Eruptive lentiginosis in resolving plaque psoriasis during treatment with risankizumab

Risankizumab is a humanized IgG1 monoclonal antibody targeting the p19 subunit of IL‐23, approved for the treatment of moderate‐severe psoriasis. ¹

Here we describe a patient who developed a lentiginous eruption on skin areas previously affected by psoriasis 6 months after treatment with risankizumab. A 30‐year‐old woman was examined for a 10‐year history of severe chronic psoriasis vulgaris. Previous treatments included cyclosporin and adalimumab, and were ineffective. Physical examination showed generalized, thick, dry, scaly plaques on the back, upper and lower limbs, involving more than 50% of body surface area (PASI 10). Subcutaneous administration of risankizumab was started at the dosage of 150 mg at time 0 and after 1 month, followed by 150 mg every 3 months. After 6 months of treatment, the patient achieved complete response (PASI 100), but she experienced the progressive occurrence of numerous densely distributed, small dark‐brown hyperpigmented macules within the psoriatic plaque areas (Figure 1). Skin lesions on the upper limbs were evaluated by means of reflectance confocal microscopy (RCM), that revealed a marked hyperpigmentation of the epidermal basal layer and of dermal‐epidermal junction, with features of bright elongated cords and bulbous projections, corresponding to elongated pigmented rete ridges at conventional histopathology (Figure 2). Due to the favorable outcome of psoriasis with risankizumab, the patient continued to be treated at a dosage of 150 mg every 3 months for an overall period of 24 months. Along the entire treatment period, the patient did not encounter disease recurrence.

FIGURE 1.

Clinical images of a 30‐year‐old woman with (A) thick, dry, scaly plaques involving the arms, (B–D) developing speckled lentiginoses in the resolving areas of psoriasis.

FIGURE 2.

Confocal (A) image and (B) close‐up showing bright elongated cords (red arrows) and bulbous projections (yellow arrows) at the dermal‐epidermal junction, due to increased pigmentation of keratinocytes. Field of view: (A) = 3.5 × 3.5 mm, (B) = 500 × 500 μm.

Eruptive lentiginosis in resolving psoriasis (ELRP), initially observed during oral psoralen ultraviolet (UV) A therapy, has been also detected with the use of corticosteroids, calcipotriol, apremilast and methotrexate. More recently, it was also associated with biologic agents such as adalimumab, infliximab, etanercept, ustekinumab, and ixekizumab. ² As RCM allows high‐resolution imaging of skin lesions comparable to a virtual histopathology, it can be employed in‐vivo to evaluate subclinical changes in psoriasis during treatment. ³ In our case investigating multiple pigmented lesions was likely to support diagnosis of ELRP, due to the detection of typical features characterizing solar lentigo, thus avoiding incisional biopsy.

As regard to ELRP etiology, it could be considered the result of an increased post‐inflammatory melanin synthesis. Wang et al. highlighted the pivotal role of IL‐17 and TNFa as drivers of its onset. IL‐17 and TNF jointly inhibit pigmentation‐related signaling and melanin production, and induce keratinocyte production of b‐defensin 3, an antagonist for melanocortin 1 receptor. ⁴ Therefore, the removal of the IL‐17/TNF brake through antipsoriatic treatments may activate melanocytes in the affected skin. Though IL‐23 does not act on tissue cells, but it contributes to the differentiation and activation of IL‐17A‐producing T cells, its blockade may exert similar effects on melanocyte stimulation of those observed with IL‐17A antagonists. Herein, our observation supports previous data correlating IL‐23 neutralization and the onset of ELRP. ⁵ Indeed, the cytokine‐mediated suppression of melanogenesis and the burst of pigmentation represent two important factors contributing to the onset of ELRP.

In conclusion, ELRP recognized as a phenomenon associated to treatment for psoriasis, may be easily detected by non‐invasive diagnostic techniques, such as RCM, hence assisting diagnostic decision‐making workflow.

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.