Hyper IgE syndrome: often a missed diagnosis
Keywords:Hyper IgE syndrome, Recurrent infection, Immunodeficiency
The hyper immunoglobulin E syndromes (HIES) are a group of primary immunodeficiency manifesting with very high levels of serum immunoglobulin E (IgE), recurrent skin abscesses, pulmonary infections, neonatal onset dermatitis and a myriad of connective tissue, vascular and skeletal abnormalities. The diagnosis of HIES relies on a combination of clinical features and laboratory studies. Heterogeneous manifestations of HIES mimics common infections prevalent in tropical areas and results in delayed diagnosis. Primary goal of treatment lies in prevention of infections with prophylactic antibiotics. We report a 6 year old boy symptomatic since early infancy with recurrent respiratory problems, rash, organomegaly, suppurative generalised lymphadenopathy. He was misdiagnosed as tuberculosis twice. Following extensive investigations, infectious causes for such manifestations were ruled out and the final diagnosis of possible HIES was made as genetic studies could not be done. He remained relatively asymptomatic on antibacterial and antifungal prophylaxis during subsequent follow up for 2 years.
Davis SD, Schaller J, Wedgwood RJ. Job’s syndrome: Recurrent, “cold” staphylococcal abscesses. Lancet. 1966;1:1013-5.
Grimbacher B, Belohradsky BH, Holland SM. Immunoglobulin E in primary immunodeficiency diseases. Allergy. 2002;57:995-1007.
Grimbacher B, Holland SM, Puck JM. Hyper-IgE syndromes. Immunol Rev. 2005;203:244-0.
Woellner C, Gertz EM, Schäffer AA. Mutations in STAT3 and diagnostic guidelines for hyper-IgE syndrome. J Allergy Clin Immunol. 2010;125:424-32.
Minegishi Y, Karasuyama H. Genetic origins of hyper-IgE syndrome. Curr Allergy Asthma Rep. 2008;8:386-91.
Holland SM, DeLeo FR, Elloumi HZ. STAT3 mutations in the hyper-IgE syndrome. N Engl J Med. 2007;357:1608-19.
Yong PF, Freeman AF, Engelhardt KR, Holland S, Puck JM, Grimbacher B. An update on the hyper-IgE syndromes. Arthritis Res Ther. 2012;14:228-38.
Szczawinska-Poplonyk A, Kycler Z, Pietrucha B, Heropolitanska-Pliszka E, Breborowicz A, Gerreth K. The hyperimmunoglobulin E syndrome--clinical manifestation diversity in primary immune deficiency. Orphanet J Rare Dis. 2011;6:76-85.
Rael EL, Marshall RT, McClain JJ. The Hyper-IgE Syndromes: Lessons in Nature, from Bench to Bedside. World Allergy Organ J. 2012;5:79-87.
Leonard GD, Posadas E, Herrmann PC. Non-Hodgkin's lymphoma in Job's syndrome: a case report and review of the literature. Leuk Lymphoma 2004;45:2521-5.
Gorin LJ, Jeha SC, Sullivan MP, Rosenblatt HM, Shearer WT. Burkitt's lymphoma developing in a 7 year old boy with hyper IgE syndrome. J Allergy Clinical Immunol. 1989;83:5-10.
Oztop I, Demirkan B, Tarhan O. The development of a pulmonary adenocarcinoma in a patient with Job's syndrome, a rare immunodeficiency condition. Tumori. 2004;90:132-5.
Yasharpour MR, Agarwal S, Jerome D, Yel L. Is It Hyper IgE Syndrome Or Something Else? MOJ Immunol. 2014;1:00010-4.
Antoniades K, Hatzistilianou M, Pitsavas G, Agouridaki C, Athanassiadou F. Co-existence of Dubowitz and hyper-IgE syndromes: a case report. Eur J Pediatr. 1996;155:390-2.
Boeck A, Gfatter R, Braun F, Fritz B. Pentasomy X and hyper IgE syndrome: co-existence of two distinct genetic disorders. Eur J Pediatr. 1999;158:723-6.
Boeck A, Kosan C, Ciznar P, Kunz J. Saethre-Chotzen syndrome and hyper IgE syndrome in a patient with a novel 11 bp deletion of the TWIST gene. Am J Med Genet. 2001;104:53-6.
Freeman AF, Holland SM. The hyper-IgE syndromes. Immunol Allergy Clin North Am. 2008;28:277-91.
King CL, Gallin JI, Malech HL, Abramson SL, Nutman TB. Regulation of immunoglobulin production in hyperimmunoglobulin E recurrent-infection syndrome by interferon gamma. Proc Natl Acad Sci U S A. 1989;86:10085-9.
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;81:153-8.