Paraneoplastic pemphigus regression after thymoma resection
© Barbetakis et al; licensee BioMed Central Ltd. 2008
Received: 03 May 2008
Accepted: 12 August 2008
Published: 12 August 2008
Among human neoplasms thymomas are associated with highest frequency with paraneoplastic autoimmune diseases.
A case of a 42-year-old woman with paraneoplastic pemphigus as the first manifestation of thymoma is reported. Transsternal complete thymoma resection achieved pemphigus regression. The clinical correlations between pemphigus and thymoma are presented.
Our case report provides further evidence for the important role of autoantibodies in the pathogenesis of paraneoplastic skin diseases in thymoma patients. It also documents the improvement of the associated pemphigus after radical treatment of the thymoma.
Paraneoplastic pemphigus is rarely associated with thymic neoplasms either alone or concomitantly with other autoimmune disorders. A case of a 42-year-old woman with paraneoplastic pemphigus as the first manifestation of thymoma is reported. Transsternal complete thymoma resection achieved pemphigus regression. The pathogenetic and clinical relationships between pemphigus and thymoma encountered in this case are presented with the purpose of strengthening the hypothesis that pemphigus in the presence of a thymoma could be a thymoma-associated autoimmune disease.
The postoperative period was uneventful. The patient was discharged home after 10 days Postoperatively anti-DSG-1 and anti-DSG-3 showed a transient increase. At the outpatient visit four weeks later both desmoglein antibodies showed a significant decrease associated with almost complete resolution of the cutaneous lesions. Twelve months later she is still disease free and with no need of steroids.
Serial analysis of various case reports correlate pemphigus with thymoma and/or myasthenia gravis although in our case there were no symptoms or signs of myasthenia gravis [4, 5]. The clinical course and titrations of antiepithelial, antimuscle, and antithymus antibodies suggested a reverse relationship between the severity of myasthenia gravis and titers of antimuscle and antithymus antibodies, and a parallel relationship between pemphigus vulgaris and antiepithelial antibody.
The association of paraneoplastic pemphigus with malignancy is strong. Only a handful of patients have had no associated diagnosis. Some patients have had benign neoplasms, including as in our case thymoma or Castleman's disease. Only a single patient without a tumor has met the diagnostic criteria, yet this patient had a rapid demise and may have died with an undiagnosed malignancy . Patients have developed paraneoplastic pemphigus while in remission of their malignancy, leading some authors to prefer the term neoplasia-induced pemphigus.
Treatment of the underlying malignancy does not necessarily halt progression of the paraneoplastic pemphigus, although some have observed that clinical manifestations improve as autoantibody titers decrease following resection of the tumor. This was also proved in our case, where anti-DSG-3 showed a significant decrease associated with almost complete resolution of the cutaneous lesions. Circulating and tissue-bound antibodies in patients with this disease are directed against a group of molecules with sequence homology and belonging to the plakin family. These molecules are found in the intracellular attachment plaques of desmosomes and hemidesmosomes, and they play a key role in intermediate filament attachment. However, the number of reported target antigens has increased over time and varies between patients. This variability likely accounts for the clinical heterogeneity of this disease. By immunoprecipitation, target antigens (in decreasing order of incidence) include desmoglein 3, desmoglein 1, envoplakin (210 kd), periplakin (190 kd), desmoplakin I (250 kd), desmoplakin II (210 kd) and bullous pemphigoid antigen I (230 kd). Plectin (> 400 kd) and an unidentified 170-kd protein have also been found .
In our case the levels of pemphigus-associated antibodies had increased postoperatively after thymectomy. In parallel, decreased titer of those antibodies preceded the resolution of cutaneous lesions. A similar beneficial effect of tumor ablation has recently also been reported in the case of Castleman's tumor, a rare lymphoproliferative disease that is sometimes associated with paraneoplastic pemphigus .
our case report provides further evidence for the important role of autoantibodies in the pathogenesis of paraneoplastic skin diseases in thymoma patients. It also documents the improvement of the associated pemphigus after radical treatment of the thymoma. Further studies are necessary to analyze possible pathogenetic mechanisms.
Conflict of interests
The authors declare that they have no competing interests.
Written informed consent was obtained from the patient for publication of this case report
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