52 - Pemphigus Flashcards
4 types of pemphigus
Vulgaris
Foliaceus
Paraneoplastic
IgA pemphigus
Localized forms of pemphigus vulgaris
Pemphigus vegetans of Hallopeau > Pemphigus vegetans of Newman (more extensive)
Localized form of pemphigus foliaceus
Pemphigus erythematosus
More common in Jews and probably in people of Mediterranean descent and from the Middle East
Pemphigus vulgaris
Endemic foci of pemphigus foliaceus in Brazil, Colombia, and Tunisia
Fogo selvagem
Fogo selvagem vs pemphigus foliaceus
Fogo selvagem - children and young adults; anyone in an endemic area may be susceptible
Sporadic PF - middle- aged and older patients; in genetically related family members
Positive Nikolsky sign differentials
Pemphigus vulgaris
SSSS
SJS-TEN
Pemphigus vegetans sites of predilection
Intertriginous areas
Scalp
Face
Pemphigus vegetans prognosis
Milder disease and higher chance of remission
Mucous membranes most often affected by PV
Orophryngeal cavity
Nasal mucosa
In the majority of patients, _____ are the presenting sign of PV
Painful mucous membrane erosions
Features of a pemphigus-lupus erythematosus overlap
Senear-Usher syndrome
Drug-induced pemphigus caused by
Penicillamine
Captopril
Thiol-containing foods such as _____ may precipitate PV
Garlic
Leek
Onion
Diseases associated with PV and PF
Myasthenia gravis
Thymoma
Pemphigus autoantigens
Desmogleins
PF antigen
Desmoglein 1
PV antigen
Desmoglein 3
Antibodies in mucosal-dominant PV
Anti-desmoglein 3 antibodies
Neonatal pemphigus resolves by approximately
6 months - concurrent with the disappearance of maternal IgG from the circulation
Constant region of the antibody is required for blister formation in _____. In _____, the variable region of the antibody is sufficient
Pemphigoid and EBA
Pemphigus
Pathogenic ang predominant IgG subclass in PV and PF
IgG4
Pathogenic PV and PF autoantibodies bind calcium-sensitive conformational epitopes in the _____, whereas nonpathogenic antibodies tend to bind more _____
Amino terminal extracellular domains of desmogleins
Membrane proximal extracellular domains
Hypothesis which proposes that pathogenic antibodies directly interfere with desmoglein adhesive interactions, causing acantholysis
Steric hindrance
Autoantibodies against one desmoglein isoform inactivate only that isoform and that another isoform co-expressed in the same area can compensate in adhesion
Desmoglein compensation
The depletion of desmogleins by pemphigus antibodies may lead to loss of desmogleins resulting in smaller desmosomes and/or their defective function in adhesion, a scenario referred to as
Dsg nonassembly depletion hypothesis
Among Ashkenazi Jews with PV, the serologically defined HLA-_____ is predominant, whereas in other ethnic groups with PV, the _____ allele is more common
DR4
DQ1
DIF sample
Perilesional skin
IIF sample
Serum
ELISA sample
Serum
Hallmark of pemphigus is the finding of _____ autoantibodies against the cell surface of keratinocytes
IgG
DIF finding in pemphigus erythematosus
IgG and C3 in the basement membrane zone in addition to the epidermal cell surface IgG
Can remain positive for weeks to months after healing of the skin lesions, making it a good diagnostic test if a patient should present with no active lesions
IIF
Substrate that is more sensitive for detecting PV antibodies
Monkey esophagus
Superior substrate for detecting PF antibodies
Guinea pig esophagus or normal skin
Test that can differentiate PV and PF
ELISA
Often the cause of death in PV and PF
Infection
Initiation of treatment for PV vs PF
PV - should be treated at its onset, because it will ultimately generalize and the prognosis without therapy is very poor
PF - may be localized for years; do not necessarily require treat with systemic therapy - use of topical corticosteroids may suffice
Mainstay of therapy for pemphigus
Systemic administration of glucocorticoids
Full systemic dose of glucocorticoids for pemphigus
1.5 mg/kg/d of prednisone equivalent for 2-3 weeks
Monoclonal anti-CD20 antibody approved by the FDA for therapy of pemphigus
Rituximab
Immunosuppressive drugs that may offer protection against Pneumocystis carinii infection
MMF
Dapsone
Side effects of IVIg
Stroke
Deep venous thrombosis
Aseptic meningitis
Treatment for pemphigus that does not increase the risk of infection
IVIg
Side effects of cyclophosphamide
Hematuria
Infection
Transitional cell carcinoma of the bladder
Infertility