Pemphigus paraneoplastic L10.8

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 16.01.2024

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Synonym(s)

paraneoplastic pemphigus

History
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Grant James Anhalt, 1990

Definition
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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.

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Etiopathogenesis
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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.

Clinical features
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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.

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

Histology
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Focal subprabasal acantholysis with dense subepithelial infiltrate of lymphocytes, monocytes and few neutrophil leukocytes.

Direct Immunofluorescence
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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!).

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

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

Therapy
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Tumor search and cleanup. Since the skin symptoms often only appear in an advanced stage, the symptomatic palliative therapy is in the foreground. External therapy see below Pemphigus vulgaris.

Case report(s)
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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.

Literature
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  1. Alarcon-Torres I (2007) Paraneoplastic pemphigus associated with Castleman's disease: usefulness of the laboratory of autoimmunity in the diagnosis of this disease. Ann NY Acad Sci 1107: 231-238.
  2. Anhalt GJ et al (1990) Paraneoplastic pemphigus. An autoimmune mucocutaneous disease associated with neoplasia. N Engl J Med 323: 1729-1735.
  3. Didona D et al (2020) Paraneoplastic dermatoses: A Brief General Review and an Extensive Analysis of Paraneoplastic Pemphigus and Paraneoplastic Dermatomyositis. Int J Mol Sci 21:2178.
  4. Ghandi N et al. (2014) Paraneoplastic pemphigus associated with inflammatory myofibroblastic tumour of the mediastinum: A favourable response to treatment and review of the literature. Australas J Dermatol doi:10.1111/ajd.12264
  5. Hoque SR, Black MM, Cliff S (2007) Paraneoplastic pemphigus associated with CD20-positive follicular non-Hodgkin's lymphoma treated with rituximab: a third case resistant to rituximab therapy. Clin Exp Dermatol 32: 172-175
  6. Kanaoka M et al (2015) Paraneoplastic pemphigus associated with fatal bronchiolitis obliterans and appearance of anti-BP180 antibodies in the late stage of the disease. J Dermatol.
  7. 41:628-630
  8. Kobayashi K et al. (2014) An autopsy case of unicentric Castleman's disease associated with bronchiolitis
  9. obliterans. Respirol Case Rep 2:105-10
  10. Mimouni D et al (2002) Paraneoplastic pemphigus in children and adolescents. Br J Dermatol 147: 725-732.
  11. Nikolskaia OV et al (2003) Paraneoplastic pemphigus in association with Castleman's disease. Br J Dermatol 149: 1143-1151.
  12. Porro AM et al (2014) Non-classical forms of pemphigus: pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus. An Bras Dermatol 89:96-106
  13. Preisz K et al (2004) Exacerbation of paraneoplastic pemphigus by cyclophosphamide treatment: detection of novel autoantigens and bronchial autoantibodies. Br J Dermatol 150: 1018-1024.
  14. Schmidt E et al (2015) S2k guideline on the diagnosis of pemphigus vulgaris/foliaceus and bullous pemphigoid. JDDG 13: 713-726
  15. Wang R et al (2015) Prevalence of myasthenia gravis and associated autoantibodies in paraneoplastic pemphigus and their correlations with symptoms and prognosis. Br J Dermatol 172:968-975
  16. Zhu X, Zhang B (2007) Paraneoplastic pemphigus. J Dermatol 34:503-511.

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Last updated on: 16.01.2024