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Facial Erythema: Keys to the Differential Diagnosis
RR - Eritema facial: claves para el diagnóstico diferencial
N. Lamas-Doménech
, H. Collgros
Corresponding author
Servicio de Dermatología, Hospital Universitario Sagrat Cor, Barcelona, Spain
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Lamas-Doménech, H. Collgros" "autores" => array:2 [ 0 => array:4 [ "nombre" => "N." "apellidos" => "Lamas-Doménech" "email" => array:1 [ 0 => "n.lamas.domenech@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "H." "apellidos" => "Collgros" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Dermatología, Hospital Universitario Sagrat Cor, Barcelona, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "RR - Eritema facial: claves para el diagnóstico diferencial" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Facial erythema is a very common reason for consulting a dermatologist. While often a manifestation of a benign condition, in some cases it may be the first sign of a more serious disorder and specific diagnostic tests are needed to rule out these diseases. Flushing can be produced by agents acting on the vascular smooth muscle receptors or by signals sent by the vasomotor nerves. It can be episodic or persistent. Episodic flushing is usually caused by endogenous vasoactive mediators or medication. Persistent flushing is caused by successive episodes over long periods, which eventually lead to the appearance of telangiectasias and enlarged vessels with slow-flowing deoxygenated blood.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the most common benign causes of flushing as well as other less common and potentially serious causes.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> The first step is to determine whether the patient's clinical history and a careful physical examination provide sufficient information to guide the diagnosis. If they do, we only have to decide whether or not additional tests are required to confirm the suspected diagnosis. Once the diagnosis is confirmed and the cause established, we can decide on an appropriate treatment. In more complex cases, the patient should keep a diary for 2 weeks and record when flushing occurs, the symptoms, any association with other symptoms (diarrhea, bronchospasm, headache, low blood pressure, tachycardia, abdominal pain, urticaria, or pruritus), and any external triggers (food, beverages, drugs, alcohol, exercise, emotions, stress, or occupational exposure). The data collected may provide the key to a suspected diagnosis, which can then be confirmed by the appropriate diagnostic studies. When the results obtained do not point to a possible cause or when the investigations undertaken do not support the suspected diagnosis, a more comprehensive battery of tests must be ordered to rule out the more common serious causes of flushing (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The recommended first step is to measure plasma levels of serotonin, tryptase, chromogranin A, and histamine and 24h-urine levels of 5-hydroxyindoleacetic, vanillylmandelic acid, norepinephrine, metanephrines, and prostaglandin D2. In the presence of elevated values, the suspected diagnosis would be carcinoid syndrome, pheochromocytoma, or mastocytosis.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> If the results are within normal limits, we would then check for the presence of the following: hematuria, which would be indicative of renal cell carcinoma; elevated vasoactive intestinal peptide, which would suggest pancreatic carcinoma; elevated calcitonin, which would point to a possible medullary thyroid carcinoma. If an anaphylactic reaction is suspected, we would measure immunoglobulin E or perform a skin prick test for a specific substance. If the findings do not clearly support a particular diagnosis, the next step should be to investigate the less common causes, such as anxiety, psychiatric disorders, idiopathic flushing, and mast cell activation syndrome.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">We currently have symptomatic treatment at our disposal: brimonidine tartrate 0.5% gel. This topical treatment, which has been shown to be safe and effective in controlled clinical trials and has recently become available in Spain, can help to control flushing and improve the patient's quality of life.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The dermatologist plays a key role in the diagnosis of patients with flushing, since correct management may have implications for the morbidity and mortality of the condition.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-07-26" "fechaAceptado" => "2014-10-02" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec540940" "palabras" => array:3 [ 0 => "Facial erythema" 1 => "Flushing" 2 => "Differential diagnosis" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Lamas-Doménech N, Collgros H. RR - Eritema facial: claves para el diagnóstico diferencial. Actas Dermosifiliogr. 2015;106:427–429.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Source: Izikson et al.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a>; Lafont et al.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a></p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Tests Required \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Common Causes</span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Benign causes</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Emotions \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Temperature \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Food and drinks \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Rosacea</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Menopause</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Follicle-stimulating hormone (plasma) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Fever</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Alcohol</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Less Common, Serious Causes</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Carcinoid tumor</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5-Hydroxyindoleacetic acid (24-h urine) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Pheochromocytoma</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Metanephrines, norepinephrine, epinephrine, dopamine, and vanillylmandelic acid (24-h urine) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Mastocytosis</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Plasma tryptase (persistently elevation), n-methyl histamine, prostaglandin D2 (24-h urine) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Anaphylaxis</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Specific immunoglobulin E, skin prick test, elevated plasma tryptase during episode \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Other causes</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Medullary thyroid carcinoma</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Plasma calcitonin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Pancreatic Tumor (VIPoma)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Plasma vasoactive intestinal peptide (VIP) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Renal cell carcinoma</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hematuria and radiologic evidence \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Psychiatric disorders</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Idiopathic flushing</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Neurologic</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Parkinson \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Migraine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Multiple sclerosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Trigeminal disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Horner syndrome \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Frey syndrome \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Autonomic epilepsy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Autonomic hyperreflexia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Orthostatic hypotension \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Streeten syndrome \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Mast cell activation syndrome</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Medication</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Rare causes</span></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Sarcoidosis, mitral stenosis, gastric dumping syndrome, arsenic poisoning, ciguatera poisoning, POEMS syndrome, bronchogenic carcinoma, malignant histiocytoma, malignant neuroblastoma, malignant ganglioneuroma, preaortic surgery, Leigh syndrome, Rovsing syndrome</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab840235.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Flushing: Causes and the Diagnostic Tests Required.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Advances in understanding and managing rosacea: Part 1: Connecting the dots between pathophysiological mechanisms and common clinical features of rosacea with emphasis on vascular changes and facial erythema" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J.Q. Del Rosso" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Clin Aesthetic Dermatol" "fecha" => "2012" "volumen" => "5" "paginaInicial" => "16" "paginaFinal" => "25" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The flushing patient: Differential diagnosis, workup, and treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "L. Izikson" 1 => "J.C. English 3rd" 2 => "M.J. Zirwas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2005.07.057" "Revista" => array:7 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2006" "volumen" => "55" "paginaInicial" => "193" "paginaFinal" => "208" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16844500" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0015028209007778" "estado" => "S300" "issn" => "00150282" ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alertas cutáneas en malignidades sistémicas (parte I)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M. Yuste-Chaves" 1 => "P. Unamuno-Pérez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.adengl.2012.03.027" "Revista" => array:7 [ "tituloSerie" => "Actas Dermosifiliogr" "fecha" => "2013" "volumen" => "104" "paginaInicial" => "285" "paginaFinal" => "298" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23578547" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S1472648312000880" "estado" => "S300" "issn" => "14726483" ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Étiologies et orientation diagnostique devant un flush" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Lafont" 1 => "H. Sokol" 2 => "M.E. Sarre-Annweiler" 3 => "E. Lecornet-Sokol" 4 => "S. Barete" 5 => "O. Hermine" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.revmed.2013.08.015" "Revista" => array:7 [ "tituloSerie" => "Rev Med Interne" "fecha" => "2014" "volumen" => "35" "paginaInicial" => "303" "paginaFinal" => "309" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24080240" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0015028207034681" "estado" => "S300" "issn" => "00150282" ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema of rosacea: Results of two randomized, double-blind, and vehicle-controlled pivotal studies" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Fowler Jr." 1 => "M. Jackson" 2 => "A. Moore" 3 => "M. Jarratt" 4 => "T. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 34 | 10 | 44 |
| 2024 October | 533 | 62 | 595 |
| 2024 September | 570 | 54 | 624 |
| 2024 August | 681 | 82 | 763 |
| 2024 July | 764 | 63 | 827 |
| 2024 June | 547 | 50 | 597 |
| 2024 May | 650 | 63 | 713 |
| 2024 April | 681 | 46 | 727 |
| 2024 March | 615 | 52 | 667 |
| 2024 February | 606 | 48 | 654 |
| 2024 January | 718 | 49 | 767 |
| 2023 December | 431 | 49 | 480 |
| 2023 November | 360 | 54 | 414 |
| 2023 October | 309 | 62 | 371 |
| 2023 September | 329 | 63 | 392 |
| 2023 August | 247 | 42 | 289 |
| 2023 July | 234 | 72 | 306 |
| 2023 June | 215 | 40 | 255 |
| 2023 May | 273 | 49 | 322 |
| 2023 April | 247 | 39 | 286 |
| 2023 March | 222 | 61 | 283 |
| 2023 February | 187 | 28 | 215 |
| 2023 January | 167 | 48 | 215 |
| 2022 December | 151 | 63 | 214 |
| 2022 November | 76 | 33 | 109 |
| 2022 October | 47 | 26 | 73 |
| 2022 September | 41 | 69 | 110 |
| 2022 August | 33 | 38 | 71 |
| 2022 July | 34 | 39 | 73 |
| 2022 June | 28 | 31 | 59 |
| 2022 May | 258 | 60 | 318 |
| 2022 April | 304 | 59 | 363 |
| 2022 March | 373 | 65 | 438 |
| 2022 February | 256 | 46 | 302 |
| 2022 January | 332 | 63 | 395 |
| 2021 December | 239 | 43 | 282 |
| 2021 November | 250 | 82 | 332 |
| 2021 October | 256 | 86 | 342 |
| 2021 September | 290 | 80 | 370 |
| 2021 August | 236 | 71 | 307 |
| 2021 July | 313 | 52 | 365 |
| 2021 June | 401 | 88 | 489 |
| 2021 May | 358 | 113 | 471 |
| 2021 April | 748 | 306 | 1054 |
| 2021 March | 482 | 170 | 652 |
| 2021 February | 288 | 124 | 412 |
| 2021 January | 250 | 164 | 414 |
| 2020 December | 137 | 125 | 262 |
| 2020 November | 100 | 97 | 197 |
| 2020 October | 75 | 84 | 159 |
| 2020 September | 122 | 99 | 221 |
| 2020 August | 76 | 123 | 199 |
| 2020 July | 75 | 128 | 203 |
| 2020 June | 63 | 109 | 172 |
| 2020 May | 64 | 147 | 211 |
| 2020 April | 67 | 122 | 189 |
| 2020 March | 82 | 108 | 190 |
| 2020 February | 5 | 36 | 41 |
| 2020 January | 5 | 47 | 52 |
| 2019 December | 6 | 25 | 31 |
| 2019 November | 4 | 68 | 72 |
| 2019 October | 1 | 59 | 60 |
| 2019 September | 4 | 79 | 83 |
| 2019 August | 6 | 70 | 76 |
| 2019 July | 5 | 61 | 66 |
| 2019 June | 4 | 49 | 53 |
| 2019 May | 4 | 79 | 83 |
| 2019 April | 2 | 129 | 131 |
| 2019 March | 2 | 70 | 72 |
| 2019 February | 1 | 51 | 52 |
| 2019 January | 4 | 37 | 41 |
| 2018 December | 1 | 7 | 8 |
| 2018 November | 1 | 0 | 1 |
| 2018 October | 5 | 0 | 5 |
| 2018 September | 6 | 33 | 39 |
| 2018 August | 0 | 68 | 68 |
| 2018 July | 0 | 71 | 71 |
| 2018 June | 0 | 63 | 63 |
| 2018 May | 1 | 82 | 83 |
| 2018 April | 0 | 88 | 88 |
| 2018 March | 112 | 123 | 235 |
| 2018 February | 655 | 135 | 790 |
| 2018 January | 570 | 97 | 667 |
| 2017 December | 414 | 76 | 490 |
| 2017 November | 389 | 99 | 488 |
| 2017 October | 325 | 61 | 386 |
| 2017 September | 224 | 54 | 278 |
| 2017 August | 191 | 58 | 249 |
| 2017 July | 119 | 62 | 181 |
| 2017 June | 117 | 51 | 168 |
| 2017 May | 116 | 81 | 197 |
| 2017 April | 88 | 44 | 132 |
| 2017 March | 82 | 71 | 153 |
| 2017 February | 73 | 29 | 102 |
| 2017 January | 65 | 27 | 92 |
| 2016 December | 42 | 23 | 65 |
| 2016 November | 47 | 52 | 99 |
| 2016 October | 37 | 75 | 112 |
| 2016 September | 0 | 46 | 46 |
| 2016 August | 0 | 34 | 34 |
| 2016 July | 9 | 5 | 14 |
| 2016 June | 13 | 1 | 14 |
| 2016 May | 10 | 33 | 43 |
| 2016 April | 7 | 45 | 52 |
| 2016 March | 6 | 3 | 9 |
| 2016 February | 5 | 2 | 7 |
| 2016 January | 9 | 1 | 10 |
| 2015 December | 4 | 1 | 5 |
| 2015 November | 0 | 1 | 1 |
| 2015 October | 0 | 3 | 3 |
| 2015 September | 0 | 2 | 2 |
| 2015 August | 0 | 3 | 3 |
| 2015 July | 12 | 9 | 21 |
| 2015 June | 16 | 6 | 22 |
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