Monday, January 30, 2023

Job Syndrome

Background

Autosomal dominant hyperimmunoglobulin E (IgE) syndrome (HIES) was first described as Job syndrome in 1966
and included the triad of eosinophilia, eczema, and recurrent skin and pulmonary infections (named after the biblical character Job, who was “smote with sore boils”). Elevated IgE level was recognized as a cardinal feature of the syndrome in 1972, and the name HIES was subsequently proposed.
The phenotype was later expanded to include many connective tissue and skeletal abnormalities. A scoring system that weighted both the immunologic and somatic features of the syndrome was designed to aid in the clinical diagnosis of these patients (see the table below).

Table. Scoring System for Job Syndrome (Open Table in a new window)

 

0

1

2

3

4

5

6

7

8

10

Clinical Findings

 

 

 

 

 

 

 

 

 

 

Highest IgE (IU/mL)

< 200

200-500

 

 

501-1000

 

 

 

1001-2000

>2000

Total # skin abscesses/boils

None

 

1-2

 

3-4

 

 

 

>4

 

Total # pneumonias

None

 

1

 

2

 

3

 

>3

 

Parenchymal lung abnormalities

None

 

 

 

 

 

Bronchiectasis

 

Pneumatocele

 

Other serious infection

None

 

 

 

Present

 

 

 

 

 

Fatal infection

None

 

 

 

Present

 

 

 

 

 

Highest eosinophils/uL

< 700

 

 

701-800

 

 

>800

 

 

 

Newborn rash

None

 

 

 

Present

 

 

 

 

 

Eczema (worst stage)

None

Mild

Moderate

 

Severe

 

 

 

 

 

Sinusitis/otitis (# in worst year)

1-2

3

4-6

 

>6

 

 

 

 

 

Candidiasis

None

Oral, vaginal

Fingernail

 

Systemic

 

 

 

 

 

Retained primary teeth

None

1

2

 

3

 

 

 

>3

 

Scoliosis (max. curvature)

< 10

 

10-14

 

15-20

 

 

 

>20

 

Minimal trauma fractures

None

 

 

 

1-2

 

 

 

>2

 

Hyperextensibility

None

 

 

 

Present

 

 

 

 

 

Characteristic face

None

 

Mild

 

 

Present

 

 

 

 

Increased interalar distance

< 1 SD

1-2 SD

 

>2 SD

 

 

 

 

 

 

High palate

None

 

Present

 

 

 

 

 

 

 

Congenital anomaly

None

 

 

 

 

Present

 

 

 

 

Lymphoma

None

 

 

 

Present

 

 

 

 

 

 

More recently, vascular abnormalities, including coronary aneurysm without atherosclerosis, and brain MRI abnormalities, including focal hyperintensities and Chiari I malformations, have been described. In 2007, autosomal dominant mutations in signal transducer and activator of transcription-3 (STAT3) gene were identified as the molecular cause of this disease.
See image below.


STAT3 gene is diagrammed with depiction of hotspo

STAT3 gene is diagrammed with depiction of hotspots (areas where higher numbers of patients were noted to have mutations).

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