Skin nontumor

Vesiculobullous and acantholytic reaction patterns

Dermatitis herpetiformis



Minor changes: 25 October 2021

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PubMed Search: Dermatitis herpetiformis[TI] "last 5 years"[dp]

Michael Occidental, M.D.
Randie H. Kim, M.D., Ph.D.
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Cite this page: Occidental M, Kim RH. Dermatitis herpetiformis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/skinnontumordermatitisherpetiformis.html. Accessed October 25th, 2021.
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 abscesses in the dermal papillae
  • Direct immunofluorescence: granular or fibrillar IgA deposition along the basement membrane and in the dermal papillae
Terminology
ICD coding
  • ICD-10: L13.0 - dermatitis herpetiformis
Epidemiology
  • Most commonly ages 20 - 40
  • 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, 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
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
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 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)
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 abscesses in perilesional skin

Virtual slides

Images hosted on other servers:

Dermatitis herpetiformis

Neutrophilic infiltration of dermal papillae

Immunofluorescence description
  • Direct immunofluoresence (An Bras Dermatol 2014;89:865)
    • Granular IgA deposits in the dermal papillae and either:
      • Granular C3 deposits pattern in dermal papillae
      • Granular or fibrillar IgA deposits along the basement membrane zone
Immunofluorescence images

Contributed by Randie H. Kim, M.D., Ph.D.

IgA on direct immunofluoresence

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
  • 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
  • Bullous lupus erythematosus:
    • Autoantibodies to type VII collagen on direct immunofluorescence (u-serrated pattern)
    • DIF may show granular or linear deposition of IgM, IgG or IgA and C3 along the basement membrane zone
  • Epidermolysis bullosa acquisita:
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?

  1. Granular IgA and C3 deposits on the tips of the dermal papillae
  2. Intracellular IgG and C3 deposition in the epidermis (chicken wire pattern)
  3. Linear IgA deposition along the basement membrane
  4. Linear IgG and C3 deposition along the basement membrane
Board review style answer #1
A. Granular IgA and C3 deposits on the tips of the dermal papillae

Comment Here

Reference: Dermatitis herpetiformis
Board review style question #2
Antibodies to what protein are formed in dermatitis herpetiformis?

  1. BPAG1 and BPAG2
  2. Desmoglein 1 and 3
  3. Desmocollin 1
  4. Tissue transglutaminase
Board review style answer #2
D. Tissue transglutaminase

Comment Here

Reference: Dermatitis herpetiformis
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