Perceived influence of health status on sexual activity in patients with psoriatic arthritis.

Objective: To examine the prevalence of self-reported problems with sexual activity among psoriatic arthritis (PsA) patients, and to explore potential associations of such problems with various demographic, musculoskeletal, and dermatological disease variables. Method: Consecutive PsA patients were recruited from an outpatient clinic. Data collected included demographics, measures of musculoskeletal and skin disease activity, and treatments. Perceived effect of health status on sexual activity was assessed using question number 15 from the health-related quality of life instrument 15D; this was explored in univariate and multivariate logistic regression analyses. Results: The study assessed 135 patients (mean age 52.1 years, disease duration 8.7 years, 51.1% male). Mean scores included Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) 2.9, Disease Activity index for PSoriatic Arthritis (DAPSA) 18.2, patient global assessment (PGA) 36.0 mm, pain 33.7 mm, fatigue 45.1 mm, modified Health Assessment Questionnaire (mHAQ) 0.42, Psoriasis Area Severity Index (PASI) 2.5, and Dermatology Life Quality Index (DLQI) 3.4. Twenty-four patients (17.8%) reported that their health status had a large negative effect and 111 (82.2%) that it had no or little effect on their sexual activity. In univariate analyses, a statistically significant association with impaired sexual activity was found for longer disease duration and higher MASES, DAPSA, PGA, fatigue, and mHAQ scores, but not for demographic variables or variables reflecting skin psoriasis involvement (PASI, DLQI). In adjusted analyses, only PsA disease duration remained independently associated with impaired sexual activity. Conclusion: One in five PsA patients perceived that their health status had a negative impact on sexual activity. Disease duration and measures reflecting musculoskeletal involvement, but not measures reflecting skin psoriasis involvement, appeared to be associated with impaired sexual activity.

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.

Exploring the relationship between demographic and disease-related variables and perceived effect of health status on sexual activity in patients with axial spondyloarthritis: associations found only with non-disease variables.

OBJECTIVE: To explore the relationship between demographic and disease-related variables and the perceived effect of health status on sexual activity in patients with axial spondyloarthritis (ax-SpA). METHOD: The study assessed 379 ax-SpA patients consecutively recruited from two rheumatology outpatient clinics. Data collection included information on demographics, markers and measures of ax-SpA disease, treatment, comorbidity, and health-related quality of life (HRQoL) using the Short Form-36. The perceived effect of health status on sexual activity was assessed using question 15 in the HRQoL instrument 15D. RESULTS: The mean age of the patients was 45.6 years, 66.5% were men, 87.3% were human leucocyte antigen-B27 positive, and mean disease duration was 13.9 years. A total of 312 patients (82.3%) reported their health status to have no/little effect and 17.7% patients reported their health status to have a large negative effect on their sexual activity. In univariate analysis, increased body mass index (BMI), smoking, alcohol consumption, unemployed status, low physical activity, comorbidities, and higher disease activity (Bath Ankylosing Spondylitis Questionnaire), impaired body movement and lower HRQoL were associated with a large effect on sexual activity. In adjusted analyses, only female gender, high BMI, current smoking, and low HRQoL showed significant associations. CONCLUSION: Approximately 20% of ax-SpA patients reported a large negative effect on their sexual activity. Female gender, high BMI, current smoking, and reduced HRQoL were associated with health status having a large effect on sexual activity, whereas no measures reflecting ax-SpA disease showed an independent association.

Gonadal function in male patients with ankylosing spondylitis.

OBJECTIVE: To assess reproductive function in male ankylosing spondylitis (AS) patients in comparison to healthy controls. METHODS: Twenty AS patients were compared to 24 healthy male subjects with regard to demographic data, urological examination, testicular ultrasound (US), semen analysis, anti-sperm antibodies, and hormone profile. Exclusion criteria were present use of sulfasalazine or methotrexate, and ever use of biological/cytotoxic agents. Disease activity of AS was evaluated by clinical and laboratory assessments. RESULTS: Demographic data were similar in AS and controls (p = 0.175). Varicocele was found significantly more frequently in AS patients than in controls (40% vs. 8%, p = 0.027). Semen analysis revealed no significant differences in sperm quality between AS patients and controls (p > 0.05). By contrast, the median of normal sperm forms was significantly lower in AS patients with vs. those without varicocele [13.5 (range 2-27) vs. 22 (range 10-32.5)%, p = 0.049] whereas no difference in sperm morphology was observed comparing AS patients and controls without varicocele (p = 0.670). Comparison of AS patients with and without varicocele showed that anti-sperm antibodies, hormones, inflammatory markers, and disease activity scores did not contribute to the impaired sperm morphology observed in AS patients with varicocele. CONCLUSIONS: An increased frequency of varicocele was found in AS patients associated with sperm abnormalities but independent of therapy, anti-sperm antibodies, hormonal alterations, or disease parameters. Investigation for varicocele should be routine in AS patients with fertility problems.

Pregnancy induces numerical and functional changes of CD4+CD25 high regulatory T cells in patients with rheumatoid arthritis.

OBJECTIVE: In a prospective study we investigated whether numerical and functional changes of CD4+CD25(high) regulatory T cells (Treg) were associated with changes of disease activity observed during pregnancy and post partum in patients with rheumatoid arthritis (RA). METHODS: The frequency of CD4+CD25(high) T cells was determined by flow cytometry in 12 patients with RA and 14 healthy women during and after pregnancy. Fluorescence-activated cell sorting (FACS) was used to sort CD4+CD25(high) T cells and CD4+CD25- T cells were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies alone or in co-culture to investigate proliferation and cytokine secretion. RESULTS: Frequencies of CD4+CD25(high) Treg were significantly higher in the third trimester compared to 8 weeks post partum in patients and controls. Numbers of CD4+CD25(high) Treg inversely correlated with disease activity in the third trimester and post partum. In co-culture experiments significantly higher amounts of IL10 and lowered levels of tumour necrosis factor (TNF)alpha and interferon (IFN)gamma were found in supernatants of the third trimester compared to postpartum samples. These findings were independent from health or disease in pregnancy, however postpartum TNFalpha and IFN gamma levels were higher in patients with disease flares. CONCLUSION: The amelioration of disease activity in the third trimester corresponded to the increased number of Treg that induced a pronounced anti-inflammatory cytokine milieu. The pregnancy related quantitative and qualitative changes of Treg suggest a beneficial effect of Treg on disease activity.

Interaction between rheumatoid arthritis and pregnancy: correlation of molecular data with clinical disease activity measures.

OBJECTIVE: The factors that induce remission of RA during pregnancy and the relapse occurring after delivery remain an enigma. In a previous study, we investigated gene-expression profiles of peripheral blood mononuclear cells (PBMC) in patients with RA and healthy women in late pregnancy and postpartum. Profiles of samples from both groups were similar in late pregnancy with elevated monocyte and decreased lymphocyte signatures. Postpartum, in RA PBMC the high level of monocyte transcripts persisted. Further increase was observed in adhesion, migration and signalling processes related to monocytes but also in lymphocytes despite similar clinical activity due to intensified drug treatment. This prompted us to investigate correlations between clinical parameters of disease activity and gene profiles. METHODS: Transcriptome data were correlated with RADAI, CRP, monocyte and lymphocyte counts. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotations, monocytes and lymphocytes signatures were used as reference information. RESULTS: Comparative analysis of PBMC expression profiles from RA patients during and after pregnancy with RADAI and CRP revealed a correlation of these disease activity parameters predominantly with monocyte transcripts. Genes related to cellular programs of adhesion, migration and response to infections were upregulated. Comparing clinically active and not-active RA patients postpartum revealed a cluster of 19 genes that could also identify active disease during pregnancy. CONCLUSION: The data suggest that an increase of the RADAI and an elevation of CRP is a consequence of molecular activation of monocytes. Furthermore, they indicate that molecular activation of T lymphocytes may remain clinically unrecognized postpartum. It is conceivable that a set of 19 genes may qualify as molecular disease activity marker.

Update on safety during pregnancy of biological agents and some immunosuppressive anti-rheumatic drugs.

A consensus paper concerning the interaction of anti-rheumatic drugs and reproduction was published in 2006, representing data collected during the year 2004 and 2005. Because of an increasing use of biological agents in women of fertile age, the information was updated for the years 2006 and 2007. Experts disagree whether TNF-inhibitors should be stopped as soon as pregnancy is recognized or may be continued throughout pregnancy. Pregnancy experience with abatacept and rituximab is still too limited to prove their safety for the developing fetus. They must be withdrawn before a planned pregnancy. LEF has not been proven to be a human teratogen. Registries of transplant recipients have shown that cyclosporin (CsA) and tacrolimus do not increase the rate of congenital anomalies, whereas mycophenolate mofetil (MMF) clearly carries a risk for congenital anomalies. Prophylactic withdrawal of drugs before pregnancy is mandatory for abatacept, rituximab, LEF and MMF. Data remain insufficient for gonadal toxicity of immunosuppressive drugs in men and for excretion of these drugs in human breast milk.

Paternal exposure to antirheumatic drugs-What physicians should know: Review of the literature.

Reproduction capacity and long-term preserved hormonal function are important aspects with big impacts on patients' quality of life. Updated information on the interaction between drug therapy and reproductive function is essential when discussing family planning with patients. Currently, limited data is published regarding paternal exposure to different medications. Thus, it may be a challenge for the practitioner to choose the right therapy for a young male patient. Therefore we reviewed the literature, for effects of antirheumatic drugs on male gonadal function with a focus on spermatogenesis and offspring.

Enhancing the care of women with rheumatic diseases during pregnancy: challenges and unmet needs in the Middle East.

Pregnancy in women with rheumatic disorders is known to be associated with risks for both the mother and fetus; however, these risks can be minimized with proper planning and careful management of the disease. In the Middle East, there are specific cultural challenges that may have a negative impact on the care that women with rheumatic disorders receive. There is a need for cross-collaboration between specialist physicians, improved awareness of rheumatic disorders among the general public and more open discussion with patients about the potential complications of pregnancy. Women in the region are often unwilling to discuss their disease with their partner and are even less likely to seek advice regarding family planning from their physician. The objective of this review is to highlight the specific challenges of pregnancy management and to discuss why establishing specialist pregnancy clinics for women with rheumatic disorders could be an effective solution. Such clinics can provide high quality care before, during and after pregnancy as shown in several European and US centers. Additionally, such clinics could be useful for the collection of pregnancy outcomes data from the Middle East, which may currently be lacking in the region, in order to highlight where further improvements can be made. With specialist care and analysis of pregnancy outcomes, the standard of care for women with rheumatic disorders in this area could be significantly improved.

Ankylosing spondylitis and pregnancy.

In contrast to what is known for RA, pregnancy does not improve the symptoms of AS. The majority of women with AS has unchanged or temporarily aggravated disease activity during pregnancy. AS associated with other inflammatory states like psoriasis, IBS, or peripheral small joint arthritis, may benefit from pregnancy. Women with AS can expect to have the same rate of fertility, course of pregnancy, and normal delivery as the healthy female population. In general, female AS patients have healthy babies. However, the chance for their offspring to develop AS later in life is slightly increased.

Pregnancy and rheumatoid arthritis.

Amelioration of rheumatoid arthritis (RA) occurs in about three quarters of pregnancies. Most women who improve experience initial relief in the first trimester. RA almost invariably recurs within 3 to 4 months of delivery. The effect of pregnancy upon the risk of first developing RA is similar in some respects but also differs from that observed in women with established disease. Analogous to women with established disease, the chance of a woman first developing RA is significantly reduced during pregnancy but increased in the first year post partum; thereafter risk is decreased. There is no indication of any adverse effects of RA on pregnancy outcome. Although limited, some medications can be used during pregnancy and during lactation without jeopardizing the well-being of the fetus.

Sex hormones and pregnancy in rheumatoid arthritis and systemic lupus erythematosus.

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are autoimmune disorders with a preponderance in females. RA and SLE differ in their response to sex hormones. Disease development of RA is mitigated by estrogen and pregnancy whereas SLE tends to flare during pregnancy and in response to estrogen. Pregnancy improves the symptoms of RA in about 75% of pregnant patients, but relapses within six months postpartum in 90% of cases. RA is regarded as a T cell-mediated and TH1 immune response-driven disease. Pregnancy induces a shift from TH1 to TH2 immune response, increasing the anti-inflammatory cytokines IL-4 and IL-10, which may contribute to gestational amelioration of RA. Prospective studies of SLE pregnancies indicate that about 50% of patients experience a flare, however, with no permanent aggravation of the disease. Lupus nephritis, presence of antiphospholipid antibodies, and a previous history of pregnancy loss increase the risk of complications during pregnancy and fetal loss. The marked increase of estrogen and progesterone during pregnancy seems to enhance some of the manifestations of SLE. The shift to a TH2 immune response may trigger SLE manifestations that are dependent on humoral immune responses such as lupus nephritis. Another factor stimulating immune responses is the pituitary hormone prolactin, which has been found elevated in SLE patients of both sexes and correlated to disease activity in several studies. The hyperprolactinemia of lactation seems to influence postpartum behavior of SLE as well as RA.

Treatment of inflammatory rheumatic disorders in pregnancy: what are the safest treatment options?

The interaction of pregnancy and the rheumatic diseases varies, ranging from life-threatening conditions such as thromboembolic events and progressive renal disease in some autoimmune disorders, to minor flares of peripheral arthritis in inflammatory rheumatic disease. As a consequence, treatment strategy will vary according to the maternal or fetal compromise expected. All nonsteroidal anti-inflammatory drugs (NSAIDs), including high dose aspirin (acetylsalicylic acid), can cause adverse effects during pregnancy related to the inhibition of prostaglandin synthesis. Prolongation of gestation and labour, constriction of the ductus arteriosus, persistent fetal circulation, impairment of renal function and bleeding are risks of third trimester exposure of pregnant women to all inhibitors of cyclo-oxygenase. Most of these adverse effects can be prevented by discontinuing NSAIDs 8 weeks prior to delivery. Low dose aspirin has not been associated with fetal or neonatal toxicity. Some corticosteroids such as prednisone and prednisolone do not readily cross the placenta and can be safely used during pregnancy as immunosuppressive drugs. Maternal complications related to corticosteroids may occur and close monitoring is therefore mandatory. There is limited information on the safety of disease-modifying antirheumatic drugs including gold, antimalarials, penicillamine (D-penicillamine), sulfasalazine and cyclosporin. Of these agents, sulfasalazine has the best record for tolerability and can be used by pregnant patients. Gold compounds and penicillamine should be discontinued when pregnancy is recognised. Hydroxychloroquine has not been associated with congenital malformations and seems preferable to chloroquine in patients requiring treatment with antimalarials. Use of cyclosporin may be an alternative to other therapy in pregnant patients with severe rheumatic disease. Indications for treatment with colchicine during pregnancy are few, except for familial Mediterranean fever. Azathioprine can be used when the maternal condition requires a cytotoxic drug during the first trimester. Cyclophosphamide, chlorambucil and methotrexate are contraindicated during pregnancy because of their teratogenic potential. Their use may be considered in late pregnancy if the mother has a life-threatening condition.

Ankylosing spondylitis and pregnancy.

The pregnancy-induced remission typical of RA does not seem to occur in pregnant women with AS. The mechanisms for this difference are not understood, but appear to be related to different pathogenetic mechanisms operating in the two diseases. The vast majority of women with ankylosing spondylitis can expect to have the same rate of fertility, course of pregnancy and birth, and to give birth to normal healthy babies to the same extent as the normal female population. The chance for the offspring to contract AS later in life is somewhat increased.

Drugs in pregnancy. Rheumatological disorders.

Rheumatic diseases occur frequently in women of childbearing years, necessitating drug treatment during a concurrent pregnancy in order to control maternal disease activity and to ensure a successful pregnancy outcome. Inflammatory rheumatic diseases with mainly musculoskeletal involvement may cause acute episodes of arthritis. Autoimmune, systemic diseases may flare with manifestations of haematological, dermatological or renal disease or give rise to thromboembolism during pregnancy. Treatment with non-steroidal anti-inflammatory drugs, corticosteroids, anticoagulants, immunosuppressive or even cytotoxic drugs may be required to acquire disease control. Unfortunately, controlled studies on the use of antirheumatic drugs during gestation exist only for a few drugs. This chapter presents data on the use of antirheumatic drugs during pregnancy, addressing the risk of teratogenicity, possible long-term effects on the infant exposed to drugs antenatally, and maternal side-effects which interfere with pregnancy. Recommendations for pre-pregnancy counselling and necessary adjustment of drug treatment before and during pregnancy are given.

[Antirheumatic therapy and reproduction. The influence on fertility, pregnancy and breast feeding]. / Antirheumatische Therapie und Reproduktion. Einfluss auf Fertilität, Schwangerschaft und Stillzeit.

Antirheumatic drugs can have a negative effect on reproduction in both men and women. Possible negative effects are impairment of fertility, harmful effects on the fetus and adverse effects on the breastfed child. In women non-steroidal antiinflammatory drugs (NSAID) and cyclophosphamide can impair fertility. In men infertility can result from the use of salazopyrine and cyclophosphamide. A desire for children should be taken into account before the start of disease modifying drugs (DMARD). Treatment with NSAID is possible at some stages of pregnancy as well as during lactation. A limited number of DMARD is compatible with pregnancy and is presented. Cytostatic drugs and leflunomide must be prophylactically withdrawn before a planned pregnancy. TNF alpha antagonists should be discontinued at the start of pregnancy. Safe birth control must be practised during therapy with drugs that are gonadotoxic or teratogenic. Treatment with immunosuppressive drugs during lactation is limited because of insufficient documentation of safety for the breastfed child.