Cryptococcus splenic abscess in primary biliary cholangitis: a case report

Chronic liver diseases, including primary biliary cholangitis (PBC), are recognized as immunosuppressive conditions due to the impaired functionality of hepatic sinusoidal Kupffer cells.[1] PBC is specifically characterized by cholangitis and progressive liver pathology, which may eventually lead to cirrhosis. The compromised liver function and reduced efficacy of Kupffer cells in patients with PBC weaken their cell-mediated immune responses, increasing their susceptibility to opportunistic pathogens such as Cryptococcus.[2] Cryptococcosis is an infectious disease caused by pathogenic encapsulated yeasts of the genus Cryptococcus, which is distributed worldwide and exhibits diverse clinical presentations.[3] Most case reports on cryptococcal infections are associated with HIV infection or other conditions that compromise the immune system.[4] Case reports related to primary biliary cholangitis are rare. Therefore, this case report underscores a rare cryptococcal infection in a patient with primary biliary cholangitis, emphasizing the need to consider opportunistic infections in those with compromised liver function and immune dysregulation.

A 67-year-old woman with a 3-month history of fatigue and a 5-day history of fever presented at our hospital. The patient had been well and fit. She received supportive treatment, including blood transfusion and fluid replacement, at a local hospital before visiting our hospital. Laboratory examination at the local hospital revealed a leukocyte count of 4.66×10⁹/L, lymphocyte count of 0.12×10⁹/L, hemoglobin concentration of 75 g/L, and platelet count of 85×10⁹/L. Blood culture examinations revealed yeast-like fungal growth. Her renal function was normal. Liver function tests revealed an albumin level of 32.3 g/L, alanine aminotransferase (ALT) level of 14 U/L, aspartate aminotransferase (AST) level of 33 U/L, alkaline phosphatase (ALP) level of 131 U/L, gamma-glutamyl transferase (GGT) level of 69 U/L, lactate dehydrogenase (LDH) level of 142 U/L, and total bilirubin level of 19.3 μmol/L. Owing to persistent fever (37.8–38.0 °C) during treatment at the local hospital, she was transferred to our hospital.

On admission, laboratory examination revealed a further decrease in the hemoglobin concentration to 63 g/L, a platelet count of 55×10⁹/L, and an increased percentage of neutrophils (91.6%). The procalcitonin level was 0.65 ng/mL, whereas the C-reactive protein level was 56.36 mg/L. Abdominal computed tomography (CT) revealed hepatic fullness, irregular margins, and increased caudal lobe volume, suggesting cirrhosis. Autoimmune hepatitis antibody examination showed positive results for the anti-mitochondrial antibody M2 and anti-nuclear envelope protein gp210 antibodies, whereas negative results were observed for the remaining antibodies. The liver function parameters were as follows: albumin 30 g/L; ALT 35 U/L; AST 36 U/L; ALP level, 230 U/L; GGT 119 U/L; LDH 157 U/L; total bilirubin 19.4 μmol/L; and direct bilirubin 10.4 μmol/L. Viral hepatitis-related test results were negative, and no history of hereditary liver disease, alcohol consumption, or drug-related hepatitis was found. Contrast-enhanced CT of the abdomen (Figure 1) revealed fluid effusion in the periphery and multi-rounded margin ring enhancement in the spleen, with no enhancing nodules in the center. Blood culture examinations revealed the presence of Cryptococcus neoformans (Figure 2). The Cryptococcus capsular polysaccharide antigen test results were weakly positive. The patient was diagnosed with a Cryptococcus splenic abscess in the PBC.

Figure 1.

The results of abdominal contrast-enhanced computed tomography. An axial image of the abdomen shows nodularity along the contour of the liver (white arrow), which is consistent with cirrhosis. The axial image of the abdomen also shows splenomegaly and multiple abscesses of spleen (red arrows).

Figure 2.

The blood cultrue examination findings. Cryptococcus neoformans cells among multiple granulocytes (ink stain, original magnification ×40).

The patient was initially administered intravenous fluconazole combined with cefotaxime to treat intermittent fever. However, the patient continued to experience intermittent fever and neck discomfort; thus, a lumbar puncture was performed to further clarify the cause of the fever. Cerebrospinal fluid (CSF) examination revealed a pressure of 200 mmHg (1 mmHg=0.133 kPa), leukocyte count of 8×10⁶/L, glucose concentration of 2.1 mmol/L, and LDH level of 26.0 U/L. CSF culture results suggested the presence of Cryptococcus neoformans, indicating cryptococcal meningitis. Therefore, the treatment plan was modified, and fluconazole with amphotericin B was administered.

Re-evaluation of the patient after anti-infective therapy revealed a red blood cell count of 3.28×10¹²/L, hemoglobin concentration of 100 g/L, platelet count of 480×10⁹/L, and albumin level of 38 g/L. Liver function test results were not significant. The patient was then transferred to the general surgery department for laparoscopic total splenectomy, perihilar vascular dissection, and abdominal drainage. The spleen specimens were grey-red or grey-brown and 21 cm × 17 cm× 6 cm in volume. Multiple grey-yellow areas, with a maximum diameter of approximately 0.5–2.0 cm, were observed on the damaged section, and the spleen adhered to some pancreatic tissues measuring 3.5 cm × 2.0 cm × 1.0 cm. A considerable degree of necrosis was observed in the damaged spleen, with abnormal mononuclear and multinucleated macrophages containing fine vacuoles. Immunohistochemical staining showed cells positive for CD68, CD163, and leukocyte common antigen; weakly positive for Ki-67; and negative for CK. Furthermore, the cells tested positive for CD20, CD3, CD8, CD34, CD117, and S-100. The patient recovered well after surgery. Laboratory examination revealed a leukocyte count of 7.22×10⁹/L, lymphocyte count of 1.24×10⁹/L, hemoglobin concentration of 100 g/L, and platelet count of 480×10⁹/L. Liver function tests showed an albumin level of 32.3 g/L, ALT level of 14 U/L, AST level of 33 U/L, ALP level of 131 U/L, GGT level of 69 U/L, LDH level of 142 U/L, and a total bilirubin level of 19.3 μmol/L.

The etiology and pathogenesis of PBC may involve genetic factors and interactions between genetic and environmental factors, resulting in immune system dysregulation. PBC is more prevalent among middle-aged to elderly women. Common clinical symptoms include fatigue and pruritus (i.e., itchy skin). Biochemical hallmarks of PBC include elevated levels of ALP and GGT in the blood, positive anti-mitochondrial antibodies, and increased serum immunoglobulin M levels. Pathologically, PBC is characterized by non-suppurative destructive cholangitis, ultimately leading to the development of liver fibrosis and cirrhosis.[2,5] Globally, the annual incidence of PBC has increased, approximately 100,000 new cases of PBC are diagnosed each year. The prevalence of PBC in China is estimated to be 20.5 cases per 100,000 people, ranking second in the Asia-Pacific region after Japan.[6]

The state of immunosuppression, whether due to chronic liver disease itself or treatment, significantly increases the risk of opportunistic infections. In particular, fungal infections such as cryptococcosis are more prevalent in immunosuppressed patients with chronic liver disease. Over the past 50 years, the prevalence of cryptococcosis has rapidly increased owing to the emergence of new populations of immunocompromised hosts because of HIV infections, cancer and its treatments, organ transplantation, and the increasing use of immunomodulatory medications.[7]

In this case, the patient presented with intermittent fever. Blood culture tests indicated a Cryptococcus infection, which could escalate to cryptococcal meningitis. Subsequent lumbar puncture revealed Cryptococcus infection in the CSF. Abdominal enhanced CT scan suggested a splenic abscess, with the patient’s medical history indicating a Cryptococcus infection. Splenic abscesses combined with Cryptococcus infection are more common in immunocompromised patients, such as those with HIV.[8] HIV infection was ruled out in this case report. Upon further examination, the patient was diagnosed with PBC.

The management of cryptococcal infections associated with PBC presents several challenges, including the impact of immunosuppression and liver function impairment on treatment plans. The efficacy of antifungal drugs with hepatotoxicity must be balanced, and dosages should be adjusted based on liver function. Close monitoring of patients’ immune status and liver function is necessary to promptly adjust treatment plans. Future research should focus on the prevention and management of opportunistic infections, possibly including personalized screening and evaluation of novel therapies. In addition, patient education and timely medical care are essential to reduce the risk of severe infections.

In conclusion, the decline in immune function caused by chronic liver diseases and PBC significantly increases the risk of cryptococcal infections. This implies that clinical practice must adopt personalized and comprehensive management strategies for this specific patient population. PBC patients can receive more holistic care, reducing the burden of their disease and improving their quality of life, with the help of these strategies.