Paraneoplastic pemphigus associated with Castleman disease: A multicenter case series

Abstract

Introduction: Paraneoplastic pemphigus (PNP) is a rare, often fatal, autoimmune blistering disease of the skin and mucous membranes. In children, PNP is frequently associated with Castleman disease (CD). This series describes five cases of PNP associated with CD.Methods: Data were collected retrospectively from the medical records of patients with a diagnosis of PNP and CD from January 2013 to June 2022. Patients ≤22 years old with clinical and immunopathologic evidence of PNP were included; CD was diagnosed histopathologically.Results: Two children, two adolescents, and one young adult (two males, three females) were included. The average age at disease presentation was 11.8 years (range: 7-22 years). Oral (n = 5) and anogenital (n = 3) mucositis were common. Four patients had "unicentric" CD (UCD); one patient had "multicentric" CD (MCD). Castleman tumors were in the retroperitoneum (n = 4) or axilla (n = 1). One patient had myasthenia gravis without thymoma. Three patients had bronchiolitis obliterans (BO).Three patients had complete resection of their CD; two had partial resection. Three patients remain alive with a median follow-up of 13 months (range: 12 months to 13 years); two are clinically stable with resolution of mucocutaneous lesions; one has persistent BO requiring ongoing ventilatory support. Patients who remain alive had UCD with complete resection; all deceased patients had partial resection and BO. Conclusion:Most patients had UCD, and the retroperitoneum was the most common location. Patients with MCD, incomplete resection, and BO died; patients with UCD and complete resection remain alive, even in the setting of BO. Consideration of PNP is critical when pediatric patients present with mucositis as PNP may be clinically indistinguishable from more common causes of mucositis.

Paraneoplastic pemphigus associated with Castleman's disease

“…PNP is an uncommon condition in paediatric patients, with few case reports and small case series described in literature, representing a diagnostic challenge. Due to the oral blistering and polymorphic skin eruption, differential diagnoses include herpes simplex virus infection, Mycoplasma pneumonia ‐induced rash and mucositis, reactive infectious mucocutaneous eruption, erythema multiforme major, Stevens‐Johnson syndrome/toxic epidermal necrolysis, lichen planus or other autoimmune blistering diseases 6 . In fact, our patient had initially been diagnosed with a SARS‐CoV‐2‐induced mucositis at another clinic, which may have represented the initial stage of PNP.…”

“…Most reported cases in children are associated with Castleman's disease. 2,3,[6][7][8] Other less frequently reported neoplasms in this age group include T-cell lymphoblastic lymphoma, 9 follicular dendritic cell sarcoma 10 and myofibroblastic tumour. 11 Castleman's disease is a rare, non-clonal neoplasm of lymphatic origin, most commonly developing in the retroperitoneal space, namely the renal fossa or the base of the bladder, and the chest.…”

“…14 Whether prognosis differs between unicentric and multicentric disease is uncertain. 6 The eradication of the underlying tumour may have some benefit in the mucocutaneous lesions; nonetheless, even after complete resection, the autoimmune process may remain active for many years. 16 Moreover, there are reports where the pulmonary involvement not only persisted but progressed after tumour resection.…”

“…13,14 Systemic therapy with thalidomide, lenalidomide, bortezomib, cytotoxic chemotherapy, rituximab or siltuximab (anti-interleukin-6 monoclonal antibody) may be considered for treatment of residual disease. 6,14 Post-operative adjunctive immunosuppression is, therefore, necessary for long periods of time and diverse agents have been used, despite their low efficacy. 3 These include oral corticosteroids, cyclosporin, cyclophosphamide, azathioprine, mycophenolate mofetil, rituximab, IVIg, plasmapheresis and immunopheresis.…”

“…Most reported cases in children are associated with Castleman's disease 2,3,6–8 . Other less frequently reported neoplasms in this age group include T‐cell lymphoblastic lymphoma, 9 follicular dendritic cell sarcoma 10 and myofibroblastic tumour 11 …”