Clinical manifestations and diagnosis of Fusarium infection
- Elias Anaissie, MD
Elias Anaissie, MD
- Medical Director
- CTI Clinical Trial & Consulting Services
- Marcio Nucci, MD
Marcio Nucci, MD
- Associate Professor, Department of Internal Medicine Federal University of Rio de Janeiro
- Head, Mycology Laboratory
- Hospital Universitario Clementino Fraga Filho
Fusarium species cause a broad spectrum of infections in humans, including superficial infections such as keratitis and onychomycosis, as well as locally invasive and disseminated infections . Invasive and disseminated infections occur almost exclusively in severely immunocompromised patients, particularly among those with prolonged and profound neutropenia and/or severe T cell immunodeficiency. Among patients with hematologic malignancy, the infection predominates during periods of neutropenia, typically among patients with leukemia receiving induction chemotherapy.
Fusarium species may also cause allergic diseases such as sinusitis in immunocompetent individuals  and mycotoxicosis following ingestion of food contaminated by toxin-producing Fusarium species . Fusarium species are also important plant pathogens that cause various diseases of cereal grains  and occasionally cause infection in animals .
The clinical manifestations and diagnosis of fusariosis will be reviewed here. The mycology, pathogenesis, epidemiology, treatment, and prevention of fusariosis are discussed separately. (See "Mycology, pathogenesis, and epidemiology of Fusarium infection" and "Treatment and prevention of Fusarium infection".)
Immunocompetent patients — Keratitis and onychomycosis are the most common manifestations of fusariosis among immunocompetent hosts.
Keratitis — Keratitis is inflammation of the cornea and can be caused by a variety of infectious and noninfectious causes  (see 'Keratitis' below). Fusarium spp are a common cause of fungal keratitis and were responsible for an outbreak among contact lens users between 2004 and 2006, which was linked to a specific brand of contact lens solution, ReNu with MoistureLoc. (See "Mycology, pathogenesis, and epidemiology of Fusarium infection", section on 'Keratitis'.)
- Nucci M, Anaissie E. Fusarium infections in immunocompromised patients. Clin Microbiol Rev 2007; 20:695.
- Wickern GM. Fusarium allergic fungal sinusitis. J Allergy Clin Immunol 1993; 92:624.
- Nelson PE, Dignani MC, Anaissie EJ. Taxonomy, biology, and clinical aspects of Fusarium species. Clin Microbiol Rev 1994; 7:479.
- Evans J, Levesque D, de Lahunta A, Jensen HE. Intracranial fusariosis: a novel cause of fungal meningoencephalitis in a dog. Vet Pathol 2004; 41:510.
- Barnes SD, Pavan-Langston D, Azar DT. Microbial keratitis. In: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 7th edition, Mandell GL, Bennett JE, Dolin R. (Eds), Churchill Livingstone Elsevier, Philadelphia 2010. Vol 1, p.1539.
- Baran R, Tosti A, Piraccini BM. Uncommon clinical patterns of Fusarium nail infection: report of three cases. Br J Dermatol 1997; 136:424.
- Calado NB, Sousa F Jr, Gomes NO, et al. Fusarium nail and skin infection: a report of eight cases from Natal, Brazil. Mycopathologia 2006; 161:27.
- Hay RJ. Fusarium infections of the skin. Curr Opin Infect Dis 2007; 20:115.
- Guilhermetti E, Takahachi G, Shinobu CS, Svidzinski TI. Fusarium spp. as agents of onychomycosis in immunocompetent hosts. Int J Dermatol 2007; 46:822.
- Nucci M, Anaissie E. Cutaneous infection by Fusarium species in healthy and immunocompromised hosts: implications for diagnosis and management. Clin Infect Dis 2002; 35:909.
- Rippon JW, Larson RA, Rosenthal DM, Clayman J. Disseminated cutaneous and peritoneal hyalohyphomycosis caused by Fusarium species: three cases and review of the literature. Mycopathologia 1988; 101:105.
- Kerr CM, Perfect JR, Craven PC, et al. Fungal peritonitis in patients on continuous ambulatory peritoneal dialysis. Ann Intern Med 1983; 99:334.
- Flynn JT, Meislich D, Kaiser BA, et al. Fusarium peritonitis in a child on peritoneal dialysis: case report and review of the literature. Perit Dial Int 1996; 16:52.
- Kurien M, Anandi V, Raman R, Brahmadathan KN. Maxillary sinus fusariosis in immunocompetent hosts. J Laryngol Otol 1992; 106:733.
- Madhavan M, Ratnakar C, Veliath AJ, et al. Primary disseminated fusarial infection. Postgrad Med J 1992; 68:143.
- Sander A, Beyer U, Amberg R. Systemic Fusarium oxysporum infection in an immunocompetent patient with an adult respiratory distress syndrome (ARDS) and extracorporal membrane oxygenation (ECMO). Mycoses 1998; 41:109.
- Murray CK, Beckius ML, McAllister K. Fusarium proliferatum superficial suppurative thrombophlebitis. Mil Med 2003; 168:426.
- Sturm AW, Grave W, Kwee WS. Disseminated Fusarium oxysporum infection in patient with heatstroke. Lancet 1989; 1:968.
- Pflugfelder SC, Flynn HW Jr, Zwickey TA, et al. Exogenous fungal endophthalmitis. Ophthalmology 1988; 95:19.
- Gabriele P, Hutchins RK. Fusarium endophthalmitis in an intravenous drug abuser. Am J Ophthalmol 1996; 122:119.
- Jakle C, Leek JC, Olson DA, Robbins DL. Septic arthritis due to Fusarium solani. J Rheumatol 1983; 10:151.
- Bourguignon RL, Walsh AF, Flynn JC, et al. Fusarium species osteomyelitis. Case report. J Bone Joint Surg Am 1976; 58:722.
- Nucci M, Anaissie E. Emerging fungi. Infect Dis Clin North Am 2006; 20:563.
- Anaissie E, Kantarjian H, Ro J, et al. The emerging role of Fusarium infections in patients with cancer. Medicine (Baltimore) 1988; 67:77.
- Carneiro HA, Coleman JJ, Restrepo A, Mylonakis E. Fusarium infection in lung transplant patients: report of 6 cases and review of the literature. Medicine (Baltimore) 2011; 90:69.
- Nucci F, Nouér SA, Capone D, et al. Fusariosis. Semin Respir Crit Care Med 2015; 36:706.
- Nucci M, Varon AG, Garnica M, et al. Increased incidence of invasive fusariosis with cutaneous portal of entry, Brazil. Emerg Infect Dis 2013; 19:1567.
- Varon AG, Nouer SA, Barreiros G, et al. Superficial skin lesions positive for Fusarium are associated with subsequent development of invasive fusariosis. J Infect 2014; 68:85.
- Liu K, Howell DN, Perfect JR, Schell WA. Morphologic criteria for the preliminary identification of Fusarium, Paecilomyces, and Acremonium species by histopathology. Am J Clin Pathol 1998; 109:45.
- Ammari LK, Puck JM, McGowan KL. Catheter-related Fusarium solani fungemia and pulmonary infection in a patient with leukemia in remission. Clin Infect Dis 1993; 16:148.
- Castagnola E, Garaventa A, Conte M, et al. Survival after fungemia due to Fusarium moniliforme in a child with neuroblastoma. Eur J Clin Microbiol Infect Dis 1993; 12:308.
- Eljaschewitsch J, Sandfort J, Tintelnot K, et al. Port-a-cath-related Fusarium oxysporum infection in an HIV-infected patient: treatment with liposomal amphotericin B. Mycoses 1996; 39:115.
- Kiehn TE, Nelson PE, Bernard EM, et al. Catheter-associated fungemia caused by Fusarium chlamydosporum in a patient with lymphocytic lymphoma. J Clin Microbiol 1985; 21:501.
- Musa MO, Al Eisa A, Halim M, et al. The spectrum of Fusarium infection in immunocompromised patients with haematological malignancies and in non-immunocompromised patients: a single institution experience over 10 years. Br J Haematol 2000; 108:544.
- Raad I, Hachem R. Treatment of central venous catheter-related fungemia due to Fusarium oxysporum. Clin Infect Dis 1995; 20:709.
- Velasco E, Martins CA, Nucci M. Successful treatment of catheter-related fusarial infection in immunocompromised children. Eur J Clin Microbiol Infect Dis 1995; 14:697.
- Boutati EI, Anaissie EJ. Fusarium, a significant emerging pathogen in patients with hematologic malignancy: ten years' experience at a cancer center and implications for management. Blood 1997; 90:999.
- Martino P, Gastaldi R, Raccah R, Girmenia C. Clinical patterns of Fusarium infections in immunocompromised patients. J Infect 1994; 28 Suppl 1:7.
- Gamis AS, Gudnason T, Giebink GS, Ramsay NK. Disseminated infection with Fusarium in recipients of bone marrow transplants. Rev Infect Dis 1991; 13:1077.
- Venditti M, Micozzi A, Gentile G, et al. Invasive Fusarium solani infections in patients with acute leukemia. Rev Infect Dis 1988; 10:653.
- Bullock JD, Warwar RE. Contact lens solution-associated Acanthamoeba and Fusarium keratitis. Emerg Infect Dis 2010; 16:1501.
- Tu EY, Joslin CE. Recent outbreaks of atypical contact lens-related keratitis: what have we learned? Am J Ophthalmol 2010; 150:602.
- Nucci M, Carlesse F, Cappellano P, et al. Earlier diagnosis of invasive fusariosis with Aspergillus serum galactomannan testing. PLoS One 2014; 9:e87784.
- Silveira FP, Queiroz-Telles F, Nucci M. Invasive mold infections. In: Diagnosis of fungal infections, Maertens JA, Marr KA (Eds), Informa Healthcare, 2007. p.171.
- Grigis A, Farina C, Symoens F, et al. Nosocomial pseudo-outbreak of Fusarium verticillioides associated with sterile plastic containers. Infect Control Hosp Epidemiol 2000; 21:50.
- Hayden RT, Isotalo PA, Parrett T, et al. In situ hybridization for the differentiation of Aspergillus, Fusarium, and Pseudallescheria species in tissue section. Diagn Mol Pathol 2003; 12:21.
- Salehi E, Hedayati MT, Zoll J, et al. Discrimination of Aspergillosis, Mucormycosis, Fusariosis, and Scedosporiosis in Formalin-Fixed Paraffin-Embedded Tissue Specimens by Use of Multiple Real-Time Quantitative PCR Assays. J Clin Microbiol 2016; 54:2798.
- Odabasi Z, Mattiuzzi G, Estey E, et al. Beta-D-glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome. Clin Infect Dis 2004; 39:199.
- Ostrosky-Zeichner L, Alexander BD, Kett DH, et al. Multicenter clinical evaluation of the (1-->3) beta-D-glucan assay as an aid to diagnosis of fungal infections in humans. Clin Infect Dis 2005; 41:654.
- Aquino VR, Goldani LZ, Pasqualotto AC. Update on the contribution of galactomannan for the diagnosis of invasive aspergillosis. Mycopathologia 2007; 163:191.
- Tortorano AM, Esposto MC, Prigitano A, et al. Cross-reactivity of Fusarium spp. in the Aspergillus Galactomannan enzyme-linked immunosorbent assay. J Clin Microbiol 2012; 50:1051.
- CLINICAL MANIFESTATIONS
- Immunocompetent patients
- - Keratitis
- - Onychomycosis and superficial skin infections
- - Deep cutaneous infections
- - Other infections
- Immunocompromised patients
- - Sinusitis
- - Pneumonia
- - Cutaneous lesions
- - Fungemia
- - Disseminated disease
- DIFFERENTIAL DIAGNOSIS
- Invasive disease
- Approach to diagnosis
- Blood cultures
- Growth of cultures
- Beta-D-glucan and galactomannan antigen
- Other techniques
- SUMMARY AND RECOMMENDATIONS