Wheat allergy

Wheat
Specialty| Immunology

Wheat allergy is an allergy to wheat that typically presents as a food allergy, but can also be a contact allergy resulting from occupational exposure. The exact mechanism of this allergy is not yet clear. Wheat allergy may be immunoglobulin E-mediated or not,[1] and may involve a mast cell response.[2] Wheat allergy is rare—its prevalence in adults was estimated to be 0.21% in a 2012 study in Japan.[3]

Wheat allergy may be a misnomer. There are many allergenic components in wheat (for example: serine protease inhibitors, glutelins and prolamins), with different responses attributed to different components. Twenty-seven potential wheat allergens have been identified.[4]

The allergy, or allergies, are often caused by reactions to the storage proteins present in a wheat seed. While many reactions are caused by wheat proteins, allergenic components are also present in other biochemical forms. The most severe response is wheat-dependent exercise-induced anaphylaxis (WDEIA). WDEIA is attributed to an omega gliadin, which happens to be a relative of the protein that causes celiac disease.[5] Symptoms include nausea, urticaria, and atopy.[6]

Gluten sensitivity and Coeliac disease are two different diseases; however, the management is similar.[7] Management of wheat allergy consists of complete withdrawal of any food containing wheat or other gluten-containing cereals.

## Contents

* 1 Types of allergies
* 1.1 Gluten allergy
* 1.1.1 Prolamin allergies
* 1.1.2 Glutelin allergies
* 1.2 Albumin and globulin allergy
* 1.3 Other allergies
* 1.3.1 Wheat pollen and grass allergies
* 1.3.2 Derivative allergies
* 2 Signs and symptoms
* 2.1 Asthma, anaphylaxis, nasal allergies
* 2.1.1 Exercise-induced anaphylaxis
* 2.1.2 Baker's allergy
* 2.2 Urticaria, atopy, eczema
* 2.3 Rheumatoid arthritis
* 2.4 Neuropathies
* 3 Diagnosis
* 4 Prevention
* 4.1 Alternative cereals
* 5 Treatment
* 6 See also
* 7 References
* 8 External links

## Types of allergies

Most wheat allergens are proteins,[4] including seed storage proteins, as noted above. There are four major classes of seed storage proteins: albumins, globulins, prolamins and glutenins.[8]

### Gluten allergy

See also: Gluten sensitivity

The relevant prolamins in wheat are gliadins. Gliadins and glutenins form the classic glutens—the causative agents of celiac disease (CD). Distinct immune cells and antibody types differentiate gluten allergy from CD (see Comparative pathophysiology of gluten sensitivities).

#### Prolamin allergies

Prolamins (gliadins) are associated with the more severe form of gluten allergy. Glutenin-induced allergies are often less severe. A proteomics-based study found a γ-gliadin isoform gene.[5]

#### Glutelin allergies

Glutenin (wheat glutelin) is a predominant allergen in wheat.[5] Nine subunits of LMW-glutenin have been found to be in connection with wheat allergies.[clarification needed]

### Albumin and globulin allergy

At present, many of the allergens of wheat have not been characterized; however, the early studies found many to be in the albumin class.[9] A recent study in Europe confirmed the increased presence of allergies to amylase/trypsin inhibitors (serpins)[5][10] and lipid transfer protein (LPT),[11] but less reactivity to the globulin fraction.[12] The allergies tend to differ between populations (Italian, Japanese, Danish or Swiss), indicating a potential genetic component to these reactivities.

### Other allergies

#### Wheat pollen and grass allergies

Respiratory allergies are an occupational disease that develops in food service workers. Previous studies detected 40 allergens from wheat; some cross-reacted with rye proteins and a few cross-reacted with grass pollens.[13] A later study showed that baker's allergy extends over a broad range of cereal grasses (wheat, durum wheat, triticale, cereal rye, barley, rye grass, oats, canary grass, rice, maize, sorghum and Johnson grass), though the greatest similarities were seen between wheat and rye,[14] and that these allergies show cross-reactivity between seed proteins and pollen proteins,[15] including a prominent cross-reactivity between the common environment rye pollen and wheat gluten.[16][17]

#### Derivative allergies

When proteins are cut into polypeptides, buried regions are exposed to the surface, and these buried regions may possibly be antigenic. Such hydrolyzed wheat protein is used as an additive in foods and cosmetics. The peptides are often 1 kD in size (9 amino acid residues in length) and may increase the allergic response.[18] These wheat polypeptides can cause immediate contact urticaria in susceptible people.[19]

## Signs and symptoms

Common symptoms of a wheat allergy include eczema (atopic dermatitis), hives (urticaria), asthma, "hay fever" (allergic rhinitis), angioedema (tissue swelling due to fluid leakage from blood vessels), abdominal cramps, nausea, and vomiting.[20] Rarer symptoms include anaphylactic shock, anxiety, arthritis, bloated stomach, chest pains, depression or mood swings, diarrhea, dizziness, headache, joint and muscle aches and pains (may be associated with progressive arthritis), palpitations, psoriasis, irritable bowel syndrome (IBS), swollen throat or tongue, tiredness and lethargy, and unexplained cough.

### Asthma, anaphylaxis, nasal allergies

#### Exercise-induced anaphylaxis

Main article: Medicine:Exercise-induced anaphylaxis

Wheat gliadins and potentially oat avenins are associated with another disease, known as wheat-dependent exercise induced anaphylaxis (WDEIA) which is similar to baker's allergy as both are mediated by IgE responses.[1] In WDEIA, however, the ω-gliadins or a high molecular weight glutenin subunit, and similar proteins in other Triticeae genera, enter the blood stream during exercise where they cause acute asthmatic or allergic reaction.[1] Wheat may specifically induce WDEIA and certain chronic urticaria because the anti-gliadin IgE detects ω5-gliadins expressed by most of the Gli-B1 alleles, but prolamins extracted from rye or wheat/rye translocates invoke almost no responses.[1] The Gli-B1 gene in wheat, Triticum aestivum, comes from the progenitor species Aegilops speltoides. This indicates that nascent mutations on the B genome of wheat are from a small number of cultivated Triticeae species.[21]

#### Baker's allergy

Baker's allergy has a ω-gliadin component and thioredoxin hB component.[22] In addition, a gluten-extrinsic allergen has been identified as aspergillus amylase, added to flour to increase its baking properties.

Allergic urticaria on the shin

### Urticaria, atopy, eczema

Contact sensitivity,[23] atopic dermatitis,[24] eczema, and urticaria appear to be related phenomena, the cause of which is generally believed to be the hydrophobic prolamin components of certain Triticeae, Aveneae cultivars. In wheat one of these proteins is ω-gliadin (Gli-B1 gene product). A study of mothers and infants on an allergen-free diet demonstrated that these conditions can be avoided if wheat sensitive cohort in the population avoid wheat in the first year of life.[25] As with exercise induced anaphylaxis, aspirin (also: tartrazine, sodium benzoate, sodium glutamate (MSG), sodium metabisulfite, tyramine) may be sensitizing factors for reactivity.[26] Studies of the wheat-dependent exercise induced anaphylaxis demonstrate that atopy and EIA can be triggered from the ingestion wheat proteins into the blood, where IgE reacts within allergens in the dermal tissues. Some individuals may be so sensitive that low dose aspirin therapy can increase risk for both atopy and WDEIA.

### Rheumatoid arthritis

There appears to be an association of rheumatoid arthritis (RA) both with gluten sensitive enteropathy (GSE) and gluten allergies.[27] RA in GSE/CD may be secondary to tissue transglutaminase (tTG) autoimmunity. In a recent study in Turkey, 8 of 20 RA patients had wheat reactivities on the radioallergosorbent test (RAST). When this allergic food and all other patient specific RAST+ foods were removed half of the patients had improved RA by serological markers. In patients with wheat allergies, rye was effectively substituted.[28] This may indicate that some proportion of RA in GSE/CD is due to downstream effects of allergic responses. In addition, cross-reactive anti-beef-collagen antibodies (IgG) may explain some rheumatoid arthritis (RA) incidents.[29]

### Neuropathies

Migraines. In the late 1970s it was reported that people with migraines had reactions to food allergens. Similarly to people with RA, the most common reaction among people with migraines was to wheat (78%), orange, eggs, tea, coffee, chocolate, milk, beef, corn, cane sugar, and yeast. When 10 foods causing the most reactions were removed, migraines fell precipitously and hypertension declined.[30] Some specific instances are attributed to wheat.[31]

Autism. Parents of children with autism often ascribe the children's gastrointestinal symptoms to allergies to wheat and other foods. The published data on this approach are sparse, with the only double-blind study reporting negative results.[32]

## Diagnosis

Diagnoses of wheat allergy may deserve special consideration.[1] Omega-5 gliadin, the most potent wheat allergen, cannot be detected in whole wheat preparations; it must be extracted and partially digested (similar to how it degrades in the intestine) to reach full activity.[33] Other studies show that digestion of wheat proteins to about 10 amino acids can increase the allergic response 10-fold. Certain allergy tests may not be suitable to detect all wheat allergies, resulting in cryptic allergies. Because many of the symptoms associated with wheat allergies, such as eczema and asthma, may be related or unrelated to a wheat allergy, medical deduction can be an effective way of determining the cause.[33] If symptoms are alleviated by immunosuppressant drugs, such as prednisone, an allergy-related cause is likely. If multiple symptoms associated with wheat allergies are present in the absence of immunosuppressants then a wheat allergy is probable.[1]

## Prevention

Management of wheat allergy consists of complete withdrawal of any food containing wheat and other gluten-containing cereals (gluten-free diet).[34][35] However, some patients can tolerate barley, rye or oats.[36]

In people with less severe forms of wheat-dependent exercise induced anaphylaxis (WDEIA), avoiding wheat consumption before exercise and other cofactors that trigger disease symptoms, such as nonsteroidal anti-inflammatory drugs and alcohol, can be sufficient to avoid an allergy.[35]

### Alternative cereals

Triticeae gluten-free oats (free of wheat, rye or barley) may be a useful source of cereal fiber. Some wheat allergies allow the use of rye bread as a substitute. Rice flour is a commonly used alternative for those allergic to wheat. Wheat-free millet flour, buckwheat, flax seed meal, corn meal, quinoa flour, chia seed flour, tapioca starch or flour, and others can be used as substitutes.

## Treatment

Epinephrine autoinjectors are portable single-dose epinephrine-dispensing devices used to treat anaphylaxis.

Treatment for accidental ingestion of wheat products by allergic individuals varies depending on the sensitivity of the person. An antihistamine such as diphenhydramine may be prescribed. Sometimes prednisone will be prescribed to prevent a possible late phase Type I hypersensitivity reaction.[37] Severe allergic reactions (anaphylaxis) may require treatment with an epinephrine pen, which is an injection device designed to be used by a non-healthcare professional when emergency treatment is warranted.[38]

## See also

* Allergy (has diagrams showing involvement of different types of white blood cells)
* Food allergy (has images of hives, skin prick test and patch test)
* Gluten immunochemistry
* List of allergens (food and non-food)

## References

1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Cianferoni, Antonella (29 January 2016). "Wheat allergy: diagnosis and management". Journal of Asthma and Allergy 9: 13–25. doi:10.2147/jaa.s81550. ISSN 1178-6965. PMID 26889090.
2. ↑ Sutton, Brian J.; Davies, Anna M.; Bax, Heather J.; Karagiannis, Sophia N. (22 Feb 2019). "IgE Antibodies: From Structure to Function and Clinical Translation". Antibodies 8 (1): 19. doi:10.3390/antib8010019. PMID 31544825.
3. ↑ "Prevalence of wheat allergy in Japanese adults". Allergol Int 61 (1): 101–5. March 2012. doi:10.2332/allergolint.11-OA-0345. PMID 22377522.
4. ↑ 4.0 4.1 "A new approach to the isolation and characterization of wheat flour allergens". Clinical & Experimental Allergy 41 (7): 1031–43. July 2011. doi:10.1111/j.1365-2222.2011.03766.x. PMID 21623965.
5. ↑ 5.0 5.1 5.2 5.3 "Proteomic analysis of wheat flour allergens". J. Agric. Food Chem. 55 (17): 6863–70. 2007. doi:10.1021/jf070843a. PMID 17655322. Bibcode: 2007JAFC...55.6863A.
6. ↑ Perr HA (2006). "Novel foods to treat food allergy and gastrointestinal infection". Current Allergy and Asthma Reports 6 (2): 153–9. doi:10.1007/s11882-006-0054-z. PMID 16566866.
7. ↑ Costantino, A., Aversano, G., Lasagni, G., Smania, V., Doneda, L., Vecchi, M., ... & Elli, L. (2022). Diagnostic management of patients reporting symptoms after wheat ingestion. Frontiers in Nutrition, 9.
8. ↑ Chrungoo, N. K.; Dohtdong, L.; Chettry, U. (2016-01-01), Zhou, Meiliang; Kreft, Ivan; Woo, Sun-Hee et al., eds., "Chapter thirty one - Diversity in Seed Storage Proteins and Their Genes in Buckwheat", Molecular Breeding and Nutritional Aspects of Buckwheat (Academic Press): pp. 387–399, ISBN 978-0-12-803692-1, https://www.sciencedirect.com/science/article/abs/pii/B9780128036921000316, retrieved 2025-01-06
9. ↑ "Immunoglobulin E antibodies to ingested cereal flour components: studies with sera from subjects with asthma and eczema". Clinical & Experimental Allergy 12 (1): 63–74. 1982. doi:10.1111/j.1365-2222.1982.tb03127.x. PMID 7067068.
10. ↑ "In vivo allergenic activities of eleven purified members of a major allergen family from wheat and barley flour". Clin. Exp. Allergy 23 (5): 410–5. 1993. doi:10.1111/j.1365-2222.1993.tb00347.x. PMID 8334538.
11. ↑ Pastorello EA; Farioli L; Conti A et al. (2007). "Wheat IgE-mediated food allergy in European patients: alpha-amylase inhibitors, lipid transfer proteins and low-molecular-weight glutenins. Allergenic molecules recognized by double-blind, placebo-controlled food challenge". Int. Arch. Allergy Immunol. 144 (1): 10–22. doi:10.1159/000102609. PMID 17496422.
12. ↑ "A comparison of the binding of IgE in the sera of patients with bakers' asthma to soluble and insoluble wheat-grain proteins". J. Allergy Clin. Immunol. 76 (1): 23–8. 1985. doi:10.1016/0091-6749(85)90799-7. PMID 3839248.
13. ↑ "Flour allergy in bakers. I. Identification of allergenic fractions in flour and comparison of diagnostic methods". Int. Arch. Allergy Appl. Immunol. 52 (1–4): 392–406. 1976. doi:10.1159/000231706. PMID 65335.
14. ↑ "Hypersensitivity to inhaled flour allergens. Comparison between cereals". Allergy 35 (1): 45–56. 1980. doi:10.1111/j.1398-9995.1980.tb01716.x. PMID 6154431.
15. ↑ "Hypersensitivity to wheat flour in bakers". Allergologia et Immunopathologia 16 (5): 309–14. 1988. PMID 3228051.
16. ↑ "Crossreactivity of IgE antibodies from sera of subjects allergic to both ryegrass pollen and wheat endosperm proteins: evidence for common allergenic determinants". Clin. Exp. Allergy 20 (5): 501–9. 1990. doi:10.1111/j.1365-2222.1990.tb03142.x. PMID 2253081.
17. ↑ "Sensitization to common allergens, especially pollens, among children with respiratory allergy in the Trakya region of Turkey". Asian Pac. J. Allergy Immunol. 22 (4): 183–90. 2004. PMID 15783130. .
18. ↑ Akiyama H; Sakata K; Yoshioka Y et al. (2006). "Profile analysis and immunoglobulin E reactivity of wheat protein hydrolysates". Int. Arch. Allergy Immunol. 140 (1): 36–42. doi:10.1159/000092000. PMID 16534217.
19. ↑ Laurière M; Pecquet C; Bouchez-Mahiout I et al. (2006). "Hydrolysed wheat proteins present in cosmetics can induce immediate hypersensitivities". Contact Derm. 54 (5): 283–9. doi:10.1111/j.0105-1873.2006.00830.x. PMID 16689814.
20. ↑ "Allergy Society of South Africa – Wheat Allergy". http://www.allergysa.org/wheat.htm.
21. ↑ Denery-Papini S; Lauriére M; Branlard G et al. (2007). "Influence of the allelic variants encoded at the Gli-B1 locus, responsible for a major allergen of wheat, on IgE reactivity for patients suffering from food allergy to wheat". J. Agric. Food Chem. 55 (3): 799–805. doi:10.1021/jf062749k. PMID 17263477. Bibcode: 2007JAFC...55..799D.
22. ↑ "Wheat and maize thioredoxins: a novel cross-reactive cereal allergen family related to baker's asthma". J. Allergy Clin. Immunol. 117 (3): 676–81. 2006. doi:10.1016/j.jaci.2005.11.040. PMID 16522470.
23. ↑ "Contact urticaria to wheat bran bath: a case report". Acta Derm. Venereol. 62 (1): 82–3. 1982. doi:10.2340/00015555628283. PMID 6175150.
24. ↑ "IgE-mediated allergy in adults with severe atopic eczema". Clin. Exp. Allergy 19 (3): 321–5. 1989. doi:10.1111/j.1365-2222.1989.tb02390.x. PMID 2736432.
25. ↑ Zeiger RS; Heller S; Mellon MH et al. (1989). "Effect of combined maternal and infant food-allergen avoidance on development of atopy in early infancy: a randomized study". J. Allergy Clin. Immunol. 84 (1): 72–89. doi:10.1016/0091-6749(89)90181-4. PMID 2754147.
26. ↑ "Food and food additives in severe atopic dermatitis". Allergy 44 (8): 588–94. 1989. doi:10.1111/j.1398-9995.1989.tb04205.x. PMID 2610332.
27. ↑ "The gut–joint axis: cross reactive food antibodies in rheumatoid arthritis". Gut 55 (9): 1240–7. 2006. doi:10.1136/gut.2005.076901. PMID 16484508.
28. ↑ Karatay S; Erdem T; Kiziltunc A et al. (2006). "General or personal diet: the individualized model for diet challenges in patients with rheumatoid arthritis". Rheumatol. Int. 26 (6): 556–60. doi:10.1007/s00296-005-0018-y. PMID 16025333.
29. ↑ "Cross linking to tissue transglutaminase and collagen favours gliadin toxicity in coeliac disease". Gut 55 (4): 478–84. 2006. doi:10.1136/gut.2005.069385. PMID 16188922.
30. ↑ Grant EC (1979). "Food allergies and migraine". Lancet 1 (8123): 966–9. doi:10.1016/S0140-6736(79)91735-5. PMID 87628.
31. ↑ "A woman with daily headaches". The Journal of Headache and Pain 6 (2): 91–2. 2005. doi:10.1007/s10194-005-0158-1. PMID 16362649.
32. ↑ Elder JH (2008). "The gluten-free, casein-free diet in autism: an overview with clinical implications". Nutr Clin Pract 23 (6): 583–8. doi:10.1177/0884533608326061. PMID 19033217.
33. ↑ 33.0 33.1 Zubrinich, C.; Puy, R.; O'Hehir, R.; Hew, M. (2021). "Evaluation of Diagnosis and Management of Omega-5-Gliadin Allergy: A Retrospective Survey". Journal of Asthma and Allergy 14: 397–403. doi:10.2147/JAA.S304444. PMID 33907425.
34. ↑ "Review article: safe amounts of gluten for patients with wheat allergy or coeliac disease". Aliment Pharmacol Ther 23 (5): 559–75. Mar 1, 2006. doi:10.1111/j.1365-2036.2006.02768.x. PMID 16480395. "For both wheat allergy and coeliac disease the dietary avoidance of wheat and other gluten-containing cereals is the only effective treatment.".
35. ↑ 35.0 35.1 "Wheat-Dependent Exercise-Induced Anaphylaxis". Clin Exp Allergy 46 (1): 10–20. Sep 18, 2015. doi:10.1111/cea.12640. PMID 26381478. "Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a rare, but potentially severe food allergy exclusively occurring when wheat ingestion is accompanied by augmenting cofactors. (...) The most reliable prophylaxis of WDEIA is a gluten-free diet. In less severe cases, a strict limitation of wheat ingestion before exercise and avoidance of other cofactors may be sufficient.".
36. ↑ Pietzak M (Jan 2012). "Celiac disease, wheat allergy, and gluten sensitivity: when gluten free is not a fad". JPEN J Parenter Enteral Nutr 36 (1 Suppl): 68S–75S. doi:10.1177/0148607111426276. PMID 22237879.
37. ↑ Tang AW (October 2003). "A practical guide to anaphylaxis". Am Fam Physician 68 (7): 1325–32. PMID 14567487.
38. ↑ The EAACI Food Allergy and Anaphylaxis Guidelines Group (August 2014). "Anaphylaxis: guidelines from the European Academy of Allergy and Clinical Immunology.". Allergy 69 (8): 1026–45. doi:10.1111/all.12437. PMID 24909803. https://kclpure.kcl.ac.uk/portal/en/publications/18fea276-3a30-4c4a-8d90-9d456bb71bb8.

## External links

Classification|

* MeSH: D021182

|

* v
* t
* e

Gluten sensitivity

Conditions|

| general|

* Wheat allergy
* Oat sensitivity

|

nervous system|

* GS idiopathic neuropathies

digestive system|

* Coeliac disease
* GSE associated conditions

integumentary system|

* Dermatitis herpetiformis

Antibodies|

* Anti-gliadin antibodies
* Anti-transglutaminase antibodies

HLA-DQ|

* HLA-DQ2
* HLA-DQ8

Other|

* Gluten immunochemistry
* Gluten-free diet
* Gluten challenge test
* List of people diagnosed with coeliac disease

* v
* t
* e

Allergic conditions

Respiratory system|

* Allergic rhinitis (hay fever)
* Asthma
* Hypersensitivity pneumonitis
* Eosinophilic pneumonia
* Eosinophilic granulomatosis with polyangiitis
* Allergic bronchopulmonary aspergillosis
* Farmer's lung
* Laboratory animal allergy

Skin|

* Angioedema
* Urticaria
* Atopic dermatitis
* Allergic contact dermatitis
* Hypersensitivity vasculitis

Blood and immune system|

* Serum sickness

Circulatory system|

* Anaphylaxis

Digestive system|

* Coeliac disease
* Eosinophilic gastroenteritis
* Eosinophilic esophagitis
* Food allergy
* Egg allergy
* Milk intolerance

Nervous system|

* Eosinophilic meningitis

Genitourinary system|

* Acute interstitial nephritis

Other conditions|

* Drug allergy
* Allergic conjunctivitis
* Latex allergy

* v
* t
* e

Hypersensitivity and autoimmune diseases (279.5–6)

Type I/allergy/atopy
(IgE)|

| Foreign|

* Atopic eczema
* Allergic urticaria
* Allergic rhinitis (Hay fever)
* Allergic asthma
* Anaphylaxis
* Food allergy
* common allergies include: Milk
* Egg
* Peanut
* Tree nut
* Seafood
* Soy
* Wheat
* Penicillin allergy

|

Autoimmune|

* Eosinophilic esophagitis

Type II/ADCC

*     * IgM
* IgG

| Foreign|

* Hemolytic disease of the newborn

|

Autoimmune|

| Cytotoxic|

* Autoimmune hemolytic anemia
* Immune thrombocytopenic purpura
* Bullous pemphigoid
* Pemphigus vulgaris
* Rheumatic fever
* Goodpasture syndrome
* Guillain–Barré syndrome

|

"Type V"/receptor|

* Graves' disease
* Myasthenia gravis
* Pernicious anemia

Type III
(Immune complex)|

| Foreign|

* Henoch–Schönlein purpura
* Hypersensitivity vasculitis
* Reactive arthritis
* Farmer's lung
* Post-streptococcal glomerulonephritis
* Serum sickness
* Arthus reaction

|

Autoimmune|

* Systemic lupus erythematosus
* Subacute bacterial endocarditis
* Rheumatoid arthritis

Type IV/cell-mediated
(T cells)|

| Foreign|

* Allergic contact dermatitis
* Mantoux test

|

Autoimmune|

* Diabetes mellitus type 1
* Hashimoto's thyroiditis
* Multiple sclerosis
* Coeliac disease
* Giant-cell arteritis
* Postorgasmic illness syndrome
* Reactive arthritis

GVHD|

* Transfusion-associated graft versus host disease

Unknown/
multiple|

| Foreign|

* Hypersensitivity pneumonitis
* Allergic bronchopulmonary aspergillosis
* Transplant rejection
* Latex allergy (I+IV)

|

Autoimmune|

* Sjögren syndrome
* Autoimmune hepatitis
* Autoimmune polyendocrine syndrome
* APS1
* APS2
* Autoimmune adrenalitis
* Systemic autoimmune disease

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