Yang Deborah J, Krishnan Ravi S, Guillen David R, Schmiege Lorenz M, Leis Paula F, Hsu Sylvia
Department of Dermatology, Baylor College of Medicine, Houston, Cockerell and Associates, Dallas, Texas 77030, USA.
Int J Dermatol. 2006 Apr;45(4):450-3. doi: 10.1111/j.1365-4632.2004.02363.x.
A 40-year-old Caucasian man presented to the dermatology clinic at Baylor College of Medicine, Houston, Texas, in February 2003, for the evaluation of three nonhealing ulcers. The patient's past medical history was significant for hypothyroidism and pulmonary sarcoidosis, the diagnosis of which was made in June 2000. In March 2000, the patient had complained of cough and shortness of breath. A purified protein derivative (PPD) (Mantoux text) was negative. Computed tomography (CT) scans of the chest revealed diffuse hilar and mediastinal adenopathy and bilateral interstitial and alveolar infiltrates. Although consistent with sarcoidosis, these findings were insufficient to exclude other etiologies, including disseminated fungal infection. Cultures and stains of subsequent bronchoscopy specimens failed to reveal any organisms, and histopathologic evaluation of the specimens was nondiagnostic. Based on the imaging studies and the negative cultures, a diagnosis of sarcoidosis was made, and the patient was started on therapy with prednisone. Before coming to our clinic, the patient had been on several courses of prednisone. In May 2002, the patient had presented to a private dermatologist with a 1-year history of a nonhealing 2.4 cm x 2.0 cm ulcer on the left medial forearm. Two biopsies were reported as nondiagnostic. The patient's presentation was interpreted as most consistent with Mycobacterium marinum infection, and so he was empirically treated with minocycline. This treatment was continued for almost 3 months without improvement in the ulcer. A few months after the minocycline had been discontinued, the patient was treated empirically for 2 months with ciprofloxacin. This treatment was also unsuccessful in ameliorating the ulcer. In between the two courses of antibiotics, specimens from the lesion were sent for bacterial and fungal cultures, which revealed normal skin flora. In January 2003, the patient returned to his private dermatologist with three ulcerations. In addition to the nonhealing ulcer on his left forearm, which he had acquired several months earlier, he had also developed a 3.0 cm ulcer on his right arm and a 3.0 cm ulcer on his central back. The patient refused biopsies at this visit. Given the patient's previous diagnosis of pulmonary sarcoidosis, it was thought that the skin lesions might represent ulcerative cutaneous sarcoidosis. Pyoderma gangrenosum was also considered to be a likely diagnosis. Therefore, the patient was started on a course of oral prednisone, an effective therapy for both sarcoidosis and pyoderma gangrenosum. Despite 1 month of treatment with 60 mg/day of prednisone, the ulcers increased, and the patient was subsequently referred to our clinic. Physical examination at the time of presentation revealed steroid acne on the trunk and upper extremities and three non-tender ulcers with erythematous, undermined borders (Figs 1-3). On the left arm, there was an adjacent nodule which the patient attributed to a scar from a previously healed ulcer. Histologic examination of biopsy specimens from all three sites showed similar findings. The lesion contained diffuse, suppurative, granulomatous, inflammatory infiltrates with extensive central necrosis. The infiltrates were composed of histiocytes, multinucleated foreign-body-type giant cells, plasma cells, lymphocytes, neutrophils, and neutrophil fragments. No organisms were seen in the initial, routinely stained sections. However, periodic acid-Schiff (PAS) staining demonstrated small fungal spores (Fig. 4) morphologically consistent with sporotrichosis, within the cytoplasm of multinucleated histiocytic giant cells (Fig. 5). Additional stains for bacteria and acid-fast organisms were negative. Cultures of the biopsy specimens from all three sites grew Sporothrix schenckii. Further questioning of the patient failed to reveal an obvious source of the infection. The patient denied any history of traumatic skin inoculation and did not engage in gardening or other outdoor activities that are classically associated with sporotrichosis. The patient did admit to blackberry picking on detailed retrospective questioning. Once the diagnosis of sporotrichosis was made, the patient was given 200 mg/day of itraconazole. After 2 months, the patient's ulcers were almost completely healed. The patient's pulmonary complaints were also much improved.
2003年2月，一名40岁的高加索男性前往德克萨斯州休斯顿贝勒医学院皮肤科诊所，接受三处不愈合溃疡的评估。患者既往有甲状腺功能减退和肺结节病病史，于2000年6月确诊。2000年3月，患者出现咳嗽和气短症状。结核菌素纯蛋白衍生物（PPD）（曼托试验）结果为阴性。胸部计算机断层扫描（CT）显示肺门和纵隔弥漫性淋巴结肿大以及双侧间质和肺泡浸润。虽然这些表现符合结节病，但不足以排除包括播散性真菌感染在内的其他病因。后续支气管镜检查标本的培养和染色未发现任何病原体，标本的组织病理学评估也未得出诊断结果。基于影像学检查和阴性培养结果，诊断为结节病，患者开始接受泼尼松治疗。在前来我们诊所之前，患者已经接受了几个疗程的泼尼松治疗。2002年5月，患者因左前臂内侧一处2.4厘米×2.0厘米的溃疡长达1年不愈合，前往一名私人皮肤科医生处就诊。两次活检报告均未得出诊断结果。患者的表现被解释为最符合海分枝杆菌感染，因此经验性地用米诺环素进行治疗。这种治疗持续了近3个月，溃疡没有改善。在停用米诺环素几个月后，患者又经验性地用环丙沙星治疗了2个月。这种治疗也未能改善溃疡。在两个抗生素疗程之间，从病变部位采集的标本进行了细菌和真菌培养，结果显示为正常皮肤菌群。2003年1月，患者带着三处溃疡再次去找他的私人皮肤科医生。除了几个月前出现的左前臂不愈合溃疡外，他的右臂又出现了一个3.0厘米的溃疡，背部中央也出现了一个3.0厘米的溃疡。此次就诊时患者拒绝活检。鉴于患者先前诊断为肺结节病，认为皮肤病变可能代表溃疡性皮肤结节病。坏疽性脓皮病也被认为是一个可能的诊断。因此，患者开始服用口服泼尼松疗程，泼尼松对结节病和坏疽性脓皮病都是有效的治疗药物。尽管每天服用60毫克泼尼松治疗了1个月，但溃疡仍在增大，随后患者被转诊至我们诊所。就诊时体格检查发现躯干和上肢有类固醇性痤疮，还有三处无压痛的溃疡，边界呈红斑状、潜行性（图1 - 3）。在左臂上，有一个相邻的结节，患者称是之前愈合溃疡留下的疤痕。对所有三个部位的活检标本进行组织学检查显示出相似的结果。病变包含弥漫性、化脓性、肉芽肿性炎性浸润，并伴有广泛的中央坏死。浸润细胞包括组织细胞、多核异物型巨细胞、浆细胞、淋巴细胞、中性粒细胞和中性粒细胞碎片。在最初的常规染色切片中未发现病原体。然而，过碘酸希夫（PAS）染色显示在多核组织细胞性巨细胞的细胞质内有形态与申克孢子丝菌一致的小真菌孢子（图4）（图5）。对细菌和抗酸菌的其他染色结果均为阴性。所有三个部位的活检标本培养均生长出申克孢子丝菌。进一步询问患者未发现明显的感染源。患者否认有任何皮肤创伤接种史，也未从事与孢子丝菌病经典相关的园艺或其他户外活动。在详细的回顾性询问中，患者确实承认曾采摘过黑莓。一旦确诊为孢子丝菌病，患者开始服用每天200毫克的伊曲康唑。2个月后，患者的溃疡几乎完全愈合。患者的肺部症状也有了很大改善。
