AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

Section 2 of 11  

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Background

Sporotrichosis is a subacute or chronic infection caused by the soil fungus Sporothrix schenckii. The characteristic infection involves suppurating subcutaneous nodules that progress proximally along lymphatic channels (lymphocutaneous sporotrichosis). Rarely, a primary pulmonary infection (pulmonary sporotrichosis) occurs, or direct inoculation into tendons, bursae, or joints occurs. Osteoarticular sporotrichosis occurs from direct inoculation or hematogenous seeding. Rarely, a disseminated infection occurs with disseminated cutaneous lesions and involvement of multiple visceral organs; this occurs most commonly in patients with acquired immunodeficiency syndrome (AIDS).

Pathophysiology

Infection with the dimorphic soil fungus S schenckii usually is acquired through cutaneous inoculation. The initial reddish, necrotic, nodular papule of cutaneous sporotrichosis generally appears 1-10 weeks after a penetrating skin injury. The lesion is a suppurating granuloma that consists of histiocytes and giant cells, with neutrophils that accumulate in the center and that are surrounded by lymphocytes and plasma cells.

The fungus spreads from the initial lesion along lymphatic channels, forming the chain of indolent nodular and ulcerating lesions that typifies the lymphocutaneous form of the disease.

Other tissues are involved by direct extension and, less often, by hematogenous dissemination. The most common extracutaneous sites are in the bones, joints, tendon sheaths, and bursae. Hematogenous dissemination—particularly in immunocompromised hosts—results in widely disseminated cutaneous and visceral infection, including meningitis.

A rare form appears to result from inhalation of the organism. A chronic, cavitary pneumonia, which is clinically and radiographically indistinguishable from tuberculosis and histoplasmosis, occurs in patients who usually have severe underlying chronic obstructive pulmonary disease (COPD). Sporotrichal infection of the larynx and paranasal sinuses has also been described.

Frequency

United States

Incidence is not precisely known but is estimated at 1-2 cases per million people. An estimated 200-250 cases occur per year.

International

Distribution is worldwide, with focal areas of hyperendemicity. Global incidence is unknown. In the highlands of Peru, incidence is approximately 1 case per 1000 people.

Mortality/Morbidity

Spontaneous resolution of cutaneous or lymphocutaneous sporotrichosis is documented. Prognosis is excellent for complete recovery after therapy. Pulmonary sporotrichosis may contribute to the decline in pulmonary function of patients with COPD. Response to therapy is variable. Osteoarticular sporotrichosis may result in significant morbidity from chronic osteomyelitis and arthritis with significant loss of joint function and deformity. Disseminated sporotrichosis is associated with significant morbidity and, possibly, mortality in immunocompromised hosts.

Race

No known racial predilection exists for sporotrichosis.

Sex

Sporotrichosis is slightly more common in males than in females, presumably due to a higher exposure risk rather than to a sex difference in susceptibility.

Age

Infection usually is recognized in adults in the developed world. Infection may be more common in children and adolescents in tropical regions and in areas of hyperendemicity.

CLINICAL

Section 3 of 11  

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History

• Cutaneous and lymphocutaneous sporotrichosis: The primary lesion develops at the site of cutaneous inoculation, most typically in the distal upper extremities. Patients typically are afebrile and not systemically ill. The lesions usually are minimally painful. Patients often have had 1 or more courses of antibacterial therapy without benefit.
• Pulmonary sporotrichosis: Patients usually have severe underlying COPD and present with subacute or chronic pneumonia. The presenting symptoms of pulmonary sporotrichosis are not specific. Patients present with increased cough and few constitutional symptoms.
• Osteoarticular sporotrichosis
• • Sporotrichosis may present as a chronic arthritis that often is confused with rheumatoid arthritis or other chronic inflammatory arthritis. This frequently occurs for 10 or more years, until destruction of adjacent bone or the development of draining fistulae encourages efforts to establish the microbial etiology of the chronic osteomyelitis by culture. Cutaneous or lymphocutaneous lesions are not prominent in these patients.
  • The process generally begins as a monoarticular arthritis, but other joints may become involved successively. The patient usually has pain on motion, but not the severe limitation characteristic of bacterial arthritis. Systemic illness usually is not present. Functional impairment resulting from osteoarticular sporotrichosis may become severe.
• Disseminated sporotrichosis: Sporotrichosis rarely may involve other organs, including the eye, the prostate, the oral mucosa, the paranasal sinuses, and the larynx. In such patients, the clinical manifestations depend on the organs involved. Central nervous system and meningeal involvement are more common in the AIDS era, but it remains rare. Patients may present with subtle changes in mental status as the only symptom. Patients with AIDS may present with cutaneous dissemination, manifested as nodules, ulcers, or both, with or without evidence of visceral involvement and meningitis.

Physical

• Cutaneous or lymphocutaneous sporotrichosis: An initial papule or nodule forms at the site of cutaneous inoculation, usually 1-10 weeks after inoculation. The initial small nodule enlarges, reddens, becomes pustular, and ulcerates. In the lymphocutaneous form, an ascending chain of nodules develops along skin lymphatic channels. Older, distal lesions ulcerate and drain, while more proximal lesions appear as nodules and undergo the same evolution.
• Pulmonary sporotrichosis: Physical examination of patients with pulmonary sporotrichosis is dominated by the findings of the underlying COPD. No physical findings are distinctive in pulmonary sporotrichosis.
• Osteoarticular sporotrichosis: Patients typically have a subacute or chronic inflammatory monoarticular arthritis. The involved joint has an effusion, may be warm, and may have overlying erythema. Draining sinus tracts complicating adjacent osteomyelitis may be apparent.
• Disseminated sporotrichosis: Physical findings vary depending on the site of involvement. Cutaneous dissemination may appear as subcutaneous mass lesions, diffuse purplish papules and nodules, or disseminated ulcerative lesions.

Causes

• Sporotrichosis is caused by infection with S schenckii, a fungus widely distributed in the natural environment. It grows on plant debris in soil and on the bark of trees, shrubs, and garden plants.
• Splinters, thorns, or woody fragments of plants usually provide the penetrating trauma that introduces the fungal conidia into the human host; however, contact with any plant or plant product (eg, sphagnum peat moss, mulch, hay, timber) that causes minor skin trauma may initiate infection.
• Activities associated with the acquisition of sporotrichosis include gardening, landscaping, farming, berry-picking, horticulture, and carpentry.
• Zoonotic transmission can occur from infected animals (eg, cats, horses with extensive skin lesions) to their animal handlers.
• Both pulmonary and disseminated sporotrichosis are more common in patients with a history of alcoholism.
• Patients with immunosuppression due to infection with human immunodeficiency virus (HIV) and AIDS develop disseminated cutaneous sporotrichosis and hematogenously disseminated sporotrichosis, including sporotrichotic meningitis, more frequently than immunocompetent hosts do. This clinical observation, combined with animal model studies, indicates the importance of cell-mediated immunity in the host defense against sporotrichosis.

DIFFERENTIALS

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Other Problems to be Considered

Erythema nodosum
Mycobacterium marinum infection

WORKUP

Section 5 of 11  

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Lab Studies

• Cell culture
• • Definitive diagnosis at any site requires the isolation of S schenckii in specimen culture from a normally sterile body site.
  • The organism can be recovered by fungal culture from sputum, pus, subcutaneous tissue biopsy, synovial fluid, synovial biopsy, bone drainage or biopsy, and cerebrospinal fluid (CSF).
  • The concentration of organisms in synovial fluid and, particularly, CSF often is low. Therefore, repeated large-volume cultures may be necessary for diagnosis.
  • Occasionally, the organism (cigar-shaped yeast) can be visualized in biopsied tissue specimens that are stained with periodic acid-Schiff, Gomori methenamine-silver, or immunohistochemical stains.
  • Granulomatous inflammation frequently occurs; this is accompanied sometimes by the presence of an asteroid body, but this picture is not specifically diagnostic.
• Serologic techniques
• • Antibody measurement techniques are available.
  • Such tests demonstrate significant interlaboratory variability in sensitivity and specificity; therefore, they rarely should serve as the sole basis for diagnosis.
  • They can be useful to raise diagnostic suspicion and inspire more aggressive attempts to acquire appropriate specimens for culture.
  • The ratio of CSF to serum antibody titer may suggest the presence of sporotrichotic meningitis (CSF antibody titer higher than serum antibody titer).
  • Polymerase chain reaction–based techniques for diagnosis of sporotrichosis have been described but are not available for routine use.

Imaging Studies

• Radiography: Conventional radiographic imaging of the chest (in patients with suspected pulmonary sporotrichosis) and other involved areas (in patients with suspected osteoarticular sporotrichosis) is warranted but does not enable etiologic diagnosis. Computed tomography of the chest is supportive, but again not specifically diagnostic.

Procedures

• Arthrocentesis
• • Patients with subacute or chronic arthritis should undergo diagnostic arthrocentesis.
  • Patients with sporotrichotic arthritis have the general findings of an inflammatory arthritis (leukocytosis), with no crystals or growth on routine bacterial cultures.
• Synovial tissue biopsy: The diagnostic yield of synovial tissue biopsy for histology and culture is better than that of synovial fluid culture alone in patients with suspected sporotrichotic arthritis.
• Bone biopsy: Bone biopsy for histopathology and culture is useful and may be necessary for diagnosis of sporotrichal osteomyelitis.
• Full-thickness skin biopsy: Culture of exuded pus from cutaneous lesions can be diagnostic; however, full-thickness skin biopsy for histology and culture may improve diagnostic yield.
• Bronchoscopy with bronchoalveolar lavage for culture and transbronchial biopsy for histopathology may be required to establish the diagnosis of pulmonary sporotrichosis.

Histologic Findings

Sporotrichosis is characterized histopathologically by granulomatous inflammation with occasional asteroid bodies. The yeast form of the organism can be demonstrated, with considerable difficulty, in biopsied tissues.

TREATMENT

Section 6 of 11  

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Medical Care

Antifungal therapy is the mainstay of treatment for all forms of sporotrichosis.

Surgical Care

• Surgical therapy is important in the management of osteoarticular sporotrichosis.
• Principles of surgical care are the same as for other bone and joint infections. Appropriate drainage of infected joints minimizes joint damage. Appropriate debridement of infected bone enhances the likelihood of eradication of infection with antimicrobial therapy.

Activity

Patients may perform routine activity as tolerated.

MEDICATION

Section 7 of 11  

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Cutaneous and lymphocutaneous sporotrichosis historically have been treated with saturated solution of potassium iodide (SSKI). Although relatively inexpensive, this form of therapy is poorly tolerated by many patients because of frequent adverse effects.

The orally available azole antifungals are the drugs of choice (DOCs) for cutaneous or lymphocutaneous sporotrichosis in the developed world. Ketoconazole has been used but, by historical comparison is less effective than itraconazole or fluconazole and, thus, is no longer indicated. Terbinafine has been demonstrated to be effective in treatment of lymphocutaneous sporotrichosis, but no comparative data with itraconazole therapy exist. Itraconazole is the DOC for cutaneous or lymphocutaneous sporotrichosis, pulmonary sporotrichosis, and osteoarticular sporotrichosis. Treat sporotrichotic meningitis with amphotericin B. Based on anecdotal experience, consider initial treatment with amphotericin B for AIDS patients with disseminated sporotrichosis. These patients may require life-long maintenance therapy with itraconazole after induction therapy with amphotericin B. Flucytosine (Ancobon) may be useful in addition to amphotericin B for treatment of sporotrichotic meningitis, although this has not been

established by controlled comparative trials; flucytosine should not be used alone for treatment of sporotrichosis.

Drug Category: Antifungal agents

Their 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.

Drug Name	Amphotericin B, liposomal (AmBisome)
Description	Novel lipid formulations of amphotericin B that deliver higher concentrations of the drug, with a theoretical increase in therapeutic potential and decreased nephrotoxicity. Produced from a strain of Streptomyces nodosus. Antifungal activity of amphotericin B results from its ability to insert itself into fungal cytoplasmic membrane at sites that contain ergosterol or other sterols. Aggregates of amphotericin B accumulate at sterol sites, resulting in an increase in cytoplasmic membrane permeability to monovalent ions (eg, potassium, sodium). At low concentrations, the main effect is increased intracellular loss of potassium, resulting in reversible fungistatic activity; however, at higher concentrations, pores of 40-105 nm in cytoplasmic membrane are produced, leading to large losses of ions and other molecules. A second effect of amphotericin B is its ability to cause auto-oxidation of the cytoplasmic membrane and release of lethal free radicals. Main fungicidal activity of amphotericin B mayreside in ability to cause auto-oxidation of cell membranes. Among the 3 lipid formulations, no data exist regarding therapeutic efficacy, safety, and dosing for these infections. No basis exists for choosing among them. Despite lack of data that support use of these preparations for amebic meningoencephalitis, they are recommended because of dismal outcomes.
Adult Dose	5 mg/kg/d or more (as tolerated) IV qd infused over at least 2 h
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Antineoplastic agents may enhance the potential of amphotericin B for renal toxicity, bronchospasm, and hypotension; corticosteroids, digitalis, and thiazides may potentiate hypokalemia; the risk of renal toxicity is increased with cyclosporine
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Monitor renal function, levels of serum electrolytes such as magnesium and potassium, liver function, CBC count, and hemoglobin concentrations; resume the therapy at the lowest level (eg, 0.25 mg/kg) when the therapy is interrupted for more than 7 d; hypoxemia, acute dyspnea, and interstitial infiltrates may occur in patients with neutropenia who are receiving leukocyte transfusions (separate time of amphotericin infusion from time of leukocyte transfusion); fever and chills are not uncommon after first few administrations of drug; rare acute reactions may include hypotension, bronchospasm, arrhythmias, and shock

Drug Name	Fluconazole (Diflucan)
Description	Comparative study demonstrates that fluconazole is less effective than itraconazole for treatment of sporotrichosis; nonetheless, may be useful in patients unable to tolerate itraconazole. A synthetic broad-spectrum bistriazole oral antifungal agent that is a highly selective inhibitor of fungal cytochrome P-450 and sterol C-14 alpha-demethylation.
Adult Dose	400 mg PO qd for lymphocutaneous sporotrichosis or disseminated sporotrichosis
Pediatric Dose	3-6 mg/kg PO qd for 14-28 d or 6-12 mg/kg qd, depending on severity of infection
Contraindications	Documented hypersensitivity
Interactions	Levels may increase with hydrochlorothiazides; fluconazole levels may decrease with chronic coadministration of rifampin; may increase concentrations of theophylline, phenytoin, tolbutamide, cyclosporine, glyburide, and glipizide; effects of anticoagulants may increase with fluconazole coadministration
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Closely monitor patients who develop rashes during treatment, discontinue drug if lesions progress; may cause clinical hepatitis, cholestasis, and fulminant hepatic failure (including fatalities), especially when a serious underlying medical condition such as AIDS or a malignancy is present and often with coadministration of multiple medications; not recommended in nursing mothers

Drug Name	Saturated solution of potassium iodide (SSKI)
Description	Difficult for many patients to tolerate. This remains a useful treatment for cutaneous or lymphocutaneous sporotrichosis. Mechanism of action in sporotrichosis is unknown.
Adult Dose	300-500 mg (6-10 gtt) PO tid
Pediatric Dose	Children: Administer as in adults Infants: 150-250 mg (3-6 gtt) PO tid
Contraindications	Documented hypersensitivity; pulmonary edema; bronchitis; tuberculosis; hyperkalemia
Interactions	Increases lithium toxicity by producing additive hypothyroid effects
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Prolonged use may result in hypothyroidism; caution in patients with renal failure or GI obstruction

Drug Name	Terbinafine (Lamisil)
Description	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 pulverized easily for use in children and is not palatable.
Adult Dose	250 mg PO bid to 500 mg PO bid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	May decrease cyclosporine effects; toxicity of terbinafine may increase with rifampin and cimetidine
Pregnancy	X - Contraindicated in pregnancy
Precautions	Discontinue use if chemical irritation develops with topical use; if hepatobiliary dysfunction, neutropenia, Stevens-Johnson syndrome, or changes in ocular lens or retina develop, discontinue use

FOLLOW-UP

Section 8 of 11  

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Further Outpatient Care

• Strains of sporotrichosis that cause cutaneous or lymphocutaneous sporotrichosis grow better at 35 rather than 37 degrees Celsius; therefore, topical heat application to lesions may be of adjunctive benefit.

Deterrence/Prevention

• Exercise efforts to minimize cutaneous inoculation. This includes wearing gloves and other protective clothing when gardening. Use of gloves when handling animals with skin lesions also minimizes the risk of zoonotic transmission.

Prognosis

• Cutaneous or lymphocutaneous sporotrichosis: Complete recovery without scarring is the expected outcome if disease is treated appropriately; however, the therapy required to cure the disease is protracted and expensive.
• Pulmonary sporotrichosis
• • Limited data are available on the response to treatment; however, the evidence suggests that most patients respond to itraconazole therapy. Those who do not respond to itraconazole require treatment with amphotericin B.
  • Pulmonary sporotrichosis contributes to the decline in respiratory function in patients with COPD.
• Osteoarticular sporotrichosis: Over 70% of patients with osteoarticular sporotrichosis have a clinical response to treatment with itraconazole. Relapse may occur. Severe disability can result from unrecognized chronic osteoarticular sporotrichosis.
• Disseminated sporotrichosis: Most patients respond to initial amphotericin B therapy. In patients with AIDS, life-long suppressive itraconazole therapy following induction therapy with amphotericin B appears to be necessary to control infection.

Patient Education

• Patients with all forms of sporotrichosis must be educated about the need for protracted antifungal therapy.
• Multiple sporotrichosis infections can occur in the same patient, suggesting that protective immunity may not always result from treated infection. Instruct patients with persistent occupational or avocational exposure about methods of prevention.
• For excellent patient education resources, visit eMedicine's Yeast and Fungal Infections Center. Also, see eMedicine's patient education article Sporotrichosis.

MISCELLANEOUS

Section 9 of 11  

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Medical/Legal Pitfalls

• The principal medical legal pitfall involves failure to consider sporotrichosis in the differential diagnosis in the appropriate setting.

MULTIMEDIA

Section 10 of 11  

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• Multimedia
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Media file 1:  This photo depicts cutaneous, disseminated sporotrichosis in an AIDS patient before and after therapy. (Courtesy of Leonard N. Slater, MD)
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Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
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• Chapman SW, Pappas P, Kauffmann C, et al. Comparative evaluation of the efficacy and safety of two doses of terbinafine (500 and 1000 mg day(-1)) in the treatment of cutaneous or lymphocutaneous sporotrichosis. Mycoses. Feb 2004;47(1-2):62-8. [Medline].
• Kauffman CA, Pappas PG, McKinsey DS, et al. Treatment of lymphocutaneous and visceral sporotrichosis with fluconazole. Clin Infect Dis. Jan 1996;22(1):46-50. [Medline].
• Kauffman CA. Sporotrichosis. Clin Infect Dis. Aug 1999;29(2):231-6; quiz 237. [Medline].
• Kauffman CA, Hajjeh R, Chapman SW. Practice guidelines for the management of patients with sporotrichosis. For the Mycoses Study Group. Infectious Diseases Society of America. Clin Infect Dis. Apr 2000;30(4):684-7. [Medline].
• Lyon GM, Zurita S, Casquero J, et al. Population-based surveillance and a case-control study of risk factors for endemic lymphocutaneous sporotrichosis in Peru. Clin Infect Dis. Jan 1 2003;36(1):34-9. [Medline].
• Ramirez J, Byrd RP, Roy TM. Chronic cavitary pulmonary sporotrichosis: efficacy of oral itraconazole. J Ky Med Assoc. Mar 1998;96(3):103-5. [Medline].
• Sharkey-Mathis PK, Kauffman CA, Graybill JR, et al. Treatment of sporotrichosis with itraconazole. NIAID Mycoses Study Group. Am J Med. Sep 1993;95(3):279-85. [Medline].
• Silva-Vergara ML, Maneira FR, De Oliveira RM, et al. Multifocal sporotrichosis with meningeal involvement in a patient with AIDS. Med Mycol. Mar 2005;43(2):187-90. [Medline].
• Smego RA, Castiglia M, Asperilla MO. Lymphocutaneous syndrome. A review of non-sporothrix causes. Medicine (Baltimore). Jan 1999;78(1):38-63. [Medline].
• Winn RE. A contemporary view of sporotrichosis. Curr Top Med Mycol. 1995;6:73-94. [Medline].

Article Last Updated: Jan 4, 2007