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.