Case Presentation:
A 58-year-old male with previously treated non-Hodgkin lymphoma and multiple myeloma was admitted with 3 weeks of progressively worsening mucocutaneous blisters. The initial pruritic blister was located on the right arm and progressively spread to include his extremities, chest, back, and groin (covering 60% TBSA), with mucosal involvement, and an inability to tolerate oral intake. Dermatologic exam was notable for involvement of the lip, past the vermillion border, as well as diffuse annular erythematous erosions, desquamative plaques, and isolated intact vesicles and bullae. At admission he was febrile and tachycardic. He was admitted to the ICU, hydrated, and started on antibiotics.
On skin biopsy, direct immunofluorescence demonstrated IgG and C3 antibodies in the squamous intercellular zone, with C3 deposited along the basement membrane, consistent with paraneoplastic pemphigus (PNP). Serum ELISA testing for desmoglein-1 and desmoglein-3 antibodies was greatly elevated, implying severe pemphigus in general, but not specifically PNP. Flow cytometry, lymph node, and bone marrow biopsies confirmed recurrence of grade IIIA follicular lymphoma.
During a long, complicated hospitalization, skin lesions progressed to 90% TBSA. Recurrent cancer was not treated due to poor prognosis and instability. Ultimately, the patient was transferred to hospice.
Discussion:
Paraneoplastic pemphigus can be the presenting sign of malignancy, especially for lymphoproliferative disorders. The presentation is nonspecific and variable and cannot be differentiated from other types of pemphigus by exam alone. Review of the patient’s outpatient oncology visits showed regular surveillance for malignancy recurrence with normal bone marrow biopsies, PET imaging, flow cytometry, and protein electrophoresis. A vigilant physical exam is also an essential component of surveillance for physicians caring for patients in cancer remission.
This case illustrated the conflict between supportive care and pursuit of a diagnosis. For PNP, treatment recommendations include suppressing the autoimmune response to limit mucocutaneous spread and in some cases identifying and treating the underlying cancer. For this patient, systemic immunosuppression was delayed in this patient until hospital day 10. This delay occurred due the extended process of DIF confirmatory testing, an initial suspicion for sepsis, and a concern that systemic steroids would lead to inaccurate diagnostic testing for evaluating cancer recurrence. Skin involvement ultimately worsened, which may have been inevitable as cases of PNP have high morbidity and mortality rates. However, temporizing mucocutaneous disease with early, empiric steroids could have been a priority over these other concerns. The instability inherent to the worsening blistering ultimately precluded potential cancer treatment from being practically feasible. Furthermore, his widespread cutaneous condition necessitated enormous nursing resources for wound treatment, forcing ICU level of care even once otherwise medically stable. Ultimately, this case demonstrated the importance of prioritizing practical, supportive measures rather than definitive diagnosis in patients with rare diseases and poor prognosis.
Conclusions:
Lymphoproliferative disorders may present as paraneoplastic pemphigous. Systemic immunosuppression is critical to prevent progression of this skin condition and may need to be initiated prior to confirming diagnosis.