In our Morning Report at WCH, we discussed the major cutaneous manifestations of adverse drug reactions, with a focus on type IV hypersensitivity.

Learning Points:

1. Differential diagnosis of pruritus
2. Major cutaneous morphologies of drug reactions
3. Differential diagnosis of morbilliform exanthems
4. Differential diagnosis of erythroderma
5. Gel & Coombs classification schema
6. Management of morbilliform drug eruptions

Differential diagnosis of pruritus:

Major Cutaneous Morphologies of Drug Reactions:

1. Morbilliform-also termed “maculopapular”
2. Urticarial
3. Erythroderma

Morbilliform Eruptions:

• three major “categories” of causes of maculopapular/morbilliform eruptions
• These will AID your diagnostic ability:

Erythroderma Differential Diagnosis:

Gel & Coombs Classification of Drug Hypersensitivity

Examples:

Type I: B lactam-induced anaphylaxis
Type II: Heparin-induced thrombocytopenia
Type III: Serum sickness
Type IV: Morbilliform eruptions, DRESS (Drug rash with eosinophillia and systemic symptoms), AGEP (acute generalized exanthematous pustolosis), SJS/TEN

Management Pearls for Morbilliform Drug Eruptions/Type IV hypersensitivity:

1. Culprit drug should be stopped
2. There is NO ROLE for premedication or desensitization subsequently
   • desensitization is ONLY an option for Type I hypersensitivity
3. Be vigilant for evolution to more severe Type IV hypersensitivity reactions like DRESS, AGEP, and SJS/TEN because morbilliform exanthems may herald these more severe forms.
   • Worrisome features suggestive of evolution may include:
     • Fever
     • Mucositis
     • Rash progression to erythroderma
     • Blistering or skin tenderness
4. Symptomatic treatment is indicated for pruritus, though may not be particularly effective due to the underlying physiologic mechanism
5. There is no role for steroids in uncomplicated, mild, morbilliform eruptions
6. If indicated, basic bloodwork would include a CBC (eosinophilia), and liver/renal indices to assess for systemic organ involvement
7. There is NO role for skin prick testing to evaluate culprit drugs in relation to type IV hypersensitivity
   • Skin prick testing is ONLY for IgE-mediated reactions
8. Patch testing to the culprit drug is SOMETIMES used, though of limited utility
9. Many drugs have “sulfa” components, including antimicrobial and non-antimicrobial agents.
   • There is little evidence of cross-reactivity between sulfa-containing antimicrobials and sulfa-containing non-antimicrobials (though not impossible)

Further Reading:

1. Warrington, R and Silviu-Dan, F. Drug Allergy.  Allergy, Asthma & Clinical Immunology 2011, 7(Suppl 1):S10. http://www.aacijournal.com/content/7/S1/S10
2. Wulf, NR and Matuszewski, KA. Sulfonamide cross-reactivity: is there evidence to support broad cross-allergenicity?American Journal of Health-System Pharmacy. 2013, 70 (17) 1483-1494; DOI: http://dx.doi.org/10.2146/ajhp120291