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History

  1. Top of page
  2. Abstract
  3. History
  4. Diagnosis
  5. Discussion
  6. References

A 29-year-old man with febrile neutropenia and skin lesions following chemotherapy for recurrent acute lymphoblastic leukemia (Figs 1–3).

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Figure 1. Erythematous and purpuric nodules on the arm, some with dusky, necrotic, “targetoid” centers

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Figure 2. Septate hyphae invading the dermal blood vessels (hematoxylin and eosin; magnification, ×40)

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Figure 3. Numerous hyphae seen with Grocott's methenamine silver stain (magnification, ×10)

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Discussion

  1. Top of page
  2. Abstract
  3. History
  4. Diagnosis
  5. Discussion
  6. References

Fusarium is a saprophytic filamentous mold commonly found in soil, and is a plant pathogen. It produces toxins that can cause human illness. Fusarium is rarely pathogenic in immunocompetent patients. When it does cause infection in healthy individuals, it is superficial, as in onychomycosis, keratitis, or at sites of wounds, burns, or deep ulcers. Less common infections include septic arthritis, endophthalmitis, brain abscesses, and cystitis.1 Fusarium can produce serious infections in immunocompromised patients and often appears as neutropenic fever unresponsive to antibacterial and antifungal agents. The three species predominantly encountered in human disease are Fusarium solani, Fusarium oxysporum, and Fusarium monoliliforme.1

The prevalence of Fusarium and other fungal infections has been increasing in patients with hematologic malignancies. This may be attributed to the increased use of aggressive chemotherapy, bone marrow and stem cell transplantations, and more aggressive immunosuppressive therapy.2 Following Aspergillus, Fusarium infections are the second most common noncandida fungal infections affecting bone marrow transplant recipients.3 As in our patient, acute leukemia is the most common underlying malignancy in fusariosis.4

The two most common sites of introduction of Fusarium in disseminated infections are the sinopulmonary tree and the skin.5 Less common portals of entry include the gastrointestinal tract and indwelling venous catheters. Skin lesions are found in 60–80% of patients with disseminated fusariosis, and can be both primary and metastatic.4,5 Multiple erythematous subcutaneous nodules or tender red or gray macules and papules, often with a necrotic center and ulceration, are typically seen. Central necrosis of the lesion is a result of invasion and thrombosis of dermal blood vessels leading to tissue necrosis.4,6,7 The classic description of Fusarium is a “target lesion,” and is not seen in other fungal infections.5,8

Fusarium can readily be isolated from skin lesions and blood cultures. Skin biopsies should include culture as well as microscopic evaluation, because Fusarium is difficult to distinguish from Aspergillus histologically, and treatment will differ.7 Molecular diagnostic techniques can distinguish Fusarium from Aspergillus and reveal the species of Fusarium in less than 48 h.9 It is difficult to grow Aspergillus from the blood; however, blood cultures are positive in up to 60% of patients with disseminated Fusarium.7 Even though disseminated Fusarium infections account for a small proportion of fungal infections in immunosuppressed patients, they are relatively resistant to antifungal agents, and mortality can approach 80 or 90%.4,6 The best predictor for recovery from disseminated infection is recovery from neutropenia. Owing to the high mortality from Fusarium in immunocompromised patients, it has been suggested that pre-bone marrow transplantation screening for onychomycosis may be beneficial.10

References

  1. Top of page
  2. Abstract
  3. History
  4. Diagnosis
  5. Discussion
  6. References
  • 1
    Fleming RV, Walsh TJ, Anaissie EJ. Emerging and less common fungal pathogens. Infect Dis Clin N Am 2002; 16: 915933.
  • 2
    Girmenia C, Lori AP, Boccklin F, et al . Fusarium infections in patients with severe aplastic anemia: review and implications for management. Haematologica 1999; 84: 114118.
  • 3
    Morrison VA, Haake RJ, Weisdorf DJ. The spectrum of non-Candida fungal infections following bone marrow transplantation. Medicine 1993; 72: 7889.
  • 4
    Bushelman SJ, Callen JP, Roth DN, et al . Disseminated Fusarium solani infection. J Am Acad Dermatol 1995; 32: 346351.
  • 5
    Boutati EI, Anaisse E. Fusarium, a significant emerging pathogen in patients with hematologic malignancy: 10 years of experience at a cancer center and implications for management. Blood 1997; 3: 9991008.
  • 6
    Bodey GP, Boktour M, Mays S, et al . Skin lesions associated with Fusarium infection. J Am Acad Dermatol 2002; 47: 659666.
  • 7
    Nelson PE, Dignani MC, Anaisse EG. Taxonomy, biology, and clinical aspects of Fusarium species. Clin Microbiol Rev 1994; 7: 479504.
  • 8
    Vincent AL, Cabrerro JE, Greene JN, et al . Voriconazole therapy of disseminated Fusarium solani in the brain of a neutropenic cancer patient. Cancer Control 2003; 10: 414419.
  • 9
    Hennequin C, Abachin E, Symoens F, et al . Identification of Fusarium species involved in human infections by 28S rRNA gene sequencing. J Clin Microbiol 1999; 37: 35863589.
  • 10
    Ninet B, Jan I, Bontems O et al . Molecular identification of Fusarium species in onychomycoses. Dermatology 2005; 210: 2125.