Co-existence of acute liver failure and mucormycosis in an immunocompetent host: A rare presentation of Wilson's disease

Introduction

Wilson's disease is a rare, autosomal recessive copper metabolism illness characterised by hepatic, neurological, and mental abnormalities caused by mutations in the ATP7B gene. ¹ Haemolysis and multi-organ dysfunction are frequently linked to acute liver failure (ALF) and can be the initial clinical presentation, a severe but rare manifestation. ² Serious opportunistic infections, such as mucormycosis, are not directly related to Wilson's disease but may be attributed to the transient immune dysfunction brought on by ALF. ³ Here we present a challenging case of a young healthy male, without any prior comorbidity, who presented with altered mental status and ALF, complicated by mucormycosis.

Case presentation

An otherwise healthy 21-year old male was brought in as an emergency with a history of fever, vomiting, and loose stools for three days, as well as headache accompanied by abnormal behaviour for one day.

On examination, he was tachycardic (heart rate = 120 bpm), hypotensive (blood pressure = 90/52 mmHg), and tachypnoeic (respiratory rate = 36/min) with an oxygen saturation of 88% on room air. He had a depressed conscious level (Glasgow Coma Scale: E4V4M5). Random blood glucose was normal, but blood gas analysis suggested metabolic acidosis with a high anion gap and high lactate levels (8.63 mmol/L). The total leucocyte count was normal in complete blood counts, but there was thrombocytopenia (44 × 10⁹/L) and anaemia (haemoglobin 86 g/L).

Initially, he was managed with intravenous crystalloids and oxygen supplementation by nasal prongs. A non-contrast brain computed tomography (CT) scan was normal, but a magnetic resonance imaging (MRI) scan suggested a viral encephalitis. Ceftriaxone, doxycycline, artesunate, acyclovir, and dexamethasone were started to target viral encephalitides and cerebral malaria, scrub typhus, and enteric fever.

Transaminase levels on initial presentation progressed to very high levels in the next two days, with ALT 14,809 U/L and AST 3094 U/L bilirubin levels were also rising (111.15 µmol/L), and coagulopathy (international normalised ratio: 3.61) was pronounced.

Despite the falling haemoglobin level from 86 to 64 g/L without any obvious blood loss, and very high lactate dehydrogenase levels found (180.78 µkat/L), no schistocytes were seen on blood film morphology. A Coombs test was negative, and the renal function remained normal throughout his illness.

Initial workup for malaria, scrub typhus, dengue, and enteric fever was negative. A lumbar puncture was deferred initially because of the thrombocytopenia and clotting disorder. Hepatitis A and E tests were negative but urinary copper levels were very high (13.5 µmol/24 h) and serum ceruloplasmin were slightly low (180 mg/L). Kaiser Fleischer rings were present. A diagnosis of Wilson's disease was made and zinc 50 mg TDS was commenced. Despite initial clinical improvement in liver function tests by the seventh day, he persistently remained febrile. Chest radiography was suggestive of consolidation in the left lower lobe, delineated by CT scan as collapse consolidation.

At this point, palatal discolouration, nasal discharge, and facial oedema were noticed (Fig. 1), which raised the possibility of early-onset invasive mucormycosis.

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Figure 1.

Blackish discolouration of the palate.

Aseptate fungal hyphae compatible with mucormycosis were confirmed by nasal biopsies. A bronchoscopy suggested a clot in the left lower lobe bronchus. Carbapenem-resistant Enterobacteriaceae (CRE-Klebsiella) were grown on Bronchoalveolar lavage culture, for which polymyxin was started.

A repeat MRI scan was subsequently suggestive of a resolution of the initial viral encephalitis, but the appearance of a small ring-enhancing lesion in the cerebellum was noted (Fig. 2). A diagnosis of disseminated mucormycosis was thus made, and liposomal amphotericin B, 7 mg/kg body weight, was commenced. Following nasal debridement, he gradually improved. After a month of treatment, his vital signs stabilised without any oxygen requirement; full consciousness was resumed without any residual neurological weakness.

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Figure 2.

Ring-enhancing lesion on magnetic resonance imaging (MRI) in the cerebellum.

Discussion

Even in the absence of conventional risk factors and chronic immunosuppressive states, immune suppression associated with hepatic failure may be a key factor in allowing fungal invasion in ALF. This causes endothelial dysfunction, elevated oxidative stress, and compromised neutrophil function, all of which foster a milieu that is conducive to fungal invasion.^4,5 This case demonstrates the challenges in diagnosing Wilson's disease and the early disseminated mucormycosis in an immunocompetent host. Since mucormycosis is still an underdiagnosed consequence of Wilson's disease-associated ALF, further data are needed to determine how hepatic dysfunction predisposes individuals to it.