scholarly journals Long-term follow-up of patients with anti-cyclic citrullinated peptide antibody-positive connective tissue disease: a retrospective observational study including information on the HLA-DRB1 allele and citrullination dependency

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Takeshi Iwasaki ◽  
Shuichiro Nakabo ◽  
Chikashi Terao ◽  
Kosaku Murakami ◽  
Ran Nakashima ◽  
...  

Abstract Background The anti-cyclic citrullinated peptide (CCP) antibody is a diagnostic biomarker of rheumatoid arthritis (RA). However, some non-RA connective tissue disease (CTD) patients also test positive for the anti-CCP antibody and, thus, may ultimately develop RA. We retrospectively investigated whether anti-CCP-positive non-RA CTD patients developed RA and attempted to identify factors that may differentiate RA-overlapping CTD from pure CTD. Methods In total, 842 CTD patients with a primary diagnosis that was not RA were selected from our CTD database as of December 2012. Anti-CCP antibody titers were obtained from a retrospective chart review or measured using stored sera. RA was diagnosed according to the 1987 revised American College of Rheumatology classification criteria. Thirty-three anti-CCP-positive non-RA CTD patients were retrospectively followed up for the development of RA. Bone erosions on the hands and feet were assessed by X-ray. Citrullination dependency was evaluated by an in-house ELISA, the HLA-DRB1 allele was typed, and the results obtained were then compared between RA-overlapping and non-RA anti-CCP-positive CTD patients. Results Two out of 33 anti-CCP-positive CTD patients (6.1%) developed RA during a mean follow-up period of 8.9 years. X-rays were examined in 27 out of the 33 patients, and only one (3.7%) showed bone erosions. The frequency of the HLA-DRB1 shared epitope (SE) and anti-CCP antibody titers were both significantly higher in anti-CCP-positive RA-overlapping CTD patients than in anti-CCP-positive non-RA CTD patients, while no significant differences were observed in citrullination dependency. Conclusions Anti-CCP-positive non-RA CTD patients rarely developed RA. HLA-DRB1 SE and anti-CCP antibody titers may facilitate the differentiation of RA-overlapping CTD from anti-CCP-positive non-RA CTD.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1412.2-1412
Author(s):  
M. Sato ◽  
M. Takemura

Background:High titers of cyclic citrullinated peptide antibodies (anti-CCP) are predictive of poor prognosis in the treatment of rheumatoid arthritis (RA). The 2010 ACR/EULAR classification criteria for early RA assign a high point value to cases having highly positive anti-CCP titers. Previous reports have claimed that osteoarthritic damage is more severe and advanced in RA patients who test positive for anti-CCP than in their negative counterparts.Objectives:To retrospectively investigate whether anti-CCP titers were associated with the extent of osteoarthritic damage in RA patients treated at our institution.Methods:Data were analyzed for 422 RA patients who received biologic agents due to resistance to methotrexate or other conventional antirheumatic drugs. Associations were explored between joint replacement history-i.e. total knee replacement (TKR), total hip replacement (THR), or lack thereof—and anti-CCP positivity rates and titers.Results:The sample consisted of 90 men and 332 women. On average, patients were put on biologics at 58.6 years of age (range: 22–85), and had a disease duration of 9.3 years. The first biologic agent chosen was infliximab (IFX) in 154 cases, etanercept (ETN) in 76, adalimumab (ADA) in 61, tocilizumab (TCZ) in 70, abatacept (ABT) in 41, golimumab (GLM) in 18, and certolizumab pegol (CZP) in 2. In total, 331/422 patients (78.4%) tested positive for anti-CCP. TKR was performed in 46 cases (M:F ratio: 7:39, mean age: 64.7 y, mean disease duration: 15.1 y), of which 46 were positive for anti-CCP (100%). THR was performed in 18 cases (M:F ratio: 2:16, mean age: 62.3 y, mean disease duration: 18.5 y), of which 17 were positive for anti-CCP (94.4%). The mean anti-CCP titer among all positive patients (n=331) was 152.9 IU/ml. This value was significantly higher in patients who underwent either joint replacement procedure than those who did not (215.4 v. 142.8 IU/ml, p<0.0005).Conclusion:With one exception, all RA patients who underwent joint replacement were positive for anti-CCP, and their titers were higher than non-surgical cases. Practitioners should be aware of this trend, and pay attention to the progression of damage in the knee and hip joints when treating RA patients with high anti-CCP titers.Disclosure of Interests:None declared


2010 ◽  
Vol 17 (6) ◽  
pp. 282-286 ◽  
Author(s):  
Shikha Mittoo ◽  
Thomas Jacob ◽  
Andrea Craig ◽  
Zoheir Bshouty

BACKGROUND: Pulmonary hypertension (PH) in patients with connective tissue disease (CTD) can occur in isolation or concomitantly with interstitial lung disease (ILD). Targeted therapies for PH can mitigate clinical deterioration in CTD patients with isolated PH; however, the effect of these therapies in CTD patients with PH and ILD (CTD-PH-ILD) are poorly characterized.OBJECTIVE: To investigate outcomes following long-term treatment of PH in patients with CTD-PH-ILD.METHODS: A retrospective evaluation of 13 CTD-PH-ILD patients who were treated with bosentan, sildenafil or bosentan plus sildenafil, was conducted. Immunosuppressants were prescribed as indicated. Patients underwent pulmonary function testing and assessment of 6 min walk distance at the time of treatment initiation and during follow-up. Patients were followed until time of death, lung transplantation or the end of the study. Kaplan-Meier estimates of survival were calculated and log-rank testing was used to analyze survival differences according to CTD subtype.RESULTS: Thirteen patients (seven with systemic sclerosis [SSc], four with overlap syndrome, and two with rheumatoid arthritis) were followed for a mean (± SD) duration of 33.8±21.7 months. The survival estimate at a median duration of 34 months was 85%; two patients with SSc died. Mortality rates were greater among patients with SSc versus other CTD subtypes (P=0.04). No changes from baseline to follow-up in mean forced vital capacity or exercise capacity, and no treatment-related toxicity, were observed.CONCLUSION: Treatment using PH-specific therapies in patients with CTD, PH and ILD was well tolerated. Further studies to investigate the efficacy of PH-specific therapies in CTD-PH-ILD patients are warranted.


Rheumatology ◽  
2014 ◽  
Vol 53 (11) ◽  
pp. 2035-2043 ◽  
Author(s):  
R. Laczik ◽  
P. Soltesz ◽  
P. Szodoray ◽  
Z. Szekanecz ◽  
G. Kerekes ◽  
...  

Diagnostics ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 49
Author(s):  
Vasiliki Kalliopi Bournia ◽  
Iraklis Tsangaris ◽  
Loukianos Rallidis ◽  
Dimitrios Konstantonis ◽  
Frantzeska Frantzeskaki ◽  
...  

Standard echocardiography is important for pulmonary arterial hypertension (PAH) screening in patients with connective tissue disease (CTD), but PAH diagnosis and monitoring require cardiac catheterization. Herein, using cardiac catheterization as reference, we tested the hypothesis that follow-up echocardiography is adequate for clinical decision-making in these patients. We prospectively studied 69 consecutive patients with CTD-associated PAH. Invasive baseline pulmonary artery systolic pressure (PASP) was 60.19 ± 16.33 mmHg (mean ± SD) and pulmonary vascular resistance (PVR) was 6.44 ± 2.95WU. All patients underwent hemodynamic and echocardiographic follow-up after 9.47 ± 7.29 months; 27 patients had a third follow-up after 17.2 ± 7.4 months from baseline. We examined whether clinically meaningful hemodynamic deterioration of follow-up catheterization-derived PASP (i.e., > 10% increase) could be predicted by simultaneous echocardiography. Echocardiography predicted hemodynamic PASP deterioration with 59% sensitivity, 85% specificity, and 63/83% positive/negative predictive value, respectively. In multivariate analysis, successful echocardiographic prediction correlated only with higher PVR in previous catheterization (p = 0.05, OR = 1.235). Notably, in patients having baseline PVR > 5.45 WU, echocardiography had both sensitivity and positive predictive values of 73%, and both specificity and negative predictive value of 91% for detecting hemodynamic PASP deterioration. In selected patients with CTD-PAH echocardiography can predict PASP deterioration with high specificity and negative predictive value. Additional prospective studies are needed to confirm that better patient selection can increase the ability of standard echocardiography to replace repeat catheterization.


Author(s):  
Antonio Fernández-Suárez ◽  
Sonsoles Reneses ◽  
Ingeborg Wichmann ◽  
Rita Criado ◽  
Antonio Núñez

AbstractThe objective of the present study was to determine the efficacy of anti-cyclic citrullinated peptide (anti-CCP) antibody detection in the early diagnosis of rheumatoid arthritis (RA), as well as to compare three commercially available enzyme-linked immunosorbent assay (ELISA) kits used to detect such antibodies. We analysed the presence of anti-CCP antibodies in the sera of 78 patients who had been newly referred from primary healthcare centres to the Early Polyarthritis Unit. We also included in the study a group of 50 healthy controls. None of the patients had previously received treatment for the disease. After 1-year follow-up, the diagnosis of RA was confirmed in 53 of these patients. The ELISA kits under study were IMMUNOSCAN RA (Euro-Diagnostica AB), QUANTA Lite™ CCP IgG ELISA (INOVA Diagnostic) and DIA-STAT™ Anti-CCP (Axis-Shield Diagnostics); the sensitivity obtained was 52.8%, 58.5% and 52.8%, respectively, with 100% specificity for all three kits. Anti-CCP antibodies detected the presence of RA in 26% of patients without positive rheumatoid factor (RF). The sum of anti-CCP antibodies or the presence of RF gave a sensitivity of up to 67%, with specificity ranging between 94 and 97%. Anti-CCP antibodies show high specificity for the diagnosis of RA. The three ELISAs analysed offer the same degree of diagnostic accuracy.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1584.1-1585
Author(s):  
I. Gaisin ◽  
Z. Bagautdinova ◽  
R. Valeeva ◽  
N. Maximov ◽  
O. Desinova ◽  
...  

Background:Systemic sclerosis (SSc) is a connective tissue disease (CTD) most frequently associated with Raynaud’s phenomenon – RP (96%), followed by mixed CTD (MCTD) (86%), systemic lupus erythematosus – SLE (31%), undifferentiated CTD (30%), rheumatoid arthritis – RA (22%) and Sjogren’s disease – SD (13%)1. RP can manifest as a classical triple-colour change with pallor (ischaemic phase) followed by cyanosis (deoxygenation) and erythema (reperfusion)2,1. However, this triple-colour change only occurs in 19% of cases2,3. Majority of patients report an episodic double-colour change, consisting of pallor and cyanosis, pallor and erythema or cyanosis and erythema2. In a 4.8-year follow-up, 37.2% of RP patients developed rheumatic diseases (RD), 8.1% had other causes, in 54,7% RP remained primary4.Objectives:To study the incidence and manifestations of secondary RP in RD.Methods:A questionnaire survey conducted in 230 patients with RD.Results:RP was detected in 45.6% of RD patients (n=105), 54.4% of patients with RD had no RP (n=125). RP was 4 times more frequent in females than in males (F:M 4:1). In RP group, 87 patients (82%) had autoimmune RD: SSc (55.2%), SLE (17.1%), RA (6%),dermatomyositis (3.8%), cross syndrome (3.8%), MCTD (1.9%), SD (0.9%).Only 84% of RP patients had positive answers to all three questions that characterizeRP (1. Is there an unusual sensitivity of fingers to cold? 2. Do fingers change colorwhen exposed to cold? 3. Do they turn white and/or bluish?). Biphasic color changes (whitening-blueness; whitening-redness; blue-redness) were observed in 33 (31.4%) patients with RP, three-phase changes – in 32 patients (30.5%). Blueness of fingers to cold was more frequent in SLE than in SSc (p=0.027).Redness of fingers to cold occurred more often in cross syndrome, MCTD, SD, RA, vasculitis than in SSc (p<0.001) and in vasculitis than in SLE (p=0.035). In SSc patients, whitening of fingers to cold was more common than redness (p=0.037) and two-/three-phase changes of fingers color in the cold were more frequent than single-phase changes (p<0.001).The frequency of RP attacks was detected more than once a day in 44 (42%) patients. In 73% of cases, RP did not show signs of deep digital ischemia. Digital ulcers (active) were observed in 13 (12.3%) patients, fractures in a finger area – 23 (21.9%), digital scars – 15 (14.2%), phalange amputations – 7 (6.6%).Conclusion:Patients with RD and secondary RP most often have SSC (55%), less often – SLE (17%), RA (6%), DM (3%). In SSc and SLE patients, Raynaud’s reddening of fingers to cold is less common than in other RD. In SSc, two-/three-phase changes of fingers color in the cold are more frequent than single-phase changes. In SLE, fingers turn blue in the cold more often than in SSc.References:[1]Prete M, Fatone MC, Favoino E, Perosa F. Raynaud’s phenomenon: from molecular pathogenesis to therapy.Autoimmun Rev2014;13:655–67.[2]Linnemann B, Erbe M. Raynaud’s phenomenon – assessment and differential diagnoses.Vasa2015;44:166–77.[3]Heidrich H, Helmis J, Fahrig C, Hovelmann R, Martini N. Clinical characteristics of primary, secondary and suspected secondary Raynaud’s syndrome and diagnostic transition in the long-term follow-up. A retrospective study in 900 patients.Vasa2008;37 (Suppl. 73):3–25.[4]Pavlov–Dolijanovic S, Damjanov NS, VujasinovicStupar NZ, Radunovic GL, Stojanovic RM, Babic D. Late appearance and exacerbation of primary Raynaud’s phenomenon attacks can predict future development of connective tissue disease: a retrospective chart review of 3035 patients.RheumatolInt2013;33:921–6.Acknowledgments:Professor LP. Anan’eva, Professor RT. AlekperovDisclosure of Interests:Ilshat Gaisin Speakers bureau: Boehringer Ingelheim, KRKA, Berlin-Chemie Menarini, Sanofi, Zukhra Bagautdinova: None declared, Rosa Valeeva: None declared, Nikolay Maximov Speakers bureau: Pfizer, KRKA, Oxana Desinova: None declared, Rushana Shayakhmetova: None declared, Irina Sabelnikova: None declared, Anna Tukmacheva: None declared, Larisa Gibadullina: None declared, Natalya Burlaeva: None declared, Elena Agareva: None declared, Yulia Ochkurova: None declared, Tatyana Bragina: None declared, Ksenia Alexandrova: None declared, Elvira Reutova: None declared


Sign in / Sign up

Export Citation Format

Share Document