Paraneoplastic Autoimmune Multiorgan Syndrome

Abstract

Background: Paraneoplastic autoimmune multiorgan syndrome (PAMS), first described as paraneoplastic pemphigus (PNP) is a heterogeneous autoimmune syndrome with a diverse spectrum of clinical and immunopathological features associated with an internal neoplasm. Materials and Methods: The details of the patients diagnosed with PAMS/PNP from an Indian tertiary center between January 2010 to December 2019 were retrieved from the hospital database. The clinical manifestations, histopathological features, immunofluorescence findings, and other relevant clinical details were obtained. Results: There were eight patients (4 males, 4 females) with PAMS, age ranging from 8 to 46 years (mean 31 years), of whom two were 8-year-old children. The mucocutaneous manifestations were polymorphic and all had recalcitrant oral mucosal involvement. The most common mucosal presentation was pemphigus-like (5/8), and the cutaneous presentation was lichen planus-like (5/8). Castleman's disease (5/8) was the commonest neoplasm followed by thymoma (2/8). Interface dermatitis was seen in all biopsies and three different patterns of direct immunofluorescence were seen, which were intercellular “fish-net” fluorescence in the epidermis (2/8), granular/linear deposition along the basement membrane (4/8) and a combination of both patterns (1/8). Indirect immunofluorescence done on rat bladder in 3 patients showed intercellular “fish-net” fluorescence. Desmoglein levels were not elevated in any of our patients. The follow-up period ranged from 1 to 112.5 months (mean, 23.6 months) with a mortality rate of 12.5%. Conclusion: In our study, Castleman's disease was the most common associated malignancy, and the mucocutaneous and histopathological findings were heterogeneous. Timely diagnosis and early intervention improved the outcome in our patients.

Refractory oral ulcers

“…Another feature that may support the diagnosis of PNP is the presence of dsDNA antibodies. These antibodies were reported in 2 out of 8 patients with PNP, one with an underlying Castleman disease and the other with thymoma 7 . High levels of interleukin‐6 expression have been associated with Castleman disease 8 .…”

“…10 However, improvement or complete remission may still take 1 to 2 years to achieve. 7,10 ACK N OWLED G M ENT All contributors have been acknowledged.…”

“…Early excision of the tumor may halt further production of the autoantibodies, therefore, prompting early remission of the ulcers 10 . However, improvement or complete remission may still take 1 to 2 years to achieve 7,10 …”

“…These antibodies were reported in 2 out of 8 patients with PNP, one with an underlying Castleman disease and the other with thymoma. 7 High levels of interleukin-6 expression have been associated with Castleman disease. 8 As interleukin-6 can also increase dsDNA antibodies, 9 it may serve as a marker of disease activity in Castleman disease-related PNP.…”

Paraneoplastic pemphigus and Castleman’s disease: a case report and a revision of the literature

“…In our review, all patients received corticosteroids with poor response. Immunosuppressant, IVIG, rituximab, tocilizumab, daclizumab, plasmapheresis were also used like adjuvant therapies for treating severe mucocutaneous lesions and BO [ 7 – 23 , 31 – 33 ]. Treatment of iMCD is challenging, and outcomes can be poor because no uniform treatment guidelines exist, few systematic studies have been conducted, and no agreed upon response criteria have been described..…”