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Table of Contents
CORRESPONDENCE
Year : 2021  |  Volume : 39  |  Issue : 2  |  Page : 89-90

Tocilizumab-induced psoriasis in a patient with rheumatoid arthritis: A case report and literature review


1 Department of Dermatology, Skin Institute, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
2 Department of Dermatology, Skin Institute, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation; Institute of Medical Sciences, Tzu Chi University; Doctoral Degree Program in Translational Medicine, Tzu Chi University and Academia Sinica, College of Medicine, Tzu Chi University, Hualien County, 970, Taiwan

Date of Submission23-Aug-2020
Date of Decision26-Nov-2020
Date of Acceptance28-Dec-2020
Date of Web Publication23-Jun-2021

Correspondence Address:
Dr. Chung-Hsing (Miriam) Chang
No. 707, Sec. 3, Chung-Yang Road, Hualien 970
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ds.ds_57_20

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How to cite this article:
Chen YT, Chang CH. Tocilizumab-induced psoriasis in a patient with rheumatoid arthritis: A case report and literature review. Dermatol Sin 2021;39:89-90

How to cite this URL:
Chen YT, Chang CH. Tocilizumab-induced psoriasis in a patient with rheumatoid arthritis: A case report and literature review. Dermatol Sin [serial online] 2021 [cited 2021 Sep 25];39:89-90. Available from: https://www.dermsinica.org/text.asp?2021/39/2/89/319153



Dear Editor,

Tocilizumab (TCZ), an anti-interleukin (IL)-6 receptor antibody, has been approved for patients with rheumatoid arthritis (RA) who show an inadequate response to disease-modifying anti-rheumatic drugs (DMARDs) or tumor necrosis factor antagonist in Taiwan. Elevated levels of IL-6 in the serum and synovial fluid contribute to the chronic inflammation in RA. By binding selectively and competitively to the soluble and membrane-bound IL-6 receptors (IL-6Rs), TCZ reduces disease activity in RA. TCZ is generally safe with tolerable adverse reactions, including upper respiratory tract infection, headache, high blood pressure, and elevation of liver enzymes and total cholesterol levels.[1] Based on its anti-inflammatory effect, TCZ rarely induces skin inflammatory disorders such as psoriasis. However, here, we report a patient with RA who developed a de novo rapidly progressive psoriasis after 4 years of TCZ treatment. Furthermore, we review available literature and discuss potential underlying mechanisms.

A 70-year-old man, fulfilled five of the six 1987 American College of Rheumatology criteria for RA, including morning stiffness, arthritis of more than 3 joint areas, arthritis of the hand joints, symmetric arthritis, and typical radiographic changes was diagnosed with seronegative RA in 1997 (also fulfilled 2010 diagnostic criteria of RA) by a rheumatologist in a medical center. He has been under care and long-term follow-up since then. TCZ of 3.5 mg/kg/4 weeks combined with methotrexate (MTX) were tried owing to poor control with DMARDs. TCZ seemed effective, allowing for MTX withdrawal after 20 TCZ infusions. He also responded well to TCZ monotherapy (5 mg/kg/4 weeks). The treatment course is shown in [Figure 1]A.
Figure 1: Time course of tocilizumab-induced cutaneous manifestations, treatment protocol, and histopathology. (A) Treatment course of the present case. The patient received TCZ 3.5 mg/kg/4wks with MTX 7.5 mg/wk for the first 20 infusions and then TCZ monotherapy. (B) Clinical photographs of the change in the skin of the patient's left forearm, extensor side (a-c), and abdomen (d-f). (g) Rete ridge elongation and suprapapillary plate thinning. Perivascular inflammatory cell infiltration in the dermal papilla and upper dermis (H and E, ×50). (h) Confluent parakeratosis with prominent neutrophilic infiltrates (H and E, ×200). (i) Prominent Munro microabscess (H and E, ×400). (j) Prominent superficial dermal vascular proliferation and dilatation (CD31, ×100). RA: Rheumatoid arthritis, TCZ: Tocilizumab, MTX: Methotrexate, DMARDs: Disease-modifying anti-rheumatic drugs, H and E: Hematoxylin and eosin.

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However, after 4 years of TCZ administration, several asymptomatic palpable purpuric plaques with scales over the abdomen and forearms were noted [Figure 1]Ba and [Figure 1]d. The patient refused skin biopsy. After 6 weeks, he returned with progressive lesions over the trunk and four limbs, especially the extensor areas, accompanied by the Koebner phenomenon [Figure 1]Bb and [Figure 1]e. A skin biopsy was performed this time showing regular acanthosis, suprapapillary plate thinning, dilated and tortuous blood vessels [Figure 1]Bg, confluent parakeratosis with neutrophilic infiltrates [Figure 1]Bh, Munro's microabscess [Figure 1]Bi, and prominent vascular proliferation and dilatation (CD31 stain) [Figure 1]Bj. The patient has been receiving TCZ as monotherapy since 2017. As there was no other possible culprit drug for psoriasis development according to his history, the patient was diagnosed with TCZ-induced psoriasis. Meanwhile, RA was well controlled by TCZ with a disease activity score of zero, and the C-reactive protein level and erythrocyte sedimentation rate were within the normal range. However, the serum IL-6 showed a markedly increased level of 606.8 pg/mL (normal <7.0 pg/mL) (April 15, 2020), which was considerably higher than the baseline level in patients with RA (rarely exceeds 100 pg/ml).[2] Topical potent steroid (fluocinonide cream 0.05%) were given. However, the skin lesions still progressed (Psoriasis Area and Severity Index score from 6.6 to 13.5) [Figure 1]Bc and [Figure 1]f. We then administered the strongest potency topical steroid (clobetasol dipropionate foaming solution 0.05%) and recommended TCZ discontinuation. Skin lesions resolved significantly after 3 weeks and at 6-month follow-up.

A literature search in PubMed using the combination of the following three terms: “tocilizumab”, “psoriasis”, and “rheumatoid arthritis” found only five relevant articles,[3],[4],[5],[6],[7] which summarized in [Supplementary Table 1].The time from TCZ exposure to the onset of psoriasis varied from the shortest of 9 weeks to the longest of 4 years as in our case. This might be explained by the relatively low dose of TCZ our patient used. TCZ was discontinued in three cases (including ours) and topical steroid well controlled the psoriasis. The other three cases continued TCZ for RA control, but they also responded well to topical steroid. Overall, it seems that topical steroid is an effective treatment for TCZ-induced psoriasis.



The pathogenesis underlying TCZ-induced psoriasis is still unclear. In the skin, IL-6 participates in the pathogenesis of psoriasis by inducing keratinocyte proliferation and Th17 differentiation.[8] Anti-IL-6 agent is expected to improve psoriasis; however, psoriasis develops in a small portion of patients with RA treated with TCZ. The level of IL-6 was found to increase after TCZ administration because the IL-6R-mediated clearance of IL-6 is blocked by TCZ.[2] We hypothesize that the tissue specificity of TCZ blockage might be uneven among different cells. While TCZ decreasing joint inflammation associated with RA, IL-6 at temporarily increased levels binds to the remaining unblocked IL-6Rs in the skin and causes psoriasis. These proposed mechanisms need further investigation.

In conclusion, although TCZ is generally safe, regular skin evaluation is necessary for patients with RA who are treated with TCZ. The use of a potent topical steroid is an effective treatment for TCZ-induced psoriasis.

Declaration of patient consent

The authors certify that they have obtained appropriate patient consent form. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initial will not be published and due efforts will be made to conceal the identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

Prof. Chung-Hsing (Miriam) Chang, an editorial board member at Dermatologica Sinica, had no role in the peer review process of or decision to publish this article. The other author declared no conflict of interest in writing this paper.



 
  References Top

1.
Oldfield V, Dhillon S, Plosker GL. Tocilizumab: A review of its use in the management of rheumatoid arthritis. Drugs 2009;69:609-32.  Back to cited text no. 1
    
2.
Nishimoto N, Terao K, Mima T, Nakahara H, Takagi N, Kakehi T. Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease. Blood 2008;112:3959-64.  Back to cited text no. 2
    
3.
Wendling D, Letho-Gyselinck H, Guillot X, Prati C. Psoriasis onset with tocilizumab treatment for rheumatoid arthritis. J Rheumatol 2012;39:657.  Back to cited text no. 3
    
4.
Grasland A, Mahé E, Raynaud E, Mahé I. Psoriasis onset with tocilizumab. Joint Bone Spine 2013;80:541-2.  Back to cited text no. 4
    
5.
Palmou-Fontana N, Sánchez Gaviño JA, McGonagle D, García-Martinez E, Iñiguez de Onzoño Martín L. Tocilizumab-induced psoriasiform rash in rheumatoid arthritis. Dermatology 2014;228:311-3.  Back to cited text no. 5
    
6.
Hayakawa M, Izumi K, Higashida-Konishi M, Ushikubo M, Tsukamoto M, Akiya K, et al. Tocilizumab-induced psoriasis-like eruption resolved by shortening the dose interval in a patient with rheumatoid arthritis: A case-based review. Rheumatol Int 2019;39:161-6.  Back to cited text no. 6
    
7.
Saito Y, Hayashi S, Gonmori T, Hamasaki Y, Igawa K. Interrupting tocilizumab therapy-induced psoriasis-like eruption in a patient with rheumatoid arthritis and Crohn's disease. Int J Dermatol 2020;59:e159-60.  Back to cited text no. 7
    
8.
Tanaka T, Narazaki M, Kishimoto T. Anti-interleukin-6 receptor antibody, tocilizumab, for the treatment of autoimmune diseases. FEBS Lett 2011;585:3699-709.  Back to cited text no. 8
    


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