Advances in Coeliac Disease

Matthew J. Armstrong; Vinod S. Hegade; Gerry Robins

Disclosures

Curr Opin Gastroenterol. 2012;28(2):104-112. 

In This Article

Complications and Associations

Long-term risks associated with coeliac disease, such as end-stage renal disease (ESRD) and ischaemic heart disease (IHD), are summarized below.

Mortality and Morbidity Risk

Over the last 28 years, mortality in coeliac disease has been prospectively studied in 1092 biopsy-confirmed coeliac disease patients in Derby, England.[72••] Although all-cause mortality has not significantly changed over time, excess overall mortality observed (SMR 1.37) was in part explained by deaths from malignancy, digestive disease and respiratory disease.[72••] The fact that streptococcal pneumonia accounted for the majority of the reported respiratory diseases supports the existing guidance that recommends pneumococcal vaccination in coeliac disease patients.

Swedish nationwide population-based cohort studies involving more than 28 000 coeliac disease cases with a median follow-up of 9 years have found that coeliac disease is associated with an increased risk of hospital admission for influenza (hazard ratio 2.1),[73] developing tuberculosis (hazard ratio 2.0),[74] lymphoproliferative malignancy (hazard ratio 2.82),[75] cataracts (hazard ratio 1.28),[76] psoriasis (hazard ratio 1.72),[77] asthma (hazard ratio 1.6),[78] atrial fibrillation (hazard ratio 1.34),[79] suicide (hazard ratio 1.55),[80] ESRD (hazard ratio 2.87)[81••] and a negligible risk of future stroke (hazard ratio 1.10).[1] Most notably, the three-fold increased risk of future ESRD was irrespective of age at coeliac disease diagnosis,[81••] prompting the need to monitor renal function in coeliac disease patients. The same Swedish researchers have shown that patients with coeliac disease, independent of the severity of their histology, are at increased risk of myocardial infection, angina and cardiovascular death (hazard ratio 1.22).[83•] Reassuringly, latent coeliac disease (normal mucosa, positive serology) was not associated with these cardiovascular endpoints[83•] or the above risk of lymphoproliferative malignancy.[1] Other European studies have identified increased cancer risk in the form of thyroid papillary cancer (hazard ratio 2.5)[84] and non-Hodgkin's lymphoma (hazard ratio 4.4),[85] whereas excluding risk of colorectal neoplasia.[1]

Male and female fertility concerns in coeliac disease patients have in large been answered by Ludvigsson et al.[87••,88] population-based cohort studies. Overall, both sexes have normal fertility with coeliac disease and even though fertility was reduced 2 years prior to diagnosis in women, data suggests that compliance with GFD should normalize fertility.[87••] It must be noted, however, women with coeliac disease are 33 times more likely to have amenorrhoea and four times more likely to have at least one complication during pregnancy.[1] A putative involvement of tTG antibodies has been suggested in these gynaecological and/or obstetric disorders during active coeliac disease.[1]

Other Associations

Recent reports, ranging from single cases to specialty- based screening studies, have highlighted the association of coeliac disease with sarcoidosis,[91] psoriasis,[92] restless leg syndrome,[93] vitiligo,[94] immune thrombocytopenic purpura,[95] idiopathic dilated cardiomyopathy,[96] primary hyperparathyroidism[97] and multiple sclerosis.[1] The clinical relevance of such associations, as in the case of psoriasis, is questioned when GFD fails to improve the course of the accompanying disease.[1]

Disease concomitance of coeliac disease and microscopic colitis[99,100•] is 50 times that expected of a general population and mainly occurs in middle-aged women.[100•] GFD-resistant diarrhoea in this age/sex group should highlight the need for colonoscopy and biopsy to rule out this well recognized overlap.[100•]

Hypertransaminaemia in untreated coeliac disease ranges from 11–27%, with the latter figure emerging from a thorough meta-analysis of 11 studies.[101,102•] Most notable in both studies is that the transaminitis resolved in the majority of cases after establishment of GFD.[101,102•] Furthermore, the finding that undetected coeliac disease may explain one in 25 cases of cryptogenic hypertransaminaemia reopens the debate as to whether coeliac disease serology should be incorporated into the noninvasive liver aetiology screen.[102•] The cost–effectiveness of this approach, however, requires further study.

Quality of Life

A case–control study of 33 children with coeliac disease and their parents identified impaired quality of life (QoL) in leisure and social dimensions, respectively.[1] Language barriers in this study prevented the use of coeliac-specific questionnaires and, thus, diet was not taken into account. Interestingly, Dorn et al.[104] highlighted that psychosocial distress and poor coping strategies rather than disease- related factors (i.e. histological severity) predict poorer daily function, QoL and utilization of medical services. Sleep disorders, which are common in coeliac disease, have been shown to be strongly associated with psychological illnesses.[1] The fact that these disorders do not solely respond to GFD[105] emphasizes the importance of psychological assessment and intervention at diagnosis.[103,106,107] Psychological stress within family members has been linked with several immunological diseases, however, albeit underpowered, study by Ma°rild et al.[108] indicates that this is not associated with the development of coeliac disease in childhood.

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