9 - 52 - PEMPHIGUS Flashcards
give examples of Intraepidermal Blistering Diseases Without Autoantibodies
■ Familial benign pemphigus (Hailey-Hailey disease)
■ Bullous impetigo, staphylococcal scalded-skin syndrome
■ Blisters from herpes simplex and zoster
■ Allergic contact dermatitis (eg, rhus dermatitis)
■ Epidermolysis bullosa simplex
■ Incontinentia pigmenti
give examples of Mouth Ulcers/Erosion Without Autoantibodies
■ Aphthous ulcers
■ Candidiasis
■ Lichen planus
■ Behçet disease
give examples of Subepidermal Blistering Diseases With Autoantibodies
■ Bullous pemphigoid
■ Herpes gestationis
■ Cicatricial pemphigoid
■ Epidermolysis bullosa acquisita
■ Linear IgA disease and chronic bullous disease of childhood
■ Dermatitis herpetiformis
■ Bullous lupus erythematosus
give examples of Subepidermal Blistering Diseases Without Autoantibodies
■ Erythema multiforme
■ Toxic epidermal necrolysis
■ Porphyria
■ Junctional or dystrophic epidermolysis bullosa
distribution of lesions in PV
The primary lesion of PV is a flaccid blister, which may occur anywhere on the skin surface, but typically not the palms and soles
primary lesion of PV
flaccid blister
erosions can be extended into visibly normal skin by pulling the remnant of the blister wall or rubbing at the periphery of active lesions; additionally, erosions can be induced in normal-appearing skin distant from active lesions by pressure or mechanical shear force.
This phenomenon is known as?
Nikolsky sign
pemphigus vegetans manifestations and areas of predilection
excessive papillimatosis and crusting, referred to as vegetating lesions occurring more frequently in intertriginous areas, in the scalp, or on the face
Conditions where nikolsky sign can be elicited?
PV, staphylococcal scalded skin syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis
mucous membranes most often affected by PV
oropharyngeal cavity and nasal mucosa
In the majority of patients, what are the **presenting sign of PV **and may be the only sign for an average of 5 months before skin lesions develop
painful mucous membrane erosions
clinical manifestations and areas of predilection of PF
- The characteristic clinical lesions of PF are scaly, crusted erosions, often on an erythematous base.
- In more localized and early disease, these lesions are usually well demarcated and scattered in a seborrheic distribution, including the face, scalp, and upper trunk
localized form of PF with better prognosis
Pemphigus erythematosus
drug-induced pemphigus is commonly caused by what medications?
penicillamine and captopril
associated conditions with PV
Myasthenia gravis, thymoma
Recent epidemiologic studies have identified that pemphigus vulgaris patients have a higher prevalence of autoimmune thyroid disease, rheumatoid arthritis, and Type 1 diabetes compared with the general population
PF antigen (as well as the fogo selvagem antigen)
desmoglein 1, a 160-kDa protein
PV antigen
desmoglein 3, a 130-kDa protein
T/F
All patients with PV have antidesmoglein 3 antibodies, and some of these patients also have anti–desmoglein 1 antibodies
True
Patients with mucosal-dominant PV tend to have only antibodies to what?
Patients with mucosal-dominant PV tend to have only antidesmoglein 3 antibodies
mucocutaneous PV usually have antibodies to what?
both **anti–desmoglein 3 and anti–desmoglein 1 **antibodies
PF patients typically have antibodies against only what antigen?
desmoglein 1
this IgG subclass , which does not fix complement, has been shown to be both pathogenic and the predominant IgG subclass in both PF and PV
IgG4
hallmark of pemphigus
finding of immunoglobulin G (IgG) autoantibodies against the cell surface of keratinocytes
substrate used to detect pemphigus antibody in PV with higher sensitivity
monkey esophagus
substrate used to detect pemphigus antibody in PF with higher sensitivity
guinea pig esophagus or normal human skin is a superior substrate for detecting PF antibodies.
more sensitive and specific than immunofluorescence, and their** titer correlates better** than that of indirect immunofluorescence with disease activity
ENZYME-LINKED IMMUNOSORBENT ASSAY
specimen for ELISA
patient serum
These assays use desmogleins 1 and 3 bound to plates, which are then incubated with patient sera and developed with anti-human IgG reagents
histopathology of early blisters in PF
acantholysis (loss of cell-to-cell contact) just below the stratum corneum and in the granular layer
characteristic histopathologic finding in PV
suprabasal blister with acantholysis
remains the mainstay of therapy for pemphigus
systemic administration of glucocorticoids, usually prednisone
full systemic dose of glucocorticoids
1.5 mg/kg/d of prednisone equivalent for 2 to 3 weeks
- However, many patients can be brought under control with a 0.5- to 1.0-mg/kg/d single daily dose, especially if used in combination with adjunctive immunosuppressive therapy
- For patients who do not initially respond or worsen, splitting the dose using a twice- or 3-timesdaily schedule may achieve disease control.
Minimal therapy definition for systemic steroids
5 to 10 mg daily of prednisone equivalent
monoclonal anti-CD20 antibody approved by the FDA for therapy of pemphigus vulgaris
rituximab
Rituximab targets B cells, the precursors of antibody-producing plasmablasts. The B cell also acts to process autoantigen and present it to T cells that provide “help” in stimulating the autoantibody response.
In patients with normal TPMT levels, the consensus dosing regimen that defines treatment failure with azathioprine
2.5 mg/kg/d for 12 weeks
