The changing clinical profile of celiac disease: a 15-year experience (1998-2012) in an Italian referral center

Abstract

Background: Celiac disease is a multiform, challenging condition characterized by extremely variable features. Our goal was to define clinical, serological and histopathological findings in a large cohort of celiacs diagnosed in a single referral center.

Methods: From January 1998 to December 2012, 770 patients (599 females, median age 36 years, range 18-78 years) were diagnosed as celiacs at St. Orsola-Malpighi Hospital (Bologna, Italy). The clinical phenotypes were classified as: 1) classical (malabsorption syndrome); 2) non-classical (extraintestinal and/or gastrointestinal symptoms other than diarrhea); 3) subclinical. Serology, duodenal histology, comorbidities, response to gluten-free diet and complications were evaluated.

Results: Disease onset was symptomatic in 610 patients (79%), while 160 celiacs showed a subclinical phenotype. In the symptomatic group the non-classical prevailed over the classical phenotype (66% vs 34%). Diarrhea was found in 27%, while other gastrointestinal manifestations were bloating (20%), aphthous stomatitis (18%), alternating bowel habit (15%), constipation (13%) and gastroesophageal reflux disease (12%). Extraintestinal manifestations included osteopenia/osteoporosis (52%), anemia (34%), cryptogenic hypertransaminasemia (29%) and recurrent miscarriages (12%). Positivity for IgA tissue transglutaminase antibodies was detected in 97%. Villous atrophy was found in 87%, while 13% had minor lesions consistent with potential celiac disease. A large proportion of patients showed autoimmune disorders, i.e. autoimmune thyroiditis (26.3%), dermatitis herpetiformis (4%) and diabetes mellitus type 1 (3%). Complicated celiac disease was very rare.

Conclusions: Our study demonstrates that the clinical profile of celiac disease changed over time with an increasing rate of non-classical and subclinical phenotypes.

Figure 1

The annual distribution of CD diagnoses in the referral center of the St. Orsola-Malpighi University Hospital from 1998 to 2012. Of the 770 diagnosed patients, 318 (41.2%) were identified in the first 10 years (1998-2007), whereas the other 452 (58.8%) were diagnosed in the last five years (2008-2012).

Figure 2

Prevalence of symptomatic and subclinical phenotypes in the 770 CD patients. Note that 610 patients (79%) were diagnosed as symptomatic, whereas the remaining 160 (21%) were classified as subclinical CD. Of the 610 symptomatic patients, 210 (34%) displayed the classical onset with diarrhea and malabsorption (regardless of extraintestinal manifestations), whereas the other 400 showed the non-classical form with gastrointestinal symptoms (other than diarrhea) and extraintestinal manifestations.

Figure 3

Gastrointestinal and extraintestinal symptoms in 770 CD patients. A) Symptoms related to gastrointestinal tract included diarrhea (27%), bloating (20%), aphthous stomatitis (18%), alternate bowel habit (15%), constipation (13%) and gastroesophageal reflux disease (GERD) (12%). B) Extraintestinal manifestations, alone or in combination with gastrointestinal symptoms/signs, included osteopenia/osteoporosis (52%), anemia (34%), cryptogenic hypertransaminasemia (29%), recurrent miscarriages (12%), IgE-mediated allergy (9%), headache (5%) and fibromyalgia-like symptoms (2.2%).