Clinical and immunological phenotype switch to prurigo nodularis in a patient receiving ixekizumab for treating psoriasis: a case report
Clinical and immunological phenotype switch to prurigo nodularis in a patient receiving ixekizumab for treating psoriasis: a case report
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接受 ixekizumab 治疗银屑病的患者临床和免疫表型转变为结节性痒疹：病例报告
DOI：
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发表时间：
2023
影响因子：
3.6
通讯作者：
J. Qiao
中科院分区：
文献类型：
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作者：
Taoming Liu;Yuqi Chu;Sheng Li;H. Fang;J. Qiao
nodularis in a patient receiving ixekizumab for treating psoriasis: a case report Dear Editor, Psoriasis is a chronic inflammatory skin disease and largely driven by interleukin (IL)-23/IL-17 immune pathway. Prurigo nodularis (PN) is an under-studied inflammatory cutaneous disease and may be associated with subset of Th2 cytokines. Ixekizumab, a human immunoglobulin G4 monoclonal antagonist, selectively blocks IL-17A, is an effective and safe biologic option for patients with psoriasis. Here, we present a patient with psoriasis developing to PN after receiving ixekizumab treatment. We also explore the dynamic changes of Th2 and Th17 subsets in this patient during ixekizumab treatment. A 54-year-old man with a 1-year history of psoriasis presented with mild itch and widespread patchy erythema and plaques along the scalp, extremities, and trunk (Figure 1a,b). The patient also had persistent joint pain for 2 months. The patient received metformin 1 g twice daily for treating diabetes for 10 years. The patient had no improvements in Psoriasis Area and Severity Index (PASI) score and joint pain visual analog scale (VAS) score during 12-month therapy with oral methotrexate 7.5 mg per week. A biopsy from thigh examination revealed alternating neutrophils and parakeratosis in the stratum corneum, loss of the granular layer, and rete ridge elongation uniformly (Figure 1c). He was then treated with ixekizumab with standard doses of 160 mg subcutaneously at week 0 and then 80 mg every 2 weeks. The baseline PASI score and pain VAS score were 44.4 and 7, respectively. At week 2, his joint pain and skin lesions were significantly improved. The PASI score decreased to 17, and pain VAS score was 0. However, intractable pruritus and hyperkeratotic nodules appeared after 8-week treatment (Figure 1d,e). Hyperkeratosis, significant irregular acanthosis, and perivascular lymphocytic infiltrate appeared in a biopsy from the thigh (Figure 1f). During ixekizumab treatment, the pruritus Numerical Rating Scale (NRS) increased from 2 to 10. Blood tests showed total serum IgE levels increased from 211 to 539 KU/l (normal range <100.0 KU/l). Then ixekizumab was discontinued. He was treated with ebastine 10 mg per day and topical halomethane cream for itch. Within 8 weeks, the pruritus NRS improved from 10 to 2, and PN skin lesions were partially clear. To determine the immunophenotype of this patient, we performed immunofluorescence for Th17 cells (RAR-orphan receptor g; RORC; 1:200, Novus Biologicals, NBP2-24503), Th2 cells (GATA binding protein 3; GATA3; 1:500, Abcam, Ab199428), and T cells (CD3; 1:200, Immunoway, YM6612) on skin samples of this patient. We also performed mRNA in situ hybridization for IL22 on specimens from this patient to describe dynamic changes in immunophenotype from psoriasis to PN. The probe for IL22 was 50-CCTATCAGATTGAGGGAACAGCACTTCTTCAAGGGTG-30. This study procedure was given ethical approval by the ethics committees of The First Affiliated Hospital, Zhejiang University School of Medicine (IIT-2023-161). We observed a trend toward a higher percentage of Th2 cells (CD3 GATA3) in ixekizumab-induced PN lesions (Figure 1h). Of note, it is shown that IL22 expression of cutaneous lesions increased after ixekizumab treatment by in situ hybridization (Figure 1g). The trend toward Th22/IL-22 profile has been revealed in both systemic and cutaneous immune responses in patients with PN. It is demonstrated that IL-22 is important in promoting epidermal hyperplasia and inhibiting epidermal differentiation, and implicated as being central to development of TNF-a-associated eczema. Transcriptional data analysis indicated genes suppressed by etanercept were significantly overlapped with ixekizumab in psoriasis lesions. We speculate that de novo production of IL-22 might be a potential trigger of PN lesions in patients with psoriasis associated with ixekizumab treatment. In sum, we demonstrate that hyperkeratotic nodules eruption appears to be an emerging condition in patients with psoriasis receiving anti-IL-17 treatment. However, the pathogenesis of nodules eruption associated with biologic use is unclear. These data may provide clues that dynamic changes of phenotype switched from Th17 to Th2/Th22 during anti-IL-17 treatment.
