Treatment of classic Whipple's disease: from in vitro results to clinical outcome.
OBJECTIVE
Patients with classic Whipple's disease have a lifetime defect in immunity to Tropheryma whipplei and frequently develop treatment failures, relapses or reinfections. Empirical treatments were tested before culture was possible, but the only in vitro bactericidal treatment consists of a combination of doxycycline and hydroxychloroquine.


METHODS
Our laboratory has been a reference centre since the first culturing of Tropheryma whipplei, and we have tested 27,000 samples by PCR and diagnosed 250 cases of classic Whipple's disease. We report here the clinical course of patients who were followed by one of our group.


RESULTS
Of 29 patients, 22 (76%) were previously treated with immunosuppressive drugs, 26 (90%) suffered from arthralgias and 22 (76%) exhibited weight loss. Intravenous initial treatment was paradoxically associated with an increased risk of failure (P = 0.0282). Treatment with doxycycline and hydroxychloroquine (± sulfadiazine or trimethoprim/sulfamethoxazole) was associated with a better outcome (0/13 failures), whereas all 14 patients who were first treated with trimethoprim/sulfamethoxazole and referred to us (P < 0.0001) experienced failure. Among the patients treated with doxycycline and hydroxychloroquine after previous antibiotic treatments, two presented with a reinfection caused by different T. whipplei strains. Finally, serum therapeutic drug monitoring allowed us to detect a lack of compliance in the only patient with failure among the 22 patients treated with lifetime doxycycline.


CONCLUSIONS
In vitro results were confirmed by clinical outcomes and trimethoprim/sulfamethoxazole was associated with failures. The recommended management is a combination of doxycycline and hydroxychloroquine for 1 year, followed by doxycycline for the patient's lifetime along with stringent therapeutic drug monitoring.
Aix Marseille Université, URMITE, UM63, CNRS 7278, IRD 198, INSERM 1095, 13005 Marseille, France.
Jean-Christophe
JC
Lagier
Florence
F
Fenollar
Hubert
H
Lepidi
Roch
R
Giorgi
Matthieu
M
Million
Didier
D
Raoult
D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004318:Doxycycline / Q000494:pharmacology / Q000627:therapeutic use*; D016903:Drug Monitoring; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D016896:Treatment Outcome; D054851:Tropheryma / Q000187:drug effects* / Q000302:isolation & purification; D008061:Whipple Disease / Q000188:drug therapy* / Q000382:microbiology
D000900:Anti-Bacterial Agents; D006886:Hydroxychloroquine; D004318:Doxycycline
Tropheryma whipplei; antimicrobial therapy; doxycycline; lifetime prophylaxis