Pemphigus paraneoplasticL10.8

Grant James Anhalt, 1990

Rare, clinically severe, autoimmunologic, obligate paraneoplasia with painful mucosal erosions of the conjunctiva, oral mucosa, esophagus, bronchi, lungs (fibrosing alveolitis), intestine. In the skin, mainly flaccid, mostly hemorrhagic, flaccid blisters as well as areal erosions impose.

Paraneoplastic pemphigus is frequently associated with non-Hodgkin's lymphoma, especially indolent B-cell lymphoma (42%). Association also with T-cell lymphomas, chronic lymphocytic leukemia (29%), Castleman lymphomas (!), malignant thymomas (10%), and sarcomas of various etiologies.

Epithelial malignancies such as adenocarcinomas or squamous cell carcinomas are absent as initiating malignancies.

Pathogenetically, it is assumed that this is due to a misregulated immune reaction in which tumour antigens cross-react with epidermal structural proteins. It is also possible that otherwise hidden epithelial proteins become autoantigens for autoreactive T cells due to a preceding inflammatory reaction.

Often acute onset with painful erosions and ulcers of the oral mucosa. Stomatitis is unusually severe and resistant to treatment (painful extensive erosions and ulcers are visible). In addition, therapy-resistant inflammation of other transitional mucous membranes (rhinitis, pharyngitis, bronchitis, brochiolitis: Remark: in contrast to other types of pemphigus, an acantholytic loss of adhesion of the bronchial epithelium may also occur, balanitis and vulvitis). Painful conjunctivitis may be associated with scarred synechia. Obstructive bronchiolitis can lead to a fatal outcome of the disease. A connection with myasthenia gravis is described.

In contrast to pemphigus vulgaris the skin lesions are multiform, resemble the bullous pemphigoid or an erythema exsudativum multiforme with the partly flabby but also bulging blisters; furthermore lichen-planus-like plaques but also blisters on palms and soles may occur (Note: the infestation of palms and/or soles is unusual for pemphigus vulgaris), also TEN-like epidermolyses are possible.

Detection of antibodies against Envoplakin, Periplakin, alpha2-macroglobulin-like1. In almost all patients Ak against desmoglein3.

IgG and IgA and mostly complement components (_C3,_C4,_C1) in the intercellular space of the epidermis/mucosa. Often also linear IgG and complement deposits in the dermo-epidermal junction zone (as in the bullous pemphigoid!).

Detection of IgA and IgG antibodies against desmocollin 3 (see DSC3 gene below) and IgG antibodies against desmocollin 2 (see DSC2 gene below).

Toxic epidermal necrolysis; Stevens-Johnson syndrome; pemphigus vulgaris, bullous pemphigoid;

48-year-old female metal worker with known follicular B-cell lymphoma for 3 years and cyclophosphamide monotherapy developed acute fever with splenomegaly, abdominal lymphadenopathy and marked shortness of breath. CT thorax and X-ray thorax: without findings. 5 days after admission to the hospital, the patient developed a severe, very painful erosive stomatitis, bilateral conjunctivitis, as well as a little pruritic, lichenoid exanthema on the trunk and extremities. At several sites, EEM-like plaques formed.

Histology (skin): Dense inflammatory infiltrate in the papillary dermis, hydropic basal cell degeneration, focal suprabasal acantholysis. Diagnosis: disease of the pemphigus group.

DIF: IgG and IgA deposits in the area of the keratinocyte surface, linear C3- deposits in the area of the basement membrane zone. Indirect DIF: IgG antibody binding to epithelium of monkey esophagus (titer 1:640), rat urinary bladder (titer 1:640); binding of IgA and IgG to bronchial epithelium of rat lung.

Immunoblot: binding of serum IgG to 210 kDa envoplakin, 190 kDa periplakin and BP 180 NC16a domain.

ELISA: detection of IgA and IgG anti desmocollin 3, IgG anti desmocollin 2.

Course: Skin symptoms and oral mucosal changes improved after high-dose therapy with glucocorticoids (prednisolone 3 mg/kg bw i.v.). 14 days later development of severe aleveolitis; exitus lethalis.

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