Sporotrichosis

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Background

Sporotrichosis, also known as rose gardener's disease, is a subacute or chronic infection caused by the saprophytic dimorphic fungus Sporothrix schenckii. Although only one species of Sporothrix was classically described, phenetic and genetic studies have identified additional Sporothrix species.[1] Knowledge of the geographic distribution, virulence, clinical presentation, and response to antifungal therapy of these newly identified species is an area of active research.[2, 3, 4]

The characteristic infection involves suppurating subcutaneous nodules that progress proximally along lymphatic channels (lymphocutaneous sporotrichosis). Primary pulmonary infection (pulmonary sporotrichosis) is rare, as is direct inoculation into tendons, bursae, or joints. Osteoarticular sporotrichosis is caused by direct inoculation or hematogenous seeding. In rare cases, disseminated S schenckii infection (disseminated sporotrichosis) occurs, characterized by disseminated cutaneous lesions and involvement of multiple visceral organs; this occurs most commonly in persons with AIDS. A thorough review of the topic was published by Barros et al in 2011.[5]

Pathophysiology

Infection with the dimorphic soil fungus S schenckii is usually acquired from organic matter through cutaneous inoculation. The mycosis has also been transmitted from animals through bites or scratches. Cats have been responsible for cases among veterinarians[6] and for a large outbreak in Rio de Janeiro, Brazil.[7] See the image below.



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Photomicrograph that shows the conidiophores and conidia of the fungus Sporothrix schenckii. Courtesy of CDC Public Health Image Library.

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 fungal infection spreads from the initial lesion along lymphatic channels, forming the chain of indolent nodular and ulcerating lesions typical of lymphocutaneous sporotrichosis.

Other tissues are involved by direct extension and, less often, by hematogenous dissemination. The most common extracutaneous infection 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 of sporotrichosis appears to result from inhalation of the organism. This form is characterized by a chronic cavitary pneumonia that is clinically and radiographically indistinguishable from tuberculosis and histoplasmosis. This form of sporotrichosis is most common in individuals with severe underlying chronic obstructive pulmonary disease (COPD) and alcoholism.[8] Sporotrichal infections affecting the sinuses, kidney, subglottic region, and retina have been described.[9, 10]

Epidemiology

Frequency

United States

The incidence of sporotrichosis is not precisely known but is estimated at 1-2 cases per million population. An estimated 200-250 cases occur per year. A large outbreak associated with Wisconsin-grown sphagnum moss involving 15 states occurred in 1988.[11]

International

Sporotrichosis occurs worldwide, with focal areas of hyperendemicity. The global incidence is unknown. In the highlands of Peru, the incidence of sporotrichosis is approximately 1 case per 1000 people.[12] China is a serious endemic region.[13] Epidemics have been described in western Australia,[14] Brazil,[7] and South Africa.

Mortality/Morbidity

Spontaneous resolution of cutaneous and lymphocutaneous forms of sporotrichosis has been documented.

The prognosis is excellent for complete recovery after therapy, although the response to therapy may vary.

Pulmonary sporotrichosis may contribute to declining pulmonary function in patients with COPD.

Osteoarticular sporotrichosis may result in significant morbidity in the form of 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

Sporotrichosis has no known racial predilection.

Sex

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

Age

In developed nations, sporotrichosis is most common among adults. However, in tropical regions and in areas of hyperendemicity, sporotrichosis may be more common in children and adolescents. See the Medscape Reference article Pediatric Sporotrichosis for more information.

History

The presentation of sporotrichosis varies and is determined mainly by the immune status of the host and the location of the infection. Other factors such as the virulence of the infecting species and ability to grow at different temperatures may also play a role.[15, 2, 3]

Sporotrichosis is typically classified as cutaneous or extracutaneous. The cutaneous form is divided into lymphocutaneous, fixed, and disseminated.

Cutaneous sporotrichosis

Lymphocutaneous sporotrichosis: The primary lesion develops at the site of cutaneous inoculation, typically in the distal upper extremities. After several weeks, new lesions appear along the lymphatic tracts. Patients with this form are typically afebrile and not systemically ill. The lesions usually cause minimal pain. Many affected patients have received one or more courses of antibacterial therapy without benefit.[16, 17]

The fixed cutaneous form is characterized by a painless violaceous or erythematous plaque that may ulcerate or become verrucous. This presentation should be considered when a wound fails to heal. There are no satellite lesions.[18]

The disseminated cutaneous form is usually seen in immunosuppressed individuals. This form of the disease can be the initial presentation of HIV infection or may develop as part of an immune reconstitution syndrome.[19, 20, 21]

Hypersensitivity reactions such as erythema nodosum or erythema multiforme have been associated with the zoonotic species Sporothrix brasiliensis.[4]

Extracutaneous sporotrichosis

Pulmonary sporotrichosis

Patients with this form of sporotrichosis usually have severe underlying COPD and present with subacute or chronic pneumonia.[22] The presenting symptoms of pulmonary sporotrichosis are not specific but typically include increased cough and few constitutional symptoms.

Osteoarticular sporotrichosis

Sporotrichosis may present as a chronic arthritis that is often confused with rheumatoid arthritis or other chronic inflammatory arthritis. In many cases, the osteoarticular sporotrichosis persists for 30 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 with culture. Cutaneous or lymphocutaneous lesions are not prominent in these patients.

The process generally begins as a monoarticular arthritis, especially of the knee, but other joints may become involved successively. The patient usually has pain upon motion, but not the severe limitation characteristic of bacterial arthritis. Systemic illness is usually absent. Functional impairment due to osteoarticular sporotrichosis may become severe.[23]

Disseminated sporotrichosis

In rare cases, sporotrichosis involves 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. In some cases, the only symptom is subtle changes in mental status. Patients with AIDS who develop disseminated sporotrichosis may present with cutaneous dissemination, which manifests as nodules, ulcers, or both, with or without evidence of visceral involvement and meningitis.[24] Sporotrichosis in persons with AIDS can also manifest as multifocal tenosynovitis or arthritis resembling disseminated gonococcal infection or a seronegative spondyloarthropathy.[25]

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. See the images below.



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Lymphocutaneous sporotrichosis.



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Lymphocutaneous sporotrichosis.



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Lymphocutaneous sporotrichosis.



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Ulcerated lesion in the cheek of a child. Note the satellite lesions. Courtesy of Todd Mollet, MD, University of Texas Southwestern Medical Center.

Pulmonary sporotrichosis: The physical examination findings in patients with pulmonary sporotrichosis are typically dominated by their underlying COPD. No physical findings are specific for 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 that complicate 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. See the image below.



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This photo depicts cutaneous disseminated sporotrichosis in a patient with AIDS before and after therapy. Courtesy of Leonard N. Slater, MD.

Causes

Sporotrichosis is caused by infection with one of the species of the S schenckii complex. More than six species, such as S schenckii sensu stricto, S brasiliensis, Sporothrix globosa, Sporothrix mexicana, and Sporothrix albicans, have been identified via molecular techniques.[1, 26]

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 persons with a history of alcoholism.

Immunosuppressing states such as HIV infections and AIDS predispose to disseminated cutaneous sporotrichosis and hematogenously disseminated sporotrichosis, including sporotrichotic meningitis.[27, 24] This clinical observation, combined with studies in animal models, indicates the importance of cell-mediated immunity in the host defense against sporotrichosis.

Laboratory Studies

Cell culture

Definitive diagnosis of sporotrichosis at any site requires the isolation of S schenckii in a specimen culture from a normally sterile body site.

The organism can be recovered with 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 is often low. Therefore, repeated large-volume cultures may be necessary for diagnosis of sporotrichosis.

Occasionally, S schenckii (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 is common; this is occasionally accompanied by the presence of an asteroid body, but this picture is not specifically diagnostic for sporotrichosis.

Serological techniques

Antibody measurement techniques are available.[28]

Such tests demonstrate significant interlaboratory variability in sensitivity and specificity; therefore, they should rarely serve as the sole basis for diagnosis of sporotrichosis.

They can be useful to raise diagnostic suspicion and to 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).[29]

Polymerase chain reaction (PCR)–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. Chest CT scanning is supportive but not specifically diagnostic of sporotrichosis.

Procedures

Arthrocentesis: Patients with subacute or chronic arthritis should undergo diagnostic arthrocentesis. Sporotrichotic arthritis causes 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 biopsy samples. See the image below.



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Cigar-shaped yeast of Sporothrix schenckii in tissue macrophages in a biopsy specimen.

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 Summary

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

The orally available azole antifungals are the drugs of choice for cutaneous or lymphocutaneous sporotrichosis in developed nations. Ketoconazole has been used but is less effective than itraconazole or fluconazole; thus, ketoconazole is no longer indicated. Fluconazole is less effective than itraconazole.[30] Itraconazole is the drug of choice for all types of sporotrichosis but CNS and disseminated sporotrichosis.[31] Terbinafine has been demonstrated to be effective in the treatment of lymphocutaneous sporotrichosis, but no comparative data with itraconazole therapy exist.[32]

The following is a summary of recent published guidelines for the medical management of sporotrichosis:[33]

Itraconazole (Sporanox)

Clinical Context:  A DOC for many forms of sporotrichosis. A synthetic triazole antifungal agent that inhibits fungal cell growth by inhibiting the cytochrome P-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.

Amphotericin B, liposomal (AmBisome)

Clinical Context:  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.

Fluconazole (Diflucan)

Clinical Context:  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.

Saturated solution of potassium iodide (SSKI)

Clinical Context:  Difficult for many patients to tolerate. This remains a useful treatment for cutaneous or lymphocutaneous sporotrichosis. Mechanism of action in sporotrichosis is unknown.

Terbinafine (Lamisil)

Clinical Context:  A fungicidal allylamine antifungal agent. An alternative agent for treatment of cutaneous or lymphocutaneous sporotrichosis unresponsive to itraconazole or if itraconazole cannot be tolerated. 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.

Class Summary

These agents have a mechanism of action that may involve an alteration of RNA and DNA metabolism.

Further Outpatient Care

S schenckii strains that cause cutaneous or lymphocutaneous sporotrichosis grow better at 35°C than at 37°C; therefore, topical heat application to lesions may be of adjunctive benefit.

Deterrence/Prevention

Exercise efforts to minimize cutaneous inoculation of S schenckii. 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 with appropriate treatment; however, the therapy required to cure the disease is protracted and expensive.

Pulmonary sporotrichosis

Limited data are available on the response to treatment; however, evidence suggests that most cases of pulmonary sporotrichosis respond to itraconazole therapy. Those who do not respond to itraconazole require treatment with amphotericin B.

Pulmonary sporotrichosis contributes to declined respiratory function in patients with COPD.

Osteoarticular sporotrichosis

More than 70% of patients with osteoarticular sporotrichosis have a clinical response to itraconazole therapy. 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 eMedicineHealth's Infections Center. Also, see eMedicineHealth's patient education article Sporotrichosis.

What is sporotrichosis?What is the pathophysiology of sporotrichosis?What is the prevalence of sporotrichosis in the US?What is the global prevalence of sporotrichosis?What is the prognosis of sporotrichosis?What is the racial predilection of sporotrichosis?What is the sexual predilection of sporotrichosis?Which patient groups have the highest prevalence of sporotrichosis?How is sporotrichosis classified?What are the signs and symptoms of cutaneous sporotrichosis?What are the signs and symptoms of pulmonary sporotrichosis?What are the signs and symptoms of osteoarticular sporotrichosis?What are the signs and symptoms of disseminated sporotrichosis?Which physical findings are characteristic of cutaneous or lymphocutaneous sporotrichosis?Which physical findings are characteristic of extracutaneous sporotrichosis?What causes sporotrichosis?What are the differential diagnoses for Sporotrichosis?What is the role of cultures in the workup of sporotrichosis?What is the role of serologic testing in the workup of sporotrichosis?What is the role of imaging studies in the workup of sporotrichosis?What is the role of arthrocentesis in the workup of sporotrichosis?What is the role of biopsy in the workup of sporotrichosis?Which histologic findings are characteristic of sporotrichosis?How is sporotrichosis treated?What is the role of surgery in the treatment of sporotrichosis?Which activity modifications are beneficial for patients with sporotrichosis?Which medications are used in the treatment of sporotrichosis?What are the guidelines for the medical management of sporotrichosis?Which medications in the drug class Antifungal agents are used in the treatment of Sporotrichosis?What is the role of topical heat in the treatment of sporotrichosis?How is sporotrichosis prevented?What is the prognosis of cutaneous or lymphocutaneous sporotrichosis?What is the prognosis of pulmonary sporotrichosis?What is the prognosis of osteoarticular sporotrichosis?What is the prognosis of disseminated sporotrichosis?What is included in patient education about sporotrichosis?

Author

Nelson Ivan Agudelo Higuita, MD, Associate Professor, Department of Internal Medicine, Section of Infectious Diseases, Program Director, Infectious Diseases Fellowship Program, University of Oklahoma Health Sciences Center; Attending Physician, Infectious Diseases Consultation Service, Department of General Internal Medicine, Oklahoma University Medical Center

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Thomas M Kerkering, MD, Chief of Infectious Diseases, Virginia Tech Carilion School of Medicine

Disclosure: Nothing to disclose.

Chief Editor

Pranatharthi Haran Chandrasekar, MBBS, MD, Professor, Chief of Infectious Disease, Department of Internal Medicine, Wayne State University School of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Pranatharthi Haran Chandrasekar, MBBS, MD, Professor, Chief of Infectious Disease, Department of Internal Medicine, Wayne State University School of Medicine

Disclosure: Nothing to disclose.

Acknowledgements

This article is an updated version of Dr. Ronald Greenfield's work.

In memory of a great physician and mentor.

References

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Photomicrograph that shows the conidiophores and conidia of the fungus Sporothrix schenckii. Courtesy of CDC Public Health Image Library.

Lymphocutaneous sporotrichosis.

Lymphocutaneous sporotrichosis.

Lymphocutaneous sporotrichosis.

Ulcerated lesion in the cheek of a child. Note the satellite lesions. Courtesy of Todd Mollet, MD, University of Texas Southwestern Medical Center.

This photo depicts cutaneous disseminated sporotrichosis in a patient with AIDS before and after therapy. Courtesy of Leonard N. Slater, MD.

Cigar-shaped yeast of Sporothrix schenckii in tissue macrophages in a biopsy specimen.

This photo depicts cutaneous disseminated sporotrichosis in a patient with AIDS before and after therapy. Courtesy of Leonard N. Slater, MD.

Photomicrograph that shows the conidiophores and conidia of the fungus Sporothrix schenckii. Courtesy of CDC Public Health Image Library.

Lymphocutaneous sporotrichosis.

Lymphocutaneous sporotrichosis.

Lymphocutaneous sporotrichosis.

Cigar-shaped yeast of Sporothrix schenckii in tissue macrophages in a biopsy specimen.

Ulcerated lesion in the cheek of a child. Note the satellite lesions. Courtesy of Todd Mollet, MD, University of Texas Southwestern Medical Center.