Professional Documents
Culture Documents
Diagnosis
May 5, 2012
ACAAI 2011
What do patients (and their doctors) want to know about drug allergy?
What are the Goals for the Allergy & Immunology Specialist
What drugs have been associated with what kinds of problems Current drug allergy status Patient education and establishment of rapport Plans for alternative medications, when to treat through, when or if desensitization would be appropriate
Clinical Assessment
Nature of the reaction allergic? Exposures drugs, latex Temporal relationships Propensity of drugs to cause reactions Prior drug allergy history Family history of drug allergy Effect of drug withdrawal or re-exposure Immunodiagnostic tests
Immunodiagnostic Tests
IgE to medications
Complete antigen - e.g. insulin Direct hapten e.g. amoxicillin Haptenation by a drug metabolite e.g. sulfamethoxazole 10-fold dilution from irritant threshold used for highest ID dose
Irritant threshold
Nonirritating Concentration
Cefotaxime Cefuroxime
Cefazolin
Nafcillin
Penicillin G generates the major determinant and many minor determinants, but alone detects only ~50% of penicillin allergic patients PrePen & penicillin G skin tests will detect ~93% of penicillin allergic patients Additional minor determinant precursors are needed to detect the remaining penicillin allergic patients
Google Elective Penicillin Skin Testing
Obtain the anesthesiologists name and record Obtain hospital records Compile a list of exposures Write prescriptions for the drugs needed for testing Test with standard concentrations of the drugs
Levy JH 1992. Anaphylactic reactions in anesthesia & critical care. Butterworth-Heinemann, Boston, 2nd edition, p129.
Maculopapular rashes
Relatively non-pruritic Resolve without residual damage Benign Drug associated may be specific lymphocyte mediated
Maculopapular rashes Negative skin and in vitro tests for specific IgE Positive patch and ID skin tests read at 48 and 72 hours Positive oral challenges in patch test positives, not in negative controls
Patriarca et. al. Ann Allergy Asthma Immunol 1999;83:257-266.
Patch tests often positive in drug associated cases Intradermal tests read at 48 to 72 hours just as good as patch tests and easier for A&I physicians to perform Positive test indicates presence of DTH. Much left to learn about interpretation of clinical implications.
105 patients with non-immediate reactions associated with cephalosporins. Patch tests (5% in petrolatum) and Intradermal skin tests (read at 48 & 72 hours) with diverse penicillins and cephalosporins ID tests more sensitive than Patch tests
Romano A, et. al. JACI 2012;129:1166-1169. Schnyder B, et. al. JACI 2012;129:1170-1171.
86 test negative patients challenged with suspected cephalosporin. All challenges were negative.
Romano A, et. al. JACI 2012;129:1166-1169. Schnyder B, et. al. JACI 2012;129:1170-1171.
Onset
When you do NOT think the problem is allergic, but the patient, family, other physicians think the patient is allergic Must be careful not to desensitize and then be misled by absence of reaction If you think allergy is a significant possibility, test or desensitize, or risk an avoidable tragedy.
Complete epidemiologic history essential Ad hoc skin test procedures In vitro assays for some relevant antigens
Opiate Sensitivity
When feasible use non-opiate medications or approaches to pain control When feasible use PCA pumps for opiate administration When feasible use fentanyl Diphenhydramine 1 mg/kg q4-6h. Possibly H2 and LT receptor antagonists Peripheral opiate receptor antagonists such as alvimopan (Entereg) P.O. or parenteral methylnaltrexone (Relistor) may be beneficial without interfering with central pain control
Tharp MD, Kagey-Sabotka A, Fox CC, Maroni G, Lichtenstein LM, Sullivan TJ. Functional heterogeneity of human mast cells from different anatomical sites: in vitro responses to morphine sulfate. JACI 1987;79:646-652.
In some instances continuing therapy is the best decision Urticarial reactions occurring greater than ~24 hours after the beginning of therapy will not progress to anaphylaxis Direct observation is necessary to assess and plan suppressive therapy
Acute Desensitization
Indications
Significant illness Best course of action Any class of medication, hapten generating or complete antigens, can be used
Imprimatur
Desensitization for drug hypersensitivity
(Now 814 citations, 20 years after CDC endorsement of desensitization for IgE sensitivity)
safe readministration of many if not most drugs associated with previous hypersensitivity reactions is not only possible but highly likely with experienced and qualified oversight by an allergyimmunology specialist.
Adkinson NF Jr. JACI September 2008. 122:581-2.
Imprimatur
Rapid desensitization should be implemented as standard of care because of their high success rates and outcomesdemonstrated safety profile. Castells, M. Rapid desensitization for hypersensitivity reactions to medications. Immunology & Allergy Clinics of America. 2009. 29(3):585-606. (Review with 97 references)
Imprimatur
Definitions matter Factor VIII tolerance induction vs. effector cell desensitization or modified drug metabolism
Immunologic Tolerance
Acquired or induced tolerance refers to the immune system's adaptation to external antigen characterized by a specific non-reactivity of the lymphoid tissues to a given antigen that in other circumstances would likely induce cell-mediated or humoral immunity.
Acute Desensitization
Begin ~10 g, doubling doses
~4 hours
Acute Desensitization
Mast Cell
Mediators
Mast Cell
Wheal (mm)
Complications of Desensitization
Patient with acute urticaria associated with fluconazole, on two separate occasions Rapid desensitization to fluconazole performed 6 different times Began with 20 g dose Increased by doubling q15min to a full dose within 4 hours
Complications of Desensitization
On one occasion she had transient urticaria 2 hours after desensitization 4 hours after the 5th desensitization she developed a circular, macular, pruritic, generalized rash that became vesicular. Resolved with prednisone and diphenhydramine therapy and did not progress over 2 weeks of fluconazole therapy 5 months later developed a maculopapular vesicular rash after desensitization that responded to prednisone therapy
Complications of Desensitization
Chemotherapy drug hypersensitivity 12 step IV or IP rapid desensitization with anti H1, H2; lorazepam, dexamethasone premedication
88% skin test positive 98 patients, 413 desensitizations Mild reactions in 111 (27%) - cutaneous Severe reactions in 24 (6%) - multisystem
Acute Desensitization
Antigen-specific mast cell desensitization can be achieved by any form of antigen Antigen presented to mast cells in a manner that allows cell control systems to extinguish or minimize responses to specific IgE Depends upon the continuous presence of antigen Anaphylactic sensitivity can return within 48 hours after discontinuation of the drug.
Anaphylaxis Urticaria
None ~30%
2% 28%
Early Late
Slow Desensitization
Begin ~10 g, doubling
Days
Slow Desensitization
Complications
In approximately 85%, no immediate or later reactions In the remainder, reactions occur despite the procedure In some cases reactions can be suppressed with anti-inflammatory medications
Insulin example
Or go to Scribd.com
Or go to Google and search Protocols for drug allergy desensitization Several dozen sample protocols for rapid or slow desensitization
Protocols for desensitization for >40 common and some unusual medications
Download all or copy specific protocols >20,000 reads (US, Australia, Iran, Canada, UK, Turkey most frequent visitors)
All of the protocols have been used successfully Address the practical aspects of desensitization
Scribd.com/timothy sullivan md
Propensity to have allergic reactions to medications ~10-fold more often than the general population. HIV + patients ~20fold higher incidence of allergic reactions to medications. 4 to 15-fold increased prevalence if a family member is affected
Accurate Diagnosis Avoidance Treating through Acute desensitization Slow desensitization Therapy of drug reactions