Dermatitis Herpetiformis Flashcards
DDx for papules on b/l elbows?
DH, papular GA, perforating dz, palisading neutrophilic granulomatous dermatitis (hx of RA).
What is the antigenic component of gluten?
Gliadin
What tissue transglutaminases are involved in the gut and skin disease?
TTG-2 in the gut and TTG-3 in the skin. Gut one forms first and then you get TTG-3 in the skin via epitope spreading
Where do you want to bx for DH?
You want the blister edge for H&E and then 1cm away from blister for DIF
DDx for subepidermal blisters w/ neuts?
DEBB LIPS: DH, EBA, bullous urticaria, bullous acute vasculitis, lupus (bullous), IGA LINEAR –> LABD, pemphigoid cicatricial (p200 pemphigoid), Sweets
Where is TTG-3 the densest in the skin?
In the dermal papillae, that is why you get the neuts in the dermal papillae
Why do you not want to do a DIF too close to the blister?
The inflammation from the neuts and such can destroy the IgA depositions
What is the primary tx for DH?
Dapsone (skin but not gut findings), and the second-line is sulfapyridine (less chance of hemolysis)
What is the half-life of the IgA antibodies?
3 weeks (so you need ~5 half-lives to clear the antibodies) (3 months or more)
What is disease progression like on dapsone?
It inhibits the neuts, but you still have antibodies for ~15 weeks so if you have an occurrence of 1-2 lesions per week that is ok. But this is reduced
Dosing of dapsone for DH?
25-50mg in adults and .5mg/kg in children. Average maintenance dose in adults is 100mg daily
How do you tx DH lesions on the face?
They are refractory to dapsone so you break blisters and apply topical CS
What should be avoided in DH pt’s?
Application or ingestion of iodine as this stimulates neutrophil production
Where can you bx if DH patients have had gluten in the last 6 months?
You can bx literally anywhere and get + DIF since the IgA and TTG-3 is everywhere
What are the two main HLA II alleles a/w DH?
HLA-DQ2 and HLA-DQ8
What percentage of DH patients have evidence of gluten-sensitive enteropathy?
90% have evidence of gluten-sensitive enteropathy but only about 20% have intestinal symptoms of celiac disease.
What is the clinical presentation of DH?
Chronic, relapsing, severely pruritic, grouped symmetrical, polymorphous, erythematous-based lesions (often extensor surfaces)
May be papular, papulovesicular, vesiculobullous, bullous, or urticarial. Can see linear petechial lesions on palms and fingers.
What is the classic distribution of DH?
Symmetric extensor extremities, buttocks, and back/neck (>face/scalp)
Hemorrhagic palmoplantar lesions (helpful clue)
What 4 findings support the dx of DH?
- Pruritic papulovesicles or excoriated papules on extensor surfaces
- Neutrophilic infiltrate in the dermal papillae w/ vesicle formation at the dermal-epidermal junction
- Granular deposition of IgA within the dermal papillae of clinically normal-appearing skin adjacent to a lesion
- A response of the skin disease, but not the intestinal disease, to dapsone therapy.
What are the 5 HLA types involved in DH and what is the most common HLA type?
HLA-DQ2 (90%) HLA-DQ8 (7%) HLA-B8 HLA-DR3 HLA-DR5, DR-7
What is gluten found in?
Wheat, rye, and barley (not oats, rice, or corn)
What is the antigenic component of gluten?
Gliadin, an alcohol-soluble fraction of gluten
What is the protein that the antibodies are formed against in the gut and cutaneous findings in DH?
TTG2 (tissue transglutaminase protein is present in GI lamina propria) for the gut enteropathy and then the TTG3 is where you get anti-TTG3 IgA antibodies responsible for skin involvement in DH (epitope spreading)
Pathogenesis of DH?
Ingestion of gluten-containing grains → gluten broken down into gliadin inside GI lumen → gliadin transported across GI mucosa to lamina propria → TTG2 in lamina propria deamidates gliadin → deamidated gliadin forms a covalent bond w/ TTG2 → TTG2-gliadin complex is a neoantigen recognized by HLA-DQ2 (or HLA-DQ8) on APCs → specific Th and B-cells activated → production of IgA autoantibodies against TTG2 or TTG2-gliadin complex → IgA antibodies bind to TTG2 complexes in lamina propria → neutrophil recruitment, damage to intestinal villi → enteropathy and villous atrophy → later, epitope spreading results in IgA autoantibodies against epidermal transglutaminase (TTG3) → circulating anti-TTG3 IgA binds locally to TTG3 within dermal papillae → neutrophils recruited to dermal papillae (“neutrophilic papillitis”) → release elastase and MMPs → subepidermal blister most prominent above papillae
What other diseases are DH associated with?
Strongly associated with other autoimmune diseases
Hashimoto’s thyroiditis (MC, 50%)>insulin dependent diabetes mellitus >Pernicious anemia >> Addison’s, alopecia areata, myasthenia gravis, vitiligo, and SLE
What malignancy is a/w DH?
Incidence of enteropathy-associated T-cell lymphoma and non-Hodgkin’s lymphoma is increased in patients with DH
Where do you want to biopsy lesions for histologic analysis?
The typical histologic features are best observed in erythematous skin adjacent to early blisters
Histology of DH?
Apoptotic keratinocytes may be noted above the papillary microabscesses.
Neutrophilic microabscesses in dermal papillae, ± subepidermal Vesicles
indistinguishable often from LABD, need DIF!
What is the DIF of DH?
DIF: granular IgA > C3 deposition in dermal papillae
IgA is not uniformly distributed throughout the skin. IgA deposits are present in greater amounts near active lesions
Granular IgA +/- C3 deposits localized to the dermal papillae are found in 85% of cases of DH
Continuous granular deposition of IgA along the basement membrane occurs in 5% to 10% of cases
What antibody tests can be performed for DH?
Anti-endomysial antibodies (IgA antibodies to TG2) are very specific for DH (80%) and celiac disease (>95%)
Do Titers of anti-endomysial antibodies correlate with disease activity in DH?
Titers correlate w/ severity of the gluten-sensitive enteropathy
good for monitoring responses to gluten-free diet
What other antibodies can be tested in DH?
IgA class antireticulin can also be looked at. Studies have suggested high sensitivity and specificity for these in DH patients with villous atrophy.
Anti-gliadin antibodies have high false + rates.
What is the physiologic role of tissue transglutaminase?
The normal physiologic function of transglutaminase is to repair injured tissue by cross-linking extracellular matrix proteins in the tissue, protecting the surrounding tissue from further damage.
As antibodies to transglutaminase are produced, the normal function of transglutaminase in repairing the damaged intestinal mucosa is impaired.
What is the treatment of choice for DH?
A gluten-free diet is the only real treatment
Sx’s can be relieved rapidly (for skin dz) with dapsone or sulfapyridine
What chemical must people with DH avoid?
Must AVOID IODINE/IODIDE (ingestion or topical)
Iodine stimulates neutrophils –> Worsening & production of new lesions
What part of the intestines are the IgA antibodies formed for DH?
Jejunum
How long on a gluten-free diet is needed to see the full response?
Several months (for the enteropathy it depends on how long they have had sx’s) but 6 months at least.
