Letter to the Editor
The Possible Combined Action of Different Trigger Agents in Rosacea
Posible acción combinada de los diferentes agentes desencadenantes en la rosácea
G. Ciccarese
, A. Parodi, A. Rebora, F. Drago
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DISSAL, Department of Dermatology, IRCCS San Martino IST, Genoa, Italy
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Ciccarese, A. Parodi, A. Rebora, F. Drago" "autores" => array:4 [ 0 => array:4 [ "nombre" => "G." "apellidos" => "Ciccarese" "email" => array:1 [ 0 => "giuliaciccarese@libero.it" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Parodi" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Rebora" ] 3 => array:2 [ "nombre" => "F." "apellidos" => "Drago" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "DISSAL, Department of Dermatology, IRCCS San Martino IST, Genoa, Italy" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Posible acción combinada de los diferentes agentes desencadenantes en la rosácea" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We read with great interest the paper entitled “Oral ivermectin to treat papulopustular rosacea in a immunocompetent patient.” by Hernández-Martín<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> that prompted us to make some observations and to report our experience. The Author described a patient with papulopustular rosacea that has been considered immunocompetent but it was not specified whether laboratory examinations have been performed to investigate the immune status of the patient (as complete blood count, human immunodeficiency virus test). Moreover, the Author stated that the past medical history of the patient included topical immunomodulators, but without defining the specific drug.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> Due to the only partial and/or transient rosacea improvement after several topical and systemic treatments, Hernández-Martín recommended a single 250<span class="elsevierStyleHsp" style=""></span>μg/kg dose of oral ivermectin leading to complete remission of the rosacea lesions.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> However, the Author did not demonstrate by skin scraping or standardized skin surface biopsy neither the presence nor an excessive number of <span class="elsevierStyleItalic">Demodex folliculorum</span> (DF) mites in the pilosebaceous units to justify the oral antiparasitic therapy.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> It is known that patients with papulopustular rosacea may have a higher density of DF mites on their faces than controls. However, in the absence of any qualitative and quantitative information on DF, it could be hypothesized that ivermectin may have operated through immunomodulating mechanism rather than through a true acaricidal action. The immunomodulatory effect of ivermectin has been reported long ago in mice,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a> and very recently confirmed by Schaller et al.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a> who found, in 20 Caucasian patients with moderate to severe rosacea treated with topical ivermectin for ≥12 weeks, that the gene expression levels LL-37, HBD3 and TNF-α was significantly reduced after and during treatment.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Regrettably, Hernández-Martín<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> neglected that also a DF-related bacterium, <span class="elsevierStyleItalic">Bacillus oleronius</span>, may express antigens that stimulates an inflammatory immune response<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a> and that other different triggers may contribute in the pathogenesis of rosacea, more specifically gastrointestinal disorders like <span class="elsevierStyleItalic">Helicobacter pylori</span> (HP) infection and small intestine bacterial overgrowth (SIBO).<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">6,7</span></a> In two previous studies, we reported our experience on 60 rosacea patients that were followed up for 3 years, in which we have investigated the prevalence of three possible trigger agents: DF (through SSSB on rosacea lesions [test was considered positive for density >5 mites/cm<span class="elsevierStyleSup">2</span>]), HP infections (through urea breath test) and SIBO (through lactulose breath test).<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">8,9</span></a> Recently, we completed the study with a 5-year follow up. Shortly after enrolment, DF was the agent most frequently found (75%) followed by SIBO (67%) and HP infection (13%). HP infection prevailed in patients with erythrosis, SIBO in patients with papulo-pustular rosacea whereas DF was not associated with specific rosacea types. DF was found as the only trigger in 16 patients whereas 29 patients were positive for more than one trigger agent (23 patients had DF<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>SIBO, 4 patients DF<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>HP and 2 patients DF<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>HP<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>SIBO). Patients that proved positive for more than one triggering agent were treated in the following order: DF acaricidal treatment (crotamiton cream once/daily associated with azelaic acid gel once/daily for 3 weeks); antibiotic therapy for SIBO (rifaximin 1200<span class="elsevierStyleHsp" style=""></span>mg/daily for 10 days), antibiotic therapy for HP (rabeprazole 10<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>amoxicillin 1000<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>metronidazole 250<span class="elsevierStyleHsp" style=""></span>mg twice/daily for 2 weeks). The topical therapy for DF was effective in reducing its population and in improving the cutaneous lesions but only 26% of the patients remitted. The 23 patients positive for both DF and SIBO underwent acaricidal treatment but the majority of them (74%) remitted only after rifaximin treatment. Among the 40 exclusively SIBO positive patients treated with rifaximin, 31 remitted, 8 improved and 1 did not. Overall, most of our patients (61%), treated in accordance with the specific causal agent, cleared and had no relapsed in the following 5 years, confirming our previous studies.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">8,9</span></a> In conclusion, we emphasize that the eradication of the underlying trigger agents in rosacea may be crucial in improving the disease and in maintaining the clinical remission over time. However, the search for the presence of SIBO should be done in rosacea patients since its treatment seems to be relevant in improving the disease and maintaining the clinical remission, also when more than one microorganisms are still present.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0050" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tratamiento con ivermectina oral en un paciente inmunocompetente con rosacea pápulo-pustulosa" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Á. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 4 | 10 | 14 |
| 2024 Octubre | 71 | 49 | 120 |
| 2024 Septiembre | 77 | 50 | 127 |
| 2024 Agosto | 82 | 63 | 145 |
| 2024 Julio | 61 | 47 | 108 |
| 2024 Junio | 77 | 35 | 112 |
| 2024 Mayo | 48 | 44 | 92 |
| 2024 Abril | 79 | 23 | 102 |
| 2024 Marzo | 70 | 43 | 113 |
| 2024 Febrero | 63 | 35 | 98 |
| 2024 Enero | 54 | 37 | 91 |
| 2023 Diciembre | 55 | 18 | 73 |
| 2023 Noviembre | 66 | 25 | 91 |
| 2023 Octubre | 76 | 28 | 104 |
| 2023 Septiembre | 38 | 39 | 77 |
| 2023 Agosto | 46 | 9 | 55 |
| 2023 Julio | 50 | 32 | 82 |
| 2023 Junio | 48 | 22 | 70 |
| 2023 Mayo | 57 | 27 | 84 |
| 2023 Abril | 57 | 24 | 81 |
| 2023 Marzo | 56 | 23 | 79 |
| 2023 Febrero | 42 | 27 | 69 |
| 2023 Enero | 49 | 30 | 79 |
| 2022 Diciembre | 46 | 33 | 79 |
| 2022 Noviembre | 24 | 29 | 53 |
| 2022 Octubre | 29 | 20 | 49 |
| 2022 Septiembre | 21 | 34 | 55 |
| 2022 Agosto | 23 | 38 | 61 |
| 2022 Julio | 26 | 34 | 60 |
| 2022 Junio | 26 | 16 | 42 |
| 2022 Mayo | 91 | 35 | 126 |
| 2022 Abril | 79 | 30 | 109 |
| 2022 Marzo | 113 | 38 | 151 |
| 2022 Febrero | 117 | 15 | 132 |
| 2022 Enero | 129 | 34 | 163 |
| 2021 Diciembre | 107 | 37 | 144 |
| 2021 Noviembre | 143 | 43 | 186 |
| 2021 Octubre | 83 | 38 | 121 |
| 2021 Septiembre | 102 | 40 | 142 |
| 2021 Agosto | 112 | 32 | 144 |
| 2021 Julio | 72 | 31 | 103 |
| 2021 Junio | 79 | 33 | 112 |
| 2021 Mayo | 55 | 43 | 98 |
| 2021 Abril | 147 | 63 | 210 |
| 2021 Marzo | 94 | 31 | 125 |
| 2021 Febrero | 88 | 30 | 118 |
| 2021 Enero | 50 | 22 | 72 |
| 2020 Diciembre | 40 | 13 | 53 |
| 2020 Noviembre | 30 | 28 | 58 |
| 2020 Octubre | 19 | 10 | 29 |
| 2020 Septiembre | 28 | 18 | 46 |
| 2020 Agosto | 31 | 17 | 48 |
| 2020 Julio | 23 | 19 | 42 |
| 2020 Junio | 23 | 32 | 55 |
| 2020 Mayo | 49 | 11 | 60 |
| 2020 Abril | 43 | 16 | 59 |
| 2020 Marzo | 27 | 17 | 44 |
| 2020 Febrero | 9 | 0 | 9 |
| 2020 Enero | 4 | 0 | 4 |
| 2019 Diciembre | 8 | 0 | 8 |
| 2019 Noviembre | 4 | 0 | 4 |
| 2019 Septiembre | 4 | 0 | 4 |
| 2019 Agosto | 4 | 0 | 4 |
| 2019 Julio | 8 | 0 | 8 |
| 2019 Junio | 4 | 0 | 4 |
| 2019 Mayo | 6 | 1 | 7 |
| 2019 Abril | 4 | 0 | 4 |
| 2019 Marzo | 2 | 0 | 2 |
| 2019 Febrero | 2 | 0 | 2 |
| 2018 Diciembre | 3 | 0 | 3 |
| 2018 Noviembre | 3 | 0 | 3 |
| 2018 Octubre | 2 | 0 | 2 |
| 2018 Septiembre | 5 | 0 | 5 |
| 2018 Junio | 0 | 1 | 1 |
| 2018 Febrero | 82 | 22 | 104 |
| 2018 Enero | 84 | 35 | 119 |
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