Infectious Diseases Case of the Month Case #37

A 62 year old hispanic male was admitted to the hospital via the emergency room for severe diarrhea and weight loss.

He had been having diarrhea, sometimes severe, for the preceding eight months with an accompanying forty pound weight loss. He had not had nausea, vomiting, abdominal pain, or fever, nor had he noticed blood in his stools. He did experience anorexia and an "aversion" to food. For perhaps the last five years he had been experiencing "rheumatic pain" (his term) which he characterized as muscle aches and swelling of his hands and fingers. He had been taking a steroid containing substance/medication he had obtained in Mexico for those symptoms.

He was Mexican born but had been living in southern California for the preceding twenty years. He had been previously healthy and had been working as a "gardener" until his illness prevented him from doing so. Recently, family member living in Oregon had prevailed upon him to move to their home when his symptoms had become debilitating.

At the time of his initial evaluation he appeared very ill, and his skin appeared hyperpigmented. He was alert and appeared to have normal cognitive abilities as best could be assessed via an interpreter. Cardiac exam was notable for a grade II/VI systolic murmur. He exhibited lower extremity edema. He did not have obvious synovitis. Stool was heme positive. Laboratory data included WBC 13.8 (H), Hgb 8.4 (L), albumin 2.1 (L), and normal hepatic enzymes. A CT scan of the abdomen and pelvis showed trace ascites but was otherwise unremarkable. Stools for enteric pathogens and ova and parasites were negative as were blood cultures.

The patient was seen in consultation by a gastroenterologist who performed esophagogastroduodenoscopy and colonoscopy. Upon entering the small bowel and to the maximum extent into which he could advance the endoscope (into the jejunum), the endoscopist observed intense erythema and edema of the bowel mucosa with an indistinct villous pattern and "millions of dilated lacteals" (see representative photo of duodenum at upper left). The colon was normal, but examination of the terminal ileum showed findings similar to those of the proximal small bowel although the erythema was less intense.

Biopsies were taken of the duodenum, jejunum, and ileum. All showed abnormal inflammatory changes as pictured at left (two lower images). Special stains for fungi and AFB were negative. A larger image of the periodic acid-Schiff (PAS) stained specimen can be seen by clicking here. An HIV antibody was negative.

 

Of the choices below what is the likely the cause of this illness?

       
What was the likely cause of this illness?
   
     
Diagnosis: Tropheryma whipplei
   

Small bowel biopsies showed periodic acid-Schiff (PAS) staining granular inclusions characteristic of Whipple's Disease (caused by Tropheryma whipplei). The diagnosis was confirmed with specific immunohistochemical stains done at Johns Hopkins Reference Laboratories.

This patient had classic symptoms of Whipple's Disease, and the diagnosis was achieved via small bowel biopsies. Routine hematoxylin and eosin (H&E) stain (upper left) showed markedly distended villi infiltrated with foamy macrophages within the lamina propria. Click here for a larger image. PAS staining (lower left) was diagnostic in this case given the classic symptomatology. Periodic acid-Schiff stain intensely stains glycoprotein granular "particles" of the organism (the cell wall). Click here for a larger image of the PAS stain.

Whipple's Disease is a rare multisysterm disorder first described by George Hoyt Whipple in 1907. The cause of this illness was poorly understood for many years. A bacterial cause came to be suspected as diagnostic and therapeutic advances occurred although a specific organism could not be cultured. In the 1990's DNA sequencing established the relationship of the bacterium to the actinomycetes and allowed for sensitive diagnostic testing using PCR. Tropheryma whipplei was finally grown in very specialized laboratory cell culture in 2000. This organism is said to be found ubiquitously in the environment, and many persons are colonized asymptomatically. It is believed that host immune factors predispose individuals who develop disease though those factors remain poorly defined.

Earlier epidemiological studies (mainly from the U.S.) suggested a higher prevalence of this disease in relatively young (mean age 49) males of European ancestry. More recent reports (mainly of German patients) suggested an increasing proportion of female patients and an increase in age at the time of diagnosis (age 57).

The principle signs and symptoms of Whipple's Disease are arthralgia, malabsorption/diarrhea, weight loss, and abdominal pain. The rheumatological symptoms may precede the gastrointestinal symptoms by years as occurred in the case described. Serious complications can include central nervous system involvement and "culture negative" infective endocarditis.

The patient in the preceding vignette underwent trans-esophageal echocardiography which did not suggest the presence of endocarditis. In addition, he underwent lumbar puncture with normal results including a negative PCR for T. whipplei. He was treated with two weeks of IV ceftriaxone and then continued on oral TMP/SMX. His intestinal symptoms quickly improved. TMP/SMX was used as it is preferred to tetracycline, a therapy commonly used in the past. Tetracycline therapy has been shown to have a disturbingly high rate of CNS relapse with a very poor response to subsequent retreatment.

In HIV patients Rhodococcus equi and Mycobacterium avium-intracellulare can rarely cause disease that could appear similarly on PAS stain of small bowel specimens. Small bowel infection with Histoplasma capsulatum could also rarely have similar appearance pathologically (see Case #6). Coccidioides immitis infection of the intestinal tract is extraordinarily rare and would be distinguishable pathologically.

Ref: Schneider, et al, Whipple's disease: new aspects of pathogenesis and treatment, http://infection.thelancet.com, Vol 8, 179-190, March 2008


 

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