Phaeohyphomycosis (Tinea Nigra, Keratomycosis nigricans, Microsporosis nigra, Pityriasis nigra Tinea palmaris nigra, Piedra Nigra, Black piedra, Infection by Piedraia hortai)

Are You Confident of the Diagnosis?

The term phaeohyphomycosis covers a broad spectrum of opportunistic infections caused by dark fungus. They are not limited to skin and subcutaneous tissues and can cause different inflammatory reactions in any organ or system of the body.

What you should be alert for in the history

The diagnosis of phaeohyphomycosis can only be made with confidence when there is an association of a history of trauma (superficial, cutaneous or subcutaneous phaeohyphomycosis) or immunodeficiency (invasive disease) with an histopathological examination revealing dark yeast-like cells, pseudo-hyphae and/or hyphae and a culture showing a dark colony.

In the presence of other structures such as sclerotic corpuscles or granules, one should think about other fungal infections.

Superficial phaeohyphomycosis- Patients will complain about dark maculae, generally in the palm of the hand (Figure 1) or soles, that grow peripherally. In general, those patients will have associated hyperhidrosis. Other manifestations would include dark nodules, of a large variety of forms and sizes, found on the hair (Figure 2).

Subcutaneous phaeohyphomycosis- In the majority of the cases, patients will complain of a unique, asymptomatic, nodular or cystic subcutaneous lesion, variable in size, with minimal adenopathy. The lesion can be ulcerated, eliminating purulent material, and rarely vegetating. It can appear in any location subject to traumatic inoculation.

Figure 1.

Figure 2.

Invasive and systemic phaeohyphomycosis – The most frequently infected sites are the lungs and the brain. Pulmonary infections are often subacute but the cerebral form is very severe, with mortality rates up to 70%. Systemic disseminated disease is rare, and the first site of involvement is normally the lungs; after hematogenous dissemination, cystic lesions and abscesses appear in the brain. Patients are always in a severe condition, with fever, often leucopenia, and, in most cases, with another underlying illness.

Allergic phaeohyphomycosis- Patients complain of asthma, rhinitis, and sinusitis.

Some rare cases of phaeohyphomycosis in large articulations of the knee have been described. So it is important to suspect this in cases of infected tenosynovitis when conventional treatments are not effective.

Expected results of diagnostic studies

The purulent material collected from aspiration of the cysts, peripheral blood or biopsy specimens from the skin, lungs or even brain, can be submitted to direct examination after being clarified with potassium hydroxide (KOH). Dark and septated hyphae can be found. Direct examination of involved hair shafts will show a dark and adherent nodule. Inside those nodules can be seen a number of asci, in which can be found 2-8 fusiform and curved asco spores.

The histopathological examinations of biopsy specimens are best viewed with Gomori methenamine silver (GMS) stain. It must show dark yeast-like cells, pseudo-hyphae and/or hyphae. Afterwards, material should be cultivated in agar-Sabouraud-dextrose with chloramphenicol and incubated in ambient temperature for about 4 weeks (Figure 3).

Figure 3.

Diagnosis confirmation

Differential diagnosis of superficial forms includes cutaneous melanoma and lentigo. Hair form must be differentiated from pediculosis. Subcutaneous and systemic forms can mimic lipomas, epidermoid cysts, myxoid cysts, syphilis, sporotrichosis, mycetoma, chromoblastomycosis, and other causes of pulmonary or disseminated infections, such as candidosis, cryptococosis, histoplasmosis/ or herpetic infections.

Who is at Risk for Developing this Disease?

The dark fungi are widely spread over the world, especially in tropical countries with high pluviometric grades. It can be found in the soil, organic material, woods and water. Typically, the infection is acquired after traumatic inoculation. Systemic forms can also occur after inhalation of spores, ingestion of contaminated food or water, or contaminated vascular catheters. Cutaneous forms can affect both sexes and all ages, being though more prevalent between the twenties. Women are affected 3-5 times more than men. Many patients have associated hyperhidrosis.

Hair forms can affect both sexes and all ages and are associated with those people who work near infected rivers and humid forests. Subcutaneous forms can occur in all individuals, principally in outdoor workers. The invasive form is associated with other diseases that compromise cellular mediated immunity, such as hematological cancers, diabetes mellitus, AIDS, transplants, or patients receiving dialysis or taking high-dose corticosteroids.

What is the Cause of the Disease?

• Etiology

• Pathophysiology

Superficial forms are caused by Hortaea werneckii (skin) and Piedraia hortae (hair). In subcutaneous forms, the most common species found nowadays are Bipolaris spinifera and Exophiala jeanselmei. In cerebral forms the agent involved in 48% of cases is Cladophialophora bantiana, due to its neurotropism. Other agents already described in literature are: Wangiella dermatitidis, Alternaria alternada (Figure 4), Exophiala moniliae, Exophiala spinifera, Phloma sp, Curvularia geniculata (Figure 5), and others not so frequent. Recently phaeohyphomycosis caused by a novel species named Pseudochaetosphaeronema martinelli was described.

Figure 4.

Figure 5.

Systemic Implications and Complications

There are some rare forms of invasive and systemic phaeohyphomycosis. The most frequently infected sites are the lungs and the brain. Pulmonary infections are often subacute but the cerebral form is very severe with mortality rates up to 70%. Systemic disseminated disease is rare, and the first site of involvement is normally the lungs; after hematogenous dissemination, cystic lesions and abscesses appear in the brain. Patients are always in a severe condition, with fever, often leucopenia, and, in most cases, with another underlying illness.

The drugs of choice are amphotericin-B and Flucitosyne. It is important to control the underlying disease. For superficial forms, it is recommended to use topical antifungal creams such as terbinafine, ciclopirox olamine or ketoconazole, associated with keratolytic agents such as salicylic acid. When hair is involved, it´s important to have a hair cut together with antifungal agents in shampoo form. In subcutaneous and systemic cases, treatment consists of surgical excision when it is possible to remove the whole lesion. For cases that cannot be assessed surgically, or in widespread disease, it is recommended to use broad spectrum antifungal drugs. The drug of choice is itraconazole 200-600 mg daily.

Trying to reduce immunosuppressive drugs is a hard but necessary job. It´s important to remove venous catheters and other invasive items and focus on the original cause of underlying disease. Diabetic patients must have their glycemic levels controlled and associated bacterial infections treated. Other causes of immunosuppression, such as cancers, AIDS, agranulocytosis, and patients submitted to dialysis programs should have specific therapy. Amphotericin-B is not the drug of choice for dark fungus but in the case of central nervous system infections, the best drug to be used is liposomal amphotericin.

Treatment Options

Treatment options are summarized in Table I.

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