Pseudoporphyria as a result of voriconazole use: a case report

Voriconazole, a second-generation triazole, has recently been approved by the Food and Drug Administration (FDA) to treat invasive aspergillosis and refractory infections with Scedosporium apiospermum or Fusarium spp. The reported side-effects of voriconazole include visual changes, headaches, elevated hepatic enzymes, Steven-Johnson syndrome, toxic epidermal necrolysis, chelitis, photosensitivity, discoid lupus erythematosus and anaphylactoid infusion reactions. Pseudoporphyria was first described in association with nalidixic acid. It has the same clinical and histologic features as porphyria cutanea tarda (PCT) but is distinguished by normal porphyrin levels in the serum, urine and stool. We present the case of a patient who developed pseudoporphyria after receiving treatment with voriconazole.     

Persistent subcutaneous Scedosporium apiospermum infection

We report the case of a 52-year-old male heart transplant recipient with a persistent localized subcutaneous infection by Scedosporium apiospermum. This form differs from the most common mycetoma by the absence of granules. The patient showed multiple nodules on the right hand that were surgically removed. Concomitantly, he received oral itraconazole, but the infection persisted for two years, and several surgical interventions were necessary to eradicate the infection. Our case demonstrates that a medical approach alone may be not sufficient to cure this fungal infection.     

Cutaneous infection due to Scedosporium apiospermum in an immunosuppressed patient

Scedosporium apiospermum, the anamorphic form of Pseudallescheria boydii, is a filamentous fungus with low inherent virulence. Increasing numbers of cases of this infection have been reported probably related to the rising number of immunosuppressed persons. Apart from mycetoma, cutaneous and subcutaneous infection is rarely encountered in clinical practice. We describe a case of cutaneous infection caused by Scedosporium apiospermum in a subject with rheumatoid arthritis and diabetes mellitus who was submitted to long-term therapy with cyclosporin and corticosteroids. Histopathologic examination of a skin biopsy showed a granulomatous infiltrate with hyaline septate hyphae. Culture of two skin biopsies taken at two different observations of the woman, 3 weeks apart, allowed isolation of Scedosporium apiospermum. Therapy with itraconazole, 400 mg/day, for 3 months was effective in curing the infection.     

Cutaneous Scedosporium apiospermum infection in an immunocompromised patient and a review of the literature

Scedosporium apiospermum (also known as Pseudallescheria boydii) is a ubiquitous filamentous fungus. This fungus is known as a cause of mycetoma, which may occur in a normally immune host following trauma. However, in an immunocompromised host, S. apiospermum may cause a life-threatening infection. We describe a case of S. apiospermum infection of the right hand in a patient who was receiving long-term immunosuppressants for adult Still's disease. We also review the cases of S. apiospermum infection with cutaneous manifestations reported between 1998 and 2003.     

SCEDOSPORIUM INFECTION IN A PATIENT WITH ANTI-TNFα THERAPY

Patients on anti-TNFα therapy are at increased risk for rare opportunistic infections. Here we are reporting a case of Scedosporium apiospermum infection in a patient treated with anti-TNF for 5 years. Patients on anti-TNFα need close follow-up and clinicians should be suspicious for atypical infections in these immunocompromised hosts.     

Severe phototoxicity associated with long‐term voriconazole treatment

Voriconazole is a second‐generation triazole antifungal approved for the treatment of invasive fungal infections, particularly with Aspergillus, Candida, Fusarium, and Scedosporium spp. Frequently reported adverse effects of voriconazole include visual disturbance (21 %), elevated liver enzymes (15.6 %) and rashes (7 %), which are largely attributable to drug‐induced photosensitivity. We report a case of serious phototoxicity in a 8 year old boy who underwent chemotherapy for AML. He received voriconazole for the treatment and subsequent re‐infection prophylaxis after pulmonary aspergillosis. One year after the start of therapy he developed blistering eruptions on his face after minimal sunlight exposure. Recent reports about the development of squamous cell carcinoma and melanoma, respectively, in children during and after oral therapy with voriconazole seem to warrant systematic follow‐up investigations of all voriconazole‐treated patients.     

Eumycetoma

Eumycetoma is caused by different fungi. Madurella mycetomatis, Madurella grisae, and Scedosporium apiospermum are the most common causative agents. This disease is more frequent on the lower extremities but can also be present in other areas. The diagnosis is made by direct microscopic examination and histologic study, which should show hyphae and vesicles characteristic of the fungi. Etiologic identification of the species of the fungus is sometimes difficult by culture and biopsy specimen; in these cases, molecular techniques can help to identify the infecting organism. Treatment has been with amphotericin B, which is now seldom used due to its side effects and limited success. The best therapeutic choice is surgical removal of the lesion, followed by medical treatment. This includes antifungals such as the azoles, ketoconazole and itraconazole; in resistant cases, posaconazole and voriconazole are currently recommended. In particular, the combination of terbinafine and itraconazole can elicit a good result in some cases.     

A case of cutaneous Scedosporium infection in an immunocompromised patient

Scedosporium apiospermum, the asexual stage of Pseudoallescheria boydii, is a fungus ubiquitous in soil as well as organically polluted areas, where nitrogen-containing compounds are abundant. It is an emerging opportunistic pathogen that can range from cutaneous to disseminated infection and can be fatal within months of diagnosis. Here we present a case of disseminated S. apiospermum infection with cutaneous manifestations in a 59-year-old woman with myelodysplastic syndrome, in remission from chronic lymphocytic leukemia, presented with pneumonia and deteriorating mental status. An X-ray computed tomography scan showed three non-contrast-enhancing hypodensities affecting the brain. Many erythematous, indurated skin lesions, measuring 3-5 mm in diameter, were noted on her chest, shoulders and arms. Biopsies were submitted for culture and histology. Histopathologic examination revealed superficial and deep perivascular and periadnexal inflammatory infiltrates of lymphocytes and neutrophils. Scattered collections of fungal organisms were noted near the eccrine glands. The periodic acid Schiff with diastase stain showed the presence of variable sized spores and hyphae with some acute angle branching. Both tissue and blood cultures were positive for a single Scedosporium species. Histologically, eccrine or peri-eccrine involvement by fungi may be an important finding for Scedosporium infection of the skin.     

Scedosporium apiospermum: an emerging opportunistic pathogen that must be distinguished from Aspergillus and other hyalohyphomycetes

We report a case of cutaneous Scedosporium apiospermum infection in an immunocompromised host. S. apiospermum is an emerging opportunistic pathogen, especially in organ transplant recipients. Prompt identification is critical because of its resistance to most antifungal drugs. Its histopathologic features are indistinct and overlap with those of more commonly recognized hyalohyphomycetes such as Aspergillus species. Cultures from infected tissue are generally required for correct identification. Clinicians and pathologists must be familiar with this organism and recognize the need for culture studies in addition to histopathology in the evaluation of specimens from immunocompromised patients with suspected fungal infection.     

波氏假阿利什菌和尖端赛多孢子菌随机扩增DNA多态性分析

目的 了解波氏假阿利什菌和尖端赛多孢子菌的基因学特征,研究DNA分型与菌种来源的关系.方法 采用随机扩增多态性DNA分析(RAPD)方法.结果 3种引物可将来自5个国家的13株波氏假阿利什菌和18株尖端赛多孢子菌分为31个基因型.多引物聚类分析所得树状图显示,除来自哥伦比亚土壤的3株波氏假阿利什菌外,其他受试菌株无地域性群集分布特点.但受试菌株中的多数波氏假阿利什菌和尖端赛多孢子菌株分别聚集成一群.结论 波氏假阿利什菌和尖端赛多孢子菌存在较大株间差异,致病菌没有明显的地域性分布趋势,RAPD分型聚类分析结果与形态学分类之间具有一定一致性.     

Persistent erythematous plaque after minor trauma in an immunocompromised woman

Scedosporium apiospermum is a ubiquitous soil fungus with a worldwide distribution. It can cause a wide range of clinical disease, from cutaneous and subcutaneous infections, to pneumonia, brain abscess, and life threatening systemic illness. The diagnosis of cutaneous disease is with biopsy and culture. We discuss the case of an elderly immunocompromised woman who presented with a persistent erythematous plaque on the elbow after minor trauma. A biopsy revealed Scedosporium apiospermum. Treatment usually requires surgical resection in conjunction with antifungal therapy.     

Voriconazole photosensitivity: 7 cases

BACKGROUND: Voriconazole is a new second-generation fluconazole-derived triazole. With greater potency against susceptible species and a broader spectrum of activity than fluconazole, it is the treatment of choice for invasive pulmonary aspergillosis and other fungal infections (Fusarium, Scedosporium/Pseudalleschezria) is indicated in a visit Candida infections refractory to fluconazole. We describe 7 cases of photosensitivity during treatment with voriconazole in a setting of immunodepression. CASE REPORTS: The patients comprised 5 women and 2 men with a mean age of 38 years (17-67 years). Five had undergone pulmonary transplantation for mucoviscidosis, one had undergone kidney transplantation for lupus nephroangiosclerosis and one was on long-term systemic steroid treatment for Sj?gren's syndrome. All patients had very severe immunosuppression and were receiving voriconazole for pulmonary aspergillosis (6 cases) or Scedosporium infection (1 case). Photosensitization appeared within 5 weeks to 14 months after the start of treatment, and in all cases followed exposure to sun, occasionally at low levels. In all cases, cutaneous lesions rapidly disappeared on discontinuation of treatment. DISCUSSION: There have been reports in the literature, although rare, of photosensitivity with voriconazole. Patients must be informed of the possibility of this adverse effect and sun protection must be recommended when voriconazole is prescribed, particularly during periods of intensive exposure.     

系统性尖端赛多孢子菌感染小鼠IL-12表达的研究

建立小鼠系统性尖端赛多孢子菌感染模型,用酶联免疫吸附试验(ELISA)及逆转录-聚合酶链反应(RT-PCR)分别检测脾内IL-12蛋白质及mRNA水平,用平皿系列稀释法检测肾内菌落形成单位(CFU),并记录平均生存时间(MST)。结果,脾内IL-12蛋白质含量:致死量组均低于正常组;亚致死量组均高于正常组,且第7天显著高于第3天;地塞米松免疫抑制组均高于正常组。此外,免疫抑制组均低于相应时间亚致死量组。脾中IL-12mRNA表达水平与蛋白质水平基本一致。致死量组及免疫抑制组肾内均有大量菌生长,亚致死量组肾内菌量少。致死量感染组平均生存时间为13.6天,免疫抑制组为14.2天,对照组和亚致死量组均超过45天。结果示健康鼠大量菌感染及免疫抑制鼠小量菌感染均可引起致死性感染,而IL-12在小鼠系统性尖端赛多孢子菌感染中可能具有保护作用。     

Primary Cutaneous Aspergillosis in an Immunocompetent Patient: Successful Treatment with Oral Voriconazole

Abstract:   We report a case of primary cutaneous aspergillosis in an immunocompetent child that responded rapidly to oral voriconazole therapy. Voriconazole may be considered as a treatment option for pediatric patients with primary cutaneous aspergillosis.     

波氏假阿利什霉和尖端赛多孢子菌的孢子、菌丝对唑类抗真菌剂敏感性的比较

目的：观察波氏假阿利什霉和有性期尖端赛多孢子菌的不同菌体形态对唑类抗真菌剂敏感性的异同。方法：参考美国NCCLS M38-A试验方案，检测氟康唑、伊曲康唑及伏力康唑对9株波氏假阿利什霉、18株尖端赛多孢子菌的孢子、发芽孢子及菌丝的MIC，并分析比较相互间的异同。结果：大多数受试波氏假阿利什霉与尖端赛多孢子菌菌株以三种不同菌体形态接种时，对上述三种唑类抗真菌剂的敏感性无显著性差异；对同一种唑类药物，两菌的敏感性无显著性差异，但两菌均对伏力康唑较敏感，其敏感性高于对氟康唑和伊曲康唑者。结论：在波氏假阿利什霉及尖端赛多孢子菌的三种唑类药物敏感试验中，其接种易于获取并易于量化的未发芽孢子时的MIC，可反映此三种唑类药物体外对发芽孢子及菌丝的抗菌活性。在受试的三种唑类药物中，伏力康唑在治疗波氏假阿利什霉及尖端赛多孢子菌感染方面值得推荐。     

Recurrent Scedosporium apiospermum mycetoma successfully treated by surgical excision and voriconazole

Scedosporium apiospermum is an emerging opportunistic fungus that can cause localized infection in healthy hosts or severe disseminated disease in immunocompromised hosts. Most cases are reported in Western Europe, Australia, and North America. We report a 52-year-old immunocompetent Taiwanese woman who presented with a 6-year history of recurrent asymptomatic papulonodular lesions on her right foot after minor trauma. Deep fungal infection caused by Scedosporium sp. was diagnosed after a skin biopsy with fungal culture of the skin specimen. She underwent two surgical excisions, each followed by a 4-month course of oral itraconazole and intralesional injections of amphotericin B as well, but similar lesions recurred at the same location 1 year later. She had another surgical excision and the pathological findings showed mycetoma. The fungus was identified as S. apiospermum by PCR assay of fungal culture specimen using the internal transcriber spacers (ITS1, similarity 99.4%; ITS2, similarity 100%) and the D1–D2 (similarity 99.0%) regions of the ribosomal operon. After 4 months of oral voriconazole (400 mg/day), no recurrence was noted in the subsequent 2 years.     

Scedosporium apiospermum infection imitating lymphocutaneous sporotrichosis in a patient with myeloblastic-monocytic leukaemia

Summary A 63-year-old man with a history of myeloblastic—monocytic leukaemia developed partly suppurating cutaneous nodules on the lower left leg. The nodules proceeded to spread in a linear fashion up the limb, following the line of the lymphatic drainage. Mycological examination of a skin biopsy demonstrated Scedoporium apiospermum. This case highlights the potential for Scedosporium species to act as opportunistic infections in immunosuppressed humans.     

PCR-RFLP技术快速鉴定八种致病丝状病原真菌的实验研究

目的 建立能快速鉴定深部丝状真菌感染病原菌的PCR-RFLP方法。方法 用真菌通用引物扩增烟曲霉、黄曲霉、土曲霉、黑曲霉、杂色曲霉、构巢曲霉、尖端赛多孢和串珠镰刀菌的ITS区,分别用HhaⅠ、HaeⅢ、HinfⅠ、TaqⅠ和MspⅠ 5种限制性核酸内切酶对PCR产物进行酶切,建立以PCR为基础的RFLP方法,然后对22株临床株和2株环境分离株进行PCR-RFLP图谱分析。结果 对PCR产物进行RFLP分析可以准确鉴定8种深部致病丝状真菌,从DNA提取到酶切分析可以在1个工作日完成。22株临床株和2株环境分离株PCR-RFLP鉴定结果与传统的形态学鉴定结果一致。结论 PCR-RFLP技术是一种能够快速鉴定丝状真菌的有效方法。     

Antistreptococcal treatment of guttate psoriasis: a controlled study

Background  The role of streptococcal infection in the initiation of guttate psoriasis is well-recognized. But the treatment results with oral erythromycin and phenoxymethylpenicillin are conflicting.
Objective  Our purpose was to evaluate the effectiveness of these antibiotics in the treatment of streptococcus associated guttate psoriasis comparing with a control group.
Methods  A total of 43 male patients with serologic evidence of a recent streptococcal infection were studied. Their mean age was 21 years (ranged between 19 and 23 years). These 43 patients were randomly allocated into three groups (no treatment group n  = 15, erythromycin group n  = 14, phenoxymethylpenicillin group n  = 14). Both the treatment groups were treated for 14 d. All the groups were followed up for additional 4 weeks.
Results  There were no statistically significant improvement in any group and among the groups.
Conclusion  There was no statistically significant improvement in streptococcus associated guttate psoriasis with or without a course of oral penicillin or erythromycin.     

Co‐infection of Scedosporium apiospermum and Mycobacterium chelonae in an immunocompetent host

A 75‐year‐old man presented with multiple, scaly, erythematous, grouped papules, nodules and plaques with tenderness ranging from the right forearm to hand dorsum and the right lower leg for 2–3 months. Five months prior to presentation, the patient had received an antibiotic skin test on his right forearm. Lesions appeared approximately 2–3 months after the antibiotic skin test, slowly progressing without clinical improvement. Culture for fungus on the right forearm revealed growth of Scedosporium apiospermum. The tissue acid‐fast bacilli (AFB) culture for the right forearm and right leg revealed growth of non‐tuberculous mycobacteria which was Mycobacterium chelonae, and subsequent tissue polymerase chain reaction of both sites reported positive signs of M. chelonae. On diastase periodic acid‐Schiff stain of the biopsy specimen of the right forearm, fungal hyphae were found while rod‐shaped bacilli could be seen in AFB stain for the biopsy specimen of the right leg. The patient was treated with oral clarithromycin and ciprofloxacin along with an oral antifungal agent for 13 weeks. After the treatment, the lesions subsided and left a scar. We report a rare case of co‐infection of S. apiospermum and M. chelonae in an immunocompetent host.