How to do skin testing for tetracycline allergy?

What are tetracyclines?

Tetracyclines are antimicrobial agents that have been in use since 1948. The chemical structure consists of four tetra- hydrocarbon rings with a “cycl” derivation.

What type of reactions are caused by tetracyclines?

Although classical hypersensitivity reactions are considered much less common than for beta-lactams and other antibiotics, tetracyclines have been implicated in both IgE- and T cell-dependent reactions such as fixed drug eruption, more severe reactions like DiHS and TEN, and reactions involving specific organs such as liver, lungs, and the central nervous system amongst others.

Tetracylcines can induce phototoxic and photoallergic reactions. These are T cell responses directed to photoadducts which originate in the skin. They usually occur after 5 days of drug administration although they may appear within hours and develop progressively spreading over the skin not exposed to ultraviolet radiation. The most common tetracycline involved in these reactions has been minocycline. Death can occur specially in those patients who develop fulminant hepatitis or respiratory failure.

How to diagnose tetracycline allergy?

General principles recommended for in vivo diagnostic tests can be followed for the diagnosis of hypersensitivity reactions to tetracyclines. These consist of:

- SPT/IDT for immediate reactions
- IDT/patch testing for non immediate reactions

For doxycycline, concentrations of 20 mg/mL can be used for SPT. For IDT with doxycline, the maximum non-irritative concentration recommended is one tenth dilution of this (2 mg/mL).

Concentrations above these can induce false positive reactions.

Concentrations for patch testing of 5% w/v or w/w in petrolatum have been recommended. In the photopatch test the drug is applied on the back using an aluminum chamber and 48 hours later irradiation with a UVA lamp is made with a dose of 10 jls/cm2. Photopatch tests with doxycycline in appropriate dilution are useful to confirm photoallergic reactions to this antibiotic.

How to interpret the skin test?

A negative skin test does not rule out IgE-mediated allergy. If the skin test is negative, the abscene of allergy should be confirmed with a graded dose drug challenge.

A positive skin test with a non-irritating concentration suggests the presence of drug-specific IgE.


Hypersensitivity reactions to non beta-lactam antimicrobial agents, a statement of the WAO special committee on drug allergy. Mario Sánchez-Borges et al. World Allergy Organization Journal 2013, 6:18.

General Considerations for Skin Test Procedures in the Diagnosis of Drug Hypersensitivity. Brockow K, et al., Allergy 2012 (January); 57(1):45-51.

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