Case and Research Letters
Topical Rapamycin Solution to Treat Multiple Facial Angiofibromas in a Patient With Tuberous Sclerosis
Utilización de solución de rapamicina tópica para el tratamiento de múltiples angiofibromas faciales en una paciente con esclerosis tuberosa
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Valerón-Almazán, M. Vitiello, A. Abuchar, F.A. Kerdel" "autores" => array:4 [ 0 => array:3 [ "nombre" => "P." "apellidos" => "Valerón-Almazán" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "M." "apellidos" => "Vitiello" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "A." "apellidos" => "Abuchar" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:4 [ "nombre" => "F.A." "apellidos" => "Kerdel" "email" => array:1 [ 0 => "dr.kerdel@fadcenter.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Florida Academic Dermatology Center, University of Miami Hospital, Miami, FL, United States" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Utilización de solución de rapamicina tópica para el tratamiento de múltiples angiofibromas faciales en una paciente con esclerosis tuberosa" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2073 "Ancho" => 1587 "Tamanyo" => 389316 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Clinical image of the lesions before the start of treatment. Multiple facial angiofibromas predominantly affecting the cheeks, with a prominent erythematous base.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We report the case of a 27-year-old woman with a 10-year history of tuberous sclerosis. Her first visit to the dermatologist revealed several of the cutaneous manifestations characteristic of the disease, namely, disseminated facial angiofibromas (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), multiple periungual Koenen tumors on both feet, hypopigmented macules on the trunk, and a shagreen plaque on the back. The patient also had epilepsy and mental retardation. She had no known internal hamartomatous lesions.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">A number of treatments—multiple shave excisions, pulsed-dye laser, electrodessication, and 0.1% topical tacrolimus ointment—had been applied in order to improve her facial appearance and reduce the number of angiofibromas. The response to treatment had been poor, with no appreciable reduction in the number of lesions and persistence of erythema. At that time, pharmacy-prepared topical rapamycin, 1<span class="elsevierStyleHsp" style=""></span>mg/mL, was applied twice daily on the affected areas of both cheeks. A clear clinical improvement was observed after 3 months’ treatment, with a reduction in the number of lesions and in the underlying erythema (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Tuberous sclerosis is an autosomal-dominant genodermatosis characterized by hamartomas affecting various organs, including the skin and central nervous system. Its pathogenesis is based on abnormalities of the proteins hamartin and tuberin, which are coded on the loci 9p34 and 16p13.3, respectively.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Symptoms comprise the classic triad of multiple angiofibromas, epilepsy, and mental retardation, although this combination is only seen in 26% of patients.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Despite its wide clinical variability and variable penetrance,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> facial angiofibromas are found in 83–90% of cases.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a> These lesions are considered pathognomic and develop mainly on the nasolabial folds, cheeks, chin, scalp, forehead, and ears.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> They usually appear during the first decade of life, stabilize during adolescence, and are lifelong. They are not malignant, although their appearance constitutes a very frequent presenting complaint in these patients.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Treatment can take several forms, including simple excision, cryosurgery, curettage, dermabrasion, carbon dioxide laser, and photodynamic therapy. No single treatment has proven sufficiently effective to control their onset or prevent recurrence.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5–7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Rapamycin (sirolimus) is an oral immunosuppressive agent used mainly in kidney transplantation. Its mechanism of action has not been clearly defined, although it is known to interfere with the mTOR protein pathway, which is responsible for cell proliferation and inhibition of apoptosis in patients with tuberous sclerosis.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> The proteins hamartin and tuberin also suppress mTOR pathway activity. These proteins are modified in tuberous sclerosis in such a way that their altered function causes permanent activation of the mTOR pathway, thus leading to the onset of hamartomatous tumors in various regions.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> It has been suggested that the mechanisms by which rapamycin reduces the number and size of tumors in tuberous sclerosis are inhibition of angiogenesis<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,10</span></a> and of aberrant growth factors,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> although these phenomena have only been verified in extracutaneous hamartomatous lesions (brain, kidney, and lung).</p><p id="par0030" class="elsevierStylePara elsevierViewall">After the failure of the therapeutic approaches adopted to control the facial angiofibromas in our patient, we decided to try topical treatment with rapamycin, an alternative that has been described in 2 previous publications.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,10</span></a> Ours is the fourth reported case in which this therapy was administered to control facial angiofibromas. A clear improvement was observed in all 4 patients, with a marked reduction or complete disappearance of the lesions. Facial erythema also improved after only a few months’ treatment. Of the 3 cases reported previously, 2 were treated with rapamycin solution (1<span class="elsevierStyleHsp" style=""></span>mg/mL) and the remaining patient with 0.1% rapamycin ointment. Treatment was administered in 1 or 2 applications per day and, as in our patient, seemed to be well tolerated, with no local or systemic adverse events. The pharmacological basis for the efficacy of rapamycin in treating facial angiofibromas in patients with tuberous sclerosis should be clarified in future studies.</p><p id="par0035" class="elsevierStylePara elsevierViewall">No commercial preparations of topical rapamycin are currently available in the United States or Europe; therefore, the formulation has to be prepared in the pharmacy. In theory, topical administration should be safer than oral medication, although longer follow-up is necessary before these observations can be confirmed. Given the small number of cases described to date, the most suitable presentation of the product has not yet been determined.</p><p id="par0040" class="elsevierStylePara elsevierViewall">In conclusion, we report a new case of multiple facial angiofibromas treated with topical rapamycin in a patient with tuberous sclerosis. This drug could be a valid alternative in this setting, although more cases must be reported in order to verify the long-term safety and efficacy profile of the medication.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please cite this article as: Valerón-Almazán P, et al. Utilización de solución de rapamicina tópica para el tratamiento de múltiples angiofibromas faciales en una paciente con esclerosis tuberosa. Actas Dermosifiliogr. 2012;103:165–6.</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" => 2073 "Ancho" => 1587 "Tamanyo" => 389316 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Clinical image of the lesions before the start of treatment. Multiple facial angiofibromas predominantly affecting the cheeks, with a prominent erythematous base.</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" => 2133 "Ancho" => 1585 "Tamanyo" => 361913 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Image of the patient after 3 months of treatment with rapamycin solution (1<span class="elsevierStyleHsp" style=""></span>mg/mL). Reduction in the number of lesions and marked improvement in the underlying erythema.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Expression of tuberous sclerosis complex gene products, hamartin and tuberin, in central nervous system tissues" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "D.H. Gutmann" 1 => "Y. Zhang" 2 => "M.J. Hasbani" 3 => "M.P. Goldberg" 4 => "T.L. Plank" 5 => "E. Petri Henske" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Acta Neuropathol" "fecha" => "2000" "volumen" => "99" "paginaInicial" => "223" "paginaFinal" => "230" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10663963" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The cutaneous features of tuberous sclerosis: a population study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "D.W. Webb" 1 => "A. Clarke" 2 => "A. Fryer" 3 => "J.P. Osborne" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Br J Dermatol" "fecha" => "1996" "volumen" => "135" "paginaInicial" => "1" "paginaFinal" => "5" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9035700" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Esclerosis tuberosa. Hallazgos clínicos en 67 pacientes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Fernández-Guarino" 1 => "P. Boixeda" 2 => "M.J. Anaya" 3 => "P. Belmar" 4 => "P. Jaén" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Actas Dermosifiliogr" "fecha" => "2009" "volumen" => "100" "paginaInicial" => "596" "paginaFinal" => "601" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19715644" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Esclerosis tuberosa. Enfermedad de Pringle Bourneville" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "R. Ruiz-Villaverde" 1 => "J. Blasco-Melguizo" 2 => "M.C. Martín-Sánchez" 3 => "R. Naranjo-Sintes" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Actas Dermosifiliogr" "fecha" => "2002" "volumen" => "93" "paginaInicial" => "1" "paginaFinal" => "7" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tuberous sclerosis complex: advances in diagnosis, genetics, and management" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "R.A. Schwartz" 1 => "G. Fernández" 2 => "K. Kotulska" 3 => "S. Józwiak" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2007.05.004" "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2007" "volumen" => "57" "paginaInicial" => "189" "paginaFinal" => "202" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17637444" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment of angiofibromas of tuberous sclerosis with 5-aminolevulinic acid blue light photodynamic therapy followed by immediate pulsed dye laser" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "C.H. Weinberger" 1 => "B. Endrizzi" 2 => "K.P. Hook" 3 => "P.K. Lee" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1524-4725.2009.01304.x" "Revista" => array:6 [ "tituloSerie" => "Dermatol Surg" "fecha" => "2009" "volumen" => "35" "paginaInicial" => "1849" "paginaFinal" => "1851" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19682000" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Seguimiento a largo plazo de angiofibromas tratados con láser de CO<span class="elsevierStyleInf">2</span> en 23 pacientes con esclerosis tuberosa" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "P. Belmar" 1 => "P. Boixeda" 2 => "O. Baniandrés" 3 => "M. Fernández-Lorente" 4 => "J.M. Arrazola" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Actas Dermosifiliogr" "fecha" => "2005" "volumen" => "96" "paginaInicial" => "498" "paginaFinal" => "503" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16476284" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Therapeutic targeting of mTOR in tuberous sclerosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J.R. Sampson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1042/BST0370259" "Revista" => array:7 [ "tituloSerie" => "Biochem Soc Trans" "fecha" => "2009" "volumen" => "37" "paginaInicial" => "259" "paginaFinal" => "264" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19143643" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0010782408000085" "estado" => "S300" "issn" => "00107824" ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Successful treatment of angiofibromata of tuberous sclerosis complex with rapamycin" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "E. Kaufman-McNamara" 1 => "A.R. Curtis" 2 => "A.B. Fleischer Jr." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Dermatol Treat" "fecha" => "2012" "volumen" => "23" "paginaInicial" => "46" "paginaFinal" => "48" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Topical rapamycin: a novel approach to facial angiofibromas in tuberous sclerosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A.K. Haemel" 1 => "A.L. O’Brian" 2 => "J.M. Teng" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/archdermatol.2010.125" "Revista" => array:6 [ "tituloSerie" => "Arch Dermatol" "fecha" => "2010" "volumen" => "146" "paginaInicial" => "715" "paginaFinal" => "718" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20644030" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/15782190/0000010300000002/v1_201304241253/S1578219012000728/v1_201304241253/en/main.assets" "Apartado" => array:4 [ "identificador" => "6169" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Cases and Research Letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15782190/0000010300000002/v1_201304241253/S1578219012000728/v1_201304241253/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219012000728?idApp=UINPBA000044" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 18 | 5 | 23 |
| 2024 October | 81 | 60 | 141 |
| 2024 September | 79 | 50 | 129 |
| 2024 August | 110 | 94 | 204 |
| 2024 July | 103 | 88 | 191 |
| 2024 June | 117 | 109 | 226 |
| 2024 May | 101 | 74 | 175 |
| 2024 April | 117 | 69 | 186 |
| 2024 March | 139 | 104 | 243 |
| 2024 February | 156 | 55 | 211 |
| 2024 January | 188 | 71 | 259 |
| 2023 December | 189 | 57 | 246 |
| 2023 November | 154 | 101 | 255 |
| 2023 October | 134 | 58 | 192 |
| 2023 September | 136 | 74 | 210 |
| 2023 August | 70 | 49 | 119 |
| 2023 July | 119 | 83 | 202 |
| 2023 June | 70 | 55 | 125 |
| 2023 May | 99 | 89 | 188 |
| 2023 April | 78 | 73 | 151 |
| 2023 March | 69 | 46 | 115 |
| 2023 February | 65 | 60 | 125 |
| 2023 January | 70 | 51 | 121 |
| 2022 December | 105 | 62 | 167 |
| 2022 November | 73 | 34 | 107 |
| 2022 October | 56 | 40 | 96 |
| 2022 September | 68 | 65 | 133 |
| 2022 August | 117 | 79 | 196 |
| 2022 July | 120 | 56 | 176 |
| 2022 June | 88 | 45 | 133 |
| 2022 May | 128 | 56 | 184 |
| 2022 April | 79 | 63 | 142 |
| 2022 March | 106 | 78 | 184 |
| 2022 February | 68 | 48 | 116 |
| 2022 January | 148 | 57 | 205 |
| 2021 December | 68 | 53 | 121 |
| 2021 November | 90 | 51 | 141 |
| 2021 October | 121 | 63 | 184 |
| 2021 September | 82 | 54 | 136 |
| 2021 August | 70 | 38 | 108 |
| 2021 July | 77 | 30 | 107 |
| 2021 June | 65 | 38 | 103 |
| 2021 May | 62 | 48 | 110 |
| 2021 April | 155 | 92 | 247 |
| 2021 March | 99 | 21 | 120 |
| 2021 February | 65 | 27 | 92 |
| 2021 January | 45 | 21 | 66 |
| 2020 December | 44 | 17 | 61 |
| 2020 November | 52 | 18 | 70 |
| 2020 October | 38 | 18 | 56 |
| 2020 September | 70 | 20 | 90 |
| 2020 August | 30 | 13 | 43 |
| 2020 July | 43 | 23 | 66 |
| 2020 June | 42 | 25 | 67 |
| 2020 May | 34 | 26 | 60 |
| 2020 April | 51 | 25 | 76 |
| 2020 March | 57 | 31 | 88 |
| 2020 February | 12 | 6 | 18 |
| 2020 January | 4 | 5 | 9 |
| 2019 December | 3 | 3 | 6 |
| 2019 November | 4 | 6 | 10 |
| 2019 October | 0 | 2 | 2 |
| 2019 September | 4 | 9 | 13 |
| 2019 August | 4 | 4 | 8 |
| 2019 July | 4 | 13 | 17 |
| 2019 June | 4 | 13 | 17 |
| 2019 May | 4 | 7 | 11 |
| 2019 April | 2 | 16 | 18 |
| 2019 March | 2 | 12 | 14 |
| 2019 February | 0 | 1 | 1 |
| 2019 January | 0 | 2 | 2 |
| 2018 December | 5 | 6 | 11 |
| 2018 November | 1 | 0 | 1 |
| 2018 October | 4 | 0 | 4 |
| 2018 September | 6 | 0 | 6 |
| 2018 June | 0 | 1 | 1 |
| 2018 May | 1 | 11 | 12 |
| 2018 March | 1 | 0 | 1 |
| 2018 February | 63 | 8 | 71 |
| 2018 January | 82 | 11 | 93 |
| 2017 December | 81 | 8 | 89 |
| 2017 November | 78 | 7 | 85 |
| 2017 October | 77 | 6 | 83 |
| 2017 September | 84 | 10 | 94 |
| 2017 August | 122 | 8 | 130 |
| 2017 July | 74 | 9 | 83 |
| 2017 June | 116 | 23 | 139 |
| 2017 May | 104 | 12 | 116 |
| 2017 April | 100 | 12 | 112 |
| 2017 March | 89 | 47 | 136 |
| 2017 February | 64 | 13 | 77 |
| 2017 January | 89 | 11 | 100 |
| 2016 December | 107 | 10 | 117 |
| 2016 November | 174 | 22 | 196 |
| 2016 October | 167 | 25 | 192 |
| 2016 September | 245 | 17 | 262 |
| 2016 August | 251 | 19 | 270 |
| 2016 July | 94 | 12 | 106 |
| 2016 June | 13 | 10 | 23 |
| 2016 May | 7 | 11 | 18 |
| 2016 April | 7 | 3 | 10 |
| 2016 March | 5 | 1 | 6 |
| 2016 February | 10 | 12 | 22 |
| 2016 January | 8 | 7 | 15 |
| 2015 December | 11 | 4 | 15 |
| 2015 November | 25 | 1 | 26 |
| 2015 October | 19 | 2 | 21 |
| 2015 September | 10 | 5 | 15 |
| 2015 August | 13 | 13 | 26 |
| 2015 July | 69 | 16 | 85 |
| 2015 June | 57 | 11 | 68 |
| 2015 May | 87 | 20 | 107 |
| 2015 April | 94 | 18 | 112 |
| 2015 March | 70 | 13 | 83 |
| 2015 February | 46 | 16 | 62 |
| 2015 January | 60 | 19 | 79 |
| 2014 December | 47 | 19 | 66 |
| 2014 November | 63 | 15 | 78 |
| 2014 October | 70 | 15 | 85 |
| 2014 September | 50 | 20 | 70 |
| 2014 August | 73 | 16 | 89 |
| 2014 July | 119 | 22 | 141 |
| 2014 June | 104 | 16 | 120 |
| 2014 May | 128 | 14 | 142 |
| 2014 April | 97 | 11 | 108 |
| 2014 March | 88 | 25 | 113 |
| 2014 February | 25 | 11 | 36 |
| 2014 January | 25 | 6 | 31 |
| 2013 December | 30 | 11 | 41 |
| 2013 November | 18 | 12 | 30 |
| 2013 October | 17 | 23 | 40 |
| 2013 September | 11 | 8 | 19 |
| 2013 August | 7 | 14 | 21 |
| 2013 July | 18 | 42 | 60 |
| 2013 June | 14 | 24 | 38 |
| 2013 May | 10 | 24 | 34 |
| 2013 April | 13 | 19 | 32 |
| 2013 March | 14 | 14 | 28 |
| 2013 February | 28 | 7 | 35 |
| 2013 January | 71 | 10 | 81 |
| 2012 December | 36 | 7 | 43 |
| 2012 November | 3 | 4 | 7 |
| 2012 October | 1 | 4 | 5 |
| 2012 July | 1 | 0 | 1 |
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