Version May 2024
INTRODUCTION — Sporotrichosis is a subacute to chronic infection caused by the dimorphic fungal genus Sporothrix. The most common cause of infection is Sporothrix schenckii. Less commonly infection is caused by Sporothrix brasiliensis, Sporothrix globosa, Sporothrix pallida, or Sporothrix mexicana [1]. Infection usually involves cutaneous and subcutaneous tissues but can occasionally occur in other sites, primarily in immunocompromised patients. Activities associated with the development of sporotrichosis include landscaping, rose gardening, and other activities that involve inoculation of soil through the skin. Most persons who develop sporotrichosis are healthy adults. Children and older adults are reported with sporotrichosis less often [2,3].
The typical and atypical clinical manifestations of sporotrichosis and the diagnosis of this infection will be reviewed here. The mycology, epidemiology, and treatment of sporotrichosis are discussed separately. (See "Basic biology and epidemiology of sporotrichosis" and "Treatment of sporotrichosis".)
CLINICAL PRESENTATION AND DIFFERENTIAL DIAGNOSIS
Spectrum of disease — Sporotrichosis usually develops as a cutaneous syndrome following inoculation of fungus from soil, moss, or other organic material [4]. Occasionally, S. schenckii conidia may be inhaled, leading to a pulmonary infection. In immunocompromised hosts, the infection can disseminate hematogenously to affect other organ systems (eg, central nervous system). Extracutaneous forms of sporotrichosis may present in isolation or as a manifestation of more disseminated disease. Symptoms of extracutaneous sporotrichosis can be subtle and diagnosis is often delayed.
Nodular lymphangitis — Lymphocutaneous sporotrichosis is the most common form of sporotrichosis seen in clinical practice and presents as nodular lymphangitis. The typical host is a healthy individual with an outdoor occupation or avocation (eg, landscaping, gardening) that provides exposure to the fungus. Days to weeks after cutaneous inoculation of the fungus, a papule develops at the site of inoculation. This primary lesion usually ulcerates but may remain nodular with overlying erythema; drainage from the lesion is not grossly purulent and has no odor. Similar lesions subsequently occur along lymphatic channels proximal to the original lesion, a finding called sporotrichoid spread or nodular lymphangitis (picture 1A-B). Pain is generally mild and systemic symptoms are typically absent [5]. The symptoms do not resolve without treatment.
The differential diagnosis for lymphocutaneous sporotrichosis includes nontuberculous mycobacterial infection (especially Mycobacterium marinum), Nocardia infections (particularly Nocardia brasiliensis), and Leishmania brasiliensis infection. Other fungal, bacterial, and viral infections can also rarely cause a lymphocutaneous syndrome [6]. Epidemiologic clues in the patient’s history may help in differentiating between the infections, but culture and histopathology evaluation are necessary for diagnosis. (See "Lymphangitis", section on 'Nodular lymphangitis'.)
Other less common presentations
Other dermatologic manifestations — Some patients have a chronic, fixed cutaneous lesion that occurs after local cutaneous inoculation; this form is seen most often in endemic regions in South America (picture 2 and picture 3 and picture 4) [7], and may be more common in children, especially those with lesions on the face [2]. These fixed lesions, frequently found on the face and extremities, tend to be plaque-like or verrucous, but they may also ulcerate. The cutaneous form will not resolve without therapy although the lesion may appear to regress and flare periodically, even in the absence of treatment.
Presence of cutaneous lesions at noncontiguous sites suggests disseminated sporotrichosis [8]. Dissemination may be limited to the skin (disseminated cutaneous sporotrichosis) or involve other organ systems (systemic disseminated sporotrichosis). Presence of disseminated cutaneous spread should prompt evaluation for systemic dissemination. Further discussion of systemic disseminated disease is found elsewhere. (See 'Disseminated disease' below.)
Pulmonary involvement — Pulmonary sporotrichosis has been reported most frequently in middle-aged men and especially in patients with chronic obstructive pulmonary disease and/or those with heavy alcohol use [9-13]. This form of disease is acquired after the inhalation of S. schenckii conidia. Patients often have constitutional complaints of fever, night sweats, weight loss, and fatigue as well as respiratory complaints including dyspnea, cough, purulent sputum, and hemoptysis.
Chest radiographic findings include unilateral or bilateral upper lobe cavities with variable amounts of fibrosis and/or scattered nodular lesions (image 1). Dissemination of infection outside of the lungs is uncommon. In almost all cases, untreated pulmonary sporotrichosis progresses to respiratory failure and death.
Clinical and radiographic features are very similar to those seen in pulmonary tuberculosis. The differential diagnosis also includes other chronic fungal infections (especially histoplasmosis) and sarcoidosis. Diagnosis requires isolation of Sporothrix on culture.
When pulmonary involvement is a manifestation of disseminated sporotrichosis, the upper respiratory tract is more likely to be involved. When the lower respiratory tract is involved, diffuse infiltrates are more often noted than localized cavitary lesions [14].
Osteoarticular involvement — Osteoarticular disease is typically seen in middle-aged men and more often in those with heavy alcohol use [15,16]. It usually arises from hematogenous spread but may also occur after local inoculation. Osteoarticular sporotrichosis is chronic with progressively decreased range of motion, pain, and swelling. Draining sinuses can be a late manifestation. Infection may involve one or several joints and may or may not be accompanied by overlying cutaneous lesions. The most commonly affected joints are the knee, elbow, wrist, and ankle. Joint infection is more common than osteomyelitis. When bone is involved, it usually occurs contiguous to an infected joint rather than as isolated osteomyelitis. Bursitis and tenosynovitis have been reported, sometimes presenting as a nerve entrapment syndrome. Because diagnosis is often delayed, the outcome is poor.
Differential diagnosis includes mycobacterial and other fungal causes of osteoarticular infection.
Neurologic involvement — Meningitis is a rare manifestation of sporotrichosis, occurring mostly in those with cellular immune defects, especially in individuals with AIDS [17-19]. Meningitis may be an isolated finding or a manifestation of disseminated disease. In those patients who have isolated meningitis, the course is usually chronic and symptoms include weeks to months of fever and headache [20,21].
The cerebrospinal fluid findings include lymphocytic pleocytosis, elevated protein, and decreased glucose.
Differential diagnosis includes tuberculosis and other fungal infections (eg, cryptococcal meningitis). Diagnosis of sporotrichosis is based on microbiological culture data obtained from the cerebrospinal fluid.
Disseminated disease — Disseminated sporotrichosis (involvement of more than one organ) is very uncommon, with cases occurring primarily in patients with AIDS and less commonly in other immunocompromised patients [8,17,18,22,23]. Some patients have associated skin lesions, although many do not. S. schenckii can also rarely cause infection of the pericardium, eye, perirectal tissues, larynx, breast, epididymis, spleen, liver, bone marrow, and lymph nodes [4,24,25]. Involvement of other organ systems discussed above can also be observed (See 'Pulmonary involvement' above and 'Osteoarticular involvement' above and 'Neurologic involvement' above.)
Patients with HIV are at risk for disseminated disease but may also present with milder forms of infection as well; those with CD4 counts <200 cells/microL are at highest risk of disseminated disease [17,23,24,26]. In a few individuals, an immune reconstitution inflammatory syndrome leading to worsening cutaneous lesions has been described when antiretroviral therapy was initiated [27].
The largest series of sporotrichosis cases among patients with HIV was reported from Rio de Janeiro, Brazil, where an ongoing zoonotic outbreak of infection with S. brasiliensis was traced back to domestic cats [18]. Among the 21 cases described, disseminated sporotrichosis and lymphocutaneous sporotrichosis were noted in seven patients each. Five others had widespread cutaneous lesions and two had fixed cutaneous lesions with no spread. Only two of the patients who had disseminated infection had meningitis. All patients with CD4 counts <200 cells/microL presented with disseminated cutaneous or systemic disease. The mean CD4 count for the 21 patients was 364 cells/microliter (range 22 to 1100) suggesting there is likely a wider spectrum of infections in patients who have HIV infection than had been previously thought. This observation could be due to earlier diagnosis during an identified outbreak.
DIAGNOSIS
When to suspect sporotrichosis — Cutaneous and extracutaneous forms of sporotrichosis should be suspected in different clinical circumstances.
●Cutaneous forms of disease – Any patient with likely environmental exposure who presents with nodular lymphangitis or a nonhealing, nonpurulent painless skin lesion should prompt the clinician to consider cutaneous sporotrichosis. (See 'Nodular lymphangitis' above and 'Other dermatologic manifestations' above.)
●Extracutaneous forms of disease – Extracutaneous sporotrichosis is rare but should be considered in certain hosts with predisposing conditions and possible environmental exposure, particularly when lesions have not responded to usual antibacterial therapy. As noted above, pulmonary sporotrichosis is more common in patients who have chronic obstructive pulmonary disease, and osteoarticular sporotrichosis is associated with heavy alcohol use. Disseminated infection occurs almost entirely in immunocompromised persons, especially those with advanced HIV (eg, low CD4 counts). (See 'Other less common presentations' above.)
Approach to diagnosis — When sporotrichosis is suspected, culture from tissue biopsy, sputum, body fluids, or aspirated material from a skin lesion should be collected. Histopathology is typically also performed simultaneously. Diagnosis of classic lymphocutaneous sporotrichosis is usually prompt given the highly suggestive clinical features. However, diagnosis of the less classic forms of sporotrichosis, such as osteoarticular or visceral disease, is almost always delayed [28,29].
Cultures are diagnostic if positive. Growth often appears within five days, but sometimes can take several weeks. Although special stains (eg, methenamine silver stain) can be performed for histopathology, they are often negative, because the number of organisms required to cause disease is small.
Although serological assays exist, they are not routinely available and are not recommended for the diagnosis of sporotrichosis.
Newer molecular techniques have been established within reference laboratories but are not readily available for diagnosis in the settings in which most cases of sporotrichosis are found [30].
Culture — Culture is the gold standard for establishing a diagnosis of sporotrichosis and is also the most sensitive method [31]. Aspirated material from a lesion or a sample from a tissue biopsy, sputum, or body fluids should be inoculated onto Sabouraud’s dextrose agar and incubated at room temperature. Incubation at this temperature facilitates growth of the mycelial phase of S. schenckii with the characteristic arrangement of conidia on the hyphae. Rarely, S. schenckii has been grown from culture of blood using the lysis-centrifugation method [32].
Growth may appear within five days, but sometimes can take several weeks. To ensure that the fungus is S. schenckii, the mold phase should be converted to the yeast phase on blood agar at 37°C [4]. Increasingly, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF) has been used to identify Sporothrix to the species level [33,34].
Histopathology — The usual histopathologic picture is a mixed granulomatous and pyogenic process. The organisms may not be visualized even with special stains for fungi, such as methenamine silver and periodic acid Schiff stains, because the number of organisms is often small. When found, the yeasts are 3 to 5 microns in diameter, oval to cigar-shaped, and may show multiple buds.
Rarely, asteroid bodies consisting of a central basophilic yeast surrounded by eosinophilic material radiating outward like spokes on a wheel can be seen (picture 5). This reaction, also known as the Splendore-Hoeppli phenomenon, is thought to represent either antigen-antibody complexes or disintegrating neutrophils and is not specific for sporotrichosis [35].
Other evaluations not routinely performed
●Polymerase chain reaction – Several reference laboratories have reported on the use of nested PCR assays for identifying S. schenckii in tissues [31,36,37]. Although multiple different approaches to PCR testing have been utilized [33,38,39], none are available commercially.
●Serology – Serology is not used routinely in the diagnosis of sporotrichosis, although work continues to develop a sensitive and specific antibody assay [31,33]. As an example, a group from Brazil developed an enzyme immunoassay for serologic testing of S. schenckii [40]. In a study evaluating this assay using serum samples collected over 10 years (177 samples from patients with sporotrichosis, 77 from patients with other fungal infections, 15 from patients with non-fungal diseases, and 38 healthy controls) the sensitivity and specificity were 89 and 82 percent, respectively [41]. This study was performed in patients who acquired sporotrichosis in the outbreak of feline-associated S. brasiliensis sporotrichosis in Rio de Janeiro; whether it will prove as useful in other cases of sporotrichosis remains to be seen. (See "Basic biology and epidemiology of sporotrichosis", section on 'Zoonotic transmission and epidemic S. brasiliensis infection'.)
Several decades ago, a latex agglutination assay was reported to be sensitive and specific for detecting antibodies in the cerebrospinal fluid of patients who had meningeal sporotrichosis [42]. A similar assay is available in some reference laboratories for use in the diagnosis of meningitis [20]. (See 'Neurologic involvement' above.)
SUMMARY AND RECOMMENDATIONS
●Environmental exposure – Sporotrichosis is a subacute to chronic infection caused by the inoculation, or less commonly inhalation, of the dimorphic fungus Sporothrix schenckii from soil, moss, or other organic material. Activities associated with the development of sporotrichosis include landscaping, rose gardening, and other activities that involve inoculation of soil through the skin. (See 'Introduction' above.)
●Spectrum of disease – Nodular lymphangitis (caused by lymphocutaneous sporotrichosis) is the most common clinical presentation. The typical host is a healthy individual with an outdoor occupation or avocation that provides exposure to the fungus. Extracutaneous forms of sporotrichosis (involvement of lungs, osteoarticular structures, meninges, and other viscera) are extremely rare and occur mostly in individuals with underlying illnesses (eg, chronic obstructive pulmonary disease, heavy alcohol use, AIDS). (See 'Spectrum of disease' above.)
●Lymphocutaneous sporotrichosis – Days to weeks after cutaneous inoculation of the fungus, a papule develops at the site of inoculation. This primary lesion usually ulcerates but may remain nodular with overlying erythema. Similar lesions subsequently occur along lymphatic channels proximal to the original lesion (picture 1A-B). (See 'Nodular lymphangitis' above.)
●Extracutaneous sporotrichosis – Extracutaneous sporotrichosis is extremely rare. The most common manifestations include pulmonary, osteoarticular, neurologic, or dermatologic involvement (picture 2 and picture 3 and picture 4 and image 1). Disseminated disease (involvement of several organs) occurs mostly in severely immunocompromised individuals (eg, patients with advanced HIV) and rarely involves the lungs. (See 'Other less common presentations' above.)
●When to suspect sporotrichosis – Sporotrichosis should be suspected in a patient with likely environmental exposure who presents with nodular lymphangitis or a nonhealing non-purulent painless skin lesion (lymphocutaneous sporotrichosis). Extracutaneous sporotrichosis is rare but should be considered in certain hosts with predisposing conditions and possible environmental exposure, particularly when lesions have not responded to usual antibacterial therapy. (See 'When to suspect sporotrichosis' above.)
●Diagnosis – When sporotrichosis is suspected, culture from tissue biopsy, sputum, body fluids, or aspirated material from a skin lesion should be collected. Growth often appears within five days but sometimes can take several weeks; a positive culture is diagnostic. Although special stains (eg, methenamine silver stain) can be performed for histopathology, they are often negative, because the number of organisms required to cause disease is small. (See 'Diagnosis' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Kieren Marr, MD, who contributed to an earlier version of this topic review.
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