化脓性汗腺炎与代谢综合征相关

土耳其伊斯坦布尔——欧洲皮肤病与性病学会(EADV)年会上报告的首个病例对照研究结果显示，化脓性汗腺炎(HS)患者代谢综合征患病率急剧增加。

柏林查理特大学医院教授、皮肤科主任Wolfram Sterry医生报告称，已知代谢综合征与心血管风险增加相关，由于HS患者发生代谢综合征的年龄远远小于非HS人群，因此这些患者的心血管风险可能尤其较高。HS属于一种皮肤性疾病，其估计患病率为1~4%。

这项单中心病例对照研究纳入了80例平均病程为12年的HS患者和100例年龄与性别相匹配的对照人群。患者平均年龄40岁(PLoS One 2012 [doi:10.1371/journal.pone.0031810])。


Wolfram Sterry医生
 
结果显示，HS组和对照组代谢综合征患病率分别为40%和13%，校正后HS组患病几率增加4.5倍。在用于判定代谢综合征的5个代谢性紊乱指标中，HS患者4个指标的患病率明显较高。HS患者罹患中心性肥胖、高血糖、低HDL胆固醇和高甘油三脂血症的几率分别是对照人群的5.9倍、4.1倍、4.6倍和2.2倍。HS患者高血压患病率为48%，而对照组为35%，二者差异未达到统计学显著水平。

值得注意的是，患有代谢综合征的HS患者与患有代谢综合征的对照者相比，出现更多的代谢异常指标。虽然5个代谢异常指标中出现3个即可判定为代谢综合征，但半数被确诊为代谢综合征的HS患者符合4个或以上诊断标准，而对照组为39%。

此外，HS患者发生代谢综合征的年龄远远小于普通人群或对照人群。实际上，40%的HS患者在35岁之前患有代谢综合征，而对照组无1例出现。与对照组相比，HS患者≤34岁罹患代谢综合征的比值比为20，35~44岁HS患者为6.2，≥45岁HS患者为2。

有文献报道，银屑病患者代谢综合征患病率也有所增加，但HS患者代谢综合征患病率似乎更高，发病年龄也更早。

Sterry医生指出，HS病程和严重程度与代谢综合征发病率未见关联。这对于皮肤科医生来说是一条非常重要的信息，意味着应尽早对这类患者进行代谢综合征评估，即便其病情仅为中等严重程度。毕竟代谢综合征的症候是可改变的心血管风险因素。

此外，这也有助于了解HS患者代谢综合征风险增加机理。研究者比较了42例HS手术治疗患者和38例非手术治疗患者的代谢综合征指标水平，结果未见显著差异，尽管手术患者炎性负担可能较低。因此，研究者推测，慢性炎症可能不是HS患者代谢异常的主要原因。

因此，研究者推测，“那一定是代谢综合征遗传易感性引起易感人群发生反复性痤疮(化脓性汗腺炎)。”其可能的机理是，代谢综合征导致腋窝、肛周和腹股沟等对磨部位皮肤血液循环不佳，这些部位也是HS最常见发生部位，导致CD4+ T细胞产生白细胞介素-10增加，后者进而抑制角质细胞产生白细胞介素-20和22(具有诱导皮肤抗菌蛋白作用)，从而为HS发生创造条件。HS的特征是细菌持续存在于阻塞的毛囊、结节以及鼻窦瘘。

但研究者承认，上述机理仅仅是推测而已。“反复性痤疮又称化脓性汗腺炎、顶浆分泌性痤疮、瘘道型脓皮病等，如果一种疾病有多个名称，往往反映出我们对其不太了解。”

在EADV年会上报告的另外一项研究中，研究者发现，在入组阿达木单抗(Humira)临床试验的154例HS患者中，最常见的共病为抑郁(定义为患者健康问卷-9评分≥10，患病率为42%)、重度肥胖(体重指数≥40 kg/m2，患病率为28%)、未得到控制的高血压(患病率为27%)。但研究者没有考察代谢综合征情况。

Sterry医生报告无相关利益冲突。

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By: BRUCE JANCIN, Cardiology News Digital Network

ISTANBUL, TURKEY – Patients with hidradenitis suppurativa have a sharply increased prevalence of the metabolic syndrome, according to the first case-control study to examine the relationship.

Metabolic syndrome is known to be associated with increased cardiovascular risk, which may be particularly high in patients with hidradenitissuppurativa (HS), a dermatologic disease with an estimated prevalence of 1%-4%, because they develop metabolic syndrome at a much younger age than do individuals without the dermatologic disease, Dr. Wolfram Sterry said at the annual congress of the European Academy of Dermatology and Venereology.

He presented highlights from a single-center, case-control study that comprised 80 patients with HS with a mean 12-year disease duration and 100 age- and gender-matched controls. Patients’ mean age was 40 years (PLoS One 2012 [doi:10.1371/journal.pone.0031810]).

The prevalence of metabolic syndrome was 40% in the HS group and 13% in controls, for an adjusted 4.5-fold increased likelihood, reported Dr. Sterry, professor and chairman of the department of dermatology at Charité University Hospital, Berlin.

Of the five metabolic derangements used in defining the metabolic syndrome, four were significantly more prevalent in subjects with HS. They were 5.9-fold more likely than were matched controls to have central obesity, 4.1-fold more likely to have hyperglycemia, 4.6-fold more likely to have low HDL cholesterol, and 2.2-fold more likely to be hypertriglyceridemic. Hypertension was present in 48% of HS patients and 35% of controls, a difference that did not achieve statistical significance.

Of note, HS patients with metabolic syndrome had more pronounced metabolic abnormalities than did controls with metabolic syndrome. While the definition of metabolic syndrome requires the presence of at least three of five metabolic alterations, half of all HS patients with metabolic syndrome met four or more of the criteria, compared with 39% of controls.

Moreover, metabolic syndrome occurred at a much younger age in subjects with HS than is typical in the general population or than was seen in controls. Indeed, 40% of HS patients under age 35 had metabolic syndrome, compared with none of the matched controls. Thus, the odds ratio for metabolic syndrome in HS patients aged 34 years or less was increased more than 20-fold compared with controls, while in the 35- to 44-year-old age group it was increased 6.2-fold, and in HS patients aged 45 and older it was 2-fold higher.

An increased prevalence of metabolic syndrome also has been documented in patients with psoriasis. But the prevalence of metabolic syndrome appears to be higher in HS patients and the metabolic disorder occurs at an earlier age than in psoriasis.

There was no correlation between duration or severity of HS and the prevalence of metabolic syndrome, according to Dr. Sterry. That’s an important message for physicians who see patients with the skin disease because it means such patients should be evaluated for metabolic syndrome early on, even if they have only moderate skin disease. After all, the elements of the metabolic syndrome are modifiable cardiovascular risk factors.

The lack of correlation between HS severity or duration and metabolic syndrome prevalence also has implications for the mechanism underlying the increased risk of metabolic syndrome in HS. When Dr. Sterry and coworkers compared the levels of metabolic syndrome parameters in the 42 patients with prior surgical treatment of their HS to the 38 patients who had not undergone surgery, they found no significant differences even though the surgical patients presumably had less inflammatory load. This led them to speculate that chronic inflammation may not be the major driver of the metabolic abnormalities in HS patients.

"It must be that a genetic predisposition for metabolic syndrome then induces the development of acne inversa [hidradenitissuppurativa] in predisposed individuals," Dr. Sterry said.

The proposed mechanism involves metabolic syndrome–induced poor blood circulation in the intertriginous axillary, perianal, and inguinal skin where HS most often occurs, with resultant increased interleukin-10 production by CD4-positive T cells. Interleukin-10, in turn, inhibits keratinocyte production of interleukins-20 and -22, which induce antimicrobial proteins in the skin. This would set the stage for HS, which is characterized by bacterial persistence in obstructed hair follicles, nodules, and fistulating sinuses.

Of course, this is speculation, Dr. Sterry was quick to acknowledge.

"Acne inversa is also known as hidradenitissuppurativa, apocrine acne, pyoderma fistulans significa ... If a disease has that many names, that’s always a sign that we don’t know too much about it," the dermatologist observed.

In a separate study presented at the EADV, investigators found that the most common comorbid conditions in a cohort of 154 patients with HS enrolled in a clinical trial of adalimumab (Humira) therapy were depression as defined by a score of 10 or more on the Patient Health Questionnaire–9, which had a prevalence of 42%; severe obesity marked by a body mass index of at least 40 kg/m2, present in 28% of patients; and uncontrolled hypertension, which was present in 27%. However, the investigators did not look at metabolic syndrome.

Dr. Sterry reported having no financial conflicts regarding this unfunded case-control study.