- 5% of all hospital admissions are for a drug reaction
- 15% of all hospitalized patients have one or more adverse reactions
- 1-3% derm related is unknown
error in prescribing or patient taking wrong dosage
- jaundiced patient
- impaired renal function
- accumulative effect over many years
most common; probably some inborn predisposition
Non-allergic secondary effects
cholasma from birth control pills, or moniliasis from antibiotic therapy, psoriasis exacerbation from beta blockers, exacerbation of hives with ASA
flu-like symptoms appearing a few hours after treatment of any stage of syphilis
assumed drug induced, a vasculitis in the skin prepared by endotoxin from existing infection -examples of localized Schwartzman would be purpura fulminans and septicemia secondary to acute meningococcemia
Immunologic reactions (small percentage)
- Type I
- Type II
- Type III
- Type IV
Type I (IgE-dependent)
- Mast cell release of histamine, vasoactive amines, ECF-A, leukotrienes (SRSA), and platelet-
- activating factor
Type II (cytotoxic, hemolysis and purpura)
- 1. Hapten, Cocktail purpura, quiinine, Hemolytic anemia, penicillin
- 2. drug-antibody complexes, innocent bystander
- 3. Cross reacting antibodies, hemolytic anemia, a-methyldopa
Type III (immune complex)
Serum Sickness, vasculitis
Type IV (cell-mediated)
drug-allergic contact dermatitis
III. Factors Concerned in Development of Sensitivity:
- Age � more frequent in adults
- Sex � no difference
- Genetics � anaphylactoid reaction 2-3 times more common in atopic than non-atopic
- Disease - approximately 50% of patients with infectious mononucleosis given ampicillin will develop drug eruption � also ampicillin should not be given to patients with lymphatic leukemia or gout, especially if they are on allopurinol
- Administration � if allergic after parenteral injection, will also show allergy to oral administration
- Onset of reaction � may be in minutes as in anaphylaxis, or even weeks after being off medication
- Duration of sensitivity � unpredictable, so consider life long
- Chemical relatives or cross sensitization � examples -common para-amino ring, also systemic and topical relationship -example sulfa
- Drug interactions �example: anticoagulation and griseofulvin
- Teratogenic effects of drugs or their use in pregnancy -example: staining of teeth with tetracycline
immune complex disease produced by deposition of circulating immunecomplexes in skin, kidney, or other organ, usually requires six days to develop (penicillin, sulfonamides, thiorreol, dyes, dilantin, etc.)
common offenders are penicillin, cephalosporins, opiates, dyes used in diagnostic radiology, local anesthetics, etc.
morbilliform or measles about one week after starting drug � like: barbiturates, penicillin, sulfonamides, chlorothiazides, chlorpromazines, tranquilizers, gold, streptomycin, etc. (symmetric, trunk, areas of pressure)
Toxic erythema or scarlet fever � like barbiturates, codeine, morphine, mercury, quinidine, atropine, etc.
Pityriasis Rosea � like
bismuth, gold, barbiturates, etc.
occupational hazard of physician, dentist, veterinarians, nurses (para-amino group) penicillin, streptomycin, local anesthetics, phenothiazines, sulfonamides, quinacrine, gold, etc.
Nummular eczema � like:
isoniazid, salicylic acid, and para-amino group meds, etc.
penicillin, sulfonamides, streptomycin, tetracycline, griseofulvin, barbiturates, phenothiazines, insulin, aspirin, opiates, dextrans, blood products, etc.
Fixed drug reaction
sharply delineated area of dermatitis recurring in same area on re-administration of drug, commonly occurring on buccal or genital mucosa, also palms and soles: phenolphthalein (Ex-Lax), antipyrine, salicylates, tetracycline, sulfonamides, barbiturates, quinine,vermouth, phenacetine, etc.
Erythema-multiforme (7-14 days after starting meds) -like:
penicillin, sulfonamides, phenothiazines, bromides, salicylates, chlorpropamide, thiazides, herpes infections, etc.
Stevens-Johnson syndrome /TEN (Toxic Epidermal Necrolysis)
allupurinol, measles vaccine, dilantin, sulfas, nonsteroidalantiinflammatory agents, fumigants, etc.
- penicillin, sulfonamides, birth control pills, salicylates, etc.
- Acneiform eruption
- bromides, iodides, corticosteroids, ACTH, cyanocobalamin, testosterone, antabuse, dilantin, INH, etc.
bromides, iodides, sulfonamides, phenylbutazone, mephenytoin, mercury, salicylates, phenolphthalein, etc.
Purpura (anticoagulants, thrombocytopenia, or vasculitis)
salicylates, chlorothiazides, long-term steroids, ampicillin, carbamides, phenylbutazine, tolbutamide, meprobamate, anti-metabolites, sulfonamides, coumadin, etc.
Exfoliative (red and scales)
arsenicals, barbiturates, mercurials, gold, phenylbutazone, quinicrine, penicillin, sulfonamide, phenothiazine, etc.
Lichen planus like
thiazides, gold, arsenic, chloroquine, quinicrine, quinidine, para-amino salicylic acid, beta blockers, etc.
Seborrhea dermatitis like
gold, ACTH, Parkinson's disease, and meds for seizure disorders
birth control pills, chlorpromazine, atabrine, chloroquine, bismuth, silver salts, minocyclin, etc.
Declomycin and others
Achromotrichia � (loss of hair pigment)
chloroquine, quinacrine, etc.
anticoagulants (heparin), antimetabolites, alkylating agents, triparonol, beta blockers, etc.
Keratoses and epitheliomas-
arsenic (Fowler's solution)
Lupus erythematosus -like syndrome
hydralazine, mephenytoin, isoniazid, PAS, trimethadione, griseofluvin, procaineamides, etc.
cholestyranine, triparanol, butyrophenone, nicotinic acid, etc.
Systemic Effects of Topical Application:
Corticosteroids, mercury, estrogenic hormones
Diagnosis of Drug Reaction:
- Sudden appearance
- Usually erythematous
- Minimal mucous membrane involvement
- Often involves palms and soles
- Laboratory tests � not very reliable
Most common drug offenders (JAMA 235:918-922, 1976)
- Drug Incidence (%)
- Amoxicillin 5.1 Cotrimoxazole 3.4 Ampicillin 3.3 Corticotropin 2.8 Erythromycin 2.3 Chepholsporins 2.1 Semisynthetic penicillins 2.1 Cyanocobalamine 1.8 Sulfisoxazole 1.7 Gentamicin 1.6 Penicillin G 1.6 Atropine 1.6 Quinine 1.3
Common Contact Sensitizers
- Compound Found in:
- Ammonia Soaps, chemicals, hair dyes Balsam of Peru Cosmetics Benzyl alcohols Cosmetics, medications Caine anesthetics Sunburn products, medications Carba Rubber Chromium Jewelry Epoxys resins Glues Ethylenediamine Stabilizers, various, hair dyes Formaldehyde Shoes, clothes, soaps, insulation, carpet, building materials Mercaptobenzothiazole Rubber Naphthyl Rubber Neomycin Topical medications Nickel sulfate Jewelry, snaps, fasteners Parabens Preservatives, various Paraphenylenediamine hair dyes, leather Potassium dichromate Shoes, leather Thiomersal Preservatives, contact lens solutions Turpentine Paints Wool alcohols Lanolin containing products