Correspondence

Insulin-Injection-Site Reactions Associated with Type I Latex Allergy

N Engl J Med 2003; 348:265-266January 16, 2003

Article

To the Editor:

A 35-year-old woman with diabetes presented with pruritic, erythematous, urticated plaques at insulin-injection sites, persisting for up to 48 hours (Figure 1Figure 1Urticated Plaques at Insulin-Injection Sites in a Patient with Diabetes.). Reactions were associated with the use of Humulin I and Humulin S (Lilly) injected with a prefilled cartridge pen and Human Monotard (Novo Nordisk) aspirated from a vial and injected with a latex-free Microfine syringe.

The patient had positive skin-prick-test reactions to an aqueous powdered-latex-glove solution and commercial solutions ALK (960) Latex 100 and 10 HEP (Soluprick SQ). Skin-prick testing directly through an insulin-vial bung was also positive. We then compared injection of 10 U of Human Monotard subcutaneously with a natural-rubber-latex–free syringe, aspirated through the stopper and directly from the glass vial. A pruritic erythemal response was noted 20 minutes after injection from the “punctured” solution but not after aspiration directly from the vial. Our patient also had a reaction to all constituents of the Novo Nordisk intradermal kit, presumably because of needle penetration of the latex-containing bung in each vial.

Total serum IgE was normal but specific IgE tests with latex and protamine were negative. Patch testing with parabens, zinc sulfate, thiuram mix, and Human Monotard solution “as is” was negative. The manufacturers of the insulin preparations subsequently informed us that the cartridge bungs contain butyl rubber with added dry natural rubber latex, whereas the vial bungs contain butyl rubber with a natural-rubber-latex diaphragm on the outside. Synthetic butyl rubber should pose no hazard to latex-sensitized persons, but the natural rubber latex added to the bungs to provide optimal durability must have been responsible for our patient's reactions. With a switch to latex-free vials of Hypurin Bovine Lente (CP Pharmaceuticals), our patient had no further injection problems.

Despite documentation of localized and systemic type I reactions to latex in patients with diabetes,1,2 the possibility of such a reaction has not been ruled out in the majority of reports of injection-site reactions in the literature. Although evidence suggests that the risk among latex-sensitive patients with diabetes is very low,3 Primeau et al. demonstrated that natural-rubber vial stoppers release sufficient latex protein into solution during storage to elicit positive intradermal skin reactions in latex-allergic persons.4

Since the introduction of highly purified human recombinant insulin, injection-site reactions have been relatively rare, but this case illustrates that type I latex allergy should be considered and that latex-specific IgE measurements may give false negative results.

M.A.B. Roest, M.R.C.P.
S. Shaw, M.B., Ch.B., F.R.C.P.
D.I. Orton, M.R.C.P.
Amersham Hospital, Amersham HP7 OJD, United Kingdom
mroest@doctors.org.uk

4 References

1. 1

   Hoffman RP. Latex hypersensitivity in a child with diabetes. Arch Pediatr Adolesc Med 2000;154:281-282
   Web of Science | Medline

2. 2

   Towse A, O'Brien M, Twarog FJ, Braimon J, Moses AC. Local reaction secondary to insulin injection: a potential role for latex antigens in insulin vials and syringes. Diabetes Care 1995;18:1195-1197
   CrossRef | Web of Science | Medline

3. 3

   Danne T, Niggemann B, Weber B, Wahn U. Prevalence of latex-specific IgE antibodies in atopic and nonatopic children with type I diabetes. Diabetes Care 1997;20:476-478
   CrossRef | Web of Science | Medline

4. 4

   Primeau M-N, Adkinson NF Jr, Hamilton RG. Natural rubber pharmaceutical vial closures release latex allergens that produce skin reactions. J Allergy Clin Immunol 2001;107:958-962
   CrossRef | Web of Science | Medline

Citing Articles (6)

Citing Articles

1. 1

   Lin Zhang, Mei Zhang, Yuan Yuan Liu, Maoqing Hu, Xuelei Zhou, Yu Luo. (2011) Successful treatment with continuous subcutaneous insulin infusion for allergy to human insulin and its analogs. Diabetes Research and Clinical Practice 94:1, e1-e2
   CrossRef

2. 2

   Mohammad K. Ghazavi, Graham A. Johnston. (2011) Insulin allergy. Clinics in Dermatology 29:3, 300-305
   CrossRef

3. 3

   L. Heinzerling, K. Raile, H. Rochlitz, T. Zuberbier, M. Worm. (2008) Insulin allergy: clinical manifestations and management strategies. Allergy 63:2, 148-155
   CrossRef

4. 4

   I. Bostancý, Y. Dallar, R. Ünsal Sac, E. Karakoc, B. Doganay. (2007) Latex allergy risk assessment in children and adolescents with type I diabetes mellitus. Pediatric Allergy and Immunology 18:8, 687-691
   CrossRef

5. 5

   R. P. Radermecker, A. J. Scheen. (2007) Allergy reactions to insulin: effects of continuous subcutaneous insulin infusion and insulin analogues. Diabetes/Metabolism Research and Reviews 23:5, 348-355
   CrossRef

6. 6

   2006. Insulin. , 1761-1783.
   CrossRef