Cutaneous Aspergillus Infection - Causes, Symptoms, Diagnosis, and Treatment

Introduction:

After Candida albicans, Aspergillus species are the most frequent opportunistic fungal infection in humans. In immunocompromised patients, it leads to severe infections that have a high mortality rate, particularly in newborns. The lungs, central nervous system (CNS), and sinuses are the typical sites of infection; however, uncommon cutaneous infection is typically accompanied by immunodeficiency. Primary cutaneous infection is extremely uncommon, especially in immunocompetent patients, but over the past 20 years, there has been a rise in incidence.

What Is Cutaneous Aspergillus Infection?

Cutaneous Aspergillus infection or cutaneous aspergillosis is an uncommon condition characterized by localized invasion of the skin caused by Aspergillus, a fungus. It typically occurs when the fungus enters the body through a compromised area of the skin, primarily affecting individuals with weakened immune systems. There are two recognized types of cutaneous aspergillosis: primary and secondary.

1. Primary Cutaneous Aspergillosis: Injuries to the skin, such as those caused by trauma, occlusive dressing use, burns, or surgical wounds, frequently result in this condition. In these cases, Aspergillus gains entry through the damaged skin.
2. Secondary Cutaneous Aspergillosis: These lesions result from the dissemination of Aspergillus through the bloodstream, leading to the development of skin infections at distant sites. This occurs when the fungus spreads to the skin from another site in the body, such as the lungs.

Aspergillus fumigatus and Aspergillus flavus are the most frequent causes of primary cutaneous disease, which is uncommon. Aspergillus terreus and Aspergillus ustus have been linked to extremely uncommon cutaneous infections. Aspergillus frequently colonizes burn eschars, and studies have linked agricultural trauma to primary cutaneous infections in immunocompetent patients. But typically, aspergillosis starts as a pulmonary infection after inhaling fungal spores.

What Are the Causes of Cutaneous Aspergillus Infection?

The following are the common causes of cutaneous aspergillosis infection:

• Direct Contact: The most common mode of spread for cutaneous Aspergillus infection is through direct contact with the fungal spores. This can happen when the spores come into contact with damaged or broken skin, such as cuts, burns, surgical wounds, or other forms of skin trauma. The spores adhere to the skin surface and can establish an infection if the conditions are favorable.
• Environmental Exposure: Cutaneous Aspergillus infections can also occur through environmental exposure to fungal spores. Aspergillus spores are ubiquitous in the environment, particularly in soil, decaying organic matter, stored grains, and indoor environments. Individuals who frequently handle contaminated materials, such as soil, compost, or organic debris, may inadvertently come into contact with the spores and develop this infection.
• Healthcare-Associated Infections: In healthcare settings, cutaneous Aspergillus infections can occur as a result of exposure to contaminated medical devices or procedures. This mode of spread is particularly relevant for individuals with compromised immune systems who require medical interventions. The common reasons include:
  1. Exposure to contaminated medical devices or procedures is another reason in hospital settings. Improper sterilization of medical equipment or the use of contaminated solutions can introduce these fungal spores into the body, leading to infection.
  2. Typically, sites of skin injury, such as those at or close to intravenous access catheter sites, sites of traumatic inoculation, and sites that involve occlusive dressings, burns, or surgery, contribute to primary cutaneous aspergillosis.
• Hematogenous Spread: Although less common, cutaneous Aspergillus infections can spread through the hematogenous route. This occurs when spores enter the bloodstream from an existing infection site, such as the lungs, and are carried to other areas of the body. Hematogenous spread can result in the development of secondary skin infections in distant sites.

What Are the Clinical Manifestations of Cutaneous Aspergillus Infection?

The clinical manifestations of cutaneous Aspergillus infection are mentioned below:

• The initial signs of cutaneous aspergillosis can manifest as various skin abnormalities such as macules, papules, nodules, or plaques.
• Infections among newborns commonly exhibit pustules or lesions with purulent discharge.
• Cutaneous aspergillosis arises from using occlusive tape or arm boards to secure an access catheter. In that case, it can form a hemorrhagic bulla at the location of the skin injury.
• Infections originating from intravenous catheter puncture sites typically start with symptoms such as erythema (redness) and induration (hardening) at the site of the puncture. This can be localized to a specific site or may spread to adjacent areas.
• Patients with primary cutaneous aspergillosis commonly experience significant fever, changes in the appearance of the wound surface, swelling, induration, and tenderness. Fever, malaise (general discomfort), chills, and in rare cases, symptoms of sepsis may be seen in cases where the infection spreads beyond the skin.
• Initially, cutaneous aspergillosis may present as areas of the skin that are red and hardened. As the condition progresses, these patches can develop into ulcers that eventually turn black in color. The affected or dead tissue frequently has an unpleasant (foul-smelling) discharge. It causes itching and discomfort at the site of the infection. The itching can range from mild to severe and may worsen with time.

How Can Cutaneous Aspergillus Infection Be Diagnosed?

Diagnosing all types of cutaneous aspergillosis relies on observing hyphal forms within the affected tissue. Following are the steps involved in the identification of these hyphal forms:

• Biopsy for Culture and Histopathology: A conclusive diagnosis of cutaneous aspergillosis usually requires a biopsy of the skin lesion for both culture and histopathology. If a single biopsy specimen is obtained, it should be divided into two portions. One half should be sent to the microbiology laboratory in saline for fungus culture, while the other half should be sent to the pathology laboratory in formalin for histopathological analysis.
• Serum Biomarkers: These can serve as valuable adjunctive tools in supporting or confirming the diagnosis of cutaneous aspergillosis alongside culture and histology. Recently, serum galactomannan and beta-D-glucan assays have become available.

What Is the Treatment for Cutaneous Aspergillus Infection?

Systemic drug therapy using antifungal medications to treat aspergillosis includes:

• Amphotericin B: In both disseminated and limited cutaneous aspergillosis, high-dose intravenous Amphotericin B (in either traditional or liposomal form) has traditionally been used as the primary antifungal treatment to eliminate the underlying fungal infection.
• Voriconazole: This medication is now approved as a first-line treatment for aspergillosis, and its usage has been increasing. It is being recognized as an effective alternative to Amphotericin B. In cases of secondary cutaneous aspergillosis, a combination of topical Voriconazole solution and systemic antifungal therapy has been reported as an effective treatment approach.
• Other Antifungal Medications: There are alternative antifungal treatment options available for aspergillosis, such as Itraconazole, Caspofungin, or a combination of Voriconazole with Terbinafine. These alternatives may be considered depending on the specific circumstances of the patient.

When there is extensive tissue involvement, the formation of abscesses or necrotic tissue occurs. Surgical debridement, which involves removing infected or dead tissue, can help promote healing and prevent the spread of infection. In severe cases, surgical excision of the infected area may be required. However, it has been observed that surgical excision, either alone or occasionally in conjunction with drug therapy, is curative for cutaneous disease.

Conclusion:

Cutaneous aspergillosis is a fungal skin infection caused by various species of Aspergillus fungus. It primarily affects individuals with compromised immune systems or those with skin trauma. Each case of this infection is unique, and the prognosis should be evaluated on an individual basis. Preventive measures, such as practicing good hygiene, minimizing exposure to contaminated environments, and ensuring proper sterilization and infection control procedures in healthcare settings, are crucial in reducing the risk of these infections.