The effect of aspirin desensitization on novel biomarkers in aspirin-exacerbated respiratory diseases.

BACKGROUND: Patients with aspirin-exacerbated respiratory disease have been shown to benefit clinically from aspirin desensitization followed by chronic high-dose aspirin therapy. However, the mechanism of this phenomenon is still unclear. OBJECTIVE: The aim of this study was to characterize the airway inflammatory response to aspirin desensitization and after treatment with high-dose aspirin for 6 months. METHODS: Twenty-one adult patients with asthma, chronic polypoid sinusitis, and a convincing history of acute respiratory reaction to the ingestion of aspirin or nonsteroidal anti-inflammatory drugs were selected. These patients underwent an oral desensitization to aspirin over a 2-day period, followed by daily ingestion of aspirin 650 mg twice daily. Induced sputum samples and exhaled nitric oxide measurements were taken before the procedure, during the second day of the procedure, and after 6 months of treatment. RESULTS: There was a significant elevation in both the exhaled nitric oxide level (P = .03) and sputum tryptase level (P = .05) during the desensitization process. After 6 months of aspirin treatment, sputum IL-4 (P = .0007) and matrix metalloproteinase 9 (MMP-9; P = .05) decreased significantly compared with baseline. Predesensitization to postdesensitization changes in MMP-9 and tissue inhibitors of metalloproteinases 1 were highly correlated (r = 0.79; P = .0003). Immediately after the desensitization, MMP-9 and tryptase were correlated (r = 0.82; P = .001), whereas IL-4 was inversely related with FMS-like tyrosine kinase 3 ligand (FLT3-L) (r = -0.79; P = .0008). There was a significant decrease in the average symptom score at 6 months. CONCLUSION: Consistent with previous reports, acute aspirin desensitization in patients with aspirin-exacerbated respiratory disease involves mast cell degranulation. In contrast, long-term treatment with aspirin involves suppression of IL-4 as well as downregulation of proinflammatory MMP-9 while T(H)1 marker FLT3-L increases.

T-cell lymphopenia associated with infliximab and cyclophosphamide.

We report the first case of T-cell lymphopenia in a woman with rheumatoid arthritis who developed molluscum contagiosum with infliximab and cyclophosphamide. She presented in July 2000 with optic neuropathy and arthritis refractory to nonsteroidal anti-inflammatory drugs. After starting prednisone and cyclophosphamide, she became leukopenic (1.8x10 cells/microL), a condition that resolved with decreasing of the cyclophosphamide dose. In June 2002, the patient continued to have synovitis despite treatment with prednisone, cyclophosphamide, gabapentin, and celecoxib; blood counts were normal and infliximab was started. Her symptoms improved, but leukocyte counts declined (nadir of 1.5x10 cells/microL) despite discontinuing cyclophosphamide. She developed molluscum contagiosum after 8 months on infliximab (CD4 count, 492; HIV enzyme-linked immunosorbent assay and Western blot negative). Her symptoms flared after 10 months on infliximab; after the dose of infliximab was increased, her CD4 count fell to 114. Infliximab was discontinued and her leukocyte and CD4 count increased. This is the first reported case of leukopenia and T-cell suppression associated with infliximab and cyclophosphamide.

Diffuse large B-cell lymphoma manifesting as acute respiratory distress syndrome.

Diffuse large B-cell lymphoma initially appears with intrathoracic manifestations in up to 26% of patients. However, pulmonary involvement with hematologic malignancies rarely manifests clinically as acute respiratory distress syndrome (ARDS). We report a case of diffuse large B-cell lymphoma manifesting as ARDS in a 39-year-old Filipina woman. This case illustrates the importance of including lymphoma in the differential diagnosis of otherwise unexplained ARDS. Early recognition and prompt treatment may affect survival.