Clinical Profile:

A three year old girl, symptomatic since six month of age, presented with cough, cold and fever. The patient has history of recurrent chronic suppurative otitis media and pneumonia. She was found to have severe anemia with thrombocytopenia.

Radiological findings:

The frontal chest radiograph shows a loculated pneumothorax on the right sided with collapse of the underlying lung and shift of the mediastinum to the left (Fig. 1)

A diagnosis of of right sided pneumothorax with consolidation was made. The patient was started on intravenous, broad spectrum antibiotics and an intercostal drain was inserted (Fig. 2).

Fig. 3a, 3b, 3c

Serial radiographs show recurrent pneumothorax and pleural fluid despite insertion of intercostal drain

Discussion:

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 .

Hyperimmunoglobulin E syndrome (hyper-IgE syndrome, Job syndrome, HIES) is a complex immunodeficiency with multiorgan clinical manifestations and diverse genetic background. Classic form of hyper-IgE syndrome inherited in an autosomal dominant manner (AD-HIES) is caused by a mutation in a transcription factor gene STAT3 (signal transducer and activator of transcription 3). Mutation of STAT3 leads to impairment of signaling of many cytokines, including interleukin (IL)-6 and IL-22, as well as dysfunction of T-helper 17 lymphocytes, which play a crucial role in immune response to infections caused by pathogens such as extracellular bacteria and fungi [1][2]

The classical clinical triad of symptoms is observed in about 75% of patients with AD-HIES and includes: recurrent abscesses of staphylococcal etiology, recurrent respiratory tract infections and elevated serum immunoglobulin E concentrations. This disorder displays abundance of symptoms such as dermatitis, furunculosis, dysmorphic facial features, skeletal and dental abnormalities as well as connective tissue defects [3,4].Chronic or recurrent respiratory tract infections and pneumonias are usually severe and associated with the risk of permanent damage to the lung tissue. Pneumonias are complicated with pneumatocele or pneumothorax formation.

The hyper-IgE syndrome can also be suspected due to the presence of dysmorphic features – prognathia, gothic palate, broad nasal bridge, hypertelorism, a double set of deciduous and permanent teeth, extensive caries, hyper-mobile joints and scoliosis.

Aside from skin lesions, the most commonly occurring complications include paranasal sinusitis, otitis media and respiratory tract infections. Etiological factors of infection include Staphylococcus aureus, Haemophilus influenzae. Moreover, microorganisms such as Pseudomonas aeruginosa or Aspiergillus fumigatus are known for causing superinfections [5].

The authors [6] analyzing medical histories of patients with hyper-IgE syndrome emphasized that pneumonias as a typical picture of the disease, are often complicated by abscess formation . Likewise, bronchiectasis and pneumatocele are described in the literature as pathognomonic in this group of patients.

Delay in the diagnosis of hyper-IgE syndrome is frequent and may be due not only to nonspecific clinical manifestation of the disease, but also lack of familiarity of the radiologist and other clinicians with this rare syndrome. The most common reported manifestation of hyper-IgE syndrome is the infectious involvement of the soft tissues, upper and lower respiratory tract. The infection in cutaneous and subcutaneous tissues may spread to neighboring tendons, bursae, bones and joints. Vascular system is less frequently involved. CT and MR imaging with typical laboratory findings provide important information that may be helpful for initiating early and correct therapeutic approach.

Complications associated with pulmonary infections are one of the most common causes of death in the course of hyper-Ig E syndrome. Late diagnosis leads to significant impairment of patients’ respiratory function and reduces the chances for normal development of a child. Introduction of comprehensive management, including prophylactic treatment, allows for a reduction in the frequency of recurrences. Therefore, the role of a radiologist who often analyzes patient’s whole medical documentation is important for guiding further diagnostics including immunological evaluation.

References:

1. Minegishi Y, Karasuyama H. Genetic origins of hyper- IgE syndrome. Curr Allergy Asthma Rep. 2008;8:386–91. [PubMed] [Google Scholar]

2. Minegishi Y, Karasuyama H. Defects in Jak -STAT-mediated cytokine signals cause hyper- IgE syndrome: lessons from a primary immunodeficiency. Int Immunol. 2008;21:105–12. [PubMed] [Google Scholar]

3. Freeman AF, Holland SM. The hyper- IgE syndromes. Immunol Allergy Clin North Am. 2008;28:2777. [PubMed] [Google Scholar]

4. Freeman AF, Holland SM. Clinical manifestations, etiology and pathogenesis of the hyper- IgE syndromes. Pediatr Res. 2009;65:32–37. [PMC free article] [PubMed] [Google Scholar]

5. Gorur K, Ozcan C, Unal M, et al. Hyperimmunoglobulin – E syndrome: a case with chronic ear draining mimicking polypoid otitis media. Int J Pediatr Otorhinolaryngol. 2003;67:409–12. [PubMed] [Google Scholar]

6. Lui RC, Inculet RI. Job’s syndrome: a rare cause of recurrent lung abscess In childhood. Ann Thorac Surg. 1990;50:992–94. [PubMed] [Google Scholar]

Acknowledgement:

We are grateful to the Department of Pediatric surgery at our institution for providing the intraoperative photographs.