A novel recessive 15-hydroxyprostaglandin dehydrogenase mutation in a family with primary hypertrophic osteoarthropathy

Abstract

We present two PHO siblings having a novel homozygous truncating mutation in HPGD. The purpose of the study was to attempt medical treatment, and to find the HPGD mutation causing the disease, in a 22-year old Turkish male and his 23-year old sister afflicted with primary hypertrophic osteoarthropathy (PHO). In combination with NSAIDs and colchicine, treatment with sulfasalazine was started in both cases, and methotrexate was added to the treatment regimen of the female patient at the end of the first year. The patients were found to be typical PHO. Ultrasonographic examination of the joints revealed synovitis and inflammation by B mode and power Doppler ultrasonography. Joint symptoms responded to sulfasalazine treatment in both patients. However, after the addition of methotrexate, the female patient had better remission. All exons of HPGD, the known disease gene, were analyzed by Sanger sequencing. A homozygous 2-bp deletion (c.310_311delCT or p.L104AfsX3) was identified. Seven relatives carrying the mutation in the heterozygous state were examined and none was found affected. Although not specific for this disease, skin, soft tissue and joint ultrasonography can be helpful for evaluation of the musculoskeletal findings in the patients.     

A Novel Diagnostic Test for End-Stage Sensory Failure Associated With Diabetic Foot Ulceration: Proof-of-Principle Study

Background:Diabetic foot ulceration (DFU) affects only a subgroup of patients with diabetic neuropathy, that is, those with pain-insensitivity due to end-stage sensory failure. Pain perception failure develops insidiously and remains asymptomatic until first DFU. As loss of pain perception is clinically significant, timely detection is mandatory.Objectives:A novel suprathreshold pinprick pain stimulus of 512 mN force made from optical glass-fiber was explored in a prospective cross-sectional diagnostic accuracy study to detect DFU-related end-stage sensory failure.Methods:A total of 116 participants were studied (25 healthy people, 22 patients with diabetes without relevant complications, 19 patients with previous painful foot or leg injuries, and 50 patients with previous or active painless DFU [reference standard]). Palmar and plantar surfaces were stimulated in a standardized fashion. At the feet, the second and third toe skinfolds and the middle of the plantar arch were stimulated. Participants scored stimulated pricking discomfort or pain intensity 0 to 10 on a numerical rating scale.Results:At hands, intensity was rated on average 5 (1-10) [median (range)] by 114/116 participants. Per foot, participants without DFU scored 5 (1-10), while those with DFU scored 0 (0-3) (P < .0001). At plantar toe skinfolds, the absence of pinprick pain perception detected DFU-associated sensory failure with an accuracy of 99.5% (sensitivity 99.5%, specificity 99.4%, positive likelihood ratio 248, and negative likelihood ratio 0.005).Conclusion:In this pilot study, nociceptive stimulation of a plantar toe skinfold with a 512 mN optical glass-fiber pinprick accurately identified DFU-associated end-stage sensory failure.     

Touraine–Solente–Gole syndrome

Touraine–Solente–Gole syndrome, also known as Pachydermoperiostosis (PDP) or Primary Hypertrophic Osteoarthropathy, is a rare hereditary disorder, which affects both bones and skin. It is characterized by a combination of dermatologic changes (pachydermia or thickening of the skin) and rheumatologic manifestations (periostosis and finger clubbing). Eyelid ptosis which is caused by thickened eyelids (blepharoptosis) is a less common symptom. We report the case of a patient with a complete form of Touraine–Solente–Gole syndrome with bilateral blepharoptosis as presenting feature.     

1例HPGD基因新缺失突变致儿童原发性肥大性骨关节病报道

目的通过对1例临床疑似原发性肥大骨关节病的患者进行HPGD基因分析并确诊,提高对该疾病的认识。方法根据患儿症状,体征及骨骼系统放射学检查进行临床诊断,提取患儿及其父亲外周血DNA,PCR扩增HPGD基因编码氨基酸的7个外显子片段,测序检测突变。结果患儿女性,5岁,具有手指及足趾末端指节肥大,手足多汗,前额皮肤增厚等典型临床表现。PCR扩增片段直接测序示患儿HPGD外显子3发生c.308₃09delCT（p.Thr103Thrfs4X）纯合改变。结论原发性肥大骨关节病为一种少见的常染色体隐性遗传疾病,典型的临床及影像学表现有助于诊断,HPGD基因突变分析是确诊的主要方法。     

温针灸配合时间医学治疗顽固性膝骨关节炎临床观察

目的:观察温针灸配合子午流注纳甲法治疗顽固性膝骨关节炎的临床疗效。方法:将98例患者(161膝)随机分为治疗组51例(82膝),温针灸犊鼻、鹤顶、血海等穴,并同时加子午流注针法;对照组47例(79膝),单纯用温针灸治疗,穴位同治疗组。经5个疗程(35次)治疗,对治疗前后膝关节功能参数进行评定。结果:治疗组总有效率86.6%,对照组总有效率73.4%,二者有显著性差异(P>0.05)。结论:温针灸配合子午流注针法治疗顽固性膝骨关节炎疗效优于单纯温针灸。     

肥大性骨关节病病例分析并文献复习

目的 提高对肥大性骨关节病(HOA)的认识、诊断和鉴别.方法 报告我院2例原发性HOA(PHOA)及3例继发性HOA(SHOA)确诊病例,并分析既往国内报道16例文献.结果 国内PHOA发病年龄多数在14～24岁,多为男性,最小者1岁起病,最大者为42岁.18例PHOA患者中2例有家族史,2例有近亲结婚史,所有患者均有杵状指(趾)、皮肤增厚粗糙、骨膜增生的临床表现,多汗14例,回状颅皮9例,关节痛和(或)关节积液10例,指(趾)端骨质溶解4例,类风湿因子阳性2例,1例弱阳性.我院报告3例SHOA均继发于肺部肿瘤,中年后起病,病程较短.以关节症状及杵状指(趾)为主要表现,面部及皮肤症状少,全身伴随症状多见.结论 PHOA青少年起病多见.男性多,主要表现为杵状指(趾)、皮肤增厚及骨膜反应.与SHOA需从起病年龄、病程及全身伴随症状等方面鉴别.     

肺癌性骨关节病的临床分析

目的警惕肺癌性骨关节病，提高诊断准确率，争取早期诊断原发病，取得良好疗效，防止误诊、误治。方法对廊坊市人民医院2003年10月至2006年10月，诊治肺癌266例。部分病例首发症状为肺性关节病，确诊肺癌32例，进行回顾分析。结果手术切除原发肺癌病灶6例，术后骨关节病症消失，存活2—5年；其余病例失去手术机会，化疗16例，化疗合并放疗5例，其症状均明显好转，存活6～15个月。放弃治疗5例，症状未缓解，存活1～5个月。结论肺癌约12％首发症状为肺性骨关节病，发病至确诊最长时间15月，常误诊为肩周炎、颈椎病、棘上棘间韧带炎、风湿病或类风湿性关节炎、肢端肥大症等。对病因不明的骨性关节病，应列入肺癌排查程序。     

Hypertrophic osteoarthropathy,tuberculoma of brain and cyanotic heart disease

A nine year old girl with tetralogy of fallot was admitted with right sided focal seizures and tender, swollen right elbow and knee joints. During the hospital stay there was no improvement. The patient deteriorated and died 25 days following admission. Radiological survey showed characteristic features of hypertrophic osteoarthropathy. Brain biopsy showed granulomas consistent with tuberculoma. The association of hypertrophic osteoarthropathy and cyanotic congenital heart disease is being increasingly recognised. The association of hypertrophic osteoarthropathy with tuberculoma of brain has not been reported earlier.