Immunodeficiency Syndromes

Question 1

Hyper IgE

Answer 1

AD (classic) – variable expressivity
STAT3 (signal transducer and activator of transcription 3)
M=F

Other distinct AR forms (DOK8 def – see below)

Presents first few months-first year.
Some have only cutaneous manifestations; Most - Recurrent sinopulmonary infections

Skin
1st month Non infectious folliculocentric papulopustular eruption Face, scalp, neck, axillae, diaper
Eczematous dermatitis – pruritis, lichenification, staph. Commonly clears but adolescence NO other ATOPY (no rhinitis, asthma)
Skin infections
- Chronic candidiasis 80% oral mucosa, periungal, nail
- Staph infections – impetiginized plaques, retroauricular fissures, folliculitis, furunculosis, abscesses, cellulitis, lymphangitis, paronychia (nail dystrophy)
- “Cold” cutaneous abscess (not red and tender)– v large -neck, scalp, periorbital, axilla, groin -commonly afebrile. Strep pygonesis, c.albicans common

Dental
Retained primary teeth
50% high arch palate

Craniofacial
Coarse facies, broad nasal bridge, prominent nose, thick doughy skin,
large follicular ostia, pitted scarring, broad nasal bridge, wide fleshy nasal tip, deep set eyes, prominent forehead, irregular proportioned cheeks, jaw

Sinopulmonary - Other than lungs visceral infection uncommon

• Bronchitis. pneumonia (s.aureus, h.influenza).
• empyemea, bronchiectasis, pneumatocoele (cam become secondary infected with fungal aspergillus)
• sometimes massive hemoptusis
• pneumocytis jiroveci pneumonia can also occur in kids.

MSK
Osteopenia
-#s long bones, ribs, pelvis
Scoliosis >16yo
Joint hyperextensibility 70%

Other
Brain anomalies may occur – chiari malformations, lacunar infarctions, focal hyperintensities in white matter on MRI
Coronary aneurysms in adulthood can occur
Increase NHL

FEADS B
Faces, Eczema, Abscess, Dental, Sinopulmonary, Bony

Ix
IgE>2000IU/ml (polyclonal)
-esp high anti-staph and candida IgE
-common urticarial rxn to food and other enviro allergens. 
Eosinophilia

Abnormal cell mediated immunity – anergy to skin testing

NORMAL IgG, IgA, IgM, lymphocyte subsets

IL-4 increases IgE in AD and normal but NOT HIES

DIAGNOSTIC CRITERIA
• IgE level >1000 IU/ml AND
• Weighted score of five clinical features AND
• lack of Th17 cells or heterozygous STAT3 mutation
Clinical features for diagnosis
-Pneumonias,Newborn papulosputular eruption in first 3 weeks; pathological bone fractires, charactersitc facies, hgih arched palate.

Mx
No prenatal diagnosis

I&D abscesses
Therapeutic + prophylactic Abs

INF-y may help control infections
IVIG may improve dermatitis, prevent infections, lower IgE
?omalizumab