Pathogenesis of liver injury in Takayasu arteritis: advanced understanding leads to new horizons

Liver injury in Takayasu arteritis (TA) is a rare phenomenon. Most symptoms are nonspecific, and the exact pathogenesis remains to be elucidated. Early diagnosis and new treatment methods are important for an improved prognosis. A summary of the clinical information and mechanistic analyses may contribute to making an early diagnosis and development of new treatment methods. A PubMed search was conducted using the specific key words “Takayasu arteritis” and “liver” or “hepatitis” or “hepatic”. Symptoms and treatment of TA with an accompanying liver injury were reviewed retrospectively. Many factors are presumed to be involved in the mechanism of TA with liver injury, including the immune response, genes, infections, and gut microbiota. There are several lines of evidence indicating that immune dysfunction is the main pathogenic factor that triggers granuloma formation in TA patients. However, the role of genetics and infections has not been fully confirmed. Recently, the gut microbiota has emerged as an essential component in the process. We reviewed in detail the current concepts that support the complex pathogenesis of TA accompanied by liver injury, and we presented recent theories from the literature. Finally, we discussed future research directions of liver injury in TA.     

组织学绒毛膜羊膜炎与早产儿脑损伤相关性分析

目的探讨组织学绒毛膜羊膜炎(HC)及合并胎儿血管炎(FV)时与早产儿脑损伤的相关性。方法回顾性分析347例住院的出生胎龄28~32周早产儿的临床资料。根据病理检查结果将早产儿分为HC组和对照组,HC组再根据是否合并胎儿血管炎分FV组及无FV组。早产儿定期行头颅B超检查,比较早产儿脑室周围白质软化(PVL)、脑室周围-脑室内出血(PVH-IVH)和脑室周围白质软化并脑室周围-脑室内出血的发生情况。结果 HC组、对照组PVL发生率分别为17.9%、10.4%,PVL合并PVH-IVH发生率分别为5.5%、1.5%,差异均有统计学意义(P0.05);而PVH-IVH的发生率分别为29.0%、26.2%,差异无统计学意义(P0.05)。在HC组中,FV组、无FV组的PVL发生率则分别28.1%、9.9%,差异有统计学意义(P0.05);PVH-IVH的发生率为34.3%、24.7%,PVL合并PVH-IVH发生率分别为7.8%、3.7%,差异均无统计学意义(P0.05)。结论 HC可使早产儿PVL、PVL合并PVH-IVH的发生率增加,而对PVH-IVH的影响不大,合并FV会增加早产儿脑损伤发生率。     

Histopathology of bilateral lower extremity inflammatory lymphedema in military basic trainees: A leukocytoclastic vasculitis of the deep vascular plexus

Bilateral lower extremity inflammatory lymphedema (BLEIL) is a recently described condition that presents with exquisite tenderness, erythema and edema of the lower leg, ankle and dorsal foot resembling an acute cellulitis. It was first reported in healthy, young adult military basic trainees with a normal body mass index during the first 72 hours of arrival to basic training. It occurs while standing at attention for many hours, and shows rapid resolution with elevation and rest. We report an additional case of BLEIL and describe the histopathology of this case and 2 of the previously reported cases. All 3 biopsies showed a deep perivascular infiltrate of neutrophils with karyorrhectic debris and prominent red blood cell extravasation. One of the 3 cases was positive for complement by direct immunofluorescence. We postulate this condition represents a deep leukocytoclastic vascultis with secondary reactive lymphedematous changes.     

ANCA-associated vasculitides: Pathogenetic aspects and current evidence-based therapy

A lot of progress has been made regarding the therapy of ANCA-associated vasculitides in the past decades. Cyclophosphamide still is standard therapy for remission induction in generalized disease, however, duration and cumulative dose of cyclophosphamide have been curtailed successfully to reduce toxicity. MTX is a safe alternative for remission induction in early systemic disease and medications available for remission maintenance have been extended. Rituximab and TNFalpha-antagonists represent promising options for refractory disease. The current evidence of therapy of ANCA-associated vasculitides is summarized in this review.     

Possible association of elevated serum collagen type IV level with skin sclerosis in systemic sclerosis

Collagen type IV is the primary collagen in the basement membranes around blood vessels and in the dermoepidermal junction in the skin. Perivascular collagen type IV is synthesized by endothelial cells and pericytes, and contributes to the homeostasis and remodeling of blood vessels. It has been well recognized that elevated serum collagen type IV levels are associated with the liver fibrosis. The objective was to examine serum collagen type IV levels and their clinical associations in patients with systemic sclerosis (SSc), and to examine the expression of collagen type IV in the fibrotic skin in SSc. Serum collagen type IV levels in SSc patients and diffuse cutaneous type SSc patients were significantly higher than those in healthy individuals. Serum collagen type IV levels were positively correlated with modified Rodnan total skin score. Serum collagen type IV levels in early stage (disease duration ≤3 years) diffuse cutaneous SSc patients were significantly elevated. Serum collagen type IV levels in SSc patients with digital ulcers (DU) were significantly elevated. In immunohistochemical staining, the expression of collagen type IV around dermal small vessels in the affected skin was reduced compared with those of normal individuals. These results suggest that elevated serum collagen type IV levels may be associated with the skin sclerosis in the early stage of SSc. The measurement of serum collagen type IV levels in SSc patients may be useful as a disease activity marker in skin sclerosis and DU.     

Clinical analysis of leg ulcers and gangrene in rheumatoid arthritis

Leg ulcers are often complicated in patients with rheumatoid arthritis (RA), however, the etiology is multifactorial. We examined the cases of leg ulceration or gangrene in seven RA patients who were hospitalized over the past 3 years. One patient was diagnosed as having pyoderma gangrenosum. Although vasculitis was suspected in three patients, no histological evidence was obtained from the skin specimens. In these patients, angiography revealed the stenosis or occlusion of digital arteries. In the remaining three patients, leg ulcers were considered to be due to venous insufficiency. Treatment should be chosen depending on the causes of leg ulcers.     

伴器官损害或威胁生命的ANCA相关性血管炎的治疗进展及挑战

随着大量临床研究的开展和各国指南的发布，伴有器官损害或威胁生命的ANCA相关性血管炎（AAV）的治疗已经获得了重要突破，从致死性疾病转变为一类慢性疾病。利妥昔单抗（RTX）在AAV诱导和维持治疗中的作用获得了有力的循证医学支持，并最终纳入现行的大部分指南。AAV患者的长期预后不仅取决于血管炎疾病本身，还取决于长期用药带来的不良反应。因此，优化治疗药物、治疗剂量和治疗周期，减少药物的不良反应，最终改善生存率是未来临床研究的工作方向。     

青斑样血管病的诊疗进展

青斑样血管病是一种非炎性、真皮内血管阻塞性皮肤病,以双下肢远端反复出现疼痛性溃疡,网状青斑以及瓷白色萎缩性瘢痕为主要临床表现。本病病因及发病机制不明,可能与机体高凝状态,纤维蛋白溶解障碍和/或与免疫系统疾病相关。目前无特效疗法,主要以缓解疼痛、防止皮损进展为目的。