Andreas V. Goules

Clinically significant and biopsy-documented renal involvement in primary Sjögren syndrome.

Clinically significant renal involvement in patients with primary Sjögren syndrome (pSS) has been described previously only in isolated case reports. The prevalence and significance of the 2 described syndromes, interstitial nephritis (IN) and glomerulonephritis (GMN), are not well known. In a cohort of 471 patients with pSS who were followed for a mean of 10 years, 20 patients (4.2%) developed overt renal disease. Eighteen patients underwent a percutaneous renal biopsy; 2 patients declined. Ten patients had IN, 8 patients had GMN, and 2 patients presented with both entities. Glomerular histology disclosed changes compatible with membranoproliferative GMN in 5 patients and mesangial proliferative GMN in 4 patients. Patients with IN had a younger disease onset compared with patients with GMN (mean, 36.8 compared with 46.0 yr, p 5 0.063). Patients with GMN had longer disease duration compared with patients with IN (mean, 2.2 compared with 8.0 yr, p 5 0.001). The majority of patients with GMN (80%) had mixed monoclonal cryoglobulinemia IgMk (type II) and lower complement C4 levels. Two patients (both with GMN) developed chronic renal failure requiring hemodialysis. Overall, clinically significant renal involvement is infrequent in pSS. IN occurs early in the disease process, while GMN is a late sequela and may have a less favorable prognosis.

Clinically Significant Renal Involvement in Primary Sjögren's Syndrome: Clinical Presentation and Outcome

OBJECTIVE To estimate the prevalence and investigate the clinical features and the outcome of clinically significant renal involvement in a large cohort of patients with primary Sjögrens syndrome (SS). METHODS Among 715 patients who met the American-European Consensus Group criteria for primary SS, those with clinically significant renal involvement were identified and their clinical and immunologic features were recorded. The prognosis in patients with primary SS with renal involvement was assessed by the clinical appearance of any of the following major outcomes: death, hemodialysis, chronic renal failure (CRF), and lymphoma. Kaplan-Meier analysis was applied to compare death rates between patients without and those with renal involvement. RESULTS Thirty-five patients with primary SS (4.9%) had clinically significant renal involvement, representing a total followup time after renal diagnosis of 252.2 person-years. Thirteen patients (37.1%) had interstitial nephritis alone, 17 patients (48.6%) had glomerulonephritis (GN) alone, and 5 patients (14.3%) had both entities. Nine patients died (25.7%), 11 developed CRF (including 4 requiring chronic hemodialysis) (31.4%), and 9 developed lymphoma (25.7%). The overall 5-year survival rate was 85%. Kaplan-Meier analysis showed statistically significant reduced survival for patients with primary SS with renal involvement compared to those without renal involvement (P < 0.0001 by log rank test), with GN patients displaying increased mortality. Eight of 9 reported deaths (89%) and 8 of 9 lymphomas (89%) were observed among patients with GN. CONCLUSION The long-term prognosis varies for patients with primary SS who have clinically significant renal involvement. Patients with interstitial nephritis display a favorable prognosis, while patients with GN are at high risk of developing lymphoma and have poor survival.

Classification criteria of Sjögren's syndrome.

Sjögrens syndrome (SS) is a chronic, systemic autoimmune disease that affects typically the exocrine glands causing mucosal dryness. Dry eyes and mouth are considered by far the most common and early symptoms of the disease but systemic complications may also occur. In 1993, the preliminary European criteria were proposed and widely accepted, consisting of both subjective and objective criteria. Almost ten years later, these classification criteria were revised by introducing more stringent rules and precise diagnostic procedures leading to the currently used American-European Consensus Group (AECG) criteria. The AECG criteria have been largely employed to conduct epidemiologic and clinical studies of patients with SS and proved to be more specific compared to the preliminary European criteria. The recent American College of Rheumatology/Sjögrens International Collaborative Clinical Alliance (ACR/SICCA) criteria that are based exclusively on objective tests, the stringency of the AECG criteria and the potential therapeutic use of biologic agents in SS clearly set the need for new classification criteria. Whether the new diagnostic approach will further encompass subclinical and early forms of the disease remains to be addressed by the scientific community.

Primary Sjӧgren's syndrome: Clinical phenotypes, outcome and the development of biomarkers.

Primary Sjӧgrens syndrome (pSS) is a complex autoimmune disease with distinct clinical phenotypes and variable outcomes. The systemic form of the disease is characterized by immune complex mediated manifestations and is complicated by lymphoma as a result of a polyclonal B cell hyperactivity that is evolving into B cell malignancy. In the past decades, well-established clinical and serological markers have been described in the literature to identify high-risk patients and to predict lymphoma development. However, specific biologic treatments have proven ineffective to control the disease. Significant research effort has been made to reveal the major underlying biological events in this subgroup and identify biomarkers for early diagnosis, prognosis and response to treatment. In this review, we summarize the current data for the proposed histological, molecular and genetic biomarkers.

Atopic dermatitis: new immunologic aspects

Atopic dermatitis (AD) is a pruritic, inflammatory skin disease that typically occurs in early childhood. AD follows a chronic and relapsing course, and is considered to be part of an atopic state. Clinical manifestations of this atopic state include asthma, allergic rhinitis, allergic conjunctivitis, and food allergies. Usually, AD precedes these allergic disorders. Anaphylaxis, urticaria, and dyshidrotic eczema are also associated with atopic state disorders. The disease has a complex genetic background with many genes involved (multigenic). When both parents are affected by AD, up to 81% of their children manifest the disease. When one parent is affected, the prevalence drops to 56%. 1

Pathogenesis of subacute cutaneous lupus erythematosus

Subacute cutaneous lupus erythematosus (SCLE) is a photosensitive form of lupus‐specific skin lesion that is strongly associated with the presence of anti‐Ro/SSA autoantibody. The pathogenesis of SCLE includes genetic, environmental and immunologic factors. Recent studies provide strong evidence for the involvement of innate and cell‐mediated immunity, underlying the important role of plasmacytoid dendritic cells, interferon‐α and antibody‐dependent cell cytotoxicity. In addition, a variety of cytokines, chemokines and adhesion molecules have been found to participate in the expansion phase of the autoimmune effector mechanisms. This article summarizes the recent immunological findings and reviews the current mechanisms which are implied in the development of the disease.

Prognostic Factors and Survival

The histological hallmark of primary Sjogren’s syndrome (pSS) is the focal lymphocytic infiltrates that slowly and steadily replace the epithelium of salivary and lacrimal glands and produce exocrine gland dysfunction, manifested mainly by xerostomia and xerophthalmia [1]. These two clinical manifestations are determinants for the term “exocrinopathy” in SS. Studies in the last 20 years have delineated the type and spectrum of other organ involvement in SS. Lungs, liver and the kidneys are usually affected in pSS. The histology and the evolution of the lesion in the above parenchymal tissues do not differ from that observed in salivary and lacrimal glands. These extragrandular manifestations are mild in severity in most cases, evolve slowly, and do not appear to respond to glucocorticoids or other immunosuppressive agents. The central role of the epithelial cell as the main target of the immune injury in the exocrine glands as well as in the lungs, the liver and the kidneys has led to the introduction of the term “autoimmune epithelitis” [1].

Imaging: Diagnostic value of ultrasonography in Sjögren's syndrome

Salivary gland ultrasonography is a promising tool for the evaluation of Sjögren’s syndrome. Cumulative data suggest that ultrasonography is comparable with older imaging modalities such as sialography and scintigraphy. However, certain issues remain to be addressed before it can be integrated into current or future classification systems.

Asymptomatic Bacteriuria in Women With Autoimmune Rheumatic Disease: Prevalence, Risk Factors, and Clinical Significance

BACKGROUND Data regarding the prevalence and clinical significance of asymptomatic bacteriuria (AB) in women with autoimmune rheumatic disease (ARD) are scarce. METHODS In this prospective, case-control study, consecutive female outpatients with ARD were screened for AB. For each patient, demographics, type, duration, and treatment of underlying ARD, and risk factors for urinary tract infection (UTI), were recorded. Age-matched women with endocrine disease, without any autoimmune disease, not receiving immunosuppressive agents were used as controls. Subjects were followed up for 1 year for the development of symptomatic UTI. RESULTS Two hundred sixty patients with ARD (mean age, 52.4 [standard deviation {SD}, 14.6] years) and 238 controls (mean age, 51.2 [SD, 16.5] years) were enrolled. The majority of patients with ARD (93.5%; 95% confidence interval [CI], 89.7%-95.9%) were receiving immunosuppressive agents. AB was detected in 24 patients with ARD (9.2%; 95% CI, 6.2%-13.4%) and in 22 controls (9.2%; 95% CI, 5.5%-12.9%) (P = 1.000). The most prevalent pathogen was Escherichia coli (16/24 [66%]). Independent predictors for AB among patients were diabetes (odds ratio [OR], 6.6; P = .008) and a longer ARD duration (>84 months; OR, 4.3; P = .018). During the 1-year follow-up, 9 patients with baseline AB remained persistently bacteriuric, whereas 11 were intermittently bacteriuric. Symptomatic UTI developed in 4 of 24 patients (16.7%; 95% CI, 6.1%-36.5%) with baseline AB vs 29 of 236 (12.3%; 95% CI, 8.6%-17.1%) without AB (P = .522). CONCLUSIONS In our study, the prevalence of AB among women with ARD was not higher than that of controls, and AB was not associated with higher risk for symptomatic UTI. Risk factors for AB were longer duration of ARD and diabetes.

Gynecological and Reproductive Complications in Primary Sjögren’s Syndrome

Primary Sjogren’s syndrome (SS) almost exclusively afflicts women. The external genitalia are commonly affected and as a result, vaginal dryness and dypareunia may occur. Other less common gynecological problems have also been described.