Tag Archives: Drug allergy

What is the Best Method for Testing Allergy to Drugs?

I must have a drug allergy….what is the best method for testing?  Countless times I have reviewed skin biopsy results that state evidence of a drug allergy.  Obviously, this is not a very specific method of diagnosis, so what does work?  I’ll copy the entire abstract for you and make some comments below.  In the meantime, if you’re interested in what doctors learn about drug allergy, this is a lecture from University of Texas–Southwestern designed for allergy fellowship training.  It’s a little long unless you’re a doctor, but have at it!  And yes, I trained at Children’s Mercy Hospital with Dr. Portnoy. 

L.M. Heinzerling; D. Tomsitz; M.D. Anliker  The British Journal of Dermatology. 2012;166(1):107-114. 

Is Drug Allergy Less Prevalent than Previously Assumed?

Background Rashes are a frequent conundrum in clinical practice as they may be reactive, drug induced or disease specific. Identification of the culprit drug is important as re-exposure may be harmful or even life-threatening and unnecessary avoidance of ‘innocent’ drugs leads to limitations of treatment options.
Objective To objectify the cause of suspected cutaneous drug reactions in a large patient population.
Method Over 5 years (2006–10), 612 patients with suspected cutaneous drug reactions were evaluated. Histology was assessed. About 200 patients were invited for complete work-up with skin tests (prick/intracutaneous testing and scratch/patch as indicated) and, if necessary, lymphocyte transformation tests (LTT). In special cases, drug provocation tests were conducted.
Results A total number of 141 cases with suspected drug reaction underwent full work-up (age 6–86 years; 75% female, 25% male). In 107 cases (76%) a drug was identified whereas 34 (24%) were reactive rashes or had other causes. Mostly, cutaneous drug reactions were maculopapular rashes, urticaria/angio-oedema; less frequently, acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms, systemic drug-related intertriginous and flexural exanthema, toxic epidermal necrolysis and fixed drug eruptions were present. Of all the cutaneous drug reactions investigated, 39·8% were caused by antibiotics, 21·2% by anti-inflammatories, 7·6% by contrast media and 31·4% by others (oral antidiabetics, antimycotics, antipsychotics, antiepileptics and others).
Conclusion Clinical assessment overestimates the role of drug allergies in cutaneous reactions. Assessment of suspected drug reactions can be greatly improved by thorough evaluation including dermatological and allergological work-up with skin testing and assays such as LTT.

Out of a total of 612 patients, 141 cases with suspected drug allergy were fully evaluated with allergy testing. Interestingly, out of the tested subjects with suspected drug reaction one-quarter could not be confirmed by objective testing, and skin changes were tracked to another trigger. This agrees with data from other studies which also found that not all the suspected drug reactions were finally confirmed.

Thus, depending on prescreening, the role of drugs in sudden exanthema is overestimated. In plain English, all of these  cases would have been FALSELY attributed as drug reactions had it not been for the testing and work-up.

However, only rigorous testing (and provocation) can rule out or confirm the drug reaction and finally identify the culprit drug. Interestingly, it was by means of a lymphocyte transformation test (LTT) that one-fifth of the cases were identified, which thus represents an important tool shown to have a sensitivity of 78%, even though this methodology is often considered experimental.

Further studies are needed to specify the sensitivity and specificity of LTT in comparison with skin tests for each substance.

Advertisements

Are we harming ourselves?

“I’m allergic to everything!”  Ah, you’re smiling.  Is this really possible to be allergic to multiple drugs?  Evidently this is true according to a recent study published in Ann Allergy Asthma Immunol 108 (2012) 88–93.

Multiple drug intolerance syndrome: prevalence, clinical characteristics, and management byEric Macy, MD and Ngoc J. Ho, PhD.

So what is this condition? Multiple drug intolerance syndrome (MDIS) is generally defined as intolerance to 3 or more unrelated medications.  This can be antibiotics, ibuprofen, or high blood pressure medication.  The problem with adverse drug reactions is that intolerances are typically recorded in the “allergy” field of the medical record. This makes doctors and patients alike worry about anaphylaxis with any accidental use.  Relax….most adverse drug reactions are not going to result in a severe reaction without warning.  The authors of this paper use the word “allergy” in quotes throughout this paper to remind us that most of the drug “allergy” reports in the medical record are not immunoglobulin (IgE)-mediated.  

Now don’t misunderstand, a true IgE-mediated allergy requires sensitization, and every systemic exposure in a sensitized individual can potentially result in anaphylaxis and death. But this is not the type of reaction we’re dealing with in this study.

If you have Multiple Drug Intolerance Syndrome, what can you do?

  1. Most individuals with a record of any drug “allergy” have only 1 implicated medication, and they simply avoid that drug or class of medication. Individuals with multiple drug “allergies” are a special case.
  2. Antibiotic overuse probably accounts for a significant proportion of the antibiotic “allergy” reported.  Not only should antibiotics be avoided to prevent resistance, but overuse of antibiotics contributes to MDIS.
  3. Challenge testing has typically shown tolerance to most medications in patients with MDIS. Schiavino et al performed 1,808 challenges on 480 patients, 84.4% female, most ages 40 to 60, with histories of ADRs to at least 3 unrelated medications.
  4. All of these patients were evaluated at a specialized drug allergy clinic in Rome between January 1, 2000 and December 31, 2005. Two hundred twenty-four (12.4%) positive challenges were seen. In virtually all patients, either the index medication was tolerated on rechallenge or an acceptable alternative was identified.  

Multiple drug “allergy” is relatively uncommon in children, and most adverse drug reactions (ADRs) in children are associated with antibiotic use. Park et al provided demographic information on 97 children with 2 or more antibiotic “allergies” seen in a specialized drug allergy center in Canada. The accompanying editorial concluded that rare individuals may truly have allergic reactions to unrelated antibiotics, but it also might just be opportunity and bad luck.

 One often may stop multiple medications safely in the elderly. This may be the most important way to reduce the incidence of MDIS. In the presence of a life-threatening condition that would benefit from a particular medication associated with a historical reaction, based on a careful history, one may possibly safely test or rechallenge most individuals with MDIS.

 So is there anyone who should NOT be challenged with a drug they suspect is causing MDIS?

  • Individuals who have experienced drug-associated toxic epidermal necrolysis, Stevens-Johnson syndrome, blistering, desquamation.  These reactions are usually MORE severe after the second exposure! 

    example of Stevens Johnson syndrome

    Here’s what this type of reaction looks like:

  • Severe hepatitis, nephritis, or hemolytic anemia should not be rechallenged.  The risk of inducing severe reactions is just too great.  Fortunately, these severe reactions are rare.

  • Angiotensin-converting enzyme inhibitor–associated angioedema can be lethal, and rechallenge is not recommended.

If I have MDIS, when would a challenge be appropriate?

  • Urticaria or angioedema associated with NSAID use outside of aspirin-exacerbated respiratory disease is often transient, and rechallenge often can be safely performed.
  • Individuals with aspirin-exacerbated respiratory disease can be challenged with aspirin and desensitized.
  • Appropriate skin testing or in vitro IgE measurements can be used to evaluate individuals with MDIS who experienced classic IgE-mediated reactions such as anaphylaxis, shortness of breath, or hives. If negative, they can be rechallenged under observation.
  • If positive, they can be desensitized for 1 therapeutic course.
  • Multiple drug intolerance syndrome subjects with most other mild ADRs such as macular papular rashes, fixed drug eruptions, nausea, vomiting, gastrointestinal upset, diarrhea, drug fevers, other mild symptoms, or unknown symptoms can generally be safely rechallenged.

In closing, what’s the bottom line for patients with multiple drug “allergies?”

  1. Multiple drug intolerance syndrome may be considered partially an iatrogenic condition.
  2. Multiple drug intolerance syndrome is most prevalent in elderly women with high overall health care and pharmaceutical utilization.
  3. Multiple drug intolerance syndrome is associated with anxiety but not with life-threatening illnesses or IgE-mediated allergy.
  4. Coordinated efforts to reduce poly-pharmacy may be helpful in reducing iatrogenic MDIS.
  5. Drug hypersensitivity testing or drug challenges can be used safely to help manage many individuals with MDIS.

Call me with questions; I’d be happy to help you out!

 

Allergic to Antihistamines—really!

 

This is from Gary Stadtmauer, MD’s blog. 

How many times have we heard patients say they are “allergic” to drugs like antihistamines and corticosteroids?  Hypersenstivities to medications used to treat allergic diseases are fortunately uncommon. 

This is Dr. Stadtmauer’s experience with “allergy” to Benadryl….check the references below–it’s legit! 

“I have seen a couple of cases of drug exanthem from antihistamines but never immediate hypersensitivity…until now.  I recently saw a young woman who has had recurrent urticaria/angioedema of immediate onset due to Benadryl.  She had no associated symptoms.  Scratch testing to Benadryl 5mg/ml was negative but ID was positive at 0.5 mg/ml (W/F of 4/10) and 5 mg/ml (W/F o 5/10).  See image below.

One could question whether this is an IgE-mediated event.  Perhaps it is or perhaps in the occasional patient the antihistamine acts as an agonist, binding to the receptor instead of blocking it thereby triggering histamine release.  Anaphylactic shock caused by a challenge with 12.5 mg oral diphenhydramine has been reported and the authors of this case suggest the mechanism was IgE-mediated.

Benadryl Skin TestSo what?  Never say never when a patient comes in with a bizarre drug allergy or states that are allergic to Benadryl….you might be surprised!

Citations re:  Antihistamine Allergy
1. Barranco P, López-Serrano MC, Moreno-Ancillo A. Anaphylactic
reaction due to diphenhydramine. Allergy. 1998; 53: 814.
2. Weidinger S, Mempel M, Ollert M, Elser I, Rakoski J, Köhn FM,
Ring J. Anaphylaxis to mizolastine. J Allergy Clin Immunol.
2004; 114:979-81.
3. Rodríguez del Río P, González-Gutierrez ML, Sánchez-López J,
Núñez-Acevedo B, Bartolomé Álvarez JM, Martínez-Cócera C.
Urticaria caused by antihistamines: report of 5 cases. J Investig
Allergol Clin Immunol. 2009; 19 (4): 317-20.
4. Gonzalo-Garijo MA, Jiménez-Ferrera G, Bobadilla-González P,
Cordobés-Durán C. Hypersensitivity reaction to mizolastine:
study of cross reactions. J Investig Allergol Clin Immunol. 2006;
16 (6): 391-3.
5. Demoly P, Messaad D, Benahmed S, Sahla H, Bousquet J.
Hypersensitivity to H1-antihistamines. Allergy. 2000; 55: 679-80.
6. Aberer W, Bircher A, Romano A, Blanca M, Campi P, Fernandez
J, Brockow K, Pichler WJ, Demoly P for EDNA and the EAACI
interest group on drug hypersentitivity. Drug provocation
testing in the diagnosis of drug hypersensitivity reactions:
general considerations. Allergy. 2003; 58: 854-63.