A case of occupational rhinitis caused by porcine pancreatic extract developing into occupational asthma.

Porcine pancreatic extracts (PPE), which are widely used as a digestive drug in Korea, are composed of alpha-amylase and lipase. Such enzymes are commonly described as occupational allergens. This is the first report of occupational rhinitis caused by PPE developing into occupational asthma in a hospital nurse. She showed strong positive response in the skin prick test (SPT) (5+, wheal ratio of allergen to histamine) and had a high serum-specific IgE level to PPE, but showed a negative response in the methacholine bronchial challenge test (MBT). She had been exposed to PPE intermittently with intermittent medications for rhinitis. Two years later, she presented with rhinitis and additional asthmatic symptoms. In contrast to her first visit, she showed a positive response in the MBT, and developed bronchoconstriction in the PPE-bronchial provocation test (BPT). These findings suggest that inhalation of PPE powder can induce IgE-mediated occupational rhinitis in a hospital setting, which will develop into occupational asthma if avoidance is not complete.

A Case of Occupational Rhinitis Caused by Porcine Pancreatic Extract Developing into Occupational Asthma

Porcine pancreatic extracts (PPE), which are widely used as a digestive drug in Korea, are composed of alpha-amylase and lipase. Such enzymes are commonly described as occupational allergens. This is the first report of occupational rhinitis caused by PPE developing into occupational asthma in a hospital nurse. She showed strong positive response in the skin prick test (SPT) (5+, wheal ratio of allergen to histamine) and had a high serum-specific IgE level to PPE, but showed a negative response in the methacholine bronchial challenge test (MBT). She had been exposed to PPE intermittently with intermittent medications for rhinitis. Two years later, she presented with rhinitis and additional asthmatic symptoms. In contrast to her first visit, she showed a positive response in the MBT, and developed bronchoconstriction in the PPE-bronchial provocation test (BPT). These findings suggest that inhalation of PPE powder can induce IgE-mediated occupational rhinitis in a hospital setting, which will develop into occupational asthma if avoidance is not complete.

The association of nephrolithiasis with cystic fibrosis.

BACKGROUND: There is a growing body of evidence regarding the association between cystic fibrosis (CF) and nephrolithiasis and the role that Oxalobacter formigenes may have in that association. METHODS: We performed a MEDLINE search of "cystic fibrosis and nephrolithiasis" and "Oxalobacter formigenes." Epidemiological and experimental evidence and possible mechanisms explaining the association were critically reviewed. RESULTS: Of patients with CF, 3.0% to 6.3% are affected with nephrolithiasis, a percentage greater than that of age-matched controls without CF, in whom the rate is 1% to 2%. Studies have suggested possible mechanisms for the association, including hyperuricosuria, hyperoxaluria, primary defects in calcium handling caused by mutation of the CF transmembrane regulator (CFTR), hypocitraturia, and lack of colonization with O formigenes, an enteric oxalate-degrading bacterium. The absence of colonization could be related to frequent courses of antibiotics. CONCLUSION: Although the incidence of stones in patients with CF may be increased compared with controls without CF, many possible mechanisms are implicated. The relative contributions of these mechanisms remain uncertain. Future directions may include specific identification of lithogenic risks and therapy aimed at stone prevention in this population.

Alpha amylase is a major allergenic component in occupational asthma patients caused by porcine pancreatic extract.

Porcine pancreatic extracts (PPE) are composed of alpha-amylase and lipase, which are common components of digestive enzymes. They have been known to cause occupational asthma in exposed workers in pharmaceutical and baking industries, as well as in a laboratory technician, but there has been no report of PPE-induced occupational asthma in medical personnel and their IgE binding components to each component. Four asthmatic subjects showing positive results on PPE-bronchoprovocation testing were enrolled. All of them were nurses working in a university hospital. Their job included grinding and mixing PPE powder for admitted patients. Serum-specific IgE antibodies to PPE, alpha-amylase, and lipase were measured by enzyme linked immunosorbent assay (ELISA). To confirm specificity of IgE binding and cross-allergenicity among the three extracts, ELISA inhibition tests were performed. In order to characterize allergenic components within these three extracts, SDS-PAGE and IgE immunoblot analysis were done. Specific IgE antibodies to PPE, alpha-amylase, and lipase were detectable by ELISA in all study subjects. An alpha-amylase ELISA inhibition test showed significant inhibitions by amylase and PPE, and minimal inhibition by lipase. However, a lipase ELISA inhibition test showed significant inhibitions by alpha-amylase and PPE with a lesser degree of inhibition by lipase. Furthermore, IgE immunoblot analysis showed one IgE binding component (55 kDa) within PPE, six components (55 kDa, 43 kDa, 41 kDa, 32 kDa, 31 kDa, 29 kDa) within alpha-amylase and two components (31 kDa, 29 kDa) within lipase extracts. Thesefindings suggest that inhalation of PPE powder can induce IgE-mediated bronchoconstriction in exposed nurses. Alpha-amylase is a major allergenic component within PPE.

Desensitization to pancreatic enzyme intolerance in a child with cystic fibrosis.

OBJECTIVE: Pancreatic enzyme is essential in the treatment of cystic fibrosis (CF), but intolerance to it occasionally occurs. We encountered a child who was intolerant to multiple commercially available preparations of pancreatic enzymes and, hence, desensitization was attempted, with success. CASE PRESENTATION: A 33-month-old girl was diagnosed with CF at 6 months of age. Initially, she was started on Pancrease MT 16, which was subsequently discontinued because fecal fat studies were normal and she seemed to do well on Nutramigen and vitamin supplements. At 29 months of age, she developed diarrhea with bulky stools and weight loss. A fecal fat 72-hour study revealed a coefficient of absorption of 50%. She was treated with Pancrease MT 16, but had consistent vomiting 1 to 2 hours after administration of enzymes. The vomiting occurred on switching to different pancreatic enzymes preparations, ie, Creon 10, Viokase, and Pancrease MT 16. Vomiting occurred even with small doses of enzymes disguised in food. She had no history suggestive of gastroesophageal reflux, peptic ulcer, or pork allergy, and no vomiting on days when enzymes were not given. This was suggestive of type I hypersensitivity reaction. Pancreatic enzymes were discontinued, and she was given a low-fat, high-carbohydrate diet with satisfactory weight gain. METHODS: Double-blind, placebo-controlled titrated oral challenges with pancreatic enzymes resulted in definite vomiting within 1 to 1.5 hours after challenges with Viokase and Pancrease MT 16, but not with placebo. Rush oral desensitization with Viokase solution was attempted, starting with 5 mg, and the dose was doubled every 20 minutes, aiming to reach a cumulative dose of 700 mg. However, the child vomited when a cumulative dose of 315 mg was reached. Another trial of slower desensitization was done using Pancrease MT 16 (1 capsule: 16 000 U of lipase, 48 000 U of amylase, and 48 000 U of protease), starting with 1/4 capsule per day, with increments of 1/4 capsule every 3 days, until an entire capsule was reached by day 10, then increased by approximately 1/2 capsule every 4 days until reaching the therapeutic dose of 1 capsule with each meal by day 25. RESULTS: The patient tolerated this fairly well and has been on this treatment and regular diet for >1 year, without any adverse reaction. This illustrates a rare case of gastrointestinal adverse reaction to pancreatic enzymes that was treated successfully with desensitization. CONCLUSION: Pancreatic enzyme intolerance, although rare, would be a major problem in the management of patients with CF. Hence, desensitization would be essential and may be accomplished successfully using the protocol described in this report.

Progressive pan-colonic fibrosis secondary to oral administration of pancreatic enzymes.

Most patients with cystic fibrosis require oral administration of pancreatic enzymes to treat pancreatic insufficiency. Recent use of higher-strength enzyme preparations in large doses has been found to be associated with fibrotic strictures of the colon. We report a case of pancolonic fibrosis due to pancreatic enzyme use.

Colonic wall thickness, pancreatic enzyme dose and type of preparation in cystic fibrosis.

Increased colonic wall thickness has been reported in patients exposed to large doses of high strength pancreatic enzyme preparations who did not develop fibrosing colonopathy. This has been interpreted as evidence for a spectrum of subclinical disease. The relation between sonographically measured colonic wall thickness and pancreatic enzyme preparation and dose was studied in 86 children with cystic fibrosis (CF). Colonic wall thickness of a control group was also measured. The average thickness in all colonic regions was higher in the CF group (overall average range 0.7-2.5 mm v 0.6-1.4 mm in the control group). There was no significant relation between colonic wall thickness and age, sex, total dose of lipase, or copolymer. Apart from one patient with an early colonic stricture, none of those exposed to high doses of lipase, or the methacrylic acid copolymer Eudragit L30 D55, showed evidence of subclinical damage to the colon. The reproducibility of the sonographic measurements was poor.

Is fibrosing colonopathy an immune mediated disease?

Fibrosing colonopathy, a recently described complication of patients with cystic fibrosis, manifests clinically approximately 7-12 months after starting high dose pancreatic enzyme treatment. Although the pathogenesis of fibrosing colonopathy is unknown, it is highly correlated with pancreatic enzyme dose. In this study, immune mediated factors which may be associated with fibrosing colonopathy were explored. Sera from 14 patients with cystic fibrosis and meconium ileus were collected at diagnosis and then longitudinally for four to five years after enzyme treatment. Sera were analysed for total IgG and antiporcine trypsin IgG using an ELISA assay. Before enzyme treatment, serum antiporcine trypsin IgG concentrations were negligible, at 2.9 (SD 0.3) micrograms/ml. Thirteen patients (93%) developed a significant antibody response to porcine trypsin after starting enzyme treatment, reaching a peak concentration of 69.4 (20.1) micrograms/ml 7-12 months after the introduction of enzymes. Since peak IgG concentrations coincided with published reports of time of onset of symptoms of fibrosing colonopathy, local injury by protease or by immune mediated mechanisms may be responsible for the pathological changes in this iatrogenic disease.

High-dose pancreatic-enzyme supplements and fibrosing colonopathy in children with cystic fibrosis.

BACKGROUND: Fibrosing colonopathy has been reported in young children with cystic fibrosis, the majority of whom take high-strength pancreatic-enzyme supplements to control intestinal malabsorption. We conducted a case-control study in the United States to investigate the relation between dose and type of pancreatic-enzyme supplement and fibrosing colonopathy. METHODS: Children with histopathologically confirmed cases of fibrosing colonopathy who required colectomy for colonic strictures from January 1, 1990, through December 31, 1994, were identified. Each of these patients was matched according to age at the time of surgery and medical center with up to four controls with cystic fibrosis who did not have fibrosing colonopathy. RESULTS: We studied 29 patients (mean age, 5.0 years) with fibrosing colonopathy (case patients) and 105 controls (mean age, 5.2 years). The mean dose of pancreatic-enzyme supplement was 50,046 units of lipase per kilogram of body weight per day for the case patients and 18,985 units per kilogram per day for the controls. A history of gastrointestinal complications attributed to cystic fibrosis and the use of histamine H2-receptor blockers, corticosteroids, or recombinant human DNase (dornase alfa) were associated with a higher incidence of fibrosing colonopathy. After adjustment for a history of such complications and the use of these medicines, the relative risk of fibrosing colonopathy that was associated with a dose of 24,001 to 50,000 units of lipase per kilogram per day, as compared with a dose of 0 to 24,000 units per kilogram per day, was 10.9 (95 percent confidence interval, 1.6 to 71.8), and that associated with a dose of more than 50,000 units per kilogram per day was 199.5 (95 percent confidence interval, 9.9 to 4026.0). The strength, coating, and manufacturer of the products used were not associated with the risk of fibrosing colonopathy. CONCLUSIONS: In young children with cystic fibrosis, we found a strong relation between high daily doses of pancreatic-enzyme supplements and the development of fibrosing colonopathy. Our findings support recommendations that the daily dose of pancreatic enzymes for most patients should remain below 10,000 units of lipase per kilogram.

Neuropathy and vasculopathy in colonic strictures from children with cystic fibrosis.

Colonic strictures are rare in patients who have cystic fibrosis, but recently have developed in those who have been treated with delayed-release high-dose pancreatic enzyme supplements. Colonic strictures from eight such pediatric patients showed neural abnormalities consisting of ganglion cell hyperplasia and ectopia, and intermyenteric plexus hyperplasia. Cholinergic and adrenergic stains of mucosal nerve fibers were more prominent in histological sections of the cystic fibrosis strictures than in sections from colons of children without cystic fibrosis. The mean grade of staining with acetylcholinesterase in the lamina propria of the strictured cystic fibrosis colons was 2.38 +/- 1.25, compared with .93 +/- .93 (P < .055) in bowels from children without cystic fibrosis. The mean grade for tyrosine hydroxylase staining in the lamina propria was 2 +/- .97 in the strictures and was .79 +/- .81 (P < .05) in the bowels of children who did not have cystic fibrosis. Vasoactive intestinal peptide staining in bowels from children with cystic fibrosis with and without stricture did not differ significantly from that of children without cystic fibrosis. Vasculopathy consisting of fibrointimal hyperplasia in submucosal veins and mesenteric arteries was found only in colonic strictures owing to cystic fibrosis. Colonic strictures in patients with cystic fibrosis who received high-dose pancreatic enzyme supplements contain ganglion cell abnormalities, and mucosal cholinergic and adrenergic activity may be increased in these strictures. The stricture vasculopathy may be drug-related and/or related to increased catecholamine activity.