SUMMARY

 

1.  Familial Intestinal Polyatresia is characterized by multiple areas of atresia found throughout the gastrointestinal tract.  

 

2.  A SCID-like phenotype with panhypogammaglobulinemia and markedly decreased T cell number/function has been reported in patients with this disease.  Less severe defects in humoral and cell-mediated immunity have also been reported. 

 

3.  The following immediate management steps should be implemented for patients with a SCID phenotype:

-Avoid all live viral vaccines
-Only irradiated, CMV negative blood products should be used (to prevent GVHD and infections)
-Pneumocystis jiroveci prophylaxis with trimethoprim-sulfamethoxazole 
-IVIG replacement therapy
-Start HLA-typing for the patient and any siblings for possible hematopoietic stem cell transplantation (HSCT)

 

4.  Patients with significant combined immunodeficiency are candidates for HSCT. 

 

 

                                                                                                               

OVERVIEW

         

    Familial Intestinal Polyatresia is characterized by multiple areas of atresia found throughout the gastrointestinal tract.  

   

    A SCID-like phenotype with panhypogammaglobulinemia and markedly decreased T cell number/function has been reported in patients with this disease.  Less severe defects in humoral and cell-mediated immunity have also been reported. 

 

 

                                 

EVALUATION

An immune evaluation should be performed for patients with intestinal polyatresia.

 

Step 1: Immune Evaluation

 

-CBC with Differential
-Lymphocyte subset enumeration by flow cytometry (CD3, CD4, CD8, CD19, CD16/56)
-Naïve (CD45RA) and memory (CD45RO) T-cell enumeration by flow cytometry
-T-cell proliferation to Mitogens (PHA)
-IgG, IgA, IgM levels 
-Specific Antibody levels (if older than 6 months)

 

-The absolute lymphocyte count (ALC) may be decreased due to CD4 lymphopenia. 

-Marked CD4 lymphopenia is present while B and NK cell numbers are normal.  

-Very low naïve (CD45RA) T-cell numbers can be a useful clue for lack of thymic output in WHN deficiency.     

-Low T cell proliferation to mitogens is seen.  The large blood volume required to perform mitogen proliferation is often an issue with small infants.  ---Performing the proliferation assay with one stimulus (PHA) is acceptable and requires less blood.  

-Immunoglobulin levels may be normal but specific antibody responses are decreased.  

                   

 

 

                                                                 

MANAGEMENT

        

Patients with significant combined immunodeficiency are candidates for HSCT.  It is critical to initiate certain measures to prevent life-threatening complications for patients with a SCID phenotype.  The following precautions should be implemented immediately: 

 

1.  Avoid all live viral vaccines (rotavirus, varicella, MMR, BCG)
Severe vaccine strain disease can occur if SCID patients receive these vaccines. 

 

2.  Only irradiated, CMV negative blood products should be used 
Leukocytes from non-irradiated blood can cause graft versus host disease and CMV can cause severe infections.   

 

3.  Pneumocystis jiroveci prophylaxis with trimethoprim-sulfamethoxazole
4-6mg/kg/day of Trimethoprim component divided twice daily 3 days per week 

 

4.  IVIG replacement therapy

 

5.  High resolution HLA-typing for the patient and any siblings 
For possible Hematopoietic Stem Cell Transplantation (HSCT)

 

 

                                                                           

RESOURCES

 

Literature Resources

 

1.  Conrad 2010 

     Multiple intestinal atresias - 2 new cases and review of literature

 

2.  Moreno 1990

     SCID associated with multiple GI atresias