Journal of Postgraduate Medicine
 Open access journal indexed with Index Medicus & ISI's SCI  
Users online: 5306  
Home | Subscribe | Feedback | Login 
About Latest Articles Back-Issues Articlesmenu-bullet Search Instructions Online Submission Subscribe Etcetera Contact
 
  NAVIGATE Here 
  Search
 
 :: Next article
 :: Previous article 
 :: Table of Contents
  
 RESOURCE Links
 ::  Similar in PUBMED
 ::  Search Pubmed for
 ::  Search in Google Scholar for
 ::  Article in PDF (229 KB)
 ::  Citation Manager
 ::  Access Statistics
 ::  Reader Comments
 ::  Email Alert *
 ::  Add to My List *
* Registration required (free) 

  IN THIS Article
 ::  Genetic Defects
 ::  Clinical Manifes...
 ::  Diagnosis
 ::  Treatment
 ::  Prophylaxis
 ::  Conclusion
 ::  References

 Article Access Statistics
    Viewed7554    
    Printed276    
    Emailed3    
    PDF Downloaded314    
    Comments [Add]    
    Cited by others 12    

Recommend this journal


 


 
GUEST EDITORIAL
Year : 2010  |  Volume : 56  |  Issue : 2  |  Page : 63-64

Hyper-IgE syndrome


1 Molecular Immunology Research Center; and Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran; Research Group for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Infection and Immunity, School of Medicine and Biomedical Sciences, The University of Sheffield, Sheffield, UK
2 Research Group for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran

Date of Web Publication8-Jul-2010

Correspondence Address:
N Rezaei
Molecular Immunology Research Center; and Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran; Research Group for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Infection and Immunity, School of Medicine and Biomedical Sciences, The University of Sheffield, Sheffield, UK

Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0022-3859.65271

Rights and Permissions




How to cite this article:
Rezaei N, Aghamohammadi A. Hyper-IgE syndrome. J Postgrad Med 2010;56:63-4

How to cite this URL:
Rezaei N, Aghamohammadi A. Hyper-IgE syndrome. J Postgrad Med [serial online] 2010 [cited 2023 Oct 4];56:63-4. Available from: https://www.jpgmonline.com/text.asp?2010/56/2/63/65271


Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency disease, characterized by increased serum levels of IgE as well as eczema and recurrent cutaneous and pulmonary infections. It was first described as Job's syndrome in 1966, in patients who suffered from recurrent sinopulmonary infections and cold skin abscesses due to Staphyloccocus auresus; however, the term was subsequently changed to "Hyper-IgE syndrome", when an elevated level of IgE was detected in the serum of affected patients. [1]


 :: Genetic Defects Top


Although autosomal dominant (AD-HIES, OMIM#147060) and autosomal recessive (AR-HIES, OMIM#243700) patterns of inheritance were described for HIES, underlying genetic defects of disease were not discovered for about four decades. Recent studies demonstrated that mutations in the signal transducer and activator of transcription 3 (STAT3, OMIM*102582) gene lead to AD-HIES, [2] whereas mutations in either the dedicator of cytokinesis 8 (DOCK8, OMIM*611432) gene [3] or the tyrosine kinase 2 (TYK2, OMIM*176941) [4] gene cause AR-HIES. There are still several patients with HIES phenotype in which the underlying genetic defect is unknown Although the pathophysiology of the disease has not been completely understood, combined B-and T-cell immunodeficiency is reported in DOCK8 deficiency, whilst impaired T-helper 17 function due to defective signal transduction for multiple cytokines could be the molecular basis of HIES phenotypes in STAT3 deficiency and TYK2 deficiency.


 :: Clinical Manifestations Top


AD-HIES. Hyper-IgE syndrome is a multi-system disorder with a wide range of clinical phenotypes, including connective tissue, skeletal, and vascular abnormalities. [5] The patients with classical form (STAT3 deficiency) often present their first manifestations early in life. Patients' coarse facial appearance is distinctive with broad nasal bridge, deep-set eyes, prominent chin and forehead, cheilitis, and thickened skin. Osteoarticular abnormalities include short stature, osteoporosis, pathologic fractures, scoliosis, craniosynostosis, and hyperflexible joints. Eczema and delay in shedding of primary teeth are common findings in the affected children, whilst they usually suffer from recurrent bacterial infections, especially skin abscesses due to Staphylococcus aureus, and pneumonia with pneumatoceles formation. Malignancies (such as lymphoma and leukemia) and arterial malformations (such as coronary artery aneurysms) have been reported in some cases. [1],[6]

AR-HIES. Although connective tissue and skeletal abnormalities are not associated with AR-HIES, these patients experience eczema and recurrent cutaneous and pulmonary infections. [7] Severe viral infections such as Molluscum contagiosum and Herpes simplex virus infections have been frequently seen in DOCK8 deficiency, whereas an increased susceptibility to intracellular bacteria such as Mycobacteria and  Salmonella More Details as well as fungi and viruses has been reported in TYK2 deficiency. Neurological symptoms, such as partial facial paralysis, hemiplegia and central nervous system hemorrhage have also been reported in a number of patients with AR-HIES. [1],[6]


 :: Diagnosis Top


The diagnosis of HIES is usually made based on characteristic clinical phenotypes associated with increased serum levels of IgE (typically >2000 IU/mL) and eosinophilia. Although the National Institute of Health scoring system (NIH-HIES) based on clinical and laboratory test criteria had been developed a decade ago, a very recent paper suggests diagnostic criteria of increased IgE (>1000 IU/mL) plus a weighted score of clinical features >30 (based on five features of recurrent pneumonia, newborn rash, pathologic bone fractures, characteristic face and high palate) as possible diagnosis of AD-HIES. [8] However, considering recently identified genetic defects, a definite diagnosis can be made by mutation analysis. Consequently, prenatal diagnosis for pregnancies at increased risk is possible, but requires prior identification of the disease-causing mutation in the family.


 :: Treatment Top


Although no curative treatment is available, prophylactic antibiotics and specific treatment based on organ involvement (e.g., surgical interventions for abscess drainage and conventional care for dermatitis) and systemic antibiotics in case of infections are suggested. Immunoglobulin replacement therapy and some other treatments such as IFN-g, Histamine-2 antagonists, and cyclosporine have been tried, which seem to be useful in the management of patients with HIES. [1],[6]


 :: Prophylaxis Top


Prophylactic antibiotic therapy (e.g., trimethoprim-sulfamethoxazole) should be recommended in the HIES patients with recurrent sinopulmonary and cutaneous infections to prevent Staphylococcal infections. The coverage of gram-negative bacteria should also be considered in selecting prophylactic antibiotics, when patients are complicated with pneumatocoeles or bronchiectasis. Antifungal prophylaxis (e.g., fluconazole) is also required because most patients are at increased risk for mucocutaneous candidiasis and invasive fungal infections. [1],[6]


 :: Conclusion Top


HIES is a complex primary immunodeficiency disease with increased serum levels of IgE and distinct phenotypes: the classical form of the disease is characterized by coarse face and connective tissue, skeletal, and vascular abnormalities which is inherited in an AD-HIES (due to STAT3 mutations). The patients with AR-HIES lack the connective tissue and skeletal manifestations, but there is an increased rate of severe viral infections (due to DOCK8 mutations) and intracellular bacteria (due to TYK2 mutations). Although mutations in STAT3 account for most cases of AD-HIES and mutations in DOCK8 were identified in some patients with AR-HIES, there are still several patients with unknown genetic defect. Indeed the exact pathophysiology of the disease has not clearly been understood. It is to be hoped that better understanding of underlying mechanisms will be achieved in the near future, in respect to recent progress in discoveries of genetic defects, which could lead to designing new therapeutic strategies for HIES.

 
 :: References Top

1.Yeganeh M, Gambineri E, Abolmaali K, Tamizifar B, Espaρol T. Other well-defined immunodeficiencies. Primary immunodeficiency diseases: definition, diagnosis and management. In: Rezaei N, Aghamohammadi A, Notarangelo LD, editors. Berlin: Springer; 2008. p. 251-90.  Back to cited text no. 1      
2.Minegishi Y, Saito M, Tsuchiya S, Tsuge I, Takada H, Hara T, et al. Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature 2007;448:1058-62.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]  
3.Zhang Q, Davis JC, Lamborn IT, Freeman AF, Jing H, Favreau AJ, et al. Combined immunodeficiency associated with DOCK8 mutations. N Engl J Med 2009;361:2046-55.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]  
4.Minegishi Y, Saito M, Morio T, Watanabe K, Agematsu K, Tsuchiya S, et al. Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity. Immunity 2006;25:745-55.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]  
5.Grimbacher B, Holland SM, Gallin JI, Greenberg F, Hill SC, Malech HL, et al. Hyper-IgE syndrome with recurrent infections-an autosomal dominant multisystem disorder. N Engl J Med 1999;340:692-702.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]  
6.Freeman AF, Holland SM. Clinical manifestations, etiology, and pathogenesis of the hyper-IgE syndromes. Pediatr Res 2009;65:32-7.  Back to cited text no. 6      
7.Renner ED, Puck JM, Holland SM, Schmitt M, Weiss M, Frosch M,et al. Autosomal recessive hyperimmunoglobulin E syndrome:A distinct disease entity. J Pediatr 2004;144:93-9.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]  
8.Woellner C, Gertz EM, Schδffer AA, Lagos M, Perro M, Glocker EO, et al. Mutations in STAT3 and diagnostic guidelines for hyper-IgE syndrome. J Allergy Clin Immunol 2010;125:424-32.  Back to cited text no. 8      



This article has been cited by
1 Agenesia ovárica unilateral y malformaciones fetales en una mujer embarazada con síndrome de hiperinmunoglobulinemia E
I.E. Bañuelos Martínez,E. Briones Lara
Clínica e Investigación en Ginecología y Obstetricia. 2015;
[Pubmed] | [DOI]
2 Recurrent Skin and Lung Infections in Autosomal Dominant Hyper IgE Syndrome with Transactivation Domain STAT3 Mutation
Chad J. Cooper,Sarmad Said,German T. Hernandez
Case Reports in Immunology. 2014; 2014: 1
[Pubmed] | [DOI]
3 Molecular diagnosis of primary immunodeficiency diseases in a developing country: Iran as an example
AmirHossein Latif,Firouzeh Tabassomi,Hassan Abolhassani,Lennart Hammarström
Expert Review of Clinical Immunology. 2014; : 1
[Pubmed] | [DOI]
4 Ocular Involvement in Primary Immunodeficiency Diseases
Sima Hosseinverdi,Hassan Hashemi,Asghar Aghamohammadi,Hans D. Ochs,Nima Rezaei
Journal of Clinical Immunology. 2013;
[Pubmed] | [DOI]
5 Investigation of underlying primary immunodeficiencies in patients with severe atopic dermatitis
A. Aghamohammadi,Z.Gholizadeh Moghaddam,H. Abolhassani,Z. Hallaji,H. Mortazavi,S. Pourhamdi,P. Mohammadinejad,N. Rezaei
Allergologia et Immunopathologia. 2013;
[Pubmed] | [DOI]
6 Bacillus Calmette-Guérin (BCG) complications associated with primary immunodeficiency diseases
Sayna Norouzi,Asghar Aghamohammadi,Setareh Mamishi,Sergio D. Rosenzweig,Nima Rezaei
Journal of Infection. 2012; 64(6): 543
[Pubmed] | [DOI]
7 The approach to children with recurrent infections
Aghamohammadi, A. and Abolhassani, H. and Mohammadinejad, P. and Rezaei, N.
Iranian Journal of Allergy, Asthma and Immunology. 2012; 11(2): 89-109
[Pubmed]
8 Bacillus Calmette-Guérin (BCG) complications associated with primary immunodeficiency diseases
Norouzi, S. and Aghamohammadi, A. and Mamishi, S. and Rosenzweig, S.D. and Rezaei, N.
Journal of Infection. 2012; 64(6): 543-554
[Pubmed]
9 The demographics of primary immunodeficiency diseases across the unique ethnic groups in Iran, and approaches to diagnosis and treatment
Rezaei, N. and Mohammadinejad, P. and Aghamohammadi, A.
Annals of the New York Academy of Sciences. 2011; 1238(1): 24-32
[Pubmed]
10 Cutaneous cytomegalovirus infection in a child with hyper IgE and specific defects in antibody response to protein vaccines
Fallah, S. and Tabatabaei, A. and Pournasir, Z. and Chavoshzadeh, Z. and Rezaei, N.
Brazilian Journal of Infectious Diseases. 2011; 15(5): 484-485
[Pubmed]
11 Cutaneous cytomegalovirus infection in a child with hyper IgE and specific defects in antibody response to protein vaccines
Shahrzad Fallah,Ahmad Tabatabaei,Zahra Pournasir,Zahra Chavoshzadeh,Nima Rezaei
The Brazilian Journal of Infectious Diseases. 2011; 15(5): 484
[Pubmed] | [DOI]
12 The demographics of primary immunodeficiency diseases across the unique ethnic groups in Iran, and approaches to diagnosis and treatment
Nima Rezaei,Payam Mohammadinejad,Asghar Aghamohammadi
Annals of the New York Academy of Sciences. 2011; 1238(1): 24
[Pubmed] | [DOI]



 

Top
Print this article  Email this article
Previous article Next article
Online since 12th February '04
© 2004 - Journal of Postgraduate Medicine
Official Publication of the Staff Society of the Seth GS Medical College and KEM Hospital, Mumbai, India
Published by Wolters Kluwer - Medknow