9 - 53 - PARANEOPLASTIC PEMPHIGUS Flashcards
Which is/are associated with a poor prognosis in BP?
a. Extensive disease
b. anti-BP180 antibodies
c. Old age
d. all of the above
B. p.952
What is the mainstay of therapy of BP?
a. Topical steroids
b. Oral steroids
c. Methotrexate
d. Rituximab
B
1 Which of the following is false regarding defining features of paraneoplastic pemphigus?
A. Painful stomatitis and a monomorphous cutaneous eruption
B. Histologic fifindings that reflflect cutaneous lesions (acantholysis, lichenoid or interface changes)
C. IgG complement deposition in the epidermal intercellular spaces and/or along basement membrane zone with granular/linear component
D. Serum IgG autoantibodies that bind of cell surface of skin and mucosae, but also to simple, columnar and transitional epithelia
A
In paraneoplastic pemphigus, the most common associated neoplasm in adults is _______ .
A. Castleman disease
B. Chronic lymphocytic leukemia
C. Non Hodgkin lymphoma
D. Thymoma
C
In paraneoplastic pemphigus, the most common associated neoplasm in children is _______ .
A. Castleman disease
B. Chronic lymphocytic leukemia
C. Non Hodgkin lymphoma
D. Thymoma
A
The most constant clinical feature of paraneoplastic pemphigus is the presence of _______ .
A. Cutaneous blisters
B. Intractable stomatitis
C. Dysphagia
D. Dyspareunia
B
The key finding in paraneoplastic pemphigus is the serologic identification of polyclonal IgG autoantibodies against _______ .
A. desmogleins 1 and 3
B. plakin proteins
C. a 2 - macroglobulin-like-1
D. BP180
B
neoplasms most commonly associated with PNP
non-Hodgkin lymphoma, chronic lymphocytic leukemia, or Castleman disease
Other:
- thymoma
- sarcomas
- waldenstrom macroglobulinemia
- myasthenia gravis
In PNP, autoantibodies are directed at what proteins?
desmogleins 1 and 3, desmoplakins, envoplakin and periplakin
Substrate used for IIF in testing PNP
rodent bladder epithelium
what are the defining features of PNP?
most characteristic and consistently recognized plakin antigens in PNP
Envoplakin and Periplakin
the only form of pemphigus that involves non-stratified epithelium
Paraneoplastic Pemphigus
studies performed on 2 different series of PNP patients revealed a significant predominance of what HLA-classes?
HLA-class II DRB∗03 and HLA-class I Cw∗14 genes
Patients with PNP have evidence of markedly elevated levels of what interleukin?
IL-6
IL-6 is known to promote B-cell differentiation and to drive Ig production, and dysregulated IL-6 production has been implicated in certain autoimmune diseases
most constant clinical feature of PNP
Intractable stomatitis
the earliest presenting sign and the one feature that persists throughout the course of the disease
Intractable stomatitis
how do the mucosal lesions of PNP differ from that of PV?
PNP mucosal lesions show MORE NECROSIS AND LICHENOID CHANGE
area of predlection of mucosal lesions of PNP?
lateral borders of the tongue, and characteristically extend onto and involve the vermilion of the lips
blisters of PNP initially involve what areas?
upper trunk, head and neck, and proximal extremities
how can you differentiate erythema multiforme and epidermal necrolysis vs PNP based of clinical course?
erythema multiforme and TEN are self-limited events that evolve and resolve over several weeks, whereas PNP is a relentlessly progressive and evolves continuously over months
how can you differentiate PNP and PV based on cutaneous involvement of palms, soles and paronychial tissue?
The common presence of both blisters and lichenoid lesions affecting the palms and the soles as well as the paronychial tissues helps distinguish PNP from pemphigus vulgaris, in which acral and paronychial lesions are uncommon.
severe pulmonary complication of PNP?
bronchiolitis obliterans
What does it mean when IgG autoantibodies by indirect immunofluorescence are reactive with rodent urinary bladder epithelium?
A positive result implies the presence of plakin autoantibodies; however, the sensitivity and specificity of this serologic test are only approximately 75% and 83%, respectively
most sensitive and specific test for demonstration of antiplakin antibodies in PNP
Immunoprecipitation using radiolabeled, nondenatured epidermal extracts and serum from a patient with PNP and PV
Target Antigens in Paraneoplastic Pemphigus
Typical Histologic Findings of PNP
In noninflammatory cutaneous blisters, what histopath finding is expected to be more prominent?
suprabasilar acantholysis
When erythematous macules and papules are sampled, what histopath finding is predominant?
interface and lichenoid dermatitis
DIF finding of PNP
deposition of immunoglobulin G and complement components on both the surface of basilar and suprabasilar keratinocytes and along the epidermal basement membrane zone
or
Immunoglobulin G and C3 on cell surfaces and along the basement membrane (false negatives common)
common terminal event
Respiratory failure
The development of shortness of breath with obstructive disease progressing to bronchiolitis obliterans is a terminal complication in most cases. Because these patients have autoantibodies that react with desmoplakins, and because desmoplakins are present in respiratory epithelium, respiratory failure may be a result of autoantibody-mediated injury to bronchial epithelium, with plugging of terminal bronchioles, resulting in airflow obstruction and ventilation–perfusion abnormalities.
Additionally, direct damage to alveolar epithelium could cause a diffusion barrier and subsequent intractable hypoxia.
T/F. Treatment of the primary malignancy does not affect the activity of the autoimmune disease.
True
First-line treatment options for PNP
