A large multi-site trial supports deferring ART for 4–6 weeks was overall preferable with 15% better 1-year survival than earlier ART initiation at 1–2 weeks after diagnosis. A 2018 Cochrane review also supports the delayed starting of treatment until cryptococcosis starts improving with antifungal treatment. IRIS
The immune reconstitution inflammatory syndrome (IRIS) has been described in those with normal immune function with meningitis caused by C. gattii and C. grubii. The increasing inflammation can cause brain injury or be fatal. Epidemiology
Data from 2009 estimated that of the almost one million cases of cryptococcal meningitis that occurred worldwide annually, 700,000 occurred in sub-Saharan Africa and 600,000 per year died. Other animals
Cryptococcosis is also seen in cats and occasionally dogs. It is the most common deep fungal disease in cats, usually leading to chronic infection of the nose and sinuses, and skin ulcers. Cats may develop a bump over the bridge of the nose from local tissue inflammation. It can be associated with FeLV infection in cats. Cryptococcosis is most common in dogs and cats but cattle, sheep, goats, horses, wild animals, and birds can also be infected. Soil, fowl manure, and pigeon droppings are among the sources of infection. References
Further reading
Perfect JR,  et al. (2010). "Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america". Clinical Infectious Diseases. 50 (3): 291–322. doi:10.1086/649858. PMC 5826644. PMID 20047480. Gullo FP,  et al. (2013). "Cryptococcosis: epidemiology, fungal resistance, and new alternatives for treatment". European Journal of Clinical Microbiology & Infectious Diseases.
Other conditions that pose an increased risk include certain malignancies (such as lymphoma), liver cirrhosis, organ transplants, and long-term corticosteroid therapy.Distribution is worldwide in soil. The prevalence of cryptococcosis has been increasing over the past 50 years for many reasons, including the increase in incidence of AIDS and the expanded use of immunosuppressive drugs.In humans, C. neoformans chiefly infects the skin, lungs, and central nervous system (causing meningitis). Less commonly it may affect other organs such as the eye or prostate. Primary Cutaneous Cryptococcosis
Primary Cutaneous Cryptococcosis (PCC) is a distinct clinical diagnosis separate from the secondary cutaneous cryptococcosis that is spread from systematic infection. Males are more likely to develop the infection and a 2020 study showed that the sex bias may be due to a growth hormone, produced by C. neoformans called gibberellic acid (GA) that is upregulated by testosterone. The upper limbs account for a majority of infections. Isolates found in PCC include Cryptococcus neoformans (most common), Cryptococcus gattii, and Cryptococcus laurentii. Prognosis for PCC is generally good outside of disseminated infection.Morphologic description of the lesions show umbilicated papules, nodules, and violaceous plaques that can mimic other cutaneous diseases like molluscum contagiosum and Kaposis sarcoma. These lesions may be present months before other signs of system infection in patients with AIDS. Pulmonary Cryptococcosis
Cryptococcus (both C. neoformans and C. gattii) plays a common role in pulmonary invasive mycosis seen in adults with HIV and other immunocompromised conditions.