Original Article
Papulopustular Rosacea: Response to Treatment with Oral Azithromycin
Rosácea papulopustulosa: respuesta al tratamiento con azitromicina oral
M. Lova Navarro
, P. Sánchez-Pedreño Guillen, A.M. Victoria Martínez, T. Martínez Menchón, R. Corbalán Vélez, J. Frías Iniesta
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Servicio de Dermatología, Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain
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Lova Navarro, P. Sánchez-Pedreño Guillen, A.M. Victoria Martínez, T. Martínez Menchón, R. Corbalán Vélez, J. Frías Iniesta" "autores" => array:6 [ 0 => array:4 [ "nombre" => "M." "apellidos" => "Lova Navarro" "email" => array:1 [ 0 => "lovamiguel@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "P." "apellidos" => "Sánchez-Pedreño Guillen" ] 2 => array:2 [ "nombre" => "A.M." "apellidos" => "Victoria Martínez" ] 3 => array:2 [ "nombre" => "T." "apellidos" => "Martínez Menchón" ] 4 => array:2 [ "nombre" => "R." "apellidos" => "Corbalán Vélez" ] 5 => array:2 [ "nombre" => "J." "apellidos" => "Frías Iniesta" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Dermatología, Hospital Virgen de la Arrixaca, El Palmar, Murcia, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Rosácea papulopustulosa: respuesta al tratamiento con azitromicina oral" ] ] "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" => 1099 "Ancho" => 1733 "Tamanyo" => 228744 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">A, Clinical deterioration after treatment with oral doxycycline. B, Complete resolution of inflammatory lesions, with just residual erythema, after treatment with oral azithromycin.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Papulopustular rosacea (PPR) is a chronic inflammatory disease characterized by facial erythema with papules and/or pustules located preferentially on the face.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Traditionally, it has been treated with oral tetracyclines (mainly doxycycline) and topical antibiotics, such as metronidazole.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">1</span></a> An increasing number of treatments have become available in recent years, including oral isotretinoin<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">2</span></a> and anti-parasite drugs such as ivermectin, which can be administered topically<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">3</span></a> or orally.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">4</span></a> In clinical practice, however, there are an appreciable number of challenging cases that do not respond to these conventional treatments. Azithromycin, a macrolide antibiotic, has been shown to a safe, effective treatment for PPR.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">5</span></a> We designed a study to evaluate the use of azithromycin to treat PPR that failed to respond to conventional treatment at our hospital.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">6</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Design</span><p id="par0015" class="elsevierStylePara elsevierViewall">We conducted a prospective pilot study of 16 patients with PPR between March 2016 and September 2017.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Inclusion and Exclusion Criteria</span><p id="par0020" class="elsevierStylePara elsevierViewall">We included patients with PPR who had received conventional treatment with doxycycline 100<span class="elsevierStyleHsp" style=""></span> mg tablets every 24<span class="elsevierStyleHsp" style=""></span>hours and metronidazole 0.75% topical gel every 24<span class="elsevierStyleHsp" style=""></span>hours for 84 days and who had <span class="elsevierStyleItalic">1</span>) experienced clinical deterioration (an increase in the number of inflammatory lesions) as a result of this treatment or <span class="elsevierStyleItalic">2</span>) experienced early recurrence (return of lesions within 8 weeks of treatment completion) despite a reduction in lesion number during treatment.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Patients with a known history of heart disease were excluded.</p><p id="par0030" class="elsevierStylePara elsevierViewall">All the patients were informed in detail about oral azithromycin and alternative treatments and about the conditions of the study. Written consent was obtained in all cases. PPR was graded according to 4 levels of progressive clinical severity<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">7</span></a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">The patients were administered azithromycin 500<span class="elsevierStyleHsp" style=""></span>mg tablets for 12 weeks following the treatment regimen proposed by Bakar et al.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">8</span></a>: 500<span class="elsevierStyleHsp" style=""></span>mg/d for 3 consecutive days a week for a month, followed by 250<span class="elsevierStyleHsp" style=""></span>mg/d (half a 500-mg tablet) for 3 consecutive days a week for another month, followed by 500<span class="elsevierStyleHsp" style=""></span>mg once a week for another month (total treatment duration: 12 weeks).</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Follow-up</span><p id="par0040" class="elsevierStylePara elsevierViewall">Patients were scheduled for 2 main visits to check the short-term effectiveness of oral azithromycin and a series of subsequent visits to check long-term effectiveness. At the baseline visit (visit 1), once the patients had given their informed consent to participate in the study, the severity of their PPR was evaluated and they were started on the established 12-week course of oral azithromycin. The second visit took place 8 weeks after the end of treatment. At this visit, clinical response was graded on a 3-point scale<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">7</span></a> according to improvement from baseline (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). A record was also made of adverse effects and of how the patients rated their improvement (mild, moderate, or marked). <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> summarizes the patients’ demographics and response to conventional treatment and oral azithromycin. The subsequent visits to evaluate the long-term effectiveness of azithromycin were held every 12 weeks. The results of the evaluation (recurrence of inflammatory lesions, number of weeks without inflammatory lesions, and response to reintroduction with oral azithromycin in patients who experienced recurrence) are summarized in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall">Sixteen patients (9 women and 7 men) with a mean age of 47 years (range, 25-82 years) were included. Conventional PPR treatment had resulted in clinical deterioration in 6 cases (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A and <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A). The remaining 10 patients had shown an initial improvement but the lesions returned within 8 weeks of stopping treatment.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">The individual levels of clinical response at 8 weeks are shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>. All 16 patients improved following treatment with oral azithromycin. At the baseline visit, 9 patients had stage II disease, 6 patients had stage III disease (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A and 2A), and 1 patient had stage IV disease. At the second visit, 8 weeks after the end of treatment, 14 patients (87.5%) showed faint or no residual erythema and complete clearance of papules and/or pustules (+++) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B and 2B). The other 2 patients showed a marked reduction in facial erythema and a significant reduction in the number of papules and/or pustules (++).</p><p id="par0055" class="elsevierStylePara elsevierViewall">None of the patients described their improvement as mild. Fourteen patients (87.5%) considered that that they had undergone a marked improvement, while 2 (12.5%) considered that they had undergone a moderate improvement.</p><p id="par0060" class="elsevierStylePara elsevierViewall">No new inflammatory lesions (papules or pustules) were observed at the follow-up visit 8 weeks after treatment completion in 14 patients (87.5%). The reintroduction of oral azithromycin in the 2 patients who did experience recurrence resolved the lesions in both cases (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).</p><p id="par0065" class="elsevierStylePara elsevierViewall">Two patients (12.5%) reported adverse gastrointestinal effects but these did not lead to treatment discontinuation.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0070" class="elsevierStylePara elsevierViewall">Azithromycin is a macrolide antibiotic that has been in use since the 1980s. It is a widely used antibiotic that is typically used to treat a range of infections, including bronchitis, pneumonia, otitis, and sexually transmitted infections.</p><p id="par0075" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Demodex folliculorum</span>,<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">9</span></a><span class="elsevierStyleItalic">Chlamydia pneumoniae</span>,<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">10</span></a><span class="elsevierStyleItalic">Helicobacter pylori</span>,<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">11</span></a> and intestinal bacteria overgrowth have all been implicated in the etiology and pathogenesis of rosacea.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">12</span></a> Environmental stress can also give rise to the overproduction of reactive oxygen species, activating the inflammatory cascade.<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">13,14</span></a> Azithromycin appears to have anti-inflammatory in addition to antibiotic properties,<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">15</span></a> as it blocks the formation of reactive oxygen species, explaining its usefulness in the treatment of PPR.<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">16,17</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Although the recommendation to use azithromycin in the treatment of PPR is based on level B evidence, compared with level A for doxycycline,<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">1,18</span></a> azithromycin has proven to be as effective as doxycycline in this setting,<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">5</span></a> and as such may be a useful option for patients who experience adverse effects or who do not respond to conventional treatment.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">19</span></a> It is also important to note that there are a substantial number of patients who experience clinical deterioration during conventional treatment,<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">6</span></a> possibly due to acquired tetracycline resistance.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">20</span></a> All the patients in our study had received conventional treatment before being treated with azithromycin; 37.5% had experienced a worsening of their PPR during treatment while the remaining 62.5% had experienced early recurrence (appearance of new inflammatory lesions in the 8 weeks after stopping treatment). Azithromycin has been found to be a very effective treatment for PPR in isolated case studies<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">6,21,22</span></a> and series.<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">7,8,23,24</span></a> In our series, 8 weeks after finishing azithromycin, 87.5% of patients had only faint or no facial erythema and their papules and pustules had completely disappeared. The remaining 12.5% experienced a marked reduction in facial redness and a significant reduction in the number of papules and/or pustules. Our series included a 44-year-old man who had had persistent solid facial edema (Morbihan disease) for 10 years that had been treated with oral doxycycline,<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">25</span></a> oral isotretinoin,<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">26</span></a> and oral ivermectin.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">4</span></a> The rest of his history was unremarkable. His manifestations had worsened with all 3 treatments, but the use of oral azithromycin led to the complete disappearance of the eyebrow swelling and inflammatory lesions. Just 2 patients (12.5%) experienced recurrence of the inflammatory lesions (papules and/or pustules) in the long-term follow-up and they both responded to the reintroduction of oral azithromycin.</p><p id="par0085" class="elsevierStylePara elsevierViewall">It is important to recall that tetracyclines are contraindicated in pregnant women. Azithromycin is a category B pregnancy drug according to the US Food and Drug Administration and it has achieved satisfactory clinical results, without adverse effects, in pregnant women with PPR.<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">27</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Azithromycin offers pharmacokinetic advantages over conventional treatments for the treatment of rosacea, including rapid uptake by cells and sustained tissue concentrations.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">28</span></a> These advantages reduce the frequency of administration and as such increase the chances of treatment adherence.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">6</span></a> Azithromycin also has a lower rate of adverse effects than tetracyclines,<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">29</span></a> although low-dose doxycycline (40<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h) has a similar effectiveness to standard-dose doxycycline (100<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h), in addition to fewer adverse effects.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">18</span></a> It is important to be familiar with the proarrhythmogenic potential of azithromycin, as the drug has been linked to QT-interval prolongation. In 1 study, the use of azithromycin to treat infections other than PPR for 5 consecutive days in patients with a high baseline cardiovascular risk was associated with a small increase in cardiovascular deaths.<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">30</span></a> Compared with amoxicillin, azithromycin therapy over 5 days was estimated to cause 47 additional cardiovascular deaths for each million courses of treatment; the corresponding figure for patients with a high risk of cardiovascular disease was 245.<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">30</span></a> A recent meta-analysis of observational studies did not find antibiotic therapy with azithromycin over 5 days to be associated with an increased risk of death in the younger population (hazard ratio [HR], 0.95; 95% CI, 0.66-1.09), although an increased risk was observed in the older population (HR, 1.64; 95% CI, 1.23-2.19).<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">31</span></a> It would therefore seem advisable to use treatments other than azithromycin in elderly patients with PPR or in patients with known heart disease, as they may be more susceptible to the drug's arrhythmogenic effects. None of the patients in our study had known heart disease (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). Two were aged over 65 years and neither of them developed adverse cardiovascular effects. The only adverse effects reported in the group were gastrointestinal complaints (epigastralgia and diarrhea in 2 patients [12.5%]). In both cases, the effects were mild, resolved spontaneously, and did not lead to treatment discontinuation.</p><p id="par0095" class="elsevierStylePara elsevierViewall">There are a number of very interesting studies analyzing the possible link between long-term macrolide treatment and bacterial resistance in the field of pulmonology, where azithromycin, thanks to its anti-inflammatory, immunomodulatory, and antibacterial properties, has been associated with reduced exacerbation frequency, reduced sputum volume, and improved lung function.<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">32</span></a> Although we used the treatment regimen proposed by Bakar et al.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">8</span></a> (500<span class="elsevierStyleHsp" style=""></span>mg/d 3 days a week for a month followed by 250<span class="elsevierStyleHsp" style=""></span>mg/d 3 days a week for a month, and finally 500<span class="elsevierStyleHsp" style=""></span>mg/d once a week for a month (total of 3 months), longer regimens have been described for azithromycin in patients with bronchiectasis (250 or 500<span class="elsevierStyleHsp" style=""></span>mg/d 3 or 7 times a week for 6–12 months).<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">32</span></a> Macrolide-resistant commensal bacteria that can be transmitted within the community (e.g., oropharyngeal streptococci) have been detected in patients with bronchiectasis. Patients treated with azithromycin for 5 to 12 months have been found to have a higher proportion of macrolide-resistant <span class="elsevierStyleItalic">Streptococcus pneumoniae</span>, although there does not appear to be a risk of domestic transmission in such cases. Finally, there have been reports of azithromycin resistance in isolated <span class="elsevierStyleItalic">S pneumoniae</span> strains after 6 months of treatment. More studies are needed to understand the as yet unclear clinical significance of increased bacterial resistance in long-term therapy with azithromycin.<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">32</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Our study has some limitations, including the fact that we did not calculate a sample size in advance, use a comparative group, or perform microbiologic or histologic studies of the inflammatory lesions.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conclusions</span><p id="par0105" class="elsevierStylePara elsevierViewall">Although more randomized controlled trials are needed to compare oral azithromycin and doxycycline, azithromycin has been shown to be an effective short-term and long-term treatment for PPR. In addition, it has a good safety profile and can therefore be considered an alternative for treating refractory PPR.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflicts of Interest</span><p id="par0110" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1066779" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and method" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1014544" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1066780" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y método" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1014543" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and Methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Design" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Inclusion and Exclusion Criteria" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Follow-up" ] ] ] 6 => array:2 [ "identificador" => "sec0030" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflicts of Interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-10-07" "fechaAceptado" => "2018-02-04" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1014544" "palabras" => array:3 [ 0 => "Papulopustular rosacea" 1 => "Azithromycin" 2 => "Treatment" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1014543" "palabras" => array:3 [ 0 => "Rosácea papulopustulosa" 1 => "Azitromicina" 2 => "Tratamiento" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Oral tetracyclines and topical antibiotics have been used to treat papulopustular rosacea (PPR) for years, but it is not uncommon to find patients who do not respond to this standard treatment. In such refractory cases, oral azithromycin has proven to be an effective option.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and method</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We conducted a prospective pilot study of 16 patients with PPR who were treated with oral azithromycin after a lack of response to oral doxycycline and metronidazole gel. At the first visit, the patients were assessed for baseline severity of PPR on a 4-point clinical scale and started on oral azithromycin. At the second visit, response to treatment in terms of improvement from baseline was evaluated on a 3-point scale. Patients were then scheduled for follow-up visits every 12 weeks to assess long-term effectiveness.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">All 16 patients experienced an improvement in their PPR following treatment with oral azithromycin. Eight weeks after completion of treatment, 14 patients (87.5%) showed complete or almost complete recovery (slight or no residual redness and complete clearance of papules and pustules). Only 2 patients experienced a new episode of inflammatory PPR lesions during follow-up.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The findings of this pilot study suggest that oral azithromycin could be a very effective short-term and long-term treatment for RPP resistant to conventional treatment.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and method" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El tratamiento de la rosácea papulopustulosa (RPP) ha consistido durante años en el uso de tetraciclinas orales y antibióticos tópicos. Pero no es infrecuente encontrar casos de RPP resistentes al tratamiento convencional. Azitromicina oral ha demostrado ser una opción eficaz para estos pacientes no respondedores.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y método</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se realizó un estudio piloto prospectivo con 16 pacientes con RPP no respondedores al tratamiento convencional (doxiciclina oral y metronidazol gel) que recibieron tratamiento con azitromicina oral. En la visita inicial (visita 1) se realizó una valoración basal del estadio clínico de la RPP, según 4 niveles de gravedad progresiva, y se inició tratamiento con azitromicina oral. A las 8 semanas de finalizar el tratamiento (visita 2) se evaluó la respuesta clínica según 3 niveles de mejoría respecto al estadio clínico basal. Posteriormente, para evaluar la eficacia de azitromicina oral a largo plazo, se realizaron visitas periódicas cada 12 semanas.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Todos los pacientes que recibieron tratamiento con azitromicina oral mejoraron de su RPP. A las 8 semanas de finalizar el tratamiento se objetivó un eritema facial residual débil o nulo, con desaparición completa de las pápulas y/o pústulas en el 87,5% de los pacientes. En cuanto al mantenimiento de la eficacia a largo plazo, únicamente 2 pacientes presentaron una recidiva de lesiones inflamatorias de RPP.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Los resultados de nuestro estudio evidencian que azitromicina oral podría ser un fármaco de gran eficacia a corto y largo plazo para el manejo de aquellos casos de RPP resistentes al tratamiento convencional.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y método" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as: Lova Navarro M, Sánchez-Pedreño Guillen P, Victoria Martínez AM, Martínez Menchón T, Corbalán Vélez R, Frías Iniesta J. Rosácea papulopustulosa: respuesta al tratamiento con azitromicina oral. Actas Dermosifiliogr. 2018;109:529–535.</p>" ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1205 "Ancho" => 1733 "Tamanyo" => 226777 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">A, Increase in number of papules and pustules during conventional treatment. B, Appearance 8 weeks after finishing treatment with oral azithromycin.</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" => 1099 "Ancho" => 1733 "Tamanyo" => 228744 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">A, Clinical deterioration after treatment with oral doxycycline. B, Complete resolution of inflammatory lesions, with just residual erythema, after treatment with oral azithromycin.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Clinical Stage \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">Clinical Signs \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">I \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Facial erythema with absence of papules and pustules \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Facial erythema with 1–12 papules and/or pustules \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Facial erythema with > 20 papules and/or pustules \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Facial erythema with papules and/or pustules and persistent solid edema (Morbihan disease) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1819384.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Adapted from Fernandez-Obregon.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">7</span></a></p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Clinical Stages of Papulopustular Rosacea<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></p>" ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Level of Clinical Response \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">Clinical Signs \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Reduction in facial erythema with no changes in the number of papules and/or pustules \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Marked reduction in facial erythema and significant reduction in the number of papules and/or pustules \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Faint or no residual facial erythema with complete disappearance of papules and pustules \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1819381.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Adapted from Fernandez-Obregon.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">7</span></a></p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Levels of Clinical Response to Treatment With Oral Azithromycin in Patients With Papulopustular Rosacea<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a></p>" ] ] 4 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient \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">Sex \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">Age, y \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">Response to Conventional Treatment \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">Clinical Stage at Week 0 \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">Clinical Response 8 Weeks After Completion of Oral Azithromycin Therapy \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">Adverse Effects of Azithromycin \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">Overall Improvement According to Patient \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Woman \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Early recurrence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Marked \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Woman \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clinical deterioration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Marked \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Woman \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clinical deterioration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Epigastralgia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Marked \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Woman \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clinical deterioration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Marked \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Man \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Early recurrence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Marked \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Woman \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Early recurrence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Marked \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Man \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Early recurrence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Marked \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Man \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Early recurrence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Marked \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Woman \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Early recurrence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Diarrhea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moderate \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Man \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">82 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Early recurrence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moderate \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Man \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Early recurrence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Marked \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Woman \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clinical deterioration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Marked \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Woman \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clinical deterioration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Marked \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Man \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Early recurrence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Marked \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Woman \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Early recurrence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Marked \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Man \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clinical deterioration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">IV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Marked \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1819382.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Demographic Characteristics, Response to Conventional Treatment, and Changes in Clinical Staging in Patients With Papulopustular Rosacea Treated With Oral Azithromycin.</p>" ] ] 5 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient \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">Recurrence of Inflammatory Lesions \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">No. of Weeks Without Inflammatory Lesions \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">Response to Reintroduction of Oral Azithromycin \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">68 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">- \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1819383.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Long-term Clinical Outcomes in Patients With Papulopustular Rosacea Following Treatment With Oral Azithromycin.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:32 [ 0 => array:3 [ "identificador" => "bib0165" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Swiss S1 guideline for the treatment of rosacea" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Anzengruber" 1 => "J. Czernielewski" 2 => "C. Conrad" 3 => "L. Feldmeyer" 4 => "N. Yawalkar" 5 => "P. Häusermann" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/jdv.14349" "Revista" => array:6 [ "tituloSerie" => "J Eur Acad Dermatol Venereol." "fecha" => "2017" "volumen" => "31" "paginaInicial" => "1775" "paginaFinal" => "1791" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28833645" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0170" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Systemic isotretinoin in the treatment of rosacea - Doxycycline- and placebo-controlled, randomized clinical study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Gollnick" 1 => "U. Blume-Peytavi" 2 => "E.L. Szabó" 3 => "K.G. Meyer" 4 => "P. Hauptmann" 5 => "G. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 10 | 35 | 45 |
| 2024 Octubre | 122 | 143 | 265 |
| 2024 Septiembre | 136 | 120 | 256 |
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| 2024 Febrero | 150 | 102 | 252 |
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| 2023 Noviembre | 305 | 56 | 361 |
| 2023 Octubre | 238 | 62 | 300 |
| 2023 Septiembre | 206 | 68 | 274 |
| 2023 Agosto | 252 | 22 | 274 |
| 2023 Julio | 226 | 64 | 290 |
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| 2023 Abril | 327 | 42 | 369 |
| 2023 Marzo | 293 | 58 | 351 |
| 2023 Febrero | 231 | 40 | 271 |
| 2023 Enero | 195 | 55 | 250 |
| 2022 Diciembre | 185 | 66 | 251 |
| 2022 Noviembre | 94 | 35 | 129 |
| 2022 Octubre | 133 | 45 | 178 |
| 2022 Septiembre | 190 | 56 | 246 |
| 2022 Agosto | 187 | 43 | 230 |
| 2022 Julio | 141 | 41 | 182 |
| 2022 Junio | 119 | 43 | 162 |
| 2022 Mayo | 272 | 53 | 325 |
| 2022 Abril | 269 | 55 | 324 |
| 2022 Marzo | 263 | 75 | 338 |
| 2022 Febrero | 191 | 45 | 236 |
| 2022 Enero | 202 | 91 | 293 |
| 2021 Diciembre | 123 | 63 | 186 |
| 2021 Noviembre | 139 | 65 | 204 |
| 2021 Octubre | 215 | 81 | 296 |
| 2021 Septiembre | 183 | 62 | 245 |
| 2021 Agosto | 221 | 51 | 272 |
| 2021 Julio | 171 | 44 | 215 |
| 2021 Junio | 281 | 49 | 330 |
| 2021 Mayo | 324 | 63 | 387 |
| 2021 Abril | 1181 | 163 | 1344 |
| 2021 Marzo | 758 | 50 | 808 |
| 2021 Febrero | 423 | 64 | 487 |
| 2021 Enero | 386 | 40 | 426 |
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| 2020 Noviembre | 243 | 53 | 296 |
| 2020 Octubre | 294 | 35 | 329 |
| 2020 Septiembre | 268 | 35 | 303 |
| 2020 Agosto | 251 | 38 | 289 |
| 2020 Julio | 276 | 32 | 308 |
| 2020 Junio | 229 | 54 | 283 |
| 2020 Mayo | 246 | 40 | 286 |
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| 2020 Febrero | 5 | 0 | 5 |
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