1. Change in Referral Diagnoses and Diagnostic Delay in Hypogammaglobulinaemic Patients. Jiri Litzman Dept. Clin. Immunol. Allergol Masaryk University, Brno, Czech Republic

2. Clinical Manifestation of Immunoglobulin Deficiency Frequent and complicated infections of the respiratory tract. Patients suffer from recurrent attacks of bronchitis, sinusitis, pneumonia, otitis. Infections are caused mainly by encapsulated bacteria: Heamohilus influenzae, Str. pmeumoniae, St. aureus, Pseudomanonas sp. Typical complications are bronchiectasis and/or lung fibrosis.

3. Dept. Clin. Immunol. Allergol. St Anne´s University Hospital in Brno Founded in 1981. Tertiary referral center for South Moravia (approx 2 237 000 inhabitants). Also patients from North Moravian region (approximately 1 910 000 inhabitants) are frequently, but not constantly referred.

4. Regions of the Czech Republic

5. Spectrum of Primary Hypogamamglobulinemic Patients Diagnosed between 1965-2008 PeriodPatientsCVIDX-LAOthers Before 1981716 1981-199019180 1 x non-X-linked HIMS 1991-200037322 2 x HIMS, 1x -chain def. 2001-2008332724x Good syndrome Total967810

6. Diagnostic Delay and Number of Pneumonias before the Diagnosis of PID Was Made TotalDiagnostic delay*No. of pneumonias* 1981-1990195; 9,6 (0-38)5; 6,3 (0-25) 1991-2000373; 11,7 (0-44)1; 2,2 (0-10) 2001-2008332; 6,6 (0-36)0; 2,6 (0-15) Mann-Whitney test: Diagnostic delay: 1981-1990 vs1991-2000: P= 0,6280 1991-2000 vs 2001-2008: P=0,0352 1981-1990 vs 2001-2008 P=0,0054 *Expressed as median; SD (range)

7. Diagnostic Delay in Hypogammaglobulinemic Patients Referred between 1981-2008 P=0,628 P=0,005 P=0.032

8. Diagnostic delay Year of Diagnosis Diagnostic Delay in Hypogammaglobulinemic Patients Referred between 1981-2008 Time trend in the length of the diagnostic delay was fitted using the exponencial regression method." Spearman´s correlation coefficient R= -0,359 (P < 0.001)

9. Diagnostic Delay and Number of Pneumonias before the Diagnosis of PID Was Made TotalDiagnostic delay*No. of pneumonias* 1981-1990195; 9,6 (0-38)5; 6,3 (0-25) 1991-2000373; 11,7 (0-44)1; 2,2 (0-10) 2001-2008332; 6,6 (0-36)0; 2,6 (0-15) Mann-Whitney test: Number of pneumonias: 1981-1990 vs1991-2000: P=0.0311 1991-2000 vs 2001-2008: P=0.0211 1981-1990 vs 2001-2008 P= 0,0002 *Expressed as median; SD (range)

10. Number of Pneumonia Episodes during Diagnostic Delay in Hypogammaglobulinemic Patients Referred between 1981-2008 P<0.001P=0,0317 P<0.001 Number of pneumonia episodes

11. Number of Pneumonias Number of Pneumonia Episodes durin Diagnostic Delay in Hypogammaglobulinemic Patients Referred between 1981-2008 Time trend in the number of pneumonias during the diagnostic delay was fitted using the polynomial regression method." Spearman´s correlation coefficient R = -0,520 (P < 0.001).

12. Number of Hypogammaglobulinemic Patients who Experienced Pneumonia before Immunological Investigation was Made 17/19 25/37 13/33 89% 68% 39% P=0.0546 P=0.0003 P=0.012

13. Age at the time of diagnosis Year of Diagnosis Age when the Diagnose of PID was Made Spearman´s correlation coefficient R = 0,0075 (N.S)

14. Number of Patients Referred after previous Immunoglobulin Determination Total No. of Patients No of Patients in whom Igs Were Determined 1981-1990196 (37%) 1991-20003720 (54%) 2001-20083318 (55%)

15. Referral Diagnoses Different from Respiratory-Tract Infections Prior to 1980 : (total 7 referred patients): none 1981- 1990: (total 19 referred patients): none 1991-2000: (total 37 referred patients) 1x hemolytic anemia, 1xhepatopathy, 1x herpes zoster, 1x family study in IgAD family, consequent progression of IgAD to CVID.

16. Referral Diagnoses Different from Respiratory-Tract Infections 2001-2008: (total 33 patients) 2x progression of IgA deficiency (both previously referred for recurrent RTI) 1x asthma, 1x herpes zoster, 1x problem with blood group determination, 1x generalized fatigue, 1x arthralgia, 1x family study in IgAD patient, 1x allopecia areata.

17. Hypogammaglobulinemic Patients without Severe Repiratory Tract Infections in the Time of Diagnosis

18. Conclusion The diagnostic delay in patients with primary antibody deficiency has markedly shortened during the observation period. Currently majority of patients did not experience pneumonia before the diagnose of hypogammaglobulinemia is made. A significant diagnostic delay in some patients was observed, even in the recently referred patients.

19. Thank you for your attention