SECTION
EDITORS:
KALMAN
L
WATSKY,
How Do You Diagnose Latex Allergy?
M.D.
jr.?0 Orchard Street, Suite 311,
AndreaApter, Boris Lushniak, Erin Warshaw,and S. Elizabeth lI4zitmore
~Yew Haaen, CT 06511, Tel: 203-789-4045, Fax: 203-789-3744, Email:
[email protected]. MARTI
JILL
ROTHE,
De@ ofDermatology,
M.D.
c’ Corm Health
The diagnosis of latex allergy is a clinical challenge that practitioners are confronting with increasing frequency. Distinguishing the causes of delayedtype reactions requires careful patch testing. For patients with immediate-type symptoms, currently available tests are imperfect. This review by four national experts presents practical approaches to a dermatologic dilemma. Copyright o 1999 by W.B. Saunders Company
Center,
Farmington, CT 06032, Tel: 860-679-4176, Fax: 860-679-1267, Email:
[email protected].
ADVICE & DISSEhT addresses relevant issues in contact dermatitis through panel discussions or point/counterpoint debates. We look forward to input from the readership, including suggestions and commentary.
From the C’niwrsi~ of Penn$uania School of Mediczna and the Dwislon of Pulmonay, Aller~, Critical Care Medicine, Section ofAllerD and Immunology, Hospztal of the Unir’ersi~ of Penn@ania, Philadelphza, PA the Unzted States Public Health Semices, Centers for Disease Control and Prevention at the lVational I&t&for Occupations Safe@ and Health, Cincinnatz,
O@ the V&ram
Affairs
Medical
Center, Minneapolti,
rind the Johns Hopkzns School ofMedicine, Baltimore, MD. Address reprint requests to Andrea IJ. Apter, MD, MSc,
.%I:
Dioision
oj
Pulmonay, AlleT-0, Critical Care Medicine, Section ofAllerB andlmmunolou, 829 Gates, Hospital ofthe l’nioersity ofPenn&anza, PhiladeQhia, PA 19104. Co&right 0 1999 ly W.B. Saunders Com,+a?p 1046.I99Xl99l1003-0010~10.00/0
American
Journal
qf Contact
Dermatitis,
E ASKED FOUR experts to describe their approaches to diagnosing latex allergy. Andrea Apter is an allergist at the University of Pennsylvania School of Medicine. Boris Lushniak is a dermatologist and supervisor medical officer for the United States Public Health Service, Centers for Disease Control and Prevention at the National Institute for Occupational Safety and Health. Erin Warshaw is Chief of the Dermatology Section at the Veterans Affairs Medical Center in Minneapolis. S. Elizabeth Whitmore is a member of the Department of Dermatology at Johns Hopkins University School of Medicine and an expert in occupational dermatology. l What role doeshistoryplay in the diagnosisof latex allergy? Dr. Lushniak: Latex allergy should be suspected in anyone who develops symptoms after latex exposure, including nasal or eye irritation; urticaria or skin rashes; shortness of breath; coughing; wheezing; or, anaphylactic reaction. A diagnosis is made by analyzing the results of the medical history and the physical examination in conjunction with confirmatory testing. Dr. Apter: Latex can cause several types of reactions. The most potentially serious is an immediate (IgE-mediated) hypersensitivity reaction. These reactions can include urticaria at the site of contact (contact urticaria), dyspnea and wheezing or nasal congestion if latex particles are inhaled or
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frank anaphylaxis. These reactions typically occur within one and certainly within two hours of exposure in patients who have previously been exposed to latex. The allergens are proteins in the native latex. Skin testing is used to assess sensitivity to IgE-mediated reactions. Another type of allergic reaction that can be caused by latex is allergic contact dermatitis and is associated with some of the chemicals used to “cure” latex such as thiurams, carbamates, and mercaptobenothiazole. This reaction occurs within one to two days of exposure in previously sensitized individuals. Patch testing is used to assessthe risk of contact dermatitis. The most common reaction to latex is nonallergic irritant dermatitis and is not immune-mediated. Available diagnostic tests for immediate IgE-mediated hypersensitivity are imperfect, and even when commercial reagents become available, they will still have some degree of imperfection. Therefore, history remains the most important part of the evaluation. One must search for an appropriate exposure with onset of characteristic symptoms within one to at most two hours. The most severe allergic reactions occur quickly, within minutes of exposure. Glove powder containing latex particles is aerosolized when gloves are donned, causing rhinitis or bronchospasm in sensitive persons. A history of exposure to aerosolized latex may be very dificult to verify as most facilities do not have equipment for measuring the amount of aerosolized latex particles. Dr. Warshaw: I have felt somewhat frustrated in diagnosing latex allergy and have relied heavily on history (with particular attention to risk factors and symptoms) and physical exam. l What diagnostic testsdoyou recommendto confirm the diagnosisof latex allergy? Dr. Lushniak: A patient with symptoms and at least one positive confirmatory test is likely to have latex allergy. Oftentimes the strategy is to continue the workup in the following order: blood test, use test, skin prick test (SPT)-until a positive confirmatory test is found. Most perplexing is the patient with a seemingly positive history and negative tests. It is more difficult to discern whether this patient is a true negative or a false negative. Repeating tests and further workup may be indicated. Dr. Apter: If the history is consistent with IgE-mediated allergy, I obtain a serum immunoassay or RAST (radioallergosorbent test). If the
immunoassay is positive, I conclude the patient has IgE-mediated latex allergy. If immunoassay is negative, I generally perform a use test. If SPT is negative, I perform skin prick tests (SPT). Dr. Whitmore: All Hopkins employees who have a clear-cut history of contact urticaria are seen by an allergist, Dr. Robert Hamilton, who has worked on the development of natural latex rubber reagents for skin testing. He performs both the serum specific latex IgE RAST ImmunoCap test (Pharmacia, Upjohn, Kalamazoo, MI) and also SPT with varying dilutions of latex reagent. If RAST and SPT are negative, I perform a glove use test as well as patch testing to assess for contact urticaria from other glove components and any other contactants which may cause urticaria. I also evaluate the Hopkins employees who have a history of glove-associated hand dermatitis without any self-reported urticaria or hives. In this subgroup of patients I order a latex RAST if there is a positive history for any of the following: 1. eye or respiratory tract symptoms on latex exposure; 2. allergic rhinitis, conjunctivitis, asthma, atopic dermatitis, or food allergy; 3. numerous surgical procedures or chronic urinary catheterization. As Johns Hopkins has recently gone latex free, I anticipate that I will be seeing fewer patients manifesting signs and symptoms of latex allergy. Dr. Warshaw: The number of diagnostic tests available for a specific condition are often indirectly proportional to sensitivity/specificity of available tests. This is certainly true for latex allergy and is probably due to the fact that we have not yet identified THE allergen (or the more likely case of multiple allergens). Thus far, over 200 proteins have been identified in latex sap; over 57 of these bind antibodies. Recently, researchers have identified several important allergens, some of which seem to be more important for certain risk groups, but these still do not identify all who have clinical symptoms. RAST, Use Test, and SPT are the three practical tests for detecting latex allergy. l How use@ is the RAST? Dr. Warshaw: The easiest diagnostic test to perform is a latex RAST. It is a simple blood test, relatively inexpensive ($4 to $20), and has no risk of anaphylaxis. The main drawback is that it is a poor screening test with a sensitivity of only 60% to 80%. So, if the test is negative, latex allergy is still possible. Low positives (Classes I-III) are difficult to interpret, especially when the patient’s occupation is at stake. Also a patient with a positive latex
RAST can later develop a negative RAST after avoiding latex. Importantly, this test only detects circulating antibodies, not clinical reactivity. Dr. Whitmore: The reported sensitivity and specificity of the serum RAST is 75% and 94%, respectively. Dr. Apter: Immunoassays using patient serum are available, but only 50% to 90% of persons who were skin-test positive had positive in vitro tests. l Haze,is the Use Testpefornzed? Dr. Warshaw: This test involves applying a highly allergenic glove to the patient’s moistened hand; a positive reaction is defined as urticarial lvheals. Sensitivity ranges between 70% and 90%, depending on the allergenicity of the glove tested. The Prick-Use test involves pricking the dorsal hand prior to glove application; this modification increases sensitivity substantially. Anaphylaxis has been reported; therefore, resuscitation skills and a latex-safe crash cart are necessary. Allergists charge approximately $30 to $200 for this test. Dr. Whitmore: I test first with a dampened, glovred finger; if there is no reaction, then a dampened, completely gloved hand. l Horn are skin prick tests(SPlJ to Latexperformed and what are the risksand benejts of theprocedure? Dr. Apter: SPT is the preferred confirmatory test for the presence of IgE for most allergens. SPT involves placing an extract of the allergen usually on the volar forearm and introducing the reagent into the epidermis with a puncture. Tests are read in 15 minutes. A positive test is manifested by a wheal and flare at the site of the puncture. As of yet, there are no FDA-approved latex reagents, although one is now undergoing FDA scrutiny. In Europe and Canada, there are commercially available reagents. I perform nonstandardized skin tests, making an extract from materials to which the patient is exposed. Latex gloves from different manufacturing processes and even different glove lots from the same manufacturer may differ in the allergens present and their bioavailability. Anaphylaxis has rarely been reported during skin testing with nonstandardized extracts. The SPT is accomplished with great caution and I recommend it only be performed by an allergist with significant experience in evaluation of latex allergy and only in those patients in whom it is critically important to define the presence of true latex allergy. These patients are usually health care workers or patients requiring future surgery.
Dr. Warsha\c: The SPT is the gold standard in Europe with reported sensitivities of 80% to 98%. Physicians have made their own solutions from highly allergenic gloves; however, the risk for anaphylaxis and potential lawsuits have deterred most American dermatologists from performing SPTs. It is important to align yourself with a good allergist who is interested in latex allergy and can help with testing. Allergists charge $4 to $10 per SPT; several dilutions cost more. Unfortunately, allergists in our area will not perform this test because a FDA-approved latex SPT solution is not yet available. Fortunately, Greer Laboratories has a latex SPT solution which is awaiting FDA approval and should be commercially available in the U.S. this year. l When do you patch test patients who are being eaaluatedfor latex allergy.) Dr. Warshaw: If any amount of dermatitis is present in a patient with rubber glove intolerance, it is helpful to patch test to rule out delayedhypersensitivity to rubber additives. Dr. Whitmore: Health care workers with gloveassociated contact urticaria and negative BAST and SPT for latex are patch tested to corn starch, rubber accelerators, and antioxidants including BHA which are present in latex gloves. Patch testing may be done with any items or chemicals other than gloves with which a patient has contact which may also cause urticaria (e.g., food, formaldehyde, xylene, chlorhexidine). Patch tests are read at 30 minutes, I hour, and 2 hours. In those patients in whom delayed hypersensitivity is also a possibility based on history, patches are left in place for a full 48 hours, and are read at 48 and 72 or 96 hours.
Suggested Reading Brehler-
R, Sedlmqr S: Contact urticaria Contact Dermatitis 373125-127,
Burton
AD:
Latex
12:609-626, Cohen
Hunt
Taylor
allergy
in health
due to rubber 1997 care workers.
chemicals? Occup
bled
1997
DE, Scheman A, Stewart L, et al: American Academy of Dermatolo,gy’s position paper on latex allergy. J Am Acad Dermatol39:98-106, 1998 LW, Boone-Orke JL, Fransway AF, et al: A medical-centerwide, multidisciplinary approach to the problem of natural rubber latex allergy. J Occup Emiron Med 38:765-770. 1996 JS: Latex allergy update: Four vignettes. Am ,J Contact Dermat 9:45-48, 1998
M:arshaxv
EM: Latex
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l-24, 1998