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Primary Invasive Cutaneous Fusariosis in Patients with STAT3 Hyper-IgE Syndrome

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Abstract

Dominant negative (DN) mutations in signal transducer and activator of transcription 3 (STAT3) are known to cause hyper-IgE syndrome, a rare primary immunodeficiency. STAT3 DN patients are prone to develop fungal infections, including chronic mucocutaneous candidiasis due to impaired IL-17-mediated immunity, and pulmonary aspergillosis. Despite having preserved phagocyte functions, STAT3 DN patients present connective tissue abnormalities and a defect in the immunological skin barrier. Fusarium species are ubiquitous molds, whose potential to infect humans depends on the host’s innate and cellular immune status. Our aim was to describe four STAT3 DN patients with fusariosis confined to the skin. Medical records were reviewed and summarized. Four patients, aged 4, 11, 30, and 33 years, presented with chronic skin lesions which started in the extremities. Two patients had remote lesions, and none had systemic involvement. Skin biopsies showed mycelial threads with deep inflammatory—occasionally granulomatous—infiltrates, reaching the dermis; cultures grew Fusarium solani. Response to treatment was heterogeneous, often requiring multimodal therapies, including topical antifungal preparations. In this work, we describe primary invasive cutaneous fusariosis as a syndromic entity in four STAT3 DN patients.

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Data Availability

All data generated or analyzed during this study are included in this published article.

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Acknowledgements

Our thanks go to Amélie Dureault, Francois Danion, and Romain Guéry, for their active participation in the management and therapeutic discussions for patient 2. We also thank Professor Christine Bodemer for offering her expertise regarding this manuscript. Finally, we thank the National Reference Center for Invasive Mycoses and Antifungals, Institut Pasteur, Molecular Mycology Unit, UMR 2000, CNRS, Paris, France, for the confirmation of the identification and the determination of the sensitivity to antifungal agents of the strain of patient 2.

Funding

This work was supported, in part, by the Division of Intramural Research (DIR) of the National Institute of Allergy & Infectious Diseases, National Institutes of Health.

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Author notes

  1. Salam Abbara and Alexandra Freeman contributed equally to this manuscript.

Authors and Affiliations

  1. Paris Cité University, Department of Infectious Diseases and Tropical Medicine, Necker-Enfants Malades Hospital, AP-HP, IHU Imagine, 149 Rue de Sèvres, 75015, Paris, France

    Salam Abbara, Claire Rouzaud, Fanny Lanternier & Olivier Lortholary

  2. Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    Alexandra F. Freeman & Michail S. Lionakis

  3. Inserm UMR 1153, Obstetrical, Perinatal and Pediatric Epidemiology Research Team, Research Centre for Epidemiology and Statistics (CRESS), Paris Cité University, Paris, France

    Jérémie F. Cohen

  4. Department of General Pediatrics and Pediatric Infectious Diseases, Necker-Enfants Malades Hospital, AP-HP, Paris Cité University, 75015, Paris, France

    Jérémie F. Cohen

  5. Reference Center for Genodermatoses (MAGEC Center), Department of Pathology, Necker-Enfants Malades Hospital, AP-HP, Paris Cité University, 75015, Paris, France

    Stéphanie Leclerc-Mercier

  6. University of California, San Francisco, SF, USA

    Lauren Sanchez

  7. Pharmacy Department, Necker-Enfants Malades Hospital, AP-HP, Paris Cité University, 75015, Paris, France

    Joel Schlatter & Salvatore Cisternino

  8. INSERM UMRS-1144, Faculté de Pharmacie, Paris Cité University, F-75006, Paris, France

    Salvatore Cisternino

  9. Clinical Center, National Institutes of Health, Bethesda, MD, USA

    Ruth Parker

  10. Dermatology Consultation Service, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA

    Edward W. Cowen

  11. Department of Mycology, Necker-Enfants Malades Hospital, AP-HP, Paris Cité University, 75015, Paris, France

    Marie Elisabeth Bougnoux

  12. Unité Biologie Et Pathogénicité Fongiques, Institut Pasteur, USC 2019 INRA, 25, Rue du Docteur Roux, 75015, Paris, France

    Marie Elisabeth Bougnoux

  13. Institut Pasteur, Molecular Mycology Unit, CNRS UMR 2000, 75015, Paris, France

    Fanny Lanternier & Olivier Lortholary

Authors
  1. Salam Abbara
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  2. Alexandra F. Freeman
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  3. Jérémie F. Cohen
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  10. Claire Rouzaud
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  11. Marie Elisabeth Bougnoux
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  13. Michail S. Lionakis
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  14. Olivier Lortholary
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Contributions

All authors were involved in the diagnosis and clinical care of the reported clinical cases. OL and ML conceptualized this study. SA wrote the first draft of the manuscript. AF edited extensively the manuscript. SA, AF, JC, SLM, LS, JS, SC, CR, MEB, FL, ML, and OL edited and revised the manuscript, until the final version. OL supervised the study. All authors revised and approved the manuscript.

Corresponding authors

Correspondence to Michail S. Lionakis or Olivier Lortholary.

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Ethics Approval

This study was performed in line with the principles of the Declaration of Helsinki.

Consent to Participate

Informed consent was obtained from all individual participants included in the study.

Consent for Publication

The authors affirm that human research participants provided informed consent for publication of their case report and of images in Figs. 1 and 2.

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The authors declare no competing interests.

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Abbara, S., Freeman, A.F., Cohen, J.F. et al. Primary Invasive Cutaneous Fusariosis in Patients with STAT3 Hyper-IgE Syndrome. J Clin Immunol 43, 647–652 (2023). https://doi.org/10.1007/s10875-022-01404-4

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  • DOI: https://doi.org/10.1007/s10875-022-01404-4

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