Dermatologic Manifestations of Job Syndrome Treatment & Management
- Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD more...
No definitive therapy is available for the treatment of hyper-IgE syndrome (HIE syndrome or Job syndrome). The mainstay of treatment is the control of bacterial infections. Early incision and drainage followed by the intravenous administration of antibiotics are used for cutaneous infections. Coverage is usually aimed at Staphylococcus and Haemophilus species. Acupuncture treatment has been reported to be of value for symptom management of patients with hyper-IgE syndrome, although further studies are required for confirmation.
Job syndrome therapy is usually longer than typical treatment because the disease in these patients responds more slowly than that of patients without Job syndrome. Intravenous antibiotic treatment for 2 weeks is typical. Chronic onychomycosis responds well to oral ketoconazole and fluconazole. Eczematous dermatitis has a varied response to high-dose topical steroids.
Chemoprophylaxis in patients with Job syndrome has varied results. Levamisole, an immunopotentiating drug, has been investigated as a therapeutic agent; in one study, it was unhelpful. Long-term trimethoprim-sulfamethoxazole treatment was used in one patient with recurrent pruritic dermatitis, with resolution of symptoms. Other patients treated with prophylactic antibiotics had both minor and major infections during therapy, often after several months of being infection free.
Cases in patients with severe hyper-IgE syndrome whose disease was unresponsive to other therapeutic modalities are reported; these cases had a marked clinical response to cyclosporin A. Treatment included low-dose cyclosporin for 6 months or longer. Both cutaneous and pulmonary infections responded to this therapy, and no adverse effects were reported. In one study, oral disodium cromoglycate (2 g/d) prevented the complications of Job syndrome over a 2-year period. Two case studies in patients with Job syndrome have shown a dramatic response in preventing infectious and eczematoid complications; patients were treated for as long as 18 months.
In one open-labeled study, high-dose intravenous immunoglobulin had no clear clinical benefit in 9 patients with Job syndrome. Another study showed an improvement in severe eczema along with a decrease in serum IgE levels in 2 patients after they were treated with high-dose intravenous gamma globulin.
The autosomal recessive variant may benefit from bone marrow transplantation and hematopoietic stem cell graft.[43, 44]
Acupuncture treatments may decrease the severity of symptoms.
Surgical excision and drainage of cutaneous infections are often performed in patients with Job syndrome (HIE syndrome, or hyper-IgE syndrome). Drainage is usually followed by intravenous antibiotic therapy.
Chronic hidradenitis suppurativa occurs in some patients with Job syndrome. Often, these lesions do not respond to antibiotics, and local excision may be required.
An allergist and immunologist may help in establishing the diagnosis of Job syndrome (HIE syndrome, or hyper-IgE syndrome). An infectious disease specialist may help in cases with infectious complications. An orthopedist should be involved in the care of those with scoliosis and fractures.
Fournier gangrene due to infectious multiple atheromas of scrotal skin that progressed to the groin and thigh has been described in a patient with Job syndrome (HIE syndrome, or hyper-IgE syndrome).
Job (hyperimmunoglobulinemia E) syndrome may predispose to the development of malignancies, especially lymphomas, mainly mature B-cell lymphomas, and classic Hodgkin lymphoma.
Initiate treatment at the first signs of infection to prevent long-term complications from Job syndrome (HIE syndrome, or hyper-IgE syndrome). Regularly screen Job syndrome patients for scoliosis so that early noninvasive treatment can be used.
Extra vigilance may be required in routine screening of Job syndrome (HIE syndrome, or hyper-IgE syndrome) patients for scoliosis. If a school-based program exists, healthcare providers should be made aware of the Job syndrome patient's greater-than-typical risk of scoliosis. Early detection with proper care can prevent progression of Job syndrome.
Grimbacher B, Holland SM, Puck JM. Hyper-IgE syndromes. Immunol Rev. 2005 Feb. 203:244-50. [Medline].
Minegishi Y, Karasuyama H. Genetic origins of hyper-IgE syndrome. Curr Allergy Asthma Rep. 2008 Sep. 8(5):386-91. [Medline].
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].
Sowerwine KJ, Holland SM, Freeman AF. Hyper-IgE syndrome update. Ann N Y Acad Sci. 2012 Feb. 1250:25-32. [Medline].
Stiehm ER. Cytokine dysregulation in the hyperimmunoglobulinemia E syndrome. J Pediatr. 2000 Feb. 136(2):141-3. [Medline].
Paslin D, Norman ME. Atopic dermatitis and impaired neutrophil chemotaxis in Job's syndrome. Arch Dermatol. 1977 Jun. 113(6):801-5. [Medline].
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].
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].
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].
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].
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].
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].
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].
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].
Minegishi Y. Hyper-IgE syndrome. Curr Opin Immunol. 2009 Oct. 21(5):487-92. [Medline].
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].
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].
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].
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].
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].
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].
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].
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].
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].
Borges WG, Hensley T, Carey JC, Petrak BA, Hill HR. The face of Job. J Pediatr. 1998 Aug. 133(2):303-5. [Medline].
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].
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].
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].
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].
Minegishi Y, Saito M. Cutaneous Manifestations of Hyper IgE Syndrome. Allergol Int. 2012 Mar 25. 0(0):[Medline].
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].
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].