Exploring the overlap between alopecia areata and major depressive disorder: Epidemiological and genetic perspectives.

BACKGROUND: Research suggests that Alopecia areata (AA) and Major Depressive Disorder (MDD) show substantial comorbidity. To date, no study has investigated the hypothesis that this is attributable to shared genetic aetiology. OBJECTIVES: To investigate AA-MDD comorbidity on the epidemiological and molecular genetic levels. METHODS: First, epidemiological analyses were performed using data from a cohort of adult German health insurance beneficiaries (n = 1.855 million) to determine the population-based prevalence of AA-MDD comorbidity. Second, analyses were performed to determine the prevalence of MDD in a clinical AA case-control sample with data on psychiatric phenotypes, stratifying for demographic factors to identify possible contributing factors to AA-MDD comorbidity. Third, the genetic overlap between AA and MDD was investigated using a polygenic risk score (PRS) approach and linkage disequilibrium score (LDSC) regression. For PRS, summary statistics from a large MDD GWAS meta-analysis (PGC-MD2) were used as the training sample, while a Central European AA cohort, including the above-mentioned AA patients, and an independent replication US-AA cohort were used as target samples. LDSC was performed using summary statistics of PGC-MD2 and the largest AA meta-analysis to date. RESULTS: High levels of AA-MDD comorbidity were reported in the population-based (MDD in 24% of AA patients), and clinical samples (MDD in 44% of AA patients). MDD-PRS explained a modest proportion of variance in AA case-control status (R2  = 1%). This signal was limited to the major histocompatibility complex (MHC) region on chromosome 6. LDSC regression (excluding MHC) revealed no significant genetic correlation between AA and MDD. CONCLUSIONS: As in previous research, AA patients showed an increased prevalence of MDD. The present analyses suggest that genetic overlap may be confined to the MHC region, which is implicated in immune function. More detailed investigation is required to refine understanding of how the MHC is involved in the development of AA and MDD comorbidity.

Quality of care predicts outcome in systemic lupus erythematosus: a cross-sectional analysis of a German long-term study (LuLa cohort).

OBJECTIVE: Our aim was to study the quality of medical care in patients with systemic lupus erythematosus (SLE) to understand gaps and to analyze the association with outcome of the disease. METHODS: Information on demographics and medical care was assessed by self-reported questionnaires among SLE patients (LuLa cohort, 2011, n = 580). In total, 21 aspects of medical care were analyzed. Univariate analysis selected 10 predictor variables for further analysis: (1) urine examination and (2) blood test in the previous year, (3) taking antimalarials, (4) taking vitamin D and calcium if the dosage of prednisolone was greater than 7.5 mg/day, counseling regarding (5) lipid metabolism, (6) vaccination, and (7) blood pressure, and treatment of the comorbidities (8) hypertension, (9) osteoporosis and (10) lipid metabolism disorder. The association of these 10 items with the outcome of the disease, assessed in 2015, was analyzed by linear regression analysis, adjusted for age, disease duration and sex. RESULTS: On average six of the 10 items were met (±1.7). Receiving more clinical care in 2013 was predictive for low disease activity (SLAQ, p = 0.024, ß = -0.104, corr. R2 = 0.048), low progress in disease-related damage (Delta Brief Index of Lupus Questionnaire, p = 0.048, ß = -0.132, corr. R2 = 0.036) and high health-related quality of life (SF-12 physical, p = 0.035, ß = 0.100, corr. R2 = 0.091) in 2015. CONCLUSION: Our study illustrates a link between the quality of care and the SLE outcome parameters disease activity, disease-related damage and quality of life. Consistent considerations of these care parameters, which are recommended in several management guidelines, could therefore be a good approach to improve the outcome of patients with SLE.

[Pregnancy with lupus erythematosus-an update]. / Schwangerschaft bei Lupus erythematodes ­ ein Update.

Current research in the field of systemic lupus erythematosus (SLE) and pregnancy focuses on predictors of adverse pregnancy outcomes, the safety and efficacy of hydroxychloroquine (HCQ) in pregnancy and the importance of preconception counselling. In particular, the prospective predictors of pregnancy outcome: biomarkers in antiphospholipid antibody syndrome and SLE (PROMISSE) study adds to the understanding of risk factors for adverse outcomes. There is increasing evidence of the numerous benefits associated with continuing HCQ treatment in pregnancy and for the use of low-dose acetylsalicylic acid in the prevention of preeclampsia. The European League Against Rheumatism (EULAR) has published evidence-based recommendations for the treatment of women with SLE and/or antiphospholipid syndrome before, during and after pregnancy. Rheumatologists caring for women with SLE should be familiar with the current state of knowledge in order to help optimize the management and thus the outcome of pregnancy in their patients.

[Pregnancy and rheumatic diseases]. / Schwangerschaft bei rheumatischen Erkrankungen.

Inflammatory rheumatic diseases preferentially affect women of childbearing age. Immunological alterations can have positive or negative effects on the maternal disease. Most of these women can have a successful pregnancy with careful medical and obstetric care. Nevertheless, complications are more frequent than in healthy women. Pregnancies should therefore be planned during inactive phases of the disease and patients should be educated in advance about possible maternal and child risks and about treatment options compatible with pregnancy. In pregnancy, individualized and interdisciplinary care can promote a stable course of the disease and reduce the risks for mother and child. Especially with respect to a compatible treatment, detailed information for the patients is necessary for a shared decision making.

Successful conception in a 34-year-old lupus patient following spontaneous pregnancy after autotransplantation of cryopreserved ovarian tissue.

Premature gonadal failure is a common problem in patients with systemic lupus erythematosus (SLE) when gonadotoxic therapies are applied. The preservation of gonadal function and fertility is of great importance to many predominantly young SLE patients. Some fertility preservation methods are well established and well known, whereas others are considered more cautiously. In particular, the cryopreservation of ovarian tissue is a rarely chosen fertility preservation option for SLE patients of (pre)fertile age. We report the first case of successful conception and pregnancy of an SLE patient after autotransplantation of cryopreserved ovarian tissue. A 26-year-old SLE patient decided to undergo cryopreservation of ovarian tissue when receiving cyclophosphamide for lupus nephritis. Tissue removal, preparation, cryopreservation and quality control was performed, as described, according to current state-of-the-art techniques. After 6 years of being in remission using azathioprine and belimumab, her ovarian tissue was autotransplanted because of premature ovarian failure, diagnosed at the age of 32, and a wish to conceive. She conceived spontaneously 8 months later, having a diamniotic-dichoriotic twin pregnancy. The children were born prematurely due to preterm premature rupture of membranes in the 32nd week of gestation; mother and children are doing very well 8 months later. We regard the procedure to be an option worth consideration for our predominantly young SLE patients.

[Hair anomalies in syndromic disorders]. / Haaranomalien bei syndromalen Erkrankungen.

Genetic diseases with hyper- and hypotrichosis are very heterogeneous, both clinically and genetically. This is especially true for ectodermal dysplasias but also for hereditary syndromes in which, beyond abnormal hair growth, other structures and organs are affected. In this review, we discuss distinct diseases with excessive and reduced hair growth, focusing on the clinical hallmarks and underlying genetic defects.

[State of the art: systemic lupus erythematosus]. / State of the Art: systemischer Lupus erythematodes.

As long as we cannot cure diseases such as systemic lupus erythematosus (SLE), it must be our goal that people with SLE can live a largely normal life. It should not be dominated by the disease. The main goal is secondary prevention, i. e. the prevention of harm. In 2020 we want to make a better contribution to this aim. For this article on SLE, being fit for 2020 therefore means applying the basic concepts of care for patients with SLE on a regular basis. The focus is on the new concepts resulting from the new classification criteria, the optimized basic care (BASIC), the complex communication with those affected, the new EULAR recommendations for monitoring SLE, the integration of biologics into the treatment regimen, the targeted therapy (T-2-T) and thus the criteria low disease activity and remission, the question of new care structures for rare and complex systemic diseases and finally the outlook on future treatment concepts, the basis of which we will all create in the coming years. If we consistently apply the current options, we will be able to further improve the life situation and quality of life of those affected even without newly approved drugs.

[Determinants of health-related quality of life in systemic lupus erythematosus: a monocentric, retrospective long-term observational study in Germany]. / Determinanten gesundheitsbezogener Lebensqualität bei systemischem Lupus erythematodes: eine monozentrische, retrospektive Langzeitobservationsstudie in Deutschland.

BACKGROUND: Improvement of health-related quality of life (HRQoL) is a prioritized treatment target in systemic lupus erythematosus (SLE). A retrospective chart review of patients with repeated HRQoL measurements from the outpatient department was conducted in order to better understand which factors drive HRQoL in established SLE. Of particular interest was the association between HRQoL and disease activity. METHODS: The medical outcomes study short form 36 (SF-36), systemic lupus activity measure (SLAM) and routine clinical data of 169 patients (83% female, mean age 40.3 ± 13 years, disease duration 9.4 ± 7 years) over an average of 7.1 ± 4.2 years were available for analysis by linear mixed modelling. Factors associated with the physical component summary (PCS) and mental component summary (MCS) of the SF-36 were assessed. The proportion of HRQoL which could be explained by the variables was estimated by marginal R2 (mR2) and conditional R2 (cR2). RESULTS: At baseline, SLE patients showed a reduced HRQoL in all subscales of the SF-36 including PCS and MCS with the exception of vitality. A higher PCS over time was significantly associated with concurrent parameters, such as intake of antimalarial drugs, no glucocorticoid use, less fatigue, lower disease activity as well as to the baseline parameters of younger age and higher PCS (mR2 54.7%, cR2 59.9%). A higher MCS was associated with concurrent use of glucocorticoids and a higher baseline MCS (mR2 21.7%, cR2 25.1%). CONCLUSION: The use of antimalarial drugs and no glucocorticoid intake as well as low current disease activity are modifiable factors associated with a better physical HRQoL. The mental component of HRQoL was poorly represented by conventional parameters and not associated with parameters of disease activity in the present study cohort.

Medical adherence in patients with systemic lupus erythematosus in Germany: predictors and reasons for non-adherence - a cross-sectional analysis of the LuLa-cohort.

Objective Adherence to medication has a major impact on treatment control and success especially in chronic diseases but often remains unrecognized. Besides clinical, socioeconomic, disease-related and treatment-related parameters, general and personal health beliefs, as well as perception of health, can affect adherence. Our aim was to investigate the adherence to lupus-specific medications in German lupus patients and to assess influencing factors including detrimental or beneficial effects of health perceptions and beliefs. Methods The Lupus Erythematosus (LE) Long-Term Study (LuLa-study) is a nationwide longitudinal study among German Caucasian patients with systemic lupus erythematosus who have been assessed annually using a self-reported questionnaire since 2001. In 2013, we included questions concerning medical adherence (Morisky Medication Adherence Scale; MMAS-4), beliefs about medication prescribed (BMQ), illness perception and about the patients' health locus of control (HLC). We present a cross-sectional analysis to assess predictors of adherence using a multivariable stepwise logistic regression. Results Five hundred and seventy-nine patients participated, 81 of whom did not take any lupus-specific medication and 40 of whom did not complete the MMAS-4 and were therefore omitted. Only 62.7% reported high adherence. Unintentional behaviour for low medical adherence exceeded the intentional behaviour by far. The use of azathioprine (OR: 1.85; 95% CI: 1.02-3.34), prednisone <7.5 mg (OR: 1.56; 95% CI: 0.97-2.49), a higher age (OR: 1.06; 95% CI: 1.03-1.08) and higher external HLC (OR: 1.15; 95% CI: 1.01-1.30) proved conducive for high adherence in our multivariable model. On the contrary, the general perception of medication being harmful or addictive (OR: 0.89; 95% CI: 0.82-0.97) was detrimental. Conclusion A low belief that one's own health is determined by healthcare providers (external HLC) and the belief of the harmfulness of medication were independent predictors of low adherence besides age and the choice of the medical agent. The recognition of these potential obstacles in physician-patient relationships is essential to ameliorate adherence. Provision of sufficient information and education might help to reach the best possible outcome.

[Sexuality in adolescents with rheumatic diseases : Contraception, HPV vaccination and pregnancy]. / Sexualität bei Jugendlichen mit rheumatischen Erkrankungen : Verhütung, HPV-Impfung und Schwangerschaft.

Young patients and adolescents with chronic rheumatic diseases have the same desires, fears and needs in terms of sexuality and pregnancy as their healthy peers. In most cases adolescents are already sexually active before transition from pediatric to adult rheumatological care takes place. Pregnancies in women with rheumatic diseases are associated with increased maternal and fetal risks, especially when they occur unplanned in the course of active disease or under teratogenic drugs. Safe contraception is therefore crucial in preventing unwanted pregnancies. The choice of contraception should anticipate the safety of the method of contraception as well as age-dependent practicability. A strategy of "double protection" through the use of condoms for contraception and prevention of sexually transmitted diseases combined with another safe contraception method should be recommended. Women with rheumatic diseases are more susceptible to acquire persisting human papilloma virus (HPV) infections and the subsequent progression to cervical cancer. In women with rheumatic diseases HPV vaccination induces high seroconversion rates, is safe and does not seem to induce disease activity. The care of adolescent women with rheumatic diseases before, during and after medical transition needs to encompass an open, early and continuous counselling regarding these topics in order to retain the individual health-related quality of life and to adapt this care to age-specific needs.

[Safety and efficacy of off-label use of biologic therapies in patients with inflammatory rheumatic diseases refractory to standard of care therapy : Data from a nationwide German registry (GRAID2)]. / Sicherheit und Wirksamkeitshinweise zum Off-label-Einsatz von Biologikatherapien nach Versagen konventioneller Therapien bei Patienten mit entzündlich rheumatischen Erkrankungen : Ergebnisse eines nationalen Registers (GRAID2).

BACKGROUND: The German Registry of Autoimmune Diseases 2 (GRAID2) is a retrospective, non-interventional, multicenter registry study collecting data from patients with inflammatory, mainly rheumatic diseases refractory to standard of care therapy and treated with an off-label biologic therapy. The retrospective documentation comprised case history, diagnosis, course of disease (including safety and global efficacy). The objective was to evaluate the global clinical outcome and safety of off-label biologic therapy in clinical practice. RESULTS: Data from 311 patients with an overall observation period of 338.5 patient-years were collected. The mean patients age was 47.8 years with 56.9% females. The most frequently documented diagnoses comprised rejection prophylaxis/therapy after renal transplantation (NTX, 18.3%), ANCA-vasculitides (17.4%), systemic lupus erythematosus (SLE, 10.3%), autoinflammatory fever syndromes (8.4%), autoimmune myositis (7.4%) and pemphigus (5.8%). Documented biologic therapies included rituximab (RTX, 70.1%), tocilizumab (TCZ, 9.3%), infliximab (IFX, 7.1%), anakinra (ANK, 5.5%), adalimumab (ADA, 3.5%), etanercept (ETA, 2.3%) and certolizumab (CTZ, 0.6%). After initiation of off-label biologic treatment, tolerability was assessed by the physicians as "very good"/"good" in 95.5%. Altogether, 275 adverse events were documented and of these, 104 were classified as serious adverse events and occurred in 62 patients. In 19 of these patients severe infections (30.6%) were documented, resulting in a rate of 5.6 severe infections per 100 patient years. A total of six deaths were documented, while five of these cases were rated as not related to the biologics treatment. Notably, the use of RTX in patients with small vessel vasculitides and of TCZ in patients with large vessel vasculitides prior to their approval support their relevance in clinical management of patients with severe diseases. CONCLUSION: The results of this registry together with data of GRAID1 provide evidence that use of off-label biologic therapies in patients with inflammatory rheumatic diseases refractory to conventional treatment did not result in any new safety signal already known for these compounds or subsequently shown by clinical trials in certain entities.

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.

[Tapering and termination of immunosuppressive therapy : Systemic lupus erythematosus]. / Ausschleichen und Beenden von immunsuppressiven Therapien : Systemischer Lupus erythematodes.

Similar to patients with other rheumatic diseases, patients with systemic lupus erythematosus (SLE) nowadays can also have the desire to terminate immunosuppressive and immunomodulatory medications. In order to provide appropriate advice to patients, the two main issues are the risk of severe adverse events under long-term therapy with any drug and the perceived risk of a flare, in particular of severe flares. The risks of long-term therapy vary greatly between drugs, ranging from severe unacceptable risks with cyclophosphamide and higher dose glucocorticoids to low risks usually outweighed by long-term benefits with hydroxychloroquine. The individual risk of flares is often difficult to estimate but clinical remission and at least 3 years of immunosuppression are recommended for lupus nephritis. The duration of remission can also be shorter in cases of milder forms of disease. This review article tries to put the available evidence into a clinical perspective and to derive concrete recommendations.

Multiparametric detection of autoantibodies in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a heterogeneous disease with respect to disease manifestations, disease progression and treatment response. Therefore, strategies to identify biomarkers that help distinguishing SLE subgroups are a major focus of biomarker research. We reasoned that a multiparametric autoantibody profiling approach combined with data mining tools could be applied to identify SLE patient clusters. We used a bead-based array containing 86 antigens including diverse nuclear and immune defense pathway proteins. Sixty-four autoantibodies were significantly (p < 0.05) increased in SLE (n = 69) compared to healthy controls (HC, n = 59). Using binary cut-off thresholds (95% quantile of HC), hierarchical clustering of SLE patients yields five clusters, which differ qualitatively and in their total number of autoantibodies. In two patient clusters the overall accumulated autoantibody reactivity of all antigens tested was 31% and 48%, respectively. We observed a positive association between the autoantibody signature present in these two patient clusters and the clinical manifestation of glomerulonephritis (GLMN). In addition, groups of autoantibodies directed against distinct intracellular compartments and/or biological motifs characterize the different SLE subgroups. Our findings highlight the relevant potential of multiparametric autoantibody detection and may contribute to a deeper understanding of the clinical and serological diversity of SLE.

Isolated recessive nail dysplasia caused by FZD6 mutations: report of three families and review of the literature.

Congenital abnormalities of the nail are rare conditions that are most frequently associated with congenital ectodermal syndromes involving several of the epidermal appendages including the skin, teeth, hair and nails. Isolated recessive nail dysplasia (IRND) is much rarer but has recently been recognized as a condition resulting in 20-nail dystrophy in the absence of other cutaneous or extracutaneous findings. A few case reports have identified mutations in the Frizzled 6 (FZD6) gene in families presenting with abnormal nails consistent with IRND. These reports have highlighted the role of Wnt-FZD signalling in the process of nail formation. We report three families presenting with features of IRND, in whom we identified mutations in FZD6, including one previously unreported mutation.

[Standards of care for people with rheumatoid arthritis in Europe : Translation and comments of the eumusc.net recommendations supported by EULAR performed by a national task force of the professional organisations DGRh and VRA supported by "Deutsche Rheumaliga"]. / Europäische Versorgungsstandards für Menschen mit rheumatoider Arthritis : Übersetzung und Kommentierung der von der EULAR unterstützten Vorschläge des eumusc.net durch eine Task Force von DGRh und VRA mit Unterstützung der Deutschen Rheuma-Liga.

In a joint initiative by the boards of the German Society for Rheumatology (DGRh) and the Association of Rheumatology Clinics (VRA) the European "standards of care" for rheumatoid arthritis, recently suggested by the European Musculoskeletal Conditions Surveillance and Information Network (eumusc.net) and supported by the European League Against Rheumatism (EULAR), were translated and annotated. The recommendations include aspects of the management of the disease, actual medical care, and access to information - this includes all types of support people with RA need, and, last but not least communication of the necessary knowledge. Furthermore, health care structures such as the availability of medical staff with relevant expertise are also important.