Dermatologic Manifestations of Aspergillosis Guidelines

Guidelines on the management of aspergillosis by the Infectious Diseases Society of America are as follows ^{[12, 21]} :

• Submit tissue and fluid specimens for histopathologic, cytologic, and culture examination to diagnose invasive aspergillosis. However, molecular techniques, such as DNA sequencing, should be used to identify Aspergillus species in cases that involve either isolates with atypical growth or concern for resistance.

• If invasive pulmonary aspergillosis is suspected, the guidelines recommend performing CT scanning of the chest, regardless of chest radiography findings. Bronchoscopy with bronchoalveolar lavage is also recommended in such cases, unless significant comorbidities (eg, bleeding, severe hypoxemia) preclude it.

• Detection of galactomannan (a component of the Aspergillus cell wall) in serum or bronchoalveolar lavage fluid is recommended as an accurate marker for the diagnosis of invasive aspergillosis in adults and children, when used in certain patient subpopulations, such as hematopoietic stem cell transplant recipients or patients with hematologic malignancies.

• Serum assays for (1 → 3)-β-D-glucan and serum galactomannan are recommended for diagnosing invasive aspergillosis in high-risk patients and their response to treatment (hematologic malignancy, allogeneic hematopoietic stem cell transplant), but are not specific for Aspergillus.

• If invasive pulmonary aspergillosis is suspected, antifungal therapy should be initiated while diagnostic evaluation is ongoing. Voriconazole is recommended for primary treatment of invasive pulmonary aspergillosis, although combination therapy with voriconazole and echinocandin may be warranted for some high-risk patients.

• Antifungal therapy for invasive pulmonary aspergillosis should continue for at least 6-12 weeks. Antifungal prophylaxis should also be instituted for patients with prolonged neutropenia who are at high risk for invasive aspergillosis. Prophylactic regimens with posaconazole, voriconazole, and/or micafungin are considered to be most effective.

• Amphotericin B deoxycholate and its lipid derivatives are appropriate options for initial and salvage therapy of Aspergillus infections when voriconazole cannot be administered. However, amphotericin B deoxycholate should be reserved for use in resource-limited settings in which no alternative agents are available. Lipid formulations of amphotericin B should be considered in settings in which azoles are contraindicated or not tolerated.

• Aerosolized formulations of amphotericin B may be considered as prophylaxis in patients with prolonged neutropenia (patients receiving induction/reinduction therapy for acute leukemia and allogeneic hematopoietic stem cell transplant recipients following conditioning or during treatment of graft versus host disease) and in lung transplant recipients.

• Echinocandins are effective in salvage therapy (either alone or in combination) against invasive aspergillosis, but they are not recommended for routine use as monotherapy for the primary treatment of invasive aspergillosis.

• Triazoles and voriconazole are preferred agents for the treatment and prevention of invasive aspergillosis in most patients.

• Surgery for aspergillosis should be considered for localized disease that is easily accessible to debridement (eg, invasive fungal sinusitis, localized cutaneous disease).

• The guidelines recommend that both surgery and either systemic voriconazole or a lipid formulation of amphotericin B be used in invasive Aspergillus fungal sinusitis, but surgical removal alone can be used to treat an Aspergillus fungal ball of the paranasal sinus. Enlargement of the sinus ostomy may be needed to improve drainage and prevent recurrence.

• Recommend prophylaxis with posaconazole, voriconazole, and/or micafungin during prolonged neutropenia for those who are at high risk for invasive aspergillosis.

• The guidelines do not recommend routine antifungal susceptibility testing. Instead, it should be reserved for cases in which infection with an azole-resistant isolate is suspected, or in which a patient is unresponsive to antifungal agents.

• The guideline recommends using the same antifungal agents for the treatment of aspergillosis in children as are used in adults. However, dosing of many of these agents may be different for children. The authors also note that although voriconazole is only approved by the US Food and Drug Administration for children aged 12 years and older, it is the cornerstone of aspergillosis treatment in children of all ages.

• Suggest a follow-up chest CT scan to assess the response of invasive pulmonary aspergillosis to treatment after a minimum of 2 weeks of treatment; earlier assessment is indicated if the patient clinically deteriorates. When a nodule is close to a large vessel, more frequent monitoring may be required.

The European Society for Clinical Microbiology and Infectious Diseases, the European Confederation of Medical Mycology, and the European Respiratory Society Joint Clinical Guidelines are summarized below. ^[22]

Strongly recommended diagnostic methods are as follows:

• Chest CT and bronchoscopy with bronchoalveolar lavage (BAL) in patients with suspicion of pulmonary invasive aspergillosis

• Direct microscopy, preferably using optical brighteners, histopathology, and culture

• Pathogen identification to species complex level for all clinically relevant Aspergillus isolates; antifungal susceptibility testing in patients with invasive disease in regions with resistance found in contemporary surveillance programs

Recommended and other diagnostic methods are as follows:

• Serum and BAL galactomannan measures as markers for the diagnosis of invasive aspergillosis

• Polymerase chain reaction should be considered in conjunction with other diagnostic tests

Treatment guidance is as follows:

• Preferred agents for first-line treatment of pulmonary invasive aspergillosis: Isavuconazole and voriconazole

• Moderately support agent: Liposomal amphotericin B

• Not recommended: Combinations of antifungal agents as primary treatment option

• Strongly recommended practice: Therapeutic drug monitoring for patients receiving posaconazole suspension or any form of voriconazole for invasive aspergillosis treatment

• Strongly recommended practice: In refractory disease, where a personalized approach may consider reversal of predisposing factors, switch drug classes and implement surgical intervention

Prophylaxis recommendations are as follows:

• Primary prophylaxis with posaconazole strongly recommended in patients with acute myelogenous leukemia or myelodysplastic syndrome receiving induction chemotherapy

• Secondary prophylaxis strongly recommended in high-risk patients