Pediatric Pulmonary Ward NRITLD

پروفسور محمد حسین سلطان زاده

      استاد دانشگاه علوم پزشکی شهید بهشتی
     متخصص کودکان ونوزادان
        طی دوره بالینی عفونی از میوکلینیک آمریکا
دبیر برگزاری کنفرانس های ماهیانه گروه اطفال
 دانشگاه علوم پزشکی شهید بهشتی


معرفی : دکتر سهیلا خلیل زاده

به اتفاق اعضای هیئت علمی گروه کودکان
 بیمارستان مسیح دانشوری



Etiology of  BCG –OSIS

30% :

 Known Primary Immune Deficiency &HIV

 ( SCID , CGD , hyper IgE , …)

70% :

 ½ Cases  due To ( IL – 12  IFN δ axis Defect )

   ½ ( Unknown ) 

Disseminated BCG infection is a typical clinical presentation in patients with an inherited disorder of the IL-12-IFN-y axis, as BCG is often the first pathogen to which patients are exposed .

BCG vaccination results in disseminated infection involving lymph nodes, lungs, kidney, spleen and other organs. Such infections are referred to as "BCG-osis" and are considered to be the most serious complication of BCG injection with high(71 %) rates of mortality.

Interferon-Gamma (IFN-δ) is a critical cytokine produced by NK and T-cells. The differentiation of T-helper cells into IFN-δ-producing cells is regulated by several     cytokines, but principally interleukin  
 Deleterious mutations in five genes involved in the IL-12-IFN-
δ circuit have been found in human patients.

The various types of mutation (dominant or recessive) in these five genes define up to ten distinct inherited disorders

All are associated with a rare human syndrome, known as Mendelian susceptibility to mycobacterial disease (MSMD)

Types of deficiency

Autosomal Recessive :

1- IFN δ R1Def  ( Complete )

2- IFN δ R1Def  ( Partial)

3- IFN δ R2 Def (Complete )

4- IFN δ R2 Def ( Partial)

5-- STAT – 1 Def

6-- IL-12 B ( P40 ) Def

7-- IL-12 Rβ1  Def


Autosomal Dominant :

8-- Autosomal Dominant IFN δ R1 Def

Conclusion :

This group of hereditary disorders should be considered in the evaluation of such patients , particularly in countries like Iran , where BCG Vaccination is part of the National Health Programme and outbreaks of non-typhoid gastroenteritis are common.

Patients with severe BCG infections and extra-intestinal   non – typhoidal salmonellosis should be investigated for the Il-12-IFN-δ circuit .

Treatment :

Anti Mycobacterial drugs

Recombinant INF δ

Gene Therapy

B.M Transplantation

GM- CSF ( Skin involvement ) 

Whole Blood Assay :

Complete IL 12 RB1 deficiency

Mutation : R521X

Final Diagnosis:

BCG-OSIS Due To Complete IL12 RB1 Def