1. VILNIUS UNIVERSITY HOSPITAL SANTARISKIU KLINIKOS

2. Common variable immunodeficiency in adults K. Cerniauskas, A. Blaziene

3. Common variable immunodeficiency - most prevalent of the primary immunodeficiency disorders. Common variable immunodeficiency - most prevalent of the primary immunodeficiency disorders. Reduction in serum levels of both IgG and IgA, with or without low IgM. Reduction in serum levels of both IgG and IgA, with or without low IgM. Recurrent bacterial sinopulmonary infections, which led to complications, especially pulmonary damage. Recurrent bacterial sinopulmonary infections, which led to complications, especially pulmonary damage. Definition

4. Prevalence 1-2 / 100 000 1-2 / 100 000 Lithuanian population 3.5 mln. Lithuanian population 3.5 mln. Expected number of patients 35-70. Expected number of patients 35-70. Number of diagnosed CVID is 5 cases in our clinic. Number of diagnosed CVID is 5 cases in our clinic.

5. Experience From 1998 to 2006. From 1998 to 2006. Five cases (3 males, 2 females). Five cases (3 males, 2 females). Diagnosis made between 23 - 48 years of life. Diagnosis made between 23 - 48 years of life. An average diagnostic delay ~ 7 y. An average diagnostic delay ~ 7 y.

6. Which specialist suspected hypogammaglobulinemia? 1 – haematologist 1 – haematologist 1 – rheumatologist 1 – rheumatologist 3 – pulmonologist 3 – pulmonologist Where is primary physician ???

7. Onset In 4 cases disease manifested with recurrent infections of upper and lower respiratory tract. In 4 cases disease manifested with recurrent infections of upper and lower respiratory tract. In 1 case recurrent infections of respiratory tract were associated with benign lymphadenopathy. In 1 case recurrent infections of respiratory tract were associated with benign lymphadenopathy. In 1 case - enterogenic reactive arthritis and urinary tract infection. In 1 case - enterogenic reactive arthritis and urinary tract infection.

8. Laboratory tests - Low level of IgG, IgA and IgM was found. - Low level of IgG, IgA and IgM was found. - Number and function of T lymphocytes – N. - Number and function of T lymphocytes – N. - Number of B lymphocytes – 7-9 %. - Number of B lymphocytes – 7-9 %.

9. Complications Bronchiectasis was detected in 3 cases (by CT). Bronchiectasis was detected in 3 cases (by CT). Amyloidosis of AA type in 3 cases (renal or gum biopsy). Amyloidosis of AA type in 3 cases (renal or gum biopsy). 1 death in 5th y after CVID was revealed. 1 death in 5th y after CVID was revealed.

10. Associated diseases Benign lymphadenopathy – 1 Benign lymphadenopathy – 1 Reactive arthritis – 2 Reactive arthritis – 2 COPD – 1 COPD – 1 Rhinosinusitis – 1 Rhinosinusitis – 1

11. Treatment Substitutional therapy with intravenous immunoglobulin (Endobulin) was initiated in 2 cases. Substitutional therapy with intravenous immunoglobulin (Endobulin) was initiated in 2 cases. Concomitant pathology treated in ordinary way. Concomitant pathology treated in ordinary way. Exacerbation of infections were treated with antibiotics. Exacerbation of infections were treated with antibiotics.

12. Cases

13. Case 1 Patient P.S., male, 38 years old. Rhinosinusitis - since 9 years old. Subfebrile fever - 12 y. Loss of weight - 16 y. Recurrent infections of the respiratory tract - since 22 years (bronchitis 3 times a year). Bronchiectasis was diagnosed - 29 y. Dyspnea, weakness, often exacerbations of bronchiectasis were presenting.

14. Laboratory test 1998 y γ-globulins - 2.7 % γ-globulins - 2.7 % IgG – 0,96 g/l, IgM <0,2 g/l, IgA <0,29 g/l IgG – 0,96 g/l, IgM <0,2 g/l, IgA <0,29 g/l CIC - 0,006 (N 0,06-0,08) CIC - 0,006 (N 0,06-0,08) B lymphocytes 9 %, 243/mm (N 11-16 %, 200-400) B lymphocytes 9 %, 243/mm (N 11-16 %, 200-400) CD4+ - 24 %, 648 /mm (N 38-46 %, 700-1100) CD4+ - 24 %, 648 /mm (N 38-46 %, 700-1100) CD4/CD8 - 0,5 CD4/CD8 - 0,5

15. Effect of treatment with intravenous immunoglobulin Since 1998 level of IgG ranges from 0,96 to 4,5 g/l Since 1998 level of IgG ranges from 0,96 to 4,5 g/l Pneumonia and acute sinusitis (2001). Pneumonia and acute sinusitis (2001). Bronchiectasis exacerbated 2-3 times a year. Bronchiectasis exacerbated 2-3 times a year. Atrophic gastritis and H.zoster (2005). Atrophic gastritis and H.zoster (2005). No hospitalisation since 1998. No hospitalisation since 1998.

16. Case 2 I. T., 50-year-old women I. T., 50-year-old women Recurrent purulent infections of upper and lower respiratory tract from childhood. Recurrent purulent infections of upper and lower respiratory tract from childhood. Bronchial asthma diagnosed in 20 y. Bronchial asthma diagnosed in 20 y. Hypogammaglobulinemia revealed in 24 y. Hypogammaglobulinemia revealed in 24 y. 8 y treated with intramuscular Ig. 8 y treated with intramuscular Ig. Hypertension and proteinuria was observed about 10 years. Hypertension and proteinuria was observed about 10 years. Admited to hospital with dyspnea, cough, crural oedema, eczema Admited to hospital with dyspnea, cough, crural oedema, eczema

17. Laboratory tests Blood count: leucocytosis. Blood count: leucocytosis. IgA - 0,69 g/L (N 0,88-4,1), IgG – 0,07 g/l (N 6,9-14), IgM - 0,17 g/L (N 0,34-2,1), IgA - 0,69 g/L (N 0,88-4,1), IgG – 0,07 g/l (N 6,9-14), IgM - 0,17 g/L (N 0,34-2,1), CIC – 0,018 (N 0,06-0,08). CIC – 0,018 (N 0,06-0,08). Lymphocytes – 1400/m3; CD19+ (B lymphocytes) – 7 %, 98/mm3; Lymphocytes – 1400/m3; CD19+ (B lymphocytes) – 7 %, 98/mm3; CD4/CD8 – 1,26. CD4/CD8 – 1,26. Serum creatinine – 149 μmol/l, urea – 24,69 mmol/l, Serum creatinine – 149 μmol/l, urea – 24,69 mmol/l, Proteinuria – 2 g/l and 2,56 g/24 h, cholesterol - 7,54 mmol/l. Proteinuria – 2 g/l and 2,56 g/24 h, cholesterol - 7,54 mmol/l.

18. Imaging studies and biopsy CT revealed pneumofibrosis, atelectasis of S10/9, mediastinal lymphadenopathy and pleural effusion. CT revealed pneumofibrosis, atelectasis of S10/9, mediastinal lymphadenopathy and pleural effusion. Pleural fluid was transudate, specific or atypical cells were absent (flow cytometry). Pleural fluid was transudate, specific or atypical cells were absent (flow cytometry). Renal ultrasound showed parenchymas changes typical to chronic renal disease. Renal ultrasound showed parenchymas changes typical to chronic renal disease. Renal biopsy elicited amyloidosis (AA). Renal biopsy elicited amyloidosis (AA).

19. Comment No bronchiectasis in the presents of amyloidosis. No bronchiectasis in the presents of amyloidosis. Long outlive without treatment. Long outlive without treatment.

20. Case 3 J.M., female, 27 years old. J.M., female, 27 years old. Gastrointestinal infection 26 y (salmoneliosis?). Gastrointestinal infection 26 y (salmoneliosis?). Urinary tract infections. Urinary tract infections. Admited to hospital with pain and swelling in the left knee, diarrhea. Admited to hospital with pain and swelling in the left knee, diarrhea.

21. Laboratory test Blood count - iron deficiency anemia. Blood count - iron deficiency anemia. CRP - 136 mg/l. CRP - 136 mg/l. RF - N. RF - N. Faeces culture - Campylobacter. Faeces culture - Campylobacter. γ-globulin – 5,1 %. γ-globulin – 5,1 %. IgG < 1,7 g/l, IgA <0,24 g/l, IgM – 1,7 g/l. IgG < 1,7 g/l, IgA <0,24 g/l, IgM – 1,7 g/l. B lymphocytes - N. B lymphocytes - N.

22. Imaging tests Chest x-ray - N Chest x-ray - N Chest CT - N. Chest CT - N. Sonography and x-ray of the knee: arthritis. Sonography and x-ray of the knee: arthritis.

23. Comment Enterogenic reactive arthritis or arthritis associated with primary agammaglobulinemia? Enterogenic reactive arthritis or arthritis associated with primary agammaglobulinemia?

24. Case 4 G.J., male, 27 y. G.J., male, 27 y. Recurrent infections of the respiratory tract since childhood. Recurrent infections of the respiratory tract since childhood. Severe pneumonias occured since 21y. Severe pneumonias occured since 21y. Pleuritis three times since 22 y. Pleuritis three times since 22 y. Hypogammaglobulinemia in 23 y Hypogammaglobulinemia in 23 y Reactive arthritis was suspected in 25 y. Reactive arthritis was suspected in 25 y.

25. Case 4 (cont.) At the age of 27 y admited to hospital because of fever, cough, diarrhoea, pain of shoulders and knees, crural oedema. At the age of 27 y admited to hospital because of fever, cough, diarrhoea, pain of shoulders and knees, crural oedema. Chest CT elicited bilateral bronchiectasis. Chest CT elicited bilateral bronchiectasis. Amyloidosis was confirmed by gum and gut biopsy Amyloidosis was confirmed by gum and gut biopsy

26. Laboratory tests IgG<1,35 g/l, IgM-0,17 g/l, IgA<0,23 g/l. IgG<1,35 g/l, IgM-0,17 g/l, IgA<0,23 g/l. CD19+ - 8 %, CD4+ - 15 %, CD4/CD8 - 0,19. CD19+ - 8 %, CD4+ - 15 %, CD4/CD8 - 0,19. Blood count - leucocytosis. Blood count - leucocytosis. CRP – 72 mg/l. CRP – 72 mg/l. Hypoproteinemia (30,9 g/l), hypoalbuminaemia (14,8 g/l). Hypoproteinemia (30,9 g/l), hypoalbuminaemia (14,8 g/l). Proteinuria (8,4 g/l, 21,42 g/24 h), granular casts in urine. Proteinuria (8,4 g/l, 21,42 g/24 h), granular casts in urine. Urea and creatinin values were normal. Urea and creatinin values were normal.

27. Comment 4 years without treatment were crucial for the development of complications. 4 years without treatment were crucial for the development of complications. Patient died 2 y after initiation of replacement therapy. Patient died 2 y after initiation of replacement therapy.

28. Problem? Long delay in diagnosis and treatment of CVID. Long delay in diagnosis and treatment of CVID.