L. Fardet

Factors associated with underlying malignancy in a retrospective cohort of 121 patients with dermatomyositis.

Demographic, clinical, and laboratory features that predict underlying malignancy in patients with dermatomyositis (DM) are poorly known. We conducted a retrospective study in all adult patients with a definite (n = 75) or probable (n = 32) diagnosis of DM according to Bohan and Peter criteria or with amyopathic DM (n = 14) who were referred to 2 departments during a 13-year period. The diagnosis of malignancy-associated DM was retained if DM occurred in a context of recently diagnosed malignancy or if a malignancy was diagnosed during the 5 years following the diagnosis of DM. The Kaplan-Meier method was used to assess the cumulative incidence rates of underlying malignancy during the first 5 years of DM. Factors associated with malignancy in patients with DM were identified by Cox proportional hazards models. During the study period, 121 patients fulfilled the inclusion criteria (median age, 52 yr; range, 19-77 yr; women: 70%). For 29 of them, the diagnosis of malignancy-associated DM was retained. The cumulative incidence rate of malignancy was 21 ± 4% and 28 ± 5%, 1 year and 5 years after the diagnosis of DM, respectively. The median duration of follow-up of the 92 patients with no malignancy diagnosed was 36 months (range, 1-140 mo). In multivariate analysis, independent factors associated with an underlying malignancy in patients with DM were an age at diagnosis >52 years (hazard ratio [HR], 7.24; 95% confidence interval [CI], 2.35-22.31), a rapid onset of skin and/or muscular symptoms (HR, 3.11; 95% CI, 1.07-9.02), the presence of skin necrosis (HR, 3.84; 95% CI, 1.00-14.85) or periungual erythema (HR, 3.93; 95% CI, 1.16-13.24), and a low baseline level of complement factor C4 (HR, 2.74; 95% CI, 1.11-6.75). Lastly, low baseline lymphocyte count (<1500/mm3) was a protective factor of malignancy (HR, 0.33; 95% CI, 0.14-0.80). Taken together, these data may help physicians focus on a group of patients who might benefit from extensive evaluation for malignancy. Abbreviations: ALT = alanine aminotransferase, AST = aspartate aminotransferase, CI = confidence interval, CPK = creatine phosphokinase, DM = dermatomyositis, HR = hazard ratio, LDH = lactate dehydrogenase.

Reactive haemophagocytic syndrome in 58 HIV-1-infected patients: clinical features, underlying diseases and prognosis.

Objective:To describe features of reactive haemophagocytic syndrome (RHS) in HIV-1-infected adult patients. To compare characteristics of patients with malignancy-associated RHS and infection-associated RHS. Design and Setting:Retrospective study in three departments of Infectious Diseases/Internal Medicine at three French tertiary centres. Patients and methods:Medical charts of HIV-1-infected adult patients and RHS seen between January 2006 and December 2007 were reviewed. Demographic, clinical and laboratory data obtained at the time of RHS episode were compared between patients with malignancy-associated RHS and infection-associated RHS using non-parametric tests. The overall survival was assessed using the Kaplan–Meier method. Results:Fifty-eight HIV-1-infected patients were diagnosed with RHS [certain RHS n = 43, possible RHS n = 15, median (range) age 42 (23–85) years, men 76%]. At time of RHS, the median duration of HIV infection was 4 (0–22) years and 57% received HAART. The median CD4 lymphocyte count was 91 (2–387)/μl and 35% of patients had a plasma HIV-1 RNA less than 50 copies/ml. Underlying haemopathy/malignancy (Hodgkin lymphoma n = 10) or infection (tuberculosis n = 9, cytomegalovirus infection n = 5) were evidenced for 31 and 23 patients, respectively. Patients with haemopathy/malignancy-associated RHS presented more frequently with splenomegaly (97 vs. 70%, P < 0.01), lower aspartate aminotransferase (36 vs. 84 UI/l, P < 0.01) and lactate dehydrogenase (530 vs. 911 UI/l, P < 0.01) levels and CD8 cell count (234 vs. 588/μl, P < 0.01). Eighteen (31%) patients died. The overall survival was not statistically different between the two groups (P = 0.68). Conclusion:In the HAART era, RHS is frequently associated with underlying haemopathy/malignancy, especially Hodgkin lymphoma. The prognosis remains poor but seems, however, better than in the pre-HAART era.

Risk of cardiovascular events in people prescribed glucocorticoids with iatrogenic Cushing's syndrome: cohort study

Objective To investigate whether there is an increased risk of cardiovascular events in people who exhibit iatrogenic Cushing’s syndrome during treatment with glucocorticoids. Design Cohort study. Setting 424 UK general practices contributing to The Health Improvement Network database. Participants People prescribed systemic glucocorticoids and with a diagnosis of iatrogenic Cushing’s syndrome (n=547) and two comparison groups: those prescribed glucocorticoids and with no diagnosis of iatrogenic Cushing’s syndrome (n=3231) and those not prescribed systemic glucocorticoids (n=3282). Main outcome measures Incidence of cardiovascular events within a year after diagnosis of iatrogenic Cushing’s syndrome or after a randomly selected date, and association between iatrogenic Cushing’s syndrome and risk of cardiovascular events. Results 417 cardiovascular events occurred in 341 patients. Taking into account only the first event by patient (coronary heart disease n=177, heart failure n=101, ischaemic stroke n=63), the incidence rates of cardiovascular events per 100 person years at risk were 15.1 (95% confidence interval 11.8 to 18.4) in those prescribed glucocorticoids and with a diagnosis of iatrogenic Cushing’s syndrome, 6.4 (5.5 to 7.3) in those prescribed glucocorticoids without a diagnosis of iatrogenic Cushing’s syndrome, and 4.1 (3.4 to 4.8) in those not prescribed glucocorticoids. In multivariate analyses adjusted for sex, age, intensity of glucocorticoid use, underlying disease, smoking status, and use of aspirin, diabetes drugs, antihypertensive drugs, lipid lowering drugs, or oral anticoagulant drugs, the relation between iatrogenic Cushing’s syndrome and cardiovascular events was strong (adjusted hazard ratios 2.27 (95% confidence interval 1.48 to 3.47) for coronary heart disease, 3.77 (2.41 to 5.90) for heart failure, and 2.23 (0.96 to 5.17) for ischaemic cerebrovascular events). The adjusted hazard ratio for any cardiovascular event was 4.16 (2.98 to 5.82) when the group prescribed glucocorticoids and with iatrogenic Cushing’s syndrome was compared with the group not prescribed glucocorticoids. Conclusion People who use glucocorticoids and exhibit iatrogenic Cushing’s syndrome should be aggressively targeted for early screening and management of cardiovascular risk factors.

Prognostic factors of early death in a cohort of 162 adult haemophagocytic syndrome: impact of triggering disease and early treatment with etoposide.

Reactive haemophagocytic syndrome is a life‐threatening disease for which factors influencing the outcome remain unclear. We sought to identify determinants of early mortality in patients with reactive haemophagocytic syndrome by conducting a non‐interventional retrospective multicentre study in three tertiary care teaching hospitals over a 6‐year period. The medical files of 162 patients fulfilling our diagnostic criteria of haemophagocytic syndrome were reviewed. Patients were classified according to 30‐d outcome following diagnosis. Thirty‐three patients (20·4%) died within 30 d. Clinical features at diagnosis associated with 30‐d death in univariate analysis were older age (P = 0·004), underlying lymphoma (P = 0·04), lower platelet count (P = 0·001) and elevated aspartate aminotransferase and lactate dehydrogenase (P = 0·04 both). The use of etoposide as a first‐line treatment tended to be associated with a better outcome (P = 0·079). In multivariate analyses, increasing age, decreasing platelet count, underlying lymphoma and no etoposide in the management were associated with a poorer prognosis (P = 0·03, 0·01, 0·003 and 0·04, respectively). These prognostic factors could help to identify those patients more severely affected by reactive haemophagocytic syndrome, who should benefit from aggressive supportive care, combined with specific treatment of the precipitating factor.

Successful outcome using rituximab as the only immunomodulation in Henoch-Schonlein purpura: case report

In the current report, we describe a patient with moderate nephritis and severe skin Henoch Schönlein purpura (HSP) who has been treated with rituximab. Complete and sustained skin and renal remission resulted from the treatment. Thus, further studies are required to confirm the efficacy of rituximab as first-line treatment in HSP, and it might be an interesting new therapeutic option.

Frequency, clinical features and prognosis of cutaneous manifestations in adult patients with reactive haemophagocytic syndrome.

Background  Cutaneous involvement has been reported in 30–40% of children with the familial form of haemophagocytic syndrome. However, few studies have focused on cutaneous manifestations in patients with reactive haemophagocytic syndrome (RHS).

Impact of glucocorticoid-induced adverse events on adherence in patients receiving long-term systemic glucocorticoid therapy

Summary Background  Factors influencing adherence to long‐term (i.e. ≥ 3 months) systemic glucocorticoid therapy are poorly understood.

Increased systemic immune activation and inflammatory profile of long-term HIV-infected ART-controlled patients is related to personal factors, but not to markers of HIV infection severity

OBJECTIVES The objective of this study was to analyse the respective roles of personal factors and HIV infection markers on the systemic immune activation/inflammatory profile of long-term antiretroviral treatment-controlled patients. PATIENTS AND METHODS A panel of soluble immune activation/inflammatory biomarkers was measured in 352 HIV-infected treatment-controlled patients from the APROCO-COPILOTE cohort, all of whom were started on a PI in 1997-99 and had a final evaluation 11 years later, and in 59 healthy controls. RESULTS A total of 81.5% of the patients were male, with the following characteristics: median age 49 years; 620 CD4 cells/mm(3); 756 CD8 cells/mm(3); CD4/CD8 ratio 0.81; BMI 23.0 kg/m(2); waist-to-hip ratio 0.95. Markers of inflammation-high-sensitivity (hs) IL-6 (median and IQR) (1.3 pg/L, 0.7-2.6), hs C-reactive protein (CRP) (2.1 mg/L, 0.9-4.5) and D-dimer (252 ng/mL, 177-374)-were elevated compared with healthy controls (P < 0.001) and strongly related to each other, as were markers of immune activation [soluble (s) CD14 (1356 ng/mL, 1027-1818), β2-microglobulin (2.4 mg/L, 2.0-3.1) and cystatin-C (0.93 mg/L, 0.82-1.1)]. Inflammatory and immune activation markers were also associated with each other. In HIV-infected patients: age was related to D-dimer, β2-microglobulin and cystatin-C levels; being a smoker was related to increased IL-6 and cystatin-C; and BMI and waist-to-hip ratio were related to CRP. Conversely, markers of HIV infection, current CD4 or CD8 values, CD4 nadir, CD4/CD8 ratio, AIDS stage at initiation of PIs, current viral load and duration of ART were not associated with immune activation/inflammation markers. CONCLUSIONS In these long-term treatment-controlled HIV-infected patients, all systemic markers of inflammation and immune activation were increased compared with healthy controls. This was related to demographic and behavioural factors, but not to markers of severity of the HIV infection. Intervention to decrease low-grade inflammation must thus prioritize modifiable personal factors.

Severe Neuropsychiatric Outcomes Following Discontinuation of Long-Term Glucocorticoid Therapy: A Cohort Study

BACKGROUND It has been estimated that, at any point in time, about 1% of the general adult population of the United Kingdom is receiving long-term (ie, ≥ 3 months) oral glucocorticoid therapy. These patients may develop neuropsychiatric disorders when the drug is discontinued. METHOD Data were obtained for all adult patients registered from January 1, 1990, through December 31, 2008, at UK general practices that were contributors to The Health Improvement Network database. Data from 21,995 adult patients who had been exposed to long-term oral glucocorticoids and who had discontinued the drugs after an exposure ranging from 1 to 3 years were analyzed. The within-person incidence rate ratios (IRRs) for Read codes and/or prescriptions for depression, delirium/confusion, mania, panic disorders, and suicide or suicide attempt during the withdrawal period were estimated using a self-controlled case series methodology. The predictors of the outcomes were ascertained using Cox proportional hazards models. RESULTS The risk of depression (IRR = 1.13; 95% CI, 1.00-1.28; P = .04) and of delirium/confusion (IRR = 2.67; 95% CI, 1.96-3.63; P < .001) was significantly higher during the discontinuation period compared to a reference period defined as ranging from 5 to 3 months before the drug cessation. Older people were at higher risk of delirium/confusion. The use of long-acting glucocorticoids was associated with a higher risk of both depression (adjusted hazard ratio [HR] = 1.92; 95% CI, 1.07-3.46) and delirium/confusion (adjusted HR = 4.96; 95% CI, 2.60-9.49) during the withdrawal period. CONCLUSIONS Discontinuation of long-term glucocorticoid therapy is associated with an increased risk of both depression and delirium/confusion. People treated with long-acting glucocorticoids are particularly at risk.

Common Infections in Patients Prescribed Systemic Glucocorticoids in Primary Care: A Population-Based Cohort Study

Background Little is known about the relative risk of common bacterial, viral, fungal, and parasitic infections in the general population of individuals exposed to systemic glucocorticoids, or about the impact of glucocorticoid exposure duration and predisposing factors on this risk. Methods and Findings The hazard ratios of various common infections were assessed in 275,072 adults prescribed glucocorticoids orally for ≥15 d (women: 57.8%, median age: 63 [interquartile range 48–73] y) in comparison to those not prescribed glucocorticoids. For each infection, incidence rate ratios were calculated for five durations of exposure (ranging from 15–30 d to >12 mo), and risk factors were assessed. Data were extracted from The Health Improvement Network (THIN) primary care database. When compared to those with the same underlying disease but not exposed to glucocorticoids, the adjusted hazard ratios for infections with significantly higher risk in the glucocorticoid-exposed population ranged from 2.01 (95% CI 1.83–2.19; p < 0.001) for cutaneous cellulitis to 5.84 (95% CI 5.61–6.08; p < 0.001) for lower respiratory tract infection (LRTI). There was no difference in the risk of scabies, dermatophytosis and varicella. The relative increase in risk was stable over the durations of exposure, except for LRTI and local candidiasis, for which it was much higher during the first weeks of exposure. The risks of infection increased with age and were higher in those with diabetes, in those prescribed higher glucocorticoid doses, and in those with lower plasma albumin level. Most associations were also dependent on the underlying disease. A sensitivity analysis conducted on all individuals except those with asthma or chronic obstructive pulmonary disease produced similar results. Another sensitivity analysis assessing the impact of potential unmeasured confounders such as disease severity or concomitant prescription of chemotherapy suggested that it was unlikely that adjusting for these potential confounders would have radically changed the findings. Limitations of our study include the use of electronic medical records, which could have resulted in some degree of misclassification of the infectious outcomes; a possible reporting bias, as general practitioners could be more prone to record an infection in those exposed to glucocorticoids; and a low number of events for some outcomes such as scabies or varicella, which may have led to limited statistical power. Conclusions The relative risk of LRTI and local candidiasis is very high during the first weeks of glucocorticoid exposure. Further studies are needed to assess whether low albumin level is a risk factor for infection by itself (e.g., by being associated with a higher free glucocorticoid fraction) or whether it reflects other underlying causes of general debilitation.