Coeliac disease: clinical signs up to 7 years before diagnosis

Analysis of data from a population of over 400,000 people has revealed that mild laboratory abnormalities and moderate digestive symptoms may appear years before a diagnosis of coeliac disease.

Coeliac disease in young adults (aged 18-40) frequently presents with atypical or extraintestinal symptoms, such as anaemia, fatigue, neuropsychiatric disorders and joint pain. This clinical variability contributes to delays in the diagnosis of coeliac disease, sometimes by several years, resulting in an increased risk of long-term complications, including malnutrition, osteoporosis and neoplasms.

A large-scale population study analysed the early clinical and laboratory signs of coeliac disease, with the aim of promoting timely recognition of the condition and reducing the burden of late diagnosis.

The retrospective study, conducted on a database of over 430,000 patients from an Israeli healthcare organisation, forms part of the body of research dedicated to identifying predictors of coeliac disease. Clinical and laboratory data were analysed up to seven years prior to diagnosis.

The results show that certain mild but persistent abnormalities precede clinical diagnosis and may represent early indicators of the disease.

Among the main predictive factors is a reduction in haemoglobin, even when values fall within the normal range. This finding, indicative of subclinical anaemia, is particularly significant in women, among whom the risk of a future diagnosis of coeliac disease is more than five times higher than in people without this condition. A significant increase in risk is also observed in men, albeit to a more moderate extent.

A further factor is a reduction in mean corpuscular volume (MCV), frequently associated with iron deficiency and malabsorption mechanisms, aspects linked to the pathogenesis of coeliac disease. Concurrently, the study highlights an increase in liver enzymes (ALT and AST), often still within normal limits, but significantly higher in individuals who will develop the disease.

BMI is a further indicator: lower values, although still within the normal range, are associated with an increased risk of future diagnosis. However, compared to haematological and liver parameters, BMI shows less marked variations over time.

From a clinical perspective, the presence of recurrent gastrointestinal symptoms, such as abdominal pain or chronic diarrhoea, significantly increases the risk of coeliac disease. These manifestations are part of the symptomatology of coeliac disease and may also be present in a mild or intermittent form in the early stages of the disease.

Even more significant is the association with chromosomal abnormalities, such as Down’s syndrome or Turner’s syndrome, conditions in which the risk of developing coeliac disease is up to ten times higher. These findings reinforce the importance of genetic factors in predisposition to the condition.

A key finding from the study is that these clinical and laboratory abnormalities can be detected up to 7 years before diagnosis, indicating a long preclinical phase characterised by weak but persistent signals. In particular, around 70% of patients presented with at least one of these indicators at the time of diagnosis, whilst a significant proportion had already exhibited them in previous years.

The research findings confirm and expand upon the evidence already present in the literature, emphasising the central role of anaemia and gastrointestinal symptoms as early signs of the disease, whilst also highlighting the importance of less commonly considered parameters, such as liver enzymes and BMI.

From a clinical perspective, the study suggests the need for greater attention to these ‘weak’ signals, particularly in young adults. The integration of decision-support systems into clinical practice could enable a more early diagnosis of coeliac disease, promptly directing at-risk individuals towards appropriate serological tests.