Malignancies and mortality in patients with coeliac disease and dermatitis herpetiformis: 30-year population-based study

Abstract

Background and aim

To assess the long-term risks of malignant diseases and mortality in patients with coeliac disease and dermatitis herpetiformis in a centre, where the prevalence of these diseases is high. The risks have probably been overestimated, as patients with subtle forms have earlier remained undetected.

Patients

The study comprised 17,245 person-years of follow-up in 1147 patients.

Methods

The observed numbers of malignancies and causes of deaths were assessed, and compared to those expected, and standardised incidence ratio and standardised mortality ratio given.

Results

The occurrence of all malignant conditions was equal to that in the population both in coeliac disease and dermatitis herpetiformis: standardised incidence ratios of 1.2 (95% confidence intervals 0.9–1.5) and 1.0 (0.6–1.5), respectively. Five patients with coeliac disease and seven with dermatitis herpetiformis had developed non-Hodgkin lymphoma; standardised incidence ratios of 3.2 (1.0–7.5) and 6.0 (2.4–12.4), respectively. Four patients with coeliac disease and one with dermatitis herpetiformis had enteropathy-associated T-cell lymphoma, associated with inadequate dietary compliance. Mortality was increased (standardised mortality ratio 1.26; 1.00–1.55) in coeliac disease, but decreased in dermatitis herpetiformis (standardised mortality ratio 0.52; 0.36–0.72).

Conclusion

The overall prognosis in our patients was good. Non-Hodgkin lymphoma emerged in patients with undiagnosed or poorly treated coeliac disease. The mortality rate in dermatitis herpetiformis was even lower than in the population. Our data support the early diagnosis and dietary treatment of these conditions.

Introduction

Coeliac disease (CD) is classified as a gluten-induced disease causing small bowel mucosal damage with villous shortening, crypt hyperplasia and inflammation, which recovers on a gluten-free diet [1]. Dermatitis herpetiformis (DH) is a blistering, itching skin disease, where the diagnosis is based on the demonstration of granular IgA deposits in the dermal papillae of uninvolved perilesional skin as observed by direct immunofluorescence [2], [3]. About 75% of our patients with DH have mucosal damage identical to that in CD, and the rest have mucosal inflammation, again consistent with CD [4].

We have, within the last 20 years, taken action to augment the diagnostics of CD and DH [5]. The disorder has been considered even in the presence of mild or atypical symptoms, and serologic tests have been widely employed in patients with other autoimmune diseases and in first-degree relatives of patients with CD and DH. As a result, we have recorded a clinical prevalence of CD and DH in our area as high as 0.3% already in 1997 [6], two to three times than usually reported [7], [8], [9]. Irrespective of the plausible symptoms at diagnosis, our policy has been to treat all the patients similarly by gluten-free diet. From our previous studies, we know that over 80% of our patients follow strict gluten-free diet, and only 2% use normal gluten-containing diet, the remainder having some dietary lapses [10], [11].

CD is associated with an increased risk of enteropathy-associated non-Hodgkin's lymphoma (NHL) [12], [13], [14], [15], [16]. Gluten-free diet treatment seems to protect patients from NHL [13]. Oesophageal, colorectal and small bowel cancers have been reported to occur in CD [14], [15], [17], whereas the risk of breast and lung cancer may be reduced [17].

Due to prolonged diagnostic delay and poor dietary compliance, NHL has thought to be the main cause of the two-fold increased mortality in CD, but when the diagnosis of CD has been made early enough, the additional risk seems to be lower or even negligible [18]. In a study by Swerdlow et al. [19] the mortality rate in DH was not increased; to our knowledge, no other studies have been carried out on mortality in patients with DH.

Our large prospective series of patients with CD and DH sampled during 30 years in a high-prevalence area enables us to determine whether the malignancy and mortality rates are really increased in these patients, when compliance with gluten-free dietary treatment has been shown to be good.