Research Letter
Severe repeated anaphylactic reactions to sublingual immunotherapy
V. Vovolis
, L. Kalogiros, D. Mitsias, E. Sifnaios
Corresponding author
Allergy and Immunology Department, Laikon General Hospital, Agiou Thoma 17 St., Athens 11525, Greece
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MW: molecular weight; PC: positive control (botulinum toxin and antibody anti-toxin); Pt: patient reported; NC: negative control (botulinum toxin alone); C1: control 1 (normal individual without previous contact with the toxin); C2: control 2 (responsive patient with previous contact with the toxin); C3: control 3 (responsive patient with previous contact with the toxin).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M.V. Aun, T.M. Chung, K.S. Santos, L.M.R. Battistella, L.V. Rizzo, J. Kalil, P. Giavina-Bianchi" "autores" => array:7 [ 0 => array:2 [ "nombre" => "M.V." "apellidos" => "Aun" ] 1 => array:2 [ "nombre" => "T.M." "apellidos" => "Chung" ] 2 => array:2 [ "nombre" => "K.S." "apellidos" => "Santos" ] 3 => array:2 [ "nombre" => "L.M.R." "apellidos" => "Battistella" ] 4 => array:2 [ "nombre" => "L.V." "apellidos" => "Rizzo" ] 5 => array:2 [ "nombre" => "J." "apellidos" => "Kalil" ] 6 => array:2 [ "nombre" => "P." "apellidos" => "Giavina-Bianchi" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S030105461200167X?idApp=UINPBA00004N" "url" => "/03010546/0000004100000004/v1_201307160011/S030105461200167X/v1_201307160011/en/main.assets" ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Research Letter</span>" "titulo" => "Severe repeated anaphylactic reactions to sublingual immunotherapy" "tieneTextoCompleto" => true "saludo" => "<span class="elsevierStyleItalic">To the Editor</span>," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "279" "paginaFinal" => "281" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "V. Vovolis, L. Kalogiros, D. Mitsias, E. Sifnaios" "autores" => array:4 [ 0 => array:4 [ "nombre" => "V." "apellidos" => "Vovolis" "email" => array:1 [ 0 => "vasvovolis@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "L." "apellidos" => "Kalogiros" ] 2 => array:2 [ "nombre" => "D." "apellidos" => "Mitsias" ] 3 => array:2 [ "nombre" => "E." "apellidos" => "Sifnaios" ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Allergy and Immunology Department, Laikon General Hospital, Agiou Thoma 17 St., Athens 11525, Greece" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Sublingual immunotherapy (SLIT) for allergic rhinitis is a well-established and effective therapy, currently considered to be safer and almost equally effective alternative to classical subcutaneous immunotherapy (SCIT).</p><p id="par0010" class="elsevierStylePara elsevierViewall">Regarding the safety of SLIT, recent meta-analyses and systematic reviews suggest a remarkably safe profile without any severe systemic reactions, anaphylaxis or use of adrenaline in 49 studies, reviewed by Radulovic et al.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> So far, only 11 cases of anaphylaxis to SLIT have been published.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2–7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">We present a case of a 35-year-old female suffering from persistent, perennial rhinoconjunctivitis and well-controlled asthma with seasonal aggravation. Symptoms appeared 15 years ago, and were becoming more severe each year, while symptomatic relief medications had been partly effective during the pollen season.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Sensitivity to <span class="elsevierStyleItalic">Olea europaea</span> pollen, <span class="elsevierStyleItalic">Dermatophagoides pteronyssinus</span> and <span class="elsevierStyleItalic">Dermatophagoides farinae</span> were identified by SPTs and serum s-IgE measurement. SLIT was carried out during the pollen season (in September) with standardised extracts of Sublivac (HAL, Netherlands) (10,000 allergy units/ml, 500<span class="elsevierStyleHsp" style=""></span>AU/drop) <span class="elsevierStyleItalic">Olea europaea</span> and Sublivac <span class="elsevierStyleItalic">D. pteronyssinus</span> 50%, <span class="elsevierStyleItalic">D. farinae</span> 50%.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Induction of immunotherapy was initiated on two consecutive weeks. During the first week SLIT with HDM extract was advanced without any side-effect and the following week we proceeded to SLIT with <span class="elsevierStyleItalic">Olea</span>. The patient was administered the first drop of <span class="elsevierStyleItalic">Olea</span> extract and was attended in our department according to current guidelines. Within 10<span class="elsevierStyleHsp" style=""></span>min, she developed an anaphylactic reaction (flushing, hoarseness, dyspnoea, dizziness and mild hypotension) and was treated with epinephrine, antihistamines and corticosteroids. In every attempt to increase the dose according to ordinary regiment she suffered a severe anaphylactic reaction (in all five reactions). Therefore, we adopted a modified build-up protocol (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>) and educated our patient to use autoinjectable adrenaline (no reaction occurred at home, where the dose remained unchanged).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">The step-up process with SLIT to olive was quite difficult to advance because she could not tolerate more than three drops of extract per day. On the contrary, SLIT to House Dust Mites advanced with no reaction, and the maintenance dose was reached in five days.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Although our patient did not have to withdraw from SLIT, she eventually remained on a lower maintenance dose (3<span class="elsevierStyleHsp" style=""></span>drops/day), because she had got tired and refused to consent to any subsequent dose increase. That maintenance dose proved to be effective, as she reported a 50% decline on symptom-medication score during the next pollen season.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Despite the fact that the safety of SLIT is well-established, adverse reactions may occur, mainly during the build-up phase. Furthermore all previously published reports of anaphylaxis during SLIT, were characterised either by a deviation from international guidelines,<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,3</span></a> or by previous frequent reactions during SCIT.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,6</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">In our case, anaphylactic episodes occurred in-hospital following the first dose and also after any subsequent dose increase, in a young female asthmatic patient lacking any history of anaphylaxis. During the build-up phase, asthma was well controlled and no predicting factor for a subsequent anaphylaxis was present. Despite these reactions, we managed to increase the tolerated dose, by administering premedication (antihistamine p.o.) during the build-up phase, increasing gradually the dose only in-hospital and maintaining the same dose for seven consecutive days at home (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><p id="par0050" class="elsevierStylePara elsevierViewall">The remarkable safety profile of SLIT allowed the recent modification of SLIT schedules, omitting the up-dosing phase and starting with the maintenance dose. However, it seems that there is a subgroup of sensitive patients who need a more conservative build-up schedule in order to avoid a severe anaphylactic reaction.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Although SLIT seems to have an excellent safety profile this does not rule out the possibility of an anaphylactic reaction even if current guidelines have been followed precisely. It is imperative to administer the first dose under medical supervision and be vigilant to immediately recognise any possible systemic reaction. Our case indicates that SLIT schedules with a large dose of allergens, omitting up-dosing phase, may not be safe enough for a minority of high sensitive patients to whom a more gradual dose increase could be necessary. So far, the majority of studies focus mainly on effectiveness of SLIT and, to a lesser extent, on side-effects (usually considered as secondary outcomes). Therefore, more studies primarily focused on adverse reactions to SLIT are needed.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest to declare.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Ethical disclosures</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Patients’ data protection</span><p id="par0065" class="elsevierStylePara elsevierViewall">Confidentiality of data. The authors declare that they have followed the protocols of their work centre on the publication of patient data and that all the patients included in the study have received sufficient information and have given their informed consent in writing to participate in that study.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Right to privacy and informed consent</span><p id="par0070" class="elsevierStylePara elsevierViewall">Right to privacy and informed consent. The authors declare that no patient data appears in this article.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Protection of human subjects and animals in research</span><p id="par0075" class="elsevierStylePara elsevierViewall">Protection of human and animal subjects. The authors declare that no experiments were performed on humans or animals for this investigation.</p></span></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interest" ] 1 => array:3 [ "identificador" => "sec0010" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients’ data protection" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Right to privacy and informed consent" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Protection of human subjects and animals in research" ] ] ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">In-hospital attempts to increase dose during build-up phase, outcomes and self-administered doses at home the subsequent days.</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Dilutions of ordinary regiment were prepared using saline and administered in 30<span class="elsevierStyleHsp" style=""></span>min intervals.</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">AH, antihistamines.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Time \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">Olea</span> regiment administration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Outcome \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Therapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Following administration at home \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Premedication \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Day 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 drop of ordinary regiment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anaphylaxis (flushing, hoarseness, dyspnoea, dizziness and mild hypotension) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Adr sc, H1-AH, H2-AH, C/S iv \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Day 7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Drop dilutions: 1/5, 2/5, 3/5, 5/5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No reaction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">None necessary \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 drop/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">H1-antihistamine p.o. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Day 14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 drops of ordinary regiment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anaphylaxis (flushing, hoarseness, dyspnoea, dizziness and mild hypotension) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Adr sc, H1-AH, H2-AH, C/S iv \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 drop/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">H1-antihistamine p.o. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Day 21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Drop dilutions: 1<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>1/3, 1<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>2/3, 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No reaction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">None necessary \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 drop/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">H1-antihistamine p.o. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Day 28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 drops of ordinary regiment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anaphylaxis (flushing, hoarseness, dyspnoea, dizziness and mild hypotension) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Adr sc, H1-AH, H2-AH, C/S iv \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 drop/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">H1-antihistamine p.o. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Day 35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Drop dilutions: 2<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>1/3, 2<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>2/3, 3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No reaction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">None necessary \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 drop/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">H1-antihistamine p.o. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Day 42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 drops of ordinary regiment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anaphylaxis (flushing, hoarseness, dyspnoea, dizziness and mild hypotension) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Adr sc, H1-AH, H2-AH, C/S iv \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 drop/day \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">H1-antihistamine p.o. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab337087.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Anaphylactic reactions to SLIT – modification of ordinary regiment.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Systematic reviews of sublingual immunotherapy (SLIT)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 4 | 2 | 6 |
| 2024 October | 16 | 6 | 22 |
| 2024 September | 35 | 9 | 44 |
| 2024 August | 28 | 2 | 30 |
| 2024 July | 21 | 11 | 32 |
| 2024 June | 27 | 10 | 37 |
| 2024 May | 34 | 8 | 42 |
| 2024 April | 17 | 11 | 28 |
| 2024 March | 35 | 6 | 41 |
| 2024 February | 34 | 3 | 37 |
| 2024 January | 38 | 9 | 47 |
| 2023 December | 37 | 12 | 49 |
| 2023 November | 33 | 9 | 42 |
| 2023 October | 32 | 8 | 40 |
| 2023 September | 32 | 8 | 40 |
| 2023 August | 33 | 8 | 41 |
| 2023 July | 28 | 7 | 35 |
| 2023 June | 17 | 4 | 21 |
| 2023 May | 22 | 8 | 30 |
| 2023 April | 17 | 10 | 27 |
| 2023 March | 19 | 5 | 24 |
| 2023 February | 17 | 5 | 22 |
| 2023 January | 13 | 6 | 19 |
| 2022 December | 16 | 10 | 26 |
| 2022 November | 14 | 3 | 17 |
| 2022 October | 14 | 9 | 23 |
| 2022 September | 16 | 8 | 24 |
| 2022 August | 15 | 12 | 27 |
| 2022 July | 12 | 9 | 21 |
| 2022 June | 10 | 9 | 19 |
| 2022 May | 14 | 13 | 27 |
| 2022 April | 17 | 8 | 25 |
| 2022 March | 17 | 12 | 29 |
| 2022 February | 6 | 6 | 12 |
| 2022 January | 12 | 8 | 20 |
| 2021 December | 7 | 14 | 21 |
| 2021 November | 10 | 9 | 19 |
| 2021 October | 18 | 14 | 32 |
| 2021 September | 10 | 10 | 20 |
| 2021 August | 6 | 9 | 15 |
| 2021 July | 12 | 21 | 33 |
| 2021 June | 15 | 9 | 24 |
| 2021 May | 16 | 14 | 30 |
| 2021 April | 25 | 19 | 44 |
| 2021 March | 19 | 10 | 29 |
| 2021 February | 8 | 8 | 16 |
| 2021 January | 5 | 7 | 12 |
| 2020 December | 0 | 4 | 4 |
| 2020 November | 0 | 1 | 1 |
| 2020 October | 0 | 3 | 3 |
| 2020 September | 0 | 1 | 1 |
| 2020 August | 0 | 4 | 4 |
| 2020 July | 0 | 2 | 2 |
| 2020 June | 0 | 1 | 1 |
| 2020 May | 0 | 2 | 2 |
| 2020 February | 0 | 1 | 1 |
| 2020 January | 0 | 2 | 2 |
| 2019 December | 0 | 2 | 2 |
| 2019 October | 0 | 3 | 3 |
| 2019 September | 0 | 2 | 2 |
| 2019 June | 0 | 11 | 11 |
| 2019 May | 0 | 32 | 32 |
| 2018 February | 8 | 3 | 11 |
| 2018 January | 7 | 4 | 11 |
| 2017 December | 4 | 1 | 5 |
| 2017 November | 7 | 4 | 11 |
| 2017 October | 3 | 5 | 8 |
| 2017 September | 8 | 3 | 11 |
| 2017 August | 5 | 18 | 23 |
| 2017 July | 9 | 10 | 19 |
| 2017 June | 14 | 17 | 31 |
| 2017 May | 10 | 16 | 26 |
| 2017 April | 10 | 13 | 23 |
| 2017 March | 11 | 4 | 15 |
| 2017 February | 16 | 10 | 26 |
| 2017 January | 10 | 5 | 15 |
| 2016 December | 8 | 9 | 17 |
| 2016 November | 17 | 11 | 28 |
| 2016 October | 24 | 2 | 26 |
| 2016 September | 5 | 4 | 9 |
| 2016 August | 8 | 3 | 11 |
| 2016 July | 5 | 7 | 12 |
| 2016 June | 14 | 8 | 22 |
| 2016 May | 7 | 9 | 16 |
| 2016 April | 9 | 13 | 22 |
| 2016 March | 8 | 19 | 27 |
| 2016 February | 11 | 22 | 33 |
| 2016 January | 10 | 22 | 32 |
| 2015 December | 8 | 13 | 21 |
| 2015 November | 8 | 11 | 19 |
| 2015 October | 9 | 16 | 25 |
| 2015 September | 11 | 8 | 19 |
| 2015 August | 4 | 5 | 9 |
| 2015 July | 3 | 3 | 6 |
| 2015 June | 5 | 6 | 11 |
| 2015 May | 4 | 5 | 9 |
| 2015 April | 9 | 10 | 19 |
| 2015 March | 4 | 8 | 12 |
| 2015 February | 5 | 16 | 21 |
| 2015 January | 18 | 2 | 20 |
| 2014 December | 13 | 7 | 20 |
| 2014 November | 9 | 4 | 13 |
| 2014 October | 15 | 9 | 24 |
| 2014 September | 24 | 3 | 27 |
| 2014 August | 8 | 5 | 13 |
| 2014 July | 15 | 6 | 21 |
| 2014 May | 0 | 2 | 2 |
| 2014 April | 2 | 0 | 2 |
| 2014 March | 35 | 21 | 56 |
| 2014 February | 36 | 14 | 50 |
| 2014 January | 37 | 12 | 49 |
| 2013 December | 34 | 9 | 43 |
| 2013 November | 24 | 14 | 38 |
| 2013 October | 25 | 15 | 40 |
| 2013 September | 26 | 16 | 42 |
| 2013 August | 19 | 9 | 28 |
| 2013 July | 9 | 10 | 19 |
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