Undifferentiated connective tissue disease (UCTD) is characterized by the presence of clinical symptoms of a systemic autoimmune disease in addition to laboratory evidence of autoimmunity with the patients not fulfilling any of the widely used classification criteria for classic autoimmune diseases. The presence of UCTD as a separate entity versus an early stage of such diseases as systemic lupus erythematosus (SLE) or scleroderma has long been debated. Given the uncertainty regarding this condition, we performed a systematic review on the topic.UCTD can be subcategorized as evolving (eUCTD) or stable UCTD (sUCTD) based on its evolution towards a definable autoimmune syndrome. Analyzing the data from six UCTD cohorts published in the literature, we found that 28% of patients have an evolving course with the majority developing SLE or rheumatoid arthritis within 5-6 years of the UCTD diagnosis. From the remaining patients, 18% do achieve remission. Published treatment regimens were similar to other mild autoimmune diseases with low-dose prednisone, hydroxychloroquine, and NSAID. One-third of patients did need immune suppressive medications. Importantly, the reported outcomes were excellent with survival rates of more than 90% over 10 years. It has to be noted though that as data on patient related outcomes are not available to date, the exact impact of this condition on quality of life is unclear. UCTD is a mild autoimmune condition with generally good outcomes. There is still great uncertainty though regarding diagnosis and management. Going forward, consistent classification criteria are needed to advance UCTD research and eventually provide authoritative guidance on the management of the condition.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

UCTD is a systemic autoimmune condition that fails to fulfil the criteria for a definite CTD. Given that there are a lack of studies on links between pregnancy and UCTD, the purpose of this study was to evaluate the risk of disease flares or development of CTD in addition to the risk of adverse pregnancy outcomes in patients with UCTD.This is a retrospective study using prospectively collected data for 100 pregnancies in 81 incidences of UCTD treated in a single referral centre.A total of 11 pregnancies (11%) ended in miscarriage in the first trimester and the remaining 89 (89%) ended with a live birth. Thirteen patients (13%) flared during pregnancy or puerperium and three (3%) suffered major flares that led to the development of SLE with renal involvement. Obstetric complications occurred in 26 of the 89 successful pregnancies (29%), including 1 case (1%) of pre-eclampsia; in some cases, a single pregnancy was affected by more than one complication. There was a significant link between disease flare and both anti-dsDNA-positive antibodies at baseline (P < 0.01) and disease activity at the beginning of pregnancy (P < 0.01).The impact on pregnancy in the study's cohort appears to be less serious in UCTD than in other CTDs. Nevertheless, disease flares and obstetric complications can represent a clinical challenge and clinical and serological disease activity would appear to represent important determinants of pregnancy outcomes. Pre-pregnancy counselling and planning as well as close monitoring during pregnancy is therefore essential.© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Systemic lupus erythematosus (SLE) patients have more pregnancy complications than healthy patients. Data regarding pregnancy outcomes in women with undifferentiated connective tissue disease (UCTD) are more limited, and existing studies are concentrated in Italy and predominantly in patients with a new diagnosis. Our objective was to compare pregnancy outcomes for UCTD and SLE patients with established disease.

自身免疫性疾病（AID）是指机体产生高滴度自身抗体和（或）自身反应性淋巴细胞攻击相应的自身正常细胞和组织，导致组织器官损伤和功能障碍的综合征，是导致复发性流产（RSA）等妊娠并发症的重要原因。临床上常见的较易导致RSA的AID有：系统性红斑狼疮、抗磷脂综合征、干燥综合征、类风湿关节炎、系统性硬化症和未分化结缔组织病等。这些AID导致的RSA的治疗主要为小剂量免疫抑制剂联合抗凝治疗，且疗效肯定。

Undifferentiated connective tissue disease (UCTD) is characterized by signs and symptoms suggestive of a connective tissue disease (CTD), but not fulfilling criteria for a specific CTD. Although UCTD is probably the most common rheumatic disease diagnosed in pregnant women, data about disease course during pregnancy and perinatal outcomes are very limited. Compared to other CTDs, UCTD seems to have milder clinical manifestations in pregnancy. Its natural history is related to disease activity at conception. In fact, if the disease is in a state of remission or minimal activity at conception, pregnancy outcomes are generally good. On the contrary, patients who become pregnant in a moment of high disease activity and/or who have multiple antibodies positivity show an increased risk of disease flares, evolution to a definite CTD and obstetric complications, such as fetal growth restriction, preeclampsia and preterm birth. Therefore, a preconception assessment is essential in women with UCTD to evaluate maternal and fetal risks, to initiate interventions to optimize disease activity, and to adjust medications to those that are least harmful to the fetus. The aim of the present study was to review the available literature about pregnancy course, maternal and fetal outcomes and therapeutic approaches of pregnant women with UCTD.

The term undifferentiated connective tissue disease (UCTD) refers to unclassifiable systemic autoimmune diseases which share clinical and serological manifestations with definite connective tissue diseases (CTDs) but not fulfilling any of the existing classification criteria. In this review we will go through the more recent evidence on UCTD and we will discuss in what extent the availability of new criteria for the CTDs could interfere with the "UCTD concept". The development of criteria able to identify early phases of defined CTD, may help in the differentiation of stable UCTD form their early stages and may offer a valuable guide to the treating physician to set up appropriate follow up schedules as well as therapeutic protocols. This simplified subset of CTD could offer a model to study clinic pathological correlations as well as the role of possible environmental factors in the development of autoimmunity. Copyright © 2014. Published by Elsevier Ltd.

The connective tissue diseases include a heterogeneous group of conditions characterized by a wide variety of signs and symptoms. There also exists, however, a group of systemic autoimmune disorders with signs and symptoms not sufficiently evolved to fulfill any of the accepted classification criteria for the defined connective tissue diseases. These conditions have been defined as undifferentiated connective tissue syndromes, latent lupus, incomplete lupus, and undifferentiated connective tissue diseases. After an analysis of the existing literature, we discuss the possible significance of the undifferentiated diseases among the already defined connective tissue diseases and make a proposal for preliminary classification criteria for these conditions.

The purpose of this study was to characterize the clinical and serological features of a large cohort of patients with antinuclear antibody (ANA) positive undifferentiated connective tissue disease (UCTD). Consecutive patients with UCTD, followed up at the Rheumatology Clinic of the participating centers, were included. Data from these patients were obtained by clinical evaluation and chart review. All patients were diagnosed as having UCTD on basis of the following criteria: positive ANA plus at least one clinical feature of connective tissue disease, but not fulfilling classification criteria for any differentiated connective tissue disease. One hundred eighty-four patients were studied (female patients-94.5%; mean age at time of evaluation-47 years). The most prevalent manifestations were arthralgia (66%), arthritis (32%), Raynaud's phenomenon (30%), sicca symptoms (30%), and leukopenia (19%). The prevalence of ANA was 100%, anti-SSA 20%, anti-dsDNA 14%, and anti-SSB 7%. Patients with anti-dsDNA/anti-Sm, anticentromere/anti-Scl70, or anti-SSA/anti-SSB antibodies more frequently presented a set of manifestations close to systemic lupus erythematosus (SLE), systemic sclerosis, or Sjögren syndrome, respectively. We analyze a large cohort of UCTD. Seventy-two percent of these UCTD patients present lupus-, scleroderma-, or Sjögren-like features but do not fulfill classification criteria and mostly present a mild disease.

The objective of this study was to evaluate the rates of previously undiagnosed rheumatic diseases during the first trimester of pregnancy and their impact on the pregnancy outcome.Pregnant women in their first trimester were screened using a two-step approach using a self-administered 10-item questionnaire and subsequent testing for rheumatic autoantibodies (antinuclear antibody, anti-double-stranded DNA, anti-extractable nuclear antigen, anticardiolipin antibodies, anti-β2-glycoprotein I antibodies and lupus anticoagulant) and evaluation by a rheumatologist. Overall, the complications of pregnancy evaluated included fetal loss, pre-eclampsia, gestational diabetes, fetal growth restriction, delivery at less than 34 weeks, neonatal resuscitation and admission to the neonatal intensive care unit.Out of the 2458 women screened, the authors identified 62 (2.5%) women with previously undiagnosed undifferentiated connective tissue disease (UCTD) and 24 (0.98%) women with previously undiagnosed definite systemic rheumatic disease. The prevalences were seven (0.28%) for systemic lupus erythematosus and Sjogren's syndrome, six (0.24%) for rheumatoid arthritis, three (0.12%) for antiphospholipid syndrome and one (0.04%) for systemic sclerosis. In multiple exact logistic regression, after adjustment for potential confounders, the OR of overall complications of pregnancy were 2.81 (95% CI 1.29 to 6.18) in women with UCTD and 4.57 (95% CI 1.57 to 13.57) in those with definite diseases, respectively, compared with asymptomatic controls.In our population approximately 2.5% and 1% of first trimester pregnant women had a previously undiagnosed UCTD and definite systemic rheumatic disease, respectively. These conditions were associated with significant negative effects on the outcome of pregnancy.

To assess the outcome of pregnancy and disease flare or differentiation into well-defined connective tissue disease (CTD), in a cohort of pregnant patients with undifferentiated connective tissue disease (UCTD) and to compare these findings with those obtained from a population of non-pregnant women with UCTD.In total, 55 pregnancies (in 50 UCTD patients) were monitored from the positive pregnancy test until the sixth month after delivery. Likewise, during a 15-month timeframe, the incidence of flares or evolution into a major CTD was also recorded in a population of 53 non-pregnant women with UCTD. The Student t-test was applied for unpaired, continuous variables and chi-square was applied when percentages were compared.The mean duration of the successful pregnancies was 38.6 weeks (range 28-42) while the mean birth weight was 3190 g (range 1200-4600 g). Three pregnancies (5.4%) ended in miscarriage. The following obstetric complications were found: five premature membrane ruptures, two preeclampsia and two intra-uterine growth restrictions. In a total of 16 patients (32%) the disease flared during pregnancy or during the 6-month post-delivery period. Of these, five developed well-defined CTD after delivery. In the control population, six patients flared (11%) and, of these, only one developed a well-defined CTD.If pregnancy is properly treated, the outcome in UCTD patients is generally good while, considering disease activity, pregnancy appears to be a clear risk factor for flare up or evolution into well-defined CTD.

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.

To investigate fetal/perinatal and maternal outcomes from a large multicentre cohort of women diagnosed with UCTD.

An increased risk of adverse maternal and foetal pregnancy complications (including pre-eclampsia, intrauterine growth restriction, and small for gestational age) is well described in women with autoimmune rheumatic disease (ARD) compared with the general population (GenPop). It is less clear, however, whether this risk of adverse pregnancy outcome (APO) also exists in women with ‘preclinical ARD’ (pre-ARD) before they are diagnosed with an ARD many years post-partum. Therefore, we have undertaken a systematic review of the available evidence on APO in patients who subsequently were diagnosed with a rheumatic disease to identify whether there is an increased risk in pre-ARD.

The objective of this study was to evaluate the role of pregnancies in the progression from the preclinical phase of autoimmune disorder to a definite rheumatic disease.

Autoimmune diseases disproportionately impact women and female-specific aspects of reproduction are thought to play a role. We investigated the time-varying association between pregnancy complications and new-onset autoimmune disease in females during the reproductive and midlife years.

Our objective was to update the EULAR recommendations for the management of systemic lupus erythematosus (SLE), based on emerging new evidence. We performed a systematic literature review (01/2007-12/2017), followed by modified Delphi method, to form questions, elicit expert opinions and reach consensus. Treatment in SLE aims at remission or low disease activity and prevention of flares. Hydroxychloroquine is recommended in all patients with lupus, at a dose not exceeding 5 mg/kg real body weight. During chronic maintenance treatment, glucocorticoids (GC) should be minimised to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn. Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of GC. In persistently active or flaring extrarenal disease, add-on belimumab should be considered; rituximab (RTX) may be considered in organ-threatening, refractory disease. Updated specific recommendations are also provided for cutaneous, neuropsychiatric, haematological and renal disease. Patients with SLE should be assessed for their antiphospholipid antibody status, infectious and cardiovascular diseases risk profile and preventative strategies be tailored accordingly. The updated recommendations provide physicians and patients with updated consensus guidance on the management of SLE, combining evidence-base and expert-opinion.© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

Develop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS).Systematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus.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.Recommendations for women's health issues in SLE and/or APS were developed using an evidence-based approach followed by expert consensus.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Systemic lupus erythematosus (SLE) is a clinically diverse, complex autoimmune disease which may present with coincident onset of many criteria or slow, gradual symptom accrual. Early intervention has been postulated to delay or prevent the development of more serious sequelae. One option for treatment in this setting is hydroxychloroquine. Using 130 US military personnel who later met ACR SLE criteria, a retrospective study of onset, development and progression of SLE with and without pre-classification hydroxychloroquine (n = 26) use was performed. Patients treated with hydroxychloroquine prior to diagnosis had a longer (Wilcoxon signed rank test, P = 0.018) time between the onset of the first clinical symptom and SLE classification (median: 1.08 versus 0.29 years). Patients treated with prednisone before diagnosis also more slowly satisfied the classification criteria (Wilcoxon signed rank test, P = 0.011). The difference in median times between patients who received NSAIDs before diagnosis, as opposed to those who did not, was not different (P = 0.19). Patients treated with hydroxychloroquine also had a lower rate of autoantibody accumulation and a decreased number of autoantibody specificities at and after diagnosis. These findings are consistent with early hydroxychloroquine use being associated with delayed SLE onset. A prospective, blinded trial testing the capacity of hydroxychloroquine to delay or prevent SLE in high risk populations is warranted.

Undifferentiated connective tissue disease (UCTD) is known to induce adverse pregnancy outcomes and even recurrent spontaneous abortion (RSA) by placental vascular damage and inflammation activation. Anticoagulation can prevent pregnancy morbidities. However, it is unknown whether the addition of immune suppressants to anticoagulation can prevent spontaneous pregnancy loss in UCTD patients. The purpose of this study is to evaluate the efficacy of hydroxychloroquine (HCQ) and low-dose prednisone on recurrent pregnancy loss for women with UCTD.