Influence of the STAT3 genetic variants in the susceptibility to psoriatic arthritis and Behcet's disease.

OBJECTIVE: Signal-transducer and activator of transcription protein 3 (STAT3) gene encodes a transducer and transcription factor that plays an important role in many cellular processes such as cell growth, apoptosis and immune response. Several STAT3 genetic variants have been associated to different autoimmune diseases. Our aim was to reveal the possible STAT3 influence in other immune-mediated diseases such as psoriatic arthritis (PsA) and Behcet disease (BD). METHODS: The STAT3 rs744166 and rs2293152 polymorphisms were genotyped using predesigned TaqMan® assays in a total of 335 PsA patients, 217 BD patients, and 1844 ethnically matched healthy controls of Spanish Caucasian origin. RESULTS: A statistically significant association of the STAT3 rs744166(∗)G allele with PsA was observed (P-value=1.36×10(-3), OR 1.35). The detected effect was more evident when the rs744166(∗)GG homozygote frequencies were compared between PsA patients and controls (genotype P-value=9.77×10(-5), OR 1.82). In contrast, the allele and genotypic distributions of rs744166 polymorphism showed no significant differences between patients with BD and control subjects (allelic P-value=0.80, OR 1.03). Additionally, no evidence of association was detected between the rs2293152 genetic variant and both studied diseases. CONCLUSION: Our results suggest for the first time that the STAT3 gene might be involved in PsA but not in Behcet's disease predisposition.

Possible association between NOD2 variants and joint surgery in psoriatic arthritis.

BACKGROUND: Psoriatic arthritis (PsA) has been inconsistently associated with common NOD2 gene variants, although some of these studies did not include patient stratification by clinical phenotype. OBJECTIVES: To analyse the association between the three common NOD2 variants (R702W, G908R and L1007fs) and clinical phenotypes of PsA, particularly with surrogate markers of severe joint destruction. PATIENTS AND METHODS: A total of 183 unrelated PsA patients and 187 controls were included. Demographic, clinical, biological and immunological characteristics were collected. Genotypes for the three common NOD2 gene variants were obtained by PCR and direct sequencing. RESULTS: NOD2 variants in PsA patients (7.6%) are just as prevalent as in healthy controls (7.5%). 18.5% of PsA patients carrying at least one NOD2 variant underwent joint surgery compared with 4.5% of those without these variants (p=0.019). Multivariate analysis confirmed this finding (OR 8.82, CI 1.7-46.3). There was no requirement for early surgery in patients carrying the NOD2 variants but there was an increased possibility of requiring surgery at similar times of disease duration. No other association with clinical features and NOD2 status carrier was found. CONCLUSIONS: Common NOD2 gene variants are not associated with PsA, but might increase the risk of undergoing joint replacement surgery, suggesting that this autoinflammatory-associated gene could act as a phenotypic modifier gene in PsA patients by increasing the risk of joint destruction. Given the small number of PsA patients with joint surgery included, we consider our findings a new hypothesis that will need further testing.

Relationship between spinal mobility and disease activity, function, quality of life and radiology. A cross-sectional Spanish registry of spondyloarthropathies (REGISPONSER).

OBJECTIVE: To determine the relationship between anthropometric measurements and disease activity, functional capacity, quality of life and radiology in Spanish patients with ankylosing spondylitis (AS). PATIENTS AND METHODS: A cross-sectional study was made of 842 patients with definite ankylosing spondylitis (REGISPONSER). Sociodemographic data, spinal mobility measurements, Bath AS disease activity index (BASDAI), nocturnal pain, Bath AS radiology index (BASRI), Bath AS functional index (BASFI), the Short-Format 12 (SF-12) and the AS specific quality of life (ASQoL) questionnaire were applied. Pearson correlation coefficient analysis and regression models were constructed. RESULTS: There was moderate correlation between fingertip-to-floor distance and lateral cervical rotation with the BASFI (p<0.01). Good correlation was evident between wall-occiput distance and lateral cervical rotation with the BASRI (p<0.01). Moderate correlation was found between chest expansion, the Schober modified test and fingertip-to-floor distance with the total BASRI (p<0.01). The anthropometric measurement with the lowest correlation value was lateral lumbar flexion. Significant association was found between the Schober modified test and BASFI, BASDAI and BASRI (R(2) = 0.37; p<0.001); chest expansion and BASFI, BASDAI and BASRI (R(2) = 0.25; p<0.001); wall-occiput distance and BASFI, BASRI and ASQoL (R(2) = 0.44; p<0.001); fingertip-to-floor distance and BASFI and BASRI (R(2) = 0.30; p<0.001); and lateral cervical rotation and BASFI and BASRI (R(2) = 0.34; p<0.001). CONCLUSION: In our study, wall-occiput distance and lateral cervical rotation showed the strongest correlation to BASRI. Similarly, fingertip-to-floor distance and lateral cervical rotation exhibited the closest correlation to BASFI.

The IL23R Arg381Gln non-synonymous polymorphism confers susceptibility to ankylosing spondylitis.

OBJECTIVES: Recent results have shown that the IL23R gene, coding for a subunit of the interleukin-23 receptor, is strongly associated with autoimmunity. The aim of the current study was to investigate, for the first time, the possible involvement of the IL23R gene in genetic susceptibility to ankylosing spondylitis (AS). METHODS: We carried out a case-control association study in which 365 patients with AS and 500 blood bank donors were included. Eight single nucleotide polymorphisms (SNPs) spanning the IL23R gene were selected as genetic markers for our association study and were genotyped using a Taqman 5' allelic discrimination assay. RESULTS: Interestingly, we observed association of two of eight IL23R genotyped SNPs. The strongest effect was conferred by the non-synonymous rs11209026 (Arg381Gln) SNP (odds ratio 0.46 95% confidence interval 0.2 to 0.7 p = 0.001). Similarly, the IL23R rs1343151 SNP showed association with AS genetic susceptibility (odds ratio 0.68 95% confidence interval 0.55 to 0.83 p = 0.0002). After a conditional case-control test we observed that the effect of these two genetic variants was independent of linkage disequilibrium. CONCLUSIONS: These results suggest that the IL23R gene seems to be involved in AS genetic predisposition.

Disease pattern of spondyloarthropathies in Spain: description of the first national registry (REGISPONSER) extended report.

OBJECTIVE: The national registry of spondyloarthropathies (REGISPONSER) is launched to classify patients with this group of diseases treated in Spanish rheumatology clinics. This manuscript describes the methodological and organizational background as well as characteristics of patients finally included, and provides a comparative analysis between characteristics of both ankylosing spondylitis and undifferentiated spondyloarthropathy groups of patients. PATIENTS AND METHODS: Twelve members of the GRESSER group have participated in the registry, for a one-year recruitment period. All consecutively registered adult patients treated in their clinics met the classification criteria of the European Spondyloarthropathies Study Group (ESSG). Data collected reflect the socio-demographic characteristics, as well as disease activity and functional status, clinical form at onset, treatment used and quality of life; all measured by standard instruments. RESULTS: Throughout 1 yr, 1385 patients have been included in the registry: 939 males (68%) and 440 females (32%), with an average age of 47 +/- 13 years (mean +/- s.d.), and an average disease duration of 12 +/- 9 years. Diagnoses of the included patients were: AS (n = 842, 61%), PsA (n = 290, 21%), u-SpA (n = 205, 15%), reactive arthritis (n = 16, 1.2%), inflammatory bowel disease arthritis (n = 13, 0.9%) and JCA-spondyloathropathy (n = 13, 0.9%). Regarding clinical form, 54% had axial disease, 20% peripheral disease, 24% mixed disease and 0.6% isolated enthesitic form. Low-back pain was the first symptom reported in 53% of the patients, and most common extra-articular disease manifestations were psoriasis (25%), anterior uveitis (16%) and intestinal inflammatory disease (4%). Some kind of work disability was reported by 353 patients (25.5%). CONCLUSIONS: Such databases are very useful to obtain information about characteristics of SpA patients treated in a certain location or following a specific treatment practice, and provide a tool for assessing the impact of the disease. Data collected in this registry provide an appropriate clinical and demographic profile of patients suffering from SpA in Spain.

La entesis como elemento diana en las espondiloartritis / Enthesis as a target element in spondylarthritides

La entesis es una estructura frecuentemente afectada en las espondiloartritis; recientemente se ha postulado que desempeña un papel clave en la patogenia de estas enfermedades. A lo largo de esta revisión se tratarán los aspectos más relevantes de los conocimientos actuales sobre la entesis, se revisarán su anatomía y los componentes de la matriz extracelular presentes en ésta. Además se tendrá en cuenta su evaluación clínica y las técnicas modernas de imagen (resonancia magnética nuclear y ultrasonidos) que complementan su evaluación. Los estudios inmunohistológicos acompañados de los modelos animales, desarrollados con componentes de la entesis, indican su importancia en la patogenia de las espondiloartritis. Finalmente, se revisarán los últimos trabajos que evalúan la respuesta de las células T en pacientes con espondilitis anquilosante a componentes de la entesis(AU)

Enthesis is a structure frequently involved in spondyloarthritides. According to a recent hypothesis, it may play a key role in the pathogenesis of these entities. The present review discusses the most important aspects of current knowledge of enthesis, such as its anatomy and the extracellular matrix components present within it. Clinical evaluation and the new imaging techniques (magnetic resonance imaging and ultrasound) that complement its evaluation will be briefly described. Immunohistological studies as well as animal models developed with enthesis molecules underline the importance of enthesis in the pathogenesis of spondyloarthritides. Finally, the latest research assessing the T cell response to enthesis components in patients with ankylosing spondylitis will be reviewed(AU)

[Enthesis as a target element in spondylarthritides]. / La entesis como elemento diana en las espondiloartritis.

Enthesis is a structure frequently involved in spondyloarthritides. According to a recent hypothesis, it may play a key role in the pathogenesis of these entities. The present review discusses the most important aspects of current knowledge of enthesis, such as its anatomy and the extracellular matrix components present within it. Clinical evaluation and the new imaging techniques (magnetic resonance imaging and ultrasound) that complement its evaluation will be briefly described. Immunohistological studies as well as animal models developed with enthesis molecules underline the importance of enthesis in the pathogenesis of spondyloarthritides. Finally, the latest research assessing the T cell response to enthesis components in patients with ankylosing spondylitis will be reviewed.

Prevalence of HLA-B27 and subtypes of HLA-B27 associated with ankylosing spondylitis in Galicia, Spain.

OBJECTIVE: To assess the prevalence of HLA-B27 and its subtypes in both the normal population and in patients with Ankylosing Spondylitis (AS) in Galicia, Northwest Spain. METHODS: The prevalence of HLA-B27 in the normal population was determined by checking the number of HLA-B27 positive samples in 308 subjects from different areas of Galicia who had donated organs over a period of 4 years. A total of 106 patients with the diagnosis of AS, according to the modified New York clinical criteria for definitive ankylosing spondylitis, were collected from three very representative areas of Galicia. HLA-B27 was determined by PCR using the primers E91s and E136as, while 11 subtypes of HLA-B27 were analyzed using a commercial kit. RESULTS: The prevalence of HLA-B27 in organ donors was 9.34%. HLA-B27 was present in 94.3% of patients with AS. Subtypes B*2701, B*2709 and B*2710 were not found. The subtypes found in the normal population were; B*2705 (79.5%), B*2702 (18%) and B*2708 (2.5%). The subtypes associated with AS were B*2705 (88%) and B*2702 (12%). CONCLUSION: The prevalence of HLA-B27 in Galicia was 9.34%, which is higher than previously published in Spain. The frequency of the subtypes associated with AS was similar to that reported for other Spanish regions.

The biological action of hyaluronan on human osteoartritic articular chondrocytes: the importance of molecular weight.

OBJECTIVES: The intra-articular injection of hyaluronan (HA) was originally used in the treatment of osteoarthritis (OA) to increase the viscosity of synovial fluid. However, some findings suggest that the activity of HA cannot be solely explained by its biomechanical properties. The aim of this study was to analyze the in vitro biological effects of HA on human OA chondrocytes and the impact of its molecular weight (MW) on those effects. METHODS: Cells were isolated from cartilage obtained during joint replacement surgery in OA patients. The chondrocytes were cultured for 24 hours to detect prostaglandin E2 (PGE2) and for 48 hours to measure nitric oxide (NO), after which they were pre-incubated with HA and stimulated with interleukin-1 (IL-1) at 5 ng/ml. Two commercial HA preparations with different MWs were used: Hyalgan (500-730 kDa, HA, Bioibérica S.A.) and Synvisc (hylan of 6,000 kDa, Biomatrix Inc). NO was detected by the Greiss reaction and PGE2 was quantified by a commercial EIA in the supernatant. Apoptosis was induced by an NO donor (sodium nitroprusside, SNP) and the effect of HA on apoptosis was quantified by flow cytometry. RESULTS: Neither HA preparation studied had any effect on the basal production of NO or PGE2. However, the 500-730 kDa HA at 200 microg/ml reduced the synthesis of both IL-1-induced NO and PGE2 by 70% and 45% respectively. Furthermore both HA preparations at 200 microg/ml decreased the apoptosis induced by SNP, 500-730 kDa to 40% and 6,000 kDa to 36%. CONCLUSION: HA may induce biological effects in addition to acting as a viscoelastic substance. This study suggests that HA preparations are different due to differences in biological activity resulting from MW.

Aceclofenac increases the synthesis of interleukin 1 receptor antagonist and decreases the production of nitric oxide in human articular chondrocytes.

OBJECTIVE: Interleukin 1 receptor antagonist (IL-1Ra) may play an important role in cartilage degradation by inhibiting IL-1 activity and therefore blocking IL-1 stimulation of prostaglandin E2 (PGE2) synthesis. Nitric oxide (NO) formation is increased during inflammation. High concentrations of NO exert negative effects on chondrocyte functions. We investigated the possible effects of 3 different nonsteroidal antiinflammatory drugs (NSAID; aceclofenac, piroxicam, aspirin) on IL-1Ra and NO production in human articular chondrocytes. METHODS: Normal and osteoarthritic (OA) cartilage samples were obtained from autopsy and prosthetic joint surgery, respectively. Chondrocytes were isolated and stimulated with 4 different stimuli: IL-1, tumor necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), and insulin-like growth factor (IGF). The 3 NSAID were added simultaneously to each different concentration of stimulus. IL-1Ra was measured in supernatant by ELISA; nitrites were quantified by the Griess reaction; PGE2 level was measured by enzyme immunoassay. RESULTS: OA samples spontaneously produced higher levels of IL-1Ra than normal samples (130+/-2.3 vs 30+/-3.1 pg/mI). IL-1, TNF-alpha, and LPS produced dose dependent increases in synthesis of IL-1Ra. In their presence, IL-1Ra was detected in supernatant at 48 h, but its highest level was measured at 144 h. The most potent stimulus was IL-1, followed by TNF-alpha. Fetal bovine serum and IGF in turn did not modify the basal levels of IL-1Ra. In contrast to piroxicam and aspirin, aceclofenac 10 microg/ml and TNF-alpha 10 ng/ml increased almost 46 times the basal amount of IL-1Ra produced by OA chondrocytes. Additionally, aceclofenac and aspirin inhibited NO synthesis. Finally, the 3 NSAID reduced the levels of PGE2 detected after stimulation with IL-1. CONCLUSION: Proinflammatory stimuli induce IL-IRa synthesis in human articular chondrocytes. Aceclofenac may modulate PGE2 production by increasing IL-IRa production and decreasing NO synthesis. Some NSAID exert diverse prostaglandin independent effects.

Risk factors and predictive models of giant cell arteritis in polymyalgia rheumatica.

OBJECTIVE: To identify in polymyalgia rheumatica the best set of predictors for a positive temporal artery biopsy and to define predictive models with either a high or low probability of giant cell arteritis (GCA). PATIENTS AND METHODS: Retrospective study of 227 patients, 137 with polymyalgia rheumatica unassociated with arteritis (group A) and 90 with polymyalgia associated with biopsy-proven giant cell arteritis (group B or training set). Data on demographic features, clinical and laboratory abnormalities were collected. Risk factors for arteritis were estimated by nonlinear logistic regressions. Simple predictive models were constructed with those predictors more related to arteritis by multivariable analysis. These models were then tested in group B and in 89 cases of arteritis without polymyalgia rheumatica (group C or test set). RESULTS: The best predictors of arteritis were a new headache odds ratio (OR) 13.6 (95% confidence interval [CI] 4.7 to 39.3); age at onset < 70 years OR 0.11 (CI 0.04 to 0.35); abnormal temporal arteries OR 4.2 (CI 1.3 to 13.7); raised liver enzymes OR 2.9 (CI 1.1 to 7.8), and jaw claudication OR 4.8 (CI 1.0 to 22.7). Amaurosis was only observed in patients with arteritis. Three subsets had a very high risk of arteritis: (1) Patients with recent headache, abnormal arteries, and > or = 70 years at disease onset: sensitivity 44%, positive predictive value (PPV) 93%, likelihood ratio (LR) 20.3; (2) patients with a new headache, jaw claudication, and abnormal arteries: sensitivity 34.4%, PPV 96.9%, LR 47.2; and (3) those, that in addition to the last 3 features, were > or = 70 years of age at disease onset: sensitivity 26.7%, PPV 100%. We could also identify a subset with a very low risk of arteritis constituted by patients < 70 years, without headache, and with clinically normal temporal arteries: sensitivity 1.1%, PPV 1.7%, LR 0.03. In group C or the test set, these four predictive models correctly identified 57.3%, 29.2%, 23.6, and 3.4% of patients, respectively. CONCLUSIONS: In polymyalgia rheumatica it is feasible to identify subsets with a very high likelihood of GCA. Although in some of these subsets the diagnosis of arteritis is almost certain, we suggest that even then it should be confirmed by temporal artery biopsy. By contrast, in those patients with polymyalgia < 70 years and without cranial features of giant cell arteritis, the risk of vasculitis is so low that the biopsy could be initially avoided and the patient treated with low-dose corticosteroids.

Polymyalgia rheumatica without significantly increased erythrocyte sedimentation rate. A more benign syndrome.

BACKGROUND: An erythrocyte sedimentation rate (ESR) of at least 40 mm/h is considered an important requisite for the diagnosis of polymyalgia rheumatica (PMR). However, the relative frequency and clinical features of PMR in patients without a significantly increased ESR are unclear. METHODS: We performed a retrospective study of patients diagnosed as having PMR at the rheumatology divisions of 3 teaching hospitals. The diagnosis of PMR was established, regardless of the ESR, in 201 consecutive patients fulfilling the following criteria: (1) age 50 years or older, (2) severe proximal pain for more than 1 month in at least 2 of 3 areas: neck, shoulder, and/or pelvic girdles, and (3) rapid resolution of the syndrome while taking low-dose prednisone. Patients with giant cell arteritis were previously excluded from the study. The frequency and clinical features of patients with PMR and an ESR lower than 40 mm/h were analyzed. A comparative study between these patients and those with high ESRs was performed. RESULTS: An ESR lower than 40 mm/h was found in 41 patients (20.4%). These patients were younger (P = .02), were more frequently men (P = .006), and experienced a lower frequency of fever (P = .003) and weight loss (P = .07). Furthermore, these patients were characterized by an absence of anemia (P = .002) and a lower frequency of abnormal protein electrophoresis results (P < .001). Otherwise, their clinical syndrome, response to therapy, and frequency of relapses were similar to those of patients with classic PMR. In the entire population of 201 patients, the ESR was related to the length of treatment, number of areas involved, presence of fever, weight loss, and laboratory test result abnormalities, but it was unrelated to the duration of the illness prior to diagnosis. CONCLUSIONS: It is not uncommon to find a patient with PMR with an ESR lower than 40 mm/h. This syndrome is more frequent in men and it is clinically less severe than the classic form of PMR. Its recognition will allow these patients to benefit from an effective treatment with low-dose corticosteroids.

Acute febrile toxic reaction in patients with refractory rheumatoid arthritis who are receiving combined therapy with methotrexate and azathioprine.

OBJECTIVE: To assess the frequency and clinical features of an acute febrile toxic reaction (AFTR) in patients with refractory rheumatoid arthritis (RA) receiving combined therapy with methotrexate (MTX) and azathioprine (AZA). METHODS: A cohort of 43 RA patients being treated with MTX/AZA combination therapy were studied. In all of them, RA had been refractory to single-therapy disease-modifying antirheumatic drugs. We analyzed the frequency and clinical features of AFTR, which consisted mainly of the development of fever, leukocytosis, and cutaneous leukocytoclastic vasculitis when AZA was added to the MTX regimen. RESULTS: Four of the 43 patients (9.3%) who had been receiving long-term, well-tolerated treatment with MTX (mean +/- SD 375.5 +/- 159.5 days, range 227-561 days) developed AFTR shortly (mean +/- SD 25.7 +/- 13.6 days, range 17-46 days) after the addition of AZA to the regimen. The AFTR resolved rapidly (3 +/- 1.4 days) after discontinuation of AZA and MTX. In 2 cases, rechallenge with AZA and MTX was linked to a new flare of AFTR. CONCLUSION: The knowledge of this side effect is particularly important because it mimics a severe infectious complication related to immunosuppressive therapy, and because rechallenge can produce severe toxicity. Most of the new combined therapies for RA do not seem to be more toxic than single-drug treatment. Nevertheless, clinicians should be aware of a possible increase in side effects due to drug interactions or some other unidentified mechanism.

Mononeuritis multiplex in systemic lupus erythematosus: response to pulse intravenous cyclophosphamide.

Severe mononeuritis multiplex in systemic lupus erythematosus (SLE) is quite rare and almost always accompanied by evidence of active disease in other organs, although occasionally it may be the presenting feature of the disease. We describe here two patients with SLE who presented a severe mononeuritis multiplex secondary to a necrotizing vasculitis which respond successfully to therapy with intravenous cyclophosphamide, and review the literature of similar cases.

T cells, but not thymic exposure to HLA-B27, are required for the inflammatory disease of HLA-B27 transgenic rats.

Rats transgenic for the human MHC class I gene HLA-B27 are susceptible to a spontaneous multisystem inflammatory disease that resembles human B27-associated disease. This disease requires a high level of expression of the B27 transgene product in cells of hemopoietic origin and can be adoptively transferred to B27 transgenic or nontransgenic rats by transplantation of bone marrow (BM) or fetal liver (FL) cells. To investigate the role played by T cells and the thymus in the disease process, we produced congenitally athymic rnu/rnu F344 rats carrying the disease-prone B27 transgenic locus of the 33-3 line. Transgenic nude rats were protected from disease manifestations. This protection was abated by reconstitution with T cells from euthymic donors of the 33-3 line, with CD4 T cells being more efficient than CD8 T cells in transferring disease. Lethally irradiated, adult-thymectomized (ATX), nontransgenic recipients reconstituted with intact BM, T cell-depleted BM, FL, or nude BM from syngeneic disease-prone lines all developed disease. Pretreatment of the ATX nontransgenic recipients to deplete T cells enhanced the subsequent transferred disease. The inflammatory disease of B27 transgenic rats is thus T cell-dependent. The relevant T cells do not need to encounter B27 in the thymus, and residual radioresistant and/or extrathymically derived host T cells are sufficient to mediate the adoptively transferred disease. The data are most consistent with a model of B27-mediated disease arising from a failure of tolerance and requiring a population of CD4 T cells.

[Giant cell arteritis. A study of 191 patients]. / Arteritis de células gigantes. Estudio de 191 pacientes.

BACKGROUND: The aim of the present was to study the clinical features of a wide series of patients with giant cell arteritis (GCA) diagnosed with accurate criteria and to evaluate the sensitivity of the criteria proposed by the ACR for classification of GCA. METHODS: A retrospective analysis of 191 patients with GCA, 184 of whom were diagnosed by biopsy and 7 due to their clinical manifestations was carried out. RESULTS: The age was 73 +/- 7 years with the most frequent symptoms being headache (87%), abnormalities in the temporal arteries (75%), general malaise (60%), rheumatic polymyalgia (49%) and mandibular claudication (40%). The frequency of GCA was equal in both genders although the most complex syndrome was observed in women with a greater frequency of polymyalgia (p < 0.005), jaw claudication (p < 0.01) and anemia (p < 0.01). The patients with polymyalgia were characterized by a predominance of the polymyalgic syndrome in the initial phases and a higher frequency of amaurosis. Out of 47 patients with amaurosis, 23 remained with permanent unit or bilateral blindness. Unilateral biopsy of the temporal artery was diagnosed in 91% of the cases (CI 95%; 86 to 95%) increasing to 96.3% (CI 95%; 92 to 98%) on biopsy of both arteries. Ninety-eight percent of the patients (CI 95%; 95 to 99%) had 3 or more GCA criteria for classification as GCA. CONCLUSIONS: The clinical manifestations of giant cell arteritis in Spain, with the exception of an equal frequency in both sexes, are similar to that described in other series of patients selected with strict criteria. The present data confirm the sensitivity of the criteria proposed by the ACR for the classification of giant cell arteritis although its application does not avoid the need for temporal artery biopsy for diagnosis. Unilateral biopsy is usually suffice in most of the cases.

Acute reversible hypoxemia in systemic lupus erythematosus: a new syndrome or an index of disease activity?

In 1991, Abramson et al reported a new syndrome of acute reversible hypoxemia (ARH) in patients with severe SLE (systemic lupus erythematosus). This syndrome was characterized by an unexplained abnormal value of arterial blood gases (ABG) without obvious parenchymal lung disease, and a good response to high-dose corticosteroid therapy. After we became aware of this entity, four of 16 patients admitted to our unit because of a SLE flare presented respiratory symptoms and abnormal ABG consistent with ARH. In none of our patients were the pulmonary manifestations a prominent clinical feature of the disease. Furthermore, in two of them, treatment with high-dose aspirin and moderate to low doses of corticosteroids was sufficient to improve the pulmonary manifestations, but not to control the systemic activity of the disease. Therefore, we believe that this new pulmonary finding more than a clinically independent syndrome represents an index of disease activity in patients with SLE.

The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats.

A number of inflammatory disease states occur with greatly increased frequency in individuals inheriting the human major histocompatibility complex class I allele HLA-B27. In a minority of cases, namely those with B27-associated reactive arthritis, there is good evidence that the disease state is triggered by infection with an enteric or genitourinary bacterial pathogen. For the majority of B27-associated disease, no definite pathogenetic role for bacteria has been established. However, in these latter cases intestinal inflammation can often be demonstrated, and it sometimes occupies a major part of the clinical picture. Rats transgenic for B27 are known to develop a disorder resembling B27-associated human disease, with prominent intestinal, joint, skin, and male genital inflammatory lesions. We report here that B27 transgenic rats raised in a germfree environment do not develop inflammatory intestinal or peripheral joint disease, whereas the skin and genital inflammatory lesions are unaffected by the germfree state. These findings support the concept that gut and joint inflammation are pathogenetically closely related, and they provide direct evidence that the commensal gut flora play an important role in the pathogenesis of B27-associated gut and joint inflammation.