Cutaneous Drug Reaction - home health advice

Overview
Definition

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.
Etiology

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

Risk Factors

* 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

Signs and Symptoms

* Acneiforms
* Lupus erythematosus with malar erythema
* Photosensitivity
* Urticaria
* Maculopapular eruptions
* Eczematous reaction
* Erythema multiforme/nodosum
* Fixed eruptions
* Lichenoid
* Vasculitis
* Dermal tissue necrosis

Differential Diagnosis

* Viral exanthem fever and other systemic symptoms to rule out more common maculopapular eruptions
* Primary dermatosis drug eruptions manifest as many types of dermatosis

Diagnosis
Physical Examination

May include:

* Urticaria
* Erythema
* Facial edema
* Skin pain
* Epidermal detachment
* Dermal necrosis
* Blisters
* Swollen tongue
* Fever
* Enlarged lymph nodes
* Wheezing/hypotension

Laboratory Tests

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

Pathology/Pathophysiology

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)

Other Diagnostic Procedures

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

Treatment Options
Treatment Strategy

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)

Drug Therapies

* 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

Surgical Procedures

Debridement of necrotic tissue in severe reactions
Complementary and Alternative Therapies

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.
Nutrition

* 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.

Herbs

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.

Homeopathy

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

Patient Monitoring

* 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

Other Considerations
Prevention

To minimize morbidity and mortality from drug reactions:

* Patient education: drugs to avoid, drugs to use; familial implication
* Medical alert jewelry identifying causative drugs

Complications/Sequelae

* Anaphylaxis, laryngeal edema, bone marrow suppression, future cross-reaction to chemically similar compounds

Prognosis

* Remission of symptoms within days of drug withdrawal
* Bullae, urticaria, angioedema potentially life-threatening

Pregnancy

Drugs of any kind should be avoided unless absolutely necessary and safety to fetus is proven.
References

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.