Adult Sibling Cases of Cutaneous Botryomycosis Leading to the Diagnosis of X-Linked Agammaglobulinemia

Michiyo Takeuchi; Yo Kaku; Keiko Hashikawa; Masaki Tominaga; Ryuta Nishikomori; Yutaka Tsutsumi; Hiroshi Koga

doi:10.1097/DAD.0000000000003306

Adult Sibling Cases of Cutaneous Botryomycosis Leading to the Diagnosis of X-Linked Agammaglobulinemia

Am J Dermatopathol. 2026 May 14. doi: 10.1097/DAD.0000000000003306. Online ahead of print.

Authors

Michiyo Takeuchi¹, Yo Kaku¹, Keiko Hashikawa¹, Masaki Tominaga², Ryuta Nishikomori³, Yutaka Tsutsumi⁴, Hiroshi Koga¹

Affiliations

¹ Department of Dermatology, Kurume University School of Medicine, Kurume, Japan.
² Division of Respirology, Neurology and Rheumatology, Department of Community Medicine, Kurume University School of Medicine, Kurume, Japan.
³ Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan; and.
⁴ Diagnostic Pathology Clinic, Pathos Tsutsumi (Tsutsumi Byori Shindanka Clinic), Inazawa, Japan.

PMID: 42358014
DOI: 10.1097/DAD.0000000000003306

Abstract

Background: X-linked agammaglobulinemia (XLA) is a primary immunodeficiency caused by pathogenic variants in the Bruton tyrosine kinase (BTK) gene, leading to severe B-cell maturation defects and pan-hypogammaglobulinemia. Botryomycosis is a rare chronic bacterial infection, typically caused by Staphylococcus aureus (S. aureus), characterized by suppurative and chronic inflammation and grape-like bacterial clusters in tissue.

Case presentation: We report 2 adult male siblings with previously undiagnosed XLA who presented with cutaneous botryomycosis. Case 1, aged 20 years, developed painless perianal nodules and plaques; laboratory tests revealed markedly decreased IgG, IgM, and IgA. Deep tissue cultures grew methicillin-resistant S. aureus, Streptococcus agalactiae, and Peptoniophilus species. Case 2, his elder brother, aged 21 years, had recurrent pneumonia and persistent verrucous nodules on both lower extremities; methicillin-resistant S. aureus was cultured from a localized abscess. Both siblings carried the same BTK pathogenic variant (c.1760T > C; p.Met587Thr). Skin lesions in both patients resolved with systemic antibiotics and subcutaneous immunoglobulin replacement therapy.

Histopathology: Biopsies revealed chronic inflammation with scattered neutrophils, fibrosis, and capillary proliferation centered on the hair follicle. Follicular infundibulum contained grape-like clusters of cocci, occasionally forming tetrads, without Splendore-Hoeppli phenomenon. The organisms were Gram-positive and nonspecifically Gomori methenamine silver-positive. Immunohistochemistry confirmed S. aureus as the causative pathogen.

Conclusions: These sibling cases highlight cutaneous botryomycosis as an under-recognized but clinically relevant manifestation of XLA. Awareness of this association can facilitate earlier diagnosis of the underlying immunodeficiency through integration of clinical history, microbiology, immunohistochemistry, and histopathology.

Keywords: Bruton agammaglobulinemia; Splendore–Hoeppli phenomenon; Staphylococcus aureus; X-linked agammaglobulinemia; botryomycosis.