Tropheryma whipplei: Difference between revisions
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Tropheryma whipplei
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− | == |
+ | ==Background== |
− | === |
+ | ===Microbiology=== |
− | * |
+ | *Fastidious [[Stain::Gram-positive]] [[Shape::bacillus]] |
− | === |
+ | ===Epidemiology=== |
− | * |
+ | *Ubiquitous environmental organism, but rarely causes disease with only about 12 new cases diagnosed annually worldwide |
− | ** |
+ | **Can be found in saliva of one third of healthy people |
− | * |
+ | *Disease is more common in white European (98%) males (85%) |
+ | *Mean age at diagnosis is 40 to 60 years |
||
+ | *Farming or occupational soil/animal/sewage exposures are common |
||
− | === |
+ | ===Pathophysiology=== |
− | * |
+ | *Lack of host immune response |
− | == |
+ | ==Clinical Manifestations== |
− | === |
+ | ===Classic Whipple Disease=== |
− | * |
+ | *Cardinal features include: [[arthralgias]] (80%), followed by [[weight loss]] (90%), [[diarrhea]] (75%), and [[abdominal pain]] (60%) |
− | * |
+ | *Arthralgias are typically migratory in the larger peripheral joints, including knees, ankles, and wrists, but can have essentially any presentation |
+ | **May be present for up to 6 years before development of other symptoms |
||
− | * The diarrhea is intermittent, with colicky abdominal pain |
||
+ | **May be polyarticular or oligoarticular |
||
− | ** Diarrhea can be watery or have steatorrhea |
||
+ | **Rarely destructive |
||
− | ** Occasional GI bleeding |
||
+ | *The diarrhea is intermittent, with colicky abdominal pain |
||
+ | **Diarrhea can be watery or have steatorrhea |
||
+ | **Occasional GI bleeding (25%) |
||
+ | **Malabsorption may lead to hypoalbuminemia, peripheral edema, and ascites |
||
+ | *Also common are fevers (45%), myalgias (25%), lymphadenopathy (45%) (mainly mesenteric or mediastinal with non-caseating granulomas) |
||
+ | *Bloodwork shows anemia (81%), leukocytosis (48%), thrombocytosis (56%), and elevated [[CRP]] (69%) |
||
− | === |
+ | === Transient Whipple Disease === |
+ | * Transient, acute presentation of fever and diarrhea |
||
− | * Fever in 25 to 40% |
||
+ | * Occurs mainly in children in Africa |
||
− | * Lymphadenopathy, mostly of mesenteric and mediastinal nodes |
||
− | * CNS disease |
||
− | ** [[Dementia]], [[supranuclear ophthalmoplegia]], [[nystagmus]], and [[myoclonus]] |
||
− | ** [[Oculomasticatory myorhythmia]] and [[oculo-facial-skeletal myorhythmia]] with a supranuclear vertical gaze palsy |
||
− | ** [[Cerebellar ataxia]] |
||
− | ** Symptoms can occur with disease or as a post-treatment relapse |
||
− | * Cardiac disease |
||
− | ** Culture-negative [[endocarditis]], [[pericarditis]], and [[myocarditis]] |
||
− | ** Endocarditis may occur on its own without other features of disease |
||
− | * Skin hyperpigmentation in 40% |
||
− | * [[Pleural effusion]], [[chronic cough]], [[interstitial lung disease]], [[pulmonary hypertension]] |
||
− | * [[Anemia]] in 80%, [[leukocytosis]] in 50%, [[thrombocytosis]] in 50% |
||
− | * Elevated C-reactive protein in 70% |
||
+ | === Asymptomatic Whipple Disease === |
||
− | == Diagnosis == |
||
+ | * Asymptomatic carriage of the bacterium, more common in sewage workers |
||
− | * Samples should be taken from involved sites, with a strong preference for small bowel biopsy if there are GI symptoms, but also synovial or cerebrospinal fluid or heart valve |
||
− | ** Up to 7 to 10 biopsies from small bowel, ideally |
||
− | * Diagnosis is based on: |
||
− | ** Periodic acid-Schiff-positive bacilli in macrophages |
||
− | ** PCR |
||
− | ** Immunohistochemistry |
||
+ | === Localised Whipple Disease === |
||
− | == Management == |
||
+ | * Causes localised [[culture-negative endocarditis]] or CNS infection without systemic systems |
||
− | * Generally treat with parenteral [[Is treated by::ceftriaxone]] 2 g IV daily or [[Is treated by::penicillin]] 2 MU IV q4h for 2 weeks followed by [[TMP-SMX]] DS PO bid for 1 year |
||
+ | * Very difficult to diagnose |
||
− | ** Treatment can precipitate a [[Jarisch-Herxheimer reaction]] |
||
− | ** May also see [[immune reconstitution inflammatory syndrome]] in early treatment |
||
− | * Other options include [[meropenem]], [[doxycycline]], [[macrolides]], [[ketolides]], [[aminoglycosides]], [[rifampin]], [[teicoplanin]], and [[chloramphenicol]] |
||
− | * Consider repeating small bowel biopsies annually for a few years |
||
− | == |
+ | ===Other Symptoms=== |
+ | *Fever in 25 to 40% |
||
− | * Clinical improvement takes 1 to 3 weeks of treatment |
||
+ | *Lymphadenopathy, mostly of mesenteric and mediastinal nodes |
||
− | * Neurologic sequelae may be permanent |
||
+ | *CNS disease |
||
− | * Relapses after treatment, including of CNS disease, can happen in up to a third of patients |
||
+ | **[[Dementia]], [[supranuclear ophthalmoplegia]], [[nystagmus]], and [[myoclonus]] |
||
+ | **[[Oculomasticatory myorhythmia]] and [[oculo-facial-skeletal myorhythmia]] with a supranuclear vertical gaze palsy |
||
+ | **[[Cerebellar ataxia]] |
||
+ | **Symptoms can occur with disease or as a post-treatment relapse |
||
+ | *Cardiac disease |
||
+ | **Culture-negative [[endocarditis]], [[pericarditis]], and [[myocarditis]] |
||
+ | **Endocarditis may occur on its own without other features of disease |
||
+ | *Skin hyperpigmentation in 40% |
||
+ | *[[Pleural effusion]], [[chronic cough]], [[interstitial lung disease]], [[pulmonary hypertension]] |
||
+ | *[[Anemia]] in 80%, [[leukocytosis]] in 50%, [[thrombocytosis]] in 50% |
||
+ | *Elevated C-reactive protein in 70% |
||
+ | |||
+ | === Immunosuppression === |
||
+ | |||
+ | * Likely related to reactivation of latent infection, often in the context of [[HIV]] and [[IRIS]] |
||
+ | * Can present with any of the above syndromes |
||
+ | |||
+ | ==Diagnosis== |
||
+ | |||
+ | *Samples should be taken from involved sites, with a strong preference for small bowel biopsy if there are GI symptoms |
||
+ | **At least 5, and ideally up to 7 to 10, biopsies from small bowel |
||
+ | **Other possible sites include synovial fluid or joint tissue biopsy, lymph node biopsy, CSF or brain biopsy, aqueous humour, cardiac valves, intervertebral disk biopsy, or PCR of blood |
||
+ | *Diagnosis is based on the presence of any of the following: |
||
+ | **Presence of oculomasticatory or oculo-facial-skeletal myorhythmia |
||
+ | **Periodic acid-Schiff-positive (PAS-positive) bacilli in macrophages on small bowel biopsy |
||
+ | **Two different positive tests (PAS, PCR, or IHC) on a single sample |
||
+ | **One positive test (PAS, PCR, or IHC) on two different samples |
||
+ | *In Canada, [https://cnphi.canada.ca/gts/reference-diagnostic-test/5435?labId=1006 PCR is done at the NML] |
||
+ | |||
+ | ==Management== |
||
+ | |||
+ | *All patients should have lumbar puncture to send CSF for PCR |
||
+ | *Consider echo to rule out valve involvement |
||
+ | *Generally treat with parenteral [[Is treated by::ceftriaxone]] 2 g IV daily or [[Is treated by::penicillin]] 2 MU IV q4h for 2 weeks (classic) or 4 weeks (endocarditis or CNS disease), followed by [[TMP-SMX]] DS PO bid for at least 1 year |
||
+ | **Treatment can precipitate a [[Jarisch-Herxheimer reaction]] |
||
+ | **May also see [[immune reconstitution inflammatory syndrome]] in early treatment |
||
+ | **Other options include [[meropenem]], [[doxycycline]], [[macrolides]], [[ketolides]], [[aminoglycosides]], [[rifampin]], [[teicoplanin]], and [[chloramphenicol]] |
||
+ | *Consider repeating small bowel biopsies annually for a few years |
||
+ | {| class="wikitable" |
||
+ | !Syndrome |
||
+ | !Induction |
||
+ | !Maintenance |
||
+ | |- |
||
+ | ! colspan="3" |Initial |
||
+ | |- |
||
+ | |General |
||
+ | |[[ceftriaxone]] 2 g IV daily for 2 weeks |
||
+ | | rowspan="4" |[[TMP-SMX]] DS 1 tablet bid for 1 year |
||
+ | |- |
||
+ | |Endocarditis |
||
+ | | rowspan="2" |[[ceftriaxone]] 2 g IV daily for 4 weeks |
||
+ | |- |
||
+ | |CNS disease |
||
+ | |- |
||
+ | |[[β-lactam allergy]] |
||
+ | |[[meropenem]] 1 g IV q8h for 2 to 4 weeks |
||
+ | |- |
||
+ | |Sulfa allergy |
||
+ | | |
||
+ | |[[doxycycline]] 100 mg p.o. bid plus [[hydroxychloroquine]] 200 mg p.o. tid for 1 year |
||
+ | |- |
||
+ | ! colspan="3" |Relapse |
||
+ | |- |
||
+ | |All |
||
+ | |[[ceftriaxone]] 2 g IV <u>q12h</u> for 4 weeks |
||
+ | |[[TMP-SMX]] DS 2 tablets bid for 1 year |
||
+ | |- |
||
+ | |Sulfa allergy |
||
+ | | |
||
+ | |[[doxycycline]] 100 mg p.o. bid plus [[hydroxychloroquine]] 200 mg p.o. tid for 1 year |
||
+ | |} |
||
+ | |||
+ | ==Prognosis== |
||
+ | |||
+ | *Clinical improvement takes 1 to 3 weeks of treatment |
||
+ | *Neurologic sequelae may be permanent |
||
+ | *Relapses after treatment, including of CNS disease, can happen in up to a third of patients |
||
{{DISPLAYTITLE:''Tropheryma whipplei''}} |
{{DISPLAYTITLE:''Tropheryma whipplei''}} |
Latest revision as of 13:52, 4 May 2023
Background
Microbiology
- Fastidious Gram-positive bacillus
Epidemiology
- Ubiquitous environmental organism, but rarely causes disease with only about 12 new cases diagnosed annually worldwide
- Can be found in saliva of one third of healthy people
- Disease is more common in white European (98%) males (85%)
- Mean age at diagnosis is 40 to 60 years
- Farming or occupational soil/animal/sewage exposures are common
Pathophysiology
- Lack of host immune response
Clinical Manifestations
Classic Whipple Disease
- Cardinal features include: arthralgias (80%), followed by weight loss (90%), diarrhea (75%), and abdominal pain (60%)
- Arthralgias are typically migratory in the larger peripheral joints, including knees, ankles, and wrists, but can have essentially any presentation
- May be present for up to 6 years before development of other symptoms
- May be polyarticular or oligoarticular
- Rarely destructive
- The diarrhea is intermittent, with colicky abdominal pain
- Diarrhea can be watery or have steatorrhea
- Occasional GI bleeding (25%)
- Malabsorption may lead to hypoalbuminemia, peripheral edema, and ascites
- Also common are fevers (45%), myalgias (25%), lymphadenopathy (45%) (mainly mesenteric or mediastinal with non-caseating granulomas)
- Bloodwork shows anemia (81%), leukocytosis (48%), thrombocytosis (56%), and elevated CRP (69%)
Transient Whipple Disease
- Transient, acute presentation of fever and diarrhea
- Occurs mainly in children in Africa
Asymptomatic Whipple Disease
- Asymptomatic carriage of the bacterium, more common in sewage workers
Localised Whipple Disease
- Causes localised culture-negative endocarditis or CNS infection without systemic systems
- Very difficult to diagnose
Other Symptoms
- Fever in 25 to 40%
- Lymphadenopathy, mostly of mesenteric and mediastinal nodes
- CNS disease
- Dementia, supranuclear ophthalmoplegia, nystagmus, and myoclonus
- Oculomasticatory myorhythmia and oculo-facial-skeletal myorhythmia with a supranuclear vertical gaze palsy
- Cerebellar ataxia
- Symptoms can occur with disease or as a post-treatment relapse
- Cardiac disease
- Culture-negative endocarditis, pericarditis, and myocarditis
- Endocarditis may occur on its own without other features of disease
- Skin hyperpigmentation in 40%
- Pleural effusion, chronic cough, interstitial lung disease, pulmonary hypertension
- Anemia in 80%, leukocytosis in 50%, thrombocytosis in 50%
- Elevated C-reactive protein in 70%
Immunosuppression
- Likely related to reactivation of latent infection, often in the context of HIV and IRIS
- Can present with any of the above syndromes
Diagnosis
- Samples should be taken from involved sites, with a strong preference for small bowel biopsy if there are GI symptoms
- At least 5, and ideally up to 7 to 10, biopsies from small bowel
- Other possible sites include synovial fluid or joint tissue biopsy, lymph node biopsy, CSF or brain biopsy, aqueous humour, cardiac valves, intervertebral disk biopsy, or PCR of blood
- Diagnosis is based on the presence of any of the following:
- Presence of oculomasticatory or oculo-facial-skeletal myorhythmia
- Periodic acid-Schiff-positive (PAS-positive) bacilli in macrophages on small bowel biopsy
- Two different positive tests (PAS, PCR, or IHC) on a single sample
- One positive test (PAS, PCR, or IHC) on two different samples
- In Canada, PCR is done at the NML
Management
- All patients should have lumbar puncture to send CSF for PCR
- Consider echo to rule out valve involvement
- Generally treat with parenteral ceftriaxone 2 g IV daily or penicillin 2 MU IV q4h for 2 weeks (classic) or 4 weeks (endocarditis or CNS disease), followed by TMP-SMX DS PO bid for at least 1 year
- Treatment can precipitate a Jarisch-Herxheimer reaction
- May also see immune reconstitution inflammatory syndrome in early treatment
- Other options include meropenem, doxycycline, macrolides, ketolides, aminoglycosides, rifampin, teicoplanin, and chloramphenicol
- Consider repeating small bowel biopsies annually for a few years
Syndrome | Induction | Maintenance |
---|---|---|
Initial | ||
General | ceftriaxone 2 g IV daily for 2 weeks | TMP-SMX DS 1 tablet bid for 1 year |
Endocarditis | ceftriaxone 2 g IV daily for 4 weeks | |
CNS disease | ||
β-lactam allergy | meropenem 1 g IV q8h for 2 to 4 weeks | |
Sulfa allergy | doxycycline 100 mg p.o. bid plus hydroxychloroquine 200 mg p.o. tid for 1 year | |
Relapse | ||
All | ceftriaxone 2 g IV q12h for 4 weeks | TMP-SMX DS 2 tablets bid for 1 year |
Sulfa allergy | doxycycline 100 mg p.o. bid plus hydroxychloroquine 200 mg p.o. tid for 1 year |
Prognosis
- Clinical improvement takes 1 to 3 weeks of treatment
- Neurologic sequelae may be permanent
- Relapses after treatment, including of CNS disease, can happen in up to a third of patients