Diffuse Erythematous Painful Nodules in a 2-Year-Old Girl with B-cell Acute Lymphoblastic Leukaemia

Case History

A 2-year-old female patient was referred to our dermatology department for painful red lesions on the face, trunk, legs, and arms since 3–4 days. She was under follow-up by pediatric hematology and oncology service with a diagnosis of B-cell acute lymphoblastic leukaemia (B-ALL). Dermatologic examination revealed erythematous painful papulonodules on the face, upper back, legs, and arms [Figure 1a and b]. There was no systemic involvement of leukaemia. The ALL-intercontinental Berlin-Frankfurt-Munster 2009 protocol (ALL-IC BFM 2009) was started (prednisone, vincristine, daunorubicin, L-asparaginase, methotrexate). Laboratory tests showed the following: Wbc: 530/mm³, Hb: 7.6 g/dl, Platelets: 66.000/mm³, Lymphocytes: 520/mm³, and Neutrophils: 10/mm³. Her family medical history was unremarkable. A punch biopsy was performed from the lesion on the upper back and sent for histopathologic examination [Figure 1c].

Figure 1.

(a) Erythematous painful nodule on the upper back. (b) Erythematous painful nodule on the face. (c) Fungal hyphae and spores localised in deep dermis-subcutaneous fatty tissue, haematoxylin and eosin staining (original magnification x100)

What is the diagnosis?

Diagnosis: Disseminated fusariosis

Preliminary diagnoses of Sweet syndrome, leukemia cutis, and fungal infection were considered.

On histopathological examination, there were fungal hyphae and spores localised in deep dermis and subcutaneous fat tissue [Figure 1c]. Gomori’s methenamine silver staining was positive [Figure 2c]. Fusarium spp. spores were detected in peripheral blood smear [Figure 2a], and thoracic computed tomography scan was performed and showed peripheral ground glass opacification due to Fusarium infection [Figure 2b].

Figure 2.

(a) Fusarium spp. spores in peripheral blood smear. (b) Thoracic computed tomography scan peripheral ground glass opacification. (c) Fungal hyphae and spores localised in deep dermis-subcutaneous fatty tissue, Gomori’s methenamine silver staining (original magnification x100)

Both fungal culture from biopsy material and blood culture were positive for Fusarium spp. with clinical manifestations and histopathological and laboratory findings, the diagnosis was consistent with the disseminated fusariosis.

Fluconazole has been started as prophylactic anti-fungal treatment at the beginning of the ALL-IC BFM 2009 protocol. After the diagnosis of disseminated fusariosis, intravenous 8 mg/kg/day voriconazole treatment was started. After 3 months, lesions were completely regressed. Secondary prophylaxis with variconazole was continued to prevent recurrence. The patient is under follow-up by the Pediatric Hematology Department, and clinical remission of her malignancy has been achieved.

Discussion

Fusarium species cause a broad spectrum of infections in humans, including superficial (such as onychomycosis and keratitis), locally invasive, and disseminated infections (occurring almost especially in seriously immuno-suppressed individuals),[1] as in our patient. The clinical form of fusariosis depends on the immune status of the patient and the entry point of infection.[2] Keratitis and onychomycosis are the most common infections among immunocompetent hosts. İnfection rarely may occur as a result of skin barrier damage, such as wounds and burns,[1] or the presence of foreign bodies, such as fusarial keratitis in contact lens users.[3]

Immuno-compromised patients at high risk for fusariosis have prolonged and severe neutropenia and/or severe T-cell deficiency.[4] According to Nucci et al.,[5] in 84 patients with haematologic diseases, the Fusarium infection occurred more frequently in patients with acute leukaemia (56%), and most patients (83%) were neutropenic at diagnosis.

The most frequent pattern of disseminated fusariosis is a combination of cutaneous lesions and positive blood cultures; involvement at other sites such as sinuses, lungs, and different organs can be seen.[2] In a report, cutanous involvement was detected in 70% of patients with fusariosis (a total of 259 patients: 232 immuno-compromised and 27 immuno-competent).[1] Cutaneous findings usually present with cellulitis as primary infection or may occur as a metastatic infection in patients with disseminated fusariosis.[1]

Disseminated infection requires the use of systemic agents and immunotherapy.[1] High-dose amphotericin B, voriconazole, and posaconazole can be used.[2]

Learning Points:

• Immuno-compromised patients at high risk for fusariosis have prolonged and severe neutropenia and/or severe T-cell deficiency.

• Skin lesions are important in the diagnosis of disseminated fusoriasis and are often the only material for laboratory and histopathological examinations.

• Fusariasis should be kept in mind in atypical skin lesions seen in immuno-suppressed patients, especially in patients with haematologic malignancies.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.