Ahealthy, RIGHT-HANDED, HIGH school boy developed acute left hand and forearm swelling and erythema suggestive of a rapidly spreading infection. Intraoperative cultures were negative. Biopsy indicated a diagnosis of eosinophilic fasciitis. Eosinophilic fasciitis can mimic dramatic infections such as flexor tenosynovitis or necrotizing fasciitis. 不健康的右撇子高中男生出现急性左手和左臂肿胀和红斑，表明感染迅速扩散。术中培养阴性。活检提示嗜酸性粒细胞性筋膜炎的诊断。嗜酸性粒细胞性筋膜炎可类似于剧烈感染，例如屈肌腱鞘炎或坏死性筋膜炎。
CASE REPORT 病例报告
A 16-year-old boy developed a swollen left little finger proximal interphalangeal joint with no discrete trauma on the first day of football practice. He subsequently presented to the emergency department with a 1-day history of considerable pain, swelling, and ascending erythema and cellulitis volarly from 一名 16 岁男孩在足球训练的第一天出现左小指近端指间关节肿胀，无离散性外伤。随后，他到急诊科就诊，有 1 天的严重疼痛、肿胀、上行性红斑和蜂窝织炎的症状
Received for publication April 2, 2013; accepted in revised form August 13, 2013. 2013 年 4 月 2 日接收出版;2013 年 8 月 13 日以修订后的形式接受。
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Corresponding author: Andréa B. Lese, MD, Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, Yale-New Haven Hospital, 800 Howard Ave., PO Box 208071, New Haven, CT 06520-8071; e-mail: andrea.lese@yale.edu. 通讯作者：Andréa B. Lese，医学博士，耶鲁大学医学院骨科和康复科，耶鲁-纽黑文医院，800 Howard Ave.， PO Box 208071， New Haven， CT 06520-8071;电子邮件：andrea.lese@yale.edu。 0363-5023/13/38A11-0018$36.00/0 0363-5023/13/38A11-0018 美元$36.00/0 http://dx.doi.org/10.1016/j.jhsa.2013.08.106
the left hand to the midforearm. He described median nerve distribution paresthesias distally. The patient exhibited clawing of all digits with fusiform swelling and tenderness over the flexor tendon sheaths extending into the palm and volar forearm. He had decreased active and passive range of motion of the wrist and fingers secondary to pain with any motion, especially on extension. The clinical presentation appeared consistent with flexor tenosynovitis. Although the patient was afebrile and stable, there was also concern for necrotizing fasciitis given the rapid progression. His white blood cell (WBC) count was 9.9 xx10^(9)//L9.9 \times 10^{9} / \mathrm{L} (normal, 4.0-10.0 xx10^(9)//L4.0-10.0 \times 10^{9} / \mathrm{L} ) with 2%2 \% eosinophils (normal, 1%-4%1 \%-4 \% ). His erythrocyte sedimentation rate was 11mm//h11 \mathrm{~mm} / \mathrm{h} (normal, 0-20mm//h0-20 \mathrm{~mm} / \mathrm{h} ), and his C-reactive protein was 23.5mg//L23.5 \mathrm{mg} / \mathrm{L} (normal, 0.1-3.0mg//L0.1-3.0 \mathrm{mg} / \mathrm{L} ). 左手到前臂中部。他描述了远端正中神经分布感觉异常。患者表现为所有手指抓挠，延伸至手掌和前臂掌侧的屈肌腱鞘出现梭形肿胀和压痛。他的手腕和手指的主动和被动活动范围缩小，继发于任何运动时的疼痛，尤其是在伸展时。临床表现似乎与屈肌腱鞘炎一致。尽管患者不发热且稳定，但鉴于进展迅速，也担心坏死性筋膜炎。他的白细胞 （WBC） 计数为 9.9 xx10^(9)//L9.9 \times 10^{9} / \mathrm{L} （正常， 4.0-10.0 xx10^(9)//L4.0-10.0 \times 10^{9} / \mathrm{L} ） 和 2%2 \% 嗜酸性粒细胞 （正常， 1%-4%1 \%-4 \% ）。他的红细胞沉降率为 11mm//h11 \mathrm{~mm} / \mathrm{h} （正常， 0-20mm//h0-20 \mathrm{~mm} / \mathrm{h} ），C 反应蛋白为 23.5mg//L23.5 \mathrm{mg} / \mathrm{L} （正常， 0.1-3.0mg//L0.1-3.0 \mathrm{mg} / \mathrm{L} ）。
The patient underwent arthrotomy of the left little finger proximal interphalangeal joint, which was thought to be the source of the infection, debridement of the distal forearm and flexor tendon sheaths on the ulnar side of the hand, and a carpal tunnel release. We encountered no purulence. However, upon deeper dissection, we noted thickening of the flexor digitorum profundus tendon tenosynovium as well as copious edema in the forearm musculature and in the carpal tunnel. The median nerve was hyperemic. 患者接受了左小指近端指间关节的关节切开术，这被认为是感染源，手尺侧前臂远端和屈肌腱鞘的清创术，以及腕管松解术。我们没有遇到脓。然而，在更深入的解剖中，我们注意到趾深屈肌腱腱增厚，以及前臂肌肉组织和腕管大量水肿。正中神经充血。
FIGURE 1: T2-weighted MRI scan shows marked edema within the carpal tunnel as well as in the overlying palmar surface. 图 1：T2 加权 MRI 扫描显示腕管内以及上覆的手掌表面有明显的水肿。
After surgery, the patient received vancomycin and then clindamycin intravenously and then clindamycin orally after marked improvement in pain, swelling, and median nerve symptoms. He was discharged with a presumptive diagnosis of infectious flexor tenosynovitis on the third postoperative day and was prescribed oral clindamycin for 10 days. The multiple intraoperative cultures from the proximal interphalangeal joint, forearm, and carpal tunnel remained negative. No biopsies were sent for pathology. 手术后，患者接受万古霉素，然后静脉注射克林霉素，然后在疼痛、肿胀和正中神经症状明显改善后口服克林霉素。他在术后第 3 天因推定诊断为感染性屈肌腱鞘炎而出院，并被开具口服克林霉素 10 天。来自近端指间关节、前臂和腕管的多次术中培养保持阴性。没有送去病理检查。
The patient completed 10 days of oral clindamycin. Four days after completing the antibiotic, he suddenly developed a complete recurrence of his earlier symptoms. His WBC count was 10.9 xx10^(9)//L10.9 \times 10^{9} / \mathrm{L} with 6%6 \% eosinophils, the erythrocyte sedimentation rate was 10 , and the C-reactive protein was 0.9 . Radiographs showed only soft tissue swelling. A magnetic resonance imaging (MRI) study displayed extensive deep fascial and muscle edema involving the superficial and deep flexor muscles and tendons suggestive of a deep fascial infection and necrotizing fasciitis (Fig. 1). He was admitted to the hospital for repeat incision with debridement, re-release of the carpal tunnel, and flexor tenosynovectomy. We sent multiple cultures as well as biopsies. The patient gradually improved. After infectious disease consultation, he was placed on vancomycin and piperacillin/ tazobactam and then transitioned to clindamycin. All cultures remained negative for bacteria, acid-fast bacteria, and fungi. However, the pathology report revealed an infiltrate of lymphocytes, abundant histiocytes, and numerous eosinophils, consistent with eosinophilic fasciitis (Figs. 2 and 3). 患者完成了 10 天的口服克林霉素治疗。完成抗生素治疗四天后，他之前的症状突然完全复发。他的 WBC 计数 10.9 xx10^(9)//L10.9 \times 10^{9} / \mathrm{L} 与 6%6 \% 嗜酸性粒细胞一起，红细胞沉降率为 10 ，C 反应蛋白为 0.9 。X 线片显示仅软组织肿胀。一项磁共振成像 （MRI） 研究显示，涉及浅表和深部屈肌和肌腱的广泛深部筋膜和肌肉水肿，提示深部筋膜感染和坏死性筋膜炎（图 1）。他被送入医院接受重复切口清创术、腕管再松解术和屈肌腱鞘切除术。我们发送了多种培养物和活检。患者逐渐好转。传染病会诊后，病人接受万古霉素和哌拉西林/他唑巴坦治疗，然后转用克林霉素。所有培养物的细菌、抗酸细菌和真菌均呈阴性。然而，病理报告显示淋巴细胞浸润、丰富的组织细胞和大量嗜酸性粒细胞，与嗜酸性筋膜炎一致（图 2 和 3）。
The patient underwent 6 weeks of oral nonsteroidal anti-inflammatory medication and clindamycin 患者接受了 6 周的口服非甾体抗炎药和克林霉素治疗
FIGURE 2: Histological slide at xx10\times 10 shows numerous cells, including lymphocytes, histiocytes, and eosinophils. 图 2：组织学幻灯片 xx10\times 10 显示许多细胞，包括淋巴细胞、组织细胞和嗜酸性粒细胞。
FIGURE 3: The same histological slide at xx20\times 20 shows many lymphocytes and eosinophils. 图 3：相同的组织学载玻片 xx20\times 20 显示许多淋巴细胞和嗜酸性粒细胞。
without relapse. Nine months later, he remained symptom free on no medications. 没有复发。9 个月后，他没有服用任何药物，仍然没有症状。
DISCUSSION 讨论
In 1974, Shulman ^(1,2){ }^{1,2} described an uncommon condition similar to scleroderma. Rodnan et al ^(3){ }^{3} designated it eosinophilic fasciitis at a meeting of the American Rheumatism Association the same year. Both Shulman and Rodnan et al had patients presenting with 1974 年，Shulman ^(1,2){ }^{1,2} 描述了一种类似于硬皮病的罕见病症。Rodnan 等人 ^(3){ }^{3} 在同年的美国风湿病协会会议上将其命名为嗜酸性粒细胞性筋膜炎。Shulman 和 Rodnan 等人都有患者出现
pain and swelling of the forearms and/or legs that developed into widespread induration of the skin and subcutaneous tissues and decreased range of motion of the extremity. Shulman ^(1,2){ }^{1,2} noted the onset in several patients after particularly vigorous activity. One of Shulman’s original patients, an 18-year-old boy, presented with claw hands. ^(1){ }^{1} The patients exhibited eosinophilia ranging from 8%8 \% to 29%29 \% of leukocyte counts and also hypergammaglobulinemia. They had, however, negative serum antinuclear antibodies, unexpected for scleroderma. Biopsies showed inflammatory infiltrates with lymphocytes, plasma cells, histiocytes, and eosinophils. ^(1-3){ }^{1-3} 前臂和/或腿部疼痛和肿胀发展为皮肤和皮下组织的广泛硬结以及肢体活动度下降。Shulman ^(1,2){ }^{1,2} 注意到几名患者在特别剧烈的活动后发病。Shulman 最初的患者之一，一名 18 岁的男孩，出现爪形手。 ^(1){ }^{1} 患者表现出从白细胞计数到 8%8 \% 到 29%29 \% 的嗜酸性粒细胞增多症以及高丙种球蛋白血症。然而，他们的血清抗核抗体呈阴性，这在硬皮病中是出乎意料的。活检显示淋巴细胞、浆细胞、组织细胞和嗜酸性粒细胞的炎性浸润。 ^(1-3){ }^{1-3}
Antic et al^(4)\mathrm{al}^{4} considered eosinophilic fasciitis to be a skin reaction to various stimuli. They reviewed 30 years of literature examining immunological and genetic factors that may be responsible, including abnormal immune response, cytokine abnormalities, and genetic causes. Nonetheless, the etiology is unknown, although associative factors have been identified. Possible etiologies may be robust exercise, medications, Lyme disease, arthropod bites, or trauma. ^(1,2,4,5){ }^{1,2,4,5} Demographic analysis in studies found that people with a mean age between 40 and 50 years are most likely to be afflicted, but children can be as well. ^(4,5){ }^{4,5} Discrepancies exist as to whether males or females are more affected, but in one study, 75%75 \% were female. ^(5){ }^{5} Antic et al^(4)\mathrm{al}^{4} 认为嗜酸性粒细胞性筋膜炎是对各种刺激的皮肤反应。他们回顾了 30 年的文献，研究了可能造成此事的免疫学和遗传因素，包括异常免疫反应、细胞因子异常和遗传原因。尽管如此，病因尚不清楚，但已确定相关因素。可能的病因可能是剧烈运动、药物、莱姆病、节肢动物咬伤或外伤。 ^(1,2,4,5){ }^{1,2,4,5} 研究中的人口统计分析发现，平均年龄在 40 至 50 岁之间的人最有可能受到影响，但儿童也可能受到影响。 ^(4,5){ }^{4,5} 关于男性或女性的影响更大存在差异，但在一项研究中， 75%75 \% 女性是女性。 ^(5){ }^{5}
Presentation is usually bilateral symmetrical edema and erythema in the extremities that subsequently exhibit orange-peel appearance and induration as well as morphea-like lesions. Joint contractures and reduced motion in the hand and other joints (ankle, elbow) follow. ^(4,5){ }^{4,5} Nonspecific systemic findings (fever, malaise, weight loss) can occur. ^(4){ }^{4} In addition, up to 20%20 \% of patients present with carpal tunnel syndrome and 44%44 \% with inflammatory arthritis. ^(4){ }^{4} Jones et al ^(6){ }^{6} reported 6 patients in a series of 8 that had clinical and electrodiagnostic characteristics consistent with carpal tunnel syndrome, including nocturnal paresthesias. Two underwent surgical release. ^(6){ }^{6} 表现通常为双侧对称性水肿和四肢红斑，随后表现为橘皮样外观和硬结以及硬斑病样病变。随后出现关节挛缩和手部和其他关节（踝关节、肘部）活动减少。 ^(4,5){ }^{4,5} 可出现非特异性全身表现（发热、不适、体重减轻）。 ^(4){ }^{4} 此外，多达 20%20 \% 的患者表现为腕管综合征和 44%44 \% 炎症性关节炎。 ^(4){ }^{4} Jones 等人 ^(6){ }^{6} 报告了 8 例系列中的 6 例患者，这些患者的临床和电诊断特征与腕管综合征一致，包括夜间感觉异常。两人接受了手术松解。 ^(6){ }^{6}
Childhood eosinophilic fasciitis is even more uncommon. Until 2008, 32 cases had been reported in English-language medical literature versus over 200 in adults. ^(7){ }^{7} The clinical presentation is similar in children, but it may present as painless joint contractures with no skin involvement. Some have hypothesized that this may be a phenotype found in specifically in children. ^(7){ }^{7} Carpal tunnel syndrome also occurs in children. ^(7){ }^{7} 儿童嗜酸性粒细胞性筋膜炎更为罕见。直到 2008 年，英语医学文献中报道了 32 例，而成人中报道了 200 多例。 ^(7){ }^{7} 儿童的临床表现相似，但可能表现为无痛性关节挛缩，无皮肤受累。一些人假设这可能是在儿童中特别发现的一种表型。 ^(7){ }^{7} 腕管综合征也发生在儿童中。 ^(7){ }^{7}
Clinical testing is similar for adults and children. Laboratory anomalies include hypergammaglobulinemia, eosinophilia, and an elevated erythrocyte 成人和儿童的临床测试相似。实验室异常包括高丙种球蛋白血症、嗜酸性粒细胞增多和红细胞升高
sedimentation rate, although these are not required to make the diagnosis. ^(4,8){ }^{4,8} Antic et al ^(4){ }^{4} found that 7 of 11 patients ( 64%64 \% ) in their series had eosinophilia. Our patient developed eosinophilia only on his second admission. 沉降率，尽管这些不是做出诊断所必需的。 ^(4,8){ }^{4,8} Antic 等人 ^(4){ }^{4} 发现，他们系列中的 11 名患者中有 7 名 （ 64%64 \% ） 患有嗜酸性粒细胞增多症。我们的患者仅在第二次入院时出现嗜酸性粒细胞增多症。
MRI can be helpful in the diagnosis. Moulton et al ^(9){ }^{9} retrospectively examined the MRI findings of 6 patients with eosinophilic fasciitis and found them to be helpful in the acute phase, defined as less than 6 months from the onset. T1-weighted images showed fascial thickening, and T2-weighted images showed enhancement of the fascia as well as of the contiguous muscle fibers; gadolinium contrast greatly increased fascial enhancement. ^(9){ }^{9} Although this was a small retrospective study, the results seem to be borne out by other studies. ^(5,7){ }^{5,7} Our patient also exhibited these specific changes on MRI. MRI 有助于诊断。Moulton 等人 ^(9){ }^{9} 回顾性检查了 6 名嗜酸性粒细胞性筋膜炎患者的 MRI 结果，发现它们在急性期有帮助，急性期定义为发病后不到 6 个月。T1 加权图像显示筋膜增厚，T2 加权图像显示筋膜和相邻肌纤维增强;钆造影剂大大增加了筋膜增强。 ^(9){ }^{9} 虽然这是一项小型回顾性研究，但结果似乎得到了其他研究的证实。 ^(5,7){ }^{5,7} 我们的患者在 MRI 上也表现出这些特定变化。
Skin and fascia biopsies are the reference standard for diagnosis. These often show unremarkable skin and subcutaneous tissues but inflammatory infiltrates of lymphocytes and plasma cells in the deep fascia. ^(4,7){ }^{4,7} Eosinophils are often, but not always, present. Administration of steroids can cause the disappearance of eosinophils. ^(4){ }^{4} Biopsies in the carpal tunnel can reveal tenosynovitis, which may compress the median nerve and cause carpal tunnel syndrome. ^(6){ }^{6} 皮肤和筋膜活检是诊断的参考标准。这些通常显示皮肤和皮下组织不明显，但深筋膜中淋巴细胞和浆细胞的炎性浸润。 ^(4,7){ }^{4,7} 嗜酸性粒细胞经常存在，但并非总是存在。类固醇的给药可导致嗜酸性粒细胞消失。 ^(4){ }^{4} 腕管活检可显示腱鞘炎，腱鞘炎可能压迫正中神经并导致腕管综合征。 ^(6){ }^{6}
Upon diagnosis, the usual first-line treatment is oral corticosteroids in pulsed doses to reduce side effects. Second-line treatments include antihistamines (hydroxyzine), methotrexate, ibuprofen, histamine-2 blockers (cimetidine), hydroxychloroquine, photochemotherapy, and cyclophosphamide. ^(4,7,8){ }^{4,7,8} All 34 patients in a study by Lebeaux et al ^(8){ }^{8} received systemic corticosteroids. Forty-seven percent received methylprednisolone pulses initially, and their symptoms improved. Forty-four percent of patients required second-line immunosuppressant medications, mostly methotrexate. Considering all treatment modalities, 69%69 \% of patients achieved complete remission and did not need long-term treatment. Factors contributing to poor results in the remaining patients included delayed diagnosis ( > 6mo>6 \mathrm{mo} ) or lack of methylprednisolone pulses initially. ^(8){ }^{8} Antitumor necrosis factor- alpha\alpha and rituximab have also been used. ^(8){ }^{8} Our patient got better while taking clindamycin. It is possible, in the absence of infection, that the secondary anti-inflammatory properties of clindamycin, which dermatology research has described, played a role. ^(10){ }^{10} In addition to medications, early physical and occupational therapy is instituted to lessen the effects of contractures. ^(4,7){ }^{4,7} 诊断后，通常的一线治疗是冲击剂量口服皮质类固醇以减少副作用。二线治疗包括抗组胺药（羟嗪）、甲氨蝶呤、布洛芬、组胺 2 阻滞剂（西咪替丁）、羟氯喹、光化学疗法和环磷酰胺。 ^(4,7,8){ }^{4,7,8} Lebeaux 等人 ^(8){ }^{8} 的一项研究中的所有 34 名患者都接受了全身性皮质类固醇治疗。47% 的患者最初接受了甲泼尼龙脉冲治疗，症状有所改善。44% 的患者需要二线免疫抑制药物，主要是甲氨蝶呤。考虑到所有治疗方式， 69%69 \% 的患者达到完全缓解，不需要长期治疗。导致其余患者结果不佳的因素包括延迟诊断 （ > 6mo>6 \mathrm{mo} ） 或最初缺乏甲泼尼龙脉冲。 ^(8){ }^{8} 抗肿瘤坏死因子和 alpha\alpha 利妥昔单抗也被使用。 ^(8){ }^{8} 我们的患者在服用克林霉素后病情好转。在没有感染的情况下，皮肤病学研究描述的克林霉素的继发性抗炎特性可能起了作用。 ^(10){ }^{10} 除了药物治疗外，还开始早期物理和职业治疗以减轻挛缩的影响。 ^(4,7){ }^{4,7}
Our young, healthy patient had an atypical unilateral presentation of a rare entity that usually 我们年轻、健康的患者有一种罕见疾病的非典型单侧表现，通常
From the Department of Orthopaedics and Rehabilitation, Yale University School of Medicine, Yale-New Haven Hospital, New Haven, Connecticut. 来自康涅狄格州纽黑文市耶鲁大学医学院骨科和康复系。
