BI42 Chronic lower-leg ulceration in a patient with X-linked hypogammaglobulinaemia: Helicobacter bilis identified as culprit organism via metagenomics pathogen detection

Abstract

A 43-year-old man presented with chronic lower-limb ulceration. His background included agammaglobulinaemia, a rare condition that can present with skin infection. Secondary to this immunodeficiency he also had chronic sinusitis and bronchiectasis. He initially presented with indurated erythematous plaques on his anterior lower limbs and forearms in May 2023, which were diagnosed as infectious and unsuccessfully treated with multiple courses of oral antibiotics. Over the following year, these plaques broke down to form superficial erosions and ulcerations and he was referred to our service. Multiple biopsies revealed a sclerodermatous process with an unclear underlying aetiology. There was no granuloma or abscess formation, or vessel inflammation, and special staining showed no evidence of microorganisms. Throughout this period he experienced intermittent pyrexia. Tuberculosis, giardia, borrelia, fungal and viral screens were all negative. He was admitted for treatment with intravenous antibiotics, with very limited improvement. He was commenced on a regimen including pentoxifylline and prednisolone. He initially showed significant improvement on prednisolone, but this subsequently slowed. During his hospital admissions he was managed by a multidisciplinary team consisting of dermatologists, immunologists and microbiologists. Multiple blood cultures were negative; however, one grew a Gram-negative rod that could not be further cultured to enable identification. Further 16S and 18S sequencing of tissue biopsies did not reveal a causative organism. Eventual metagenomic sequencing of a deep-tissue biopsy finally revealed a likely causative organism: Helicobacter bilis. Helicobacter bilis has been recently reported as a rare cause of refractory lower-limb cellulitis in X-linked agammaglobulinaemia. Here, we present an extremely clinical case in which a multidisciplinary approach, combined with advanced diagnostic microbiology techniques, revealed a rare underlying diagnosis. Despite modern metagenomic testing identifying the culprit organism, it has not responded to antibiotic therapy and the patient is therefore being considered for bone marrow transplantation.