Given the lack of evidence on the subject, the current recommendation is to schedule a first follow-up visit 3–6 months after initiation of the GFD, or earlier if the clinical condition of the patient so requires. Subsequent visits will be scheduled every 6–12 months depending on the course of disease.4

Clinical evaluation:

Follow-up visits should include an assessment of the signs and symptoms that were present at diagnosis to verify their resolution.4 The development of new symptoms may signal the development of comorbidities associated with CD.

It is important to monitor nutritional status and growth, especially in patients with impaired growth at the time of CD diagnosis. Catch-up growth is expected within 6 months of initiation of the GFD. Other causes of short stature should be ruled out if catch-up linear growth does not occur after 1 year of strict adherence to the diet, especially in prepubertal patients.

Diagnostic tests:

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  IgA tissue transglutaminase (tTG) antibody testing is the preferred choice for serological monitoring. In half of paediatric cases, levels become negative at 1 year of the GFD,4,7 usually with greater delay in patients with higher antibody titres at diagnosis and when testing is done with chemiluminescence techniques.7 Follow-up serology testing to verify normalization of antibodies is recommended starting from 1 year of the GFD, with re-evaluation of patients in whom positive serology persists longer than 2 years.

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  At the time of diagnosis, the patient may have decreased levels of micronutrients such as iron, folate, vitamin B12 or vitamin D, which should be monitored until they normalise, with consideration of supplementation in the case of anaemia or significant deficiency.4 Thus, measurement of micronutrient levels will be performed throughout the follow-up in select cases.8,9

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  There may be mild elevation of liver enzymes at diagnosis, especially in younger patients, which usually resolves by 1 year of the GFD.10,11 Autoimmune liver disease should be considered in the differential diagnosis of persistent hypertransaminasaemia.12

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  Coeliac disease is associated with an increased risk of autoimmune thyroid disease.4 Although there is no evidence on the need to monitor thyroid function during follow-up, regular measurement of thyroid-stimulating hormone (TSH) seems reasonable in patients with other autoimmune diseases, especially type 1 diabetes (T1D), during puberty (especially in female patients) and in the case of persistent positive serology for CD.13

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  Decreased bone mineral density (BMD) has been observed in paediatric patients with CD at the time of diagnosis,14 with subsequent improvement with the GFD. However, studies assessing the risk of bone fracture in paediatric patients with CD have yielded contradictory results, so the current evidence does not support the recommendation of a bone density scan at diagnosis or during the follow-up.15 A bone density scan should be performed in patients with risk factors such as suspected bone disease (more than 2–3 long bone fractures or vertebral fracture in absence of local disease or high-energy trauma), persistent malabsorption syndrome, potential CD with a regular diet or lack of adherence to the GFD.

The usefulness of clinical evaluations and symptom monitoring to assess adherence to the GFD is limited, as there is an increasing number of oligosymptomatic patients. Standardised dietary interviews conducted by a dietitian/nutritionist or dietary questionnaires have proven more sensitive for the identification of dietary transgressions.4 There are brief and easy to administer questionnaires16 that may be useful in clinical practice, but they have not been validated in paediatric patients, with the exception of the Coeliac Dietary Adherence Test (CDAT), validated for use in patients aged more than 12 years.17

Normalization of tTG antibody titres can serve as an indirect marker of mucosal healing. Any elevation thereafter can be indicative of significant dietary transgressions, but negative results do not guarantee strict adherence to the diet.4

Following gluten consumption, gluten immunogenic peptides (GIPs) are detectable in urine for 3–24 hours and in faeces for up to 7 days, and the test offers a good sensitivity and specificity. Repeated measurement of GIPs improves performance of this test for monitoring of adherence in the long term, as opposed to isolated transgressions. The interpretation of results has yet to be standardised, so it is recommended that they are used in combination with the other methods described above.4,18–20

Although symptoms tend to resolve within one year, more than half of the patients may experience some symptoms after that point in spite of the GFD.21 Dietary transgressions are the most frequent cause, but symptoms may also be due to coexisting conditions, such as functional gastrointestinal disorders.2,22

Healing of the intestinal mucosa and normalization of tTG antibodies tend to occur after 2 years of the GFD. Performance of an intestinal biopsy (IB) should be considered if serology continues to be positive after 2 years of GFD with adequate adherence or if there is uncertainty regarding the original diagnosis.2,4

In the case of suspected refractory CD (persistence of malabsorption with villous atrophy), rule out gluten intake and coexisting gastrointestinal disorders, as refractory CD is rare in the paediatric age group.4

If gluten was eliminated before the diagnosis was confirmed or after an inadequate diagnosis (criteria not met),2 a gluten challenge (GC) should be performed to reach a certain diagnosis. Human leukocyte antigen (HLA) testing can help identify patients at risk of CD. In patients with genetic risk, the first clinical and laboratory evaluation follow-up evaluation should be scheduled 1–3 months after initiation of the GC to minimise exposure to gluten, with successive follow-up evaluations every 3−6 months through 1 year. The GC should follow an established protocol, preferably avoiding critical periods of growth and development (age <5 years or puberty), with a limited gluten intake in the first year of 10−15 g (1 slice of bread has 3−5 g) and an unrestricted diet thereafter. If at 2 years of gluten exposure tTG levels continue to be negative and the patient remains asymptomatic, the probability of developing CD is low,4 although the patient should remain in follow-up and possibly undergo an IB, as there have been reports of late diagnosis.

Patients with T1D and CD tend to be asymptomatic and exhibit poorer adherence to the GFD. Notwithstanding, the recommended follow-up is the same as the one for patients with CD without T1D, with emphasis on adherence to the GFD24 and screening for thyroid disease.4

There is no evidence supporting changes in follow-up compared to immunocompetent patients, except for testing for IgG antibodies and repeating IgA antibody testing after 4 years to rule out transient IgA deficiency. The longitudinal trend in IgG antibody levels is different compared to the trends in IgA antibodies observed in immunocompetent patients, as IgG antibodies become negative in fewer than half of patients at 2 years of diagnosis and may remain positive or fluctuate for years even if mucosal healing has been achieved.25 Repetition of the IB has been proposed in patients with persistence of positive IgG antibodies for more than 2 or 3 years, especially if there is concern about adherence to treatment.26

It is defined as the presence of tTG antibodies and a compatible HLA with normal duodenal architecture (Marsh 0–1), with or without symptoms.4 Correct diagnosis requires ensuring an adequate gluten intake and number and orientation of intestinal biopsies.27 In the case of asymptomatic potential CD, the possibility of maintaining gluten in the diet while monitoring clinical and laboratory parameters every 6–12 months will be discussed with the family/patient, as more than 50% of these patients never develop the disease,4 with close monitoring of growth and bone health as well. Repetition of the IB is recommended if symptoms develop, there is an increase in antibody titres or antibody titres continue to be positive at 2 years of follow-up. Initiation of the GFD should be considered in patients with symptomatic potential CD.4,28

Starting from 1 year after initiation of the GFD, in patients with adequate control of the disease, follow-up visits can be scheduled every 1–2 years.

In certain situations (Table 2), referral to hospital-based care will be considered, and, likewise, if the patient is in follow-up at hospital, transfer to PC can be contemplated if the required conditions are met (Fig. 1).

Figure 1.

Follow-up algorithm based on the stage of disease.

(0.17MB).

The recommendations are the same as for active CD and can be found in Table 3.

According to experts, the paediatrician should start discussing the transition at age 12–13 years, develop the transition plan at 14–15 years and implement it at 18 years, although age does not seem to influence subsequent adherence to the GFD.36 This plan may be subject to variations depending on local health care organisation, the level of disease activity, the degree of adherence to the diet and the autonomy of the patient. In patients with delayed puberty, deferring transition until puberty is complete is recommended. In Spain, the transition will probably take place earlier if the patient is followed up in the paediatric PC setting compared to a paediatric gastroenterology unit.

The predictors of successful transition include long-term adequate adherence to the GFD, diagnosis before age 12 years, regular follow-up and clinical remission and negative serology before 18 years. Poor adherence to the diet is associated with lack of follow-up, having T1D and economic difficulties in relation to the GFD. The current approach is to individualise the transition to adult care and the followup in adulthood taking into account the factors mentioned aboves.39

Although the use of emerging technologies, e-health and telehealth is currently infrequent in the follow-up of patients with CD, paediatricians consider them an adequate alternative to in-person visits for patients in remission.37,40