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Treating Rare Fungal Infections: Sporotrichosis

Treating Rare Fungal Infections: Sporotrichosis

This ongoing feature series was taken from the 4th annual postgraduate course and workshop in medical mycology-dermatomycology, July 27-30, 1979, Newport Beach, CA.

Sporotrichosis is a deep cutaneous mycotic infection caused by the dimorphic organism Sporothrix schenckii (Figure 1). Classically, it is known as rose gardener’s disease, since the infection can result after being pricked by a contaminated rose thorn. There is a primary inoculation site, followed by spread along the lymphatics in a characteristic sporotrichoid pattern.

Rarely, the disease spreads hematogenously, resulting in systemic manifestations.

Epidemiology and Pathogenesis

Figure 2. Primary inoculation of sporotrichosis. Source: Graham Library of Digital Images, Wake Forest University Department of Dermatology © 2009 Wake Forest University DermatologySporothrix schenkii is present in soil worldwide, and the organism is endemic to Mexico, Central America, South America, and South Africa1. Risk factors include working outdoors in these endemic areas. Specifically in the United States, gardeners are at an increased risk of infection, especially from roses and orchids1. All age groups can be affected; however, it is more common in adults.

Injury due to a splinter or thorn causes a primary inoculation or several inoculations at once2. Lesions most commonly occur on the hand or arm2. Its subsequent course depends on several factors, including host immune response, the size and virulence of the organism, and any history of previous exposure2.

Figure 3. Sporotrichosis with lymphatic spread. Source: Graham Library of Digital Images, Wake Forest University Department of Dermatology © 2009 Wake Forest University DermatologyAfter an immunocompetent host with no prior history of exposure is inoculated, the incubation period lasts from a few days to several weeks with regional lymph node involvement during this period (1). Following the incubation period, a single erythematous papule or nodule arises in the deep cornium or subcutaneous tissue and develops into an ulcer (1,2). A few weeks after the initial nodule forms, multiple nodules and ulcers develop along the lymphatics in a characteristic
sporotrichoid pattern and regional lymph nodes become enlarged (Figure 3).

Involvement at the primary lesion can spread peripherally to produce a scaly, crusted plaque with a verrucous or

papillomatous surface (2). Generalized cutaneous lesions occasionally appear and result fromhematogenous and lymphatic spread from subcutaneous nodules (2). In disseminated disease, lesions of the oral and nasal mucosa are seen rarely (1-3). In immunocompromised hosts, there is a greater chance for excessive cutaneous disease with or without syste

mic features (1). Reports have also demonstrated respiratory tract sporotrichosis after localized or generalized immunosuppression (4,5).


Figure 4. Sporotrichosis. Hyperplasia of the epidermis with microabscess formation and granulomatous infiltrate of superficial dermis. (DPAS x 10) Source: Graham Library of Digital Images, Wake Forest University Department of Dermatology © 2009 Wake Forest University DermatologyThe primary lesion in sporotrichosis reveals ulceration of epidermis with acanthosis to pseudoepitheliomatous hyperplasia at the periphery. There is a nonspecific granulomatous cellular infiltrate at the cornium with capillary hyperplasia, and microabscesses containing polymorphonuclear cells are present in the cornium and epidermis (Figure 4). The cellular
infiltrate consists of large numbers of lymphocytes and plasma cells with a variable amount of epithelioid and giant cells (2).

Figure 5. Multiple fungal organisms are apparent on silver stain showing rounded spore forms and the characteristic cigar shape. (GMS x 100) Source: Graham Library of Digital Images, Wake Forest University Department of Dermatology © 2009 Wake Forest University DermatologyFungal organisms are rarely seen on biopsy, and visualization may require multiple sections. PAS and GMS nitrate techniques can be used to aid in visualization of fungal forms. When seen, asteroid, cigar-shaped, and oval to round or budding forms are present (Figure 5). The cigar-shaped forms are 1 to 2 microns in diameter and 4 to 5 microns in length. The rounded yeast-like forms have a more variable size from 3 to 7-8 microns in diameter. Within the center of asteroid bodies are rounded or oval budding spore forms (Figure 6). The acidophilic staining at the periphery of the asteroid is either produced by the host or is a result of the interaction between the fungus and host. Nonspecific asteroid bodies without organisms can also be seen in sporotrichosis as well as in sarcoidosis and other granulomas. In the later stages of the primary lesion, the microscopic appearance resembles other suppurative deep mycoses with pseudoepitheliomatous hyperplasia, miliary abscesses, and a tuberculoid cellular infiltrate.

Figure 6. Asteroid body with spore in its center. (PAS-PA x 250) Source: Graham Library of Digital Images, Wake Forest University Department of Dermatology © 2009 Wake Forest University DermatologyThe secondary nodule in sporotrichosis is seen along the lymphatics and is located in the deep cornium or subcutaneous tissue. It is characterized by three distinct zones: the central, middle, and outer zones. The central zone, or chronic suppurative zone, is necrotic with abscesses containing polymorphonuclear cells. The middle, or tuberculoid, zone consists of epithelioid cells and giant cells, which are predominantly Langerhan’s type cells. The outer zone, or syphiloid zone, is rich in plasma cells, lymphocytes, and fibrocytes, and it shows prominent capillary hyperplasia. These three zones may not be as distinct in older lesions. Fungal organisms are rarely demonstrated in secondary lesions. When present, they appear as described in primary cutaneous lesions. Rarely, branching, non-septate hyphae have been reported (6).

Differential Diagnosis

The early stage of a primary lesion is non-specific and can resemble ulcerations due to injuries, foreign bodies, and other infective processes (2). Other disease processes resembling a sporotrichoid pattern are also included in the differential diagnosis and include atypical mycobacterial infections most commonly caused by M. marinum (Table 1). (1,2,7).

Histologically, except in unusual instances in which the fungal organisms can be demonstrated, a diagnosis cannot be made on the basis of the microscopic features of a primary nodule.2 The secondary nodule occurring along the lymphatics shows a more characteristic pattern that can be
seen in other chancriform lesions spread by lymphatics, such as tularemia (2). However, this reaction is still highly suggestive of sporotrichosis despite the absence of organisms. In fixed plaque and disseminated lesions, the differential is again broad and includes other granulomatous disorders (1).

TABLE 1: Sporotrichosis - Clinical Differential Diagnosis (1,2,7)

Ulcer due to injury

Ulcer due to foreign body
Atypical mycobacteria
Pyogenic bacteria
Cat scratch disease
Acanthamoeba spp.
Primary syphilis
Opportunistic fungi in immunocompromised hosts

Diagnostic Tests

Figure 7. Culture is required to make a definitive diagnosis of sporotrichosis. Source: Graham Library of Digital Images, Wake Forest University Department of Dermatology © 2009 Wake Forest University DermatologyCulture of either pus or tissue is required for definitive diagnosis, and at 25°C grows white to brown mold that over time becomes darkly pigmented (Figure 7). Microscopic analysis of the culture demonstrates condida clustered at the ends of conidiophores.1 Incubation at 37°C on
enriched glucose-containing media shows slow-growing, white, pasty, yeast-like colonies which on microscopic analysis shows cigar-shaped budding yeasts. Nested PCR assay is also of use for analysis (8).


Topical therapy is largely ineffective for sporotrichosis. Oral therapy with itraconazole is effective and is recommended by the mycoses study group of the Infectious Diseases Society of America (9) (Kaufmann, 2007). Itraconazole 100 to 200 mg/day for 3 to 6 months is the treatment of choice for lymphocutaneous or fixed cutaneous sporotrichosis (Table 2). It is safe and well-tolerated, with a low relapse rate. When continuous use for 3 weeks versus pulsed treatment were compared, it was found that there was no significant difference in efficacy, so pulsed therapy can also be used as an option in treatment (10).

Oral therapy with saturated solution of potassium iodide (SSKI) is also successful and is low-cost; however, it has a range of potential adverse effects such as gastrointestinal upset and bitter taste (1). It is thought to work by affecting the host’s immune reaction to the organism, but is not inherently fungistatic or fungicidal (1). Ketoconazole has been found ineffective in the treatment of sporotrichosis (1,9). Amphotericin B can be used in severe life-threatening or disseminated disease. For pregnant and nursing women, hyperthermia is an alternative option to oral antifungal treatment. Hyperthermia decreases the cutaneous lesions of sporotrichosis, and infrared and far
infrared wave lengths are recommended for use in this population (11,12).

TABLE 2: Treatment Options for Cutaneous and Lymphocutaneous Sporotrichosis

Drug                 Route                Dose                 Frequency

Itraconazole    Oral                    200 mg             Daily
Itraconazole*   Oral                    200 mg             Twice daily
Terbinafine*     Oral                    500 mg             Twice daily
SSKI*              Oral                    5 drops             3 times daily
Fluconazole*   Oral                    400–800 mg     Daily

Local hyperthermia†

*Alternative option for patients who do not respond to initial treatment
† for pregnant or nursing women who cannot take above medications

Key Points

• Sporotrichosis is a deep cutaneous mycotic infection caused by the dimorphic organism Sporothrix schenckii.

• Clinically, sporotrichosis classically presents as subcutaneous nodules at the primary inoculation site and spreads linearly along the lymphatic channels on the hand and forearm.

• Histology reveals pseudoepitheliomatous hyperplasia, granulomatous Langerhans-type giant cells, and a mixed cellular infiltrate.

• Biopsy rarely reveals fungal organisms, but when present, rounded or budding spores, cigar-shaped fungal elements, and asteroid bodies are characteristic.

• Histology alone cannot identify the causative organism, but either fungal culture or PCR analysis can confirm the diagnosis of sporotrichosis.

• Itraconazole is used as first-line treatment for lymphocutaneous or
fixed cutaneous sporotrichosis.

• Alternative treatment options include other antifungal agents, SSKI, and hyperthermia.

Ms. Feneran is a medical student at Wake Forest University School of Medicine in Winston-Salem, NC, and is associated with the Center for Dermatology Research there. Dr. Feldman is with the Center for Dermatology Research, and the Departments of Dermatology, Pathology and Public Health Sciences at Wake Forest University School of Medicine, Winston-Salem, NC.
The Center for Dermatology Research is supported by an unrestricted educational grant from Galderma Laboratories, L.P.

Disclosure: Ms. Feneran and Dr. Feldman disclose that they have no real or apparent conflicts of interest or financial interests or arrangements with any companies or products mentioned in this article.








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