Paraneoplastic Pemphigus
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Direct answer
Paraneoplastic pemphigus is a rare, life-threatening autoimmune blistering disease that signals an underlying neoplasm, most often a lymphoproliferative disorder. Persistent, severe stomatitis is the dominant early clue, and the skin lesions are polymorphic, with bullae, erosions and lichenoid papules. Autoantibodies against plakin proteins such as desmoplakin and envoplakin drive the disease, bronchiolitis obliterans is a major cause of death, and the outcome depends on controlling the tumour.
What you must remember
- Association: chronic lymphocytic leukaemia and non-Hodgkin lymphoma are the neoplasms most often linked, with Castleman disease also reported.
- Mucosal clue: severe, painful stomatitis with lip crusting often precedes the skin disease.
- Skin morphology: flaccid bullae, erosions and targetoid or lichenoid papules that can mimic erythema multiforme or lichen planus.
- Antigens: desmoplakin, envoplakin, periplakin and BP230 are the principal targets identified by specialist testing.
- Histology: suprabasal acantholysis with interface change, lichenoid inflammation and apoptosis of basal keratinocytes.
- Immunofluorescence: direct IF shows both intercellular and basement membrane zone deposits of IgG and C3 in the same biopsy.
- Lung disease: bronchiolitis obliterans is often fatal and responds poorly to treatment, so lung function needs follow-up.
A stepwise route from mouth ulcers to the tumour search
A middle-aged patient with refractory mouth erosions, polymorphic skin lesions and a recent diagnosis of chronic lymphocytic leukaemia raises the question of paraneoplastic disease. The steps below show how the diagnosis is built and why the tumour search comes early.
- Recognise the mucosal pattern. Persistent, painful stomatitis out of proportion to the skin disease should prompt a search for an underlying neoplasm.
- Take a perilesional biopsy. Histology and direct immunofluorescence show acantholysis with interface change, along with intercellular and basement membrane deposits.
- Search for the neoplasm. Examine lymph nodes, check blood counts and image the chest, abdomen and pelvis, so that a lymphoma is found or excluded.
- Confirm the antibodies. Indirect immunofluorescence on rat bladder epithelium gives a characteristic pattern, and immunoprecipitation identifies the plakin targets.
- Screen the lungs. Baseline lung function and high-resolution CT help detect bronchiolitis obliterans, which can progress regardless of skin control.
- Treat the tumour and suppress immunity. Treat the neoplasm where possible, add corticosteroids and an immunosuppressant such as cyclosporine or rituximab, and expect the outcome to remain guarded.
Where candidates lose marks
Examiners separate this disease from commoner pemphigus variants with a few fixed discriminators.
- Trap: calling oral erosions with bullae pemphigus vulgaris and stopping the work-up Correct: the disease is driven by an underlying neoplasm, so the lymphoma search is part of the diagnosis itself.
- Trap: judging the disease by the skin alone Correct: the mucosal clue, the associated tumour and the bronchiolitis risk define paraneoplastic pemphigus more reliably than skin appearance.
- Trap: assuming the lungs are spared once the skin clears Correct: bronchiolitis obliterans can progress even when the skin responds, so lung function is monitored throughout.
Frequently asked questions
Which neoplasm is most often associated with paraneoplastic pemphigus?
Chronic lymphocytic leukaemia and non-Hodgkin lymphoma are the neoplasms most often linked with paraneoplastic pemphigus, although Castleman disease is also reported. Recognising this association guides the search for an underlying tumour.
Which antigens are targeted in paraneoplastic pemphigus?
Paraneoplastic pemphigus autoantibodies target plakin proteins, including desmoplakin, envoplakin and periplakin, and BP230 has also been identified. Demonstrating these antibodies by specialist testing supports the diagnosis.
How does paraneoplastic pemphigus differ from pemphigus vulgaris on biopsy?
Paraneoplastic pemphigus shows suprabasal acantholysis with interface change and lichenoid inflammation, whereas pemphigus vulgaris shows acantholysis without a prominent interface reaction. This difference helps when the clinical picture is unclear.
Why does bronchiolitis obliterans matter in paraneoplastic pemphigus?
Bronchiolitis obliterans is a serious lung complication of paraneoplastic pemphigus and a major cause of death. It may develop or progress despite control of the skin and mucosal disease, so lung function needs regular monitoring.
Which substrate helps confirm paraneoplastic pemphigus on indirect immunofluorescence?
Rat bladder epithelium is the characteristic substrate, since serum from patients with paraneoplastic pemphigus stains it. Classic pemphigus sera usually lack this reaction, which helps separate the two diseases.