原发性肥大性骨关节病--附2例报告

目的提高对原发性肥大性骨关节病的认识.方法报告我院收治的2例原发性肥大性骨关节病的临床表现、实验室检查及X线改变,并复习相关文献.结果2例为同胞两兄妹,自幼即表现为杵状指（趾）、关节肿大、疼痛,X线表现为管状骨对称性的分层状骨膜新骨形成.随访显示症状反复,短期予糖皮质激素、非甾体类抗感染药治疗可控制病情发作.结论本病较为罕见,病因未明,临床特点为杵状指（趾）、脑回样头皮和对称性骨膜增厚,诊断成立尚需排除继发性因素.     

Touraine-Soulente-Golé Syndrome: A Rare Case Report and Review of the Literature

Touraine-Soulente-Golé Syndrome (TSG) or pachydermoperiostosis is a rare disorder characterized by pachydermia, periostosis & digital clubbing. Herein, we report a case of a 27 year old male, with the looks of a 47 year old. He presented with excessive wrinkling on his face since past 8 years. TSG syndrome was suspected and examined by histopathological, endocrinological and radiological studies for the confirmation of clinical diagnosis.     

原发性肥大性骨关节病并SLCO2A1基因突变2 例

收集中南大学湘雅三医院内分泌科诊断的2例原发性肥大性骨关节病(primary hypertrophic osteoarthropathy, PHO)患者的临床资料,提取全部患者及其家族成员外周血进行基因组DNA抽提,应用PCR扩增15-羟基前列腺素脱氢 酶(hydroxyprostaglandin dehydrogenase,HPGD)及SLCO2A1致病基因全部外显子、外显子和内含子交界区。PCR产物进 行直接测序,并利用在线数据库PolyPhen-2及SIFT对发现的突变致病性进行预测。通过基因测序,发现该2例患者的 SLCO2A1基因分别存在c.1106G>A(p.G369D)纯合子突变和c.611C>T(p.S204L)纯合子突变,均未检出HPGD基因突变。 经SIFT和PolyPhen2生物信息学工具预测得出SLCO2A1基因这两个突变为致病性错义突变,证实SLCO2A1基因突变在 PHO发病机制中的作用。对PHO患者进行SLCO2A1基因检测不仅有助于明确病因,也有利于产前诊断及遗传咨询。     

原发性肥大性骨关节病临床与基础研究进展

肥大性骨关节病（HO）是以杵状指和长骨骨膜增生为特征的骨关节病综合征,按病因不同分为原发性（PHO）和继发性（SHO）2个亚型。人类对该疾病的认识可以追溯到希波克拉底时代,但该病发病机制至今尚不十分明确。对PHO家系的遗传学研究为认识HO发病机制提供了机会。随着PHO致病基因的发现,PHO的发病机制业已明确,即前列腺素降解障碍导致循环和局部微环境前列腺素E2（PGE2）水平显著增高。SHO同样由前列腺素代谢障碍所致。本文就PHO临床表现及其发病机制的研究进展和治疗手段的革新作一综述。     

Calcaneal ultrasonometry in patients with Charcot osteoarthropathy and its relationship with densitometry in the lumbar spine and femoral neck and with markers of bone turnover.

AIMS: To assess calcaneal ultrasonometry in Charcot osteoarthropathy (CO) and to compare it with densitometry measured by dual energy X-ray absorptiometry (DEXA) and with bone remodelling markers. PATIENTS AND METHODS: A group of 16 diabetic patients in the acute stage of CO with a mean age (+/- SD) of 51 +/- 13 years was compared with 26 sex- and age-matched control subjects. Both calcaneal quantitative ultrasound (QUS) parameter stiffness and bone mineral density (BMD) measured in lumbar spine and femoral neck by DEXA were compared. Collagen type I cross-linked C-telopeptides (ICTP) were used for assessment of bone resorption. RESULTS: Patients with acute CO had significantly lower stiffness of the calcaneus in the Charcot and non-Charcot foot (both P < 0.001) and significantly lower femoral neck BMD (P < 0.05) in comparison with the control group. The T-score of stiffness was significantly lower in the Charcot foot compared with the non-Charcot foot (-3.00 +/- 1.39 vs. -2.36 +/- 1.12; P < 0.01) and significantly lower than the mean T-score of BMD in the lumbar spine (-0.57 +/- 1.28; P < 0.001) and femoral neck (-1.58 +/- 1.24; P < 0.05). A significant difference in ICTP (8.49 +/- 4.37 vs. 3.92 +/- 2.55 ng/ml; P < 0.001) between patients with CO and the control group was found, and a significant correlation was demonstrated between ICTP and the T-score of stiffness (r = -0.73; P < 0.01). CONCLUSION: The lower calcaneal QUS parameter stiffness in the Charcot foot in comparison with the control group, with the non-Charcot foot and with BMD in the lumbar spine and femoral neck, and its association with increased bone resorption indicate that calcaneal ultrasonometry may be useful in diagnosing the acute stage of CO and in assessing the risk of foot fracture. Diabet. Med. 18, 495-500 (2001)     

Bone changes associated with cystic fibrosis

Musculoskeletal symptoms are known to occur frequently in patients with cystic fibrosis. Radiographs of the hands and wrists, and of the tibia and fibula of 56 patients with cystic fibrosis were reviewed. No radiographic joint abnormalities were detected. However, it was noted that the fourth metacarpal was shortened in 5 of 56 patients (9%), a finding that has not been previously documented. Hypertrophic pulmonary osteoarthropathy was present in 3 patients (5.5%).     

Cutaneous manifestations of lung cancer

Skin findings can serve as a clue to internal disease. In this article, cutaneous manifestations of underlying lung malignancy are reviewed. Paraneoplastic dermatoses are rare, but when recognized early, can lead to early diagnosis of an underlying neoplasm. Malignancy-associated dermatoses comprise a broad group of hyperproliferative and inflammatory disorders, disorders caused by tumor production of hormonal or metabolic factors, autoimmune connective tissue diseases, among others. In this review, paraneoplastic syndromes associated with lung malignancy are discussed, including ectopic ACTH syndrome, bronchial carcinoid variant syndrome, secondary hypertrophic osteoarthropathy/digital clubbing, erythema gyratum repens, malignant acanthosis nigricans, sign of Leser-Trélat, tripe palms, hypertrichosis lanuginosa, acrokeratosis paraneoplastica, and dermatomyositis.     

Miscellaneous non-inflammatory musculoskeletal conditions. Pachydermoperiostosis

Pachydermoperiostosis (PDP), also known as primary hypertrophic osteoarthropathy, is a rare disease of the skin and bones that has clear genetic predisposition and well-defined clinical features. PDP is characterised by the presence of exuberant skin hypertrophy that, at the most distal parts of the extremities, takes a drumstick configuration. This deformity is conventionally known as digital clubbing. In advanced stages, skin hypertrophy may also be present in the head with furrowing of the facial features and eyelids ptosis. Another characteristic feature of the disease is periosteal proliferation of the long bones. Abnormal vascular endothelial growth factor and/or genetically determined prostaglandins overexpression may play a key role on its pathogenesis. No therapy has been shown to be effective in reversing hypertrophic changes. When bone pain is present, non-steroidal anti-inflammatory drugs are frequently useful. Isolated case reports have described that bisphosphonates may ease recalcitrant bone pain.