Introduction
Liraglutide is a glucagon-like peptide 1 receptor agonist used for the treatment of obesity, and type 2 diabetes and skin-related side effects are rarely reported. Here, we report a case of a delayed type of hypersensitivity reaction at the injection site and induction of tolerance to liraglutide.
Case report
A 39-year-old male White patient presented with obesity and a history of failure of nonpharmacologic strategies for weight reduction and was treated with liraglutide administered subcutaneously. The initial dose of liraglutide (approved for obesity treatment with a daily dose of 3 mg) 0.6 mg daily was increased weekly by 0.6 mg to the therapeutic dose of 3 mg daily. On reaching a daily dose of 1.8 mg, pruritic erythematous patches appeared on the injection sites 1 day after the medication application. The itch was negligible for the patient, and he continued the drug administration reaching 3 mg/d.
The clinical examination revealed round erythematous plaques on the abdomen at the injection sites of liraglutide (Fig 1, A).
Fig 1.
A, Round erythematous plaques at the injections site of liraglutide. B, Positive delayed reaction of the intradermal test to liraglutide.
The patient did not report any allergies, previous history of atopy, or concomitant disease beyond obesity, class 2 and a body mass index of 39.2 kg/m2.
Patch test with European baseline series, propylene glycol (5% in petrolatum) (Chemotechnique Diagnostics), as well as liraglutide (6 mg/mL; aqueous solution and in petrolatum), was conducted on the back and the abdomen (on a site of receding lesion of the abdomen), but no positive reaction was noted during the readings of days 2 and 3. Skin prick test with liraglutide (6 mg/mL; aqueous solution) yielded a negative result. Intradermal test with liraglutide (6 mg/mL) diluted 1:10 in saline was negative at the 20th minute and positive at the 24-hour reading (Fig 1, B).
The same concentration intradermal test was performed in 5 healthy controls and all results were negative. The patient refused skin biopsy and histopathologic examination because of benign course and the complete healing of the skin lesions.
Based on the clinical presentation of the skin lesions and the tests performed, a diagnosis of delayed hypersensitivity to liraglutide was rendered. Symptomatic treatment was administered with a twice-daily application of clobetasol propionate ointment 0.05% for 2 weeks, followed by 30 days of once-daily mometasone furoate ointment 0.1% use. The patient continued his treatment with liraglutide 3 mg/daily. He was able to tolerate the drug without any skin reaction at the end of the treatment and during the 6-month follow-up.
Discussion
Liraglutide is a glucagon-like peptide 1 receptor agonist used for the treatment of obesity and type 2 diabetes. Side effects are mainly from the gastrointestinal tract, and only several cases of adverse skin reactions have been reported in the literature. A vesiculo-pustular rash,1 acute exanthematous pustulosis,2 and generalized erythematous plaques and nodules3 associated with liraglutide treatment have been described. Injection site reactions are listed as adverse drug reactions of liraglutide (for obesity or diabetes indications); however, the product information does not specify whether these can be delayed or immediate onset.4 Injection site reactions include hemorrhage, deep nodular infiltrate, and pruritic erythematous macules.5,6 Only a single case of delayed hypersensitivity to liraglutide has been published, confirmed by a skin test.7 We would recommend intradermal test as a first-line test in the diagnosis of cases with suspected delayed liraglutide hypersensitivity.8 The explanation for the negative patch test could be the large size of the drug molecule (3751 Da), which cannot penetrate the skin barrier permeable for molecules <500 Da.9 On the other hand, the short contact time and the small concentration of tested drugs could result in a negative prick test. No positive prick test to liraglutide has been documented, despite the observations of such to other glucagon-like peptide 1 receptor agonists, such as exenatide and lixisenatide.10
Conflicts of interest
None disclosed.
Footnotes
Funding: None.
IRB approval status: Not applicable.
References
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