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Atypical Localization of Eczema Discriminates DOCK8 or STAT3 Deficiencies from Atopic Dermatitis

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Abstract

Purpose

Autosomal recessive dedicator of cytokinesis 8 (DOCK8−/−) and autosomal dominant signal transducer and activator of transcription 3 (STAT3−/+) deficiencies are inborn errors of immunity (IEI) disorders present with the classic features of eczema and create a dilemma during differentiation from atopic dermatitis (AD). Therefore, an appropriate approach is required for eczema to diagnose DOCK8−/− and STAT3−/+ early. Here, we described a set of clinical and immunological variables, including atypical AD localizations and lymphocyte subsets, to differentiate DOCK8−/− or STAT3−/+ from AD.

Methods

This multicenter study involved 100 patients with DOCK8−/− and STAT3−/+ and moderate/severe AD. We recruited disease manifestations, including detailed localizations of eczema, infections, and allergy. Principle component analysis (PCA) was used to discriminate DOCK8−/− or STAT3−/+ from AD.

Results

There were 43 patients with DOCK8−/−, 23 with STAT3−/+, and 34 with AD. Pneumonia, severe infections, mucocutaneous candidiasis, and skin abscesses were commonly observed in DOCK8 and STAT3 deficiencies. Atypical skin involvement with neonatal rash, retro auricular, axillary, sacral, and genital eczema discriminate DOCK8−/− and STAT3−/+ from AD with high specificity ranges between 73.5 and 94.1% and positive predictive index ranges between 55 and 93.1%. Together with using absolute numbers of CD3+, CD4+, and CD8+ T cells, the combined clinical and laboratory features showed perfect differentiation between DOCK8−/− or STAT3−/+ and AD via PCA.

Conclusions

The described features can be easily implemented by physicians providing early diagnosis of DOCK8 and STAT3 deficiencies.

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Data Availability

The data generated during the study are included in this published article and its supplementary file.

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Funding

This work was supported by the Scientific and Technological Research Council of Turkey to S.B. (318S202).

Author information

Authors and Affiliations

  1. Division of Pediatric Allergy/Immunology, Faculty of Medicine, Pediatric Allergy and Immunology, Marmara University, Fevzi Çakmak Mah. No: 41, Pendik, Istanbul, Turkey

    Nurhan Kasap, Sevgi Bilgic Eltan, Ahmet Ozen, Elif Karakoc-Aydiner & Safa Baris

  2. Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey

    Nurhan Kasap, Sevgi Bilgic Eltan, Ahmet Ozen, Elif Karakoc-Aydiner & Safa Baris

  3. The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey

    Nurhan Kasap, Sevgi Bilgic Eltan, Ahmet Ozen, Elif Karakoc-Aydiner & Safa Baris

  4. TUBITAK Marmara Research Center, Gene Engineering and Biotechnology Institute, Gebze, Turkey

    Altan Kara

  5. Faculty of Medicine, Pediatric Allergy and Immunology, Trakya University, Edirne, Turkey

    Velat Celik

  6. Department of Pediatric Allergy and Immunology, Dr Behçet Uz Children’s Hospital, Izmir, Turkey

    Idil Akay Haci, Nesrin Gulez & Ferah Genel

  7. Department of Pediatric Immunology and Rheumatology, Medical Faculty, Uludag University, Bursa, Turkey

    Hulya Kose, Sukru Cekic & Sara Sebnem Kilic

  8. Department of Pediatrics, Division of Immunology, Faculty of Medicine, Ege University, Izmir, Turkey

    Ayse Aygun & Neslihan Edeer Karaca

  9. Pediatric Allergy and Immunology Department, Sancaktepe Training and Research Hospital, Istanbul, Turkey

    Emre Akkelle

  10. Pediatric Allergy and Immunology Department, Faculty of Medicine, Karadeniz Teknik University, Trabzon, Turkey

    Nalan Yakici

  11. Division of Pediatric Allergy and Immunology, Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey

    Sukru Nail Guner, Ismail Reisli & Sevgi Keles

  12. Department of Dermatology, Faculty of Medicine, Marmara University, Istanbul, Turkey

    Ayse Deniz Yucelten

  13. Division of Immunology, Boston Children’s Hospital, Boston, MA, USA

    Klaus Schmitz-Abe

  14. Department of Pediatrics, Harvard Medical School, Boston, MA, USA

    Klaus Schmitz-Abe

  15. The Manton Center for Orphan Disease Research, Boston Children’s Hospital, Boston, MA, USA

    Klaus Schmitz-Abe

Authors
  1. Nurhan Kasap
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  22. Safa Baris
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Contributions

N.K. and S.B. conceptualized the study. N.K., A.K., and S.B. wrote the manuscript. A.K., V.C., K.S.A., and S.B. performed the statistical analysis. N.K., V.C., S.B.E., I.A.H., H.K., A.A., E.A., N.Y., S.N.G., I.R., S.K., S.C., S.S.K., N.E.K., N.G., F.G., A.O., A.D.Y., E.K.A., and S.B. cared for patients and provided samples intellectually contributed to the manuscript and discussions. All authors read the manuscript and contributed to the revision and discussions.

Corresponding author

Correspondence to Safa Baris.

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The Ethics Committee of Marmara University School of Medicine approved the study.

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Kasap, N., Kara, A., Celik, V. et al. Atypical Localization of Eczema Discriminates DOCK8 or STAT3 Deficiencies from Atopic Dermatitis. J Clin Immunol 43, 1882–1890 (2023). https://doi.org/10.1007/s10875-023-01554-z

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  • DOI: https://doi.org/10.1007/s10875-023-01554-z

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