Pancreatic enzyme rash
Question:
8/6/2018
Any validated test for pancreatic enzyme (Creon) allergy? We have been asked to evaluate a 94 year-old patient for potential Creon allergy which presents as an urticarial dermatitis (Bx shows dermatitis with eosinophils) two months after changing Creon strengths. Changing him back to the original strength has left him with pruritic papules with crust. The two strengths are manufactured by the same company but in different countries. The literature describes treating through the rash with cetirizine or desensitization but no mention of tests (either patch or prick). Is there theoretical concern of skin injury from patch testing to pancreatic enzyme? Would switching brands to pancreaze, viokace, pertzye etc. make sense (although they are all porcine in origin)? We were planning to perform unvalidated patch tests to his other chronic medications losartan, pravastatin, bupropion as they have been associated with dermatitis reactions.
Answer:
I would be concerned about the rash being pemphigoid but in light of the negative immunofluorescence I will discount that possibility. Another cause should be considered if the rash does not completely clear with discontinuation of the pancreatic enzyme. I would try to stop both strengths of the enzyme to verify that the rash completely clears before proceding.
I could not find any information related to patch testing with the various products. It seems plausible that the higher dose may have evoked and a stronger immune response, but I am skeptical that the pancreatic enzyme is responsible since the individual has been on long term treatment without interruption. It is difficult for me to understand long term tolerance being broken by an increase in dose. All alternative products are porcine derived but have different concentrations of enzymes and vary in formulation with or without enteric coating. There does not seem to be sufficient differences to argue that changing products will be helpful. Nevertheless, I think it is worth trying a different product.
Immediate skin testing has been described in subjects with respiratory or immediate symptoms. Presumably the concentrations used would not be irritating if used for patch testing. The concentrations reported were 0.01 mg- 1mg/ml (1).
The case you cited describing desensitization was for a child with an immediate reaction characterized by vomiting (2). It is difficult to draw comparisons with your patient. I do agree that if pancreatic enzymes are necessary, a slow progressive challenge/desensitization seems to make the most sense, similar to what is done with sulfonamides or anticonvulsants. I do not think there would be much value in skin testing or patch testing.
In summary, I would favor review of the histology to be sure an alternative diagnosis is not possible, particularly pemphigoid, which affects this age group. I would discontinue all pancreatic enzymes to determine if the rash completely resolves as would be expected. I would then use a progressive challenge as described by Chamarthy et al with an alternative product.
I shared this information with Dr. Latha Chamarthy, the lead author of the desensitization paper. She agreed with the recommendations and also was concerned there is alternative explanation if the rash does not completely clear with discontinuation of the pancreatic enzyme.
I hope this information is of help to you and your practice.
All my best.
Dennis K. Ledford, MD, FAAAI
1. Griese, Matthias, Kathi Dokupil, and Philipp Latzin. "Skin prick test reactivity to supplemental enzymes in cystic fibrosis and pancreatic insufficiency." Journal of pediatric gastroenterology and nutrition 40.2 (2005): 194-198.
2. Chamarthy, Latha M., et al. "Desensitization to pancreatic enzyme intolerance in a child with cystic fibrosis." Pediatrics 102.1 (1998): e13-e13.