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Diagnosis and Treatment of Cutaneous Aspergillosis

Kyung Duck Park
10.17966/JMI.2021.26.4.83 Epub 2022 January 01

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Abstract

Aspergillosis is an opportunistic mycosis caused by fungi in the genus Aspergillus, mostly A. fumigatus and A. flavus. Typical entry portals in primary cutaneous aspergillosis include burns, trauma sites, surgical wounds, intravenous catheters, and macerated skin in underlying occlusive dressings. In individuals who are immunocompromised, the dissemination risk is significant. Skin findings range from firm papules and necrotic papulonodules to hemorrhagic bullae and ulcers. The prognosis is poor but improves when the patient is no longer neutropenic or when corticosteroids are discontinued. Localized primary cutaneous aspergillosis can be excised surgically, followed by oral antifungal administration. For the first-line treatment of pulmonary invasive aspergillosis, isavuconazole and voriconazole are the preferred agents, whereas liposomal amphotericin B is supported moderately.



Keywords



Aspergillosis Cutaneous aspergillosis



INTRODUCTION

Several studies have been conducted to elucidate the multiple aspects of pulmonary and invasive aspergillosis in patients who are immunocompromised; however, only a few reports are available on primary cutaneous aspergillosis. Aspergillosis is an opportunistic infection that is caused by fungi in the genus Aspergillus, mostly A. fumigatus and A. flavus. Several host factors and clinical conditions are asso- ciated with aspergillosis, including (1) neutropenia, immuno- suppression, immunodeficiency, or structural lung disease for invasive pulmonary aspergillosis and (2) burns, sites of trauma, surgical wounds, intravenous catheters, and macerated skin in underlying occlusive dressings as entry portals in primary cutaneous aspergillosis. The prognosis could be poor; thus, clinicians should be aware of this disease. This study aimed to briefly describe the definition, skin findings, histologic exam- ination, prophylaxis, and treatment of cutaneous aspergillosis.

DEFINITION

Cutaneous aspergillosis is defined as a skin infection caused by fungi in the genus Aspergillus1 and is categorized into primary and secondary cutaneous aspergillosis. Primary cutaneous aspergillosis presents skin lesions without visceral involvement, whereas in secondary cutaneous aspergillosis, the conidia are inhaled, resulting in a primary lung infection followed by dissemination to the skin. Most aspergillosis cases are Aspergillus infection of the lungs, and cutaneous aspergillosis is considered an opportunistic infection2,3. There- fore, disseminated secondary cutaneous aspergillosis accounts for most cutaneous aspergillosis, and cutaneous aspergillosis cases are rarely reported in patients who are immunocom- petent4,5. Patterson et al. and D'Antonio et al. reported cuta- neous involvement of invasive aspergillosis in 5% and 4% of cases, respectively6,7.

SKIN FINDINGS

As previously explained, cutaneous aspergillosis is considered an opportunistic infection. Thus, secondary cutaneous lesions are well documented, which result from contiguous extension of infected underlying structures to the skin or widespread blood-borne skin embolism4,8. Host factors, such as neutropenia, allogeneic hematopoietic stem-cell transplantation, long-term use of immunosuppressants, and immuno-deficiency are important in secondary cutaneous lesion development. Skin lesions appear as scattered erythematous macules or papules that evolve to hemorrhagic bullae or ulcerative nodules because of the infected internal organs' dissemination9, which often develop as an eschar in time10. Hematogenously disseminated embolic lesions may occur because of the Aspergillus organism's angiotropic nature10. Primary cutaneous aspergillosis arises from either direct physical inoculation, such as a penetrating wound or occlusive dressing site of a wounded skin11. Primary cutaneous lesions usually develop in patients with burns, trauma sites, surgical wounds, intravenous catheters, and macerated skin12. Some patients are immunocompetent, but patients with underlying risk factors, such as malignancies, organ transplantation, and congenital or acquired immunodeficiency syndrome, were also reported13,14. Some cases were reported in infants who were premature15,16. Additionally, onychomycosis caused by Aspergillus was also reported17. According to this article, the clinical presentation of onychomycosis was nonspecific, but a distal-lateral pattern was commonly observed17. The reports show that skin manifestations of primary cutaneous aspergillosis vary from macules, papules, nodules, or plaques to pustules10. Among neonates, lesions occurred with purulent discharge16,18. Infection of the paranasal sinuses was also reported as another clinical presentation19,20. This study states that in the inoculated type, the primary lesion develops from macule or papule to nodule or granulated tissue, whereas in the wounded skin type, superficial spreading natured macerated and ulcerative lesion. Additionally, host factors are also important because dissemination occurs easily in patients who are immunocompromised.

HISTOLOGIC EXAMINATION

Histologic examination of lesions of cutaneous aspergillosis includes the following: (1) 45° dichotomous branching of hyaline hyphae; (2) septate hyphae best demonstrated with methenamine silver or PAS staining; (3) suppurative and granulomatous inflammation and/or necrosis; and (4) striking tendency of the fungal hyphae to invade large and small arteries and veins, causing inflammation, thrombosis, and infarction. Inflammation is dominant in the superficial dermis with or without subcutaneous fat layer sparing in primary cutaneous aspergillosis cases. Contrarily, the epicenter of in- flammation in the secondary cutaneous aspergillosis tends to be solely in the deep dermis or subcutaneous fat layer13.

PROPHYLAXIS

For aspergillosis prevention, prophylactic antifungals are commonly administered to patients undergoing chemotherapy and hematopoietic stem-cell transplantation, both before and during neutropenic periods. Additionally, a patient with febrile neutropenia who is unresponsive to broad-spectrum antibiotic therapy might empirically receive voriconazole, posaconazole, or one of the echinocandins21.

TREATMENT

Nowadays, isavuconazole and voriconazole are the preferred agents for the first-line treatment of invasive aspergillosis21,22, whereas liposomal amphotericin B is moderately supported21. However, the cutaneous aspergillosis treatment guideline is currently unavailable. Localized primary cutaneous aspergillosis can be excised surgically, followed by oral antifungal administration. In this study, disseminated cutaneous aspergillosis was treated appropriately according to invasive aspergillosis. Voriconazole or isavuconazole treatments for severe primary cutaneous aspergillosis were reported15,16. Until recently, itraconazole treatment case reports of patients with primary cutaneous aspergillosis who are immunocompetent are reported5,23.

CONCLUSION

In patients with this disease, invasive aspergillosis is the major cause of death; thus, dermatologists should be aware of its cutaneous findings. There is limited information on the prevalence, diagnosis, and treatment of primary cutaneous aspergillosis and onychomycosis caused by Aspergillus, only case reports or small case series in the literature. This study therefore suggests a preliminary classification as presented in Table 1. Further studies are needed to find the optimal treatment for invasive and primary cutaneous aspergillosis.

Type

Risk factors

Skin findings

Treatment

Primary

(Inoculated)

Injury

Catheter

Macule

Papule

Nodule

Granulation tissue

Amphotericin B

Itraconazole

Primary

(Wounded)

Burn

Trauma

Surgical wound

Neonate

Superficial spreading erosive patch

Ecthyma gangrenosum

Hemorrhagic bulla

 

Secondary

(Disseminated)

Neutropenia

Allo-HSCT

Immunosuppressants

Malignancy

Congenital immunodeficiency

Structural lung disease

Sporotrichoid nodules

Embolic

Ulceration

Necrosis

Eschar

Isavuconazole

Voriconazole

 

Table 1. The study's preliminary suggestion of cutaneous aspergillosis classification


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