Plaque psoriasis and morphea in a patient on ustekinumab: A case report

Abstract

A large number of autoimmune and fibrosing conditions associated with psoriasis and morphea have been reported in the literature. Currently, the relationship between psoriasis and morphea is unknown, and the coexistence of these conditions is quite rare. Due to the few patients affected by both conditions, and the lack of knowledge concerning their pathogenic mechanisms, the cause behind this co-occurrence is poorly understood. Here, we present a case of morphea under a plaque of psoriasis in a patient managed on ustekinumab.

Introduction

Psoriasis is a chronic immunologically mediated inflammatory dermatosis characterized by skin inflammation and epidermal hyperplasia, while morphea (localized scleroderma) is a fibrosing autoimmune condition that presents as localized sclerotic skin changes. Studies have identified a greater incidence of autoimmune and fibrosing conditions in those with psoriasis compared to the general population.^1–3 The association between psoriasis and morphea is currently unknown, and the co-occurrence of these conditions is believed to be quite uncommon. Psoriasis has been confirmed in 11.6% of documented immune-mediated conditions seen in conjunction with morphea, making it one of the most common co-occurring autoimmune conditions. ⁴ Here, we describe a case of morphea under a plaque of psoriasis in a patient on ustekinumab.

Case report

We report the case of a 64-year-old male who presented to the clinic in July 2015 with well-demarcated erythematous scaly plaques on his lower abdomen, back, gluteal cleft, and legs. He reported a long-standing history of psoriatic arthritis and severe plaque psoriasis since 1998 localized to his lower abdomen, forearms, gluteal cleft, arms, and legs, with a remote history of methotrexate, adalimumab, and etanercept treatment. His medical history is significant for recurrent cellulitis infections of his right lower leg; long-standing joint pains in his knees, lower back, and hands (minimally responsive to biologics); arthroscopic knee debridement; kidney stones; bilateral inguinal hernia repairs; a colonic adenoma; and obesity. His external medications included lorazepam, hydrochlorothiazide, baclofen, and naproxen. He has a family history of psoriatic arthritis and fibromyalgia. Review of symptoms was otherwise negative.

Since his initial presentation in July 2015 until November 2022, he received various anti-psoriatic therapies which included topicals (corticosteroids, calcipotriol, tazarotene), as well as systemic agents (cetirizine) and various biologics (ustekinumab, secukinumab, and ixekizumab), all of which produced minimal benefit apart from ustekinumab (Figure 1). At the time of presentation, he was managed on ustekinumab 90 mg every 8 weeks; however, the response was not satisfactory, so he trialed the biologics secukinumab and ixekizumab before ultimately returning to ustekinumab due to the lack of sufficient response with these treatments. He had persistent and treatment-resistant thick plaques of psoriasis with silvery scale on his lower back and the left posterior calf, necessitating these biologic switches.

Figure 1.

Medication timeline detailing the treatments, dosages, and responses since the initial presentation in July 2015.

In November 2020, he presented with resolution of the psoriasis on the posterior left calf but mentioned it had left a scar. Examination revealed a thick waxy white plaque. A tissue sample was obtained; however, histologic findings were non-diagnostic. Beclomethasone dipropionate was prescribed to use topically. In July 2022, he returned with several hard, waxy, white, thick plaques with violaceous edges on his left calf, which resembled morphea (Figure 2(a) and (b)). His lower back revealed a similar clinical appearance but with more scale (Figure 3). Histologic examination of a biopsy specimen from one of the lesions on his calf confirmed the diagnosis of morphea in association with lichen sclerosus on the superficial aspect of the lesion (Figure 2(c)–(e)).

Figure 2.

Clinical and histologic images of the patient’s left calf. (a) Hard, lichenified, pearly plaques with violaceous edges beneath a plaque of psoriasis. (b) A more magnified image clearly illustrating the coexistence of erythematous well-demarcated plaques with a psoriasiform appearance and morpheaform plaques below. (c–e) Shave biopsy demonstrating upper dermal sclerosis with eosinophilic homogenization of the papillary dermis overlying a sparse inflammatory cell infiltrate. Focally within the dermis and extending to the base of the biopsy there is an interstitial and perivascular lymphocytic infiltrate with scattered plasma cells (hematoxylin and eosin, 10×, 25×, and 40× for (c), (d), and (e), respectively).

Figure 3.

Clinical image of several hard, waxy, white, thick plaques with significant scale and violaceous edges on the patient’s lower back.

Discussion

This case presents a patient with long-standing plaque psoriasis managed on ustekinumab who developed morphea under a plaque of psoriasis. The etiology of morphea is believed to involve an imbalance between the synthesis and breakdown of collagen. ⁵ It is theorized to develop in response to vascular injury which results in the increased expression of vascular cell adhesion molecules and recruitment of the profibrotic cytokines interleukin (IL)-4, IL-6, and transforming growth factor-beta (TGF-beta) to the affected tissue. This upregulation in profibrotic cytokines leads to the production and deposition of collagen while also inhibiting the degradation of the extracellular matrix. ⁶ In addition, the T-helper 2 (Th2) pathway involved in humoral immunity is also implicated in morphea development. ⁷

Psoriasis, a chronic immunologically mediated inflammatory condition, develops in response to self-antigens which may be triggered by a combination of immune defects and genetic, hormonal, and environmental factors. In psoriasis, an inflammatory cascade involving IL-12 and IL-23 leads to the activation of Th17 and Th1 cells, resulting in increased levels of the pro-inflammatory IL-17 cytokine family that contributes to the inflammatory process in psoriasis.^8,9

Presently, the coexistence of psoriasis and morphea is uncommon, with only 22 cases documented in the literature.^7,10–12 Due to the minimal amount of patients affected by both conditions and the lack of knowledge concerning the precise pathogenic mechanisms, the cause behind this co-occurrence is poorly understood. Both morphea and psoriasis have a common immunologic basis involving inappropriate immune activation against self-antigens, which provides a possible explanation for their coexistence. The Th17 pathway and cytokines IL-17, IL-21, and IL-23 are believed to significantly impact the pathogenesis of inflammatory autoimmune conditions.^6,13 Both the Th2 and Th1 pathways implicated in the pathogenesis of morphea and psoriasis, respectively, interact with the Th17 pathway; thus, it is postulated that dysregulation of this pathway may lead to the coexistence of these conditions in the same patient.^6,7,14–16

Ustekinumab is a monoclonal antibody used to treat moderate-to-severe psoriasis that blocks both IL-12 and IL-23 through their shared p40 protein subunit, which leads to the suppression of the Th1 and Th17 pathways. ¹⁷ Initiation of ustekinumab to treat psoriasis by suppressing the Th1 pathway results in enhanced Th2 expression and may consequently lead to the development of morphea plaques in a patient with an elevated baseline risk.^6,14 The development of morphea in patients undergoing biologic treatment is a rare complication with only 10 cases reported in the literature, 2 of which involved patients treated with ustekinumab. ¹⁸

Currently, we cannot definitively identify the trigger leading to the development of morphea in this patient, nor can we confirm whether the morphea existed beneath the plaque prior to the initiation of ustekinumab. A limitation of this case report is the lack of photos of the psoriatic plaque in the area of morphea on the posterior calf; however, the plaques in the photo of the lower back are similar to these on the left posterior calf but with more silvery scale. A biopsy of the lower back could have been taken; however, the patient declined.

Furthermore, it is highly probable that a combination of the aforementioned explanations for the coexistence of psoriasis and morphea may be implicated in this case. This patient presentation is one of only three documented incidences of the coexistence of these conditions in a patient treated with ustekinumab.^7,11 Ustekinumab has been proven to be both a safe and effective therapy for psoriasis; however, it is worth considering that use in psoriasis patients may be associated with the development of morphea in rare occurrences associated with long-term use. Additional reports of similar cases detailing the coexistence of psoriasis and morphea in patients treated with biologics, as well as an improved understanding of their pathophysiology are required to elucidate the mechanism responsible for their dual presentation.