Change in Referral Diagnoses and Diagnostic Delay in

Hypogammaglobulinaemic Patients.

Jiri LitzmanDept. Clin. Immunol. Allergol

Masaryk University, Brno, Czech Republic

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.

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.

Regions of the Czech Republic

Spectrum of Primary Hypogamamglobulinemic Patients

Diagnosed between 1965-2008

PeriodPatient

sCVID X-LA Others

Before 1981

7 1 6

1981-1990 19 18 01 x non-X-linked

HIMS

1991-2000 37 32 22 x HIMS,

1x -chain def.

2001-2008 33 27 24x Good

syndrome

Total 96 78 10  

Diagnostic Delay and Number of Pneumonias before the Diagnosis of

PID Was Made

  Total Diagnostic delay* No. of pneumonias*

1981-1990 19 5; 9,6 (0-38) 5; 6,3 (0-25)

1991-2000 37 3; 11,7 (0-44) 1; 2,2 (0-10)

2001-2008 33 2; 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)

Diagnostic Delay in Hypogammaglobulinemic Patients

Referred between 1981-2008

P=0,628

P=0,005

P=0.032

Dia

gnos

tic d

elay

Year of Diagnosis

1980 1984 1988 1992 1996 2000 2004 2008

0

10

20

30

40

50

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)

Diagnostic Delay and Number of Pneumonias before the Diagnosis of

PID Was Made

  Total Diagnostic delay* No. of pneumonias*

1981-1990 19 5; 9,6 (0-38) 5; 6,3 (0-25)

1991-2000 37 3; 11,7 (0-44) 1; 2,2 (0-10)

2001-2008 33 2; 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)

Number of Pneumonia Episodes during Diagnostic Delay in

Hypogammaglobulinemic Patients Referred between 1981-2008

P<0.001 P=0,0317

P<0.001

Num

ber

of

pneum

onia

epis

odes

Num

ber

of P

neum

onia

s

1980 1984 1988 1992 1996 2000 2004 2008

0

2

4

6

8

10

12

14

16

18

20

22

24

26

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).

Number of Hypogammaglobulinemic Patients who Experienced Pneumonia before Immunological

Investigation was Made

0%10%20%30%40%50%60%70%80%90%

100%

1981-1990 1991-2000 2001-200817/19 25/37 13/33

89% 68% 39%

P=0.0546P=0.0003 P=0.012

Age

at t

he ti

me

of d

iagn

osis

Year of Diagnosis1980 1984 1988 1992 1996 2000 2004 2008

0

10

20

30

40

50

60

70

80

Age when the Diagnose of PID was Made

Spearman´s correlation coefficient R = 0,0075 (N.S)

Number of Patients Referred after previous Immunoglobulin

Determination

Total No. of Patients

No of Patients in whom Igs Were

Determined

1981-1990

19 6 (37%)

1991-2000

37 20 (54%)

2001-2008

33 18 (55%)

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.

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.

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

0%10%20%30%40%50%60%70%80%90%

100%

1981-1990 1991-2000 2001-2008

0% 11% 27%

0/19 4/37 9/33

P =0.1798 P =0.0537

P =0.0104

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.

Thank you for your attention