Pulmonary Tropheryma whipplei infection in a patient with systemic lupus erythematosus: diagnosis supported by BALF tNGS with subsequent doxycycline-based treatment: a case report

Whipple’s disease is a rare systemic infection caused by Tropheryma whipplei ( T. whipplei ). Pulmonary involvement is uncommon and may mimic sarcoidosis, tuberculosis, or malignancy, delaying diagnosis. Pulmonary presentations may be atypical and nonspecific. We report the case of a 40-year-old woman with a 10-year history of systemic lupus erythematosus (SLE) treated with prednisone and hydroxychloroquine. She had bilateral pulmonary ground-glass opacities and solid nodules that were found incidentally on routine chest CT and remained asymptomatic. Empirical levofloxacin treatment did not lead to radiological improvement, and follow-up imaging showed enlargement of the dominant solid nodule, which raised concern for malignancy. Bronchoscopy was nondiagnostic, and routine microbiological tests and cytology were unremarkable. The diagnosis was supported by targeted next-generation sequencing (tNGS) of bronchoalveolar lavage fluid (BALF), which detected a high burden of T. whipplei (raw reads 4,647,325; normalized reads 417,876; estimated concentration 10 4 copies/mL). Initial treatment with ceftriaxone and trimethoprim-sulfamethoxazole (TMP-SMX) was complicated by severe drug fever. The regimen was then changed to oral doxycycline while hydroxychloroquine was continued for SLE. Serial follow-up CT demonstrated enlargement from February to March, followed by a stepwise interval decrease of the dominant solid nodule, while the other ground-glass and small solid nodules remained broadly stable. This case shows that tNGS can provide useful microbiological support for identifying pulmonary T. whipplei infection when routine evaluation is inconclusive. After TMP-SMX intolerance, doxycycline was used as an individualized treatment in this case, while hydroxychloroquine was continued at the patient’s existing dose for SLE.