Diagnosis and treatment
New recommendations for pneumococcal vaccination in patients with autoimmune and inflammatory diseases
Nuevas recomendaciones para la vacunación antineumocócica en pacientes con enfermedades autoinmunitarias e inflamatorias
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Both vaccines induce an immune response mediated by B lymphocytes. Only PCV13 has been shown to produce a T cell-dependent response at the same time. B: B cell; DC: dendritic cell; T: T cell; SCT: subcutaneous tissue.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Streptococcus pneumoniae</span> or pneumococcus is a gram-positive coccus that has an outer capsule formed by polysaccharides which protects it from being removed by the host's phagocytic cells. 91 different pneumococcal serotypes have been identified to date, defined by genetic differences observed in the composition of the capsular polysaccharides.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The most common pneumococcal disease is pneumonia, followed by bacteraemia and meningitis.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">1–3</span></a> The detection of pneumococci in peripheral blood or cerebrospinal fluid occurs more often in children under 2, adults over 65 and in patients who are immunosuppressed due to functional or anatomic asplenia, HIV infection, chronic renal failure, cancer, transplant and immunosuppression by glucocorticoids or other immunomodulatory treatments.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">4</span></a> Among these, we find synthetic and biological disease modifying drugs used to treat diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), spondyloarthropathies (SpA), inflammatory bowel disease and systemic sclerosis (SSc).</p><p id="par0015" class="elsevierStylePara elsevierViewall">Patients with autoimmune and inflammatory diseases are at increased risk of infections, especially those under immunomodulatory treatments.<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">5–9</span></a> The considerable morbidity and mortality associated with invasive infections underscores the importance of pneumococcal prophylaxis, especially in our more susceptible patients. At present, we have 2 inactivated vaccines approved for use in adults, capable of inducing immune response in most pneumococcal serotypes. Both have proven effective in immunocompromised adults, but should not be given at the same time:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">•</span><p id="par0020" class="elsevierStylePara elsevierViewall">PPSV23 Pneumococcal vaccine (<span class="elsevierStyleItalic">Pneumovax</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">®</span></span><span class="elsevierStyleItalic">23, Merck & Co., Inc., New Jersey, NJ, USA</span>): containing 23 purified capsular polysaccharide serotypes (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, 33F). It provides between 3 and 5 years of immunity.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">•</span><p id="par0025" class="elsevierStylePara elsevierViewall">PCV13 Pneumococcal vaccine (<span class="elsevierStyleItalic">Prevenar</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">®</span></span><span class="elsevierStyleItalic">13, Pfizer Inc</span>., New York, NY, USA) containing 13 capsular polysaccharide serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) conjugated covalently to a carrier protein. It is indicated as a single dose.</p></li></ul></p><p id="par0030" class="elsevierStylePara elsevierViewall">From an immunological point of view, response induction against antigens by specific T and B lymphocytes requires activation by antigen presenting cells, mainly dendritic cells. When exposed to antigens, these cells migrate to secondary lymphoid organs, such as lymph nodes and spleen, inducing T and B lymphocyte response.</p><p id="par0035" class="elsevierStylePara elsevierViewall">According to recent studies, the two available vaccines induce an immune response mediated by B lymphocytes. Only PCV13 has shown to obtain a T-cell dependent response, which contributes to B-cell response maturation and the development of long term immune memory (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). As indicated by Jackson et al., the immune response to PCV13 in apparently healthy individuals is more robust than to PPSV23 regarding the formation of antibodies.<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">10,11</span></a> With respect to the sequence of administration of both vaccines in healthy controls, it has been observed that when PPSV23 is administered before PCV13, the immune response induced by PCV13 is reduced, therefore, PCV13 should be administered first in patients who have not been previously vaccinated.<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">11,12</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">The efficacy of a vaccine represents the ability to produce a protective immune response; studies on vaccine efficacy addressing the clinical situation in patients with autoimmune and inflammatory diseases are rare. Furthermore, it should be noted that immune responses determined <span class="elsevierStyleItalic">in vitro</span> do not always correlate with post-vaccination clinical efficacy.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Data on PPSV23 and PCV7, a pneumococcal conjugate vaccine containing 7 serotypes of capsular polysaccharides were included in the EULAR <span class="elsevierStyleItalic">(European League Against Rheumatism)</span> 2011 recommendations, based on a systematic review of the literature between 1966 and 2009.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">13</span></a> Pneumococcal vaccination is recommended in all patients with autoimmune and inflammatory diseases, with or without immunomodulatory therapy. The subsequent humoral response to vaccination can vary and be adequate or slightly reduced in patients with RA, SLE, SpA and SSc, depending on the study assessed. This is observed in patients treated with methotrexate, with or without concomitant administration of anti-tumor necrosis factor drugs.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">13</span></a> Given the depletion of B cells induced by rituximab, it is recommended that patients be vaccinated before the first infusion to avoid reducing its efficacy.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">13</span></a> It has also been reported that patients over 65 years of age produce fewer protective antibodies compared to younger individuals, regardless of the treatment. This could be the result of immune senescence, which also includes impaired ability of B-cells to respond to a new antigenic stimulation.<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">14,15</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">A posteriori</span>, a reduced production of protective antibodies was observed in a study of patients with established RA treated with rituximab and abatacept after pneumococcal vaccination, especially in the case of rituximab.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">16</span></a> Possibly, due to the modulating effect of abatacept on lymphocyte B, pneumococcal vaccination should be encouraged before starting treatment, as it occurs with rituximab. Pneumococcal conjugate vaccine administered during treatment with tocilizumab was associated with a normal antibody production.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">16</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">EULAR 2011 recommendations include no data on PCV13 vaccine, marketed in 2010. Since 2016, and according to the recommendations published by the <span class="elsevierStyleItalic">Advisory Committee on Immunization Practices of the US Centers for Disease Control and Prevention</span> (ACIP), immunocompromised patients should be vaccinated depending on whether they received prior pneumococcal vaccination or not. The aim is to provide a robust production of antibodies against the largest possible number of pathogenic serotypes (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>),<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">17</span></a> although the correlation between detectable concentrations of protective antibodies after vaccination and the incidence of pneumococcal disease in adults is controversial.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">18</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Details about which vaccines the patient has already received should be known, so that the recommendations are suitable for each individual patient, especially before starting immunomodulator therapy. Live attenuated vaccines should be avoided whenever possible in patients under immunomodulatory treatment. Ideally, they should be administered during stable phases of the disease because, while it is true that there have been no studies comparing efficacy and among patients with stable and unstable disease, almost all vaccination studies in patients with autoimmune and inflammatory diseases have been conducted among patients with stable disease.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">13</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">In short, the new pneumococcal vaccination recommendations highlight the need to evaluate and complete the vaccination schedule before starting any immunomodulatory treatment or during stable phases of the disease. Adherence to the guidelines of the ACIP is very important to identify candidates for pneumococcal vaccination, determine the ideal sequence to implement it and reduce the incidence of pneumococcal infections in immunocompromised patients.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">13,17</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interests</span><p id="par0070" class="elsevierStylePara elsevierViewall">DHF: none to declare. RGB: none to declare. LV: Abbvie, Celgene, Roche Farma, Bristol-Myers Squibb, Pfizer, Takeda, UCB, MSD and GSK.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interests" ] 1 => array:2 [ "identificador" => "xack275556" "titulo" => "Acknowledgements" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-09-16" "fechaAceptado" => "2016-10-21" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Hernández-Flórez D, González-Benítez R, Valor L. Nuevas recomendaciones para la vacunación antineumocócica en pacientes con enfermedades autoinmunitarias e inflamatorias. Med Clin (Barc). 2017;148:181–183.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1351 "Ancho" => 2660 "Tamanyo" => 225383 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Effect of intramuscular administration of PCV13 and PPSV23 pneumococcal vaccines. Both vaccines induce an immune response mediated by B lymphocytes. Only PCV13 has been shown to produce a T cell-dependent response at the same time. B: B cell; DC: dendritic cell; T: T cell; SCT: subcutaneous tissue.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "<span class="elsevierStyleItalic">Source</span>: Adapted from Palotta and Rehm.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">17</span></a>" "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1412 "Ancho" => 2468 "Tamanyo" => 192343 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Sequence and administration intervals of PCV13 and PPSV23 pneumococcal vaccines in immunocompromised patients.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:18 [ 0 => array:3 [ "identificador" => "bib0095" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Estimating the burden of pneumococcal pneumonia among adults: a systematic review and meta-analysis of diagnostic techniques" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "AGEDD Adult Pneumococcal Burden Study Team" "etal" => false "autores" => array:5 [ 0 => "M.A. Said" 1 => "H.L. 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