Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenopathy Syndrome and Vitamin D: A Possible Treatment Option?

array:23 ["pii" => "S2173574316300703" "issn" => "21735743" "doi" => "10.1016/j.reumae.2015.11.015" "estado" => "S300" "fechaPublicacion" => "2016-11-01" "aid" => "851" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología" "copyrightAnyo" => "2015" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Reumatol Clin. 2016;12:363-4" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1346 "formatos" => array:3 [ "EPUB" => 60 "HTML" => 1005 "PDF" => 281 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S1699258X15001928" "issn" => "1699258X" "doi" => "10.1016/j.reuma.2015.11.006" "estado" => "S300" "fechaPublicacion" => "2016-11-01" "aid" => "851" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Reumatol Clin. 2016;12:363-4" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 6038 "formatos" => array:3 [ "EPUB" => 185 "HTML" => 4227 "PDF" => 1626 ] ] "es" => array:11 [ "idiomaDefecto" => true "cabecera" => "Carta al Editor" "titulo" => "Síndrome de fiebre periódica, estomatitis aftosa, faringitis y adenopatías y vitamina D. ¿Una posible opción terapéutica?" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "363" "paginaFinal" => "364" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Periodic fever, aphtous stomatitis, pharyngitis and adenopathy syndrome and vitamin D: A possible treatment option?" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1441 "Ancho" => 2989 "Tamanyo" => 167790 ] ] "descripcion" => array:1 [ "es" => "Evolución de la paciente en las diferentes formas de enfermedad y tras el inicio del tratamiento con colecalciferol." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Angela Rico Rodes, Gema Sabrido Bermúdez, Alicia Llombart Vidal, Pedro Jesús Alcalá Minagorre" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Angela" "apellidos" => "Rico Rodes" ] 1 => array:2 [ "nombre" => "Gema" "apellidos" => "Sabrido Bermúdez" ] 2 => array:2 [ "nombre" => "Alicia" "apellidos" => "Llombart Vidal" ] 3 => array:2 [ "nombre" => "Pedro Jesús" "apellidos" => "Alcalá Minagorre" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173574316300703" "doi" => "10.1016/j.reumae.2015.11.015" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574316300703?idApp=UINPBA00004M" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X15001928?idApp=UINPBA00004M" "url" => "/1699258X/0000001200000006/v1_201610280501/S1699258X15001928/v1_201610280501/es/main.assets" ] ] "itemAnterior" => array:19 [ "pii" => "S2173574316300764" "issn" => "21735743" "doi" => "10.1016/j.reumae.2016.07.001" "estado" => "S300" "fechaPublicacion" => "2016-11-01" "aid" => "860" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "cor" "cita" => "Reumatol Clin. 2016;12:362-3" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 938 "formatos" => array:3 [ "EPUB" => 56 "HTML" => 570 "PDF" => 312 ] ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "Letter to the Editor" "titulo" => "Spondylodiscitis Without Endocarditis Caused by Streptoccocus mitis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "362" "paginaFinal" => "363" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Espondilodiscitis sin endocarditis causada por Streptococcus mitis" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Águeda Prior-Español, Lourdes Mateo, Melania Martínez-Morillo, Anne Riveros-Frutos" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Águeda" "apellidos" => "Prior-Español" ] 1 => array:2 [ "nombre" => "Lourdes" "apellidos" => "Mateo" ] 2 => array:2 [ "nombre" => "Melania" "apellidos" => "Martínez-Morillo" ] 3 => array:2 [ "nombre" => "Anne" "apellidos" => "Riveros-Frutos" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S1699258X15002090" "doi" => "10.1016/j.reuma.2015.11.014" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X15002090?idApp=UINPBA00004M" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574316300764?idApp=UINPBA00004M" "url" => "/21735743/0000001200000006/v1_201611050033/S2173574316300764/v1_201611050033/en/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "Letter to the Editor" "titulo" => "Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenopathy Syndrome and Vitamin D: A Possible Treatment Option?" "tieneTextoCompleto" => true "saludo" => "To the Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "363" "paginaFinal" => "364" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Angela Rico Rodes, Gema Sabrido Bermúdez, Alicia Llombart Vidal, Pedro Jesús Alcalá Minagorre" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Angela" "apellidos" => "Rico Rodes" "email" => array:1 [ 0 => "angelarico89@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Gema" "apellidos" => "Sabrido Bermúdez" ] 2 => array:2 [ "nombre" => "Alicia" "apellidos" => "Llombart Vidal" ] 3 => array:2 [ "nombre" => "Pedro Jesús" "apellidos" => "Alcalá Minagorre" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Pediatría, Hospital General Universitario de Alicante, Alicante, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Síndrome de fiebre periódica, estomatitis aftosa, faringitis y adenopatías y vitamina D. ¿Una posible opción terapéutica?" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1441 "Ancho" => 2989 "Tamanyo" => 160607 ] ] "descripcion" => array:1 [ "en" => "Course of the disease in different stages before and after treatment with cholecalciferol." ] ] ] "textoCompleto" => "PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis and adenitis), or Marshall syndrome,<a class="elsevierStyleCrossRef" href="#bib0050">1</a> is an autoinflammatory disease with no known genetic basis. It predominantly affects patients in the first decade of life. It is characterized by recurrent episodes of high fever of 3–6 days’ duration, accompanied by symptoms that define the condition: pharyngitis, cervical adenitis and aphthous stomatitis. The diagnosis is based on the clinical findings, and is reaffirmed by the elevation in acute phase reactants during the attacks, which returns to normal during asymptomatic periods, and negative results on microbiological tests. Although the episodes become increasingly less frequent until complete remission is achieved, the recurrence of the flares has a negative effect on the quality of life of the patient. The therapeutic options may have certain controversial aspects. Oral corticosteroids are the treatment of choice to resolve the attacks. However, after their use, an increase in the frequency of recurrence of the episodes has been reported.<a class="elsevierStyleCrossRef" href="#bib0055">2</a> Tonsillectomy is performed in cases of refractory disease, but its use is questionable, given that the majority of the patients eventually achieve complete remission. Different drugs, like cimetidine and colchicine, have been employed as prophylaxis in the attempt to reduce the number and severity of the episodes.<a class="elsevierStyleCrossRef" href="#bib0060">3</a> In recent years, a possible relationship between PFAPA syndrome and low serum vitamin D levels is being studied, and the question has been raised as to whether treatment with this vitamin could modify the course of the disease.<a class="elsevierStyleCrossRef" href="#bib0065">4</a>We report the case of a 32-month-old girl with a previous history of multiple visits to the emergency department due to episodes of fever, vomiting and recurrent tonsillitis, which occurred every 6–8 weeks. During these episodes, she had a transient elevation of acute phase reactants (maximum C-reactive protein: 15.39mg/dL) and of leukocytes of up to 15,000/μL with 85% neutrophils, and negative microbiological tests. As PFAPA syndrome was suspected, in one of the flares, she was given a single dose of oral prednisolone (1mg/kg/dose) as a diagnostic-therapeutic test, and the symptoms resolved immediately. It was observed that, after several flares in which she was treated with corticosteroids, the episodes became increasingly frequent. The serum 25-OH-vitamin D level was determined, and was found to be deficient (23.7ng/mL). Treatment was begun with 400IU of cholecalciferol and was maintained until the patient achieved a normal serum vitamin D level (40ng/mL). Since the initiation of treatment she has experienced a reduction in the number and severity of the episodes (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), and had only 2 mild attacks over the following 12 months.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>In recent years, we have begun to realize the importance of the role of vitamin D as an immune modulator.<a class="elsevierStyleCrossRef" href="#bib0070">5</a> Several epidemiological studies have focused on determining the correlation between vitamin D deficiency and the risk of inflammatory diseases, including allergic and autoimmune disorders,<a class="elsevierStyleCrossRefs" href="#bib0075">6,7</a> and the possibility that vitamin D could be a therapeutic option in some of these diseases is being taken into consideration.<a class="elsevierStyleCrossRef" href="#bib0085">8</a> Uncontrolled studies have found that, in patients with PFAPA, vitamin D therapy reduces the number, duration and severity of the episodes.<a class="elsevierStyleCrossRef" href="#bib0090">9</a> However, there are no clinical trials comparing vitamin D with other therapeutic options or placebo. With our current level of knowledge, it is impossible to determine whether the favorable outcome is due to the treatment or to the natural course of the disease. Moreover, the dose of vitamin D and the required duration of treatment have yet to be defined. Therefore, in our patient, we opted for a standard dose until her serum 25-OH-vitamin D level had returned to normal. Despite these limitations, the use this therapy can be considered in patients with PFAPA with vitamin D deficiency, above all, because of its safety profile as compared to other therapeutic alternatives." "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Rico Rodes A, Sabrido Bermúdez G, Llombart Vidal A, Alcalá Minagorre PJ. Síndrome de fiebre periódica, estomatitis aftosa, faringitis y adenopatías y vitamina D. ¿Una posible opción terapéutica? Reumatol Clin. 2016;12:363–364." ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1441 "Ancho" => 2989 "Tamanyo" => 160607 ] ] "descripcion" => array:1 [ "en" => "Course of the disease in different stages before and after treatment with cholecalciferol." ] ] ] "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" => "Syndrome of periodic fever, pharyngitis, and aphthous stomatitis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "G.S. Marshall" 1 => "K.M. Edwards" 2 => "J. Butler" 3 => "A.R. Lawton" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Pediatr" "fecha" => "1987" "volumen" => "110" "paginaInicial" => "43" "paginaFinal" => "46" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3794885" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0055" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A clinical review of 105 patients with PFAPA (a periodic fever syndrome)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "H.M. Feder" 1 => "J.C. Salazar" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Acta Pediatr" "fecha" => "2010" "volumen" => "99" "paginaInicial" => "178" "paginaFinal" => "184" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0060" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Colchicine prophylaxis for frequent periodic fever, aphthous stomatitis, pharyngitis and adenitis episodes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "D. Tasher" 1 => "M. Stein" 2 => "I. Dalal" 3 => "E. Somekh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1651-2227.2008.00837.x" "Revista" => array:6 [ "tituloSerie" => "Acta Paediatr" "fecha" => "2008" "volumen" => "97" "paginaInicial" => "1090" "paginaFinal" => "1092" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18462461" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0065" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D linked to PFAPA syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Mahamid" 1 => "K. Agbaria" 2 => "A. Mahamid" 3 => "W. Nseir" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ijporl.2012.11.027" "Revista" => array:6 [ "tituloSerie" => "Int J Pediatr Otorhinolaryngol" "fecha" => "2013" "volumen" => "77" "paginaInicial" => "362" "paginaFinal" => "364" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23246421" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0070" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The implication of vitamin D and autoimmunity: a comprehensive review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P.S. Leung" 1 => "I.E. Adamopoulos" 2 => "M.E. Gershwin" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Rev Allergy Immunol" "fecha" => "2013" "volumen" => "45" "paginaInicial" => "217" "paginaFinal" => "226" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0075" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Does vitamin D affect risk of developing autoimmune disease? A systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.A. Kriegel" 1 => "J.E. Manson" 2 => "K.H. Costenbader" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.semarthrit.2010.07.009" "Revista" => array:6 [ "tituloSerie" => "Semin Arthritis Rheum" "fecha" => "2011" "volumen" => "40" "paginaInicial" => "512" "paginaFinal" => "531" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21047669" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0080" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D in systemic and organ-specific autoimmune diseases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "N. Agmon-Levin" 1 => "E. Theodor" 2 => "R.M. Segal" 3 => "Y. Shoenfeld" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Rev Aller Immunol" "fecha" => "2013" "volumen" => "45" "paginaInicial" => "256" "paginaFinal" => "266" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0085" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Can supplementation with vitamin D reduce the risk or modify the course of autoimmune diseases? A systematic review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Antico" 1 => "M. Tampoia" 2 => "R. Tozzoli" 3 => "N. Bizzaro" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.autrev.2012.07.007" "Revista" => array:6 [ "tituloSerie" => "Autoimmun Rev" "fecha" => "2012" "volumen" => "12" "paginaInicial" => "127" "paginaFinal" => "136" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22776787" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0090" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vitamin D levels and effects of vitamin D replacement in children with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S. Stagi" 1 => "F. Bertini" 2 => "D. Rigante" 3 => "F. Falcini" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Int J Pediatr Otorhinolaryngol" "fecha" => "2014" "volumen" => "78" "paginaInicial" => "964" "paginaFinal" => "968" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735743/0000001200000006/v1_201611050033/S2173574316300703/v1_201611050033/en/main.assets" "Apartado" => array:4 [ "identificador" => "8400" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735743/0000001200000006/v1_201611050033/S2173574316300703/v1_201611050033/en/main.pdf?idApp=UINPBA00004M&text.app=https://reumatologiaclinica.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574316300703?idApp=UINPBA00004M"]