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although at times they manifest as autoinflammation or autoimmunity&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1&#44;3</span></a> These less typical presentations may result in delay diagnosis&#44; when early identification has an impact on outcomes&#44; prevents morbidity and reduces mortality in PIDs requiring stem cell transplantation&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In 2012&#44; a specialised clinic was created within our department for follow-up of patients with confirmed PID and screening of patients with suspected PID&#46; From its inception to 2017&#44; the clinic has provided care for 135 children&#44; 57&#37; of who were referred in the past 2 years and 41&#37; in 2017&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Of this total&#44; 57&#37; of patients have PID confirmed by the Department of Immunology of our hospital &#40;77&#47;135&#41; and 15&#37; are still under evaluation &#40;21&#47;135&#41;&#44; while PID was ruled out in the remaining 27&#37; &#40;37&#47;135&#41;&#46; Of the children referred from other hospitals&#44; 78&#37; had a PID &#40;25&#47;32&#41;&#44; as did 50&#37; of children referred from other departments in our hospital &#40;39&#47;79&#41; and 42&#37; of children referred from primary care &#40;8&#47;19&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#46;</span>009&#41;&#46; The reason for referral was severe&#47;recurrent infections in 51&#37; &#40;69&#47;135&#41;&#44; diagnosis of PID in 22&#37; &#40;30&#47;135&#41;&#44; lymphopaenia or hypogammaglobulinaemia in 19&#37; &#40;26&#47;135&#41;&#44; family history of PID in 6&#37; &#40;8&#47;135&#41; and delayed separation of the umbilical cord in 1&#46;4&#37; &#40;2&#47;135&#41;&#46; Before referral&#44; 20&#37; were receiving antibiotic prophylaxis or immunoglobulin replacement therapy &#40;28&#47;135&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarises the diagnosed PIDs&#44; and <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> the characteristics of the patients&#46; A history of consanguinity was present in 9&#37; of patients &#40;6&#47;71&#41;&#46; All children with symptomatic infection by cytomegalovirus &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41; had a PID&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Of all patients with PID&#44; 34&#37; required admission at the time of the first visit &#40;26&#47;75&#41; compared to 11&#37; of patients ultimately found to be healthy &#40;4&#47;37&#41; &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#46;</span>006&#41;&#46; Of the children with PID referred from a different hospital&#44; 68&#37; &#40;17&#47;25&#41; were admitted at the time of the first visit&#44; as were 18&#37; &#40;7&#47;39&#41; of those referred from another department in our hospital and 12&#37; &#40;1&#47;8&#41; of patients referred from primary care &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#46;</span>0001&#41;&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Fifty-seven percent of children with PID required immunoglobulin replacement therapy &#40;42&#47;74&#41; and 41&#37; antibiotic prophylaxis &#40;31&#47;75&#41;&#44; while 36&#37; underwent or require stem cell transplantation &#40;28&#47;77&#41;&#46; The mortality in our study was of 13&#37; &#40;10&#47;77&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Each passing day&#44; we learn of additional genetic abnormalities associated with PIDs&#46; These diseases carry a high morbidity and mortality&#44; especially in cases of delayed diagnosis&#46; Recurrent infection is a frequent reason for consultation and determining which patients require an immunologic evaluation is challenging&#46; A history of consanguinity is a risk factor that should alert clinicians of the possibility of a PID&#46; A recent case series of children with a history of recurrent infection found that 21&#37; had a PID&#44;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">4</span></a> a high prevalence that could be explained by the large proportion of consanguinity &#40;38&#37;&#41;&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">However&#44; infection is not always the initial presentation&#46; In recent years&#44; the classic signs used to detect PIDs have been questioned&#44;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">5</span></a> as they cannot be used to identify patients with PID due to immune dysregulation&#44; who have onset with autoimmunity or inflammation&#46; Fischer et al&#46; have reported that children with PID have a risk that is 830&#44; 80 and 40 times greater of haemolytic anaemia&#44; inflammatory bowel disease and rheumatoid arthritis&#44; respectively&#44; compared to the general paediatric population&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The data suggest that failure to thrive&#44; symptomatic cytomegalovirus infection and a family history of PID are relevant warning signs&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">3&#8211;5</span></a> Patients with more severe disease&#44; referred from hospitals or requiring admission are also at higher risk&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">We have recently observed an increase in the referral of patients&#44; many with well-founded diagnostic suspicion and more than half with a final diagnosis of PID&#46; This is due to the increasing number of cases diagnosed in the Department of Immunology of our hospital and the growing awareness of referring physicians of the existence of this specialised clinic&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Referred patients get appointments in a paediatrics clinic that does not have a waitlist&#46; When the reason for referral is recurrent infection or suspected PID&#44; patients are managed by paediatric specialists and a team of clinical immunologists&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">There are limitations to our findings&#46; Due to the retrospective nature of the analysis&#44; there were incomplete data&#44; as some variables were not documented in the records of some of the patients&#46; Since the study was not multicentric&#44; it contributes a particular perspective of the patients managed in a hospital with specific characteristics&#46; Nevertheless&#44; our findings reflect the increasing need for this type of clinic as a resource for paediatricians&#44; so early and appropriate care can be offered to these children&#44; thus reducing the associated morbidity&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Mill&#225;n-Longo C&#44; Rodr&#237;guez Molino P&#44; del Rosal Rabes T&#44; Corral S&#225;nchez D&#44; M&#233;ndez Echevarr&#237;a A&#46; Utilidad de una consulta especializada en inmunodeficiencias primarias&#46; An Pediatr &#40;Barc&#41;&#46; 2019&#59;91&#58;408&#8211;409&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Personal and family history in children in who PID was confirmed and ruled out&#46;</p>"
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        "fuente" => "<span class="elsevierStyleItalic">Source</span>&#58; Adapted from Picard et al&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">1</span></a>"
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          "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">CID&#44; combined immunodeficiency&#59; SCID&#44; severe combined immunodeficiency&#46;</p>"
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Diagnosed PID&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patients&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">1&#46; Combined IDs</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">50&#37; &#40;39&#47;77&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">SCID</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Adenosine deaminase deficiency&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#947;c deficiency&nbsp;\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="char" valign="\n
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                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>RAG2 deficiency&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>CD3&#948; deficiency&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>DCLRE1C &#40;Artemis&#41; deficiency&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>RAG1 deficiency&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>SCID without molecular confirmation&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " colspan="2" align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>MHC class II deficiency&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>CD40 ligand deficiency&nbsp;\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="char" valign="\n
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                  \t\t\t\t">1&nbsp;\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  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">CID with associated or syndromic features</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Ataxia-telangiectasia&nbsp;\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="char" valign="\n
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                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>DiGeorge syndrome&nbsp;\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="char" valign="\n
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                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Kabuki syndrome&nbsp;\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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Dyskeratosis congenita&nbsp;\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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Wiskott-Aldrich syndrome&nbsp;\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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Cartilage hair hypoplasia&nbsp;\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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Immunodeficiency with multiple intestinal atresias &#40;TTC7A&#41;&nbsp;\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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Calcium channel defects &#40;ORAI-1&#41;&nbsp;\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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Autosomal dominant hyper-IgE syndrome &#40;STAT3&#41;&nbsp;\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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">2&#46; Predominantly antibody deficiencies</span>&nbsp;\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="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&#37; &#40;26&#47;77&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">X-linked agammaglobulinaemia</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleBold">3&#46; Diseases of immune dysregulation</span>&nbsp;\t\t\t\t\t\t\n
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