Clinical And Experimental Research Of Psoriatic Athritis

Part I Epidemiology and Clinical Characteristics of Psoriatic ArthritisChapter I Prevalence and Characteristics of Psoriatic Arthritis in Chinese Patients with PsoriasisBackground Discordant data have been reported on the prevalence of psoriatic arthritis (PsA), ranging from 6.25% to 48% among psoriatic patients in Western countries. From a population-based national survey of psoriasis in China conducted in 1984,the prevalence of PsA was 0.69% of patients with psoriasis, which appeared to be extremely lower than other countries.Objective To evaluate the prevalence and clinical characteristics of PsA in a Chinese population of patients with psoriasis.Methods A large cross-sectional observational study was conducted in our outpatient dermatology department. Consecutive Patients(≥18 years)were included in the study after giving written informed consent. Patients were screened for psoriatic arthritis by methods that combined screening questionnaires, sonography and radiography examination,dermatological evaluation and rheumatology consultation. The diagnosis of PsA was considered according to CASPAR criteria. Data were recorded including gender, age, age of psoriasis onset, the type of psoriasis, Psoriasis Area and severity index(PASI),sites of psoriasis lesions, family history of psoriasis,age of arthritis onset,the presence of peripheral arthritis, spinal involvement, enthesitis and dactylitis,and the results of accessory examinations.Results Altogether 1928 adult patients with psoriasis were enrolled consecutively at outpatients department and 256 patients(13.3%) with joint symptoms underwent subsequent examination of joints. In addition, 160 symptomatic patients without a previous diagnosis of rheumatologic disease were reevaluated by a experienced rheumatologist. According to CASPAR criteria, 112 patients(5.8%) were considered to have PsA, of which 92% was newly diagnosed. Thus, the prevalence of PsA in the entire population of psoriatic patients was 5.8% . Among patients with PsA, a total of 87 (77.7%) subjects presented with inflammatory peripheral arthritis, followed by spinal involvement in 30 (26.8%) subjects, and enthesitis in 30 (26.8%) subjects. Twelve patients(10.7%) had both peripherial arthritis and axial involvement. Fifteen patients (13.4%) have dactylitis and 27 patients ( 24.1%) have DIP involvement. Some clinical features were analysed between PsA and cutaneous psoriasis. Patients with PsA was older ( 44.9 vs.35.5 years ) and had a slightly later manifestation of skin lesions(30.8 vs. 27.7 years) and higher percentage of type II psoriasis than patients without PsA(23.2% vs.15.6%). The duration of psoriasis of patients with PsA was also longer than those without PsA(14.1 vs.7.8 years). Patients with PsA had higher mean PASI score(9.7 vs. 6.0)and a higher rate of erythrodermic psoriasis (4.5% vs. 0.9%) than those without PsA. Nail (46.4% vs. 21.0%) and scalp (90.2% vs. 76.4%) involvement were significantly more common in patients with PsA than those without PsA. Conclusion The prevalence of PsA in psoriatic patients was 5.8%. Psoriatic arthritis was not rare in chinese patients with psoriasis and there is a high percentage of undiagnosed cases with active arthritis among PsA patients in dermatologist's office. Dermatologists should screen for PsA in their patients, especially those with risk characteristics and early signs.Chapter II Clinical Analysis of Rare Subtypes of Psoriatic ArthritisSection I SAPHO Syndrome: a Clinical Analysis of 22 CasesBackground The acronym SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) represents a syndrome characterized by the variable association of peculiar osteoarticular manifestations and various chronic dermatologic conditions. The spectrum of PsA includes a subset of SAPHO syndrome.Objective To investigate the clinical features of SAPHO syndrome.Methods Clinical information of 22 cases were analysed. Results The average age of skin lesion onset was 45 years old,and osteoarticular lesion onset was 44 years old. The ratio of male to female was 7:15. Twenty-one patients had palmoplantar pustolosis and 1 had acne fulminans. Anterior chest wall(ACW) was the most frequent site of osteoarticular lesions (19 cases affected), followed by the peripheral joints(4 cases) and sacroiliac joints(2 cases). The osteoarticular manifestations antedated the skin lesions in 10 cases, whereas the opposite occurred in 9 cases. And they developed simultaneously in the remaining 3 patients. The mean interval between the onset of cutaneous lesions and the osteoarticular manifestations was 2.7 years and the longest interval was 20 years.Conclusion Middle-aged onset and female preference may be related to SAPHO syndrome patients in dermatological clinics. Palmoplantar pustolosis and ACW involvement was the most common clinical manifestations.Section II Clinical Analysis of 14 cases with Distal Interphalangeal Psoriatic ArthritisBackground Finger joints involvement is a common manifestation of psoriatic arthritis. However, predominant distal interphalangeal(DIP)arthritis is a separate subtype of PsA by Moll and Wright's classification criteria with low frequency in patients.Objective To Investigate the clinical features of Psoriatic arthritis (PsA) with predominant distal interphalangeal(DIP)arthritis. Methods Clinical data of 14 PsA patients primarily with DIP arthritis were collected and analysed.R esults Among the patients,the average age of arthritis onset was 37 years old,and the ratio of male to female was 4:3. The skin lesions manifested prior to arthritis in all the patients, and the average interval between lesion and arthritis was 13 years. Scalp lesion was present in 100% and Nail psoriasis in 71.4% of the patients. Over time there were pattern changes of 8 patients(57.1%)with other joints involvement besides DIP. The rate of incorrect and delayed diagnosis was 71.4% and the average interval between disease onset and correct diagnosis was 6 years.Conclusion Skin lesions preceding arthritis, scalp lesion and nail psoriasis may be related to PsA of this type. The Clinical patterns may change over time and further studies were needed to investigate the value of Moll and Wright Classification. The phenomenon of misdiagnosis and delayed diagnosis was quite common for this disease and it required that dermatologist should be vigilant for arthritic symptoms accompanying psoriasis.Part II Investigation of Susceptibility Loci in Patients with Psoriatic A rthritisChapter I Investigation of Psoriasis Susceptibility Loci Found by GWAS in Patients with Psoriatic ArthritisBackground psoriatic arthriti(sPsA) is a sever subtype of psoriasis characterized by a chronic inflammatory arthritis in the presence of skin lesions. The genetic factors p redisposing to PsA were not clear. Recently,genome-wide association studies (GWAS) of psoriasis identified a number of psoriasis susceptibility loci, most of which were not investigated in patients with PsA.Objective To investigate the susceptibility loci of psoriasis found by GWAS in Chinese patients with PsA, PsC and healthy controls.Methods Forty-six SNPs from 30 loci/genes were selected for genotyping in 379 PsA, 595 PsC and 1181 healthy controls using Sequenom MassARRAY platform. The Cochran-Armitage trend test was used to test the genotype–phenotype association. Allel heterogeneity beween PsA and PsC,and between the two subgroups of PsA was estimated using the Cochran Q and I2 Statistics.Results Significant association with PsA was found for TNIP1(rs17728338, p=1.84×10^-8, OR1.98), IL12B(rs2546890,p =4.20×10^-7 ,OR=1.52), ERAP1( rs151823,p =2.82×10^-6,OR=1.47), IL28RA(rs4649203,p =6.14×10^-6,OR=0.66)and GJB2(rs3751385,p= 6.59×10^-4,OR=1.33), and suggestive evidence of association(p<0.05)were found for PTTG1 , IL1, NOS2 and IL23A. By comparison between PsC and control samples, IL28RA(rs4649203,p= 2.64×10^-6,OR= 0.70), ERAP1 (rs151823, p=2.72E×10^-6,OR=1.39), TNIP1(rs=17728338,5.29E×10^-5 , OR=1.59)and IL12B (rs2546890, p = 5.21E×10^-4 OR=1.28) were found to be also significantly associated with PsC. There were modest evidence of allelic heterogeneity between PsA and PsC groups for ZNF816A(P of Q test = 0.4,I² =75.97%).Conclusion Variants in ERAP1, IL28RA, GJB2, TNIP1 and IL12B are associated with susceptibility to both PsA and PsC. ZNF816A may be unique PsC genes that does not associated with PsA.Chapter II Investigation of Susceptibility Loci of Ankylosing Spondylitis and Rheumatoid Arthritis Found by GWAS in Patients with Psoriatic ArthritisBackground Psoriatic arthritis (PsA) share some similarity in clinical phenotypes, pathological features and genetic variants with rheumatoid arthritis and ankylosing spondylitisObjective To investigate the susceptibility loci of rheumatoid arthritis and ankylosing spondylitis found by GWAS in Chinese patients with PsA.Methods Thirty-six SNPs from 29 loci/genes were selected for genotyping in 379 PsA, 595 PsC and 806 healthy controls using Sequenom MassARRAY platform. The Cochran-Armitage trend test was used to test the genotype–phenotype association. Allel heterogeneity beween PsA and PsC,and between the two subgroups of PsA was estimated using the Cochran Q and I2 Statistics.Results Significant association with PsA was found for ERAP1(rs27037,p=6.66×10^-5,OR=1.43)and chromosome 21q22.2 (rs2242944,P=1.07×10^-3, OR= 0.72). There were no evidence of heterogeneity between PsA and PsC groups for variants at ERAP1 and modest evidence of heterogeneity for rs2242944 on chromosome 21q22.2. The latter is not associated with PsC in this study. Suggestive evidence was found for IL23R(rs1004819,p=4.58×10^-3,OR=1.28 ),2p15 (rs10865331,p=7.00×10^-3,OR=1.28)and KIF5A-PIP4K2C(rs1678542,p=3.66×10^-2,OR= 0.81)with PsA . IL23R(rs11209032), one risk loci of ankylosing spondylitis was found to be associated with axial PsA with suggestive evidence(p=1.57×10^-3,OR= 1.52)and three rheumatoid arthritis risk loci (2q11.2/AFF3, 7q32.3, KIF5A-PIP4K2C) was associated with peripheral PsA with suggestive evidence.Conclusion Our research supports the concept that common variants exist between similar phenotypes. ERAP1 is a shared susceptibility gene for PsA , PsC and ankylosing spondilitis. Common variants exist in chromosome 21q22.2 between PsA and ankylosing spondilits. Axial PsA and ankylosing spondylitis may shared some genetic factors, while peripheral PsA and rheumatoid arthritis also shared some genetic background.