Hyper-IgE-Syndrome 5 D82.4

Autosomal recessive hyper IgE recurrent infection syndrome-5, or HIES5, is an immunodeficiency syndrome characterized by the occurrence of recurrent sinopulmonary as well as bacterial skin infections in early childhood. The sinopulmonary and cutaneous infections are mostly bacterial in nature (H. influenza and Staphylococcus aureus). Other clinical features include:

• atopic dermatitis
• bronchial asthma
• elevated serum IgE
• elevated interleukin-6.

Hyper IgE syndrome 5 is associated with mutations in the IL6R gene.

Spencer et al (2019) reported 2 unrelated patients with a similar immunologic disorder.

Pat.1. 29-year-old woman of unrelated English parents presented with neonatal mastitis, as well as later recurrent sinopulmonary infections. Furthermore, she suffered from staphylococcal skin abscesses as well as recurrent erysipelas. Other features included bronchial asthma and pruritic atopic dermatitis. She had a normal response to standard childhood immunizations. Laboratory tests showed elevated IgE, eosinophilia, a slight decrease in other immunoglobulins, elevated IL6, and an absence of inflammatory signs associated with infections (absence of fever, only weak neutrophilia, no increase in C-reactive protein.

Pat.2. 15-year-old boy born to consanguineous Pakistani parents had a similar phenotype with early-onset recurrent infections, atopic dermatitis, elevated serum IgE, and impaired inflammatory response. None of the patients had significant viral or fungal infections. Comprehensive immunologic studies showed that both patients had decreased gamma interferon (IFNgamma) production, expansion of proatopic subsets of CD4+ T helper cells, increased GATA3 expression, and decreased levels of circulating T follicular helper cells.

1. Spencer S et al (2019) Loss of the interleukin-6 receptor causes immunodeficiency, atopy, and abnormal inflammatory responses. J Exp Med 216: 1986-1998.