Longitudinal associations of active renal disease with irreversible organ damage accrual in systemic lupus erythematosus.

OBJECTIVE: To examine longitudinal associations of active lupus nephritis with organ damage accrual in patients with systemic lupus erythematosus (SLE). METHODS: This study was performed using data from a large multinational prospective cohort. Active lupus nephritis at any visit was defined by the presence of urinary casts, proteinuria, haematuria or pyuria, as indicated by the cut-offs in the SLE Disease Activity Index (SLEDAI)-2K, collected at each visit. Organ damage accrual was defined as a change of SLICC-ACR Damage Index (SDI) score >0 units between baseline and final annual visits. Renal damage accrual was defined if there was new damage recorded in renal SDI domains (estimated glomerular filtration rate <50%/proteinuria >3.5 g per 24 h/end-stage kidney disease). Time-dependent hazard regression analyses were used to examine the associations between active lupus nephritis and damage accrual. RESULTS: Patients (N = 1735) were studied during 12,717 visits for a median (inter-quartile range) follow-up period of 795 (532, 1087) days. Forty per cent of patients had evidence of active lupus nephritis at least once during the study period, and active lupus nephritis was observed in 3030 (24%) visits. Forty-eight per cent of patients had organ damage at baseline and 14% accrued organ damage. Patients with active lupus nephritis were 52% more likely to accrue any organ damage compared with those without active lupus nephritis (adjusted hazard ratio = 1.52 (95% confidence interval (CI): 1.16, 1.97), p < 0.02). Active lupus nephritis was strongly associated with damage accrual in renal but not in non-renal organ domains (hazard ratios = 13.0 (95% CI: 6.58, 25.5) p < 0.001 and 0.96 (95% CI: 0.69, 1.32) p = 0.8, respectively). There was no effect of ethnicity on renal damage accrual, but Asian ethnicity was significantly associated with reduced non-renal damage accrual. CONCLUSION: Active lupus nephritis measured using the SLEDAI-2K domain cut-offs is associated with renal, but not non-renal, damage accrual in SLE.

Disease-specific quality of life in patients with lupus nephritis.

Background Patient-reported outcomes in lupus nephritis (LN) are not well studied. Studies with disease-targeted PRO tool in LN do not exist. Herein, we describe quality of life (QOL: HRQOL & non-HRQOL) among LN patients using LupusPRO. Methods International, cross-sectional data from 1259 patients with systemic lupus erythematosus (SLE) and LupusPRO were compared, stratified by (a) presence of LN (ACR classification criteria (ACR-LN)) at any time and, (b) active LN (on SLEDAI) at study visit. Damage was assessed by SLICC/ACR-SDI. Multivariate regression analyses for QOL against ACR-LN (active LN) after adjusting for age, gender, ethnicity and country of recruitment were performed. Results Mean (SD) age was 41.7 (13.5) yrs, 93% were women. Five hundred and thirty-nine of 1259 SLE patients had ACR-LN. ACR-LN group was younger, were more often on immunosuppressive medications, had worse QOL on lupus medications and procreation than non-ACR-LN patients. HRQOL and non-HRQOL scores were similar in both groups. One hundred and twenty-nine of 539 ACR-LN patients had active LN. Active LN group was younger, had greater disease activity and had worse HRQOL and non-HRQOL compared to patients without active LN. Specific domains adversely affected were lupus symptoms, lupus medications, procreation, emotional health, body image and desires-goals domains. Patients with ACR-LN and active LN fared significantly worse in lupus medications and procreation HRQOL domains, even after adjusting for age, ethnicity, gender and country of recruitment. Conclusions Lupus nephritis patients have poor QOL. Patients with active LN have worse HRQOL and non-HRQOL. Most domains affected are not included in the generic QOL tools used in SLE. LN patients must receive discussion on lupus medications and procreation issues. Patients with active LN need comprehensive assessments and addressal of QOL, along with treatment for active LN.

Cross-cultural validation of a disease-specific patient-reported outcome measure for lupus in Philippines.

OBJECTIVE: LupusPRO is a disease-targeted patient-reported outcome measure that was developed and validated among US patients with systemic lupus erythematosus (SLE). We report the cross-cultural validation results of the LupusPRO English-language version among Filipino SLE patients. METHOD: The 43-item LupusPRO was pretested in 15 SLE individuals, then administered to 106 SLE patients, along with short-form SF36 and the EQ5D visual analogue scale. A mail/drop-back LupusPRO and change in health status item survey were returned within two to three days. Demographics, clinical and serological characteristics, disease activity and damage measured by PGA, SELENA-SLEDAI, LFA Flare, and SLICC-ACR SLE damage index (SDI) were collected. Internal consistency reliability (ICR), test-retest reliability (TRT), convergent validity (corresponding SF36 domains) and criterion validity (against general health and disease activity measures) were tested. Reported p values are two tailed. RESULTS: A total of 121 Filipino SLE subjects (95% women, median age 31.0 ± 16 years) with at least a high school level of English instruction participated. Median (IQR) PGA, SLEDAI and SDI were 0.0 (1.0), 2.0 (10) and 0 (1), respectively. ICR exceeded 0.7 for all domains except the lupus symptoms domain. TRT was greater than 0.85 for all LupusPRO domains. Convergent and criterion validity were observed against corresponding SF36 domains and disease activity measures. The tool was well received by patients. Confirmatory factor analysis showed good fit. CONCLUSION: English LupusPRO has fair psychometric properties among SLE patients in the Philippines, and is now available for inclusion in clinical trials and longitudinal studies to test responsiveness to change.

Safety profile of belimumab: pooled data from placebo-controlled phase 2 and 3 studies in patients with systemic lupus erythematosus.

Safety data were pooled and analyzed from one phase 2 and two phase 3 double-blind, placebo-controlled, repeat-dose systemic lupus erythematosus (SLE) trials of belimumab 1, 4 (phase 2 only), and 10 mg/kg. Types and rates of adverse events (AEs) were similar across treatment groups. Rates of patients experiencing any serious AE were 16.6%, 19.5%, 13.5%, and 18.0% with placebo, and belimumab 1, 4, and 10 mg/kg, respectively; rates of serious infusion reactions (including hypersensitivity reactions) occurring on the same days as infusions were 0.4%, 0.9%, 0%, and 0.9%, and rates of serious infections were 5.5%, 7.1%, 6.3%, and 5.3%. Malignancy rates/100 patient-years (excluding non-melanoma skin cancer) were 0.29 with placebo vs. 0.20 with all belimumab doses combined; mortality rates/100 patient-years were 0.43 vs. 0.73. These data support the conclusion that belimumab in combination with standard SLE therapy was generally well tolerated in a predominantly autoantibody-positive population with active SLE.

Systemic lupus erythematosus following HPV immunization or infection?

BACKGROUND AND PURPOSE: The link between autoimmunity and infectious agents has been strongly suggested by reports of lupus or lupus-like syndromes following immunization. This report describes three patients with either newly diagnosed systemic lupus erythematosus (SLE) or SLE flare, following vaccination for human papilloma virus (HPV). CASE 1: A 17-year-old female completed two doses of HPV vaccine uneventfully. Two months later, she developed arthralgias with pruritic rashes on both lower extremities, later accompanied by livedo reticularis, bipedal edema with proteinuria, anemia, leucopenia, hypocomplementemia and high titers of anti-nuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA). Kidney biopsy showed International Society of Nephrology/Renal Pathology Society Class III lupus nephritis. She was started on high dose steroids followed by pulse cyclophosphamide therapy protocol for lupus nephritis, and subsequently went into remission. CASE 2: A 45-year-old housewife, previously managed for 11 years as having rheumatoid arthritis, had been in clinical remission for a year when she received two doses of HPV immunization. Four months later, she developed fever accompanied by arthritis, malar rash, oral ulcers, recurrent ascites with intestinal pseudo-obstruction, and behavioral changes. Cranial MRI showed vasculitic lesions on the frontal and parietal lobes. Laboratory tests showed anemia with leucopenia, hypocomplementemia, proteinuria, ANA positive at 1:320, and antibodies against dsDNA, Ro/SSA, La/SSB and histone. She improved following pulse methylprednisolone with subsequent oral prednisone combined with hydroxychloroquine. CASE 3: A 58-year-old housewife diagnosed with SLE had been in clinical remission for 8 years when she received two doses of HPV immunization. Three months later, she was admitted to emergency because of a 1-week history of fever, malar rash, easy fatigability, cervical lymph nodes, gross hematuria and pallor. Laboratory exams showed severe anemia, thrombocytopenia, active urine sediments, and hypocomplementemia. Despite pulse steroid therapy, blood transfusions, intravenous immunoglobulin and aggressive resuscitative measures, she expired a day after hospital admission. SUMMARY: These cases narrate instances of the onset or exacerbation of lupus following HPV immunization suggesting adjuvant-induced autoimmunity. On the other hand, there are reports of higher incidence of HPV infection in SLE, with the infection per se possibly contributing to disease activity. Thus, the benefit of HPV immunization may still outweigh the risk among these individuals.

Studies of Filipino patients with systemic lupus erythematosus: autoantibody profile of first-degree relatives.

This study surveyed the frequency of autoantibodies among un-affected first-degree relatives (FDRs) of Filipino systemic lupus erythematosus (SLE) patients compared with healthy un-related Filipino controls. The sensitivity, specificity and predictive value of the autoantibodies for SLE diagnosis were also assessed in this Filipino cohort. Filipino patients included in the University of Santo Tomas (UST) Lupus Database and un-affected FDRs were recruited. Healthy controls included those with no known personal or family history of autoimmune disease. The following autoantibodies were tested in all subjects: anti-nuclear antibody (ANA), anti-dsDNA, anti-Ro/SSA, anti-chromatin, anti-thyroid microsome, and anti-cardiolipin antibodies. Participants included 232 SLE patients, 546 FDRs, and 221 healthy controls. Median age of patients was 27 (range 8-66) years with median disease duration of 27.5 (range 1-292) months. Median age of FDRs was 42.0 (range 5-87) years. Compared with healthy controls, there were significantly more FDRs with positive ANA at titers 1 : 40 to 1 : 160 (p < 0.001) and 1 : 320 (p = 0.003), anti-Ro/SSA (4.94% versus 0.45%, p = 0.003), and anti-dsDNA ≥ 5.0 IU/ml (4.58% versus 1.36%, p = 0.031). ANA titer ≥1 : 160, anti-dsDNA, anti-Ro/SSA and anti-chromatin had the highest predictive value for SLE diagnosis. These findings reinforce the role of genetic influence in SLE risk among Filipinos, with a significant proportion of un-affected FDRs of SLE patients testing positive for autoantibodies compared with healthy Filipino controls. A longitudinal observational study in this same cohort will determine which proportion of these un-affected FDRs will evolve into clinical SLE disease in the future.

Delayed intracranial hemorrhage after mild traumatic brain injury in patients on oral anticoagulants: is the juice worth the squeeze?

OBJECTIVE: Mild Traumatic Brain Injury (MTBI) in anticoagulated patients is a common challenge for Emergency Department (ED) Physicians. Anticoagulation is considered a risk factor for developing delayed intracranial hemorrhage (ICH) after MTBI. The occurrence of this event in patients on Vitamin K Antagonists (VKA) or Direct Oral Anticoagulants (DOACs) remains unclear. Primary endpoint: to analyze the role of anticoagulants as risk factors for developing delayed ICH after MTBI and evaluate the indications to repeat a cranial computed tomography (CT) after a period of observation. Secondary endpoint: to assess the difference in the prevalence rate of delayed ICH in patients on VKA versus those on DOACs. PATIENTS AND METHODS: We evaluated all consecutive patients admitted to our ED for MTBI, which had a control CT for late ICH after a negative CT at admission. We used a propensity score match (PSM) on factors affecting the need for oral anticoagulation to adjust the comparison between anticoagulated vs. non-anticoagulated patients for the baseline clinical characteristics. RESULTS: Among 685 patients enrolled, 15 (2.2%) developed ICH at control CT. After PSM, the incidence of ICH, although slightly higher, was not statistically different in anticoagulated patients vs. non-anticoagulated (2.3% vs. 0.6%, p=0.371). Among the 111 patients on VKA, 5 (4.5%) had a late ICH, compared to 4 out of 99 (4.0%) on DOACs; the difference was not statistically significant (p=0.868). CONCLUSIONS: The risk of developing delayed ICH after MTBI in patients on anticoagulation therapy is low. After correction for baseline covariates, the risk does not appear higher compared to non-anticoagulated patients. Thus, a routine control CT scan seems advisable only for patients presenting a clinical deterioration. Larger, prospective trials are required to clarify the safety profile of DOACs vs. VKA in MTBI.

Infections in systemic lupus erythematosus.

Infections are an important cause of morbidity and mortality in systemic lupus erythematosus (SLE). Survival rates for SLE patients in developing countries are comparatively lower than those reported in industrialized countries, with early death from infection and active disease. In addition to the role of immunosuppressive agents in enhancing susceptibility to infection, infectious agents are also known to trigger lupus disease expression and activity. The endemicity of certain infections like tuberculosis further poses a special health issue in developing countries.

Gigantomastia in a patient with systemic lupus erythematosus successfully treated by reduction mammoplasty.

The objective of the study was to describe a Filipino woman with systemic lupus erythematosus (SLE) who developed gigantomastia associated with hyperoestrogenemia and successfully treated by reduction mammoplasty. A 37-year-old Filipino woman with SLE of 5-year duration presented with enlargement of breasts, which became more noticeable and progressive during disease flares requiring increased steroid dose (+ or - 40 mg/day). Following control of the last SLE flare, with prednisone effectively tapered to 15 mg/day, she consented to surgical breast reduction. Preoperative physical examination recorded the right and left breast measurement of 61 cm and 54.5 cm from sternal notch to nipple tip, respectively. serum oestrogen assay was elevated. She successfully underwent reduction mammoplasty with free nipple graft, with an uneventful postoperative course. The breast tissue oestrogen and progesterone receptor assays were strongly positive. In the succeeding months, SLE disease remained stable with prednisone tapered to 10 mg daily. This case illustrates a rare occurrence of gigantomastia associated with hyperoestrogenemia in a patient with SLE, successfully treated with reduction mammoplasty.

Beware of the dog - Capnocytophga Canimorsus septic shock: a case report.

Capnocytophaga canimorsus is a Gram-negative rods frequently isolated as commensal in the saliva of pets that can be transmitted to humans. We report a case of septic shock caused by this pathogen. A 78-year-old man affected by diabetes and hypertension was admitted for fever in our Emergency Department. He reported fever (37.7°C) with normal values of blood pressure, heart rate and saturation of oxygen. Laboratory studies showed increased values of procalcitonin and normal white-cell level. Blood cultures were collected and an empirical antibiotic therapy was started. He reported six days earlier a bite of a dog at the right hand. During the following days the patient presented a deterioration of clinical conditions with fever, asthenia and comparison of petechial lesions. C. canimorsus was isolated from blood cultures. He was treated with fluids and appropriate antibiotic therapy with a full recovery. Dog wounds are frequent minor injuries with an underestimated worldwide incidence because only few patients develop complications. C. canimorsus could be an emerging cause of sepsis, also in immunocompetent patients. The current understanding of risk factors for C. canimorsus associated sepsis and a prompt approach to anamnesis and treatment of early stage injuries, could have a considerable medical outcome.

Genetic determinants of basal C-reactive protein expression in Filipino systemic lupus erythematosus families.

Basal C-reactive protein (CRP) is a heritable trait associated with long-term cardiovascular disease risk. Existing studies leave ambiguity over the key functional polymorphisms and fail to adjust for trans-acting effects. In a novel cohort of 285 Filipino systemic lupus erythematosus probands and their first-degree relatives, we quantified serum CRP and typed a dense map of CRP single-nucleotide polymorphisms (SNPs), along with SNPs in the interleukin-1 beta, interleukin-6 and apolipoprotein E genes. Ten CRP SNPs demonstrated association with basal CRP in a regression model (P=0.011-0.002). These delineated two haplotypes associated with high and low basal CRP expression (P=0.002). Differences in allele frequency were seen compared with Caucasian populations, enabling us to argue for an independent genetic effect from a phylogenetically distinct haplotype tagged by SNP rs1800947. We demonstrated an association between Apo epsilon 2 and higher basal CRP. Interleukin-6 genotype was associated with basal CRP, highlighting a role for acute-phase cytokines even in basal expression. Identifying these trans-acting variants may improve the use of basal CRP as a predictor cardiovascular risk, and increase our power to detect associations between CRP and disease.

Tuberculosis among Filipino patients with systemic lupus erythematosus.

A retrospective review of the clinical records of 54 patients with systemic lupus erythematosus (SLE) and documented tuberculosis (TB) infection seen at the University of Santo Tomas Hospital was accomplished. There were 53 women and one man, with a mean age of 32.2 +/- 10 years and a total of 57 TB occurrences. Pulmonary involvement was recorded in 42 (74%): upper lungfield in 25, mid to lower lungfield in 7, and miliary pattern or diffuse infiltrates in 10. TB arthritis was noted in 8, osteomyelitis in 4, and soft tissue abscesses in 4. Central nervous system involvement consisted of brain abscesses (tuberculomas) in two and meningitis in one. Two patients each had TB lymphadenitis, genitourinary TB, ileocecal TB, and TB peritonitis. Hepatobiliary and cutaneous TB occurred in one patient each. Eight of 10 patients with disseminated or miliary TB died primarily of respiratory failure; six of these eight patients also had some form of extrapulmonary involvement. Using the Wilcoxon rank-sum test, there were significant differences in the mean SLE Disease Activity Index (SLEDAI) and Severity of Disease Index (SDI) scores between those with limited TB (SLEDAI 24 +/- 7 SD; SDI 19 +/- 18 SD) versus those with extensive TB (SLEDAI 41 +/- 16 SD; SDI 36 +/- 21 SD), P < .05. There was no significant difference in the average daily prednisone dose (mg) between those with limited TB (25 +/- 17 SD) versus those with extensive TB (31 +/- 16 SD). The contributory role of tuberculous infection in the morbidity and mortality of patients with SLE must be emphasized, especially in areas endemic for TB.

[Hormone receptors in breast cancer]. / I recettori ormonali nel carcinoma mammario.

Following a review of studies on the presence of hormonal receptors in breast carcinoma, reference is made to personal experience with hormone treatment of 96 patients with breast cancer. On the basis of data obtained in clinical practice, it is concluded that in order to apply target hormone treatment, it is essential to carry out a full study of hormone receptors, not just as regards oestradiol, progesterone and prolactin but the others too (testosterone, glycocorticoids, insulin, thyroid and growth hormone).

[Hormone treatment of metastasizing breast carcinoma]. / Il trattamento ormonale del carcinoma metastatizzante della mammella.

The hormone-dependence of breast cancer is recalled in a review of 448 metastasies cases observed between 1958 and 1978. It is shown that the percentage of positive response to hormone therapy is related to the type of treatment, menstrual age, metastasis site, and above all to the presence or absence of receptors for oestradiol, progesterone, and prolactin in the tumour tissue. The fact that hormone dependence can be evaluated via the search for such receptors means that projectine hormone management can be employed. This should lead to a marked improvement in the percentage of positive responses obtained in the treatment of metastasing breast carcinoma.

[Hypocobaltemia in chronic obstructive arteriopathy. Physiopathologic and therapeutic importance]. / L'ipocobaltemia nelle arteriopatie croniche ostruttive. Suo significato fisiopatologico e terapeutico.

The role of some so-called primary and secondary (or oligo-elements) elements in the physiopathology of the cardiocirculatory system has been well known from a number of years and they have been regularly included in the treatment protocols. Some, including K, Ca, Mg and Zn, are extremely well known and widely used in clinical practice. Recently, however, a growing number of studies have focused on the biological importance of other oligo-elements in the pathogenetic mechanisms of atherogenesis and its clinical manifestations. This study aimed to verify the exact role of free cobalt in the physiopathology of the chronic obstructive arterial diseases (COAD). A total of 80 patients affected by 2nd stage COAD were examined and the levels of some oligo-elements, including Co, were assayed. Constantly low levels were found (85% of cases) in relation to other oligo-elements studied (Cu, Zn, Mg, Ca). This findings is particularly interesting since it confirms the biochemical hypothesis of atherosclerosis according to which parietal damage plays a central role in the pathogenetic mechanism. Some enzymatic deficiencies, which lead to changes in membrane stability at the level of the endothelial cells, are closely related to the presence of tissutal and humoral peroxidation products. These peroxides (lipid peroxides), which are formed following the interaction of fatty acids with oxygen free radicals, have been identified by a number of studies as being responsible for endothelial damage. Several authors have shown that lipid peroxidation is involved in the atherogenic process through several mechanisms entailing monocytic activity and reduced prostacyclin (PG2) synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

[Treatment of idiopathic retroperitoneal fibrosis]. / Le traitement de la fibrose rétropéritonéale idiopathique.

Idiopathic retroperitoneal fibrosis is a rare disease and a delay in diagnosis may cause renal failure. Medical treatment i.e. corticotherapy or more recently, tamoxifene has been used successfully. This approach is recommended in patients either with moderate obstruction of the upper urinary, risk of major surgery or in cases of recurrence after surgical treatment. Ureterolysis using conventional surgery or laparoscopy remains the treatment of choice. This procedure should be considered in patients with neoplasic fibrosis, corticoresistant fibrosis or in cases of peri-aneurysm fibrosis.

[ST52 treatment of cancer of the prostate during the hormonal resistance phase]. / Traitement par ST52 du cancer de la prostate au stade d'échappement hormonal.

OBJECTIVE: Stilboestrol phosphate (ST 52) was evaluated on pain, general status, life expectancy and PSA, in a retrospective study of patients with prostatic carcinoma and relapse to hormonal treatment. MATERIAL AND METHODS: 32 patients were treated by infusion of Stilboestrol phosphate at a daily escalating dose from 1.2 to 3 g over a period of 10 days, then subsequently oral administration. RESULTS: Minor complications, especially nausea were observed in 12 cases but no major complication or interruption of treatment. Improvement for pain alone or with general status was obtained in 50% (16 cases) at 3 months, but at one year only 10% were still improved. Median survival was 8 months, with 19.4 months for responders at the end of infusions and 4.2 months for non-responders-respectively. CONCLUSION: Stilboestrol phosphate can obtain a clinical response with low morbidity when relapse to hormonal treatment occurs. Infusion responders have a better life expectancy.

[Parietal recurrence after resection of colorectal carcinoma]. / La recidiva parietale dopo chirurgia resettiva del carcinoma colo-rettale.

The incidence of local recurrence of colo-rectal carcinoma is about 15-50%. The parietal recurrence is localized next parietal incision and its incidence is rare (0.2-2%). The treatment of this lesion is based on palliative radiotherapy and chemotherapy; the surgical treatment is based on parietal resection. The Authors describe a case of parietal recurrence after colo-rectal adenocarcinoma and conclude that the prognosis of this lesions is infaust.

[Recurrent febrile infections of the urinary tract and diverticulum of the urachus]. / Infections multirécidivantes fébriles du tractus urinaire et diverticule de l'ouraque.

The urachus can present a partial or complete obliteration defect. If the defect is situated in its vesical extremity, it then forms a diverticulum. The authors report a case of diverticulum of the urachus in a young adult, responsible for recurrent febrile urinary tract infections since the beginning of adolescence. The diagnosis was suggested by ultrasonography and magnetic resonance imaging and confirmed by cystoscopy and histological examination. Treatment consisted of complete surgical resection via a suprapubic incision.

[Malignant neuroendocrine tumor of the bladder: an entity not to be unrecognized]. / Tumeur neuro-endocrine maligne de vessie: une entité à ne pas méconnaître.

The authors report a case of primary malignant neuroendocrine bladder tumour. This rare bladder tumour presents the morphological and immunohistochemical characteristic common to all neuroendocrine tumours observed in other organs. The urologist must recognise this histological entity, which requires multidisciplinary management.