Discussion:
This case of severe anemia and cardiomyopathy, without gastrointestinal
symptoms, highlights the extra-intestinal findings that should raise a
high clinical suspicion for celiac disease. Celiac disease has a wide
spectrum of clinical presentations, with both gastroenterological and
extra-intestinal manifestations. Different clinical categories of CD
have been described in literature, ranging from silent CD, which is
generally asymptomatic, to classic or typical CD, which is characterized
by intestinal symptoms, and atypical or subclinical CD, which also
includes extra-intestinal symptoms [1]. As the duodenum is the site
of iron absorption and the major site of inflammation in patients with
CD, iron deficiency anemia (IDA) is one of the most common clinical
manifestations of CD, and is present in over half of patients at the
time of diagnosis [1,2]. IDA can be the only sign of CD,
particularly in patients with atypical CD. Some studies have suggested
that the degree of villous atrophy correlates with anemia severity
[4]. For example, in a study of 405 adult celiac patients, Harper et
al. documented a significantly higher prevalence of IDA (34%) in
patients with subtotal/total villous atrophy, when compared with
patients with partial villous atrophy (13%; p >
0.001)[5]. Annibale et al. also found a significant inverse
correlation between hemoglobin concentration and the pathologic severity
of duodenal biopsies in patients with CD [4].
Recent studies, with advanced diagnostic cardiac imaging, have
highlighted the relationship between CD and cardiovascular diseases.
Severely dilated left ventricle, left ventricular dysfunction, very low
ejection fraction, pulmonary hemosiderosis, and heart block have all
been reported in cardiomyopathy patients with CD [6]. Several
mechanisms have been proposed to explain the etiology and progression of
cardiomyopathy in celiac disease. Firstly, severe nutritional
deficiencies due to chronic malabsorption can cause cardiomyopathy
[3]. It has also been suggested that derangements in intestinal
permeability in patients with CD may allow the absorption of luminal
antigens or infectious agents and lead to myocardial damage through
immune-mediated mechanisms [3]. Finally, direct myocardial injury
may result from an immune response against an antigen present in both
the myocardium and the small intestine [3]. Understanding the
relationship between celiac disease and cardiomyopathy can help explain
the effects of a gluten -free diet in patients with cardiac
manifestations. One case series described the effect of a gluten-free
diet on cardiac performance in three patients with idiopathic dilated
cardiomyopathy and celiac disease. In the two patients that strictly
observed the gluten-free diet, a 28-month follow-up showed an
improvement in echocardiographic parameters and quality of life
measures. The third patient did not observe the gluten-free diet and
presented with worsening echocardiographic parameters and cardiologic
symptoms, and required additional medication therapy [7]. These data
suggest that a gluten-free diet may have a significant beneficial effect
on cardiac performance in patients with CD and idiopathic dilated
cardiomyopathy [7].
Autoimmune disease is also strongly associated with CD, with an
approximate prevalence of 20% in adults [8]. Hypothyroidism is the
most common autoimmune manifestation, and occurs in 5%-15% of patients
with CD [8]. Although the mechanism underlying the correlation
between CD and hypothyroidism is unknown, the association is believed to
be independent of gluten exposure, and is most likely related to a
common genetic predisposition [9].