Discussion
STAT3 is a critical regulator of multiple processes, including cellular proliferation, survival, differentiation, fetal development, cancer, wound healing, angiogenesis, autoimmunity and inflammation.5 Defect in its function results in multisystem disorders such as dental abnormalities and connective tissue defects.5 In the present study, we investigated a boy with acute asthma attacks, eczema, and dental abnormalities.
Abnormalities in the dentition are frequently observed in AD-HIES, although its mechanism(s) is not well identified yet. It is reported that STAT3 as a transcription factor play indispensable roles in signaling pathways of various cytokine such as IL-6, IL-10, IL-21, IL-22, and IL-23. 8, 9 Among these cytokines, IL-6 has a positive role in bone resorption through inducing osteoclastogenesis.10, 11 Thus, impaired STAT3 signaling may disrupt the role of IL-6 in osteoporosis and thereby contribute to the retention of primary teeth in AD-HIES. 12 In line with this notions, some reports have revealed that retention of deciduous teeth is owing to reduced resorption of tooth roots leading to failure of eruption of permanent teeth.7 Grimbacher et al evaluated 30 patients with HIES and 70 of their relatives and reported primary teeth retention in 72% of them. 13 In another study by O’Connel et al on 34 HIES patients, it was indicated that 75% of subjects older than 7 years had problem with permanent tooth eruption, in the form of prolonged retention of primary teeth or the need for extraction of primary teeth. 14 In another report of 60 patients with the HIES, 76.7% of subjects suffered from intraoral lesions such as fibrotic bridges in the hard palate or keratotic plaques which were more prevalent than the characteristic facial traits. 15 Considering the above findings in the literature, abnormal dentition in our patient is a common feature but as the prominent finding in an adolescent is particularly noteworthy.
Asthma and anaphylaxis were two atypical presentations in this patient. According to the literature, allergic manifestations including allergic rhinitis, asthma, urticaria, and anaphylaxis are not common clinical features in these patients despite their high serum IgE concentrations. Wjst et al tested whether STAT3 mutations were responsible for increased IgE levels in asthmatic children and found it unlikely.16 Furthermore, some studies have reported no significant association between STAT3 gene expression and either mild or severe refractory asthma. 17 However, positive findings regarding an allergic background in our case including neonatal dermatitis with positive skin prick test to milk, egg, and wheat and a favorable response to an elimination diet, recurrent asthma exacerbations, as well as a history of anaphylaxis may denote an underlying atopic predisposition.
Taken together, our findings indicate that clinical evaluations of some atypical presentations, such as asthma and anaphylaxis, along with immunological and genetic analyses can be helpful to better diagnosis and management of AD-HIES, which can improve life quality of patients. Therefore, patients suffering from allergic and infectious diseases, autoimmune disorders, and dental abnormalities should be investigated by clinical, immunological, and genetic tests to determine possible mutations in STAT3 gene.