Treatment and Follow-Up
On admission, intravenous albumin infusions were administered because of symptomatic severe hypoalbuminemia in all 3 patients. Metronidazole 20 mg/kg/day for 15 days was commenced in all patients. Dietary modification with high protein content was recommended, and vitamin B12, vitamin D and iron were also supplemented. After metronidazole treatment, signs, symptoms and laboratory findings were found to be dramatically improved. The first and second cases were reevaluated with upper GI endoscopy 3 months after cessation of treatment, and histopathologic examination demonstrated resolution of previous findings (Figure 1B). All patients have been asymptomatic, and their laboratory examinations have been normal for the last 12 months of follow-up (Table 1).
PLE is characterized by severe loss of serum protein into the intestinal lumen; therefore, hypoproteinemia is the most prominent clinical finding.1 The differential diagnosis of hypoproteinemia also includes inadequate dietary intake, impaired synthetic capacity of the liver, proteinuria, lymphatic obstruction and widespread inflammation of vasculature, as in sepsis. Two of our patients had mild malnutrition, but this finding could not account for severe hypoalbuminemia. Fecal α-1 antitrypsin is a noninvasive test for the diagnosis of PLE6 and was found to be higher than normal in 2 of our 3 patients. Thus, PLE was suspected because of concomitant GI signs and symptoms in the absence of proteinuria or liver dysfunction.
Various causes of PLE are mostly secondary to enteric lymphatic obstruction, cardiac disorders associated with increased systemic venous pressure and mucosal inflammation, in association with defective enterocyte barrier function.6 Several GI pathogens (Strongyloides stercoralis, Salmonella, Shigella, rotavirus) including G. lamblia can damage the intestinal mucosa and impair the enterocyte barrier function by disrupting the epithelial brush border and tight junctions. Giardiasis usually presents with mild symptoms such as abdominal pain and chronic diarrhea in immunocompetent individuals. However, children who are repeatedly exposed to contaminated water sources or those who are immunocompromised may present with a variety of symptoms, ranging from malabsorption to severe villous atrophy. Diarrhea was the predominant complaint in our patients. Abdominal distention and edema were other findings compatible with malabsorption. Anemia, vitamin deficiencies and low serum ferritin level may be associated with inadequate dietary intake or malabsorption, or both. Iron deficiency is a known complication of giardiasis; consistent with the literature, severe anemia was observed in all 3 cases.7
Examination of concentrated, iodine-stained wet stool preparations and modified trichrome-stained permanent smears has been the conventional approach to the diagnosis of Giardia infection. However, intermittent excretion of cysts and trophozoites in feces might hinder the detection of parasites despite multiple stool examinations. Therefore, molecular tests based on enzyme-linked immunosorbent assay for detection of Giardia antigens have high sensitivity and specificity and should be considered for initial diagnostic testing. One study compared microscopic examination of stool samples for parasites with stool antigen tests, and the sensitivity of the tests was reported as 83% and 95%, respectively.8 Repeated stool examination for Giardia antigen was positive in all of our cases, and trophozoites were recognized on microscopic examination of feces in case 3. The reported sensitivity of stool examination is 85%, and repeated examinations contributed to the accuracy, while the microscopic analysis of duodenal aspirate for Giardia trophozoites had a sensitivity of 44%.9 As a routine endoscopic procedure in our unit, duodenal aspirates are collected for microscopic analysis for Giardia trophozoites, which were detected in case 1. Identification of trophozoites within small intestinal biopsy specimens may require careful examination of multiple microscope fields, while direct sampling of duodenal aspirate in the same patient may improve sensitivity.10
Giardiasis is a known cause of non-celiac villous atrophy.2,3 Consistent with the literature, duodenal biopsies of all cases in our study demonstrated villous abnormalities such as total or subtotal atrophy of intestinal villi and lymphoplasmocytic inflammation in the lamina propria of the intestinal epithelium. After treatment, follow-up endoscopies performed in 2 of the 3 patients demonstrated complete resolution of histopathologic findings. Thus, we clearly identified a causal association between PLE and giardiasis based on symptom resolution, in addition to laboratory and histopathologic findings. To our knowledge, this is the second published report demonstrating histopathologic recovery after treatment of Giardia infection.3
In conclusion, Giardia is a common cause of diarrhea, particularly in developing countries. It may rarely be complicated by PLE in association with common GI symptoms. Giardiasis is a treatable cause of PLE, which can be associated with severe comorbidities. Early recognition and treatment of Giardia infection presenting with PLE results in rapid clinical, laboratory and histopathologic recovery, thus, preventing malnutrition, particularly in growing children.
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Keywords:Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
giardiasis; protein-losing enteropathy; hypoalbuminemia