Journal List > Ann Dermatol > v.32(2) > 1143885

Choi, Jang, Byun, Oh, Kim, Park, Lee, and Lee: Psoriasiform Dermatitis Related with T-Cell Immunoreceptor with Immunoglobulin and Immunoreceptor Tyrosine-Based Inhibitory Motif Domains Inhibitor in a Patient with Non-Small-Cell Lung Cancer
Dear Editor:
MK-7684, an antagonistic agent targeting T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT), is on phase 1 trial for the treatment of advanced solid tumors sinceDecember 2016. We present a case of psoriasiform dermatitis after treatment with MK-7684. Until date, there exists no reported case in English literature about psoriasiform dermatitis associated with TIGIT inhibitor.
A 63-year-old male with non-small-cell lung cancer (NSCLC) failed to respond to classic chemotherapy and was subsequently treated with pembrolizumab (Fig. 1A). After nine months, he developed erythematous plaques on his arms and legs without changes in his nails (Fig. 1B, C). The skin lesion was mild and controlled by topical steroids. Five months later, due to the progression of NSCLC, pembrolizumab was discontinued and MK-7684 was started subsequently. After one month, he developed erythematous scaly plaques on his whole body (Fig. 1D, E). He also developed trachyonychia on his twenty nails (Fig. 1F). He was a non-smoker and had been taking metformin and atorvastatin for more than two years. He denied a past medical history of psoriasis. After a skin biopsy, the lesion was histologically diagnosed as psoriasiform dermatitis (Fig. 2). He was treated with topical steroids and phototherapy. MK-7684 was stopped after the second injection due to exacerbation of psoriasiform dermatitis. No new lesions had developed after the discontinuation.
Drug-related psoriasis is a side effect of several drugs, such as NSAIDs, antimalarial agents, lithium, beta-blockers and anti-programmed cell death 1 (PD-1) antibodies1. These drugs can induce psoriasis or exacerbate preexisting psoriasis1. The time interval from drug administration to the appearance of the lesion varies from less than four weeks to three months or more1.
TIGIT is a new checkpoint receptor target for cancer immunotherapy and thought to be upregulated on T-cells in multiple cancer models2. By blocking TIGIT, the interaction of CD155 and CD112 with the costimulatory receptor CD226 can be enhanced in association with activation of T-cell mediated immune response against cancer cells3.
In our case, although mild psoriasiform eruption was induced during treatment with pembrolizumab, skin lesions progressed to biopsy-proven psoriasiform dermatitis during treatment with MK-7684. It has been hypothesized that over-activation of T-helper 1 and 17 cells through anti-PD-1 could contribute towards the development of psoriasis4. Although the pathological mechanisms of developing psoriasiform dermatitis by TIGIT inhibitor are unknown, increased production of cytokines related to psoriasis could be one of the mechanisms5. Wang et al.5 reported about TIGIT+ CD4+ T-cells and cytokine levels in patients with psoriasis. The researchers reported that the activation of TIGIT inhibited psoriatic CD4+ T-cell proliferation, decreased the production of IFN-γ and IL-17A, and increased the IL-10 level5. They also reported an increase in the production of IFN-γ and IL-17A subsequent to treatment with TIGIT inhibitor5. We believe that downregulation of TIGIT on CD4+ T-cells might have contributed towards the pathogenesis of psoriasiform dermatitis in our case5. Therefore, we claim that clinicians should be aware of the potential development or aggravation of psoriasiform dermatitis when opting for TIGIT inhibitor treatment.

Figures and Tables

Fig. 1

(A) Timeline of chemotherapy. (B) Erythematous plaques and papules during pembrolizumab treatment. (C) Normal nail plate during pembrolizumab treatment. (D, E) Hyperkeratotic scaly erythematous plaques during T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) inhibitor treatment. (F) Nail dystrophy during TIGIT inhibitor treatment. We received the patient's consent form about publishing all photographic materials.

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Fig. 2

Histopathological images of skin biopsy specimen of the leg. (A) Acanthosis with elongated rete ridges on epidermis and papillary dermal inflammatory infiltrations (H&E, ×100). (B) Parakeratosis and microabscess in stratum corneum (H&E, ×400).

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Notes

CONFLICTS OF INTEREST The authors have nothing to disclose.

References

1. Hong J, Bernstein D. A review of drugs that induce or exacerbate psoriasis. J Psoriasis Psoriatic Arthritis. 2012; 18:2–11.
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2. Kurtulus S, Sakuishi K, Zhang H, Joller N, Tan D, Smyth M, et al. Mechanisms of TIGIT-driven immune suppression in cancer. J Immunother Cancer. 2014; 2:Suppl 3. O13.
crossref
3. Dixon KO, Schorer M, Nevin J, Etminan Y, Amoozgar Z, Kondo T, et al. Functional Anti-TIGIT antibodies regulate development of autoimmunity and antitumor immunity. J Immunol. 2018; 200:3000–3007.
crossref
4. Voudouri D, Nikolaou V, Laschos K, Charpidou A, Soupos N, Triantafyllopoulou I, et al. Anti-PD1/PDL1 induced psoriasis. Curr Probl Cancer. 2017; 41:407–412.
crossref
5. Wang FF, Wang Y, Wang L, Wang TS, Bai YP. TIGIT expression levels on CD4+ T cells are correlated with disease severity in patients with psoriasis. Clin Exp Dermatol. 2018; 43:675–682.
crossref
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ORCID iDs

YoungHwan Choi
https://orcid.org/0000-0003-4177-7724

Donghwi Jang
https://orcid.org/0000-0002-3495-4772

Hyun Jeong Byun
https://orcid.org/0000-0002-4354-5655

Se Jin Oh
https://orcid.org/0000-0001-7525-4740

Cho Rok Kim
https://orcid.org/0000-0003-4168-4245

Ji-Hye Park
https://orcid.org/0000-0002-6699-5202

Jong Hee Lee
https://orcid.org/0000-0001-8536-1179

Dong-Youn Lee
https://orcid.org/0000-0003-0765-9812

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