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Hyperimmunoglobulinemia E (Job) Syndrome Follow-up

  • Author: Harumi Jyonouchi, MD; Chief Editor: Russell W Steele, MD  more...
 
Updated: Oct 21, 2015
 

Further Outpatient Care

Dental care must be provided when primary teeth fail to be shed and interfere with eruption of permanent teeth in patients with AD HIES.

There is on case report of the use of IFN-α for treatment of severe molluscum skin infection in one patient with HIES.[35]

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Further Inpatient Care

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  • Pneumonia in patients with HIES may be extremely complicated and require prolonged inpatient management. The abnormal inflammatory response with progression to pneumatoceles requires close observation and possible surgical intervention. Empyemas, bronchopleural fistulas, and hemoptysis caused by erosion into bronchial arteries are potential emergencies.
  • Other infections requiring inpatient care include osteomyelitis, which may be difficult to distinguish clinically from fractures, and deep-seated abscesses or myositis requiring incision, drainage, and packing.
  • When vigorous antibiotic therapy is required for infection, fungal prophylaxis is also required because most patients are at increased risk for mucocutaneous and invasive fungal infections, predominantly Candida and Aspergillus. Pay careful attention to signs of superinfection of lung abscesses with Aspergillus.
  • In patients with AR HIES, cutaneous viral infection can be very treatment-resistant and a prolonged treatment may be required.
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Inpatient & Outpatient Medications

See the list below:

  • See Medical Care.
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Transfer

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  • Most clinical immunologists feel strongly that the great complexity of medical problems for any primary immunodeficiency disease requires treatment of those patients by an immunologist. Subtle signs of infection, complex clinical features, and high complication rates in patients with HIES suggest a vital role for a clinical immunologist for the care of patients with HIES.
  • A major reason for transfer is for thoracic surgery management of a lung abscess, bronchopulmonary fistula, or erosion of infection into a bronchial artery.
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Deterrence/Prevention

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  • Prophylactic oral antibiotic coverage for S aureus and an antifungal agent against Candida species are required for most patients.
  • Prenatal diagnosis may be possible in a child born to parents with know mutations with STAT3 or DOCK8.
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Complications

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  • Pulmonary complications of infection, such as bronchopulmonary fistula or bleeding, are surgical emergencies.
  • Craniosynostosis has been reported in several patients with AD HIES.
  • Occasional cases of malignancy have been reported mainly in AR-HIES patients, mainly originating from skin. Careful monitoring is indicates.
  • In 13 patients with AR HIES, 5 were reported to have CNS symptoms associated with vascular anomalies (stenosis, occlusion, and aneurysm formation), and 3 of 5 these patients died with subsequent complications (cerebral infarction and subarachnoid hemorrhages).
  • Recently, fatal aneurysmal dilatation of the thoracic aorta was reported in 2 adolescents with AR HIES. Coronary artery aneurysms were also reported in 2 patients with AD HIES who were in their fifth decade of life when aneurysms were diagnosed.
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Prognosis

Follow-up care for patients with HIES is not well documented, but most patients with AD HIES survive into mid adulthood. Chronic pulmonary disease compromises function and affects the mortality rate. Most deaths in the second to third decade of life result from lung abscesses superinfected with Aspergillus species or gram-negative bacteria. More aggressive medical and surgical care may decrease this mortality rate.

Failure of hematopoietic stem cell transplantation to correct HIES in one patient raises the question of whether therapy for HIES with any form of stem-cell reconstitution would be effective. This may also be associated with mutations causing HIES. Patients with DOCK8 deficiency may be expected to benefit from stem-cell reconstitution more so than other HIES patients.

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Patient Education

See the list below:

  • Patients and their families must be alert to early subtle signs of infection and seek appropriate medical care. In the author's experience, primary care physicians and surgeons also often underestimate the extent of deep abscess formation and need for surgical drainage.
  • Daily care for eczema is tedious. Persuading patients and their families of the use of daily care is difficult when dermatitis does not respond uniformly to medical management.
  • The Immune Deficiency Foundation is an important resource for education and for support for patients and families with any primary immunodeficiency disease. The foundation's address is 40 W Chesapeake Ave, Suite 308, Towson, MD 21204; some states have local chapters. The telephone number for consultation calls is (800) 296-4433.
  • The Jeffrey Modell Foundation at 747 3rd Avenue, New York City, NY 10017 also provides support and patient education. The telephone number is (212) 819-0200.
  • For excellent patient education resources, visit eMedicineHealth's Skin Conditions and Beauty Center. Also, see eMedicineHealth's patient education article Eczema.
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Contributor Information and Disclosures
Author

Harumi Jyonouchi, MD Faculty, Division of Allergy/Immunology and Infectious Diseases, Department of Pediatrics, Saint Peter's University Hospital

Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Pediatric Research, Society for Mucosal Immunology

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David J Valacer, MD 

David J Valacer, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association for the Advancement of Science, American Thoracic Society, New York Academy of Sciences

Disclosure: Nothing to disclose.

Chief Editor

Russell W Steele, MD Clinical Professor, Tulane University School of Medicine; Staff Physician, Ochsner Clinic Foundation

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, Southern Medical Association

Disclosure: Nothing to disclose.

Additional Contributors

James M Oleske, MD, MPH François-Xavier Bagnoud Professor of Pediatrics, Director, Division of Pulmonary, Allergy, Immunology and Infectious Diseases, Department of Pediatrics, Rutgers New Jersey Medical School; Professor, Department of Quantitative Methods, Rutgers New Jersey Medical School

James M Oleske, MD, MPH is a member of the following medical societies: Academy of Medicine of New Jersey, American Academy of Allergy Asthma and Immunology, American Academy of Hospice and Palliative Medicine, American Association of Public Health Physicians, American College of Preventive Medicine, American Pain Society, Infectious Diseases Society of America, Infectious Diseases Society of New Jersey, Medical Society of New Jersey, Pediatric Infectious Diseases Society, Arab Board of Family Medicine, American Academy of Pain Management, National Association of Pediatric Nurse Practitioners, Association of Clinical Researchers and Educators, American Academy of HIV Medicine, American Thoracic Society, American Academy of Pediatrics, American Public Health Association, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

References
  1. Dinauer MC. Disorders of neutrophil function: an overview. Methods Mol Biol. 2014. 1124:501-15. [Medline].

  2. Buckley RH. Disorders of the IgE system. Steigm ER, ed. Immunologic Disorders in Infants and Children. 4th ed. 1996. 413-422.

  3. Minegishi Y, Saito M, Tsuchiya S, et al. Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature. 2007 Aug 30. 448(7157):1058-62. [Medline].

  4. Holland SM, DeLeo FR, Elloumi HZ, Hsu AP, Uzel G, Brodsky N, et al. STAT3 mutations in the hyper-IgE syndrome. N Engl J Med. 2007 Oct 18. 357(16):1608-19. [Medline].

  5. Minegishi Y, Karasuyama H. Hyperimmunoglobulin E syndrome and tyrosine kinase 2 deficiency. Curr Opin Allergy Clin Immunol. 2007 Dec. 7(6):506-9. [Medline].

  6. Minegishi Y, Saito M, Morio T, et al. Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity. Immunity. 2006 Nov. 25(5):745-55. [Medline].

  7. Renner ED, Pawlita I, Hoffmann F, et al. No indication for a defect in toll-like receptor signaling in patients with hyper-IgE syndrome. J Clin Immunol. 2005 Jul. 25(4):321-8. [Medline].

  8. Zhang Q, Davis JC, Lamborn IT, Freeman AF, Jing H, Favreau AJ. Combined immunodeficiency associated with DOCK8 mutations. N Engl J Med. 2009 Nov 19. 361(21):2046-55. [Medline].

  9. Su HC, Jing H, Zhang Q. DOCK8 deficiency. Ann N Y Acad Sci. 2011 Dec. 1246:26-33. [Medline].

  10. Borges WG, Augustine NH, Hill HR. Defective interleukin-12/interferon-gamma pathway in patients with hyperimmunoglobulinemia E syndrome. J Pediatr. 2000 Feb. 136(2):176-80. [Medline].

  11. Netea MG, Kullberg BJ, van der Meer JW. Severely impaired IL-12/IL-18/IFNgamma axis in patients with hyper IgE syndrome. Eur J Clin Invest. 2005 Nov. 35(11):718-21. [Medline].

  12. Casanova J-L, Newport M, Fischer A. Inherited interferon gamma receptor deficiency. Primary Immunodeficiency Diseases: A Molecular and Genetic Approach. 1999. 209-221.

  13. Hawn TR, Ozinsky A, Williams LM, et al. Hyper-IgE syndrome is not associated with defects in several candidate toll-like receptor pathway genes. Hum Immunol. 2005 Jul. 66(7):842-7. [Medline].

  14. Renner ED, Puck JM, Holland SM, et al. Autosomal recessive hyperimmunoglobulin E syndrome: a distinct disease entity. J Pediatr. 2004 Jan. 144(1):93-9. [Medline].

  15. Simon HU, Seger R. Hyper IgE syndrome associated with an IL-4-producing gamma/delta T-cell clone. J Allergy Clin Immunol. 2007. 119:246-8.

  16. Renner ED, Rylaarsdam S, Anover-Sombke S, et al. Novel signal transducer and activator of transcription 3 (STAT3) mutations, reduced T(H)17 cell numbers, and variably defective STAT3 phosphorylation in hyper-IgE syndrome. J Allergy Clin Immunol. July. 122:181-187. [Medline]. [Full Text].

  17. Tangye SG, Cook MC, Fulcher DA. Insights into the role of STAT3 in human lymphocyte differentiation as revealed by the hyper-IgE syndrome. J Immunol. 2009 Jan 1. 182(1):21-8. [Medline].

  18. Wolach O, Kuijpers T, Ben-Ari J, Gavrieli R, Feinstein-Goren N, et al. Variable clinical expressivity of STAT3 mutation in hyperimmunoglobulin E syndrome: genetic and clinical studies of six patients. J Clin Immunol. 2014 Feb. 34 (2):163-70. [Medline].

  19. Stepkowski SM, Chen W, Ross JA, Nagy ZS, Kirken RA. STAT3: an important regulator of multiple cytokine functions. Transplantation. 2008 May 27. 85(10):1372-7. [Medline].

  20. Milner JD, Brenchley JM, Laurence A, et al. Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature. 2008 Apr 10. 452(7188):773-6. [Medline].

  21. Speckmann C, Enders A, Woellner C, et al. Reduced memory B cells in patients with hyper IgE syndrome. Clin Immunol. 2008 Dec. 129(3):448-54. [Medline].

  22. Engelhardt KR, McGhee S, Winkler S, Sassi A, Woellner C, Lopez-Herrera G. Large deletions and point mutations involving the dedicator of cytokinesis 8 (DOCK8) in the autosomal-recessive form of hyper-IgE syndrome. J Allergy Clin Immunol. 2009 Dec. 124(6):1289-302.e4. [Medline]. [Full Text].

  23. Rezaei N, Hedayat M, Aghamohammadi A, Nichols KE. Primary immunodeficiency diseases associated with increased susceptibility to viral infections and malignancies. J Allergy Clin Immunol. 2011 Jun. 127(6):1329-41.e2; quiz 1342-3. [Medline].

  24. Jabara HH, McDonald DR, Janssen E, et al. DOCK8 functions as an adaptor that links TLR-MyD88 signaling to B cell activation. Nat Immunol. 2012 May 13. 13(6):612-20. [Medline]. [Full Text].

  25. Alsum Z, Hawwari A, Alsmadi O, Al-Hissi S, Borrero E, Abu-Staiteh A, et al. Clinical, Immunological and Molecular Characterization of DOCK8 and DOCK8-like Deficient Patients: Single Center Experience of Twenty Five Patients. J Clin Immunol. 2012 Sep 12. [Medline].

  26. Schimke LF, Sawalle-Belohradsky J, Roesler J, Wollenberg A, Rack A, Borte M. Diagnostic approach to the hyper-IgE syndromes: immunologic and clinical key findings to differentiate hyper-IgE syndromes from atopic dermatitis. J Allergy Clin Immunol. 2010 Sep. 126(3):611-7.e1. [Medline].

  27. Dasouki M, Okonkwo KC, Ray A, et al. Deficient T Cell Receptor Excision Circles (TRECs) in autosomal recessive hyper IgE syndrome caused by DOCK8 mutation: implications for pathogenesis and potential detection by newborn screening. Clin Immunol. 2011 Nov. 141(2):128-32. [Medline].

  28. Joshi AY, Iyer VN, Hagan JB, St Sauver JL, Boyce TG. Incidence and temporal trends of primary immunodeficiency: a population-based cohort study. Mayo Clin Proc. 2009. 84(1):16-22. [Medline]. [Full Text].

  29. Freeman AF, Kleiner DE, Nadiminti H, et al. Causes of death in hyper-IgE syndrome. J Allergy Clin Immunol. 2007 May. 119(5):1234-40. [Medline].

  30. Martin S, Wolters P, Billings N, Toledo-Tamula MA, Hammoud DA, et al. Neurobehavioral profiles in individuals with hyperimmunoglobulin E Syndrome (HIES) and brain white matter hyperintensities. J Clin Immunol. 2013 Oct. 33 (7):1175-84. [Medline].

  31. [Guideline] Leung DY, Nicklas RA, Li JT, et al. Disease management of atopic dermatitis: an updated practice parameter. Joint Task Force on Practice Parameters. Ann Allergy Asthma Immunol. 2004 Sep. 93(3 Suppl 2):S1-21. [Medline]. [Full Text].

  32. [Guideline] Hanifin JM, Cooper KD, Ho VC, et al. Guidelines of care for atopic dermatitis, developed in accordance with the American Academy of Dermatology (AAD)/American Academy of Dermatology Association "Administrative Regulations for Evidence-Based Clinical Practice Guidelines". J Am Acad Dermatol. 2004 Mar. 50(3):391-404. [Medline]. [Full Text].

  33. Ozcan E, Notarangelo LD, Geha RS. Primary immune deficiencies with aberrant IgE production. J Allergy Clin Immunol. 2008 Dec. 122(6):1054-62; quiz 1063-4. [Medline].

  34. [Guideline] Bonilla FA, Bernstein IL, Khan DA, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. Ann Allergy Asthma Immunol. 2005 May. 94(5 Suppl 1):S1-63. [Medline]. [Full Text].

  35. Kilic SS, Kilicbay F. Interferon-alpha treatment of molluscum contagiosum in a patient with hyperimmunoglobulin E syndrome. Pediatrics. 2006 Jun. 117(6):e1253-1255. [Medline].

  36. Bennett CL, Christie J, Ramsdell F, et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet. 2001 Jan. 27(1):20-1. [Medline].

  37. Freeman AF, Davis J, Anderson VL, et al. Pneumocystis jiroveci infection in patients with hyper-immunoglobulin E syndrome. Pediatrics. 2006 Oct. 118(4):e1271-5. [Medline].

  38. Grimbacher B, Holland SM, Puck JM. Hyper-IgE syndromes. Immunol Rev. 2005 Feb. 203:244-50. [Medline].

  39. Ling JC, Freeman AF, Gharib AM, et al. Coronary artery aneurysms in patients with hyper IgE recurrent infection syndrome. Clin Immunol. 2007 Mar. 122(3):255-8. [Medline].

  40. Van der Meer JW, Weemaes CM, van Krieken JH, et al. Critical aneurysmal dilataion of the thoracic aorta in young adolescents with variant hyperimmunoglobulin e syndrome. J Intern Med. 2006. 259:615-8. [Medline].

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Chest radiograph of a patient with autosomal dominant (AD) hyperimmunoglobulin E syndrome (HIES) and a lung abscess following multiple staphylococcal pneumonias. Aspergillus fumigatus was isolated from the abscess.
Father and daughter with autosomal dominant (AD) hyperimmunoglobulin E syndrome (HIES). Note the father's distinctive facies with prominent forehead, deep-set eyes, broad nasal bridge, and wide interalar distance.
Mother and son with autosomal dominant (AD) hyperimmunoglobulin E syndrome (HIES). Note the mother's distinctive facies. She had a history of multiple deep-seated abscesses that took months to heal after incision and drainage.
 
 
 
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