Paraneoplastic Pemphigus

Clinical Background

Paraneoplastic pemphigus (paraneoplastic autoimmune multi-organ syndrome) is a severely debilitating blistering disease affecting skin and mucous membranes in patients with malignancy, particularly hematologic malignancies.

Epidemiology

Incidence – very rare
Age – mean onset is ≥60 years
Sex – M<F

Risk Factors

Malignancies
- Most common – lymphoma, leukemia, Castleman syndrome
- Less common – thymoma, sarcomas, Waldenström macroglobulinemia
- Other malignancies – pancreatic adenocarcinoma, hepatocellular carcinoma, colon, breast, prostate

Pathophysiology

IgG antibodies to epithelial cell surface molecules with suprabasilar acantholysis and basal cell vacuolation; IgG antibodies to basement membrane zone may also be present
May have interface inflammatory changes, as in lichen planus
May have features of pemphigus vulgaris and erythema multiforme
Disease process may involve multiple organs

Clinical Presentation

Skin lesions – polymorphous skin eruption
- Flaccid bullae
- Lichenoid lesions
- Erythematous maculopapular lesions with dusky centers mimicking erythema multiforme
- Erythroderma
Oral mucosal – characteristically involves vermilion border of lips (may be first symptom)
Other organ systems involved
- Gastrointestinal – esophagus (mainly)
- Respiratory – bronchiolitis obliterans
- Renal – nephrotic syndrome, glomerular nephritis

Treatment

Treat malignancy
Supportive care
Potential therapies include glucocorticoids, other immunosuppressives, plasmapheresis

Indications for Laboratory Testing

Tests generally appear in the order most useful for common clinical situations
Click on number for test-specific information in the ARUP Laboratory Test Directory

Test Name and Number	Recommended Use	Limitations	Follow Up
Paraneoplastic Pemphigus Antibody Screen 0092107 Method: Indirect Immunofluorescence	Indirect immunofluorescence testing of serum for paraneoplastic pemphigus IgG antibodies in patient suspected of having a blistering disease associated with malignancy Uses substrates from rodents, including mouse heart, liver, bladder and rat bladder to detect characteristic staining Consider concurrent pemphigus panel test to detect and monitor pemphigus antibodies, if present (including IgG desmoglein-1 and desmoglein-3 antibodies)	Clinical correlation is necessary because results may overlap with other types of pemphigus and with pemphigoid Rarely, patients may also have IgA paraneoplastic pemphigus antibodies; IgA paraneoplastic pemphigus testing can be performed by request	Monitor paraneoplastic pemphigus antibodies and/or pemphigus panel, particularly if IgG desmoglein-1 and/or -3 antibodies are increased
Cutaneous Direct Immunofluorescence, Biopsy 0092572 Method: Direct Immunofluorescence	Determine presence and staining pattern of immunoglobulins (IgG, IgM, IgA), third component of complement (C3) and fibrinogen in perilesional skin or mucosal biopsy specimens from patients suspected of having paraneoplastic pemphigus or other immunobullous disease	May be inaccurate if tissue not taken from correct location; type and age of lesion may also be important (perilesional is optimal with intact epithelium/epidermis) Tissue must be submitted in Michel’s or Zeus medium; this test cannot be performed on formalin-fixed tissue

Test Name and Number

Recommended Use

Limitations

Follow Up

Paraneoplastic Pemphigus Antibody Screen 0092107

Method: Indirect Immunofluorescence

Indirect immunofluorescence testing of serum for paraneoplastic pemphigus IgG antibodies in patient suspected of having a blistering disease associated with malignancy

Uses substrates from rodents, including mouse heart, liver, bladder and rat bladder to detect characteristic staining

Consider concurrent pemphigus panel test to detect and monitor pemphigus antibodies, if present (including IgG desmoglein-1 and desmoglein-3 antibodies)

Clinical correlation is necessary because results may overlap with other types of pemphigus and with pemphigoid

Rarely, patients may also have IgA paraneoplastic pemphigus antibodies; IgA paraneoplastic pemphigus testing can be performed by request

Monitor paraneoplastic pemphigus antibodies and/or pemphigus panel, particularly if IgG desmoglein-1 and/or -3 antibodies are increased

Cutaneous Direct Immunofluorescence, Biopsy 0092572

Method: Direct Immunofluorescence

Determine presence and staining pattern of immunoglobulins (IgG, IgM, IgA), third component of complement (C3) and fibrinogen in perilesional skin or mucosal biopsy specimens from patients suspected of having paraneoplastic pemphigus or other immunobullous disease

May be inaccurate if tissue not taken from correct location; type and age of lesion may also be important (perilesional is optimal with intact epithelium/epidermis)

Tissue must be submitted in Michel’s or Zeus medium; this test cannot be performed on formalin-fixed tissue

Additional Tests Available

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Pemphigus Panel - IgG Epithelial Cell Surface Antibodies and Levels of IgG Desmoglein 1 and Desmoglein 3 Antibodies, Serum 0090650 Method: Enzyme-Linked Immunosorbent Assay/Indirect Immunofluorescence	IgG cell surface antibody staining is found in all cases; IgG desmoglein-1 and/or IgG desmoglein-3 antibody levels may be increased