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Clinical research and prevention

Whipple disease treatment

Updated : 26/07/2016.

Tropheryma whipplei infections and Whipple’s disease : 
diagnostic criteria and treatment protocols.

 

 


In the following recommendations we will use:

PAS for periodic acid-Schiff staining

IHC for T. whipplei-specific immunohistochemistry

PCR for T. whipplei-specific polymerase chain reaction

D for doxycycline

OHCQ for hydroxychlorquine

IRIS for immune reconstitution inflammatory syndrome

CSF for cerebrospinal fluid

 

I- Classical Whipple’s disease.

 

Criteria

Diagnosis

Treatment

Positive PAS* and/or positive IHC on duodenal biopsy

Classical Whipple’s disease

D+ OHCQ for 1 year

Then lifelong D treatment

Negative PCR on saliva and stools (patient without antibiotic treatment)

Exclude Whipple’s disease (predictive negative value = 99%)

No treatment

Positive PCR on saliva and stools

Possible Whipple’s disease :

Perform duodenal biopsy

Or cutaneous biopsy

Or blood PCR

No treatment

Positive PCR on saliva or stools

Perform duodenal biopsy if typical clinical history

No treatment

Positive PCR on duodenal biopsy and/or stools and/or saliva but negative PAS and IHC on duodenal biopsy

Exclude Whipple’s disease

Search for T. whipplei localised infection.

No treatment

 

*Rare mycobacterial digestive infections are PAS shift positive

 

 

Whipple’s disease and IRIS:

 

At the beginning of Whipple’s disease treatment, cases of IRIS have been reported. They are characterized by persistent fever or other inflammatory symptoms (cutaneous nodules, arthritis, or intestinal perforation).

We suggested a treatment with thalidomide 200 mg/d to begin with followed by reduced doses for 9 month.

If you notice an absence of response or increased symptoms with the treatment please contact us.

 

 

II- Tropheryma whipplei Chronic localized infections.

 

Tropheryma whipplei endocarditis :

 

Criteria

Diagnosis

Treatment

Positive IHC and/or PCR on heart valve4

Definite T. whippleiendocarditis

D + OHCQ for 1 year

Then lifelong D treatment*

Positive blood PCR and valvular vegetation seen in echography or vavular intensity in PET scan

Definite T. whipplei  endocarditis

D + OHCQ for 1 year

Then lifelong D treatment*

Positive blood PCR and vavular lesion but without vegetation and with normal PET scan

Possible T. whippleiendocarditis

Please consult us

For all other situations

 

Please consult us

 

* There is a risk of secondary classical Whipple’s disease.

 

Tropheryma whipplei  encephalitis :

 

Criteria

Diagnosis

Treatment

Positive PCR and/or culture** on CSF

Or positive IHC*** and/or PCR on cerebral biopsy

Definite T. whippleiencephalitis

D + OHCQ for 1 year

Then lifelong D treatment*

For all other situations

 

Please consult us

 

* There is a risk of Secondary classical Whipple disease

** Culture is more sensible than PCR in the CSF.

***PAS shift on cerebral biopsy is not specific, IHC makes the diagnosis.

 

 

Tropheryma whipplei  localized arthritis :

 

Criteria

Diagnosis

Treatment

Positive PCR on articular liquid.

Or positive PCR and/or PAS and/or IHC on synovial biopsy

Definite T. whipplei articular infection

D + OHCQ for 1 year

For all other situations

 

Please consult us

 

 

Tropheryma whipplei uveitis :

 

Criteria

Diagnosis

Treatment

Positive PCR on acqueous humor

Definite T. whipplei uveitis

D+ OHCQ for 1 year

For all other situations

 

Please consult us

 

 

III- Tropheryma whipplei acute infection.

 

Criteria

Diagnosis

Treatment

Positive PCR on bronchoalveolar lavage

Pneumonia

No systematic treatment.

Please consult us for acute respiratory distress syndrom or severe immunosuppression

Positive PCR on stools

Diarrhea

No treatment

 

 

IV- Specificities.

 

Criteria

Recommendations

T. whipplei infection and pregnancy

No doxycycline

Please consult us

Classical whipple’s disease relapse after discontinuation of treatment

Usually relapse with neurological form

-       Cognitive disorders

-       Ataxia

-       Oculomotricity disorders

PET scan

D+ OHCQ even without microbiological documentation

For all other situations

Please consult us

 

 

V- Treatment and follow up.

 


  • Doxycycline = 100 mg twice a day
  • Hydroxychloroquine = 200 mg three times a day
  • Dosages:
    1. Hydroxychloroquine : 1 µg/ml +/- 0.2 µg/ml
    2. Doxycycline : 4 µg/ml

 

VII- References.

 

1. Fenollar F, Lagier JC, Raoult D. Tropheryma whipplei and Whipple's disease. J Infect. 2014 Aug; 69(2):103-12.

2. Fenollar F, Puéchal X, Raoult D. Whipple's disease. N Engl J Med. 2007 Jan 4; 356(1):55-66.

3. Lagier JC, Fenollar F, Lepidi H, Raoult D. Evidence of lifetime susceptibility to Tropheryma whipplei in patients with Whipple’s disease. J Antimicrob Chemother. 2011 May; 66(5):1188-9.

4. Lagier JC, Fenollar F, Lepidi H, Giorgi R, Million M, Raoult D. Treatment of classic Whipple's disease: from in vitro results to clinical outcome. J Antimicrob Chemother. 2014 Jan; 69(1):219-27. 

5. Lagier JC, Raoult D. Immune reconstitution inflammatory syndrome associated with bacterial infections. Expert Opin Drug Saf. 2014 Mar; 13(3):341-50.

6. Lagier JC , Fenollar F, Lepidi H, Liozon E, Raoult D. Successful treatment of immune reconstitution inflammatory syndrome in Whipple's disease using thalidomide. J Infect. 2010 Jan; 60(1):79-82.

7. Fenollar F, Célard M, Lagier JC, Lepidi H, Fournier PE, Raoult D. Tropheryma whipplei endocarditis. Emerg Infect Dis. 2013 Nov19(11):1721-30.

8. Lagier JC, Cammilleri S, Raoult D. Classic Whipple's disease diagnosed by (18) F-fluorodeoxyglucose PET. Lancet Infect Dis. 2016 Jan; 16(1):130.


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