INTRODUCTION:Paraneoplastic pemphigus, recently renamed paraneoplastic autoimmune multiorgan syndrome (PAMS) was first described in 1990 and involves multiple organs, including lung, kidney and muscles. We report a fatal case of constrictive bronchiolitis associated with PAMS in a previously healthy 33 yo patient.
CASE PRESENTATION:A previously healthy 33-year-old Caucasian woman, never smoker, was hospitalized for evaluation of progressive oral and genital ulcerations. Three years prior to presentation, she had been evaluated for recurrent episodes of genital lesions diagnosed as lichen planus and treated with repeated courses of corticosteroids. Seven months prior to presentation, she had developed an extensive erosive gingivostomatitis poorly responsive to treatment. Biopsy results suggested lichen planus or pemphigus vulgaris. She also reported a progressively worsening shortness of breath, but denied any fever or chills. She had lost 100 pounds due to poor oral intake. Her vital signs were stable and she was afebrile. She appeared dyspneic at rest but had normal oxygen saturation on room air. There was no external skin lesion but the examination of the mouth revealed diffuse mucosal ulcerations extending to the oropharynx. The lung examination was significant for diffuse wheezes. The remainder of the physical examination was normal. A biopsy of the oral mucosa with direct immunofluorescence revealed findings characteristic of pemphigus. Indirect immunofluorescence revealed the presence of circulating antibodies to bladder epithelium suggesting paraneoplastic pemphigus. A CT scan of the chest revealed minimal hazy parenchymal infiltrates [Figure 1], contrasting with severe obstructive findings on pulmonary function testing [Figure 2]. A 6-cm pre-sacral mass was identified on an abdominal CT scan. Surgical resection revealed Castleman disease (angiofollicular lymph node hyperplasia) [Figures 3 and 4]. Her obstructive lung disease continued to worsen and she eventually expired 2 years after her presentation.
DISCUSSIONS:Paraneoplastic autoimmune multiorgan syndrome is associated with several neoplastic diseases including Castleman disease, chronic lymphocytic leukemia, lymphoma and thymoma. The reported mortality rate is approximately 90%. Constrictive (or obliterative) bronchiolitis has been reported in 30% of the cases. In approximately 30% of patients the underlying neoplasm is not apparent at initial presentation .The diagnosis is established on the basis of findings on direct and indirect immunofluorescence microscopy. Indirect immunofluorescence staining of rat bladder epithelium is both sensitive and specific. The diagnosis is often difficult due to varied clinical and pathological presentations. The intracellular antigens, envo- and periplakin, are expressed by respiratory cells and are targeted by autoantibodies expressed in PAMS. They are thought to play a significant role in the development of constrictive bronchiolitis . Treatment options remain limited and aim at decreasing the amount of circulating antibodies. Plasmapheresis, rituximab, intravenous immunoglobulins have been used with inconsistent results. Constrictive bronchiolitis associated with PAMS is usually progressive and fatal.
CONCLUSION:Constrictive bronchiolitis associated with PAMS is a relentlessly progressive and is usually fatal. Recent insights in the humoral and cellular mechanisms of PAMS may shed some light on the pathogenesis of constrictive bronchiolitis and, hopefully, lead to new therapies.
DISCLOSURE:Fabien Maldonado, No Financial Disclosure Information; No Product/Research Disclosure Information