Bullous Diseases

Question 1

3 most common bullous diseases

Answer 1

1. bullous pemphigoid
2. pemphigus vulgaris
3. dermatitis herpetiformis

Question 2

diagnosing bullous disease invollves:

Answer 2

skin biopsy for histopathology and immunofluorescence, as well as direct antibody testing

Question 3

____ ____(BP) is a chronic autoimmune sub-epidermal blistering disease most frequently seen in the elderly.

Answer 3

bullous pemphigoid

Question 4

explain the mechanism of BP

Answer 4

IgG autoantibodies bind to antigens that comprise the hemidesmosome adhesion complex in the basement membrane of the skin (BP180 or BP230).
This triggers complement activation and release of inflammatory mediators, resulting in the formation of local or generalized tense bullae.
The disease can occur on any, body surface, but mucous membrane involvement is rare.

Question 5

in bp: ____ ____ bind to antigens that comprise the ____ adhesion complex in the _____ membrane of the skin (BP180 or BP230).
This triggers ____ activation and release of inflammatory mediators, resulting in the formation of local or generalized ____ bullae.
The disease can occur on any, body surface, but mucous membrane involvement is rare.

Answer 5

IgG autoantibodies bind to antigens that comprise the hemidesmosome adhesion complex in the basement membrane of the skin (BP180 or BP230).
This triggers complement activation and release of inflammatory mediators, resulting in the formation of local or generalized tense bullae.
The disease can occur on any, body surface, but mucous membrane involvement is rare.

Question 6

____ should always be highly considered when tense bullae are present in patients older than 60 years.

Answer 6

BP should always be highly considered when tense bullae are present in patients older than 60 years.

Question 7

compare and contrast BP and PV

Answer 7

BP rarely has mucosal lesions, as compared with pemphigus vulgaris, which frequently begins with oral erosions.

Question 8

why is BP usually tense?

Answer 8

bulla is often intact because it’s a sub-epidermal blister– the full thickness of the epidermis comprises the roof of the blister

Question 9

what would you see on an immunofluorescnece of a skin biopsy of someone with BP?

Answer 9

deposition of igG at the dermal/epidermal junction

Question 10

treatment for BP

Answer 10

Therapeutic options depend upon the extent of the skin disease. Localized disease can be treated with potent topical corticosteroids. More extensive disease requires systemic corticosteroids (prednisone) in the short term in order to get the blistering under control.
Oral Doxycycline may be used as a steroid sparing agent once prednisone has blistering under control. Other immunosuppressive agents such as Methotrexate or Azothioprine are also options.

Question 11

steroid sparing options for BP

Answer 11

Oral Doxycycline may be used as a steroid sparing agent once prednisone has blistering under control. Other immunosuppressive agents such as Methotrexate or Azothioprine are also options.

Question 12

Pemphigus vulgaris is a chronic autoimmune blistering disease that can cause significant morbidity and serious complications. what genetic predispositions are there towards PV?

Answer 12

Pemphigus vulgaris is a chronic autoimmune blistering disease that can cause significant morbidity and serious complications.

There is a genetic predisposition for Ashkenazi Jews and certain HLA types

Question 13

key feature of PV that distinguishes it from BP

Answer 13

firstly, Patients usually complain of painful sores in the mouth and bleeding of the gums when brushing their teeth. The oral cavity is frequently the first site of involvement, with painful skin lesions appearing months or years later. Other mucosal sites such as the nasal mucosa, throat, eyes, and genital areas may also have lesions.

Look for painful erosions and ulcers anywhere on the oral mucosa, but particularly on the hard and soft palate. The gingiva may have lesions in a “desquamative gingiva” pattern with marked erythema and peeling of the attached gingiva. It is rare to see intact vesicles or bullae in the oral cavity.

Question 14

etiology/mechanism of pemphigus vulgaris

Answer 14

The etiopathogenesis is antibody-mediated cell damage, known classically as acantholysis and more recently as apoptolysis. A variety of antigens including desmoglein 1 and 3 (mucosal) are involved.

Question 15

PV: The etiopathogenesis is antibody-mediated cell damage, known classically as ____ and more recently as ____. A variety of antigens including ___ 1 and 3 (mucosal) are involved.

Answer 15

The etiopathogenesis is antibody-mediated cell damage, known classically as acantholysis and more recently as apoptolysis. A variety of antigens including desmoglein 1 and 3 (mucosal) are involved.

Question 16

bulla differences in BP vs PV

Answer 16

BP: tense because entire epidermis is the roof of the blister

PV: bulla are flaccid and break easily.

Question 17

in PV:Lateral pressure on adjacent lesional skin or rubbing normal-appearing skin will extend the bullae or cause erosion, respectively. This is a positive ____ sign. Lesions will not remit without treatment and may become extensive.

Answer 17

Lateral pressure on adjacent lesional skin or rubbing normal-appearing skin will extend the bullae or cause erosion, respectively. This is a positive Nikolsky’s sign. Lesions will not remit without treatment and may become extensive.

Question 18

in PV, what would you see on the histopathological slide and the immunofluorescent slide?

Answer 18

Histopathology shows Intraepithelial vesicles with acantholysis. The bullae rupture easily because of the immunologic deconstruction of the epidermis

Direct immunofluorescence exhibits “chicken-wire” deposition of IgG and C3 between keratinocytes

Question 19

treatment for PV

Answer 19

Systemic immunosuppression is used if oral disease cannot be successfully managed with topical steroids, or if skin disease develops.
Systemic therapy such as Mycophenolate mofetil. IVIG or Cyclosporine however is more often required to treat pemphigus vulgaris

Newer studies have shown that rituximab* either alone or combined with intravenous immunoglobulin (IVIG) or prednisone may lead to durable remission for many patients with skin disease and allow patients to be discontinued from prednisone completely.

Question 20

_____ ____ is a chronic pruritic autoimmune blistering disorder associated with gluten-sensitive enteropathy.
It most commonly affects patients of Northern European descent and occurs more frequently in ___ than ____.

Answer 20

Dermatitis herpetiformis (DH) is a chronic pruritic autoimmune blistering disorder associated with gluten-sensitive enteropathy.
Dermatitis Herpetiformis most commonly affects patients of Northern European descent and occurs more frequently in men than women.

Question 21

Even those DH is a bullous disease, why are blisters often absent? where do you usually find the blisters?

Answer 21

Blisters are usually small, between 1 and 2 mm in diameter. Symmetrically grouped, extremely pruritic urticarial plaques with pinpoint vesicles over extensor arms, legs, scalp, and buttocks.
Because of the intense pruritus, blisters are often absent and instead multiple excoriations are more commonly seen as secondary morphology

Question 22

treatment of DH

Answer 22

. Many patients who adhere to a strict gluten-free diet experience complete remission of their disease.

Dapsone, for more extensive disease, can be started at 25 mg p.o. daily with gradual increase to an average maintenance dose of 0.5-1.0 mg/kg p.o. daily. Dapsone will improve cutaneous disease but has no effect on intestinal involvement.
Dapsone however, may produce hemolysis, methemoglobinemia, a hypersensitivity syndrome, and peripheral neuropathy as known side effects and should be used with caution.

Question 23

DH predisposes patients to which other diseases?

Answer 23

Patients with DH are at an increased risk of developing Hashimoto’s thyroiditis, Diabetes mellitus, and enteropathy associated T cell lymphoma, and therefore warrant close surveillance.

Question 24

what would you see on histopathology of someone with DH?

Answer 24

collections of neutrophils at the top of the papillary dermis

Question 25

etiology/pathogenesis of DH. genetic predisposition?

Answer 25

The pathogenesis involves the deposition of IgA immune complexes in the papillary dermis. The associated autoantigen is an epidermal transglutaminase.

There is a genetic predisposition to the disease, as certain human leukocyte antigen (HLA) haplotypes, HLA class II DQ2, demonstrate increased expression.

Question 26

Answer 26

BP. tense bulla

Question 27

Answer 27

BP. entire epidermis makes up the roof of the blister, giving it a tense appearance

Question 28

Bp or PV?

Answer 28

PV. oral ulcers are often the first presentation

Question 29

Answer 29

Severe PV is life threatening without predisone— secondary infections can occur because of the immunosuppressed

cantholysis Apoptolysis is is common and causes the lesions. Desmoglian I and III are involved

Bulla are flaccid and break easily. Rubbing normal appearing skin can cause more lesions. Lesions will not remit without treatment.

Question 30

Answer 30

PV

Histology shows intravascular-epithelial vesicles with acantholysis. The bulla rupture easily because of the immunologic deconstruction of the epidermis.

Question 31

Answer 31

DH

While more than 90% of patients have a gluten sensitivity on small biopsy, only 20% exhibit symptoms of the intestinal disease. Blisters are usually small and symmetrically grouped.

Urticaria plaques with pin point vessicles seen in scalp, extensors surfaces, and bum.

Question 32

Answer 32

Pathology of DV shows collections of neutrophils at the top of Pap pillars dermis. The pathogenesis involves deposition fo igA immune complexes in the papillary dermis.

The associated auto antigen is an epidermal transglutamase. There is a genetic predisposition to the disease as certain HLA class II Dq2 demonstrate increased expression