whipple’s disease ana mae h. quintal medical resident

Whipple’s disease

Ana Mae H. QuintalMedical Resident

General Objectives

To present and discuss a case of a 33/F who presented with chronic diarrhea

To discuss the diagnostic approach to chronic diarrhea;

To discuss Whipple’s disease:EpidemiologyPathogenesisClinical manifestationsDiagnostic methodsTreatmentPrevention and control

General Data

33 year oldFemaleFilipinoSingleManila resident

Chief Complaint

diarrhea

History of Present Illness

18 mos PTAReferred to an ID specialist due to recurrent diarrhea despite more

than 1 year of anti- koch’s medication.

Managed as a case of Tropical sprue; started on folic acid, cyanocobalamin, vitamin C and ferrous sulfate.

3 weeks PTA Presented with soft, non-bloody, non- mucoid, loose stools, ~3 episodes per day, accompanied by bouts of abdominal pain and flatulence.

No fever or no vomiting; still noted to have anorexia and progressive weight loss

2 weeks PTA Diarrhea increased in severity to >10 episodes per day.

Day of admission Persistence of diarrhea with generalized body weakness

Review of SystemsSKIN No easy bruisability, sores, rashes, pruritus, or

hyperpigmentationHEENT No headaches, dizziness or vertigo. Does not wear

corrective glasses. No history of eye pain, blurring of vision, excessive tearing, diplopia; gross hearing is intact. No ear pain, discharge or infection. No post-nasal drip or sinus pain. No history of frequent sore throats

PULMO No cough, hemoptysis, or dyspnea CVS No history of orthopnea, PND, palpitations, chest

pain, or bipedal edema.

Review of systemsURINARY No history of UTIs, intermittency, decreased

caliber of urine flow, or incontinence.RHEUMA Back pain. Generalized myalgia.

No joint pains.NEURO Memory lapses

No history of syncope, seizures or tremors. No numbness or loss of sensation.

HEMA No history of prolonged bleeding.ENDOCRINE No history of polyuria, polyphagia, polydipsia.

No excessive sweating.

Past Medical History

1999- abdominal pain (Status post EGD:

pseudodiverticulum)1999- PTB (treated with anti-Koch’s medication for

6 months then was lost to follow- up)2001- diffuse non- toxic goiter (no meds taken; last

thyroid test 2004- normal)

Personal/Social and Family HistoryNon- alcoholic beverage drinker; non- smokerDenies illicit drug useFamily history of DM type 2; no other herido-

familial diseases

Physical ExamVITAL SIGNS BP 80/ 50mm Hg, CR 121bpm, RR 22 cpm

T 36.8C JVP 4 cm H2OGENERAL Cachectic, conscious, coherent, oriented to person,

place, and timeWeight 23 kg, Height 1.57 m, BMI 9.3 kg/m2

SKIN All extremities were warm to touch. No discolorations, bruises or rashes. No hyperpigmentation

HEENT Normocephalic; anicteric sclerae, pale conjunctivae; no naso-aural discharge; dry oral mucosa; no tonsillopharyngeal congestion; no neck mass; no cervicolymphadenopathy.

Physical examCHEST/LUNGS Equal chest expansion, no retractions, clear breath

sounds, equal tactile and vocal fremitusCVS Adynamic precordium, tachycardic, regular rhythm,

distinct S1/S2, no S3 or S4, no murmurs/gallops, PMI and apex beat at the 5th intercostal space left midclavicular line; full

and equal pulses bilaterally.ABDOMEN flat, normoactive bowel sounds, soft; no

guarding, direct tenderness, or rebound tenderness;no splenomegaly

EXTREMITIES no cyanosis, edema or deformities; no limitation of motion; pale nail beds

RECTAL good sphincteric tone, no fissures, no masses, stool on examining finger

Salient Features

33/ FPreviously treated with anti- Koch’s

Previously treated as a case of Tropical sprueChronic diarrhea

Weight loss

Chronic Diarrhea

To Flow Through

DiarrheaAGA definition:

Decrease in fecal consistency lasting for >4 weeks

Stool >= 200grams/day, or>3 loose or watery stools/day, orIncreased water content of stool

Impaired water absorption, Active water secretion

Lab work- upsCBC, electrolytes, total protein, albumin, thyroid

function tests, radiologic work- ups, endoscopy

Stool analysis- stool osmolality, ph, occult blood, fecal leukocytes, stool fat (quantitative, sudan III)

Fecalysis, stool culture, C. difficile toxin

Selective testing for plasma peptides

Laxative screen

Classification of DiarrheaBy time course ( acute vs chronic )Site ( large vs small )Pathophysiology ( secretory vs osmotic )Epidemiology ( epidemic vs travel- related vs

immunosuppression- related )Stool characteristics ( watery vs fatty vs

inflammatory)

Time courseAcute: < 2 weeks in durationPersistent: > 14 daysChronic: >4 weeksSevere: >4 fluid stools/day for > 3 days

Small vs. Large Bowel DiarrheaSmall bowel:

secretory & nutrient absorbing functions Watery, large volume

diarrhea Bloating, gas,

cramping, profound weight loss, electrolyte disturbances, malabsorption (D-xylose, B12)

Large bowel: storage organ, addtitional absorption of water Frequent, small

volume, painful stools

Bloody, mucoid

Infectious

Parasites: Giardia lamblia, Entamoeba histolytica, Cyclospora

AIDS-related: Viral: Cytomegalovirus,

HIV infection (?) Bacterial: Clostridium

difficile, Mycobacterium avium complex

Protozoal: Microsporida, Cryptosporidium, Isospora belli

Non- infectious

Primary GI diseases – IBS, IBD, malabsorption,celiac, etc.

Non-GI disease states – hyperthyroid, carcinoid, etc.

Drugs (laxatives)Carbohydrate

(Lactose) intolerance

Principal causes of diarrhea depend upon the socioeconomic status of the population.In developing

countries, chronic infections, although functional

disorders, malabsorption, and inflammatory bowel disease are also common.

In developed countries,irritable bowel

syndrome (IBS),inflammatory bowel

disease, malabsorption

syndromes (as lactose intolerance and celiac disease), and

chronic infections (particularly in the immunocompromised).

Secretory vs. OsmoticSecretory

Volumes > 1L/day Occurs day and

night Continues despite

fasting Osmotic gap < 50

Osmotic Due to an

unabsorbable solute High osmotic

pressure -> increased water output

Stops with fasting Osmotic gap > 125

Osmotic gap = 290 – 2x [(stool Na + stool K)]

Osmotic diarrhea

CLUES: Stool volume decreases with fasting; increased stool osmotic gap

1. Medications: antacids, lactulose, sorbitol

2. Disaccharidase deficiency: lactose intolerance

3. Factitious diarrhea: magnesium (antacids, laxatives)

Secretory Diarrhea CLUES: volume ( >1 L/d);

little change with fasting; normal stool osmotic gap

1. Hormonally mediated: VIPoma, carcinoid, medullary carcinoma of thyroid (calcitonin), Zollinger-Ellison syndrome (gastrin)

2. Factitious diarrhea (laxative abuse): phenolphthalein, cascara, senna

3. Villous adenoma4. Bile salt malabsorption

(ileal resection; Crohn's ileitis; postcholecystectomy)

5. Medications

Inflammatory Fever, hematochezia, abdominal pain

1. Ulcerative colitis2. Crohn's disease3. Microscopic colitis4. Malignancy: lymphoma, adenocarcinoma

(with obstruction and pseudodiarrhea)5. Radiation enteritis

Malabsorption:weight loss, abnormal laboratory values, fecal fat > 7- 10 g/ day

Causes:Intraluminal

maldigestion

Pancreatic insufficiency

Bacterial overgrowth

Defective bile secretion

Mucosal – malabsorption

Celiac diseaseTropical sprueInfection – bacteria,

parasitesWhipple’s diseaseIntestinal resection –

short gutAbetalipoproteinemiaCrohn’s disease

Motility disordersSystemic disease or prior abdominal surgery1. Postsurgical: vagotomy, partial gastrectomy,

blind loop with bacterial overgrowth2. Systemic disorders: scleroderma, diabetes

mellitus, hyperthyroidism3. Irritable bowel syndrome

CaseHistory

Gradual onsetIntermittent, watery,

non- bloody diarrheaWeight lossMore than 4 wks

durationNon- diabeticNo history of travelNon- promiscuousNo family history of

malabsorption (celiac disease)

Physical examCachexiaSigns of anemiaNo mouth ulcers, skin

rash, anal fissures/ fistula, no blood on EF on rectal

No exolphthalmos, no thyroid enlargement

Good sphincteric toneNo glossitis,

protruberant abdomen, pedal edema

Admitting Impression

Chronic diarrhea probably secondary to GITB (TB Ileitis) vs Inflammatory Bowel Disease vs Tropical Sprue

Hypovolemic Shock sec to GI Loss

Problem#1: HYPOVOLEMIC SHOCK sec to GI Loss

Upon admission, BP 85- 90/ 70- 75, HR 121, cvp 4- 6;

Impression : Hypotension secondary to hypovolemia sec to GI Loss; TB Ileitis vs Inflammatory Bowel disease vs Tropical

sprue.

ER: Fast dripped a total of 900 cc PNSS. IVF rate increased

Patient was referred to Nephrology service for fluid and electrolyte management.

On 1st HD, CVP was noted to be at 10- 12, BP 90- 110/ 60- 80, HR 120s, afebrile, I and O=3625 vs 1180.

On the 3rd HD, BP stabilized at 90- 100/ 60- 70, HR 90- 100.

However, later on the 3rd HD, CVP was noted to be elevated at 15- 16 cm H2O, RR 24, with neck vein distention. Clear breath sounds by auscultation.

Chest XRAY : pulmonary congestion.

Lasix 20 mg/SIVP was given ; Aldactone 50 mg/tab together with Lasix

Problem #2: ELECTROLYTE IMBALANCE and Hypoalbuminemia

Upon admission, HYPOKALEMIA was noted. K= 2 – 2.6 – 3 – 4Central line insertion was done.KCL drip started: 40 meq KCl in 100 cc PNSS

to run for 8 hours and Kalium durule 1 tab TID

On 1st HD, HYPOALBUMINEMIA Alb= 0.6 – 1.6

Albumin 25% infusion.

On 3rd HD, HYPOCALCEMIA and HYPOMAGNESEMIA

Calcium gluconate 4 amps + 5 grams MgSO4 in 2500 cc D5W at 10 cc/ hr. Despite resolution of diarrhea, hypokalemia was still noted; subsequent potassium correction was done.

Problem #3: DIARRHEAAnd Seizure

Impression on admission was TB Ileitis vs Inflammatory Bowel disease vs Tropical sprue.

Ciprofloxacin 500 mg/ tab BID, and Isoniazid + Rifampicin +Pyrazinamide+ Etambutol (Myrin P Forte) 3 tabs once daily were started upon admission.

On 1st HD, 4 episodes of generalized tonic- clonic seizures of both upper and lower extremities, lasting for 5 secs each, associated with upward rolling of eyeballs; PE: motor 2/5 in the Right UE/LE.

Referred to Neurology service. Impression: Hypokalemic Periodic Paralysis;

Seizure, etiology to be determined. O2 at 2LPM PRN Diazepam 5 mg IV PRN and started on Epival

250 BID.

On 2nd HD, still with seizure episode ~6x. complained of difficulty moving head to the

right, nape pain, numbness of Left LE. On PE: left- sided hemiplegia, flaccidity, hyperactive DTR, L.

Impression: Todd’s paralysis. EEG was abnormal due to excess theta

waves.

MRI/ MRA of the brain- Small, acute infarct, Left parietal subcortical white

matter; consider low- grade glioma, Right frontal lobe; filling defect in the superior sagittal sinus with

tortuous cortical vessels, consider superior sagittal sinus thrombosis with collateral formation.

Impression : Acute Infarct left parietal subcortical white matter.

On the 3rd HD, Medical Junta was done On consensus, impression was Whipple’s

Disease. Plan : EGD with biopsy and PAS tissue

staining, once patient is hemodynamically and nutritionally stable, to confirm diagnosis

Ciproflaxacin and Myrin P Forte were discontinued

Co- Trimoxazole 800/ 100 mg/ tab I tab BID was started.

Cyanocobalamin 1 cc IM every 10 days, Vitamin A 25, 000 units, 2 caps 4x a day for 8 doses, Folic Acid 5 mg/ tab I tab OD, Ferrous sulfate 325 mg/ tab 1 tab OD.

Epival 250 BID was discontinued; Depacon 1 amp in 100 cc PNSS in 1 hour every 6

hours was started and Dexamethasone was discontinued.

On the 4th HD, diarrhea and seizure resolved.

However, on the 7th HD, noted to have recurrence of loose- watery stools~ 5x but resolved the next day.

Repeat EEG on the 13th HD showed abnormal EEG due to mild diffuse slowing of background activity at 7Hz and frequent delta slow waves or sharp waves R>L frontocentroccipital region

On the 12th HD, she underwent EGD and biopsyResults: mild erythema and friability of gastric

especially antral mucosa; mild granularity of jejunal mucosa.

Histopathology result showed only chronic inflammation, moderate (jejunum)

tissue PAS staining negative for histiocytes.

Pathology ReportJEJUNUM BIOPSY

Specimen consists of five pieces of pink-red, soft, ovoid tissues

Measurement : 0.3 to 0.4 cmBlock all

LYMPHOCYTES

Control Test

Negative in histiocytes

Final diagnosisCHRONIC INFLAMMATION,

MODERATE, JEJUNUMPERIODIC ACID SCHIFF(PAS) :

NEGATIVE IN HISTIOCYTES

On 13th HD, rashes on neck, abdomenImpression : Hypersensitivity Reaction sec to

Co- Trimoxazole.

Bactrim was discontinued; Doxycycline 100 mg/ tab 1 tab OD was started.

A 1st 2nd 3rd 4th 5th 6th 7th 8th 9th 10th 11th 12th 13th 14th 15th 16th

Diarrhea

Myrin P

Hospital Days

Ciprofloxacin

Seizure

Co-trimoxazole

Folic Acid, Cyanocobalamin, Depakote

Doxycycline

Hyp

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Whi

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23.4 kg23 kg

24.2 kg

Problem #5: ANEMIA

On 8th HD, Hgb 6.6, Hct 22; Repeat Hgb: 6.7, 2 unit PRBC was transfused. Peripheral blood smear, RBC indices were

normal. Serum iron, serum ferritin were slightly decreased and stool for occult blood was positive.

On the 9th HD, anemia resolved. Repeat Hgb= 12.

Final Diagnosis:

Whipple’s Disease

On 16th HD, dischargedHome Meds:

Doxycycline 100 mg/ tab 1 tab OD

Cyanocobalamin 1cc IM every 5 days

Folic Acid 0.5 mg 1 tab TID

Ferrous Sulfate gr5 1 tab OD

Vitamin C 500mg/ tab, 1 tab OD

1/06 1/07 1/08 1/09 1/10 1/11 1/13 1/14 1/16 1/17 1/19

Na 134 139 143 145 143 138 136

K 2-- 2.6

3– 2.8 4 3.8 2.8 3.3 2.8 3.6 3.8 3.5

Chloride 114

Albumin 0.6 1.6 1.9 2 1.8 2.3

Urea 9 7 6 6 11 9

Creatinine 0.6 0.5 0.5 0.6 0.6 0.5

Magnesm(1.8- 2.4)

1.5 1.5 2.4 1.3 2.3 1.6

Ion Calcium(1.12- 1.32)

5.8 1.01 1.23 1.18 1.11

SGPT 23

SGOT 17

Alka phos 125

TB 1.1

Cholesterol 41

1/06 1/14 1/14 1/15 1/17 1/22

Hgb 10.5 6.6 6.7 12.1 11.6 12

Hct 31 22 22 37.2 36.9 38

RBC 4.6 4.5 4.6

MCV 80.4 (82-92)

MCH 24.4 (27- 31)

MCHC

30.3 (32- 36)

WBC 14, 150 7,200 7390 8,380 6400

Eeos 1

Myelo 1

Meta 1

Seg 94 90 89 83 70

Lym 3 5 9 7 18

Mono 3 2 2 9 10

Platelet 211, 000 130, 000 136, 000 225, 000 538,000

Retic Ct 1.1% (5-15)

PTH intact- 93.8 (10- 65) TSH normal 0.3, FT3 dec

3.8 (4.2- 12), FT4 normal 11 1/10 Lupus panel- negative 1/15 Anti- Cardiolipin

antibody- 6 (<15) 1/15 occult blood- positive 1/15 Peripheral Blood

Smear- hypochromic anemia with

anisocytosis; few polychromasia; relative neutrophilia; no abnormal cells seen; platelets slightly decreased

1/12 Blood CS- no growth

1/13 Blood CS- no growth

1/04 stool CS- no growth

1/14 Iron studies

Serum iron- 35 (35- 150)

Serum TIBC – 67 (250- 450)

Total Sat- 35/ 67 = 52.23

1/06 Chest Xray- normal

1/09 Chest Xray-- veil of haziness in the

R mid to lower hemithoraces obliterating the right hemidiaphragms compatible with pleural effusion;

accentuation of pulmonary vasculature due to congestion

1/06 ecg- sinus tachycardia, left axis deviation

1/09 2D- Echo- normal, ejection fraction 61%, mitral regurg- mild, tricuspid regurg- trace; minimal pericardial effusion

1/08 MRI of brain

Small, acute infarct, Left parietal subcortical white matter

Consider low- grade glioma, Right frontal lobe

Filling defect in the superior sagittal sinus with tortuous cortical vessels, consider superior sagittal sinus thrombosis with collateral formation

1/07 EEG- abnormal eeg due to excess theta waves bilaterally

1/18 EEG- abnormal; eeg due to diffuse slowing of background activity, Left frontocentrooccipital region

DiscussionWhipple’s Disease

Epidemiologya rare infectious disorder caused by Tropheryma

whipplei. first described in1907 (35), only 696 cases reported between 1907 and 1987,

annual incidence of approximately 30 cases per year since 1980.

chronic, systemic infection affecting mostly middle-aged males (28, 33).

underlying genetic predisposition that leads to colonization of T. whipplei throughout the intestinal tract, lymphoreticular system, and central nervous system

Tropheryma whippleiisolated in a cell culture from a patient with

endocarditis (24).aerobic, rod-shaped, gram-positive, non- acid

fast, periodic acid-Schiff (PAS) positive bacillusmember of the Actinomycetes (placed between

the genus Cellulomonas and the Actinomycetes clade)

found both intracellularly and extracellularly (8).grow slowly in acidic vacuoles of cells

Pathogenesis /Immunology

host immune deficiency and possibly secondary immune downregulation are reponsible

source of transmission is unknown - likely per oralThe bacteria most commonly invades the intestinal lamina

propria and the vacuoles of "foamy" macrophagestissue macrophages are unable to kill and clear

T.whipplei. CD11b on macrophages mediates intracellular degradation of ingested bacteria

This deficiency in killing then causes Whipple’s disease

Pathogenesis

The route of invasion is via the lamina propria and basal intercellular spaces, rather than the intestinal lumen

accumulation of massive numbers of organisms within the intestinal tract, subsequent impaired nutrient absorption.

Noncaseating granulomas are found in surprisingly few patients (less than 10%)

Clinical Manifestations There are four cardinal clinical

manifestations of Whipple's disease

Arthralgias Weight loss Diarrhea Abdominal pain

Symptoms of 21 patients with Whipple disease ( Hamburg Series 1965 - 1983 )

von Herbay A, Otto HF (1988). Whipple´s disease. A report of 22 patients. Klin Wochenschr 66: 533-539

Weight Loss 14 (67%)

Chronic Diarrhea 13 (62%)

Arthralgias/Arthritis 13 (62%)

Abdominal Pain 11 (52%)

Skin Hyperpigmentation 8 (38%)

Myalgia 6 (28%)

Lymphadenopathy 3 (14%)

Fever 2 (10%)

Abdominal Tumor 1 ( 5%)

Sleeping Disorder 1 ( 5%)

Cerebral Syncope 1 ( 5%)

Gastric Ulcer 1 ( 5%)

Dyspnea 1 ( 5%)

Less common symptoms include

fever and skin hyperpigmentation symptoms or signs related to cardiac disease

(dyspnea, pericarditis, culture-negative endocarditis),

pleuropulmonary (pleural effusion), mucocutaneous disease;

nonthrombocytopenic purpura can also occur

GI FeaturesWeight loss: usually 20-30 lbs. May present years

before diagnosis.

Early GI symptoms are nondescript, often diagnosed as IBD.

Diarrhea: steatorrhea, but may be watery.

Abdominal pain tends to be epigastric and exacerbated following meals.

CNS Features21–43% of cases of Whipple's disease have

neurologic symptoms 43% - 100% have central nervous colonization Characteristic triad:

DementiaExternal opthalmoplegiaFacial myoclonus

Oculomasticatory myorhythmia (OMM) is diagnostic.

CNS colonization may serve as a repository for bacteria and a mechanism for CNS relapse

CNS FeaturesImaging:

generalized cerebral atrophy, scattered small chalky nodules in cortical and subependymal gray matter (true granulomas that contain PAS-positive foamy macrophages)

Areas of intense demylination resembling MSMicro-infarcts

CNS disease — Cognitive dysfunction is the most common

abnormality but two findings, at least one of which is present

in approximately 20 percent of such patients, are considered pathognomonic for Whipple's disease:oculomasticatory myorhythmia (continuous

rhythmic movements of eye convergence with concurrent contractions of the masticatory muscles), and

oculo-facial-skeletal myorhythmia

A variety of other neurologic findings have been described in case series, including dementia, myoclonus, hemiparesis, peripheral neuropathy, seizures, and upper motor neuron disorders

supranuclear ophthalmoplegia, nystagmus, and myoclonus occur more frequently (21 percent in one series) in the later stages of the disease

Endocarditis — Whipple endocarditis has been described in a small number of patients. Affected patients may have no clinical or histologic evidence of gastrointestinal disease or arthralgias. Endocarditis caused by T. whipplei may not be associated with the classical clinical presentation of Whipple's disease.

Common clinical syndromes that suggest the possible diagnosis of Whipple's disease include

fever of unknown origin, chronic serositis, progressive central nervous system disease with myoclonus or ophthalmoplegia, migratory polyarthropathy, and generalized lymphadenopathy.

Vitamin or iron deficiency anemia, hypoalbuminemia, and relative lymphopenia should increase the level of suspicion.

Among the disorders which should be excluded prior to making a diagnosis of Whipple's disease are:

Hyperthyroidism Connective tissue disease Inflammatory bowel disease with migratory

polyarthropathy AIDS

Diagnosis Periodic acid schiff:

PAS-positive, diastase-resistant inclusions on light microscopy

Confirmed by characteristic trilaminar cell wall

Polymerase Chain reaction:

PCR-sequenced bacterial 16sRNA

PCR can be applied to duodenal tissue, lymph node, pleural-fluid cells, and peripheral blood

Abnormal Labs:

ESR, CRP

anaemia of chronic disease

hypoalbuminaemia

DiagnosisThe diagnosis of Whipple's disease is usually

readily apparent upon Periodic Acid- Fast Schiff Stain (PAS)staining of jejunal biopsies

extensive PAS-positive material (granular foamy macrophages stained purple with PAS)

and villous atrophy

The hallmark of Whipple’s disease is the histopathological finding of macrophages containing diastase-resistant p-aminosalicylic acid (PAS)-positive material, which are T. whipplei bacteria or partly digested remnants thereof.

Bacilli with a characteristic trilamellar wall is specific for Whipple's disease.

List of organisms that stain positively with the periodic acid Schiff reagentActinomycetes Atypical mycobacteria Mycobacterium avium intracellulare55 Mycobacterium genavense Bacillus cereus56 Corynebacterium spp Fungi Histoplasma Rhodococcus equi57 (Corynebacterium equi)

Evaluation

*** the patient may not have any finding due to suppression by preceding anti- tuberculous treatment inclusive of Rifampicin, which has a bactericidal effect on t. whipplei

Definitive Diagnosisincludes immunohistochemistry and PCR assays for

various target genes on biopsy samples

The PCR assay has become an important diagnostic tool for the diagnosis of Whipple’s disease, especially :in patients with unusual presentations and

in patients in which the diagnosis cannot be confirmed histologically.

The mere presence of DNA of T. whipplei, as demonstrated by PCR, without a demonstration of the macrophages harboring it, is not Whipple’s disease.

Treatment Tetracycline became the mainstay of therapy

for many years. high relapse rate of 35 percent among patients

treated primarily with tetracycline. Even more alarming was a high rate of CNS relapse, and a dismal response (five percent) to retreatment of CNS relapse with tetracycline.

A combination of streptomycin (1 g) and benzylpenicillin

(penicillin G; 1.2 million units) for 14 days and thereafter

oral cotrimoxazole (trimethoprim-sulfamethoxazole; 160 mg/800 mg twice daily) for 1 year

With this treatment regimen, however, relapses have been reported after cessation of antibiotic therapy (5, 11, 17).

may be because trimethoprim-sulfamethoxazole is

only bacteriostatic despite the high intracellular concentrations

These observations led the authors to recommend an initial course of

parenteral ceftriaxone followed by maintenance therapy with oral

trimetophrim- sulfamethoxazole (TMP-SMX, one double-strength tablet twice daily) for one year.

These observations led the authors to recommend an initial course of

parenteral ceftriaxone followed by maintenance therapy with oral

trimetophrim- sulfamethoxazole (TMP-SMX, one double-strength tablet twice daily) or oral doxycycline (100 mg twice daily) for 1 year.

Doxycycline, rifampin, macrolides, and aminoglycosides have been shown to be highly active against strict intracellular bacteria such as T. Whipplei, Rickettsia spp., C. burnetii, and Ehrlichia spp.

• combination of doxycycline and hydroxychloroquine was bactericidal.

Pen G 6- 24M U IV OD+ Streptomycin 1g IM OD

Ceftrixone 2g IV OD

Co- Trimoxazole 160/ 800 PO BID

Doxycycline (or tetracycline) 100 mg PO BID

- induction (first 10- 14 days)

- induction (first 10- 14 days)

-long- term therapy; first line drug; good CNS penet but prone to relapse

-used for many years

The rationale for prolonged therapy is to permit complete eradication of the organism, thereby reducing the likelihood of relapse.

No prospective studies are available on the choice or duration of antibiotic treatment.

At present, therapy is based on observations in small patient groups and personal experience.

ConclusionsWhipple’s disease is a systemic infectious disorder

The disease requires an immunologic disposition in order for the disease to manifest itself.

Although Whipple's disease has a reputation as a great mimicker of many different illnesses, the difficulty in diagnosis is probably more a function of its rarity than its stealth.

should be considered in all patients with the four cardinal manifestations mentioned

ConclusionsThe diagnosis should be considered in:

Unexplained malabsorption on a background of systemic disease

Unexplained systemic granulomatous disease resembling sarcoidosis

Neurological disease characterized by myoclonus, dementia, and supranuclear ophthalmoplegia

Unexplained culture negative endocarditisUnexplained uveitis

ConclusionsDiagnosis can be made by PAS staining or PCR

Biopsies can be taken from the small intestine, lymph nodes, bone marrow, muscle, synovium, and the spinal cord.

Antibiotic treatment options are effective.

Follow up is important to diagnose relapse.

Case OutcomeWeight upon discharge

Jan22’08: 24.8 kgHome Meds:Doxycycline 100 mg/

tab 1 tab ODCyanocobalamin 1cc

IM every 5 daysFolic Acid 0.5 mg 1 tab

TIDFerrous Sulfate gr5 1

tab ODVitamin C 500mg/ tab,

1 tab OD

Follow- up Feb’08Weight: 29.5 kgNo recurrence of

diarrhea

Current weight: 35 kg

RecommendationsRequires a strong index of suspicion, but PCR

is a definitive diagnosis