Dermatitis Herpetiformis (DH) is a very itchy, autoimmune skin blistering
disorder. It was once regarded as a classic autoimmune blistering skin
disease. However, mounting evidence against such a view suggests that
dermatitis herpetiformis is an allergic skin reaction to gluten, a protein
found in wheat and other food grains. Dermatitis herpetiformis usually
occurs in young adults and it is a lifelong condition, with chances of
remission in only 10% to 20% patients. It is a very difficult disease
to cope with, since young people tend to rebel against a life-long gluten
free diet that deprives them of foods like bread and cakes.
Dermatitis Herpetiformis Symptoms
Symptoms are burning, stinging and itching around the elbows, knees,
scalp, buttocks and back. Dermatitis herpetiformis can spread to more
sites and the severity can vary from person to person and over time in
the same person. The watery blisters are not permanent and may be scratched
away. But new blisters reappear.
Clinical and pathological features
On the skin, there are commonly erythema, urticarial plaques, papules,
herpetiform vesicles, and excoriations, but large blisters are rare.
Some of the unique features of dermatitis herpetiformis are a strong
association with gluten-sensitive enteropathy (GSE) or celiac disease
(spelt coeliac disease in Europe), affecting the guts; association with
iodine; and a common association with autoimmune thyroid disease and rarely
with other autoimmune diseases. It has a characteristic pattern of skin
signs involving the elbows, knees and buttocks. It is usually a life long
disease with frequent remissions and relapses. Remissions occur with a
strict and long lasting gluten-free diet and relapses occur with gluten
containing diets. There is improvement under UV light exposure, suggesting
seasonal variations in severity can be involved.
Allergies are usually initiated by the body’s IgE (immunoglobulin
type E antibody) production system. In dermatitis herpetiformis, however,
the allergy is triggered by the antibody IgA present in the body. This
makes standard allergy treatments, which mostly target IgE type allergic
responses, ineffective. Dermatitis herpetiformis is caused when IgA antibodies
precipitate in the papillary skin dermis, triggering an autoimmune response
in the skin. Recently, epidermal transglutaminase (TGe) has been identified
as the main antigen target of these IgA precipitates, an enzyme, hitherto
undetected. Although IgA deposition is crucial for disease development,
an increased serum IgA is not necessary for pathogenesis. There are even
case reports of dermatitis herpetiformis occuring in patients with a partial
IgA deficiency.
Role of gluten
One theory says that dermatitis herpetiformis is an immunologic response
to chronic stimulation of the gut by dietary gluten. Gluten combines with
IgA and with help of iodine produces inflammation – first and foremost
in the stomach. Though we all need iodine for our general health dermatitis
herpetiformis patients generally avoid iodized salts (iodine is artificially
added to many common brands of salt) and get their iodine from other natural
sources in their diet.
Almost 90% of dermatitis herpetiformis patients have an associated GSE
or celiac disease. About 15% to 25% of patients with celiac disease
develop dermatitis herpetiformis. Cases of severe celiac diseases are
never associated with a skin rash. It is the latent and silent forms
of GSE, occurring without major clinical signs, which are associated
with this skin disease. It is this skin disease which usually signals
a probable GSE.
The critical role of GSE in dermatitis herpetiformis development is confirmed
by relapses due to resumption of glutinous diets. However, there are exceptions
in case of people with spontaneous remissions of skin symptoms.
One major argument for a strict gluten-free diet in dermatitis herpetiformis
would be to prevent the development of cancerous conditions which occur
significantly more in dermatitis herpetiformis and contact dermatitis
patients who don’t control their diets.
Immune complexes
It has long been argued that dermatitis herpetiformis is an immune complex
disease due to the presence of dermatitis herpetiformis bodies in the
papillary dermis and the absence of IgA circulating antibodies binding
to the skin. The detection of IgA immune complexes in the symptom-free
and damage-free kidneys of dermatitis herpetiformis patients supports
this view. It further supports the hypothesis that IgA immune complexes
circulate and can get stuck in different organs.
Genetics
The leading theory is that genetic predisposition for gluten sensitivity,
coupled with a diet high in gluten, leads to dermatitis herpetiformis.
Patients with dermatitis herpetiformis have a clear genetic background
as indicated by the fact that 10% to 15% of their first-degree relatives
also have dermatitis herpetiformis or celiac disease. All patients with
gluten sensitivity, affecting the skin, have the same sets of genes. Gluten
sensitivity is considered as a multifactorial and polygenic disease with
possibly more susceptible zones. Monozygous twin studies, showing concordance
for gluten sensitivity in the majority but not all the sib-pairs, suggesting
that environmental as well as other genetic factors also determine the
phenotype.
Some individuals, with a distinct genetic background, tend to lose the
oral tolerance to gluten. Depending on how the immunological system and
environmental factors interact, these individuals might develop either
a mild to severe gluten-induced enteropathy or a mild gluten induced enteropathy
with skin disease.
Conclusion
The task before researchers now is to determine whether the skin rash
in dermatitis herpetiformis is a classic autoimmune blistering skin disease
or whether it has an immune complex basis. The latter alternative seems
most likely, though it has not been proven clearly.
