Late onset of Severe Combined ImmunoDeficiency

(?)

Bernadett Mosdósi, Pécs-Hungary

• 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

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: 10 800/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.: normalThe 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 20210GA,

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

Patient Normal value

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

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

patient normal range

CD3+/μlCD4+/μl

619135

2700±600980266

CD4+/CD8+ 0.3 0.92-4.11

CD25+(IL-2R) T cell 1.0% 4.82.9

CD45RA+/μl T cell 159 600-1900

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

• 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

Ulcerative skin lesions

Hemicolectomy

• Histology: acute ulcerative CMV colitis

• Serum CMV antigen: positive

• CMV number:– Serum: 104/ml– Urine: 105/ml

CMV colitis

Therapy

• Antiviral: Gancyclovir – After 1 week treatment

• Serum: 500/ml• Urine: 5000/ml

• Combined antibiotic treatment• Antimycotic treatment• IVIG• BMT

BMT

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

septic shock, haemorrhagic shockdeath

Conclusion

• Precise case history

• Early diagnosis

• CMV colitis

• Primary / Secondary ID (?)

Thank You for Your Attention!