The diagnosis and management of temporal arteritis

Temporal arteritis (TA), or giant cell arteritis, is a systemic autoimmune vasculitis affecting patients over 50 years of age. It can cause rapid, irreversible bilateral vision loss in older adults and is therefore considered an ophthalmological emergency. Many of the symptoms and signs of TA can be vague, non-specific and gradual in onset, often leading to a delayed or inaccurate diagnosis. As such, it is important for a wide variety of primary optometrists and health practitioners to maintain a robust understanding of the clinical presentation, key investigations and time-sensitive management of this disease, as early initiation of treatment for TA can be vision- and life-saving.     

28例风湿性多肌痛和颞动脉炎随诊分析

目的评价28例风湿性多肌痛(PMR)和颞动脉炎(TA)患者治疗过程,分析影响激素治疗时间和复发的因素。方法回顾性分析1992年至2001年本院诊治的28例PMR和TA患者,其中22例患单纯性PMR,3例PMR合并TA,3例单纯性TA,全部患者均应用糖皮质激素。其中13例加用免疫抑制剂。平均治疗时间25.5±24.0个月。按患者对激素有无抵抗及治疗后有无复发分组,对临床资料分析比较并分析影响PMR和TA治疗及预后的因素。结果激素抵抗组治疗前血沉和外周血白细胞水平较无抵抗组明显升高(P<0.01);复发组激素减量速度较无复发组快(P<0.05)。结论治疗前血沉快和外周血白细胞高者易发生激素抵抗。激素减量过快易复发。对激素治疗抵抗和复发者,或PMR合并TA者应加用免疫抑制剂治疗。     

Analysis of the B cell repertoire against autoantigens in patients with giant cell arteritis and polymyalgia rheumatica

The analysis of the antibody repertoire of patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) might identify target antigens of the autoimmune response with potential relevance to our understanding of the pathogenesis of the disease and to the development of serodiagnostic tests. To detect such antigens, we screened a cDNA library derived from normal human testis for antigens reacting with IgG antibodies in the 1 : 250 diluted sera of three patients with untreated GCA using SEREX, the serological identification of antigens by recombinant cDNA expression cloning. Of 100 000 clones screened with each serum, six, 28 and six clones, respectively, were positive, representing a total of 33 different antigens. Most of the antigens reacted only with the serum used for identification and/or at a similar frequency with normal control sera. However, lamin C and the nuclear antigen of 14 kD reacted specifically with 32% of GCA/PMR, but with none of the control sera, while human cytokeratin 15, mitochondrial cytochrome oxidase subunit II, and a new gene product were detected preferentially, but not exclusively by sera from GCA/PMR patients. We conclude that patients with GCA/PMR develop antibodies against a broad spectrum of human autoantigens. Antibodies against human lamin C, the nuclear autoantigen of 14 kD as well as human cytokeratin 15, mitochondrial cytochrome oxidase subunit II and the product of a new gene should be investigated further to determine their value as tools for the diagnosis and/or the definition of clinical subgroups of patients with GCA/PMR.     

Tocilizumab controls bone turnover in early polymyalgia rheumatica

ObjectivesThis study explores changes in the bone homeostasis by testing the N-terminal collagen type I extension propeptide (PINP) marker for osteo-formation and the carboxy-terminal region of collagen type I (CTX-I) marker for osteo-resorption in patients taking tocilizumab for polymyalgia rheumatica (PMR).MethodsTwenty patients were included in the prospective open-label TENOR study (Clinicaltrials.gov NCT01713842) and received three monthly tocilizumab infusions, followed by corticosteroids starting at week (W) 12. PINP and CTX-I were tested at inclusion (W0), after tocilizumab but before steroid initiation (W12), at the end of the protocol (W24) and were compared to healthy controls. Information regarding disease activity, bone mineral density using scanographic bone attenuation correlation (SBAC), inflammatory parameters and interleukin (IL)-6 levels were collected during the follow-up of the patients.ResultsPMR patients were characterised by a reduction in bone mineral density and a higher level of CTX-I relative to healthy controls matched in age and sex at baseline. PINP levels increased at W12 (P < 0.001, versus W0) following tocilizumab introduction and CTX-I levels decreased at W24 and after steroid initiation (P = 0.001, versus W0). Such modifications explain the altered correlation observed between PINP and CTX-I at W0 (r = 0.255 at W0 versus r = 0.641 in healthy controls) and its correction after treatment (r = 0.760 at W12 and r = 0.767 at W24). Finally, greater changes in PINP were observed in patients whose circulating IL-6 levels decreased after tocilizumab therapy.ConclusionsControl of bone turnover, in part through the inhibition of the IL-6 axis, is observed during tocilizumab and subsequent steroid treatment of PMR.     

Acute Phase Reactants in the Initial Phase of Giant Cell Arteritis

ABSTRACT The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fibrinogen and haptoglobin were followed weekly during the initial phase of corticosteroid treatment in 18 patients with 19 episodes of giant cell arteritis (GCA). Fibrinogen and CRP decreased most rapidly, with normal values in 67% of the patients after two weeks of treatment. After two weeks 56% of the patients had normal ESR values and 76% after five weeks. Haptoglobin normalised most slowly, no patient having a normal value after one week, 29% after two weeks and 75% after six weeks. For routine clinical use, we found the ESR alone sufficient for monitoring the initial steroid treatment.     

Mechanistic immunological based classification of rheumatoid arthritis

The classical autoimmunity paradigm in rheumatoid arthritis (RA) is strongly supported by immunogenetics suggesting follicular helper T-cell responses driving high titre specific autoantibodies that pre-dates disease onset. Using the immunological disease continuum model of inflammation against self with “pure” adaptive and innate immune disease at opposite boundaries, we propose a novel immune mechanistic classification describing the heterogeneity within RA. Mutations or SNPs in autoinflammatory genes including MEFV and NOD2 are linked to seronegative RA phenotypes including some so called palindromic RA cases. However, just as innate and adaptive immunity are closely functionally integrated, some ACPA+ RA cases have superimposed “autoinflammatory” features including abrupt onset attacks, severe attacks, self-limiting attacks, relevant autoinflammatory mutations or SNPs and therapeutic responses to autoinflammatory pathway therapies including colchicine and IL-1 pathway blockade. An emergent feature from this classification that non-destructive RA phenotypes, both innate and adaptive, have disease epicentres situated in the extracapsular tissues. This mixed innate and adaptive immunopathogenesis may be the key to understanding severe disease flares, resistant disease subsets that are unresponsive to standard therapy and for therapies that target the autoinflammatory component of disease that are not currently considered by expert therapeutic recommendations.     

加味阳和汤配合糖皮质激素治疗风湿性多肌痛临床观察

目的观察加味阳和汤对糖皮质激素治疗风湿性多肌痛使用剂量的影响。方法风湿性多肌痛患者61例,随机分为2组,中药组（加味阳和汤加泼尼松组）32例,对照组（单用泼尼松组）29例,两组均给予泼尼松20mg／d,2周后根据病情酌情减量,中药组加服加味阳和汤煎剂,每天l剂,共治疗12用。结果两组对风湿性多肌痛活动性疗效：中药组32例临床缓解9例（28．1％）,显效15例（46．9％）,有效7例（21．9％）,无效l例（3．1％）,总有效率96．9％;对照组29例分别为3例（10．3％）,ll例（37．9％）,10例（34．5％）,5例（17．2％）及82．8％。两组比较,差异有显著性（U=2．109,P〈0．05）;中药组血沉比对照组下降快（t=2．957,P〈0．05）;中药组泼尼松用量比对照组用量小（t=10．23,P〈0．05）。结论加味阳和汤有助于缩短治疗风湿性多肌痛的疗程,减少糖皮质激素的剂量,提高疗效。     

Medical management of polymyalgia rheumatica

Importance of the field: Polymyalgia rheumatica (PMR) is a relatively frequent condition in individuals older than 50 who originate from Western countries. Corticosteroids constitute the cornerstone therapy in the management of patients with PMR.

Areas covered in this review: This review summarizes the current literature on clinical clues for the diagnosis of PMR, conditions mimicking PMR, relapses in the setting of PMR and the main therapeutic strategies.

What the reader will gain: With this information, the reader receives an overview on the current available data on clinical diagnosis and treatment options in PMR.

Take-home messages: An initial dose of prednisone of 10 – 20 mg/day yields clinical improvement in the majority of patients with PMR. This is generally achieved within 7 days of the onset of this therapy. Conditions different from isolated PMR should be considered in atypical cases or when a good response to 20 mg/day of prednisone is not achieved. Relapses of PMR are not uncommon when the dose of prednisone is equal to or below than 5 mg/day. Methotrexate is the most commonly used corticosteroid sparing agent. Osteoporosis prophylaxis is also recommended.