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Cutaneous adverse drug reactions range from mild to severe and from those localized
only to skin to those associated with systemic disease. The following are some smooth
erythematous drug reactions.

1. Morbilliform (exanthematous)

• The commonest pattern of cutaneous drug reaction.
• Presents within 1–3 weeks of drug exposure.
• A symmetrical morbilliform rash (erythematous macules and papules of 2–10mm in
diameter with a tendency to confluence) starts on the trunk. The rash spreads to the arms
and legs and may become confluent.
• The rash may be itchy (not painful).
• The patient may have a slight (not high) temperature.
• Mucosal are normal.
• Settles with desquamation within 7–10 days of withdrawing the drug. Thick sheets of
scale may detach from the palms or soles—do not confuse with the full-thickness loss of
epidermis seen in TEN.
• Erythroderma is a rare complication.
• If the causative drug is essential, it may be possible to treat through a morbilliform
reaction, but the patient may become erythrodermic.
• Morbilliform reactions may resemble urticaria, but lesions are fixed, or (most often in
children) a viral exanthem (take a thorough history).
• Morbilliform reactions may also precede a serious drug reaction such as TEN,
hypersensitivity syndrome (DRESS), or serum sickness. Monitor for signs that suggest a
serious reaction, e.g. facial swelling, mucosal involvement.
• Common causes: ampicillin (particularly if the patient has glandular fever),
sulfonamides, allopurinol, captopril, barbiturates, thiazides.

2. Urticaria and/or angio-oedema; anaphylactoid reactions

• IgE-mediated reactions may present within minutes of exposure, if previously
sensitized. ACE inhibitors are the commonest cause of admission with angiooedema.
• Urticaria: itchy erythematous wheals (no scale) that move around. Wheals fade within
24h to leave normal skin.
• Subcutaneous oedema (angiooedema) affecting the lips, periorbital skin, tongue (when
patient may have difficulty swallowing or breathing), external genitalia—an emergency.
• Common causes—penicillins, captopril, cephalosporins, thiazides, phenytoin, NSAIDs,
ACE inhibitors (cause angiooedema without urticaria and may not present until > 4 weeks
after the drug is started), aspirin, radiocontrast agents, opiates, quinine.
• Anaphylactoid reactions (not IgE-mediated) may present several weeks after the
medication is started. Histamine is released directly from mast cells and basophils.
Present as red man syndrome with flushing, erythema, and itching of the face and upper
trunk, and sometimes angiooedema, hypotension, dyspnoea, and chest pain. Caused by
drugs such as vancomycin, ciprofloxacin, amphotericin, rifampicin, and teicoplanin.

3. Drug rash, eosinophilia, systemic symptoms (DRESS)

• DRESS is a life-threatening cutaneous drug reaction with systemic symptoms (high
fever) that is frequently misdiagnosed as infection.
• DRESS may be associated with reactivation of HHV-6.
• The morbilliform rash is associated with facial oedema, simulating angiooedema.
• Some patients progress to liver failure.
• Causes include allopurinol, anticonvulsants, minocycline, dapsone, sulfonamides, and
other antibiotics.

4. Acute generalized exanthematous pustulosis (AGEP)

• Patients suddenly develop an uncomfortable oedematous erythema that burns or itches,
and then becomes studded with tiny pustules.
• Caused by a wide range of drugs, including antibiotics such as penicillins,
erythromycin, and tetracyclines.

5. Serum sickness

• Presents within 1–3 weeks of starting the medication.
• Erythema on the sides of fingers, toes, and hands progresses to a widespread
morbilliform rash. Some patients also have urticaria.
• Malaise, fever, arthralgia, and arthritis are common.
• Causes include serum preparations and vaccines.

6. Interstitial granulomatous dermatitis

• Described in association with a range of drugs, including calcium channel blockers, β-
blockers, lipid-lowering agents, ACE inhibitors, antihistamines, anticonvulsants,
antidepressants, and TNF-α inhibitors. Also seen in association with connective tissue
diseases, including RA, and lymphoproliferative disorders.
• Presents months to years after initiation of treatment.
• Annular purplish red (violaceous) plaques on the arms, medial thighs, and flexures.
May be mildly itchy.
• Histologically diffuse interstitial granulomatous infiltrate in the mid and deep dermis
with lymphocytes, histiocytes, mucin deposition, and variable collagen necrosis.

7. Erythema nodosum

A4GPRC Erythema nodosum

• Causes: oral contraceptive pill, sulfonamides, gold (but more often triggered by an
infection (TB) or underlying systemic disease such as sarcoidosis or IBD).
• Tender erythematous subcutaneous nodules on the shins and sometimes forearms.
• Resolves in weeks, without loss of fat or scarring.
• NSAIDs relieve discomfort. Gentle compression with stockings that control swelling
may speed resolution.

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