Multimodality imaging in connective tissue disease-related interstitial lung disease.

Interstitial lung disease is a well-recognised manifestation and a major cause of morbidity and mortality in patients with connective tissue diseases. Interstitial lung disease may arise in the context of an established connective tissue disease or be the initial manifestation of an otherwise occult autoimmune disorder. Early detection and characterisation are paramount for adequate patient management and require a multidisciplinary approach, in which imaging plays a vital role. Computed tomography is currently the imaging method of choice; however, other imaging techniques have recently been investigated, namely ultrasound, magnetic resonance imaging, and positron-emission tomography, with promising results. The aim of this review is to describe the imaging findings of connective tissue disease-related interstitial lung disease and explain the role of each imaging technique in diagnosis and disease characterisation.

Immunodeficiency and autoimmunity coming together: a nearly missed diagnosis.

The coexistence of human immunodeficiency virus (HIV) and systemic lupus erythematosus (SLE) appears to be unusual and the prevalence of patients who carry the dual diagnosis is currently unknown. We hereby present a case of a C4 deficient HIV-1 positive Caucasian female under highly active antiretroviral therapy for the past eight years, admitted to hospital with an aggressive and potentially fatal clinical presentation of SLE. There was a favorable outcome despite a significant diagnostic delay. Despite its rarity, the case highlights that this association is remarkable and may be overlooked by clinicians familiar with either condition.

Two separate effects contribute to regulatory T cell defect in systemic lupus erythematosus patients and their unaffected relatives.

Forkhead box P3 (FoxP3)+ regulatory T cells (Tregs ) are functionally deficient in systemic lupus erythematosus (SLE), characterized by reduced surface CD25 [the interleukin (IL)-2 receptor alpha chain]. Low-dose IL-2 therapy is a promising current approach to correct this defect. To elucidate the origins of the SLE Treg phenotype, we studied its role through developmentally defined regulatory T cell (Treg ) subsets in 45 SLE patients, 103 SLE-unaffected first-degree relatives and 61 unrelated healthy control subjects, and genetic association with the CD25-encoding IL2RA locus. We identified two separate, uncorrelated effects contributing to Treg CD25. (1) SLE patients and unaffected relatives remarkably shared CD25 reduction versus controls, particularly in the developmentally earliest CD4+ FoxP3+ CD45RO- CD31+ recent thymic emigrant Tregs . This first component effect influenced the proportions of circulating CD4+ FoxP3high CD45RO+ activated Tregs . (2) In contrast, patients and unaffected relatives differed sharply in their activated Treg CD25 state: while relatives as control subjects up-regulated CD25 strongly in these cells during differentiation from naive Tregs , SLE patients specifically failed to do so. This CD25 up-regulation depended upon IL2RA genetic variation and was related functionally to the proliferation of activated Tregs , but not to their circulating numbers. Both effects were found related to T cell IL-2 production. Our results point to (1) a heritable, intrathymic mechanism responsible for reduced CD25 on early Tregs and decreased activation capacity in an extended risk population, which can be compensated by (2) functionally independent CD25 up-regulation upon peripheral Treg activation that is selectively deficient in patients. We expect that Treg -directed therapies can be monitored more effectively when taking this distinction into account.

EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome.

OBJECTIVES: Develop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). METHODS: Systematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus. RESULTS: Family planning should be discussed as early as possible after diagnosis. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes. Risk stratification includes disease activity, autoantibody profile, previous vascular and pregnancy morbidity, hypertension and the use of drugs (emphasis on benefits from hydroxychloroquine and antiplatelets/anticoagulants). Hormonal contraception and menopause replacement therapy can be used in patients with stable/inactive disease and low risk of thrombosis. Fertility preservation with gonadotropin-releasing hormone analogues should be considered prior to the use of alkylating agents. Assisted reproduction techniques can be safely used in patients with stable/inactive disease; patients with positive antiphospholipid antibodies/APS should receive anticoagulation and/or low-dose aspirin. Assessment of disease activity, renal function and serological markers is important for diagnosing disease flares and monitoring for obstetrical adverse outcomes. Fetal monitoring includes Doppler ultrasonography and fetal biometry, particularly in the third trimester, to screen for placental insufficiency and small for gestational age fetuses. Screening for gynaecological malignancies is similar to the general population, with increased vigilance for cervical premalignant lesions if exposed to immunosuppressive drugs. Human papillomavirus immunisation can be used in women with stable/inactive disease. CONCLUSIONS: Recommendations for women's health issues in SLE and/or APS were developed using an evidence-based approach followed by expert consensus.

Neuropsychiatric questionnaires in systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) can be affected by a multitude of neurologic and psychiatric symptoms with a wide range of prevalence and severity. Irrespectively from attribution to SLE or other causes, neuropsychiatric (NP) symptoms strongly impact short-term and long-term outcomes, thus NP evaluation during routine clinical practice in SLE should be undertaken regularly. The assessment of NP involvement in SLE patients is challenging and the available diagnostic tools fail to guarantee optimal diagnostic accuracy, sensitivity to changes as well as feasibility in routine clinical care. Standardised questionnaires (both physician-administered and self-reported) can offer valuable help to the treating physician to capture all possible NP syndromes; few SLE-specific NP questionnaire have been developed but validation in large cohort or cross-cultural adaptations are still pending. On the other hand, general instruments have been largely applied to SLE patients. Both kinds of questionnaires can address all possible NP manifestations either globally or, more frequently, focus on specific NP symptoms. These latter have been mainly used in SLE to detect and classify mild and subtle symptoms, more likely to be overlooked during routine clinical assessment such as headache, cognitive impairment and psychiatric manifestations. In conclusion, this literature review highlights a clear case for validation studies in this area and the wider implementation of questionnaires to assess NP involvement is still warranted. The broader use of such instruments could have important consequences; first of all, by standardising symptom assessment, a better definition of the prevalence of NP manifestation across different centres could be achieved. Secondly, prospective studies could allow for the evaluation of clinical significance of mild symptoms and their impact on the patient's function and quality of life.