Case and Research Letter
Quinacrine: A Treatment Option That Should Not Be Overlooked
Quinacrina, un escalón terapéutico que no debemos obviar
P. García-Montero
, J. del Boz, J.F. Millán-Cayetano, M. de Troya-Martín
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Departamento de Dermatología, Hospital Costa del Sol, Marbella, Málaga, Spain
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García-Montero, J. del Boz, J.F. Millán-Cayetano, M. de Troya-Martín" "autores" => array:4 [ 0 => array:4 [ "nombre" => "P." "apellidos" => "García-Montero" "email" => array:1 [ 0 => "garciamonteropablo@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "J." "apellidos" => "del Boz" ] 2 => array:2 [ "nombre" => "J.F." "apellidos" => "Millán-Cayetano" ] 3 => array:2 [ "nombre" => "M." "apellidos" => "de Troya-Martín" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Departamento de Dermatología, Hospital Costa del Sol, Marbella, Málaga, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Quinacrina, un escalón terapéutico que no debemos obviar" ] ] "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" => 834 "Ancho" => 1500 "Tamanyo" => 309917 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A. Purpuric papules on the lower limbs. B. Significant improvement after 3 months of quinacrine 100<span class="elsevierStyleHsp" style=""></span>mg/d.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Quinacrine, or mepacrine as it is also known, is a synthetic quinine analog that was the drug of choice for malaria prevention during World War II.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> It was during this period that its effectiveness in the treatment of connective tissue diseases became obvious, when many soldiers taking the drug to prevent malaria experienced improvements in the symptoms of lupus and rheumatoid arthritis. With the advent of hydroxychloroquine and chloroquine, both of which proved to be more effective antimalarial agents, quinacrine fell into disuse.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Clinical Cases</span><p id="par0010" class="elsevierStylePara elsevierViewall">The patient, a 45-year-old woman (nonsmoker), had been diagnosed with cutaneous lupus erythematosus (CLE) when she was 38 years of age. Six years later her condition met the criteria for systemic lupus erythematosus (SLE). Clinically, her condition was characterized by photosensitivity, malar eruption, scattered erythematous papules (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>a), and aphthous mouth ulcers. Laboratory test results revealed chronic lymphocytopenia and a positive antinuclear antibody titer of 1:640. Despite treatment with several different topical and systemic agents (prednisone, hydroxychloroquine, methotrexate, and colchicine), the patient never achieved optimal control of the disease. Seven months ago, after quinacrine 100<span class="elsevierStyleHsp" style=""></span>mg/d was added to her treatment regimen (colchicine 1<span class="elsevierStyleHsp" style=""></span>mg/d and hydroxychloroquine 200<span class="elsevierStyleHsp" style=""></span>mg/d), the patient experienced marked improvement in her skin lesions (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>b) and a decrease in the frequency and severity of disease flares. The only side effect was a slight yellowing of the skin and mucous membranes.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The second patient is a 35-year-old woman (smoker) with a history of chronic juvenile arthritis, who had been diagnosed with SLE at 26 years of age. She reported almost daily episodes of fever, frequent outbreaks of aphthous ulcers, arthritis, and vasculitis in the form of purpuric papules on the lower limbs (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>a). Laboratory test findings included a positive ANA value of 1:1280 and chronic leukopenia. The response to treatment with many different systemic agents (prednisone, hydroxychloroquine, methotrexate, sulfones, rituximab, belimumab, and thalidomide) was poor. Twelve months ago, quinacrine 100 mg/d was added to the basic treatment regimen of hydroxychloroquine 200 mg/d. Since then, the patient has experienced considerable improvement in her condition (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>b), with a significant decrease in the number of flares and no adverse effects.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The third case involves a 47-year-old woman (smoker) diagnosed 4 years ago with amyopathic dermatomyositis (negative ANA, negative anti-melanoma differentiation-associated gene 5, and negative transcriptional intermediary factor 1-γ). The salient clinical features in this case were photosensitivity, heliotrope erythema, and edematous erythematous plaques on the face (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>a), upper chest, elbows, and knees. The patient had undergone treatment with several systemic drugs (prednisone, methotrexate, azathioprine, and rituximab) with little improvement. Since she started a combination regimen of hydroxychloroquine 400<span class="elsevierStyleHsp" style=""></span>mg/d, prednisone 5<span class="elsevierStyleHsp" style=""></span>mg/d, and quinacrine 100<span class="elsevierStyleHsp" style=""></span>mg/d some 7 months ago, the patient has experienced marked improvement in her skin lesions (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>b), with no adverse effects.</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Discussion</span><p id="par0025" class="elsevierStylePara elsevierViewall">The usefulness of antimalarial agents in the treatment of connective tissue disorders has been amply demonstrated and the treatment of lupus is the setting in which the most evidence has been accumulated.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> The evidence shows that, in patients with lupus, antimalarial therapy not only reduces the number of disease flares and improves skin symptoms, but also improves glucose control and lipid profiles, has a potent antithrombotic effect, and is useful in the treatment and prevention of nephritis.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3,4</span></a> Thus, antimalarial therapy significantly reduces the mortality of patients with different forms of lupus. However, the use of hydroxychloroquine and chloroquine, the 2 best known and most often prescribed antimalarial agents is limited by certain drawbacks, including a lack of response to single-drug therapy and an association with retinal abnormalities. Owing to its chemical structure, quinacrine offers certain advantages over its analogs and can therefore prove very useful in certain cases. Several studies have demonstrated its effectiveness in combination with its analogs and reported good response rates in patients with refractory lupus<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5–9</span></a> or dermatomyositis.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">It is also important to highlight that quinacrine has no ocular toxicity, making it a suitable alternative for patients with retinopathy who are candidates for antimalarial therapy. The use of quinacrine has also recently been proposed as a way to reduce the accumulated dose of hydroxychloroquine and chloroquine in patients with lupus on long-term antimalarial therapy.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> The daily recommended dose of quinacrine is 100 mg, and the drug is available in this dosage.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> However, quinacrine can only be acquired in Spain by requesting it as a foreign medication. The cost, while higher than that of chloroquine and hydroxychloroquine, is significantly less than that of other drugs used to treat connective tissue disorders (in our cases, belimumab and rituximab). The possible adverse effects of treatment with quinacrine include the appearance of a yellowish discoloration of the skin and mucous membranes, which resolves when treatment is withdrawn, and the risk of aplastic anemia, which is rare and usually preceded by a lichenoid eruption. Follow-up of patients on quinacrine should include quarterly laboratory testing and annual ophthalmological examinations.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> Hypersensitivity to the active ingredient is the main contraindication for this drug; however, physicians should also bear in mind that quinacrine can exacerbate psychoses, myasthenia gravis, and psoriasis.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Because of the complexity of the management of connective tissue diseases, we consider it opportune to underscore the importance of being aware of this alternative treatment option, which can prove very useful in clinical practice.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">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:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Clinical Cases" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Discussion" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflicts of Interest" ] 3 => 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: García-Montero P, del Boz J, Millán-Cayetano JF, de Troya-Martín M. Quinacrina, un escalón terapéutico que no debemos obviar. Actas Dermosifiliogr. 2016;107:870–872.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 948 "Ancho" => 1501 "Tamanyo" => 233952 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A. Erythematous papules on the lower limbs. B. Reduction in the number, intensity, and inflammation of the lesions 6 months after the addition of quinacrine 100 mg/d to the treatment regimen.</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" => 834 "Ancho" => 1500 "Tamanyo" => 309917 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A. Purpuric papules on the lower limbs. B. Significant improvement after 3 months of quinacrine 100<span class="elsevierStyleHsp" style=""></span>mg/d.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1115 "Ancho" => 1500 "Tamanyo" => 292323 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A. Heliotrope erythema and infiltrated pink plaques on the forehead, cheeks, and nasolabial folds. B. Significant improvement 6 months after the addition of quinacrine 100<span class="elsevierStyleHsp" style=""></span>mg/d to the regimen.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The use of quinacrine (Atabrine) in rheumatic diseases: A reexamination" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "D.J. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 38 | 6 | 44 |
| 2024 Octubre | 304 | 55 | 359 |
| 2024 Septiembre | 306 | 44 | 350 |
| 2024 Agosto | 337 | 61 | 398 |
| 2024 Julio | 394 | 50 | 444 |
| 2024 Junio | 294 | 61 | 355 |
| 2024 Mayo | 290 | 42 | 332 |
| 2024 Abril | 283 | 40 | 323 |
| 2024 Marzo | 340 | 48 | 388 |
| 2024 Febrero | 328 | 35 | 363 |
| 2024 Enero | 338 | 45 | 383 |
| 2023 Diciembre | 322 | 34 | 356 |
| 2023 Noviembre | 316 | 31 | 347 |
| 2023 Octubre | 292 | 34 | 326 |
| 2023 Septiembre | 227 | 35 | 262 |
| 2023 Agosto | 192 | 28 | 220 |
| 2023 Julio | 230 | 28 | 258 |
| 2023 Junio | 257 | 32 | 289 |
| 2023 Mayo | 210 | 30 | 240 |
| 2023 Abril | 254 | 22 | 276 |
| 2023 Marzo | 255 | 40 | 295 |
| 2023 Febrero | 187 | 30 | 217 |
| 2023 Enero | 197 | 33 | 230 |
| 2022 Diciembre | 124 | 47 | 171 |
| 2022 Noviembre | 81 | 35 | 116 |
| 2022 Octubre | 91 | 29 | 120 |
| 2022 Septiembre | 65 | 43 | 108 |
| 2022 Agosto | 43 | 36 | 79 |
| 2022 Julio | 40 | 59 | 99 |
| 2022 Junio | 41 | 39 | 80 |
| 2022 Mayo | 172 | 31 | 203 |
| 2022 Abril | 230 | 31 | 261 |
| 2022 Marzo | 157 | 50 | 207 |
| 2022 Febrero | 166 | 37 | 203 |
| 2022 Enero | 226 | 57 | 283 |
| 2021 Diciembre | 116 | 33 | 149 |
| 2021 Noviembre | 158 | 50 | 208 |
| 2021 Octubre | 146 | 54 | 200 |
| 2021 Septiembre | 129 | 47 | 176 |
| 2021 Agosto | 120 | 56 | 176 |
| 2021 Julio | 134 | 21 | 155 |
| 2021 Junio | 169 | 31 | 200 |
| 2021 Mayo | 130 | 38 | 168 |
| 2021 Abril | 396 | 87 | 483 |
| 2021 Marzo | 119 | 25 | 144 |
| 2021 Febrero | 57 | 35 | 92 |
| 2021 Enero | 37 | 24 | 61 |
| 2020 Diciembre | 50 | 17 | 67 |
| 2020 Noviembre | 31 | 23 | 54 |
| 2020 Octubre | 35 | 13 | 48 |
| 2020 Septiembre | 35 | 16 | 51 |
| 2020 Agosto | 27 | 22 | 49 |
| 2020 Julio | 16 | 17 | 33 |
| 2020 Junio | 29 | 31 | 60 |
| 2020 Mayo | 21 | 14 | 35 |
| 2020 Abril | 24 | 18 | 42 |
| 2020 Marzo | 19 | 17 | 36 |
| 2020 Febrero | 1 | 0 | 1 |
| 2019 Diciembre | 4 | 0 | 4 |
| 2019 Octubre | 1 | 0 | 1 |
| 2019 Septiembre | 5 | 0 | 5 |
| 2019 Agosto | 2 | 0 | 2 |
| 2019 Julio | 4 | 0 | 4 |
| 2019 Mayo | 2 | 1 | 3 |
| 2019 Abril | 4 | 3 | 7 |
| 2019 Febrero | 4 | 0 | 4 |
| 2019 Enero | 2 | 0 | 2 |
| 2018 Diciembre | 1 | 0 | 1 |
| 2018 Noviembre | 10 | 0 | 10 |
| 2018 Octubre | 3 | 0 | 3 |
| 2018 Septiembre | 1 | 0 | 1 |
| 2018 Abril | 2 | 0 | 2 |
| 2018 Febrero | 34 | 3 | 37 |
| 2018 Enero | 62 | 18 | 80 |
| 2017 Diciembre | 56 | 9 | 65 |
| 2017 Noviembre | 46 | 7 | 53 |
| 2017 Octubre | 39 | 7 | 46 |
| 2017 Septiembre | 24 | 12 | 36 |
| 2017 Agosto | 35 | 8 | 43 |
| 2017 Julio | 34 | 7 | 41 |
| 2017 Junio | 35 | 10 | 45 |
| 2017 Mayo | 27 | 7 | 34 |
| 2017 Abril | 37 | 26 | 63 |
| 2017 Marzo | 25 | 21 | 46 |
| 2017 Febrero | 22 | 8 | 30 |
| 2017 Enero | 22 | 13 | 35 |
| 2016 Diciembre | 61 | 36 | 97 |
| 2016 Noviembre | 21 | 27 | 48 |
| 2016 Octubre | 1 | 3 | 4 |
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