A 38-year-old Caucasian man without significant past medical history presented to the hospital with unintentional 20-pound weight loss, diarrhea, intermittent fevers up to 103 degrees, and fatigue over the preceding two months. On review of systems, he also had chronic joint pains in his feet and shoulders for the past year. He had been recently diagnosed with iron deficiency anemia the month prior, but this did not improve despite iron supplementation. CT of his abdomen revealed diffuse intraabdominal, chest, and axillary lymphadenopathy. Initial suspicion was for a malignant process such as lymphoma or multicentric Castleman’s disease, or infectious process such as HIV, tuberculosis or atypical mycobacterium, Epstein-Barr virus, histoplasmosis, Whipple’s disease, or syphilis. PET scan demonstrated low-grade activity of these lymph nodes. Axillary lymph node biopsy was non-diagnostic and negative for lymphoma. Mediastinal R4 lymph node biopsy showed benign features with non-necrotizing granulomatous inflammation. Stains for acid-fast bacilli, fungal organisms, and occult Hodgkin’s lymphoma were negative. The finding of non-necrotizing granuloma raised suspicion for sarcoidosis. Patient underwent an esophagoduodenoscopy and colonoscopy, and multiple biopsies were taken from the stomach, duodenum, and colon. Pathology from the duodenum showed infiltration of CD68 histiocytes with foamy cytoplasm and intracytoplasmic PAS positive granular inclusions, consistent with Whipple’s disease. He was started on intravenous ceftriaxone, and his nightly fevers, fatigue, and diarrhea improved. Lumbar puncture was done to look for central nervous system involvement, and PCR for Tropheryma whipplei
in the CSF was positive. Patient remained asymptomatic from a neurologic standpoint. He clinically did well and was sent home on intravenous ceftriaxone for two weeks, followed by trimethoprim-sulfamethoxazole to continue for at least one year.
Discussion: This case demonstrates the importance of checking for CNS involvement in all patients with Whipple’s disease (which is already in itself extremely rare – approximately 30 reported cases per year since 1987) even if they do not have neurologic symptoms. Fewer than 1000 cases of CNS Whipple’s disease have been confirmed in the literature, and less than one half of these patients had neurologic manifestations. CNS involvement may be associated with a higher likelihood of disease recurrence. Though there are too few reported cases in the literature to prove a correlation, earlier recognition and treatment of CNS Whipple’s disease may lead to fewer neurologic complications and better long-term prognosis.
Another noteworthy feature of this case was that the pathologic appearance of non-necrotizing granulomas resembled that of sarcoidosis. Since both Whipple’s disease and sarcoidosis can cause a multitude of clinical findings, many of which overlap, it is important to perform diagnostic stains for Whipple’s disease on small bowel biopsies showing granulomas before giving a definitive diagnosis of sarcoidosis.
Conclusions: All patients with confirmed diagnosis of Whipple’s disease, usually by small bowel biopsy, should undergo lumbar puncture for cerebrospinal fluid analysis for Tropheryma whipplei, even if the patient has no abnormal neurologic findings.