Paraneoplastic pemphigus associated with Castleman tumor, myasthenia gravis and bronchiolitis obliterans.
BACKGROUND
Cases of paraneoplastic pemphigus (PNP) have been reported associated with various lymphoproliferative malignancies and benign Castleman tumors, with the most severe course and fatal outcome seen in patients with bronchiolitis obliterans.


OBJECTIVE
The aim was to establish immunologic associations by coexistence of Castleman tumor, myasthenia gravis, and bronchiolitis obliterans and to evaluate the treatment modalities.


METHODS
Clinical studies included computed tomography of the mediastinum, computed tomography and magnetic resonance imaging of the abdominal cavity, and quantitative electromyography. Direct and indirect immunofluorescence on various substrates, immunoblot analysis, immunoprecipitation, and specific enzyme-linked immunosorbent assay using recombinant desmogleins (Dsg) were performed as immunologic assays.


RESULTS
Direct and indirect immunofluorescence including rat bladder showed intercellular antibodies. Immunoblotting disclosed antibodies to envoplakin (210 kd protein) and periplakin (190 kd protein); in addition, immunoprecipitation detected antibodies to desmoplakin I (250 kd protein). Antibodies to Dsg3 (pemphigus vulgaris antigen) were detected by specific enzyme-linked immunosorbent assay. Myasthenia gravis was controlled by drugs; however, mucocutaneous changes were not fully responsive to corticosteroids and cyclophosphamide pulses, cyclosporine, and intravenous immunoglobulins. The surgical removal of Castleman tumor did not change the course of the disease. The fatal outcome was the result of bronchiolitis obliterans that occurred after the surgery and was only transitionally controlled by plasmapheresis.


CONCLUSIONS
This is the first case of paraneoplastic pemphigus associated with Castleman tumor, myasthenia gravis, and bronchiolitis obliterans. Despite a benign character of the tumor the patient died, as do all patients with bronchiolitis obliterans. Massive plasmapheresis has only a transient effect. We confirmed the presence of antibodies to Dsg 3, in addition to the set of specific paraneoplastic pemphigus antibodies against various proteins of plakin family.
Chorzelski
T
T
Department of Dermatology, Warsaw School of Medicine, Poland.
Hashimoto
T
T
Maciejewska
B
B
Amagai
M
M
Anhalt
G J
GJ
Jablonska
S
S
D000328:Adult; D000906:Antibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D001989:Bronchiolitis Obliterans / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D005871:Castleman Disease / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D003598:Cytoskeletal Proteins / Q000276:immunology; D051182:Desmogleins; D051180:Desmoplakins; D003896:Desmosomes / Q000276:immunology; D003937:Diagnosis, Differential; D018450:Disease Progression; D017809:Fatal Outcome; D006801:Humans; D008297:Male; D009157:Myasthenia Gravis / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D010257:Paraneoplastic Syndromes / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D010392:Pemphigus / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D013262:Stevens-Johnson Syndrome / Q000175:diagnosis
D000906:Antibodies; D003598:Cytoskeletal Proteins; C495294:DSP protein, human; D051182:Desmogleins; D051180:Desmoplakins