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LayoutREGIS VAILLANCOURT, RABIAH SIDDIQUI, CHRIS VADEBONCOEUR, MARION RATTRAY, and DORIS LARIVIÈRE, Roger’s House Pediatric Palliative Hospice, Ottawa, Ontario, Canada INTRODUCTION
Lactose intolerance is a clinical deficiency of the C.H., a three-and-a-half-year-old Caucasian boy, intestinal enzyme lactase, which is responsible for was admitted for a routine respite stay at a hydrolyzing the milk sugar lactose into glucose pediatric palliative care hospice in the fall of 2006.
and galactose for absorption. Such a deficiency C.H. was born with complex congenital anomalies results in abdominal pain, distention, borborygmi, including pontine dysplasia, optic pituitary dys- flatulence, diarrhea, or, occasionally, systemic plasia, central diabetes insipidus, adrenal insuf- ficiency, hypothyroidism, epilepsy, and gastric symptoms such as muscle and joint pain, fatigue, eczema, and mouth ulcers upon ingestion of dis- glycemia. In 2004, a fundoplication procedure had accharide (1). In children, symptoms can become been performed to manage his severe gastro- severe and prolonged, and may also be associated esophageal reflux disease. Although there was with complications such as bacterial proliferation, no prior history of lactose intolerance, he was on dehydration, and metabolic acidosis. Infants with an enteral lactose-free feed with a strict volume galactosemia, a condition in which galactose intake of 1,845 ml daily. In the summer of 2006, cannot be converted to the metabolically useful a dietary switch from the formula Peptamen sugar glucose, experience similar illness with Jr. (Nestlé Inc.) to Nutren Jr. (Nestlé Inc.) was lactose ingestion (2). Lactose intolerance affects concurrent with resolution of his dumping syn- 33 to 50 percent of the world’s population and drome and hypoglycemia, as well as his seizures.
becomes increasingly common with age, as most Although these symptoms had resolved, C.H.
mammals lose 70 to 90 percent of their lactase continued to suffer from gastrointestinal discom- enzyme within a few years of weaning (3, 4).
fort and intense pain, manifested as sporadic Lactase deficiency varies widely with race: Afri- screaming episodes and abdominal distention.
can American, Native American, Middle Eastern, C.H. communicated only via touch, since he could and Asian populations have the highest incidence not see, hear or speak. C.H.’s mother described his (60 to 90 percent), whereas only 10 percent of symptoms as “neurological screeching;” his bloat- ing was so intense that venting of his gastric tube affected (5). While there is patient variation in using a syringe yielded 1,000 ml of gas at a time.
C.H. was on a complex medication regimen that tolerance, the majority experience gastrointestinal included desmopressin (Ferring Pharmaceuticals, symptoms after the ingestion of approximately 0.025 mg p.o bid, 0.05 mg p.o qhs), clonidine 10 g of lactose, equivalent to one glass of milk (5).
(Novopharm Ltd., 0.05 mg p.o qhs), hydrocorti- Currently, diagnostic tests employ loads of 50 to sone (Pfizer Inc., 3.5 mg p.o bid), clobazam 100 g of lactose, but the use of such high quanti- (Novopharm Inc., 5 mg p.o daily), levothyroxine ties has been questioned since sensitivity to (Abbott Laboratories., 0.025 mg p.o daily), lactose levels of 3 g or less has been demonstrated omeprazole (AstraZeneca Inc., 10 mg p.o bid), (5, 6). In fact, the modest presence of lactose as a metronidazole (Apotex Inc., 180 mg p.o bid), mor- bulking agent in pharmaceutical products has phine hydrochloride (ICN Pharmaceuticals. 1 mg been the source of medication intolerance in p.o. q3h prn) and Microlax enemas (Pharmacia several instances. We report the case of a complex Inc., prn). Small bowel bacterial overgrowth was pediatric patient who experienced such a reaction, the working diagnosis for his gastrointestinal and in whom treatment with exogenous lactase symptoms, and a formulation of L. acidophilus & L. casei (Bio-K+ International Inc., 30 ml p.o qid) was given in addition to the metronidazole for followed the ingestion of flutamide capsules, this purpose. C.H.’s mother and the palliative care which contain at least 210 mg of lactose each (11).
team finally resorted to morphine to alleviate his In another case, inhalation of cromolyn sodium pain (1 mg three to four times daily), which capsules containing only 20 mg of lactose each.
calmed him down and induced sleep, but did not induced similar symptoms (10). It should be noted that up to 80 percent of the cromolyn dose inhaled In September 2006, the pharmacist suspected from a turbuhaler can be swallowed, indicating lactose intolerance after discerning the number of that the patient reacted to an exposure of less than tablets containing lactose as a binding agent, as per their drug monographs in the Compendium of Pharmaceuticals and Specialties (CPS) (7).
taking, five contained lactose. The quantity of Exogenous β-galactosidase with 3000 units of lactose in each of those medications is outlined in lactase activity (known under the generic name of Table 1. C.H. had a total intake of approximately lactase, Life Brand, 3000 Units) was initiated with 360 mg of lactose per day. Consistent with previ- C.H.’s medications and feeds, and he improved ous case reports, this quantity is sufficient to drastically. His screaming abated, his abdominal induce medication intolerance in a highly sensi- swelling decreased, and he was able to discon- tinue the morphine within three weeks. Metronid- Symptoms of lactose intolerance occur when azole was also removed from his regimen within undigested lactose reaches the large intestine, one month. C.H.’s abdominal girth also improved osmotically draws in fluid, and is fermented by over subsequent weeks; according to his mother colonic bacteria (12). The precise pathogenesis of he eventually decreased by two pant sizes. Most C.H.’s symptoms may not be entirely explained notably, C.H. began to grow. For a full year prior by this mechanism, since the quantity of lactose he to starting the lactase supplements he weighed consumed was so small relative to the symptoms 11 kg; within nine months after the lactase, he he experienced. Petrini et al. have proposed a gained more than three kilograms. C.H. has since mucosal hypersensitivity, perhaps immune-medi- remained a more content boy, and the effect on his ated etiology for this type of reaction (9). It is clear, however, that lactase deficiency was the source of C.H.’s medication intolerance. A temporal rela- DISCUSSION
tionship between lactase supplementation and Lactase deficiency varies widely in severity but clinical improvement supports this finding.
the majority of patients can tolerate a dose of 12 to Following the administration of lactase, three sig- 18 g of lactose (8). Certain patients, however, have nificant changes occurred: (1) the resolution of been noted to experience gastrointestinal symp- C.H.’s screaming and a drastic reduction in gas- toms after exposure to much lower quantities (6), trointestinal distention, (2) the successful discon- and there appears to be no minimal threshold of tinuation of gastrointestinal and pain medications, lactose consumption required for inducing sensi- and (3) an increased rate of weight gain. Although tivity. There have been documented cases of no hydrogen breath test or intestinal biopsy was performed to definitively diagnose lactose intoler- adverse reactions to the lactose filler in their med- ance, C.H.’s case provides indirect but strong evi- ications (9-17). In one report, the onset of diarrhea, dence that medication intolerance can occur due borborygmi, flatulence, and abdominal discomfort Table 1 / Lactose content of C.H.’s medications
Quantity of lactose
per tablet (mg/tab)a
(no. of tablets/day)
a Obtained from contacting respective manufacturersb Not disclosed by manufacturer CONCLUSION
Date received, August 22, 2008; date accepted, After months of discomfort, treatment with exoge- nous lactase supplements alleviated the distress REFERENCES
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