Rossella Neri

The validity of the ECLAM index for the retrospective evaluation of disease activity in systemic lupus erythematosus

Aim: To determine whether the European Consensus Lupus Activity Measurement Index (ECLAM) can be used to evaluate disease activity in patients retrospectively from the data provided in their clinical charts. Methods: The ECLAM score was calculated twice in a series of 64 consecutive SLE patients: first for each patient during the course of a standard clinical evaluation (direct-ECLAM), and then one to two weeks later solely on the basis of the data provided in the patients clinical chart (chart-ECLAM). The scorings for each patient were performed by two different assessors. Results: The direct-ECLAM and chart-ECLAM scores were highly correlated (Spearmans rank correlation coefficient = 0.86). The regression line was not significantly different from the identity line (t-test). The Pearsons coefficient was 0.88. The interobserver variability of the chart-ECLAM showed a low inter-rater variability. Conclusion: ECLAM could represent a valid and reliable instrument for the retrospective analysis of disease activity in SLE patients.

Fibromyalgia Features in Patients with Primary Sjögren's Syndrome: Evidence of a Relationship with Psychological Depression

The prevalence of musculoskeletal complaints suggestive of the fibromyalgia syndrome (FS) was evaluated in 30 patients with primary Sjögrens syndrome (1 degree SS) and in two control groups of patients with osteoarthritis (OA) and diabetes mellitus (DM). In addition, the presence of depressive state was investigated in patients and controls using the Hamilton rating scale and an Italian self-evaluating test. Fibromyalgia features were found in 14 1 degree SS patients (47%), in 21 OA (70%) and in 10 DM (33%) controls. 1 degree SS patients showed the highest prevalence (47%) of moderate-severe depression with respect to OA (20%) and DM (7%) groups (p less than 0.01). Furthermore, while FS features correlated closely with both tests for depression in 1 degree SS (p less than 0.001), this correspondence was absent or much less significant in the other disease groups. Finally, neither psychopathological features nor FS complaints appeared to be related to the other clinical and serological findings of 1 degree SS.

Clinical Spectrum Time Course in Anti Jo-1 Positive Antisynthetase Syndrome: Results From an International Retrospective Multicenter Study.

AbstractAnti Jo-1 antibodies are the main markers of the antisynthetase syndrome (ASSD), an autoimmune disease clinically characterized by the occurrence of arthritis, myositis, and interstitial lung disease (ILD). These manifestations usually co-occur (for practical purpose complete forms) in the same patient, but cases with only 1 or 2 of these findings (for practical purpose incomplete forms) have been described. In incomplete forms, the ex novo occurrence of further manifestations is possible, although with frequencies and timing not still defined. The aim of this international, multicenter, retrospective study was to characterize the clinical time course of anti Jo-1 positive ASSD in a large cohort of patients. Included patients should be anti Jo-1 positive and with at least 1 feature between arthritis, myositis, and ILD. We evaluated the differences between complete and incomplete forms, timing of clinical picture appearance and analyzed factors predicting the appearance of further manifestations in incomplete ASSD. Finally, we collected 225 patients (58 males and 167 females) with a median follow-up of 80 months. At the onset, complete ASSD were 44 and incomplete 181. Patients with incomplete ASSD had frequently only 1 of the classic triad findings (110 cases), in particular, isolated arthritis in 54 cases, isolated myositis in 28 cases, and isolated ILD in 28 cases. At the end of follow-up, complete ASSD were 113, incomplete 112. Only 5 patients had an isolated arthritis, only 5 an isolated myositis, and 15 an isolated ILD. During the follow-up, 108 patients with incomplete forms developed further manifestations. Single main feature onset was the main risk factor for the ex novo appearance of further manifestation. ILD was the prevalent ex novo manifestation (74 cases). In conclusion, ASSD is a condition that should be carefully considered in all patients presenting with arthritis, myositis, and ILD, even when isolated. The ex novo appearance of further manifestations in patients with incomplete forms is common, thus indicating the need for an adequate clinical and instrumental follow-up. Furthermore, the study clearly suggested that in ASSD multidisciplinary approach involving Rheumatology, Neurology, Pneumology, and Internal Medicine specialists is mandatory.

A case of SLE with acute, subacute and chronic cutaneous lesions successfully treated with Dapsone

We describe a patient with systemic lupus erythematosus (SLE) who exhibited severe cutaneous involvement characterized by the simultaneous presence of acute, subacute and discoid lesions in association with anti-Sl antibodies. After she failed to respond to chloroquine, medium to low dose steroids, steroid pulses, retinoids and cyclophosphamide, the patient was treated with Dapsone and a dramatic improvement in the cutaneous lesions was seen after only one month.

Thyroid Cancer in Systemic Lupus Erythematosus: A Case-Control Study

CONTEXT Although advances in treatment have permitted patients with systemic lupus erythematosus (SLE) to live longer, the rates of several types of cancers in these patients appear to be increasing. OBJECTIVE We used a prospective study to investigate the prevalence and features of thyroid cancer in SLE patients. DESIGN AND PATIENTS The prevalence of thyroid cancer in 153 unselected SLE patients was compared with that in two population-based, gender- and age-matched control groups: 1) 459 subjects from an iodine-deficient area (iodine-deficient control) and 2) 459 subjects from an iodine-sufficient area (iodine-sufficient control). Thyroid function was assessed by measuring circulating thyroid hormones and autoantibodies, thyroid ultrasonography, and where necessary, fine-needle aspiration cytology. MAIN OUTCOME AND RESULTS The levels of circulating TSH, and anti-thyroglobulin and anti-thyroperoxidase antibodies were significantly higher in SLE patients (P < 0.001 for all). In addition, patients with SLE also exhibited a higher prevalence of hypothyroidism (P < 0.001). Five cases of papillary thyroid cancer were detected among SLE patients, whereas no cases were observed among iodine-deficient controls (P = 0.001), and only one case was observed among iodine-sufficient controls (P = 0.001). Among SLE patients with confirmed thyroid cancer, 80% showed evidence of thyroid autoimmunity, whereas only 31% of SLE patients without thyroid cancer exhibited evidence of thyroid autoimmunity (P = 0.02). CONCLUSIONS These data suggest that the prevalence of papillary thyroid cancer in SLE patients is higher than in age-matched controls, particularly in patients with thyroid autoimmunity. Consequently, careful thyroid surveillance is recommended during the follow-up of these patients.

Immunocytochemical characterization of human NOR-90 (upstream binding factor) and associated antigens reactive with autoimmune sera : two Mr forms of NOR-90/hUBF autoantigens

The 90-kDa nucleolus organizer region autoantigen (NOR-90) was previously shown to be identical to the human upstream binding factor (hUBF) and composed of twoMr forms. In this study, thirteen human anti-NOR-90/hUBF autoimmune sera were used to further characterize NOR-90/hUBF and its associated autoantigens. Nucleolar and nucleoplasmic staining of interphase cells and NOR staining in mitosis were observed with all sera by immunofluorescence. All sera showed equal reactivity with both high and lowMr forms in Western blotting and immunoprecipitation, suggesting that the cellular content and distribution for bothMr forms were approximately equal. Using extracts of [35S]methionine- and [32P]orthophosphate-labeled cells, phosphorylated and nonphosphorylated NOR-90/hUBF were identified for bothMr forms and these two populations were recognized by human autoantibodies. In immunoprecipitation analyses, the nonphosphorylated population was readily extracted while the phosphorylated population was tightly bound. Clinical data were available for 8 patients in whom anti-NOR-90/hUBF autoantibodies were present. They had diverse diagnoses including SLE, rheumatoid arthritis and malignancies. Although only one patient was diagnosed as scleroderma, Raynauds phenomenon was observed in 4 of the 8 patients. Interestingly, one NOR-90/hUBF serum was shown to contain additional antibodies to RNA polymerases I and II.Abbreviations: ANA=Antinuclear antibody; HCC=hepatocellular carcinoma; hUBF=human upstream binding factor; NOR=nucleolus organizer region; RNA pol I=RNA polymerase I; RNA pol II=RNA polymerase II; rRNA=ribosomal RNA; SLE=systemic lupus erythematosus.

HLA antigens in Italian patients with primary Sjögren's syndrome.

Twenty eight Italian patients with primary Sjögrens syndrome were typed for class I and class II alloantigens of the major histocompatibility complex. Patients with Sjögrens syndrome had higher prevalence of DR3 (46.4% v 14% in the control population, p corrected less than 0.02), while similar prevalence was found for DR2 and DRw52 alloantigens. DR3 correlated with DRw52 (p less than 0.0001), anti-Ro(SSA) (p less than 0.0002) and anti-La(SSB) (p less than 0.02) antibodies, and extraglandular manifestations (p less than 0.02). In addition, extraglandular involvement was associated with anti-Ro antibodies (p less than 0.05) and raised gammaglobulins (p less than 0.02). In Italian patients with primary Sjögrens syndrome DR3 is the genetic marker related to this clinical entity and seems to identify a disease subset characterised by autoantibody production and extraglandular manifestations.

Pregnancy outcome in patients with undifferentiated connective tissue disease: a preliminary study on 25 pregnancies

Undifferentiated connective tissue disease (UCTD) is a group of systemic autoimmune conditions not fulfilling the classification criteria for a definite connective tissue disease (CTD). While an average of 20% of UCTD patients develop a defined CTD during follow-up, the remaining patients maintain an undefined disease. Since pregnancy is considered to be an important factor that may alter the course of autoimmune diseases, we examined 25 pregnancies in 20 UCTD patients being followed at our unit in order to evaluate: (i) the pregnancy outcome; (ii) whether pregnancy is associated with flares of disease activity; and (iii) whether pregnancy may be a trigger for the development of a defined CTD. Twenty-two pregnancies (88%) were successfully brought to term, while the remaining three (12%) ended in an abortion in the first trimester. Obstetric complications were observed in six out of the 22 successful pregnancies (27%). Six patients (24%) experienced a disease flare during pregnancy or puerperium, one of whom presented a major flare and developed systemic lupus erythematosus. In the other five patients the manifestations at flare were mild and included arthritis, fever and skin rash. The incidence of flares in a control population of non-pregnant UCTD patients over a period of 1 year was 7%. Although UCTD is a mild condition, the risk of flares during pregnancy appears increased and therefore careful monitoring is as necessary as in other CTD patients. Further prospective studies will be necessary to confirm these preliminary observations.

Therapy with pulse methylprednisolone and short course pulse cyclophosphamide for diffuse proliferative glomerulonephritis

The incidence of renal flares and the long-term outcome in a group of 33 systemic lupus erythematosus (SLE) patients with diffuse proliferative glomerulonephritis (DPGN) treated with pulse steroids and a short course of pulse cyclophosphamide (CYC) are evaluated. Fifteen patients (45%) experienced a flare of renal disease at some time after the discontinuation of the immunosuppressive (IS) therapy; among these half (24%) were ‘early’ flares occurring shortly after the discontinuation of therapy, and the other half (21%) were ‘late’ flares occurring more than 2 y after the discontinuation of the treatment. Nine patients (27%) showed a poor renal outcome at the end of follow-up. On multiple regression analysis, a younger age and a high activity index (AI) on renal histology were found to be correlated with the occurrence of renal flares. Our results suggest that the combination of pulse steroids with a short course of pulse CYC (six to nine pulses) is effective in both controlling disease activity and in preventing the occurrence of renal flares in DPGN. However, short term IS therapy might not be sufficient to maintain disease control in younger patients with active lesions on renal histology. Such patients might be candidates to receive more prolonged IS treatment.

Clinical follow-up predictors of disease pattern change in anti-Jo1 positive anti-synthetase syndrome: Results from a multicenter, international and retrospective study

OBJECTIVE Arthritis, myositis and interstitial lung disease (ILD) constitute the classic clinical triad of anti-synthetase syndrome (ASSD). These patients experience other accompanying features, such as Raynauds phenomenon, fever or mechanics hands. Most ASSD patients develop the complete triad during the follow-up. In the present study we aimed to determine whether the subsequent appearance of accompanying features may suggest the development of triad findings lacking at the onset in anti-Jo1 positive ASSD patients. METHODS Anti-Jo1 positive patients presenting with incomplete ASSD (no >2 classic triad features) were assessed. Clinical characteristics and clusters of disease manifestations were retrospectively collected and analyzed in a large international multicenter cohort of ASSD patients. RESULTS 165 patients (123 women) with incomplete ASSD were identified. Ninety-five patients (57.5%) developed new classic triad manifestations after 15months median (IQR 9-51) and 40 (24%) developed new accompanying features after 19months median (IQR 6-56) from disease onset. During the follow-up, the ex-novo occurrence of triad features was observed in 32 out of 40 patients (80%) with new accompanying findings and in 63 out of 125 patients (50.5%) without new accompanying findings (p=0.002). In patients with at least one new accompanying feature the odds ratio for the occurrence of new triad manifestations was 3.94 with respect to patients not developing ex-novo accompanying findings (95% CI 1.68-9.21, p=0.002). CONCLUSION Anti-Jo1 ASSD patients with incomplete forms at disease onset are at high risk for the subsequent occurrence of lacking classic triad findings. Although all ASSD patients should be carefully assessed for the occurrence of new triad features, a closer follow-up should be considered in the subgroup of patients developing ex novo accompanying findings. These patients, indeed, have near four-fold increased risk for new classic triad manifestation occurrence with respect to patients not presenting ex novo accompanying findings.