Current Allergy and Clinical Immunology - March 2008

APPROACH TO THE CHILD WITH RECURRENTINFECTIONS – PRESENTATION ANDINVESTIGATION OF PRIMARY IMMUNODEFICIENCYMonika Esser, MMed PaedClinical Immunology & Rheumatology Service,Immunology Unit, NHLS & Stellenbosch University,Department of Pathology, Tygerberg Academic HealthComplex, Tygerberg, South AfricaABSTRACTInfants and children, as part of normal developmentof immune competence, experience and survivemany infections – mostly subclinical – and a fairnumber of clinically apparent infectious illnesses.Mature immunity is generally achieved by the time achild reaches school age. An abnormal number andseverity of infections are the hallmarks of deficientimmunity.The commonest causes of immunodeficiencyworldwide are malnutrition, HIV and immunosuppressive-iatrogenicagents.Primary immunodeficiencies (PIDs), generally theresult of genetic defects, are rare conditions. Theseare suspected when a child or adult suffers fromrecurrent, prolonged, severe or unusual infectionswhich would not normally cause problems inotherwise healthy individuals.Early diagnosis of PID improves quality of life asmany PIDs are treatable. The related morbidity andmortality which inevitably accompanies a delayeddiagnosis can often be prevented. Unfortunatelydelayed diagnosis and its consequences are frequentlyseen in practice in South Africa.Algorithms for detecting PIDs exist for clinical andlaboratory investigations. Guidelines for patient managementare easily accessed via the Internet andantenatal diagnosis and genetic counselling arebecoming a reality. Gene transfer may offer hope forcures eventually.An overview of approach to history, clinical examinationand appropriate laboratory investigation forsuspected diagnosis of PID in children is presented.INTRODUCTIONWith the advent of the African AIDS pandemic the term‘immunodeficiency’ has gained new meaning. Some ofthe infection patterns seen as a result of HIV infectionare similar to those seen in the patient with PID.Cluster Differentiation – CD4 counts have becomecommon knowledge and medical staff are aware ofthe need for HIV testing in the patient with recurrentor unusual infections. But when HIV infection has beenexcluded, there is no evidence of malnutrition, allergieshave been addressed as possible causes, the child hasbeen taken out of the crèche, second-hand smokingCorrespondence: Dr M Esser, Immunology Unit, Department ofPathology, PO Box 19063, Tygerberg 7505, Cape Town, South Africa.Tel. 021-938-5228, fax 021-938-4005, e-mail monika@sun.ac.zahas been avoided and recurrent infections continue,the question of primary or inborn deficiencies as acause should arise. The majority of these present ininfancy with a 5:1 male over female predominancebecause of the X-linked inherited PIDs, but a largenumber are not recognised until adolescence or earlyadulthood.They may occur as frequently as 1/2 000 live births formilder defects 1 and even as frequently as 1/400 in thecase of IgA deficiencies which are asymptomatic in themajority of cases. There are currently more than 120PIDs with known genetic causes – the recent increasein classifications has been facilitated by the completionof the Human Genome Project in April of 2003.Accurate figures for prevalence in South Africa are notavailable but probably approach those quoted internationallyfor the well-recognised syndromes. Unusuallyhigh incidences of late complement deficiencies havehowever been reported by Orren et al. 2 for the Caperegion and other genetic immunodeficiencies particularto the Southern African region may yet be researched.Despite awareness about immunodeficiency related tothe HIV pandemic, the investigation of the child withrecurrent infections is still frequently delayed inSouth Africa, and if diagnosed correctly, is managed suboptimallyin many cases. Even in developed countriessuch as the UK diagnostic delays for antibody deficienciesof a median of 5.5 years in adults and 2.5 years inchildren have been shown. 3 Late diagnosis in this groupof patients is tragic as effective intravenous preparationsof gammaglobulin became available as early as 1980. 4Seamless monitoring is essential but follow-up is frequentlyinterrupted and suboptimal with transfer of theadolescent to the adult service – as happens to manyyoungsters with other chronic illnesses too.WHAT IS UNACCEPTABLE/ABNORMALFOR A CHILD IN TERMS OF RECURRENTINFECTIONS?Most doctors with some years of clinical experiencedevelop a good investigative threshold for this question.It is surprising therefore that the diagnosis of PID isoften equally if not more delayed in more affluentcommunities in South Africa. The easy access to broadspectrumantibiotics, nutritional support – even hyperalimentation,antireflux procedures and the practice ofchanging doctors if all else fails often mark the trail ofa late diagnosis in the face of good health care access.Neglect and lack of resources however may precipitatea more catastrophic course and paradoxically sometimesearlier investigation and diagnosis.Healthy young children may experience up to 6 upperrespiratory tract infections per year and even 10 ormore if exposed to day care, schoolgoing sibs or smoking.5 These infections should clear promptly and in thecase of bacterial infections they should respond rapidlyto antibiotics.While respiratory and gastrointestinal infections arecommon in immunodeficiency, skin infections such asulcerating BCG marks or with organisms such as8 Current Allergy & Clinical Immunology, March 2008 Vol 21, No. 1