What is Cutaneous Cryptococcus?
Cryptococcus is a type of fungus that naturally has a protective outer covering. This fungus can exist in the environment both sexually and asexually. It becomes a problem when it infects people with weak immune systems, but it can also affect those with healthy immune systems. Cryptococcus has a tendency to infect the central nervous system but it’s also known to cause skin reactions.
What Causes Cutaneous Cryptococcus?
The Cryptococcus fungus was first discovered in peach juice in Italy by Sanfelice in 1894. It was found in a human for the first time a year later, in a young woman with a skin ulcer on her leg that wouldn’t heal. When examining her ulcer and her internal organs after her death, scientists discovered yeast which they named Cryptococcus neoformans.
The fungus’ sexual form was identified in 1976 and was called Filobasidiella neoformans. So far, 19 different species of Cryptococcus have been discovered, and two of them can cause disease in humans. Each of these two species has two different serotypes, or variations. The details of the Cryptococcus neoformans’ genetic makeup were published in 2005.
Cryptococcus is typically found in soil that’s been contaminated by bird droppings. One type of Cryptococcus, called Cryptococcus gattii, is specifically associated with eucalyptus and coniferous trees.
This fungus has two stages in its life cycle: sexual and asexual. The asexual stage is a yeast that divides itself, and it’s usually what we see in clinical samples. The sexual forms are found in nature as two mating types, known as “alpha” and “a.” When these two types mate, meiosis (a type of cell division) occurs, resulting in chains of basidiospores. These are the particulates that can be inhaled and reach the tiny air sacs in our lungs called alveoli.
Cryptococcus can grow well on certain culture mediums used for studying microbes. It usually takes around 48 to 72 hours for the fungus to grow and the colonies it forms have a slimy appearance.
Risk Factors and Frequency for Cutaneous Cryptococcus
Cryptococcus neoformans is a type of fungus that’s most commonly found along the Pacific coast of the United States and Canada. On the other hand, Cryptococcus gattii is mostly found in northern California, Canada’s Vancouver Island, Papua New Guinea, and northern Australia. People with AIDS or weakened immune systems are most likely to be affected by C. neoformans. However, about one in four people who gets infected with C. gattii is healthy and has a normal immune system.
- Before the AIDS epidemic, Cryptococcus disease was rare in the United States, with only 0.8 cases per million people.
- However, during the peak of the AIDS epidemic in 1992, the rate went up to 5 cases per 100,000 people.
- With the introduction of antiretroviral therapy (ART), the number of Cryptococcus disease cases dropped significantly.
- Despite the overall decline, the disease is still a major problem in sub-Saharan Africa due to the ongoing AIDS epidemic.
- In fact, Cryptococcus is the most common cause of culture-positive meningitis there, causing half a million deaths each year. That’s even more than the number of deaths from tuberculosis.
- This disease is especially prevalent among HIV patients who lack adequate healthcare access.
People who are most likely to have a widespread or disseminated Cryptococcus disease usually have a compromised immune system. This includes people with AIDS, organ transplant patients, those taking long-term steroid medication, and those treated with monoclonal antibodies.
Signs and Symptoms of Cutaneous Cryptococcus
Cryptococcus infections can lead to a variety of skin issues. These skin problems may indicate a spread of the disease throughout the body, but sometimes they are confined to the skin in otherwise healthy individuals. The primary skin issue may appear as a small raised lesion, a bumpy and flat lesion with a raw central portion, or a purplish, lump-like lesion. Sometimes a tube-like tract discharging pus may connect to a deeper abscess or even bone beneath the skin. While some varieties of Cryptococcus preferentially affect the skin, identifying a Cryptococcus infection as the cause of a skin problem is usually a process of ruling out other possibilities.
In individuals with HIV, the skin issues caused by a Cryptococcus infection can mimic those caused by a bacterial abscess. Cutaneous Cryptococcus infection may show up as an abscess that’s not accompanied by fever or inflammation, mimicking a “cold” abscess. This is why it’s important to send samples for testing from any abscess in people with compromised immune systems. Skin issues due to Cryptococcus in those with AIDS might be crusty, raw lesions that progress slowly. Sometimes, the lesions might be dimpled, causing them to be mistaken for a different condition called Molluscum contagiosum. Often, if a person has Cryptococcus skin lesions, they will also have lung involvement and central nervous system issues.
Cryptococcus is the third most common fungal infection to affect organ transplant recipients, showing up more often years after the transplant. People who have had solid organ transplants seem to be more prone to Cryptococcus skin infections compared to those who had bone marrow transplants, for reasons that aren’t clear. Cryptococcus skin issues can appear similar to bacterial skin infection in solid organ transplant patients. They can mimic an abscess, present as cellulitis that later forms an ulcer, blisters and shows dying tissue, or look like inflammation of the fatty tissue. While primary skin issues can occur in transplant recipients, it’s more common for them to have widespread disease. In one study, one-third of patients with Cryptococcus skin issues had nodules, papules, ulcers/abscesses, or cellulitis. The majority of these skin problems were on the lower extremities, and most patients actually had widespread disease. In 90% of cases with widespread disease, the central nervous system was involved.
Cryptococcus infections can lead to a variety of skin issues, including:
- Small raised lesion
- Bumpy and flat lesion with a raw central portion
- Purplish, lump-like lesion
- Tubes discharging pus connected to deeper abscesses or bones
These skin problems may be seen in conjunction with issues in the lungs and central nervous system.
Testing for Cutaneous Cryptococcus
Cutaneous cryptococcosis, a type of skin infection, doesn’t have a distinctive appearance, so a skin biopsy is usually necessary to diagnose it. A detailed medical history is vital and clinicians will often check if the patient’s immune system is weakened, as this can make them more susceptible to this infection.
In addition to a biopsy, doctors may check for the presence of cutaneous cryptococcosis by looking for a specific antigen — a molecular marker that the immune system reacts to — known as the polysaccharide capsule antigen. Tests for this antigen can be nearly 100% sensitive, meaning they rarely miss the presence of the infection, and can be between 96-99.5% specific in blood tests and 93.5-99.8% specific in cerebrospinal fluid tests, meaning they rarely mistake the antigen for something else.
In addition, other types of tests such as India-ink preparations and Grocott’s methenamine silver stain (GMS) can be used as part of the diagnostic process. An infection in the bloodstream (cryptococcemia) is fairly easy to detect with automated systems and it rarely results in severe symptoms or shock.
Treatment Options for Cutaneous Cryptococcus
To treat patients with HIV who also have a widespread cryptococcal disease, use a two-step treatment approach combining different drugs. The first step or “induction phase” involves administering Amphotericin B through an intravenous drip and taking flucytosine orally in four doses throughout the day. This phase should last for two weeks.
After this, begin the “consolidation phase” by taking fluconazole orally every day for at least eight weeks. It’s important to mention that all versions of amphotericin drugs work equally well, but the liposomal form may be a better choice for those with kidney problems.
After these two phases, move to a “maintenance” phase where the patient takes a daily oral dose of fluconazole. This can last between six months to two years. However, for those taking antiretroviral drugs, it may be reasonable to stop this maintenance phase after a year, particularly if tests show the virus levels are very low and their CD4 count (a type of immune system cell) remains above 100 for three months.
For organ transplant patients with this spread-out disease, the treatment plan is similar. However, liposomal amphotericin may be a preferred choice. The dose may need to be increased if there’s a high level of fungus in the body. If flucytosine isn’t available during the induction phase, extend the amphotericin treatment to four weeks. Then follow this with at least six to 12 months of maintenance therapy using fluconazole. It may also be advisable to gradually reduce the doses of immunosuppressant drugs during this period, starting with corticosteroids.
In patients without any immune system issues (“immunocompetent” patients), the treatment strategy is the same. However, the induction phase with AmB and flucytosine should last at least four weeks followed by eight weeks of consolidation therapy with a higher dose of fluconazole. After that, commence maintenance therapy with a lower dose of fluconazole for six to 12 months.
What else can Cutaneous Cryptococcus be?
- Common acne
- Sudden issues caused by sarcoidosis (a disease that leads to inflammation in the body’s organs)
- Diseases caused by uncommon types of bacteria known as mycobacteria
- A type of skin cancer known as basal cell carcinoma
- Skin infection known as cellulitis
- Skin-related symptoms of Coccidioidomycosis (a fungal infection often known as Valley Fever)
- Skin-related symptoms of Kaposi sarcoma (a type of cancer that affects the skin and mouth)
- A common viral skin infection named Molluscum contagiosum
- A condition called syphilis in children
- Tuberculosis, a bacterial infection that primarily affects the lungs
