Fungal species of the genus Fusarium are opportunistic pathogens and may cause fusariosis. Immunocompromised patients are particularly prone to Fusarium infection and in these individuals, hematogenous spread of pathogens may lead to disseminated, life-threatening disease.
Presentation
Patients suffering from fusariosis usually have a medical history of immunosuppression and/or hospitalization, i.e., they belong to any of the aforementioned risk groups. Long-term use of corticosteroids as well as neutropenia or lymphopenia may indicate an immunosuppression in people not previously diagnosed with disorders of the immune system. In contrast, immunocompetent individuals may not report recently sustained minor traumas that may have facilitated Fusarium infection unless inquired about.
Most frequent initial manifestations of fusariosis are dermatitis, onychomycosis, and keratitis. In immunocompetent individuals, an exacerbation of symptoms is unlikely since pathogens don't typically spread from the primary site of entry. In immunocompromised patients, dermatitis may turn into ecthyma, cellulitis, panniculitis and soft-tissue necrosis. The appearance of multiple subcutaneous nodules indicates the hematogenous spread of pathogens. Furthermore, patients may develop sinusitis and pneumonia. Less commonly, fusariosis may trigger septic arthritis [7] and osteomyelitis [8]. Dissemination is common in those patients who suffer from Fusarium-induced thrombophlebitis or peritonitis. Infiltration of neighboring tissues as well as systemic spread are generally associated with constitutive symptoms like malaise and fever.
Entire Body System
- Fever
Disseminated Fusarium infection should be suspected in immunocompromised patients with fever and neutropenia who have generalized, eroded, violaceous papules, vesicles, and pustules, particularly with associated myalgias. [ncbi.nlm.nih.gov]
Fever was the main symptom and it lasted for 15 weeks. [go.gale.com]
In the immunocompromised, disseminated fusariosis is more common and it manifests with refractory fever, skin lesions (ecthyma-like, target, and multiple subcutaneous nodules), severe myalgias and sino-pulmonary infections. [orpha.net]
- Pain
The patient had fever and neutropenia, and scattered violaceous papules and vesicles with central erosions that rapidly progressed to generalized, painful, violaceous, papulovesicular lesions with central necrosis. Severe myalgias were associated. [ncbi.nlm.nih.gov]
There was no history of itching, pain or discharge from the lesion. Case 2 A 70-year-old male presented with erythematous scaly plaques on the left little finger since 3 years with no itching, pain and discharge from the lesion. [e-ijd.org]
This is a painful condition referred to as onycholysis. Tips for Avoiding Fusarium Fungal Infections of the Nails It’s much better to prevent fusarium fungal infections of the nails than it is to try to treat them. [hubpages.com]
[…] disseminated infection in rare and is only seen with any frequency in severely immunocompromised patients. that being said, superficial or localized infection does have the potential to spread and therefore if your mother starts to develop fevers, joint/muscle pain [zocdoc.com]
- Weakness
Cerebral aneurysm caused by infections differ from congenital brain aneurysm, which often occur the junctions where these arteries come together and form weak spots. [bloodjournal.org]
If the infected seedlings emerge, they may be stunted and weak with chlorotic cotyledons. [wiki.bugwood.org]
In the medical field, the species cause opportunistic infections of human eyes, skin or nails and may also cause systemic infections in individuals with weak immune system. [moldbacteria.com]
Those most at risk are individuals with weak or compromised immune systems. [sciencedaily.com]
A fusarium fungal infection is much more likely in those with weak immune systems. These patients lack the “fighter” cells to defend the body against the fusarium fungus. [hubpages.com]
- Fatigue
[…] fracture[pseudarthrosis] 골절의 불유합(가관절증) M84.2 Delayed union of fracture 골절의 지연된 결합 Z09.4 Follow-up examination after treatment of fracture 골절치료후 추후검사 Z54.4 Convalescence following treatment of fracture 골절치료후 회복기 한국표준질병사인분류 약자 유사 검색 결과 : 5 페이지: 1 M48.4 Fatigue [kmle.co.kr]
Patients with pulmonary fusariosis presented with shortness of breath (n = 6), fever (n = 6), cough (n = 3), fatigue (n = 2), and chest pain (n = 1), and Fusarium species were isolated from bronchial washings (n = 7) and sputum (n = 1). [journals.lww.com]
- Malaise
Infiltration of neighboring tissues as well as systemic spread are generally associated with constitutive symptoms like malaise and fever. [symptoma.com]
[…] secondary relapse despite achieving complete leukaemic remission. fusarium disseminated neutropenia remission Statistics from Altmetric.com fusarium disseminated neutropenia remission A 67 year old man presented with a three to four week history of general malaise [jcp.bmj.com]
After that, in the next 4 weeks, the patient presented with high temperature every day (Graph 1), (taken 2 to 3 times per day) associated with malaise, loss of appetite, and occasional vomiting without diarrhea. [go.galegroup.com]
Respiratoric
- Pneumonia
Woman with pulmonary sarcoidosis necessitating bilateral lung transplants 4 months prior to her demise who was soon readmitted with viral pneumonia. [ncbi.nlm.nih.gov]
Fusarium growing on agar media Some of the infections attributed to some species of Fusarium are: Fusarium keratitis Onychomycosis (nail infection) Certain skin infections Fusarium osteomyelitis (bone and joint infections) Pneumonia In the industrial [moldbacteria.com]
During chemotherapy, she developed Klebsiella pneumoniae, which was treated with piperacillin-tazobactam, ciprofloxacin hydrochloride, and vancomycin hydrochloride. [jamanetwork.com]
- Dyspnea
Patients presented with dyspnea, fever, nonproductive cough, hemoptysis, and headache. Blood tests showed elevated white blood cell counts with granulocytosis and elevated inflammatory markers. [ncbi.nlm.nih.gov]
In October 2012, during a routine medical consultation, she complained of palpitation and dyspnea starting 10 days before. The patient presented with hypercalcemia and had to be admitted for the treatment of this condition. [springerplus.springeropen.com]
- Dry Cough
The clinical presentation is non-specific, with some presenting with a clinical picture similar to that of invasive aspergillosis, with dry cough, pleuritic chest pain and shortness of breath ( 46 ). [antimicrobe.org]
- Nasal Discharge
The clinical manifestations of fusarial sinusitis are indistinguishable from those caused by Aspergillus : nasal discharge and obstruction. Necrosis of the mucosa is a hallmark, and is a consequence of the angioinvasive nature of these mycoses. [antimicrobe.org]
Gastrointestinal
- Abdominal Pain
The initial symptoms of the infection included fever, abdominal pain, vomiting, and diarrhea. Within days, the victims suffered from bloody diarrhea, bloody urine, vaginal bleeding, tarry stools, and ulcers of the larynx and stomach. [hubpages.com]
Symptoms began with abdominal pain, diarrhea, vomiting, and prostration, and within days, fever, chills, myalgias and bone marrow depression with granulocytopenia and secondary sepsis occurred. [en.wikipedia.org]
Cardiovascular
- Chest Pain
The clinical presentation is non-specific, with some presenting with a clinical picture similar to that of invasive aspergillosis, with dry cough, pleuritic chest pain and shortness of breath ( 46 ). [antimicrobe.org]
Patients with pulmonary fusariosis presented with shortness of breath (n = 6), fever (n = 6), cough (n = 3), fatigue (n = 2), and chest pain (n = 1), and Fusarium species were isolated from bronchial washings (n = 7) and sputum (n = 1). [journals.lww.com]
Eyes
- Excessive Tearing
Symptoms of fungal keratitis include: Eye pain Eye redness Blurred vision Sensitivity to light Excessive tearing Eye discharge If you experience any of these symptoms, remove your contact lenses (if you wear them) and call your eye doctor right away. [cdc.gov]
- Eye Pain
Symptoms of fungal keratitis include: Eye pain Eye redness Blurred vision Sensitivity to light Excessive tearing Eye discharge If you experience any of these symptoms, remove your contact lenses (if you wear them) and call your eye doctor right away. [cdc.gov]
Musculoskeletal
- Myalgia
Disseminated Fusarium infection should be suspected in immunocompromised patients with fever and neutropenia who have generalized, eroded, violaceous papules, vesicles, and pustules, particularly with associated myalgias. [ncbi.nlm.nih.gov]
In the immunocompromised, disseminated fusariosis is more common and it manifests with refractory fever, skin lesions (ecthyma-like, target, and multiple subcutaneous nodules), severe myalgias and sino-pulmonary infections. [orpha.net]
Refractory fever despite broad-spectrum antibiotics, as well as nausea, myalgia, pulmonary symptoms with detection of pulmonary infiltrates, liver and spleen involvement indicated an invasive fungal infection. [go.gale.com]
The typical clinical presentation is neutropenic fever in patients with myalgia and sudden appearance of erythematous papular or nodal painful skin lesions with central necrosis. [go.galegroup.com]
Skin
- Ecthyma
In the immunocompromised, disseminated fusariosis is more common and it manifests with refractory fever, skin lesions (ecthyma-like, target, and multiple subcutaneous nodules), severe myalgias and sino-pulmonary infections. [orpha.net]
KEYWORDS: Disseminated fusariosis; Ecthyma gangrenosum-like lesions; Pseudomonas aeruginosa sepsis [ncbi.nlm.nih.gov]
Turkish Journal of Hematology Ecthyma Gangrenosum-like Lesions in a Febrile Neutropenic Patient with Simultaneous Pseudomonas Sepsis and Disseminated Fusariosis [Turk J Hematol] Turk J Hematol. 2013; 30(3): 321-324 | DOI: 10.4274/Tjh.2012.0030 Ecthyma [tjh.com.tr]
In immunocompromised patients, dermatitis may turn into ecthyma, cellulitis, panniculitis and soft-tissue necrosis. The appearance of multiple subcutaneous nodules indicates the hematogenous spread of pathogens. [symptoma.com]
- Subcutaneous Nodule
In the immunocompromised, disseminated fusariosis is more common and it manifests with refractory fever, skin lesions (ecthyma-like, target, and multiple subcutaneous nodules), severe myalgias and sino-pulmonary infections. [orpha.net]
Skin lesions associated with disseminated infection included red or gray macules, papules (some with central necrosis or eschar), pustules, and subcutaneous nodules. Most patients had a variety of lesions simultaneously. [ncbi.nlm.nih.gov]
The appearance of multiple subcutaneous nodules indicates the hematogenous spread of pathogens. Furthermore, patients may develop sinusitis and pneumonia. Less commonly, fusariosis may trigger septic arthritis and osteomyelitis. [symptoma.com]
- Intertrigo
A cutaneous portal of entry was identified in 14 (66.7%) of the 21 cases: onychomycosis with periungueal cellulitis in 6 cases, onychomycosis with interdigital intertrigo in 1 case, intertrigo with lymphangitis in 2 cases, intertrigo alone in 4 cases, [ncbi.nlm.nih.gov]
Fusarium spp. can also infect the nails, causing melanonychia and onychomycosis (1, 17) and rarely causes interdigital intertrigo, abscesses and mycetoma (2, 18). [medicaljournals.se]
A strong association between invasive Fusarium infection and a superficial skin lesion, especially onychomycosis or intertrigo, has been demonstrated in recent studies. 6, 7 Moreover, the presence of a Fusarium skin lesion at admission was associated with [scielo.br]
- Plantar Hyperkeratosis
Plantar hyperkeratosis due to Fusarium verticilloides in a patient with malignancy. Clin Exp Dermatol 1999; 24: 175–178. 6. Chade ME, Mereles BE, Medvedeff MG, Vedoya MC. Micosis subcutánea postraumática por Fusarium solani. [medicaljournals.se]
- Dermatitis
Usually, affected people suffer from dermatitis or cellulitis, onychomycosis, keratitis, and respiratory infection, possibly accompanied by constitutive symptoms like malaise and fever. [symptoma.com]
Psychiatrical
- Suggestibility
In vitro susceptibility tests of antifungal drugs suggest that terbinafine is a potent additional antifungal drug for disseminated cutaneous fusariosis. [ncbi.nlm.nih.gov]
Sabouraud-Dextrose agar culture without cycloheximide grew whitish grey cottony colonies suggestive of Fusarium species. [indianjnephrol.org]
- Negativism
Liposomal amphotericin B allowed blood culture negativation. The patient died from a bacterial septic shock. Zusammenfassung. [onlinelibrary.wiley.com]
Neurologic
- Confusion
Due to the confusion in identifying many Fusarium species, the classification is also based on the plant’s symptomatology. [canna-uk.com]
This unusual presentation potentially can be confused with early rhinocerebral zygomycosis clinically and histologically. Distinguishing morphologic features and the possible role of diabetes in promoting this infection are discussed. [ncbi.nlm.nih.gov]
In countries with Moko disease, which is caused by Ralstonia solanacearum race 2, and also causes vascular discoloration, it is possible to confuse the two diseases. [promusa.org]
In severely immunocompromised patients, this fungus may cause disseminated disease and is often confused with Aspergillus, as the two pathogens have similar histopathological appearances. [spandidos-publications.com]
The results of the isolation of fungi are somehow confusing since some samples contaminated with toxin did not contain any of the investigated Fusarium species that could explain the toxin production. [stud.epsilon.slu.se]
Workup
Although fusariosis is generally considered a rare disease, Fusarium spp. are among the most common fungal pathogens isolated from immunodeficient patients. Thus, characteristic skin lesions or keratitis in immunocompromised individuals should prompt a strong suspicion of Fusarium infection. Histopathological examination of tissue samples is strongly recommended to confirm this suspicion, although in vivo confocal microscopy and anterior segment optical coherence tomography may be utilized to diagnose ocular fungal infections [9]. Fusarium spp. grow in form of hyaline, septate hyphae that measure up to 8 μm in diameter and largely resemble Aspergillus filaments. Hyphae branch at right or acute angles. Canoe- or banana-shaped macroconidia may be observed and are characteristic of the genus; the precise appearance of microconidia is of importance to distinguish species [10]. If histopathological analyses don't allow for a reliable diagnosis, fungi have to be cultured. Of note, Fusarium spp. spread hematogenously, and blood cultures do yield positive results in about half of patients. Nevertheless, negative results don't rule out fusariosis or fungal infections triggered by pathogens of other genera. For a long time, isolation of Fusarium spp. from infected sites has been the diagnostic measure of choice, but more recently, the identification of fungal pathogens by means of molecular biological techniques has been gaining importance [11]. Antimicrobial susceptibility testing is recommended to assure an optimum response to therapy and to avoid further dissemination of the disease.
Although diagnostic imaging is not required to confirm Fusarium infection, plain radiography or computed tomography scans of the thoracic cavity often reveal poorly demarcated, angioinvasive masses in the lungs of patients presenting with respiratory infection. The latter technique is more sensitive than the former, but both lack specificity to diagnose fusariosis [12].
Serum
- Neutropenia
The actuarial survival rate of patients without any of these factors was 67% compared with 30% for patients who recovered from neutropenia but were receiving corticosteroids and 4% for patients with persistent neutropenia only. [ncbi.nlm.nih.gov]
- Leukopenia
The combination of treatment with immunosuppressive agents and total lymphoid radiation (TLI), which subsequently resulted in leukopenia, may have made the patient described in the present study more susceptible to Fusarium infection. [academic.oup.com]
Microbiology
- Fusarium
A dry bean stem showing symptoms of fusarium wilt also caused by fusarium oxysporum f.sp.phaseoli. [canna-uk.com]
The discussion of Fusarium-related mycotoxicosis is beyond the scope of this article, though. Fusarium infection or fusariosis refers to an infection with fungal species of the genus Fusarium. [symptoma.com]
Fruit rot caused by Fusarium oxysporum f. sp. melonis Figure 9. Butternut rot caused by a Fusarium spp. [vegetablemdonline.ppath.cornell.edu]
Fusarium wilt at a glance See Musapedia page on TR4 Fusarium wilt of banana, popularly known as Panama disease, is a lethal fungal disease caused by the soil-borne fungus Fusarium oxysporum f. sp. cubense ( Foc ). [promusa.org]
Effect of inoculation time and point of entry on disease severity in Fusarium graminearum, Fusarium verticillioides, or Fusarium subglutinans inoculated maize ears. Canadian Journal of Plant Pathology 24 (2): 162–167. DOI: 10.1080/07060660309506991. [progress.plantprotection.pl]
Treatment
Antimycotic treatment is the mainstay of fusariosis therapy, but isolates may vary largely with regards to their susceptibility to determined compounds [4]. Clinical trials have not yet been conducted and according to empiric evidence, amphotericin B deoxycholate, lipid-based amphotericin B formulations, voriconazole and posaconazole are most indicated to this end. Amphotericin B deoxycholate is more likely to provoke side effects than lipid-based formulations; posaconazole should be reserved for patients suffering from severe fusariosis and those infected with multi-resistant strains [11]. Furthermore, ketoconazole and nystatin as well as combined regimens have occasionally been applied with success. In contrast, fluconazole and itraconazole have repeatedly been proven ineffective. Fusarium spp. commonly show multiple resistance and thus, the selection of an effective antimycotic drug should be based on the results of susceptibility testing. An early initiation of treatment is of particular importance in immunocompromised individuals and may avoid systemic spread. Here, systemic administration of the aforementioned antifungal drugs should be complemented with surgical debridement of infected tissues. Whenever possible, the underlying immunosuppression should be remedied.
Evidence regarding the efficacy of an adjuvant therapy with granulocyte colony-stimulating factor or granulocyte–macrophage colony-stimulating factor is scarce. At this moment, such an approach can thus not be recommended.
Prognosis
Immunocompetent patients diagnosed with localized fusariosis generally respond well to antimycotic therapy and have an excellent prognosis. In contrast, disseminated fusariosis is often refractory to antimicrobial therapy and Fusarium infection of immunocompromised individuals is related to mortality rates of 50 to 80%. Intractable immunosuppression accompanied by persistent neutropenia, graft-versus-host disease and continued immunosuppressive therapy are unfavorable prognostic factors to this end [2] [6]. Moreover, these conditions are associated with a high risk of recurrence in survivors.
Etiology
Fusariosis may be caused by a wide variety of fungi of the genus Fusarium. The respective species are widely distributed in soil, air and plants, and may be encountered in virtually all geographic regions, including deserts and polar regions [3]. Accordingly, large parts of the population are exposed to Fusarium spp. and indeed, these fungi have been proven to colonize mucous membranes of healthy individuals. More than a dozen species have been related to fusariosis, with the following species being isolated most commonly [4]:
- F. solani (accounts for about 50% of all cases)
- F. oxysporum (isolated from about 20% of affected individuals)
- F. verticillioides (formerly F. moniliforme; triggers approximately 10% of all cases)
Species occasionally causing Fusarium infection are [1]:
- F. anthophilum
- F. chlamydosporum
- F. dimerum
- F. equiseti
- F. falciforme
- F. fujikuroi
- F. lichenicola
- F. napiforme
- F. proliferatum
- F. sacchari
- F. semitecum
- F. subglutinans
Fusarium spp. differ in their propensity for cutaneous, ocular and respiratory infection. Morover, minimal inhibitory concentrations of distinct antimycotics against Fusarium isolates may vary considerably [4]. These facts emphasize the need for a reliable identification of the causative agent.
Immunosuppression is the most important risk factor for Fusarium infection and subsequent systemic spread. In this context, patients suffering from hematological malignancies or neutropenia, and those in need of solid organ or stem cell transplants and adjuvant immunosuppressive therapy constitute major risk groups. Use of catheters and peritoneal dialysis may be associated with Fusarium-induced thrombophlebitis, fungemia and peritonitis. On the other hand, skin-penetrating trauma and burns as well as use of contact lenses predispose immunocompetent individuals for fusariosis.
Epidemiology
Although Fusarium infection is generally considered a rare disease, Fusarium spp. are second only to Aspergillus spp. as causative agents of life-threatening fungal infections in immunodeficient patients. As has been indicated above, Fusarium infection is a major complication of hematological malignancies and neutropenia. In this context, incidence rates of up to 4.5 per 1,000 patient-years have been observed [5]. According to a retrospective study on fusariosis after hematopoietic stem cell transplantation, this fungal infection is to be expected in 0.5 and 2% of patients who receive transplants from matched, related and unmatched donors, respectively [6]. Epidemiological data regarding racial and gender predilection as well as the patients' age at symptom onset are largely influenced by the underlying disease. Patient cohorts considered in the aforementioned studies consisted of approximately equal parts of men and women, and their reported age at diagnosis ranged from 2 to 77 years.
Pathophysiology
Fungal pathogens are present in distinct environments and rigorous measures have to be undertaken to reduce a patient's exposure to Fusarium spp. Accordingly, the vast majority of the population is constantly exposed to these opportunistic agents. In healthy individuals, an infection is prevented by the mechanical barrier posed by the skin, by antimicrobial compounds in tears and the integrity of the cornea, and by immune cells that act upon inhalation of Fusarium spp. or in case fungi overcome the aforementioned barriers. The latter happens rather frequently, e.g., in case of cutaneous lesions, micro-lesions of the cornea provoked by the use of contact lenses, or skin-penetrating medical procedures. Thus, immune cells like neutrophil granulocytes play the key role in avoiding Fusarium infection. In healthy individuals, an inoculation of pathogens does usually not even result in a localized infection with clinical symptoms. In contrast, neutropenic patients are most susceptible to fusariosis.
Prevention
No specific measures can be recommended to prevent Fusarium infection in immunocompetent individuals. However, adequate measures should be undertaken to minimize the exposure of immunodeficient patients to fungal pathogens, and to avoid systemic dissemination of etiological agents in case of a suspected infection:
- Severely immunocompromised patients should be hospitalized in positive-pressure rooms equipped with HEPA filters, and these individuals should not consume tap water.
- Sinks, showers, other wet areas and people suffering from onychomycosis may also serve as sources of infection and every possible effort should be made to keep those free from Fusarium spp. [13] and to avoid contact with infected personnel and visitors.
- Cutaneous as well as corneal lesions should be avoided whenever possible, and patients presenting with wounds should be provided appropriate wound care.
Due to wide-spread resistances among Fusarium spp., prophylactic administration of antimycotics is not generally recommended.
Summary
Fusarium infection or fusariosis refers to an infection with fungal species of the genus Fusarium. Fusarium spp. are opportunistic pathogens and while there are case reports regarding fusariosis triggered by many distinct species, F. solani, F. oxysporum and F. verticillioides are most commonly isolated from men [1]. Immunosuppression is the single most important risk factor for Fusarium infection and also increases the individual risk of hematogenous spread and systemic disease. However, immunocompetent patients may present with fusariosis if an infection is facilitated by the breakdown of mechanical and functional barriers or the presence of foreign bodies. Usually, affected people suffer from dermatitis or cellulitis, onychomycosis, keratitis, and respiratory infection, possibly accompanied by constitutive symptoms like malaise and fever.
Treatment should comprise antimycotic medication and therapy of the underlying immunosuppression. With regards to the former, both polyene and azole antimycotics have been used. Unfortunately, most patients presenting with fusariosis suffer from non-curable primary diseases like hematological malignancies, or require prolonged immunosuppressive therapy to prevent organ transplant rejection. These conditions are unfavorable prognostic factors and therefore, mortality rates in immunocompromised patients by far exceed 50% [2].
Of note, Fusarium spp. may release mycotoxins, mainly trichothecenes and fumonisins. Ingestion of contaminated products may thus lead to different forms of food poisoning. For instance, mycotoxin T2 exposure has been associated with Kashin-Beck disease. The discussion of Fusarium-related mycotoxicosis is beyond the scope of this article, though.
Patient Information
Fusarium infection or fusariosis refers to an infection with fungal species of the genus Fusarium. These fungi may release mycotoxins and are more commonly known for poisoning of livestock and men, since otherwise healthy individuals rarely contract an infection with live pathogens. Occasionally, dermatitis, onychomycosis, and keratitis may be triggered by Fusarium species. In this context, skin-penetrating traumas and use of contact lenses are important predisposing factors. Such fungal infections are curable and patients have an excellent prognosis.
In contrast, fusariosis is a life-threatening disease in immunodeficient individuals. Patients suffering from hematological malignancies, neutropenia, and those in need of solid organ or stem cell transplants and adjuvant immunosuppressive therapy are at rather high risks of Fusarium infection. Initially, the disease manifests as described for immunocompetent patients, but fungi tend to spread via blood vessels throughout the whole body. Systemic fusariosis is typically accompanied by malaise and fever, and the majority of affected individuals respond poorly to antifungal medication. Disseminated Fusarium infection is associated with mortality rates of more than 50% and thus, every possible effort should be undertaken to avoid an infection in the first place. At home, preventive measures consist in avoiding cutaneous as well as corneal lesions whenever possible. Medical attention should be sought to receive proper wound care when necessary. In hospitals, severely immunodeficient patients are generally placed in special rooms equipped with air filters.
References
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