AgammaglobulinemiaAgammaglobulinemia

Vilnius University Children’s Hospital Vilnius University Children’s Hospital PediatricPediatric CenteCenter, r, RR..DuobieneDuobiene

Case reportCase report

R.B., male, born on February R.B., male, born on February 1997.1997.

The parents are The parents are consanguineous.consanguineous.

Eyes’ pathology in fathers’ Eyes’ pathology in fathers’ familyfamily

(2 brothers, sister, mother).(2 brothers, sister, mother).

The bThe boy has healthy brotheroy has healthy brother..

Case reportCase report

Second delivery after Second delivery after thethe 37 weeks 37 weeks of normal pregnancy.of normal pregnancy.

Birth weight 2,4 kg, height 52 cm.Birth weight 2,4 kg, height 52 cm.

Respiratory dyspnea Respiratory dyspnea was mentioned was mentioned during the first days (4) after the during the first days (4) after the birth.birth.

Case reportCase report

Breast fed till 3 monthsBreast fed till 3 months old old..

Normal development till 3 months.Normal development till 3 months.

BCG, polio, DTP, HB vaccines BCG, polio, DTP, HB vaccines withoutwithout apparent adverse reactions. apparent adverse reactions.

Medical historyMedical history

Recurrent respiratory infections Recurrent respiratory infections - s- since 3 mince 3 months.onths.

7 m. – severe right pneumonia.7 m. – severe right pneumonia. (APV 5d., EM transfusion).(APV 5d., EM transfusion).

Diarrhea.Diarrhea.

Failure to thriveFailure to thrive..

Medical historyMedical history 1year – 1year – cystic fibrosiscystic fibrosis due to : due to :

malabsorbtion, malabsorbtion, failure to thrive, failure to thrive, recurrent bronchitis. recurrent bronchitis.

Further investigations excluded CF:Further investigations excluded CF: CFTR gene 508f mutation(-);CFTR gene 508f mutation(-);

Serum chloride max until 53 Serum chloride max until 53 mmol/l.mmol/l.

3 year – 3 year – asthma bronchialeasthma bronchiale.. Treatment without positive effect.Treatment without positive effect.

Medical historyMedical history 3 - 6 year : 3 - 6 year : reccurent sinopulmonary infections reccurent sinopulmonary infections

every month,every month, pneumonia 4 times/year.pneumonia 4 times/year.

2004.08.162003.01.07

Medical historyMedical history

6 year – 6 year – bronchiectatic diseasebronchiectatic disease..

bronchiectasibronchiectasiaas in left lung s in left lung (S 8,9,10) (S 8,9,10) by CT;by CT;

bbilateral purulent endobronchitis ilateral purulent endobronchitis

by bby bronchofibroscopyronchofibroscopy;;

bbronchial secretions bacteriological ronchial secretions bacteriological examination – Moraxella.examination – Moraxella.

Chest CT Chest CT (27.02.(27.02.20032003))

Bronchiectasias

Chest CTChest CT ((28.01.28.01.20042004))

Medical historyMedical history5,5, 7,7, 8 y8 yearear old - old - recurrent abscessesrecurrent abscessesof femur, fof femur, fingeringer, head, neck, e, head, neck, earar,, nnoseose..Bacteriologicaly - Bacteriologicaly - Staph.aureusStaph.aureus..

Medical historyMedical history

Scarring afterabscesses

Medical historyMedical history

6 year - onset of 6 year - onset of arthritisarthritis..

7 year – 7 year – poliarthritis.poliarthritis.

Medical historyMedical history

Medical historyMedical history

Knee joint x-rayKnee joint x-ray

Osteoporosis

Oedema of soft tissue

Laboratory analysisLaboratory analysis

Anemia – Hb 82-115g/l, MCV ~ 60fl, Anemia – Hb 82-115g/l, MCV ~ 60fl,

MCH ~ 20pg, Fe 3,2 mmol/lMCH ~ 20pg, Fe 3,2 mmol/l, feritin – 10 , feritin – 10 g/l.g/l.

Thrombocytosis from 1 year old:Thrombocytosis from 1 year old:

PLT 430 - 600 – 1474 x 10PLT 430 - 600 – 1474 x 1099/l./l.

Immunoglobulins: Immunoglobulins:

IgA - 0.22, IgG -IgA - 0.22, IgG - 0.07, IgM 0.07, IgM -- 0.17 0.17 mg/lmg/l..

LYMPHOCYTES SUBPOPULATIONS LYMPHOCYTES SUBPOPULATIONS 01.06.01.06.20200404

ParameterParameter ValueValue Normal value (7-17 y)Normal value (7-17 y)

Absolute lymphocytes Absolute lymphocytes count count

2121 % / 3402 % / 3402 36 – 43 % / 2000-2700 36 – 43 % / 2000-2700 mm3 mm3

CD3+CD3+ 96 % / 326696 % / 3266 66 - 76 % / 1400 – 66 - 76 % / 1400 – 2000 mm3 2000 mm3

CD3+CD4+CD3+CD4+ 38 % / 129338 % / 1293 33 – 41 % / 700 – 33 – 41 % / 700 – 1100 mm3 1100 mm3

CD3+CD8+CD3+CD8+ 51 %/ 173551 %/ 1735 27 – 35 % / 600 - 900 27 – 35 % / 600 - 900 mm3mm3

CD4+/CD8+CD4+/CD8+ 0,750,75 1,1-1,41,1-1,4

CD16+/CD56+CD16+/CD56+ 9 % / 136 9 % / 136 mm3mm3

89– 16 % / 200 – 3400 89– 16 % / 200 – 3400 mm3 mm3

CD19+CD19+ 00 12 - 22 % / 300 – 500 12 - 22 % / 300 – 500 mm3mm3

NBTNBT 00 15-25%15-25%

NBTNBT after stimulation after stimulation 9494 45-65%45-65%

TreaTreattmentment IVIG (EndobulinIVIG (Endobulinumum) ) 5500 mg/kg every 300 mg/kg every 3 -- 4 4

weeksweeks.. (2004.06 – ...(2004.06 – ...

PrednisolonPrednisolonumum 1.5 mg/kg p/os 1.5 mg/kg p/os (2004.04.05 – 2005.04)(2004.04.05 – 2005.04)

Triamcinolonum (Triamcinolonum (KenalogKenalog)) 40mg 40mg intraarticular (x2)intraarticular (x2)

MetMethhotrexatotrexatumum 7,5 mg x 1 / week (7,5 mg x 1 / week (x2x2) p/os) p/os (2005.03 -04)(2005.03 -04)

SulfasalazinSulfasalazinum (2004.05 -06)um (2004.05 -06)

TreaTreattmentment NAP (nimesil, NAP (nimesil, meloxicamum (meloxicamum (movalmoval)), ,

didicclofenac, ibuprofenlofenac, ibuprofenumum) ) (2004 - ...(2004 - ... IInhnhaleraler Flixotide Flixotide (Fluticasonum), (Fluticasonum),

SeretidSeretide (Fluticasonum, salmeterolum)e (Fluticasonum, salmeterolum) (2000 – 2005.04)(2000 – 2005.04)

FeFerrosirrosi sulfa sulfass, ac. folici., ac. folici.

Antibiotics (Antibiotics (cefuroximum/, cefuroximum/, clarythromycinum/, oxacillinum/, clarythromycinum/, oxacillinum/, ampicilinum, ceftriaxonum, ampicilinum, ceftriaxonum, vancomycinum/, ceftazidimum, vancomycinum/, ceftazidimum, gentamycinum/, cephazolinum, biseptol).gentamycinum/, cephazolinum, biseptol).

ImmunoglobulinsImmunoglobulins

15.115.12.2.

20020044

12.012.01.1.

20020055

19.0119.01..

10.010.02.2.

03.003.03.3.

18.018.033

30.030.03.3.

Ig AIg A g/ g/LL

<0,2<0,255

<0,2<0,255

<0,2<0,244

<0,2<0,233

IgG IgG

g/g/LL

5,635,63 1,931,93 5,365,36 6,456,45 2,542,54 7,147,14 2,442,44

IgMIgM g/ g/LL

<0,1<0,177

<0,1<0,177

<0,1<0,177

<0,1<0,188

IgEIgE

IU/mIU/mll

<4,5<4,5

Blood countBlood count12.012.011

20052005

21.021.022

20052005

05.005.033

20052005

16.016.033

20052005

21.021.033

20052005

27.0427.04..

20052005

WBC WBC x10x1099/L/L 17,917,9 25,625,6 30,130,1 52,352,3 41,241,2 17,317,3

LYMLYM x10x1099/L/L

%%8,18,1

45454,44,4

17,217,27,67,6

25,425,45,75,7

11116,66,6

16166,626,62

38,338,3

HGBHGB g/Lg/L

9292 7878 9090 8989 8888

MCVMCV flfl 63,663,6 5757 65,365,3 58,958,9 59,659,6 6363

MCH MCH pgpg 18,518,5 18,518,5 17,017,0 18,618,6 18,518,5 19,319,3

PLTPLT x10x1099/L/L

880880 508508 13891389 849849 708708 722722

EESRSR mmmm//hh (W)(W)

3636 1919 6464 4040 3434 3636

CRPCRP mg/l mg/l 298298

Disease CourseDisease Course (9 months later)(9 months later)

12.03.200512.03.2005

Disease Course Disease Course (9 months later)(9 months later)

22.03.2022.03.200505

MTS?

MTS?

Disease CourseDisease Course (23.03.2005)(23.03.2005)

CT:Neuroblastoma in susp.

MTS ?

Disease CourseDisease Course (23.03.2005) (23.03.2005)

Chest CT:Neuroblastoma in susp.

MTS?

Disease CourseDisease Course

Spinal prominence

Thoracic spine x-ray Thoracic spine x-ray (07.04.2005)(07.04.2005)

Paravertebral additional opacityTh VIII –XI

Thoracic spine x-ray Thoracic spine x-ray (07.04.2005)(07.04.2005)

Prolabation of intervertebral disk L5 - S1

Painful lowerPainful lower backback

Laboratory investigatLaboratory investigatiioonnss

Culture from synovial fluid (-).Culture from synovial fluid (-).

HemoHemoculture culture for aerobes, anaerobes, fungi (for aerobes, anaerobes, fungi (––)). .

Stool for Stool for giardia giardia cysts –cysts – giardia intestinalis (+).giardia intestinalis (+).

Bone marrow: haemophagocytosisBone marrow: haemophagocytosis..

Chest x-rayChest x-ray

1111..0404.2005.2005

2222..0303.2005.2005

Chest CTChest CT ((1212.04.2005).04.2005)

Chest CTChest CT ((1818.04.2005).04.2005)

Primary immunodeficiency: agamaglobulinemia

Recurrent sinopulmonary infections: bronchitis, pneumonia, sinusitis

Bronchiectatic diseaseAstma bronchiale

Cystic fibrosis

Recurrent abscesses

Poliarthritis

?

Since 3 months

At 1 year old

At 3 year old

At 6 year old

At 5.6,7 years old

At 7 year old

First mention at 3,5 year old

At 8 year old

ConclusionsConclusions 85% 85% of agammaglobulinemia patients are of agammaglobulinemia patients are

males suffering from males suffering from XLA XLA due to defect in the due to defect in the gene encoding BTK.gene encoding BTK.

So we consider that our case could be So we consider that our case could be conjuncted with mutation in this gene.conjuncted with mutation in this gene.

Persisting, recurrent pulmonary infections led Persisting, recurrent pulmonary infections led to bronchiectasias.to bronchiectasias.

Agamaglobulinemia and recurrent infections –Agamaglobulinemia and recurrent infections – the reason of autoimmune poliarthritis.the reason of autoimmune poliarthritis.

Patient’s family members should be genetically Patient’s family members should be genetically tested.tested.

Delay diagnosis.Delay diagnosis.

QuestionsQuestions

Flow cytometric analysis of PB showed complete absence of B-lymphocytes. Could we have another type of mutation such as IGH-C ?

Could we escape poliarthritis with the earlier started substitution IVIG therapy?

What etiology of lungs changes could it be?

What further management do you suggest?

Does a lobotomy of the lung would be helpful ?

Thank you for Thank you for attentionattention