INTRODUCTION
Psoriasis is a chronic, immune-mediated inflammatory disease characterized by erythematous, scaly plaques. It is associated with a high prevalence of comorbidities, including other autoimmune diseases and malignancies. Chronic inflammation related to psoriasis, as well as immunosuppressive, immunomodulatory, and phototherapy treatments, may contribute to the development of malignancies. Treatment of moderate-to-severe psoriasis often requires systemic therapy, including biologic agents [1]. Secukinumab is an interleukin-17A inhibitor that has demonstrated significant efficacy and a rapid onset of action in the treatment of moderate-to-severe psoriasis [2].
OBJECTIVE
We report a case of papillary thyroid carcinoma in a patient with psoriasis treated with secukinumab.
CASE REPORT
A 35-year-old man had been followed for psoriasis vulgaris since 2018. He presented with scaly erythematous plaques on the body and scalp. His initial Psoriasis Area and Severity Index (PASI) score was 7.6. The symptoms had started 5 years before his first visit, during which time he had only used topical treatments.
In addition to topical therapy, methotrexate (MTX) 15 mg/week was initiated. The patient remained in remission for 1.5 years while receiving MTX. However, after relapse, MTX was discontinued and secukinumab was introduced. Complete remission (PASI: 0) was achieved, and treatment was continued for 2.5 years. Secukinumab was later discontinued because the patient’s symptoms had completely resolved and he requested to stop the medication.
One year later, the patient experienced a relapse, and secukinumab therapy was restarted. After 3 months of treatment, routine follow-up thyroid ultrasonography revealed a 10 × 6 mm hypoechoic nodule with punctate echogenic foci located at the junction of the left thyroid lobe and isthmus. Fine-needle aspiration biopsy of the nodule confirmed papillary thyroid carcinoma. The patient was evaluated by the departments of endocrinology and general surgery, and a total thyroidectomy was performed. Postoperative staging was T1aN0M0, and radioactive iodine (RAI) therapy was not administered.
Following the last dose of secukinumab, the treatment was discontinued because of marked improvement in psoriasis lesions (PASI < 1) and concerns regarding its potential association with malignancy. The patient was treated with topical emollients and scheduled for follow-up after 3 months. However, he did not attend the visit, and the recurrence status remains unknown.
The patient had previously used MTX for 1.5 years and secukinumab for a total of 2 years and 9 months. He had not received phototherapy. Six months earlier, he had been diagnosed with type 2 diabetes mellitus (DM). No other comorbidities were present. His body mass index (BMI) was 23.94 kg/m2. The patient reported no alcohol consumption and had a 20-pack-year smoking history. There was no history of head and neck radiation exposure and no first-degree family history of cancer.
DISCUSSION
The association between psoriasis and malignancy risk in the context of immunomodulatory therapies has been widely investigated and remains a subject of debate. Several studies have reported an increased risk of malignancies in patients with psoriasis. The elevated risk may be related to chronic inflammation and cytokine production, genetic predisposition, comorbidities, lifestyle factors such as smoking and alcohol consumption, and therapeutic interventions including phototherapy and systemic immunosuppressive or immunomodulatory agents such as MTX, cyclosporine, and biologic therapies [3]. A meta-analysis encompassing 112 cohort studies reported an overall cancer prevalence of 4.78% (95% CI: 4.02–5.59%) among patients with psoriasis [4]. Trafford et al. [5], in a systematic review and meta-analysis of 58 observational studies, demonstrated an increased risk of several solid tumors, including colorectal, renal, laryngeal, hepatic, esophageal, and pancreatic cancers in patients with psoriasis. Similarly, Lee et al. [6] suggested a possible association between psoriasis and thyroid, prostate, liver, ovarian, lung, skin, and testicular cancers.
The relationship between psoriasis and thyroid cancer (TC) remains uncertain. One case-control study reported a 1.113-fold increased risk of TC in patients with mild psoriasis, whereas two observational studies found no significant association [6–8]. However, a recent study investigating thyroid cancer in patients with psoriasis identified a higher risk among younger individuals (< 55 years) and in patients without hypothyroidism [9].
Treatment options for psoriasis include phototherapy, topical therapies, and systemic agents. The choice of therapy depends on disease severity, comorbidities, and access to healthcare [10]. Evidence regarding the association between MTX therapy for psoriasis and malignancy remains limited. The potential malignancy risk associated with MTX is still debated. A meta-analysis evaluating psoriatic patients treated with MTX reported a malignancy incidence of 1.2% [11]. A cohort study from Korea demonstrated no significant difference in malignancy incidence between MTX-treated patients and individuals without psoriasis [12]. Similarly, the PSOLAR registry, a post-marketing cohort study evaluating the safety of systemic psoriasis therapies, reported no increased risk of malignancy in MTX-treated patients, excluding non-melanoma skin cancer [13].
The impact of IL-17 inhibition with secukinumab on malignancy development is uncertain. The relationship between IL-17 and tumor immunopathology is complex. T helper 17 cells (Th17) and Th17-related cytokines have demonstrated both pro- and anti-tumorigenic effects in preclinical studies [14]. IL-17 activates antitumor natural killer cells (NK), dendritic cells, and macrophages through increased expression of IL-1, IL-6, IL-12, and TNF. It has also been shown to induce apoptosis of cancer cells via caspase activation [15]. Furthermore, IL-17 may promote a cytotoxic cytokine environment by shifting immune responses toward a Th1 profile and inducing IFN-γ-mediated tumor destruction pathways. Therefore, IL-17A inhibitors may theoretically influence the course of malignant disease [15]. However, available clinical studies evaluating the safety of secukinumab indicate that it does not significantly increase the risk of malignancy [16, 17].
Clear and up-to-date guidelines regarding the use of biologic agents in patients with malignancy remain limited. According to the EuroGuiDerm guidelines, patients with psoriasis and active cancer or a cancer diagnosis within the previous 5 years should preferentially receive topical therapy, narrow-band UVB phototherapy, or acitretin. MTX, apremilast, and biologic agents targeting TNF-α, IL-12/23, IL-17, and IL-23 receive weaker recommendations. Treatment decisions should be individualized and made in consultation with an oncology specialist, taking into account disease severity and patient preferences [18].
In the FUTURE 4 study evaluating the safety and efficacy of secukinumab in psoriatic arthritis, papillary thyroid carcinoma was reported in 1 case [19]. In our patient, the tumor may have developed de novo or in association with secukinumab therapy. It should also be noted that this malignancy is relatively common in the general population, and the patient’s baseline cancer risk may have been increased due to psoriasis. Routine thyroid ultrasonography performed during follow-up enabled early detection of the tumor and curative treatment with total thyroidectomy.
CONCLUSIONS
The relationship between anti-psoriatic therapies and malignancy development remains incompletely understood. Further real-world observational studies and case series are needed to clarify the potential oncologic risks associated with secukinumab and other biologic agents. Therefore, careful monitoring, including detailed medical history, physical examination, and appropriate laboratory and radiological evaluation, should be performed before and during treatment.
