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__NOTOC__
__NOTOC__
{{Celiac disease}}
{{Celiac disease}}
{{CMG}}
{{CMG}} {{AE}} {{MIR}}
==Overview==
The [[symptoms]] of celiac disease usually develop in the first decade of life, and start with features suggestive of [[malabsorption]] such as [[abdominal pain]] and [[Abdominal distension|distension]], [[diarrhea]], [[malnutrition]], and [[failure to thrive]] within the first few years of life. The classic [[malabsorption]] manifestation of disease is just the tip of the iceberg, and other more specific manifestations are invisible below the waterline. Natural history of celiac disease is not completely understood but if left untreated it may result in serious complications, such as [[malignancy]]. Complications of celiac disease may include [[vitamin deficiencies]], essential [[nutrient]] deficiencies, [[Tooth enamel|enamel]] [[hypoplasia]], [[neurological]] abnormalities, [[gastrointestinal]] [[malignancies]], [[hyposplenism]], [[Ulcer|ulcerative]] [[jejunitis]], and [[infertility]]. The [[prognosis]] may vary depending upon the extent of the celiac disease at the time of diagnosis and also the extent of complications and [[dietary]] deficiencies. However, the [[prognosis]] is generally regarded as good. The presence of [[Gastrointestinal tract|gastrointestinal]] [[malignancies]] is associated with a particularly poor [[prognosis]] among patients with celiac disease.
 
==Natural History, Complications, and Prognosis==
 
===Natural History===
The [[symptoms]] of celiac disease usually develop in the firs decade of life, and start with symptoms suggestive of [[malabsorption]] such as [[pain]] and [[distension]], [[Diarrhea|diarrhea,]] [[malnutrition]], and [[failure to thrive]] within the first few years of life. These are classical celiac disease findings also known as “celiac disease iceberg” manifestations. Clinical presentations in celiac disease have been described as an iceberg model. Based on the iceberg model of celiac disease, the classic [[malabsorption]] manifestation of disease is just the tip of the iceberg, and other more specific manifestations are invisible below the waterline. According to iceberg model of celiac disease, the traditional method of diagnosing celiac disease based on [[malnutrition]] manifestations is unreliable due to different [[disease]] variation with more subtle manifestations that may be unrecognized. <ref name="pmid20868314">{{cite journal |vauthors=Catassi C, Kryszak D, Bhatti B, Sturgeon C, Helzlsouer K, Clipp SL, Gelfond D, Puppa E, Sferruzza A, Fasano A |title=Natural history of celiac disease autoimmunity in a USA cohort followed since 1974 |journal=Ann. Med. |volume=42 |issue=7 |pages=530–8 |year=2010 |pmid=20868314 |doi=10.3109/07853890.2010.514285 |url=}}</ref>
 
Most people with either diagnosed or undiagnosed celiac disease have only minor [[Symptom|symptoms]] that are more inconvenient than life threatening. The few data available regarding [[quality of life]] of patients with celiac disease suggest that health‐related quality of life and [[psychological]] general well‐being are poor in undiagnosed patients, and improve with treatment in men but not significantly in women.<ref name="pmid11197241">{{cite journal |vauthors=Green PHR, Stavropoulos SN, Panagi SG, Goldstein SL, Mcmahon DJ, Absan H, Neugut AI |title=Characteristics of adult celiac disease in the USA: results of a national survey |journal=Am. J. Gastroenterol. |volume=96 |issue=1 |pages=126–31 |year=2001 |pmid=11197241 |doi=10.1111/j.1572-0241.2001.03462.x |url=}}</ref> The frequency of [[psychiatric disorders]] are also high among celiac disease patients, and the severity of [[depression]] is associated with the duration of disease left without treatment. A [[questionnaire]] study in USA reported a mean duration of [[depression]] and [[anxiety]] symptoms for 11 years before the diagnosis of celiac disease. The mentioned [[depression]] was reported to get improved in 77% of cases after treatment. A high prevalence of [[depression]] was well documented in patients with celiac disease.<ref name="pmid9548616">{{cite journal |vauthors=Ciacci C, Iavarone A, Mazzacca G, De Rosa A |title=Depressive symptoms in adult coeliac disease |journal=Scand. J. Gastroenterol. |volume=33 |issue=3 |pages=247–50 |year=1998 |pmid=9548616 |doi= |url=}}</ref><ref name="pmid20868314">{{cite journal |vauthors=Catassi C, Kryszak D, Bhatti B, Sturgeon C, Helzlsouer K, Clipp SL, Gelfond D, Puppa E, Sferruzza A, Fasano A |title=Natural history of celiac disease autoimmunity in a USA cohort followed since 1974 |journal=Ann. Med. |volume=42 |issue=7 |pages=530–8 |year=2010 |pmid=20868314 |doi=10.3109/07853890.2010.514285 |url=}}</ref><ref name="pmid25922673">{{cite journal |vauthors=Zingone F, Swift GL, Card TR, Sanders DS, Ludvigsson JF, Bai JC |title=Psychological morbidity of celiac disease: A review of the literature |journal=United European Gastroenterol J |volume=3 |issue=2 |pages=136–45 |year=2015 |pmid=25922673 |pmc=4406898 |doi=10.1177/2050640614560786 |url=}}</ref>
 
The adult patients with celiac disease are at higher risk of:<ref name="pmid25922673">{{cite journal |vauthors=Zingone F, Swift GL, Card TR, Sanders DS, Ludvigsson JF, Bai JC |title=Psychological morbidity of celiac disease: A review of the literature |journal=United European Gastroenterol J |volume=3 |issue=2 |pages=136–45 |year=2015 |pmid=25922673 |pmc=4406898 |doi=10.1177/2050640614560786 |url=}}</ref>
* Mortality from [[malignancy]] especially [[lymphomas]] in patients aged 45-65
* [[Suicide]]
* [[Diabetes]]
* [[Inflammatory bowel disease]]
 
[[Natural history of disease|Natural history]] of celiac disease variations is not completely understood. Particularly, the long-term risk of [[complications]] in patients who are asymptomatic or silent is not available. Undiagnosed celiac disease has been shown to be associated with a nearly 4-fold increased risk of death compared with asymptomatic patients whom are negative for [[Serology|serologic]] evidence of celiac disease.


==Overview==
As the risk of [[malignancy]] in celiac disease exist, it is recommended to asymptomatic and silent patients should patients to comply with a [[gluten-free diet]]. The majority of patients with celiac disease respond to a [[gluten-free diet]]. The most common reason for a lack of response are poor compliance or inadvertent gluten ingestion.


==Natural History==
===Complications===
The most important complications of celiac disease are listed in the table below:<ref name="pmid20431755">{{cite journal |vauthors=Freeman HJ |title=Adult celiac disease and its malignant complications |journal=Gut Liver |volume=3 |issue=4 |pages=237–46 |year=2009 |pmid=20431755 |pmc=2852736 |doi=10.5009/gnl.2009.3.4.237 |url=}}</ref><ref name="pmid23155333">{{cite journal |vauthors=Gujral N, Freeman HJ, Thomson AB |title=Celiac disease: prevalence, diagnosis, pathogenesis and treatment |journal=World J. Gastroenterol. |volume=18 |issue=42 |pages=6036–59 |year=2012 |pmid=23155333 |pmc=3496881 |doi=10.3748/wjg.v18.i42.6036 |url=}}</ref><ref name="pmid15610706">{{cite journal |vauthors=Chin RL, Latov N |title=Peripheral Neuropathy and Celiac Disease |journal=Curr Treat Options Neurol |volume=7 |issue=1 |pages=43–48 |year=2005 |pmid=15610706 |doi= |url=}}</ref><ref name="pmid21682114">{{cite journal |vauthors=Choi JM, Lebwohl B, Wang J, Lee SK, Murray JA, Sauer MV, Green PH |title=Increased prevalence of celiac disease in patients with unexplained infertility in the United States |journal=J Reprod Med |volume=56 |issue=5-6 |pages=199–203 |year=2011 |pmid=21682114 |pmc=3122153 |doi= |url=}}</ref><ref name="pmid19340898">{{cite journal |vauthors=Freeman HJ |title=Malignancy in adult celiac disease |journal=World J. Gastroenterol. |volume=15 |issue=13 |pages=1581–3 |year=2009 |pmid=19340898 |pmc=2669940 |doi= |url=}}</ref><ref name="pmid23041739">{{cite journal |vauthors=Ghoshal UC, Mehrotra M, Kumar S, Ghoshal U, Krishnani N, Misra A, Aggarwal R, Choudhuri G |title=Spectrum of malabsorption syndrome among adults & factors differentiating celiac disease & tropical malabsorption |journal=Indian J. Med. Res. |volume=136 |issue=3 |pages=451–9 |year=2012 |pmid=23041739 |pmc=3510892 |doi= |url=}}</ref><ref name="pmid24084055">{{cite journal |vauthors=Wierdsma NJ, van Bokhorst-de van der Schueren MA, Berkenpas M, Mulder CJ, van Bodegraven AA |title=Vitamin and mineral deficiencies are highly prevalent in newly diagnosed celiac disease patients |journal=Nutrients |volume=5 |issue=10 |pages=3975–92 |year=2013 |pmid=24084055 |pmc=3820055 |doi=10.3390/nu5103975 |url=}}</ref>
{| class="wikitable"
! colspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" |Disease
! align="center" style="background:#4479BA; color: #FFFFFF;" |Manifestations
|-
! rowspan="3" style="padding: 5px 5px; background: #DCDCDC;" align="center" |Vitamine deficiencies
! style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Vitamin  K deficiency]]
|
* Easy [[bruising]]
* [[Mucosal bleeding]]
* [[Splinter hemorrhages]]
* [[Melena]]
* [[Hematuria]]
|-
! style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[B12 deficiency|Vitamin B12 deficiency]]
|
* Unexplained [[anemia]] with [[macrocytosis]]
* [[Pancytopenia]]
* Hypersegmented [[neutrophils]]
* Unexplained [[neurologic]] or [[Psychiatric disease|psychiatric symptoms]]
** Symmetric [[paresthesias]] or [[numbness]] and gait problems
** Subacute combined [[degeneration]] of the dorsal (posterior) and [[lateral column]] (white matter) of the spinal cord due to [[demyelination]]
|-
! style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Vitamin D deficiency]]
| rowspan="2" |
* Secondary [[hyperparathyroidism]]
** [[Phosphaturia]]
** [[Bone loss|Demineralization of bones]]
** [[Osteomalacia]] in adults
** [[Rickets]] and [[osteomalacia]] in children
* [[Bone pain]] and [[tenderness]]
* [[Muscle weakness]]
* [[Fracture]]
* [[Difficulty walking]]
|-
! rowspan="3" style="padding: 5px 5px; background: #DCDCDC;" align="center" |Micronutrient deficiencies
! style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Calcium deficiency]]
|-
! style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Iron deficiency]]
|
* [[Microcytic]] [[hypochromic]] [[anemia]] with non-specific symptoms include:
** [[Fatigue]]
** [[Weakness]] and [[irritability]]
** [[Headache]]
** [[Vertigo]]
|-
! style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Folate deficiency]]
|
* Unexplained [[anemia]] with [[macrocytosis]]
* [[Pancytopenia]]
|-
! colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |Enamel hypoplasias
|
* Occur in greater than twenty percent of celiac disease cases in children
* Linear [[hypoplasia]] on the [[Tooth|teeth]]
|-
! colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Dermatitis herpetiformis]] 
|
* [[Cutaneous]] manifestations of [[gluten sensitivity]]:
** Multiple intensely [[Pruritis|pruritic]] [[papules]] and [[vesicles]] that occur in grouped, herpetiform arrangements
** Mainly in The [[elbows]], dorsal [[Forearm|forearms]], [[Knee|knees]], [[scalp]], [[back]], and [[buttocks]]


==Complications==
* [[Oral]] manifestations of [[gluten sensitivity]]:
* [[B12 deficiency]]
** [[vesicles]], [[Erosion (dental)|erosions]], or [[Erythematous rash|erythematous macules]] on the oral mucosa or [[tongue]]
* [[Iron deficiency]]
|-
* [[Folate deficiency]]
! colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Neurological disease|Neurological abnormalities]]
* [[Anemia]]
|
* [[Hypoalbuminemia]]
* More common in children
* [[Osteoporosis]]
* Include:
* [[Osteomalacia]]
** [[Hypotonia]]
* Increased risk of small bowel [[lymphoma]]  
** [[Developmental delay]]
** [[Learning disorder|Learning disorders]]
** [[ADHD]]
** [[Headache]]
** [[Cerebellar ataxia]]
|-
! style="padding: 5px 5px; background: #DCDCDC;" align="center" |Gastrointestinal malignancies
! style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Small bowel lymphoma]]
|
* [[Fever]]
* [[Hepatosplenomegaly]]
* [[Duodenum|Duodenal]] mass
* [[Ascites]]
|-
! colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Hyposplenism]]
|
* Increase risk of [[sepsis]] and [[bacteremia]] due to encapsulated pathogens:
** [[Pseudomonas aeruginosa]] (especially [[respiratory infections]])
** [[Streptococcus pneumonia]]
** [[Streptococcus, Group B|Streptococcus group B]]
** [[Hemophilus influenza]]
** [[Neisseria meningitidis]]
** [[Escherichia coli]]
** [[Salmonella]] (especially [[osteomyelitis]])
** [[Klebsiella]]
|-
! colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |Ulcerative jejunitis 
|
* Multiple chronic, benign-appearing [[ulcers]], most frequently in the [[jejunum]]
* Recurrent symptoms of despite being on a gluten-free diet:
** [[Malabsorption]]
** [[Lassitude|Fatigue]]
** [[Anorexia]]
** [[Weight loss]]
** [[Fever]]
|-
! colspan="2" style="padding: 5px 5px; background: #DCDCDC;" align="center" |[[Infertility]]
|
* The failure of a couple to [[Conceive a child|conceive]]:
** In women under age 35 after 12 months of frequent intercourse without use of [[contraception]]
** In women over age 35, and after six months of frequent intercourse without use of [[contraception]]
|}


==Prognosis==
===Prognosis===
*Depending on the extent of the celiac disease at the time of diagnosis and also extent of complications and diet complication, the prognosis may vary. However, the prognosis is generally regarded as good.<ref name="pmid21990301">{{cite journal |vauthors=Leffler D |title=Celiac disease diagnosis and management: a 46-year-old woman with anemia |journal=JAMA |volume=306 |issue=14 |pages=1582–92 |year=2011 |pmid=21990301 |pmc=3373262 |doi=10.1001/jama.306.14.1582 |url=}}</ref>
*People with celiac disease are at higher risk of mortality than the general population. Although people with celiac disease had an increased risk of [[Gastrointestinal Tract Cancer|gastrointestinal]] and [[Lymphoproliferative neoplasm|lymphoproliferative malignancies]] compared with the general population, it has been shown that they are in a lower risk of [[Breast cancer|breast]] or [[lung cancer]].<ref name="pmid21990301">{{cite journal |vauthors=Leffler D |title=Celiac disease diagnosis and management: a 46-year-old woman with anemia |journal=JAMA |volume=306 |issue=14 |pages=1582–92 |year=2011 |pmid=21990301 |pmc=3373262 |doi=10.1001/jama.306.14.1582 |url=}}</ref>
*The presence of [[Gastrointestinal tract cancer|gastrointestinal malignancies]] is associated with a particularly poor prognosis among patients with celiac disease.<ref name="pmid21990301">{{cite journal |vauthors=Leffler D |title=Celiac disease diagnosis and management: a 46-year-old woman with anemia |journal=JAMA |volume=306 |issue=14 |pages=1582–92 |year=2011 |pmid=21990301 |pmc=3373262 |doi=10.1001/jama.306.14.1582 |url=}}</ref>


==References==
==References==
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mahshid Mir, M.D. [2]

Overview

The symptoms of celiac disease usually develop in the first decade of life, and start with features suggestive of malabsorption such as abdominal pain and distension, diarrhea, malnutrition, and failure to thrive within the first few years of life. The classic malabsorption manifestation of disease is just the tip of the iceberg, and other more specific manifestations are invisible below the waterline. Natural history of celiac disease is not completely understood but if left untreated it may result in serious complications, such as malignancy. Complications of celiac disease may include vitamin deficiencies, essential nutrient deficiencies, enamel hypoplasia, neurological abnormalities, gastrointestinal malignancies, hyposplenism, ulcerative jejunitis, and infertility. The prognosis may vary depending upon the extent of the celiac disease at the time of diagnosis and also the extent of complications and dietary deficiencies. However, the prognosis is generally regarded as good. The presence of gastrointestinal malignancies is associated with a particularly poor prognosis among patients with celiac disease.

Natural History, Complications, and Prognosis

Natural History

The symptoms of celiac disease usually develop in the firs decade of life, and start with symptoms suggestive of malabsorption such as pain and distension, diarrhea, malnutrition, and failure to thrive within the first few years of life. These are classical celiac disease findings also known as “celiac disease iceberg” manifestations. Clinical presentations in celiac disease have been described as an iceberg model. Based on the iceberg model of celiac disease, the classic malabsorption manifestation of disease is just the tip of the iceberg, and other more specific manifestations are invisible below the waterline. According to iceberg model of celiac disease, the traditional method of diagnosing celiac disease based on malnutrition manifestations is unreliable due to different disease variation with more subtle manifestations that may be unrecognized. [1]

Most people with either diagnosed or undiagnosed celiac disease have only minor symptoms that are more inconvenient than life threatening. The few data available regarding quality of life of patients with celiac disease suggest that health‐related quality of life and psychological general well‐being are poor in undiagnosed patients, and improve with treatment in men but not significantly in women.[2] The frequency of psychiatric disorders are also high among celiac disease patients, and the severity of depression is associated with the duration of disease left without treatment. A questionnaire study in USA reported a mean duration of depression and anxiety symptoms for 11 years before the diagnosis of celiac disease. The mentioned depression was reported to get improved in 77% of cases after treatment. A high prevalence of depression was well documented in patients with celiac disease.[3][1][4]

The adult patients with celiac disease are at higher risk of:[4]

Natural history of celiac disease variations is not completely understood. Particularly, the long-term risk of complications in patients who are asymptomatic or silent is not available. Undiagnosed celiac disease has been shown to be associated with a nearly 4-fold increased risk of death compared with asymptomatic patients whom are negative for serologic evidence of celiac disease.

As the risk of malignancy in celiac disease exist, it is recommended to asymptomatic and silent patients should patients to comply with a gluten-free diet. The majority of patients with celiac disease respond to a gluten-free diet. The most common reason for a lack of response are poor compliance or inadvertent gluten ingestion.

Complications

The most important complications of celiac disease are listed in the table below:[5][6][7][8][9][10][11]

Disease Manifestations
Vitamine deficiencies Vitamin K deficiency
Vitamin B12 deficiency
Vitamin D deficiency
Micronutrient deficiencies Calcium deficiency
Iron deficiency
Folate deficiency
Enamel hypoplasias
  • Occur in greater than twenty percent of celiac disease cases in children
  • Linear hypoplasia on the teeth
Dermatitis herpetiformis 
Neurological abnormalities
Gastrointestinal malignancies Small bowel lymphoma
Hyposplenism
Ulcerative jejunitis 
Infertility
  • The failure of a couple to conceive:
    • In women under age 35 after 12 months of frequent intercourse without use of contraception
    • In women over age 35, and after six months of frequent intercourse without use of contraception

Prognosis

  • Depending on the extent of the celiac disease at the time of diagnosis and also extent of complications and diet complication, the prognosis may vary. However, the prognosis is generally regarded as good.[12]
  • People with celiac disease are at higher risk of mortality than the general population. Although people with celiac disease had an increased risk of gastrointestinal and lymphoproliferative malignancies compared with the general population, it has been shown that they are in a lower risk of breast or lung cancer.[12]
  • The presence of gastrointestinal malignancies is associated with a particularly poor prognosis among patients with celiac disease.[12]

References

  1. ↑ 1.0 1.1 Catassi C, Kryszak D, Bhatti B, Sturgeon C, Helzlsouer K, Clipp SL, Gelfond D, Puppa E, Sferruzza A, Fasano A (2010). "Natural history of celiac disease autoimmunity in a USA cohort followed since 1974". Ann. Med. 42 (7): 530–8. doi:10.3109/07853890.2010.514285. PMID 20868314.
  2. ↑ Green P, Stavropoulos SN, Panagi SG, Goldstein SL, Mcmahon DJ, Absan H, Neugut AI (2001). "Characteristics of adult celiac disease in the USA: results of a national survey". Am. J. Gastroenterol. 96 (1): 126–31. doi:10.1111/j.1572-0241.2001.03462.x. PMID 11197241. Vancouver style error: initials (help)
  3. ↑ Ciacci C, Iavarone A, Mazzacca G, De Rosa A (1998). "Depressive symptoms in adult coeliac disease". Scand. J. Gastroenterol. 33 (3): 247–50. PMID 9548616.
  4. ↑ 4.0 4.1 Zingone F, Swift GL, Card TR, Sanders DS, Ludvigsson JF, Bai JC (2015). "Psychological morbidity of celiac disease: A review of the literature". United European Gastroenterol J. 3 (2): 136–45. doi:10.1177/2050640614560786. PMC 4406898. PMID 25922673.
  5. ↑ Freeman HJ (2009). "Adult celiac disease and its malignant complications". Gut Liver. 3 (4): 237–46. doi:10.5009/gnl.2009.3.4.237. PMC 2852736. PMID 20431755.
  6. ↑ Gujral N, Freeman HJ, Thomson AB (2012). "Celiac disease: prevalence, diagnosis, pathogenesis and treatment". World J. Gastroenterol. 18 (42): 6036–59. doi:10.3748/wjg.v18.i42.6036. PMC 3496881. PMID 23155333.
  7. ↑ Chin RL, Latov N (2005). "Peripheral Neuropathy and Celiac Disease". Curr Treat Options Neurol. 7 (1): 43–48. PMID 15610706.
  8. ↑ Choi JM, Lebwohl B, Wang J, Lee SK, Murray JA, Sauer MV, Green PH (2011). "Increased prevalence of celiac disease in patients with unexplained infertility in the United States". J Reprod Med. 56 (5–6): 199–203. PMC 3122153. PMID 21682114.
  9. ↑ Freeman HJ (2009). "Malignancy in adult celiac disease". World J. Gastroenterol. 15 (13): 1581–3. PMC 2669940. PMID 19340898.
  10. ↑ Ghoshal UC, Mehrotra M, Kumar S, Ghoshal U, Krishnani N, Misra A, Aggarwal R, Choudhuri G (2012). "Spectrum of malabsorption syndrome among adults & factors differentiating celiac disease & tropical malabsorption". Indian J. Med. Res. 136 (3): 451–9. PMC 3510892. PMID 23041739.
  11. ↑ Wierdsma NJ, van Bokhorst-de van der Schueren MA, Berkenpas M, Mulder CJ, van Bodegraven AA (2013). "Vitamin and mineral deficiencies are highly prevalent in newly diagnosed celiac disease patients". Nutrients. 5 (10): 3975–92. doi:10.3390/nu5103975. PMC 3820055. PMID 24084055.
  12. ↑ 12.0 12.1 12.2 Leffler D (2011). "Celiac disease diagnosis and management: a 46-year-old woman with anemia". JAMA. 306 (14): 1582–92. doi:10.1001/jama.306.14.1582. PMC 3373262. PMID 21990301.

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