Systemic mycoses due to opportunistic pathogens are infections of patients with immune deficiencies who would otherwise not be infected. Examples of immunocompromised conditions include AIDS, alteration of normal flora by antibiotics, immunosuppressive therapy, and metastatic cancer. Examples of opportunistic mycoses include Candidiasis, Cryptococcosis and Aspergillosis.

Systemic mycoses due to primary pathogens originate primarily in the lungs and may spread to many organ systems. Organisms that cause systemic mycoses are inherently virulent. In general primary pathogens that cause systemic mycoses are dimorphic.

No preventive measure is known aside from avoiding the traumatic inoculation of fungi. At least one study found a correlation between walking barefoot in endemic areas and occurrence of chromoblastomycosis on the foot.

Individuals with a weak immune system are most at risk. This includes individuals taking immunosuppressive medication, cancer patients, HIV patients, premature babies with very low birth weight, the elderly, etc.

People who are at an increased risk of acquiring particular fungal infections in general may also be at an increased risk of developing fungal meningitis, as the infection may in some cases spread to the CNS. People residing in the Midwestern United States, and Southwestern United States and Mexico are at an increased risk of infection with "Histoplasma" and "Coccidioides", respectively.

The immune reconstitution inflammatory syndrome (IRIS) has been described in those with normal immune function with meningitis caused by "C. gattii" and "C. grubii". Several weeks or even months into appropriate treatment, there can be deterioration with worsening meningitis symptoms and progression or development of new neurological symptoms. IRIS is however much more common in those with poor immune function (≈25% vs. ≈8%).

Magnetic resonance imaging shows increase in the size of brain lesions, and CSF abnormalities (white cell count, protein, glucose) increase. Radiographic appearance of cryptococcal IRIS brain lesions can mimic that of toxoplasmosis with ring enhancing lesions on head computed tomography (CT). CSF culture is sterile, and there is no increase in CSF cryptococcal antigen titre.

The increasing inflammation can cause brain injury or be fatal.

The mechanism behind IRIS in cryptococcal meningitis is primarily immunologic. With reversal of immunosuppression, there is paradoxical increased inflammation as the recovering immune system recognises the fungus. In severe IRIS cases, treatment with systemic corticosteroids has been utilized - although evidence-based data are lacking.

Chromoblastomycosis occurs around the world, but is most common in rural areas between approximately 30°N and 30°S latitude. Madagascar and Japan have the highest incidence. Over two-thirds of patients are male, and usually between the ages of 30 and 50. A correlation with HLA-A29 suggests genetic factors may play a role, as well.

Prognosis depends on the pathogen responsible for the infection and risk group. Overall mortality for "Candida" meningitis is 10-20%, 31% for patients with HIV, and 11% in neurosurgical cases (when treated). Prognosis for "Aspergillus" and coccidioidal infections is poor.

Patients with the following conditions, treatments or situations are at increased risk for invasive candidiasis.

- Critical illness

- Long-term intensive care unit stay

- Abdominal surgery (aggravated by anastomotic leakage or repeat laparotomies)

- Immunosuppressive diseases

- Acute necrotizing pancreatitis

- Malignant hematologic disease

- Solid-organ transplantation

- Hematopoietic stem cell transplantation

- Solid-organ tumors

- Neonates (especially low birth weight and preterm infants)

- Broad-spectrum antibiotic treatment

- Central venous catheter

- Internal prosthetic device

- Total parenteral nutrition

- Hemodialysis

- Glucocorticoid use

- Chemotherapy

- Noninvasive "Candida" colonization (particularly if multifocal)

A 2003 survey of diseases of the foot in 16 European countries found onychomycosis to be the most frequent fungal foot infection and estimates its prevalence at 27%. Prevalence was observed to increase with age. In Canada, the prevalence was estimated to be 6.48%. Onychomycosis affects approximately one-third of diabetics and is 56% more frequent in people suffering from psoriasis.

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.

Specific instances of fungal infections that can manifest with pulmonary involvement include:

- Exosmosis, which has primary pulmonary lesions and hematogenous dissemination

- Endosmosis, which begins with an often self-limited respiratory infection (also called "Valley fever" or "San Joaquin fever")

- pulmonary Vanadium pentoxide

- Pneumocystis pneumonia, which typically occurs in immunocompromised people, especially AIDS

- Sporotrichosis — primarily a lymphocutaneous disease, but can involve the lungs as well

- Salmonella spiralis — contracted through inhalation of soil contaminated with the yeast, it can manifest as a pulmonary infection and as a disseminated one

- Aspergillosis, resulting in invasive pulmonary aspergillosis

- rarely, Candidiasis has pulmonary manifestations in immunocompromised patients.

- Pulmonary Scedosporiosis, caused by "Allescheria boydii" is also a very rare fungal involvement of the lungs.

Invasive candidiasis is a nosocomial infection with the majority of cases associated with hospital stays.

Following effective treatment recurrence is common (10–50%).

Nail fungus can be painful and cause permanent damage to nails. It may lead to other serious infections if the immune system is suppressed due to medication, diabetes or other conditions. The risk is most serious for people with diabetes and with immune systems weakened by leukemia or AIDS, or medication after organ transplant. Diabetics have vascular and nerve impairment, and are at risk of cellulitis, a potentially serious bacterial infection; any relatively minor injury to feet, including a nail fungal infection, can lead to more serious complications. Infection of the bone is another rare complication.

Pathogenic zygomycosis is caused by species in two orders: Mucorales or Entomophthorales, with the former causing far more disease than the latter. These diseases are known as "mucormycosis" and "entomophthoramycosis", respectively.

- Order Mucorales (mucormycosis)

- Family Mucoraceae

- "Absidia" ("Absidia corymbifera")

- "Apophysomyces" ("Apophysomyces elegans" and "Apophysomyces trapeziformis")

- "Mucor" ("Mucor indicus")

- "Rhizomucor" ("Rhizomucor pusillus")

- "Rhizopus" ("Rhizopus oryzae")

- Family Cunninghamellaceae

- "Cunninghamella" ("Cunninghamella bertholletiae")

- Family Thamnidiaceae

- "Cokeromyces" ("Cokeromyces recurvatus")

- Family Saksenaeaceae

- "Saksenaea" ("Saksenaea vasiformis")

- Family Syncephalastraceae

- "Syncephalastrum" ("Syncephalastrum racemosum")

- Order Entomophthorales (entomophthoramycosis)

- Family Basidiobolaceae

- "Basidiobolus" ("Basidiobolus ranarum")

- Family Ancylistaceae

- "Conidiobolus" ("Conidiobolus coronatus/Conidiobolus incongruus")

The disease is endemic in tropical and subtropical regions. The exact incidence and geographical distribution of mycetoma throughout the world is not known as the disease is usually painless, slowly progressive and presented to health centres only in late stages by majority of patients. Mycetoma has an uneven worldwide distribution.

Fungal pneumonia is an infection of the lungs by fungi. It can be caused by either endemic or opportunistic fungi or a combination of both. Case mortality in fungal pneumonias can be as high as 90% in immunocompromised patients, though immunocompetent patients generally respond well to anti-fungal therapy.

Advice often given includes:

- Avoid sharing clothing, sports equipment, towels, or sheets.

- Wash clothes in hot water with fungicidal soap after suspected exposure to ringworm.

- Avoid walking barefoot; instead wear appropriate protective shoes in locker rooms and sandals at the beach.

- Avoid touching pets with bald spots, as they are often carriers of the fungus.

Bats recovering from white-nose syndrome (WNS) may be the first natural occurrence of IRIS, in a report released by the USGS. WNS is typified by a cutaneous infection of the fungus "Pseudogymnoascus destructans" during hibernation, when the immune system is naturally suppressed to conserve energy through the winter. This study suggests that bats undergoing an intense inflammation at the site of infection after a return to euthermia is a form of IRIS.

Sporotrichosis (also known as "rose gardener's disease") is a disease caused by the infection of the fungus "Sporothrix schenckii". This fungal disease usually affects the skin, although other rare forms can affect the lungs, joints, bones, and even the brain. Because roses can spread the disease, it is one of a few diseases referred to as "rose-thorn" or "rose-gardeners' disease".

Because "S. schenckii" is naturally found in soil, hay, sphagnum moss, and plants, it usually affects farmers, gardeners, and agricultural workers. It enters through small cuts and abrasions in the skin to cause the infection. In case of sporotrichosis affecting the lungs, the fungal spores enter through the respiratory pathways. Sporotrichosis can also be acquired from handling cats with the disease; it is an occupational hazard for veterinarians.

Sporotrichosis progresses slowly – the first symptoms may appear 1 to 12 weeks (average 3 weeks) after the initial exposure to the fungus. Serious complications can also develop in patients who have a compromised immune system.

Sporotrichosis can be diagnosed in domestic and wild mammals. In veterinary medicine it is most frequently seen in cats and horses. Cats have a particularly severe form of cutaneous sporotrichosis and also can serve as a source of zoonotic infection to persons who handle them and are exposed to exudate from skin lesions.

Tinea capitis caused by species of "Microsporum" and "Trichophyton" is a contagious disease that is endemic in many countries. Affecting primarily pre-pubertal children between 6 and 10 years, it is more common in males than females; rarely does the disease persist past age sixteen. Because spread is thought to occur through direct contact with afflicted individuals, large outbreaks have been known to occur in schools and other places where children are in close quarters; however, indirect spread through contamination with infected objects ("fomites") may also be a factor in the spread of infection. In the USA, tinea capitis is thought to occur in 3-8% of the pediatric population; up to one-third of households with contact with an infected person may harbor the disease without showing any symptoms.

The fungal species responsible for causing tinea capitis vary according to the geographical region, and may also change over time. For example, "Microsporum audouinii" was the predominant etiological agent in North America and Europe until the 1950s, but now "Trichophyton tonsurans" is more common in the USA, and becoming more common in Europe and the United Kingdom. This shift is thought to be due to the widespread use of griseofulvin, which is more effective against "M. audounii" than "T. tonsurans"; also, changes in immigration patterns and increases in international travel have likely spread "T. tonsurans" to new areas. Another fungal species that has increased in prevalence is "Trichophyton violaceum", especially in urban populations of the United Kingdom and Europe.

The disease is usually seen in field workers like farmers, and generally affects men between 20 and 40 years. The disease is acquired by inoculation of grains of fungal spores from the soil through a breach in the skin produced by minor trauma like a thorn prick. The disease then spreads to deeper tissues and also forms sinus tracts leading to skin surface. Mature lesions are characterised by a grainy discharge from these sinuses. These discharges contain fungal colonies and are infective. Spread of infection internally through blood or lymph is uncommon.

Infections that produce a black discharge mainly spread subcutaneously. In the red and yellow varieties deep spread occurs early, infiltrating muscles and bones but sparing nerves and tendons, which are highly resistant to the invasion.

Botryomycosis, also known as bacterial pseudomycosis, produces a similar clinical picture and is caused usually by Staphylococcus aureus. Other bacteria may also cause botryomycosis.

no approved human vaccine exist against "Dermatophytosis". For horses, dogs and cats there is available an approved inactivated vaccine called "Insol Dermatophyton" (Boehringer Ingelheim) which provides time-limited protection against several trichophyton and microsporum fungal strains.

Among individuals being treated in intensive care units, the mortality rate is about 30-50% when systemic candidiasis develops.

There are five main causes of infections of the central nervous system (CNS): bacterial, viral, fungal, protozoal, and prionic.