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Deep Fungal Infections
Key Points: Deep Fungal Infections
- 1.
Deep fungal infections can be divided into subcutaneous (localized), systemic, and opportunistic categories.
- 2.
Neutropenic patients are particularly at risk for systemic phaeohyphomycosis, aspergillosis, fusariosis, and mucormycosis.
- 3.
Patients with impaired cellular immunity are particularly at risk for disseminated sporotrichosis, histoplasmosis, coccidioidomycosis, penicilliosis, Cryptococcus , and Candida .
- 4.
The differential diagnosis of lymphocutaneous (sporotrichoid) spread includes SLANTS : S porotrichosis, L eishmaniasis, A typical mycobacteria, N ocardia, T ularemia, and cat S cratch disease.
1
What is a deep fungal infection?
In contrast to the superficial dermatophytes, which are typically confined to dead keratinous tissue, certain mycotic infections have the capacity for deep invasion of the skin or production of skin lesions secondary to systemic infection. They are typically acquired through direct inoculation, ingestion, and/or inhalation of spores from soil or other organic matter. In this chapter, the deep fungal diseases are organized into three categories based on clinical presentation ( Table 31.1 ).
Table 31.1
The deep fungal infections
| Subcutaneous fungal infections | Systemic or respiratory fungal infections | Opportunistic fungal infections |
|---|---|---|
|
|
|
Subcutaneous fungal infections
2
Discuss the characteristics of subcutaneous mycotic infections.
Subcutaneous mycotic infections are caused by a heterogeneous group of fungi and are infections of implantation (inoculated directly into the skin through local trauma). The four most important infections are sporotrichosis, chromomycosis, phaeohyphomycosis, and mycetoma. Lobomycosis and rhinosporidiosis are significantly less common. As a group, these infections involve primarily the skin and subcutaneous tissues and rarely disseminate in the immunocompetent host. These organisms are ubiquitous in soil, plants, and trees.
3
What is a dimorphic fungus?
Dimorphic fungi are capable of growing in both the mold and yeast forms. Examples of diseases caused by dimorphic fungi include sporotrichosis, histoplasmosis, blastomycosis, paracoccidioidomycosis, and penicilliosis.
4
What occupations are at increased risk of sporotrichosis?
Sporotrichosis is caused by a dimorphic fungus, Sporothrix schenckii. This organism is found worldwide, except in the polar regions, and is most common in subtropical and tropical climates. It is endemic in Africa and Central and South America. In the United States, infection is most common in the Midwest. The habitat includes soil, thorny plants (especially roses), hay, sphagnum moss, and animals. Cats may carry Sporothrix on their paws and can cause infection by scratching their owners or animal handlers. Occupations at risk of cutaneous inoculation include farmers, gardeners (especially rose), florists, masonry workers, Christmas tree farmers, veterinarians, and animal handlers (especially cats, rodents, and armadillos).
5
Describe the clinical manifestations of sporotrichosis.
The classic form of sporotrichosis (lymphocutaneous) begins at the site of inoculation (most commonly, upper extremity) as a painless pink papule, pustule, or dermal nodule, which rapidly enlarges and ulcerates ( Fig. 31.1 A ). Without treatment, the infection ascends along the lymphatics, producing secondary nodules and regional lymphadenopathy that may ulcerate ( Fig. 31.1 B). The fixed cutaneous variant is confined to the site of inoculation. The organisms rarely disseminate hematogenously to the joints, bone, meninges, or eye.
6
How is the diagnosis of cutaneous sporotrichosis made?
A strong clinical suspicion is most important. Skin biopsy shows granulomatous inflammation with neutrophilic microabscesses. In the immunocompetent patient, fungal elements are only found in about 60% of cases even when special stains are utilized. When suspecting sporotrichosis, cultures (of tissue or pus) on Sabouraud's medium are both more specific and sensitive. Colonies grow rapidly in 3 to 5 days.
7
How do you treat cutaneous sporotrichosis?
Itraconazole (100 to 200 mg/day) for 3–6 months is the treatment of choice for lymphocutaneous and fixed cutaneous sporotrichosis, with a success rate of 90% to 100%. Terbinafine (250 mg/day) is second-line treatment, and because potassium iodide (SSKI) is less costly than other agents, it is still recommended, especially in developing-world epidemics. Local hyperthermia has also been shown to be effective. Children may be safely treated with itraconazole. The treatment of choice for disseminated disease is a lipid formulation of amphotericin B (3 to 5 mg/kg per day intravenously) until the patient shows a favorable response, followed by itraconazole 200 mg twice a day for a total treatment time of at least 12 months.
8
What other organisms may present with lymphocutaneous disease?
Several other diseases may present with a distal ulcer, proximal secondary nodules along the lymphatics, and regional lymphadenopathy. The most important include nontuberculous Mycobacterium ( Mycobacterium marinum , Mycobacterium kansasii , Mycobacterium fortuitum complex), Nocardia , leishmaniasis, cat scratch disease, and tularemia. A patient with this clinical presentation should have tissue biopsies for routine histology and cultures to include bacteria, mycobacteria, and fungi. This pattern of disease is also called sporotrichoid and can be remembered using the SLANTS mnemonic: S porotrichosis, L eishmaniasis, A typical mycobacteria, N ocardia, T ularemia, cat S cratch disease.
9
What are dematiaceous fungi?
Dematiaceous fungi are brown or black pigmented fungi. The pigment is due to melanin. They are slow growing and can be found in the soil, decaying vegetation, rotting wood, and the forest carpet. Subcutaneous-cutaneous disease is caused by traumatic inoculation into the skin. There are three broad categories of dematiaceous fungal infections, including chromoblastomycosis, phaeohyphomycosis, and eumycotic mycetoma (Madura foot).
10
How do you differentiate chromoblastomycosis from phaeohyphomycosis?
Chromoblastomycosis (also called chromomycosis) is a chronic subcutaneous infection characterized by the appearance in tissue biopsies of an intermediate, vegetative, pigmented fungal form with a yeastlike appearance that is arrested between yeast and hyphal formation. These pigmented, thick-walled fungal elements are called Medlar bodies ( Fig. 31.2 ). Medlar bodies, also called copper pennies or sclerotic bodies, are diagnostic of chromoblastomycosis, differentiating it from phaeohyphomycosis. Tissue biopsies of phaeohyphomycosis are characterized by lightly pigmented filamentous hyphae.
11
Which organisms may cause chromoblastomycosis?
Five fungal species account for most infections. The most frequent organism worldwide is Fonsecaea pedrosoi. Other organisms include Phialophora verrucosa , Fonsecaea compactum , Rhinocladiella aquaspersa , and Cladophialophora carrionii. Memory device: Compact (Fonsecaea compactum) dead (Cladophialophora carrionii) wet (Rhinocladiella aquaspersa) warty (Phialophora verrucosa) feet (Fonsecaea pedrosoi) .
12
Which organisms cause phaeohyphomycosis?
Phaeohyphomycosis may occur in both immunocompetent and immunocompromised patients and has been attributed to over 60 genera and more than 100 species. The most important genera include Scedosporium (Pseudallescheria), Alternaria , Bipolaris , Curvularia , Exophiala , Phialophora , and Wangiella .
13
How does chromoblastomycosis present?
Chromoblastomycosis is a chronic cutaneous and subcutaneous infection that is usually present for years with minimal discomfort. The inciting injury is often not recalled. The infection is most common on the lower extremity, and 95% of cases occur in males. The typical patient is a barefoot, rural agricultural worker in the tropics. At the inoculation site, red papules develop that eventually coalesce into a plaque, which slowly enlarges and acquires a verrucous or warty surface. Lesions can evolve into a cauliflower-like mass, leading to lymphatic obstruction and elephantiasis-like edema of the lower extremity ( Fig. 31.3 ) if left untreated. Neoplastic transformation to squamous cell carcinoma can occur.
14
How is chromoblastomycosis diagnosed and treated?
Diagnosis is made through potassium hydroxide (KOH) mounts from scrapings, biopsies of the lesions showing the organism with suppurative and granulomatous inflammation, and culture. Chromoblastomycosis is typically resistant to treatment. The treatment of choice for small lesions is surgical excision with a wide margin of normal skin. Chronic or extensive lesions should be treated with a combination of itraconazole therapy and surgical excision. Combination therapy with terbinafine, posaconazole, cryotherapy, and local heat therapy also appear to be effective. Treatment is continued for months.
15
Describe the clinical features of phaeohyphomycosis.
The spectrum of clinical infections is broad. The most typical presentation is a subcutaneous cyst or abscess at the site of trauma, and Exophiala jeanselmei and E. dermatitidis are the most common organisms. The primary lesion is a painless nodule that evolves into a fluctuant abscess. Immunocompromised patients present with multiple nodules. Scedosporium proliferans (42% of cases), Bipolaris spicifera (8%), and Wangiella dermatitidis (7%) are the most common causes of rare disseminated disease. The primary risk factor is decreased host immunity, especially prolonged neutropenia. The outcome is poor, despite antifungal therapy, with a 79% overall mortality rate.
16
What is Madura foot?
Madura foot, a type of mycetoma, is a localized, destructive infection of the skin and subcutaneous tissue that eventually involves deeper structures. It may be caused by filamentous bacteria, aerobic actinomycetes (actinomycetomas), and true fungi (eumycetoma). The most common causative fungi are Madurella mycetomatis and Madurella grisea. Less frequent causes are Acremonium kiliense , E. jeanselmei , and Scedosporium apiospermum (also called Pseudallescheria boydii ).
17
What are the three characteristic clinical features of Madura foot?
The first is the formation of nodules in the skin at the site of inoculation, usually a penetrating injury. The second feature is purulent drainage and fistula formation. The third and most characteristic feature is the presence of grains or granules that are visible in the purulent drainage. Madura foot is a progressive infection leading to marked swelling and deformity in its later stages ( Fig. 31.4 ). Additionally, the lesions have a tendency to become painful in the later stages, when bone involvement and deformity ravage the site.
Systemic fungal infections
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