Medical Mystery of the Week

      Because of the COVID19 pandemic, you are practicing telemedicine. You interview a 45-year-old woman who is on dialysis for chronic renal failure. For the past 10 days she has been running low grade fever and has developed numerous cutaneous lesions, some with crusts (scabs), others pustular in nature. The largest is a hemorrhagic pustule on her thigh. A microscopic view of a silver stain of an aspirate of the pustule along with pictures of the patient's face and thigh lesion are shown below. 
      What is your diagnosis, what lab test(s) would you order to confirm you suspicions, and what treatment, if any, do you recommend? 

DIAGNOSIS: Cutaneous cryptococcosis due to infection with Cryptococcus neoformans (CN). Cryptococcal spp (CN and Cryptococcus gatti) are found in a variety of environments worldwide. These yeast-like fungi have a predilection to infect persons with impaired cell-mediated immunity and are usually acquired via the respiratory route. 
   Pigeon droppings provide a particularly rich medium for the growth of cryptococci although the fungi can flourish on other sources, including soil and fruits.
   The initial infection with cryptococcal spp occurs via the respiratory route where they can cause a variety of pulmonary infiltrates (mass lesions, lobar consolidation, cavities, miliary lesions, and interstitial infiltrates) or leave no identifiable marker. The commonest extrapulmonary sites to be infected include the central nervous system (cryptococcal meningitis), bone, lymph nodes, the prostate, or, as in the presented case, the skin. Infection is more common in men than in women perhaps because the cell-mediated immune responses in men are less robust than in women.
   It is important to recognize that persons with chronic kidney disease are immunocompromised. They have a reduction of naive T cells with a shift to more differentiated forms, a subsequent oligoclonal expansion of naive T cells with repertoir restriction, and replicative insufficiency - all characteristics of immunosenescence of the type seen with aging. 
   The diagnosis of cutaneous cryptococcal infection is best made by "going where the money is" and aspirating (as done in the presented case) or biopsing skin lesions. A silver stain will show  yeast-like organisms with narrow-based buds and a polysaccharide capsule - the latter being the most distinguishing feature of Cryptococcus neoformans. Cryptococcal antigens may be detected in the blood of persons with disseminated disease and in the CSF of those with cryptococcal meningitis. In immunocompetent hosts, cryptococcal meningitis has been documented to persist for as long as 20 years; this may reflect the ability of CN to take on pleiotropic phenotypes and to enter a period of domancy.
   The currently recommended treatment of cryptococcal infection in  immuno-compromised hosts includes one week of intravenous liposome bilayer-coated amphotericin B (LAmB) plus intravenous 5-flucytosine, followed by one week of high dose  fluconazole, eight weeks of intermediate dose fluconazole, and then maintainence with low dose fluconazole until immune reconstitution is complete. Cryptococcal antigen testing is recommended for all AIDs patients with fluconazole prophylaxis indicated if testing is not available or if the antigen test is positive.