Sporotrichosis (Rose gardener’s disease)
Are You Confident of the Diagnosis?
What you should be alert for in the history
Sporotrichosis occurs worldwide, but is more common in tropical and temperate climates. Patients living in endemic regions such as Central and South America, Africa, and the Missouri and Mississippi River Valleys of the United States are at increased risk for exposure.
Many patients will describe a history of recent outdoor activity; penetrating trauma with plant thorns, wood splinters, or decaying vegetation; or close interaction with animals such as cats, rodents, and armadillos.
Characteristic findings on physical examination
Clinically, sporotrichosis may be classified into lymphocutaneous, fixed cutaneous, disseminated, and extracutaneous forms.
The lymphocutaneous form (over 75% of cases) manifests as indurated papules, pustules, or nodules that may ulcerate and spread with satellite lesions along the path of lymphatic vessels. Regional lymphadenopathy is common. The upper and lower extremities are most frequently affected (
Sporotrichosis. (Reprinted from Clinic in Derm, Vol 25 (2), Marcia Ramos-e-Silva, Camila Vasconcelos, Sueli Carneiro, Tania Cestari, Sporotrichosis, pp 181-187, Copyright (2007), with permission from Elsevier.)
The fixed cutaneous form (20% of cases) is characterized by papules, plaques, nodules, verrucous lesions, or superficial ulcers confined to a single area. Satellite lesions and lymphadenopathy are not typically seen. This is the most common form of sporotrichosis in children; the lesions usually occur on the face.
The disseminated form typically occurs in immunosuppressed individuals, and may involve the skin, lungs, meninges, osteoartricular system, and bony skeleton. Skin lesions have a variable presentation, including: ulcerative lesions, acneiform lesions, indurated plaques, or crusts.
The extracutaneous form is the rarest variant, and typically manifests without skin lesions. The predominant sites of infection are the osteoarticular structures. Clinically, patients may present with monoarthritis, synovial effusion, edema, and limited joint function. The hands, wrists, elbows, ankles, and knees are most commonly affected.
Epidemic sporotrichosis presents with variable morphologies, and has been associated with transmission from cats in Rio de Janeiro, Brazil. Presentations include: nodules, tubercules, pustules, cysts, gummatous lesions, ulcers, ulcerovegetative lesions, verrucous papules, and plaques, and all may occur with or without lymphadenopathy.
The most frequently involved areas are the upper extremities, followed by the lower extremities and face. Other associated manifestations may include erythema nodosum or erythema multiforme, in addition to arthralgias and arthritis.
Expected results of diagnostic studies
Fungal culture of pus, blood, or tissue fragment is the gold standard for the diagnosis of cutaneous sporotrichosis.
In vitro fungal dimorphism on microscopy is definitive, and direct examination using potassium hydroxide occasionally identifies the fungus.
Incubation is performed at 25°C, using sabouraud dextrose agar or potato dextrose agar, with the appearance of colonies within 3-5 days, but as long as 4 weeks, in some cases.
The cigar-shaped yeast is not readily visualized in hematoxylin-eosin stain or periodic acid-Schiff stain.
Histopathology demonstrates a nonspecific granulomatous inflammation with epithelial hyperplasia and a histiocytic plasma cell infiltrate, with occasional identification of the fungal asteroid body (
Sporotrichosis histopathology (H&E). (Reprinted from Clinic in Derm, Vol 25 (2), Marcia Ramos-e-Silva, Camila Vasconcelos, Sueli Carneiro, Tania Cestari, Sporotrichosis, pp 181-187, copyright 2007, with permission from Elsevier)
There are no reliable serologic tests for diagnosing sporotrichosis.
Imaging studies such as x-ray and computed tomography scan may help diagnose pulmonary and osteoarticular sporotrichosis.
Pulmonary disease is characterized by fibrosis of the lungs, as seen on chest x-ray, with cavitations, occasional hilar lymphadenopathy, and pleural effusions. Sputum culture, bronchoscopy with broncoalveolar lavage for culture, and transbronchial biopsy may be required for definitive diagnosis.
Meningeal sporotrichosis is diagnosed via cerebrospinal fluid (CSF) examination. CSF may demonstrate lymphocytic pleocytosis, increased protein, and hypoglycorrhachia. CSF fungal culture is confirmatory.
Synovial fluid aspiration and culture, and bone biopsy for histopathology and culture, are diagnostic tests for osteoartricular disease.
Intradermal sporotrichin skin testing is rarely used because it has a high false-postive and false-negative rate.
The differential diagnosis of cutaneous sporotrichosis particularly includes those conditions presenting with sporotrichoid spread, such as Mycobacterium marinum infections, but may also include leishmaniasis; other mycotic infections such as paracoccidioidomycosis, coccidioidomycosis, chromoblastomycosis, and blastomycosis; as well as other typical and atypical mycobacterial infections.
Bacterial pyodermas, primary syphilis, subcutaneous abscesses of tularemia, and cat-scratch disease are also mimickers of sporotrichosis. Pulmonary disease may present similarly to pulmonary tuberculosis, and extracutaneous disease may manifest as arthritis.
Common diagnostic tests to help distinguish sporotrichosis from diseases with similar presentations include mycobacterial cultures and acid-fast stains to rule out mycobacterial infections, and tissue Gram stains to rule out other infectious or foreign body processes.
Lack of tenderness and warmth, and failed antibiotic therapy, in addition to the presence of lymphadenopathy on physical exam, helps distinguish sporotrichosis from bacterial infections.
Who is at Risk for Developing this Disease?
People living in endemic regions of Central and South America, Africa, and the Missouri and Mississippi River Valleys of the United States are at increased risk for developing disease.
Veterinary workers, animal caretakers, cat owners, agricultural workers, and armadillo hunters are recognized as at-risk groups.
Typically, patients are healthy young adults under 30 years of age, although sporotrichosis may occur at any age. In general, there is no gender predilection.
Cat-transmitted epidemics of sporotrichosis have been well characterized in Rio de Janeiro, Brazil.
Immunocompromised patients are at increased risk for developing disseminated infection.
What is the Cause of the Disease?
Sporotrichosis is typically caused by Sporothrix schenckii, a dimorphic fungus ubiquitously found in soil, wood, or grain. Additionally, It may be found in association with certain animals. Other known related species of the genus Sporothrix that may cause the disease are S. albicans, S. brasiliensis, S. globosa, and S. mexicana.
Modes of transmission include:
- cutaneous implantation of the organism by abrasion or puncture wound from decaying vegetation, sphagnum moss, rosebush thorns, or soil
- zoonotic transmission from scratches or bites from cats, rodents, or armadillos
- inhalation of fungal conidia (rare)
Virulence factors include fungal dimorphism, protective melanin on cell walls, and antigenic polysaccharides involved in the induction of a cellular immune response and adhesion of the fungus to host cells.
The lesions of sporotrichosis are characterized as suppurative granulomas consisting of histiocytes and giant cells, neutrophils, and surrounding lymphocytes and plasma cells.
The predominant lymphocutaneous form results in the lymphatic spread of infection, with resulting satellite lesions along the path of the lymphatic vessels. In contrast, the fixed cutaneous form remains localized without lymphatic spread. Disseminated and extracutaneous forms are uncommon in immunocompetent individuals.
Systemic Implications and Complications
Other rare forms of sporotrichosis may occur systemically, via deep innoculation, inhalation, extension to nearby tissues, or hematogenous dissemination.
The meninges, osteoarticular system, lungs, eyes, genitals, and other viscera may be affected.
Systemic complications are found in immunosuppressed individuals with conditions such as human immunodeficiency virus or acquired immunodeficiency syndrome (AIDS), chronic alcoholism, diabetes mellitus, sarcoidosis, or tuberculosis. History of organ transplantation, malignancy, or use of immunosuppresive agents are also associated with risk of systemic manifestations.
Treatment options are summarized in
Treatment options for sporotrichosis.
|Disease Form||Medical (Oral/IV)||Surgical||Physical|
|Itraconazole||Surgical resection of involved lung|
Optimal Therapeutic Approach for this Disease
1. Itraconazole is an effective first-line therapy, with response rates shown to be greater than 90%, that is generally safe and well tolerated. We recommend therapy with itraconazole (200mg orally daily) until 2-4 weeks after all lesions have resolved, which usually results in a total of 3-6 months of treatment.
Historically, saturated solution of potassium iodide (SSKI) was the treatment of choice. Some clinicians currently maintain SSKI as first-line therapy (starting with 1 gram orally daily, and increasing to 3-6 grams daily) for an average of 3 months, with additional 2 months of therapy after all lesions have resolved. It should be noted that increased induration or erythema of the cutaneous lesions, or the development of local lymphadenopathy, may be expected after treatment initiation secondary to the immune response to killed fungal antigenic components.
2. Treatment of sporotrichosis in pediatric or pregnant patients is discussed below.
3. In nonresponders, we recommend higher doses of itraconazole (initially 200mg orally twice daily, which may be increased to 500mg twice daily as required), or one may add terbinafine (500mg orally twice daily), or SSKI.
4. In patients who cannot tolerate itraconazole, SSKI, or terbinafine, we recommend fluconazole (400-800mg daily) or local hyperthermia, as the fungus does not survive above 39° C.
Epidemic (cat-transmitted) sporotrichosis
1. Itraconazole (100mg orally once daily) for 4-36 weeks (median of 12 weeks) has successfully treated many patients in endemic areas such as Brazil.
2. In patients nonresponsive to the initial dose, higher doses of itraconazole (200-400mg orally daily) have proven efficacious.
1. In osteoarticular disease, we recommend coordination of therapy with infectious disease physicians, rheumatologists, or orthopedic surgeons. Often, itraconazole (200mg orally twice daily) for at least 12 months is the treatment of choice.
2. Amphotericin B lipid formulation (3-5mg/kg intravenously daily) or amphotericin B deoxycholate (0.7-1.0mg/kg intravenously daily) may be used until clinical improvement is evident, with a subsequent switch to itraconazole (200mg orally twice daily) for a combined total of at least 12 months.
3. Surgical debridement or draining of a septic joint may be beneficial in some cases, but surgery is not effective as monotherapy, and is rarely performed.
1. For severe lung disease, we recommend treatment in consultation with pulmonologists and infectious disease physicians. Often, amphotericin B lipid formulation (3-5mg/kg intravenously daily) is commenced as first-line therapy, as the lipid formulation is most well-tolerated by patients, but amphotericin B deoxycholate (0.7-1.0mg/kg intravenously daily) may also be an option.
Itraconazole (200mg orally twice daily) is recommended as step-down maintenance therapy, after the patient responds to initial treatment with amphotericin B, to complete a total of at least 12 months of therapy.
2. For less severe lung disease, we recommend itraconazole (200mg orally twice daily) for at least 12 months.
3. Surgical resection combined with amphotericin B is recommended for localized pulmonary disease.
1. For meningeal disease, we recommend internist, infectious disease, and subspecialist consultation. Most likely, amphotericin B lipid formulation (3-5mg/kg intravenously daily) will be first-line therapy, or possibly amphotericin B deoxycholate (0.7-1.0mg/kg intravenously daily). Once the patient initially responds to treatment, we recommend switching to itraconazole (200mg twice daily) as step-down therapy for a total of at least 12 months of therapy.
In general, patients with lymphocutaneous/cutaneous disease should be maintained on systemic therapy for 3-6 months, and patients with disseminated forms should be maintained on systemic therapy for at least 12 months. Patients with localized forms of disease respond well to treatment, while systemic disease in immunosuppressed hosts may be life threatening and require long-term systemic medications with potential toxicities.
Itraconazole and SSKI are both considered first-line agents in the treatment of lymphocutaneous/cutanous forms of disease, although there are no controlled studies comparing their efficacy and safety. In our opinion, itraconazole is generally better tolerated than SSKI.
It is important to consider common adverse effects and contraindictations of primary treatment modalities.
Itraconazole may cause gastritis, transaminitis, and pruritus, and is contraindicated in pregnancy. The capsule formulation has fewer gastrointestinal side effects than the oral solution. The capsule formulation is best absorbed with food, while the oral solution is best absorbed on an empty stomach. Serum levels of itraconazole should be determined after 2 weeks of use to ensure adequate drug bioavailability. Levels greater than or equal to 1ug/mL are considered adequate.
SSKI may result in a metallic taste in the mouth, gastritis, rhinitis, urticaria, angioedema, parotiditis, and hypothyroidism. SSKI may be mixed with juice or water for intake.
Amphotericin may cause fevers, chills, gastritis, and electrolyte, renal, and hematologic abnormalities. Amphotericin lipid formulations have fewer adverse effects than the amphotericin B deoxycholate formulation.
It is important to encourage preventive measures for epidemic sporotrichosis such as avoiding direct contact with causal agents by using protective eyewear, gloves, masks, and footwear.
Unusual Clinical Scenarios to Consider in Patient Management
In pediatric sporotrichosis, the treatment principles are the same, but the doses are different. Recommended pediatric doses include: itraconazole (6-10mg/kg to a maximum of 400mg orally daily), oral SSKI (1 drop into water or juice using a standardized eyedropper three times daily, increased as tolerated to a maximum 1 drop/kg or 40-50 drops three times daily, whichever is lower) and amphotericin B (0.7 mg/kg intravenously daily).
Pregnant or nursing patients
Pregnant or nursing women with sporotrichosis also require specialized care because of significant contraindications to first-line agents such as itraconazole (teratogenic) and SSKI (fetal thyroid toxicity). Terbinafine passes into breast milk, but is generally not considered harmful to the unborn child. It is recommended to use amphotericin in severe disease, or local hyperthermia in cutaneous disease. In less severe disease, another option is delay of initiation of itraconazole therapy until after delivery. Sporotrichosis does not pass to the unborn child.
Disseminated forms of disease in these patients are difficult to control, may be life threatening, or may result in chronic osteomyelitis, arthritis, and joint deformity or recurrent meningeal infection. Lifelong prophylactic therapy with itraconazole is a strong consideration in these patients.
What is the Evidence?
Bonifaz, A, Vazquez-Gonzalez, D. "Sporotrichosis: an update". G Ital Dermatol Venerol. vol. 145. 2010. pp. 659-73.(The authors from the departments of mycology and dermatology, General Hospital of Mexico, Mexico City, review the most recent aspects of sporotrichosis. Epidemiology, etiology, clinical features, diagnosis, and treatment modalities are discussed. The causative agents include dimorphic fungi of Sporothrix schenckii complex. The clinical manifestations are variable, with localized and systemic forms of infection. Treatment options include SSKI, itraconazole, terbinafine, thermotherapy, and amphotericin B.)
Davis, BA. "Sporotrichosis". Dermatol Clin. vol. 14. 1996. pp. 69-76.(The author at the University of Pittsburgh School of Medicine, Pennsylvania, reviews the clinical and diagnostic features of sporotrichosis. Sporothrix schenckii is a ubiquitous fungus found in decaying agricultural matter. The most common clinical infection is characterized by cutaneous and subcutaneous lesions with lymphatic spread. Systemic disease may involve bone, muscle, lungs, and the central nervous system. Diagnosis is based on both clinical presentation and laboratory studies.)
Kauffman, C, Bustamante, B, Chapman, S, Pappas, P. "Clinical practice guidelines for the management of sporotrichosis: 2007 update by the Infectious Disease Society of America". Infec Dis Clin. vol. 45. 2007. pp. 1255-65.(A panel of experts from the University of Michigan Medical School, University of Mississippi Medical Center, University of Alabama at Birmingham, and Universidad Peruana Cayetano Heredia recommend management guidelines for patients with sporotrichosis. The panel addressed important clinical questions regarding optimal treatment options, including dose, rate of response, and duration of treatment. Management principles were addressed for lymphocutaneous and cutaneous, osteoarticular, pulmonary, meningeal, and disseminated sporotrichosis in adults, children, and pregnant women. The authors also review the quality of evidence from case series and nonrandomized controlled trials.)
Limper, H, Knox, KS, Sarosi, GA, Ampel, NM, Bennett, JE, Catanzaro, A. "An official American Thoracic Society statement: treatment of fungal infections in adult pulmonary and critical care patients". Am J of Resp and Critic Care Med. vol. 183. 2011. pp. 96.(The American Thoracic Society updated the clinical guidelines for treating various pulmonary fungal infections, including sporotrichosis. The authors recommended itraconazole and amphotericin B as treatment options for pulmonary sporotrichosis. For mild to moderately severe disease, itraconazole was the suggested therapy, while amphotericin B followed by itraconazole therapy was suggested for severe disease.)
Silva, MR, Vasconcelos, C, Carneiro, S, Cestari, T. "Sporotrichosis". Clinic in Derm. vol. 25. 2007. pp. 181-7.(The authors from the Federal University of Rio de Janeiro, Brazil, review the pathogenesis, etiology, epidemiology, clinical manifestations, diagnosis, and treatment guidelines for sporotrichosis. The authors suggest that itraconazole is the drug of choice for treating localized disease, while amphotericin B is the drug of choice for disseminated infection.)
Reed, KD, Moore, FM, Geiger, GE, Stemper, ME. "Zoonotic transmission of sporotrichosis: case report and review". Clin Infect Dis. vol. 16. 1993. pp. 384-7.(The authors from the microbiology section, Marshfield Laboratories, Wisconsin, report a case of sporotrichosis in a veterinarian who acquired infection from a cat. A literature review on zoonotic transmission of sporotrichosis identified cats as the major source of zoonotic spread. Preventive measures were also addressed.)
Schechtman, RC. "Sporotrichosis: part II". Skinmed. vol. 8. 2010. pp. 275-80.(The authors from the Instituto de Dermatologia, Rio de Janeiro, Brazil, review the current diagnostic criteria and recommended treatment options for sporotrichosis. Sporotrichosis is caused by implantation of Sporothrix schenckii fungus, and diagnosis is based primarily on isolation of the fungus in culture. SSKI and itraconazole are regarded as primary treatments, while terbinafine is another therapeutic alternative. The authors also review studies on the epidemiology and antifungal susceptibility of Sporothrix strains through molecular diagnosis.)
Schubach, A, Barros, MB, Wanke, B. "Epidemic sporotrichosis". Curr Opin Infect Dis. vol. 21. 2008. pp. 129-33.(The authors from the Instituto de Pesquisa Clinica Evandro Chagas, Rio de Janeiro, Brazil, review epidemic sporotrichosis in association with zoonotic transmission from cats. The clinical features of human and feline sporotrichosis were discussed, in addition to experiences in treating this epidemic form of disease.)
Tlougan, B, Podjasek, J, Patel, S, Nguyen, X, Hansen, R. "Neonatal sporotrichosis". Pediatr Dermatol. vol. 26. 2009. pp. 563-5.(The authors from the departments of dermatology at New York University Langone Medical Center, Mayo Clinic, Northwestern University Feinberg School of Medicine, and Phoenix Children’s Hospital present a case of the youngest reported neonate with fixed cutaneous sporotrichosis. The authors also review the literature on pediatric sporotrichosis.)
Ware, AJ, Cockerell, CJ, Skiest, DJ, Kussman, HM. "Disseminated sporotrichosis with extensive cutaneous involvement in a patient with AIDS". J Am Acad Dermatol. vol. 40. 1999. pp. 350-5.(The authors from the University of Texas Southwestern Medical Center describe a case report of disseminated sporotrichosis in a patient with AIDS. The authors reviewed the unusual clinical presentation of this form of infection, diagnostic studies, and treatment options.)
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