Pediatric Sporotrichosis

Sporotrichosis is caused by the acquisition of Sporothrix schenckii, a dimorphic, saprophytic, and geophilic fungus. Although this fungal infection has been reported in semiarid environments, it is most typically found in warmer temperatures and tropical climates around the world.[1] S schenckii usually grows amidst decaying vegetable matter and in the soil as a saprophyte. Saprophyte can also be commonly found in soil, straw, wheat grain, fruits, tree bark, wood, shrubs, thorns, rose shrubs, decaying vegetation and timber. However, it is most acquired by humans when a form of traumatic inoculation occurs after in contact with animals. The most common animals known to have spread Sporotrichosis are cats, dogs and horses. Sporotrichosis spreading from human to human is quite rare (international Journal of Dermatology).

Because sporotrichosis may be difficult to initially diagnose, a differential diagnosis should always be generated during the clinical evaluation (see Differentials).

Benjamin Schenck first noted Sporotrichosis in 1896. In the year 1900, Hekton and Perkins officially named the pathogenic fungus Sporothrix Schenkii after its original founder (international journal of dermatology). The association between sporotrichosis and acquired immunodeficiency syndrome (AIDS) was first reported in 1985. Although it is not considered an AIDS marker, it is included in a list of AIDS-related conditions. In immunocompromised patients, especially those with an impaired cell-mediated immunity, it can become an opportunistic infection with a possible life-threatening course.

The fungus is most commonly acquired by traumatic implantation into the skin, causing a local pustule or ulcer with nodules developing proximally along the draining lymphatics. Once implanted, this saprophytic fungus can grow in human tissues.

When recognized by the immune system, an inflammatory response occurs. Physical signs and symptoms related to the location and degree of inflammation then ensues. Primary organ systems involved in sporotrichosis include the skin and subcutaneous tissues. Dissemination to osteoarticular structures, viscera, and the CNS is uncommon unless the fungus is inhaled or acquired by a patient who is immunocompromised.[2, 3] Inhalation may affect the lungs and cause a granulomatous pneumonitis. In a host who is immunocompromised, disseminated infection can occur from skin involvement or from primary pulmonary infection. For instance, one case has been reported of laryngeal and respiratory tract sporotrichosis after steroid inhaler use.[4]

Clinically, sporotrichosis may manifest as either an acute or a chronic subcutaneous mycotic infection. Although the acute phase is most common, chronic nodular lymphangitis also reportedly develops in some cases. A minor puncture wound or splinter is sufficient to inoculate the fungus into the tissue. Infection can also be related to zoonotic spread from infected cats or scratches from digging animals, such as armadillos.[2] Among animals that can spread sporotrichosis, cats have been found to be the most common. Cats most often transfer sporotrichosis through bites and scratches (Molecular Epidemiology of Feline Sporotrichosis).

Frequency

United States

Sporotrichosis is an uncommon fungal infection of unknown frequency.

International

Distribution is global, but incidence is unknown. Deep mycoses have mainly been reported in the tropics and subtropics. A recent endemic of lymphocutaneous sporotrichosis were reported in Peru[5] where the epidemic has been occurring for three decades.[6] Brazil has also had a high outcome of sporotrichosis, and it was found to be due to zoonotic transmission most commonly as well through cats. It was found to have stemmed from the Rio de Janeiro[7] . A cluster of sporotrichosis cases occurred in Western Australia; a commercial hay supplier was the source of the outbreak.[8] Jilin Province, Northeast China, has recently been reported as a serious endemic region, as well as in the tropics and subtropics of Malaysia.[9]

Mortality/Morbidity

Sporotrichosis is usually associated with minimal morbidity. Increased morbidity and, rarely, mortality may occur if the diagnosis is delayed, if the fungus infects patients who are immunologically compromised, or if inadequate or inappropriate therapy is rendered.

Race

Sporotrichosis has no racial predilection.

Sex

Sporotrichosis occurs in men, women, and children. Men have a higher risk of acquiring this fungus because they have greater environmental exposure from outdoor occupations.

Age

Sporotrichosis may occur in people of any age. Yet, in children, sporotrichosis tends to present more frequently with a solitary ulcerative nodule. This is in contrast to adults in which a classic lymphocutaneous form is more common.

To evaluate a patient with possible sporotrichosis, investigate the history of risk factors for acquiring the fungus. Several predisposing factors may place a person at increased risk for developing sporotrichosis. Contact with certain plants known to harbor this fungus (eg, roses, sphagnum moss, salt-marsh hay, prairie hay) places patients at increased risk for the disease. The risk of this contact-acquired infection is increased among people in certain occupations, such as farmers or florists. Typical introduction of S schenckii into the skin has been described as occurring via a thorn or wood splinter. Transmission is also possible from infected cats or scratches from digging animals (ie, armadillos), with notable increased incidence in veterinarians.[10] Cats have been the animal found most common to transmit sporotrichosis. As said prior, they transmit most frequently through bites or scratches, however it is common for the exact transmission point from felines to humans to go unnoticed until infection occurs (Cutaneous Sporotrichosis). Infections have also been reported in medical technicians who were exposed to tissue or culture specimens of S schenckii.

Certain diseases, such as diabetes mellitus and alcoholism, also predispose a patient to develop localized disorders. In certain settings, patients who are immunocompromised are at risk for developing disseminated sporotrichosis.

Overall, this fungal infection most commonly affects the dorsum of the hands or fingers. Various primary lesions have been described, ranging from an erythematous papule or pustule to an ulcerating nodule.

Sporotrichosis can be divided clinically into 2 main categories: cutaneous and systemic.

• Cutaneous sporotrichosis

  • The primary lesion is typically a pustule at the site of implantation. Erythematous papules, nodules, and verrucous plaques may also develop, along with secondary features such as ulceration and serosanguineous fluid drainage. Surprisingly, these lesions produce relatively few symptoms.

  • Lymphangitic cutaneous sporotrichosis is the most common form of the disease.

    • Lymphangitic cutaneous sporotrichosis is usually found on an exposed skin surface at the site of traumatic inoculation. A classic clinical setting would be an adult male who acquired a splinter that, despite removal, continued to produce an area of inflammation.

    • A pustule may slowly grow and may develop into a plaque or nodule. This nodule may eventually ulcerate. Examination proximally along the affected limb usually reveals small, deep-seated, satellite erythematous nodules along lymphatic drainage. If left untreated, the fungal infection continues to spread proximally, producing a significant amount of skin inflammation, abscesses, thickened lymphatic cords, lymphadenitis, and, eventually, systemic spread.

  • Spontaneous resolution may occur. Typically, early in the course of the disease, the patient's health is minimally affected, and the infection site bears minimal symptoms.

  • Cutaneous forms of sporotrichosis also include fixed cutaneous, cellulitic, and mycetomalike. Of these, fixed cutaneous sporotrichosis is the second main cutaneous form of the disease.

    • In its fixed cutaneous form, the fungus remains localized to the implantation site and no proximal lymphangitis or lymphadenopathy develops.

    • The fixed cutaneous form may tend to take on more of a verrucous plaquelike appearance. This form may represent enhanced host immune response to the fungus, possibly because of prior exposure. Skin surveys using the sporotrichin skin test have demonstrated that a positive test result occurs in up to 10% of certain populations, suggesting a history of prior exposure to S schenckii.

• Systemic sporotrichosis

  • Less common systemic forms of sporotrichosis usually follow inhalation of the fungus. A pulmonary infection ensues, which serves as the primary dissemination route. Systemic sporotrichosis can be divided into a pulmonary form and a disseminated form, both causing higher morbidity and mortality than cutaneous sporotrichosis.

  • Pulmonary infection may remain localized to the lung or may disseminate to other body sites, including the skin, joints, bones, internal organs, and meninges. For instance, one case has been reported of laryngeal and respiratory tract sporotrichosis after steroid inhaler use.

  • This clinical situation has often been found in persons with alcoholism.

  • Erythema nodosum and vascular lesions resembling polyarteritis nodosum have also been reported in patients with sporotrichosis.

• Clinical types of sporotrichosis

  • Localized cutaneous (chancriform) type: A subcutaneous papule or pustule develops at the site of inoculation after several weeks. Surrounding skin develops a pink-to-violaceous papulonodule, which may subsequently develop into a painless ulcer. The ulcer border is often ragged and undermined and draining a serosanguineous exudate. Draining lymph nodes may become tender and swollen.

  • Chronic lymphangitic (sporotrichoid) type: This is the most common and best recognized form of sporotrichosis; it may follow the chancriform type described above. Lymphangitic spread of the fungus produces nodular swellings in a linear array, spreading proximally up the affected extremity. Palpable lymphadenopathy is often an associated finding.

  • Fixed cutaneous sporotrichosis: Crusted verrucous plaques may occur in this type and are often found on the faces of children or the upper extremities of adults.

  • Disseminated sporotrichosis: The fungus spreads hematogenously to the skin, joints, eyes, and CNS. Multiple crusted and ulcerating papulonodules may occur. This form may have a widespread distribution (sparing the palms of the hands and the soles of the feet).[11, 12] The primary source of infection may be the lungs, or dissemination may occur from a cutaneous site in a patient who is immunocompromised.

See the list below:

• Sporotrichosis is typically acquired by inoculation of the fungus into the skin during contact with certain plants or animals.

• Classic scenarios include skin puncture by a splinter or rose thorn.

• Bites or scratches from infected animals such as cats, dogs, and armadillos represent another source of infection.

See the list below:

• Sporotrichosis is a thermally dimorphic fungus that can be grown from infected tissues.

• S schenckii is easy to grow and is not sensitive to cycloheximide, which is often added to fungal culture media to inhibit growth of saprophytes and to promote growth of dermatophytes.

• At 25°C on Sabouraud agar, the fungus forms a white-to-cream–colored mold that turns dark brown or black as it ages, often forming a leathery, wrinkled surface.

• Microscopic examination of a cotton blue or Scotch tape preparation reveals long and slender septate hyphae with hyaline pyriform conidia, often forming flowerlike arrangements.

• In tissue at 37°C, S schenckii takes on an elongated yeast form, approximately 6-8 mm in length, with rounded ends resembling cigars. Budding from the main yeast bodies may be observed in the tissues.

• To confirm the identity of this fungus, the hyphal form may be converted into the yeast phase. This is often best achieved by growing the fungus on brain-heart infusion agar supplemented with sheep's blood then raising the temperature from 25°C to 37°C.

• Fine-needle aspiration of lymphocutaneous sporotrichosis can be followed by periodic-acid Schiff (PAS) and Grocott's methenamine silver (GMS) method.

• Further laboratory studies (eg, tuberculosis test, antinuclear antibody test) may be needed to identify other potential infectious or noninfectious causes that may mimic sporotrichosis.

See the list below:

• If primary pulmonary sporotrichosis is suspected, chest radiography may be helpful.

See the list below:

• Immunoelectrophoresis and agglutination techniques are available in the serodiagnosis of this mycosis. A limitation of these tests, however, is their lack of sensitivity in diagnosing cutaneous sporotrichosis.

• An enzyme-linked immunosorbent assay (ELISA) has been developed for specific antibody detection in serum specimens of patients with sporotrichosis, which has shown to have higher sensitivity; however, cross-reactions between S schenckii and Leishmania have been reported when using ELISA.

See the list below:

• Diagnosis must often await the results of tissue culture. Despite the usual difficulty in visualizing S schenckii yeast cells on routine hematoxylin and eosin (H&E) stains, the organism is usually cultured relatively easily. A punch biopsy or incisional biopsy may provide the best sample for these 2 tests. When tissue is obtained for culture, submit the specimen in (nonbacteriostatic) normal saline to the laboratory without delay.

See the list below:

• S schenckii is often very difficult to recognize in regular H&E tissue sections or even when tissue is stained with PAS or GMS. The cigar-shaped yeast cells are usually quite sparse within the tissue. Although geographic differences have been reported in the abundance of S schenckii found in the tissues, as have differences in the ease of identifying them with special stains, the reasons for these differences are unknown.

• Because these yeast cells are usually difficult to find in the tissue, seeking clues to their presence may increase the likelihood of finding the organism.

• From a low-power view, the tissue often manifests a pseudoepitheliomatous hyperplasia with microabscess formation. This is a nonspecific finding but is often a clue to deep fungal infection, prompting the investigator to make a close survey of the tissue for infective organisms.

• A diffuse, mixed, inflammatory cell infiltrate is often found throughout the dermis, extending into the subcutaneous fat. When found, the yeast often resides within microabscesses or within macrophages and giant cells.

• Asteroid bodies may also be a clue to sporotrichosis. These entities are eosinophilic round bodies with pink material radiating outward from their center. Asteroid bodies most likely form as a result of accumulation of immunoglobulins surrounding a yeast cell.

• A fluorescent antibody technique may enhance diagnostic specificity. This technique uses anti-Sporothrix immunoglobulins labeled with fluorescein dye to enhance identification of the yeast cells in tissue.

• Fortunately, even if the fungus cannot be observed in the tissues, it is often very easy to grow in culture.

• One case reported a histology mimicking that of cutaneous cryptococcosis.[13]

Medical therapy is the standard of care for sporotrichosis. Patients are commonly treated with an oral antifungal agent on an outpatient basis. Surgical therapy, other than to perform a biopsy from a lesion for establishing the diagnosis, is rarely used as a form of treatment. Aggressive treatments are seldom necessary. This fungus does not grow well in temperatures higher than 38.5°C, so warm compresses are often used as adjunctive therapy. See the Medication section for a suggested pharmaceutical approach to treating sporotrichosis.

Consult with a dermatologist.

Activity limitations, determined on a case-by-case basis, may be necessary for optimal care. Wearing long sleeves and gloves is recommended when gardening or handling plant matter that may cause sporotrichosis.

Approach the treatment of sporotrichosis based upon each patient's clinical presentation and severity of illness. Most patients are treated with some form of antifungal therapy. Many agents are reported to be successful. For simple cutaneous forms, a saturated solution of potassium iodide is often used and is the least expensive form of treatment.

Systemic antifungal medications, such as amphotericin B, itraconazole,[14, 15] terbinafine, or fluconazole, may be used to treat more severe forms of sporotrichosis (eg, lymphonodular, pulmonary, osteoarticular, disseminated). For all clinical types of sporotrichosis, continue the treatment course for at least 1 week after clinical cure.

Class Summary

The mechanism of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell.

Potassium iodide (SSKI)

For simple cutaneous lesions, the least expensive medication for treatment is a saturated solution of potassium iodide. This approach is commonly used in developing countries because of its low cost. SSKI can be administered on average for approximately 4-6 wk, but as long as 6 months. However, prolonged use should be undertaken with caution (see interactions below). The mechanism of action is unknown. Ineffective for systemic disease.

Itraconazole (Sporanox)

DOC for cutaneous sporotrichosis. A fungistatic azole with broad spectrum of activity because of its inhibition of enzyme 14-alpha-demethylase, which is needed by the fungus for cell wall synthesis. Particularly effective for lymphocutaneous forms of sporotrichosis but may be used for fixed cutaneous and systemic forms. The caps and PO solution are not interchangeable (PO solution exhibits higher bioavailability).

Amphotericin B (Fungizone)

DOC for disseminated or meningeal forms of systemic sporotrichosis. Some providers even consider this DOC for lymphocutaneous forms of sporotrichosis.

Polyene antibiotic produced by a strain of Streptomyces nodosus; can be fungistatic or fungicidal. Binds to sterols, such as ergosterol, in the fungal cell membrane, causing intracellular components to leak with subsequent fungal cell death.

Terbinafine (Daskil, Lamisil)

A fungicidal allylamine antifungal agent. Considered a third-line agent against sporotrichosis. Blocks ergosterol synthesis by inhibiting squalene epoxidase. Effective against S schenckii and other fungi and fungal infections, including most dermatophytes, Aspergillus species, blastomycosis, histoplasmosis, and Scopulariopsis brevicaulis. Terbinafine is well absorbed PO and has a long half-life.

No elixir form is available; 250-mg tab is not scored and cannot be easily pulverized for use in children and is not palatable.

Fluconazole (Diflucan)

A broad-spectrum azole antifungal agent. Considered a third-line agent for sporotrichosis treatment. Effective for various fungi, including dermatophytes, candidal species, S schenckii, and some molds. It inhibits the enzyme 14-alpha-demethylase, preventing fungal cell wall formation.

See the list below:

• The primary therapeutic approach to managing cutaneous lesions of sporotrichosis involves administration of systemic medications to eradicate the fungus. If a cutaneous plaque, nodule, or ulcer is present, consider teaching the patient about supportive local wound care to facilitate healing. Such education typically involves instruction on keeping lesions clean and free from further contamination. If the lesion is ulcerated, a topical ointment may be applied to prevent occurrence of secondary bacterial infections. Follow up with the patient in the clinic every 1-2 weeks to monitor progress. Instruct the patient about potential sources of this fungus to help avoid further infections.

See the list below:

• Sporotrichosis is usually managed on an outpatient basis. A few patients with the more severe forms (eg, disseminated sporotrichosis) may require hospitalization.

See the list below:

• See Medical Care.

See the list below:

• Educate every patient who has acquired sporotrichosis about the fungus and provide information about how to prevent occurrence of further infections. S schenckii is a saprophytic fungus, usually found in the soil. Instruct patients to be careful when working with soils, sphagnum moss, decaying wood, roses, thorn bushes, and salt marsh or prairie hay. If exposure to these materials or plants is anticipated, instruct patients to wear personal protective equipment, particularly gloves, to minimize thorn or splinter punctures of the skin.

• Sporotrichosis has also been acquired from pets, particularly cats, so the physician should consider this potential source of acquisition if the aforementioned soil and plant exposures do not apply.

Prognosis for patients with sporotrichosis depends on its clinical type (eg, fixed cutaneous, localized cutaneous, lymphocutaneous, disseminated), associated underlying diseases, and the patient's immune response to this fungus.

• Patients with fixed cutaneous and lymphocutaneous sporotrichosis have an excellent prognosis. These lesions usually respond well to therapy and typically resolve after 4-6 weeks of therapy.

• Patients with the osteoarticular form of sporotrichosis usually have a moderately good prognosis, but they may require higher doses of medication, longer courses of therapy to achieve cure, or both.

• Patients with pulmonary or disseminated forms of sporotrichosis usually have some underlying medical condition or immune deficit that allows the fungus to grow and spread unchecked. For example, patients who have insulin-dependent diabetes mellitus, chronic alcoholism, or AIDS may be unable to mount an adequate immune response to keep this fungal infection localized. Such patients typically have a worse prognosis and require longer courses of therapy.

See the list below:

• See Deterrence/Prevention.

• For excellent patient education resources, visit eMedicineHealth's Infections Center. Also, see eMedicineHealth's patient education article Sporotrichosis.