本期小编精心编辑了美国临床医生应用功能医学思维干预银屑病性关节炎的临床案例，从临床实用方案到生理机制分析，中英文对照，供临床医生参考。 Autoimmune diseases (Ads) are chronic, often debilitating and potentially life-threatening conditions that collectively affect up to 23.5 million Americans, and their incidence is rising. They are heterogeneous in pathology but share common etiopathogenic factors such as intestinal hyperpermeability. Although up to 100 ADs have been identified, there are likely more. Genetics plays clear role in the predisposition for the development and phenotype AD, but various combinations of factors, such as toxins, endogenous hormone imbalances, microbes (including ofGI origin), infections, stress and food antigens, are involved in disease . Standard treatments include NSAIDs, steroids, anti-neoplastic agents and tumor necrosis factor-alpha antagonists. These tools have potentially devastating side effects and are often applied regardless of the diagnosis. Frequently, they are only modestly effective in relieving symptoms and limiting the advancing disease process. Direct healthcare costs of AD are estimated at around 100 billion dollars per year in the United States. By comparison, cancer care costs about 57 billion dollars per year. The rising incidence of this debilitating and costly group of conditions dictates that safe, alternative approaches to treatment be considered now. 自身免疫系统疾病是一种慢性的、逐渐使人虚弱并危及生命的疾病，它几乎影响了两千三百五十多万美国人，且发病率还在持续增加。这些疾病的病理多样化，但发病机理几乎相同，例如肠道通透性。尽管人们已知了100多种自身免疫系统疾病，但这种疾病的数量远远不止于此。遗传因素是免疫性疾病发生和表现的一个明显诱因，例如：毒素、荷尔蒙失衡、微生物（包括胃肠道中微生物的来源）、感染、压力和食物抗原等，均对疾病表现有所影响。标准疗法包括非类固醇抗炎药、类固醇、抗肿瘤剂和肿瘤坏死因子—α拮抗剂，这些治疗方法均有潜在的严重副作用。然而，人们通常对这些诊断结论置之不理，这些药物通常只在缓解临床症状或阻止疾病发展等方面有适当作用。据估计，美国每年在免疫型疾病方面直接花费的医保费用在1亿美元左右，与之对比的是，美国每年花费在癌症上的医保费用只有5700万美元，这一不断增加的数字要求人们进一步寻找治疗消耗性疾病和花费性疾病等方面的安全、可供选择的治疗方法。 CASE HISTORY 案例 At age 56, MP presented with a diagnosis of psoriatic arthritis that was progressively worsening despite aggressive medication therapy. He experienced severe pain, decreased range of motion, and swelling in his feet, ankles, knees, and hands. He walked with a limp. His left shoulder was also frequently painful. All symptoms became worse in the morning. He had been taking etodolac and methotrexate for the past 3 years, and adalimumab for the past 6 months. The onset of psoriatic arthritis occurred with the development of pain and redness in his right great toe, for which he was treated unsuccessfully with antibiotics. Shortly thereafter, he developed psoriasis behind his knees, on his feet, and behind his ears. He had psoriatic nails for most of his life. 患者MP，56岁，有银屑病性关节炎，积极的药物治疗仍不能阻止其继续恶化。患者痛感强烈，运动范围缩小，脚部、关节处、膝盖及手部肿胀，走路跛行，左肩频繁疼痛。所有症状在清晨最为明显。服用依托度酸类及氨甲蝶呤类药物超过3年时间，服用阿达木单抗时间超过6个月。其银屑病关节炎发病时伴有疼痛感增加，右脚拇指红热等症状，且经抗生素治疗无效。发病片刻后，其膝盖、脚部、耳后出现牛皮癣，有较长银屑病甲患病史。 Just prior to receiving the diagnosis of psoriatic arthritis, he had a left knee arthroscopy that was negative for degenerative disease but positive for synovitis. He also developed a hemorrhagic Baker's cyst, causing complained of esophageal reflux, a severe recent swelling and pain in his left foot and knee. MP also 15-pound weight gain, and intermittent depression. 银屑病性关节炎确诊前，患者曾做过膝关节镜检查，检查结果表明退行性疾病呈阴性但关节膜炎呈阳性，伴有一个出血的贝克囊肿，且食管返流现象严重，近期左脚和左膝肿胀及疼痛严重，患者增重15磅，有间歇性抑郁。 MP's past medical history included migraine headaches and disc protrusion with sciatica at L5一S1. His mother, at age 82, was diagnosed with congestive heart failure, malnutrition, rheumatoid arthritis, depression, and schizophrenia. MP's father died at age 62; he had suffered from cancer, obesity, and alcoholism. His brothers were diagnosed with cancer, inflammatory arthritis, inflammatory bowel disease, alcoholism, and depression and his sisters with alcoholism, depression, and bipolar disorder. MP's son was diagnosed with schizophrenia and his daughter with ADHD. There was hypertension, diabetes, heart disease, and depression on both sides of the extended family. 患者既往病史包括偏头痛及伴有坐骨神经痛，第5腰椎至第1骶椎椎间盘突出。其母亲年龄82岁，诊断患有充血性心力衰竭、营养不良、类风湿性关节炎、抑郁症和酗酒；患者父亲62岁离世，生前患有癌症、肥胖症并且酗酒；患者弟弟被诊断有癌症、炎性关节炎、炎性肠病，且伴有酗酒和抑郁；患者姐姐酗酒、抑郁、双相情感障碍；患者儿子被诊断有精神分裂症；女儿患有儿童注意缺陷多动障碍；夫妻二人旁系家族均患有高血压、糖尿病、心脏病和抑郁症。 In addition to etodolac, methotrexate, and adalimumab, MP took aspirin, omega-3 fatty acids, and a multivitamin and mineral. His past history included multiple courses of antibiotics. MP led a stressful life with a highly demanding job. His schedule had little time anon, although he reported meditating daily. MP was married with two children one who had been diagnosed with schizophrenia and lived at home. 除依托度酸、甲氨蝶呤和阿达木单抗等药物外，患者还服用阿司匹林、ω3脂肪酸和多种维生素及矿物质。病人曾服用多种抗生素，入院前生活压力、工作强度极大。工作日程表中少有时间休息，但患者表示每天都进行冥想训练，已婚并育有两个孩子，其中一个因被诊断为精神分裂在家休息。 MP's usual dietary intake included oatmeal with milk and sugar for breakfast; tuna with soup and cookies for lunch; fish or meat with vegetables and potato or pasta for dinner. He snacked on cookies and protein bars. He avoided chocolate and fatty foods. He ate out more than 5 times per week and craved sweets and caffeine, consuming 3 to 4 cups of coffe and one diet soda per day (357 to 464 mg caffeine). MP drank about 12 alcoholic beverages per week, including wine and the occasional scotch. He reported that his liver enzymes had been elevated, and he showed some concern about his drinking. Because of his schedule, he didn't exercise regularly, but he was interested in starting. He had a history of mold exposure and his teeth contained many mercury amalgams. 患者每日的饮食习惯如下： 患者尽量避免食用巧克力或高脂食物，每周在外吃饭5次以上，且对甜食和咖啡因渴望强烈，每天消费3到4杯咖啡及一杯苏打水（含有357到464mg咖啡因）,每周喝12杯酒精类饮料，包括葡萄酒及少量威士忌。患者表示其自身肝酶升高，且对自身饮酒状况表示担心。由于紧张的工作日程安排，患者从不定期锻炼，但对开始锻炼并不排斥。患者有模具接触史，且牙齿含有许多水银汞合金。 In his systems review, it was found that he was sensitive to loud noises, had dry eyes crusty secretions, was intolerant of perfumes and auto exhaust, and had canker esophageal reflux, and chronic constipation. He also had some difficulty with concentration irritability. His blood pressure was 138/87, height 70.5, weight 204 pounds and body mass index was 28.85. 通过其系统综述来看，患者对噪声极其敏感，眼睛干涩、易怒，对香水及汽车尾气不耐受，患有食管返流症、慢性便秘，控制易怒情绪能力较弱。血压为138/87mmHg，身高70.5英寸，体重204磅，体重指数为28.85。 Initial Laboratory Results 1. IgG foods: Food reactions have been associated with psoriatic arthritis pathogenesis, and may contribute to inflammation. Many IgG reactions demonstrate intestinal hyper permeability also a factor in inflammatory arthritis. Removing offending foods, if present, will reduce systemic inflammation. 2. DQ genotype (celiac genes) and celiac panel: Celiac disease and psoriatic arthritis have been linked, and share common inflammatory etiopathogenic features. 3. Inflammatory markers: Monitoring general inflammatory markers is standard practice for assessment of treatment efficacy 4. Multiprofile panel: A comprehensive assessment including fatty acids, amino acids, organic acids, oxidative stress markers, and whole blood toxic metals. These tests assist in finding individual etiopathogenic factors that can affect treatment considerations. (Not all findings are discussed below. Panel results not grouped together) 5. Metabolic panel and lipids: General assessment of metabolic imbalances associated with inflammation 6. Thyroid panel: Subclinical hypothyroidism is frequently found in those with complex, chronic disease. 7. DNA microbial stool profile: Assessment of GI microbial status and GI function. GI imbalances are a common finding in inflammatory conditions. 初步化验结果： Pertinent Negative Laboratory Results Given MP's high number of amalgams, there was concern about mercury. According to the CDC, up to 75% of an individual's mercury exposure may be from amalgams. MP's whole blood toxic metals were within normal limits, ruling out significant current toxic release from amalgams. A DMPS-challenged urine toxic element test was also ordered to assess body burden, but MP had not completed the test at the time of this publication. 实验室检查呈阴性的结果： Initial Assessment Psoriatic arthritis Psoriasis Psoriatic nails Blepharitis Aphthous stomatitis Gastroesophageal reflux disease Chronic constipation Migraine headaches Depression Intestinal hyperpermeability Gluten sensitivity Multiple IgG food sensitivities Hypovitaminosis D Inflammation and oxidative stress Suspected fatty liver Metabolic syndrome Subclinical hypothyroidism GI yeast overgrowth Mercury toxicity (multiple amalgams) Family history of heart disease, hypertension, psychiatric disorders, diabetes, autoimmunity 初步评估： Initial plan Dietary changes: 100% gluten and dairy free; avoid yeast and eggs; discontinue alcohol, caffeine, sugar; eat whole, low glycemic-index foods, good fats, and proteins. Recommend prepared hypoallergenic meals. Anti-inflammatory medicinal food, 2 scoops QD 450 billion CFU probiotic, 1 packet BID Vitamin D3 5000 IU, 2 caps QD EPA/DHA 6:1, 1 cap BID Methyl donors (B12, folic acid and B6), 1 cap BID Amino acids (taurine, glycine, N-acetyl-cysteine, methionine), 3 caps BID High-dose multivitamin and mineral without iron, 4 tabs BID Fluconazole 100 mg, 1 tab QD*30 days Continue daily meditation practice 初步计划 Treatment plan rationale: Treatment for MP was focused on removing the antigenic foods and GI yeast, reducing inflammation, restoring GI mucosa, and providing needed nutrients. It was expected that thyroid and metabolic imbalances would normalize with these general interventions. Given his busy lifestyle, MP benefited from hypoallergenic, low glycemic-index prepared meals. Fluconazole was given for the Candida, followed by a mucosal-restoring medicinal food and high-dose probiotic. 治疗理念 Omega-3 fatty acids were given to support production of anti-inflammatory eicosanoids. Vitamin D (10,000 IU/day) was given to increase serum D levels to within 55 to 70 ng/mL, which is considered an optimal range in complex chronic disease. A supplement containing methyl donors was given to improve methylation and sulfuration activity based on the understanding that increased activity in these pathways may help with mood, metabolic imbalances, cardiovascular health and hepatic detoxification. The amino acid combination of taurine, glycine, N-acetyl-cysteine (NAC), and methionine was also prescribed to support hepatic methylation and sulfuration. Taurine, glycine, and NAC are also known to have anxiolytic properties. A high-dose multivitamin and mineral supplement was given for general micronutrient support, and to ensure adequate availability of cofactors and coenzymes. Metabolic polymorphisms can result in a lowered affinity of an enzyme for its coenzyme; thus, increased levels may be needed for optimal (or even adequate) functioning. MP was encouraged to continue with his meditation practice as meditation has been shown to improve well-being by reducing stress, inflammation and depression. ω3脂肪酸可帮助廿烷类物质的生成。维生素D（每日10,000IU）可将血清D水平提升至55~70ng/ml，这一数值被人们一致认为是慢性复杂性疾病中的最佳水平。甲基供体的补充可增强甲基化作用和硫化活性，据目前所知，这些通道活性对平抚患者情绪，保证新陈代谢平衡，促进心血管健康和肝脏解毒都有重要作用。人们认为氨基酸如牛磺酸、甘氨酸、乙酰半胱氨酸以及蛋氨酸都可促进肝甲基化和硫化。牛磺酸、甘氨酸和乙酰半胱氨酸也具有人们所熟知的抗焦虑作用。大剂量补充多种维生素和矿物质可增加体内微量元素水平，并确保体内有足量有益的辅因子和辅酶。代谢多态性可减弱酶对其自身辅酶的关联性，因此，这一水平的增加需要最佳的（甚至足够的）功能型。患者可继续坚持冥想练习，因为冥想练习在提升幸福感、减少压力、缓解炎症和抑郁方面已经显示有积极作用。 Five-Month Follow-up MP arrived pain-free the day of the office visit, stating that he hadn't felt so good in years. He reported an 80% reduction in pain on average with improved mobility. He could climb stairs more quickly and was no longer limping. Morning pain and stiffness were gone. Previously, his hands were swollen and difficult to open. Now, the swelling was resolved and movement was normal. MP had not used any non-steroidal anti-inflammatory or adalimumab for two months. He reduced his usage of methotrexate from 15 to 5 mg per week。 5个月后续跟进 His reflex and migraines were gone. His mood had improved and he was less irritable. He was no longer constipated. He reported having a single, well-formed bowel movement daily. He was still under a great deal of stress, working 80 hours a week, but meditation continued to be helpful. He reported that he was still getting occasional canker sores. 患者反射反应和偏头痛症状消失。情绪改善且易怒有所缓解。便秘症状消失，患者表示每天排便一次且有规律。然而，工作压力依旧很大，一周工作时间80小时，但持续冥想练习可帮助缓解压力。患者说偶尔会出现口腔溃疡。 He quit caffeine and reduced alcohol intake considerably. He started hypoallergenic, gluten-, yeast-, dairy-, and soy-free prepared meals, which were perfect for his busy lifestyle, enabling him to follow the dietary suggestions. He was taking his supplements regularly. He was losing weight, his clothes fit much better and he was satisfied with his dietary changes. Overall, he was pleased with his progress. 患者戒掉了咖啡因并适当减少了酒精摄入量，开始食用低敏性、无谷蛋白、无酵母、无乳制品和无大豆类的食物，这些食物可以很好地适应患者繁忙的生活方式，且患者应继续实行医生提供的饮食建议。患者有规律的服用补充剂，近几个月坚持减肥，衣物更加合身，且患者对自身饮食的改变很满意。总体来看，患者对自身状况的改善十分满意。 Blood pressure: 118/73 LAS (5 months ago: 138/87) Pulse: 58 BPM Weight: 190 pounds (5 months ago: 204 lbs) 血压：118/73mmHg（5个月前：138/87mmHg） 未完待续，关于银屑病性关节炎的干预思路，请继续关注下期：功能医学案例分析——银屑病性关节炎（下） 注：文章部分内容来自Case Studies in Integrative and Functional Medicine
早餐：含糖燕麦片及牛奶
午餐：金枪鱼、汤类及曲奇饼
晚餐：鱼/肉、蔬菜、土豆或通心粉
加餐：曲奇饼，蛋白棒
1. 免疫球蛋白G：银屑病关节炎的发病机制和食物反应存在关系，食物可能造成炎症。许多免疫球蛋白G反应证实，肠道通透性增高也是炎症性关节炎的一个诱因。如果现在停止食用这些食物，那么感染全身炎症的可能性就会降低。
2. DQ基因型（腹腔基因型）和腹部检查：腹腔疾病和银屑病关节炎存在关系，且炎症发病机理特征相同。
3. 感染标志：跟踪调查显示，一般炎症感染标准是由实际治疗效果评估来决定的。
4. 多型检查：广泛评估包括脂肪酸、氨基酸、有机酸、氧化应激指标和血液中有毒金属等，这些检测有助于找到个体的发病机理因素，从而用来决定治疗方法。（并没有讨论完所有研究结果且检查结果未分类。）
5. 新陈代谢检查及脂类：新陈代谢失调的一般性评估和炎症存在关系。
6. 甲状腺检查：这些复杂的慢性疾病通常伴有临床症状不明显的甲状腺功能减退。
7. DNA微生物粪便评估：肠道微生物状况评估和肠道功能，炎症状况下通常伴有肠道菌群不均衡现象。
鉴于患者的高数值的汞合金指标，考虑有汞中毒情况。疾病控制和预防中心数据显示，超过75%接触汞的人是从汞合金里接触到的。患者的血液毒性在正常范围内，目前排除严重的汞合金泄漏状况。一项名为骨髓细胞生成障碍综合征的尿毒性测试也可指示身体负担，但截止测试结果发表前，患者尚未完成该测试。
※ 银屑病性关节炎
※ 牛皮癣
※ 银屑病甲
※ 眼睑缘炎
※ 抑郁症
※ 口疮性口炎
※ 胃食管返流
※ 慢性便秘
※ 偏头痛
※ 肠道通透性
※ 麸质敏感性
※ 多种抗体食物过敏
※ 维生素D缺乏
※ 炎症和氧化应激
※ 疑似脂肪肝
※ 代谢综合征
※ 亚临床甲状腺功能减退
※ 胃肠道酵母增多
※ 汞毒性（多汞合金）
※ 家庭病史，包括心脏病、高血压、精神病史、糖尿病、自身免疫系统疾病。
※ 改变饮食：限制谷蛋白和奶制品，避免食用酵母和鸡蛋，戒酒、咖啡因和糖，只吃低糖食物、有益脂肪和蛋白质。建议食用低致敏食物。
※ 有抗炎作用的药用食品，2匙/天
※ 4500亿益生菌，一包/天
※ 维生素D3 5000IU，2粒/天
※ EPA/DHA 6：1，1粒，BID
※ 甲基供体（B12、叶酸和B6），1粒，BID
※ 复合氨基酸（牛磺酸、甘氨酸、乙酰基半胱氨酸、蛋氨酸），3粒，BID
※ 高剂量复合维生素和（不含铁）微量元素，4粒/天
※ 氟康唑100mg，一粒/天，服用30天
※ 坚持每日冥想练习
治疗重点集中在避免摄入食物性抗原和酵母，从而缓解炎症，修复胃肠道黏膜，并提供所需营养。尽量保证普通干预疗法可以调节甲状腺功能并改善新陈代谢失调状况。鉴于患者忙碌的生活状态，患者可从低敏、低糖饮食中获益。所需氟康唑从假丝酵母中获取，且假丝酵母也是一种可修复黏膜的医疗食品，并含有大剂量益生菌。
患者就医时已经达到了几天无疼痛的状态，并表示这是近几年来身体状况最好的时候。患者报告说随移动频率增加，他的疼痛已经减少了近80%。上楼速度明显增快且不再有跛行状况。清晨疼痛和僵直现象消失。在此之前，患者手掌肿胀且张开困难。现在，肿胀现象已经消失且活动正常。两个月来，患者已经停用所有非甾体抗炎药或阿达木单抗药物，且将氨甲蝶呤药物的用量从每周15mg降至每周5mg。
脉搏：58次/分
体重：190磅（5个月前：204磅）
联系客服
