Job Syndrome Clinical Presentation

Updated: Apr 05, 2016
  • Author: Jennifer Heimall, MD; Chief Editor: Michael A Kaliner, MD  more...
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Presentation

History

Eczematoid dermatitis starts in the newborn period and is typically associated with and driven by Staphylococcus aureus infection. Skin abscesses due to S aureus are common and typically not associated with a robust inflammatory response either locally or systemically, hence the term cold abscesses. Mucocutaneous candidiasis, including onychomycosis, occurs frequently. Conversely, severe warts and Molluscum species are not features of autosomal dominant (AD) HIES.

Pneumonias start in early childhood, typically due to S aureus, Streptococcus pneumoniae, and Haemophilus influenzae. Similar to the skin abscesses, signs of systemic toxicity are modest. Even when treated aggressively and promptly, the pneumonias often resolve with pneumatocele formation (see image below), presumably due to dysregulated local inflammation and resultant tissue destruction. Later superinfection of the pneumatoceles with Pseudomonas aeruginosa and molds such as Aspergillus and Scedosporium species can be associated with significant morbidity and mortality. Opportunistic infections including Pneumocystis jiroveci pneumonia, disseminated histoplasmosis, cryptococcosis, and coccidioidomycosis also occur, although less frequently. Recurrent bacterial sinusitis and otitis are common, but susceptibility to viral pathogens is not increased.

Recurrent pneumonias, particularly those due to S Recurrent pneumonias, particularly those due to S aureus, may lead to pneumatocele formation. Pneumatoceles such as those demonstrated in this CT image may then allow fungal superinfection.

HIES is also associated with multiple connective tissue and skeletal abnormalities, including scoliosis, hyperextensibility, pathologic fractures, retained primary dentition, craniosynostosis, and vascular abnormalities. Many patients have hyperextensibility of at least one joint. Despite these connective tissue abnormalities, HIES patients typically demonstrate normal wound healing. Most patients report at least one nontraumatic fracture, such as broken ribs with coughing. Osteoporosis is common but does not appear to correlate with frequency of fractures. Retention of primary teeth is due to failure of primary tooth exfoliation; [12] characteristic palatal, tongue, and oral mucosal changes are often present as well. Arterial tortuosity and aneurysm occur, typically of the middle-sized vessels, such as coronary arteries. [13] Brain MRI abnormalities include focal hyperintensities and an increased incidence of Chiari I malformations. [14]

Despite the increased IgE and eosinophilia, patients do not typically have significant atopy with regard to foods or seasonal allergens.

A detailed family history may help identify other cases, but most cases are spontaneously arising mutations or autosomal dominant. The clinical diagnosis of HIES has been based on a composite profile of immunologic and nonimmunologic features, leading to a score that correlates well with identifying STAT3 mutations.

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Physical

Individuals share a characteristic facial appearance, with a broad nose, deep-set eyes with prominent forehead, and generalized coarsening of the facial features with age. A high arched palate is often present, and double-rowed teeth may be present. Oral thrush may be seen. The tympanic membrane may be scarred from recurrent otitis.

Both pediatric and adult patients may demonstrate an erythematous, scaly pruritic rash, typical of eczematous dermatitis. Scarring from incision and drainage of boils may be present. The nails, vagina, and inguinal region often demonstrate candidiasis.

The pulmonary examination varies depending on previous pulmonary infections and lung parenchymal changes. The examination ranges from normal to decreased tactile fremitus and decreased air exchange associated with large pneumatoceles. Clubbing of the nails is common.

Scoliosis >10 degrees is seen in 60% of patients. Hyperextensibility of at least one joint is present in 70% of patients.

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Causes

Most, if not all, cases of autosomal dominant HIES are due to dominant negative mutations in STAT3, a key signaling molecule for immunologic and somatic gene transcription.

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