1. Late onset of Severe Combined ImmunoDeficiency (?) Bernadett Mosdósi, Pécs-Hungary

2. T.V. ( 1995.12.26.) Family history Uneventful perinatal adaptation Vaccination in usual time At the age 2: recurrent mild sino-pulmonary infection At the age of 5: autoimmune haemolytic anaemia (transfusion!) At the age of 9: varicella pneumonitis

3. At the age of 10 : fever, bloody diarrhoea Candida, Salmonella infection ulcerative skin lesion elevated infection parameters Autoimmune disease?

4. I. clinical admission Physical examination : pale appereance, hepatosplenomegaly Next day morning … …. getting up from the bed, she collapsed physical examination: Dysarthria, facial paraesis l.d., hemiparaesis l.d., Babinski  l.d. MR-angiography

6. MR-angiography: –multiplex infarction of putamen l.s. –stenosis art. cerebri mediae l.s. Laboratory investigation: –WBC: 10 800/μl, CRP: 168 mg/l, –D-dimer: 1409, Lp: neg. Therapy: combined antibiotic, antithrombotyc Systemic autoimmune disease (SLE ?), Extraintestinal manifestation of Salmonella (???)

7. Chest X-ray : neg. Abdominal ultrasound : –hepatosplenomegaly –hyperperistaltic, thickened loops of the ileum, colon transversum and descendens Abdominal MR : - splenomegaly, thickened loops of the ileum - art. mesenterica sup.: normal The state of her health and neurologic abnormality is improving.

8. Elevated infection parameters IgA: 0.13 g/l, IgG: 1.3 g/l, IgM: 0.12 g/l Stool culture : negative Immunoserology : neg. Haptoglobin, homocystein: norm. Thrombophylia : FV Q506, PTB 20210G  A, MTHFR C677T: neg. Bloody diarrhoea is persistent. Control laboratory test :

9. Colonoscopy: –Stricture of colon sigmoideum, descendens,flexura hepatica, ileocoecal region –Confluent ulcerations Histology : –Ulceration, eosinophil cells infiltration → Crohn disease –Epitheloid granuloma can’t be detected Treatment: 5-ASA + steroid

10. Immunological analysis PatientNormal value Absolute ly number 25901100-5900 CD19 ly/μl 9200-1600 CD3 ly/μl 2012700-4200 CD4 ly/μl414300-2000

11. Common Variable Immunodeficiency? Therapy: IVIG: 400-600 mg/kg /month Combined antibiotic Antithrombotyc Steroid+ 5-ASA Stool is normal, neurologic abnormality is improving WBC: 6500/μl, We: 22 mm/h, CRP: 48 mg/l IgA: 0.16 g/l, IgG: 2.7 g/l, IgM: 0.18 g/l

12. patientnormal range CD3+/μl CD4+/μl 619 135 2700±600 980  266 CD4+/CD8+0.30.92-4.11 CD25+(IL-2R  ) T cell 1.0%4.8  2.9 CD45RA+/μl T cell159600-1900 CD19+ B cell 1.9%11.8  4.6 HIV serology, ag test : neg. Controll CD25 (IL-2R  ) level: 0,7 % Immunological analysis Flow cytometry

13. Blastic transformation (PHA, ConA, PWM): abnormal Genetic analysis Monocyte (LPS)T cell (PMA) IL-2 (pg/ml)2429 (  ) IL-6 (pg/ml)20 790 (  )397 (  ) IFNγ (pg/ml)109 032 (  ) Stimulation test Severe combined immunodeficiency

14. Ulcerative skin lesions

15. Hemicolectomy

17. Histology: acute ulcerative CMV colitis Serum CMV antigen : positive CMV number : –Serum: 10 4 /ml –Urine: 10 5 /ml CMV colitis

18. Therapy Antiviral: Gancyclovir –After 1 week treatment Serum: 500/ml Urine: 5000/ml Combined antibiotic treatment Antimycotic treatment IVIG BMT

19. 15. th day: ileus, shock Laparotomy ( 4 times) hepatic encephalopathy, TTP sy 72.th day: septic shock, haemorrhagic shock death

20. Conclusion Precise case history Early diagnosis CMV colitis Primary / Secondary ID (?)

21. Thank You for Your Attention!