Phenotypic Shift during Treatment of Plaque Psoriasis with Ixekizumab

J Clin Aesthet Dermatol. 2024;17(11):32–33.

by Caroline Sulich-Moore, DNP, FNP-C, and David Altman, MD, FAAD

Drs. Sulich-Moore and Altman are with the Midwest Center for Dermatology and Cosmetic Surgery in Warren, Michigan.

FUNDING: No funding was provided for this article.

DISCLOSURES: Dr. Sulich-Moore has no conflicts of interest to declare. Dr. Altman reports speaking fees from AbbVie, Amgen, Arcutis, BMS, Dermavant, Incyte, Janssen, Lilly, and UCB.

ABSTRACT: We present a case of a patient with longstanding psoriasis vulgaris who developed an atopic dermatitis-like eruption following long-term IL-17A inhibitor therapy. Following many years of excellent disease control with secukinumab and later ixekizumab, he developed a de novo eczematous eruption, which showed spongiotic dermatitis upon biopsy. The patient was successfully treated for both psoriasis and atopic dermatitis with upadacitinib, a Janus kinase inhibitor. This case suggests an interplay between Th1/Th17 and IL-4/IL-13 immune axes during prolonged biologic therapy, potentially due to upregulation of IL-4 following IL-17 blockade. It highlights the complex immune interactions in inflammatory skin diseases and demonstrates the utility of broader cytokine inhibition in managing evolving presentations.

Keywords: Psoriasis, atopic dermatitis, phenotypic shift, upadacitinib

Introduction

Psoriasis is a common inflammatory condition involving dysregulation of cellular immunity.¹ Driven by the Th1/Th17 cytokine axis, it is generally considered a distinct entity from the Th2-mediated pathogenesis of atopic dermatitis.² However, experience in clinical practice, particularly after years of cytokine manipulation with targeted biologic therapies, suggests a more complicated interplay between these two arms of the immune system. In some cases, patients demonstrate what appears to be a shift in clinical phenotype and presumed cytokines driving inflammation.

Case report. A 49-year-old Filipino male patient presented for biologic treatment of plaque psoriasis affecting 35 percent maximum body surface area (BSA) following therapeutic failure of apremilast (Figure 1). The patient began therapy with secukinumab and achieved disease control within four months of initiating therapy. Although treatment was successful, the patient discontinued secukinumab therapy due to cessation of copay assistance and was transitioned to therapy with ixekizumab. 

Following two years of continuous disease control with ixekizumab (maximum BSA: 3%), the patient reported novel episodes of pruritus and rash. The patient, who had no previous history of atopy, developed a widespread patchy and eczematous eruption that was clinically distinct in appearance from his original presentation (Figure 2). A punch biopsy of this eruption revealed subacute spongiotic dermatitis with eosinophilic infiltrate. History and examination did not suggest an allergic contact response. With these findings and the patient’s original phenotypic presentation in mind, upadacitinib was initiated in lieu of ixekizumab. The patient’s spongiotic eruption resolved completely within four weeks of upadacitinib initiation and his psoriasis has remained clear (Figure 3). 

Discussion

This case illustrates an increasingly common clinical presentation in patients undergoing treatment with targeted biologic therapies. In our clinical experience, some psoriasis patients on long-term treatment with interleukin (IL)-17A inhibitors exhibit this phenotypic shift with greater frequency than those treated with IL-23 inhibitors. We have observed a similar phenomenon in our patients undergoing therapy with TNF inhibitors, particularly infliximab, in which control of psoriasis was usurped by the development of spongiotic eczematous dermatitis that is clinically suggestive of atopic dermatitis following years of therapy. 

This phenomenon suggests an interplay between the respective Th1/Th17 and IL-4/IL-13 axes of psoriasis and atopic dermatitis, which had previously been described as relatively distinct.² Similar phenotypic shifts have been observed in patients undergoing dupilumab therapy for atopic dermatitis, who subsequently developed symptoms of inflammatory arthritis similar to psoriatic arthritis.³ Laboratory studies in mice have shown interplay between deficient IL-4 signaling and increased concentrations of IL-17.^4,5

We believe that this patient’s clinical presentation illustrates upregulation of IL-4 in the context of effective blockade of IL-17, a phenomenon that may be observed in select patients undergoing targeted biologic therapies. This case also illustrates a favorable application of the broader cytokine inhibition associated with Janus kinase (JAK) inhibitors, which can mitigate other components of inflammatory cascades involved in the pathophysiology of distinct clinical presentations. 

Biologic therapies for psoriasis and atopic dermatitis have positively transformed treatment approaches and patient outcomes. The more we glean from the nature and interplay between these conditions and their respective therapies, the more we are able to illuminate the complexities of our immune system.

References 

1. Yamanaka K, Yamamoto O, Honda T. Pathophysiology of psoriasis: a review. J Dermatol. 2021;48(6):722–731. 
2. Nomura I, Goleva E, Howell M, et al. Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J Immunol. 2003; 171(6): 3262–3269. 
3. Jay R, Rodger J, Zirwas M. Review of dupilumab-associated inflammatory arthritis: an approach to clinical analysis and management. JAAD Case Rep. 2022;21:14–18.
4. Haertlé J, Kienlin P, Begemann G, et al. Inhibition of IL-17 ameliorates keratinocyte-borne cytokine responses in an in vitro model for house-dust-mite triggered atopic dermatitis. Sci Rep. 2023;13(1):16628.
5. Schnyder-Candrian S, Togbe D, Couillin I, et al. Interleukin-17 is a negative regulator of established allergic asthma. J Exp Med. 2006;203(12):2715–2725.