- Skin Testing - 12/8/05 re: Contra-indications for skin testing Could you please tell me where I can find information about contraindications for performing skin tests especially prick tests. I have enclosed below material I excerpted from the Practice Parameters in this area of clinical practice. These and other parameters are posted in the website of the Joint Council of Allergy Asthma and Immunology (www.jcaai.org). I would add to this information that prick skin testing is usually contra indicated in patients taking beta blocker drugs and possibly also in those taking ACE inhibitor drugs. However, skin tests can usually be done without increased risk if these drugs are stopped for 24 hours prior to skin testing. Skin testing must be done with particular caution in any patient at particularly increased risk if hypotension occurs (e.g. someone with coronary artery disease/previous myocardial infarction). Although not a contra-indication to skin testing, a possible limiting factor is the validity of the extract used for testing. Some allergens (e.g. some fruits) are present in relatively low concentrations in commercial extracts. Therefore, if such tests are negative in someone with a strongly suggestive history, one can repeat the test using a skin pricking instrument stuck into the natural food (example-melon) and then immediately used to make the skin puncture Diagnostic Test of IgE Dependent Reactions (IMMEDIATE HYPERSENSITIVITY) A. General Principles of Testing for Immediate Hypersensitivity *The hazards of blood contamination with the use of all instruments must be given appropriate attention and all testers need to observe appropriate bonier techniques. *First generation antihistamines should be discontinued for 24 to 72 hours prior to testing. Hydroxyzine may affect the skin test if taken within up to 96 hours before the test. Astemizole may suppress skin tests for as long as 2 to 3 months or more. Other non-sedating antihistamines may need to be withheld for up to one week. Tricyclicantidepressants may require 7 to 14 days for recovery of skin test reactivity. H2 antagonists may cause mild sup-pression and should be discontinued for 24 hours prior to testing. *Although short-term systemic corticosteroids (30 mg daily for I week) do not suppress skin tests, chronic and relatively high dose corticosteroids (>20 mg/day) can partially suppress skin test reactions. Also, regular administration of potent topical corticosteroids for a period of weeks may suppress immediate skin tests over areas where they have been applied and therefore should be discontinued over these sites for 2 to 3 weeks prior to testing. *Skin tests should not be performed at skin sites with active dermatitis. If they are done in the presence of dermatographism, they must be interpreted with caution. *There are virtually no age limitations for performance of skin tests. However, skin test reactivity may be diminished in infants and the elderly. *The proper interpretation of skin tests requires that allergen extracts be of known composition and potency (see "Allergen Standardization"). Unfortunately, these data are not available for all manufactured allergens currently being used by clinicians. *The potency of allergen extracts deteriorates with time, dilution and ex-posure to increasing temperatures. Skin test reagents should be properly stored in a temperature-monitored refrigerated space. Expiration dates should be checked on a regular basis. Precautions to prevent cross contamination or bacterial contamination should be in place. *To properly interpret allergy skin tests that detect immediate hyper-sensitivity, both positive (histamine) and negative (diluent) controls need to be performed. *The proficiency of the skin tester should be validated by intra-patient and interpatient test results. The testing techniques used for these validation tests will vary depending on the device being used. Ongoing staff inservice programs are important to ensure quality. *Histamine control tests should be read 15 minutes after application for determination of their peak reactivity. *Although allergy skin testing is considered to be a safe procedure, adverse events, such as large local reactions and systemic symptoms, may occur in extremely sensitive individuals. Deaths from anaphylaxis after skin testing have been reported. These extremely rare systemic symptoms are less likely with prick/puncture than intracutaneous tests. However, it is recommended that full emergency equipment and drugs should be on hand for treatment of a potentially life-threatening event. Special precautions should be considered in patients receiving beta-adrenergic blocking agents or monoaminoxidase inhibitors. 9/13/05 re: How to design allergy evaluation service I have a difficult task despite of my immunological background, because I have not worked with allergy tests like Prick's, and I should design virtually an allergy lab from zero point. What would be the most relevant equipment and materials needed excluding the basic stuff from allergen extracts, papers, tubes and injection material? To analyze results? What kind of microscopes and readers do you use? Do you run ELISA by labeling serum samples by monoclonal antibodies and a substrate? Extracts are old-fashioned technique to detect skin allergies (metals etc.)? What are the parts of GCP and FDA guidelines you would emphasize to be read? Limited space does not permit presentation of the considerable amount of information you have requested, not to mention the various quality control measures needed for reliable allergy skin testing and in vitro IgE antibody assays. Indeed, Fellows in Allergy and Immunology training programs spend a good deal of their time in their first year of training becoming adept in these approaches. I suggest that you first read the Practice Parameters dealing with allergy diagnostic approaches. This can be found in the website of the Joint Council of Allergy, Asthma and Immunology (www.jcaai.org). Click on practice parameters, then on the parameter dealing with allergy diagnostic approaches. Background material concerning both skin testing and in vitro testing can be found in the latest edition of “Middleton's Allergy-Principles and Practice” textbook. Details concerning the type of lancets and extract solutions used for prick skin testing can be obtained in the catalogues sent by the major commercial companies which sell allergy testing materials (e.g.- Greer, ALK, Hollister-Stier). The in vitro assay system used most commonly in my experience has been the CAP-ELISA system of Pharmacia. Most in vitro assays for IgE antibodies involve use of an enzyme-labeled IgG anti-IgE antibody as a “second antibody.” 9/9/05 re: Effects of proton pump inhibitor drugs on immediate skin test reactivity I had a patient yesterday for allergy testing who had a very diminished response to our standard control solution of morphine 10gs/ml diluted 1:10. The patient was on a proton pump inhibitor. A literature search has not answered my question. Do protein pump inhibitors interfere with skin tests? I am not aware of evidence that treatment with proton pump inhibitor (PPI) drugs inhibits immediate skin test reactivity. I could not find reference to such an effect in a Medline search. Therefore, I referred your question to Dr. Estelle Simons of the Univ. of Manitoba in Winnipeg . Dr. Simons is an expert in the study of medication effects on immediate skin test responses. Her response is enclosed below. Dr. Simons' comments: There is no published evidence that PPI inhibitors suppress skin tests. Omeprazole has been reported to cause anaphylaxis, and skin prick tests and intradermal tests with omeprazole and with pantoprazole and lansoprazole are positive in most of these patients. We could find no information about the effect of PPI inhibitors on the morphine skin test. 9/2/05 re: Triatoma skin test reagent I work in an allergy office in southern California and I'm searching for a source of Triatoma (Kissing Bug) antigen. Or a lab that can do RAST testing for it. Do you have any suggestions? A review of triatoma sensitivity by a group in the Univ. of Mississippi in 2003 concluded that there was no commercially available supply of triatoma antigen. Therefore, I contacted Dr. Andrew Saxon of the UCLA Medical Center . His group reported the use of a triatoma extract for testing and immunotherapy in a case of triatoma-induced anaphylaxis. His response is enclosed below. I have also enclosed the e-mail address of Dr. Donald Hoffman in E. Carolina Univ. to whom Dr. Saxon referred in case you wish to contact him re possible RAST-type testing. That triatoma extract material is long gone from here and I know of no source for Dx or Tx materials anymore. However, I think Dr. Don Hoffman in E. Carolina may be doing in vitro testing for triatoma sensitivity. 7/6/05 re: Value of intradermal allergy testing There is currently a trend to suggest that intradermal testing has no value. I find that very difficult to accept in that for example, there are patients who clinically fit the criteria of being allergic to ragweed based on symptoms, seasonality, but react only on IDs. Many of these patients do well with immunotherapy. I find it hard to believe that all those who do well do so based on placebo. Intradermal testing is used for penicillin testing, bee venom testing, etc.While there can clearly be false poitives with intradermals, that's also true with pricks. One needs to correlate symptoms with the lab results. Perhaps they are other unrecognized confounding variables not occuring in a lab study. Could you shed some light on this? You raise some points of considerable practical importance. I think that it is somewhat of an over-statement to describe I.D. allergy skin testing as of no value. My impression from reading of reviews and guidelines as well as a long practice experience is that the prick skin test approach is preferable to I.D. testing as the initial allergy skin testing approach. This conclusion is based mainly on: 1) The more frequent occurrence of clinically irrelevant positive I.D. tests than irrelevant positive prick tests. This finding likely reflects irritant effects of I.D. testing in some cases. More commonly such reactions may be related to the fact that the I.D. technique is probably at least 500 times as sensitive as the prick test techniques when serial dilutions of the same stock allergen are compared. Expert panels have stated that the evidence supports the conclusion that positive prick test results correlate better than positive I.D. findings with current clinical sensitivity to the aeroallergen involved (see Allergy 1989;44 (Suppl 10), pg 1)2) The occasional occurrence of systemic allergic reactions to I.D. testing done as the initial approach. Unfortunately, some of these reactions have been very serious, even fatal. Such systemic reactions are much less commonly associated with positive prick tests. However, it is recognized that occasionally individuals with clear-cut histories of seasonal allergies will exhibit reactions to only I.D. but not with prick skin testing with the relevant allergen, likely because of low levels of the specific IgE antibodies present. Indeed, this conclusion is stated by Bousquet et al on pg 633-634 in their chapter on allergy skin testing in the Middleton's Allergy text (6th edition). Another possibility is that an individuals exhibiting I.D.skin test reactivity but neither prick skin test response or a convincing clinical history for allergy to a particular allergen at the time may subsequently become more sensitive to that allergen in the future, then manifested clinically. I have seen such situations fairly often in adolescents. Therefore, the policy of my group has been to do all initial testing by the prick technique. In cases where the prick test is negative for an allergen in which the history is strongly suggestive of clinical sensitivity, skin testing to such allergens is carried out by I.D. technique .Of course, much of what I say depends on the concentration of the allergenic extract used in the I.D. test. Therefore, an alternative approach could be to do serial dilution I.D. testing starting with a very high dilution of the stock extract and testing with progressively higher concentrations of that extract if the previous responses are negative. This should give a better idea of the degree of sensitivity of the patient as well as reducing the chance of a systemic reaction occurring. However, such an approach is more time consuming than the approach using screening prick tests followed by selective I.D. testing mentioned above. 11/29/04 re: Pregnancy, allergy test; immunotherapy post Do you believe that hormone fluctuations can change the outcome of allergy testing in relation to pregnancy? Do you wait any amount of time after delivery to do allergy testing and immunotherapy in a new mother? To help respond to your questions, I obtained input from Dr. Michael Schatz of the Kaiser-Permanente Medical Group in San Diego, CA. Dr. Schatz is an expert in the subject of the effects of pregnancy on allergies and asthma (and vice versa). His response is enclosed below. As you can see, when to allergy immunotherapy (IT) after the pregnancy is completed is a judgment based on: 1) the need to get beneficial effects as soon as feasible (since the beneficial effects generally are not seen until at least 6 months of IT); 2) any post-partum problems in the mother that may make a delay starting IT prudent; 3) logistics.A question not asked by you is what one does concerning the IT in this patient if she becomes pregnant again. The usual recommendation is continue the last pre-pregnancy IT dose as a maintenance dose during pregnancy but do not increase the dose to be injected. Dr. Schatz's comments I know of no data on which to base a direct answer to the question. I would do allergy testing during pregnancy as early in the pregnancy as possible so as to use the results as early as possible. I prefer in vitro testing to skin tests during pregnancy to eliminate the remote chance of a systemic reaction to the testing.I think practical considerations would determine when to test and treat with immunotherapy post-partum. Although not systematically studied, I know of no anecdotal experience to suggest that the presence or absence of breast-feeding would influence the decision to start immunotherapy. 9/23/04 re: Food skin test significance I am a Registered Nurse and my son is undergoing Allergy testing. He is a 5 year old with significant family history of allergies in both parents. He took the mRAST test and was a class VI >100 on grasses. He also had some III-V on weeds and trees. He has a strong family history of food Allergies. He has had past reactions to peanuts and strawberry's. His mRAST came up class IV for Wheat Class III for corn Class III Peanut class III for Soybean. He gets a fine itchy rash and stomach pain when he eats meals with grains but we have not excluded these foods from his diet. His IGE was 1867 when he took this test. He has RAD which seems to be aggravated by his allergies. It is treated with singular, claratin, flonase, Zadadir (sp?) Albuterol PRN and Pulmocort PRN. Off of the antihistamines for 7 days he went in to have skin testing done to verify the results of the mRAST. His skin tests showed 5+ for grasses some weeds and trees but the food allergies were negative. What perplexes me is the Histamine site was negative as well. Why would the Histamine site be non reactive? Dose this bring the other negative reaction sites into question as to the validity of the test? Should one or both tests be redone before ordering Allergy shots? Will the mRAST be affected if the child is reacting to an environmental allergen when the blood is drawn? Should the foods be eliminated or restricted in the diet? Will antihistamines effect how strongly a food allergy presents itself? I will attempt to address your questions in turn: 1) Reason for negative histamine skin test? The first possibility that comes to mind is that there was still some medication or other effect suppressing the response to the histamine test. A less likely possibility is that the particular batch of histamine solution used in a positive control skin test had somehow lost its potency (this can be investigated by finding out from the allergist whether other children skin tested using the same batch of histamine solution had the expected or decreased responses. Another way would be to re-test your child with histamine on a different day (off antihistamine treatment). 2) When there is some question about the validity of skin test responses, we commonly rely more on results of the in vitro tests. However, the situation may be complicated in the case of your child because of the very high total IgE levels in the serum. Although you did not mention it, I would not be surprised if your child previously or currently had atopic dermatitis. Sera with such very high IgE levels will often show positive responses to a number of allergens that do not appear to be clinically relevant at the time. The mRAST results should not be affected in a major way if the patient is currently exposed to usual levels of allergens in the environment. 3) Therefore, it would be prudent to limit allergy injection immunotherapy to those allergens to which IgE antibodies have been detected that the history suggests are clinically important. With regards to foods in this category, I would suggest a graded dose challenge with each of the suspect foods (based on the mRAST results) carried out individually under medical supervision before deciding whether to exclude them from the diet. It is true that maintenance antihistamine therapy can at least partially inhibit a clinical reaction induced by such food challenges. However, if one withholds antihistamine therapy in preparation for such challenges one has to first assess the clinical symptoms when no food challenge (or placebo challenge) is carried out since the appearance of symptoms may be due just to the absence of a suppressive effects of the antihistamine therapy. Such food challenges should be feasible in the office of the allergist involved. 7/26/04 re: Concentration for prick and ID testing I am a practicing allergist in Honolulu. Is there any official recommendation from AAAAI about the concentration for prick and ID testing for standardized extracts (mites, cat dander)? I saw your skin test form, which has Timothy (100,000 BAU) and Bermuda (10,000BAU) for skin testing, I do not see any mention for mites and cat. My understanding is that ID skin test concentration is usually 10 folr mre diluted than prick testing. The form uses the same concentration for prick and ID, any comment? To obtain input on your question I consulted Dr. Linda Cox, Chair of the AAAAI Immunotherapy and Allergy Diagnostics Testing Committee. Dr. Cox's response is enclosed below. Dr. Cox's Response: I can see where you may have gotten confused on the example of a completed skin test. It does appear that the same concentration may have been used for the intradermal and percutaneous but if you read the details in the general information on the skin testing box, it provides you with the information about testing dilution indicating that the percutaneoous is listed as allergen: testing concentraion: extract company and line 2 specifies the intradermal testing concentration (see below) I personally use a separate form for intradermal and percutaneous testing. General information about skin test protocol 1. Percutaneous reported as: Allergen: Testing concentration: Extract company (*see below) Location: back X arm Device: HS Quintip 2. Intradermal: 0.02ml injected, Location: arm Testing concentration: 1:500 w/v, 100 BAU or AU/ml, 400 PNU I do not believe the current immunotherapy practice parameter addresses concentration for intradermal testing but is addressed in the older Allergy Diagnostic Practice Parameters, which I believe is still in the process of being updated (see below). As you can see the recommended intradermal testing dose for a preceding prick negative patient is 100 to 1000 fold dilution of the prick concentration. From Bernstein L Storms W Joint Task Force on Practice Parameters Practice Parameters for Allergy Diagnostic Testing Annals of Allergy, Asthma, & Immunology. Volume 75 (6), December 1995. Intracutaneous tests are generally used when increased sensitivity is the main goal of testing (i.e., when prick/puncture tests are negative despite a compatible history of exposure). They permit identification of a larger number of clinically reactive patients, especially those with lower skin test sensitivity. In addition, sensitivity to low potency allergenic extracts may best be evaluated by this method. As a general rule, the starting test dose of intracutaneous extract solutions in patients with a preceding negative prick/puncture test should range between 100 and 1,000 fold dilutions of the prick/puncture test solution. The reproducibility of intracutaneous tests is affected by the same variables as those described for prick/puncture tests. Both erythema and wheal diameters should be measured and recorded. Any reaction larger than the negative control may indicate the presence of specific IgE antibody. However, given the lower specificity of intracutaneous testing, small positive reactions may not be clinically relevant. 3/11/04 re: Effects of antihistamines on allergy skin testing Are skin tests accurate? Would an antihistamine intentionally administered prior to skin testing, foil the attempt to find a specific allergen? Can an antihistamine given prior to skin tests of varying strengths eventually be metabolized and allow a delayed minimal reaction at a histamine test site? I.e., can an antihistamine initially block skin testing results, but then be metabolized sufficiently to become incapable of blocking histamine release? These are concerns of a divorcing parent under my care. Thank you. The immediate wheal and flare responses to prick or intradermal allergy skin tests are the ones used diagnostically in the evaluation of possible allergic disorders. Treatment with the usual H1 antihistamines (AH) can suppress the immediate responses in allergy skin testing to a varying degree so that a ‘false negative' response can occur. The onset of this suppressive effect is generally seen within 1-2 hours after ingestion of a single dose of a potent AH and can persist for up to 24-36 hours. There is no cumulative effect of daily dosing with such AH so that the suppressive effects are also for the same period-up to 24-36 hours, even after chronic AH therapy. Some older reports described a somewhat longer persistent (3-4 days) after dosing with the AH hydroxyzine (Atarax). However, such AH therapy does not inhibit the late phase (delayed) reactions in such allergy skin test sites. Extensive studies by my colleagues and me have shown that treatment with either hydroxyzine or its metabolite cetirizine (Zyrtec) which significantly suppresses the immediate skin test responses to allergen has no inhibitory effect on the late phase reaction in such sites (see references below). Therefore, my bottom line response to your question is that it would be extremely unlikely that an AH used in treatment or its metabolite would exert an inhibitory effect on the immediate response in allergy skin tests more than 24-36after ingestion of the last dose. There is no inhibitory effect on late phase reactions in such sites. I suggest that that you read one of the several excellent reviews of AH effects by Dr. FE Simons (for example - H1-Antihistamines: more relevant than ever in the treatment of allergic disorders.J Allergy Clin Immunol. 2003 Oct;112(4 Suppl):S42-52. Review) if you wish more information in this area. REFERENCES Slott RI , Zweiman B. A controlled study of the effect of corticosteroids on immediate skin test reactivity. J Allergy Clin Immunol. 1974 Oct;54(4):229-34 J Allergy Clin Immunol. 1997 Jun;99(6 Pt 1):806-11. Cellular inflammatory responses and mediator release during early developing late-phase allergic cutaneous inflammatory responses: effects of cetirizine. Atkins PC, Zweiman B, Moskovitz A, von Allmen C, Ciliberti M. Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104-6057, USA . BACKGROUND: Events in developing cutaneous late-phase allergic reactions can be characterized by a combination of skin chamber and biopsy approaches. In some previous studies, cetirizine reportedly inhibited mediator release and/or inflammatory cell responses in late-phase reactions. OBJECTIVE: This study was carried out to determine the effects of cetirizine on early late-phase reactions by using skin chamber and skin biopsy specimens. METHODS: Skin chamber responses during a 6-hour challenge with pollen antigens were assessed in 15 sensitive subjects during randomized, crossover treatment with cetirizine (20 mg/day) or placebo for 7-day periods with measurements of humoral and cellular components. Biopsy specimens of the underlying dermis were obtained. RESULTS: During cetirizine treatment, there was significant (p < 0.01) inhibition of immediate wheal and flare reactions to pollen antigens (34, 46%), codeine (41, 65%), and histamine (38, 68%). However, gross late-phase reactions at 6 hours were unaffected. During both cetirizine and placebo treatment, there was significantly greater accumulation at antigen sites in: (1) skin chamber levels of histamine, total cells, lactoferrin, and eosinophil cationic protein; (2) eosinophils (total and activated) on appended cover glasses; (3) deposition of lactoferrin and eosinophil cationic protein in the underlying dermis. However, these responses were not significantly different during cetirizine treatment compared with placebo treatment periods. CONCLUSION: A persistent pattern of inflammatory cell accumulation with release of granule proteins during early late-phase reactions was unaffected by cetirizine treatment. 12/17/03 I am a second year Internal Medicine Resident. I have two questions that come up often in my outpatient clinic. First, when should patients diagnosed with asthma be referred for allergy testing? Everyone? Those with history of allergic diseases? Those with clear-cut triggers? Those without clear triggers? Difficult to manage patients? Second, how do you routinely differentiate between older patients with asthma who smoke versus those with COPD. Does it matter, or do you treat everyone with reversible airways disease the same (ie a 70 year old smoker with an FEV1 that improves by 12% after bronchodilator challenge treated the same as a 30 year old nonsmoker with the same reversibility)? You have raised two very thoughtful questions about which there has been much recent discussion and some differences of opinion. I will give you my impressions and recommendations based on my personal experience and review of the pertinent recent literature. A. Referral of asthmatics for allergy evaluation- Defined allergic mechanisms play a pathogenic role in many but not all asthmatics. An allergic pathogenesis is suggested by: 1) History of atopy/asthma in the immediate family, particularly in the mother 2) Presence of allergic rhinitis in the patient. Almost all allergic asthmatics have concomitant allergic rhinitis, often perennial. 3) Onset early in life. Most allergic asthma starts in childhood/adolescence. However, it may remit (spontaneously or with appropriate therapy) in teenage years only to recur in young to middle-age adulthood. So a careful history dating back to childhood is necessary. 4) History suggestive of triggering of symptoms by exposure to allergens. This sometimes requires questioning by someone with considerable experience in this area to pick up on subtle clues. Therefore, a referral to an allergist may be needed if the history is suggestive but not clear-cut. One possible exception to the statement just above is occupational asthma (responsible for perhaps about 10% of asthma in adults). Some non-atopic individuals may experience asthma in the workplace but no where else. Again, a detailed history is often necessary keeping in mind that secondary gain (disability payments) issues are sometimes present.Another particular situation is exercise-induced bronchoconstriction (EIB), seen most commonly with running sports. Most asthmatics will have increased symptoms with such exercise. However, there are individuals who wheeze with exercise but not at other times. Such individuals are sometimes non-atopic. The underlying mechanism has traditionally been considered an exaggerated response to dehydration/temperature changes in the bronchial mucosa although some recent studies have suggested a possible chronic inflammatory reaction in the airways as an underlying mechanism. B. Differentiation of asthma from COPD It has been recognized for some time that wheezing can be a manifestation of COPD. However, in the past, COPD was thought to be different from asthma in that the airflow obstruction was not reversible, while it was reversible in asthma. More recent evidence suggests that the picture is more complex and the differentiation between COPD and asthma is less clear-cut: 1) A subset of patients with otherwise typical smoking-related COPD exhibit significant reversibility of airflow obstruction following inhalation of beta 2 agonist agents (e.g., albuterol). A smaller sub-set of COPD patients may not exhibit this response to inhaled albuterol but do manifest an increase of over 12% in the FEV-1 following a 2-3 week trial of oral corticosteroids (but generally not as much as seen in typical asthma). Some studies have found that COPD patients with a prominent accumulation of eosinophils in their sputum are the ones more likely to manifest a significant improvement in airflow with steroid therapy. 2) Although reversibility of airflow obstruction (spontaneously or with therapy) has been considered a hallmark of asthma, it is now recognized that such reversibility is diminished in those with long-standing, chronic, uncontrolled asthma, even of modest degree. Some investigators believe that this "irreversibility" occurs secondary to airway remodeling due to increased deposition of collagen and other connective tissue components in the bronchial walls. For these "overlap" reasons, many clinical research studies of asthma exclude all smokers and demand a prominent bronchodilator response to inhaled beta agonists for inclusion. One way that has been used to differentiate COPD from asthma in clinical practice is to obtain a diffusing capacity in the PFT. This test is normal in asthma and decreased in COPD although the decrease in the DL-CO in COPD is generally most impressive in those with emphysema as well as chronic bronchitis. Another approach is to obtain a biopsy of the bronchi (see enclosed abstract) although this approach is generally done only in research studies. Then what does one do in usual clinical practice? If there is significant airflow reversibility (regardless of the diagnosis given) in the untreated patient, and particularly if one is able to get an induced sputum examined for inflammatory cells (and find increased % eosinophils compared to that in the blood), then prescribe a trial of inhaled corticosteroids (ICS-400 to 800mcg/day depending in the particular ICS used) for several weeks, reducing the dose somewhat thereafter if there is a good response. Some clinicians use a different approach. They prescribe a 3 week course of oral steroids (about 0.5 mg/kg/day of prednisone). If there is a good airflow response during re-evaluation after 3 weeks, an ICS is added and the oral steroid dosage is tapered off. If one cannot be sure of the patient's reliability in taking the oral steroids (with possibly a misleading interpretation about steroid responsiveness) one can give a single injection of about 80 mg of Depo-Medrol or equivalent and then re-evaluate in 3 weeks as described above. 1: Chest. 2000 May;117(5 Suppl 1):251S-60S. Comparison of the structural and inflammatory features of COPD and asthma. Giles F. Filley Lecture. Jeffery PK. Imperial College School of Medicine at the Royal Brompton Hospital, London, UK. At least three conditions contribute to COPD. (1) Chronic bronchitis (mucous hypersecretion) is an inflammatory condition in which CD8+ T-lymphocytes, neutrophils, and CD68+ monocytes/macrophages predominate. The condition is defined clinically by the presence of chronic cough and recurrent increases in bronchial secretions sufficient to cause expectoration. There is enlargement of mucus-secreting glands and goblet cell hyperplasia, which can occur in the absence of airflow limitation. (2) Adult chronic bronchiolitis (small or peripheral airways disease) is an inflammatory condition of small bronchi and bronchioli in which there are predominantly CD8+ and pigmented macrophages. The functional defect is difficult to detect clinically but may be recognized by sophisticated tests of small airway function. There is mucous metaplasia, enlargement of the mass of bronchiolar smooth muscle, and loss of alveolar attachments. (3) Emphysema is an inflammatory condition of the alveoli in which T-lymphocytes, neutrophils, and pigmented alveolar macrophages are involved, associated with the release of excessive amounts of elastases. It is defined anatomically by permanent, destructive enlargement of airspaces distal to terminal bronchioli without obvious fibrosis. In contrast, asthma is a clinical syndrome characterized by allergic inflammation of bronchi and bronchioli in which CD4+ (helper) T-lymphocytes and eosinophils predominate. There is increased production and release of interleukin (IL)-4 and IL-5, which is referred to as a Th2-type response. There is usually increased tracheobronchial responsiveness to a variety of stimuli, and the condition is usually manifest as variable airflow obstruction. While differences between COPD and asthma have been highlighted, new data are emerging that indicate there may also be similarities. 10/16/03 re: Effect of general anesthesia on allergy skin testing In our community we have a young ENT who is doing allergy testing while patients are under anesthesia. He indicates to the parents that it is more humane and that testing is just as accurate. He usually does it in conjunction with tonsillectomy or adenoidectomy or even when inserting pressure equalization tubes. This is the first time we have encountered this, and feel it can lead to unforseen problems. What is the effect of anesthesia on allergy testing results? Does anyone advocate doing testing in such a manner? What are your sentiments about this? This approach you described of doing allergy skin testing while a patient is under general anesthesia certainly sounds very strange to me. I have not heard or read about such an approach. I cannot categorically say whether the agents used in the general anesthesia you mentioned would affect allergic skin test reactivity because the agents employed may differ among patients. In some cases, use of more than one agent is involved. In some cases, direct histamine release may be induced by the anesthetic agent (e.g. propofol), see enclosed abstract. One would have to compare the skin test responses to several concentrations of allergen and of a non-immune mast cell activator such as codeine obtained in testing under anesthesia and without anesthesia before making a definitive statement about anesthesia effects on skin test reactivity. I would not recommend that skin testing be done under general anesthesia for at least these reasons: 1) If there is an adverse systemic event during or shortly after the operative procedure (e.g. - hypotension), one cannot be sure whether this was due to a systemic reaction to the testing vs other events (effects of anesthetics or other medications employed, the operation itself) 2) If the allergy test results are negative, I would not accept such findings, requiring that the tests be repeated when the child id not anesthetized. _____________________________________________ Inflamm Res. 1999 Nov;48(11):582-7. Histamine release during the induction of anesthesia with propofol in allergic patients: a comparison with the induction of anesthesia using midazolam-ketamine. Kimura K, Adachi M, Kubo K. Department of Dental Anesthesiology, Faculty of Dentistry, Kyushu University, Fukuoka, Japan. OBJECTIVE: A prospective randomized controlled study was performed for patients with a history of allergy to evaluate the effect of the induction of anesthesia with propofol against histamine release, skin reactions, hemodynamic changes and other clinical symptoms, while also comparing these parameters during the induction of anesthesia with midazolam-ketamine for patients with a history of allergy. SUBJECTS: We examined 40 patients undergoing oral surgery, who had a history of allergy and/or the percentage of eosinophils in the leukocytes was more than 3%. METHODS: Forty patients were randomly allocated into two groups and thus received either midazolam-ketamine (M-K group, n = 20) or fentanyl-propofol (propofol group, n = 20) for the induction of anesthesia. Venous blood samples (4 ml each) were obtained before induction as a control and at 0.5, 1, 3, 5 minutes after the administration of each induction agent, and then furthermore at 0.5, 1, 3, 5 minutes after tracheal intubation in order to measure the plasma histamine level by using the HPLC post-label system. In addition, the blood pressure and heart rate were also simultaneously recorded. Skin reactions were also evaluated by two anesthesiologists. RESULTS: The incidence of 50% histamine release during the induction of anesthesia with propofol occurred in 15% of the patients with a history of allergy. Sixteen patients out of 20 (80%) showed a decrease in the systolic blood pressure after the administration of propofol without any evidence of histamine release. The incidence of 50% histamine release, skin reactions and an increase in the heart rate between the two groups were not statistically significant after the administration of each anesthetic agent. Moreover, some patients also demonstrated histamine release after tracheal intubation. Hemodynamic changes after tracheal intubation showed a similar tendency in both groups. No significant difference was observed regarding the incidence of histamine release, skin reactions and hemodynamic changes between both groups after tracheal intubation. CONCLUSIONS: Propofol was found to show a similar incidence of histamine release during the induction of anesthesia using midazolam-ketamine, and thus was also found to be a useful induction agent against histamine release for patients with a history of allergy when hydroxizine was used as a premedication. 3/17/03 re: False negative allergy skin tests Can you please tell me the different rates of false-negative allergy skin testing. I'm a PA who has prescribed anti-histamines with good success to people who have had "normal" pin-prick skin testing but still allergy-like symptoms/signs. Are these false-negatives or just the drying effect of the anti-histamine? It is quite unusual for allergy prick skin tests to be truly negative in individuals clinically sensitive to the offending allergen provided that high quality skin test reagents (well within their expiration date and appropriately stored) are used by those experienced in skin testing techniques and interpretation. More commonly, individuals who are atopic may exhibit positive skin test reactivity to allergens which do not currently cause clinical allergic reactions (as well as to allergens to which the patient is clinically sensitive). Possible reasons for a lack of skin test reactivity that you mention include: 1) The relevant allergen is not used in the skin test panel. Some individuals may be exhibiting clinical sensitivity to just one relatively unusual aeroallergen or food allergen. 2) The patient was taking antihistamines at the time that skin testing was carried out. Use of certain other medications can possibly, but much less likely, inhibit reactivity in allergy skin testing. For most antihistamines, withdrawal of the medications for 48 hours prior to skin testing is sufficient. 3) The patient has another clinical syndrome which looks like an allergic reaction. Your statement that patients' symptoms are controlled by antihistamines did not state what sort of symptoms or the type of antihistamines used in treatment. Rhinorrhea (running nose) whether due to allergic reactions or other causes may be reduced by use of some of the older antihistamine such as diphenhydramine (Benadryl) because of the anti-cholinergic action of such drugs. However, the more recent non-sedating antihistamines such as Clarinex or Allegra have very little anti-cholinergic activity and would not be expected to exert a non-specific drying effect on nasal secretions. Nasal congestion is generally not reduced impressively by any type of antihistamine. If your patients does not have prominent itching in the nose, eyes, or roof of the mouth (sometimes intermittent), an allergic cause of the nasal symptoms is much less likely. In practices set up to examine the leukocyte profile in a smear of nasal mucosal scrapings, the detection of a high frequency of eosinophils in such secretions also increases the likelihood that one is dealing with an allergic problem. However, occasionally such inflammatory cell responses are seen in the so-called NARES picture (non-allergic rhinitis eosinophilia syndrome). 8/12/02 re: What criterion for a positive prick skin test We are conducting a RCT of the efficacy of in-home interventions for reducing asthma morbidity. We will be doing skin prick testing to assess for sensitization to various indoor allergens and then intervene for patients who are sensitized and exposed. My question regards the definition of a positive skin test. The Joint Task Force Practice Parameters mention using 3mm greater than control as the threshold, but some studies like the Inner City Asthma Study have used 2 mm. Do data exist on the trade-offs of sensitivity and specificity using different thresholds? What would you recommend? I know that some studies, generally epidemiologic surveys, have used a mean diameter 2mm greater than the size of the reaction to a diluent control as a minimally positive prick skin test response to allergens. However, in practical terms, I have found that there is too much inter-tester variability using the "2mm plus" criterion and even variability in repeated tests of the same patient to get reliable information on which to base a diagnosis of clinically relevant allergy in an individual patient. To get another opinion, I consulted an expert who has carried out many clinical studies employing prick skin tests, Dr. Estelle Simons of the Children's Hospital and Univ. of Manitoba in Winnipeg, Canada. Her response is enclosed below. FROM: Dr. Estelle Simons Ask the Expert: Threshold for Positive Skin Tests We generally use the cut-off of 3 mm larger than diluent. 7/30/02 re: Clinical relevance of a 2+ intradermal skin test I am looking for help in regards to the dust mite D Pteronyssinus, and assistance in finding a chart that shows what a 2+ intradermal reading means as to the severity of an allergy. The skin test for the same dust mite was negative. All other allergy tests were negative. I have been able to get verbal input that a 2+ is very insignificant but I cannot seem to find anything in print. Is there a chart or something that explains those readings? If you could direct me to where I can find that information, I would appreciate it. Before answering your question, I think it worthwhile to emphasize some background material of which you may already be aware: 1) The information I am providing assumes that standardized dust mite extracts were used by testing personnel with sufficient experience in performing and reading both the prick type and intradermal (I.D.) type skin tests. Also, I assume that you were referring to prick skin tests in your statement that "The skin test for the same dust mite was negative." 2) The I.D. approach is anywhere from 500-10,000 times as sensitive intrinsically as the prick test, depending on the nature of the testing allergen. For that reason, the concentrations of the extracts used for prick tests are usually much higher than used in intradermal testing However, even then, the I.D. test is more sensitive than the prick skin test. 3) The degree of sensitivity of the patient cannot be determined reliably by the size of the whealing reaction to the relatively high concentration of allergen used in screening I.D. skin tests. A more reliable assessment of such sensitivity comes from careful intradermal testing with a panel of serially diluted preparations of a particular extract. 4) The prick skin test is not as sensitive for detecting IgE-mediated sensitivity as the I.D. test (about 80-90% as sensitive in most studies) even when higher allergen concentrations are employed in the prick test. However, the prick test reaction is more specific for clinically-relevant sensitivity to aeroallergens. One of the best demonstrations of the relative clinical relevance of prick and I.D. approaches was the study by Nelson's group, one of the most experienced investigators of skin test techniques (see enclosed abstracts). Using a model of grass-pollen allergy (where the history is usually much more clear-cut than the perennial symptoms due to mite allergy), they found 0% incidence of individuals with seasonal allergic rhinitis and positive reaction to grass pollen nasal challenge in those who were prick test neg/ I.D. test positive. This compared with a sizable frequency of clinical reactions to grass pollen in those who were prick test and I.D. test positive. Others have carried out studies using dust mite allergens (see enclosed abstract). Other groups have reported occasional individuals with fairly convincing histories of allergic rhinitis thought due to a particular aeroallergen who were prick test neg/ I.D. test positive to that allergen. However, it is not clear how many of such individuals were subjected to double-blind nasal challenges with the suspect allergen, as carried out by Nelson's group. My bottom line impression - individuals with relatively weak (1+-2+) reactions on I.D. testing and negative response to carefully performed prick skin test using the same source of extract are unlikely to be clinically reactive to the usual ambient concentrations of that allergen. It is conceivable that they may react symptomatically following exposure to very high airborne levels of the allergen. Reference Textbook by Middleton et al - "Allergy, Principles and Practice, 5th  Edition, pg. 432   J Allergy Clin Immunol 1996 Jun;97(6):1193-201 An assessment of the role of intradermal skin testing in the diagnosis of clinically relevant allergy to timothy grass. Nelson HS, Oppenheimer J, Buchmeier A, Kordash TR, Freshwater LL. Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA. BACKGROUND: Immediate skin testing is generally the preferred method for establishing the presence of allergy in clinical practice. There is no agreement, however, as to whether intradermal testing should be routinely performed if skin prick test results are negative. PURPOSE: The study was done to address the value of intradermal skin testing in the diagnosis of clinically significant sensitivity to grass pollen in patients exhibiting negative skin prick test responses to timothy extract. METHODS: Four groups were studied. Group I had a history of seasonal allergic rhinitis, negative skin prick test responses to timothy and Bermuda grass, but positive intradermal skin test responses to timothy grass. Group II had a history of seasonal allergic rhinitis and positive skin prick test responses to timothy grass. Group III had a history of seasonal allergic rhinitis but had negative responses to both prick and intradermal testing with timothy and Bermuda grass. Group IV had no history of rhinitis, had negative responses to skin testing with a panel of locally important allergens, as well as Bermuda and timothy grass, and had a serum IgE value of less than 20 IU/ml. Clinical sensitivity to grass was assessed by two methods: (1) nasal challenge with threefold increasing amounts of timothy pollen performed out of the pollen season and (2) correlation of subjects' daily symptom and medication scores with daily grass pollen counts during the grass pollen season. RESULTS: On the basis of nasal challenge with timothy grass, pollen allergic reactions were present in 11% of group I, 68% of group II, 11% of group III, and 0% of group IV. As determined by correlation of symptoms during the grass pollen season with grass pollen counts, 22% of group I, 64% of group II, 21% of group III, and 0% of group IV were considered allergic. If both criteria were required for a diagnosis of clinical allergy to grass, the percent positive was 0 for group I, 46 for group II, 0 for group III, and 0 for group IV. CONCLUSION: Under the conditions of this study the presence of a positive intradermal skin test response to timothy grass (1000 AU/ml) in the presence of a negative skin prick test response to timothy grass (100,000 AU/ml) did not indicate the presence of clinically significant sensitivity to timothy grass, and by inference, to other cross-reacting grass Ann Allergy Asthma Immunol 1997 Nov;79(5):427-30 Skin prick reaction and nasal provocation response in diagnosis of nasal allergy to the house dust mite. Kanthawatana S, Maturim W, Fooanan S, Trakultivakorn M. Department of Pharmacology, Chiang Mai University, Faculty of Medicine, Thailand. BACKGROUND: The allergen skin test is commonly used to ensure the diagnosis of allergic rhinitis even though positive results do not necessarily indicate that rhinitis is of allergic origin. OBJECTIVE: To determine the association between skin prick reactions and nasal provocation responses to Dermatophagoides pteronyssinus (Der p) allergen extract. METHODS: Twenty-six patients with perennial rhinitis and 25 controls underwent skin prick and nasal provocation tests to standardized Der p allergen extract. With the use of allergen extract titration delivered by a metered dose pump, nasal stuffiness, itching, and sneezing were noted, the amount of secretions measured, and nasal airway resistance was recorded by active anterior rhinomanometry. RESULTS: The majority of the patients with rhinitis (20/26), but none of the controls, exhibited strong skin test positivity (4+) to Der p allergen extract. In addition, the majority of the patients with 4+ skin reactions (16/20) had moderate to severe rhinitis. Significantly increased nasal reactivity to the allergen was also observed among those with 4+ skin test positivity. The controls exhibited nasal provocation responses only with significantly higher end-point doses of the allergen extract regardless of the skin test results. CONCLUSION: Only 4+ skin test positivity was closely associated with increased nasal reactivity to Der p allergen among the patients with perennial rhinitis. The nasal provocation technique would be a useful adjunct testing to ensure the diagnosis of nasal allergy to the Der p mite, particularly among those patients with rhinitis with only mild to moderate skin test positivity.   5/14/02 re: Approach to possible allergic rhinitis with negative skin tests I have referred several patients in the 5-10 yr old age category for allergy evaluations who have had negative skin prick test results. They have had classic symptoms of allergic rhinitis with wet, pale, swollen nasal mucosa, some sneezing, occasionally itchy eyes, frequently a seasonal pattern to their symptoms, and complications of sinusitis. One of these children has been tested 3 years in a row with no reactions to the prick tests. Their parents seem appropriately concerned and assure me that the children were not on oral antihistamines at the time of their testing. (I regularly ask parents to alert the allergist's office regarding any medications and to ask for any special instructions regarding discontinuation of these meds prior to their appointments.) What explanations are there for these results? Would RAST testing be appropriate or reliable? Any other suggestions? I have been recommending to most to continue treatment with antihistamines and occasionally nasal steroids, particularly when the children appear to do better and experience improvement of their symptoms when on these meds. There are several possible reasons why an individual with a history suggestive of allergic rhinitis may have exhibited negative responses to allergy prick skin tests. These include: 1) Technical factors- I assume that you have referred your patients to highly qualified and experienced allergists whose skin testing techniques are very reliable 2) The skin of the individual is incapable of exhibiting a good whealing reaction (due to medication effects and other factors). Most of these factors can be eliminated from consideration if the patient exhibits strong whealing reactions to the "positive control" tests with appropriate concentrations of histamine and/or codeine. I assume that such positive controls were carried out in skin testing of your patients. 3) Skin testing with the particular offending allergens in those patients were not carried out. I assume that experienced allergist consultants seeing your patients will have tested for the unusual, as well as the common, aeroallergens in your region. A suggested approach to the patients you mentioned: 1) Determine whether the seasonal rhinitis is truly allergic (a seasonal pattern does not always indicate allergic etiology). During the time period when the patient is particularly symptomatic, obtain a gentle scraping of the nasal mucosa (preferably, the middle turbinate area), smear gently on microscope slides, fix with ethanol and stain with special stains for eosinophils. This requires some experience and facilities to do this. I would suppose that the allergist seeing your patient should be set up to do this. In almost all cases of allergic rhinitis, particularly seasonal allergic rhinitis, there is a prominent eosinophilic inflammatory response (eosinophils at least 20% of the inflammatory cells in the scraping specimen). However, the patient must not have used nasal steroids for several weeks before the specimen is obtained since nasal steroids (but usually not antihistamines) may suppress the eosinophil inflammatory response However, an eosinophil accumulation in the nose can occasionally be seen in some non-allergic rhinitis, called by some as NARES (non-allergic rhinitis eosinophilia syndrome). However, in NARES, there is generally little sneezing or itching, two common features of allergic rhinitis. Also, there is usually not the history of typical allergies in parents and/or siblings seen in a large percentage of those with true allergic rhinitis. 2) If the history, as noted above, is strongly suggestive (including a family history of atopy) and there is a prominent eosinophil accumulation, but careful and thorough allergy skin tests yield negative responses, then a search with the RAST or ELISA techniques for specific IgE antibodies in the serum would be reasonable, provided: a) These tests are done in a reliable lab. I have found that a number of commercial labs report overly sensitive or misleading results. You could ask your allergist consultant to assist you in this regard. b) Do not draw too much implication from a modestly positive test (1+ or 2+ values). I have found that clinically verified positive RAST tests are usually in the 3-4+ ranges. 3) Meanwhile, your approach with therapeutic trials sounds very reasonable. However, I should emphasize that H1 antihistamines of any type or brand may help the sneezing or itching of allergic rhinitis, but do little to reduce the nasal congestion that becomes more prominent as the rhinitis becomes subacute/chronic. In my experience, added oral decongestants (usually pseudoephedrine) are helpful somewhat irregularly and only in some individuals, sometimes with stimulatory side effects (relatively narrow therapeutic index). Nasal steroids are usually more effective, controlling nasal congestion as well as sneezing and itching. However, they may take several days of use before any improvement is noted. Also, associated conjunctivitis will likely require additional therapy. 1/21/02 re: Testing for IgE-mediated sensitivity to cockatoo Are specific tests, skin, IgE, etc, available for the diagnosis of allergy to avian, particularly cockatoo, powder down? Studies by several groups over the years have shown the allergens present in the feathers/down of psittacine birds such as cockatoos are generally present in the serum of such birds (see enclosed abstract). Therefore, commercial suppliers of allergenic extract have sometimes provided diluted serum of this species of birds for prick skin testing. I do not know whether the commercial labs in your area performing RAST-type tests will analyze patient sera for specific anti-psittacine IgE antibodies. If they do not provide this service, I suggest that you contact the D.A.C.I. labs in Johns Hopkins University Medical Center or the Mayo Clinical Labs in Rochester MN, two large, high-quality labs, to see if they perform such assays Allergy 1994 Jul;49(6):448-53 Allergens causing bird fancier's asthma. Tauer-Reich I, Fruhmann G, Czuppon AB, Baur X. Pneumology Section, Klinikum Grosshadern, University of Munich, Germany. The study investigates to what extent bird feathers contain relevant allergens/antigens involved in bird fancier's asthma. The study group consisted of two budgerigar fanciers, two parrot fanciers and one canary fancier. All subjects complained of asthmatic symptoms, caused by contact with their birds, and they showed a significant bronchial hyperactivity to acetylcholine. Positive IgE antibody reactions to bird sera as well as to extracts of feathers were observed in RAST. Well-defined major allergenic bands could be detected and identified in the IgE immunoblots with feather extracts as well as with serum proteins of budgerigar, parrot, pigeon, canary, and hen (mol. mass 20-30 kDa and 67 kDa). The most pronounced bands appeared with the extracts of species to which an exposure had taken place. Weaker IgG-binding patterns were also observed. Our results show that inhalable feather dust contains several allergenic components, which cross-react with serum allergens/antigens of the same as well as of other bird species. This emphasizes the significance of bird feathers for immediate-type allergic reactions. 10/10/01 re: Cause of exaggerated skin test responses? I recently saw a 36 yr. old male with an unusual history of non granulomatous iritis, a reported haplotype of HLA B27 and a 4 year history of subjective vertigo. He was sent for skin testing due to very mild allergic rhinitis and a recent onset of RAD. He has been a long distance runner and scores well on structured PT testing. He is also seeing a neurologist and otolaryngologist. Present medications consist of albuterol, loratadine, sudafed and cerivastatin. Spirometry was obstructive and did not change with albuterol nebulization. Had primarily EIB until recently. FVC 114, FEV-1 87 and Mmef 38. He is a non-smoker. He gets symptoms near cats and rabbits but has no collateral allergies but the record notes sulfa allergy. His skin tests were exaggerated and hopefully can be seen on the attachment. I have never experienced the amount of erythema in any patient I can recall even with the most severe SAR. He also had large wheals as outlined. He did not have any systemic symptoms, wheeze or show any change in his spirometry after the testing. He has not demonstrated any collagen-vascular symptoms one would look for with his history. The question at this time is why or what could lead to the exaggerated responses and in one with meager symptomology? The first explanation for your findings that comes to my mind is that your patient has an exaggerated end organ response- either: 1) very sensitive or increased number of skin mast cells or 2) excessive vascular response to released mast cell mediators. Another possibility is that your patient has very high levels of the relevant IgE antibodies, despite very modest allergic respiratory symptoms (seen occasionally). I suggest these approaches to explore these possible explanations: 1) Obtain an assay for IgE antibodies to 1or 2 of the allergens that induced the exaggerated skin test responses. I would send such sera to a highly reputable lab such as the DACI lab of Johns Hopkins (check with the office of Dr. Bob Hamilton, listed in the AAAAI directory if you are not familiar with the DACI lab operation) or the Mayo Clinic labs in Minnesota. You can rely on very good quantitative assays done in both those places. 2) Perform serial dilution intradermal skin testing with codeine (a non-immunologic mast cell activator), as reported by David Rosenstreich's group in urticaria patients some years ago. That report describes the sort of response you should expect in normal individuals. 3) Perform serial dilution intradermal skin testing with histamine. If there is an exaggerated response to codeine, but not to histamine, I would obtain a punch biopsy of the area you used for the serial dilution skin testing (wait several weeks after the skin testing was done). Ask the pathologist (preferably a dermatopathologist) to stain specifically for mast cells -what is really best, if available, is to do immunohistochemistry with anti-tryptase antibodies. If there is a striking increase in the frequency of skin mast cells, you should consider other studies looking for a mastocytosis variant. 9/6/01 re: Skin testing during olanzapine therapy I’m a specialist of internal medicine. I have two questions. 1. Can we make Prick test in patient on olanzapin (ZYPREXA)? 2. If no, how long must patient avoid this drug before testing? I am not familiar with any reported inhibition of allergic skin test responses by olanzapine treatment. Reviews of the actions of this drug do not mention any antihistaminic activity (see enclosed abstract). However, to be on the safe side, I would have the olanzapin withheld for 24 hours prior to skin testing, if feasible. Also, the responses to positive control skin tests (histamine, codeine) carried out at the same time as the allergy skin tests should be evaluated. If such positive control test responses are much smaller than in your usual experience, then negative responses to the allergy skin tests may not be valid. Am J Health Syst Pharm 1998 May 15; 55(10): 1003-1016 Olanzapine: a serotonin-dopamine-receptor antagonist for antipsychotic therapy. Bever KA, Perry PJ. College of Pharmacy, University of Iowa, Iowa City 52242-0123, USA. "The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, dosage and administration, and cost of olanzapine are reviewed. Olanzapine is a serotonin-dopamine-receptor antagonist indicated for use in the treatment of schizophrenia and other psychotic disorders. The affinity of olanzapine for neuroreceptors is similar to that of clozapine. The drug is well absorbed from the GI tract; food has no effect. Olanzapine is more effective than placebo and equal to haloperidol in reducing psychotic symptoms on two rating scales. However, unlike typical dopamine-receptor antagonists used for antipsychotic therapy, olanzapine is more effective in reducing the negative symptoms of schizophrenia. The most frequent adverse drug reactions (ADRs) associated with olanzapine are somnolence, agitation, insomnia, and headache. Constipation and dry mouth occur as dose-dependent ADRs. Unlike clozapine, olanzapine does not cause agranulocytosis. No cases of tardive dyskinesia or neuroleptic malignant syndrome have been reported. Olanzapine has been associated with slight increases in hepatic transaminases. More study is needed to determine whether olanzapine interacts significantly with other drugs. The recommended starting dosage is 5-10 mg orally once daily. Efficacy beyond six weeks has not been evaluated; patients treated for longer than six weeks should be periodically reassessed. Olanzapine costs about 10 times more than typical antipsychotics because a generic version is not available; however, olanzapine costs less than clozapine therapy and may cost less than haloperidol in terms of total health care costs. Olanzapine offers an effective alternative for treating schizophrenia and has a favorable adverse-effect profile." 8/3/01 re: In vitro vs. skin testing for peanut allergy Would you be so kind as to tell me if there is a position statement on RAST food testing in severely peanut (etc) food patients as opposed to skin tests? I have perused the Academy site and the information in the position statement is not specific to this point but more open ended. HMOs are denying even this. I do think there is a place for RAST evaluation when skin tests are in doubt or if there may be a danger. I am not aware of a Position Statement of the AAAAI which directly addresses your question. Therefore, I consulted Dr. Wesley Burks, a leading investigator of food allergy, including peanut allergy. His response is enclosed below. I have also enclosed the abstract of the article by Sampson and Ho to which Dr. Burks refers and the abstract of a report by Burks and others dealing with peanut skin testing. I hope that this information will be of assistance. "The only in vitro testing that should be done is the CAP-FEIA from Pharmacia. Personally, I would do prick skin testing first and then if it is positive do the CAP-FEIA. There is an article that Sampson and Ho published in the Oct. 1997 issue of JACI that outlines the sensitivity and specificity of the peanut RAST. There are values outlined in the manuscript that give good positive and negative predictive values for children with possible peanut allergy." J Allergy Clin Immunol 1997 Oct;100(4):444-51 Relationship between food-specific IgE concentrations and the risk of positive food challenges in children and adolescents. Sampson HA, Ho DG. Johns Hopkins University School of Medicine, Baltimore, MD 21287-3923, USA. BACKGROUND: The double-blind, placebo-controlled food challenge (DBPCFC) is the "gold standard" for diagnosis of food hypersensitivity. Skin prick tests and RASTs are sensitive indicators of food-specific IgE antibodies but poor predictors of clinical reactivity. Previous studies suggested that high concentrations of food-specific IgE antibody were predictive of food-induced clinical symptoms. Because the CAP System FEIA (Pharmacia Diagnostics, Uppsala, Sweden) provides a quantitative assessment of allergen-specific IgE antibody, this study was undertaken to determine the potential utility of the CAP System FEIA in diagnosis of IgE-mediated food hypersensitivity. METHODS: Sera from 196 patients with food allergy were analyzed for specific IgE antibodies to egg, milk, peanut, soy, wheat, and fish by CAP System FEIA. Sera were randomly selected from 300 stored samples of children and adolescents who had been evaluated by history, skin prick tests, and DBPCFCs. The study population was highly atopic; all patients had atopic dermatitis, and approximately 50% had asthma and allergic rhinitis at the time of initial evaluation. The performance characteristics of the CAP System FEIA were compared with those of skin prick tests and the outcome of DBPCFCs or "convincing" histories of anaphylactic reactions. RESULTS: The prevalence of specific food allergies in the study population varied from 22% for wheat to 73% for egg. Allergy to egg, milk, peanut, and soy accounted for 87% of confirmed reactions. The performance characteristics of skin prick tests and CAP System FEIA (egg, milk, peanut, fish) were comparable, with excellent sensitivity and negative predictive accuracy but poor specificity and positive predictive accuracy. The performance characteristics of the CAP System FEIA for soy and wheat were poor. For egg, milk, peanut, and fish allergy, diagnostic levels of IgE, which could predict clinical reactivity in this population with greater than 95% certainty, were identified: egg, 6 kilo units of allergen-specific IgE per liter (kU[A]/L); milk, 32 kU (A)/L; peanut, 15 kU(A)/L; and fish, 20 kU(A)/L. CONCLUSIONS: When compared with the outcome of DBPCFCs, results of CAP System FEIA are generally comparable to those of skin prick tests in predicting symptomatic food hypersensitivity. Furthermore, by measuring the concentrations of food-specific IgE antibodies with the CAP System FEIA, it is possible to identify a subset of patients who are highly likely (>95%) to experience clinical reactions to egg, milk, peanut, or fish. This could eliminate the need to perform DBPCFCs in a significant number of patients suspected of having IgE-mediated food allergy.   J Allergy Clin Immunol 1995 Apr;95(4):837-42 Comparison of commercial peanut skin test extracts. Hefle SL, Helm RM, Burks AW, Bush RK. Department of Medicine, University of Wisconsin, Madison, USA. BACKGROUND: Skin prick testing is a major tool for diagnosing food allergy. Food allergen extracts have not been standardized; this may lead to great variability in the predictive accuracy of skin prick tests. METHODS: Six commercial peanut skin test extracts were compared in vitro with RAST inhibition assays, ELISA, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoblotting with sera from peanut-allergic adults and in vivo by skin prick testing. RESULTS: ELISA showed that the content of peanut allergens Ara h I and Ara h II in the extracts ranged from 0.0015 to 0.0236 and 0.0001 to 0.0164 mg Eq/ml, respectively. RAST inhibition studies showed that the extracts produced curves of similar slope, suggesting conservation of allergenic epitopes. SDS-PAGE revealed differences in protein profiles because roasted extracts generally possessed the same number and proportion of major protein bands but raw extracts varied more in both respects. SDS-PAGE and immunoblotting showed that two of the extracts contained major IgE-binding protein bands that did not appear in the others. One roasted extract gave little protein banding and consequently little IgE binding. CONCLUSIONS: Skin-testing results showed no differences in the ability of the extracts to provoke a positive skin test response in peanut-sensitive subjects. 5/29/01 re: Sensitivity of skin test vs RAST for venom allergy What are the relative merits of skin testing and RAST testing for insect sting allergy? Based on earlier studies, the usual clinical practice has been to consider individuals who exhibit negative skin test responses to a panel of the currently available hymenoptera venom extracts to be at no significantly increased risk for a systemic reaction to a subsequent sting. This was thought to be the case even in individuals who gave a fairly convincing history of a systemic reaction to a previous sting. However, the recent report by Golden et al (which you may have seen) indicates that about 20% of their "history positive/skin test negative" individuals manifested a systemic reaction to a sting challenge. In some of these individuals there had been evidence of serum IgE antibodies against one or more venom allergens by their sensitive in vitro immunoassay. I have enclosed below a review of their report which I wrote for the Current Literature section of this AADMC website. The Insect Committee of the AAAAI, including Dr. Golden, is in the process of writing a committee report which should include recommendations in this area. Insect sting allergy with negative venom skin test Summary There have been reports of individuals with histories of severe systemic reactions to hymenoptera insect stings despite being skin test negative to the relevant venom. Golden et al of Johns Hopkins University in Baltimore, MD prospectively examined the prevalence of negative venom skin test responses in 307 patients with positive histories of systemic hymenoptera sting reactions. In 99 (32%) of these patients, venom skin tests up to 1 microgr/ml were negative. In 36 of these 99 patients there were low positive venom in vitro (RAST) tests. Occasionally a repeat venom skin test was positive. In another 7 of the 99, high levels of anti-venom IgE antibody were found in the RAST tests. Sting challenges were performed in 141 of 196 patients with positive venom skin tests, resulting in 30 systemic reactions. Sting challenges in 37 of 43 patients with negative skin tests and positive venom-specific RAST tests elicited systemic reactions in 9 individuals. Sting challenges in 14 negative skin test/negative in vitro test subjects elicited systemic reactions in 2 individuals. The authors concluded that negative venom skin test responses can be seen in some individuals with convincing histories of systemic reactions to field stings. The serum of some of these subjects contains venom-specific IgE, as detected by a sensitive RAST. Up to 24% of the venom skin test-negative subjects will manifest a systemic reaction to a sting challenge. Better skin testing reagents are required.  Reference J Allergy Clin Immunol 2001;107:897-901 Editor's Comments For years, most clinicians have been assured that patients with histories of apparent systemic reactions to a previous hymenoptera insect sting but now venom skin test negative are not at increased risk for a systemic reaction to a subsequent sting. The findings described above by one of the most experienced groups investigating venom sensitivity are therefore quite disturbing. Screening venom skin testing, using currently available reagents, is not apparently sensitive enough to detect all systemically sensitive individuals. Indeed, the percentage of these patients with negative venom skin tests who subsequently reacted to a sting challenge was not that much different than the percentage of venom-skin-test-positive individuals who reacted to a sting challenge. Is there anyway that one can increase the sensitivity of the venom skin testing procedure used in clinical practice? One could try skin testing with higher concentration venom extracts in individuals with convincing histories of sting systemic reactions who exhibit negative skin test responses to the top concentration of 1 microgram/ml of venom extract currently recommended. However, there are a sizable number of false positive skin test reactions to such venom concentrations greater than 1 microg/ml. The in vitro tests used by Golden et al may increase the sensitivity of screening approaches but they are research lab procedures not necessarily paralleled by the RAST-type assays used in commercial clinical labs. Obviously, improved approaches are needed. 5/17/01 re: Guidelines for skin testing in children Does The Academy have any appropriateness guidelines for allergy skin testing of pediatric patients? Much has been written about allergy skin testing in children by leading members of the AAAAI .However, the Position Statements of the AAAAI concerning skin testing does not deal specifically with skin testing in children. I have enclosed a portion of the Joint Task Force Practice Parameters dealing with allergy skin testing, including some comments about skin testing in children. The whole document, written by a committee of highly respected allergist-immunologists in the USA, can be accessed through a link from this AADMC website. I have enclosed abstracts of several articles dealing with aspects of skin testing in children. Excerpted from Practice Parameter Document Prick/Puncture Tests Prick/puncture tests are widely used for confirmation of clinical immediate hypersensitivity induced by a wide variety of naturally occurring inhalant and food allergens. On a per test basis they are generally considered to be the most convenient, least expensive and most specific screening method for detecting the presence of IgE antibodies in patients with appropriate exposure histories. Under carefully defined circumstances, these tests are also useful in the diagnosis of drug and chemical hypersensitivity (e.g. chloroplatinate salts, sulfone-chloramides, acid anhydrides, etc.) reactions. Since it is impossible to quantify the exact amount of injected material by prick/puncture tests, allergic skin responses are dependent upon the skill of the individual tester, the reliability of the device, the color of the skin, the status of skin reactivity on the day of the test, the potency and stability of test extracts (especially optimum concentrations), the depth of the puncture needle and the force, duration and the angle of the application device. If these quality controls are not assiduously applied, interpretation of the tests could vary from one technician to another. Prick/puncture tests are usually performed on the upper back or volar surface of the forearm. Prick/puncture tests with allergens should be read at the peak of the reaction, usually 15 to 20 minutes after application. Both erythema and wheal should be measured in a standardized manner and the method(s) of measuring should be recorded. A prick/puncture skin test wheal response of at least 3 mm (with equivalent erythema) > than the diluent control done at the same time is required as proof of the presence of allergen specific IgE. The larger the prick/puncture skin test reaction, the more likely it is to be of clinical significance. However, the presence of a positive prick/puncture skin test per se does not establish whether clinical sensitivity currently is present. Prick/puncture tests are generally less sensitive than intracutaneous tests. For inhalant allergens, prick/ puncture tests are generally felt to correlate better with the presence of clinical allergy. However, intracutaneous testing may detect relevant sensitivity and should be considered when the prick/puncture test is negative or equivocal to allergens strongly suggested by the patient's history or exposure, or when skin sensitivity may be decreased such as in infants or older patients. When using specific purified allergens, "false-positive" (non IgE-mediated) irritant reactions are less likely, and true sensitization can be more easily established with prick/ puncture than with intracutaneous tests, with certain important exceptions (i.e., Hymenoptera venom and penicillin). Prick/puncture tests are generally considered to be more specific than the usual test strength of intracutaneous tests when both are compared with inhalation or ingestion challenges.  Generally, fewer prick tests need to be performed in infants and very young children because these age groups are not likely to be sensitized to as many allergens as older children and adults. In younger patients, sensitization is more apt to reflect intense, prolonged exposure to allergens encountered earliest in life (i.e., foods, house dust mites, indoor molds, indoor insects and animal danders) rather than pollen. Recognition of a positive skin test by the patient may be useful in gaining cooperation for allergy avoidance measures.  Clin Rev Allergy Immunol 1999 Fall;17(3):323-38 Skin testing and food challenges in allergy and immunology practice. Williams LW, Bock SA. Division of Pediatric Allergy and Immunology, Duke University School of Medicine, Durham, NC 27710, USA. Skin tests by prick technique offer considerable guidance in the diagnosis of food allergy. Negative prick skin tests are powerful evidence against food allergy. Positive food skin tests are slightly to moderately predictive of reaction to a food on DBPCFC. Oral food challenge is necessary for confirmation of food allergy, except where the history is overwhelmingly convincing. Open, incremental food challenge as described is diagnostic if negative, but only 50% of all positive open challenges are confirmed on blinded challenge. DBPCFC can be designed for any food with simple blinding techniques. The technique of DBPCFC can be modified for investigation of atypical symptoms  Pediatr Allergy Immunol 1998 Nov;9(4):186-91 Comment in: Pediatr Allergy Immunol. 1999 Nov;10(4):274-5 Interpreting skin prick tests in the evaluation of food allergy in children.  Eigenmann PA, Sampson HA. Division of Pediatric Allergy, Johns Hopkins School of Medicine, Baltimore, USA. Background: Skin prick tests (SPTs) are utilized routinely in the evaluation of food allergy and several authors have discussed their utility. Efforts to standardize SPT reagents and procedures have been made, but the accuracies of different recording techniques have not been clearly defined. The aim of this study was to compare different SPT recording methods with the outcome of oral food challenge and determine whether they offer any advantage over the criteria proposed by Bock and May (1).  Patients and Methods: Children suspected of IgE-mediated symptoms to any of five common food allergens (egg, milk, peanut, soy and wheat) were skin tested by the prick technique utilizing commercial extracts. The wheal reactions were recorded by two different methods: first by measuring the largest diameter of the wheal and the diameter orthogonal to it (mean wheal diameter), and second by recording the surface area of the wheal with a hand-held scanner. Wheal sizes above the 95% confidence interval of tolerant individuals were considered positive. The results of double-blind, placebo-controlled food challenges were considered the "gold standard" for diagnosis. Cut-off values were compared for positive responses in our study population (mean diameter/surface area of wheal): 4 mm/16 mm2 for egg, 5 mm/29 mm2 for milk, 6 mm/40 mm2 for peanut, 3 mm/9 mm2 for soy, and 3 mm/7 mm2 for wheat.  Results: Significant differences in wheal sizes were seen between individuals who were allergic or tolerant to egg (P < 0.001), milk (P < 0.001), wheat (P < 0.005), and peanut (P < 0.05). Reactivity to soy could not be predicted based on SPT results (P = n.s.). The sensitivities and the specificities of the two recording methods were similar. The predictive values were not significantly different from that of the commonly utilized method of grading SPTs (i.e. positive = mean diameter 3 mm or greater than the negative control).  Conclusions: Skin prick tests are a useful procedure for evaluating clinical reactivity to egg, milk, peanut and wheat, but not to soy. While the size of the SPT wheals may be interpreted utilizing mean diameter or surface area cut-offs, the predictive values of these measurement methods were no better than the commonly utilized grading method where a positive skin test was recorded as a mean wheal diameter 3 mm greater than the negative control.  Ann Allergy Asthma Immunol 1998 Apr;80(4):303-8 Erratum in: Ann Allergy Asthma Immunol 1998 Aug;81(2):126 Skin test reactivity to indoor allergens as a marker of asthma severity in children with asthma. Sarpong SB, Karrison T. Department of Pediatrics, the University of Chicago, Illinois, USA. Background: Specific IgE responses to common indoor aeroallergens in children with asthma have been found to be associated with acute asthma.  Objective: The purpose of this study was to examine the association between asthma severity and skin test reactivity to four common indoor allergens.  Methods: The charts of 139 asthmatic children, aged 5 to 18 years, seen in a pediatric allergy clinic were reviewed to obtain the results of skin tests to cat, dog, cockroach, and dust mite allergens, FEV1, anti-asthma medication requirements and demographic characteristics. Logistic regression for ordinal data was used to examine the association between skin test reactivity and asthma severity (mild, moderate or severe) as determined from FEV1 and medication usage.  Results: The rate of allergen sensitivities were dust mite 55%, cockroach 50%, cat 29% and dog 17%. Children with positive skin test to cat allergen were more likely to have a higher asthma severity rating than children with a negative cat allergen skin test [proportional odds ratio (OR) = 3.0, 95% confidence interval (CI) = 1.4 to 6.1, P = .003]. This association remained significant after we controlled for skin test reaction to the other three allergens and various sociodemographic factors (adjusted OR = 3.0, 95% CI = 1.3 to 7.2, P = .013). The ORs for sensitivity to dog, cockroach, and dust mite allergen did not differ significantly from one, but children who were sensitized to all four allergens had an OR of 4.8 (95% CI = 1.3 to 18, P = .019) relative to children who were not sensitized to any of the four allergens. This association also remained significant after controlling for sociodemographic variables (P = .030).  Conclusion: Children with combined sensitivity to cat, dog, dust mite, and cockroach allergens were at increased risk of having more severe asthma. Our data also suggest that sensitization to cat allergen per se is a risk factor for more severe disease in these asthmatic children.   3/23/01 re: Treatment agents to stop before skin testing We do epidemiological research on childhood asthma and allergy. We are beginning a phase where we will do methacholine challenge testing and skin testing on our 6.5-7.5 year olds. Some of these children are on allergy and asthma medication. We are compiling a list to advise parents how long to withhold these meds before the testing is performed. Any insight you may provide will be much appreciated. I am not aware of a single publication by the AAAAI. Therefore, I consulted Dr. FE Simons, a leading investigator in that area of study and former chair of the Pharmacotherapeutics committee of the AAAAI (see enclosed abstracts of some of her reports). Dr. Simons' response is enclosed below.  Because of the lack of a single document to assist, I will mention my own approach, based on clinical experience and not extensive controlled studies: Antihistamines- stop all. The duration of cessation will vary with the type of antihistamine from 48 hours for diphenhydramine (Benadryl) to a week for hydroxyzine/cetirizine (Zyrtec)  Pseudoephedrine (Sudafed or component in antihistamine -decongestant)- stop for 18 hours  Tranquilizers- varies with the agent used. For example, doxipen (Sinequan, Adipen) is a potent, relatively long-lasting antihistamine.  Leukotriene antagonist, inhaled medications (all)- not necessary to stop  Oral steroids- no effect of moderate doses for several weeks. There may be suppression by long-term doses of at least 10 mg/day prednisone or equivalent.  FROM: Dr. Estelle Simons To the best of my knowledge, there is no comprehensive review of the various medications which need to be withheld before allergy skin tests, methacholine challenge tests, etc., and the duration of time for which each medication needs to be withheld.  With my very best regards... The following abstracts can be viewed at www.medline.com J Allergy Clin Immunol 2001 Mar;107(3 Pt 1):526-30  Ann Allergy Asthma Immunol 2001 Jan;86(1):44-50  J Allergy Clin Immunol 1995 Mar;95(3):759-64  J Allergy Clin Immunol 1992 Oct;90(4 Pt 2):705-15    11/14/00 re: Skin test forms Do you have recommendations for skin testing forms? Your request is not clear. Which skin test form were you interested in? There are many different forms used by different clinicians to record the results of different types of skin tests (e.g.inhalants, food, penicillin agents, etc., etc.). It is not feasible to transmit all of these by e-mail. I assume that you are not a trained allergist-immunologist since such individuals would have had ready access to a wide variety of skin test forms. A reasonable way of obtaining a sizable number of forms of one source (though not all types) is by contacting one of the large allergy extract suppliers such as Hollister-Stier (Tel # 1-800-992-1120). Identify yourself as a physician and ask for the Professional Relations Dept. Explain to that department that you are interested in allergy skin testing and request their catalogue and a set of skin test forms . 11/9/00 re: Skin Testing  vs  in Vitro Testing in allergy diagnosis Could you please give me information regarding skin testing vs in Vitro testing in allergy diagnosis. The response to your question is made more difficult because of the considerable variation in the quality and costs of both skin test and in vitro approaches in different facilities. If we assume that both approaches are done in a high-quality way and interpreted appropriately by experienced observers, we can make several helpful comparisons. The sensitivity of prick skin testing  and in vitro tests to inhalant allergens are similar. Intradermal (I.D.) skin testing is more sensitive than prick or in vitro testing but is frequently positive when the history does not suggest that the particular allergen is causing symptoms. Therefore, I do prick test first, reserving the I.D. tests for situations where the history is strongly suggestive, but the prick tests are negative. The advantages of skin testing include: Fast with answers available within and hour or so while the patient is still in the office (compared to days to weeks for usual commercial in vitro tests) Can test for certain allergens for which there are no reliable in vitro tests (e.g.- penicillin, certain foods) Can do serial dilution skin testing  where appropriate with a capacity to quantitate better  than feasible in the usual commercial in vitro tests. The advantages of in vitro test include: Less discomfort  (one blood draw vs. multiple prick/I.D. skin tests). A factor mainly in small children Not limited by extensive skin disease or current antihistamine treatment (both of which may interfere with skin testing). Can do in the rare case where you are concerned that the skin test may itself induce a systemic allergic reaction in very sensitive subjects (e.g.-latex, ,-however,  the in vitro test is less sensitive than skin testing so have to skin test if the in vitro test is negative) Insofar as costs are concerned, I have found that commercial lab costs for in vitro tests are almost always more than we charge for skin tests yielding the same information. My preference has been   to do skin testing unless contra-indicated or limited (as described above) so that I can get a faster answer and be able to advise the patient promptly. 8/16/00 re: Adverse reactions during skin testing in patients receiving beta blockers therapy Could you please give me information regarding adverse reactions in patients receiving oral beta blockers undergoing allergy skin testing. A common recommendation is to with hold beta blocker agents for awhile (the length of time depending on the particular agent) before the patient undergoes allergy testing .If beta blockers cannot be discontinued, special caution should be taken in doing the testing (see enclosed excerpt from the Joint Force Practice Parameters). However, there is relatively little "firm" evidence on which to base such recommendations. Most of the data of which I am aware comes from study of serious/severe reactions during allergy immunotherapy (see enclosed report by Reid et al). Others have concluded that there is no increased frequency of anaphylactic reactions in those on beta-blockers (see abstract at www.medline.com). However, of note, 7 of 180 individuals diagnosed in the Mayo Clinic as having experienced anaphylactic reactions had been on beta blocker therapy. Because of the unsettled state of knowledge in this area, I think that one should try to with hold beta blocker therapy for at least 24 hours prior to skin testing if at all feasible. J Allergy Clin Immunol 1993 Jul;92(1 Pt 1):6-15 5/11/00 re: Skin testing guidelines I am an Italian dermatologist and I am looking for "guidelines about skin testing." In particular, I have doubts about the age in which it is reasonable (and useful) to start performing skin tests (and other allergologic investigations), in infants with atopic dermatitis or other allergic diseases. I assume that you mean the use of allergy skin testing in diagnosis. This subject is discussed in detail in one of the Practice Parameter reports of the Task Force on Allergic and Immunologic Disorders written by a national panel of highly experienced specialists in the field. These Task Force Parameters are included in the Current Literature section of this AADMC web site. Click on Practice Parameters, then on Allergy Testing . Scroll down the Table of Contents under Allergy Testing, choosing the subjects of interest to you.  2/4/00 re: Skin testing for narcotic allergies Could you comment on skin testing for narcotic allergies since narcotic such as morphine release histamine. Is skin testing for narcotic allergies valid? Does the histamine release affect the results? Skin testing to narcotics such as morphine and codeine to detect possible allergic reactions are usually not feasible because of the non-immunologic activation of skin mast cells by these agents. Indeed, in our clinic, skin testing with codeine has been used to assess the capacity of the patient's skin mast cells to release histamine. It is conceivable that an individual "allergic to opiates" could react to skin testing with a very low concentration of morphine, insufficient to non-immunologically activate skin mast cells. However, I have never observed that situation because systemic anaphylactic/anaphylactoid reactions to opiates are very uncommon though postulated as one of the causes of "intra-operative anaphylaxis." This low frequency may be because there are opiate receptors on skin mast cells but not on mast cells present in internal organs. Therefore, incubation of opiates with the latter type of mast cells does not result in histamine release. Also, opiates are considered "incomplete" mast cell stimulants, inducing release of pre-formed mast cell mediators (such as histamine) but not formation of newly synthesized mediators, including certain cytokines Of interest, fentanyl, a commonly used opiate, is a poor non-immunologic activator of skin mast