Whipple's disease medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sadaf Sharfaei M.D.[2]

Overview

Antimicrobial therapy is the mainstay of therapy for Whipple's disease. Intravenous ceftriaxone or penicillin G is indicated in the acute phase of Whipple's therapy. For maintenance therapy, patients are typically treated with sulfamethoxazole-trimethoprim for at least 1 year. Patients who experience either Whipple's disease or allergy to sulfamethoxazole-trimethoprim require a combination of doxycycline and hydroxychloroquine. Dietary supplements including vitamins, iron, folic acid, calcium and magnesium is needed. Following antibiotic therapy, immune reconstitution inflammatory syndrome (IRIS) might occur that requires oral corticosteroid. Lifelong follow-up is needed to detect relapse.

Medical Therapy

Whipple's disease

  • 2 CNS infection
    • 2.1 Initial therapy
      • 2.1.1 Preferred regimen (1): Ceftriaxone 2 g IV qd for 14-28 days
      • 2.1.2 Preferred regimen (2): Penicillin G 4 million units IV q4h for 14-28 days
      • 2.1.3 Alternative regimen (1): Meropenem 1 g IV q8h for 14-28 days
    • 2.2 Maintenance therapy
  • 3 Endocarditis
    • 3.1 Initial therapy
      • 3.1.1 Preferred regimen (1): Penicillin G 2 million units IV q4h for 28 days
        • 3.1.2 Preferred regimen (2): Ceftriaxone 2 g IV qd for 28 days
        • 3.1.3 Alternative regimen (1): Meropenem 1 g IV q8h for 28 days
    • 3.2 Maintenance therapy
  • 4 Relapse
    • 4.1 Initial therapy
      • 4.1.1 Preferred regimen (1): Penicillin G 4 million units IV q4h for 28 days
      • 4.1.2 Preferred regimen (2): Ceftriaxone 2 g IV qd for 28 days
    • 4.2 Maintenance therapy

Note (1): Dietary supplements including vitamins, iron, folic acid, calcium, and magnesium is needed.[9]

Note (2): Interferon gamma is used in refractory cases.[10]

Note (3): Lifelong clinical followup is recommended.[11]

Adverse effects of treatment and complications


Indication Initial therapy Maintenance therapy
Prefered Alternative Preferred Alternative
Classic Whipple's disease Ceftriaxone 2 g IV qd for 14 days

OR

penicillin G 2 million units IV q4h for 14 days

Meropenem 1 g IV q8h for 14 days Sulfamethoxazole-trimethoprim one DS tablet (160 mg TMP/800 mg SMX) PO q12h for 1 year Doxycycline 100 mg PO q12h AND hydroxychloroquine 200 mg PO q8h for 1 year
CNS Whippl'es disease Ceftriaxone 2 g IV qd for 14-28 days

OR

penicillin G 4 million units IV q4h for 14-28 days

Meropenem 1 g IV q8h for 14-28 days Sulfamethoxazole-trimethoprim one DS tablet (160 mg TMP/800 mg SMX) PO q12h for 1 year Doxycycline 100 mg PO q12h AND hydroxychloroquine 200 mg PO q8h for 1 year
Endocarditis Penicillin G 2 million units IV q4h for 28 days

OR

ceftriaxone 2 g IV qd for 28 days

Meropenem 1 g IV q8h for 28 days Sulfamethoxazole-trimethoprim one DS tablet (160 mg TMP/800 mg SMX) PO q12h for 1 year Doxycycline 100 mg PO q12h AND hydroxychloroquine 200 mg PO q8h for 1 year
Relapse Penicillin G 4 million units IV q4h for 28 days

OR

ceftriaxone 2 g IV qd for 28 days

Doxycycline 100 mg PO q12h AND hydroxychloroquine 200 mg PO q8h for 1 year Sulfamethoxazole-trimethoprim one DS tablet (160 mg TMP/800 mg SMX) PO q12h for 1 year

References

  1. Feurle, Gerhard E.; Junga, Natascha S.; Marth, Thomas (2010). "Efficacy of Ceftriaxone or Meropenem as Initial Therapies in Whipple's Disease". Gastroenterology. 138 (2): 478–486. doi:10.1053/j.gastro.2009.10.041. ISSN 0016-5085.
  2. Durand DV, Lecomte C, Cathébras P, Rousset H, Godeau P (1997). "Whipple disease. Clinical review of 52 cases. The SNFMI Research Group on Whipple Disease. Société Nationale Française de Médecine Interne". Medicine (Baltimore). 76 (3): 170–84. PMID 9193452.
  3. Schnider, P. J.; Reisinger, E. C.; Berger, T.; Krejs, G. J.; Auff, E. (1997). "Treatment guidelines in central nervous system Whipple's disease". Annals of Neurology. 41 (4): 561–562. doi:10.1002/ana.410410425. ISSN 0364-5134.
  4. Boulos A, Rolain JM, Raoult D (2004). "Antibiotic susceptibility of Tropheryma whipplei in MRC5 cells". Antimicrob. Agents Chemother. 48 (3): 747–52. PMC 353111. PMID 14982759.
  5. Feurle GE, Marth T (1994). "An evaluation of antimicrobial treatment for Whipple's Disease. Tetracycline versus trimethoprim-sulfamethoxazole". Dig. Dis. Sci. 39 (8): 1642–8. PMID 7519538.
  6. Keinath RD, Merrell DE, Vlietstra R, Dobbins WO (1985). "Antibiotic treatment and relapse in Whipple's disease. Long-term follow-up of 88 patients". Gastroenterology. 88 (6): 1867–73. PMID 2581843.
  7. Marth, Thomas; Moos, Verena; Müller, Christian; Biagi, Federico; Schneider, Thomas (2016). "Tropheryma whipplei infection and Whipple's disease". The Lancet Infectious Diseases. 16 (3): e13–e22. doi:10.1016/S1473-3099(15)00537-X. ISSN 1473-3099.
  8. Bureš, Jan; Kopáčová, Marcela; Douda, Tomáš; Bártová, Jolana; Tomš, Jan; Rejchrt, Stanislav; Tachecí, Ilja (2013). "Whipple's Disease: Our Own Experience and Review of the Literature". Gastroenterology Research and Practice. 2013: 1–10. doi:10.1155/2013/478349. ISSN 1687-6121.
  9. "www.cghjournal.org".
  10. Schneider, Thomas (1998). "Treatment of Refractory Whipple Disease with Interferon-γ". Annals of Internal Medicine. 129 (11_Part_1): 875. doi:10.7326/0003-4819-129-11_Part_1-199812010-00006. ISSN 0003-4819.
  11. Marth, Thomas; Raoult, Didier (2003). "Whipple's disease". The Lancet. 361 (9353): 239–246. doi:10.1016/S0140-6736(03)12274-X. ISSN 0140-6736.
  12. Biagi, Federico; Trotta, Lucia; Di Stefano, Michele; Balduzzi, Davide; Marchese, Alessandra; Vattiato, Claudia; Bianchi, Paola I.; Fenollar, Florence; Corazza, Gino R. (2012). "Previous immunosuppressive therapy is a risk factor for immune reconstitution inflammatory syndrome in Whipple's disease". Digestive and Liver Disease. 44 (10): 880–882. doi:10.1016/j.dld.2012.05.008. ISSN 1590-8658.
  13. 13.0 13.1 Moos, V.; Feurle, G. E.; Schinnerling, K.; Geelhaar, A.; Friebel, J.; Allers, K.; Moter, A.; Kikhney, J.; Loddenkemper, C.; Kuhl, A. A.; Erben, U.; Fenollar, F.; Raoult, D.; Schneider, T. (2013). "Immunopathology of Immune Reconstitution Inflammatory Syndrome in Whipple's Disease". The Journal of Immunology. 190 (5): 2354–2361. doi:10.4049/jimmunol.1202171. ISSN 0022-1767.
  14. Lagier, Jean-Christophe; Fenollar, Florence; Lepidi, Hubert; Liozon, Eric; Raoult, Didier (2010). "Successful treatment of immune reconstitution inflammatory syndrome in Whipple's disease using thalidomide". Journal of Infection. 60 (1): 79–82. doi:10.1016/j.jinf.2009.09.017. ISSN 0163-4453.

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