Chapter 32 - Dermatitis Herpetiformis and Linear IgA Bullous Dermatosis Flashcards
What is the eponym associated with dermatitis herpetiformis?
Duhring’s disease
True or false: the majority of patients with dermatitis herpetiformis are aware of having gluten sensitivity.
False; although virtually every patient with dermatitis herpetiformis has celiac disease, only 20% have intestinal symptoms, and thus patients tend to be unaware of their gluten sensitivity
How can linear IgA bullous dermatosis be distinguished from dermatitis herpetiformis on DIF?
Linear IgA bullous dermatosis will show linear IgA along the basement membrane, while dermatitis herpetiformis will show granular deposition of IgA within the dermal papillae
True or false: the first-line therapy for the treatment of dermatitis herpetiformis, and the associated intestinal disease, is dapsone.
False; dapsone is considered first-line for the skin, but the intestinal disease will not respond at all to dapsone
True or false: DH is more common in African-Americans and Asians than people of northern European origin.
False; DH occurs most commonly in people of northern European origin and it’s uncommon in African-Americans and Asians
True or false: men get DH more often than women.
True; men outnumber women two to one
Which HLA type is most closely associated with DH?
90% of patients have HLA-DQ2, and the remaining patients have HLA-DQ8
Use the “BROW” mnemonic to list the grains that contain gliadin, the alcohol-soluble fraction of gluten that is believed to be the antigen in celiac disease.
Barley, rye, oats, and wheat (oats don’t technically contain gliaden, although they’re usually produced in facilities that also produce wheat, contaminating them)
What is the specific target antigen found in the skin of patients with DH?
Epidermal transglutaminase
What is the hallmark of DH on DIF?
Granular deposition of IgA in the dermal papillae
Consumption of which non-metal element is known to dramtically worsen DH?
Iodine (found ubiquitously, but in highest concentrations in seafood and seaweed)
Which two autoimmune diseases are most closely associated with DH?
Thyroid disease (especially Hashimoto’s thyroiditis) and DM1
Which specific type of thyroid disease is most commonly associated with DH?
Hashimoto’s thyroiditis
Does adhering to a gluten-free diet for patients with DH protect against the development of gut lymphoma?
Yes (well, it reduces the risk anyways)
True or false: isolated scalp involvement is one way DH can present.
True
Where should a biopsy of DH be taken for H&E? What about DIF?
- Small intact vesicle for H&E
- Perilesional skin for DIF
If no intact vesicle can be found in a patient with DH for H&E, where should the biopsy be taken from?
An area of erythema
On H&E of DH, subepidermal blisters will be seen filled with inflammatory cells. Which inflammatory cells are most frequently present?
Neutrophils (although sometimes eosinophils are seen)
True or false: eosinophils are sometimes present in biopsies of DH, so on H&E, bullous pemphigoid, linear IgA bullous dermatosis, and bullous SLE cannot be distinguished.
True
True or false: antiendomysial antibodies are very specific for celiac disease and DH.
True
Can antiendomysial antibody levels be used to determine a patient’s compliance to dietary gluten restriction?
Yes
What is “endomysium”?
Endomysium is the connective tissue cover of the smooth muscle layer of gut; anti-endomysial antibodies are very specific for celiac disease and DH
What is the specific endomysial antigen that has been identified in celiac disease and DH?
Tissue transglutaminase
How quickly does the pruritus associated with DH subside after starting dapsone?
Within 48-72 hours
Does dapsone help improve intestinal pathology in patients with celiac disease?
No
What is the usual initial dose of dapsone in adults? In kids?
25-50 mg in adults and 5 mg/kg in kids
*Note: higher initial doses may result in severe hemolysis and subsequent cardiac failure
Is developing one to two new lesions of DH per week while on dapsone therapy acceptable?
Yes; this is expected, even on the optimal dose of dapsone, and typically increasing the dose of dapsone doesn’t eliminate this, but increases side effects
True or false: all patients, even those with normal G6PD levels, will develop hemolysis on dapsone.
True; patients with G6PD deficiency will develop severe hemolysis though
Can dapsone cause hemolysis in breastfeeding babies if their mothers are taking dapsone?
Yes
If dapsone cannot be tolerated, what is the second-line drug?
Sulfapyridine
What serious side effect of dapsone can affect the white blood cells?
Agranulocytosis
Can patients on a gluten-free diet eat corn, rice, or oats?
Yes; although patients should be very careful that their oats are not processed in a facility that also processes wheat (this is a very common source of contamination)
Which disease clinically often has annular erythema and bliters referred to as a “crown of jewels”.
Linear IgA bullous dermatosis
What are the two types of linear IgA bullous dermatosis?
Lamina lucida type and sublamina densa type
What is the most frequent cause of LABD in adults?
Drugs
What is the autoimmune target of LABD, lamina lucida type?
97 kDa antigen (cleaved ectodomain of BPAG2)
What is the autoimmune target of LABD, sublamina densa type?
It’s not known, although collagen VII has been postulated to be the target
What drug is most commonly implicated in drug-induced LABD?
Vancomycin
How long does it take for drug-induced LABD to remit after cessation of the drug?
Typically between 2-6 weeks
Can the oral, nasal, pharyngeal, or esopahgeal mucosa be involved in LABD?
Yes to all of the above
What is the first-line treatment of LABD?
Dapsone or sulfapyridine
What is the natural history of LABD?
Persistence for several years with eventual spontaneous remission
What is the natural history of chronic bullous disease of childhood?
Remission within 2-4 years
What % of patients with dermatitis herpetiformis also have a gluten sensitive enteropathy? What % also have celiac disease?
90%; 20%
What HLA class II DQ2 genotype is associated with 90% of patients with DH/CD?
DQA10501, DQB102
What 4 findings support a diagnosis of DH? Hint: 2 clinical, 2 laboratory findings
1) Pruritic papulovesicles, excoriated papules, extensor surfaces, 2) neutrophilic infiltrate of dermal papillae, vesicle at DEJ, 3) granular deposition of IgA in perilesional “normal” skin, 4) skin response (not GI) to dapsone
What % of DH patients may have spontaneous remission?
10%
Which grains contain gluten?
Barley, rye, wheat (NOT oats). They are processed by digestive enzymes to become gliadin, the Ag in gluten-sensitive enteropathy
What is the Ab and Ag (GI vs. skin) in DH/CD?
Ab = IgA antiendomysial Ab; Ag = transglutaminase (TG); in the GI = tissue TG; in the skin = epidermal TG
What are the most common automimmune disorders associated with DH?
Hashimoto’s tyroiditis, insulin dependent diabetes mellitus. Uncommonly pernicious anemia
What is the treatment for DH?
Dapsone (start 25-50mg PO daily, eventually 100mg PO daily), gluten free diet. Pruritus resolves in 2-3d after initiating dapsone
What are some side effects of dapsone?
Blood toxicity (rbc, wbc), hypersensitivity, skin, GI, CNS, fever, nephrotic syndrome
What are the 2 types of LABD?
Lamina lucida type, sublamina densa type
What is the usual etiology of LABD in adults?
?
Drugs (especially vancomycin)
Where do the Ab bind on BPAG2 in LABD?
Carboxy terminus. Linear deposition of IgA along BMZ
What is the treatment of LABD?
Dapsone, sulfapyridine, +/- prednisone
What is the histological DDx on h&e for DH?
DH
PB
Bullous LE
LABD
What percentage of DH patients have symptomatic gluten-sensitive enteropathy?
20%
What part of the small intestine is most commonly affected in DH & CD?
Jejunum
What are the major side effects of Dapsone?
Hemolysis
Agranulocytosis
Methylglubenimia
Peripheral neuropathy
True of false: peripheral neuropathy is a side effect of Dapsone that is not dose dependent?
False
