Current Allergy and Clinical Immunology - March 2008

More documents

Recommendations

Info

$latex allerGy revisited : a review - Allergy Society of South Africa$

$Cross-reactivity of food allegens with latex - ALLSA$

Fig. 4. Sweat test.Stage 3Lymphocyte phenotyping is requested together withlymphocyte proliferation studies when not already testedin stage 2. Here one can further define lymphocytefunctional problems.The gold standard for lymphocyte proliferation measuresradioactive thymidine uptake of actively dividingcells upon stimulation with mitogens (or new flowmethod) phylo haemagglutinin A (PHA), Con A, proteinA and pokeweed and, where available, antigens(Candida).The patient’s clinical picture is taken into account whendeciding which further investigations to request, suchas neutrophil or other specialised lymphocyte investigations.Where chronic granulomatous disease is suspectedthe neutrophil burst test (flow cytometry) (Fig. 6) is indicated.Stage 4Access to highly specialised stage 4 investigationssuch as enzyme measurements, cytokine studies andgenetic investigations is limited in South Africa.Detailed complement fraction studies, Bruton’s tyrosinekinase (Btk) assays, neutrophil chemotactic/phagocytic assays, leukocyte adhesion studies andCD40 ligand screening are available at specialised laboratories.Following these steps of investigation the laboratoryguides the clinician to the early diagnosis of PID.Early screening in stages 1 and 2 is very cost-effectiveas it identifies most of the commoner antibody deficiencies.An algorithm for suspected antibody deficit is presentedin Figure 7.Fig 5. Complement C6 deficiency.A response to conjugate pneumococcal vaccine or topolyvalent pneumococcal (pure polysaccharide response)vaccine in older children may also be used as afurther screen of antibody production after vaccination.Haemophilus influenzae to b (Hib) vaccine responsecan also be used as a screen for conjugate vaccineresponse.Where appropriate, lymphocyte phenotyping isrequested in stage 2.CD3 (total T cells)CD4 (helper T cells)CD8 (suppressor T cells)CD19 (B cell)CD16 + 56 (NK cell)IgG subclass analysis can be used inselected patients to differentiate deficienciesand to delineate subclassdeficiencies if antibody responses aredefective. Practically these have beenRsuperseded by the antibody responseswhich yield better results for func-0 200 400 600 800 1000FSC-Htional and treatment implications.A total complement screen functionalFile: Data .004evaluation on ice is also included at anSample ID: monika ecoliearlier stage where patients are fromTube: Untitleddistant referral hospitals. More extensiveinvestigations at the initial visit aimX Parameter: FL1-H (Log)Acquisition Date: 21-Feb-06Gated Events: 12379to contain costs of repeat visits.Where certain indicator diseases arepresent (e.g. recurrent Neisserial10infections, indicative of C6 deficiency0 10 1 10 2 10 3 10 4FL1-H(Fig. 5)) complement fractions arerequested.Fig. 6. Neutrophil burst response flow cytometer.Counts SSC-410 40 80 120 160 200 0 200 400 600 800 1000SUMMARYThe above guidelines for history, examination and astructured approach to laboratory investigations shouldbe followed, including baseline:• full blood count and differential count• serum immunoglobulin isotypes• specific antibody studies and T- and B-cell phenotypesData .004 Data .004Counts0 30 60 90 120 150R510 0 10 1 10 2 10 3 10 4FL2-HHistogren StatisticsLog Date Units: Linear ValuesPatient ID: kontrolePanel: Untitled Acquisition Tube LisGate: G5Total Events: 15000Marker Left Right Events % Gated % Total Mean Geo MeanAll 1, 9910 12379 100.00 82.53 196.84 56.79M1 42, 9910 8021 64.80 53.47 299.98 220.11Current Allergy & Clinical Immunology, March 2008 Vol 21, No. 1 11
Recurrent URTI, OM+/– pneumonia orsystemic infections➞Ig levels normal ➞ B-cell number (N) and antibodies (N). Considerother immune defects and cystic fibrosis or ciliarydyskinesia➞ B-cell number (N) but antibodies deficient:selective/antibody deficiencydeficient ➞ B-cell number (N) common variableimmunodeficiency (CVID), CD40 ligand deficiencywith (N) or IgM➞ B cells absent (CD19–,CD20–): X-linkedagammaglobulinaemialow/normal ➞ B cells and specific antibody test normal:possible transient hypogammaglobulinaemia ofinfancy, malabsorption➞URTI – upper respiratory tract infection, OM – otitis mediaFig. 7. Algorithm for recurrent infections with serum immunoglobulin (SeIg) evaluation if antibody deficit is suspected.• when indicated a total complement screen and• neutrophil burst testwill diagnose the majority of the commoner immunodeficienciessuch as the antibody deficiencies, thecomplement disorders and chronic granulomatousdiseaseWhen this outline is followed, most children with PIDsshould be diagnosed adequately enough to decide on adysfunctional category and, very important, to decideon an appropriate treatment plan.Because of the diversity of immune defects and theclinical overlap with the immune competent host,where conditions which occur in immunodeficientpatients are also common in patients with normalimmune systems some clinicians use scoring systemsfor diagnosis of PID. 10Accurate diagnosis is crucial as an incorrect diagnosismay lead to high-risk interventions such as bone marrowtransplants or years of unnecessary and costlytreatment. 11For the diagnosed child the empowerment of theparent with information regarding their child'simmunodeficiency and follow-up is probably one of themost important predictors for better outcome in countrieswith low level of awareness for rare diseases.Support organisations such as PINSA (PrimaryImmunodeficiency Network South Africa) and nationalregistries further assist in creating awareness and supportstrategies with statistics.Other useful contacts include:For immunoglobulin replacement – NationalBioproducts Information Centre – www.nbi-kzn.org.zaFor immunology case histories – Immunopaedia –www.immunopaedia.org.zaDeclaration of conflict of interestThe author declares no conflict of interest.REFERENCES1. Verbsky JW, Grossman WJ. Cellular and genetic basis of primaryimmune deficiencies. Pediatr Clin N Am 2006; 53: 649-684.2. Orren A, Potter PC. Complement component C6 deficiency andsusceptibility to Neisseria meningitidis infections. S Afr Med J2004; 94: 345-346.3. Seymour B, Miles J, Haeney M. Primary antibody deficiency anddiagnostic delay. J Clin Pathol 2005; 58: 546-547.4. Ballow M. Primary immunodeficiency disorders: antibody deficiency.J Allergy Clin Immunol 2002; 109: 581-591.5. Woroniecka M, Ballow M. Office evaluation of children with recurrentinfection. Primary Immune Deficiencies: Presentation,Diagnosis and Management 2000; 47: 1211-1225.6. Jeffrey Modell Foundation Medical Advisory Board. 10 warningsigns of primary immunodeficiency diseases. 4 stages of primaryimmunodeficiency diseases. (Available at: http://www.info4pi.org.Accessed 24 January 2008.)7. Bonilla FA, Bernstein IL, Khan DA, et al. Practice parameter for thediagnosis and management of primary immunodeficiency. AnnAllergy Asthma Immunol 2005; 94: S1-S63.8. Notarangelo L, Casanova J-L, Fischer A, et al. Primary immunodeficiencydiseases: an update. J Allergy Clin Immunol 2004; 114:677-687.9. De Vries E. Patient-centred screening for primary immunodeficiency:a multi-stage diagnostic protocol designed for non-immunologists.Clin Exp Immunol 2006; 145: 204-214.10. Yarmohammadi H, Estrella L, Doucette J, Cunningham-Rundles C.Recognizing primary immune deficiency in clinical practice. ClinVaccine Immunol 2006; 13: 329-332.11. Buckley RH. Primary immunodeficiency or not? Making the correctdiagnosis. J Allergy Clin Immunol 2006; 117: 756-758.12 Current Allergy & Clinical Immunology, March 2008 Vol 21, No. 1
Page 6 and 7: with memory T-cell phenotypes. 18 T
Page 8 and 9: Burkholderia cepacia may be serious
Page 12 and 13: AN UPDATE OF THE PRIMARY ANTIBODYDI
Page 14 and 15: lymphocytes refine the primary anti
Page 16 and 17: ange of haematological problems occ
Page 19 and 20: SEVERE COMBINED IMMUNODEFICIENCY(SC
Page 21 and 22: tinely from all neonates at birth i
Page 23 and 24: tions to the use of antiviral drugs
Page 25 and 26: therapeutic IVIG are complex. In ma
Page 27 and 28: TABLE III. Recommendations for the
Page 29 and 30: 5. Ballow M. Mechanisms of action o
Page 31 and 32: Fig. 2. Surface epidermis with unde
Page 33 and 34: sone). Unfounded steroidophobia is
Page 35 and 36: tant reaction fades by 72 hours. Fo
Page 37 and 38: try worker: case report and review
Page 39 and 40: ➞Step up if needed (first check i
Page 41 and 42: NEWSALLSA hosts a symposium at the
Page 43 and 44: PRODUCT NEWSNEW DESIGN FOR SYMBICOR
Page 45 and 46: PRODUCT NEWSBOEHRINGER INGELHEIM LA
Page 47 and 48: PRODUCT NEWSNASONEX IS NOW INDICATE
Page 49 and 50: PRODUCT NEWSNew Nestlé NAN H.A. 1
Page 51: INSTRUCTIONS FOR AUTHORSCurrent All

Current Allergy and Clinical Immunology - March 2008

Create successful ePaper yourself

Delete template?

Save as template?