Recurrence of psoriasis on the resolution sites left with lentiginous pigmented patches after TNF inhibitor therapy^☆

Dear Editor,

To date, several cases of multiple lentigines in resolved psoriasis lesions have been reported. Herein, we describe a rare case of psoriasis that resolved leaving multiple small lentiginous patches in the lesions after successful treatment with a Tumor Necrosis Factor (TNF) inhibitor. Moreover, a recurrence of psoriasis was observed in the pigmentary patches.

A 55-year-old male was diagnosed with psoriasis vulgaris 6 years previously and had been treated with topical corticosteroid ointment. Joint pain appeared on the bilateral fingers, wrists, and ankles 3 years previously, and he received systemic therapy with adalimumab (subcutaneous injection of 80 mg, and 40 mg thereafter every other week). Both cutaneous and joint manifestations responded well to adalimumab. Psoriasis Activity and Severity Index (PASI) score was reduced from 6.0 to 0 (PASI clear), and also, he was relieved from joint pain. After the complete disappearance of psoriasis, pigmentation emerged. However, during maintenance therapy with adalimumab, cutaneous psoriasis relapsed 7 months later, but without recurrence of joint pain. Physical examination showed multiple brownish plaques on the lower extremities. A few psoriatic plaques were observed in some, but not all, of the resolved lesions (Fig. 1A‒C). In one of the lesions, psoriatic lesions appeared within the pigmented macule and spread beyond the pigmented macule (Fig. 1C).

Figure 1
(A) A number of small brownish lentiginous patches appeared after improvement of psoriasis. (B) Psoriatic plaques were observed within part of the pigmentary macule. (C) Psoriasis occurred within the pigmentary macule and spread beyond the pigmentary macule

There are several cases of psoriatic plaques that were treated with biologics such as TNF inhibitors, Interleukin-17 (IL-17) inhibitors, IL-12/23 inhibitors, T-cell inhibitors, and phosphodiesterase 4 inhibitors, and left lentiginous lesions in the resolved area.¹-⁴ Previous studies have shown that inflammatory cytokines such as TNF-α and IL-17 can inhibit melanocyte growth, downregulate pigmentation-related gene expression, and render tyrosinase activity.⁴ Therefore, inhibitors of those cytokines may cause hyperpigmentation in susceptible individuals’ skin type and genetic predisposition. It is known that psoriasis arises in the resolved areas, which is considered to be an isomorphic response of Köbner. In the present case, scaly erythematous lesions recurred on some of the pre-existing lesions. The recurred psoriasis plaques did not perfectly but mostly correspond to the pre-existing areas. In another lesion, psoriasis initially recurred in the resolved areas and extended beyond the pigmentary macule. Previous studies showed that epidermal CD8+ T-cells increased in the Köbner-positive psoriasis skin, and CD8⁺ tissue Resident Memory T-cells (T_RM) enriched in the resolved lesion preferentially produced IL-17 and IL-22 upon restimulation.⁵ However, triggering factors that stimulate T-cell activation are currently unknown. One possible cause may be the decrease in the efficacy of TNF inhibitors on cutaneous psoriasis. Unfortunately, we could not compare the frequency of epidermal T_RM on the non-lesional skin, improved skin with pigmentation, recurred psoriasis lesion in the resolved area, and recurred psoriasis lesion in the previously non-lesional area, because the patient refused biopsy. Further studies are necessary to elucidate the mechanism of lentiginous pigmentation after the improvement of psoriasis and the role of T_RM in such conditions.

• ⋆
  Study conducted at the Fukushima Medical University, Fukushima, Japan.

• Financial support
  None declared.

References

• ¹
  Dogan S, Atakan N. Multiple lentigines confined to psoriatic plaques induced by biologic agents in psoriasis therapy: a case and review of the literature. Cutan Ocul Toxicol. 2015;34:262-4.
• ²
  Maria PS, Valenzuela F, Morales C, Fuente RD, Cullen R. Lentiginous eruption in resolving psoriasis plaques during treatment with ixekizumab: a case report and review of the literature. Dermatol Rep. 2017;9:7079.
• ³
  Lee EB, Reynolds KA, Pithadia DJ, Wu JJ. Appearance of lentigines in psoriasis patient treated with guselkumab. Dermatol Online J. 2019;25:13.
• ⁴
  Zhang S, Liang J, Tian X, Zhou X, Liu X, Chen X, et al. Secukinumab-induced multiple lentigines in areas of resolved psoriatic plaques: a case report and literature review. Dermatol Ther. 2021;34:e15048.
• ⁵
  Yamamoto T, Kurihara K, Tokura Y. Tissue resident memory T cells in the lesional and unlesional psoriatic skin on the scar. J Dermatol. 2020;47:e210-e11.

Publication Dates

• Publication in this collection
  03 Nov 2023
• Date of issue
  Nov-Dec 2023

History

• Received
  23 Feb 2022
• Accepted
  13 Apr 2022
• Published
  23 June 2023