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]] [[ | [[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|sulfamethoxazole-trimethoprim]] for at least 1 year. Patients who experience either Whipple's disease or [[allergy]] to [[Sulfamethoxazole-Trimethoprim|sulfamethoxazole-trimethoprim]] require a combination of [[doxycycline]] and [[hydroxychloroquine]]. Following [[antibiotic]] therapy, [[immune reconstitution inflammatory syndrome]] ([[IRIS]]) might occur that requires oral [[corticosteroid]]. Lifelong follow-up is needed to detect [[relapse]]. | ||
==Medical Therapy== | ==Medical Therapy== | ||
=== Whipple's disease === | === Whipple's disease === | ||
*Pharmacologic medical therapy for Whipple's disease includes long-term [[Antibiotic|antibiotics]]. Preferred regimens for initial therapy include [[ | *Pharmacologic medical therapy for Whipple's disease includes long-term [[Antibiotic|antibiotics]]. Preferred regimens for initial therapy include [[ceftriaxone]] or [[penicillin G]] or [[meropenem]] if allergic. One year of [[Sulfamethoxazole-Trimethoprim|sulfamethoxazole-trimethoprim]] is used for maintenance therapy. In case of [[sulfa allergy]], the combination of [[doxycycline]] and [[hydroxychloroquine]] is used.<ref name="FeurleJunga2010">{{cite journal|last1=Feurle|first1=Gerhard E.|last2=Junga|first2=Natascha S.|last3=Marth|first3=Thomas|title=Efficacy of Ceftriaxone or Meropenem as Initial Therapies in Whipple's Disease|journal=Gastroenterology|volume=138|issue=2|year=2010|pages=478–486|issn=00165085|doi=10.1053/j.gastro.2009.10.041}}</ref><ref name="pmid9193452">{{cite journal |vauthors=Durand DV, Lecomte C, Cathébras P, Rousset H, Godeau P |title=Whipple disease. Clinical review of 52 cases. The SNFMI Research Group on Whipple Disease. Société Nationale Française de Médecine Interne |journal=Medicine (Baltimore) |volume=76 |issue=3 |pages=170–84 |year=1997 |pmid=9193452 |doi= |url=}}</ref><ref name="SchniderReisinger1997">{{cite journal|last1=Schnider|first1=P. J.|last2=Reisinger|first2=E. C.|last3=Berger|first3=T.|last4=Krejs|first4=G. J.|last5=Auff|first5=E.|title=Treatment guidelines in central nervous system Whipple's disease|journal=Annals of Neurology|volume=41|issue=4|year=1997|pages=561–562|issn=0364-5134|doi=10.1002/ana.410410425}}</ref><ref name="pmid14982759">{{cite journal |vauthors=Boulos A, Rolain JM, Raoult D |title=Antibiotic susceptibility of Tropheryma whipplei in MRC5 cells |journal=Antimicrob. Agents Chemother. |volume=48 |issue=3 |pages=747–52 |year=2004 |pmid=14982759 |pmc=353111 |doi= |url=}}</ref><ref name="pmid7519538">{{cite journal |vauthors=Feurle GE, Marth T |title=An evaluation of antimicrobial treatment for Whipple's Disease. Tetracycline versus trimethoprim-sulfamethoxazole |journal=Dig. Dis. Sci. |volume=39 |issue=8 |pages=1642–8 |year=1994 |pmid=7519538 |doi= |url=}}</ref><ref name="pmid2581843">{{cite journal |vauthors=Keinath RD, Merrell DE, Vlietstra R, Dobbins WO |title=Antibiotic treatment and relapse in Whipple's disease. Long-term follow-up of 88 patients |journal=Gastroenterology |volume=88 |issue=6 |pages=1867–73 |year=1985 |pmid=2581843 |doi= |url=}}</ref><ref name="MarthMoos2016">{{cite journal|last1=Marth|first1=Thomas|last2=Moos|first2=Verena|last3=Müller|first3=Christian|last4=Biagi|first4=Federico|last5=Schneider|first5=Thomas|title=Tropheryma whipplei infection and Whipple's disease|journal=The Lancet Infectious Diseases|volume=16|issue=3|year=2016|pages=e13–e22|issn=14733099|doi=10.1016/S1473-3099(15)00537-X}}</ref><ref name="BurešKopáčová2013">{{cite journal|last1=Bureš|first1=Jan|last2=Kopáčová|first2=Marcela|last3=Douda|first3=Tomáš|last4=Bártová|first4=Jolana|last5=Tomš|first5=Jan|last6=Rejchrt|first6=Stanislav|last7=Tachecí|first7=Ilja|title=Whipple’s Disease: Our Own Experience and Review of the Literature|journal=Gastroenterology Research and Practice|volume=2013|year=2013|pages=1–10|issn=1687-6121|doi=10.1155/2013/478349}}</ref> | ||
* '''1 Classic Whipple's disease''' | * '''1 Classic Whipple's disease''' | ||
**'''1.1 Initial therapy''' | **'''1.1 Initial therapy''' | ||
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***1.1.3 Alternative regimen (1): [[Meropenem]] 1 g IV q8h for 14 days | ***1.1.3 Alternative regimen (1): [[Meropenem]] 1 g IV q8h for 14 days | ||
**'''1.2 Maintenance therapy''' | **'''1.2 Maintenance therapy''' | ||
***1.2.1 Preferred regimen (1): [[Sulfamethoxazole-Trimethoprim| | ***1.2.1 Preferred regimen (1): [[Sulfamethoxazole-Trimethoprim|Sulfamethoxazole-trimethoprim]] 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 <u>'''AND'''</u> [[ | ***1.2.2 Alternative regimen (1): [[Doxycycline]] 100 mg PO q12h <u>'''AND'''</u> [[hydroxychloroquine]] 200 mg PO q8h for 1 year | ||
* '''2 CNS infection''' | * '''2 CNS infection''' | ||
| Line 25: | Line 25: | ||
***2.1.3 Alternative regimen (1): [[Meropenem]] 1 g IV q8h 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 Maintenance therapy''' | ||
***2.2.1 Preferred regimen (1): [[Sulfamethoxazole-Trimethoprim| | ***2.2.1 Preferred regimen (1): [[Sulfamethoxazole-Trimethoprim|Sulfamethoxazole-trimethoprim]] 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 '''<u>AND</u>''' [[ | ***2.2.2 Alternative regimen (1): [[Doxycycline]] 100 mg PO q12h '''<u>AND</u>''' [[hydroxychloroquine]] 200 mg PO q8h for 1 year | ||
* '''3 Endocarditis''' | * '''3 Endocarditis''' | ||
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****3.1.3 Alternative regimen (1): [[Meropenem]] 1 g IV q8h for 28 days | ****3.1.3 Alternative regimen (1): [[Meropenem]] 1 g IV q8h for 28 days | ||
**'''3.2 Maintenance therapy''' | **'''3.2 Maintenance therapy''' | ||
***3.2.1 Preferred regimen (1): [[Sulfamethoxazole-Trimethoprim| | ***3.2.1 Preferred regimen (1): [[Sulfamethoxazole-Trimethoprim|Sulfamethoxazole-trimethoprim]] 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 '''<u>AND</u>''' [[ | ***3.2.2 Alternative regimen (1): [[Doxycycline]] 100 mg PO q12h '''<u>AND</u>''' [[hydroxychloroquine]] 200 mg PO q8h for 1 year | ||
* '''4 Relapse''' | * '''4 Relapse''' | ||
**'''4.1 Initial therapy''' | **'''4.1 Initial therapy''' | ||
***4.1.1 Preferred regimen (1): [[Penicillin]] | ***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 | ***4.1.2 Preferred regimen (2): [[Ceftriaxone]] 2 g IV qd for 28 days | ||
**'''4.2 Maintenance therapy''' | **'''4.2 Maintenance therapy''' | ||
***4.2.1 Preferred regimen (1): [[Doxycycline]] 100 mg PO q12h '''<u>AND</u>''' [[hydroxychloroquine]] 200 mg PO q8h for 1 year | ***4.2.1 Preferred regimen (1): [[Doxycycline]] 100 mg PO q12h '''<u>AND</u>''' [[hydroxychloroquine]] 200 mg PO q8h for 1 year | ||
***4.2.2 Alternative regimen (1): [[Sulfamethoxazole-Trimethoprim| | ***4.2.2 Alternative regimen (1): [[Sulfamethoxazole-Trimethoprim|Sulfamethoxazole-trimethoprim]] one DS tablet (160 mg TMP/800 mg SMX) PO q12h for 1 year | ||
'''Note (1):''' Interferon gamma is used in refractory cases.<ref name="Schneider1998">{{cite journal|last1=Schneider|first1=Thomas|title=Treatment of Refractory Whipple Disease with Interferon-γ|journal=Annals of Internal Medicine|volume=129|issue=11_Part_1|year=1998|pages=875|issn=0003-4819|doi=10.7326/0003-4819-129-11_Part_1-199812010-00006}}</ref> | '''Note (1):''' [[Interferon-gamma|Interferon gamma]] is used in refractory cases.<ref name="Schneider1998">{{cite journal|last1=Schneider|first1=Thomas|title=Treatment of Refractory Whipple Disease with Interferon-γ|journal=Annals of Internal Medicine|volume=129|issue=11_Part_1|year=1998|pages=875|issn=0003-4819|doi=10.7326/0003-4819-129-11_Part_1-199812010-00006}}</ref> | ||
'''Note (2):''' Lifelong clinical followup is recommended.<ref name="MarthRaoult2003">{{cite journal|last1=Marth|first1=Thomas|last2=Raoult|first2=Didier|title=Whipple's disease|journal=The Lancet|volume=361|issue=9353|year=2003|pages=239–246|issn=01406736|doi=10.1016/S0140-6736(03)12274-X}}</ref> | '''Note (2):''' Lifelong clinical followup is recommended.<ref name="MarthRaoult2003">{{cite journal|last1=Marth|first1=Thomas|last2=Raoult|first2=Didier|title=Whipple's disease|journal=The Lancet|volume=361|issue=9353|year=2003|pages=239–246|issn=01406736|doi=10.1016/S0140-6736(03)12274-X}}</ref> | ||
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'''<u>OR</u>''' | '''<u>OR</u>''' | ||
[[ | [[penicillin G]] 2 million units IV q4h for 14 days | ||
|[[Meropenem]] 1 g IV q8h for 14 days | |[[Meropenem]] 1 g IV q8h for 14 days | ||
| [[Sulfamethoxazole-Trimethoprim| | | [[Sulfamethoxazole-Trimethoprim|Sulfamethoxazole-trimethoprim]] one DS tablet (160 mg TMP/800 mg SMX) PO q12h for 1 year | ||
|[[Doxycycline]] 100 mg PO q12h <u>'''AND'''</u> [[ | |[[Doxycycline]] 100 mg PO q12h <u>'''AND'''</u> [[hydroxychloroquine]] 200 mg PO q8h for 1 year | ||
|- | |- | ||
| style="font-weight: bold;" | CNS Whippl'es disease | | style="font-weight: bold;" | CNS Whippl'es disease | ||
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'''<u>OR</u>''' | '''<u>OR</u>''' | ||
[[ | [[penicillin G]] 4 million units IV q4h for 14-28 days | ||
| [[Meropenem]] 1 g IV q8h for 14-28 days | | [[Meropenem]] 1 g IV q8h for 14-28 days | ||
| [[Sulfamethoxazole-Trimethoprim| | | [[Sulfamethoxazole-Trimethoprim|Sulfamethoxazole-trimethoprim]] one DS tablet (160 mg TMP/800 mg SMX) PO q12h for 1 year | ||
|[[Doxycycline]] 100 mg PO q12h '''<u>AND</u>''' [[ | |[[Doxycycline]] 100 mg PO q12h '''<u>AND</u>''' [[hydroxychloroquine]] 200 mg PO q8h for 1 year | ||
|- | |- | ||
| style="font-weight: bold;" | Endocarditis | | style="font-weight: bold;" | Endocarditis | ||
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'''<u>OR</u>''' | '''<u>OR</u>''' | ||
[[ | [[ceftriaxone]] 2 g IV qd for 28 days | ||
| [[Meropenem]] 1 g IV q8h for 28 days | | [[Meropenem]] 1 g IV q8h for 28 days | ||
| [[Sulfamethoxazole-Trimethoprim| | | [[Sulfamethoxazole-Trimethoprim|Sulfamethoxazole-trimethoprim]] one DS tablet (160 mg TMP/800 mg SMX) PO q12h for 1 year | ||
|[[Doxycycline]] 100 mg PO q12h '''<u>AND</u>''' [[ | |[[Doxycycline]] 100 mg PO q12h '''<u>AND</u>''' [[hydroxychloroquine]] 200 mg PO q8h for 1 year | ||
|- | |- | ||
| style="font-weight: bold;" | Relapse | | style="font-weight: bold;" | Relapse | ||
| [[Penicillin]] | | [[Penicillin G]] 4 million units IV q4h for 28 days | ||
'''<u>OR</u>''' | '''<u>OR</u>''' | ||
[[ | [[ceftriaxone]] 2 g IV qd for 28 days | ||
| | | | ||
| [[Doxycycline]] 100 mg PO q12h '''<u>AND</u>''' [[hydroxychloroquine]] 200 mg PO q8h for 1 year | | [[Doxycycline]] 100 mg PO q12h '''<u>AND</u>''' [[hydroxychloroquine]] 200 mg PO q8h for 1 year | ||
|[[Sulfamethoxazole-Trimethoprim| | |[[Sulfamethoxazole-Trimethoprim|Sulfamethoxazole-trimethoprim]] one DS tablet (160 mg TMP/800 mg SMX) PO q12h for 1 year | ||
|} | |} | ||
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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 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. 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
- 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 sulfamethoxazole-trimethoprim 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): Sulfamethoxazole-trimethoprim 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): Sulfamethoxazole-trimethoprim 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): Sulfamethoxazole-trimethoprim 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): Sulfamethoxazole-trimethoprim 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 | 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
- ↑ 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.