Gluten-sensitive enteropathy–associated conditions

Avitaminosis. Avitaminosis caused by malabsorption in GSE can result in decline of fat soluble vitamins and vitamin B, as well as malabsorption of essential fatty acids. This can cause a wide variety of secondary problems. Hypocalcinemia is also associated with GSE.{{cite journal | vauthors = Rakover Y, Hager H, Nussinson E, Luboshitzky R | title = Celiac disease as a cause of transient hypocalcemia and hypovitaminosis D in a 13 year-old girl | journal = The Journal of Pediatric Endocrinology | volume = 7 | issue = 1 | pages = 53–5 | year = 1994 | pmid = 8186825 | doi =10.1515/JPEM.1994.7.1.53 | s2cid = 33701186 }} In treated GSE, the restrictions on diet as well as reduced absorption as a result of prolonged damage may result in post-treatment deficiencies.{{cite journal | author = Hallert C | title = Evidence of poor vitamin status in coeliac patients on a gluten-free diet for 10 years | journal = Aliment. Pharmacol. Ther. | volume = 16 | issue = 7 | pages = 1333–1339 | year = 2002 | pmid = 12144584 | doi =10.1046/j.1365-2036.2002.01283.x |name-list-style=vanc| author2 = Grant C | author3 = Grehn S | display-authors = 3 | last4 = Granno | first4 = C. | last5 = Hulten | first5 = S. | last6 = Midhagen | first6 = G. | last7 = Strom | first7 = M. | last8 = Svensson | first8 = H. | last9 = Valdimarsson | first9 = T. | s2cid = 20758464 | doi-access = free }}

• Vitamin A – Poor absorption of vitamin A has been seen in coeliac disease.{{cite journal |vauthors=Johnson EJ, Krasinski SD, Howard LJ, Alger SA, Dutta SK, Russell RM | title = Evaluation of vitamin A absorption by using oil-soluble and water-miscible vitamin A preparations in normal adults and in patients with gastrointestinal disease | journal = Am. J. Clin. Nutr. | volume = 55 | issue = 4 | pages = 857–64 | year = 1992 | pmid = 1550069 | doi = 10.1093/ajcn/55.4.857}} and it has been suggested that GSE-associated cancers of the esophagus may be related to vitamin A deficiency{{cite journal | author = Wright DH | title = The major complications of coeliac disease | journal = Baillière's Clinical Gastroenterology | volume = 9 | issue = 2 | pages = 351–369 | year = 1995 | pmid = 7549031 | doi =10.1016/0950-3528(95)90035-7 }}{{cite journal |vauthors=Mellow MH, Layne EA, Lipman TO, Kaushik M, Hostetler C, Smith JC | title = Plasma zinc and vitamin A in human squamous carcinoma of the esophagus | journal = Cancer | volume = 51 | issue = 9 | pages = 1615–1620 | year = 1983 | pmid = 6831364 | doi =10.1002/1097-0142(19830501)51:9<1615::AID-CNCR2820510911>3.0.CO;2-O | doi-access = free }}
• Folate – Folate deficiency is believed to be primary to the following secondary conditions:
• Megaloblastic anemia
• Calcification of brain channels – epilepsy, dementia, visual manifestations.
• B₆ deficiency. Vitamin B₆ deficiency can result in neuropathies and increases in pain sensitivity.{{cite journal |vauthors=Reinken L, Zieglauer H | title = Vitamin B-6 absorption in children with acute celiac disease and in control subjects | journal = J. Nutr. | volume = 108 | issue = 10 | pages = 1562–5 | year = 1978 | pmid = 702197 | doi = 10.1093/jn/108.10.1562}} may explain some of the peripheral neuropathies, pain and depression associated with GSE.{{cite journal |vauthors=Hallert C, Aström J, Walan A | title = Reversal of psychopathology in adult coeliac disease with the aid of pyridoxine (vitamin B₆) | journal = Scand. J. Gastroenterol. | volume = 18 | issue = 2 | pages = 299–304 | year = 1983 | pmid = 6369511 | doi =10.3109/00365528309181597}}
• B₁₂ deficiency
• Megaloblastic anemia
• Pernicious anemia
• Vitamin D – Vitamin D deficiency can result in osteopenia and osteoporosis
• Hypocalcemia{{cite journal | author = Shaker JL | title = Hypocalcemia and skeletal disease as presenting features of celiac disease | journal = Arch. Intern. Med. | volume = 157 | issue = 9 | pages = 1013–1016 | year = 1997 | pmid = 9140273 | doi =10.1001/archinte.157.9.1013 |name-list-style=vanc| author2 = Brickner RC | author3 = Findling JW | display-authors = 3 | last4 = Kelly | first4 = TM | last5 = Rapp | first5 = R | last6 = Rizk | first6 = G | last7 = Haddad | first7 = JG | last8 = Schalch | first8 = DS | last9 = Shenker | first9 = Y }}
• Vitamin K – Coeliac disease has been identified in patients with a pattern of bleeding that treatment of vitamin K increased levels of prothrombin.{{cite journal |vauthors=Mitterstieler G, Zieglauer H | title = [Vitamin K deficiency bleeding as a leading symptom in celiac disease (author's transl)] | language = de | journal = Pädiatrie und Pädologie | volume = 13 | issue = 2 | pages = 175–82 | year = 1978 | pmid = 643295 }}
• Vitamin E – deficiency of vitamin E can lead to CNS problems{{cite journal |vauthors=Mauro A, Orsi L, Mortara P, Costa P, Schiffer D | title = Cerebellar syndrome in adult celiac disease with vitamin E deficiency | journal = Acta Neurol. Scand. | volume = 84 | issue = 2 | pages = 167–170 | year = 1991 | pmid = 1950453 | doi =10.1111/j.1600-0404.1991.tb04927.x | s2cid = 19090624 }} and possibly associated with myopathy{{cite journal |vauthors=Kleopa KA, Kyriacou K, Zamba-Papanicolaou E, Kyriakides T | title = Reversible inflammatory and vacuolar myopathy with vitamin E deficiency in celiac disease | journal = Muscle Nerve | volume = 31 | issue = 2 | pages = 260–265 | year = 2005 | pmid = 15389648 | doi = 10.1002/mus.20144| s2cid = 34027981 }}

Mineral deficiencies. GSE is associated with the following mineral deficiencies:

• Calcium – Hypocalcemia causing Oesteopenia
• Magnesium – Hypomagnesemia,{{cite journal |vauthors=Rude RK, Olerich M | title = Magnesium deficiency: possible role in osteoporosis associated with gluten-sensitive enteropathy | journal = Osteoporosis International | volume = 6 | issue = 6 | pages = 453–461 | year = 1996 | pmid = 9116391 | doi =10.1007/BF01629578 | s2cid = 10964149 }} may lead to parathyroid abnormalities.
• Iron – Iron deficiency anemia
• Phosphorus – Hypophosphatemia,{{cite journal |vauthors=Van Dyk D, Inbal A, Kraus L, Grifel B, Ravid M | title = The watery diarrhea syndrome with hypercalcemia--a symptomatic response to phosphate buffer | journal = Hepatogastroenterology | volume = 28 | issue = 1 | pages = 58–9 | year = 1981 | pmid = 7216140 }} causing Oesteopenia
• Zinc – Zinc deficiencies{{cite journal |vauthors=Solomons NW, Rosenberg IH, Sandstead HH | title = Zinc nutrition in celiac sprue | journal = Am. J. Clin. Nutr. | volume = 29 | issue = 4 | pages = 371–5 | year = 1976 | pmid = 1266787 | doi = 10.1093/ajcn/29.4.371| doi-access = free }} are believed to be associated with increased risk of Esophagus Carcinoma
• Copper – Deficiency
• Selenium – Deficiency{{cite journal |vauthors=Yüce A, Demir H, Temizel IN, Koçak N | title = Serum carnitine and selenium levels in children with celiac disease | journal = Indian Journal of Gastroenterology | volume = 23 | issue = 3 | pages = 87–8 | year = 2004 | pmid = 15250563 }} – Selenium and zinc deficiencies may play a role increasing risk of cancer.{{cite journal |vauthors=Hinks LJ, Inwards KD, Lloyd B, Clayton BE | title = Body content of selenium in coeliac disease | journal = British Medical Journal (Clinical Research Ed.) | volume = 288 | issue = 6434 | pages = 1862–1863 | year = 1984 | pmid = 6428578 | doi =10.1136/bmj.288.6434.1862 | pmc = 1441793 }} Selenium deficiency may also be an aggravating factor for autoimmune hyperthyroidism (Graves disease).{{cite journal |vauthors=Kucharzewski M, Braziewicz J, Majewska U, Góźdź S | title = Concentration of selenium in the whole blood and the thyroid tissue of patients with various thyroid diseases | journal = Biological Trace Element Research | volume = 88 | issue = 1 | pages = 25–30 | year = 2002 | pmid = 12117262 | doi = 10.1385/BTER:88:1:25 | s2cid = 1448985 }}

Blood factors

• Carnitine – Deficiency.
• Prolactin – Deficiency (childhood).{{cite journal |vauthors=Várkonyi A, Boda M, Endreffy E, Németh I, Timár E | title = Coeliac disease: always something to discover | journal = Scand. J. Gastroenterol. Suppl. | volume = 33 | issue = 228| pages = 122–129 | year = 1998 | pmid = 9867122 | doi =10.1080/003655298750026651 }}
• homocysteine – Excess.{{cite journal |vauthors=Wilcox GM, Mattia AR | title = Celiac sprue, hyperhomocysteinemia, and MTHFR gene variants | journal = J. Clin. Gastroenterol. | volume = 40 | issue = 7 | pages = 596–601 | year = 2006 | pmid = 16917400 | doi =10.1097/00004836-200608000-00007 | s2cid = 27387815 }}

Megaloblastic anemia (MA) is associated with GSE and is believed to be the result of B₁₂ and folate deficiency.{{cite journal |vauthors=Forshaw J, Harwood L | title = Diagnostic value of the serum folate assay | journal = J. Clin. Pathol. | volume = 24 | issue = 3 | pages = 244–249 | year = 1971 | pmid = 5573438 | doi =10.1136/jcp.24.3.244 | pmc = 476963 }} In GSE, it appears to be associated with the IgA-less phenotype.{{cite journal |vauthors=Hauser GJ, Heiman I, Laurian L, Diamant S, Spirer Z | title = Selective IgA deficiency with multiple autoimmune disorders | journal = Journal of Clinical & Laboratory Immunology | volume = 6 | issue = 1 | pages = 81–5 | year = 1981 | pmid = 7196455 }} Unlike other forms of megaloblastic anemia, GSEA MA is not a form of autoimmune gastritis.{{cite journal | author = Dickey W | title = Low serum vitamin B₁₂ is common in coeliac disease and is not due to autoimmune gastritis | journal = European Journal of Gastroenterology & Hepatology | volume = 14 | issue = 4 | pages = 425–427 | year = 2002 | pmid = 11943958 | doi =10.1097/00042737-200204000-00016 | s2cid = 24979028 }}

Pernicious anemia (PA). Pernicious anemia is associated with GSE and is believed to result primarily from malabsorption phenomena.

Iron-deficiency anemia. Iron-deficiency anemia (IDA) may be the only symptom for CD,{{cite journal |vauthors=Depla AC, Bartelsman JF, Mulder CJ, Tytgat GN | title = Anemia: monosymptomatic celiac disease. A report of 3 cases | journal = Hepatogastroenterology | volume = 37 | issue = 1 | pages = 90–1 | year = 1990 | pmid = 2312047 }} detected in subclinical CD{{cite journal | author = Corazza GR | title = Subclinical coeliac disease is a frequent cause of iron-deficiency anaemia | journal = Scand. J. Gastroenterol. | volume = 30 | issue = 2 | pages = 153–156 | year = 1995 | pmid = 7732338 | doi =10.3109/00365529509093254 |name-list-style=vanc| author2 = Valentini RA | author3 = Andreani ML | display-authors = 3 | last4 = d'Anchino | first4 = M. | last5 = Leva | first5 = M. T. | last6 = Ginaldi | first6 = L. | last7 = De Feudis | first7 = L. | last8 = Quaglino | first8 = D. | last9 = Gasbarrini | first9 = G. }} and is accompanied by a decrease in serum ferritin levels.{{cite journal |vauthors=Ståhlberg MR, Savilahti E, Siimes MA | title = Iron deficiency in coeliac disease is mild and it is detected and corrected by gluten-free diet | journal = Acta Paediatrica Scandinavica | volume = 80 | issue = 2 | pages = 190–193 | year = 1991 | pmid = 2035309 | doi =10.1111/j.1651-2227.1991.tb11832.x | s2cid = 19745356 }} This can cause addition problems (see:symptoms of IDA and certain conditions like such as Paterson-Brown Kelly (Plummer–Vinson syndrome).{{cite journal |vauthors=Dickey W, McConnell B | title = Celiac disease presenting as the Paterson-Brown Kelly (Plummer-Vinson) syndrome | journal = Am. J. Gastroenterol. | volume = 94 | issue = 2 | pages = 527–529 | year = 1999 | doi = 10.1111/j.1572-0241.1999.889_r.x | pmid = 10022662 | s2cid = 35004650 }} Whereas IDA is corrected on GF diet, refractory disease or gluten-sensitive malignancies can cause persistent IDA.{{cite journal |vauthors=Kingham JG, Ramanaden D, Dawson A | title = Metachronous small-bowel adenocarcinoma in coeliac disease: gluten-free diet is not protective | journal = Scand. J. Gastroenterol. | volume = 33 | issue = 2 | pages = 218–222 | year = 1998 | pmid = 9517536 | doi =10.1080/00365529850166987 }}

Thromboembolism is a well-described complication of IBD, with a clinical incidence of up to 6% and a three-fold higher risk of disease,{{cite journal |vauthors=Talbot RW, Heppell J, Dozois RR, Beart RW | title = Vascular complications of inflammatory bowel disease | journal = Mayo Clin. Proc. | volume = 61 | issue = 2 | pages = 140–5 | year = 1986 | pmid = 3080643 | doi =10.1016/S0025-6196(12)65200-8 }}{{cite journal |vauthors=Srirajaskanthan R, Winter M, Muller AF | title = Venous thrombosis in inflammatory bowel disease | journal = European Journal of Gastroenterology & Hepatology | volume = 17 | issue = 7 | pages = 697–700 | year = 2005 | pmid = 15947544 | doi =10.1097/00042737-200507000-00001 | s2cid = 31333056 | doi-access = free }} and the Factor V Leiden mutation further increases the risk of venous thrombosis.{{cite journal |vauthors=Liebman HA, Kashani N, Sutherland D, McGehee W, Kam AL | title = The factor V Leiden mutation increases the risk of venous thrombosis in patients with inflammatory bowel disease | journal = Gastroenterology | volume = 115 | issue = 4 | pages = 830–834 | year = 1998 | pmid = 9753484 | doi =10.1016/S0016-5085(98)70253-7 | title-link = venous thrombosis | doi-access = free }} Recent studies describe the co-occurrence between coeliac disease, in which IBD is common in venous thrombosis.{{cite journal |vauthors=Casella G, Perego D, Baldini V, Monti C, Crippa S, Buda CA | title = A rare association between ulcerative colitis (UC), celiac disease (CD), membranous glomerulonephritis, leg venous thrombosis, and heterozygosity for factor V Leiden | journal = J. Gastroenterol. | volume = 37 | issue = 9 | pages = 761–762 | year = 2002 | pmid = 12375154 | doi = 10.1007/s005350200126| s2cid = 6734431 }}{{cite journal |vauthors=Mari T, Zullo A, Hassan C, Di Giulio L, Morini S | title = Genetic association between factor V Leiden and coeliac disease | journal = Gut | volume = 55 | issue = 11 | pages = 1677–1678 | year = 2006 | pmid = 17047127 | doi = 10.1136/gut.2006.104786 | pmc = 1860115}}

A study of patients with dermatitis herpetiformis or coeliac disease revealed significantly more gluten in the blood than controls.{{cite journal |vauthors=Lane AT, Huff JC, Weston WL | title = Detection of gluten in human sera by an enzyme immunoassay: comparison of dermatitis herpetiformis and celiac disease patients with normal controls | journal = J. Invest. Dermatol. | volume = 79 | issue = 3 | pages = 186–189 | year = 1982 | pmid = 7050253 | doi =10.1111/1523-1747.ep12500053 | doi-access = free }} This increases the risk of asthma, anaphylaxis and dermatological conditions.

Triticeae glutens are the primary cause of dermatitis herpetiformis (DH). Epidermal transglutaminase (eTG) is related to tTG and is the autoantigen of DH. It appears that all DH patients have or are susceptible to CD after wheat ingestion. Within the pathology of CD, DH is relatively rare or underdiagnosed, with about 5% of patients presenting with DH. Aphthous stomatitis is a common mouth lesion found in those with coeliac disease.

Chronic urticaria has been seen in a few cases of CD.{{cite journal |vauthors=Haussmann J, Sekar A | title = Chronic urticaria: a cutaneous manifestation of celiac disease | journal = Can. J. Gastroenterol. | volume = 20 | issue = 4 | pages = 291–3 | year = 2006 | pmid = 16609761 | doi = 10.1155/2006/871987| pmc = 2659909 | doi-access = free }} and are likely the result of fortuitous allergies to wheat, or allergies secondary to GSE. Atopy disorders have been found to be more common in coeliacs and in first degree relatives.{{cite journal |vauthors=Hodgson HJ, Davies RJ, Gent AE | title = Atopic disorders and adult coeliac disease | journal = Lancet | volume = 1 | issue = 7951 | pages = 115–117 | year = 1976 | pmid = 54635 | doi =10.1016/S0140-6736(76)93155-X | s2cid = 24439525 }} Coeliac disease is associated with a number of epidermal conditions including psoriasis{{cite journal |vauthors=Abenavoli L, Leggio L, Gasbarrini G, Addolorato G | title = Celiac disease and skin: Psoriasis association | journal = World J. Gastroenterol. | volume = 13 | issue = 14 | pages = 2138–9 | year = 2007 | pmid = 17465464 | pmc = 4319141 | doi = 10.3748/wjg.v13.i14.2138 | doi-access = free }}{{cite journal | vauthors = Abenavoli L, Proietti I, Leggio L, Ferrulli A, Vonghia L, Capizzi R, Rotoli M, Amerio PL, Gasbarrini G, Addolorato G | title = Cutaneous manifestations in celiac disease | journal = World J. Gastroenterol. | volume = 12 | issue = 6 | pages = 843–52 | year = 2006 | pmid = 16521210 | pmc = 4066147 | doi=10.3748/wjg.v12.i6.843 | doi-access = free }}

Prurigo nodularis. Prurigo nodularis has been identified with coeliac disease.{{cite journal |vauthors=McKenzie AW, Stubbing DG, Elvy BL | title = Prurigo nodularis and gluten enteropathy | journal = Br. J. Dermatol. | volume = 95 | issue = 1 | pages = 89–92 | year = 1976 | pmid = 952746 }}{{cite journal | author = Francesco Stefanini G | title = Prurigo nodularis (Hyde's prurigo) disclosing celiac disease | journal = Hepatogastroenterology | volume = 46 | issue = 28 | pages = 2281–4 | year = 1999 | pmid = 10521982 |name-list-style=vanc| author2 = Resta F | author3 = Marsigli L | display-authors = 3 | last4 = Gaddoni | first4 = G | last5 = Baldassarri | first5 = L | last6 = Caprio | first6 = GP | last7 = Degli Azzi | first7 = I | last8 = Giuseppe Foschi | first8 = F | last9 = Gasbarrini | first9 = G }}

Rothmund–Thomson syndrome. Rothmund–Thomson syndrome, or poikiloderma congenitale, is a rare disorder, generally attributed to mutations of the RECQL4 helicase gene on 8q24 with features that include photosensitivity and poikilodermatous skin changes, etc., and has been reported in one coeliac patient.{{cite journal |vauthors=Popadić S, Nikolić M, Gajić-Veljić M, Bonaci-Nikolić B | title = Rothmund-Thomson syndrome. The first case with plantar keratoderma and the second with coeliac disease | journal = Acta Dermatovenerologica Alpina, Pannonica et Adriatica | volume = 15 | issue = 2 | pages = 90–3 | year = 2006 | pmid = 16998609 }}

GSE has been found to be associated with alopecia areata (patchy baldness),{{cite journal |vauthors=Corazza GR, Andreani ML, Venturo N, Bernardi M, Tosti A, Gasbarrini G | title = Celiac disease and alopecia areata: report of a new association | journal = Gastroenterology | volume = 109 | issue = 4 | pages = 1333–1337 | year = 1995 | pmid = 7557104 | doi =10.1016/0016-5085(95)90597-9 | doi-access = free }} however hair regrowth did not necessarily occur after taking up a gluten free diet.{{cite journal |vauthors=Bardella MT, Marino R, Barbareschi M, Bianchi F, Faglia G, Bianchi P | title = Alopecia areata and coeliac disease: no effect of a gluten-free diet on hair growth | journal = Dermatology | volume = 200 | issue = 2 | pages = 108–10 | year = 2000 | pmid = 10773696 | doi =10.1159/000018340 | s2cid = 44430157 }}{{cite journal |vauthors=Bondavalli P, Quadri G, Parodi A, Rebora A | title = Failure of gluten-free diet in celiac disease-associated alopecia areata | journal = Acta Derm. Venereol. | volume = 78 | issue = 4 | pages = 319 | year = 1998 | pmid = 9689318 | doi =10.1080/000155598442098 | doi-access = free }}

[Section under construction]

Grave's Disease, Hashimoto's thyroiditis. Grave's disease and Hashimoto's thyroiditis are greatly increased in patients with CD.{{cite journal |vauthors=Wortsman J, Kumar V | title = Case report: idiopathic hypoparathyroidism co-existing with coeliac disease: immunologic studies | journal = Am. J. Med. Sci. | volume = 307 | issue = 6 | pages = 420–427 | year = 1994 | pmid = 8198149 | doi =10.1097/00000441-199406000-00008 | title-link = coeliac disease }} Grave's disease is an autoimmune hyperthyroidism, as GSE is a potentiator for autoimmune disease, but GD is more commonly found and avitaminosis of selenium and other minerals may be a factor in this increase.

Type 1 (Juvenile onset). The incidence of juvenile Type 1 Diabetes (T1D) is about 1:500 in the U.S. population, and is the result of autoimmune damage to the Islets of Langerhans cells in the pancreas. The level of adult onset T1D plus ambiguous T1D/T2D is unknown. It is unclear how large a role Triticeae has in T1D, which also shows strong linkage to DQ2.5 and DQ8. Childhood (male) Type 1 diabetes increases the risk for GSE and vice versa{{cite journal |vauthors=Lampasona V, Bonfanti R, Bazzigaluppi E, Venerando A, Chiumello G, Bosi E, Bonifacio E | title = Antibodies to tissue transglutaminase C in type I diabetes | journal = Diabetologia | volume = 42 | issue = 10 | pages = 1195–1198 | year = 1999 | pmid = 10525659 | doi = 10.1007/s001250051291| doi-access = free }} and it now appears that GSE precedes T1D in many cases{{cite journal |vauthors=Ludvigsson J, Ludvigsson J, Ekbom A, Montgomery S | title = Celiac disease and risk of subsequent type 1 diabetes: a general population cohort study of children and adolescents | journal = Diabetes Care | volume = 29 | issue = 11 | pages = 2483–2488 | year = 2006 | pmid = 17065689 | doi = 10.2337/dc06-0794| doi-access = free }} and an active search for coeliac disease in early juvenile diabetes patients revealed that GF diet resulted in some improvements.{{cite journal |vauthors=Hansen D, Brock-Jacobsen B, Lund E, Bjørn C, Hansen L, Nielsen C, Fenger C, Lillevang S, Husby S | title = Clinical benefit of a gluten-free diet in type 1 diabetic children with screening-detected celiac disease: a population-based screening study with 2 years' follow-up | journal = Diabetes Care | volume = 29 | issue = 11 | pages = 2452–2456 | year = 2006 | pmid = 17065683 | doi = 10.2337/dc06-0990| doi-access = free }} A high frequency of diabetes patients have anti-transglutaminase antibodies{{cite journal |vauthors=Bao F, Yu L, Babu S, Wang T, Hoffenberg EJ, Rewers M, Eisenbarth GS | title = One third of HLA DQ2 homozygous patients with type 1 diabetes express celiac disease-associated transglutaminase autoantibodies | journal = J. Autoimmun. | volume = 13 | issue = 1 | pages = 143–148 | year = 1999 | pmid = 10441179 | doi = 10.1006/jaut.1999.0303}} along with increased levels of gluten specific T-cells in T1D patients. From an evolutionary point of view it is difficult to explain the high association of T1D and DQ2.5 given negatively selective nature of the disease in NW European population given the number of studies suggesting that the "Super B8" haplotypes has been under positive selection, and appears to be the most characteristic HLA type in NW Europeans indicating an advanced natural history of the haplotype. A T. aesitivum storage globulin, Glb-1 (locus), was identified that is similar to the hypersensitizing peanut protein Ara h 1 and other known plant hypersensitizing proteins. Antibodies to this protein correlated with levels of lymphocyte infiltration into Islet regions of the pancreas.{{cite journal | author = MacFarlane AJ | title = A type 1 diabetes-related protein from wheat (Triticum aestivum). cDNA clone of a wheat storage globulin, Glb1, linked to islet damage | journal = J. Biol. Chem. | volume = 278 | issue = 1 | pages = 54–63 | year = 2003 | pmid = 12409286 | doi = 10.1074/jbc.M210636200 |name-list-style=vanc| author2 = Burghardt KM | author3 = Kelly J | display-authors = 3 | last4 = Simell | first4 = T | last5 = Simell | first5 = O | last6 = Altosaar | first6 = I | last7 = Scott | first7 = FW| doi-access = free }} Gastrointestinal viruses may play a role.{{cite journal |author= Van Der Werf, Nienke|title=Viral infections as potential triggers of type 1 diabetes |journal=Diabetes Metab Res Rev |volume= 23|issue= 3|pages= 169–183|year= 2007|pmid=17103489|doi=10.1002/dmrr.695|s2cid=31145812 |doi-access=free}}{{cite journal |vauthors=Mäkelä M, Oling V, Marttila J, Waris M, Knip M, Simell O, Ilonen J |title=Rotavirus-specific T cell responses and cytokine mRNA expression in children with diabetes-associated autoantibodies and type 1 diabetes |journal=Clin Exp Immunol |volume=145 |issue=2 |pages=261–270 |year=2006 |pmid=16879245 |doi=10.1111/j.1365-2249.2006.03146.x |pmc=1809689}}{{cite journal |vauthors=Mäkelä M, Vaarala O, Hermann R, Salminen K, Vahlberg T, Veijola R, Hyöty H, Knip M, Simell O, Ilonen J |title=Enteral virus infections in early childhood and an enhanced type 1 diabetes-associated antibody response to dietary insulin |journal=J Autoimmun |volume=27 |issue=1 |pages=54–61 |year=2006 |pmid=16757149 |doi=10.1016/j.jaut.2006.04.003}}{{cite journal |vauthors=Collin P, Reunala T, Pukkala E, Laippala P, Keyriläinen O, Pasternack A | title = Coeliac disease--associated disorders and survival | journal = Gut | volume = 35 | issue = 9 | pages = 1215–1218 | year = 1994 | pmid = 7959226 | doi =10.1136/gut.35.9.1215 | pmc = 1375696 }}

Studies from Sweden suggest that persons with coeliac disease are 11 times more likely to have Addison's disease (primary adrenal insufficiency) relative to the normal population.{{cite journal |vauthors=Elfström P, Montgomery SM, Kämpe O, Ekbom A, Ludvigsson JF | title = Risk of primary adrenal insufficiency in patients with celiac disease | journal = Journal of Clinical Endocrinology & Metabolism| volume = 92| issue = 9| pages = 3595–3598| year = 2007 | pmid = 17595243 | doi = 10.1210/jc.2007-0960| doi-access = free}}

GSE can result in high risk pregnancies{{cite journal | author = Ogborn AD | title = Pregnancy in patients with coeliac disease | journal = British Journal of Obstetrics and Gynaecology | volume = 82 | issue = 4 | pages = 293–6 | year = 1975 | pmid = 1125150 | doi =10.1111/j.1471-0528.1975.tb00637.x | s2cid = 37897288 }} and infertility. Some infertile women have GSE and iron deficiency anemia{{cite journal |vauthors=Collin P, Vilska S, Heinonen PK, Hällström O, Pikkarainen P | title = Infertility and coeliac disease | journal = Gut | volume = 39 | issue = 3 | pages = 382–384 | year = 1996 | pmid = 8949641 | doi =10.1136/gut.39.3.382 | pmc = 1383343 }} others have zinc deficiency{{cite journal | author = Jameson S | title = Zinc deficiency in malabsorption states: a cause of infertility? | journal = Acta Med. Scand. Suppl. | volume = 593 | pages = 38–49 | year = 1976 | pmid = 1067747 | doi = 10.1111/j.0954-6820.1976.tb12825.x}} and birth defects may be attributed to folic acid deficiencies.

It has also been found to be a rare cause of amenorrhea.{{cite journal |vauthors=Pradhan M, Manisha, Singh R, Dhingra S |title=Celiac disease as a rare cause of primary amenorrhea: a case report |journal=The Journal of Reproductive Medicine |volume=52 |issue=5 |pages=453–5 |year=2007 |pmid=17583254}}

Image:Peptic stricture.png image of peptic stricture, or narrowing of the esophagus near the junction with the stomach due to chronic gastroesophageal reflux. This is the most common cause of dysphagia, or difficulty swallowing, in scleroderma.]] While GI disease is one of the major symptoms of GSE that are characterized by increased levels of IgA/IgG to food proteins,{{cite journal |vauthors=Ratnaike RN, Wangel AG | title = Immunological abnormalities in coeliac disease and their response to dietary restriction. I. Serum immunoglobulins, antibodies and complement | journal = Australian and New Zealand Journal of Medicine | volume = 7 | issue = 4 | pages = 349–52 | year = 1977 | pmid = 270982 | doi =10.1111/j.1445-5994.1977.tb04393.x }} many conditions like chronic constipation and irritable bowel disease persist after GF diet. Some of this may be due to persistent undetected food allergies, increased sensitivity of the damaged gut, or problems masked by GSE itself.

In diarrhea dominant IB - a common symptom of GSE - increased coeliac disease-associated serum IgG was found in treated and untreated CD patients. IgG was most common in untreated patients with more active DQ2 expression, which dropped on GF diet.{{cite journal |vauthors=Wahnschaffe U, Schulzke JD, Zeitz M, Ullrich R | title = Predictors of Clinical Response to Gluten-Free Diet in Patients Diagnosed With Diarrhea-Predominant Irritable Bowel Syndrome | journal = Clinical Gastroenterology and Hepatology| volume = 5| issue = 7| pages = 844–850| year = 2007 | pmid = 17553753 | doi = 10.1016/j.cgh.2007.03.021| doi-access = free}} Some cases of irritable bowel can be the result of other food intolerances, such as casein intolerance, lactose intolerance, or intolerances to non-dextrose sugars in other foods. It can also be result of overgrowth of yeast or bacteria as a result of excesses of unabsorbed nutrients. IB may not resolve on GF diet, even becoming more severe in rare cases, as it may not have initially been directly linked to gluten consumption.

A recent study of inflammatory bowel disease and coeliac disease found that anti-tTG was increased in inflammatory bowel disease, although most cases were not clinical CD. IBD was increased 10 fold in coeliac disease.{{cite journal |vauthors = Leeds JS, Höroldt BS, Sidhu R, Hopper AD, Robinson K, Toulson B, Dixon L, Lobo AJ, McAlindon ME, Hurlstone DP, Sanders DS|display-authors=3 |title=Is there an association between coeliac disease and inflammatory bowel diseases? A study of relative prevalence in comparison with population controls |journal=Scand. J. Gastroenterol. |volume=42 |issue=10 |pages=1214–20 |year=2007 |pmid=17918008 |doi=10.1080/00365520701365112 |s2cid=25575750 }} Inflammatory bowel disease consists of Crohn's disease, ulcerative colitis and microscopic colitis.

Gastroesophageal reflux disease (GERD) is the indirect result of many factors and some autoimmune diseases like scleroderma. GSE can cause inflammation and delayed gastric emptying, which can persist through most of the sleeping hours causing GERD. GSE is associated with an increase of food allergies - in some patients this can cause diarrhea, but in others, constipation. In some patients, food allergies and GERD are an apparent symptom of GSE, but these allergies and GERD often persist on a GF diet. While GERD associated with GSE can be treated with acid blockers, it is most effectively treated with proper eating habits and elimination diet. The more powerful

acid blockers (omeprazole, esomeprezole) can interfere with calcium adsorption and can aggravate preexisting hypocalcaemia and hypomagnesemia, which are more common GSE{{cite journal | author = Robb-Nicholson C | title = By the way, doctor. I heard that taking a proton-pump inhibitor could cause hip fractures. I've been taking 20 mg of Prilosec every day for a year. Should I be concerned? | journal = Harvard Women's Health Watch | volume = 14 | issue = 7 | pages = 8 | year = 2007 | pmid = 17396273 }}

One study of 17 children in Italy who were diagnosed with eosinophilic oesophagitis found 6 of them also had coeliac disease.{{cite journal |vauthors=Quaglietta L, Coccorullo P, Miele E, Pascarella F, Troncone R, Staiano A | title = Eosinophilic oesophagitis and coeliac disease: is there an association? | journal = Alimentary Pharmacology & Therapeutics| volume = 26 | issue = 3 | pages = 487–493 | year = 2007 | pmid = 17635383 | doi = 10.1111/j.1365-2036.2007.03388.x| s2cid = 25628864 | doi-access = free }} However a systematic review of several similar studies suggested a publication bias and that any association was uncertain.{{cite journal | vauthors = Lucendo AJ, Arias Á, Tenias JM | title = Systematic review: the association between eosinophilic oesophagitis and coeliac disease | journal = Alimentary Pharmacology & Therapeutics | volume = 40 | issue = 5 | pages = 422–34 | date = September 2014 | pmid = 25041372 | doi = 10.1111/apt.12859 | s2cid = 26049195 | url = }}

Primary biliary cholangitis. CD is prevalent in primary biliary cholangitis (previously known as primary biliary cirrhosis, PBC).{{cite journal |vauthors=Logan RF, Ferguson A, Finlayson ND, Weir DG | title = Primary biliary cirrhosis and coeliac disease: an association? | journal = Lancet | volume = 1 | issue = 8058 | pages = 230–233 | year = 1978 | pmid = 74661 | doi =10.1016/S0140-6736(78)90480-4 | s2cid = 54278759 }}{{cite journal |vauthors=Volta U, Rodrigo L, Granito A, Petrolini N, Muratori P, Muratori L, Linares A, Veronesi L, Fuentes D, Zauli D, Bianchi FB|display-authors=3 |title=Celiac disease in autoimmune cholestatic liver disorders |journal=Am. J. Gastroenterol. |volume=97 |issue=10 |pages=2609–13 |year=2002 |doi=10.1111/j.1572-0241.2002.06031.x |pmid=12385447 |s2cid=17375127 }} In PBC anti-mitochondrial antibodies are directed toward three mitochondrial autoantigens (pyruvate dehydrogenase, oxoglutarate dehydrogenase, branched-chain alpha-keto acid dehydrogenase), two or more nuclear proteins (nucleoporin 210kDa, nucleoporin 62kDa, centromere protein, and sp100), and 57% of acute liver failure patients have anti-transglutaminase antibodies.

Cholangitis. CD also found at higher than expected frequencies in autoimmune cholangitis and primary sclerosing cholangitis. CD is frequently linked to pancreatitis but also to papillary stenosis{{cite journal |vauthors=Patel RS, Johlin FC, Murray JA | title = Celiac disease and recurrent pancreatitis | journal = Gastrointest. Endosc. | volume = 50 | issue = 6 | pages = 823–827 | year = 1999 | pmid = 10570344 | doi =10.1016/S0016-5107(99)70166-5 }} and, in India, tropical calcific pancreatitis appears also to be associated with CD.{{cite journal |vauthors=Nanda R, Anand BS | title = Celiac disease and tropical calcific pancreatitis | journal = Am. J. Gastroenterol. | volume = 88 | issue = 10 | pages = 1790–2 | year = 1993 | pmid = 8213729 }}

Neuropathies tend to be associated with late-onset coeliac disease. Dementia and ataxia appear to be more common. A recent study of children with neuropathies revealed no increase of CD in early-onset neuropathies.{{cite journal |vauthors=Lahat E, Broide E, Leshem M, Evans S, Scapa E | title = Prevalence of celiac antibodies in children with neurologic disorders | journal = Pediatr. Neurol. | volume = 22 | issue = 5 | pages = 393–396 | year = 2000 | pmid = 10913732 | doi =10.1016/S0887-8994(00)00129-6 }} Although many studies link CD to various neuropathies such as migraine, encephalopathy, chorea, brain stem dysfunction, myelopathy, mononeuritis multiplex, Guillain–Barré-like syndrome, and antiganglioside-positive neuropathy with antibodies, strong associations remain largely unconfirmed in epidemiologic studies.{{cite journal | author = Bushara KO | title = Neurologic presentation of celiac disease | journal = Gastroenterology | volume = 128 | issue = 4 Suppl 1 | pages = S92–S97 | year = 2005 | pmid = 15825133 | doi =10.1053/j.gastro.2005.02.018 | doi-access = free }} A recent study looking for changes in the physiology of the brain found regional cerebral hypoperfusion in 73% of untreated CD.{{cite journal | author = Addolorato G | title = Regional cerebral hypoperfusion in patients with celiac disease | journal = Am. J. Med. | volume = 116 | issue = 5 | pages = 312–317 | year = 2004 | pmid = 14984816 | doi = 10.1016/j.amjmed.2003.09.037 |name-list-style=vanc| author2 = Di Giuda D | author3 = De Rossi G | display-authors = 3 | last4 = Valenza | first4 = V | last5 = Domenicali | first5 = M | last6 = Caputo | first6 = F | last7 = Gasbarrini | first7 = A | last8 = Capristo | first8 = E | last9 = Gasbarrini | first9 = G}} The calcification of channels at the surface of the brain appears to be a leading phenomenon associated with migraine, visual, auditory, schizophrenia, epilepsy, dementia. The problem is that while these are found increased in GSE, the cause of these calcifications is unclear and this may extend beyond GSE to other immunological or allergic phenomena.

A 2007 study in Sweden of 14,000 GSE patients revealed no association of CD with

multiple sclerosis, Parkinson's disease, Alzheimer's disease, hereditary ataxia, ataxia (the symptom), Huntington's disease, myasthenia gravis, or spinal muscular atrophy, but prior polyneuropathy was associated with subsequent CD.{{cite journal |vauthors=Ludvigsson JF, Olsson T, Ekbom A, Montgomery SM | title = A population-based study of coeliac disease, neurodegenerative and neuroinflammatory diseases | journal = Aliment. Pharmacol. Ther. | volume = 25 | issue = 11 | pages = 1317–1327 | year = 2007 | pmid = 17509100 | doi = 10.1111/j.1365-2036.2007.03329.x| s2cid = 20170972 | doi-access = free }} However, a 2009 study of myasthenics revealed that 1 in 23 had high levels of anti-transglutaminase.{{cite journal |vauthors=Freeman HJ, Gillett HR, Gillett PM, Oger J |title=Adult celiac disease with acetylcholine receptor antibody positive myasthenia gravis |journal=World J. Gastroenterol. |volume=15 |issue=38 |pages=4741–4 |date=October 2009 |pmid=19824105 |pmc=2761549 |doi= 10.3748/wjg.15.4741 |doi-access=free }}

Peripheral neuropathies are greatly increased in people who have GSE. In clinical CD there is an obvious reason; avitaminosis and the inability to adsorb essential fatty acids and vitamins can lead to nervous system problems, including sensitivity of the peripheral nervous system. In addition to these problems there are a number or rare autoimmune conditions, secondary autoimmunities, such as fibromyalgia that are more frequent in GSE than in the normal population. Gulliane-Barre syndrome is associated with peripheral neuropathies, and it has been found that anti-ganglioside autoantibodies take part in the binding to axons and schwann cells. Antibodies to these gangliosides have been found elevated in coeliac disease{{cite journal |vauthors=Volta U, De Giorgio R, Granito A, Stanghellini V, Barbara G, Avoni P, Liguori R, Petrolini N, Fiorini E, Montagna P, Corinaldesi R, Bianchi FB|display-authors=3 |title=Anti-ganglioside antibodies in coeliac disease with neurological disorders |journal=Dig Liver Dis |volume=38 |issue=3 |pages=183–7 |year=2006 |pmid=16458087 |doi=10.1016/j.dld.2005.11.013 }}

A sizable fraction of individuals who have gluten ataxia have signs of GSE (either CD or elevated intraepitheal lymphocytes) and ataxia is a common symptom in GSE.{{cite journal |vauthors = Hadjivassiliou M, Grünewald RA, Chattopadhyay AK, Davies-Jones GA, Gibson A, Jarratt JA, Kandler RH, Lobo A, Powell T, Smith CM|display-authors=3 |title=Clinical, radiological, neurophysiological, and neuropathological characteristics of gluten ataxia |journal=Lancet |volume=352 |issue=9140 |pages=1582–5 |year=1998 |pmid=9843103 |doi =10.1016/S0140-6736(98)05342-2|s2cid=21937254 }} Studies of clinically undefinable ataxia generally had higher proportion of late onset gait ataxia, mild upper limb symptoms, and evidence of peripheral neuropathy, questions were raised about the specificity of testing and false positives. Patients with ataxia and CD have antibodies that react with Purkinje fibers but is restricted to the anti-gliadin IgA/IgG.{{cite journal |vauthors=Hadjivassiliou M, Boscolo S, Davies-Jones GA, Grünewald RA, Not T, Sanders DS, Simpson JE, Tongiorgi E, Williamson CA, Woodroofe NM|display-authors=3 |title=The humoral response in the pathogenesis of gluten ataxia |journal=Neurology |volume=58 |issue=8 |pages=1221–6 |year=2002 |pmid=11971090 | doi = 10.1212/wnl.58.8.1221 }} A recent Swedish study of 14,000 registered coeliacs showed no association of GSE with Ataxia.

Epilepsy has been noticed in a sampling of coeliac disease patients.{{cite journal |vauthors=Chapman RW, Laidlow JM, Colin-Jones D, Eade OE, Smith CL | title = Increased prevalence of epilepsy in coeliac disease | journal = British Medical Journal | volume = 2 | issue = 6132 | pages = 250–251 | year = 1978 | pmid = 678891 | doi =10.1136/bmj.2.6132.250 | pmc = 1606375 }} One prime example is calcium channel obstruction in the brain and dementia.{{cite journal |vauthors=Molteni N, Bardella MT, Baldassarri AR, Bianchi PA | title = Celiac disease associated with epilepsy and intracranial calcifications: report of two patients | journal = Am. J. Gastroenterol. | volume = 83 | issue = 9 | pages = 992–4 | year = 1988 | pmid = 3414652 }}{{cite journal |vauthors=Gobbi G, Ambrosetto P, Zaniboni MG, Lambertini A, Ambrosioni G, Tassinari CA | title = Celiac disease, posterior cerebral calcifications and epilepsy | journal = Brain Dev. | volume = 14 | issue = 1 | pages = 23–9 | year = 1992 | pmid = 1590524 | doi =10.1016/S0387-7604(12)80275-0 | s2cid = 4782109 }} There is a growing body of evidence suggesting that subclinical cases in older adults will typically progress toward dementia,{{cite journal |vauthors=Hu WT, Murray JA, Greenaway MC, Parisi JE, Josephs KA | title = Cognitive impairment and celiac disease | journal = Arch. Neurol. | volume = 63 | issue = 10 | pages = 1440–1446 | year = 2006 | pmid = 17030661 | doi = 10.1001/archneur.63.10.1440| doi-access = free }} a large number of studies in Italy and Spain have documented earlier onset cases, though the autoimmune condition is not known, folic acid malabsorption may be the cause.

According to recent studies, calcifications of channels seen in dementia can also occur in specific brain areas such as the visual complex in the occipital lobe. Such calcium channel blockages can cause visual problems or partial field hallucinations (Paroxysmal visual manifestations).{{cite journal |vauthors=Pfaender M, D'Souza WJ, Trost N, Litewka L, Paine M, Cook M | title = Visual disturbances representing occipital lobe epilepsy in patients with cerebral calcifications and coeliac disease: a case series | journal = J. Neurol. Neurosurg. Psychiatry | volume = 75 | issue = 11 | pages = 1623–1625 | year = 2004 | pmid = 15489401 | doi = 10.1136/jnnp.2003.031229 | pmc = 1738780}} Other papers show a link between migraine, visual aura and cerebral calcifications.{{cite journal |vauthors=D'Amico D, Rigamonti A, Spina L, Bianchi-Marzoli S, Vecchi M, Bussone G | title = Migraine, celiac disease, and cerebral calcifications: a new case | journal = Headache | volume = 45 | issue = 9 | pages = 1263–1267 | year = 2005 | pmid = 16178961 | doi = 10.1111/j.1526-4610.2005.00253_2.x| s2cid = 38602698 }} Disturbances may be followed by

convulsions and associated with gastrointestinal phenomena.

Ten (of 75) young patients had neurologic findings such as febrile seizures, single generalized seizures, mild ataxia, and muscular hypotonia with retarded motor development, but magnetic resonance imaging detected unilateral and bilateral T2-hyperintensive white-matter lesions in 15 patients (20%){{cite journal |vauthors=Kieslich M, Errázuriz G, Posselt HG, Moeller-Hartmann W, Zanella F, Boehles H | title = Brain white-matter lesions in celiac disease: a prospective study of 75 diet-treated patients | journal = Pediatrics | volume = 108 | issue = 2 | pages = e21 | year = 2001 | pmid = 11483831 | doi = 10.1542/peds.108.2.e21 | doi-access = free }}

Depression in GSE has several causes; in the more severe CD, depression can be the result of lower vitamin adsorption and essential fatty acid adsorption. Depression and anger may also be the result of lower quality of life issues as a result of gluten-free diet.{{cite journal |vauthors=Ciacci C, Iavarone A, Siniscalchi M, Romano R, De Rosa A | title = Psychological dimensions of celiac disease: toward an integrated approach | journal = Dig. Dis. Sci. | volume = 47 | issue = 9 | pages = 2082–2087 | year = 2002 | pmid = 12353859 | doi =10.1023/A:1019637315763 | s2cid = 10308376 }} Depression appears to persist on gluten free diet in a sizable fraction of GSE.{{cite journal | author = Addolorato G | title = Anxiety but not depression decreases in coeliac patients after one-year gluten-free diet: a longitudinal study | journal = Scand. J. Gastroenterol. | volume = 36 | issue = 5 | pages = 502–506 | year = 2001 | pmid = 11346203 | doi =10.1080/00365520119754 |name-list-style=vanc| author2 = Capristo E | author3 = Ghittoni G | display-authors = 3 | last4 = Valeri | first4 = C | last5 = Mascianà | first5 = R | last6 = Ancona | first6 = C | last7 = Gasbarrini | first7 = G | s2cid = 210160 }} Elevated anger has been noted also with GSE.

Anxiety is a common feature of GSE; treatment on a gluten-free diet is effective at reducing anxiety, some aspect of which may be due to malabsorption phenomena and cytokine activity (i.e. constant stress).

Fibromyalgia was found in 9% of adult patients relative to 0.03% in the general population with a link common to IBD.{{cite journal |vauthors=Zipser RD, Patel S, Yahya KZ, Baisch DW, Monarch E | title = Presentations of adult celiac disease in a nationwide patient support group | journal = Dig. Dis. Sci. | volume = 48 | issue = 4 | pages = 761–764 | year = 2003 | pmid = 12741468 | doi =10.1023/A:1022897028030 | s2cid = 37702479 }} Concurrent IBS is found in 30% to 70%. Small intestinal bacterial overgrowth is associated is common with a transient response to antimicrobial therapy.{{cite journal |vauthors=Wallace DJ, Hallegua DS | title = Fibromyalgia: the gastrointestinal link | journal = Current Pain and Headache Reports | volume = 8 | issue = 5 | pages = 364–368 | year = 2004 | pmid = 15361320 | doi =10.1007/s11916-996-0009-z | s2cid = 34122137 }}

Chronic fatigue associated with GSE is a systemic disorder, however there are neurological components that are especially manifest in blood deficiencies like avitaminosis, amineralosis and anemia. Reduced iron and the lack of vitamins folate, B₆, B₁₂ and malabsorption of essential fatty acids can cause depression and chronic fatigue.{{cite journal | author = Siniscalchi M | title = Fatigue in adult coeliac disease | journal = Aliment. Pharmacol. Ther. | volume = 22 | issue = 5 | pages = 489–494 | year = 2005 | pmid = 16128688 | doi = 10.1111/j.1365-2036.2005.02619.x |name-list-style=vanc| author2 = Iovino P | author3 = Tortora R | display-authors = 3 | last4 = Forestiero | first4 = S. | last5 = Somma | first5 = A. | last6 = Capuano | first6 = L. | last7 = Franzese | first7 = M. D. | last8 = Sabbatini | first8 = F. | last9 = Ciacci | first9 = C.| s2cid = 43543388 | doi-access = free }} Anti-gliadin antibodies correlate with higher risk for chronic-fatique when no clinical finding of CD is present.{{cite journal |vauthors=Arnason JA, Gudjónsson H, Freysdóttir J, Jónsdóttir I, Valdimarsson H | title = Do adults with high gliadin antibody concentrations have subclinical gluten intolerance? | journal = Gut | volume = 33 | issue = 2 | pages = 194–197 | year = 1992 | pmid = 1541415 | doi =10.1136/gut.33.2.194 | pmc = 1373929 }}

While fatigue is reduced on gluten-free diet, bouts of depression can become worse.

Some instance of arthritis with small bowel villous atrophy have been found to resolve

on gluten free diet,{{cite journal | author = Pinals RS | title = Arthritis associated with gluten-sensitive enteropathy | journal = J. Rheumatol. | volume = 13 | issue = 1 | pages = 201–4 | year = 1986 | pmid = 3701733 }} and anti-connective tissue antibodies have been found in increased levels in coeliac disease.{{cite journal |vauthors=Williamson N, Asquith P, Stokes L, Jowett W, Cooke WT | title = Anticonnective tissue and other antitissue 'antibodies' in the sera of patients with coeliac disease compared with the findings in a mixed hospital population | journal = J. Clin. Pathol. | volume = 29 | issue = 6 | pages = 484–494 | year = 1976 | pmid = 939804 | doi =10.1136/jcp.29.6.484 | pmc = 476105 }} Anti-rheumatoid factor antibodies are also increased.{{cite journal |vauthors=Sökjer M, Jónsson T, Bödvarsson S, Jónsdóttir I, Valdimarsson H | title = Selective increase of IgA rheumatoid factor in patients with gluten sensitivity | journal = Acta Derm. Venereol. | volume = 75 | issue = 2 | pages = 130–2 | year = 1995 | pmid = 7604641 | doi = 10.2340/0001555575130132| doi-access = free }} In addition, cross-reactive anti-beef-collagen antibodies (IgG) may explain some rheumatoid arthritis (RA) incidences.{{cite journal |vauthors=Dieterich W, Esslinger B, Trapp D, Hahn E, Huff T, Seilmeier W, Wieser H, Schuppan D | title = Cross linking to tissue transglutaminase and collagen favours gliadin toxicity in coeliac disease | journal = Gut | volume = 55 | issue = 4 | pages = 478–484 | year = 2006 | pmid = 16188922 | doi = 10.1136/gut.2005.069385 | pmc = 1856150}} Although the presence of anti-beef collagen antibodies does not necessarily lead to RA, the RA association with Triticeae consumption is secondary to GSE and involves DRB1*0401/4 linkages to DQ8{{cite journal |vauthors=Molberg O, Sollid LM | title = A gut feeling for joint inflammation - using coeliac disease to understand rheumatoid arthritis | journal = Trends Immunol. | volume = 27 | issue = 4 | pages = 188–194 | year = 2006 | pmid = 16530013 | doi = 10.1016/j.it.2006.02.006}} and is debatable. In one instance rheumatoid arthritis was tied directly to refractory disease.{{cite journal | author = Volta U | title = Autoimmune enteropathy and rheumatoid arthritis: a new association in the field of autoimmunity | journal = Digestive and Liver Disease | volume = 38 | issue = 12 | pages = 926–929 | year = 2006 | pmid = 16920048 | doi = 10.1016/j.dld.2006.02.003 |name-list-style=vanc| author2 = De Angelis GL | author3 = Granito A | display-authors = 3 | last4 = Petrolini | first4 = N | last5 = Fiorini | first5 = E | last6 = Guidi | first6 = M | last7 = Muratori | first7 = P | last8 = Bianchi | first8 = F}}

Still's disease (AOSD) is a rheumatic disorder of unknown etiology characterized by a triad of fever, polyarthritis and evanescent rash. An idiopathic case has been reported with coeliac disease.{{cite journal |vauthors=Kumar S, Gupta N, Jhamb R, Mishra D | title = Celiac disease: Association with adult-onset Still's disease: Apropos of a clinical case | journal = Indian Journal of Medical Sciences | volume = 61 | issue = 7 | pages = 414–7 | year = 2007 | pmid = 17611347 | doi =10.4103/0019-5359.33191 | doi-access = free }}

Some myopathies may be the indirect result of malabsorption of fat soluble vitamins such as vitamin E.

Dermatomyositis is associated with CD in children and more recently established in adults.{{cite journal | author = Marie I | title = An uncommon association: celiac disease and dermatomyositis in adults | journal = Clin. Exp. Rheumatol. | volume = 19 | issue = 2 | pages = 201–3 | year = 2001 | pmid = 11326486 |name-list-style=vanc| author2 = Lecomte F | author3 = Hachulla E | display-authors = 3 | last4 = Antonietti | first4 = M | last5 = François | first5 = A | last6 = Levesque | first6 = H | last7 = Courtois | first7 = H }}{{cite journal |vauthors=Song MS, Farber D, Bitton A, Jass J, Singer M, Karpati G | title = Dermatomyositis associated with celiac disease: response to a gluten-free diet | journal = Can. J. Gastroenterol. | volume = 20 | issue = 6 | pages = 433–5 | year = 2006 | pmid = 16779462 | doi = 10.1155/2006/574074| pmc = 2659927 | doi-access = free }}

Coeliac disease is associated with immune complex glomerulonephritis.{{cite journal |vauthors=Katz A, Dyck RF, Bear RA | title = Celiac disease associated with immune complex glomerulonephritis | journal = Clin. Nephrol. | volume = 11 | issue = 1 | pages = 39–44 | year = 1979 | pmid = 428155 }} Anti-gliadin IgA antibodies are found also more commonly in patients with IgA Nephropathy. The paper finds a link between GSE and IgA Nephropathy, but not between CD and nephropathy.{{cite journal |vauthors=Almroth G, Axelsson T, Müssener E, Grodzinsky E, Midhagen G, Olcén P | title = Increased Prevalence of Anti-Gliadin IgA-Antibodies with Aberrant Duodenal Histopathological Findings in Patients with IgA-Nephropathy and Related Disorders | journal = Ups. J. Med. Sci. | volume = 111 | issue = 3 | pages = 339–352 | year = 2006 | pmid = 17578801 | doi =10.3109/2000-1967-060 | s2cid = 25201041 | doi-access = free }} Calcium oxalate correlates with severity of fat malabsorption in coeliac disease.{{cite journal |vauthors=McDonald GB, Earnest DL, Admirand WH | title = Hyperoxaluria correlates with fat malabsorption in patients with sprue | journal = Gut | volume = 18 | issue = 7 | pages = 561–566 | year = 1977 | pmid = 873337 | doi =10.1136/gut.18.7.561 | pmc = 1411579 }}{{cite journal | author = Stauffer JQ | title = Hyperoxaluria and intestinal disease. The role of steatorrhea and dietary calcium in regulating intestinal oxalate absorption | journal = The American Journal of Digestive Diseases | volume = 22 | issue = 10 | pages = 921–8 | year = 1977 | pmid = 920694 | doi =10.1007/BF01076170 | s2cid = 5804667 }}

CD is associated with two grades of disease linked precancerous states. This condition

is known as refractory coeliac disease (RCD), defined as malabsorption due to gluten-related enteropathy (villous atrophy or elevated intraepitheal lymphocytes) after initial or subsequent failure of a strict gluten-free diet (usually 1 year) and after exclusion of any disorder mimicking coeliac disease.{{cite journal |vauthors=Daum S, Cellier C, Mulder CJ | title = Refractory coeliac disease | journal = Best Practice & Research. Clinical Gastroenterology | volume = 19 | issue = 3 | pages = 413–424 | year = 2005 | pmid = 15925846 | doi = 10.1016/j.bpg.2005.02.001}}{{cite journal | author = Goerres MS | title = Azathioprine and prednisone combination therapy in refractory coeliac disease | journal = Aliment. Pharmacol. Ther. | volume = 18 | issue = 5 | pages = 487–494 | year = 2003 | pmid = 12950421 | doi =10.1046/j.1365-2036.2003.01687.x |name-list-style=vanc| author2 = Meijer JW | author3 = Wahab PJ | display-authors = 3 | last4 = Kerckhaert | first4 = J. A. M. | last5 = Groenen | first5 = P. J. T. A. | last6 = Van Krieken | first6 = J. H. J. M. | last7 = Mulder | first7 = C. J. J. | s2cid = 137361 }}

• RCD 1 involves precancerous tissues in which transformed T-cells continue to produce a response even though gluten is no longer present.{{cite journal |vauthors=Al-Toma A, Verbeek WH, Mulder CJ | title = Update on the management of refractory coeliac disease | journal = Journal of Gastrointestinal and Liver Diseases | volume = 16 | issue = 1 | pages = 57–63 | year = 2007 | pmid = 17410290 }} Some RCD1 patients have been treated successfully with immunosuppressants (azathioprine, prednisone) when caught early. Elemental diet (proteins digested to amino acids) seems to be an effective alternative diet,{{cite journal | vauthors = Olaussen RW, Løvik A, Tollefsen S, Andresen PA, Vatn MH, De Lange T, Bratlie J, Brandtzaeg P, Farstad IN, Lundin KE | title = Effect of elemental diet on mucosal immunopathology and clinical symptoms in type 1 refractory celiac disease|display-authors=3 | journal = Clin. Gastroenterol. Hepatol. | volume = 3 | issue = 9 | pages = 875–885 | year = 2005 | pmid = 16234025 | doi =10.1016/S1542-3565(05)00295-8 | doi-access = free }} indicating other proteins are stimulating the IEL. 5 year viability is high when treated. DQ representation is similar to non-RCD coeliacs.
• RCD 2 involves neoplastic tissues that the lack of surface expression of usual T-cell markers.{{cite journal |vauthors=Krauss N, Schuppan D | title = Monitoring nonresponsive patients who have celiac disease | journal = Gastrointest. Endosc. Clin. N. Am. | volume = 16 | issue = 2 | pages = 317–327 | year = 2006 | pmid = 16644460 | doi = 10.1016/j.giec.2006.03.005}}{{Retracted|doi=10.1016/j.giec.2006.03.005|intentional=yes}}
• Increased expression of: Intracytoplasmic CD3e, Surface CD103
• Decreased expression of: CD8, CD4, TCR-alpha/beta

:Clonal T-cell expansion in RCD2 is not manageable with steroids (see: RCD 1) and sometimes manageable with chemotherapeutic drugs,{{cite journal | author = Al-Toma A | title = Cladribine therapy in refractory celiac disease with aberrant T cells | journal = Clin. Gastroenterol. Hepatol. | volume = 4 | issue = 11 | pages = 1322–1327 | year = 2006 | pmid = 16979946 | doi = 10.1016/j.cgh.2006.07.007 |name-list-style=vanc| author2 = Goerres MS | author3 = Meijer JW | display-authors = 3 | last4 = Von Blomberg | first4 = B. Mary E. | last5 = Wahab | first5 = Peter J. | last6 = Kerckhaert | first6 = Jo A.M. | last7 = Mulder | first7 = Chris J.J.}} however, more aggressive therapies seem more affective. A high percentage of RCD 2 patients spontaneously develop lymphoma (EATL), the 5 year survival rate is markedly lower than RCD1 but higher than lymphoma. DQ2.5/DQ2 individuals are more frequently found.{{cite journal |vauthors=Al-Toma A, Goerres MS, Meijer JW, Peña AS, Crusius JB, Mulder CJ | title = Human leukocyte antigen-DQ2 homozygosity and the development of refractory celiac disease and enteropathy-associated T-cell lymphoma | journal = Clin. Gastroenterol. Hepatol. | volume = 4 | issue = 3 | pages = 315–319 | year = 2006 | pmid = 16527694 | doi = 10.1016/j.cgh.2005.12.011}}

Causes of RCD.

• Coeliac disease
• Age at CD/GSE diagnosis – most people are over the age of 50 when first diagnosed at RCD
• Dietary noncompliance – Some EATL appears years after diagnosis with non-GF diets.
• Length of latency – The length of time, often unknown in which the person is GSE+.
• Severity – The severity of the microscopic destruction appears to be a factor, and genetics appears now to play a role.{{cite journal | author = Jores RD | title = HLA-DQB1*0201 homozygosis predisposes to severe intestinal damage in celiac disease | journal = Scand. J. Gastroenterol. | volume = 42 | issue = 1 | pages = 48–53 | year = 2007 | pmid = 17190762 | doi = 10.1080/00365520600789859 |name-list-style=vanc| author2 = Frau F | author3 = Cucca F | display-authors = 3 | last4 = Grazia Clemente | first4 = Maria | last5 = Orrù | first5 = Sandra | last6 = Rais | first6 = Marco | last7 = De Virgiliis | first7 = Stefano | last8 = Congia | first8 = Mauro| s2cid = 7675714 }}
• Genetics – For RCD 2 and EATL, genetics plays large role DQ2.5/DQ2+ individuals are over-represented in the patient set

GSE, particularly coeliac disease, increases the risk of cancers of specific types.{{cite journal |vauthors=Holmes GK, Stokes PL, Sorahan TM, Prior P, Waterhouse JA, Cooke WT | title = Coeliac disease, gluten-free diet, and malignancy | journal = Gut | volume = 17 | issue = 8 | pages = 612–619 | year = 1976 | pmid = 789184 | doi =10.1136/gut.17.8.612 | pmc = 1411326 }} There are two predominant cancers associated with coeliac disease, cancer of the esophagus and lymphoproliferative diseases such as gluten-sensitive enteropathy-associated T-cell lymphoma (EATL).{{cite journal |vauthors=Ferguson A, Kingstone K | title = Coeliac disease and malignancies | journal = Acta Paediatrica Supplement | volume = 412 | pages = 78–81 | year = 1996 | pmid = 8783767 | doi =10.1111/j.1651-2227.1996.tb14259.x | s2cid = 156686 }} For non-EATL cancers it is thought the mineralemias such as zinc and selenium may play a role in increasing risk. GSE associated cancers are invariably associated with advanced coeliac disease, however, in de-novo EATL, the cancer is frequently detected in advance of the coeliac diagnosis, also EATL is the most common neoplasm.

Squamous carcinoma of the esophagus is more prevalent in coeliac disease.{{cite journal |vauthors=Selby WS, Gallagher ND | title = Malignancy in a 19-year experience of adult celiac disease | journal = Dig. Dis. Sci. | volume = 24 | issue = 9 | pages = 684–688 | year = 1979 | pmid = 487922 | doi =10.1007/BF01314465 | s2cid = 3200328 }} The increased prevalence may be secondary to GERD that results from chronic delayed gastric emptying. Other studies implicate the malabsorption of vitamin A and zinc as a result of multi-vitamin and mineral deficiencies seen in coeliac disease.

Adenocarcinoma of the bowel has been associated with coeliac disease.{{cite journal |vauthors=Petreshock EP, Pessah M, Menachemi E | title = Adenocarcinoma of the jejunum associated with nontropical sprue | journal = The American Journal of Digestive Diseases | volume = 20 | issue = 8 | pages = 796–802 | year = 1975 | pmid = 1155420 | doi =10.1007/BF01070840 | s2cid = 1201520 }}

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{{Gluten sensitivity}}

{{DEFAULTSORT:Gluten-Sensitive Enteropathy Associated Conditions}}

Enteropathy