Cryptococcus in pleural fluid cytology in a patient with hepatitis B virus-associated chronic liver disease.

Sir,

Cryptococcosis, usually due to Cryptococcus neoformans (CN), is more common in human immunodeficiency virus (HIV) infection and other immunodeficient states such as hematolymphoid malignancies, in patients on prolonged corticosteroid therapy, and less frequently occurs in immunocompetent hosts.[1-3] Cryptococcal pleuritis is per se rare.[14] To our knowledge, Cryptococcus in pleural fluid cytology in a case of chronic hepatitis B virus (HBV)-associated liver disease has never been reported. We describe a case of an HBV-associated decompensated cirrhosis of liver with hepatic encephalopathy who developed cryptococcal pleural effusion and cryptococcal yeasts were demonstrated microscopically in stained smears of pleural fluid.

A 49-year-old man, with a six-year history of HBV-associated cirrhosis of liver and portal hypertension, was admitted with sudden onset history of abnormal behavior in the form of not understanding verbal commands and not recognizing relatives. There was no history of fever, upper gastrointestinal bleed, diuretic overdose, or constipation. In the past, patient had been admitted with recurrent episodes of subacute bacterial peritonitis (SBP) and hepatorenal syndrome, which had resolved without any complications. Patient was on antiviral therapy; however, his HBV DNA titres and hepatitis B core antigen status were unknown.

On examination, the patient was afebrile, confused and disoriented. The blood pressure was 104 / 68 mmHg, pulse was 96 per minute and respiratory rate was 26 per minute. Icterus, pedal edema and asterixis were present. Breath sounds were reduced over right lung field. Abdomen was distended with flank dullness. Central nervous system examination showed a localized response to painful stimuli. Muscle tone was normal and plantars were flexor. No signs of meningeal irritation were noted. Chest radiograph showed massive right-sided pleural effusion. Investigations showed deranged hepatic and renal function and hyponatremia. Enzyme linked immunosorbent assay for HIV and hepatitis C were negative. Clinical diagnosis of pleural effusion secondary to ascites with hepatic encephalopathy, hepatorenal syndrome and SBP was considered. Diagnostic paracentesis of pleural fluid was performed. The fluid was exudative with predominant mononuclear cells, and markedly increased protein content (5.8 g/dL). Acid fast staining and malignant cytology were negative. A cytologic preparation of pleural fluid [Figure 1] showed numerous rounded fungal elements observed as narrowly budding Gram-positive yeasts characteristic of Cryptococcus. The mucinous capsule appeared as a clear halo on Leishman and Papanicolaou stains. The patient developed grade IV encephalopathy, hypotension and died one day after admission.

Figure 1

Cytologic preparation of pleural fluid showing numerous narrowly budding (arrow) cryptococcal yeast [a. Leishman stain, b. Papanicolaou stain, c. Gram stain, ×1000]

Pleural effusion is an unusual manifestation of pulmonary cryptococcosis. Although the respiratory tree is the normal portal of entry for Cryptococcus, pulmonary cryptococcosis is often clinically “silent,”[1] as was in this case too. Cell-mediated immunity is the main defensive mechanism against cryptococcal infection.[2] Patients with chronic liver disease have qualitative or quantitative impairment of humoral and cell-mediated immunity which may increase the risk of cryptococcosis.[3] Furthermore, failure of antiviral therapy to achieve sustained viral control has been attributed to the profoundly depleted HBV-specific T cell response characteristic of patients with chronic HBV infection.[5] In the absence of coexisting HIV infection, CN is rarely considered in the differential diagnosis of pleural effusions that occur in patients with cirrhosis and ascites. Severe liver disease has not been fully recognized as a predisposing factor in the development of CN infection, particularly pleural effusion, but the scattered case reports in the medical literature[3] and this case augment the association between the advanced liver disease and cryptococcal infection. The case highlights the unusual demonstration of cryptococcal yeasts in pleural fluid cytology in a case of HBV-associated decompensated cirrhosis of liver.