Edit concept Question Editor Create issue ticket

Celiac Disease

Refractory celiac disease

Coeliac disease (celiac sprue, nontropical sprue, endemic sprue, gluten enteropathy) is a chronic autoimmune disorder of the small intestine that results in an inability to tolerate gliadin, a prolamin found in wheat. Symptoms include pain, chronic constipation, chronic diarrhoea, failure to thrive and fatigue.


Presentation

Diarrhea is the most common symptom in untreated celiac sprue and is present in 45-85% of all patients. Diarrhea caused by celiac disease is due to the maldigestion and malabsorption of ingested nutrients. The stools might be watery or semiformed, light tan or gray, and oily or frothy and have a characteristic foul odour. In infants and young children, extensive diarrhea often leads to severe dehydration, electrolyte depletion, and metabolic acidosis [6].

Malabsorption of ingested fat (steatorrhea) results in the delivery of excessive dietary fat to the large bowel. This results in the production of hydroxy fatty acids by bacteria, which causes secretion of fluids into the intestine. Flatulence (seen in 28% of patients) and borborygmus (seen in 35-72% of patients) results from the release of intestinal gas by the bacterial florae feasting on undigested and unabsorbed food materials and often becomes excessive and in some cases, explosive.

Weight loss (seen in 45% of all patients) is variable because some patients might compensate for the malabsorption by increasing food intake. In infants and young children with untreated celiac disease, failure to thrive and growth retardation are relatively common.

Anemia (seen in 10-15% of patients) is usually due to impaired absorption of iron or folate from the proximal small intestine. In severe celiac disease with ileal involvement, absorption of vitamin B-12 might be impaired. A bleeding diathesis is usually caused by prothrombin deficiency due to impaired absorption of fat-soluble vitamin K.

Osteopenia and osteoporosis might cause bone pain for several reasons, including defective calcium transport by the diseased small intestine, vitamin D deficiency, and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids.

Easy Bruising
  • bruising Depression or anxiety Fatigue Growth delay in children Hair loss Itchy skin with a rash ( dermatitis herpetiformis ) Missed menstrual periods Mouth ulcers Muscle cramps and joint pain Nosebleeds Seizures Tingling or numbness in the hands or[nlm.nih.gov]
  • bruising Bone/joint pain Swollen ankles/hands Mouth ulcers/canker sores Infertility in both sexes, miscarriages Feeling depressed/depression Migraine headaches Unexplained neurological conditions Table 2.[web.archive.org]
  • bruising and nose bleeds fluid retention infertility persistent hunger iron deficiency anemia malnutrition and nutrition deficiencies, including a lack of vitamin B12, D, and K mouth sores and tooth discoloration muscle wasting, muscle weakness, and[medicalnewstoday.com]
Anemia
  • METHODS: This cross-sectional analytical study was conducted among children aged 1 to 12 years of age with moderate-to-severe iron deficiency anemia and control children without anemia.[ncbi.nlm.nih.gov]
Weight Loss
  • This article describes a toddler who initially presented with recurrent diarrhea and weight loss with a significant secondary hypokalemia. His initial examination included screening for celiac disease, but the serology was negative.[ncbi.nlm.nih.gov]
Fatigue
  • Our patient presented to clinic with complaints of a burning tongue for the past two years as well as occasional loose stools and fatigue. Work-up revealed iron deficiency anemia, zinc deficiency and an abnormal celiac panel.[ncbi.nlm.nih.gov]
Weakness
  • Improvement of patient's weakness and laboratory abnormalities was obvious after treatment with gluten free diet, vitamin D, calcium and iron.[ncbi.nlm.nih.gov]
  • She had reached a serious state of depletion and weakness from her self imposed starvation, refusing all food and regurgitating that fed to her by gavage.[doi.org]
Malnutrition
  • Neurological symptoms were preceded by two months of gastrointestinal symptoms such as vomiting, abdominal distention, and clear signs of malnutrition and weight loss.[ncbi.nlm.nih.gov]
  • Damage of the small intestine may cause a variety of clinical signs ranging from isolated long-standing iron-deficiency anemia refractory to iron supplementation to forms of severe malnutrition that may become life threatening.[doi.org]
Diarrhea
  • The patient's diarrhea resolved after initiation of a gluten free diet. He gained 25 kilograms after discharge and did not require further hospitalizations for diarrhea.[ncbi.nlm.nih.gov]
Abdominal Pain
  • We report here a 6-year-old girl presenting with malaise, abdominal pain, loss of appetite, abdominal distension.[ncbi.nlm.nih.gov]
Failure to Thrive
  • In young children, gastrointestinal presentations are common and include chronic diarrhea, failure to thrive, and abdominal distention; however, extraintestinal manifestations are becoming increasingly more common.[ncbi.nlm.nih.gov]
Chronic Diarrhea
  • A fifteen-year-old girl was presented for chronic diarrhea and abdominal pain. Her physical examination had determined multiple hypopigmented patches.[ncbi.nlm.nih.gov]
  • In young children, gastrointestinal presentations are common and include chronic diarrhea, failure to thrive, and abdominal distention; however, extraintestinal manifestations are becoming increasingly more common.[doi.org]
Nausea
  • The most common treatment-emergent adverse events in the Nexvax2 participants were headache (52%), diarrhoea (48%), nausea (37%), abdominal pain (26%), and abdominal discomfort (19%).[ncbi.nlm.nih.gov]
  • […] include: Abdominal pain, bloating, gas, or indigestion Constipation Decreased appetite (may also be increased or unchanged) Diarrhea, either constant or off and on Lactose intolerance (common when the person is diagnosed, often goes away after treatment) Nausea[nlm.nih.gov]
  • These symptoms include: Nausea or vomiting Bloating or a swelling in the belly Diarrhea Constipation Pale, foul-smelling stool (steatorrhea) Weight loss Not everyone with celiac disease will have these symptoms.[webmd.com]
Aphthous Stomatitis
  • Recurrent aphthous stomatitis was reported in 26 patients (53.0%) and in 13 (25.5%) controls ( p 0.005). Dental enamel disorders were reported in 7 patients (14.3%) and in 0 controls ( p 0.002), with none having geographic tongue.[ncbi.nlm.nih.gov]
  • Slebioda Z, Szponar E, Kowalska A: Etiopathogenesis of recurrent aphthous stomatitis and the role of immunologic aspects: literature review. Arch Immunol Ther Exp (Warsz) 2014;62:205-215.[dx.doi.org]
  • Gluten sensitivity enteropathy in patients with recurrent aphthous stomatitis. BMC Gastroenterol. 2009;9:44. Cheng J, Malahias T, Brar P, Minaya MT, Green PH.[jcda.ca]
Osteoporosis
  • Secondary osteoporosis occurs in many diseases. Celiac disease-induced osteoporosis is the consequence of secondary hyperparathyroidism.[ncbi.nlm.nih.gov]
Bone Pain
  • In patients with bone pain, non traumatic fractures and muscle weakness, osteomalacia should be kept in mind and proper diagnostic work-up should be performed to identify the underlying cause of osteomalacia such as celiac disease.[ncbi.nlm.nih.gov]
  • Symptoms of celiac disease vary and may include digestive problems, anemia, skin rash, and joint and bone pain. If you have celiac disease, you should not eat foods that contain gluten (including wheat, rye, barley, and oats).[my.clevelandclinic.org]
  • They may experience weight loss, gastric distension, features of other associated disorders such as diabetes, dermatitis herpetiformis (a particular type of skin disorder), and bone pain from osteoporosis/osteomalacia.[ddc.musc.edu]
  • Further symptoms vary and can include mouth ulcers, extreme fatigue, bone pain and others. A serious skin condition (called dermatitis herpetiformis) that results in an itchy rash with bumps and blisters is sometimes a result of this disease.[canada.ca]
  • Osteopenia and osteoporosis might cause bone pain for several reasons, including defective calcium transport by the diseased small intestine, vitamin D deficiency, and binding of luminal calcium and magnesium to unabsorbed dietary fatty acids.[symptoma.com]
Arthralgia
  • After three weeks she developed other symptoms such as arthralgias, malar rash, being finally diagnosed with SLE and possible autoimmune hepatitis.[ncbi.nlm.nih.gov]
  • Anemia Elevated transaminase concentrations Dementia Secretory diarrhea Folate or iron deficiency Recurrent pancreatitis Spinocerebellar syndrome Weight loss Neuropathy Occult blood Tetany Constipation Osteoporosis Enteropathy-associated T cell lymphoma Arthralgia[ajcn.nutrition.org]
Restless Legs Syndrome
  • leg syndrome (Polysdefkir et al, 2005; Gemignai et al, 2009), neuroma, fasciitis, or somatic pains resulting from anxiety or depression.[web.archive.org]
  • Central and peripheral nervous system excitability in restless legs syndrome.[dx.doi.org]
Muscular Atrophy
  • atrophy Headache Hypertransaminasemia Anemia Pubertal delay Extraintestinal symptoms A tendency towards lower clinical manifestations can be observed as age increases[ 4 ].[doi.org]
Eczema
  • Assessment for publication bias in analyses of eczema was not possible because of the limited number of studies.[doi.org]
  • Browning and Sylvia Hsu, Medical Pearl: Dermatitis herpetiformis—Potential for confusion with eczema, Journal of the American Academy of Dermatology, 54, 2, (327), (2006).[dx.doi.org]
  • In order of prevalence, clinical presentations observed in early research include 15,17 : abdominal pain eczema and/or rash headache foggy mind fatigue diarrhea depression anemia numbness in the legs, arms or fingers joint pain Despite the overlapping[questdiagnostics.com]
Purpura
  • Consider serologic testing for celiac disease with any of following: Addisons disease, amenorrhea, apthous stomatitis, autoimmune myocarditis, chronic thrombocytopenic purpura, neuropsychiatric disease, epilepsy, low trauma fracture, lymphoma, metabolic[clinicaladvisor.com]
  • Celiac disease and keratoconjunctivitis: occurrence with thrombocytopenic purpura. Arch Intern Med 1982 ; 142 : 1037. Stenhammar L and Ljunggren CG. Thrombocytopenic purpura and coeliac disease. Acta Paediatr Scand 1988 ; 77 : 764 –766.[bloodjournal.org]
  • Specifically, CE can be useful in diagnosing systemic diseases and vasculitis[ 46 ] with small bowel involvement, such as Henoch-Schonlein purpura, Churg-Strauss syndrome and Behçet disease)[ 47 - 49 ].[doi.org]
  • […] vol. 96 (pg. 146 - 149 ) 49 Gynaecological and obstetric disorders in coeliac disease: frequent clinical onset during pregnancy or the puerperium, Eur J Gastroenterol Hepatol, 1996, vol. 8 (pg. 63 - 89 ) 50 Increased risk of immune thrombocytopenic purpura[dx.doi.org]
Hyperpigmentation
  • The usual clinical presentation of DH consists of diffuse, symmetrical, grouped polymorphic lesions consisting of erythema, urticarial plaques, papules, herpetiform vesiculae, and blisters followed by erosions, excoriations, and hyperpigmentation[ 38,[dx.doi.org]
Pruritic Rash
  • Dermatitis herpetiformis, an intensely pruritic rash found most commonly on the extensor surfaces of the extremities, is a common non-gastrointestinal manifestation.[ncbi.nlm.nih.gov]
Anxiety Disorder
  • Reactive anxiety that usually ameliorates with a GFD is the predominant form of anxiety disorder in these patients.[dx.doi.org]
Headache
  • We present a 39-year-old woman with celiac disease who was on gluten-free diet for 8 years and presented with diarrhea, headache, insomnia, loss of appetite, abnormal taste, and impaired short-term memory and concentration, but with no skin lesions.[ncbi.nlm.nih.gov]
  • Credit: istockphoto Another vague complaint, headaches are common in people with celiac disease. In some cases, the disorder causes migraine headaches.[cbsnews.com]
  • Headaches are another potential symptom, but their prevalence adds a layer of complexity when it comes to diagnosis.[glutenfreeliving.com]
Peripheral Neuropathy
  • […] differential diagnosis of peripheral neuropathy in children.[ncbi.nlm.nih.gov]
  • The sensation is evidence of a nerve condition known as peripheral neuropathy. Credit: istockphoto Another vague complaint, headaches are common in people with celiac disease. In some cases, the disorder causes migraine headaches.[cbsnews.com]
  • They may suffer from abdominal distension and pain, and/or other symptoms such as: iron-deficiency anemia, chronic fatigue, chronic migraine, peripheral neuropathy (tingling, numbness or pain in hands or feet), unexplained chronic hypertransaminasemia[celiac.org]
Cerebellar Ataxia
  • ataxia in diseases classified elsewhere 2016 2017 2018 2019 Billable/Specific Code Manifestation Code Code First underlying disease, such as: celiac disease (with gluten ataxia) ( K90.0 ) cerebellar ataxia (in) neoplastic disease (paraneoplastic cerebellar[icd10data.com]
  • In two studies, cerebellar ataxia was documented in 2.7 to 5.4% of participants; in two further studies, the risk of cerebellar dysfunction was zero. Two studies found an association between coeliac disease and peripheral neuropathy.[ncbi.nlm.nih.gov]
  • Testing is also recommended when any of the following conditions are present: 1st or 2nd degree relative with celiac disease; autoimmune thyroid disease; peripheral neuropathy; cerebellar ataxia; irritable bowel syndrome; selective IgA deficiency; Type[questdiagnostics.com]
  • Bürk K, Bösch S, Müller CA, Melms A, Zühlke C, Stern M et al (2001) Sporadic cerebellar ataxia associated with gluten sensitivity. Brain 124:1013–1019 CrossRef PubMed Google Scholar 13.[dx.doi.org]
  • “Less-common neurological conditions include cerebellar ataxia with unsteadiness or incoordination, seizures or neuropsychiatric disorders,” he says.[glutenfreeliving.com]
Paresthesia
  • Carpal spasms and paresthesias of her extremities were present. Neuromuscular irritability was demonstrated by positive Chvostek and Trousseau signs.[ncbi.nlm.nih.gov]
  • Painful paresthesias can be treated using oral medications for neuropathic pain such as Lyrica or Cymbalta, or with topical medications such as Lidoderm.[web.archive.org]
  • Other symptoms of celiac disease may include: Headache Fatigue and weakness Joint pain Numbness and tingling (paresthesia) of the hands and feet Osteoporosis due to decreased absorption of calcium and vitamin D Skin rash Abdominal pain GERD and heartburn[medicinenet.com]
  • […] abdominal pain - 34-64% of patients Extraintestinal symptoms Extraintestinal symptoms may include the following: Anemia - 10-15% of patients Osteopenia and osteoporosis - 1-34% of patients Neurologic symptoms - 8-14% of patients; include motor weakness, paresthesias[emedicine.com]

Workup

The diagnosis is focused on testing for specific antibodies. For instance, if excessively high levels of endomysial and anti-tissue transglutaminase antibodies are found, the individual most definitely has celiac disease.

High levels of another antibody, anti-gliadin, may also be detected, but this doesn’t always mean a person has celiac disease [7]. However, anti-gliadin antibody levels are important when monitoring response to treatment, this is because they will usually begin to fall after a few months of successful treatment of celiac disease with a gluten-free diet.

People who test positive for celiac disease antibodies will be subjected to intestinal biopsy to confirm the diagnosis. A small intestinal biopsy is performed with an esophagogastroduodenoscopy (EGD). Loss of villi and other characteristics of celiac disease, such as an increased number of lymphocytes are present.

Thrombocytosis
  • Nelson EW, Ertan A, Brooks FP, et al: Thrombocytosis in patients with celiac sprue. Gastroenterology 1976;70:1042-1044. Caroccio A, Giannitrapani L, Di Prima L, et al: Extreme thrombocytosis as a sign of coeliac disease in the elderly; case report.[dx.doi.org]
  • Extreme thrombocytosis as a sign of coeliac disease in the elderly: case report. Eur J Gastroenterol Hepatol 2002 ; 14 : 897 –900. Schafer AI. Thrombocytosis. N Engl J Med 2004 ; 350 : 1211 –1219. Pittschieler K.[bloodjournal.org]
  • […] transaminase and alanine transaminase levels Minimal elevation common in celiac disease; presumably autoimmune Decreased albumin level Malnutrition Elevated calcium level, decreased phosphate level Vitamin D deficiency, secondary hyperparathyroidism Thrombocytosis[aafp.org]
Macrocytosis
  • Concomitant iron deficiency as can be seen in CD can result in atypical findings on the blood smear, and patients with deficiencies of folate and vitamin B 12 may not present with the characteristic macrocytosis.[bloodjournal.org]
Hyponatremia
  • The patient had normal anion-gap metabolic acidosis (pH   7.16) with persisting hypokalemia, hyponatremia, hypomagnesemia and hypophosphatemia. In addition, severe vitamin deficiencies and coagulopathy were present.[ncbi.nlm.nih.gov]
HLA-DQ2
  • CONCLUSION: HLA-CeD is not more frequent in IBD patients, with an even lower frequency of HLA-DQ2 and -DQ8 in UC and CD respectively.[ncbi.nlm.nih.gov]
HLA-DR3
  • We confirmed the high frequency of HLA-DR3 in this population, and we were also able to demonstrate the additional risk of developing celiac disease imparted by HLA-DR7.[ncbi.nlm.nih.gov]
  • Altogether 655 schoolchildren (18.1 percent) carried the HLA-DQA1*05-DQB1*02 (HLA-DR3–DQ2) haplotype, and 1411 (39 percent) carried either the HLA-DR3–DQ2 or the HLA-DQ-A1*03-DQB1*0302 (HLA-DR4–DQ8) haplotype.[nejm.org]
  • We confirmed the high frequency of HLADR3 in this population, and we were also able to demonstrate the additional risk of developing celiac disease imparted by HLA‐DR7.[doi.org]

Treatment

The primary management of celiac disease is dietary. Complete elimination of gluten-containing grain products (including wheat, rye, and barley) is essential to treatment. However, complete avoidance of gluten-containing grain products is often difficult for patients to achieve and maintain. This is because certain products like wheat flour are virtually ever present in the American diet [8].

A small percentage of patients with celiac disease fail to respond to a gluten-free diet. In some patients who are refractory, corticosteroids can prove very helpful. In patients who fail to respond to corticosteroids, other comorbid conditions, such as lymphomas of the small intestine, have to be ruled out [9] [10].

Prognosis

With early removal of gluten from the diet, it becomes less likely for health complications to develop. The body quickly returns to health, in many cases, after the individual begins strict gluten-free nutrition.

To achieve optimal health, the gluten free diet must be maintained for life [5].

Etiology

Celiac disease is caused by a reaction to gliadin, a prolamin (gluten protein) found in wheat, and similar proteins found in the crops of the tribe Triticeae (which includes other common grains such as barley and rye).

Wheat subspecies (like spelt and durum) and related species (such as barley, rye, triticale and Kamut) also induce symptoms of celiac disease [2]. A small minority of people with celiac disease also react to oats. It is most probable that oats produce symptoms due to cross-contamination with other grains in the fields or in the distribution channels. Therefore, oats are generally not recommended. However, many companies assure the 'purity' of oats and are therefore still able to be consumed through these sources.

Other cereals like maize, millet, sorghum, teff, rice, and wild rice are safe for individuals with coeliac to ingest, as well as non-cereals like amaranth, quinoa, and buckwheat. Non-cereal carbohydrate-rich foods such as potatoes and bananas do not contain gluten and do not trigger symptoms of celiac disease.

Epidemiology

Celiac disease isn’t common. Its prevalence is decreased among blacks and those of Hispanic or Asian ethnicity. The incidence of symptomatic celiac disease in adults is estimated at 2 to 13 per 100,000 per year [3].

Sex distribution
Age distribution

Pathophysiology

Celiac disease has a strong hereditary connotation. The prevalence of the condition in first-degree relatives is 10% approximately.

A strong association exists between celiac disease and two human leukocyte antigen (HLA) haplotypes (DQ2 and DQ8). Damage to the intestinal mucosa is seen with the presentation of gluten-derived peptide gliadin, made up of 33 amino acids, by the HLA molecules to helper T cells. Helper T cells mediate the inflammatory response. Endogenous tissue transglutaminase deamidates gliadin into a negatively charged protein thereby increasing its immunogenicity. Absence of intestinal villi and lengthening of intestinal crypts characterize mucosal lesions in untreated celiac disease. More lymphocytes infiltrate the epithelium (intraepithelial lymphocytes). Destruction of the absorptive surface of the intestine leads to a maldigestive and malabsorption syndrome [4].

Prevention

The disease cannot be prevented.

Summary

Also known as celiac sprue and gluten sensitive enteropathy, celiac disease is mostly a chronic disorder of the digestive tract which brings about an inability to tolerate gliadin which is the alcohol soluble fraction of gluten. The protein gluten is mostly found in rye, barley and wheat [1].

In patients with ciliac sprue, ingestion of giladin triggers an immunologically mediated inflammatory response which ends up damaging the mucosa of the intestines. This brings about maldigestion and malabsorption of food nutrients.

Patient Information

Celiac disease is reaction to eating gluten. Gluten is a protein that is seen in wheat, rye and barley. 

In people that have celiac disease, consumption of this protein causes an immune response in your small intestine. Over a period of time the reaction damages the small intestine and this leads to malabsorption (inability to absorb other nutrients). 

With this intestinal damage, weight loss, bloating and diarrhea in some cases sets in. After a while, the brain, nervous system, liver, and other organs end up getting deprived of important nutrients. 

In children with this condition, malabsorption can affect development and growth. This intestinal irritation can lead to stomach pain especially after eating. 

There is no total cure for this disease but it can be controlled by following a strict gluten free diet. The diet can also lead to gradual healing of the intestine. 

References

Article

  1. Cristofori F, Fontana C, Magistà A, Capriati T, Indrio F, Castellaneta S, et al. Increased Prevalence of Celiac Disease Among Pediatric Patients With Irritable Bowel Syndrome: A 6-Year Prospective Cohort Study. JAMA Pediatr. Apr 21 2014.
  2. Squires JE, Fei L, Cohen MB. Role of Celiac Disease Screening for Children With Functional Gastrointestinal Disorders. JAMA Pediatr. Apr 21 2014.
  3. Ludvigsson JF, Zingone F, Tomson T, Ekbom A, Ciacci C. Increased risk of epilepsy in biopsy-verified celiac disease: A population-based cohort study. Neurology. May 1 2012;78(18):1401-7.
  4. Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA. ACG Clinical Guidelines: Diagnosis and Management of Celiac Disease. Am J Gastroenterol. May 2013;108(5):656-76.
  5. Green PH, Cellier C. Celiac disease. N Engl J Med. Oct 25 2007;357(17):1731-43.
  6. Ludvigsson JF, Leffler DA, Bai JC, et al. The Oslo definitions for coeliac disease and related terms. Gut 2013; 62:43.
  7. AGA Institute. AGA Institute Medical Position Statement on the Diagnosis and Management of Celiac Disease. Gastroenterology 2006; 131:1977.
  8. Bai JC, Fried M, Corazza GR, et al. World Gastroenterology Organisation global guidelines on celiac disease. J Clin Gastroenterol 2013; 47:121.
  9. Rubio-Tapia A, Hill ID, Kelly CP, et al. ACG clinical guidelines: diagnosis and management of celiac disease. Am J Gastroenterol 2013; 108:656.
  10. Stenson WF, Newberry R, Lorenz R, et al. Increased prevalence of celiac disease and need for routine screening among patients with osteoporosis. Arch Intern Med 2005; 165:393.

Ask Question

5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.
By publishing this question you agree to the TOS and Privacy policy.
• Use a precise title for your question.
• Ask a specific question and provide age, sex, symptoms, type and duration of treatment.
• Respect your own and other people's privacy, never post full names or contact information.
• Inappropriate questions will be deleted.
• In urgent cases contact a physician, visit a hospital or call an emergency service!
Last updated: 2019-07-11 22:02