美专家提出皮肤科住院患者三大诊断规则

旧金山——在太平洋皮肤病学会(PDA)2013年会上，美国加利福尼亚大学皮肤病咨询服务中心主任Lindy P. Fox医生称，三条规则可用于指导皮肤科住院患者的最有效诊疗。

第一，临床情况可能涉及不止一种感染或病因，尤其是免疫缺陷患者。如果存在不止一种形态学表现，则应逐一检查。第二，大部分病例都需要在一定程度上了解临床病理相关性。第三，对于皮肤科住院患者，“想想斑马”(非常规思维)有时候会有帮助，因为这样你才有机会作出罕见病的诊断。


Lindy P. Fox医生
 
Fox医生对医院皮肤科经常遇到的一些形态学表现进行了阐述：

· 麻疹样：对于麻疹样皮疹，我们通常会考虑药疹、病毒性疹、移植物抗宿主病(GVHD)以及可能表现为这种形式的其他病因。而罕见的情况是，在免疫缺陷患者中，播散性组织胞浆菌病、隐球菌病或者球孢子菌病也可能出现类似于药疹的表现，因此在这些情况下对你怀疑是药疹的地方进行活检就显得十分重要。

急性GVHD通常见于移植后25天左右，但是超急性GVHD可能发生于移植后14天，因此在肿瘤科医生告诉你还没有取移植物活检之前，应该考虑这种可能性。GVHD麻疹样发疹的两个特征有助于鉴别诊断：毛囊突显以及耳周、手和甲周区域肢端分布。患者的恶心、呕吐、腹泻以及高胆红素血症也可以支持这一诊断。

· 丘疹/丘疹结节：鉴别诊断的名单比较长，包括真菌病、脓毒性栓子、Sweet综合征、白血病或皮肤淋巴瘤、Kaposi肉瘤、皮肤转移、结节病等等。但是，如果你看到的是紫色丘疹，那么鉴别诊断的范围可以缩小至淋巴瘤、Kaposi肉瘤、杆菌性血管瘤病、黑色素瘤或者皮肤转移。

· 蜂窝组织斑块：通常考虑蜂窝组织炎或者与之类似的淤滞性皮炎，以及一些深部真菌感染、丹毒样癌、中性粒细胞疾病和ICU急性炎症性水肿。记住隐球菌性蜂窝组织炎是器官移植受者最常见的隐球菌感染症状。与细菌性蜂窝组织炎不同，隐球菌性蜂窝组织炎大多为双侧。这几乎不可能是单纯的皮肤疾病。Fox医生指出：“如果你在皮肤上看到了隐球菌感染，则应该寻找感染的全身性来源。”

·可触及紫癜：这通常提示小血管或混合血管性血管炎。但是你还可能发现丘疹顶端有继发性出血；这可能是因白血病、皮肤淋巴瘤或Sweet综合征所致；或者也可能是阿糖胞苷导致的皮肤反应。Fox医生说她常见的是下肢紫癜性丘疹。如果仔细观察，几天后可能会发现麻疹样发疹蔓延至躯干。活检通常提示皮肤海绵层水肿，这是阿糖胞苷良性、自限性反应“非常可靠”的指征。如果患者再次用药，这种反应可能复发也可能不复发。她说：“类固醇激素对此有用，患者的情况会很好。”

· 网状紫癜：考虑血管性(血管壁上)或者血管内(血管腔内)潜在病因的话，鉴别诊断的名单又会很长。累及血管腔内则提示栓塞或者血栓形成。Fox医生说：“如果当天你确实在病灶发展早期观察到了同时存在的血栓形成和血管炎，那么鉴别诊断的范围会大大缩小。只有很少的病因可以导致这种情况：冷球蛋白血症、脓毒性血管炎以及暴露于左旋咪唑。”

·  硬皮病样：鉴别诊断的名单也比较长，包括铠甲状癌、放射性皮炎、GVHD、硬皮病、石蜡瘤、脂肪皮肤硬化症、硬肿病、硬化性粘液水肿等等。Fox医生说她见过一名“抗生素性难治性蜂窝组织炎”女性患者，她出于整形目的在小腿上注射了矿物油之后出现了罕见的游走性石蜡瘤。

· 坏死性丘疹/斑块：其中一种潜在病因是钙化防御，它被视为发生在皮肤上的心肌梗死。患者往往有长期的血管狭窄和动脉中膜钙化病史。一旦发生急性血栓形成性事件，患者就会出现钙化防御，表现为组织缺血、疼痛和星状紫癜性斑块。Fox医生说：“这提示我们需要从不同的角度来考虑治疗方案。”除了常规调整钙、磷酸和甲状旁腺激素水平之外，还应该考虑采用组织型纤溶酶原激活剂来治疗血栓。不要使用华法林；许多钙化防御病例都是华法林诱发的，华法林会促进钙化。

· 溃疡：在医院里最常见的病因是静脉功能不全、坏疽性脓皮病、深部真菌感染和慢性病毒性感染。对于长期卧床的免疫缺陷患者，常见的原因是慢性单纯疱疹病毒感染。Fox医生说：“我见过的臀部溃疡或者褥疮病例中，可能有50%以上都合并了单纯疱疹病毒感染。”

· 脓疱：播散性念珠菌病是病因之一，它在免疫缺陷患者中可能出现类似于痤疮的表现。病灶通常中央苍白，有时候为脓疱性。Fox医生说：“你可以采用氢氧化钾法来证明这是念珠菌病。”如果没有脓疱，那么诊断播散性念珠菌病可能会比较困难，因为能采集到的生物太少，皮肤病理科在连续切片时很容易就遗漏掉了。要求进行连续切片和染色以识别致病生物。

·红斑：Fox医生说她通常将红斑分为斑疹性、亚急性和糜烂性。斑疹性红斑可能是毒素介导的红斑或者是因药疹、GVHD、病毒性疹或Kawasaki病所致。对于毒素介导的红斑，通常存在嗜酸性粒细胞增多。她说：“我会根据这一指标来考虑红斑，而不是排除红斑。”

当亚急性或慢性红皮病是因药物超敏反应所致时，需要警惕两种长期后遗症：甲状腺干扰和迟发性心脏损害，表现为你没有预料到会出现心脏问题的患者发生了危及生命的心衰。Fox医生说，她会每月检查一次促甲状腺激素水平，连续检查6个月，并且提醒患者一旦出现心脏症状应立即前往急诊室就诊，并请急诊科的医务人员通知皮肤科医生。

对于糜烂性红皮病，不太常见的一个病因是化疗导致的中毒性红斑。这可能需要大量的病历资料以及与初级医疗保健团队讨论以确定这不是中毒性红斑坏死，比如GVHD。

Fox医生声明无相关经济利益冲突。

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By: SHERRY BOSCHERT, Oncology Practice

SAN FRANCISCO – Three rules can guide inpatient dermatology for the most effective practice, according to Dr. Lindy P. Fox, director of the dermatology consultation service at the University of California, San Francisco.

First, more than one infection or etiology may account for the clinical picture, especially in immunocompromised patients. If there’s more than one morphology present, work up each one separately, she said.

Second, most cases require some degree of clinicopathologic correlation.

Third, for inpatient dermatology it helps to think of "zebras," because that’s how you’ll make the rare diagnosis, she said at the annual meeting of the Pacific Dermatologic Association.

She provided tips on some of the more common morphologies encountered in hospital dermatology:

· Morbilliform. Most commonly, morbilliform brings to mind a drug eruption, viral exanthema, graft vs. host disease (GVHD), and other entities that can present in this pattern. Rarely in immunocompromised patients, disseminated histoplasmosis, cryptococcosis, or coccidiomycosis can mimic a drug eruption, so it’s important in those situations to biopsy what you think might be a drug eruption.

Acute graft vs. host disease on average occurs 25 days after a transplant, but hyperacute GVHD occurs 14 days post transplant, so think of this before your oncologist tells you the patient’s graft hasn’t taken, she said. Two features of GVHD morbilliform eruption distinguish it from other differential diagnoses: a perifollicular accentuation, and an acral distribution around the ears, hand, and periungual areas. A patient’s nausea, vomiting, diarrhea, and hyperbilirubinemia support the diagnosis.

· Papules/papulonodules. The differential diagnosis is long – fungal diseases, septic emboli, Sweet’s syndrome, leukemia or lymphoma cutis, Kaposi sarcoma, cutaneous metastasis, and sarcoidosis, among others. But if you see purple plumb-colored papules, the list shrinks to lymphoma, Kaposi sarcoma, bacillary angiomatosis, melanoma, or cutaneous metastasis.

· Cellulitic plaques. These bring to mind cellulitis or its mimic, stasis dermatitis, as well as some deep fungal infections, carcinoma erysipeloides, neutrophilic diseases, and acute inflammatory edema of the ICU. Keep in mind that cryptococcal cellulitis is the most common presentation of Cryptococcus in an organ transplant recipient. Unlike bacterial cellulitis, it tends to be bilateral. It is almost never purely a cutaneous disease. "If you ever see Cryptococcus on the skin, you are obligated to look for the systemic source of infection," she said.

· Palpable purpura. This typically points to small or mixed-vessel vasculitis. But you can also have secondary hemorrhage into a papular process; it can be due to leukemia, lymphoma cutis, or Sweet’s syndrome; or it can be a cutaneous reaction to cytarabine. What Dr. Fox said she commonly sees are purpuric papules on the lower extremities. If looked at closely, there’s a morbilliform eruption that can spread to the trunk in a few days. Biopsy typically demonstrates spongiosis, which is a "very reassuring" sign that this is a benign and self-limiting reaction to cytarabine. The reaction may or may not recur if the patient takes the drug again. "Steroids do help, and patients do very well," she said.

· Retiform purpura. Another very long differential diagnosis can be organized by thinking about potential causes as vascular (in the vessel wall) or intravascular (in the lumen of the wall). Lumen involvement is a sign of embolization or thrombosis. "If you see concomitant thrombosis and vasculitis truly on the same day early on in lesion development, that differential diagnosis shrinks considerably. There are very few things that can do that: cryoglobulinemia, septic vasculitis, and exposure to levamisole," Dr. Fox said.

· Sclerodermoid. The long differential diagnosis includes carcinoma en cuirasse, radiation dermatitis, GVHD, scleroderma, paraffinoma, lipodermatosclerosis, scleredema, and scleromyxedema, among others. Dr. Fox said she saw an unusual presentation in a woman with "antibiotic refractory cellulitis" who had developed a migrating paraffinoma after mineral oil injections to her calves for cosmetic purposes.

· Necrotic papules/plaques. One of the many potential causes – calciphylaxis – can be thought of as analogous to a myocardial infarction that occurs in the skin, she said. Patients more often than not have a long history of vascular stenosis and medial arterial calcification. An acute thrombotic event occurs, and the patient presents with calciphylaxis with tissue ischemia, pain, and stellate purpuric plaques. "This implies that we need to think about our therapeutics differently," she said. Address the calcium, phosphorous, and parathyroid hormone, as usual, but also consider treating the thrombus with tissue plasminogen activator. Don’t use warfarin; many cases of calciphylaxis are triggered by warfarin, and the drug promotes calcification, Dr. Fox said at the annual meeting of the Pacific Dermatologic Association.

· Ulcers. The most common causes in the hospital are venous insufficiency, pyoderma gangrenosum, deep fungal infection, and chronic viral infections. Chronic herpes simplex virus frequently is the culprit in bedridden, immunosuppressed patients. "Any buttock ulcer or any decubitis ulcer that I see gets ruled out for concomitant herpes simplex virus because I find it probably more than 50% of the time," she said.

· Pustules. One cause – disseminated candidiasis – can mimic acne in the immunosuppressed patient. The lesions tend to have a pale center that sometimes is pustular. "You can KOH that center to prove that you’ve got candidiasis," she said. If there’s no pustule, diagnosing disseminated candidiasis can be difficult because the collection of organisms is so small that it’s easily missed on serial sectioning by dermatopathology. Ask for serial sectioning and staining to identify the organism.

· Erythema. Dr. Fox said she divides erythemas into macular, subacute, and erosive. Macular erythema can be a toxin-mediated erythema or due to drug eruption, GVHD, viral exanthema, or Kawasaki disease. Eosinophilia is a common finding in toxin-mediated erythema. "I use it to help rule [erythema] in, rather than to help rule it out," she said.

When a subacute or chronic erythroderma is due to drug hypersensitivity reaction, be aware of two long-term sequellae: thyroid disruption and late-onset cardiac involvement presenting as life-threatening heart failure in people you wouldn’t expect to have heart problems. Dr. Fox said she checks thyroid-stimulating hormone levels monthly for 6 months and warns patients to go to the emergency department if they develop heart symptoms and tell the staff there to call the dermatologist.

One of the lesser-known causes of erosive erythroderma is toxic erythema of chemotherapy. It can take a lot of charts and talking with the primary medical team to make sure this is not toxic erythema necrolysis like GVHD, she said.

Dr. Fox reported having no relevant financial disclosures.