Dermatology

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.

Tinea Nigra.

Figure 2.

Piedra nigra.

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.

Culture in agar-Sabouraud.

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.

Alternaria alternada.

Figure 5.

Curvularia geniculata.

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.

Table I.

Treatment options for phaeohyphomycosis
Surgical Procedures Medical Treatment Physical Modalities
Excisional surgery with grafting Keratolytic agents (salicylic acid) Hair cut
  Topical antifungal agents  
  Itraconazole (oral) Amphotericin-B (intravenous) Flucytosine(intravenous)  

Optimal Therapeutic Approach for this 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 anti-fungal 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 in 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.

Patient Management

Explain the natural history, causes, way of transmission, and cures rates of phaeohyphomycosis to the patient before beginning treatment. This is an infectious disease that can bring physical deformities if not adequately treated, but there have never been described human-to-human transmission. Explain to the patient and family members the importance of safety clothing for outside workers. For patients with severe predisposing conditions, explain to the family about the immunosuppressive nature of the underlying disease and that systemic phaeohyphomycosis not a cause, but a consequent complication.

In the case of local disease requiring excisional surgery with grafting and oral medication, patients need to be seen periodically (every 4-6 months) to check for relapses; for those patients on aggressive systemic treatments (systemic corticosteroids, liposomal amphotericin, venous antibiotic, cytotoxicagents, etc), patients need to be seen in accordance with the appropriate monitoring guidelines for that drug or modality.

Unusual Clinical Scenarios to Consider in Patient Management

Remember that although rare, unusual presentations of phaeohyphomycosis may occur. Allergic phaeohyphomycosis very difficult to diagnose, and the patient´s history must be carefully checked. If the disease is left untreated for a long time (4-5 years), patients can have physical disabilities that may be irreversible.

What is the Evidence?CostaRO. Subcutaneous phaeohyphomycosis. An Bras Dermatol. 2010 Oct;85(5):727-8.

(Brief review of the disease emphasizing the importance of the differential diagnosis of other dermatoses, including noninfectious dermatoses.)

CristiniAGarcia-HermosoDCelardMAlbrandGLortholaryO. Cerebral phaeohyphomycosis caused by Rhinocladiella mackenziei in a woman native to Afghanistan. J Clin Microbiol2010 Sep;48(9):3451-4.

(Case reporting cerebral phaeohyphomycosis, demonstrating the ominous prognosis of this form of the disease.)

Ramos-E-SilvaMLimaCMSchechtmanRCTropeBMCarneiroS. Superficial mycoses in immunodepressed patients (AIDS). Clin Dermatol 201;28(2):217-25

(Discusses the diagnosis and treatment of superficial mycosis in HIV patients, including cutaneous alterations caused by Candida, dematiaceous fungi agents of phaeohyphomycosis, Malassezia spp, dermatophytes, and filamentous nondermatophyte fungi.)

GarnicaMNucciMQueiroz-TellesF. Difficult mycoses of the skin: advances in the epidemiology and management of eumycetoma, phaeohyphomycosis and chromoblastomycosis. Curr Opin Infect Dis2009;22(6):559-63.

(This article reviews recent data regarding the epidemiology and treatment of these infections.)

RevankarSG. Phaeohyphomycosis. Infect Dis Clin North Am2006;20(3):609-20.

(Emphasizes the importance of a high degree of clinical suspicion associated with appropriate pathologic and mycologic examination, in the diagnosis of phaeohyphomycosis.)

LevinTPBatyDEFeketeTTruantALSuhB. Cladophialophora bantiana brain abscess in a solid-organ transplant recipient: Case report and review of the literature. J Clin Microbiol2004;42(9):4374-8.

(Another case report and review of a case of cerebral phaeohyphomycosis.)

BrandtMEWarnockDW. Epidemiology, clinical manifestations, and therapy of infections caused by dematiaceous fungi. J Chemother2003 Nov;15 Suppl 2:36-47

(Review of the epidemiology, clinical manifestation, and therapy of infections caused by dematiaceous fungi.)

FungFTappenDWoodG.Alternaria-associated asthma. Appl Occup Environ Hyg2000;15:924-7.

(This paper show allergic phaeohyphomycosis as an occupational disease and reviews its diagnosis, treatment and management.)

SadigurskyDLuisaNogueira e FerreiraLiz Moreno de OliveiraCorrêa. Phaeohyphomycosis Infection in the Knee. Revista Brasileira de Ortopedia51.2 (2016): 231234. PMC. Web. 27 Apr. 2016.AhmedSarah A. et al. Phaeohyphomycosis Caused by a Novel Species, Pseudochaetosphaeronema Martinelli. Ed. WarnockD. W.. Journal of Clinical Microbiology53.9 (2015): 29272934. PMC. Web. 27 Apr. 2016.

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