Fusarium species are a known cause of ocular infection. The misuse of contact lenses is the main risk factor in immunocompetent people. In immunocompromised patients, Fusarium infection can produce local and/or systemic invasive fusariosis, which is associated with complications, poor prognosis and low response to treatment.
Fusarium ocular infection can evolve to keratitis, endophthalmitis and, in extreme cases, ocular perforation. We report, for the first time in children, the case of a 5-year-old girl diagnosed with toxic epidermal necrolysis (TEN), who developed Fusarium ocular infection requiring ocular enucleation.
A 5-year-old girl, previously healthy was admitted to the pediatric intensive care unit because of toxic shock syndrome. The patient presented with a 48 hours history of fever and sore throat that quickly evolve to a full-body maculopapular rash with lips and eyelid edema. A dermatologic examination at admission revealed bullous mucocutaneous lesions involving more than 30% of the body surface.
She was diagnosed with TEN and interdisciplinary treatment was started involving specialists in intensive care, dermatology, ophthalmology, gynecology and plastic surgery.
On the fourth hospital day, the eyes were affected as superficial punctate and infectious keratitis. The patient was treated with ophthalmic corticosteroids, antibiotics and immunosuppressive agents added to lubricant and serum eye drops. Despite of these measures, she developed extensive corneal and conjunctival de-epithelialization complicated by corneal abscess and perforation. At the same time, periocular facial skin lesions evolved to necrotic scabs (Fig. 1), so facial skin and ocular cultures were collected again.
Three days later, the cultures were positive to Fusarium. Ophthalmic corticosteroids and immunosuppressive drugs were discontinued and eye topical voriconazole was initiated, as well as intravenous voriconazole and amphotericin B.
On the 25th day of admission given the significant ocular involvement and lack of response to the previous therapy, the patient underwent urgent bilateral amniotic membrane grafts with placement of an amniotic membrane ring (ProKera, Biotissue, Doral, FL). However, the infection progressed in the right eye, so it had to be enucleated 1 week later, to avoid the risk of local (bone and central nervous system) and/or systemic dissemination. Histologic analysis showed the presence of Fusarium (Fig. 2).
The patient spent 6 weeks making an excellent recovery without postoperative complications. No more clinical or analytical signs of fungal infection were observed. At transfer to the inpatient pediatric ward, more than 70% body surface area was re-epithelializated and scarless, oral mucosa did not show signs of bleeding and the vaginal mucosa remained intact.
Fusarium species cause a broad spectrum of infections in humans. These pathogens are able to produce superficial infections, such as keratitis and onichomycosis, as well as locally invasive and disseminated infections by angioinvasion and direct tissue destruction.
Fusarium species are widely distributed in soil, subterranean and aerial plant parts and other organic matter. Microscopically, Fusarium’s hyphae (Fig. 2) resemble Aspergillus species. Despite more than 100 Fusarium species being described, only a few can infect humans and Fusarium solani is the most frequent cause of keratitis and invasive disease.
The signs and symptoms will vary and depend on the host immune status and site of infection. In immunocompetent patients, keratitis and onichomycosis are the most common infections. Fusarium keratitis may be associated with traumatic introduction of Fusarium-contaminated soil or poor hygiene practices among soft contact lens wearers, particularly those with glucocorticoid eye drop treatment.
Nonlocal or invasive fusariosis have been mainly reported in immunocompromised patients, like our case, especially those having prolonged and profound neutropenia and/or severe T cell immunodeficiency.1 In fact, our patient developed TEN (characterized by epidermal necrosis, skin detachment and erosions in mucous membranes) involving the complete body surface. Consequently, the epidermal protective barrier broke down allowing Fusarium to cause infection. Furthermore, this effect was potentially exacerbated by the immunosuppressive treatment initiated. Ocular involvement is common in TEN patients (50%–70%) and encompasses a wide range of clinical manifestations including dry eye, photophobia, trichiasis, keratitis, symblapheron, corneal and conjunctival scars and blindness. Fusarium sp. endophthalmitis may occur; however, locally invasive fusariosis have mainly been reported in solid-organ recipients.
The diagnosis must be firstly suspected and subsequently confirmed by culture and/or biopsy of the affected region. In our patient, it was not possible to perform a biopsy before surgical treatment, because of the frailty of the ocular tissue. Nevertheless, the clinical evolution associated with the macroscopic characteristic of the skin (Fig. 2) and the positive cultures guided the management until enucleation.
All suspected Fusarium keratitis should be urgently evaluated and treated.2 Treatment is challenging because of the limited and variable susceptibility of Fusarium to antifungal agents,3 the poor tissue penetration of topical antifungal agents and the potential seriousness of infection. It usually involves a combination of topical and systemic antifungal therapy. Appropriate topical agents include natamycin,4 voriconazole or amphotericin B, which should be initially applied hourly with subsequent modification based on response. In combination with them, systemic voriconazole is generally proposed in the literature. However, in immunocompromised patients with invasive fusariosis, a lipid formulation of amphotericin B is recommended, considering its combination with voriconazole in cases of severe immunosuppression and/or severe disease.
Surgical therapy (wide exeresis to obtain free surgical margins) is suggested if there is no response to conservative treatment or to prevent local dissemination in immunocompromised patients with invasive fusariosis (central nervous system affection in our case). Besides conservative therapy should be maintained between 4 and 8 weeks after local and systemic cultures return negative.
In summary, to the best of our knowledge, this is the first report of Fusarium endophthalmitis in a child with TEN, who required enucleation. This case emphasizes the relevance of early suspicion and treatment in patients with defective epidermal barrier combined with an abnormal immune response, both risk factors for opportunistic infections caused by Fusarium.