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

T.V. ( ) 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

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

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

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

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.

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 :

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

Immunological analysis PatientNormal value Absolute ly number CD19 ly/μl CD3 ly/μl CD4 ly/μl

Common Variable Immunodeficiency? Therapy: IVIG: 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

patientnormal range CD3+/μl CD4+/μl ±  266 CD4+/CD CD25+(IL-2R  ) T cell 1.0%4.8  2.9 CD45RA+/μl T cell 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

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

Ulcerative skin lesions

Hemicolectomy

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

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

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

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

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