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{{Whipple's disease}}
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==Overview==
==Overview==
The mainstay of treatment for Whipple's disease is systemic long-term antibiotic therapy.  
[[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|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]]. [[Dietary supplement|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]].
Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
 
==Medical Therapy==
==Medical Therapy==
*Pharmacologic medical therapy for Whipple's disease includes long-term antibiotics.


*Classic Whipple's disease
=== Whipple's disease ===
**Initial therapy
*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>
***Preferred regimen (1): [[drug name]] 100 mg PO q12h for 10-21 days '''(Contraindications/specific instructions)'''  
* '''1 Classic Whipple's disease'''
***Preferred regimen (2): [[drug name]] 500 mg PO q8h for 14-21 days
**'''1.1 Initial therapy'''
***Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days   
***1.1.1 Preferred regimen (1): [[Ceftriaxone]] 2 g IV qd for 14 days 
**Maintenance therapy
***1.1.2 Preferred regimen (2): [[Penicillin]] G 2 million units IV q4h for 14 days
***Preferred regimen (1): [[drug name]] 100 mg PO q12h for 10-21 days '''(Contraindications/specific instructions)'''  
***1.1.3 Alternative regimen (1): [[Meropenem]] 1 g IV q8h for 14 days 
***Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 
**'''1.2 Maintenance therapy'''
***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> [[hydroxychloroquine]] 200 mg PO q8h for 1 year
 
* '''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|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>''' [[hydroxychloroquine]] 200 mg PO q8h for 1 year
 
* '''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'''
***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>''' [[hydroxychloroquine]] 200 mg PO q8h for 1 year
 
* '''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 '''<u>AND</u>''' [[hydroxychloroquine]] 200 mg PO q8h for 1 year   
***4.2.2 Alternative regimen (1): [[Sulfamethoxazole-Trimethoprim|Sulfamethoxazole-trimethoprim]] one DS tablet (160 mg TMP/800 mg SMX) PO q12h for 1 year


*CNS infection
'''Note (1):''' Dietary supplements including [[vitamins]], [[iron]], [[folic acid]], [[calcium]], and [[magnesium]] is needed.<ref name="urlwww.cghjournal.org">{{cite web |url=http://www.cghjournal.org/article/S1542-3565(04)00387-8/pdf |title=www.cghjournal.org |format= |work= |accessdate=}}</ref>
**Initial therapy
**** Preferred regimen (1): [[drug name]] 100 mg PO q12h for 10-21 days '''(Contraindications/specific instructions)''' 
**** Preferred regimen (2): [[drug name]] 500 mg PO q8h for 14-21 days
**** Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 
**Maintenance therapy
***Preferred regimen (1): [[drug name]] 100 mg PO q12h for 10-21 days '''(Contraindications/specific instructions)''' 
***Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 


*Endocarditis
'''Note (2):''' [[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>
**Initial therapy
**** Preferred regimen (1): [[drug name]] 100 mg PO q12h for 10-21 days '''(Contraindications/specific instructions)'''  
**** Preferred regimen (2): [[drug name]] 500 mg PO q8h for 14-21 days
**** Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 
**Maintenance therapy
***Preferred regimen (1): [[drug name]] 100 mg PO q12h for 10-21 days '''(Contraindications/specific instructions)''' 
***Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 


*Relapse
'''Note (3):''' 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>
**Initial therapy
**** Preferred regimen (1): [[drug name]] 100 mg PO q12h for 10-21 days '''(Contraindications/specific instructions)'''  
**** Preferred regimen (2): [[drug name]] 500 mg PO q8h for 14-21 days
**** Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 
**Maintenance therapy
***Preferred regimen (1): [[drug name]] 100 mg PO q12h for 10-21 days '''(Contraindications/specific instructions)''' 
***Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 


===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.<ref name="BiagiTrotta2012">{{cite journal|last1=Biagi|first1=Federico|last2=Trotta|first2=Lucia|last3=Di Stefano|first3=Michele|last4=Balduzzi|first4=Davide|last5=Marchese|first5=Alessandra|last6=Vattiato|first6=Claudia|last7=Bianchi|first7=Paola I.|last8=Fenollar|first8=Florence|last9=Corazza|first9=Gino R.|title=Previous immunosuppressive therapy is a risk factor for immune reconstitution inflammatory syndrome in Whipple's disease|journal=Digestive and Liver Disease|volume=44|issue=10|year=2012|pages=880–882|issn=15908658|doi=10.1016/j.dld.2012.05.008}}</ref><ref name="MoosFeurle2013">{{cite journal|last1=Moos|first1=V.|last2=Feurle|first2=G. E.|last3=Schinnerling|first3=K.|last4=Geelhaar|first4=A.|last5=Friebel|first5=J.|last6=Allers|first6=K.|last7=Moter|first7=A.|last8=Kikhney|first8=J.|last9=Loddenkemper|first9=C.|last10=Kuhl|first10=A. A.|last11=Erben|first11=U.|last12=Fenollar|first12=F.|last13=Raoult|first13=D.|last14=Schneider|first14=T.|title=Immunopathology of Immune Reconstitution Inflammatory Syndrome in Whipple's Disease|journal=The Journal of Immunology|volume=190|issue=5|year=2013|pages=2354–2361|issn=0022-1767|doi=10.4049/jimmunol.1202171}}</ref>
** 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:<ref name="LagierFenollar2010">{{cite journal|last1=Lagier|first1=Jean-Christophe|last2=Fenollar|first2=Florence|last3=Lepidi|first3=Hubert|last4=Liozon|first4=Eric|last5=Raoult|first5=Didier|title=Successful treatment of immune reconstitution inflammatory syndrome in Whipple's disease using thalidomide|journal=Journal of Infection|volume=60|issue=1|year=2010|pages=79–82|issn=01634453|doi=10.1016/j.jinf.2009.09.017}}</ref><ref name="MoosFeurle2013">{{cite journal|last1=Moos|first1=V.|last2=Feurle|first2=G. E.|last3=Schinnerling|first3=K.|last4=Geelhaar|first4=A.|last5=Friebel|first5=J.|last6=Allers|first6=K.|last7=Moter|first7=A.|last8=Kikhney|first8=J.|last9=Loddenkemper|first9=C.|last10=Kuhl|first10=A. A.|last11=Erben|first11=U.|last12=Fenollar|first12=F.|last13=Raoult|first13=D.|last14=Schneider|first14=T.|title=Immunopathology of Immune Reconstitution Inflammatory Syndrome in Whipple's Disease|journal=The Journal of Immunology|volume=190|issue=5|year=2013|pages=2354–2361|issn=0022-1767|doi=10.4049/jimmunol.1202171}}</ref>
*** Oral [[corticosteroid]]
*** [[Thalidomide]]
<br>
{| class="wikitable"
! rowspan="2" style="text-align: center; font-weight: bold;" | Indication
! colspan="2" style="text-align: center; font-weight: bold;" | Initial therapy
! colspan="2" style="text-align: center; font-weight: bold;" | Maintenance therapy
|-
| style="text-align: center; font-weight: bold;" | Prefered
| style="text-align: center; font-weight: bold;" | Alternative
| style="text-align: center; font-weight: bold;" | Preferred
| style="text-align: center; font-weight: bold;" | Alternative
|-
| style="font-weight: bold;" | Classic Whipple's disease
|[[Ceftriaxone]] 2 g IV qd for 14 days
'''<u>OR</u>'''


*'''1. Initial Parenteral Therapy'''<ref>{{cite book | last = Bennett | first = John | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Elsevier/Saunders | location = Philadelphia, PA | year = 2015 | isbn = 978-1455748013 }}</ref>
[[penicillin G]] 2 million units IV q4h for 14 days
:*Preferred regimen: [[Ceftriaxone]] 2 g IV daily for 2 weeks
|[[Meropenem]] 1 g IV q8h for 14 days
| [[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> [[hydroxychloroquine]] 200 mg PO q8h for 1 year
|-
| style="font-weight: bold;" | CNS Whippl'es disease
| [[Ceftriaxone]] 2 g IV qd for 14-28 days


*'''2. Long-term Therapy'''<ref>{{cite book | last = Bennett | first = John | title = Mandell, Douglas, and Bennett's principles and practice of infectious diseases | publisher = Elsevier/Saunders | location = Philadelphia, PA | year = 2015 | isbn = 978-1455748013 }}</ref>
'''<u>OR</u>'''
:*Preferred regimen: [[Trimethoprim-sulfamethoxazole]] 160/800 mg PO bid for at least 1 year
 
:*Alternative regimen: [[Doxycycline]] 100 mg PO bid {{and}} [[Hydroxychloroquine]] 200 mg PO tid in cases of allergy or relapse.
[[penicillin G]] 4 million units IV q4h for 14-28 days
| [[Meropenem]] 1 g IV q8h for 14-28 days
| [[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>''' [[hydroxychloroquine]] 200 mg PO q8h for 1 year
|-
| style="font-weight: bold;" | Endocarditis
| [[Penicillin]] G 2 million units IV q4h for 28 days
 
'''<u>OR</u>'''
 
[[ceftriaxone]] 2 g IV qd for 28 days
| [[Meropenem]] 1 g IV q8h for 28 days
| [[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>''' [[hydroxychloroquine]] 200 mg PO q8h for 1 year
|-
| style="font-weight: bold;" | Relapse
| [[Penicillin G]] 4 million units IV q4h for 28 days
 
'''<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
|[[Sulfamethoxazole-Trimethoprim|Sulfamethoxazole-trimethoprim]] one DS tablet (160 mg TMP/800 mg SMX) PO q12h for 1 year
|}


==References==
==References==
{{reflist|2}}
{{reflist|2}}


 
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[[Category:Medicine]]
[[Category:Gastroenterology]]
[[Category:Infectious disease]]
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Latest revision as of 00:44, 30 July 2020

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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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