Enfermedad celíaca

Sinónimos: enteropatía sensible al gluten, enfermedad celíaca, esprue celíaco

Antecedentes

Coeliac disease, also known as gluten-sensitive enteropathy, is an autoimmune inflammatory systemic disorder provoked by an immune-mediated response to dietary gluten, a protein found in wheat, rye and barley. It is characterized by small bowel enteropathy (villous atrophy, intra-epithelial lymphocytosis, and crypt hyperplasia), a wide range of gastrointestinal and/or systemic symptoms, and the presence of coeliac-specific autoantibodies.

Etiología

The aetiology of coeliac disease is multifactorial, involving a combination of genetic, environmental, and immunological factors. HLA types HLA-DQ2 (90%) or HLA-DQ8 are found in most patients with coeliac disease; however many people with these genes do not develop coeliac disease, suggesting that other environmental or immunological factors are needed to trigger the development of the condition. HLA typing indicating lack of DQ2 or DQ8 has a high negative predictive value, which can be useful if trying to exclude coeliac disease.

Environmental risk factors for coeliac disease include:¹

• Being small for gestational age.

• Elective (but not emergency) caesarean delivery.

• Infection with rotavirus or campylobacter. (Rotavirus vaccination may be protective).

• Lack of helicobacter pylori colonisation.

• Use of proton pump inhibitors.

• Use of antibiotics.

• Higher maternal educational achievement.

• Maternal non-smoking status.

Epidemiología²

Coeliac disease has historically been reported to affect 1% of the global population. The prevalence is the same in the UK; however, only 10-20% will have been diagnosed as having coeliac disease. Coeliac disease affects all ethnic groups but there are higher rates in those of European descent, people from Saudi Arabia and people from the Saharawi (an ethnic group from the Western Sahara). Women are diagnosed more frequently than men.

There is evidence that the incidence of coeliac disease has increased over the past 50 years with some estimates of current prevalence being as high as over 3%.¹

Coeliac disease is more common in those with other autoimmune conditions. It occurs in up to 16.4% of those with type 1 diabetes.

There is a familial tendency; 7.5% of first degree relatives will be affected with 8.9% of siblings, 7.9% of offspring, 3% of parents and 70% of identical twins also having the disease.

Coeliac disease can develop at any age, including in the elderly. This may be as a result of longstanding previously undiagnosed coeliac disease, but it is also may result from new loss of gluten tolerance. However, recent studies suggest that the majority of people with coeliac disease develop it before the age of 10 years.¹

Presentación

Coeliac disease can be difficult to recognise because of the wide variation in symptoms and signs. Many cases may be asymptomatic. There may be a very long delay from the onset of coeliac disease symptoms until the diagnosis is made.

Symptoms can be divided into gastro-intestinal and extra-intestinal and also separately into those most typically experienced by adults and children. There are few pathognomonic symptoms but this is a list of the most commonly reported.

Síntomas gastrointestinales:

Adultos:

• Diarrea.

• Pérdida de peso inexplicada.

• Hinchazón.

• Distensión abdominal.

• Molestias abdominales.

• Náuseas.

• Vómitos.

• Steatorrhea.

• Estreñimiento.

Niños:

• Poor weight gain.

• Decreased appetite.

• Irritabilidad.

• Diarrea.

• Distensión abdominal.

• Vómitos.

• Estreñimiento.

Extra-intestinal symptoms

These are mostly the result of nutritional deficits due to the malabsorption caused by the enteropathy.

Adultos:

• Dermatitis herpetiforme. This intensely itchy vesicular rash is pathognomonic for coeliac disease. Almost all patients with the rash have either detectable villous atrophy (approximately 75%) or minor mucosal changes.

• Symptoms of anaemia: fatigue, pallor, breathlessness.

• Debilidad muscular.

• Chronic headaches.

• Ataxia.

• Parestesias.

• Artralgia.

• Mialgia.

• Bone pain.

• Osteopenia or osteoporosis with associated fractures.

• Infertilidad.

• Recurrent pregnancy loss.

Niños:

• Dermatitis herpetiforme. This intensely itchy vesicular rash is pathognomonic for coeliac disease. Almost all patients with the rash have either detectable villous atrophy (approximately 75%) or minor mucosal changes.

• Symptoms of anaemia: fatigue, pallor, breathlessness.

• Symptoms of ADHD (though this remains controversial).

• Artralgia.

• Mialgia.

• Bone pain.

• Short stature.

• Defectos del esmalte dental.

• Pubertad retrasada.

NICE Guidance³

The National Institute for Health and Care Excellence (NICE) recommends that serological testing for coeliac disease should be offered for people:

• Quienes tienen síntomas abdominales o gastrointestinales persistentes e inexplicables.

• Quienes tienen un crecimiento vacilante.

• Con fatiga prolongada.

• Con pérdida de peso inesperada.

• Con úlceras bucales severas o persistentes.

• Quienes tienen deficiencia inexplicada de hierro, vitamina B12 o folato.

• Con diabetes tipo 1 (en el momento del diagnóstico).

• Con enfermedad tiroidea autoinmune (en el momento del diagnóstico).

• Con síndrome del intestino irritable (SII) - en adultos.

• Quiénes son los familiares de primer grado de personas con enfermedad celíaca.

NICE también recomienda pruebas serológicas para la enfermedad celíaca en personas con cualquiera de los siguientes:

• Trastorno metabólico óseo (reducción de la densidad mineral ósea u osteomalacia).

• Síntomas neurológicos inexplicados (particularmente neuropatía periférica o ataxia).

• Subfertilidad inexplicada o aborto recurrente.

• Enzimas hepáticas persistentemente elevadas de causa desconocida.

• Defectos del esmalte dental.

• Síndrome de Down.

• Síndrome de Turner.

Lamellar ichthyosis has also been reported in association with CD.⁴

Síntomas neurológicos en la enfermedad celíaca⁵

Coeliac disease is associated with neurological and psychiatric disorders. Cerebellar ataxia is the most common of these; peripheral neuropathy, epilepsy, headaches and mild cognitive impairment ("brain fog") have also been described alongside depression, bipolar disorder, excessive anxiety, irritability, schizophrenia, attention-deficit/hyperactivity disorder, autism, and sleep complaints dementia and depression.

The pathophysiology of these associations remains controversial but includes gluten-mediated pathogenesis, including antibody cross-reaction, deposition of immune-complex, direct neurotoxicity, and vitamin or nutrient deficiency. Also anti-neuronal antibodies may be an additional aetiological factor for neurological involvement in CD. One study detected the presence of anti-neuronal antibodies in 61% of patients with coeliac disease and neurological symptoms; in more than 50% of patients, the antibodies disappeared after one year of adherence to a gluten-free diet, accompanied by improvement/disappearance of neurological symptoms.

Investigaciones⁶

Siempre tenga un umbral bajo para volver a evaluar a las personas si desarrollan algún síntoma de enfermedad celíaca.

Autoanticuerpos específicos

Coeliac disease-specific antibodies include auto-antibodies against tissue transglutaminase type 2 (tTGA2), including endomysial antibodies (EMAs), and antibodies against deamidated forms of gliadin peptides (DGPs). These are measured in blood. NICE recommends:⁶

• Para sospecha de enfermedad celíaca en jóvenes y adultos:

  • Inmunoglobulina A total (IgA) y transglutaminasa tisular IgA (tTG) como primera opción.

  • EMAs IgA si tTG IgA es débilmente positivo.

  • Considere usar IgG EMA, IgG DGP o IgG tTG si IgA es deficiente.

• Para sospecha de enfermedad celíaca en niños:

  • IgA total e IgA tTG como primera opción.

  • Considere usar IgG EMA, IgG DGP o IgG tTG si IgA es deficiente.

• HLA DQ2 (DQ2.2 and DQ2.5)/DQ8 testing should only be used in the diagnosis of coeliac disease in specialist settings (eg, children who are not having a biopsy, or people who already have limited gluten ingestion and choose not to have a gluten challenge).

Otras investigaciones

• FBC shows anaemia in 50%; iron and folate deficiency are both common (microcytes and macrocytes), hypersegmented leukocytes and Howell-Jolly bodies (splenic atrophy). B12, folate, ferritin, LFTs, calcium and albumin should also be tested.

• LFTs may show elevated transaminases which should return to normal on a gluten-free diet (GFD). If they don't, associated autoimmune disease, for example, primary biliary cirrhosis, autoimmune hepatitis or primary sclerosing cholangitis should be considered.

• Los estudios de bario del intestino delgado son ocasionalmente necesarios para excluir otras causas de malabsorción y diarrea y para diagnosticar complicaciones raras como obstrucción o linfoma.

Confirmación de biopsia

The established diagnostic process for coeliac disease has been a two-step process, involving both a blood test to look for antibodies, and endoscopic biopsy to assess damage to the intestine. However, the British Society of Gastroenterology (BSG) issued interim new guidance for the diagnosis of coeliac disease, supported by Coeliac Disease UK, during the covid pandemic, prompted by the pause in non-urgent endoscopies. The new recommendations are that for many adults, the diagnosis can be made on the basis of blood tests alone. The guidelines were due to be updated again in 2025 but, at the time of writing, no update was available.⁷ International guidance still recommends biopsy diagnosis in adults.⁸

No todos los pacientes serán aptos para el enfoque sin biopsia. Para cumplir con los criterios, el paciente debe tener menos de 55 años, presentar síntomas de enfermedad celíaca, y que:

• No necesita una endoscopia para descartar otras condiciones.

• Tiene niveles de anticuerpos (IgA transglutaminasa tisular) al menos 10 veces por encima del límite superior de lo normal.

• Tiene una segunda prueba de sangre positiva para anticuerpos (anticuerpos antiendomisio (EMA) o transglutaminasa tisular si EMA no está disponible).

Guidelines have recommended a no-biopsy diagnosis for most children since 2013.⁹

El análisis de sangre inicial puede ser realizado por un médico de cabecera, pero la decisión de si se necesita una endoscopia con biopsia y el diagnóstico final de la enfermedad celíaca aún deben ser realizados por un gastroenterólogo.

Patients still requiring a biopsy need to stay on gluten until it has been performed - this needs to be at least 6 weeks of 3 meals a day containing gluten. The biopsy is obtained by upper gastrointestinal endoscopy or by suction capsule.

El examen histológico de la mucosa muestra clásicamente 'atrofia vellosa subtotal' y resulta en malabsorción - sin embargo, la mucosa tiene un grosor normal, la atrofia vellosa es compensada por la hiperplasia de criptas. Debería haber una remisión clínica completa al excluir el gluten de la dieta.

Bajo estas circunstancias, la presencia de tTGA o EMAs en el momento del diagnóstico y su desaparición tras la exclusión del gluten, significa que solo es necesario realizar una biopsia adicional (e incluso un desafío con gluten adicional y más biopsias) si aún hay dudas.

Derivación⁶

• Refer young people and adults with positive serological test results to a gastrointestinal specialist for endoscopic intestinal biopsy to confirm or exclude coeliac disease.

• Refer children with positive serological test results to a paediatric gastroenterologist or paediatrician with a specialist interest in gastroenterology for further investigation for coeliac disease.

• Refer people with negative serological test results to a gastrointestinal specialist for further assessment if coeliac disease is still clinically suspected.

Diagnóstico diferencial

SII, lactosa u otro intolerancias alimentarias, colitis (incluyendo enfermedad inflamatoria intestinal), and other causes of malabsorción.

Sensibilidad al gluten no celíaca¹⁰

This is an umbrella term and may incorporate a wide range of possible clinical features. Some people report gluten-related symptoms but without evidence of coeliac disease. There is evidence suggesting that, even in the absence of coeliac disease, gluten-based products can induce abdominal symptoms which may present as IBS. The spectrum of gluten-related disorders includes coeliac disease, wheat allergy and non-coeliac gluten sensitivity. In all three conditions symptoms improve on the withdrawal of gluten.

La verdadera prevalencia en la población general es desconocida y actualmente no existen biomarcadores específicos para identificar la sensibilidad al gluten no celíaca. El resultado a largo plazo para estos pacientes también es desconocido.

Manejo

Treatment with a lifelong strict gluten-free diet is the only coeliac disease treatment of known effectiveness. A low-gluten diet is ineffective; it is important that all gluten, including traces and cross-contamination, is avoided completely.

Starting a gluten-free diet rapidly induces clinical improvement, which is mirrored by the mucosa. The diet consists of no wheat, barley, rye, or any food containing them. Information regarding foods that can be prescribed for people with coeliac disease can be found in Appendix 2 (Borderline substances) of the British National Formulary (BNF) and the BNF for children.^{11 12}

Información y soporte⁶

Explique a las personas que se considera que están en riesgo de desarrollar enfermedad celíaca que un diagnóstico tardío, o una enfermedad celíaca no diagnosticada, puede resultar en problemas de salud continuos y complicaciones graves a largo plazo.

Provide sources of information on the disease, including national and local specialist coeliac groups and dieticians with a specialist knowledge of coeliac disease.

A dietician should explain the importance of a gluten free diet and give them information to help them follow it. This should include:

• Información sobre qué tipos de alimentos contienen gluten y alternativas adecuadas, incluyendo sustitutos sin gluten.

• Explicaciones sobre el etiquetado de alimentos. Las Regulaciones de Información Alimentaria (2014) establecen que todos los alérgenos (por ejemplo, trigo, centeno, cebada y avena) deben destacarse en la lista de ingredientes.

• Information sources about gluten free foods, recipe ideas and cookbooks.

• Cómo manejar situaciones sociales, comer fuera y viajar lejos de casa, incluyendo viajes al extranjero.

• Evitar la contaminación cruzada en el hogar y minimizar el riesgo de ingesta accidental de gluten al comer fuera.

• El papel de los grupos de apoyo para celíacos a nivel nacional y local, incluyendo Coeliac UK.

• Food labelling in the UK and the EU is clear with all allergens being labelled in bold. Some foods are specifically labelled "Gluten Free" but any foods not containing (or which do not state "may contain") wheat, barley, rye or oats are safe for people with coeliac disease. Some foods contain wheat starch from which the gluten has been removed. These are safe for people with coeliac disease to eat although a proportion of people with coeliac disease will also have a separate wheat intolerance.

Explique a las personas con enfermedad celíaca (y a sus familiares o cuidadores, cuando sea apropiado):

• Que pueden necesitar tomar suplementos específicos como calcio o vitamina D si su ingesta dietética es insuficiente.

• Que pueden optar por incluir avena sin gluten en su dieta en cualquier etapa y se les aconsejará si deben continuar consumiendo avena sin gluten dependiendo de su respuesta inmunológica, clínica o histológica.

Monitoreo⁶

• Consider referring people with coeliac disease for endoscopic intestinal biopsy if continued exposure to gluten has been excluded and:

  • Los títulos serológicos se mantienen persistentemente altos y muestran poco o ningún cambio después de 12 meses; o

  • They have persistent symptoms, including diarrhoea, abdominal pain, weight loss, fatigue, or unexplained anaemia.

• Ofrecer una revisión anual a las personas con CD. Durante la revisión:

  • Mide peso y altura.

  • Revisar síntomas.

  • Consider the need for assessment of diet and adherence to the gluten free diet.

  • Considere la necesidad de asesoramiento dietético y nutricional especializado.

• Consider the need for a dual-energy X-ray absorptiometry (DXA) scan (in line with the NICE guideline on osteoporosis) or active treatment of bone disease.¹³

• También considere la necesidad de pruebas de sangre específicas, el riesgo de complicaciones a largo plazo y comorbilidades, y la necesidad de derivación a un especialista.

• Las pruebas de sangre que pueden necesitar ser consideradas incluyen FBC, LFTs, calcio y albúmina, B12, folato, ferritina sérica. La baja hemoglobina, folato de glóbulos rojos y ferritina sérica pueden sugerir una malabsorción persistente que justifique una evaluación adicional.

Enfermedad celíaca no responsiva y refractaria⁶

For people with coeliac disease who have persistent symptoms despite advice to exclude gluten from their diet, most will be due to ongoing gluten intake. However it is important to:

• Revisar la certeza del diagnóstico original.

• Remitir a la persona a un dietista especializado para investigar la exposición continua al gluten.

• Investigar posibles complicaciones o condiciones coexistentes que puedan estar causando síntomas persistentes, como el SII, intolerancia a la lactosa, sobrecrecimiento bacteriano, colitis microscópica o colitis inflamatoria.

• Refer people with apparent refractory CD to a specialist centre for further investigation.

Complicaciones⁶

Delayed diagnosis of CD may result in continuing ill health, osteoporosis, miscarriage, and a modest increased risk of intestinal malignancy (in adults), as well as growth failure, delayed puberty, and dental problems (in children).

• Nutrient deficiencies - for example, vitamin D and iron.

• Osteoporosis.

• Cancer risk - there is a 3-times higher risk of lymphoma than the general population.¹⁴ Intestinal lymphoma usually presents with the return of bowel symptoms, although it usually responds poorly to treatment.

• Yeyunitis ulcerativa.

• Functional hyposplenism: some degree of splenic atrophy is present in most patients with coeliac disease. They are eligible for flu vaccines and other vaccines reserved for those with immunosuppression.

• Untreated coeliac disease is associated with infertility in men and women but this resolves on a gluten-free diet.

• Poor foetal outcome in pregnant women with undiagnosed coeliac disease but not in diagnosed coeliac disease.⁷

It has historically been difficult for people to maintain a fully gluten-free diet, avoiding all cross-contamination. There are more gluten-free foods available than ever before and many restaurants are aware of the needs of someone with coeliac disease. The long-term health risks for patients who comply poorly with a gluten free diet include nutritional deficiency and reduced bone mineral density. Many coeliac patients have an inadequate energy intake. Poor absorption often leads to inadequate intake of calcium and vitamin B6 and vitamin D. About a quarter of patients with coeliac disease have osteoporosis of the lumbar spine compared with 5% of matched controls. Bone mineral density improves significantly with a gluten free diet.