32 Dermatitis Herpetiormis and Linear IgA Bullous Dermatosis

Question 1

What percentage of patients with dermatitis herpetiformis have intestinal symptoms of celiac disease?

Answer 1

20%

Question 2

what 4 findings support the diagnosis of dermatitis herpetiformis?

Answer 2

• pruritic papulovesicles or excoriated papules on the extensor surfaces
• neutrophilic infiltration of the dermal papillae with vesicle formation at the dermal-epidermal junction.
• granular deposition of IgA in the dermal papillae of clinically normal appearing skin.
• dramatic response of the skin to dapsone therapy.

Question 3

what HLA genotype is dermatitis herpetiformis strongly associated with?

Answer 3

HLA DQ A1*501 which encodes HLA DQ2 heterodimers.

Question 4

described the proposed pathogenesis of dermatitis herpetiformis

Answer 4

1. Wheat ingested
2. Broken down into gliadin
3. gliadin is absorbed via the lamina propria.
4. glutamine resides are deaminated by tissue transglutminase
5. the deaminated gliadin binds to HLADQ2 molecule on the dendritic antigen-presenting cells and the gliadin antigen is presented to sensitized helper T cells.

this process activates circulating neutrophils.
degranulation of the eutrophils releases proteases which disrupt the lamina lucida.

Question 5

Ingestion or application of which substance makes DH worse (asides from gluten) ?

Answer 5

iodide makes DH dramatically worse if ingested and even application onto the normal skin can produce lesions.

Question 6

What are the clinical features of dermatitis herpetiformis?

Answer 6

DH favours the elbows, extensor forearms, back, buttocks and knees.

urticarial plaques, papules and vesicles.

Question 7

What are the histological features of dermatitis herpetiformis?

Answer 7

• subepidermal blister
• contains predominantly neutrophils
• granular IgA deposits in the dermal papillae (optimal biopsy site is IMMEDIATELY adjacent the lesion).

Question 8

what test is a reflection of compliance with dietary gluten restriction in DH?

Answer 8

antiendomysial antibody levels. They are found in 80% of patients with dermatitis herpetiformis and 95% of patients with active coeliac disease.

Question 9

What are the characteristic features that differentiate dermatitis herpetiformis, bullous pemphigoid and linear IgA from each other? (Hint: describe cutaneous lesions, distribution, histology, direct IF, sites to biopsy for direct IF, indirect IF, presence of enteropathy, HLADQ2 status and dapsone responsiveness)

Answer 9

• page 451

Question 10

what is the treatment for dermatitis herpetiformis?

Answer 10

1. dapsone 25-50 mg daily (0.5 mg/kg in children).
2. gluten free diet.

1-2 lesions a week is expected on the optimal dose.

Question 11

What treatment can be used for facial DH?

Answer 11

• refractory to dapsone.

- break vesicles and use topical corticosteroid gel.

Question 12

What are the side effects of dapsone?

Answer 12

Blood side effects:

• heamolytic anaemia
• methemoglobinaemia (present in blood of most patients taking 100 mg of dapsone).
• leukopenia
• agranulocytosis
• Dapsone hypersensitivity syndrome:
• cuatneous reactions including:
  
  • urticaria, fixed drug eruption, SJS/TEN/ drug inuduced lupus
• GIT symptoms
• Neurological symptoms (peripheral neuropathy)
• secreted in breast milk

Question 13

what pregnancy category is dapsone?

Answer 13

B2

Question 14

with regards to agranulocytosis when using dapsone. When does this occur?

Answer 14

2 - 12 weeks of continuous dapsone treatment. (Due to the formation of leukoctye agglutinins).

Question 15

When does peripheral neuropathy occur in dapsone treatment?

Answer 15

Peripheral neuropathy occurs in the first 4 months of treatment with dapsone. The distal upper and lower extremity muscles and the muscles of the hand are commonly affected.

Question 16

What treatment can be used for DH if a patient is not able to have dapsone?

Answer 16

Sulfapyridine is 500 mg TDS.

Question 17

What blood tests should be done to monitor the use of dapsone?

Answer 17

full blood counts, liver function test and G6PD as a baseline, the weekly FBC for 1 month then monthly FBE for 5 months then 6 monthly FBE.

Question 18

what are the clinical manifestations of linear IgA?

Answer 18

• annular erythema and blisters which have developed predominantly in flexural areas - e.g trunk, thigh and grown.
• there may be oral or occular findings.
• Drug induced linear IgA can have a TEN like presentation.

Question 19

what are the 2 types of linear IgA?

Answer 19

1. The lamina lucida type
2. sublamina densa type.

• most linear Ig A is of the lamina lucida subtype.

Question 20

What is the pathogenesis of linear IgA?

Answer 20

• IgA which reacts against BPAG2 - (LABD97 - cleaved ectodomain).
• in the sublamina densa type of linear IgA this binds to type VII collagen in achoring fibrils.

Question 21

What diseases are linear IgA associated with?

Answer 21

Possibly ulcerative colitis, Chron’s disease, gastric hypochlorhydria. May also be associated with B-cell lymphoma, chronic lymphocytic leukemia an carcinoma of the bladder, thyroid and oesophagus.

Question 22

what are the histological findings of Linear IgA?

Answer 22

• subepidermal vesicle,
• predominantly netrophils
• linear distribution of neutrophils along the basement membrane (and dermal papillae)
• may have eosinophils.
• most patients have IgA deposits within the lamina lucida.

Question 23

Which drugs can cause linear IgA?

Answer 23

Vancomycin is the most common cause.

• penicillins
• cephalosporins
• captopril/ACE
• NSAIDs

Question 24

What is the treatment of linear IgA?

Answer 24

• oral dapsone
  or sulfapyridine therapy.

may need to add in pred (especially if there are linear IgG and IgA deposides in the BMZ).

-reports of erythromycin and dicloxacillin reported.

MMF, AZA, IVIg andCsA can be used.