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Author: Dr Aarthy Uthayakumar, Core Medical Trainee, University College Hospital London, London, United Kingdom. DermNet NZ Editor in Chief: Adjunct A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand. Copy edited by Gus Mitchell/Maria McGivern. March 2018.
Antibiotics are drugs used to treat bacterial infections.
An adverse drug reaction (ADR) is an unintended response to a drug at doses normally used for disease therapy. Cutaneous ADRs are ADRs affecting the skin.
ADRs are common, particularly in hospital inpatients, with estimates of 2–3% of hospitalised patients experiencing an ADR, and one in 20 of them being potentially fatal. [1,2].
Cutaneous ADRs account for 10–30% of ADRs, and are most commonly due to antibiotics . The reactions can vary in severity; most are mild-to-moderate, but severe reactions are estimated to occur in 0.1–2% of cases .
ADRs can be classified as either non-immunological or immunological.
Non-immunological ADRs caused by antibiotics include:
There are four main types of immunologically mediated hypersensitivity or allergic responses to drugs. These immunological ADRs make up approximately 20% of ADRs .
Severe ADRs to some antibiotics, such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) due to sulphonamides, are caused by complex immunological mechanisms .
It usually takes 7–10 days to become allergic to a drug, so if a reaction is rapid, it is either non-immunological, or it is due to a previous encounter with the same drug or a chemically similar substance .
Several other ADRs affecting the skin can be due to antibiotics and are listed below alphabetically.
It is sometimes difficult to determine whether an antibiotic has caused a rash. Drugs are rarely deliberately given to the affected patient again, as re-challenge has the potential to cause a life-threatening response in some cases. This means the true incidence of ADRs is difficult to calculate.
There are important differential diagnoses to consider when examining a suspected cutaneous drug reaction; these include :
A large number of antibiotics have the potential to cause cutaneous drug reactions.
The four classes of beta-lactam antibiotics are penicillins, cephalosporins, carbapenems, and monolactams. Allergic reactions to beta-lactam antibiotics are the most common cause of immunological ADRs. This is thought to be due to the structure of beta-lactams. IgG antibodies to penicillin can be detected in allergic patients and non-allergic patients taking penicillin [10,11].
There is some cross-reactivity between penicillins and cephalosporins. If a patient has an anaphylactic response to penicillins, cephalosporins should be avoided.
Cutaneous ADRs caused by beta-lactams include:
Though structurally similar, carbapenems can usually be safely used in patients with anaphylactoid reactions to penicillin. The major non-cutaneous side effects of beta-lactam use are diarrhoea, increased Clostridium difficile, and drug-induced liver injury, particularly due to clavulanic acid/amoxicillin.
In comparison to most other antibiotics, macrolides are considered relatively safe drugs.
Tetracycline antibiotics are frequently used in dermatology. Possible cutaneous reactions include:
Several older generation fluoroquinolones have been withdrawn from the market due to severe adverse reactions including photosensitivity .
Side effects of current-generation quinolones include tendinopathy and QT prolongation. Common cutaneous reactions include:
Co-trimoxazole is a sulfonamide antibiotic commonly used in immunocompromised individuals, who are already more at risk of ADRs. The most frequent ADRs are morbilliform or urticarial rash; however, serious ADRs can result, most commonly SJS/TEN . Observed cutaneous drug reactions with sulfonamides include:
Non-cutaneous reactions with sulfonamides include thrombocytopenia, anaemia, and electrolyte abnormalities .
It is essential to take a careful history in the diagnosis of cutaneous drug reactions. Many affected patients have been taking several drugs. In these cases, it helps to form a timeline, including the initiation of any new drugs and the rash onset.
Sometimes, a skin biopsy will be taken to clarify the inflammatory pattern. The presence of eosinophils can be a helpful clue of an underlying drug cause but is non-specific.
The first principle of management is the withdrawal of the causative drug.
Other measures include:
Antibiotics are one of the most significant discoveries in medicine, but they are not without complications.
Cutaneous side effects are commonly experienced and have the potential to be life-threatening, especially in at-risk groups. Among the classes, penicillins, cephalosporins, sulfonamides, and fluoroquinolones are the most common causes of cutaneous reactions, particularly severe ones.
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