A 56 year-old man with a history of immunosuppressive therapy with prednisone and tacrolimus for a cadaveric kidney transplant presented with 1 month of personality change and lethargy. He was also noted to have generalized weakness and fatigue. He was initially seen 3 weeks prior to admission for these symptoms, which were attributed to hyponatremia and improved with correction of his serum sodium level. However, the symptoms recurred following his return home and were persistent until a family member brought him back to our hospital. The patient had slowed speech and impaired memory. He had decreased attention span and alertness. He was able to follow simple commands and showed no focal motor or sensory deficits. He had impaired balance and difficulty with fine motor skills. Serum chemistries revealed a sodium level of 131 and a creatinine at the patient’s baseline of 1.4 mg/dL. HIV 1 and 2 Ag/Ab testing was negative and tacrolimus level was subtherapeutic. CT head was negative for any acute process, however MRI brain revealed ill-defined leptomeningeal enhancement overlying the cerebellar hemisphere. Lumbar puncture was performed with an opening pressure of 12 cm H2O. Cerebral spinal fluid analysis revealed 25 white blood cells, glucose of 10 mg/dL, protein of 286 mg/dL, and a positive cryptococcal antigen at a titer of >1:256. Serum cryptococcal antigen was additionally found to be positive.
Discussion: There are currently an estimated 400,00 people living with kidney transplants, with approximately 110,000 patients registered on the United Network of Organ Sharing (UNOS) kidney transplant waiting list in the United States. Infections represent 20.9% of all-death-causes in renal transplant patients. Cryptococcus neoformans is an opportunistic fungal infection with increased incidence in solid organ transplant recipients. Between 20-60% of cryptococcosis in HIV-negative patients occur in this population with a prevalence of 2.8%. The most common risk factor predisposing to cryptococcosis is immunosuppressive medication used to prevent donor organ rejection. Steroids in particular appear to increase the risk 61-87% of organ transplant recipients were on prednisone at the time of diagnosis with cryptococcosis. The central nervous system and lungs are the main sites of infection in solid organ transplant recipients, although it may spread diffusely to other organs. Cryptococcal meningitis in solid organ transplant presents mainly in the form of encephalopathy, nausea/vomiting, fever, headache, nuchal rigidity, visual loss, and seizure. Solid organ transplant recipients, in contrast to HIV-positive patients, often have lower fungal burden in the CSF and less frequently have increased intracranial pressure.
Conclusions: In summary, given the widely increasing success of solid organ transplant, the internist should be aware of the development of symptoms and signs of cryptococcal meningitis in this population.