SUMMARY

 

1. Netherton syndrome (Comel-Netherton syndrome) is an autosomal recessive disorder that affects the skin, hair, and immune system. It is characterized by the following clinical features: 

 

       -Trichorrhexis (bamboo hair) 
       -Congenital ichthyosis 
       -Erythroderma 
       -Staphylococcal skin infections 
       -Bacterial sinopulmonary infections and sepsis 
       -Immunologic abnormalities 
       -Atopic diathesis (allergic rhinitis, food allergy, asthma, eczema) 

 

2. Patients have dry and brittle hair that break easily. Examination of hair under light microscopy reveals a characteristic ball-and-socket appearance (this abnormality is most consistently visualized on hairs from the eyebrow). 

 

3. The Immunologic abnormalities reported in Netherton syndrome include low IgG, impaired vaccine responses to protein and polysaccharide antigens, decreased CD27+ memory B cells, elevated IgE, eosinophilia, and decreased NK cell function (with normal numbers). 

 

4. Netherton syndrome is caused by mutations in SPINK5. This encodes a serine protease inhibitor (LEKTI) which is highly expressed in the thymus and epithelium. 

 

5. The diagnosis is suspected in patients with characteristic cutaneous/hair findings and immune abnormalities. SPINK5 gene sequencing can confirm the diagnosis. 

 

6. The differential diagnosis for dermatitis and immunodeficiency includes Omenn, IPEX, Wiskott-Aldrich, AD Hyper IgE syndrome (STAT3), and AR Hyper IgE syndrome (DOCK8, Tyk2). 

 

7. The management of the clinical manifestations is as follows: 


-Dermatitis - Topical emollients, keratolytics, corticosteroids, and topical calcineurin inhibitors may be useful. 

-Asthma, Allergic Rhinitis, Food Allergy - Standard treatment regimens for these conditions should be used. 

-Immunodeficiency - IVIG replacement therapy may be considered for patients with recurrent infections who have low IgG or impaired vaccine responses. Improvement of infections, decreased skin inflammation, and improved NK cell function following initiation of IVIG has been reported. Prophylactic antibiotic therapy is an adjunctive treatment option for patients who continue to have infections. 

 

 

 

                                                                                                             

OVERVIEW

 

      Netherton syndrome (Comel-Netherton syndrome) is an autosomal recessive disorder that affects the skin, hair, and immune system. It is characterized by the following clinical features: 

Trichorrhexis (bamboo hair) 
Congenital ichthyosis 
Erythroderma 
Staphylococcal skin infections 
Bacterial sinopulmonary infections and sepsis 
Immunologic abnormalities 
Atopic diathesis (allergic rhinitis, food allergy, asthma, eczema) 

 

     Patients have dry and brittle hair that break easily. Examination of hair under light microscopy reveals a characteristic ball-and-socket appearance (this abnormality is most consistently visualized on hairs from the eyebrow). 

 

     The Immunologic abnormalities reported in Netherton syndrome include low IgG, impaired vaccine responses to protein and polysaccharide antigens, decreased CD27+ memory B cells, elevated IgE, eosinophilia, and decreased NK cell function (with normal numbers). 

Netherton syndrome is caused by mutations in SPINK5. This encodes a serine protease inhibitor (LEKTI) which is highly expressed in the thymus and epithelium. 

 

 

                                 

EVALUATION

 

The diagnosis of Netherton syndrome should be suspected for patients with erythroderma, dermatitis, recurrent skin and sinopulmonary infections, and humoral immunodeficiency. 
    
 Step 1:  Immune Evaluation

 

-CBC with Differential 
-Lymphocyte subset enumeration by flow cytometry (CD3, CD4, CD8, CD19, CD16/56) 
-Memory B cell enumeration by flow cytometry (CD19+CD27+) 
-IgG, IgA, IgM, IgE levels 
-Specific Antibody levels (if older than 6 months) 
-T-cell proliferation to Mitogens (PHA) 
-NK cell functional assay 

 

-The CBC with differential may reveal eosinophilia. 
-T, B and NK cell numbers are typically normal. 
-Low unswitched memory (CD27+IgM+IgD+) and low switched memory (CD27+IgM-IgD-) B cell numbers have been reported 
-Low IgG and elevated IgE may be present. 
-Vaccine responses to protein (Tetanus, Diphtheria) and polysaccharide (Pneumococcal) antigens should be evaluated. Low specific antibody responses have been reported in Netherton syndrome. 
-T-cell proliferation to mitogens is typically normal. 
-Decreased NK cell cytotoxicity has been reported. 

 

Step 2:  Gene Sequencing  


-SPINK5 Gene Sequencing 

 

-The diagnosis can be confirmed by gene sequencing (this test is available commercially through Gene Dx). 

 

 

 

                                                                   

MANAGEMENT

 

The management of the clinical manifestations is as follows: 


Dermatitis - Topical emollients, keratolytics, corticosteroids, and topical calcineurin inhibitors may be useful. 

 

Asthma, Allergic Rhinitis, Food Allergy - Standard treatment regimens for these conditions should be used. 

 

Immunodeficiency - IVIG replacement therapy may be considered for patients with recurrent infections who have low IgG or impaired vaccine responses. Improvement of infections, decreased skin inflammation, and improved NK cell function following initiation of IVIG has been reported. Prophylactic antibiotic therapy is an adjunctive treatment option for patients who continue to have infections. 

 

 

 

 

                                                                           

RESOURCES

 

Diagnostic Resources   

 

1. Gene Dx - SPINK5 sequencing

 

 

 

Literature Resources

 

1.  Renner 2009 
     Netherton syndrome defined as a primary immunodeficiency