Case Report
Good Response of Scleromyxedema and Dermato-Neuro Syndrome to Treatment With Intravenous Immunoglobulins
Escleromixedema y síndrome dermato-neuro: buena respuesta al tratamiento con glucocorticoides e inmunoglobulinas endovenosas
I. Bielsa
, F. Benvenutti, R.M. Guinovart, C. Ferrándiz
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Servicio de Dermatología, Hospital Universitari Germans Trias i Pujol, Badalona, Universitat Autònoma de Barcelona, Barcelona, Spain
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Keratoacanthoma with an area of incipient squamous cell carcinoma (SCC). C and D. Focal but strong staining in the region of incipient SCC. (A: Hematoxylin/eosin [H/E] x40, inset shows lower-magnification view of H/E. B. H/E x200. C. Laminin x40. D. Laminin x100.) The asterisks indicate amplified areas.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "R. Corbalán-Vélez, E. Martínez-Barba, M.J. López-Poveda, I. Vidal-Abarca Gutiérrez, J.A. Ruíz-Maciá, I. Oviedo-Ramirez, T. Martínez-Menchón" "autores" => array:7 [ 0 => array:2 [ "nombre" => "R." "apellidos" => "Corbalán-Vélez" ] 1 => array:2 [ "nombre" => "E." "apellidos" => "Martínez-Barba" ] 2 => array:2 [ "nombre" => "M.J." "apellidos" => "López-Poveda" ] 3 => array:2 [ "nombre" => "I." "apellidos" => "Vidal-Abarca Gutiérrez" ] 4 => array:2 [ "nombre" => "J.A." "apellidos" => "Ruíz-Maciá" ] 5 => array:2 [ "nombre" => "I." "apellidos" => "Oviedo-Ramirez" ] 6 => array:2 [ "nombre" => "T." 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Bielsa, F. Benvenutti, R.M. Guinovart, C. Ferrándiz" "autores" => array:4 [ 0 => array:4 [ "nombre" => "I." "apellidos" => "Bielsa" "email" => array:1 [ 0 => "ibielsa.germanstrias@gencat.cat" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "F." "apellidos" => "Benvenutti" ] 2 => array:2 [ "nombre" => "R.M." "apellidos" => "Guinovart" ] 3 => array:2 [ "nombre" => "C." "apellidos" => "Ferrándiz" ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Servicio de Dermatología, Hospital Universitari Germans Trias i Pujol, Badalona, Universitat Autònoma de Barcelona, Barcelona, Spain" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Escleromixedema y síndrome dermato-neuro: buena respuesta al tratamiento con glucocorticoides e inmunoglobulinas endovenosas" ] ] "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" => 488 "Ancho" => 650 "Tamanyo" => 64040 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Rigid appearance of the hands and depression over the proximal interphalangeal joint surrounded by redundant skin forming the characteristic donut sign.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Scleromyxedema is an uncommon disease characterized by mucin deposits, fibrosis, and proliferation of fibroblasts in the dermis. It is often associated with paraproteinemia and very varied systemic manifestations,<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1-3</span></a> the most notable of which—because of its rarity—is the so-called dermato-neuro syndrome.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Response to the treatment of this disease and its complications is often disappointing, although favorable results have been achieved in recent years with intravenous immunoglobulin (IVIG).</p><p id="par0010" class="elsevierStylePara elsevierViewall">We report on 2 patients with scleromyxedema, one of whom developed neurocutaneous syndrome. Both patients had an excellent response to IVIG.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Case Descriptions</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Patient 1</span><p id="par0015" class="elsevierStylePara elsevierViewall">A 72-year-old man with a diagnosis of scleromyxedema was referred to our department in 2005 for follow-up and treatment. Physical examination revealed firm, waxy papules (2-3<span class="elsevierStyleHsp" style=""></span>mm) arranged close together on the auricle of the ear, the face, and the dorsum of the hands. In addition, the skin was hard and thick to the touch at these sites and on the neck, chest, and arms (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a>). Microscopy revealed an irregularly distributed proliferation of fibroblasts in the dermis, together with increased collagen fibers and diffuse mucin deposits in the middle reticular and papillary dermis (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). Protein electrophoresis revealed a monoclonal band of immunoglobulin (Ig) Gλ; bone marrow aspirate was normal. Echocardiography revealed mild asymptomatic pulmonary hypertension. The patient received various treatments over the following years, including melphalan, retinoids, corticosteroids, thalidomide, and photochemotherapy; however, the response was poor. In March 2008, the patient began treatment with IVIG (2<span class="elsevierStyleHsp" style=""></span>g/kg/mo) and initially experienced a notable improvement (skin less thickened, greater mobility of the limbs, and increased mouth opening) that did not continue during the following months. IVIG was, therefore, stopped after 7 cycles. The patient then received chlorambucil for 4 months, with no improvement. In April 2009, following placement of a partially tunneled central catheter, extracorporeal photopheresis was started. After the second session of the first cycle, the patient went to the emergency department complaining of fever (38<span class="elsevierStyleHsp" style=""></span>°C) that had started 24<span class="elsevierStyleHsp" style=""></span>hours earlier with no accompanying symptoms. The laboratory workup showed neutrophilia (90%) with no leukocytosis. Blood cultures were positive for <span class="elsevierStyleItalic">Streptococcus lugdunensis</span>, although this entity was not detected in the catheter culture. The patient's initial progress with antibiogram-guided antibiotic therapy was good; however, on the fifth day of admission he presented 2 episodes of tonic-clonic seizures preceded by high fever (39<span class="elsevierStyleHsp" style=""></span>°C) and hypertension in less than 24<span class="elsevierStyleHsp" style=""></span>hours. The second episode was followed by diminished level of consciousness and stupor. The patient went into coma and was intubated for mechanical ventilation. His condition did not improve despite therapy with anticonvulsants. Two new blood cultures and a catheter tip culture were negative. No abnormal findings were detected in electroencephalography, lumbar puncture, cranial computed tomography, magnetic resonance imaging, or magnetic resonance angiography. On suspicion of dermato-neuro syndrome associated with scleromyxedema, treatment with IVIG (2<span class="elsevierStyleHsp" style=""></span>g/kg) and methylprednisolone (100<span class="elsevierStyleHsp" style=""></span>mg/d) was started for 2 days and then tapered. The neurological symptoms gradually improved, and the patient gradually recovered consciousness. Progress was good, and no neurological sequelae were observed. One year and 9 months later, the patient continues to receive IVIG, which is administered once monthly. He has not experienced seizures or any further episodes of reduced consciousness. The monoclonal band persisted despite treatment.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Patient 2</span><p id="par0020" class="elsevierStylePara elsevierViewall">A 52-year-old woman with hypothyroidism and dyslipidemia consulted with a 6-month history of skin lesions that had first appeared on the dorsum of the hands and gradually extended to the arms, legs, face, and auricle of the ears. The patient also reported paresthesia in her hands, which she found difficult to close. No other symptoms were recorded. The lesions took the form of skin-colored papules (1 to 3<span class="elsevierStyleHsp" style=""></span>mm) that coalesced in some areas, with mild erythema and induration of the skin (<a class="elsevierStyleCrossRefs" href="#fig0020">Figs. 4 and 5</a>). One biopsy specimen was taken from the dorsum of the hand and another from the arm. The changes observed were characteristic of scleromyxedema. Additional investigations revealed bilateral carpal tunnel syndrome, and protein electrophoresis revealed a monoclonal band of IgGλ, with no evidence of myeloma. Treatment was started with IVIG (2<span class="elsevierStyleHsp" style=""></span>g/kg/mo) and prednisone (0.5<span class="elsevierStyleHsp" style=""></span>mg/kg/d [30<span class="elsevierStyleHsp" style=""></span>mg/d]). Symptoms improved notably after 2 months, with increased mobility in the hands and reduced infiltration of the skin. Prednisone was tapered from this point and discontinued 2 months later. After 1 year of uninterrupted treatment with IVIG and no systemic corticosteroids, the patient remains stable with no complications, although the monoclonal band has persisted.</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Discussion</span><p id="par0025" class="elsevierStylePara elsevierViewall">Scleromyxedema is a chronic, unpredictable, and occasionally fatal systemic disease, and no consensus has been reached on its treatment.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The 2 cases we report presented unequivocal manifestations of scleromyxedema. Two findings are of particular interest, namely, the development in 1 patient of dermato-neuro syndrome and the favorable response to IVIG,initially combined with systemic corticosteroids.</p><p id="par0035" class="elsevierStylePara elsevierViewall">One of the most unusual neurologic complications, affecting less than 10% of patients with scleromyxedema,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> is dermato-neuro syndrome, which involves a combination of fever, seizures, and coma that is often preceded by flu-like symptoms.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Some 10 cases have been reported.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> The first of our patients developed the symptoms of this syndrome 6 months after discontinuing IVIG and after 2 sessions of his first cycle of extracorporeal photopheresis. Although fever has been described as a side effect of extracorporeal photopheresis, a relationship between this procedure and other more severe manifestations (eg, seizures and coma) seems unlikely. Therefore, after ruling out other possible causes, we reached a diagnosis of dermato-neuro syndrome.</p><p id="par0040" class="elsevierStylePara elsevierViewall">The mechanism responsible for dermato-neuro syndrome remains unknown. Paraproteinemia is thought to increase blood viscosity or favor the formation of neutrophil aggregates that alter microcirculation. Increased levels of endogenous benzodiazepines have also been postulated.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> The syndrome has been associated with increased intervals between IVIG infusions<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> and reduced doses of immunoglobulins.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,9</span></a> In our case, the onset of this complication coincided with the discontinuation of IVIG.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The very low incidence of scleromyxedema and our poor understanding of its pathogenesis explain why no consensus has been reached on treatment and randomized clinical trials are lacking. Given the presence of paraproteinemia, and following the approach used to treat myeloma, drugs such as melphalan, thalidomide, and corticosteroids, both alone and in combination, have proven successful in specific cases.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,10,11</span></a> However, the toxicity of long-term melphalan<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and the risk of peripheral neuropathy with thalidomide limit the use of these drugs over extended periods. Treatment of severe and disfiguring disease with hematopoietic stem cell transplantation<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,13</span></a> and high-dose IVIG has proven increasingly successful in the last 10 years. In patient 1, we achieved no response whatsoever with melphalan, thalidomide, or photochemotherapy; consequently, and given the considerable progression of the disease, we successfully administered high-dose IVIG, which was followed by a rapid initial response and reversal of dermato-neuro syndrome. Our previous experience meant that our first option for patient 2 was IVIG, which was also successful.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Treatment schedules for dermato-neuro syndrome are not clear, and the outcome of plasmapheresis<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> and corticosteroids,<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> both alone and in combination,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> has varied. IVIG combined with corticosteroids, as in our patient 1, has been used in only 1 case.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> The mechanism by which scleromyxedema and its complications respond to IVIG is unknown; however, the drug is thought to reduce fibrosis by blocking an as yet unidentified circulating fibroblast-stimulating factor.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">To conclude, the growing number of cases of scleromyxedema with dermato-neuro syndrome seems to confirm the syndrome as a potentially fatal complication of the disease. Furthermore, IVIG combined with corticosteroids during the early stages of the disease is seen as a relatively safe first-line option, although it is not free of side effects.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflicts of Interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:2 [ "identificador" => "xres95842" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec83002" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres95843" "titulo" => "Resumen" ] 3 => array:2 [ "identificador" => "xpalclavsec83001" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Case Descriptions" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patient 1" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Patient 2" ] ] ] 6 => array:2 [ "identificador" => "sec0025" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflicts of Interest" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec83002" "palabras" => array:4 [ 0 => "Scleromyxedema" 1 => "Neurological complications" 2 => "Dermato-neuro syndrome" 3 => "Intravenous immunoglobulins" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec83001" "palabras" => array:4 [ 0 => "Escleromixedema" 1 => "Complicaciones neurológicas" 2 => "Síndrome dermato-neuro" 3 => "Inmunoglobulinas endovenosas" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Scleromyxedema is a potentially serious disease that can have various systemic complications. One of the most frequent forms of central nervous system involvement is dermato-neuro syndrome. High-dose intravenous immunoglobulins are among the drug treatments that have been used for this syndrome. We describe 2 patients with scleromyxedema, one of whom developed dermato-neuro syndrome. Both patients responded well to treatment with high-dose intravenous immunoglobulins. We suggest this therapy as a suitable first-line treatment for scleromyxedema and for its neurological complications.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El escleromixedema es una enfermedad potencialmente grave que puede asociarse a complicaciones sistémicas diversas, entre las que se encuentran las que involucran al sistema nervioso central, siendo el síndrome dermato-neuro una de las más infrecuentes. Se han utilizado para su tratamiento fármacos variados, entre ellos, altas dosis de inmunoglobulinas endovenosas. Se describen dos casos de escleromixedema, uno de los cuales desarrolló un síndrome dermato-neuro, ambos con una excelente respuesta al tratamiento con inmunoglobulinas endovenosas. El uso de altas dosis de inmunoglobulinas endovenosas en el tratamiento de esta enfermedad y sus complicaciones neurológicas se perfila como un tratamiento de primera línea.</p>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please cite this article as: Bielsa I, et al. Escleromixedema y syndrome dermato-neuro: Buena respuesta al tratamiento con glucocorticoides e inmunoglobulinas endovenosas. Actas Dermosifiliogr.2012;103:317-20.</p>" ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 866 "Ancho" => 650 "Tamanyo" => 117098 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Minute skin-colored papules that are waxy to the touch are visible on the forehead. The wrinkles around the eyes and mouth have disappeared as a consequence of mucin deposits in the skin.</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" => 488 "Ancho" => 650 "Tamanyo" => 64040 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Rigid appearance of the hands and depression over the proximal interphalangeal joint surrounded by redundant skin forming the characteristic donut sign.</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" => 1000 "Ancho" => 750 "Tamanyo" => 298286 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Irregular proliferation of fibroblasts with mucin deposits in the superficial and middle dermis (hematoxylin-eosin, original magnification ×20).</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 561 "Ancho" => 750 "Tamanyo" => 80820 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Multiple skin-colored papules (2-3<span class="elsevierStyleHsp" style=""></span>mm in diameter) that are firm to the touch can be observed on the skin covering the metacarpophalangeal joints.</p>" ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 599 "Ancho" => 800 "Tamanyo" => 67839 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Thickening of the folds that is typical of scleromyxedema can be observed symmetrically on both elbows. Unlike systemic scleroderma, scleromyxedema leads to redundant skin that is soft to the touch.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Escleromixedema con lesiones hiperqueratósicas especiales y calcificaciones" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C. Ferrándiz" 1 => "M. Lecha" 2 => "P. 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| año/Mes | Html | Total | |
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| 2023 Agosto | 69 | 17 | 86 |
| 2023 Julio | 102 | 48 | 150 |
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| 2023 Marzo | 86 | 44 | 130 |
| 2023 Febrero | 66 | 35 | 101 |
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| 2022 Noviembre | 48 | 32 | 80 |
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| 2022 Septiembre | 53 | 51 | 104 |
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| 2022 Junio | 56 | 30 | 86 |
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| 2021 Diciembre | 45 | 50 | 95 |
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| 2020 Diciembre | 54 | 26 | 80 |
| 2020 Noviembre | 48 | 50 | 98 |
| 2020 Octubre | 61 | 44 | 105 |
| 2020 Septiembre | 66 | 47 | 113 |
| 2020 Agosto | 36 | 77 | 113 |
| 2020 Julio | 35 | 45 | 80 |
| 2020 Junio | 35 | 45 | 80 |
| 2020 Mayo | 28 | 42 | 70 |
| 2020 Abril | 32 | 39 | 71 |
| 2020 Marzo | 38 | 28 | 66 |
| 2020 Febrero | 1 | 5 | 6 |
| 2020 Enero | 4 | 10 | 14 |
| 2019 Diciembre | 4 | 4 | 8 |
| 2019 Noviembre | 4 | 4 | 8 |
| 2019 Octubre | 0 | 7 | 7 |
| 2019 Septiembre | 4 | 6 | 10 |
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| 2018 Diciembre | 2 | 9 | 11 |
| 2018 Noviembre | 2 | 0 | 2 |
| 2018 Octubre | 1 | 0 | 1 |
| 2018 Septiembre | 5 | 0 | 5 |
| 2018 Marzo | 15 | 1 | 16 |
| 2018 Febrero | 60 | 8 | 68 |
| 2018 Enero | 92 | 9 | 101 |
| 2017 Diciembre | 92 | 10 | 102 |
| 2017 Noviembre | 81 | 8 | 89 |
| 2017 Octubre | 76 | 5 | 81 |
| 2017 Septiembre | 74 | 7 | 81 |
| 2017 Agosto | 68 | 10 | 78 |
| 2017 Julio | 87 | 8 | 95 |
| 2017 Junio | 103 | 11 | 114 |
| 2017 Mayo | 117 | 7 | 124 |
| 2017 Abril | 94 | 10 | 104 |
| 2017 Marzo | 124 | 20 | 144 |
| 2017 Febrero | 177 | 10 | 187 |
| 2017 Enero | 127 | 7 | 134 |
| 2016 Diciembre | 79 | 18 | 97 |
| 2016 Noviembre | 171 | 18 | 189 |
| 2016 Octubre | 180 | 34 | 214 |
| 2016 Septiembre | 247 | 16 | 263 |
| 2016 Agosto | 213 | 13 | 226 |
| 2016 Julio | 83 | 20 | 103 |
| 2016 Junio | 11 | 26 | 37 |
| 2016 Mayo | 7 | 21 | 28 |
| 2016 Abril | 6 | 2 | 8 |
| 2016 Marzo | 7 | 2 | 9 |
| 2016 Febrero | 5 | 1 | 6 |
| 2016 Enero | 7 | 1 | 8 |
| 2015 Diciembre | 10 | 3 | 13 |
| 2015 Noviembre | 38 | 2 | 40 |
| 2015 Octubre | 51 | 1 | 52 |
| 2015 Septiembre | 43 | 1 | 44 |
| 2015 Agosto | 15 | 3 | 18 |
| 2015 Julio | 189 | 10 | 199 |
| 2015 Junio | 123 | 12 | 135 |
| 2015 Mayo | 161 | 28 | 189 |
| 2015 Abril | 166 | 24 | 190 |
| 2015 Marzo | 188 | 14 | 202 |
| 2015 Febrero | 163 | 17 | 180 |
| 2015 Enero | 140 | 16 | 156 |
| 2014 Diciembre | 109 | 9 | 118 |
| 2014 Noviembre | 109 | 10 | 119 |
| 2014 Octubre | 130 | 26 | 156 |
| 2014 Septiembre | 96 | 26 | 122 |
| 2014 Agosto | 117 | 26 | 143 |
| 2014 Julio | 98 | 17 | 115 |
| 2014 Junio | 147 | 14 | 161 |
| 2014 Mayo | 161 | 25 | 186 |
| 2014 Abril | 76 | 6 | 82 |
| 2014 Marzo | 85 | 7 | 92 |
| 2014 Febrero | 76 | 8 | 84 |
| 2014 Enero | 72 | 6 | 78 |
| 2013 Diciembre | 65 | 13 | 78 |
| 2013 Noviembre | 72 | 8 | 80 |
| 2013 Octubre | 56 | 7 | 63 |
| 2013 Septiembre | 44 | 9 | 53 |
| 2013 Agosto | 44 | 16 | 60 |
| 2013 Julio | 16 | 30 | 46 |
| 2013 Junio | 14 | 19 | 33 |
| 2013 Mayo | 14 | 21 | 35 |
| 2013 Abril | 17 | 32 | 49 |
| 2013 Marzo | 21 | 16 | 37 |
| 2013 Febrero | 36 | 7 | 43 |
| 2013 Enero | 56 | 10 | 66 |
| 2012 Diciembre | 25 | 6 | 31 |
| 2012 Noviembre | 1 | 1 | 2 |
| 2012 Agosto | 0 | 1 | 1 |
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