Ustekinumab for pyoderma gangrenosum-like skin ulcerations in late-onset leukocyte adhesion deficiency

Florian Schmid; Kerstin Kerl-French; Barbara Meier-Schiesser; Kai Lehmberg; Peter H Hoeger

doi:10.1016/j.jacig.2024.100233

Ustekinumab for pyoderma gangrenosum-like skin ulcerations in late-onset leukocyte adhesion deficiency

J Allergy Clin Immunol Glob. 2024 Feb 29;3(2):100233. doi: 10.1016/j.jacig.2024.100233. eCollection 2024 May.

Authors

Florian Schmid¹, Kerstin Kerl-French², Barbara Meier-Schiesser², Kai Lehmberg³, Peter H Hoeger^{1

4}

Affiliations

¹ Department of Pediatrics, Catholic Children's Hospital Wilhelmstift, Hamburg, Germany.
² Department of Dermatology, University of Zurich, Zurich, Switzerland.
³ Department of Pediatric Haematology and Oncology, University of Hamburg, Hamburg, Germany.
⁴ Department of Pediatric Dermatology, Catholic Children's Hospital Wilhelmstift, Hamburg, Germany.

Abstract

Background: Leukocyte adhesion deficiency type 1 (LAD-1) is a congenital immunodeficiency leading to impaired trafficking of neutrophils to inflammation sites. Solitary or multiple pyoderma gangrenosum (PG)-like skin ulcers (PGLUs) have been reported previously in 13 children (aged 0.5-19 years) with LAD-1.

Objective: Our aim was to report the case of a 10-year-old boy presenting with PGLUs as the first manifestation of LAD-1 treated with ustekinumab.

Methods: We obtained in situ cytokine profiles.

Results: PGLUs were triggered by cutaneous ringworm infection (Trichophyton tonsurans). Skin biopsy samples showed increased intralesional expression of IL-17A, Il-23, and IL-1β as compared with their expression in healthy controls. After an unsuccessful attempt at treatment with oral methylprednisolone, ustekinumab induced regression of the ulcerations, associated with complete normalization of the cytokine profile.

Conclusions: PGLUs, triggered by ringworm infection, can be a late harbinger of LAD-1. Ustekinumab is a safe and effective therapeutic option for patients with LAD-1 and PGLUs while bridging the time until stem cell transplantation.

Keywords: Leukocyte adhesion deficiency; in situ cytokine profiles; pyoderma gangrenosum–like ulcers; ustekinumab therapy.