Introduction
An opportunistic pathogen, Cryptococcus is a hetero-basidiomycetous fungus that is encapsulated. Both sexual and asexual forms of these fungi can be found in the environment. These fungi can infect both immunocompetent and immunocompromised hosts. Although they exhibit a strong dermatographism, these fungus also have a significant affinity for the central nervous system.
What Is the Etiology of Cutaneous Cryptococcus Neoformans Infection?
Sanfelice discovered Cryptococcus in peach juice for the first time in 1894 in Italy. The first human case was documented in 1895. A young woman with a persistent, non-healing skin lesion on the shin presented in this instance. The ulcer contained yeast, and later, during the autopsy, yeasts were discovered in several internal organs. They were Cryptococcus neoformans yeasts. The name Filobasidiella neoformans was given to the sexual form of this fungus when it was discovered in 1976. There are now 19 known species of Cryptococcus. Two are infectious. Each of these species has two different serotypes. Serotype D is assigned to Cryptococcus neoformans var. neoformans, serotype A to Cryptococcus neoformans var. grubii, and serotypes B and C to Cryptococcus gattii. In 2005, the genome of Cryptococcus neoformans was released.
Various Cryptococcus species have been identified in guano (seabirds or bats excrement)-contaminated soil. Several coniferous species, including eucalyptus trees, have a strong relationship with Cryptococcus gattii.
This fungus has two separate sexual and asexual stages in its life cycle. The yeast that divides by narrow-based budding is the asexual type. Clinical specimens are the main place where yeast forms are found. The two sorts of mating for sexual forms in nature are "alpha" and "a." Meiosis (a type of cell division) happens as a result of opposite kinds of mating, producing chains of basidiospores. These 1 to 2-micrometer-long basidiospores are the infectious particles that enter the alveoli through inhalation.
In 48 to 72 hours, Cryptococcus grows effectively on bacterial or fungal culture mediums. Colonies have a mucoid appearance.
What Is the Pathophysiology of Cutaneous Cryptococcus Neoformans Infection?
For Cryptococcus species, the polysaccharide capsule, melanin synthesis, and growth at high temperatures are regarded as virulence factors. Basidiospores (1 to 2 micrometers in length) or appropriately sized dried yeast are inhaled to cause the initial exposure, which happens through the lungs. Unless the inoculum is excessive, the majority of immunocompetent patients do not die from illness. Alveolar macrophages (a type of immune cell) produce an efficient immune response that gets rid of the yeast. When a person has a damaged immune system, the yeast multiplies inside macrophages, causing the infection to spread throughout the body. After the lungs and the central nervous system, the skin is the third most frequently affected organ system.
What Are the Clinical Features of Cutaneous Cryptococcus Neoformans Infection?
Numerous different skin lesions can appear in patients with Cryptococcus infections. Skin lesions are typically a sentinel for widespread illness. However, immunocompetent people can also develop primary cutaneous (skin) lesions.
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A papule, a maculopapular lesion (a flat or raised red bump in the skin) with an ulcerated center, or a violaceous nodular lesion could represent the primary cutaneous lesion.
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A discharging sinus is frequently connected to the bone beneath or the deep abscess beneath.
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Dermatropism (affinity towards the skin) is present in several C. neoformans strains. Primary cutaneous cryptococcosis, however, is an excluding diagnosis.
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HIV patients' skin lesions can resemble bacterial abscesses in both appearance and clinical presentation. When cutaneous cryptococcosis does not have a fever or other symptoms of inflammation, it may appear as a cold abscess. Therefore, it is essential to transmit cultures from any abscess that was drained from a patient who was immunocompromised. In an AIDS patient, crusty, ulcerative lesions that take time to form may be the first sign of cutaneous cryptococcal lesions. When Cryptococcus skin lesions are umbilicated, they can be confused for Molluscum contagiosum. Often, both the pulmonary and central nervous systems (CNS) are affected simultaneously.
After candidiasis and aspergillosis, cryptococcosis is the third most prevalent invasive fungal infection among organ transplant recipients. Three to 10 years after the transplant, it is frequently a late illness. Contrary to hematopoietic stem cell transplant recipients, solid organ transplant (SOT) recipients have an increased risk of Cryptococcus skin infections for unknown causes. Cutaneous cryptococcosis in solid organ transplant recipients can resemble acute bacterial cellulitis. Cutaneous symptoms can take a variety of forms, including those that resemble an abscess or blister and exhibit necrosis, imitate panniculitis (inflammation of subcutaneous fat), and cellulitis (serious bacterial infection) that develops into an ulcer.
Patients who have received a solid organ transplant can develop primary cutaneous lesions, although a disseminated illness is more typical. In a study of 146 individuals with cutaneous cryptococcosis, nodular mass, papule, ulcer or abscess, and cellulitis were all present in one-third of the patients. In 70 percent of cases, individuals had disseminated illness, and the lower extremities accounted for two-thirds of the skin lesions. 90 percent of cases of disseminated illness impacted the CNS (central nervous system).
How Is Cutaneous Cryptococcus Neoformans Infection Evaluated?
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Biopsy: A biopsy is crucial since cutaneous cryptococcosis is not characterized by any skin lesions. An accurate epidemiological history is crucial. A patient's condition needs to be assessed for immunosuppression at the root. Patients with cutaneous cryptococcosis need to be examined to see if other organ systems, like the lungs and the central nervous system, are involved.
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Cryptococcal Polysaccharide Antigen Assay: Due to the size of the polysaccharide capsule antigen, tests have been created to identify it in serum and other bodily fluids. Cerebrospinal fluid (CSF) contains cryptococcal polysaccharide antigen (CA). Hence there is a significant likelihood that yeast is also present. In serum, the cryptococcal polysaccharide antigen assay has a sensitivity of nearly 100 percent, a specificity of 96 percent to 99.5 percent, and a sensitivity of 96 percent to 100 percent, a specificity of 93.5 percent to 99.8 percent in CSF.
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Microbiological Assays: Both Grocott's methenamine silver stain (GMS) and India-ink preparations are further microbiological assays for the detection of Cryptococcus. Automated techniques can quickly identify cryptococcemia, which rarely results in shock or sepsis-like symptoms.
How Is Cutaneous Cryptococcus Neoformans Infection Treated?
1. Immunocompromised patients:
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HIV or Human Immunodeficiency Virus Patients:
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Induction Phase: Amphotericin B (0.7 mg/kg/d to 1.0 mg/kg/d intravenously (IV)) and Flucytosine (100 mg/kg/d to 125 mg/kg/d divided into four oral doses) are administered to HIV patients with a disseminated cryptococcal illness for two weeks during the induction phase.
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Consolidation Phase: The consolidation phase of this therapy should be continued with Fluconazole (400 mg [6 mg/kg] daily orally) for a minimum of eight weeks. While liposomal Amphotericin (AmB) may be recommended in the case of renal impairment, all Amphotericin formulations operate equally well.
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Maintenance Therapy: Next, suppressive or maintenance therapy is administered with Fluconazole 200 mg once daily by mouth. Maintenance therapy might last anywhere between six months and two years. When the viral load is undetectable, and the CD4 count has remained above 100 for three months while the patient is receiving antiretroviral therapy (ART), it is appropriate to terminate suppression after 12 months of treatment.
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Organ Transplant Patients: The treatment is the same for organ transplant recipients with widespread illness, though liposomal Amphotericin (AmB) (3 mg/kg/d to 4 mg/kg/d IV) may be recommended. AmB should be administered at a higher dose (6 mg/kg/d) if there is a significant fungal load. The induction phase of Amphotericin therapy should be extended to four weeks if Flucytosine is not available. Fluconazole maintenance therapy should then be continued for a minimum of six to twelve months. Management of immunosuppressive conditions should involve a stepwise reduction in immunosuppressants, starting with corticosteroids.
2. Immunocompetent Patients:
The fundamentals of treatment are the same in patients who have immunocompetence. Start the induction therapy with Flucytosine (100 mg/kg per day orally in four divided doses) and AmB (0.7 mg/kg to 1.0 mg/kg per day IV) for at least four weeks. Fluconazole should thereafter be given for eight weeks as a consolidation therapy (800 mg [12 mg/kg] daily orally). Following that, continue Fluconazole maintenance medication for six to twelve months at a dose of 200 mg [3 mg/kg] per day orally.
Conclusion
In conclusion, cutaneous Cryptococcus neoformans is an uncommon skin infection caused by a fungus. The Cryptococcus neoformans fungus spreads from other infected locations or penetrates the skin through a break or wound to cause it. The infection typically affects the face, scalp, or limbs and manifests as firm, painless purplish skin lesions or nodules. Despite the rarity of cutaneous Cryptococcus, quick medical care and effective treatment are essential to managing the infection and avoiding consequences. It is crucial to seek medical advice from a healthcare provider if it appears one may have cutaneous Cryptococcus or if there are any other concerns.
