Exploring Treatment Challenges in Whipple's Disease: Two Case Reports and Review of the Literature.

OBJECTIVES:To review the literature concerning the antimicrobial treatment of Whipple's disease and to highlight consequences of diagnostic delay (including inappropriate use of immunosuppressants). This in the context of two illustrative case reports in which the standard treatment regimen of intravenous (IV) ceftriaxone for two weeks followed by oral trimethoprim-sulfamethoxazole (TMP-SMX) was either ineffective or poorly tolerated. METHODS:A narrative review of the literature on antimicrobial treatment and the interplay of Whipple's disease with immunosuppressants was conducted alongside the clinical case descriptions. RESULTS:A review of the literature identified two principal treatment strategies in use: the standard IV ceftriaxone/TMP-SMX regimen and the doxycycline/hydroxychloroquine oral-only combination. Debate regarding optimal approach is ongoing, however several studies report on the failure or relapse of the standard IV regimen. Diagnostic delay and inappropriate use of immunosuppressants can lead to severe complications. CONCLUSION:In patients with Whipple's disease who fail or cannot tolerate the standard IV regimen, combination of doxycycline and hydroxychloroquine represents a viable and effective alternative in patients without cerebral involvement. Clinical awareness of this condition and its treatment options is essential for a timely diagnosis and appropriate management.