Cutaneous adverse drug reactions can arise from topically or systemically administered drugs. The clinical presentation of an adverse cutaneous drug reaction is seldom pathognomonic and may vary from an erythematous, macular or morbilliform rash to erythema multiforme. Such reactions generally occur within the first one or two weeks of therapy. However, immunologically mediated reactions may take months to become clinically manifest. Contact dermatitis is usually
eczematous and is most commonly seen with antimicrobial drugs or antihistamines. Sometimes the vehicle is the culprit.
The diagnosis of a drug-induced cutaneous reaction requires an accurate drug history from the patient, especially defining the temporal relationship of the skin disorder to concomitant drug therapy. In milder cases and fixed drug eruptions, re-administration (rechallenge) with the suspect agent may be justified. Patch testing is useful for contact dermatitis. The treat- ment of drug-induced skin disorders involves removing the cause, applying cooling creams and antipruritics, and reserving topical steroids only for severe cases.
Table 51.6 lists some of the most common drug-related cutaneous reactions.
PHOTOSENSITIVITY
The term ‘photosensitivity’ combines both phototoxicity and photoallergy. Phototoxicity (like drug toxicity) is a predictable ADVERSEDRUGREACTIONSINVOLVING THESKIN 417
Table 51.5:Summary of the treatments for other common dermatological infections
Disease Causal agent Treatment Toxicity of therapy Additional comments
Lice Caused by Pediculus 0.5% malathion or carbamyl Use aqueous rather than Apply to affected area and humanus capitis are recommended – leave alcohol preparations in repeat in 7 days to kill lice
in contact for 12 h asthmatics and small children that have just emerged from eggs
Scabies Caused by transmission Lindane 1% (apply Major toxicity is skin Do not use lindane or ofSarcoptes scabei topically and leave for 24 h, irritation malathion during pregnancy
then repeat after 7 days if or in children. Permethrin is
needed) or malathion 0.5% an effective alternative
applied to hair and left for pyrethroid
12 h (if on whole body leave for 24 h) Table 51.4:Summary of drug therapy of viral skin infections
Viral skin infection Drug therapy Comment
Initial or recurrent genital Topical 5% aciclovir cream, Topical penciclovir (2% cream) is an labial or herpes simplex 4-hourly for 5 days is used, but is of alternative for recurrent orolabial
questionable benefit. Systemic herpes. Systemic valaciclovir or aciclovir therapy is required for famciclovir are new alternatives to buccal and vaginal herpes simplex aciclovir
Skin warts, papilloma All treatments are destructive. For plantar warts use 1.5%
virus infections Cryotherapy (solid carbon dioxide, formaldehyde or 10% glutaraldehyde.
liquid nitrogen). Daily keratolytics, For anal warts use podophyllin resin such as 12% salicylic acid 15% or podophyllotoxin 0.5% solution
applied precisely on the lesions once or twice weekly
418 DRUGS AND THE SKIN
Table 51.6:Adverse effects of drugs on the skin
Cutaneous eruption Drugs commonly associated Comment
Acne Glucocorticosteroids, androgens, anabolic
steroids, phenytoin
Alopecia Cytotoxic chemotherapy, retinoids, gold, long-term heparin, oral contraceptives, sodium valproate
Eczema β-Lactams, phenothiazines
Erythema multiforme Sulphonamides, penicillins (β-lactams), Inclusive of Stevens Johnson syndrome barbiturates, allopurinol, rifampicin,
all NSAIDs, phenytoin, carbamazepine and lamotrigine
Erythema nodosum Sulphonamides, antimicrobials (especially β-lactams), oral contraceptives
Exfoliative dermatitis and Allopurinol, carbamazepine, gold, erythroderma penicillins, phenothiazines
Fixed eruptions Barbiturates, laxatives, phenolphthalein, These eruptions recur at the same site (often naproxen, nifedipine, penicillins, circumorally) with each administration of the sulphonamides, tetracyclines, quinidine drug and may be purpuric or bullous
Lichenoid eruptions Captopril, chloroquine, furosemide, gold, phenothiazines, thiazides
Lupus erythematosus with Hydralazine, isoniazid, phenytoin,
butterfly rash procainamide
Photosensitivity
Systemic drugs Amiodarone, chlorodiazepoxide, furosemide, griseofulvin, nalidixic acid, thiazides, tetracyclines, piroxicam
Topical drugs Coal tar, hexachlorophane, p-aminobenzoic acid and its esters
Pigmentation Amiodarone, chloroquine, oral contraceptives, AZT causes grey nails; chloroquine causes hair
phenothiazines and skin depigmentation
Pruritus Oral contraceptives, phenothiazines, Without any rashes – rifampicin causes biliary
rifampicin stasis
Purpura Thiazides, phenylbutazone, sulphonamides, May be thrombocytopenic or vasculitic sulphonylureas, quinine
Toxic epidermal necrolysis NSAIDs, penicillins (β-lactams), phenytoin, sulphonamides
Toxic erythema Ampicillin, sulphonamides, sulphonylureas, Usually occurs after 7–9 days of therapy or after furosemide, thiazides 2–3 days in those previously exposed
Urticaria
Acute Radiocontrast media
Acute/chronic Aspirin (NSAIDs), ACE inhibitors, gold, penicillins
Vasculitis – allergic NSAIDs, phenytoin, sulphonamides, thiazides, penicillins and retinoids
NSAIDs, non-steroidal anti-inflammatory drugs; ACE, angiotensin-converting enzyme; AZT, azidothymidine.
effect of too high a dose of UVB in a subject who has been exposed to a drug. The reaction is like severe sunburn and the threshold returns to normal when the drug is discontinued.
Photoallergy (like drug allergy) is a cell-mediated immune reaction that only occurs in certain individuals, is not dose related and may be severe. It is due to a photochemical reac- tion caused by UVA where the drug combines with a tissue protein to form an antigen. These reactions are usually eczema- tous, and may persist for months or years after withdrawal of the drug. Some agents that commonly cause photosensitivity are shown in Table 51.6.
FURTHER READING
Series of articles relating to current treatment of dermatological condi- tions.Clinical Medicine2005;5: 551–75.
ADVERSEDRUGREACTIONSINVOLVING THESKIN 419
Key points
• Treatment of skin disorders depends on accurate diagnosis; steroids are not useful for all rashes and indeed may cause harm if used inappropriately.
• Acne is treated first line with keratolytics; if systemic antibiotics are indicated, use oral oxytetracycline or erythromycin (but do not use tetracyclines in children under 12 years). Vitamin A analogues should only used in refractory cases.
• In eczema, it is important to identify the causal agent and minimize/eradicate exposure if possible.
• For dry, scaly eczema, use emollients plus a keratolytic;
for wet eczema use drying lotions or zinc-medicated bandages.
• Topical glucocorticosteroids are often required, but do not use high-potency glucocorticosteroids on the face.
Use the lowest potency steroid for the shortest time possible required to produce clinical benefit.
• In psoriasis, simple emollients should be used to treat mild cases. Keratolytics may be used in moderate cases.
• Additional therapies for more severe cases of psoriasis include topical vitamin D analogues, PUVA, oral acitretin and cytotoxic drugs. Although
glucocorticosteroids are effective, tachyphylaxis occurs, and on withdrawal pustular psoriasis may appear.
Case history
A 45-year-old white woman with a previous history of one culture-positive urinary tract infection (UTI) presents with a three-day history of dysuria and frequency of micturition.
Her urinalysis shows moderate blood and protein and is posi- tive for nitrates. She is started on a seven-day course of co-trimoxazole, two tablets twice a day, as she has a history of penicillin allergy with urticaria and wheezing. In the early morning of the last day of therapy, she develops a general- ized rash on her body, which is itchy and worsens, despite the
fact that she has not taken the last two doses of her anti- biotic, her UTI symptoms having resolved. By the following morning she feels much worse, with itchy eyes, has had fevers overnight and is complaining of arthralgia and buccal sore- ness, and is seen by her community physician. He notes con- junctivitis, with swollen eyelids, soreness and ulceration on her lips and buccal and vaginal mucosa. She has a generalized maculo-papular rash which involves her face and has become confluent in areas on her abdomen and chest, and there is evidence of skin blistering and desquamation on her chest.
Question
What is the most likely diagnosis here? What is the prob- able cause, and how should this patient be managed?
Answer
The most likely diagnosis of a rapidly progressive general- ized body rash involving the eyes, mouth and genitalia with systemic fever and early desquamation is erythema multiforme-major (Stevens Johnson syndrome, see Chapter 12, Figures 12.2 and 12.3). The most common causes of this syndrome are viral infections, especially her- pes virus, drugs and (less frequently) systemic bacterial infections, such as meningitis, nephritis and streptococcal infection. Many drugs can cause this adverse reaction, but the most commonly incriminated classes of drugs are anti- bacterial agents such as sulphonamides, β-lactams (especially penicillins), vancomycin and rifampicin, anticonvulsants, salicylates and other NSAIDs, and allopurinol. In this patient the most likely aetiology is that she is taking co-trimoxa- zole, which contains 400 mg of sulphamethoxazole and 80 mg of trimethoprim per tablet. Stopping the offending agent is the most important part of her initial management.
Her further management should include admission to hospi- tal for intravenous fluids to maintain hydration, supportive care for the skin in order to minimize further desquama- tion and secondary infection with sterile wet dressings and an aseptic environment, analgesia if necessary, and mainte- nance and monitoring of her hepatic and renal function. If her condition is very severe, the patient may need to be transferred to a burns unit. Short courses of high-dose gluco- corticosteroids early in the disease have been recommended, but controlled clinical studies have not demonstrated the benefit of glucocorticosteroids in this condition. The disease may progress for up to four or five days and recovery may take from one to several weeks. The mortality rate for Stevens Johnson syndrome is 5%, but increases to about 30% if the diagnosis is toxic epidermal necrolysis with more extensive desquamation.
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PART XIII