D1.93 - Isolated Generalized Pruritus Associated with SGLT2 Inhibitors: A Case Series with Negative Allergy Work-up

Type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic diseases worldwide. In the last decade, type 2 sodium–glucose cotransporter inhibitors (SGLT2i) were approved as an alternative pharmacological treatment for T2DM. Their anti-hyperglycemic mechanism of action involves glycosuria, therefore urinary tract infections are among the most common adverse effects. However, the summary of product characteristics also describes skin pruritus as a common adverse event (≥1/100 to <1/10). Despite this, the underlying mechanism of SGLT2i-associated pruritus remains unclear.

We conducted a retrospective descriptive study of patients referred to the Allergy department with generalized pruritus without skin lesions after initiation of SGLT2i therapy (empagliflozin or dapagliflozin). Demographic variables, comorbidities, laboratory findings, time of  symptom onset, and response to treatment were collected. Allergy work-up included skin prick tests (SPT) with the suspected drug in all patients and patch tests were performed in 3 of the patients. 

Seven patients (5 males, 2 females) were included, with a mean age of 82.1 years. Onset of pruritus occured an average of 4.1 months after SGLT2i therapy was initiated. Five of the seven patients had chronic kidney disease as a relevant comorbidity. None of the patients presented peripheral blood eosinophilia in laboratory studies.

While on SGLT2i treatment and undergoing allergy testing, patients were treated with antihistamines (up to four tablets daily); however, pruritus persisted. A clear temporal relationship between drug initiation and symptom onset was observed in all cases. After drug withdrawal, pruritus improved in all patients, allowing reduction or complete discontinuation of antihistamines.

Skin prick tests with the implicated drug were negative in all cases. Patch tests were performed in three patients and were also negative at 48 and 96 hour reading.

In this elderly cohort, isolated generalized pruritus associated with SGLT2i initiation showed a consistent temporal relationship, poor response to antihistamines, absence of eosinophilia, and resolution after drug discontinuation. Negative allergy testing suggests a mechanism that is neither IgE-mediated nor type IV delayed hypersensitivity. To avoid misdiagnosis as drug hypersensitivity, SGLT2i-associated pruritus should be considered in elderly as an adverse reaction.