Alternariosis: causes, symptoms, diagnosis, and treatment

Alternariosis is a fungal infection caused by alternaria, which is an extensively distributed dematiaceous hyphomycete, and is common saprophytes in soil, air, and industrial materials, generally nonpathogenic. However, with the extensive use of corticosteroids and immunosuppressants, the incidence of alternariosis is increasing.


Causes

Alternaria can be found on normal human and animal skin and conjunctiva, and is associated frequently with hypersensitivity pneumonitis, bronchial asthma, allergic sinusitis, and rhinitis. The pathogen can also cause several human infections, such as paranasal sinusitis, ocular infections, onychomycosis, cutaneous and subcutaneous infections, as well as granulomatous pulmonary diseases, soft palate perforations, and disseminated disease. Occasionally, Alternaria can be a contaminant of soft contact lenses or emollient creams.


Signs and Symptoms

Alternaria infects mainly immunocompromised individuals, although infections in immunocompetent persons have also been reported. The portal of entry is usually the corneal trauma or breach of the skin. The clinical manifestations are predominantly cutaneous and subcutaneous alternariosis, other infections, such as oculomycosis, sinusitis, onychomycosis, and invasive disease, are less common.

Ocular alternariosis

The incidence of oculomycosis ranges from 3.3% to 10.4%, depending on the geographical location, and is probably related to the risk of trauma caused by organic matter. Symptoms are mainly keratitis and endophthalmitis. In general, patients are farmers or gardeners exposed to soil and garbage. In many cases, accidental or surgical ocular traumas are the predisposing factors.

Rhinosinusitis

Although Aspergillus is the most common mold causing fungal sinusitis, other fungi, such as alternaria, can also be involved. Alternaria can cause invasive and non-invasive sinusitis. Immunosuppression is not a significant risk factor for rhinosinusitis caused by alternaria. Neutropenia is a common predisposing factor.

Onychomycosis

The incidence of onychomycosis is low, ranging from 0.08% to 2.5% in various epidemiological studies. Clinical manifestations include dystrophy and distal subungual hyperkeratosis or onycholysis. No significant difference is found between the involvement of fingernails or toenails.

Cutaneous and subcutaneous alternariosis

Skin is the most frequent infection site caused by alternaria. The course of the disease varies from several months to several years. The epidermal fungi are limited to the epidermis and do not invade the dermis. Most patients present with erythema and desquamation of skin, with or without red papules, developing into erosion and ulceration, particularly after steroid treatment. When the infection is associated with penetrating trauma, clinical manifestations are usually unilocular red plaques with central ulceration, sometimes developing into ulcerous lesions. Multilocular skin lesions, papulonodular lesions, and cutaneous nodules, usually painless, are generally associated with disseminated alternariosis.


Histopathology

The epidermal fungi limited to the epidermis without invading the dermis can be seen. Hyperkeratosis, infiltration of degenerative leukocytes, parakeratosis, thinning of the stratum spinosum, infiltration of neutrophils under the stratum corneum, and epidermal septate hyphae can be seen. The dermal histopathological changes are chronic inflammatory granuloma, epidermal hyperplasia, and mixed infiltration of dermal neutrophils, histiocytes, epithelioid cells, plasma cells, and giant cells. Infiltration can involve subcutaneous tissues and various layers of the dermis. Brown, 3 - 15μm in diameter, septate hyphae can be seen in the inflammatory infiltration or giant cells. Hyphae and spores can be stained by PAS stain. There is no neutrophil infiltration in the histological sections of this disease caused by alternaria dianthicola. The epidermal alternaria is usually present as hyphae, while the dermal alternaria is present as hyphae or spores or both.


Diagnosis

The diagnosis is mainly based on the histopathology and fungal culture and microscopy.


Treatment

It is more difficult to cure the disease. Although many therapies and various antifungals have been used to treat this disease, there is no optimal treatment regimen. Epidermal alternariosis can be cured by topical antifungals, such as natamycin. Topical oxiconazole is also effective in treating nail infections caused by alternaria. Dermal alternariosis is often accompanied by scars and hyperplasia, and surgical resection or electrocoagulation followed by antifungals can be considered. Local ablation followed by intravenous amphotericin B may be effective. Fluconazole is not effective in small doses. Amphotericin B 1mg/mL or miconazole 1mg/mL intralesionally twice weekly for many months can be administered in patients who have failed systemic medication. Itraconazole 100 mg/d is also effective, but the course of treatment generally lasts from several months to 2 years.

Because this disease is often accompanied by other diseases, it is necessary to improve systemic conditions while antifungal treatment. Particularly, the reduction of amount of glucocorticoids is essential for the treatment of this disease.