Dermatitis Herpetiformis



Dermatitis herpetiformis is an exquisitely pruritic eruption classically seen on the buttocks and the extensor surfaces of the arms and legs. Severe cases may involve larger surface areas.

Dermatitis herpetiformis is an autoimmune blistering disorder that is often associated with a gluten-sensitive enteropathy (GSE). The disease was described and named in 1884 by Dr. Louis Duhring at the University of Pennsylvania.[1] It is also known as Duhring disease or Duhring-Brocq disease.[2]

Dermatitis herpetiformis is characterized by grouped excoriations, erythematous, urticarial plaques, and papules with vesicles. The classic location for dermatitis herpetiformis lesions is on the extensor surfaces of the elbows, knees, buttocks, and back. It is extremely pruritic, and the vesicles are often excoriated to erosions by the time of physical examination, as shown in the image below.

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Classic vesicles of dermatitis herpetiformis.

See Autoimmune Disorders: Making Sense of Nonspecific Symptoms, a Critical Images slideshow, to help identify several diseases that can cause a variety of nonspecific symptoms.

Diagnosis requires direct immunofluorescence of a skin biopsy specimen showing deposition of immunoglobulin A (IgA) in a granular pattern in the upper papillary dermis. Although most patients are asymptomatic, greater than 90% have an associated gluten-sensitive enteropathy upon endoscopic examination.[3] Among patients with celiac disease, 15-25% develop dermatitis herpetiformis. The mainstays of treatment are dapsone and a gluten-free diet. A vertically oriented fibrillar staining pattern is noted in a subset of patients, with immune deposits along dermal microfibrils, creating a characteristic “picket fence” pattern of immunofluorescence. This fibrillar pattern is present in a third of Japanese patients, and this group lacks the typical distribution of skin lesions and has a low association with celiac disease.[4]


Dermatitis herpetiformis is the result of an immunologic response to chronic stimulation of the gut mucosa by dietary gluten.[5] It is a complex disease of the skin caused by the deposition of IgA in the papillary dermis; this triggers an immunologic cascade resulting in neutrophil recruitment, complement activation, and a variety of other immunologic responses.

An underlying genetic predisposition to the development of dermatitis herpetiformis has been demonstrated. Both dermatitis herpetiformis and celiac disease (CD) are associated with an increased expression of HLA-A1, HLA-B8, HLA-DR3, and HLA-DQ2/DQ8 haplotypes. Environmental factors are also important; monozygotic twins may have dermatitis herpetiformis, celiac disease, and/or gluten-sensitive enteropathy with variable symptomatology.

The leading theory for dermatitis herpetiformis is that a genetic predisposition for gluten sensitivity, coupled with a diet high in gluten, leads to the formation of IgA antibodies against gluten-tissue transglutaminase (t-TG), which is found in the gut. These antibodies cross-react with epidermal transglutaminase (e-TG),[6] which is highly homologous with t-TG. Serum from patients with gluten-sensitive enteropathy, with or without skin disease, contains IgA antibodies to both skin and gut types.[7] Deposition of IgA and e-TG complexes in the papillary dermis cause the lesions of dermatitis herpetiformis.

In patients with gluten-sensitive enteropathy, levels of circulating antibodies to t-TG and e-TG have been found to correlate with each other, and both appear to correlate with the extent of enteropathy.[8] Most patients with dermatitis herpetiformis have histologic evidence of enteropathy, even in the absence of symptoms of malabsorption. In one study, all dermatitis herpetiformis patients had increased intestinal permeability (as measured by the lactulose/mannitol ratio) and up-regulation of zonulin, a regulator of tight junctions.[9] Thus, increased expression of zonulin may be involved in the pathogenesis of enteropathy in patients with dermatitis herpetiformis.

Co-localized IgA and eTG deposits have been demonstrated in the papillary dermis in patients with dermatitis herpetiformis and, to lesser extent, in the healthy skin of gluten-sensitive enteropathy patients.[10] eTG has not been demonstrated in normal papillary dermis, suggesting it is part of the circulating complex that is deposited in the papillary dermis, rather than originating from the papillary dermis.

Cutaneous IgA deposits in dermatitis herpetiformis have been shown to function in vitro as a ligand for neutrophil migration and attachment. Although IgA deposition is pivotal for disease, an increased serum IgA is not necessary for pathogenesis; in fact, case reports have described dermatitis herpetiformis in patients with a partial IgA deficiency.[11] When the disease is active, circulating neutrophils express a higher level of CD11b on the cell surface and demonstrate an increased ability to bind IgA. The characteristic histologic finding of dermatitis herpetiformis is neutrophil accumulation at the dermoepidermal junction, frequently localizing to the papillary tips of the basement membrane zone.

Interleukin (IL)–8 is a potent neutrophil activator; gluten, UVB exposure, and trauma have all been shown to induce IL-8 production.[12] It has been demonstrated that dietary gluten increases levels of serum IL-8 in patients with dermatitis herpetiformis. A study in transgenic mice expressing IL-8 in the intestine has shown it to increase local neutrophil migration into the area. Other immunologic changes include reduction of IL-10 and regulatory T cells.[13]

Collagenase and stromelysin 1 may be induced in basal keratinocytes either by cytokines released from neutrophils or by contact with keratin from damaged basement membrane matrix. Stromelysin 1 may contribute to blister formation.

One study found levels of E-selectin mRNA expression in normal-appearing skin of patients with dermatitis herpetiformis to be 1271 times greater that that of controls.[14] Additionally, the same study observed increased soluble E-selectin, IgA antitissue transglutaminase antibodies, tumor necrosis factor-alpha, and serum interleukin 8 (IL-8) levels in patients with dermatitis herpetiformis, providing further evidence of endothelial cell activation and a systemic inflammatory response as part of the pathogenic mechanism of the disease. Mild local trauma may also induce the release of cytokines and attract the partially primed or activated neutrophils, which is consistent with the typical location of dermatitis herpetiformis lesions on frequently traumatized areas, such as the knees and elbows.

Deposits of C3 also may be present in a similar pattern at the dermoepidermal junction. The membrane attack complex, C5-C9, also has been identified in perilesional skin, although it may be inactive and not contribute to cell lysis.[15]

A 2009 study showed an increased expression of disintegrin and metalloproteinase (ADAMs) 8, 10, 15, and 17 in lesional skin of patients with dermatitis herpetiformis compared with controls.[16] The high affinity of ADAMs for the basement membrane led the authors to hypothesize a role in blister formation in dermatitis herpetiformis.

Hormonal factors may also play a role in the pathogenesis of dermatitis herpetiformis, and reports describe dermatitis herpetiformis induced by treatment with leuprolide acetate, a gonadotropin-releasing hormone analog.[17] Androgens have a suppressive effect on immune activity, including decreased autoimmunity, and androgen deficient states may be a potential trigger for dermatitis herpetiformis exacerbation. Exacerbation of dermatitis herpetiformis by oral contraceptives has also been reported.

Apoptosis may contribute to the pathogenesis of epidermal changes in dermatitis herpetiformis, and research demonstrates a markedly increased apoptotic rate within the epidermal compartment in dermatitis herpetiformis.[18] In addition, Bax and Bcl-2 proteins are increased in the dermal perivascular compartment and Fas proteins showed epidermal staining in dermatitis herpetiformis lesions.

Keratinocytes express elafin to down-regulate neutrophil-mediated inflammatory responses. Patients with dermatitis herpetiformis have deficient expression of elafin.[19]


Dermatitis herpetiformis is generally accepted as a cutaneous manifestation of celiac disease. The genetic predisposition to the development of gluten sensitivity underlies the disease. The standard criterion for the diagnosis of dermatitis herpetiformis is the presence of granular deposits of IgA in normal-appearing perilesional skin. It is positive in 92.4% of patients.

Gluten is a protein present in grasses of the species Triticeae, which includes barley, rye, and wheat. Gliadin protein in these grains are high-affinity substrates for tissue transglutaminase (TTG). Gliadins can also be found in rice, corn, and oats, but these proteins are poor substrates for TTG and thus these tend to be tolerated. Buckwheat is also tolerated.[20, 21] Strict compliance with a gluten-free diet results in normalization of the small bowel mucosal changes and control of the cutaneous manifestations of dermatitis herpetiformis in most patients. levels of circulating antibodies also tend to normalize.

Although cornstarch does not contain gluten, two case reports describe patients with well-controlled dermatitis herpetiformis who had disease flares after ingesting cornstarch.[22] Ingestion of iodide-rich dietary supplements can also cause a flare.[23]

The gluten-sensitive enteropathy does not cause symptoms in most dermatitis herpetiformis patients. Less than 10% exhibit symptoms of bloating, diarrhea, or malabsorption. However, greater than 90% show abnormalities upon endoscopic examination. Two thirds have villous atrophy detected on intestinal biopsy specimens. The other third shows elevated intraepithelial lymphocyte counts, increased T-cell receptor gamma/delta intraepithelial lymphocyte counts, or both.

The critical role of associated gluten-sensitive enteropathy in the pathogenesis of dermatitis herpetiformis is confirmed by the fact that resumption of a gluten-containing diet in patients with dermatitis herpetiformis results in a return of the characteristic skin disease.

Mild steatorrhea or other signs of mild malabsorption (eg, altered D-xylose absorption, iron or folate deficiency) can be demonstrated in 20-30% of patients with dermatitis herpetiformis.

Patients with dermatitis herpetiformis and no apparent GI disease can be induced into developing dermatitis herpetiformis by increasing gluten intake, which is often termed latent gluten-sensitive enteropathy.

IgA circulating immune complexes are present in 25-35% of patients with dermatitis herpetiformis, although no association with disease severity has been noted. These immune complexes also have been noted in patients with isolated gluten-sensitive enteropathy and are believed to be related to the presence of the gut disease.[8]

IgA antibodies to gliadin (a portion of wheat protein), reticulum, and smooth muscle endomysium have also been noted in patients with dermatitis herpetiformis and in those with isolated gluten-sensitive enteropathy.

IgA endomysial antibodies are most specific for gluten sensitivity and are found in 80% of patients with dermatitis herpetiformis and greater than 95% of patients with celiac disease. The presence of IgA antiendomysial antibodies correlates with the extent of the gut disease;[8, 24] however, some dermatitis herpetiformis patients do not have detectable IgA antiendomysial antibodies, even during episodes of active skin disease.

Patients with bullous pemphigoid,[25]  cicatricial pemphigoid, Henoch-Schönlein purpura, and alcoholic liver disease also may have IgA deposits in normal skin; however, the pattern of IgA deposits is different from that seen in patients with dermatitis herpetiformis.

In patients with dermatitis herpetiformis, 10-15% of their first-degree relatives have dermatitis herpetiformis or celiac disease. HLA studies have conclusively established the presence of a genetic predisposition for dermatitis herpetiformis. Patients with dermatitis herpetiformis have an increased expression of the HLA-A1, HLA-B8, HLA-DR3, and HLA-DQ2 haplotypes. This is identical to the HLA association found in patients with isolated gluten-sensitive enteropathy. Most persons with these HLA types do not have dermatitis herpetiformis or gluten-sensitive enteropathy. Associations of HLA and dermatitis herpetiformis are as follows:

Other associations

Associated GI conditions include gluten enteropathy, gastric atrophy, gastric hypochlorhydria, and pernicious anemia.

Associated autoimmune diseases include dermatomyositis, type 1 diabetes mellitus, myasthenia gravis, rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, and thyroid abnormalities. Thyroid abnormalities are present in as many as 50% of dermatitis herpetiformis patients and include hypothyroidism, hyperthyroidism, thyroid nodules, and thyroid cancer.[26]

Neurologic manifestations such as ataxia have been rarely described.[27]

Associated neoplastic conditions include GI lymphomas and non-Hodgkin lymphoma; patients are at increased risk of developing these cancers.[28] A gluten-free diet may reduce the incidence of dermatitis herpetiformis–associated lymphomas.

Celiac disease usually involves more severe and widespread intestinal involvement. Celiac disease has been associated with genetic abnormalities, including Down syndrome, Turner syndrome, and William syndrome. Liver disease, neurologic disorders, and other skin diseases are also increased in celiac disease, possibly due to common HLA regions on chromosome 6 or immune molecule cross-reactivity.

Gastric manipulation (surgery) may induce dermatitis herpetiformis.

Several chemicals have been associated with induction of dermatitis herpetiformis, including potassium iodide and cleaning solutions.

Case reports have described dermatitis herpetiformis induced by medications. Leuprolide acetate, inhibitors of tumor necrosis factor-alpha, anti-influenza medications, and progesterone-containing contraceptives have been reported in association with development of dermatitis herpetiformis.[17, 29] NSAIDs, specifically indomethacin and ibuprofen, have been reported to cause flares.[23]



United States

The only US study showed a dermatitis herpetiformis prevalence of 11.2 cases per 100,000 population.


Prevalence of dermatitis herpetiformis has been reported as high as 10 cases per 100,000 population.


Dermatitis herpetiformis occurs more frequently in individuals of Northern European ancestry and is rare in Asians and persons of African descent. Dermatitis herpetiformis is most common in Ireland and Sweden. This can be attributed to the shared HLA associations of dermatitis herpetiformis and celiac disease including DQA1*0501 and B1*-02, which encode HLA-DQ2 heterodimers.


US studies show a male-to-female ratio of 1.44:1, but international studies have demonstrated a male-to-female ratio up to 2:1. In one study of patients with gluten-sensitive enteropathy, 16% of the men and 9% of the women had dermatitis herpetiformis.[30]


Typically, the onset of dermatitis herpetiformis is in the second to fourth decade; however, persons of any age may be affected.[31] Dermatitis herpetiformis is rare in children.


Dermatitis herpetiformis (DH) is an ongoing disease process of variable severity. The prognosis is good for patients who can tolerate dapsone and the few who can maintain a gluten-free diet (which may decrease the risk of lymphoma).


In an English study, patients with dermatitis herpetiformis (152 total) were followed from the date of diagnosis to the end of 1989 for mortality and from 1971 or the date of diagnosis (if later) to 1986 for cancer incidence.[32] Death occurred in 38 patients younger than 85 years, slightly fewer than expected on the basis of national general population rates. Cancer incidence was significantly increased. Cancer of the small intestine caused 1 death, and lymphoma caused 1 death. Another English study, which compared 846 dermatitis herpetiformis patients with 4225 controls, found that dermatitis herpetiformis conferred no increased risk of lymphoproliferative cancer and no increase in fracture, malignancy, or mortality.[33]

A 30-year population-based study of 1147 celiac disease and dermatitis herpetiformis patients in Finland also revealed an overall good prognosis for patients with dermatitis herpetiformis.[34] The total occurrence of malignancies was equal to that of the general population in both celiac disease and dermatitis herpetiformis patients, but an increased incidence of lymphoma was noted among both celiac disease and dermatitis herpetiformis patients, with standardized incidence ratios of 3.2 and 6.0, respectively. Most were T-cell lymphomas, although B-cell lymphoma has occurred as well. Interestingly, a lower incidence of lymphoma was seen in the first-degree relatives of dermatitis herpetiformis patients.[35] Overall mortality was actually decreased in dermatitis herpetiformis patients compared with that in the general population.

Dermatitis herpetiformis lesions are extremely pruritic. Morbidity results from scarring, discomfort, and insomnia due to itching. Secondary infection may also develop, requiring antibiotic therapy.

Patient Education

Educate patients regarding the use of a gluten-free diet as well as the adverse effects and complications of dapsone. Patients should also be aware of medications, particularly NSAIDs, that can cause flares.


Patients typically present with a waxing and waning pruritic eruption on the extensor surfaces of the arms, knees, and buttocks. It may become generalized. Small vesicles may have been noted but have often been excoriated by the time of presentation to the physician. They may have associated worsening of disease with dietary intake of gluten. Many do not report any GI symptoms, even when prompted.

Physical Examination

The diagnosis is suspected based on the distribution of the eruption.

Flesh-colored–to–erythematous excoriated papules or plaques with herpetiform (ie, small, clustered) vesicles are symmetrically distributed over extensor surfaces, including the elbows, knees, buttocks, and shoulders.

Dermatitis herpetiformis rarely occurs on the posterior (nuchal) scalp and face. Lesions occur infrequently on the oral mucosa, but males are more likely than females to have involvement of the oral and genital membranes. Palms and soles are spared. Digital purpura resembling vasculitis can occur. Erythematous papules and urticarialike plaques occur less frequently; bullae are rare.

The eruption is intensely pruritic; patients often present with erosions and crusts in the absence of vesicles, which have ruptured due to excoriation.

Typical symptoms include burning, stinging, and intense itching. Rarely, if ever, are patients totally asymptomatic, although the degree of itching varies.

Dermatitis herpetiformis is a lifelong disease, although periods of exacerbation and remission are common.

See the image below.

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Polymorphic lesions on extensor surface of arm.


Complications are related to the gluten-sensitive enteropathy, the risk of developing lymphomas, and the potential adverse effects of medications, particularly dapsone.

Laboratory Studies

The diagnosis of dermatitis herpetiformis (DH) is made on the basis of skin biopsy results. However, other tests should be performed depending on the presence of symptoms of associated syndromes. Serum markers, such as IgA endomysial antibodies, are negative in as many as 10-37% of patients with dermatitis herpetiformis.[37, 38] Arguments have been made in favor of testing for tissue transglutaminase for diagnosis,[39] but tissue transglutaminase enzyme-linked immunosorbent assay positivity can occur in many autoimmune diseases because of impurities and cross-reactivity.[40]


The diagnosis is made after observing characteristic findings from skin biopsy specimens. The biopsy sample should be taken from the edge of a lesion for hematoxylin and eosin staining and from normal-appearing perilesional skin for direct immunofluorescence staining.

Results of direct immunofluorescence of lesional skin are often falsely negative. The vigorous immune response degrades the IgA antibody at the site. Therefore, biopsy specimens for the direct immunofluorescence studies should be taken from healthy-appearing skin.

See the image below.

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Immunofluorescence showing immunoglobulin A at the dermoepidermal junction (direct immunofluorescence stain).

Histologic Findings

Biopsy specimens of lesional skin reveal neutrophils in the dermal papillae, with fibrin deposition, neutrophil fragments, and edema. Eosinophils may be present. Papillary microabscesses form and progress to subepidermal vacuolization and vesicle formation. Vesicles form in the lamina lucida, the weakest portion of the dermoepidermal junction, due to neutrophil lysosomal enzymes.[41] See the image below.

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Papillary microabscesses form and progress to subepidermal vacuolization and vesicle formation in the lamina lucida, the weakest portion of the dermoe....

The histologic differential diagnosis of early skin lesions includes bullous lupus erythematosus, bullous pemphigoid, epidermolysis bullosa acquisita, and linear IgA disease.[42] The histologic differential diagnosis of late skin lesions includes bullous drug eruption, bullous pemphigoid, erythema multiforme, and herpes gestationis.

Granular IgA deposits in dermal papillae of perilesional skin observed by direct immunofluorescence is the criterion standard of diagnosis. However, the presence of both granular and linear IgA deposits has been reported on direct immunofluorescence testing in a patient with dermatitis herpetiformis.[43, 44]

Inflammation in lesional skin degrades the immunoreactants and is usually negative for the diagnostic granular pattern. Because deposits are found more reliably in the surrounding normal-appearing skin, the standard practice is to obtain biopsy specimens from normal-appearing perilesional skin for direct immunofluorescent staining.

Medical Care

Treatment of dermatitis herpetiformis (DH) include avoidance of gluten by consuming a gluten-free diet and pharmacotherapy.[45]

A gluten-free diet is a lifelong commitment, and adherence to a strict diet is difficult to achieve. Improvement of skin disease with a gluten free diet takes several months. Gluten is present in various foods that are consumed on an everyday basis, most importantly wheat, barley, and rye. Concern has surrounded oats containing gluten, but studies have shown that consumption of a moderate amount of oats does not worsen dermatitis herpetiformis or celiac disease.[46, 47] Contamination of gluten-free products with gluten remains a potential problem.[48] Nutritional supplementation with multivitamins and iron may be prudent in patients on a strict gluten-free diet.[49]

Dapsone (diaminodiphenyl sulfone) and sulfapyridine (no longer available in most countries) are the primary medications used to treat dermatitis herpetiformis. The exact mechanism of action is unknown but is thought to be related to inhibition of neutrophil migration and function. Patients report a symptomatic improvement within hours after initiation of dapsone therapy. Patients should be monitored for the adverse effects of dapsone, primarily hemolytic anemia, methemoglobinemia, agranulocytosis, and neuropathy. For patients unable to tolerate dapsone, particularly those who develop hemolysis, sulfapyridine may be substituted. New lesion formation is suppressed for up to 2 days after a dose of dapsone; however, dapsone does not improve GI mucosal pathology.

A retrospective study has shown remission, defined as 2 years with no symptoms, in 12% of patients.[50] When dermatitis herpetiformis is well-controlled, attempts can be made to taper off dapsone and perhaps attempt a diet with gluten. Although sulfapyridine is no longer available in the United States, sulfasalazine may be prescribed. Sulfasalazine is partly metabolized to sulfapyridine. Sulfasalazine has been used by itself or in combination with dapsone.[51]

Other, less effective treatments for dermatitis herpetiformis include colchicine, cyclosporine, azathioprine, and prednisone.[41] Ultraviolet light may provide some symptomatic relief. The combination of tetracycline and niacinamide has been reported to successfully treat it. Cyclosporine should be used with caution in patients with dermatitis herpetiformis because of a potential increase in the risk of developing intestinal lymphomas. Because it is an antibody-induced autoimmune disease, therapies aimed at removal of the antibodies may be helpful; rituximab and intravenous immunoglobulin may be helpful in particularly severe cases not improved by other medications that are less expensive and carry fewer adverse effects.[52]

One case report described resolution of dermatitis herpetiformis after initiation of the Atkins diet.[53]

NSAIDs may exacerbate dermatitis herpetiformis.[54]

Iodides may elicit or exacerbate dermatitis herpetiformis.


Consider consultation with a gastroenterologist for evaluation and for recommendations regarding gluten-sensitive enteropathy (GSE).

Consult with a dietitian regarding patients who are modifying dietary intake to avoid gluten or who are instituting an elemental diet.


Dietary intake of gluten causes the disease, and elimination of gluten from the diet improves it.

A position statement by the American Gastroenterological Association (AGA) Institute advises that treatment for patients with dermatitis herpetiformis, like that of all patients with celiac disease, requires a strict, lifelong adherence to a gluten-free diet. The AGA stresses the importance of patient education, motivation, and support in maintaining adherence, and recommends consultation with an experienced dietician, referral to a support group, and clinical follow up for compliance, as well as treatment of nutritional deficiency states.[55]

Most patients (as many as 80%) who can maintain a gluten-free diet respond with control of their skin disease. Some patients are able to discontinue dapsone therapy. Compliance with a gluten-free diet is difficult and requires a motivated patient, and the best treatment response occurs with absolute gluten restriction in the diet.

Strict dietary vigilance may be required for 5-12 months before the dapsone dose can be reduced.

Maintaining a gluten-free diet is the only sustainable method of eliminating the disease, not only from the skin, but also from the GI mucosa.

Patients on a gluten-reduced diet may experience a decrease in symptoms; therefore, such a diet can reduce the dosage of dapsone required for disease control.

Neither IgA deposition nor circulating antibodies correlate with gluten intake in short-duration studies; however, some studies have suggested a correlation with complement deposition. Avoidance of dietary gluten for 10 years or more has resulted in loss of cutaneous IgA deposits, which then return upon reinstitution of gluten in the diet.

Elemental diets may improve the disease within weeks.[56, 57] These diets consist of free amino acids, small amounts of triglycerides, and short-chain polysaccharides; they are marketed by pharmaceutical companies. One report has suggested that this improvement may be independent of gluten ingestion; however, this finding has not been confirmed.[57]

Medication Summary

Treatment consists of a gluten-free diet plus pharmacotherapeutic agents. Dapsone is indicated as a primary treatment for dermatitis herpetiformis. Sulfapyridine, a previous mainstay of therapy for dermatitis herpetiformis, is no longer available in most countries. However, sulfasalazine is partly metabolized to sulfapyridine. It may be considered for off-label use in dermatitis herpetiformis in patients who are unable to tolerate a high enough dose of dapsone.[51] Corticosteroids may also be considered.

Case reports have described use of rituximab for recalcitrant dermatitis herpetiformis.[52, 58] Cases have also been described using colchicine[59] and tetracycline.[60, 61, 62]


Clinical Context:  The precise mechanism by which dapsone works in dermatitis herpetiformis has not been established. It is a competitive antagonist of para-aminobenzoic acid (PABA) and prevents bacteria from using PABA for folic acid synthesis. It is indicated as a primary treatment for dermatitis herpetiformis.

Sulfasalazine (Azulfidine)

Clinical Context:  Sulfasalazine elicits anti-inflammatory effects. It has a high affinity for distribution to connective tissues. Sulfasalazine is metabolized to 5-aminosalicylic acid and sulfapyridine.

Rituximab (Rituxan, Truxima)

Clinical Context:  Rituximab is a humanized monoclonal antibody. It binds to CD20 antigen, inducing complement- or antibody-mediated cytolysis.

Colchicine (Colcrys, Gloperba, Mitigare)

Clinical Context:  Colchicine elicits various effects on neutrophil migration, degranulation, and activation that may diminish inflammation.


Clinical Context:  The mechanism by which tetracycline may act for use in dermatitis herpetiformis is not established.

Class Summary

Dapsone is considered the treatment of choice. Other anti-inflammatory and immunomodulatory agents may be required if dapsone is insufficient or not tolerated.

Prednisone (Deltasone)

Clinical Context:  Prednisone is a glucocorticosteroid that elicits mild mineralocorticoid activity and moderate anti-inflammatory effects. It controls or prevents inflammation by controlling the rate of protein synthesis, suppressing migration of polymorphonuclear leukocytes (PMNs) and fibroblasts, reversing capillary permeability, and stabilizing lysosomes at cellular level.

Class Summary

Systemic corticosteroids may be considered.

What is dermatitis herpetiformis?How is dermatitis herpetiformis diagnosed?What is the pathophysiology of dermatitis herpetiformis?What is the role of co-localized immunoglobulin A (IgA) and ethyl glucuronide (eTG) in the pathophysiology of dermatitis herpetiformis?What is the role of E-selectin messenger RNA (mRNA) in the pathophysiology of dermatitis herpetiformis?What is the role of hormones in the pathophysiology of dermatitis herpetiformis?What is the role of gluten in the etiology of dermatitis herpetiformis?What is the role of gluten-sensitive enteropathy in the etiology of dermatitis herpetiformis?What is the role of immunoglobulin A (IgA) in the etiology of dermatitis herpetiformis?What is the role of genetics in the etiology of dermatitis herpetiformis?Which other conditions are associated with dermatitis herpetiformis?What is the prevalence of dermatitis herpetiformis in the US?What is the global prevalence of dermatitis herpetiformis?What are the racial predilections of dermatitis herpetiformis?How does the prevalence of dermatitis herpetiformis vary by sex?How does the prevalence of dermatitis herpetiformis vary by age?What is the prognosis of dermatitis herpetiformis?What is the mortality and morbidity of dermatitis herpetiformis?What information about dermatitis herpetiformis should patients receive?What are the signs and symptoms of dermatitis herpetiformis?What are the physical findings characteristic of dermatitis herpetiformis?What are the complications of dermatitis herpetiformis?Which condition should be included in the differential diagnoses for dermatitis herpetiformis?What are the differential diagnoses for Dermatitis Herpetiformis?What is the role of lab studies in the diagnosis of dermatitis herpetiformis?What is the role of skin biopsy in the diagnosis of dermatitis herpetiformis?Which histologic findings are characteristic of dermatitis herpetiformis?What are the treatment options for dermatitis herpetiformis?Which interventions have been found to be less effective for treatment of dermatitis herpetiformis?Which specialist consultations are beneficial for patients with dermatitis herpetiformis?What is the role of gluten-free diet in the treatment of dermatitis herpetiformis?Which medications in the drug class Corticosteroids are used in the treatment of Dermatitis Herpetiformis?Which medications in the drug class Anti-inflammatory and Immunomodulatory Agents are used in the treatment of Dermatitis Herpetiformis?


Jami L Miller, MD, Assistant Professor, Division of Dermatology, Department of Internal Medicine, Vanderbilt University Medical School; Director of Phototherapy Unit, Vanderbilt University Medical Center; Consulting Attending Physician, Nashville Veterans Affairs Medical Center

Disclosure: Nothing to disclose.


Shehnaz Aysha K Zaman, MD, Resident Physician, Department of Dermatology, Vanderbilt Medical Center

Disclosure: Nothing to disclose.

Specialty Editors

Michael J Wells, MD, FAAD, Dermatologic/Mohs Surgeon, The Surgery Center at Plano Dermatology

Disclosure: Nothing to disclose.

Julia R Nunley, MD, Professor, Department of Dermatology, Virginia Commonwealth University Medical Center

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Board of Dermatology<br/>Co-Editor for the text Dermatological Manifestations of Kidney Disease for: Author Up-to-date.

Chief Editor

Dirk M Elston, MD, Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Russell Hall, MD, J Lamar Callaway Professor And Chair, Department of Dermatology, Duke University Medical Center, Duke University School of Medicine

Disclosure: Received consulting fee from Novan for consulting; Received consulting fee from Stieffel, a GSK company for consulting; Received salary from Society for Investigative Dermatology for board membership.


The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors, Kristina Collins, MD, and Hunter Sams, MD, to the development and writing of this article.


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Classic vesicles of dermatitis herpetiformis.

Polymorphic lesions on extensor surface of arm.

Immunofluorescence showing immunoglobulin A at the dermoepidermal junction (direct immunofluorescence stain).

Papillary microabscesses form and progress to subepidermal vacuolization and vesicle formation in the lamina lucida, the weakest portion of the dermoepidermal junction (hematoxylin and eosin stain).

Light micrograph shows neutrophils in the dermal papillae, with fibrin deposition, neutrophil fragments, and edema (hematoxylin and eosin stain).

Papillary microabscesses form and progress to subepidermal vacuolization and vesicle formation in the lamina lucida, the weakest portion of the dermoepidermal junction (hematoxylin and eosin stain).

Classic vesicles of dermatitis herpetiformis.

Immunofluorescence showing immunoglobulin A at the dermoepidermal junction (direct immunofluorescence stain).

Polymorphic lesions on extensor surface of arm.