An invasive fungal infection caused by the encapsulated yeastlike fungus C neoformans.
Exposure to pigeon nesting sites or to soil with bird guano associated risk factors for Cryptococcus neoformans infection.
Typically the primary infection is asymptomatic and occurs when airborne spores are inhaled and results in alveolar deposition and uptake by macrophages.
The primary infection in most immunocompetent individuals results in no further clinical manifestations.
Well characterized in people living with HIV, however in the present era the incidence in patients with HIV have decreased considerably.
Presently transplant recipients, are making an increased proportion of new cases.
The fungus cryptococcus is the most common cause of adult meningitis where high rates of HIV infection are present.
Cryptococcus is responsible for 180,000 deaths each year worldwide and accounts for 68% of HIV related cases of meningitis.
The increased use of immunomodulatory therapy and underlying natural susceptibility have changed the epidemiology such that deaths now are non-HIV infected patients account for approximately 1/3 of the deaths related to cryptococcal meningitis or meningoencephalitis.
Risk factors in persons without HIV infection include glucocorticoid treatment, sarcoidosis, and idiopathic CD4 lymphopenia.
Case reports implicated immunosuppressive therapy, including: anti-tumor necrosis factor alpha, anti-CD 52, BTK inhibitors and sphingosine-1 phosphate receptors, tacrolimus and srolimus.
The primary infection in immunocompromised hosts and in a few normal individuals may manifest in pneumonia or extrapulmonary disease of the CNS, bone, skin, urinary tact and virtually any other organ.
In a susceptible host C neoformans may avoid phagocytosis by alveolar macrophages in the lung due to its production of sialic acid residues.
C neoformans may avoid phagocytosis by the linking of galactase in its cell wall to sialic acid residues blocking the galactase receptors in macrophages.
The cryptococcal capsule is antiphagocytic and blocks inflammatory cell recruitment, antibody formation and delayed hypersensitivity reactions.
Affects the skin in 10% of patients with systemic infection.
Skin lesions can be pustules, abscesses, plaques, nodules, cellulitis or solid lesions.
Primary cutaneous involvement by direct inoculation of the skin can occur in both immunocompetent and immunocompromised patients.
Most skin involvement s a result of hematogenous spread of the fungus.
Skin primary site of inoculation is rare but can occur in 10-20% of infections and represent a distant foci of disease.
Disseminated disease is characterized by multiple umbilicated papules with multicentric skin involvement.
Meningoencephalitis is the predominant form of opportunistic cryptocococcis in patients with HIV.
In HIV patients extraneural disease involving the skin, eyes, bones and visceral are also highly likely.
Cryptococcal antigens can be identified with high sensitivity in blood and CSF, with sensitivity and specificity is exceeding 99%.
Diagnostic delays result in higher mortality in all patient groups.
Elevated white blood cell counts, with predominately, lymphocytes, and total protein levels and low glucose levels in CSF are suggestive of cryptococcal meningitis.
Increased intracranial pressure is an important complication of cryptococcal meningitis.
CSS fungal cultures are useful to establish the diagnosis into a differentiate from inflammatory sequelae.
Treatment recommended is amphotericin B based combinations with flucytocine for disseminated disease followed by flucoazole consolidation therapy.