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A systematic review regarding the prevalence of malignancy in patients with the hyper-IgE syndrome

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Abstract

The hyper-immunoglobulin E syndrome (HIES) is a primary immunodeficiency disease originally described as Job syndrome. The fundamental causative variant of the HIES is an autosomal dominant mutation in the signal transducer and activator of transcription 3 (STAT3) gene. It is characterized by recurrent staphylococcal cold skin abscess, sinopulmonary infection, eczema, head and face anomalies, frequent bone fractures, eosinophilia and extremely high serum IgE levels (IgE ≥ 2000 IU/mL). However, multiple other genetic defects are also known as HIES-like disorders. Apart from infectious manifestations, STAT3, DOCK8 and TYK2 gene mutations are associated with various malignancies. The most common malignancies reported in these patients are lymphomas, including Hodgkin’s and non-Hodgkin’s lymphomas (NHL) of B and T cells. This systematic review aimed to investigate the prevalence of malignancies in HIES and the factors associated with malignancy in these patients. In this survey, all articles published until April 1st, 2023, in Scopus, PubMed and Web of Science databases based on three groups of keywords related to HIES syndrome and malignancy were reviewed by three different researchers. Finally, 26 articles were evaluated from which 24 papers were meta-analyzed. In the current study, the demographic information of 1133 patients with HIES, which was mentioned in 24 articles enrolled in the project, was collected, and the information related to patients who had malignancy was analyzed and meta-analyzed. A total of 96 patients out of 1133 studied patients had at least one type of malignancy, the overall prevalence of malignancies reported in the articles was 6.5% (95% confidence interval 4.1–9%), and the total prevalence of malignancy in patients with NHL type and patients with squamous cell carcinoma (SCC) was 2.9% (95% confidence interval 1.7–4.4%) and 2.2% (95% confidence interval 0.3–4.1%), respectively. The results of this study indicated that in 6.5% of cases, HIES was complicated with malignancy, and considering the higher rate of these malignancies in women as well as in DOCK8 mutation sufferers, it is necessary for physicians to be aware of this association and includes malignancy screening in follow-up and periodic examinations of these patients. Indeed, more studies in this field will help to clarify the precise figures and predisposing factors of the relationship between HIES and malignancy.

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Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Abbreviations

PID:

Primary immunodeficiency disease

HIES:

Hyper-immunoglobulin E syndrome

AD:

Autosomal dominant

AR:

Autosomal recessive

PRISMA:

Reporting systematic reviews and meta-analyses

DLBCL:

Diffuse large B cell lymphoma

BL:

Burkitt’s lymphoma

CTCL:

Cutaneous T cell lymphoma

TCL:

T cell lymphoma

BCL:

B cell lymphoma

ALCL:

Anaplastic large cell lymphoma

NHL:

Non-Hodgkin's lymphoma

MCL:

Mantle cell lymphoma

CVID:

Common variable immunodeficiency

SCC:

Squamous cell carcinoma

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Authors and Affiliations

  1. Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran

    Tayebeh Mohammadi, Gholamreza Azizi, Hosein Rafiemanesh, Pouria Farahani & Marzieh Tavakol

  2. Alborz University of Medical Sciences, Karaj, Iran

    Matineh Nirouei

  3. Department of Pediatrics, Alborz University of Medical Sciences, Karaj, Iran

    Marzieh Tavakol

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  1. Tayebeh Mohammadi
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Contributions

MT and GA and TM and PF contributed to conception; MT and GA and HR contributed to design of the work; TM and PF and HR contributed to acquisition, analysis and interpretation of data; MN and MT have drafted the work and substantively revised it; all authors read and approved the final manuscript.

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Correspondence to Marzieh Tavakol.

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The authors declare no competing interests.

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The Ethical Committee at the Alborz University of Medical Sciences approved this project (Ethical number: IR.ABZUMS.REC.1400.193).

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Mohammadi, T., Azizi, G., Rafiemanesh, H. et al. A systematic review regarding the prevalence of malignancy in patients with the hyper-IgE syndrome. Clin Exp Med 23, 4835–4859 (2023). https://doi.org/10.1007/s10238-023-01228-5

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