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Overview |
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Definition |
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Adverse drug reactions affect up to 30% of hospitalized patients. Cutaneous
drug reactions are estimated at 2.2 per 100 inpatients and 3 per 1,000 drug
courses. Penicillins, sulfonamides, and blood products account for two-thirds of
these. Prevalence in outpatient settings is unknown. Reactions may be
immunologic or nonimmunologic, the latter being more prevalent. Although most
reactions are obvious within a week of drug-therapy initiation, some may take up
to four weeks to manifest. Clinical effects range from acneiforms and
phototoxicity to exfoliative dermatitis and toxic epidermal necrolysis (TEN).
Most common reactions are exanthems and urticarial eruptions; however, multiple
morphologic types may occur. Inpatient treatment should be considered for
anaphylactic reactions, Stevens-Johnson syndrome, TEN, and widespread bullous
reactions as they may be life-threatening. Risk of these reactions is 1 to 10
per 1,000,000. Causative drugs include sulfonamide antibiotics,
aminopenicillins, phenytoin (and structurally related anticonvulsants),
allopurinol, and oxicam nonsteroidal anti-inflammatories. Because many skin
disorders mimic drug reactions and certain reactions are specific to drug type,
accurate assessment is critical. Reactions specifically induced by drugs include
fixed drug eruptions, argyria, and arsenical keratosis. |
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Etiology |
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Adverse reaction is either immunologic or nonimmunologic.
- Immunologic responses—defined as drug
allergies—stem from activation of the host immunologic
pathways, inducing the release of histamines.
- Nonimmunologic reactions—the more common
type—can be attributed to several factors, including
overdose, interaction between drugs, metabolic alterations, inherited protein or
enzyme deficiencies, and cumulative toxicity.
Major causative drugs include:
- Allopurinol
- Androgens
- Aspirin
- Barbiturates
- Chemotherapeutic agents
- Corticosteroids
- Diuretics
- Heavy metals (gold, copper)
- Hydralazine
- NSAIDs
- Penicillins
- Phenothiazines
- Procainamide
- Sulfonamides
- Sulfonylureas
- Tetracyclines
- Certain hypertensive agents
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Risk Factors |
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- 3 per 1,000 drug courses/2.2 per 100 patients
- Elderly more susceptible, otherwise unrelated to age
- Prevalence greater among women
- Previous drug reactions
- Drug interactions
- Genetic predisposition
- Drug therapy
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Signs and Symptoms |
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- Acneiforms
- Lupus erythematosus with malar erythema
- Photosensitivity
- Urticaria
- Maculopapular eruptions
- Eczematous reaction
- Erythema multiforme/nodosum
- Fixed eruptions
- Lichenoid
- Vasculitis
- Dermal tissue
necrosis
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Differential
Diagnosis |
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- Viral exanthem—fever and other systemic
symptoms to rule out more common maculopapular eruptions
- Primary dermatosis—drug eruptions manifest
as many types of dermatosis
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Diagnosis |
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Physical Examination |
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May include:
- Urticaria
- Erythema
- Facial edema
- Skin pain
- Epidermal detachment
- Dermal necrosis
- Blisters
- Swollen tongue
- Fever
- Enlarged lymph nodes
- Wheezing/hypotension
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Laboratory Tests |
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Laboratory tests are generally nonspecific. These tests may be
helpful.
- Eosinophilia (>1,000/mm3), indicates possible allergic
reaction
- Lymphocytosis with atypical lymphocytes
- Abnormal liver function test
- Drug levels/possible overdose; nonallergic reaction
- Enzymes/metabolites
- Skin culture/biopsy
- CBC/differential
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Pathology/Pathophysiology |
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Although certain drugs will cause specific reactions, some general
pathologies include:
- Urticaria: pruritic, red wheals ranging from small spots to large
area; swelling of deep dermal/subcutaneous tissue indicates angioedema, which
may involve mucous membranes
- Photosensitivity eruptions:
Phototoxic—resemble sunburn, are dose-related, may
occur with first exposure to drug and exposure to light
Photoallergic—require drug immune response and
light, often delayed reaction; eruptions range from lichenoid papules to
eczematous changes.
- Pigmentation (type of change determined by type of drug): oral
contraceptives—increase melanocytic activity; heavy
metals (like inorganic arsenic, silver, gold)—drug
deposition; zidovudine (AZT)—pigmentation in nails;
nicotinic acid—brown pigmentation
- Cutaneous necrotizing vasculitis: palpable purpuric lesions, ulcers,
hemorrhagic blisters (may involve organs)
- Phenytoin hypersensitivity reaction (from inherited deficiency of
expoxide hydrolase): becomes purpuric—with fever,
edema, tender lymphadenopathy, leukocytosis, hepatitis
- Warfarin skin necrosis: rare, usually in women; sharply demarcated
erythematous; indurated, purpuric lesions (associated with protein C/vitamin K
deficiency)
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Other Diagnostic
Procedures |
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Assessment of possible reaction includes:
- History of drug use—including OTCs,
prescriptions, illegal drugs, herbs, vitamins—in prior
four weeks
- Drug level/evidence of overdose
- Previous history (personal and populational) with the suspected
causative agent
- Similar etiology to existing/new disease unrelated to drug (drug may,
however, modify these reaction rates)
- Timing of reaction in relation to drug administration
- Discontinuation of medication or—if multiple
medications in use—withdrawal of suspected agent based
on its likelihood to cause the current reaction
- Response of symptoms to drug withdrawal
- Recurrence of symptoms with drug rechallenge
- Special tests: skin test for IgE-mediated reaction; IgG/IgM for
drug-specific antibodies; prick/scratch/patch tests for allergic reaction
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Treatment Options |
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Treatment Strategy |
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Choice of treatment will depend on:
- Type, severity, and natural history of
eruption—urticaria, angioedema, and bullous lesions can
be more serious and should be aggressively managed. Consider inpatient
management for anaphylactic reactions and toxic epidermal necrolysis, and
Stevens-Johnson syndrome extensive bullous reactions.
- Importance of drug in disease/disorder control
- Availability of pharmacologically similar yet chemically unrelated
drugs
- Risk:benefit ratio of drug reaction compared to disease
- Consideration of overall patient management
Common therapies include the following.
- Cessation of suspect or proven offending drugs
- Alteration of dosage/administration route
- Pharmacotherapy
- Inpatient treatment for serious reactions
- Surgery (when necessary)
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Drug Therapies |
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- Corticosteroids (systemic/IV): for anaphylaxis, severe urticaria,
angioedema—prednisone 40 to 60 mg/day, 5 to 10
days
- Corticosteroids (topical): for limited eczematous or lichenoid
eruptions (Group I to III)
- Antihistamines: for pruritic—diphenhydramine
(Benadryl) 25 to 50 mg every six hours; hydroxyzine (Atarax) 10 to 25 mg every
six to eight hours; for anaphylaxis/widespread
urticaria—epinephrine (0.01 ml/kg to 0.3 ml
max.)
- Epinephrine: for severe respiratory/cardiovascular
implications
- Topical antipruritics/lubricants/emollients: for eczematous
reactions
- Baths (with or without additives)
- Special treatments: for severe reactions (depending upon
severity)
- H2 blockers (e.g., Tagamet): in severe
cases
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Surgical Procedures |
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Debridement of necrotic tissue in severe reactions |
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Complementary and Alternative
Therapies |
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Severe cutaneous drug reactions require immediate medical attention. Mild to
moderate reactions may be safely and effectively treated with alternative
therapies. Begin with vitamin C, flavonoids, and anti-inflammatory herbs. Add
other nutritional supplements and herbs as needed for pain relief and immune
support. |
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Nutrition |
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- Vitamin C (1,000 mg tid to qid) stabilizes mast cells and prevents
the secretion and breakdown of histamines.
- B-complex with extra B12 (1,000 mcg) aids in overall dermal health,
can ease nerve pain, and promotes normal skin growth.
- Vitamin E (400 to 800 IU/day) improves dermal circulation.
- Zinc (30 to 50 mg/day) supports the immune system and promotes
healing.
- Bromelain (125 to 250 mg bid to tid) is a proteolytic enzyme that
reduces inflammation.
- Magnesium (400 to 800 mg) may help prevent spasms in the bronchial
passages.
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Herbs |
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Herbs are generally a safe way to strengthen and tone the body's systems. As
with any therapy, it is important to ascertain a diagnosis before pursuing
treatment. Herbs may be used as dried extracts (capsules, powders, teas),
glycerites (glycerine extracts), or tinctures (alcohol extracts). Unless
otherwise indicated, teas should be made with 1 tsp. herb per cup of hot water.
Steep covered 10 to 20 minutes and drink 2 to 4 cups/day. Tinctures may be used
singly or in combination as noted.
Anti-inflammatory herbs help to stabilize mast cells and reduce inflammation.
Those herbs include the following.
- Turmeric (Curcuma longa), 100 mg bid to tid potentiates
bromelain when taken together.
- Quercetin (may be given up to 1,000 mg tid)
- Hesperidin (200 mg tid to qid)
An infusion of equal parts of coneflower (Echinacea angustifolia),
yarrow (Achillea millefolium), chamomile (Matricaria recutita),
peppermint (Mentha piperita), and red clover (Trifolium pratense)
will give immune support, reduce inflammation, and aid in lymph drainage.
For urticaria:
- Skin wash—To provide symptomatic relief of
itching use one or more of the following herbs brewed as a tea 1 tsp./cup,
cooled, and applied as needed: peppermint, chickweed (Stellaria media),
and chamomile. To aid healing, add one or more of the following: marigold
(Calendula officinalis), comfrey (Symphytum officinale), or
coneflower.
- Skin poultice—For open sores use powdered
slippery elm (Ulmus fulva), goldenseal (Hydrastis canadensis), and
marshmallow root (Althea officinalis). Add enough skin wash to make a
paste. Apply as needed.
- Aloe vera gel applied topically can soothe burning
inflammations.
- Oatmeal baths—Add powdered oatmeal (or 1 cup
of oatmeal in a sock) to tepid bath.
- Skin balm—Flaxseed oil (2 tbsp.) plain or
with 5 drops of oil of chamomile or marigold. Specifically for eczema-type
reactions.
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Homeopathy |
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An experienced homeopath should assess individual constitutional types and
severity of disease to select the correct remedy and potency. For acute
prescribing use 3 to 5 pellets of a 12X to 30C remedy every one to four hours
until acute symptoms resolve.
Cutaneous drug reactions may be life-threatening, and need immediate medical
attention. Homeopathic remedies can be used successfully for symptomatic relief
of itching, burning, and swelling.
- Apis mellifica for acute swelling with burning pains that are
relieved by cold applications
- Graphites for eczema or urticaria with tremendous
itching
- Ledum palustre for cellulitis or eczema with severe
inflammation
- Rhus toxicodendron for burning and itching that are relieved by
hot applications
- Urtica urens for burning and
itching
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Patient Monitoring |
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- Close physical follow-up/monitoring to ensure no progression of
reaction
- Telephone contact until eruption completely cleared
- Inpatient observation in severe reactions
- Clearly indicate on patient records suspected causative
agent/specific reaction
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Other
Considerations |
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Prevention |
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To minimize morbidity and mortality from drug reactions:
- Patient education: drugs to avoid, drugs to use; familial
implication
- Medical alert jewelry identifying causative
drugs
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Complications/Sequelae |
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- Anaphylaxis, laryngeal edema, bone marrow suppression, future
cross-reaction to chemically similar
compounds
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Prognosis |
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- Remission of symptoms within days of drug withdrawal
- Bullae, urticaria, angioedema potentially
life-threatening
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Pregnancy |
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Drugs of any kind should be avoided unless absolutely necessary and safety to
fetus is proven. |
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References |
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American Academy of Dermatology. Guidelines of care for cutaneous adverse
drug reactions. J Am Acad Dermatol. 1996;35:458-461. Available at
www.aad.org/guidelinecutaneousdrug.html.
Balch JF, Balch PA. Prescription for Nutritional Healing. 2nd ed.
Garden City Park, NY: Avery Publishing Group; 1997.
Dambro MR, ed. Griffith's 5 Minute Clinical Consult. Baltimore, Md:
Lippincott, Williams & Wilkins; 1998.
Fauci AS, Braunwald E, Isselbacher KJ, et al,, eds. Harrison's Principles
of Internal Medicine. 14th ed. New York, NY: McGraw-Hill; 1998.
Morrison R. Desktop Guide to Keynotes and Confirmatory Symptoms.
Albany, Calif: Hahnemann Clinic Publishing; 1993.
Murray MT, Pizzorno JE. Encyclopedia of Natural Medicine. 2nd ed.
Rocklin, Calif: Prima Publishing;
1998. |
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Copyright © 2000 Integrative Medicine
Communications This publication contains
information relating to general principles
of medical care that should not in any event be construed as specific
instructions for individual patients. The publisher does not accept any
responsibility for the accuracy of the information or the consequences arising
from the application, use, or misuse of any of the information contained herein,
including any injury and/or damage to any person or property as a matter of
product liability, negligence, or otherwise. No warranty, expressed or implied,
is made in regard to the contents of this material. No claims or endorsements
are made for any drugs or compounds currently marketed or in investigative use.
The reader is advised to check product information (including package inserts)
for changes and new information regarding dosage, precautions, warnings,
interactions, and contraindications before administering any drug, herb, or
supplement discussed herein. | |