Dr.Jerin.K.John,Dr.Suma Balan(Ped Rheumat ,AIMS Kochi), Dr.C.Jayakumar (Paediatrics)
A 14-year-old male, the second child of non-consanguineous parents, presented with a history of worsening low back pain and radicular pain for three years, with increased intensity over the last two months. The pain radiated to the back, chest, and abdomen, exacerbated coughing, sneezing, and bending. There were no associated sensory disturbances, muscle weakness, or joint pains. He had been on alternative medicine for the past five years.
The patient also experienced intermittent fever for several months, accompanied skin lesions on the lower back, described as vesicular lesions that ruptured and discharged pus. He developed deep-seated skin lesions on the dorsum of his legs, suspicious for abscesses.
His medical history included recurrent infections and abnormal craniofacial development. He had eczema-like skin lesions since birth and was also diagnosed with craniosynostosis and scaphocephaly.
Labs
CRP – 1.31 mg/l
IgE – > 2500 Iu/ ml
IgA – 71 mg/ dl
IgG – 1610mg / dl
IgM – 117 mg / dl
MRI and CT scans of the brain revealed sinus pericranii with abnormal communication of the torculaheterophili(confluence of Sinuses) with the scalp veins. The patient also had recurrent parotid abscesses, cervical lymphadenitis, and epididymo orchitis in infancy.
Recently, a Basic Lymphocytic panel revealed an increased absolute lymphocyte count, as well as elevated CD3+ and CD8+ T lymphocytes based on scatter parameters and antigen expression profile from flow cytometry.
Whole ExomeSequencing (WES) confirmed a STAT3 mutation, establishing the diagnosis of Hyper IgE Syndrome (Job Syndrome). There was no family history of immunodeficiency or recurrent infections.
The child is currently managed with Fluconazole and Septrantablets.
Discussion:
Hyperimmunoglobulin E Syndrome (HIES), also known as Job Syndrome, is a rare primary immunodeficiency disorder characterized a triad of high serum IgE levels, eczema, and recurrent skin and pulmonary infections. First described Davis et al. in 1966, the syndrome was later refined Buckley in 1972, who reported distinct facial features and elevated IgE, referring to it as Buckley’s Syndrome.
HIES presents in two distinct patterns: Autosomal Dominant (AD) and Autosomal Recessive (AR). The AD form, which was identified as a result of missense or in-frame deletions in the STAT3 gene, is the more common form. Patients with AD-HIES exhibit a wide spectrum of immunologic and non-immunologic manifestations. Immunologic symptoms include recurrent skin abscesses, pneumonias, mucocutaneouscandidiasis, and an elevated serum IgE level, while non-immunologic features include characteristic coarse facial features, scoliosis, and retained primary teeth.
The patient in this case demonstrated many hallmark features of AD-HIES, including recurrent skin abscesses, abnormal craniofacial development, and infections like pneumonia and lymphadenitis. His history of musculoskeletal complaints, including back pain and radicular symptoms, may reflect underlying bone abnormalities, such as scoliosis and vertebral fractures, commonly associated with AD-HIES.
Management of HIES focuses on controlling infections and preventing complications. Skin care, particularly in managing eczema and abscesses, is crucial, often requiring topical corticosteroids, antibiotics, and hydrating agents. Antimicrobial prophylaxis, particularly against Staphylococcus aureus, is essential for preventing recurrent infections. In more severe cases, hematopoietic stem cell transplantation and immunomodulators are considered.
Carry Home Message:
Hyper IgE Syndrome is a complex immunodeficiency disorder that requires early recognition and a multi-disciplinary approach to management. Diagnosis, aided genetic testing, is essential for guiding treatment. Ongoing management focuses on preventing and treating infections while addressing systemic complications. Regular follow-up and supportive care are crucial in maintaining the patient’s quality of life.