Radiation-Induced Pemphigus or Pemphigoid Disease in 3 Patients With Distinct Underlying Malignancies

A number of adverse cutaneous effects may result from radiation therapy, including radiodermatitis, alopecia, and radiation-induced neoplasms. Radiation therapy rarely induces pemphigus or pemphigoid disease, but awareness of this disorder is of clinical importance because these cutaneous lesions may resemble other skin diseases, including recurrent underlying cancer. We report 3 cases of pemphigus or pemphigoid disease that occurred after radiation therapy for in situ ductal carcinoma of the breast, cervical squamous cell carcinoma, and metastatic squamous cell carcinoma of unknown origin, respectively.

Case Reports

Figure 1. Radiation-induced pemphigus vulgaris with superficial erosion on irradiated right breast.

To identify all the patients with radiation-induced pemphigus, pemphigoid diseases, or both diagnosed and treated at Mayo Clinic (Rochester, Minnesota) from 1988 to 2009, we performed a computerized search of dermatology, laboratory medicine, and pathology medical records using the following keywords: radiation, pemphigoid, pemphigus vulgaris, pemphigus foliaceus, pemphigus erythematosus, and blistering disease. Inclusion criteria were a history of radiation therapy and subsequent development of pemphigus or pemphigoid disease within the irradiated fields. Patients with a history of immunobullous disease preceding radiation therapy and patients with a diagnosis of paraneoplastic pemphigus or paraneoplastic autoimmune multiorgan syndrome were excluded. The diagnoses were confirmed by routine pathology as well as direct and indirect immunofluorescence examinations.

We identified 3 patients with severe extensive radiation-associated pemphigus/pemphigoid disease that had developed within 14 months after they received radiation therapy for their underlying cancer. The identified patients’ medical records were reviewed for underlying malignancy, symptoms at the time of diagnosis, treatment course, and follow-up. The protocol was reviewed and approved by the Mayo Clinic institutional review board.

Patient 1—A 58-year-old woman was diagnosed with in situ ductal carcinoma of the right breast and underwent a lumpectomy with subsequent radiation therapy at an outside institution. Fourteen months after the final radiation treatment, she developed localized flaccid blisters and a superficial erosion on the right areola (Figure 1). Routine pathologic and direct immunofluorescence studies performed on shave biopsies in conjunction with serum analysis by indirect immunofluorescence confirmed the diagnosis of pemphigus vulgaris (Figure 2). Additionally, a deeper 4-mm punch biopsy ruled out metastatic breast carcinoma. The patient initially was treated with prednisone 60 mg and azathioprine 50 mg daily. The prednisone was tapered over 4 to 5 months to a dose of 5 mg every other day for another 4 to 5 months. Azathioprine was discontinued after a few months because of increased liver enzyme levels and a rapid clinical response of the pemphigus to this regimen.

Subsequently, she developed oral and ocular erosions that were compatible with pemphigus and were believed to be precipitated by trauma secondary to dental work and to the use of contact lenses. These flares were treated and stabilized with short courses of prednisone at higher doses that were successfully tapered to a maintenance dose of 5 mg every other day to control the pemphigus. With that prednisone dosage, her disease has remained clinically stable.

Patient 2—A 40-year-old woman was diagnosed with stage IIIB cervical squamous carcinoma with para-aortic adenopathy. She was initially treated with primary radiation therapy directed at the pelvis and para-aortic regions using a 4-field approach at our institution, and she received weekly cisplatin chemotherapy at another institution. Nine months later, the patient was admitted to our institution with persistent metastatic cervical carcinoma of the retroperitoneum. She was scheduled for intraoperative radiation therapy as well as aggressive surgical cytoreduction. The day before her surgery she presented to our dermatology clinic with a generalized pruritic rash of 1 month’s duration and occasional blistering without mucosal involvement. Biopsy specimens from the lower back and abdomen were sent for routine histologic studies and direct immunofluorescence. Serum was sent for analysis by indirect immunofluorescence. Pathology results were consistent with a diagnosis of bullous pemphigoid with an infiltrate of eosinophils in the papillary dermis; direct immunofluorescence revealed continuous strong linear deposition of C3, which also was consistent with pemphigoid.

At that time, we recommended application of topical clobetasol 0.05% twice daily to affected areas before initiating prednisone. Postoperatively, her rash improved dramatically with clobetasol monotherapy. However, 4 months after discharge from our hospital, her local dermatologist called us for a telephone consultation regarding clinical and laboratory evidence of pemphigoid relapse. A direct immunofluorescence study showed both linear IgG and C3 deposition. The patient had healed well from the surgery, and the metastatic cervical carcinoma was quiescent. Prednisone in combination with a second immunosuppressive agent was recommended, pending approval by her local oncologist. No further follow-up information is available at this time.