Mechanisms of DiseaseCastleman's tumours and production of autoantibody in paraneoplastic pemphigus
Introduction
Paraneoplastic pemphigus is an autoimmune mucocutaneous disorder, characterised by an associated neoplasm and the presence of a unique IgG autoantibody that recognises epidermal proteins.1, 2, 3, 4, 5 Neoplasms associated with the disease are often of lymphocytic origin and include non-Hodgkin's lymphoma,6, 7 chronic lymphocytic leukaemia,1, 8 and Castleman's disease.9, 10, 11, 12, 13 One of the characteristic features of paraneoplastic pemphigus associated with Castleman's disease and other benign tumours is the remarkable improvement in symptoms noted after removal of the tumour.11, 12, 13, 14 In some individuals accompanied bronchiolitis obliterans occasionally may result in respiratory failure and death.9, 10
The role of the neoplasm in the pathogenesis of paraneoplastic pemphigus is controversial, with detailed data unavailable possibly because of the limited number of affected individuals. Clinically, an IgG autoantibody against epidermal proteins is often used as a diagnostic marker for the disease,15, 16 but might also be involved in autoimmune injuries.1, 5 Our aim was to ascertain the mechanism by which the autoantibody is generated and to investigate the possible role of Castleman's tumours in the process.
Section snippets
Participants
We included in our analyses seven patients with paraneoplastic pemphigus associated with localised hyaline vascular-type Castleman's tumours who were diagnosed and treated at the Department of Dermatology, Peking University First Hospital between May, 1999, and December, 2002.
The patients all had clinically similar lesions of pemphigus vulgaris, pemphigus erythematosus, and lichen planus (figure 1). Histological examination of the cutaneous lesions indicated epidermal acantholysis or
Results
The table shows the characteristics of the seven patients, most of whom responded badly or only partially to routine treatment, including corticosteroids and other immunosuppressive drugs. After resection of Castleman's tumours, however, cutaneous lesions improved gradually and disappeared within 6–11 weeks without recurrence in the six patients with paraneoplastic pemphigus (figure 2), and erosions of the mucosa and ulcers also improved. However, mucosal lesions recovered only slowly, and one
Discussion
Our findings suggest that Castleman's tumours are involved in the production of autoantibodies in patients with paraneoplastic pemphigus, and that this production is important in the pathogenesis of the disease. As previously reported,20, 21 our findings indicate a close relation between the presence of a Castleman's tumour and the mucocutaneous manifestations seen in patients with paraneoplastic pemphigus, which do not respond to routine immunosuppressive treatment but resolve rapidly after
GLOSSARY
- complementarity determining region
- The heavy and light chains of antibodies each contain three regions of hypervariability, termed complementarity determining regions (CDR), which interact with antigen.
References (26)
- et al.
cDNA cloning of the 210-kDa paraneoplastic pemphigus antigen reveals that envoplakin is a component of the antigen complex
J Invest Dermatol
(1997) - et al.
The members of the plakin family of proteins recognized by paraneoplastic pemphigus antibodies include periplakin
J Invest Dermatol
(1998) - et al.
Accuracy of indirect immunofluorescence testing in the diagnosis of paraneoplastic pemphigus
J Am Acad Dermatol
(1995) - et al.
Indirect immunofluorescence on rat bladder transitional epithelium: a test with high specificity for paraneoplastic pemphigus
J Am Acad Dermatol
(1993) - et al.
Use of family specific leader region primers for PCR amplification of the human heavy chain variable region gene repertoire
Molec Immun
(1992) - et al.
The new pemphigus variants
J Am Acad Dermatol
(1999) - et al.
Paraneoplastic pemphigus: an autoimmune mucocutaneous disease associated with neoplasia
N Engl J Med
(1990) - et al.
Human autoantibodies against desmoplakins in paraneoplastic pemphigus
J Clin Invest
(1992) - et al.
Antibodies against desmoglein 3 (pemphigus vulgaris antigen) are present in sera from patients with paraneoplastic pemphigus and cause acantholysis in vivo in neonatal mice
J Clin Invest
(1998) - et al.
Paraneoplastic pemphigus occurring in a patient with B-cell non-Hodgkin's lymphoma
Cutis
(1998)
Paraneoplastic pemphigus in a patient with non-Hodgkin's lymphoma
Am J Hematol
Paraneoplastic pemphigus: a report of two cases associated with chronic B-cell lymphocytic leukaemia
Br J Dermatol
Paraneoplastic pemphigus with fatal pulmonary involvement in a woman with a mesenteric Castleman tumour
Br J Dermatol
Cited by (123)
Paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome: Part I. clinical overview and pathophysiology
2023, Journal of the American Academy of DermatologyEpidemiology of Pemphigus
2021, JID InnovationsCastleman Disease
2019, Surgical Pathology ClinicsCitation Excerpt :Symptoms, when present, are often related to the size of the mass and compression of adjacent structures, such as airway compression with shortness of breath or vascular compression that can lead to esophageal varices.5,11,15 HV-CD is associated with paraneoplastic pemphigus, but in less than 5% patients.16 Rare patients with HV-CD involving the mediastinum also have had myasthenia gravis.17
Paraneoplastic pemphigus: A clinical, laboratorial, and therapeutic overview
2019, Anais Brasileiros de DermatologiaAutoimmune bullous skin diseases: Pemphigus and pemphigoid
2019, The Autoimmune DiseasesParaneoplastic autoimmune multiorgan syndrome (PAMS): Beyond the single phenotype of paraneoplastic pemphigus
2018, Autoimmunity ReviewsCitation Excerpt :Autoimmunity to these plakins in lymphoproliferative states may be attributed to the presence of basement membrane components in lymphoid tissue [46]. Resected tumors have in fact shown the ability to secrete autoantibodies that react with epidermal proteins similar to that seen in PAMS [47, 48]. While most cases of PAMS are related to lymphoproliferative disorders/malignancies, the occurrence of PAMS in solid tumors suggests that other mechanisms are involved in the development of autoantibodies to plakins.