Psoriasis is a chronic inflammatory systemic skin disease characterized by erythematous scaly plaque formation and is often comorbid with other diseases such as cardiovascular disease, other inflammatory skin diseases, and tumors. Recently, research on the pathogenesis of psoriasis has revealed a strong connection between the disease and IL-17. The pathogenic mechanism of IL-17A is initiated by the aberrant activation of Th17 cells. In the skin, local microenvironmental stimuli induce dendritic cells to secrete factors such as IL-23, which promote the differentiation of CD4⁺T cells into Th17 cells and result in the substantial release of IL-17A. Upon binding to receptors on keratinocytes, IL-17A activates the NF-κB and MAPK signaling pathways, thereby driving excessive proliferation of keratinocytes and the secretion of pro-inflammatory cytokines (e.g., IL-6, IL-8) and chemokines (e.g., CCL20). This process recruits neutrophils and T cells to the lesion site, establishing a synergistic vicious cycle of “inflammatory cytokine secretion - immune cell infiltration - abnormal epidermal hyperplasia” in conjunction with other cytokines such as IL-22 and TNF-α. Ultimately, this cascade leads to characteristic pathological changes, including acanthosis (1, 2). Among them, IL-17A and IL-23 are the key factors in the pathogenesis of psoriasis. A clinical study has demonstrated that psoriasis patients treated with secukinumab (an IL-17A antibody) for 12 weeks exhibited a reversal of plaque histopathology, along with a significant reduction in the levels of upstream cytokines IL-23 and IL-17A (3). Furthermore, in patients with nail psoriasis, treatment with IL-17A inhibitors (secukinumab and ixekizumab) over 24 weeks resulted in significantly lower PASI, BSA, DLQI, and NAPSI scores compared to baseline, accompanied by marked improvement in skin lesions (4). Biologic therapies targeting these cytokines have gradually become an indispensable part of the treatment of psoriasis (5).

Hidradenitis suppurativa is also a chronic inflammatory skin disease characterized by recurrent episodes of painful nodules, abscesses, sinus tracts, and scar formation (2). Studies in recent years have confirmed that its pathogenesis shares commonalities with psoriasis, such as both including the involvement of TNF-α and IL-17A (6). The study conducted by Alexa et al. revealed that bimekizumab, a dual inhibitor of IL-17F and IL-17A originally developed for psoriasis treatment, exhibited significant therapeutic efficacy in patients with moderate-to-severe hidradenitis suppurativa. Notably, the therapeutic benefits were sustained for up to 48 weeks (7). In addition, it has been shown that elevated serum levels of IL-17A may be associated with the development and metastasis of many tumors, especially colorectal cancer (8, 9). IL-17A has the potential to be a new target for inhibiting tumor metastasis and recurrence (10).

While biologics are traditionally contraindicated in patients with malignancies and hepatitis B, emerging evidence supports the safety of IL-17A inhibitors in these populations (11, 12). This case demonstrates xeligekimab—a novel fully humanized anti-IL-17A IgG4 monoclonal antibody (China-approved, August 2024)—effectively managing concurrent psoriasis, hidradenitis suppurativa, hepatitis B, and metastatic colorectal cancer, providing clinical validation for this paradigm shift.

This complex case—involving plaque psoriasis, hidradenitis suppurativa, chronic hepatitis B, and metastatic colorectal cancer—presented unique therapeutic challenges. Xeligekimab achieved concurrent inflammatory disease control while maintaining oncological stability, suggesting targeted IL-17A blockade may be feasible in such multimorbid scenarios.

Despite concerns that biologics (e.g., TNF-α inhibitors) may trigger tumor recurrence or HBV reactivation, rendering malignancies and hepatitis B relative contraindications, emerging evidence supports IL-17A inhibitors’ safety in these populations (12–14).Secukinumab significantly improved quality of life without increasing cancer recurrence risk in psoriasis patients with malignancy history (13), while IL-17A blockade showed safety in chronic hepatitis B (12).Thus, when clinically warranted after traditional treatment failure, anti-IL-17A therapy represents a feasible option requiring rigorous benefit-risk assessment and informed consent (11, 15).

There are limited previous case report data on the use of biologics for the treatment of psoriasis comorbid with hidradenitis suppurativa, chronic hepatitis B, and metastatic colorectal cancer. Yen, C.F. et al. successfully treated three cases of psoriasis comorbid with hidradenitis suppurativa using adalimumab (16). In 2018, Lasagnas et al. reported a successful treatment with secukinumab in a 59-year-old woman with plaque psoriasis, hepatitis B, and a 12-year history of breast cancer (17). Additionally, some studies have evaluated the use of ixekizumab in treating linear psoriasis and pediatric generalized pustular psoriasis (18, 19), as well as the successful use of spesolimab in a case of generalized pustular psoriasis during pregnancy (20). Our case extends these findings, demonstrating xeligekimab’s efficacy in this challenging clinical scenario. Notably, in 2024, Yousefian et al. described a case of paradoxical psoriasis emerging in a 25-year-old woman with hidradenitis suppurativa following secukinumab therapy, likely due to compensatory IL-23 overexpression (21). Therefore, to prevent exacerbation or recurrence of psoriasis and its comorbidities, a personalized treatment plan must be carefully tailored for each patient.

Biologic therapy was considered due to suboptimal response to conventional treatments. TNF-α inhibitors were excluded over safety concerns in hepatitis B and malignancy (14, 22). Although head-to-head trials are lacking, xeligekimab achieved PASI75 and PASI100 comparable to secukinumab, with potentially superior PASI100 rates (23–25). As a fully human antibody, xeligekimab may offer safety advantages over ixekizumab (23). Given concomitant hidradenitis suppurativa, IL-17 inhibitors appear more effective than IL-23 agents (26). TYK2/PDE4 inhibitors demonstrated significantly inferior efficacy versus IL-17 blockers, with unproven efficacy in hidradenitis suppurativa (27, 28).

Building on these reports, our case further highlights the potential of biologics in managing complex cases of psoriasis with significant comorbidities. The dramatic improvement in our patient’s condition—with PASI reduction from 51 to 0.8, BSA from 87% to 6%, and DLQI from 20 to 1—demonstrates xeligekimab’s potent efficacy. Importantly, the treatment addressed all three conditions simultaneously without adverse effects on hepatitis B viral load or tumor markers, supporting its safety in this complex clinical context.

This case report also has certain limitations, including a relatively short follow-up period and the inherent nature of single-case studies. Further investigations, such as randomized controlled trials, are warranted to confirm the efficacy and safety of xeligekimab in treating psoriasis with complex comorbidities.

This patient demonstrated significant efficacy and acceptable safety with xeligekimab over 28 weeks of treatment. We will conduct extended longitudinal follow-up to evaluate long-term safety and efficacy outcomes. The benefit-risk profile of biologics in such complex cases requires further validation through larger prospective studies.