Whipple's disease medical therapy: Difference between revisions
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==Overview== | ==Overview== | ||
[[Antimicrobial]] therapy is the mainstay of therapy for Whipple's disease. Without [[antibiotic]] therapy Whipple's disease is fatal. 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|Trimethoprim-sulfamethoxazole]] for at least 1 year. Patients who experience either Whipple's disease or allergy to [[Sulfamethoxazole-Trimethoprim|Trimethoprim-sulfamethoxazole]] require a combination of [[Doxycycline]] and [[Hydroxychloroquine]]. Lifelong follow-up is needed to detect relapses. | [[Antimicrobial]] therapy is the mainstay of therapy for Whipple's disease. Without [[antibiotic]] therapy Whipple's disease is fatal. 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|Trimethoprim-sulfamethoxazole]] for at least 1 year. Patients who experience either Whipple's disease or allergy to [[Sulfamethoxazole-Trimethoprim|Trimethoprim-sulfamethoxazole]] require a combination of [[Doxycycline]] and [[Hydroxychloroquine]]. Following antibiotic therapy, ([[IRIS]]) might be occurred. Lifelong follow-up is needed to detect relapses. | ||
==Medical Therapy== | ==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. Without antibiotic therapy Whipple's disease is fatal. Intravenous Ceftriaxone or Penicillin G is indicated in the acute phase of Whipple's therapy. For maintenance therapy, patients are typically treated with Trimethoprim-sulfamethoxazole for at least 1 year. Patients who experience either Whipple's disease or allergy to Trimethoprim-sulfamethoxazole require a combination of Doxycycline and Hydroxychloroquine. Following antibiotic therapy, (IRIS) might be occurred. Lifelong follow-up is needed to detect relapses.
Medical Therapy
Whipple's disease
- Pharmacologic medical therapy for Whipple's disease includes long-term antibiotics. Preferred regimens for initial therapy include Ceftriaxone or Penicillin G or Meropenem if allergic. One year of Trimethoprim-sulfamethoxazole is used for maintenance therapy. In case of sulfa allergy, the combination of Doxycycline and Hydroxychloroquine is used.[1][2][3][4][5][6][7][8]
- 1 Classic Whipple's disease
- 1.1 Initial therapy
- 1.1.1 Preferred regimen (1): Ceftriaxone 2 g IV qd for 14 days
- 1.1.2 Preferred regimen (2): Penicillin G 2 million units IV q4h for 14 days
- 1.1.3 Alternative regimen (1): Meropenem 1 g IV q8h for 14 days
- 1.2 Maintenance therapy
- 1.2.1 Preferred regimen (1): Trimethoprim-sulfamethoxazole one DS tablet (160 mg TMP/800 mg SMX) PO q12h for 1 year
- 1.2.2 Alternative regimen (1): Doxycycline 100 mg PO q12h AND Hydroxychloroquine 200 mg PO q8h for 1 year
- 1.1 Initial therapy
- 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
- 2.2.1 Preferred regimen (1): Trimethoprim-sulfamethoxazole one DS tablet (160 mg TMP/800 mg SMX) PO q12h for 1 year
- 2.2.2 Alternative regimen (1): Doxycycline 100 mg PO q12h AND Hydroxychloroquine 200 mg PO q8h for 1 year
- 2.1 Initial 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
- 3.1.1 Preferred regimen (1): Penicillin G 2 million units IV q4h for 28 days
- 3.2 Maintenance therapy
- 3.2.1 Preferred regimen (1): Trimethoprim-sulfamethoxazole one DS tablet (160 mg TMP/800 mg SMX) PO q12h for 1 year
- 3.2.2 Alternative regimen (1): Doxycycline 100 mg PO q12h AND Hydroxychloroquine 200 mg PO q8h for 1 year
- 3.1 Initial 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
- 4.2.1 Preferred regimen (1): Doxycycline 100 mg PO q12h AND hydroxychloroquine 200 mg PO q8h for 1 year
- 4.2.2 Alternative regimen (1): Trimethoprim-sulfamethoxazole one DS tablet (160 mg TMP/800 mg SMX) PO q12h for 1 year
- 4.1 Initial therapy
Note (1): Interferon gamma is used in refractory cases.[9]
Note (2): Lifelong clinical followup is recommended.[10]
Adverse effects of treatment and complications
- Immune reconstitution inflammatory syndrome (IRIS) is a side effect that occurred following initiation of antibiotic therapy in Whipple's disease. It is characterized as a flare-up of inflammation and considered fatal.[11][12]
- Previous immunosuppressive therapy increases the risk of IRIS.
- Clinical features of the IRIS including:
- Fever (common)
- Arthritis (common)
- Erythema nodosum
- Meningitis
- Brain abscess
- Pleuritis
- Endocarditis
- Orbitopathy
- Treatment for IRIS includes:[13][12]
| 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 | Trimethoprim-sulfamethoxazole 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 | Trimethoprim-sulfamethoxazole 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 | Trimethoprim-sulfamethoxazole 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 | Trimethoprim-sulfamethoxazole one DS tablet (160 mg TMP/800 mg SMX) PO q12h for 1 year | |
References
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 12.0 12.1 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.
- ↑ 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.