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{{Whipple's disease}}
{{Whipple's disease}}
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{{CMG}}; {{AE}} {{SSH}}
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{{CMG}}; {{AE}}  


==Overview==
==Overview==
There is no treatment for [disease name]; the mainstay of therapy is supportive care.
[[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]].


OR
==Medical Therapy==
 
Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].
 
OR


The majority of cases of [disease name] are self-limited and require only supportive care.
=== Whipple's disease ===
*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'''
**'''1.1 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|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


OR
* '''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


[Disease name] is a medical emergency and requires prompt treatment.
* '''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


OR
* '''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


The mainstay of treatment for [disease name] is [therapy].
'''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>


OR
'''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>
 
The optimal therapy for [malignancy name] depends on the stage at diagnosis.


OR
'''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>


[Therapy] is recommended among all patients who develop [disease name].
===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>'''


OR
[[penicillin G]] 2 million units IV q4h for 14 days
|[[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


Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
'''<u>OR</u>'''


OR
[[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


Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
'''<u>OR</u>'''


OR
[[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


Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
'''<u>OR</u>'''


OR
[[ceftriaxone]] 2 g IV qd for 28 days
 
|
Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].
| [[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
==Medical Therapy==
|}
*Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
*Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
*Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
*Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].
===Disease Name===
 
* '''1 Stage 1 - Name of stage'''
** 1.1 '''Specific Organ system involved 1'''
*** 1.1.1 '''Adult'''
**** 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
**** Preferred regimen (3): [[drug name]] 500 mg q12h for 14-21 days
**** Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 
**** Alternative regimen (2): [[drug name]] 500 mg PO q12h for 14–21 days
**** Alternative regimen (3): [[drug name]] 500 mg PO q6h for 14–21 days
*** 1.1.2 '''Pediatric'''
**** 1.1.2.1 (Specific population e.g. '''children < 8 years of age''')
***** Preferred regimen (1): [[drug name]] 50 mg/kg PO per day q8h (maximum, 500 mg per dose) 
***** Preferred regimen (2): [[drug name]] 30 mg/kg PO per day in 2 divided doses (maximum, 500 mg per dose)
***** Alternative regimen (1): [[drug name]]10 mg/kg PO q6h (maximum, 500 mg per day)
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h (maximum, 500 mg per dose)
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
****1.1.2.2 (Specific population e.g. ''''''children < 8 years of age'''''')
***** Preferred regimen (1): [[drug name]] 4 mg/kg/day PO q12h（maximum, 100 mg per dose）
***** Alternative regimen (1): [[drug name]] 10 mg/kg PO q6h (maximum, 500 mg per day)
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h (maximum, 500 mg per dose) 
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
** 2.1 '''Specific Organ system involved 2'''
*** 2.1.1 '''Adult'''
**** Preferred regimen (1): [[drug name]] 500 mg PO q8h
*** 2.1.2  '''Pediatric'''
**** Preferred regimen (1): [[drug name]] 50 mg/kg/day PO q8h (maximum, 500 mg per dose)
 
* 2 '''Stage 2 - Name of stage'''
** 2.1 '''Specific Organ system involved 1 '''
**: '''Note (1):'''
**: '''Note (2)''':
**: '''Note (3):'''
*** 2.1.1 '''Adult'''
**** Parenteral regimen
***** Preferred regimen (1): [[drug name]] 2 g IV q24h for 14 (14–21) days
***** Alternative regimen (1): [[drug name]] 2 g IV q8h for 14 (14–21) days
***** Alternative regimen (2): [[drug name]] 18–24 MU/day IV q4h for 14 (14–21) days
**** Oral regimen
***** Preferred regimen (1): [[drug name]] 500 mg PO q8h for 14 (14–21) days
***** Preferred regimen (2): [[drug name]] 100 mg PO q12h for 14 (14–21) days
***** Preferred regimen (3): [[drug name]] 500 mg PO q12h for 14 (14–21) days
***** Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 
***** Alternative regimen (2): [[drug name]] 500 mg PO q12h for 14–21 days
***** Alternative regimen (3):[[drug name]] 500 mg PO q6h for 14–21 days
*** 2.1.2 '''Pediatric'''
**** Parenteral regimen
***** Preferred regimen (1): [[drug name]] 50–75 mg/kg IV q24h for 14 (14–21) days (maximum, 2 g)
***** Alternative regimen (1): [[drug name]] 150–200 mg/kg/day IV q6–8h for 14 (14–21) days (maximum, 6 g per day)
***** Alternative regimen (2):  [[drug name]] 200,000–400,000 U/kg/day IV q4h for 14 (14–21) days (maximum, 18–24 million U per day) ''''''(Contraindications/specific instructions)''''''
**** Oral regimen
***** Preferred regimen (1):  [[drug name]] 50 mg/kg/day PO q8h for 14 (14–21) days  (maximum, 500 mg per dose)
***** Preferred regimen (2): [[drug name]] '''(for children aged ≥ 8 years)''' 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg per dose)
***** Preferred regimen (3): [[drug name]] 30 mg/kg/day PO q12h for 14 (14–21) days  (maximum, 500 mg per dose)
***** Alternative regimen (1):  [[drug name]] 10 mg/kg PO q6h 7–10 days  (maximum, 500 mg per day)
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h for 14–21 days  (maximum, 500 mg per dose)
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h for 14–21 days  (maximum,500 mg per dose)
** 2.2  '<nowiki/>'''''Other Organ system involved 2''''''
**: '''Note (1):'''
**: '''Note (2)''':
**: '''Note (3):'''
*** 2.2.1 '''Adult'''
**** Parenteral regimen
***** Preferred regimen (1): [[drug name]] 2 g IV q24h for 14 (14–21) days
***** Alternative regimen (1): [[drug name]] 2 g IV q8h for 14 (14–21) days
***** Alternative regimen (2): [[drug name]] 18–24 MU/day IV q4h for 14 (14–21) days
**** Oral regimen
***** Preferred regimen (1): [[drug name]] 500 mg PO q8h for 14 (14–21) days
***** Preferred regimen (2): [[drug name]] 100 mg PO q12h for 14 (14–21) days
***** Preferred regimen (3): [[drug name]] 500 mg PO q12h for 14 (14–21) days
***** Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 
***** Alternative regimen (2): [[drug name]] 500 mg PO q12h for 14–21 days
***** Alternative regimen (3):[[drug name]] 500 mg PO q6h for 14–21 days
*** 2.2.2 '''Pediatric'''
**** Parenteral regimen
***** Preferred regimen (1): [[drug name]] 50–75 mg/kg IV q24h for 14 (14–21) days (maximum, 2 g)
***** Alternative regimen (1): [[drug name]] 150–200 mg/kg/day IV q6–8h for 14 (14–21) days (maximum, 6 g per day)
***** Alternative regimen (2):  [[drug name]] 200,000–400,000 U/kg/day IV q4h for 14 (14–21) days (maximum, 18–24 million U per day)
**** Oral regimen
***** Preferred regimen (1):  [[drug name]] 50 mg/kg/day PO q8h for 14 (14–21) days  (maximum, 500 mg per dose)
***** Preferred regimen (2): [[drug name]] 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg per dose)
***** Preferred regimen (3): [[drug name]] 30 mg/kg/day PO q12h for 14 (14–21) days  (maximum, 500 mg per dose)
***** Alternative regimen (1):  [[drug name]] 10 mg/kg PO q6h 7–10 days  (maximum, 500 mg per day)
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h for 14–21 days  (maximum, 500 mg per dose)
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h for 14–21 days  (maximum,500 mg per dose)
 
 
*'''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>
:*Preferred regimen: [[Ceftriaxone]] 2 g IV daily for 2 weeks
 
*'''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>
:*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.


==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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