Cutaneous aspergillosis in a patient with follicular lymphoma

ARTICLE

Sir,

We read with great interest the article by Nenoff et al., reporting a case of secondary cutaneous aspergillosis (CA) developing during therapy against acute leukemia [1]. CA has been considered a very rare entity, although it has been recognized as one of the nosocomial infections arising in immunocompromised patients [2-6]. However, with an increasing number of immunocompromised patients, including those with acquired immunodeficiency syndrome and transplant recipients, the frequency of reports of CA and the spectrum of its manifestations have increased [2-6]. We recently experienced a case of CA that developed during therapy for non-Hodgkin's lymphoma. In contrast with a case of typical CA, it was difficult to determine whether the lesion was primary or secondary in this case.

A 44-year-old woman was diagnosed with follicular lymphoma involving the bone marrow and the pleura. Initially, she had been treated with several courses of chemotherapy, including CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and COP, which had failed to achieve complete remission. These chemotherapies did not cause severe or long-term neutropenia. Prednisolone alone had been administered daily at a dose of 10-15mg/day for 4 months to control disease activity. The patient had been receiving oral fluconazole (200mg daily) for the prophylaxis of fungal infection. Eighteen months after diagnosis of lymphoma, she presented with a subcutaneous tumor 3 x 3 cm in diameter in the left femur. The tumor was not accompanied by epidermal changes except for a mild purple coloration, and the site was not associated with any previous traumas or adhesive dressings. The tumor was excised, and histological examination revealed necrotizing granulomas with fungal elements (branching septate hyphae) consistent with Aspergillus species. Based upon the histological and serological findings, diagnosis of CA was made. To rule out the possibility of hematogenous dissemination, meticulous examinations, including X-ray, computed tomography, and gallium citrate scanning, were repeatedly performed; no other focus of aspergillosis was found. Intravenous amphotericin-B (0.5mg/kg daily) followed by oral intraconazole (200mg daily) was given. No recurrence of aspergillosis at the primary site or at any other site was subsequently observed even after undergoing high-dose chemotherapy combined with allogeneic hematopoietic stem cell transplantation (HSCT), and the administration of high-dose prednisolone for graft-versus-host disease.

It was difficult to determine definitively whether the lesion of CA was primary or secondary in this case for the following reasons. The typical skin manifestation of primary CA is an erythematous, edematous, indurated plaque that progresses to a necrotizing ulceration. Such lesions are generally associated with traumas, intravenous access devices, and adhesive dressings [3, 7-9]. Only rarely have cases of primary CA without predisposing skin injuries been reported [10, 11]. The lesion of secondary CA usually occurs at multiple sites, and is caused by hematogenous spread from the primary site of aspergillosis, which is typically the lung. Our patient developed solitary CA at a site that had no history of predisposing skin injuries or adhesive dressings. In addition, the lesion was not associated with significant epidermal reactions. Based upon these findings, secondary CA was initially suspected. Repeated examinations, however, did not disclose any other focus of aspergillosis, and no recurrence of aspergillosis was observed even after allogeneic HSCT and administration of high-dose glucocorticoid. Furthermore, successful treatment by local excision and subsequent anti-fungal treatment in this case reinforced the possibility of primary CA, since the outcome of primary CA is generally much better than that of secondary CA [2, 3]. We conclude that physicians should be aware of the possibility of CA and its wide spectrum of clinical manifestations in immunocompromised patients.

References

1
Nenoff P, Kliem C, Mittag M, Horn M-C, Niederwieser D, Haustein U-F. Secondary cutaneous aspergillosis due to Aspergillus flavus in an acute myeloid leukaemia patient following stem cell transplantation. Eur J Dermatol 2002; 12: 93-8.

2
van Burik JAH, Colven R, Spach DH. Cutaneous aspergillosis. J Clin Microbiol 1998; 36: 3115-21.

3
Walsh TJ. Primary cutaneous aspergillosis: an emerging infection among immunocompromised patients. Clin Infect Dis 1998; 27: 453-7.

4
Galimberti R, Kowalczuk A, Parra IH, Ramos MG, Flores V. Cutaneous aspergillosis: a report of six cases. Br J Dermatol 1998; 139: 522-6.

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D'Antonio D, Pagano L, Girmenia C, Parruti G, Mele L, Candoni A, Ricci P, Martino P. Cutaneous aspergillosis in patients with haematological malignancies. Eur J Clin Microbiol Infect Dis 2000; 19: 362-5.

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Murakawa GJ, Harvell JD, Lubitz P, Schnoll S, Lee S, Berger T. Cutaneous aspergillosis and acquired immunodeficiency syndrome. Arch Dermatol 2000; 136: 365-9.

7
Grossman ME, Fithian EC, Behrens C, Bissinger J, Fracaro M, Neu HC. Primary cutaneous aspergillosis in six leukemic children. J Am Acad Dermatol 1985; 12: 313-8

8
Allo MD, Miller J, Townsend T, Tan C. Primary cutaneous aspergillosis associated with Hickman intravenous catheters. N Engl J Med 1987; 317: 1105-8.

9
Chakrabarti A, Gupta V, Biswas G, Kumar B, Sakhuja VK. Primary cutaneous aspergillosis: our experience in 10 years. J Infect 1998; 37: 24-7.

10
Epstein MD, Brook S, Segalman KA, Mulholland JH, Orbegoso CM. Successful treatment of primary cutaneous Aspergillus flavus infection of the hand with oral itraconazole. J Hand Surg 1996; 21A: 1106-8.

11
Richard KA, Mancini AJ. A painful erythematous forearm nodule in a girl with Hodgkin's disease. Arch Dermatol 2000; 136: 1165-70.

Answers to the CME in EJD 6, 2002