Medscape is available in 5 Language Editions – Choose your Edition here.


Dermatologic Manifestations of Job Syndrome Differential Diagnoses

  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD  more...
Updated: Jun 09, 2016

Diagnostic Considerations

Differentiation from other disorders associated with eczema and increased serum IgE levels, such as other primary immunodeficiencies and atopic dermatitis, can be challenging.[33, 34, 15]

Chronic granulomatous disease with markedly elevated IgE levels may mimic hyperimmunoglobulin E syndrome.[35] However, tuberculosis may be associated with Job syndrome and may be first evident as miliary tuberculosis.[36]

The relevance of eosinophilia and hyper-IgE in immigrant children from Africa and Latin America has been explored. The prevalence and causes of eosinophilia and hyper-IgE in 362 immigrant children in Spain was prospectively evaluated, with the most frequent causes of absolute eosinophilia being filariasis (52.6%), strongyloidiasis (46.8%), and schistosomiasis (28.9%) and the most frequent causes of increased levels of IgE being filariasis (41.9%), strongyloidiasis (29.6%), and schistosomiasis (22.2%).[37] Thus, eosinophilia and hyper-IgE are important biomarkers of helminthiasis in children coming from tropical and subtropical areas.

Differential Diagnoses

Contributor Information and Disclosures

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.


Mordechai M Tarlow, MD Clinical Assistant Professor of Dermatology, University of Pennsylvania School of Medicine

Mordechai M Tarlow, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Society for MOHS Surgery, American College of Aesthetic and Cosmetic Physicians; American Society of Aesthetic/Cosmetic Physicians, American Medical Association, Sigma Xi

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: American Medical Association, Alpha Omega Alpha, Association of Military Dermatologists, American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Phi Beta Kappa

Disclosure: Nothing to disclose.

Jeffrey J Miller, MD Associate Professor of Dermatology, Pennsylvania State University College of Medicine; Staff Dermatologist, Pennsylvania State Milton S Hershey Medical Center

Jeffrey J Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Society for Investigative Dermatology, Association of Professors of Dermatology, North American Hair Research Society

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

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

  2. Minegishi Y, Karasuyama H. Genetic origins of hyper-IgE syndrome. Curr Allergy Asthma Rep. 2008 Sep. 8(5):386-91. [Medline].

  3. Ma CS, Chew GY, Simpson N, et al. Deficiency of Th17 cells in hyper IgE syndrome due to mutations in STAT3. J Exp Med. 2008 Jul 7. 205(7):1551-7. [Medline]. [Full Text].

  4. van de Veerdonk FL, Marijnissen R, Joosten LA, et al. Milder clinical hyperimmunoglobulin E syndrome phenotype is associated with partial interleukin-17 deficiency. Clin Exp Immunol. 2010 Jan. 159(1):57-64. [Medline]. [Full Text].

  5. Sowerwine KJ, Holland SM, Freeman AF. Hyper-IgE syndrome update. Ann N Y Acad Sci. 2012 Feb. 1250:25-32. [Medline].

  6. Stiehm ER. Cytokine dysregulation in the hyperimmunoglobulinemia E syndrome. J Pediatr. 2000 Feb. 136(2):141-3. [Medline].

  7. Paslin D, Norman ME. Atopic dermatitis and impaired neutrophil chemotaxis in Job's syndrome. Arch Dermatol. 1977 Jun. 113(6):801-5. [Medline].

  8. Simon HU, Seger R. Hyper-IgE syndrome associated with an IL-4-producing gamma/delta(+) T-cell clone. J Allergy Clin Immunol. 2007 Jan. 119(1):246-8. [Medline].

  9. Vargas L, Patino PJ, Rodriguez MF, et al. Increase in granulocyte-macrophage-colony-stimulating factor secretion and the respiratory burst with decreased L-selectin expression in hyper-IgE syndrome patients. Ann Allergy Asthma Immunol. 1999 Sep. 83(3):245-51. [Medline].

  10. Shirafuji Y, Matsuura H, Sato A, Kanzaki H, Katayama H, Arata J. Hyperimmunoglobin E syndrome: a sign of TH1/TH2 imbalance?. Eur J Dermatol. 1999 Mar. 9(2):129-31. [Medline].

  11. Tanaka T, Takada H, Nomura A, Ohga S, Shibata R, Hara T. Distinct gene expression patterns of peripheral blood cells in hyper-IgE syndrome. Clin Exp Immunol. 2005 Jun. 140(3):524-31. [Medline].

  12. 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].

  13. Engelhardt KR, McGhee S, Winkler S, et al. 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].

  14. Koskenvuo M, Kainulainen L, Vanto T, Lukkarinen H, Lähteenmäki P, Ruuskanen O. [Severe atopy and allergy--rare hyper-IgE syndrome caused by the DOCK8 mutation as underlying condition]. Duodecim. 2015. 131 (6):541-4. [Medline].

  15. Hagl B, Heinz V, Schlesinger A, et al. Key findings to expedite the diagnosis of hyper-IgE syndromes in infants and young children. Pediatr Allergy Immunol. 2016 Mar. 27 (2):177-84. [Medline].

  16. Minegishi Y. Hyper-IgE syndrome. Curr Opin Immunol. 2009 Oct. 21(5):487-92. [Medline].

  17. Halacli SO, Ayvaz DC, Sun-Tan C, Erman B, Uz E, Yilmaz DY, et al. STK4 (MST1) deficiency in two siblings with autoimmune cytopenias: A novel mutation. Clin Immunol. 2015 Jun 25. [Medline].

  18. Conti HR, Baker O, Freeman AF, Jang WS, Holland SM, Li RA, et al. New mechanism of oral immunity to mucosal candidiasis in hyper-IgE syndrome. Mucosal Immunol. 2011 Feb 23. [Medline].

  19. Vigliante CE, Costello BJ, Quinn PD. Life-threatening cervicofacial infection in a child with hyperimmunoglobulin-E syndrome. J Oral Maxillofac Surg. 2001 May. 59(5):561-5. [Medline].

  20. O'Connell AC, Puck JM, Grimbacher B, et al. Delayed eruption of permanent teeth in hyperimmunoglobulinemia E recurrent infection syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000 Feb. 89(2):177-85. [Medline].

  21. Onal IK, Kurt M, Altundag K, Aksoy S, Dincer M, Gullu I. Peripheral T-cell lymphoma and Job's syndrome: a rare association. Med Oncol. 2006. 23(1):141-4. [Medline].

  22. 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].

  23. Sarmento KM Jr, Tomita S, Caliman e Gurgel JD. Association between nasal polyposis, Dubowitz syndrome and hyper-IgE syndrome. Int J Pediatr Otorhinolaryngol. 2008 May. 72(5):711-4. [Medline].

  24. Kharkar V, Kardekar S, Gutte R, Mahajan S, Thakkar V, Khopkar U. Disseminated molluscum contagiosum infection in a hyper IgE syndrome. Indian J Dermatol Venereol Leprol. 2012 May. 78(3):371-4. [Medline].

  25. Siah TW, Gennery A, Leech S, Taylor A. Gross generalized molluscum contagiosum in a patient with autosomal recessive hyper-IgE syndrome, which resolved spontaneously after haematopoietic stem-cell transplantation. Clin Exp Dermatol. 2013 Mar. 38(2):196-7. [Medline].

  26. Borges WG, Hensley T, Carey JC, Petrak BA, Hill HR. The face of Job. J Pediatr. 1998 Aug. 133(2):303-5. [Medline].

  27. Freeman AF, Domingo DL, Holland SM. Hyper IgE (Job's) syndrome: a primary immune deficiency with oral manifestations. Oral Dis. 2009 Jan. 15(1):2-7. [Medline].

  28. Rana C, Krishnani N, Kumari N, Shastri C, Poddar U. Rectal histoplasmosis in Job's syndrome. Indian J Gastroenterol. 2013 Jan. 32(1):64-5. [Medline].

  29. Grimbacher B, Holland SM, Gallin JI, et al. Hyper-IgE syndrome with recurrent infections--an autosomal dominant multisystem disorder. N Engl J Med. 1999 Mar 4. 340(9):692-702. [Medline].

  30. Grimbacher B, Schaffer AA, Holland SM, et al. Genetic linkage of hyper-IgE syndrome to chromosome 4. Am J Hum Genet. 1999 Sep. 65(3):735-44. [Medline].

  31. Minegishi Y, Saito M. Cutaneous Manifestations of Hyper IgE Syndrome. Allergol Int. 2012 Mar 25. 0(0):[Medline].

  32. Hsu AP, Sowerwine KJ, Lawrence MG, Davis J, Henderson CJ, Zarember KA, et al. Intermediate phenotypes in patients with autosomal dominant hyper-IgE syndrome caused by somatic mosaicism. J Allergy Clin Immunol. 2013 Jun. 131(6):1586-93. [Medline].

  33. Schimke LF, Sawalle-Belohradsky J, Roesler J, et al. 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].

  34. Khan K, Wozniak SE, Giannone AL, Abdulmassih ME. A Boy with Relentless Pruritus: Job's Syndrome. Am J Case Rep. 2016 Feb 21. 17:104-10. [Medline].

  35. Patiroglu T, Gungor HE, Lazaroski S, Unal E. Chronic granulomatous disease with markedly elevated IgE levels mimicking hyperimmunoglobulin E syndrome. Acta Microbiol Immunol Hung. 2013 Jun. 60(2):155-62. [Medline].

  36. Gamberale A, Moreira I, Bartoletti B, Cruz V, Bezrodnik L, Alberti F, et al. [Job's syndrome and miliary tuberculosis]. Medicina (B Aires). 2014. 74(4):311-4. [Medline].

  37. Belhassen-García M, Pardo-Lledías J, Pérez del Villar L, Muro A, Velasco-Tirado V, Blázquez de Castro A, et al. Relevance of eosinophilia and hyper-IgE in immigrant children. Medicine (Baltimore). 2014 Jul. 93(6):e43. [Medline].

  38. Kumanovics A, Wittwer CT, Pryor RJ, et al. Rapid Molecular Analysis of the STAT3 Gene in Job Syndrome of Hyper-IgE and Recurrent Infectious Diseases. J Mol Diagn. 2010 Jan 21. [Medline].

  39. Ge AX, Ryan ME, Holland SM, et al. Acupuncture for symptom management in patients with hyper-IgE (Job's) syndrome. J Altern Complement Med. 2011 Jan. 17(1):71-6. [Medline]. [Full Text].

  40. Tanaka H, Ito R, Onodera N, Waga S. Efficacy of long-term sulfamethoxazole-trimethoprim therapy in a boy with hyperimmunoglobulin E syndrome. Tohoku J Exp Med. 1998 Sep. 186(1):61-6. [Medline].

  41. Kojima K, Inoue Y, Katayama Y, et al. Improvement with disodium cromoglycate of neutrophil phagocytosis and respiratory burst activity in a patient with hyperimmunoglobulin E syndrome. Allergy. 1998 Nov. 53(11):1101-3. [Medline].

  42. Wakim M, Alazard M, Yajima A, Speights D, Saxon A, Stiehm ER. High dose intravenous immunoglobulin in atopic dermatitis and hyper-IgE syndrome. Ann Allergy Asthma Immunol. 1998 Aug. 81(2):153-8. [Medline].

  43. Bittner TC, Pannicke U, Renner ED, et al. Successful long-term correction of autosomal recessive hyper-IgE syndrome due to DOCK8 deficiency by hematopoietic stem cell transplantation. Klin Padiatr. 2010 Nov. 222(6):351-5. [Medline].

  44. Metin A, Tavil B, Azik F, Azkur D, Ok-Bozkaya I, Kocabas C, et al. Successful bone marrow transplantation for DOCK8 deficient hyper IgE syndrome. Pediatr Transplant. 2012 Jan 17. [Medline].

  45. Ge AX, Ryan ME, Holland SM, et al. Acupuncture for symptom management in patients with hyper-IgE (Job's) syndrome. J Altern Complement Med. 2011 Jan. 17(1):71-6. [Medline]. [Full Text].

  46. Hori J, Yamaguchi S, Watanabe M, Osanai H, Hori M. Fournier gangrene associated with hyper IgE syndrome (Job syndrome). Int J Urol. 2008 Apr. 15(4):372-3. [Medline].

  47. Kumanovics A, Perkins SL, Gilbert H, Cessna MH, Augustine NH, Hill HR. Diffuse large B cell lymphoma in hyper-IgE syndrome due to STAT3 mutation. J Clin Immunol. 2010 Nov. 30(6):886-93. [Medline].

All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.