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Dapsone and gluten intolerance. Dermatitis Herpetiformis |
- Dermatitis Herpetiformis - Dermatologic Disorders - MSD Manual Professional Edition
All rights reserved. According to one expert, a gluten-free diet is the best approach to treating dermatitis herpetiformis. In those genetically predisposed individuals, gliadin found in glutens is widely accepted as the antigenic trigger that causes dermatitis herpetiformis or Duhring's disease.
Though not the rule, some patients may experience a remission and are able to return to a normal diet. According to the literature, this occurs in approximately 10 percent to 20 percent of patients with gluten sensitivity. Within a couple of months, it will be very clear to the patient as to whether or not they can tolerate a normal diet. If a gluten-free diet is ineffective or if the patient does not want to follow this diet modification, dapsone is readily used to treat these patients," says Warren R.
Heymann M. Dapsone is the only Food and Drug Administration FDA approved drug used in the treatment of dermatitis herpetiformis and is the drug of choice if a gluten-free diet modification is not an option, for whatever reason.
Patients respond very well to dapsone with pruritus improving within 24 to 48 hours and the papulovesicular lesions improving within a week of therapy induction. Recently, 5 percent dapsone gel Aczone has become available for the treatment of dermatitis herpetiformis. To date, there have not been any studies on topical dapsone, however, according to Dr. Heymann, there may be certain scenarios where the patient could benefit from a topical approach.
There are patients who can have very extensive disease over large body surface areas. Topical dapsone will likely be useful only in those patients where disease extent is localized or minimal. It would not make sense to use it in extensive disease, as there is no data supporting this approach," Dr.
Heymann says. Dermatitis herpetiformis: Gluten-free diet, dapsone therapy cornerstone approach. October 1, Ilya Petrou, M. Key Points.
❿Dapsone and gluten intolerance.Dermatitis herpetiformis: Gluten-free diet, dapsone therapy cornerstone approach
Dapsone and gluten intolerance -
The skin sample must be taken from skin directly adjacent to the suspected dermatitis herpetiformis lesion, as opposed to directly from the lesion, since inflammation in the lesion can destroy the IgA deposits. Blood tests for other antibodies commonly found in people with celiac disease —antiendomysial and anti-tissue transglutaminase antibodies — supplement the diagnostic process.
If the antibody tests are positive and the skin biopsy has the typical findings of DH, patients do not need an intestinal biopsy to confirm the diagnosis of celiac disease. If you are diagnosed with dermatitis herpetiformis, your dermatologist may prescribe dapsone for short-term relief from the itching. According to Dr. Zone, the rash responds dramatically to dapsone, usually in 48 to 72 hours.
Skin lesions usually clear on the gluten-free diet. There are exceptions, however. Dapsone or sulfapyridine therapy may need to be continued for 1—2 years to prevent further DH outbreaks. In some cases, a diet high in iodine may worsen DH symptoms. If you are experiencing DH flare-ups, you should consult with a dermatologist expert in celiac disease to determine if foods or medicines high in iodine are the cause. Neutrophilic infiltrate in the papillary dermis is suggested to lead to the release of cytokines, chemokines, and proteases as well as induce collagenases or stromelysin-1 in basal keratinocytes, which lead to blister formation [ 26 , 27 ].
However, our study of DH in Japanese patients showed that only These factors may also explain the low prevalence of DH in Asia.
Given that the prerequisite HLA type for gluten antigen processing is scarce in the Japanese population, gluten may be unlikely to initiate DH in Japanese patients [ 9 ]. Severe pruritus is the principal clinical manifestation in DH. The characteristic clinical manifestations of the illness are grouped polymorphic lesions consisting of erythematous papules surmounted by vesicles, erosions, and excoriations Figure 1a [ 2 , 8 ].
Large bullae are unusual, and only crusted lesions may be observed without apparent vesicles. The most commonly involved sites are the extensor surfaces of the elbows Figure 1b and the knees Figure 1c , as well as the shoulders, buttocks, sacral region, and face [ 2 , 8 ].
Most patients also have lesions in the scalp and the nucha. Mucosal involvement may occur [ 30 ]. Figure 1: a Erythema with vesicles and crust in dermatitis herpetiformis; b Only erythema and hypopigmented lesionsare seen on the elbows; c Grouped erythema, vesicles, and crusts on the knees. Courtesy of Prof. Jason Bok Lee. View Figure 1. Biopsy of an early lesion shows collections of neutrophils at the papillary tips with occasional eosinophilic infiltrate Figure 2a. DIF reveals non-linear mostly granular, or fibrillar IgA deposition in the papillary dermis Figure 2b and Figure 2c [ 31 , 32 ].
IgA deposition along the basement membrane zone maysometimes occur [ 2 ]. Compared with that in lesional skin, IgA deposition is greater in normal appearing perilesional skin, and these deposits disappearslowly with adherence to a strict gluten free diet GFD [ 32 ].
Complete resolution of IgA deposition may take several years [ 2 ]. Although the deposition in most Caucasian patients has a granular pattern, that in more than one-third of Japanese patients has afibrillar pattern [ 8 ]. IgG, IgM, and C3 are also deposited in the lower percentages [ 33 ].
Indirect immunofluorescence reveals no reactivity [ 23 ]. View Figure 2. One case study reported that IgA anti-eTG antibody levels decreased over time with adherence to GFD, which suggests that testing for IgA anti-eTG antibodies may be useful to monitor disease activity [ 35 ].
DH is closely associated with gluten sensitivity [ 36 ]. Compared with CD patients, DH patients usually have milder gastrointestinal symptoms [ 37 , 38 ]. Atrophic gastritis sometimes occurs and may be a precursor to pernicious anemia [ 39 ]. Untreated patients may develop malabsorption, and consequently, anemia and bone loss [ 40 ].
Small bowel lymphoma can develop owing to GSE [ 41 ]. In addition, non-Hodgkin lymphoma can occur in patients with DH [ 42 , 43 ]. DH is associated with a number of autoimmune conditions, including thyroid disease [ 44 ], type I diabetes mellitus [ 45 , 46 ], and autoimmune connective tissue diseases such as Sjogren syndrome [ 45 ], rheumatoid arthritis [ 47 ] and lupus erythematosus [ 48 ].
Addison disease [ 45 , 49 ] and vitiligo [ 50 , 51 ] have also been associated with DH. Although neurologic diseases, including epilepsy, ataxia, and dementia, have been reported in patients with CD [ 52 ], no evidence to date supports an association between neurologic disease and DH [ 53 ].
Because DH is characterized by polymorphic lesions, the differential diagnosis includes various skin diseases such as chronic eczema, atopic dermatitis, scabies, pemphigoid, and linear IgA bullous dermatosis.
DIF differentiates DH from these diseases. A skin biopsy for DIF should be considered for refractory pruritic rashes even if no apparent gastrointestinal symptoms are found. Recently described nonceliac gluten sensitivity NCGS may involve the skin [ 54 ]. A recent study identified C3 deposition at the basement membrane zone in a granular or micro-granular pattern in DIF of NCGS lesions despite the absences of specific histopathological changes [ 55 ].
Because the entity of NCGS remains controversial, further study is necessary to elucidate its characteristic skin mainfestations. GFD is the first-line therapy for DH [ 56 - 58 ], and may protect against the development of lymphoma. Because strict GFD adherence is time-consuming and requires extensive knowledge of food ingredients, patients should be encouraged to consult with a dietitian and join DH support groups. Gluten comprises the proline- and glutamine-rich proteins of wheat, barley, rye, and oat.
However, a recent study revealed that oats can be safely consumed by individuals with DH [ 59 - 61 ], likely because 1 compared with the gluten-like molecules in the other cereals, those in oats have only two antigenic sequences, and 2 the amount of gluten in oats is much lower than that in the other cereals [ 62 ].
Although dapsone is effective in skin lesions because it suppressesthe migration of neutrophils to extravascular sites [ 64 ], it does not improve GSE.
The adverse effects of dapsone administration, including hemolytic anemia, should be monitored. Other sulfonamide drugs have effects similar to those of dapsone and can be used in dapsone-intolerant patients [ 65 , 66 ].
Systemic corticosteroids are ineffective, whereas potent topical steroids are useful in decreasing pruritus. This outcome may be attributable to the rare occurrence of GSE in Japanese DH patients, who can be successfully treated with dapsone with or without topical corticosteroids. Five patients required only several-month administration of dapsone to clear the skin lesions, and the lesions did not recur after ceasing dapsone [ 8 ]. If these patients had GSE, their skin lesions should have recurred after cessation of dapsone.
DH is a chronic disease that requires long-term GFD adherence. Those who can comply with good response are likely to have reduced mortality [ 67 ] and may be able to stop dapsone treatment. Although patients with CDwho respond poorly to a GFD may have high mortality and shortened survival time [ 68 ], DH patients who is non-responsive to a GFD have relatively favorable prognosis [ 69 ]. Clinicians can use guidelines to optimize the diagnosis and management of DH.
However, although several guidelines for DH have been published [ 2 , 71 - 73 ], only one is available in English [ 2 ]. These guidelines were established for Caucasian patients, in which DH is most commonly diagnosed. Additional studies of patients with DH in other Asian countries or in African countries would be useful to elucidate the features of DH further. Join Us Latest Articles Contact. Dapsone is the only Food and Drug Administration FDA approved drug used in the treatment of dermatitis herpetiformis and is the drug of choice if a gluten-free diet modification is not an option, for whatever reason.
Patients respond very well to dapsone with pruritus improving within 24 to 48 hours and the papulovesicular lesions improving within a week of therapy induction. Recently, 5 percent dapsone gel Aczone has become available for the treatment of dermatitis herpetiformis. To date, there have not been any studies on topical dapsone, however, according to Dr. Heymann, there may be certain scenarios where the patient could benefit from a topical approach. There are patients who can have very extensive disease over large body surface areas.
Topical dapsone will likely be useful only in those patients where disease extent is localized or minimal.
The vast majority of patients with DH also have an associated gluten sensitive enteropathy celiac disease. Extremely itchy bumps or blisters appear on both sides of the body, most often on the forearms near the elbows, as well as on knees and buttocks, and along the hairline. They are caused by gluten ingestion. However, DH patients with a normal intestinal biopsy and normal celiac serology blood test will still respond to a gluten-free diet.
Symptoms tend to come and go, and DH is commonly diagnosed as eczema. Symptoms normally resolve with a strict, gluten-free diet. DH patients frequently have no digestive symptoms. DH can affect people of all ages, but most often appears for the first time in those between the ages of 30 and People of northern European descent are more likely than those of African or Asian heritage to develop DH. The condition is somewhat more common in men than women, and men are more likely to have atypical oral or genital lesions.
How does a disorder that damages the intestines show up on the skin? These IgA antibodies are directed against epidermal transglutaminase. The antibodies then travel to the skin where they bind with the epidermal transglutaminase protein. Gluten ingestion seems to trigger this reaction. A skin biopsy is used to confirm a diagnosis of DH. After injecting a local anesthetic, your dermatologist will use a tiny, cookie-cutter-like punch to remove a 4mm sample of skin.
The incision can be closed with one stitch, and generally heals with very little scarring. A skin sample is taken from the area immediately next to a lesion and a fluorescent dye is used to look for the presence of Immunoglobulin A IgA deposits that appear in a granular pattern. Skin biopsies of people with DH are almost always positive for this granular IgA pattern.
It is important to have your dermatitis herpetiformis skin biopsy performed by someone who has diagnosed the skin condition before and knows how to do the biopsy. The skin sample must be taken from skin directly adjacent to the suspected dermatitis herpetiformis lesion, as opposed to directly from the lesion, since inflammation in the lesion can destroy the IgA deposits.
Blood tests for other antibodies commonly found in people with celiac disease —antiendomysial and anti-tissue transglutaminase antibodies — supplement the diagnostic process. If the antibody tests are positive and the skin biopsy has the typical findings of DH, patients do not need an intestinal biopsy to confirm the diagnosis of celiac disease.
If you are diagnosed with dermatitis herpetiformis, your dermatologist may prescribe dapsone for short-term relief from the itching. According to Dr. Zone, the rash responds dramatically to dapsone, usually in 48 to 72 hours. Skin lesions usually clear on the gluten-free diet. There are exceptions, however. Dapsone or sulfapyridine therapy may need to be continued for 1—2 years to prevent further DH outbreaks.
In some cases, a diet high in iodine may worsen DH symptoms. If you are experiencing DH flare-ups, you should consult with a dermatologist expert in celiac disease to determine if foods or medicines high in iodine are the cause. Gluten-Free Gluten-Free Recipes. Treatment for DH with Dapsone and the Gluten-Free Diet If you are diagnosed with dermatitis herpetiformis, your dermatologist may prescribe dapsone for short-term relief from the itching.
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According to one expert, a gluten-free diet is the best approach to treating dermatitis herpetiformis. If you are diagnosed with dermatitis herpetiformis, your dermatologist may prescribe dapsone for short-term relief from the itching. According to Dr. Zone, the. Gluten free diet is the first-line therapy for patients with DH and dapsone is also effective. DH preferentially affects Caucasians who carry human. Treatment is usually with dapsone or sulfapyridine and a gluten-free diet. Dermatitis herpetiformis often occurs in young adults but can occur in children. Thereafter, a gluten-free diet should be started in association with drugs, such as dapsone, that are able to control the skin. Best Pract Res Clin Gastroenterol Gluten-Free Gluten-Free Recipes.Submit Manuscript. Journal Home. Editorial Board. Submit to this journal. Current issue. DOI: J Dermatol Res Ther This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Dermatitis herpetiformis DH is an autoimmune bullous disease characterized by intensely pruritic, chronic, and recurrent vesicles on extensor surfaces such as the elbows, knees, and buttocks. The collection of neutrophils at the papillary tips is the typical histopathological finding, and a characteristic diagnostic feature is granular immunoglobulin A deposition in the papillary dermis by direct immunofluorescence.
DH is closely associated with gluten sensitive enteropathy and is considered a cutaneous manifestation of gluten sensitivity; i. Gluten free diet is the first-line therapy for patients with DH and dapsone is also effective. The major autoantigen is epidermal transglutaminase. This review focuses on the confirmedfeatures of DH and our recent findings specific to DH in Japanese patients.
Dermatitis herpetiformis, Gluten sensitive enteropathy, Celiac disease, Gluten free diet, Epidermal transglutaminase. Dermatitis herpetiformis DH was first reported by Duhring in [ 1 ]. Patients with DH develop intensely pruritic papulovesicular skin lesions predominantly on the elbows, knees, and buttocks [ 2 ]. DH is associated with enteropathy, and both are caused by gluten intake. Therefore, DH is considered an extra-intestinal presentation of CD.
This review details recent advances in understanding the pathogenesis, clinical manifestations, diagnosis, and treatment of DH. DH is most prevalent among the Caucasian population, particularly those of northern European descent, including the North American population. The prevalence ranges from 10 to 39 per 1,, individuals [ 5 - 7 ]. By contrast, DH is rare among Asian and African populations [ 8 , 9 ].
DH commonly develops in the second, third, and fourth decades, but it may appearin children or aging adults [ 7 , 8 , 10 - 12 ]. DH is more common in men than women, with a male-to-female ratio of 1. DH closely associated with gluten sensitive enteropathy GSE , the symptoms of which range from severe to silent [ 13 ]. However, small bowel biopsy is unnecessary for diagnosing DH because the disease is the cutaneous counterpart of CD [ 2 , 14 ].
A Finnish population study reported that However, controversy exists regarding the rarity of GSE in Japanese DH patients because a few patients were reported to have villous atrophy in a small bowel biopsyand small intestine of most of Japanese DH patients were not examined endoscopically nor histopathologically [ 8 ].
More knowledge about the small bowel mucosal alterations may be required to fully elucidate the association between Japanese DH patients and GSE, but most of Japanese DH patients, particularly who do not have abdominal symptoms, usually refuse examinations of small intestine. Zone, et al. Moreover, they reproduced the characteristic pattern of human granular IgA deposition in dermal papillae by transferring DH serum with high levels of IgA anti-eTG antibodies [ 23 ]. Because the only source of human eTG in this system is the human epidermis adjacent to the immune deposition.
A recent study showed that the number of regulatory T cells Tregs in DH skin lesions is significantly lowerthan that in healthy skin [ 24 ]. This reduction of Tregs may suppress the downregulation of the inflammation caused by the deposition of IgA anti-eTG antibodies in the papillary dermis.
Interleukin 4, interleukin 5, and granulocyte macrophage colony-stimulating factor secreted by Th2 cells are powerful chemotactic agents for neutrophils and eosinophils [ 25 ]. Neutrophilic infiltrate in the papillary dermis is suggested to lead to the release of cytokines, chemokines, and proteases as well as induce collagenases or stromelysin-1 in basal keratinocytes, which lead to blister formation [ 26 , 27 ].
However, our study of DH in Japanese patients showed that only These factors may also explain the low prevalence of DH in Asia. Given that the prerequisite HLA type for gluten antigen processing is scarce in the Japanese population, gluten may be unlikely to initiate DH in Japanese patients [ 9 ].
Severe pruritus is the principal clinical manifestation in DH. The characteristic clinical manifestations of the illness are grouped polymorphic lesions consisting of erythematous papules surmounted by vesicles, erosions, and excoriations Figure 1a [ 2 , 8 ]. Large bullae are unusual, and only crusted lesions may be observed without apparent vesicles.
The most commonly involved sites are the extensor surfaces of the elbows Figure 1b and the knees Figure 1c , as well as the shoulders, buttocks, sacral region, and face [ 2 , 8 ]. Most patients also have lesions in the scalp and the nucha. Mucosal involvement may occur [ 30 ]. Figure 1: a Erythema with vesicles and crust in dermatitis herpetiformis; b Only erythema and hypopigmented lesionsare seen on the elbows; c Grouped erythema, vesicles, and crusts on the knees. Courtesy of Prof.
Jason Bok Lee. View Figure 1. Biopsy of an early lesion shows collections of neutrophils at the papillary tips with occasional eosinophilic infiltrate Figure 2a. DIF reveals non-linear mostly granular, or fibrillar IgA deposition in the papillary dermis Figure 2b and Figure 2c [ 31 , 32 ]. IgA deposition along the basement membrane zone maysometimes occur [ 2 ].
Compared with that in lesional skin, IgA deposition is greater in normal appearing perilesional skin, and these deposits disappearslowly with adherence to a strict gluten free diet GFD [ 32 ]. Complete resolution of IgA deposition may take several years [ 2 ]. Although the deposition in most Caucasian patients has a granular pattern, that in more than one-third of Japanese patients has afibrillar pattern [ 8 ]. IgG, IgM, and C3 are also deposited in the lower percentages [ 33 ].
Indirect immunofluorescence reveals no reactivity [ 23 ]. View Figure 2. One case study reported that IgA anti-eTG antibody levels decreased over time with adherence to GFD, which suggests that testing for IgA anti-eTG antibodies may be useful to monitor disease activity [ 35 ]. DH is closely associated with gluten sensitivity [ 36 ]. Compared with CD patients, DH patients usually have milder gastrointestinal symptoms [ 37 , 38 ]. Atrophic gastritis sometimes occurs and may be a precursor to pernicious anemia [ 39 ].
Untreated patients may develop malabsorption, and consequently, anemia and bone loss [ 40 ]. Small bowel lymphoma can develop owing to GSE [ 41 ]. In addition, non-Hodgkin lymphoma can occur in patients with DH [ 42 , 43 ]. DH is associated with a number of autoimmune conditions, including thyroid disease [ 44 ], type I diabetes mellitus [ 45 , 46 ], and autoimmune connective tissue diseases such as Sjogren syndrome [ 45 ], rheumatoid arthritis [ 47 ] and lupus erythematosus [ 48 ].
Addison disease [ 45 , 49 ] and vitiligo [ 50 , 51 ] have also been associated with DH. Although neurologic diseases, including epilepsy, ataxia, and dementia, have been reported in patients with CD [ 52 ], no evidence to date supports an association between neurologic disease and DH [ 53 ]. Because DH is characterized by polymorphic lesions, the differential diagnosis includes various skin diseases such as chronic eczema, atopic dermatitis, scabies, pemphigoid, and linear IgA bullous dermatosis.
DIF differentiates DH from these diseases. A skin biopsy for DIF should be considered for refractory pruritic rashes even if no apparent gastrointestinal symptoms are found.
Recently described nonceliac gluten sensitivity NCGS may involve the skin [ 54 ]. A recent study identified C3 deposition at the basement membrane zone in a granular or micro-granular pattern in DIF of NCGS lesions despite the absences of specific histopathological changes [ 55 ].
Because the entity of NCGS remains controversial, further study is necessary to elucidate its characteristic skin mainfestations. GFD is the first-line therapy for DH [ 56 - 58 ], and may protect against the development of lymphoma. Because strict GFD adherence is time-consuming and requires extensive knowledge of food ingredients, patients should be encouraged to consult with a dietitian and join DH support groups.
Gluten comprises the proline- and glutamine-rich proteins of wheat, barley, rye, and oat. However, a recent study revealed that oats can be safely consumed by individuals with DH [ 59 - 61 ], likely because 1 compared with the gluten-like molecules in the other cereals, those in oats have only two antigenic sequences, and 2 the amount of gluten in oats is much lower than that in the other cereals [ 62 ].
Although dapsone is effective in skin lesions because it suppressesthe migration of neutrophils to extravascular sites [ 64 ], it does not improve GSE. The adverse effects of dapsone administration, including hemolytic anemia, should be monitored. Other sulfonamide drugs have effects similar to those of dapsone and can be used in dapsone-intolerant patients [ 65 , 66 ].
Systemic corticosteroids are ineffective, whereas potent topical steroids are useful in decreasing pruritus. This outcome may be attributable to the rare occurrence of GSE in Japanese DH patients, who can be successfully treated with dapsone with or without topical corticosteroids. Five patients required only several-month administration of dapsone to clear the skin lesions, and the lesions did not recur after ceasing dapsone [ 8 ].
If these patients had GSE, their skin lesions should have recurred after cessation of dapsone. DH is a chronic disease that requires long-term GFD adherence. Those who can comply with good response are likely to have reduced mortality [ 67 ] and may be able to stop dapsone treatment. Although patients with CDwho respond poorly to a GFD may have high mortality and shortened survival time [ 68 ], DH patients who is non-responsive to a GFD have relatively favorable prognosis [ 69 ].
Clinicians can use guidelines to optimize the diagnosis and management of DH. However, although several guidelines for DH have been published [ 2 , 71 - 73 ], only one is available in English [ 2 ].
These guidelines were established for Caucasian patients, in which DH is most commonly diagnosed. Additional studies of patients with DH in other Asian countries or in African countries would be useful to elucidate the features of DH further. Join Us Latest Articles Contact. All Rights Reserved. Review Process.
Open Access. Join Us. Abstract Dermatitis herpetiformis DH is an autoimmune bullous disease characterized by intensely pruritic, chronic, and recurrent vesicles on extensor surfaces such as the elbows, knees, and buttocks.
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