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

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. Control laboratorytest: • 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.

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 Patient Normal value Absolute ly number 2590 1100-5900 CD19 ly/μl 9 200-1600 CD3 ly/μl 2012 700-4200 CD4 ly/μl 414 300-2000

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. Immunological analysis Flow cytometry HIV serology, ag test: neg. Controll CD25 (IL-2R) level: 0,7 %

13. Stimulation test • Blastic transformation (PHA, ConA, PWM): abnormal • Genetic analysis Severe combined immunodeficiency

14. Ulcerative skin lesions

15. Hemicolectomy

17. CMV colitis • Histology: acute ulcerative CMV colitis • Serum CMV antigen: positive • CMV number: • Serum: 104/ml • Urine: 105/ml

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

19. BMT • 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!