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].