JEADV (2003) 17, 440– 442
CASE REPOR T
Lethal systemic dissemination from a cutaneous infection due to Curvularia lunata in a heart transplant recipient Blackwell Publishing Ltd.
G Tessari,†* A Forni,§ R Ferretto,‡ M Solbiati,‡ G Faggian,§ A Mazzucco,§ A Barba† †Department of Biomedical and Surgical Sciences, Section of Dermatology and Venereal Disease, §Department of Biomedical and Surgical Sciences, Institute of Cardiac Surgery, ‡Institute of Infectious Diseases University of Verona, Verona Italy. *Corresponding author, Gianpaolo Tessari MD, Department of Medical Sciences, Section of Dermatology and Venereal Disease, University of Verona, Verona Italy, c/o Ospedale Civile Maggiore, Piazzale Stefani 137126 Verona (VR), Italy, tel. +39 45 8072547; fax +39 45 8300521; E-mail:
[email protected]
ABSTRAC T A 69-year-old male heart transplant recipient, being treated with Cell Cept, FK 506 and methylprednisolone had multiple deep brown skin nodules and nodes, on the upper right arm. Skin biopsy and culture detected a strain of Curvularia lunata. The infection disseminated to the whole skin surface, oral mucosa, upper third of the oesophagus and to the lungs. Therapy with antibiotics and antifungal drugs was ineffective. The patient died of sepsis. We did not find any other case of systemic dissemination from a skin infection due to C. lunata among heart transplant recipients. We feel that heart transplant recipients need adequate education to prevent situations that would put them at risk for infection and to seek medical advice immediately for an early diagnosis and an effective therapy. Key words: Curvularia lunata, heart transplant recipients, phaeohyphomycosis Received: 6 July 2002, accepted 12 July 2002
Introduction The term phaeohyphomycosis refers to subcutaneous and deepseated infections due to brown-pigmented (dematiaceous) moulds adopting a septate mycelial form in tissue and irregular small chains in culture.1,2 The number of organisms implicated as aetiological agents of phaeohyphomycosis is increasing; more than 80 different moulds, classified into 40 different genera have been incriminated. Among the more important aetiological agents can be included: Exophiala species, Bipolaris species, Exserohilum species, Phialophora species, Alternaria species, Curvularia species and Xylohypha bantiana. Phaeohyphomycosis can be divided into a number of distinct clinical forms: skin nodules and nodes, usually evolving into abscesses, infections of paranasal sinuses sometimes extending to the central nervous system, infections of the lung and abdominal organs. Skin infections are due mainly to Alternaria and Curvularia. In immunosuppressed people (patients affected by cancer or transplant recipients) systemic dissemination of phaeohyphomycosis and exitus can occur.3,4 440
A 69-year-old caucasian male had a heart transplant in September 1997. The reason for chronic heart failure was ischaemic cardiomyopathy. Immediately after the heart transplant standard triple drug immunosuppressive therapy was started. A course of antithymocyte globulins (Bad Homburg®) was given as well. The patient initially had a good recovery, but diagnosis of continuous acute ongoing rejection was made histologically starting from the second postoperative month. For 3 days intravenous pulses of methylprednisolone (four times) along with oral methotrexate (5 mg/week) were orally administrated. This rescue therapy failed and therefore the patient was switched to FK 506 (6 mg /d), Cell Cept (2 g /d) and methylprednisolone (10 mg /d). Eventually, reversal of continuous acute ongoing rejection was achieved; however, at the tenth postoperation month he was admitted as an emergency to the hospital. Skin examination revealed multiple deep brown, firm tender cutaneous nodules and nodes, ranging from 1 to 3 cm in diameter, on the upper right arm. Skin lesions were firmly attached to the skin, but not to the underlying tissues. The lesions were very painful. The patient was febrile (body temperature 38 °C). © 2003 European Academy of Dermatology and Venereology
Lethal systemic dissemination from a cutaneous infection due to C. lunata 441
On admission he admitted that he had got a splinter while working in his garden, 4 weeks before. He paid no attention to the wound and treated it only with common antiseptics. The first nodule appeared 1 week later, on the dorsum of the right hand. Three weeks later, the cutaneous lesions disseminated to the whole of the upper arm. Skin biopsy for microbiology and histology was obtained. General physical examination was negative, weight was 71.5 kg, blood pressure was 110/70 mmHg, pulse rate 105 beats/min. Routine laboratory tests were all normal except for red blood cells 3.99 × 1012 (normal 4.6 – 6.1), haemoglobin 108 g /L (normal 140 –180), glucose 9.3 mmol/ L (normal 3.5– 6.0), nitrogen 27.0 mmol / L (normal 2.8 –7.8), creatinine 212 µmol/ L (normal 44 –106) and, erythrocyte sedimentation rate 74 mm/h (normal 1–20). Total daily urine was 2300 mL. Amphotericin B 350 mg/d i.v. and Imipenem 500 mg twice daily were started. A few days after admission multiple hyperchromic maculopapular skin lesions, pink to brown in colour disseminated on the whole skin surface (figs 1 and 2) and to the oral mucosa. Over the next several days these lesions became necrotic centrally with a target configuration.
fig. 2 A detail of a big lesion on the upper right arm.
fig. 3 Histology of a skin lesion. Dermal granulomas containing bizarre hyphae (haematoxylin and eosin; original magnification × 250).
fig. 1 Dissemination of cutaneous lesions on the body surface.
The patient’s condition worsened: he had dysphagia, dyspnoea and oliguria. Serum nitrogen and creatinine rose to 44.4 mmol/ L and 409 µmol/L, respectively. Arterial blood gas analysis detected only a lower pO2 (68 mm/h; normal 75–100). Chest X-ray found a 2-cm nodule on the upper right lobe and a shadow on the median lobe. Endoscopy found the involvement of the upper third of the oesophagus. Computed axial tomography scan of the central nervous system and ultrasound abdomen examination were negative. Ten days later culture grew a strain of Curvularia lunata. Histology found a phaeohyphomycosis evolving into an abscess and a splinter (fig. 3–fig. 5). Fifteen days after hospital admission many clear, tense vesicles and bullae, some of them with purulent content, disseminated on the whole skin. Culture was positive for varicella zoster virus. Intravenous administration of acyclovir (400 mg/day i.v.) was started. In a few days the patient’s condition worsened further, and he died from sepsis. Autopsy found a disseminated phaeohyphomycosis involving the skin, lungs, mouth and the upper third of the oesophagus. Curvularia affected the whole upper lobe of the right lung. There were multiple disseminated foci, some of them evolving into abscesses, both in the right lung either in the left. Multiple
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442 Tessari et al.
fig. 4 Histology of a skin lesion: GIACATT (original magnification × 250).
ulcerated fungal lesions were detected on the tongue, on the oral mucosa and on the upper third of the oesophagus. No fungal lesions were found in the abdominal organs or in the central nervous system.
Discussion C. lunata is an environmental saprophyte, easily found in water, soil and vegetables, and at all latitudes. It grows in 1–3 weeks on agar Sabouraud at 30 °C. The mycelium has white septate hyphae that usually become deep green or black.1,2 Humans can be infected through the respiratory route or minimal skin traumas. Skin lesions are multiple deep brown nodules or nodes, 1–2 cm in diameter, sometimes evolving into abscesses. The overlying skin can be inflamed but it is usually normal. Skin lesions occur mainly on the extensory surface of the upper and lower arms. Other less common sites are the buttocks, face and neck. C. lunata can cause keratitis, sinusitis, infections of the lung, central nervous system, liver, sometimes evolving into abscesses. In immunodeficient people, systemic dissemination, sometimes with exitus can occur.4–7 The diagnosis requires culture or histological examination; hyphae are periodic acid-Schiff, GIEMSA and Fontana–Masson positive, but haematoxylin and eosin negative. C. lunata is an emerging pathogen among preterm infants, patients undergoing surgery or affected by cancer. Among preterm infants (less than 1 kg body weight) infections, C. lunata causes invasive fungal dermatitis, hepatitis, sinusitis and of urinary apparatus. Sometimes systemic dissemination and exitus can occur.8 Mycotic keratitis due to C. lunata may happen after laser in situ keratomilieusis.1 Among elderly people patients affected by cancer or other chronic disease, C. lunata may infect catheters and venous canulae.2,3 Peritonitis due to C. lunata occurred after contamination of catheters used for peritoneal dialysis.2 C. lunata has infected chronic vascular ulcers, burns and
mechanical heart valves.7 Atypical skin lesions due to C. lunata have been described in patients after allogeneic bone marrow transplantation.9 There is no consensus on the best antifungal chemotherapy for C. lunata, although amphotericin B has been most commonly used with variable success in invasive or systemic infection. In vitro susceptibility studies suggest possible efficacy of treatment with amphotericin B, miconazole and ketoconazole, fluconazole and itraconazole.1 Surgical treatment of cutaneous and subcutaneous lesions may be useful in some cases.4 We did not find any other case of lethal systemic dissemination from a skin infection due to C. lunata among heart transplant recipients. Chemotherapy was ineffective. The patient was infected 1 month before admission to the hospital. In that period of time, he did not seek medical advice. Strong drug-induced immunosuppression and delay in the diagnosis encouraged the fungus to disseminate and assisted the varicella zoster virus infection. As the patient had previous acute rejections, we chose to maintain immunosuppressive therapy at a lower level to avoid acute rejection. We feel that heart transplant recipients need adequate education to prevent situations that would put them at risk for infection and to seek medical advice immediately for an early diagnosis and an effective therapy.
References 1 Fernandez M, Noyola DE, Rossmann SN, Edwards MS. Cutaneous phaeohyphomycosis caused by Curvularia lunata and a review of Curvularia infections in pediatrics. Pediatr Infect Dis J 1999; 18: 727–731. 2 Lopes JO, Alves SH, Benevenga JP et al. Curvularia lunata peritonitis complicating peritoneal dialysis. Mycopathologia 1994; 127: 65– 67. 3 Guarner J, Del Rio C, Williams P, McGowan JE Jr. Fungal peritonitis caused by Curvularia lunata in a patient undergoing peritoneal dialysis. Am J Med Sci 1989; 298: 320 –323. 4 Heinz T, Perfect J, Schell W et al. Soft-tissue fungal infections: surgical management of 12 immunocompromised patients. Plast Reconstr Surg 1996; 97: 1391–1399. 5 Chung MS, Goldstein MH, Driebe WT Jr, Schwartz B. Fungal keratitis after laser in situ keratomileusis: a case report. Cornea 2000; 19: 236–237. 6 Ebright JR, Chandrasekar PH, Marks S et al. Invasive sinusitis and cerebritis due to Curvularia clavata in an immunocompetent adult. Clin Infect Dis 1999; 28: 687–689. 7 Still JM Jr, Law EJ, Pereira GI, Singletary E. Invasive burn wound infection due to Curvularia species. Burns 1993; 19: 77–79. 8 Berg D, Garcia JA, Schell WA et al. Cutaneous infection caused by Curvularia pallescens: a case report and review of the spectrum of disease. J Am Acad Dermatol 1995; 32: 375 –378. 9 Bonduel M, Santos P, Turienzo CF et al. Atypical skin lesions caused by Curvularia sp and Pseudoallescheria boydii in two patients after allogeneic bone marrow transplantation. Bone Marrow Transplant 2001; 27(12): 1311–1313.
© 2003 European Academy of Dermatology and Venereology JEADV (2003) 17, 440– 442
