Patient-reported outcomes before treatment for localized prostate cancer: are there differences among countries? Data from the True North Global Registry.

INTRODUCTION: Similar Patient-Reported Outcomes (PROs) at diagnosis for localized prostate cancer among countries may indicate that different treatments are recommended to the same profile of patients, regardless the context characteristics (health systems, medical schools, culture, preferences…). The aim of this study was to assess such comparison. METHODS: We analyzed the EPIC-26 results before the primary treatment of men diagnosed of localized prostate cancer from January 2017 onwards (revised data available up to September 2019), from a multicenter prospective international cohort including seven regions: Australia/New Zealand, Canada, Central Europe (Austria / Czech Republic / Germany), United Kingdom, Italy, Spain, and the United States. The EPIC-26 domain scores and pattern of three selected items were compared across regions (with Central Europe as reference). All comparisons were made stratifying by treatment: radical prostatectomy, external radiotherapy, brachytherapy, and active surveillance. RESULTS: The sample included a total of 13,483 men with clinically localized or locally advanced prostate cancer. PROs showed different domain patterns before treatment across countries. The sexual domain was the most impaired, and the one with the highest dispersion within countries and with the greatest medians' differences across countries. The urinary incontinence domain, together with the bowel and hormonal domains, presented the highest scores (better outcomes) for all treatment groups, and homogeneity across regions. CONCLUSIONS: Patients with localized or locally advanced prostate cancer undergoing radical prostatectomy, EBRT, brachytherapy, or active surveillance presented mainly negligible or small differences in the EPIC-26 domains before treatment across countries. The results on urinary incontinence or bowel domains, in which almost all patients presented the best possible score, may downplay the baseline data role for evaluating treatments' effects. However, the heterogeneity within countries and the magnitude of the differences found across countries in other domains, especially sexual, support the need of implementing the PRO measurement from diagnosis.

Pulmonary arterial hypertension: guidelines and unmet clinical needs.

The term pulmonary arterial hypertension (PAH) identifies a heterogeneous group of diseases characterized by a progressive increase in pulmonary arterial resistance (PVR), which causes a significant burden in terms of quality of life, right heart failure and premature death. The pathogenesis of PAH is not completely clear: the remodeling of the small pulmonary vessels is crucial, causing an increase in the resistance of the pulmonary circle. Its diagnosis is based on cardiac catheterization of the right heart. According to the present hemodynamic definition of pulmonary hypertension (PH) proposed by the Guidelines of the European Society of Cardiology/European Respiratory Society (ESC-ERS), the mean pulmonary arterial pressure (mPAP) values are ≥25 mmHg. In case of PAH, apart from an mPAP value ≥25 mmHg, patients must have a >3 Wood units increase in PVR and normal pressure values of the left heart. PH is a pathophysiological condition observed in more than 40 different diseases, while PAH is a primary disease of the pulmonary bloodstream potentially treatable with specific drugs. PAH is a severe complication of systemic sclerosis (SSc) affecting about 10% of the patients. Due to the devastating nature of SSc-PAH, there is a clear need to systematically adopt appropriate screening programs. In fact, despite awareness of the negative impact of SSc-PAH on quality of life and survival, as well as on the severity of lung function, at the moment standardized and shared guidelines and/or screening programs for the diagnosis and the subsequent early treatment of PAH in SSc are not available. The aim of the present paper is to highlight the lights and shadows of SSc-PAH, unraveling the unmet clinical needs on this topic with a proposal of clinical-diagnostic and therapeutic guidelines.

Cardiopulmonary assessment of patients with systemic sclerosis for hematopoietic stem cell transplantation: recommendations from the European Society for Blood and Marrow Transplantation Autoimmune Diseases Working Party and collaborating partners.

Systemic sclerosis (SSc) is a rare disabling autoimmune disease with a similar mortality to many cancers. Two randomized controlled trials of autologous hematopoietic stem cell transplantation (AHSCT) for SSc have shown significant improvement in organ function, quality of life and long-term survival compared to standard therapy. However, transplant-related mortality (TRM) ranged from 3-10% in patients undergoing HSCT. In SSc, the main cause of non-transplant and TRM is cardiac related. We therefore updated the previously published guidelines for cardiac evaluation, which should be performed in dedicated centers with expertize in HSCT for SSc. The current recommendations are based on pre-transplant cardiopulmonary evaluations combining pulmonary function tests, echocardiography, cardiac magnetic resonance imaging and invasive hemodynamic testing, initiated at Northwestern University (Chicago) and subsequently discussed and endorsed within the EBMT ADWP in 2016.

Total and beverage-specific alcohol intake and the risk of aggressive prostate cancer: a case-control study.

BACKGROUND: Ethanol in alcoholic beverages is a known carcinogen, but its association with aggressive prostate cancer (APC) is uncertain. Recent studies have shown a modest increase in risk of APC associated with heavy alcohol intake while association for beverage types remain inconsistent. METHODS: Using a case-control design and self-administered questionnaire, we examined the association between APC (high grade and/or advanced stage) and frequency and quantity of alcohol intake 2 years prior to enrolment. Furthermore, we delineated the relationships for beverage-specific intakes of beer, red wine, white wine and spirits. RESULTS: The study included 1282 APC cases and 951 controls. Beer intake frequency of ⩾5 days per week was associated with increased risk compared with no beer intake (odds ratio=1.66, 95% confidence interval: 1.12-2.48) whereas wine was protective at all frequencies of consumption compared with those with no wine intake. For every 10 g per week ethanol intake from beer increase, the odds of advanced PC rose by 3% (OR=1.03, 95% CI: 1.02-1.05). No such increased risk was observed for red or white wine while a marginal dose-response relationship was found for spirits (OR=1.03, 95% CI: 0.99-1.07). CONCLUSIONS: Heavy beer and possibly spirits consumption is associated with increased risk while no dose-response relationship was found for red or white wine. Wine drinkers at all frequencies have a decreased risk of APC compared with those who did not drink wine.

Autologous hematopoietic stem cell transplantation has better outcomes than conventional therapies in patients with rapidly progressive systemic sclerosis.

We retrospectively evaluated the efficacy of autologous hematopoietic stem cell transplantation (AHSCT) in 18 patients with rapidly progressive diffuse cutaneous systemic sclerosis (rp-dcSSc), and compared their disease outcomes with those of 36 demographically- and clinically-matched patients treated with conventional therapies. Cutaneous involvement, by performing modified Rodnan skin score (mRss), lung diffusion capacity, by measuring diffusing capacity of lung for carbon monoxide (DLCO), and disease activity, by applying the European Scleroderma Study Group (ESSG) scoring system, were the outcome variables measured at the baseline time and then every 12 months for the following 60 months in both the AHSCT-treated patients and the control group. In the AHSCT group, treatment-related mortality was 5.6%. In this group, both mRss and ESSG scores showed a significant reduction 1 year after AHSCT (P<0.002); and these results were maintained until the end of follow-up. Conversely, DLCO values remained stable during the whole period of follow-up. Survival rate of AHSCT group was much higher than that observed in the whole control group (P=0.0005). The probability that the ESSG score and mRss would remain at a high level, and DLCO could decrease, was significantly higher in the control group as a whole and in the subgroup of control patients treated with cyclophosphamide than in the AHSCT group. This study confirms that the AHSCT is effective in prolonging survival, as well as in inducing a rapid reduction of skin involvement and disease activity, and preserving lung function in patients with rp-dcSSc.

Detection of Malawi polyomavirus sequences in secondary lymphoid tissues from Italian healthy children: a transient site of infection.

BACKGROUND: The novel Malawi polyomavirus (MWPyV) was initially detected in stool specimens from healthy children and children with gastrointestinal symptoms, mostly diarrhea, indicating that MWPyV might play a role in human gastroenteric diseases. Recently, MWPyV sequences were additionally identified in respiratory secretions from both healthy and acutely ill children suggesting that MWPyV may have a tropism for different human tissues. This study was designed to investigate the possible sites of latency/persistence for MWPyV in a cohort of healthy Italian children. METHODS: Specimens (n° 500) of tonsils, adenoids, blood, urines and feces, from 200 healthy and immunocompetent children (age range: 1-15 years) were tested for the amplification of the MWPyV LT antigen sequence by quantitative real-time PCR. Samples (n° 80) of blood and urines from 40 age-matched children with autoimmune diseases, were screened for comparison. Polyomaviruses JC/BK and Epstein-Barr Virus (EBV) were also tested as markers of infection in all samples using the same molecular technique. RESULTS: In our series of healthy children, MWPyV was detected only in the lymphoid tissues showing a prevalence of 6 % in tonsils and 1 % in adenoids, although with a low viral load. No JCPyV or BKPyV co-infection was found in MWPyV positive samples, while EBV showed a similar percentage of both in tonsils and adenoids (38 and 37 %). Conversely, no MWPyV DNA was detected in stool from babies with gastroenteric syndrome. With regards to autoimmune children, neither MWPyV nor BKPyV were detected in blood, while JCPyV viremia was observed in 15 % (6/40) of children treated with Infliximab. Urinary BKPyV shedding was observed in 12.5 % (5/40) while JCPyV in 100 % of the samples. CONCLUSIONS: The detection of MWPyV sequences in tonsils and adenoids of healthy children suggests that secondary lymphoid tissues can harbour MWPyV probably as transient sites of persistence rather than actual sites of latency.

Does ex vivo CD34+ positive selection influence outcome after autologous hematopoietic stem cell transplantation in systemic sclerosis patients?

This EBMT Autoimmune Disease Working Party study aimed to evaluate the influence of CD34+ positive graft selection (CD34+) on the outcome of systemic sclerosis (SSc) patients after autologous hematopoietic stem cell transplantation (AHSCT). Clinical and laboratory data from 138 SSc patients at diagnosis, before and after AHSCT were retrospectively analyzed. CD34+ selection was performed in 47.1% (n=65) patients. By multivariate analysis adjusting for all factors differing between the two groups (without or with CD34+), there was no statistically significant difference in terms of overall survival (hazard ratio (HR): 0.98, 95% confidence interval (CI) 0.40-2.39, P=0.96), PFS (HR: 1.55, 95% CI 0.83-2.88, P=0.17) and incidence of relapse or progression (HR: 1.70, 95% CI 0.85-3.38, P=0.13). We demonstrate that CD34+ does not add benefit to the outcome of SSc patient treated with AHSCT. These findings should be further confirmed by prospective randomized trials.

Candida growth in urine cultures: a contemporary analysis of species and antifungal susceptibility profiles.

BACKGROUND: Recent publications suggest the distribution of Candida species causing candiduria may vary geographically, which has implications for the continued efficacy of antifungal therapy and emerging resistance. AIM: To investigate the incidence of Candiduria at a university hospital in the UK. Further, to assess the distribution of species and the accompanying antifungal susceptibility profile, in order to monitor the clinical utility of current antifungal treatment guidelines for candiduria so that patients receive the best possible outcomes from the most up to date care. DESIGN: Retrospective audit. METHODS: From 1st January 2005 to 31st October 2014, we retrospectively reviewed 37 538 positive urine cultures recorded in a computerized laboratory results database. Identification and susceptibility testing was performed using the VITEK® 2 fungal susceptibility card (bioMérieux, Marcy d'Etoile, France). RESULTS: In total, 96 cultures were positive for Candida species, of which 69 (72%) were C.albicans, which translates to a prevalence of 2.6 per 1000 positive urine cultures. Candiduria was more common in younger patients, males and catheterized females. We report 94 and 73% of isolates of C.albicans and other non-C.albicans Candida species were susceptible to fluconazole. All isolates were susceptible to amphotericin B. CONCLUSIONS: Our results add weight to the evidence supporting current European and North American guidelines recommending fluconazole or amphotericin B for treatment of candiduria, if antifungal treatment is clinically indicated.

An operational comparative study of quinine and artesunate for the treatment of severe malaria in hospitals and health centres in the Democratic Republic of Congo: the MATIAS study.

BACKGROUND: The Democratic Republic of the Congo (DRC) has the highest number of severe malaria cases in the world. In early 2012, the National Malaria Control Programme (NMCP) changed the policy for treating severe malaria in children and adults from injectable quinine to injectable artesunate. To inform the scaling up of injectable artesunate nationwide, operational research is needed to identify constraints and challenges in the DRC's specific setting. METHODS: The implementation of injectable quinine treatment in 350 patients aged 2 months or older in eight health facilities from October 2012 to January 2013 and injectable artesunate in 399 patients in the same facilities from April to June 2013 was compared. Since this was an implementation study, concurrent randomized controls were not possible. Four key components were evaluated during each phase: 1) clinical assessment, 2) time and motion, 3) feasibility and acceptability, and 4) financial cost. RESULTS: The time to discharge was lower in the artesunate (median=2, 90% central range 1-9) compared to the quinine group (3 (1-9) days; p<0.001). Similarly, the interval between admission and the start of intravenous (IV) treatment (2 (0-15) compared to 3 (0-20) hours; p<0.001) and parasite clearance time (23 (11-49) compared to 24 (10-82) hours; p<0.001) were lower in the artesunate group. The overall staff pre-administration time (13 (6-38) compared to 20 (7-50) minutes; p<0.001) and the personnel time spent on patient management (9 (1-24) compared to 12 (3-52) minutes; p<0.001) were lower in the artesunate group. In hospitals and health centres, the mean (standard deviation, SD) total cost per patient treated for severe malaria with injectable artesunate was USD 51.94 (16.20) and 19.51 (9.58); and USD 60.35 (17.73) and 20.36 (6.80) with injectable quinine. CONCLUSIONS: This study demonstrates that injectable artesunate in the DRC is easier to use and it costs less than injectable quinine. These findings provide the basis for practical recommendations for rapid national deployment of injectable artesunate in the DRC.

Urinary tract infection in infancy is a risk factor for chronic abdominal pain in childhood.

OBJECTIVE: Adverse early life events are key factors for development of functional gastrointestinal disorders (FGIDs). Urinary tract infection (UTI) is associated with chronic pelvic pain in adults, a finding that has been recapitulated in murine models, but the relation between UTI and chronic pelvic and abdominal pain has not been studied in children. We hypothesized that UTI in infancy increases the risk of FGIDs and chronic abdominal pain (CAP) in childhood. METHODS: The present study included children, ages 4 to 18 years, with a single UTI in the first year of life and their siblings with no history of UTI. Parents completed the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III Version (QPGS-III) by telephone. Children meeting QPGS-III criteria for FGIDs but with pain less than once weekly were considered to have CAP. RESULTS: A total of 57 patients with UTI and 58 sibling controls were identified. Mean age at UTI was 4.8 months, and mean time since UTI was 9.3 years. At the time of survey, mean age of patients was 9.7 years (5-16 years, 40% boys) and that of controls was 9.6 years (range 4-17 years, 57% boys). FGIDs were diagnosed in 6 of 57 (11%) patients, and 1 of 58 (2%) controls (P = 0.06). CAP was identified in 10 of 57 (18%) patients and 2 of 58 (3%) controls (P = 0.02). Predominant sex (female), infecting organism (E coli), and treatment (third-generation cephalosporin) were similar in patients with UTI with and without CAP. CONCLUSIONS: We show for the first time that UTI is associated with CAP in childhood. We speculate that pelvic organ sensory convergence explains our findings.

Prospective evaluation of post-implantation inflammatory response after EVAR for AAA: influence on patients' 30 day outcome.

OBJECTIVES: The aim was to prospectively evaluate post-implantation syndrome (PIS) after elective endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAAs) and to investigate its association with clinical and laboratory parameters and the clinical outcome of the patients. METHODS: From January 2010 till June 2013, 214 consecutive patients treated electively by EVAR for AAA were prospectively included. PIS was defined according to systemic inflammatory response syndrome criteria. Adverse events included any major adverse cardiovascular events (MACE), acute renal failure, re-admission and death from any cause. RESULTS: PIS was diagnosed in 77 (34%) patients. Pre-operative white blood cell (WBC) count values (p < .001), endograft material (polyester) (p < .001), and heart failure (p = .03) were independent predictors of PIS. Mean post-operative temperature (p < .001), length of hospital (p < .001) and intensive care unit (p = .008) stay, as well as maximum post-operative WBC count (p < .001) and hs-CRP values (p < .001) were significantly higher in the PIS group. Post-operative hs-CRP (p = .001) and duration of fever (p = .02) independently predicted the occurrence of MACE. Post-operative hs-CRP (p = .004), maximum temperature (p = .03), and the presence of PIS (p = .01) were independent predictors of an adverse event during the first 30 days. A threshold of post-operative hs-CRP value of 125 mg/L was highly associated with the occurrence of MACE, with a sensitivity of 82% and specificity of 75%. CONCLUSIONS: A systematic inflammatory response is observed in a significant number of patients after EVAR. The type of endograft material seems to play a significant role in this inflammatory process. The intensity of inflammation, as assessed mainly by the post-operative hs-CRP values, correlates with the presence of a cardiovascular or any other adverse event during the first 30 days after the procedure.

Health & demographic surveillance system profile: Bandafassi Health and Demographic Surveillance System (Bandafassi HDSS), Senegal.

The Bandafassi Health and Demographic Surveillance System (Bandafassi HDSS) is located in south-eastern Senegal, near the borders with Mali and Guinea. The area is 700 km from the national capital, Dakar. The population under surveillance is rural and in 2012 comprised 13 378 inhabitants living in 42 villages. Established in 1970, originally for genetic studies, and initially covering only villages inhabited by one subgroup of the population of the area (the Mandinka), the project was transformed a few years later into a HDSS and then extended to the two other subgroups living in the area: Fula villages in 1975, and Bedik villages in 1980. Data have been collected through annual rounds since the project first began. On each visit, investigators review the composition of all the households, checking the lists of people who were present in each household the previous year and gathering information about births, marriages, migrations and deaths (including their causes) since then. One specific feature of the Bandafassi HDSS is the availability of genealogies.

Umbilical hernia repair increases the rate of functional gastrointestinal disorders in children.

OBJECTIVES: To hypothesize that hernia repair would not change the incidence of functional gastrointestinal disorders (FGIDs) due to the benign and limited nature of the procedure. STUDY DESIGN: This cohort study assessed a randomized selection of children aged 4-18 years who underwent hernia repair more than 4 years prior at Ann and Robert H. Lurie Children's Hospital of Chicago. Controls were siblings who had not undergone surgery previously. Parents completed the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III Version by telephone for subjects and controls. The primary outcome was the presence of FGIDs. RESULTS: Fifty children with hernia repair and 43 sibling controls were identified. At the time of survey, subjects with hernia repair were average age 12.9 years (range 5-18 years, 60% male) and controls were average age 12.2 years (range 4-18 years, 49% male). Average age at surgical repair was 5.2 years (median 5.2 years, range 0.2-10.4 years) and average time since surgical repair was 7.8 years (range 4.8-13.7 years). FGIDs were diagnosed in 10/50 (20%) cases of hernia repair and 2/43 (5%) controls (P = .033, Fisher 2-tailed test). CONCLUSIONS: Umbilical hernia repair increases the likelihood of FGIDs in childhood. Additional studies are needed to identify aspects of surgery that may be associated with development of FGIDs.

Emerging concepts on inhibitors of indoleamine 2,3-dioxygenase in rheumatic diseases.

The enzyme indoleamine 2,3-dioxygenase 1 (IDO1) finely regulates both innate and adaptive immune responses through the degradation of the essential amino acid tryptophan into kynurenine and other downstream metabolites, which suppress effector T-cell function and promote the differentiation of regulatory T cells. A novel role for IDO1 as a signaling molecule and a modifier of innate inflammatory responses is now emerging. In particular, IDO1 can either support or antagonize inflammation in a context- and tissuedependent manner. Studies in experimental arthritis have unravelled a previously unappreciated role for IDO in controlling B-cell activation and autoantibody production. IDO dysregulation has been documented in patients with systemic lupus erythematosus, systemic sclerosis and Sjogren's syndrome, as well as in severe sepsis and chronic kidney disease. This article summarizes the contribution of IDO to the pathophysiology of inflammatory/autoimmune disorders, and discusses whether strategies to restore metabolic equilibrium in the kynurenine pathway might be pursued in diseases states such as rheumatoid arthritis and systemic sclerosis.

Recombinant human erythropoietin stimulates vasculogenesis and wound healing in a patient with systemic sclerosis complicated by severe skin ulcers.

Systemic sclerosis (SSc) is often complicated by severe skin ulcers that are unresponsive to traditional treatments. Vascular alterations are responsible for the ischaemic features of the disease in both the skin and visceral organs. Defective neoangiogenesis correlates with an abnormally reduced quantity of circulating endothelial progenitor cells (EPCs) caused by impaired maturation potential and proliferative capacity of bonemarrow endothelial stem cells. We report a patient with nonhealing cutaneous ulcers successfully treated with recombinant human erythropoietin (rHuEPO). The possible biological effects of this drug were also investigated. Before rHuEPO treatment, the bone-marrow sample contained reduced numbers of EPCs, which were functionally impaired. After a 6-month rHuEPO cycle, a marked increase in endothelial progenitor markers was seen, along with a significant reduction in their apoptotic rates. The clinical and laboratory data variations before and after rHuEPO treatment give new insights into the pathogenetic role of impaired endothelial stem-cell maturation and defective neoangiogenesis in patients with SSc.

Recurrent headaches in children: an epidemiological survey of two middle schools in inner city Chicago.

OBJECTIVES: The aim of this study was to longitudinally evaluate the epidemiological characteristics of headaches in a school-based, community setting and to determine the impact of headache symptoms on the health of children. METHODS: After institutional review board approval, a prospective cohort study was conducted at two Chicago public schools for a period of 6 months. Members of the research team surveyed both schools weekly for headache and other pain symptoms. The students rated each pain symptom on a 5-point scale from 0 ("not at all") to 4 ("a whole lot"). Demographic information was collected at the time of enrollment, and all participants were asked to complete age-appropriate and validated pediatric surveys to assess the severity of concurrent somatic complaints, anxiety symptoms, functional limitations, and quality of life issues. RESULTS: Of the participating children, 89.5% reported at least one headache during the study period. Females experienced more frequent headaches compared with males (P < 0.05). Children reporting headaches had a significantly increased risk of experiencing other troubling somatic symptoms (P < 0.05). Headache severity showed a moderate correlation with increased feelings of anxiety, functional disability, and a diminished quality of life (P < 0.05). CONCLUSIONS: School-aged children commonly experience headaches. Children experiencing headaches are more likely to report other somatic symptoms, feelings of anxiety, functional limitations, and quality of life impairments.

Prevalence and factors associated with left ventricular dysfunction in the EULAR Scleroderma Trial and Research group (EUSTAR) database of patients with systemic sclerosis.

OBJECTIVES: To measure the prevalence of, and factors associated with, left ventricular (LV) dysfunction in systemic sclerosis (SSc). METHODS: The EUSTAR database was first searched. A case-control study of a patient subset was then performed to further identify independent factors associated with LV dysfunction by simple and multiple regression. RESULTS: Of 7073 patients, 383 (5.4%) had an LV ejection fraction (EF) of <55%. By multiple regression analysis, age, sex, diffuse cutaneous disease, disease duration, digital ulcerations, renal and muscle involvement, disease activity score, pulmonary fibrosis and pulmonary arterial hypertension were associated with LV dysfunction. In the second phase, 129 patients with SSc with LVEF <55% were compared with 256 patients with SSc with normal LVEF. Male sex (OR 3.48; 95% CI 1.74 to 6.98), age (OR 1.03; 95% CI 1.01 to 1.06), digital ulcerations (OR 1.91; 95% CI 1.05 to 3.50), myositis (OR 2.88; 95% CI 1.15 to 7.19) and use of calcium channel blockers (OR 0.41; 95% CI 0.22 to 0.74) were independent factors associated with LV dysfunction. CONCLUSION: The prevalence of LV dysfunction in SSc is 5.4%. Age, male gender, digital ulcerations, myositis and lung involvement are independently associated with an increased prevalence of LV dysfunction. Conversely, the use of calcium channel blockers may be protective.

Leflunomide-induced subacute cutaneous lupus erythematosus with erythema multiforme-like lesions.

Leflunomide is an immunosuppressive agent that acts by inhibiting pyrimidine synthesis in lymphocytes and other rapidly proliferating cells, as well as by suppressing tumor necrosis factor-alpha-induced cellular responses. A number of leflunomide-related adverse events have been reported. Among cutaneous side effects, a few cases of subacute cutaneous lupus erythematosus have been described. We report a previously undocumented reaction to leflunomide, manifesting as subacute cutaneous lupus erythematosus and erythema multiforme-like lesions, in a young woman treated with this drug for ankylosing spondylitis. Withdrawal of leflunomide combined with a short cycle of systemic corticosteroid led to the resolution of the patient's rash, indicating this drug as being responsible for the development of the disease. We conclude that leflunomide might have triggered the occurrence of both subacute cutaneous lupus erythematosus and erythema multiforme in a patient with pre-existing autoimmune diathesis. The suppressive effect of this drug on tumor necrosis factor-alpha-related mechanisms might have played a role in the induction of such a unique reaction to leflunomide.