Whipple disease is a chronic infection that is fatal without treatment. It normally resolves completely with antibiotic treatment. However, irreversible CNS or joint damage may result in persisting problems independent of bacterial colonization. Furthermore, an Italian case series revealed that although effectively treated, patients with Whipple disease suffer more frequently from life-threatening infective or neoplastic and thromboembolic disorders.[82]Schiepatti A, Nicolardi ML, Marone P, et al. Long-term morbidity and mortality in Whipple's disease: a single-center experience over 20 years. Future Microbiol. 2020 Jul;15:847-54.
http://www.ncbi.nlm.nih.gov/pubmed/32662657?tool=bestpractice.com
There are rare cases of resistance to trimethoprim-sulfamethoxazole.[83]Fenollar F, Rolain JM, Alric L, et al. Resistance to trimethoprim/sulfamethoxazole and Tropheryma whipplei. Int J Antimicrob Agents. 2009 Sep;34(3):255-9.
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[84]Lagier JC, Fenollar F, Lepidi H, et al. Failure and relapse after treatment with trimethoprim/sulfamethoxazole in classic Whipple's disease. J Antimicrob Chemother. 2010 Sep;65(9):2005-12.
https://www.doi.org/10.1093/jac/dkq263
http://www.ncbi.nlm.nih.gov/pubmed/20639526?tool=bestpractice.com
In these cases, an alternative treatment should be used. With insufficient treatment Whipple disease can relapse, resulting in a much more severe disease course, especially if the CNS is involved.[85]Marumganti AR, Murphy TF. Whipple's disease: neurological relapse presenting as headache for two years. J Gen Intern Med. 2008 Dec;23(12):2131-3.
http://www.ncbi.nlm.nih.gov/pubmed/18784966?tool=bestpractice.com
[86]Garas G, Cheng WS, Abrugiato R, et al. Clinical relapse in Whipple's disease despite maintenance therapy. J Gastroenterol Hepatol. 2000 Oct;15(10):1223-6.
http://www.ncbi.nlm.nih.gov/pubmed/11106107?tool=bestpractice.com