A case of psoriasiform drug eruption revealed by a drug‐induced lymphocyte stimulation test

Abstract

We here report a case of psoriasiform drug eruption in which significant improvements in intractable itching and psoriatic lesions were observed only 6 weeks after discontinuing drug-induced lymphocyte stimulation test (DLST)-positive drugs without using any biologics or other systemic treatments. A 33-year-old obese man (body mass index = 36.9) with metabolic syndrome attended our clinic for treatment of intractable psoriasis. He had typical large psoriatic plaques with a Psoriasis Area and Severity Index (PASI) score of 20.7 (Figure 1a), along with extreme itching (numerical rating scale [NRS] score 9). He had no family history of psoriasis and a slight dry skin rash had developed on the nape about 22 months previously in winter, but it resolved once. He had started taking febuxostat for hyperuricemia 14 months previously and developed psoriasis with itching 6 months later, again in winter, but this time the rash continued. He had also started taking ezetimibe and canagliflozin for hyperlipidemia and diabetes 6 months previously and experienced immense exacerbation of the itching and psoriasis 3 months later, with the lesions expanding systemically. Blood tests showed elevations of eosinophils (893/μl), low-density lipoprotein (LDL) cholesterol (145.6 mg/dL), and mild liver dysfunctions. Skin biopsy taken from one such plaque (Figure 1b) showed psoriasis histologically, but eosinophil infiltration and crusting were conspicuous (Figure 1c–e). Because of the extreme itching, elevated eosinophils, drug history, and his concern about the cost of biologics, DLSTs for his current medications were tentatively conducted to possibly rule out a complicated drug eruption. These tests revealed positive results for febuxostat and ezetimibe (stimulation index [SI] 2.3 and 8.2, respectively). Topical therapy with a fingertip unit of a mixture of corticosteroids and vitamin D was not sufficiently effective, but only 6 weeks after switching from the two DLST-positive drugs, the PASI score significantly decreased to 4.5 (Figure 1f), with NRS-itch of 1, therefore, the commencement of treatment with biologics was no longer necessary. His psoriasis did not clear up completely, but he now only uses moisturizers in winter as the symptoms have remained quite mild for the last 2 years. Psoriasiform drug eruption was originally defined as psoriasis caused or aggravated by a drug that occurs via the drug's pharmacological action.1 However, febuxostat and ezetimibe could correct hyperuricemia and/or hyperlipidemia, factors associated with psoriasis, implying that his psoriatic lesions are unlikely to have occurred in that way. Another possible mechanism could be that obesity itself is a risk factor for psoriasis, as shown by a Mendelian randomization study2 and a mouse model.3 Increased interleukin (IL)-23, a key cytokine for psoriasis, within the adipose tissue in people with high LDL cholesterol has also been identified as an inflammatory biomarker.4 In such “pre-psoriatic” individuals with obesity and high LDL cholesterol, such as the present patient, drug allergy-induced itching/scratching is potentially causative of psoriatic lesions via the Koebner phenomenon, presumably upregulating CCL20 and CXCL8 (chemokines for Th17 cells and neutrophils, respectively) in keratinocytes.5 We have been unable to perform another set of DLSTs or other tests to examine possible false-positive results for either drug due to lack of availability of the patient. In conclusion, our findings suggest that, for patients with intractable psoriasis exhibiting intense itching and/or elevated blood eosinophils, DLST might be worthwhile to identify drugs causative of psoriasiform drug eruption and to decrease disease severity, before considering high-cost medications. None declared. Written informed consent for publication and use of photographs was obtained from the patient.