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Hyper-IgE recurrent infection syndrome 5, autosomal recessive(HIES5)

MedGen UID:
1716052
Concept ID:
C5394550
Disease or Syndrome
Synonym: HYPER-IgE SYNDROME 5, AUTOSOMAL RECESSIVE, WITH RECURRENT INFECTIONS
 
Gene (location): IL6R (1q21.3)
 
Monarch Initiative: MONDO:0030069
OMIM®: 618944

Definition

Hyper-IgE syndrome-5 with recurrent infections (HEIS5) is an autosomal recessive immunologic disorder characterized by onset of recurrent sinopulmonary and deep skin infections in early childhood. The infections are mostly caused by bacteria, including H. influenza and Staphylococcus aureus. Additional features include atopic dermatitis, impaired inflammatory responses during infection, increased serum IgE, and increased IL6 (147620) (summary by Spencer et al., 2019). For a discussion of genetic heterogeneity of hyper-IgE syndrome, see HIES1 (147060). [from OMIM]

Clinical features

From HPO
Cellulitis
MedGen UID:
40174
Concept ID:
C0007642
Disease or Syndrome
A bacterial infection and inflammation of the skin und subcutaneous tissues.
Recurrent upper respiratory tract infections
MedGen UID:
154380
Concept ID:
C0581381
Disease or Syndrome
An increased susceptibility to upper respiratory tract infections as manifested by a history of recurrent upper respiratory tract infections (running ears - otitis, sinusitis, pharyngitis, tonsillitis).
Atopic eczema
MedGen UID:
41502
Concept ID:
C0011615
Disease or Syndrome
Atopic dermatitis (ATOD), also known as eczema, is a common chronic pruritic inflammatory skin disease with a strong genetic component. Onset typically occurs during the first 2 years of life (review by Soderhall et al., 2007). Genetic Heterogeneity of Atopic Dermatitis Many inflammatory diseases, such as atopic eczema, are genetically complex, with multiple alleles at several loci thought to be involved in their pathogenesis. Several susceptibility loci for atopic dermatitis have been identified: ATOD1 on chromosome 3q21, ATOD2 (605803) on chromosome 1q21, ATOD3 (605804) on chromosome 20p, ATOD4 (605805) on chromosome 17q25.3, ATOD5 (603165) on chromosome 13q12-q14, ATOD6 (605845) on chromosome 5q31-q33, ATOD7 (613064) on chromosome 11q13.5, ATOD8 (613518) on chromosome 4q22.1, and ATOD9 (613519) on chromosome 3p24.
Cutaneous abscess
MedGen UID:
450991
Concept ID:
C0149777
Pathologic Function
A circumscribed area of pus or necrotic debris in the skin.
Increased circulating IgE level
MedGen UID:
116018
Concept ID:
C0236175
Finding
An abnormally increased overall level of immunoglobulin E in blood.
Decreased circulating total IgM
MedGen UID:
116095
Concept ID:
C0239989
Finding
An abnormally decreased level of immunoglobulin M (IgM) in blood.
Recurrent otitis media
MedGen UID:
155436
Concept ID:
C0747085
Disease or Syndrome
Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media.
Recurrent skin infections
MedGen UID:
377848
Concept ID:
C1853193
Disease or Syndrome
Infections of the skin that happen multiple times.
Decreased proportion of class-switched memory B cells
MedGen UID:
892709
Concept ID:
C4072925
Finding
A reduction in the normal proportion of class-switched memory B cells (CD19+/CD27+/IgM+/IgD+) relative to the total number of B cells. Marginal zone B cells undergo limited somatic hypermutation and produce high-affinity IgM and some IgG, whereas class-switched memory B cells synthetize IgG, IgM, and IgA.
Increased circulating interleukin 6 concentration
MedGen UID:
901461
Concept ID:
C4280771
Finding
The concentration of interleukin-6 in the blood circulation is above the upper limit of normal.
Decreased circulating IgG level
MedGen UID:
1720114
Concept ID:
C5234937
Finding
An abnormally decreased level of immunoglobulin G (IgG) in blood.
Reduced circulating C-reactive protein concecntration
MedGen UID:
1704066
Concept ID:
C5139347
Finding
An abnormal decrease of the C-reactive protein level in serum.
Inappropriate absence of fever
MedGen UID:
1745742
Concept ID:
C5421614
Finding
Failure to develop fever in the presence of an infection that normally would be expected to elicit a febrile response.

Professional guidelines

PubMed

Ollech A, Mashiah J, Lev A, Simon AJ, Somech R, Adam E, Barzilai A, Hagin D, Greenberger S
J Dermatol 2021 Sep;48(9):1386-1393. Epub 2021 May 27 doi: 10.1111/1346-8138.15955. PMID: 34043252
Aydin SE, Kilic SS, Aytekin C, Kumar A, Porras O, Kainulainen L, Kostyuchenko L, Genel F, Kütükcüler N, Karaca N, Gonzalez-Granado L, Abbott J, Al-Zahrani D, Rezaei N, Baz Z, Thiel J, Ehl S, Marodi L, Orange JS, Sawalle-Belohradsky J, Keles S, Holland SM, Sanal Ö, Ayvaz DC, Tezcan I, Al-Mousa H, Alsum Z, Hawwari A, Metin A, Matthes-Martin S, Hönig M, Schulz A, Picard C, Barlogis V, Gennery A, Ifversen M, van Montfrans J, Kuijpers T, Bredius R, Dückers G, Al-Herz W, Pai SY, Geha R, Notheis G, Schwarze CP, Tavil B, Azik F, Bienemann K, Grimbacher B, Heinz V, Gaspar HB, Aydin R, Hagl B, Gathmann B, Belohradsky BH, Ochs HD, Chatila T, Renner ED, Su H, Freeman AF, Engelhardt K, Albert MH; inborn errors working party of EBMT
J Clin Immunol 2015 Feb;35(2):189-98. Epub 2015 Jan 28 doi: 10.1007/s10875-014-0126-0. PMID: 25627830

Recent clinical studies

Etiology

Ollech A, Mashiah J, Lev A, Simon AJ, Somech R, Adam E, Barzilai A, Hagin D, Greenberger S
J Dermatol 2021 Sep;48(9):1386-1393. Epub 2021 May 27 doi: 10.1111/1346-8138.15955. PMID: 34043252
Abolhassani H, Chou J, Bainter W, Platt CD, Tavassoli M, Momen T, Tavakol M, Eslamian MH, Gharagozlou M, Movahedi M, Ghadami M, Hamidieh AA, Azizi G, Yazdani R, Afarideh M, Ghajar A, Havaei A, Chavoshzadeh Z, Mahdaviani SA, Cheraghi T, Behniafard N, Amin R, Aleyasin S, Faridhosseini R, Jabbari-Azad F, Nabavi M, Bemanian MH, Arshi S, Molatefi R, Sherkat R, Mansouri M, Mesdaghi M, Babaie D, Mohammadzadeh I, Ghaffari J, Shafiei A, Kalantari N, Ahanchian H, Khoshkhui M, Soheili H, Dabbaghzadeh A, Shirkani A, Nasiri Kalmarzi R, Mortazavi SH, Tafaroji J, Khalili A, Mohammadi J, Negahdari B, Joghataei MT, Al-Ramadi BK, Picard C, Parvaneh N, Rezaei N, Chatila TA, Massaad MJ, Keles S, Hammarström L, Geha RS, Aghamohammadi A
J Allergy Clin Immunol 2018 Apr;141(4):1450-1458. Epub 2017 Sep 12 doi: 10.1016/j.jaci.2017.06.049. PMID: 28916186
Sasihuseyinoglu AS, Yilmaz M, Altintaş DU, Dogruel D, Serbes M, Uğuz AH, Kiroğlu M
J Pediatr Hematol Oncol 2018 Aug;40(6):e380-e382. doi: 10.1097/MPH.0000000000000954. PMID: 28902078
Broides A, Mandola AB, Levy J, Yerushalmi B, Pinsk V, Eldan M, Shubinsky G, Hadad N, Levy R, Nahum A, Ben-Harosh M, Lev A, Simon A, Somech R
Immunol Res 2017 Jun;65(3):651-657. doi: 10.1007/s12026-016-8883-x. PMID: 28070732
Sarmento KM Jr, Tomita S, Caliman e Gurgel JD
Int J Pediatr Otorhinolaryngol 2008 May;72(5):711-4. Epub 2008 Mar 10 doi: 10.1016/j.ijporl.2008.01.018. PMID: 18329728

Diagnosis

Kasap N, Kara A, Celik V, Bilgic Eltan S, Akay Haci I, Kose H, Aygun A, Akkelle E, Yakici N, Guner SN, Reisli I, Keles S, Cekic S, Kilic SS, Karaca NE, Gulez N, Genel F, Ozen A, Yucelten AD, Karakoc-Aydiner E, Schmitz-Abe K, Baris S
J Clin Immunol 2023 Nov;43(8):1882-1890. Epub 2023 Jul 29 doi: 10.1007/s10875-023-01554-z. PMID: 37507632
Ollech A, Mashiah J, Lev A, Simon AJ, Somech R, Adam E, Barzilai A, Hagin D, Greenberger S
J Dermatol 2021 Sep;48(9):1386-1393. Epub 2021 May 27 doi: 10.1111/1346-8138.15955. PMID: 34043252
Özyurt K, Atasoy M, Ertaş R, Ulaş Y, Akkuş MR, Kiraz A, Hennies HC
Turk J Pediatr 2019;61(4):604-607. doi: 10.24953/turkjped.2019.04.020. PMID: 31990481
Lopes J, Teixeira D, Sousa C, Baptista A, Moreira D, Ferreira EO
Pediatr Dermatol 2019 Sep;36(5):693-696. Epub 2019 Jul 24 doi: 10.1111/pde.13919. PMID: 31338855
Abolhassani H, Chou J, Bainter W, Platt CD, Tavassoli M, Momen T, Tavakol M, Eslamian MH, Gharagozlou M, Movahedi M, Ghadami M, Hamidieh AA, Azizi G, Yazdani R, Afarideh M, Ghajar A, Havaei A, Chavoshzadeh Z, Mahdaviani SA, Cheraghi T, Behniafard N, Amin R, Aleyasin S, Faridhosseini R, Jabbari-Azad F, Nabavi M, Bemanian MH, Arshi S, Molatefi R, Sherkat R, Mansouri M, Mesdaghi M, Babaie D, Mohammadzadeh I, Ghaffari J, Shafiei A, Kalantari N, Ahanchian H, Khoshkhui M, Soheili H, Dabbaghzadeh A, Shirkani A, Nasiri Kalmarzi R, Mortazavi SH, Tafaroji J, Khalili A, Mohammadi J, Negahdari B, Joghataei MT, Al-Ramadi BK, Picard C, Parvaneh N, Rezaei N, Chatila TA, Massaad MJ, Keles S, Hammarström L, Geha RS, Aghamohammadi A
J Allergy Clin Immunol 2018 Apr;141(4):1450-1458. Epub 2017 Sep 12 doi: 10.1016/j.jaci.2017.06.049. PMID: 28916186

Therapy

Purkait R, Kar S, Bhadra R, Sinhamahapatra T
J Coll Physicians Surg Pak 2014 Nov;24 Suppl 3:S256-8. PMID: 25518794
Ozgur TT, Asal GT, Gurgey A, Tezcan I, Ersoy F, Sanal O
J Pediatr Hematol Oncol 2007 May;29(5):327-9. doi: 10.1097/MPH.0b013e318059c236. PMID: 17483712

Prognosis

Kasap N, Kara A, Celik V, Bilgic Eltan S, Akay Haci I, Kose H, Aygun A, Akkelle E, Yakici N, Guner SN, Reisli I, Keles S, Cekic S, Kilic SS, Karaca NE, Gulez N, Genel F, Ozen A, Yucelten AD, Karakoc-Aydiner E, Schmitz-Abe K, Baris S
J Clin Immunol 2023 Nov;43(8):1882-1890. Epub 2023 Jul 29 doi: 10.1007/s10875-023-01554-z. PMID: 37507632
Ollech A, Mashiah J, Lev A, Simon AJ, Somech R, Adam E, Barzilai A, Hagin D, Greenberger S
J Dermatol 2021 Sep;48(9):1386-1393. Epub 2021 May 27 doi: 10.1111/1346-8138.15955. PMID: 34043252
Abolhassani H, Chou J, Bainter W, Platt CD, Tavassoli M, Momen T, Tavakol M, Eslamian MH, Gharagozlou M, Movahedi M, Ghadami M, Hamidieh AA, Azizi G, Yazdani R, Afarideh M, Ghajar A, Havaei A, Chavoshzadeh Z, Mahdaviani SA, Cheraghi T, Behniafard N, Amin R, Aleyasin S, Faridhosseini R, Jabbari-Azad F, Nabavi M, Bemanian MH, Arshi S, Molatefi R, Sherkat R, Mansouri M, Mesdaghi M, Babaie D, Mohammadzadeh I, Ghaffari J, Shafiei A, Kalantari N, Ahanchian H, Khoshkhui M, Soheili H, Dabbaghzadeh A, Shirkani A, Nasiri Kalmarzi R, Mortazavi SH, Tafaroji J, Khalili A, Mohammadi J, Negahdari B, Joghataei MT, Al-Ramadi BK, Picard C, Parvaneh N, Rezaei N, Chatila TA, Massaad MJ, Keles S, Hammarström L, Geha RS, Aghamohammadi A
J Allergy Clin Immunol 2018 Apr;141(4):1450-1458. Epub 2017 Sep 12 doi: 10.1016/j.jaci.2017.06.049. PMID: 28916186
Al Shekaili L, Sheikh F, Al Gazlan S, Al Dhekri H, Al Mousa H, Al Ghonaium A, Al Saud B, Al Mohsen S, Rehan Khaliq AM, Al Sumayli S, Al Zahrani M, Dababo A, AlKawi A, Hawwari A, Arnaout R
Clin Immunol 2017 May;178:39-44. Epub 2016 Nov 23 doi: 10.1016/j.clim.2016.08.002. PMID: 27890707
Engelhardt KR, Gertz ME, Keles S, Schäffer AA, Sigmund EC, Glocker C, Saghafi S, Pourpak Z, Ceja R, Sassi A, Graham LE, Massaad MJ, Mellouli F, Ben-Mustapha I, Khemiri M, Kilic SS, Etzioni A, Freeman AF, Thiel J, Schulze I, Al-Herz W, Metin A, Sanal Ö, Tezcan I, Yeganeh M, Niehues T, Dueckers G, Weinspach S, Patiroglu T, Unal E, Dasouki M, Yilmaz M, Genel F, Aytekin C, Kutukculer N, Somer A, Kilic M, Reisli I, Camcioglu Y, Gennery AR, Cant AJ, Jones A, Gaspar BH, Arkwright PD, Pietrogrande MC, Baz Z, Al-Tamemi S, Lougaris V, Lefranc G, Megarbane A, Boutros J, Galal N, Bejaoui M, Barbouche MR, Geha RS, Chatila TA, Grimbacher B
J Allergy Clin Immunol 2015 Aug;136(2):402-12. Epub 2015 Feb 25 doi: 10.1016/j.jaci.2014.12.1945. PMID: 25724123Free PMC Article

Clinical prediction guides

Kumar Jindal A, Sil A, Aggarwal R, Tyagi R, Mondal S, Singh A, Barman P, Chawla S, Loganathan SK, Gupta K, Vinay K, Mahajan R, Saikia B, Kaur G, Sharma R, Saka R, Bhatia A, Sankhyan N, Pandiarajan V, Pilania R, Dhaliwal M, Sharma S, Vyas S, Suri D, Rawat A, Singh S
Clin Exp Dermatol 2024 Feb 14;49(3):226-234. doi: 10.1093/ced/llad345. PMID: 37815217
Kasap N, Kara A, Celik V, Bilgic Eltan S, Akay Haci I, Kose H, Aygun A, Akkelle E, Yakici N, Guner SN, Reisli I, Keles S, Cekic S, Kilic SS, Karaca NE, Gulez N, Genel F, Ozen A, Yucelten AD, Karakoc-Aydiner E, Schmitz-Abe K, Baris S
J Clin Immunol 2023 Nov;43(8):1882-1890. Epub 2023 Jul 29 doi: 10.1007/s10875-023-01554-z. PMID: 37507632
Ollech A, Mashiah J, Lev A, Simon AJ, Somech R, Adam E, Barzilai A, Hagin D, Greenberger S
J Dermatol 2021 Sep;48(9):1386-1393. Epub 2021 May 27 doi: 10.1111/1346-8138.15955. PMID: 34043252
Aydin SE, Kilic SS, Aytekin C, Kumar A, Porras O, Kainulainen L, Kostyuchenko L, Genel F, Kütükcüler N, Karaca N, Gonzalez-Granado L, Abbott J, Al-Zahrani D, Rezaei N, Baz Z, Thiel J, Ehl S, Marodi L, Orange JS, Sawalle-Belohradsky J, Keles S, Holland SM, Sanal Ö, Ayvaz DC, Tezcan I, Al-Mousa H, Alsum Z, Hawwari A, Metin A, Matthes-Martin S, Hönig M, Schulz A, Picard C, Barlogis V, Gennery A, Ifversen M, van Montfrans J, Kuijpers T, Bredius R, Dückers G, Al-Herz W, Pai SY, Geha R, Notheis G, Schwarze CP, Tavil B, Azik F, Bienemann K, Grimbacher B, Heinz V, Gaspar HB, Aydin R, Hagl B, Gathmann B, Belohradsky BH, Ochs HD, Chatila T, Renner ED, Su H, Freeman AF, Engelhardt K, Albert MH; inborn errors working party of EBMT
J Clin Immunol 2015 Feb;35(2):189-98. Epub 2015 Jan 28 doi: 10.1007/s10875-014-0126-0. PMID: 25627830
Minegishi Y
Curr Opin Immunol 2009 Oct;21(5):487-92. Epub 2009 Aug 28 doi: 10.1016/j.coi.2009.07.013. PMID: 19717292

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