drug allergy and desensitization

Immune-mediated hypersensitivity ADRs

mediated by IgE or T cells

Immediate ADRs

may present as anaphylaxis, angioedema, bronchospasm

Non immune-mediated hypersensitivity ADRs

mediated by mast cell and basophil-derived mediators

Non immediate ADRs

may present as maculopapular rash

Type I hypersensitivity

onset within 1 hour, IgE mediated

presents as anaphylaxis

Type II hypersensitivity

onset within hours-days, IgG or IgM mediated

presents as hemolytic anemia

Type III hypersensitivity

onset within 1-3 weeks, immune complex mediated

presents as serum sickness/SLE

Type IV hypersensitivity

onset within days-weeks, T cell mediated

presents as various skin rashes, including SJS/TEN

Anaphylaxis treatment: initial

epinephrine 0.3-0.5 mg IM

Anaphylaxis treatment: hypotension

1-2 L NS 5-10 mL/kg in first 5-10 minutes

Anaphylaxis treatment: lower airway obstruction

nebulized albuterol 2.5-5 mg in 3 mL saline, repeat as necessary

Anaphylaxis treatment: patient on beta-blockers

may require IV glucagon 1-5 mg

Anaphylaxis treatment: secondary

diphenhydramine 25-50 mg IV/IM ± famotidine 20 mg IV push over 2 minutes

Anaphylaxis treatment: late phase

methylprednisolone 1-2 mg/kg up to 125 mg IV (or equivalent)

Hemolytic anemia common drug causes

piperacillin, diclofenac, fludarabine, oxaliplatin, and cephalosporins

Serum sickness-like disease common drug causes

ciprofloxacin, bupropion, hydantoins, minocycline, sulfonamides, penicillins, and cefaclor

Maculopapular eruptions

most common drug-induced reaction

nonblanching, dusky, bright-red macules

mucosal involvement may be cause for concern

Maculopapular eruptions treatment

PO antihistamines, emollients, topical corticosteroids

DRESS common drug causes

allopurinol, anticonvulsants, vancomycin, minocycline, dapsone, lamotrigine, and sulfonamides

DRESS

type IV

fever following triad of rash, eosinophilia, and internal organ involvement

onset ~6 weeks after drug initiation

DRESS

strongly associated with hydroxylamine, metabolite of sulfamethoxazole (but not other sulfa compounds)

Serum sickness-like disease

type III

rash (urticarial or maculopapular) preceded by prodromal phase of fever, malaise, lymphadenopathy, and arthralgias

Serious cutaneous adverse reactions (SCAR, SJS/TEN)

type IV

widespread blistering with mucosal membrane erosion and epidermal detachment

onset 5-21 days after drug administration.

Serious cutaneous adverse reactions (SCAR, SJS/TEN) treatment

d/c offending drug, supportive burn ward care

SJS

<10% detachment of body surface area

TEN

>30% detachment of body surface area

also includes organ involvement, including AKI, neutropenia, respiratory failure, and death

Acute generalized exanthematous pustulitis (AGEP)

type IV

acute onset (days), pustules on folds and/or face, spiking fever, and neutrophilia

usually starts within 24-48 hours of drug exposure

Acute generalized exanthematous pustulitis (AGEP)

common drug causes: beta-lactams, macrolides, radiocontrast, CCBs

risk factor: personal or family history of psoriasis

Acute generalized exanthematous pustulitis (AGEP) treatment

d/c agent, corticosteroids

Drug induced thrombocytopenia

platelet count <100,000 cells/mL or >50% reduction from baseline

Drug induced thrombocytopenia treatment

d/c offending drug, platelet transfusion, corticosteroids

HIT treatment

direct thrombin inhibitors, fondaparinux, and DOACs

VITT treatment

IV immunoglobulin

Cutaneous small-vessel vasculitis (CSVV)

type II or III

inflammation and necrosis of blood vessel walls

may be limited to skin or involve vital organs

Cutaneous small-vessel vasculitis (CSVV)

common drug causes: beta lactams, sulfonamides, thiazides, phenytoin, and vancomycin

Cutaneous vasculitis

purpuric lesions that vary in size and number

Photosensitivity common drug causes

fluoroquinolones, tetracyclines, trim/sulfa, chlorpromazine, thiazides, NSAIDs, BRAF inhibitors, voriconazole

Drug-induced hair loss common causes

antineoplastic agents, anticonvulsants, beta blockers, antidepressants, antithyroid drugs, IFNs, oral contraceptives, cholesterol-lowering agents

Drug-induced hair growth common causes

anabolic steroids, OC, corticotropin, anti-inflammatory drugs (including glucocorticoids), vasodilators, acetazolamide, phenytoin, cyclosporine A, psoralens, and zidovudine