings consistent with CD have been
described; these patients had a poor response to, or poor
compliance with, a gluten-free diet [2]. In a study from Israel
[3] of 21 SLE patients, malabsorption was noted in two
patients, of whom one had villous atrophy on duodenal
biopsy specimens.
Since the SLE–CD combination is infrequent, it is as-
cribed to coincidence by many authors. In a study from Texas
of the prevalence of CD among SLE patients [4], 24 (23.3%)
of the 103 patients had antibodies to gliadin but none had
antibodies to endomysium. Antibodies to endomysium and
transglutaminase have nearly 100% sensitivity and specific-
 M. Zitouni et al. / Joint Bone Spine 71 (2004) 344–346 345

Table 1
Clinical and immunologic features in five patients with both SLE and CD
Patient
Number 1 Number 2 Number 3 Number 4 Number 5
Age (years) 28 24 18 23 34
Age at CD diagnosis (years) 3 23 18 23 34
Age at SLE diagnosis (years) 24 23 16 20 33
Butterfly rash + + +
Photosensitivity + + +
Discoid lupus +
Polyarthralgia + + + +
Pleuritis + +
Alopecia +
Renal disease + +
Leukopenia + + + +
Lymphopenia + +
ANA + + + + + +
anti-dsDNA + + + + + +
anti-Sm – +
anti-SSA + + + +
anti-SSB + + + +
Low C3, C4 Normal Normal Low Low Low
Presenting manifestations of CD
Chronic diarrhea + +
Abdominal pain +
Abdominal distension +
Steatorrhea +
Fortuitous discovery of laboratory evidence of +
malabsorption
Fortuitous discovery of anti-reticulin antibodies +
Anti-gliadin antibodies +IgG and IgA – +IgA +IgG and IgA +IgG and IgA
Anti-transglutaminase antibodies + – + + +
Anti-endomysium antibodies + – + + +
Villous atrophy + + + + +
Response to a gluten-free diet Positive Positive Positive Positive Positive
CD, celiac disease; SLE, systemic lupus erythematosus; ANA, anti-nuclear antibodies; anti-DSDNA, antibodies to double-stranded DNA.

ity, as compared to 90% and 85%, respectively, for anti-
gliadin IgAs and 75% and 90%, respectively, for anti-gliadin
IgGs. Upper gastrointestinal tract endoscopy done in the
24 anti-gliadin-positive patients found no endoscopic or his-
tological evidence of CD. The authors interpreted their data
as militating against a specific relation between SLE and CD.
In addition, few cases of the SLE–CD combination have been
reported, and CD has not been described in patients with
other autoimmune disorders such as rheumatoid arthritis [5].
However, since both diseases are now recognized to be au-
toimmune disorders, they might occur together as part of the
multiple autoimmune syndrome. Thus, hypotheses to explain
the SLE–CD combination in our five patients include mul-
tiple autoimmune disorder occurring in association with sus-
ceptibility genes, a specific link between CD and SLE, and a
role of medications used to treat SLE in the genesis of CD. It
would be of interest to determine which medications were
used for SLE treatment.
Of interest is the high prevalence of HLA-DR3 in both,
patients with CD [6] and patients with SLE [7]. Among
patients with CD, 95% are positive for HLA-DQ2, which is
in linkage disequilibrium with DR3, explaining why this last
is found in 70–90% of patients with CD [6]. Similarly,
HLA-DR3 is present in 40–70% of patients with SLE [7].
Given that SLE and CD share a similar immunogenetic
background, the association between these two conditions
deserves to be investigated. Larger studies would be useful to
obtain an accurate evaluation of the prevalence of the
SLE–CD combination. Preliminary studies from Tunisia, as
yet unpublished, suggest a particularly high incidence of
these two diseases in the population at large. Should an
increase in the prevalence of the SLE–CD combination be
confirmed, routine detection of these two diseases by immu-
nological tests and gastrointestinal endoscopy in a defined
population might be in order.
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