CURRENT ABSTRACTS

Shared Epitopes and Rheumatoid Arthritis: Disease Associations in Greece and Meta-Analysis ofMediterranean European Populations . . . By John P.A. Ioannidis, Katerina Tarassi,Ioannis A. Papadopoulos, Paraskevi V. Voulgari, Kyriaki A. Boki, Chryssa A. Papasteriades, andAlexandros A. Drosos

Objectives:To assess the strength of the associations between HLA shared epitopes (SE) and rheumatoid arthritis (RA)susceptibility, articular disease severity, and extra-articular features in Mediterranean European populations.Methods:One hundred and seventy-four Greek RA patients and 103 controls were evaluated. Data were then includedin a meta-analysis of 9 studies of Mediterranean European populations (959 RA patients and 1,405 controls).Results:In our study population, SE alleles were significantly more common in RA patients than in controls (odds ratio[OR], 2.5; 95% confidence interval [CI], 1.4-4.3). Larsen radiologic score was predicted by SE and disease duration. SEdid not increase the risk of any extra-articular manifestation. The meta-analysis showed a pooled OR of 3.7 (95% CI,2.6-5.2) for susceptibility to RA conferred by SE (OR, 3.4v 3.9 in Greekv non-Greek populations).Conclusions:SE determine articular destruction without increasing the risk of extra-articular manifestations. Theimmunogenetic associations of RA susceptibility are consistent, but their strength may depend on the SE prevalence indifferent ethnic groups.Semin Arthritis Rheum 31:361-370. Copyright 2002, Elsevier Science (USA). All rights reserved.

Genotype/Phenotype Correlations in Arab Patients With Familial Mediterranean Fever . . . ByHasan A. Majeed, Hatem El-Shanti, Mohammed S. Al-Khateeb, and Z. Abu Rabaiha

Objectives:To study the phenotype/genotype correlations in Arab patients with familial Mediterranean fever (FMF).Patients and Methods:The study was performed in a 3-year period (February 1998–February 2001). Patients were seenin the pediatric FMF clinic of Jordan University Hospital, and the diagnosis of FMF was made according to publishedcriteria. Screening for mutations was carried out by direct sequencing of the entire coding sequence of exon 10 and itsdonor splice site and by restriction endonuclease testing for mutations in exon 2. A total of 278 patients with clinicallypositive FMF were screened.Results:Of the 278 patients, 50 (18%) had 2 mutations identified, and 76 (27%) other patients had only 1 mutationidentified. The 50 patients with 2 mutations are the subject of this report. The M694V/M694V and the M694V/V726Aand M694I/M694I genotypes were the most common (30%, 16%, and 14%, respectively). Three homozygous genotypes(M694V/M694V, V726A/V726A, and M694I/M694I) and 2 compound heterozygous genotypes (M694V/V726A andV726A/M680I) accounted for 78% of mutations. The difference in the mean severity score (14� 2) of theM694V/M694V group and the V726A/V726A (mean severity score, 10� 3) and M694I/M6941 (mean severity score,6 � 1) groups was statistically significant (P � .003 and .0, respectively). The difference between the M649V/M694Vgroup and the M694V/V726A (mean severity score, 15� 2) was not statistically significant (P � 0.31).Conclusions:The genotypes M694V/M694V and M694V/V726A have a severe clinical course in Arab patients withFMF, whereas the M694I/M694I is associated with mild disease.Semin Arthritis Rheum 31:371-376. Copyright 2002, Elsevier Science (USA). All rights reserved.

Polyarteritis Nodosa Presenting as Polymyositis. . .By Spencer G. Plumley, Ronald Rubio, Said Alasfar,and Hugo E. Jasin

Background:Skeletal muscle involvement has been well documented in patients with polyarteritis nodosa (PAN), andsymptoms referable to skeletal muscle are not uncommon. However, polymyositis as a mode of presentation of PANis uncommon. This unusual presentation of PAN has been reported only once previously in the English literature.

Seminars in

Arthritis and RheumatismVOL 31, NO 6 JUNE 2002

Objective:This study describes a patient who had diffuse weakness, myalgias, and markedly elevated serum creatininephosphokinase, mimicking polymyositis. The literature dealing with the clinical aspects of muscle involvement in PANis reviewed.Results:A 24-year-old man was admitted to the hospital with a 1-month history of fever, myalgia, and muscle weakness.Necrotizing vasculitis was shown on subsequent muscle biopsy, consistent with PAN. Literature review indicated thatmuscle involvement is common in PAN, as has been shown by the frequency of muscular symptoms and by histologicevidence obtained from both clinical and autopsy studies. Nineteen percent of patients with PAN had documentedmyopathy, and autopsy series have shown skeletal muscle involvement in 30% to 48% of cases. However, polymyositisas a mode of presentation of PAN is rare. We found only 1 other patient with PAN who had elevated creatininephosphokinase and diffuse myopathy suggestive of polymyositis.Conclusions:PAN should be suspected in cases of focal or diffuse myopathy, especially in the context of a systemicdisease. Biopsy of symptomatic muscles or EMG-directed biopsies can be helpful in establishing a diagnosis of PANto provide early treatment.Semin Arthritis Rheum 31:377-383. Copyright 2002, Elsevier Science (USA). All rights reserved.

Relapsing Polychondritis: A Clinical Review . . . By Erik Letko, Panayotis Zafirakis, Stefanos Baltatzis,Adamantia Voudouri, Charalampos Livir-Rallatos, and C. Stephen Foster

Objective:This study comprehensively reviews the literature related to relapsing polychondritis (RP).Methods:A detailed search via MEDLINE (PubMed) was performed usingrelapsing polychondritisas the key term.Relevant articles were analyzed with a focus on history, epidemiology, etiology, pathogenesis, clinical manifestations,diagnosis, treatment, and prognosis of RP.Results:RP is a rare episodic and progressive inflammatory disease of presumed autoimmune etiology first describedin 1923. RP affects cartilage in multiple organs, such as the ear, nose, larynx, trachea, bronchi, and joints. In addition,it can affect proteoglycan-rich tissues, such as the eyes, aorta, heart, and skin. The diagnosis of RP is based on thepresence of clinical criteria. A standardized therapeutic protocol for RP has not been established. Nonsteroidalanti-inflammatory drugs, dapsone and/or colchicine, may control disease activity in some patients. In other patients,immunosuppressive drugs and prednisone have been effective. RP is a potentially lethal disease; pulmonary infection,systemic vasculitis, airway collapse, and renal failure are the most common causes of death. Earlier studies indicatesurvival rates between 70% at 4 years and 55% at 10 years. In a recent study, a survival rate of 94% at 8 years may bedue to improved medical and surgical management.Conclusions:RP is a rare, multisystemic, and potentially fatal disease. The pathogenesis and optimal therapeuticapproach to patients with RP is poorly understood.Semin Arthritis Rheum 31:384-395. Copyright 2002, Elsevier Science (USA). All rights reserved.

TAP, HLA-DQB1, and HLA-DRB1 Polymorphism in Colombian Patients With Primary Sjogren’sSyndrome . . . By Juan-Manuel Anaya, Paula A. Correa, Ruben D. Mantilla, and Mauricio Arcos-Burgos

Objective: Although primary Sjogren’s syndrome (pSS) has a worldwide distribution, little data is available on pSSimmunogenetics in non-white populations. Thus, we investigated the influence of transporters associated with antigenprocessing (TAP), human leukocyte antigen (HLA)-DQB1, and HLA-DRB1 gene polymorphism in mestizo Colombianpatients with pSS.Methods: In this cross-sectional and controlled study, all patients met the European criteria for classification of pSS.TAP and HLA typing was performed by polymerase chain reaction techniques. Genetic data analysis was performed todetect deviations from the expected Hardy-Weinberg (H-W) proportions and to determine the presence of populationstratification or subdivision and the existence of linkage disequilibrium between pairs of loci.Results: Seventy-three Colombian patients with pSS (95% women) and 76 healthy controls were studied. Althoughsignificant associations were not observed between TAP or HLA polymorphism and disease, strong linkage disequi-librium among the loci TAP2 and DQB1 was found in patients. Deviations from the H-W expected value were foundin the DQB1 locus of patients (P� .02). HLA-DRB1*0301-DQB1*0201 haplotype was associated with more severehistopathologic disease (odds ratio [OR], 15.5; 95% confidence interval [CI], 1.9-129;P � .001) and the presence ofanti-Ro (OR, 3.8; 95% CI, 1-15;P � .04) and anti-La antibodies (OR, 4.3; 95% CI, 1.3-14;P � .01).Conclusion: The data show genetic evidence suggesting that, in Colombians, a region immersed or in the vicinity in theHLA class II system is strongly associated with a predisposition to acquire pSS, which is probably located betweenthe TAP2 and HLA-DQB1 locus. Our results confirm that the HLA-DRB1*0301-DQB1*0201 haplotype participates inthe pathogenesis of pSS.Semin Arthritis Rheum 31:396-495. Copyright 2002, Elsevier Science (USA). All rights reserved.

Abdominal Scintigraphy Using Technetium Tc 99m Hexylmethylpropylene Amine Oxime–LabeledLeukocytes in Patients With Seronegative Spondyloarthropathies. . .By Ori Elkayam, Daphna Paran,Einat Even-Sapir, Irena Litinsky, Irena Wigler, Michael Yaron, and Dan Caspi

Objectives:To assess the potential benefits of technetium Tc 99m hexylmethylpropylene amine oxime (Tc 99m HMPAO)–labeled leukocyte scintigraphy in a group of patients with spondyloarthropathies (SpAs), overt gastrointestinal symptoms, andnegative extensive endoscopic/radiologic test results.Patients and Methods:Ten patients with SpAs and overt gastrointestinal symptoms were included in this study. Allpatients underwent colonoscopy and small bowel barium studies, and results were negative. Abdominal scintigraphywith Tc 99m HMPAO–labeled leukocytes was performed in all the patients. Clinical and laboratory data and responseto treatment was recorded.Results:The Tc 99m HMPAO–labeled leukocyte scintigraphy was positive in 5 of 10 patients, demonstrating uptakeat the terminal ileum which is very suggestive of Crohn disease. The 5 scintigraphically positive patients were treatedwith sulfasalazine (SSZ). Four patients responded to SSZ with significant improvement of both gastrointestinal and jointsymptoms.Conclusion:In 5 of 10 patients with SpA and suspected inflammatory bowel disease on clinical grounds, evidence ofinflammatory bowel disease was shown by scintigraphic studies in which conventional invasive procedures failed. Tc99m HMPAO–labeled leukocyte scintigraphy should be considered in the evaluation of patients with SpA.Semin Arthritis Rheum 31:406-412. Copyright 2002, Elsevier Science (USA). All rights reserved.

Psoriatic Spondyloarthropathy: A Comparative Study Between HLA-B27 Positive and HLA-B27Negative Disease . . . By Ruben Queiro, Cristina Sarasqueta, Joaquin Belzunegui, Carlos Gonzalez,Manuel Figueroa, and Juan C. Torre-Alonso

Objectives:To evaluate the relative contribution of the human leukocyte antigen (HLA)-B27 to psoriatic spondyloar-thropathy (PsSpA) susceptibility and to analyze whether this antigen contributes to disease expression.Methods:This cross-sectional study included 70 patients (mean age 48� 14.5 years; 44 men and 26 women). PsSpAwas defined according to radiological findings (grade 2 or more sacroiliitis), and patients were classified into 3 mainsubtypes: isolated axial disease (n� 16), axial plus oligoarthritis (n� 29) and axial plus polyarthritis (n� 25). Allpatients were studied following a standard protocol that included the collection of demographic and epidemiologicaldata, clinical history, radiographs, complementary tests, physical examination, and HLA-B27 testing (serologicalmethod). For functional evaluation, the Health Assessment Questionnaire-Specific for spondyloarthropathy (HAQ-S)was used. Patients with and without HLA-B27 antigen were compared on the basis of the data.Results:Twenty-four patients (34%) carried the HLA-B27 antigen (RR 6.4,P �.0004). Fifty-six percent of thosepatients with the isolated axial pattern had this antigen, compared with 24% in the poly-arthritis axial pattern and 31%of those in the oligo-arthritis axial group (P� .016). Univariate analysis demonstrated correlations between HLA-B27and an earlier age of onset for both psoriasis (P � .028) and arthritis (P� .006), male gender (P� .002), bilateralsacroiliitis (P� .002), and uveitis (P� .026). HLA-B27 negative patients developed more peripheral erosions thanHLA-B27 positive patients (P� .05). No correlation was found between B27 and clinical symptoms of backinvolvement, syndesmophytes, or functional impairment.Conclusions:The HLA-B27 antigen is not only important for PsSpA susceptibility, but also determines some clinicalfeatures. This antigen was associated with earlier age of psoriasis and arthritis onset, bilateral sacroiliitis, and malegender. However, it was not associated with either the severity or extension of the spondylitic process or with functionalimpairment.Semin Arthritis Rheum 31:413-418. Copyright 2002, Elsevier Science (USA). All rights reserved.