A Textbook of Clinical Pharmacology and Therapeutics

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 reaction
caused by UVA where the drug combines with a tissue
protein to form an antigen. These reactions are usually eczematous,
and may persist for months or years after withdrawal of
the drug. Some agents that commonly cause photosensitivity
are shown in Table 51.6.
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 positive
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 generalized
rash on her body, which is itchy and worsens, despite the
ADVERSE DRUG REACTIONS INVOLVING THE SKIN 419
fact that she has not taken the last two doses of her antibiotic,
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 soreness,
and is seen by her community physician. He notes conjunctivitis,
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 probable
cause, and how should this patient be managed?
Answer
The most likely diagnosis of a rapidly progressive generalized
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 herpes
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 antibacterial
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-trimoxazole,
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 hospital
for intravenous fluids to maintain hydration, supportive
care for the skin in order to minimize further desquamation
and secondary infection with sterile wet dressings and
an aseptic environment, analgesia if necessary, and maintenance
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 glucocorticosteroids
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.
FURTHER READING
Series of articles relating to current treatment of dermatological conditions.
Clinical Medicine 2005; 5: 551–75.