C-antineutrophil cytoplasmic antibody positivity in vasculitis patients is associated with the Z allele of alpha-1-antitrypsin, and P-antineutrophil cytoplasmic antibody positivity with the S allele

BACKGROUND.: Antineutrophil cytoplasmic antibodies (ANCA) in vasculitis haveeither cANCA or pANCA patterns as defined by immunofluorescence.The target autoantigen of cANCA is usually proteinase 3 (PR3),whereas that of pANCA is usually myeloperoxidase (MPO). Alpha-1-antitrypsin(1AT) is the major physiological inhibitor of PR3, while MPOis an inhibitor of 1AT. METHODS.: To determine whether there was an association between ANCA positivevasculitis, ANCA pattern, and 1AT deficiency alleles, we studied1AT phenotypes of 99 cANCA and 99 pANCA positive vasculitispatients by isoelectric focusing and immunoblotting, and comparedthem with 2310 controls from the same geographical area. RESULTS.: C-ANCA patients showed an increased frequency of the Z allele(0.055 versus 0.018 in controls), conferring a relative riskof 3. They showed no increase in frequency of the S allele.P-ANCA patients showed an increased frequency of the S allele(0.091 versus 0.046 in controls) conferring a relative riskof 2. The frequency of the Z allele also appeared to be increased(0.030 versus 0.018 in controls), but this was not statisticallysignificant. CONCLUSIONS.: These findings demonstrate an association between ANCA-positivevasculitis and deficiency phenotypes of 1AT, and suggest a rolefor 1AT in the development of systemic vasculitis.     

The pathological diagnosis of nerve biopsies: a practical approach

The approach to the neuropathological assessment of nerve biopsies is the main focus of this review. Nerve biopsies are invasive diagnostic procedures resulting in a permanent neurological deficit, and are therefore carried out only following an in-depth clinical assessment including laboratory, imaging, electrophysiological, and where appropriate also genetic studies. This review will outline the key diagnostic approaches and will discuss neuropathies relevant in clinical practice, caused by vasculitis, inflammatory demyelination, dysproteinaemic, amyloid, toxic agents, and neuropathies due to genetic conditions.     

Disorders characterized by predominant or exclusive dermal inflammation

Some cutaneous inflammatory disorders are typified by a predominant or exclusive localization in the dermis. They can be further subdivided by the principal cell types into lymphocytic, neutrophilic, and eosinophilic infiltrates, and mixtures of them are also seen in a proportion of cases. This review considers such conditions. Included among the lymphoid lesions are viral exanthems, pigmented purpuras, gyrate erythemas, polymorphous light eruption, lupus tumidus, and cutaneous lymphoid hyperplasia. Neutrophilic infiltrates are represented by infections, Sweet syndrome, pyoderma gangrenosum, and hidradenitis suppurativa, as well as a group of so-called “autoinflammatory” dermatitides comprising polymorphonuclear leukocytes. Eosinophil-dominated lesions include arthropod bite reactions, cutaneous parasitic infestations, the urticarial phase of bullous pemphigoid, Wells syndrome (eosinophilic cellulitis), hypereosinophilic syndrome, and Churg-Strauss disease. In other conditions, eosinophils are admixed with neutrophils in the corium, with or without small-vessel vasculitis. Exemplary disorders with those patterns include drug eruptions, chronic idiopathic urticaria, urticarial vasculitis, granuloma faciale, and Schnitzler syndrome (chronic urticarial with a monoclonal gammopathy).     

Development of anti-neutrophil cytoplasmic antibody-associated vasculitis in a patient with Graves’ disease independent of anti-thyroid drug therapy

Abstract

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) in patients with Graves’ disease (GD) is linked with the use of anti-thyroid drugs (ATDs). We report the co-occurrence of AAV and GD in a patient that was independent of ATD therapy. A 38-year-old white male presented with systemic symptoms, palpitations, tremors, purpuric skin lesions, and digital pain. Physical examination and biological tests confirmed GD. He quickly developed multiple digital gangrenes and testicular pain/mass. Skin and testicular biopsies showed granulomatous vasculitis of the small- and medium-sized vessels, while his serum contained anti-proteinase-3 antibody.     

Factors associated to temporal artery biopsy result in suspects of giant cell arteritis: a retrospective,multicenter, case–control study

Purpose: To evaluate the positivity rate of temporal artery biopsies (TAB) performed in suspects of giant cell arteritis (GCA) and to study the epidemiological and clinical factors associated to the biopsy result. Methods: A retrospective, multicenter, case–control study was performed, including three hundred and thirty‐five patients who underwent TAB for a suspicion of GCA from 2001 to 2010. Clinical, epidemiological and pathology data were recovered from the patients’ clinical records. Histologic diagnosis of GCA was made when active inflammation or giant cells were found in the arterial wall. Results: Eighty‐one biopsies (24.2%) were considered positive for GCA. Clinical factors independently associated to TAB result in a logistic regression analysis were temporal cutaneous hyperalgesia (OR = 10.8; p < 0.001), jaw claudication (OR = 4.6; p = 0.001), recent‐onset headache (OR = 4.4; p = 0.001), decreased temporal pulse (OR = 2.8; p = 0.02), pain and stiffness in neck and shoulders (OR = 2.3; p = 0.05), unintentional weight loss (OR = 1.33; p = 0.003) and age (OR = 1.085; p = 0.004). Other factors such as length of the surgical specimen (OR = 1.079; p = 0.028) and erythrocyte sedimentation rate (OR = 1.042; p < 0.001) were also statistically significant. The model was accurate (C‐index = 0.921), reliable (p_{Hosmer–Lemeshow} = 0.733) and consistent in the bootstrap sensitivity analysis. No significant association was detected between TAB result and number of days of previous systemic corticosteroid treatment (p = 0.146). However, an association was observed between TAB result and the total accumulated dose of previous systemic corticotherapy (p = 0.043). Conclusions: Exhaustive anamnesis and clinical examination remain of paramount importance in the diagnosis of GCA. To improve the yield of TAB, it should be performed specially in older patients with GCA‐compatible clinic. TAB could be avoided in patients with an isolated elevation of acute phase reactants, without GCA‐compatible clinic.     

活血化瘀联合温阳生肌法治疗青斑样血管炎临床分析

目的分析青斑样血管炎的临床特征及中医证候特点,提高对本病的诊断及中医辨证水平。方法对12例确诊的青斑样血管炎患者的临床表现、组织病理、中医证候、中医治则、方药、预后进行回顾性分析。结果12例患者中男3例,女9例,年龄15~45岁,平均年龄20.17岁,中医药治疗时间为14~70 d,平均时间为54.60 d。12例患者均为对称皮疹,均伴有疼痛;皮损特点均为红斑、水疱、紫癜、坏死、水肿、溃疡,呈现线状或放射状分布;皮损痊愈后见色素沉着斑或线状象牙白色萎缩性瘢痕。所有患者经过组织病理确诊。12例患者均符合寒凝血瘀证。坏死期选用活血化瘀法,应用桃红四物汤加减;溃疡期选用温阳生肌法,应用自拟方温阳生肌汤加减。局部使用黄连膏换药。12例患者经中医药治疗后皮损均完全消退,溃疡愈合,遗留色素沉着斑及象牙白色萎缩性瘢痕。停药后随访6个月无1例复发。结论活血化瘀联合温阳生肌法为中医治疗青斑样血管炎提供了新的思路,并能明显降低复发率,值得进一步研究。     

Cutaneous necrotizing vasculitis as a manifestation of familial Mediterranean fever

Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease, which is characterized by recurrent and paroxysmal fever, peritonitis, arthritis, myalgia, and skin rashes. Although various skin lesions such as “erysipelas‐like erythema”, urticaria, nonspecific purpura, and subcutaneous nodules have been described, cutaneous vasculitis is rare. We report a Japanese case of sporadic FMF accompanied by cutaneous arteritis at the time of febrile attacks of FMF. Gene analysis revealed M694I mutation in a single allele of the MEFV gene, and oral colchicine successfully controlled both periodic fever and subcutaneous nodules of arteritis. Cutaneous necrotizing vasculitis repeatedly emerging with febrile attacks should be included among the skin manifestations of FMF.     

Cross-talk between the complement system and endothelial cells in physiologic conditions and in vascular diseases

The endothelial layer represents a continuous physical barrier that controls coagulation and allows selective passage of soluble molecules and circulating cells across the vessel wall into the tissue. The functional activity of the endothelial cells may be influenced by their interaction with components of the complement system. In this review we shall discuss the complex interplay that can be established between the endothelium and complement proteins or activation products. Endothelial cells may also secrete several complement components which contribute to the circulating pool. This process can be regulated by cytokines and other pro-inflammatory stimuli. In addition, complement activation products stimulate endothelial cells to acquire a pro-inflammatory and pro-coagulant status. Expression of regulatory molecules on the cell surface provides protection against an undesired attack by complement activation products. Unrestricted complement activation under pathological conditions may lead to structural and functional changes of the endothelium resulting in vascular disease.