A novel association of Legionella pneumophila‐induced haemophagocytic lymphohistiocytosis and the ‘atoll’ sign

Haemophagocytic lymphohistiocytosis (HLH) is an inflammatory condition which can be primary (genetic) or secondary (acquired) [1]. It is characterised by inflammation, fever, lymphadenopathy, and elevated ferritin, CD25 (α chain of the high‐affinity IL‐2 receptor) and triglycerides.

Legionnaire's disease is an atypical pneumonia caused by the gram‐negative bacterium Legionella pneumophila. It is associated with a flu‐like prodrome, gastrointestinal symptoms and electrolyte abnormalities. It is a notifiable disease in the United Kingdom. Here, we present a case of HLH secondary to Legionella infection, with an organising pneumonia pattern on computed tomography (CT) imaging, characterised by the ‘atoll sign’. To our knowledge, the presence of the ‘atoll sign’ is novel in the context of Legionella‐induced HLH.

A young man presented to hospital with shortness of breath and a productive cough. There was no history of recent foreign travel or animal exposure. His only past medical history was depression. On presentation, he was cardiovascularly unstable and severely hypoxic. Initial laboratory findings included an acute kidney injury and hyponatraemia. Computed tomography (CT) imaging was negative for pulmonary embolus, but demonstrated an organising pneumonia pattern featuring the ‘atoll sign’ (Fig. 1). Following stabilisation, he was admitted to the intensive care unit (ICU). He was treated with broad‐spectrum antimicrobials, and required sedation for tracheal intubation and mechanical ventilation including prone positioning. Vasopressors and active cooling were used when required.

Figure 1.

CT images demonstrating typical features of organising pneumonia; (a) axial slice showing multiple focal areas of ground‐glass opacification surrounded by a ring of consolidation (white arrows). This is the ‘atoll’ or reversed halo sign; (b) a further axial slice from the same patient showing both bronchocentric (white arrow) and peripheral consolidation (black arrow).

Clinical and biochemical features included refractory hyperthermia, raised C‐reactive protein, procalcitonin, creatine kinase, ferritin (8129 μg.L⁻¹), triglycerides (8.24 mmol.L⁻¹), IL‐2 receptor antibody (> 10,000 U.ml⁻¹), lymphopenia (< 1 × 10⁹.L⁻¹) and thrombocytopenia (113 × 10⁹.L⁻¹). Bronchoalveolar lavage polymerase chain reaction testing for Legionella pneumophila and urinary Legionella antigen were positive. All other microbiology results were negative.

Given the clinical, laboratory and radiological findings, advice was sought from the lung inflammation team, who diagnosed HLH. Recommendations included treatment with intravenous methylprednisolone 1 mg.kg⁻¹ twice daily. Significant clinical and biochemical improvement occurred, and the patient was discharged from ICU after 10 days.

Whilst we were unable to find any detailed case reports describing Legionella‐induced HLH in the literature, Legionella infection was listed as an HLH trigger in a recent review [2]. The diagnosis of HLH is assisted with the use of the H‐score, which predicts an individual's risk of HLH using clinical and biochemical variables [3]. Our patient had an H‐score of 187, corresponding to a 70–80% likelihood of the diagnosis being HLH. Clinical and laboratory features in our case correspond well with the Histiocyte Society diagnostic criteria [4].

The ‘atoll sign’ is a radiological finding defined as a crescenteric or ring‐shaped opacity, surrounding a central area of ground glass opacity [5]. Whilst an organising pneumonia pattern has been described in association with Legionella pneumonia, to our knowledge we present the first case of Legionella‐associated HLH presenting with the ‘atoll sign’ on CT.

For radiologists, our case adds to the ever‐increasing differential diagnosis associated with the ‘atoll sign’ and for critical care physicians, it is a reminder that secondary HLH should be considered in patients presenting with an intense and refractory inflammatory response to a potential infectious trigger.