Skin nontumor
Vesiculobullous and acantholytic reaction patterns
Dermatitis herpetiformis
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Last author update: 15 February 2022
Last staff update: 24 June 2022
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PubMed Search: Dermatitis herpetiformis[TI] "last 5 years"[dp]
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Diagrams / tables | Clinical features | Diagnosis | Laboratory | Prognostic factors | Case reports | Treatment | Clinical images | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Immunofluorescence description | Immunofluorescence images | Videos | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Occidental M, Kim RH. Dermatitis herpetiformis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/skinnontumordermatitisherpetiformis.html. Accessed August 15th, 2022.
Definition / general
- Acquired autoimmune subepidermal blistering disease due to gluten exposure and characterized by neutrophilic microabscesses and IgA deposits in the dermal papillae
Essential features
- Most cases are triggered by gluten ingestion and subsequent intolerance
- Anti tissue transglutaminase antibodies cross react with epidermal transglutaminase and leads to cutaneous deposits of IgA (J Exp Med 2002;195:747)
- Subepidermal vesicles and blisters with papillary neutrophilic microabscesses that may contain eosinophils
- Periphery of blister: neutrophilic interface inflammatory infiltrate and neutrophilic microabscesses in the dermal papillae
- Direct immunofluorescence: granular or fibrillar IgA deposition along the basement membrane and in the dermal papillae
Terminology
- Duhring-Brocq dermatitis (An Bras Dermatol 2014;89:865)
ICD coding
Epidemiology
- Most commonly occurs in second to fourth decade
- Mainly seen in Caucasians of Northern European descent (An Bras Dermatol 2014;89:865)
- M > F
- Commonly seen in association with gluten sensitive enteropathies
Sites
- Common locations: elbows, knees, buttocks and back, posterior shoulder, neck
- May rarely involve oral mucosa
Pathophysiology
- Most cases are triggered by gluten ingestion (specifically, gliadin protein)
- Causes antibody formation against gliadin and autoantibody formation against transglutaminases (An Bras Dermatol 2014;89:865)
- Anti tissue transglutaminase antibodies cross react with epidermal transglutaminase (TG3), leading to cutaneous deposits of IgA (J Exp Med 2002;195:747)
Etiology
- Autoantibody formation to tissue transglutaminase following ingestion of gluten
Diagrams / tables
Images hosted on other servers:
Dermatitis
herpetiformis
physiopathogenesis
Clinical features
- Pinhead sized and grouped vesicles on an erythematous base
- May appear as erosions due to intense scratching
- Associated with gluten sensitive enteropathies (e.g. celiac disease)
- Both celiac disease and dermatitis herpetiformis have strong genetic association with HLA DQ2 and HLA DQ8 on chromosome 6 (J Invest Dermatol 2000;115:990)
Diagnosis
- Enzyme linked immunoassay (ELISA)
- Circulating IgA antibodies to tissue transglutaminase
- Histologic evaluation and direct immunofluorescence
- Biopsy should include samples of perilesional skin (routine stains, DIF) and lesional skin (H&E) (Clin Cosmet Investig Dermatol 2015;8:257)
- Specimens submitted for direct immunofluorescence (DIF) can come from normal appearing perilesional skin
Laboratory
- ELISA: circulating IgA antibodies to tissue transglutaminase
Prognostic factors
- Strong association with HLA DQ2 and HLA DQ8 (Tissue Antigens 1997;49:29)
- Same HLA haplotypes associated with celiac disease
- Gluten free diet may cause prolonged remission in some patients or lower daily dapsone requirement in others
Case reports
- 17 year old adolescent boy with dermatitis herpetiformis (An Bras Dermatol 2019;94:495)
- 44 year old woman with vesicular facial rash (J Cutan Med Surg 2019;23:35)
- 46 year old man with a petechial rash and left arm swelling (JAAD Case Rep 2017;3:444)
Treatment
- Gluten free diet (GFD): first line treatment
- Bridge therapy with dapsone: can take up to 2 years for rash to disappear with gluten free diet alone (Dermatol Ther 2003;16:214)
- Dapsone
- Used in combination with gluten free diet to reduce symptoms
- Rash returns 2 - 3 days after discontinuation of dapsone if used as the sole therapy
Clinical images
Images hosted on other servers:
Grouped papules,
vesicles and
hypopigmentation
Microscopic (histologic) description
- In early lesions, superficial perivascular lymphocytic and neutrophilic infiltrate
- Subepidermal vesicles or blisters with papillary neutrophilic microabscesses that may contain eosinophils
- Vacuolar interface changes and nuclear dust may be seen
- Dermal infiltrate contains lymphocytes, histiocytes and abundant neutrophils
- Periphery of blister: neutrophilic interface inflammatory infiltrate and neutrophilic abscesses in the dermal papillae (An Bras Dermatol 2014;89:865)
- Occasionally, findings may be nonspecific with just perivascular lymphocytes (requiring DIF for confirmation) (Am J Dermatopathol 2002;24:305)
- Acantholysis may also be present (Front Immunol 2019;10:1290)
Microscopic (histologic) images
Contributed by Michael Occidental, M.D. and Randie H. Kim, M.D., Ph.D.
Blister
Skin directly adjacent to blister
Perilesional skin
Blister and perilesional skin
Neutrophilic microabscesses in perilesional skin
Virtual slides
Images hosted on other servers:
Dermatitis herpetiformis
Neutrophilic infiltration of dermal papillae
Immunofluorescence description
- Direct immunofluorescence (An Bras Dermatol 2014;89:865)
- Most commonly granular IgA deposits in the dermal papillae
- Granular C3 deposits pattern in dermal papillae may be present
- Rare but characteristic fibrillar IgA deposits along the basement membrane zone (J Cutan Pathol 2010;37:475)
- Most commonly granular IgA deposits in the dermal papillae
Immunofluorescence images
Contributed by Randie H. Kim, M.D., Ph.D.
IgA on direct immunofluorescence
Videos
Dermatitis herpetiformis
Sample pathology report
- Skin, shoulder, left, shave biopsy:
- Dermatitis herpetiformis (see comment)
- Comment: There is a subepidermal blister with associated lymphocytes, histiocytes and abundant neutrophils. The periphery of the lesion shows prominent vacuolar interface changes and collections of neutrophils at the tips of the dermal papillae. The associated immunofluorescence sample displays granular IgA and C3 deposits in the dermal papillae. The findings are consistent with dermatitis herpetiformis.
Differential diagnosis
- Histopathological findings of neutrophil rich subepidermal autoimmune blistering diseases may be identical and include linear IgA dermatosis, bullous systemic lupus erythematosus, neutrophil rich bullous pemphigoid, inflammatory epidermolysis bullosa acquisita and p200 pemphigoid
- Linear IgA dermatosis:
- Homogenous band of IgA at the dermal epidermal junction
- No anti endomysial or anti tissue transglutaminase IgA antibodies
- Not gluten sensitive
- Bullous pemphigoid:
- Large tense blisters on flexor surfaces, trunk, intertriginous regions and mucosa
- No neutrophil microabscesses in classical bullous pemphigoid
- Neutrophil rich variants however may look very similar; rely on DIF to distinguish
- Bullous systemic lupus erythematosus:
- Autoantibodies to type VII collagen on direct immunofluorescence (u-serrated pattern)
- Sublamina densa blistering disease that may have a linear u-serrated pattern on direct immunofluorescence
- DIF may show granular or linear deposition of IgM, IgG or IgA and C3 along the basement membrane zone (full house staining)
- Epidermolysis bullosa acquisita:
- Immunofluorescence positive on dermal side of salt split skin (u-serrated pattern) (Br J Dermatol 2004;151:112)
- IgG > C3 > IgA
Board review style question #1
A 20 year old man presents with chronic diarrhea, weight loss and vesicular skin lesions on his upper extremities. The man was referred for an esophagogastroduodenoscopy and colonoscopy, which showed villous blunting and increased intraepithelial lymphocytes within the duodenum. The skin lesions were concurrently biopsied (shown in above image). What do you expect to see on direct immunofluorescence?
- Granular IgA with or without C3 deposits on the tips of the dermal papillae
- Intracellular IgG and C3 deposition in the epidermis (chicken wire pattern)
- Linear IgA deposition along the basement membrane
- Linear IgG and C3 deposition along the basement membrane
Board review style answer #1
A. Granular IgA with or without C3 deposits on the tips of the dermal papillae
Comment Here
Reference: Dermatitis herpetiformis
Comment Here
Reference: Dermatitis herpetiformis
Board review style question #2
Antibodies to what protein are formed in dermatitis herpetiformis?
- BPAG1 and BPAG2
- Desmoglein 1 and 3
- Desmocollin 1
- Epidermal transglutaminase (TG3)
Board review style answer #2
