Vesiculobullous Disease Flashcards
List the 2 vesiculobullous diseases
- Bullous Pemphigoid
2. Pemphigus Vulgaris
Define vesiculobullous disease
- Uncommon chronic skin disorders caused by autoantibodies against various cutaneous proteins
- Significant quality of life issues
Epidemiology of bullous pemphigoid (BP)
- Bullous pemphigoid occurs equally in males and females.
- More prevalent in elderly patients.
- Usually in patients > 65 years of age with other comorbidities
- Median age of onset is 68-82
Causes of BP
- A drug, an injury, or skin infection can trigger the onset of disease
- There are HLA associations indicating genetic predisposition to the disease
Drug causes of BP
- furosemide
- captopril
- penicillamine
- antibiotics
Pathophysiology of BP
- Bullous pemphigoid is associated with the production of autoantibodies (IgG, +/- IgE immunoglobulins) targeting the basement membrane
- The binding of the autoantibodies to the proteins at the basement membrane stimulates destructive inflammatory cascade, predominantly mast cells and eosinophils
Name the 2 BP antigens that are autoantibody targets
Antibodies directed against 2 antigens: BP180 and BP230
Why is the basement membrane important in BP?
The basement membrane is important for the adhesion of the epidermis to the dermis, and so when targeted, leads to a separation (blister) in this space
What is the result of autoantibodies targeting the basement membrane in BP?
Results in the separation of the epidermis from the dermis forming a subepidermal blister
How does BP present on clinical exam?
- Prodromal erythematous, pruritic urticarial or papular eruption.
- Pruritus can be severe**
Where are the lesions with BP?
- Lesions usually bilateral and symmetric
- Predilection for groin, axillae, trunk, legs and flexural forearms.
What is the timeline for BP lesions?
-Evolves in weeks to months to bullae: small expanding to large, tense bullae, which rupture forming erosions.
Are the mucous membranes involved in BP?
- yes, but involvement rare - less than 10-20%
- if there is involvement, generally oral cavity.
Dx of BP
- Diagnosis is made based upon clinical, histologic, and IF features
- Most cases diagnosis confirmed by a skin biopsy (2 kinds: H&E + DIF)
Explain the H&E biopsy for BP
- biopsy of lesional skin (involved skin)
- report would reveal: “subepidermal blister with an inflammatory cell infiltrate containing eosinophils in the superficial dermis the presence of C3 deposition along the epidermal basement membrane zone”
- used for the confirmation of the diagnosis
Explain the DIF biopsy for BP
- Direct immunofluorescence (DIF) staining of normal-appearing perilesional skin (uninvolved skin)
- Reveals linear IgG &/or complement C3 along basement membrane
What other test for dx of BP?
ELISA test for detection of circulating antigen specific, BP180 and BP230,IgG and IgE antibodies is available.
What is involved with DIF biopsy?
- Refrigerated in Michel’s media
- The antibodies IgG fluoresce neon green for pathologist
- Necessity in diagnosis of blistering diseases
- If perilesional (noninvolved skin) sample is taken, recommend > 3.0 mm away from blister edge
Tx of bullous pemphigoid
- treatment is directed at reducing the inflammatory response and autoantibody production*
- Goal of therapy is to decrease blister formation
- Use immunosuppressing systemic therapy
- Promote healing of blisters and erosions (wound care, prevent /treat secondary infections)
- Determine the minimal dose of medication necessary to control the disease process.
- Clear patient of blisters with high dose medication, then slow taper
For specific bullous pemphigoid tx…
See Dr. Letassy’s handout :)
Prognosis of BP
- Characterized by a waxing and waning course
- Occasional spontaneous remission in the absence of treatment
- Localized disease often resolves spontaneously, but spontaneous remission can even occur in patients with more generalized disease
- One study reported that 8 of 30 adults with bullous pemphigoid went into remission after approximately 15 months (range, 3–38 months) of active disease
Pemphigus Vulgaris (PV) epidemiology
- Equal frequency in men and women
- Usually 5th and 6th decades (slightly younger than BP)
- MC in Jewish and those of Mediterranean descent and from Middle East
Etiology of PV
Autoimmune blistering disease with IgG autoantibodies directed against desmogleins 3 and 1
What are desmogleins?
desmosomal proteins that help the keratinocytes in the epidermis attach to each other
Which PV lesions dominate with autoantibodies towards Dsg3?
mucosal lesions dominate
Which PV lesions dominate with autoantibodies towards both Dsg1 and 3?
mucocutaneous disease
What do autoantibodies towards Dsg1 and 3 cause in PV?
**acantholysis – separation of the skin
Clinical presentation of PV
- Characterized by painful mucosal erosions and thin-walled (i.e. more flaccid, not as tense), easily ruptured bullae
- Blisters typically arise on normal-appearing skin but can be erythematous skin
- *No preceding urticarial stage line in BP
- Because PV blisters are fragile, MC for skin lesions observed to be erosions resulting from broken blisters
Clinical findings in PV
- sign
- location of 1st involvement
+ Nikolsky sign – epidermis easily shears away from underlying dermis with pressure, twisting or rubbing
-usually appears first in the mouth (60% cases) or at site of skin injury
Other mucosal involvement with PV
Mucosal involvement usually oral cavity but may involve nasal mucosa, pharynx, larynx, esophagus, conjunctiva, and genitals
Define pemphigus foliaceus
- no mucosal lesions; scaly, crusted lesions on an erythematous base
- Also calledsuperficial pemphigus as occurs higher in epidermis
Dx of PV
- Made by histology from lesional skin + confirmatory immunochemical study via direct immunofluorescence or Enzyme-Linked Immunosorbent Assay
- Histology shows acantholysis with intraepidermal blister formation
What does PV show on DIF?
staining reveals “chicken wire” pattern of intercellular IgG deposited in perilesional skinbound to the cell surface of keratinocytes
ELISA for PV
Autoantibodies against desmoglein 3 &/or, desmoglein 1
PV prognosis
- Prior to glucocorticoid therapy, PV was almost always fatal from malnutrition, dehydration and sepsis
- Still a disease associated with a significant morbidity and mortality, now approximately 10% or less mortality
- Infection +/- immunosuppression of tx is often the cause of death
- Remission is possible +/- relapses
Tx of PV
- No FDA approved treatments
- Approach to tx varies widely
- Topical steroids may suffice for localized dz
- Systemic glucocorticoids is mainstay; 2.0 mg/kg/day single daily dose
- Once disease activity is controlled, taperingprednisone to as low a dose as possible is the goal
Tx of PV continued…
- If continued relapses with daily prednisone dose of 10 mg or higher, adjunctive immunosuppressive agents should be considered
- Mucosal disease may benefit from the use of glucocorticoid elixirs as a swish and spit or dental trays to help apply class I corticosteroid gels or ointments to the gingiva
Considerations when using immunosuppressive therapy for PV
- Monitor all patients closely for potential side effects- blood count, liver and kidney laboratory abnormalities, gastrointestinal ulcer disease, high blood pressure, diabetes, glaucoma, cataracts, osteoporosis, and infection
- Consider potential incidence of malignancies that might be associated
- Consider risks of infertility and teratogenicity
For specific PV tx…
See Dr. Letassy’s handout :)
