Mittermayer Barreto Santiago

A comparison of the frequency of antibodies to cyclic citrullinated peptides using a third generation anti-CCP assay (CCP3) in systemic sclerosis, primary biliary cirrhosis and rheumatoid arthritis

The objective was to investigate the frequency of anti-cyclic citrullinated peptides (CCP) antibodies in systemic sclerosis (SSc) and primary biliary cirrhosis (PBC), utilizing a new “third generation” anti-CCP ELISA (anti-CCP3) kit and a conventional anti-CCP2 assay. Patients with PBC, SSc, RA, and normal controls were included in the study. Serum samples were screened for autoantibodies by indirect immunofluorescence (IIF), antibodies to CCP by a second- and third-generation ELISA, antibodies to “scleroderma” antigens (CENP B, Scl-70, PM/Scl and fibrillarin—Scl-34) by a line immunoassay (LIA), and IgM RF by ELISA. The frequency of anti-CCP2 antibodies in SSc and PBC samples was 14.8% (11/74) and 6.2% (5/80), respectively, and the frequency of anti-CCP3 antibodies in SSc was 13.5% (10/74) and in PBC was 3.7% (3/80). By comparison, in the RA group the frequency of anti-CCP3 and anti-CCP2 antibodies was 79.1% (38/48) and 77% (37/48), respectively. Anti-CCP3 ELISA had a sensitivity, specificity, and positive and negative likelihood ratios (LR) of 79% (95% confidence interval [CI] = 64–89%), 93% (95% CI = 88–96%), 11.8 (95% CI = 6.8–20.3), and 0.22 (95% CI = 0.12–0.38), respectively. By comparison, the anti-CCP2 assay had a sensitivity, specificity, and positive and negative LRs of 77% (95% CI = 62–87), 90% (95% CI = 85–94), 8.3 (95% CI = 5.2–13.2), and 0.25 (95% CI = 0.15–0.42), respectively. In patients with SSc, there was an association of anti-CCP2 antibodies with the presence of arthritis, but there was no association of anti-CCP2 or anti-CCP3 with anti-CENP B, anti-Scl 70, or RF. This study confirmed the high specificity and sensitivity of both anti-CCP assays for the diagnosis of RA. The presence of anti-CCP antibodies in SSc was only correlated with the presence of arthritis.

Kikuchi-Fujimoto’s disease associated with systemic lupus erythematosus: case report and review of the literature

Kikuchi-Fujimoto’s disease (KFD) or histiocytic necrotising lymphadenitis is a benign and self-limited disease, of unknown aetiology, which affects mainly young women. It presents with localised lymphadenopathy, predominantly in the cervical region, accompanied by fever and leukopenia in up to 50% of the cases. KFD has been rarely described in association with systemic lupus erythematosus (SLE), and its diagnosis can precede, postdate or coincide with the diagnosis of SLE. We present a patient with the diagnosis of SLE characterised by arthritis, leukopenia, malar rash, photosensitivity and positive ANA, besides cervical lymphadenopathy whose biopsy was compatible with KFD, which improved after using prednisone. Although the presence of lymphadenopathy is not uncommon in SLE patients, particularly in the phases of disease activity, the concomitance with KFD has rarely been reported in the literature. Its recognition is necessary because one can avoid laborious investigation for infectious and lymphoproliferative diseases.

Systemic lupus erythematosus, human papillomavirus infection, cervical pre-malignant and malignant lesions: a systematic review.

The purpose of this study was to review and evaluate systematically the scientific evidence on the relationship between systemic lupus erythematosus (SLE), human papillomavirus (HPV) infection, pre-cancerous cervical abnormalities, and cervical cancer. Establishing strict inclusion and exclusion criteria, we performed an extensive search for studies in MEDLINE and BIREME databases to assess the studies that evaluated the frequency of HPV infection, pre-cancerous cervical abnormalities, and cervical cancer in women with SLE. Secondary references were additionally obtained from the included articles. Thirty-three articles met the criteria previously established. Fifteen out of 18 studies that performed cytological analysis showed a higher frequency of squamous intraepithelial lesions in SLE patients compared with normal women. Moreover, three studies found a higher frequency of high-grade squamous intraepithelial lesions. Additionally, it was observed that women with SLE had a higher frequency of HPV infection, confirmed by molecular biology techniques. Curiously, despite the above findings, no increased frequency of cervical cancer was observed in the majority of the studies which addressed this issue. Five studies observed a relationship between cervical abnormalities and previous use of immunosuppressive drugs. This review suggests that SLE patients seem not to be at increased risk for developing cervical cancer; however, they should be considered at higher risk for HPV infection and cervical dysplasia than the general population. Thus, gynecological visits at shorter intervals seem to be a reasonable approach for those patients.

Jaccoud arthropathy in systemic lupus erythematosus: analysis of clinical characteristics and review of the literature.

Jaccoud arthropathy (JA) was initially described in patients with rheumatic fever and later in several other rheumatologic conditions, particularly systemic lupus erythematosus (SLE). In patients with the latter disorder, a prevalence of about 5% has been observed. We conducted the current study to describe a series of patients with SLE with JA, followed at the Hospital Santa Izabel, Salvador, Brazil, during the year 2006. We reviewed the literature on JA, with emphasis on the histologic, clinical, radiologic, and therapeutic aspects of the condition. Twenty-one patients with JA were identified, corresponding to a prevalence of 3.47% in the population of 606 patients with the diagnosis of SLE attended in our service. Twenty patients were women, and the mean age was 40.2 ± 8.8 years (range, 24-55 yr). The most frequently found joint deformities were swan neck and thumb subluxation, both identified in 14 patients. Ulnar deviation was seen in 8, boutonniere deformity in 3, and hallux valgus in 2 patients. We found no difference in the clinical or laboratory features in SLE patients with or without JA. The patients with JA presented a trend toward a lower quality of life compared with the patients with SLE without JA, but without statistical significance. Abbreviations: CRP = C-reactive protein, JA = Jaccoud arthropathy, MCP = metacarpophalangeal joint, NMR = nuclear magnetic resonance, RF = rheumatic fever, SLE = systemic lupus erythematosus.

The use of extracorporeal shock waves in the treatment of osteonecrosis of the femoral head: a systematic review

Osteonecrosis is a progressive clinical condition with significant morbidity, which primarily affects weight-bearing joints and is characterized by the death of the bone, or part of it, because of insufficient circulation. The hip is the most common compromised joint. In osteonecrosis of the femoral head (ONFH), the collapse of the femoral head is a result of mechanically weak bone submitted to a load of weight, and can be associated with incapacitating pain and immobility. Both nonsurgical and surgical treatment options have been used with differing levels of success, and nonoperative treatment modalities such as bisphosphonates, statins, anticoagulants, and extracorporeal shock wave therapy (ESWT) for early-stage disease have been described, but exact indications have not been established yet. The aim of this study was to make a systematic review of the use of ESWT in the treatment of ONFH. MEDLINE, LILACS, and Scielo databases were searched using the keywords “shock wave”, “osteonecrosis”, “avascular necrosis”, “aseptic necrosis” and “femoral head”. The search period was between 1966 and 2009. Only five articles that fulfilled the previously established criteria were obtained. Of these five articles, two were randomized clinical trials, one open label study, one comparative prospective study, and one was a case report. The present review demonstrated that there are no controlled and double-blind studies about the efficacy of ESWT in the treatment of ONFH. On the other hand, the published noncontrolled studies appear to demonstrate some favorable result, which justifies new research in this area.

The use of bisphosphonate in the treatment of avascular necrosis : a systematic review

Up to now, there is no uniformly accepted treatment for avascular necrosis (AN) that alleviates pain and retards its progression. The aim of clinical and surgical treatments is usually only to improve blood support in the avascular area. The objective of the present study was to make a systematic review of the use of bisphosphonates in the treatment of AN. Studies in which bisphosphonate was used for the treatment of AN were researched through the MEDLINE databases (from 1966 to 2007) and the Cochrane Central Register of Controlled Trials and using the following terms: “avascular necrosis,” “aseptic necrosis,” “bisphosphonates,” “alendronate,” “pamidronate,” “zoledronate,” and “risedronate”. Only seven articles that met the previously established criteria were obtained from MEDLINE, and none were obtained from the Cochrane Central Register of Controlled Trials. Of these seven articles, two were randomized clinical trials and five were prospective comparative studies; one of them corresponded to an extension of a previous study. The present review demonstrates that there are no controlled and double-blind studies about the efficacy of bisphosphonates in the treatment of AN. Therefore, the data are still insufficient for justifying its use for this indication. On the other hand, noncontrolled studies appear to demonstrate favorable results, particularly in diminishing pain, improving mobility, and lowering the incidence of articular collapse, which justifies new studies being developed in this area.

Autoimmune Response of IgE Antibodies to Cellular Self-Antigens in Systemic Lupus Erythematosus

Background: Systemic lupus erythematosus (SLE) patients may exhibit high total IgE and antinuclear IgE antibodies (ANA-IgE). Here, we investigated the specificity of ANA-IgE in SLE patients and the involvement of cytokines in this immune response. Methods: Sera from 92 SLE patients and 68 healthy controls were evaluated for the presence of antinuclear IgE antibodies by immunoperoxidase with HEp-2,000® cells and immunoblotting with IgG-depleted sera. Total IgE, IgE specific to allergens, and serum cytokine levels were determined by ELISA. Results: Antinuclear IgE antibodies were detected only in SLE patients (29/92, 31.5%). High total IgE was associated with ANA-IgE (p < 0.0001), but was not associated with IgE antibodies to allergens. In the immunoblotting, ANA-IgE reacted with nucleosomes (23/29, 79.3%), dsDNA (14/29, 48.3%), SS-A/Ro (14/29, 48.3%), SS-B/La (2/29, 18.7%), Sm (14/29, 48.3%) and RNP (18/29, 62.1%). Patients with ANA-IgE had very low serum IL-4, less IL-5 than controls (p < 0.05), more IL-10 than seronegative patients (p < 0.05), and unaltered IFN-γ levels. The IL-5/IL-10 ratio was lower in ANA-IgE seropositive patients in comparison with either seronegative patients (p < 0.05) or healthy controls (p = 0.001). Controls displayed higher IL-5/IFN-γ ratios than either SLE patients with ANA-IgE (p < 0.05) or patients without these immunoglobulins (p < 0.01). Conclusions: We conclude that IgE antibodies against cell autoantigens involved in protein expression, cellular proliferation, and cell death are present in patients with SLE. Interleukin-10 seems to down-regulate this IgE autoimmune response in SLE.

Magnetic resonance imaging of Jaccoud's arthropathy in systemic lupus erythematosus.

OBJECTIVE To perform a detailed magnetic resonance imaging (MRI) analysis of the hands of patients with Jaccouds arthropathy (JA) secondary to systemic lupus erythematosus (SLE). METHODS The hand with more expressive deformities compatible with JA from a group of SLE patients was examined by 1.5-T MRI. The protocol included coronal, sagittal, and axial turbo-spin-echo images before and after the administration of contrast medium. The presence of synovitis, edema, erosion, cysts, and tenosynovitis in the carpometacarpal, metacarpophalangeal, and proximal interphalangeal joints were scored based on a modified Outcome Measures in Rheumatology recommendations. RESULTS Twenty SLE patients, (19 women and one man) with median age of 44.7 years (range: 20-76 years), median disease duration of 14.7 years (range: 5-26 years), and median arthritis duration of 13.7 years (range: 4-26 years) were studied. Of the 300 joints evaluated, 202 (67.3%) had some degree of synovitis. Sixteen out of 300 examined joints (5.3%) small areas of erosion were seen in 10 out of the 20 patients (50%). Subchondral bone edema was found in eight out of the 20 (40%) patients or a total of 18 joints (6%). A total of 200 compartments tendons were evaluated, and changes were found in 77 (38.5%) of them. In four out of the 20 patients, the MRI revealed bone cysts. CONCLUSIONS The MRI seems to be a non-invasive diagnostic tool in patients with JA secondary to SLE, and may contribute to understanding the mechanism involved in the development of this deformity.

NK and NKT cell dynamics after rituximab therapy for systemic lupus erythematosus and rheumatoid arthritis

Biomarkers of clinical response to rituximab (RTX) therapy and early predictors of outcome are still under investigation. We report a flow cytometric immunophenotyping analysis from peripheral blood leukocyte subpopulations of two patients with systemic lupus erythematosus (SLE) associated thrombocytopenia and one patient with rheumatoid arthritis (RA), before and after 6 weeks of treatment with RTX. Our results show a reduced population of CD19+ expressing cells (B cells) after RTX treatment in all three patients. Increased frequency of peripheral regulatory CD4+CD25high T cell subset and the CD3−CD16−CD56bright NK cell subset after RTX therapy were also observed in all patients, the latter being more pronounced in the SLE patient with sustained clinical response. In addition, an increased population of NKT cell subsets was observed in the patients with clinical response. This is the first evaluation of NK and NKT cells as biomarkers of clinical response after rituximab therapy in rheumatic diseases.

Anti-C1q Antibodies: Association With Nephritis and Disease Activity in Systemic Lupus Erythematosus

Background: Anti‐C1q antibodies have been described in systemic lupus erythematosus (SLE) as well as in other connective tissue diseases. They have been considered as a marker for disease activity and presence of nephritis.