1

Introduction

Pemphigus vulgaris (PV) and granulomatosis with polyangiitis (GPA) are two rare autoimmune disorders which can potentially be fatal. PV is an autoimmune blistering disorder with primary involvement of mucosal and cutaneous tissues. GPA is a vasculitis with multisystem necrotizing granuloma formation, which can be limited to the upper airways, or can have pulmonary, renal, or other organ involvement. This report describes a patient who initially presented with PV and was also later diagnosed to have findings suggestive of coexisting GPA. This case represents an interesting diagnostic challenge due to certain overlapping symptoms of upper respiratory tract involvement.

2

Case report

A 34 year-old African American woman initially presented with a five-month history of painful oral erosions and hoarseness. She denied any other associated symptoms such as dyspnea or hematuria. A biopsy of the buccal mucosal taken at that time confirmed the diagnosis of pemphigus vulgaris. The patient was treated with prednisone 60 milligrams per day (mg/d) and methotrexate 12.5 mg once weekly. The patient noticed an improvement over one month and tapering of the prednisone dosage was initiated. When the patient reached an alternating prednisone dose of 20 mg and 10 mg every other day, recurrence of the oral mucosal lesions was observed along with new symptoms of epistaxis, dyspnea, and dysphagia. Despite increasing the dose of prednisone, her extra-oral symptoms persisted over the next 2 months. Evaluation by otolaryngology confirmed extensive ulcerations of the nasal and oral cavity along with laryngeal tissues. These findings were attributed to an exacerbation of PV and treatment failure with methotrexate. Hence, methotrexate was discontinued and azathioprine 100 mg/d was begun, in addition to prednisone (20 mg/d). Her symptoms and lesions resolved after four months. A prednisone taper was again attempted and after six months, the patient presented with worsening symptoms similar to those she experienced prior to initiating azathioprine, along with a new symptoms of hemoptysis. The dose of azathioprine was then increased to 150 mg/d and prednisone increased again to 20 mg/d.

A chest X-ray and pulmonary bronchoscopy were normal at this time and the conclusion was made that the patient’s bleeding was most likely caused by aspirated blood from nasal erosions. After a barium swallow performed for dysphagia showed gastroesophageal reflux but no strictures, the patient was given omeprazole and counseled on lifestyle modifications to prevent reflux.

Over the next six months, the patient had very few oral mucosal lesions. However, during this same period, the patient did report rhinorrhea, sore throat, cough, and ear pain on two occasions and was treated with antibiotics. She was also prescribed fexofenadine 180 mg daily and loratadine 10 mg daily for seasonal allergies.

Due to persistent difficulty breathing, the patient was reexamined by otolaryngology. A nasal endoscopy and stroboscopy examination revealed extensive vesicles, crusting, and erosions affecting the larynx diagnosed to be consistent with lesions of pemphigus vulgaris. However this time, septal perforation and rearrangement of soft tissues of the nose was also observed such that the laryngoscope could not pass through the nose. A CT scan of the sinuses subsequently revealed near-complete occlusion of the left nasal cavity with erosion of the anterior bony nasal septum and mucosal thickening in the paranasal sinuses. The patient also complained of arthritis at this time. Due to presumed progression of PV despite continual dosage of prednisone at 15 mg daily and azathioprine 150 mg daily, rituximab was initiated per the lymphoma protocol of 375 mg/m ² .

During the first infusion cycle with rituximab, the patient developed a persistent pyoderma in the umbilical area that was recalcitrant to multiple antibiotic courses. Hence, immunosuppressant therapy was held until the pyoderma resolved. It is during this interruption of therapy that the patient complained of worsening arthritis. Further evaluation including laboratory testing revealed an elevated ANA titer of 1:160 (normal < 1:80), an elevated c-ANCA titer of 1:1280 (normal < 1:20), and an elevated PR3 antibody level of 75 (normal < 30). Based on clinical findings and laboratory values, a diagnosis of GPA was made. The patient was restarted on rituximab and methotrexate was added back to her regimen as an adjuvant agent. The patient received rituximab infusions every six months along for a total of three cycles with continuing methotrexate at 15 mg once weekly with significant improvement in all her symptoms.

Renal function studies have remained stable along with no significant abnormalities on urinalysis. Pulmonary function testing and imaging of the lungs have likewise remained normal.