Agammaglobulinemia. Vilnius University Children s s Hospital Pediatric Center, R.Duobiene
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1 Agammaglobulinemia Vilnius University Children s s Hospital Pediatric Center, R.Duobiene
2 Case report R.B., male, born on February The parents are consanguineous. Eyes pathology in fathers family (2 brothers, sister, mother). The boy has healthy brother.
3 Case report Second delivery after the 37 weeks of normal pregnancy. Birth weight 2,4 kg, height 52 cm. Respiratory dyspnea was mentioned during the first days (4) after the birth.
4 Case report Breast fed till 3 months old. Normal development till 3 months. BCG, polio, DTP, HB vaccines without apparent adverse reactions.
5 Medical history Recurrent respiratory infections - since 3 months. 7 m. severe right pneumonia. (APV 5d., EM transfusion). Diarrhea. Failure to thrive.
6 Medical history 1year cystic fibrosis due to : malabsorbtion, failure to thrive, recurrent bronchitis. Further investigations excluded CF: CFTR gene 508f mutation(-); Serum chloride max until 53 mmol/l. 3 year asthma bronchiale. Treatment without positive effect.
7 Medical history 3-6 year : reccurent sinopulmonary infections every month, pneumonia 4 times/year year
8 Medical history 6 year bronchiectatic disease. bronchiectasias s in left lung (S 8,9,10) by CT; bilateral purulent endobronchitis by bronchofibroscopy; bronchial secretions bacteriological examination Moraxella.
9 Chest CT ( ( ) Bronchiectasias
10 Chest CT ( )
11 Medical history 5, 7, 8 yeary old - recurrent abscesses of femur,, fingerf inger, head, neck,, eare ar, nose. Bacteriologicaly - Staph.aureus.
12 Medical history Scarring after abscesses
13 Medical history 6 year - onset of arthritis. 7 year poliarthritis.
14 Medical history
15 Medical history
16 Knee joint x-ray Oedema of soft tissue Osteoporosis
17 Laboratory analysis Anemia Hb g/l, MCV ~ 60fl, MCH ~ 20pg, Fe 3,2 mmol/l, feritin 10 µg/l. Thrombocytosis from 1 year old: PLT x 10 9 /l. Immunoglobulins: IgA , IgG , IgM mg/l.
18 LYMPHOCYTES SUBPOPULATIONS Parameter Value Normal value (7-17 y) Absolute lymphocytes count 21 % / % / mm3 CD3+ 96 % / % / CD3+CD4+ 38 % / % / mm mm3 CD3+CD8+ 51 %/ % / mm3 CD4+/CD8+ 0,75 1,1-1,4 1,4 CD16+/CD56+ 9 % / 136 mm % / mm3 CD % / mm3 NBT % NBT after stimulation %
19
20 Treatment IVIG (Endobulin( Endobulinum) 500 mg/kg every 3-4 weeks. ( Prednisolonum 1.5 mg/kg p/os ( ) Triamcinolonum (Kenalog) 40mg intraarticular (x2) Methotrexat otrexatum 7,5 mg x 1 / week (x2)) p/os ( ) Sulfasalazinum um ( )
21 Treatment NAP (nimesil( nimesil, meloxicamum (moval), diclofenac lofenac, ibuprofenum um) ( Inhaler Flixotide (Fluticasonum), Seretide (Fluticasonum, salmeterolum) ( ) Ferrosi sulfas,, ac. folici. Antibiotics (cefuroximum( cefuroximum/, clarythromycinum/, oxacillinum/, ampicilinum, ceftriaxonum, vancomycinum/, ceftazidimum, gentamycinum/, cephazolinum, biseptol).
22 Immunoglobulins Ig A g/l IgG g/l IgM g/l IgE IU/ml <0, <0,25 <0,24 <0,23 5,63 1,93 5,36 6,45 2,54 7,14 2,44 <0,1 7 <0,17 <0,17 <0,18 <4,
23 Blood count PLT WBC x10 9 /L 17,9 25,6 30,1 52,3 LYM x10 9 /L % HGB MCV MCH 8,1 45 4,4 17,2 7,6 25,4 5,7 11 g/l fl 63, ,3 58,9 pg 18,5 18,5 17,0 18, ,2 17,3 6,6 16 6,62 38, ,3 x10 9 /L ESR mm/h (W) CRP mg/l ,6 18,
24 Disease Course (9 months later)
25 Disease Course (9 months later) MTS? MTS?
26 Disease Course ( ) MTS? CT: Neuroblastoma in susp.
27 Disease Course ( ) Chest CT: Neuroblastoma in susp. MTS?
28 Disease Course Spinal prominence
29 Paravertebral additional opacity Th VIII XI Thoracic spine x-ray x ( )
30 Thoracic spine x-ray x ( ) Prolabation of intervertebral disk L 5 -S 1 Painful lower back
31 Laboratory investigations Culture from synovial fluid (-). Hemoculture for aerobes, anaerobes, fungi ( ).( Stool for giardia cysts giardia intestinalis (+). Bone marrow: haemophagocytosis.
32 Chest x-rayx
33 Chest CT ( )
34 Chest CT ( )
35 At 8 year old At 7 year old? Poliarthritis At 5.6,7 years old At 6 year old At 3 year old At 1 year old ince 3 months First mention at 3,5 year old Recurrent abscesses Bronchiectatic disease Astma bronchiale Cystic fibrosis Recurrent sinopulmonary infections: bronchitis, pneumonia, sinusitis Primary immunodeficiency: agamaglobulinemia
36 Conclusions 85% of agammaglobulinemia patients are males suffering from XLA due to defect in the gene encoding BTK. So we consider that our case could be conjuncted with mutation in this gene. Persisting, recurrent pulmonary infections led to bronchiectasias. Agamaglobulinemia and recurrent infections the reason of autoimmune poliarthritis. Patient s family members should be genetically tested. Delay diagnosis.
37 Questions Flow cytometric analysis of PB showed complete absence of B-lymphocytes. Could we have another type of mutation such as IGH-Cµ? 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?
38 Thank you for attention
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