Successful guselkumab treatment of a refractory psoriasis patient with Graves’ disease: a case report

Introduction

Psoriasis is a common, chronic, immune-mediated skin disease that is characterized by erythematous scaling plaques brought on by excessive keratinocyte growth and skin inflammation. ¹ The prevalence of psoriasis is 2%–3%; and it is frequently made worse by psoriatic arthritis, as well as by metabolic syndrome, cardiovascular disease and thyroid disorders, which result in significant psychosocial burdens and negatively impact patients’ and their families’ quality-of-life.^2,3

Autoimmune thyroid disease is considered to be closely related to psoriasis, because free thyroxine is increased significantly in psoriatic patients and patients with thyroiditis have more extended disease periods; ⁴ and in severe psoriasis, there are increased levels of thyroid-stimulating hormone (TSH). ⁵ Previous studies have demonstrated a link between psoriasis and thyroid illness as well as the involvement of type 1 helper T (Th1) cell cytokines in the pathogenesis of both psoriasis and Graves’ disease, which is the most common cause of hyperthyroidism in iodine-replete areas. ⁵ A previous study indicated that methimazole, the first-line treatment for hyperthyroidism, could alleviate psoriasis through a variety of pathways by lowering the psoriasis area and severity index (PASI) scores of the patients after 6–8 weeks of treatment. ⁶ These studies provide some evidence that thyroid illness exacerbates the severity of psoriasis.

The pathogenesis of psoriasis involves T cells, particularly the interleukin (IL)-23/Th17 immune axis. ⁷ The major regulator of pathogenic Th17 cells found in psoriatic lesions is IL-23, which is produced by activated monocytes and dendritic cells. ⁸ Dysregulation of IL-23 production promotes autoimmune inflammation and stimulates the production of effector cytokines such as IL-17A, IL-17F and tumour necrosis factor (TNF)-α. ⁹ Th17 cells and IL-17 were also reported to play important roles in Graves’ disease pathogenesis and are related to disease severity and duration. ¹⁰ These results provide the possible reasons for the increased rate of psoriasis in patients with Graves’ disease and the difficulty with treatment. Guselkumab is a human immunoglobulin G1λ monoclonal antibody that selectively binds to the p19 subunit of IL-23 with high specificity and affinity and blocks the IL-23//Th17 pathway, which plays a critical role in the pathogenesis of psoriasis. ¹¹

This current case report describes a refractory psoriasis patient with Graves’ disease who was successfully treated with guselkumab after failing to respond to the prior use of biologics, small molecule inhibitors or conventional therapies.

Case report

In April 2020, a 34-year-old female patient with severe plaque psoriasis was referred to the Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. The patient was diagnosed with Graves’ disease based on the clinical manifestations (tremor, heat sensitivity, weight loss, enlargement of the thyroid gland), elevations in serum thyroxine and a suppressed TSH value, so she was treated with 10 mg thiamazole oral three times a day for 1 month. After treatment, she had a large area of erythema and papules with scales attached on the trunk and both upper limbs (Figure 1a). According to the patient’s medication history and typical clinical manifestations, drug eruption was identified, so methimazole and propranolol were discontinued. However, the results of thyroid ultrasound and thyroid function suggested that Graves’ disease had not improved (see supplementary materials, Figure 1). After multidisciplinary discussions, it was decided to control the patient’s drug eruption first, so the treatment of Graves’ disease was temporarily suspended.

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Figure 1.

Clinical photographs of a 34-year-old female patient with Graves’ disease who presented with severe plaque psoriasis showing the response to treatment throughout the course of her treatment: (a) drug eruption lesions on the patient’s trunk when admitted; (b) the patient’s initial skin lesions receded after conventional therapies; (c) psoriatic lesions relapsed after treatment with adalimumab; (d) psoriatic lesions continued after treatment with secukinumab; (e) psoriatic lesions partly improved after phototherapy; psoriatic lesions resolved before (f) and after treatment with ustekinumab (g); (h) psoriatic lesions relapsed after treatment with ustekinumab for 1 year and (i) psoriatic lesions resolved after treatment with guselkumab for 3 months. The colour version of this figure is available at: http://imr.sagepub.com.

After administering 40 mg glycyrrhizin intravenous once daily for three consecutive days to treat the drug eruption, her lesions receded (Figure 1b), but continued to recur. The patient was then administered 40 mg adalimumab subcutaneous (s.c.) injection once every 2 weeks for 1 month as a step-up therapy for both psoriasis and drug eruption. After 1 month, the drug eruption lesions were improved. However, fresh scaly erythema and papules developed on both lower limbs (Figure 1c) and she developed new psoriatic lesions with a PASI score of 9.3, so it was suggested that she might have presented with paradoxical psoriasis caused by adalimumab. Meanwhile, the patient underwent iodine-131 treatment in the Department of Nuclear Medicine Department, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China in order to treat the Graves’ disease.

The patient was then administered 300 mg secukinumab s.c. once weekly. Unfortunately, after 1 month of treatment, the psoriasis lesions were exacerbated, especially her scalp lesions (Figure 1d). It was decided to discontinue secukinumab treatment and use phototherapy with topical calcipotriol-betamethasone twice a day. After 6 months, her scalp lesions had not improved (Figure 1e). In addition, the phototherapy was discontinued and 5 mg tofacitinib oral twice a day for 1 month was used due to the propensity of the lesions to recur and her intolerance to the side-effects of phototherapy. After 1 month of tofacitinib treatment, she continued to develop additional lesions especially on the face (PASI score of 15.8) (Figure 1f). Treatment was switched to 45 mg ustekinumab s.c. every 12 weeks and a PASI 90 response were obtained (Figure 1g). However, 17 months later, the patient experienced a second failure of ustekinumab (Figure 1h). After this occurred, the patient was administered 100 mg guselkumab s.c. every 8 weeks. Her psoriatic lesions essentially vanished after being treated with guselkumab for 3 months and she achieved a PASI 75 response (Figure 1i). The clinical symptoms and medication regimens are shown in Figure 2. The patient’s condition of Grave’s disease remains stable (see supplementary materials, Table 1).

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Figure 2.

Changes in psoriatic lesions and medication regimen of a 34-year-old female patient with Graves’ disease who presented with severe plaque psoriasis. w, week; PASI, psoriasis area and severity index; SSPGA, SELENA SLEDAI Physician’s Global Assessment; TS, topical steroids. The colour version of this figure is available at: http://imr.sagepub.com.

The patient was informed about the possibility of the use of their data in research publications with the preservation of confidentiality and privacy. Written informed consent was obtained. The patient details were de-identified. Upon the receipt of patient consent, the requirement for ethics committee approval was waived at our institution. The reporting of this study conforms to the CARE guidelines. ¹²

Discussion

This current case report describes a female patient with refractory psoriasis that was complicated with Graves’ disease. Previous research has demonstrated that thyroid hormones and their receptors are essential in stimulating skin proliferation and are associated with the pathogenesis and development of psoriasis. ⁴ This appears to complicate the treatment of psoriasis in patients with concomitant thyroid diseases. There have been few case reports on the management of psoriasis patients with Graves’ disease. ¹³ The present patient was initially admitted to the hospital for drug eruption after taking thiamazole. The patient was treated with adalimumab after the drug eruption had greatly improved, but fresh erythema and scaling had developed on both lower limbs, which was assumed to be paradoxical psoriasis induced by TNF-α inhibitors. And after receiving treatment with IL-17A inhibitors, paradoxical psoriasis remained uncontrolled. It has been demonstrated that 2%–5% of individuals on TNF-α inhibitors developed new skin lesions that mimicked psoriasis. ¹⁴ Although prior studies have shown that IL-17A inhibitors are safe,^15–17 there is evidence suggesting that they can cause psoriasis exacerbation and induce paradoxical reactions such as pustular psoriasis. ¹⁸ As IL-17A inhibition might result in the upregulation of IL-23, followed by a rise in levels of IL-22, IL-17F and TNF-α, the mechanism of action may be connected to the imbalance of cytokine pathways, similar to the paradoxical psoriasis induced by TNF-α inhibitors. ¹⁸ When TNF-α and IL17A inhibitors are used as the treatment of psoriasis, clinicians need to be aware of the potential for paradoxical psoriasis.

Previous research suggests that there are several commonalities in the pathophysiology shared between psoriasis and Graves’ disease, such as hormones, genetic factors and oxidative stress. ⁵ Therefore, when the current patient showed poor responses to a variety of treatments, including conventional therapies, Janus kinase inhibitor inhibitors and biologics, her medical team speculated that this was related to the underlying Graves’ disease, so she underwent iodine-131 treatment at same time. Finally, her treatment was switched to the IL-23 inhibitor, guselkumab, which resulted in the resolution of her psoriatic lesions. A previous study found that the IL23A gene polymorphism (rs11171806) was significantly associated with susceptibility to Graves’ disease and that serum IL-23 levels were significantly higher in patients with Graves’ disease compared with the healthy controls. ¹⁹ These findings suggest that IL-23 inhibition might reduce the impact of Grave’s disease on psoriasis. Furthermore, IL-23 is the key cytokine in the development of psoriasis. In a phase III study in patients with psoriasis, guselkumab enhanced the clearance of skin lesions with better efficacy than adalimumab, secukinumab and ustekinumab. ²⁰ Moreover, the results of a recent cohort study suggested that guselkumab had the highest drug survival in terms of treatment persistence that was associated with effectiveness compared with the other biologics used in the study; and that it had the highest drug survival for safety compared with other the biological agents used except ustekinumab. ²¹ The current patient’s Grave’s disease remains stable and although she experienced adverse reactions to hypothyroidism after receiving iodine-131 treatment, the treatment with biologics has not worsened it.

In conclusion, the management of psoriasis patients with Graves’ disease is challenging. In the current patient, her psoriasis was rapidly and sustainably controlled following treatment with guselkumab without adverse effects. Guselkumab may be a promising therapy for psoriasis patients with concomitant Graves’ disease, but further clinical studies are needed to support the findings observed in this current case.

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