Case and Research Letters
Plaque Psoriasis Flare and Peripheral Edema in a Patient Treated With Atezolizumab
Brote de psoriasis en placas y edema periférico en un paciente tratado con atezolizumab
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Santos-Juanes, P. Munguia-Calzada, C. Álvarez-Fernádez" "autores" => array:3 [ 0 => array:4 [ "nombre" => "J." "apellidos" => "Santos-Juanes" "email" => array:1 [ 0 => "jorgesantosjuanes@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "P." "apellidos" => "Munguia-Calzada" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "C." "apellidos" => "Álvarez-Fernádez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Dermatología, Hospital Universitario Central de Asturias, Oviedo, España" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Oncología Médica, Hospital Universitario Central de Asturias, Oviedo, España" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Brote de psoriasis en placas y edema periférico en un paciente tratado con atezolizumab" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">A 75-year-old man was referred to the dermatology clinic for evaluation of skin lesions after receiving his first dose of atezolizumab (1200<span class="elsevierStyleHsp" style=""></span>mg) for treatment of poorly differentiated stage <span class="elsevierStyleSmallCaps">iv</span> urothelial carcinoma of the prostatic urethra (metastasis to the lungs, liver, bone, and lymph nodes). Twelve months previously, the patient had completed systemic treatment with chemotherapy (cisplatin 75<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span> day 1<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>gemcitabine 1250<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span> on days 1 and 8 and every 21 days) in 4 cycles. No clinical or radiological response was observed, and the treatment was poorly tolerated (asthenia, vomiting, and moderate kidney failure). He had a 42-year history of mild psoriasis affecting the elbows and knees.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Twelve days after the first infusion of atezolizumab, his existing lesions began to worsen, and new lesions began to appear on the extensor aspects of both limbs and the trunk. These were intensely pruritic and compatible with a clinical diagnosis of psoriasis (Psoriasis Area Severity Index<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>12, body surface area affected<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6, visual analog scale for itching<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>10). These findings were accompanied by distal edema affecting both lower limbs. The patient was prescribed oral prednisone 30<span class="elsevierStyleHsp" style=""></span>mg for 7 days to be tapered by 10<span class="elsevierStyleHsp" style=""></span>mg every week, bilastine 20<span class="elsevierStyleHsp" style=""></span>mg every 12<span class="elsevierStyleHsp" style=""></span>hours, and topical treatment with clobetasol propionate 0.1% cream every 12<span class="elsevierStyleHsp" style=""></span>hours for 15 days. His lesions resolved in 3 weeks, and no residual lesions were observed. Atezolizumab was discontinued because of the skin toxicity. Given the patient's poor general status, he refused all cancer medication and is currently receiving palliative care. He was diagnosed with probable adverse reaction to atezolizumab (Naranjo algorithm, 6 points).</p><p id="par0015" class="elsevierStylePara elsevierViewall">Programmed death 1 (PD-1) is a key immune checkpoint receptor that is expressed on T cells and functions mainly in peripheral tissue.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> Atezolizumab is the first PD ligand 1 (PD-L1) inhibitor approved by the United States Food and Drug Administration. This human immunoglobulin G1 monoclonal antibody binds selectively to PD-L1 and prevents interaction with PD-1 and B7-1 (also known as CD80), while sparing the interaction between PD ligand 2 (PD-L2) and PD-1.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a> When PD-1 is activated, the immune system is inhibited, thus enabling tumor growth. In their various indications for different cancers, new anti–PD-1 drugs (nivolumab, pembrolizumab, pidilizumab) and anti–PD-L1 drugs (atezolizumab and durvalumab) curb this inhibition by enabling the immune system to control tumor progression.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">There have been various reports of adverse reactions to PD-1 and PD-L1 inhibitors in up to 50% of patients. These were mainly cutaneous (lichenoid reactions, eczema, vitiligo, and pruritus) and mild and did not require treatment to be discontinued.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">3,4</span></a> However, other authors report these inflammatory reactions to be severe, requiring treatment with oral corticosteroids, and highlight an objective antitumor response.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> One group of cutaneous reactions to this drug are those based on neutrophils, which, owing to their increased count in the skin, cause Sweet syndrome, acute generalized exanthematous pustulosis, intracorneal pustular drug eruption, and psoriasis.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a> Other, less common cutaneous adverse reactions include actinic keratosis, squamous cell carcinoma, and seborrheic keratosis.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> Peripheral edema is an adverse reaction that affects 10% of patients receiving treatment with atezolizumab.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Cases of psoriasis triggered or exacerbated by this drug family are starting to be reported, although the condition was due to atezolizumab in only 1 case.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">8,9</span></a> In a recent series, 66% of patients had a previous history of psoriasis, which, in most cases, was controlled with topical treatment. Given the intensity of skin involvement, it was rarely necessary to suspend treatment or prescribe oral corticosteroids, as in the present case.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">8,9</span></a> In most cases, psoriasis is triggered after several doses. In the only case where psoriasis was triggered by atezolizumab, onset was after the first dose, as occurred in the present case.</p><p id="par0030" class="elsevierStylePara elsevierViewall">In terms of etiology and pathogenesis, murine models have shown that PD-1 deficiency increases the likelihood of the psoriasis-like skin disease phenotype and that PD-1 can play a regulatory role in the development of the disease.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">10</span></a> Under normal conditions, the PD-1 pathway maintains normal immune homeostasis, which prevents autoimmune reactions or damage to healthy tissue. T-cell activation induced by PD-1 inhibitors—together with other factors—can contribute to development of psoriasis or exacerbations of existing psoriasis.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The low number of cases of psoriasis associated with atezolizumab is probably due to the mechanism of action, which spares PD-1 and PD-L2 binding. Owing to the different nature (IgG4 isotopes or IgG1 isotope), mechanisms of action, and antitumor action of anti–PD-1 and –PD-L1 agents, it has been recommended not to consider them as a group.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">9</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of Interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Santos-Juanes J, Munguía Calzada P, Álvarez Fernández C. Brote de psoriasis en placas y edema periférico en un paciente tratado con atezolizumab. Actas Dermosifiliogr. 2019;110:410–411.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib0060" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety, activity, and immune correlates of anti-PD-1 antibody in cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.L. Topalian" 1 => "F.S. Hodi" 2 => "J.R. Brahmer" 3 => "S.N. Gettinger" 4 => "D.C. Smith" 5 => "D.F. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 17 | 9 | 26 |
| 2024 October | 73 | 39 | 112 |
| 2024 September | 131 | 25 | 156 |
| 2024 August | 114 | 57 | 171 |
| 2024 July | 81 | 28 | 109 |
| 2024 June | 91 | 33 | 124 |
| 2024 May | 113 | 41 | 154 |
| 2024 April | 88 | 36 | 124 |
| 2024 March | 102 | 37 | 139 |
| 2024 February | 95 | 30 | 125 |
| 2024 January | 90 | 37 | 127 |
| 2023 December | 82 | 22 | 104 |
| 2023 November | 90 | 35 | 125 |
| 2023 October | 77 | 32 | 109 |
| 2023 September | 93 | 40 | 133 |
| 2023 August | 78 | 15 | 93 |
| 2023 July | 55 | 34 | 89 |
| 2023 June | 52 | 39 | 91 |
| 2023 May | 63 | 18 | 81 |
| 2023 April | 53 | 22 | 75 |
| 2023 March | 61 | 27 | 88 |
| 2023 February | 59 | 22 | 81 |
| 2023 January | 44 | 19 | 63 |
| 2022 December | 60 | 54 | 114 |
| 2022 November | 33 | 35 | 68 |
| 2022 October | 32 | 24 | 56 |
| 2022 September | 33 | 43 | 76 |
| 2022 August | 22 | 37 | 59 |
| 2022 July | 27 | 48 | 75 |
| 2022 June | 38 | 25 | 63 |
| 2022 May | 46 | 34 | 80 |
| 2022 April | 56 | 29 | 85 |
| 2022 March | 75 | 53 | 128 |
| 2022 February | 55 | 14 | 69 |
| 2022 January | 54 | 38 | 92 |
| 2021 December | 32 | 42 | 74 |
| 2021 November | 42 | 40 | 82 |
| 2021 October | 56 | 54 | 110 |
| 2021 September | 41 | 38 | 79 |
| 2021 August | 44 | 31 | 75 |
| 2021 July | 37 | 16 | 53 |
| 2021 June | 29 | 25 | 54 |
| 2021 May | 55 | 38 | 93 |
| 2021 April | 132 | 51 | 183 |
| 2021 March | 88 | 20 | 108 |
| 2021 February | 54 | 26 | 80 |
| 2021 January | 50 | 18 | 68 |
| 2020 December | 31 | 13 | 44 |
| 2020 November | 44 | 25 | 69 |
| 2020 October | 44 | 14 | 58 |
| 2020 September | 58 | 15 | 73 |
| 2020 August | 47 | 17 | 64 |
| 2020 July | 42 | 21 | 63 |
| 2020 June | 30 | 24 | 54 |
| 2020 May | 347 | 25 | 372 |
| 2020 April | 24 | 13 | 37 |
| 2020 March | 35 | 7 | 42 |
| 2020 February | 4 | 0 | 4 |
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