警惕牛皮癣与皮肤T细胞淋巴瘤的关联

夏威夷毛伊岛——在全球医学教育学会/皮肤病教育基金会(SDEF)主办的夏威夷皮肤病学研讨会上，数位专家强调，鉴于银屑病与皮肤T细胞淋巴瘤之间存在强相关性，加之这两种疾病难以区别，有必要对银屑病患者更积极地开展皮肤活检。

Joel M. Gelfand博士

宾夕法尼亚大学的Joel M. Gelfand博士表示，皮肤活检适用于任何具有非典型特征或治疗无效的银屑病患者。有关银屑病和实体恶性肿瘤的文献比较杂乱，有些观察性研究显示两者呈正相关，而另一些研究则未观察到这一现象。相比之下，探讨银屑病与皮肤T细胞淋巴瘤(CTCL)的研究始终显示二者呈正相关。Gelfand博士及其同事采用英国综合诊所研究数据库的资料，对超过153,000例银屑病患者和近800,000例对照者进行了研究，发现轻度银屑病患者发生CTCL的相对风险是对照者的4.1倍，而重度银屑病患者的风险是对照者的10.75倍(J. Invest. Dermatol. 2006;126:2194-201)。大型观察性研究的局限性在于其难以确定一些发生CTCL的银屑病患者最初是被误诊还是实际上一直患有CTCL。Gelfand博士所在的宾州淋巴瘤研究小组发现，一些患者明确患有银屑病多年，然后发生红皮病性CTCL，而一些患者则明确被误诊为银屑病。

目前尚不清楚淋巴瘤风险的增加是由银屑病本身引起还是由长期使用治疗皮肤病的免疫抑制剂引起。既往研究大多显示银屑病药物不会显著增加风险。然而，在误诊银屑病而接受强效免疫抑制治疗的患者中，CTCL可非常快速地进展。Gelfand博士表示，对于肿瘤期蕈样肉芽肿患者，不要使用TNF抑制剂治疗。

Craig L. Leonardi博士

圣路易斯大学的资深银屑病研究者Craig L. Leonardi博士表示，重度银屑病和CTCL的鉴别非常棘手。目前，随着生物制剂的发展，这些药物已能够使70%~85%的患者获得PASI-75应答。如果发现患者未获得应答，则应考虑其他诊断。

Gelfand博士在产生怀疑时通常会在患者停用局部类固醇药物至少1周后(因为药物可减少表皮浸润)对1处或2处代表性病变进行活检。Gelfand博士表示，如果病理样本由综合病理科医生检查，并且返回的报告结果明确银屑病或CTCL，则情况相当明了。但如果报告显示“非特指型(NOS)银屑病样皮肤病”，则应该坚持让皮肤病理科医生检查样本。

Guy F. Webster博士

费城托马斯杰斐逊大学的Guy F. Webster博士表示曾遇到许多治疗不当的情况，“无法诊断”始终是一个大问题。一些患者长时间存在皮疹，看起来像是湿疹、银屑病或其他疾病。对于治疗后未见改善的患者，医生却很少对诊断产生质疑。

Alan Menter博士

达拉斯贝勒大学医学中心的 Alan Menter博士指出，有确切证据表明，在治疗前基线时，银屑病患者与类风湿关节炎患者一样，发生淋巴瘤的风险会轻微增加。与患者讨论癌症话题是一件敏感的事情。患者通常会问使用生物制剂是否可能导致癌症，而实际上患者的风险已经轻微增加了。至于使用TNF抑制剂是否会增加癌症风险，答案是，在超过2百万使用TNF抑制剂治疗的患者中，未观察到癌症风险在统计学上出现高于基线风险的增加。

SDEF和本新闻机构隶属于同一母公司。Menter博士、Gelfand博士、Webster博士和Leonardi博士从多家药企获得研究资金和/或担任其顾问。

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By: BRUCE JANCIN, Internal Medicine News Digital Network

MAUI, HAWAII – The strong association between psoriasis and cutaneous T-cell lymphoma warrants a low threshold for skin biopsy in psoriasis patients, particularly since the two diseases can be tough to differentiate, experts emphasized at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.

Indeed, skin biopsy is appropriate in any psoriasis patient with atypical features or psoriasis that isn’t responding to treatment, according to Dr. Joel M. Gelfand of the University of Pennsylvania, Philadelphia.

"I’ve found that my psoriasis patients actually like to be biopsied. They’ve been living with their disease for an average of 20 years, and they’re curious," he said. "And they’re also suspicious. They wonder, ‘How could I have this for 20 years and it’s still here?’ They’re worried that it’s really cancer or something else. So my patients never decline a biopsy of psoriasis," he said.

The literature on psoriasis and solid malignancies is "a mess," with some observational studies showing a positive association and others not, Dr. Gelfand noted.

In contrast, the studies looking at psoriasis and cutaneous T-cell lymphoma (CTCL) have been consistently positive. Case in point: when Dr. Gelfand and colleagues turned to the U.K. General Practice Research Database to study more than 153,000 psoriasis patients and nearly 800,000 controls, they found participants with mild psoriasis had a 4.1-fold increased relative risk of developing CTCL, while those with severe psoriasis had a 10.75-fold increased risk (J. Invest. Dermatol. 2006;126:2194-201).

One limitation of large, observational studies is that it’s hard to know whether some psoriasis patients who developed CTCL were initially misdiagnosed and actually had CTCL all along, Dr. Gelfand said.

"We have a large lymphoma study group at Penn, and we see all kinds: we see some patients who clearly had psoriasis for many years and then developed erythrodermic CTCL, and we have people who clearly were misdiagnosed as having psoriasis," he said.

Whether the increased lymphoma risk is caused by psoriasis itself, as opposed to the chronic use of immunosuppressive drugs employed in treating the skin disease, remains uncertain. To date, the studies are mostly reassuring that the psoriasis medications don’t significantly increase the risk. One thing that is clear, however, is that CTCL can progress very rapidly in a patient who is on potent immunosuppressive therapy for what is mistakenly thought to be psoriasis.

"The patient with tumor-stage mycosis fungoides is not a person you want to hit with a TNF inhibitor," Dr. Gelfand observed.

The distinction between severe psoriasis and CTCL can be tricky, according to veteran psoriasis researcher Dr. Craig L. Leonardi of Saint Louis University.

"In the last 13 years, while we’ve been developing the biologic agents, every now and then we’ll get a patient in a research trial who actually has CTCL. This is in an environment where patients are being examined closely, and yet the clinician is totally fooled by it," Dr. Leonardi said. "These drugs have evolved to the point that we get PASI-75 responses in the 70%-85% range. Most patients will have a rocking experience on these medications. So it’s a good general rule that if you find somebody who doesn’t respond, it’s time to start thinking about other diagnoses."

When Dr. Gelfand’s suspicions are raised, he typically biopsies one or two representative lesions after the patient has been off of topical steroids for at least a week, since the medication can reduce the epidermal infiltrate.

Be cautious if the histologic specimen is going to be read by a general pathologist. The situation is fairly straightforward if the report comes back as unequivocally psoriasis or CTCL. But if the report says, ‘psoriasiform dermatitis NOS’ it’s appropriate to insist that a dermatopathologist takes a look at the slides, Dr. Gelfand said.

"A lot of malpractice cases come across my desk, and ‘failure to diagnose’ is always a big one," said Dr. Guy F. Webster of Thomas Jefferson University, Philadelphia.

"It’s not always melanoma, either," he continued. "The story is always that somebody had a rash for a long time. It looked like eczema, psoriasis, whatever. And the physician treated it without ever questioning the diagnosis when the patient didn’t get better."

Dr. Alan Menter noted convincing evidence that, at pretreatment baseline, psoriasis patients, like those with rheumatoid arthritis, have a slightly increased risk of lymphoma.

"It’s kind of sensitive to talk to patients about the cancer issue. They all ask, ‘Is there a chance you’ll cause cancer by giving me this biologic drug?’ You have to gently tell them they are already at slightly increased risk," Dr. Menter said.

"Is the use of an anti-TNF agent going to increase that risk? The answer is that in all of the more than 2 million patients who’ve been treated with TNF inhibitors, there does not appear to be a statistical increase above the baseline risk," said Dr. Menter of Baylor University Medical Center, Dallas, and chair of the American Academy of Dermatology psoriasis guidelines committee.

SDEF and this news organization are owned by the same parent company. Dr. Menter, Dr. Gelfand, Dr. Webster, and Dr. Leonardi have received research funds and/or served as consultants to numerous pharmaceutical companies.