Case and Research Letters
Refractory Subacute Cutaneous Lupus Erythematosus Treated With Rituximab
Lupus eritematoso cutáneo subagudo refractario tratado con rituximab
D.E. Cieza-Díaz
, J.A. Avilés-Izquierdo, C. Ceballos-Rodríguez, R. Suárez-Fernández
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Servicio de Dermatología, Hospital General Universitario Gregorio Marañón, Madrid, Spain
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Cieza-Díaz, J.A. Avilés-Izquierdo, C. Ceballos-Rodríguez, R. Suárez-Fernández" "autores" => array:4 [ 0 => array:4 [ "nombre" => "D.E." "apellidos" => "Cieza-Díaz" "email" => array:1 [ 0 => "deysycieza@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "J.A." "apellidos" => "Avilés-Izquierdo" ] 2 => array:2 [ "nombre" => "C." "apellidos" => "Ceballos-Rodríguez" ] 3 => array:2 [ "nombre" => "R." "apellidos" => "Suárez-Fernández" ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Servicio de Dermatología, Hospital General Universitario Gregorio Marañón, Madrid, Spain" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Lupus eritematoso cutáneo subagudo refractario tratado con rituximab" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2022 "Ancho" => 983 "Tamanyo" => 244176 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A, Patient with extensive crusted subacute cutaneous lupus erythematosus lesions before starting therapy with rituximab. B, The patient is lesion-free 8 months after her second cycle of rituximab.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Subacute cutaneous lupus erythematosus (SCLE) is a variant of photosensitive cutaneous lupus erythematosus that is often associated with anti-Ro antibodies.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We present 3 cases of treatment-refractory SCLE that resolved satisfactorily with rituximab.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Patient 1 was a 54-year-old woman (smoker) diagnosed with SCLE. She had annular lesions on her back (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a><span class="elsevierStyleHsp" style=""></span>A), upper chest, and arms. Testing for antinuclear antibody (ANA) was positive (titer, 1/640), with a homogeneous pattern; the results for other antibodies were negative.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The patient received high-dose prednisone (50<span class="elsevierStyleHsp" style=""></span>mg/d), antimalarial agents (chloroquine 250<span class="elsevierStyleHsp" style=""></span>mg/d and hydroxychloroquine 400<span class="elsevierStyleHsp" style=""></span>mg/d) for 3 years, thalidomide 50-150<span class="elsevierStyleHsp" style=""></span>mg/d for 16 months, cyclophosphamide 100<span class="elsevierStyleHsp" style=""></span>mg/d, mycophenolate 500<span class="elsevierStyleHsp" style=""></span>mg/d, etanercept (50<span class="elsevierStyleHsp" style=""></span>mg, 2 doses per week), and intravenous immunoglobulins (2<span class="elsevierStyleHsp" style=""></span>g/kg). Improvement was partial, and the patient experienced the following side effects: blurred vision (antimalarial agents), sensory axonal polyneuropathy (thalidomide), and leukopenia (cyclophosphamide).</p><p id="par0025" class="elsevierStylePara elsevierViewall">In view of the lack of response, rituximab was started at a weekly dose of 375<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span> (4 doses) combined with prednisone 5-10<span class="elsevierStyleHsp" style=""></span>mg/d. Remission was complete after 2 months. The same regimen was repeated annually (1<span class="elsevierStyleHsp" style=""></span>g/15 d, 2 doses) for 4 years because of the appearance of new outbreaks, and control of the cutaneous lesions was excellent (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a><span class="elsevierStyleHsp" style=""></span>B).</p><p id="par0030" class="elsevierStylePara elsevierViewall">Patient 2 was a 37-year-old woman (smoker) with epilepsy, for which she was receiving carbamazepine but later switched to valproic acid. She had been diagnosed with SCLE at age 34 years and had annular lesions on her upper chest, back, and arms. Her ANA pattern was homogeneous (titer, 1/640), anti-La was positive, and testing for the remaining antibodies, including antihistone antibodies, was negative.</p><p id="par0035" class="elsevierStylePara elsevierViewall">She had responded well to prednisone 50<span class="elsevierStyleHsp" style=""></span>mg/d, hydroxychloroquine 400<span class="elsevierStyleHsp" style=""></span>mg/d (18 months), and azathioprine 100<span class="elsevierStyleHsp" style=""></span>mg/d, which was discontinued because of drug-induced leukopenia. Her skin lesions worsened considerably when azathioprine was stopped (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a><span class="elsevierStyleHsp" style=""></span>A); therefore, rituximab was started at a weekly dose of 375<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span> (4 doses) combined with low-dose prednisone (10<span class="elsevierStyleHsp" style=""></span>mg/d) and antimalarial agents. The patient progressed favorably, with no active lesions after 3 months. The regimen was repeated 1 year later (1<span class="elsevierStyleHsp" style=""></span>g/15 d, 2 doses), and the patient remained free of active lesions during the 8 months following the last infusion of rituximab (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a><span class="elsevierStyleHsp" style=""></span>B). Control of the disease was maintained with hydroxychloroquine 200-400<span class="elsevierStyleHsp" style=""></span>mg/d.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Patient 3 was a 28-year-old woman who consulted with malar rash, asthenia, arthritis, low-grade fever, and annular lesions on the upper chest, back, and arms. Skin biopsy confirmed a clinical diagnosis of SCLE. A blood workup revealed reduced C3 and C4 levels, ANA (titer, 1/320) with a homogeneous pattern, and positive results for double-strand anti-DNA, anti-Ro, antiribonucleoprotein, and anti-Sm antibodies. The patient was diagnosed with systemic lupus erythematosus (SLE) and started treatment with prednisone 40<span class="elsevierStyleHsp" style=""></span>mg/d combined with hydroxychloroquine 400<span class="elsevierStyleHsp" style=""></span>mg/d for 6 months. The response was good, although her condition deteriorated when the dose of corticosteroid was reduced. Given our previous experience, we started treatment with rituximab at a weekly dose of 375<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span> (4 doses). Two months later, the patient's skin and clinical symptoms had improved considerably, although the malar rash persisted on the center of her face. Positive results were found for ANA, anti-DNA, and anti-Ro antibodies; the results for the remaining antibodies were negative. She is currently receiving prednisone at 10-20<span class="elsevierStyleHsp" style=""></span>mg/d in combination with oral antimalarial agents.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Treatment of SCLE is based on strict photoprotection and administration of antimalarial agents as the first-line systemic approach. These drugs enable the disease to be controlled in up to 75% of cases.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> However, the remaining 25% require other types of systemic immunomodulatory or immunosuppressive therapy, which have variable efficacy and are not free of side effects.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Rituximab is a chimeric monoclonal antibody that targets the CD20 antigen, which is expressed in pre-B cells, mature B cells, and memory cells, and leads to depletion of B lymphocytes.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> It is indicated mainly for B-cell lymphoproliferative disorders involving expression of CD20 (chronic lymphocytic leukemia and non-Hodgkin lymphoma),<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> as well as in rheumatoid arthritis.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Case series show its efficacy in pemphigus vulgaris, paraneoplastic pemphigus, cutaneous B-cell lymphoma, chronic graft-versus-host disease, and dermatomyositis.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">In SLE, depletion of B cells could lead to diminished production and expansion of autoreactive antibody-forming cells and to loss of the costimulatory signals delivered by B cells to T cells (CD40-CD40L interaction), thus blocking the antibody-dependent and antibody-independent tissue damage that occurs in lupus.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Furthermore, the clinical efficacy and safety of rituximab has been reported in case series and open-label trials in patients with SLE. The duration of the drug's effectiveness varies, and it usually lasts from at least 5 months to around 14 months.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,7</span></a> However, few case reports show successful management of refractory cutaneous lupus with rituximab.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Risselada and Kallenberg<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> reported the first 2 cases of refractory cutaneous lupus treated with rituximab in patients with SLE (2<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>1000<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>). The improvement in skin lesions was both marked and persistent. Uthman et al<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> reported the case of a patient with SLE and extensive recalcitrant SCLE lesions that had been treated with rituximab (1<span class="elsevierStyleHsp" style=""></span>g/wk, 2 doses) and improved considerably.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Kieu et al<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> presented the first case of SCLE that did not fulfill the criteria for SLE and was refractory to antimalarial agents and immunosuppressants. Treatment was with rituximab at a weekly dose of 375<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span> (4 doses). The same dose was administered a year later because the lesions recurred. The patient remained lesion-free for 2 years with maintenance therapy (375<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span> every 8 weeks).</p><p id="par0065" class="elsevierStylePara elsevierViewall">We present 3 cases of refractory SCLE treated successfully with rituximab, which was well tolerated. Limited published experience and our findings in the present manuscript allow us to propose rituximab as an alternative for treatment of SCLE refractory to the usual approaches. However, larger-scale studies will enable us to set limits for this indication and establish the safety profile in this group of patients.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please cite this article as: D.E. Cieza-Díaz, J.A. Avilés-Izquierdo, C. Ceballos-Rodríguez, R. Suárez-Fernández. Lupues eritematoso cutáneo subagudo refractario tratado con rituximab. Actas Dermosifiliogr.2012;103:555-557.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1936 "Ancho" => 987 "Tamanyo" => 243522 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A, Patient with extensive subacute cutaneous lupus erythematosus lesions before starting therapy with rituximab. B, The patient is lesion-free 8 months after her fourth cycle of rituximab.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2022 "Ancho" => 983 "Tamanyo" => 244176 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A, Patient with extensive crusted subacute cutaneous lupus erythematosus lesions before starting therapy with rituximab. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 16 | 6 | 22 |
| 2024 Octubre | 122 | 38 | 160 |
| 2024 Septiembre | 121 | 36 | 157 |
| 2024 Agosto | 176 | 102 | 278 |
| 2024 Julio | 131 | 38 | 169 |
| 2024 Junio | 134 | 46 | 180 |
| 2024 Mayo | 113 | 53 | 166 |
| 2024 Abril | 106 | 30 | 136 |
| 2024 Marzo | 114 | 42 | 156 |
| 2024 Febrero | 119 | 33 | 152 |
| 2024 Enero | 119 | 29 | 148 |
| 2023 Diciembre | 135 | 22 | 157 |
| 2023 Noviembre | 206 | 36 | 242 |
| 2023 Octubre | 361 | 37 | 398 |
| 2023 Septiembre | 373 | 36 | 409 |
| 2023 Agosto | 264 | 31 | 295 |
| 2023 Julio | 241 | 68 | 309 |
| 2023 Junio | 238 | 39 | 277 |
| 2023 Mayo | 384 | 45 | 429 |
| 2023 Abril | 276 | 27 | 303 |
| 2023 Marzo | 184 | 28 | 212 |
| 2023 Febrero | 166 | 23 | 189 |
| 2023 Enero | 175 | 43 | 218 |
| 2022 Diciembre | 156 | 43 | 199 |
| 2022 Noviembre | 120 | 38 | 158 |
| 2022 Octubre | 126 | 37 | 163 |
| 2022 Septiembre | 132 | 44 | 176 |
| 2022 Agosto | 182 | 33 | 215 |
| 2022 Julio | 87 | 37 | 124 |
| 2022 Junio | 175 | 29 | 204 |
| 2022 Mayo | 193 | 37 | 230 |
| 2022 Abril | 205 | 68 | 273 |
| 2022 Marzo | 271 | 47 | 318 |
| 2022 Febrero | 251 | 37 | 288 |
| 2022 Enero | 289 | 56 | 345 |
| 2021 Diciembre | 187 | 61 | 248 |
| 2021 Noviembre | 176 | 48 | 224 |
| 2021 Octubre | 189 | 66 | 255 |
| 2021 Septiembre | 174 | 41 | 215 |
| 2021 Agosto | 194 | 38 | 232 |
| 2021 Julio | 175 | 41 | 216 |
| 2021 Junio | 158 | 56 | 214 |
| 2021 Mayo | 109 | 49 | 158 |
| 2021 Abril | 176 | 115 | 291 |
| 2021 Marzo | 142 | 34 | 176 |
| 2021 Febrero | 75 | 40 | 115 |
| 2021 Enero | 103 | 25 | 128 |
| 2020 Diciembre | 77 | 23 | 100 |
| 2020 Noviembre | 66 | 23 | 89 |
| 2020 Octubre | 52 | 26 | 78 |
| 2020 Septiembre | 38 | 16 | 54 |
| 2020 Agosto | 30 | 17 | 47 |
| 2020 Julio | 42 | 12 | 54 |
| 2020 Junio | 32 | 23 | 55 |
| 2020 Mayo | 34 | 21 | 55 |
| 2020 Abril | 35 | 23 | 58 |
| 2020 Marzo | 37 | 16 | 53 |
| 2020 Febrero | 3 | 7 | 10 |
| 2020 Enero | 0 | 4 | 4 |
| 2019 Diciembre | 3 | 2 | 5 |
| 2019 Octubre | 0 | 1 | 1 |
| 2019 Septiembre | 4 | 2 | 6 |
| 2019 Agosto | 0 | 2 | 2 |
| 2019 Julio | 0 | 14 | 14 |
| 2019 Junio | 2 | 37 | 39 |
| 2019 Mayo | 0 | 55 | 55 |
| 2019 Abril | 0 | 27 | 27 |
| 2019 Marzo | 2 | 10 | 12 |
| 2019 Febrero | 0 | 2 | 2 |
| 2019 Enero | 2 | 0 | 2 |
| 2018 Diciembre | 0 | 6 | 6 |
| 2018 Noviembre | 3 | 0 | 3 |
| 2018 Octubre | 2 | 0 | 2 |
| 2018 Marzo | 8 | 1 | 9 |
| 2018 Febrero | 64 | 12 | 76 |
| 2018 Enero | 80 | 5 | 85 |
| 2017 Diciembre | 71 | 5 | 76 |
| 2017 Noviembre | 63 | 7 | 70 |
| 2017 Octubre | 41 | 2 | 43 |
| 2017 Septiembre | 72 | 6 | 78 |
| 2017 Agosto | 97 | 14 | 111 |
| 2017 Julio | 104 | 7 | 111 |
| 2017 Junio | 95 | 10 | 105 |
| 2017 Mayo | 94 | 3 | 97 |
| 2017 Abril | 87 | 12 | 99 |
| 2017 Marzo | 78 | 10 | 88 |
| 2017 Febrero | 59 | 2 | 61 |
| 2017 Enero | 51 | 11 | 62 |
| 2016 Diciembre | 77 | 5 | 82 |
| 2016 Noviembre | 169 | 3 | 172 |
| 2016 Octubre | 150 | 5 | 155 |
| 2016 Septiembre | 208 | 8 | 216 |
| 2016 Agosto | 203 | 11 | 214 |
| 2016 Julio | 51 | 11 | 62 |
| 2016 Junio | 10 | 0 | 10 |
| 2016 Mayo | 8 | 0 | 8 |
| 2016 Abril | 5 | 0 | 5 |
| 2016 Marzo | 10 | 0 | 10 |
| 2016 Febrero | 8 | 0 | 8 |
| 2016 Enero | 9 | 0 | 9 |
| 2015 Diciembre | 9 | 0 | 9 |
| 2015 Noviembre | 23 | 2 | 25 |
| 2015 Octubre | 15 | 3 | 18 |
| 2015 Septiembre | 16 | 5 | 21 |
| 2015 Agosto | 12 | 5 | 17 |
| 2015 Julio | 147 | 7 | 154 |
| 2015 Junio | 92 | 5 | 97 |
| 2015 Mayo | 118 | 13 | 131 |
| 2015 Abril | 122 | 14 | 136 |
| 2015 Marzo | 116 | 9 | 125 |
| 2015 Febrero | 135 | 8 | 143 |
| 2015 Enero | 90 | 11 | 101 |
| 2014 Diciembre | 99 | 10 | 109 |
| 2014 Noviembre | 87 | 12 | 99 |
| 2014 Octubre | 96 | 18 | 114 |
| 2014 Septiembre | 75 | 15 | 90 |
| 2014 Agosto | 100 | 17 | 117 |
| 2014 Julio | 107 | 23 | 130 |
| 2014 Junio | 54 | 2 | 56 |
| 2014 Mayo | 61 | 13 | 74 |
| 2014 Abril | 62 | 4 | 66 |
| 2014 Marzo | 74 | 12 | 86 |
| 2014 Febrero | 56 | 13 | 69 |
| 2014 Enero | 57 | 8 | 65 |
| 2013 Diciembre | 52 | 11 | 63 |
| 2013 Noviembre | 41 | 6 | 47 |
| 2013 Octubre | 38 | 7 | 45 |
| 2013 Septiembre | 34 | 9 | 43 |
| 2013 Agosto | 19 | 19 | 38 |
| 2013 Julio | 13 | 54 | 67 |
| 2013 Junio | 13 | 24 | 37 |
| 2013 Mayo | 11 | 21 | 32 |
| 2013 Abril | 12 | 24 | 36 |
| 2013 Marzo | 16 | 11 | 27 |
| 2013 Febrero | 27 | 9 | 36 |
| 2013 Enero | 37 | 7 | 44 |
| 2012 Diciembre | 22 | 5 | 27 |
| 2012 Noviembre | 3 | 2 | 5 |
| 2012 Octubre | 2 | 9 | 11 |
| 2012 Septiembre | 0 | 19 | 19 |
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