Chapter 160 Dermatitis Herpetiformis
Diagnostic Summary
• Pruritic papulovesicular eruption, usually on the extensor surfaces
• Most common in middle-aged white males but may be seen in individuals of any age
• IgA deposits in the dermal papillae; confirmed by immunofluorescence
• Asymptomatic celiac disease (gluten-sensitive enteropathy) in 75% to 90% of patients
General Considerations
Dermatitis herpetiformis (DH) is a cutaneous manifestation of gluten-sensitive enteropathy (celiac disease). Patients with DH demonstrate serum IgA antibodies against epidermal transglutaminase and tissue transglutaminase.1 The putative autoantigen of DH is epidermal transglutaminase. DH has been referred to as “celiac disease of the skin.”2 Just as in celiac disease (CD), a gluten-free diet is most often all that is required to resolve the lesions. Absorption studies (see Chapter 20) can be used to assess the degree of enteropathy.
Most individuals with CD have celiac-associated antibodies and specific pairs of allelic variants in two HLA genes, HLA-DQA1 and HLA-DQB1.3 Only 3% of individuals with one or both of these alleles develops CD, yet 30% of the general population has one of them. Therefore, their presence is not diagnostic of CD but their absence excludes a diagnosis of CD. Genetic testing is available for the assessment of CD.
The average age at onset of DH is 7.2 years; it has a predilection for the elbows, knees, and buttocks. Skin biopsy shows granular or fibrillar IgA deposits.4 The characteristic skin lesions found in patients with DH are extremely itchy grouped vesicles most frequently located on extensor surfaces. Intense pruritus is the predominate symptom; however, DH is a clinical chameleon and can present with excoriations, eczematous lesions, or minimal patterns of discrete erythema or digital purpura.5
Therapeutic Considerations
Gluten
The most important factor in the treatment of patients with DH is the elimination of all sources of gluten. Frazer’s criteria for the diagnosis of gluten-sensitive enteropathy (improvement on a gluten-free diet and relapse after reintroduction) have been used in many studies and have shown conclusively that the rash and villous atrophy of DH are largely gluten dependent.6–11 Gluten elimination results in improvement in virtually all patients, including elimination of the reticulin and gluten antibodies found in patients with DH.2,12
Further study of the wheat connection has shown that the gliadin polypeptide of gluten is most likely the key antigen. Indirect immunofluorescence shows antibodies to gliadin in the sera of 45% of patients with DH. The titer and correlation increase with increasing severity of the disease; 81% of patients with severe jejunal abnormalities show antibodies to gliadin.13
Despite the published benefits of a gluten-free diet in the treatment of DH for more than 30 years now, this treatment is still often omitted from conventional dermatology and medical textbooks. The advantage of a gluten-free diet over drugs like dapsone (the most widely prescribed drug for DH) is obvious, as this drug is often associated with severe side effects. With the gluten-free diet, on the other hand:
• Most patients (more than 65%) experience complete resolution and the rest improve substantially.
• There is complete resolution of the enteropathy associated with DH.
• Harsh medications can be eliminated or substantially reduced.
Also of interest is the fact that those who used a gluten-free diet rather than drugs appear also to be protected against developing lipomas.14
Food Allergy
Although gluten control is critical in the treatment of patients with DH, some (about 35%) are not adequately helped. In particular, only one half the patients totally eliminate the cutaneous IgA deposits and develop normal jejunal tissue. This is probably because of the presence of other food allergies that, although probably not initiating, developed as a result of the increased leakage of macromolecules across the damaged gastrointestinal membranes. Milk, in particular, has been found to be significantly problematic in some patients.15,16 Using a sensitive enzyme-linked immunoassay (ELISA), 75% of DH patients were shown to have serum antibodies reactive against gliadin, bovine milk, or ovalbumin.17 These results suggest that other food sensitivities are implicated in DH. An elemental diet followed by careful food reintroduction usually produces better results than a simple gluten-free diet.18
Para-aminobenzoic Acid
Para-aminobenzoic acid (PABA) has been used successfully in the control of DH, even in those patients who are not controlling the gluten content of their diet.19 However, because its use is recommended only for symptom control and it probably does not result in repair of the villous atrophy, it is not recommended as the treatment of choice but rather as an adjunct in unresponsive cases or to help in particularly severe cases.
Therapeutic Approach
After all sources of gluten and gliadin have been eliminated (see Appendix for the gluten content of foods), a careful search should be made for other food allergies (for more detail, see Chapter 15) Once the allergens are under control, a therapeutic regimen similar to that for atopic dermatitis (see Chapter 149) should be used. Patience is necessary because a response may take several weeks to 6 months to be seen.
1. Rose C., Armbruster F.P., Ruppert J., et al. Autoantibodies against epidermal transglutaminase are a sensitive diagnostic marker in patients with dermatitis herpetiformis on a normal or gluten-free diet. J Am Acad Dermatol. 2009 Jul;61(1):39–43.
2. Fry L., Leonard J.N., Swain F., et al. Long term follow-up of dermatitis herpetiformis with and without dietary wheat gluten withdrawal. Br J Derm. 1982;107:631–640.
3. Snyder CL, Young DO, Green PHR, et al. In: Pagon RA, Bird TC, Dolan CR, et al eds. Celiac Disease, Coeliac Disease, Celiac Sprue, Nontropical Sprue, Gluten-Sensitive Enteropathy. Bookshelf. U.S. National Library of Medicine, National Institutes of Health. Gene Reviews.[Internet] 2008 Jul 03; NBK1727 PMID: 20301720
4. Ko C.J., Colegio O.R., Moss J.E., et al. Fibrillar IgA deposition in dermatitis-herpetiformis: an underreported patern with potential clinical significance. J Cutan Pathol. 2010 Apr;37(4):475–477.
5. Pfeiffer C. Dermatitis herpetiformis: a clinical chameleon. Hautarzt. 2006 Nov;57(11):1021–1028.
6. Leonard J., Haffenden G., Tucker W., et al. Gluten challenge in dermatitis herpetiformis. N Engl J Med. 1983;308:816–819.
7. Savilahti E., Reunala T. Is dermatitis herpetiformis a gluten-sensitive enteropathy? Int J Dermatol. 1990;10:706–708.
8. Reunala T. Dermatitis herpetiformis: coeliac disease of the skin. Ann Med. 1998;30:416–418.
9. Kumar V., Zane H., Kaul N. Serologic markers of gluten-sensitive enteropathy in bullous diseases. Arch Derm. 1992;128:1474–1478.
10. Frodin T., Gotthard R., Hed J., et al. Gluten-free diet for dermatitis herpetiformis: the long term effect on cutaneous, immunological and jejunal manifestations. Acta Derm Venereol (Stockholm). 1981;61:405–411.
11. Garioch J.J., Lewis H.M., Sargent S.A., et al. 25 years’ experience of a gluten-free diet in the treatment of dermatitis herpetiformis. Br J Dermatol. 1994;131:541–545.
12. Fry L. Dermatitis herpetiformis: problems, progress and prospects. Eur J Dermatol. 2002;12:523–531.
13. Volta U., Cassani F., DeFranchis R., et al. Antibodies to gliadin in adult coeliac disease and dermatitis herpetiformis. Digestion. 1984;30:263–270.
14. Lewis H.M., Renaula T.L., Garioch J.J., et al. Protective effect of gluten-free diet against development of lymphoma in dermatitis herpetiformis. Br J Derm. 1996;135:363–367.
15. Engquist A., Pock-Steen O.C. Dermatitis herpetiformis and milk-free diet. Lancet. 1971;2:438–439.
16. Pock-Steen O.C., Niordson A.M. Milk sensitivity in dermatitis herpetiformis. Br J Derm. 1970;83:614–619.
17. Barnes R.M., Lewis-Jones M.S. Isotype distribution and serial levels of antibodies reactive with dietary protein antigens in dermatitis herpetiformis. J Clin Lab Immunol. 1989;30:87–91.
18. Kadunce D.P., McMurry M.P., Avots-Avotins A., et al. The effect of an elemental diet with and without gluten on disease activity in dermatitis herpetiformis. J Invest Dermatol. 1991;97:175–182.
19. Zarafonetis C.J., Johnwick E.B., Kirkman L.W., et al. Paraaminobenzoic acid in dermatitis herpetiformis. Arch Dermatol Syph. 1951;63:115–132.
