Intravenous Immunoglobulins Improve Survival in Monoclonal Gammopathy-Associated Systemic Capillary-Leak Syndrome.

BACKGROUND: Monoclonal gammopathy-associated systemic capillary-leak syndrome, also known as Clarkson disease, is a rare condition characterized by recurrent life-threatening episodes of capillary hyperpermeability in the context of a monoclonal gammopathy. This study was conducted to better describe the clinical characteristics, natural history, and long-term outcome of monoclonal gammopathy-associated systemic capillary-leak syndrome. METHODS: We conducted a cohort analysis of all patients included in the European Clarkson disease (EurêClark) registry between January 1997 and March 2016. From diagnosis to last follow-up, studied outcomes (eg, the frequency and severity of attacks, death, and evolution toward multiple myeloma) and the type of preventive treatments administered were monitored every 6 months. RESULTS: Sixty-nine patients (M/F sex ratio 1:1; mean ± SD age at disease onset 52 ± 12 years) were included in the study. All patients had monoclonal gammopathy of immunoglobulin G type, with kappa light chains in 47 (68%). Median (interquartile range) follow-up duration was 5.1 (2.5-9.7) years. Twenty-four patients (35%) died after 3.3 (0.9-8) years. Fifty-seven (86%) patients received at least one preventive treatment, including intravenous immunoglobulins (IVIg) n = 48 (73.8%), theophylline n = 22 (33.8%), terbutaline n = 22 (33.8%), and thalidomide n = 5 (7.7%). In the 65 patients with follow-up, 5- and 10-year survival rates were 78% (n = 35) and 69% (n = 17), respectively. Multivariate analysis found preventive treatment with IVIg (hazard ratio 0.27; 95% confidence interval, 0.10-0.70; P = .007) and terbutaline (hazard ratio 0.35; 95% confidence interval, 0.13-0.96; P = .041) to be independent predictors of mortality. CONCLUSIONS: We describe the largest cohort to date of patients with well-defined monoclonal gammopathy-associated systemic capillary-leak syndrome. Preventive treatment with IVIg was the strongest factor associated with survival, suggesting the use of IVIg as the first line in prevention therapy.

Multiple sclerosis broke my heart.

We report 5 cases of acute heart failure (AHF) related to multiple sclerosis (MS) relapses. AHF was inaugural in 3 patients, always preceded or accompanied by signs of brainstem dysfunction; it was severe, requiring intensive care management. Echocardiography showed left ventricular hypokinesis. No other cause of AHF has been found. All patients showed a new medullary lesion on brain magnetic resonance imaging. All had rapid and complete recovery of ventricular function after intravenous corticosteroids. We concluded that the cases represent a takotsubo phenomenon. Physicians should be aware of rare cases of takotsubo cardiomyopathy in MS relapses. Ann Neurol 2017;81:754-758.

Factors associated with Clostridium difficile infection: A nested case-control study in a three year prospective cohort.

BACKGROUND: Clostridium difficile infection (CDI) is a serious medical condition that is associated with substantial morbidity and mortality. Identification of risk factors associated with CDI and prompt recognition of patients at risk is key to successfully preventing CDI. METHODS: A 3-year prospective, observational, cohort study was conducted in a French university hospital and a nested case-control study was performed to identify risk factors for CDI. Inpatients aged 18 years or older, suffering from diarrhea suspected to be related to CDI, were asked to participate. RESULTS: A total of 945 patients were included, of which 233 cases had a confirmed CDI. CDI infection was more common in men (58.4%) (P = 0.04) compared with patients with diarrhea not related to C. difficile. Previous hospitalization (P < 0.001), prior treatment with antibiotics (P = 0.001) or antiperistaltics (P = 0.002), liver disease (P = 0.003), malnutrition (P < 0.001), and previous CDI (P < 0.001) were significantly more common in patients with CDI. Multivariate logistic regression analysis showed that exposure to antibiotics in the last 60 days (especially third generation cephalosporins and penicillins with ß-lactamase inhibitor), chronic renal or liver disease, malnutrition or previous CDI, were associated with an independent high risk of CDI. Age was not related with CDI. CONCLUSIONS: This study showed that antibiotics and some comorbid conditions were predictors of CDI. Patients at high risk of acquiring CDI at the time of admission may benefit from careful monitoring of antibiotic prescriptions and early attention to infection control issues. In future, these "high-risk" patients may benefit from novel agents being developed to prevent CDI.

How Admission to a Vascular Surgery Department Improves Medical Treatment in Patients with Lower Extremity Peripheral Arterial Disease.

BACKGROUND: All patients with lower extremity peripheral arterial disease (LE-PAD) should benefit from recommended pharmacologic therapies including antiplatelet agents, angiotensin-converting enzyme (ACE) inhibitors, or angiotensin receptor blockers (ARBs), and hydroxy-methyl-glutaryl-coenzyme A reductase inhibitors (statins). In the present study, this triple therapy was defined as the best medical treatment. This study was designed to determine the number of patients who received best medical treatment at admission and at discharge from a vascular surgery department. We also examined the number of patients who received adapted medical treatment and every pharmacologic class separately. Finally, we investigated whether there were differences in prescribing rates according to patient characteristics and cardiovascular history, clinical grade of LE-PAD, and the type of surgery practiced. MATERIALS AND METHODS: This study is a retrospective chart analysis of 140 consecutive patients admitted to the vascular surgery department of our university hospital, between January 1, 2013, and June 30, 2013. To be included, patients required a vascular surgery for peripheral arterial disease with atherosclerosis. Data from guideline-recommended classes of medications (antiplatelet agents, ACE, ARBs, and statins) at the time of admission and discharge were collected and compared. RESULTS: Best medical treatment was prescribed in 44% patients before hospital admission and in 50% at discharge (P = 0.10). Before hospital admission, 84% of patients had antiplatelet therapy compared with 96% at discharge (P = 0.0004); 73% had a statin, compared with 83% at discharge (P = 0.001); 64% had an ACE inhibitor or ARB, compared with 63% at the time of discharge (P = 1).The proportion of patients receiving best medical treatment at admission and discharge increased in case of coronary artery disease (P = 0.004). There was no difference in prescriptions of best medical treatment and best or adapted treatments at admission and discharge according to the severity of LE-PAD or type of revascularization. CONCLUSIONS: Admission to a vascular department significantly increased the rate of prescription of antiplatelet and statin therapy, but no significant improvement was achieved for the prescription of best medical treatment and best or adapted treatments.

Rituximab versus azathioprine for ANCA-associated vasculitis maintenance therapy: impact on global disability and health-related quality of life.

OBJECTIVES: To investigate the effects on health-related quality of life (HRQOL) and functional capability of rituximab vs azathioprine for ANCA-associated vasculitis (AAV) maintenance therapy. METHODS: In a 24-month phase III randomised-controlled trial, 115 patients over time received rituximab or azathioprine for AAV maintenance therapy. Mean changes of 36-item Short-form Health Survey (SF-36) and Health Assessment Questionnaire (HAQ) scores from baseline were analysed. RESULTS: Mean improvements of HAQ scores, from baseline to month 24 were significantly better for the rituximab (0.16 points lower) than the azathioprine group (p=0.038). As demonstrated by SF-36, study patients' baseline HRQOL was significantly impaired compared with age- and sex-matched US norms. At month 24, mean changes from baseline of SF-36 physical component score tended to be better for the rituximab group (+3.95 points, p=0.067) whereas mean changes from baseline of the SF-36 mental component score were significantly better for the azathioprine group (+4.23 points, p=0.041). CONCLUSIONS: Azathioprine-treated patients' for AAV maintenance therapy showed a decline in physical abilities when compared to RTX at M24 in the MAINRITSAN trial. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00748644.

Observational Study of a French and Belgian Multicenter Cohort of 23 Patients Diagnosed in Adulthood With Mevalonate Kinase Deficiency.

The aim of this study was to describe the clinical and biological features of Mevalonate kinase deficiency (MKD) in patients diagnosed in adulthood. This is a French and Belgian observational retrospective study from 2000 to 2014. To constitute the cohort, we cross-check the genetic and biochemical databases. The clinical, enzymatic, and genetic data were gathered from medical records. Twenty-three patients were analyzed. The mean age at diagnosis was 40 years, with a mean age at onset of symptoms of 3 years. All symptomatic patients had fever. Febrile attacks were mostly associated with arthralgia (90.9%); lymphadenopathy, abdominal pain, and skin lesions (86.4%); pharyngitis (63.6%); cough (59.1%); diarrhea, and hepatosplenomegaly (50.0%). Seven patients had psychiatric symptoms (31.8%). One patient developed recurrent seizures. Three patients experienced renal involvement (13.6%). Two patients had angiomyolipoma (9.1%). All but one tested patients had elevated serum immunoglobulin (Ig) D level. Twenty-one patients had genetic diagnosis; most of them were compound heterozygote (76.2%). p.Val377Ile was the most prevalent mutation. Structural articular damages and systemic AA amyloidosis were the 2 most serious complications. More than 65% of patients displayed decrease in severity and frequency of attacks with increasing age, but only 35% achieved remission. MKD diagnosed in adulthood shared clinical and genetic features with classical pediatric disease. An elevated IgD concentration is a good marker for MKD in adults. Despite a decrease of severity and frequency of attacks with age, only one-third of patients achieved spontaneous remission.

Long-Term Followup of a Multicenter Cohort of 101 Patients With Eosinophilic Granulomatosis With Polyangiitis (Churg-Strauss).

OBJECTIVE: To assess the long-term outcome in eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA). METHODS: A total of 101 patients fulfilling the American College of Rheumatology criteria for EGPA were included between 1990 and 2011. Clinical features, antineutrophil cytoplasm autoantibodies (ANCAs), and Five-Factors Score (FFS) were assessed at diagnosis. Overall and cumulative survival rates, relapse-free survival, and sequelae were studied based on ANCA status and FFS. RESULTS: The rate of cardiomyopathy did not differ according to ANCA status. A total of 79.6% of patients achieved first remission, but 81.1% relapsed. ANCA-positive patients did not relapse more frequently but exhibited more severe disease with mononeuritis (P = 0.0004) and renal involvement (P = 0.02). Being Italian was the only prognostic factor associated with a higher relapse-free survival (P = 0.01), thanks to a longer maintenance of immunosuppressive drugs, suggesting the need for prolonged low-dose corticosteroids. Overall, survival reached 93.1% after a median followup of 6 years. No factor was associated with mortality, but patients over age 65 years with cardiomyopathy or ANCA positivity had more serious outcomes. Sequelae affected 83.2% of patients. Ear, nose, and throat (ENT) involvement was a protective factor for renal (P = 0.04) and cardiac (P = 0.03) morbidity. ANCA positivity was correlated with chronic kidney disease (P = 0.03) and chronic neurologic disability (P = 0.02). CONCLUSION: The actual challenges of EGPA management concern morbidity prevention and quality of life improvement. Long-term corticosteroid treatment appears to reduce relapse risk. ENT involvement is associated with less renal and cardiac morbidity. ANCA positivity predicts renal and neurologic damage.

Hemophagocytic Lymphohistiocytosis in Intensive Care Unit: A 71-Case Strobe-Compliant Retrospective Study.

Hemophagocytic lymphohistiocytosis (HLH) is a critical condition that may lead to organ failure and early death. The aim of this retrospective observational study was to describe a cohort of HLH patients admitted to intensive care unit (ICU) and investigate the risk factors of early death.A positive HLH diagnosis was defined by an HScore ≥ 169. Univariate and multivariate analyses were carried out to investigate hospital and 28-day mortality risk factors. Between January 2002 and July 2014, 71 HLH cases were seen at our institution.The overall 28-day mortality (start at ICU admission) and hospital mortality were 38% and 68%, respectively. The factors associated with increased 28-day mortality were the sequential organ failure assessment score at ICU admission (P < .001) and advance in age (P = 0.03). The factors associated with increased hospital mortality were a high sequential organ failure assessment score at ICU admission (P < 0.01), advance in age (P = 0.04), and the presence of lymphoma-related HLH or HLH of unknown origin (P < 0.01).Organ failure overtops the classical early-death risk factors in adult ICU-admitted HLH patients. This failure and the subsequent early death may be prevented by timely specific cytotoxic therapies and the control of the underlying disease.

Validity of the global anti-phospholipid syndrome score to predict thrombosis: a prospective multicentre cohort study.

OBJECTIVE: To investigate the validity of the global APS score (GAPSS) to predict thrombosis in patients with autoimmune diseases. METHODS: This prospective cohort study included consecutive patients with aPL or SLE. aPL, aPS-PT and GAPSS were determined. A Cox proportional hazards model assessed the validity of GAPSS and identified other potential independent predictors of thrombosis. RESULTS: One hundred and thirty-seven patients [43.5 (s.d. 15.4) years old; 107 women] were followed up for a mean duration of 43.1 (s.d. 20.7) months. Mean GAPSS was significantly higher in patients who experienced a thrombotic event compared with those without [10.88 (s.d. 5.06) vs 8.15 (s.d. 5.31), respectively, P = 0.038]. In univariate analysis, age [hazard ratio (HR) = 1.04 (95% CI 1.01, 1.08)] and GAPSS above 16 [HR = 6.86 (95% CI 1.90, 24.77)] were each significantly associated with thrombosis during follow-up, while history of arterial thrombosis [HR = 2.61 (95% CI 0.87, 7.82)] failed to reach significance. Among aPL assays, IgG aPS/PT--a component of the GAPSS--was significantly associated with thrombosis [HR = 2.95 (95% CI 1.02, 8.51)]. In multivariate analysis, GAPSS above 16 remained the only significant predictor of thrombosis [HR = 6.17 (95% CI 1.70, 22.40)]. CONCLUSION: This first external validation study confirmed that GAPSS can predict thrombosis in patients with aPL and associated autoimmune diseases.

Treatment of systemic necrotizing vasculitides in patients aged sixty-five years or older: results of a multicenter, open-label, randomized controlled trial of corticosteroid and cyclophosphamide-based induction therapy.

OBJECTIVE: To investigate a new therapeutic strategy, with rapid corticosteroid dose tapering and limited cyclophosphamide (CYC) exposure, for older patients with systemic necrotizing vasculitides (SNVs; polyarteritis nodosa [PAN], granulomatosis with polyangiitis [Wegnener's] [GPA], microscopic polyangiitis [MPA], or eosinophilic GPA [Churg-Strauss] [EGPA]). METHODS: A multicenter, open-label, randomized controlled trial comprising patients ≥65 years old and newly diagnosed as having SNV was conducted. The experimental treatment consisted of corticosteroids for ∼9 months and a maximum of six 500-mg fixed-dose intravenous (IV) CYC pulses, every 2-3 weeks, then maintenance azathioprine or methotrexate. The control treatment included ∼26 months of corticosteroids for all patients, combined with 500 mg/m(2) IV CYC pulses, every 2-3 weeks until remission, then maintenance for all patients with GPA or MPA and for those with EGPA or PAN with a Five-Factors Score (FFS) of ≥1. Randomization used a 1:1 ratio computer-generated list and was performed centrally with sealed opaque envelopes. The primary outcome measure was ≥1 serious adverse event (SAE) occurring within 3 years of followup. Secondary outcome measures included remission and relapse rates. RESULTS: Among the 108 patients randomized, 4 were excluded (early consent withdrawal or protocol violation). Mean ± SD age at diagnosis was 75.2 ± 6.3 years. Analysis at 3 years included 53 patients (21 GPA, 21 MPA, 8 EGPA, and 3 PAN) in the experimental arm and 51 patients (15 GPA, 23 MPA, 6 EGPA, and 7 PAN) in the conventional arm. In total, 32 (60%) versus 40 (78%) had ≥1 SAE (P = 0.04), most frequently infections; 6 (11%) versus 7 (14%) failed to achieve remission (P = 0.71); 9 (17%) versus 12 (24%) died (P = 0.41); and 20 (44%) of 45 versus 12 (29%) of 41 survivors in remission experienced a relapse (P = 0.15). CONCLUSION: For older SNV patients, an induction regimen limiting corticosteroid exposure and with fixed low-dose IV CYC pulses reduces SAEs in comparison to conventional therapy, and does not affect the remission rate. Three-year relapse rates remain high for both arms.

Myocarditis in adult-onset still disease.

This study highlights the clinical features, treatments, and outcomes of the rare myocarditis in adult-onset Still disease (AOSD). Among a case series of 57 patients fulfilling either Yamaguchi or Fautrel AOSD criteria and seen between 1998 and 2010, we identified 4 cases of myocarditis. From a comprehensive literature review, we collected 20 additional cases of myocarditis-complicated AOSD. The characteristics of patients with myocarditis were compared with those of AOSD patients without myocarditis.In these 24 myocarditis-complicated AOSD cases, myocarditis occurred early and was present at AOSD onset in 54% of the cases. Myocarditis was often symptomatic (96% of patients) with nonspecific electrocardiographic abnormalities (79% of patients) and a left ventricle ejection fraction ≤50% (67% of patients). Cardiac magnetic resonance imaging and endomyocardial biopsies showed features consistent with myocarditis in 4 patients and a mononuclear interstitial inflammatory infiltrate in 4 others. Steroids alone were effective in 50% of patients with myocarditis. Intravenous immunoglobulins, methotrexate, and tumor necrosis factor-α-blockers were also prescribed and often found effective. Only 1 patient died from cardiogenic shock. Patients with myocarditis-complicated AOSD were younger and more frequently male than patients with AOSD alone. Pericarditis was more frequent in the myocarditis group; white blood cell count, polymorphonuclear cell count, and serum ferritin levels were also higher.Myocarditis is a potentially life-threatening complication of AOSD but responds positively to steroids and other immunomodulatory drugs. Its prognosis remains good (only 1 death occurred), but the condition requires close monitoring of heart function.

Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis.

BACKGROUND: The combination of cyclophosphamide and glucocorticoids leads to remission in most patients with antineutrophil cytoplasm antibody (ANCA)-associated vasculitides. However, even when patients receive maintenance treatment with azathioprine or methotrexate, the relapse rate remains high. Rituximab may help to maintain remission. METHODS: Patients with newly diagnosed or relapsing granulomatosis with polyangiitis, microscopic polyangiitis, or renal-limited ANCA-associated vasculitis in complete remission after a cyclophosphamide-glucocorticoid regimen were randomly assigned to receive either 500 mg of rituximab on days 0 and 14 and at months 6, 12, and 18 after study entry or daily azathioprine until month 22. The primary end point at month 28 was the rate of major relapse (the reappearance of disease activity or worsening, with a Birmingham Vasculitis Activity Score >0, and involvement of one or more major organs, disease-related life-threatening events, or both). RESULTS: The 115 enrolled patients (87 with granulomatosis with polyangiitis, 23 with microscopic polyangiitis, and 5 with renal-limited ANCA-associated vasculitis) received azathioprine (58 patients) or rituximab (57 patients). At month 28, major relapse had occurred in 17 patients in the azathioprine group (29%) and in 3 patients in the rituximab group (5%) (hazard ratio for relapse, 6.61; 95% confidence interval, 1.56 to 27.96; P=0.002). The frequencies of severe adverse events were similar in the two groups. Twenty-five patients in each group (P=0.92) had severe adverse events; there were 44 events in the azathioprine group and 45 in the rituximab group. Eight patients in the azathioprine group and 11 in the rituximab group had severe infections, and cancer developed in 2 patients in the azathioprine group and 1 in the rituximab group. Two patients in the azathioprine group died (1 from sepsis and 1 from pancreatic cancer). CONCLUSIONS: More patients with ANCA-associated vasculitides had sustained remission at month 28 with rituximab than with azathioprine. (Funded by the French Ministry of Health; MAINRITSAN ClinicalTrials.gov number, NCT00748644; EudraCT number, 2008-002846-51.).

Long-term effectiveness and safety of interleukin-1 receptor antagonist (anakinra) in Schnitzler's syndrome: a French multicenter study.

The aim of this study is to assess the long-term effectiveness and safety of IL1Ra in Schnitzler syndrome (SchS). Between 2010 and 2012, we performed a nationwide survey among French internal medicine departments to identify SchS patients. We retrospectively analyzed the long-term efficacy and safety of IL1Ra and the outcome of patients that did not receive this treatment. Forty-two patients were included in the study, 29 of whom received IL1Ra. The mean age at disease onset was 59.9years. Disease manifestations included urticaria (100%), fever (76%), bone/joint pain (86%), bone lesions (76%), anemia (67%), and weight loss (60%). The monoclonal gammopathy was overwhelmingly IgM kappa (83%). The mean follow-up was 9.5years (range: 1.6-35). Two patients developed Waldenström's macroglobulinemia and one developed AA amyloidosis. All of the 29 patients who received IL1Ra responded dramatically. After a median follow-up of 36months (range: 2-79), the effectiveness remained unchanged. All patients remained on anti-IL-1 therapy. Twenty-four patients (83%) went into complete remission and five (17%) into partial remission. Three patients experienced grade 3-4 neutropenia. Six patients developed severe infections. No lymphoproliferative diseases occurred while on IL1Ra. When last seen, all patients without anakinra had an active disease with variable impact on their quality of life. Their median corticosteroids dosage was 6mg/d (range: 5-25). IL1Ra is effective in SchS, with a sharp corticosteroid-sparing effect. Treatment failures should lead to reconsider the diagnosis. Long-term follow-up revealed no loss of effectiveness and a favorable tolerance profile. The long-term effects on the risk of hemopathy remain unknown.

Adult-onset still disease: manifestations, treatment, outcome, and prognostic factors in 57 patients.

We conducted a retrospective observational study to describe a cohort and identify the prognostic factors in adult-onset Still disease (AOSD). Patients enrolled in this retrospective chart review fulfilled either Yamaguchi or Fautrel criteria. Candidate variables were analyzed with logistic unadjusted and adjusted regression models. Fifty-seven patients were seen in the internal medicine (75%) and rheumatology (25%) departments over a mean period of 8.4 years. The median time to diagnosis was 4 months. The course of AOSD was monocyclic in 17 patients, polycyclic in 25, and chronic in 15. The assessment of glycosylated ferritin (GF) in 37 patients was correlated with early diagnosis. Nine F-fluorodeoxyglucose positron emission tomography (FDG-PET) scans identified the lymph nodes and glands as the main sites of hypermetabolism. Complications were frequent (n = 19), including reactive hemophagocytic syndrome (n = 8). None of the 3 deaths could be attributed to AOSD. Corticosteroid dependence, as predicted by a low GF level, occurred in 23 patients (45%). A quarter of the patients received tumor necrosis factor-α blockers or anakinra with good tolerance. Fever >39.5 °C was predictive of monocyclic AOSD, while arthritis and thrombocytopenia were associated with chronic and complicated AOSD, respectively. The youngest patients had the highest risks of resistance to first-line treatments.AOSD remains difficult to diagnose. Mortality is low despite frequent complications. GF and FDG-PET scans were of value in the diagnostic approach. The condition in highly symptomatic patients evolved to systemic AOSD, whereas more progressive patterns with arthritis predicted chronic AOSD.

Safety and efficacy of rituximab treatment for vasculitis in hepatitis B virus-associated type II cryoglobulinemia: a case report.

INTRODUCTION: Systemic B-cell depletion and clinical remission of the systemic effects of cryoglobulins have already been achieved using rituximab in hepatitis C virus-positive immunocompetent patients. Conversely, to the best of our knowledge there are no reports in the literature regarding the use of rituximab in hepatitis B virus-associated cryoglobulinemia. CASE PRESENTATION: We report here the case of a 60-year-old Caucasian man who presented with hepatitis B virus-associated type II cryoglobulinemia with severe multisystem disease, including membranoproliferative glomerulonephritis with acute renal failure. The vasculitis was refractory to conventional and antiviral therapy but rituximab use led to a fall in cryoglobulin levels and disease control. The B-cell depletion was safe and efficient to induce a complete remission of the disease. CONCLUSION: Our case highlights the benefit and the efficacy of rituximab in association with antiviral therapy in small vessel vasculitis related to hepatitis B virus-associated mixed cryoglobulinemia.

The systemic capillary leak syndrome: a case series of 28 patients from a European registry.

BACKGROUND: The systemic capillary leak syndrome (SCLS) is a rare disease characterized by life-threatening attacks of capillary hyperpermeability. OBJECTIVE: To describe the clinical characteristics, laboratory findings, treatments, and outcomes of patients with SCLS who were not previously reported in the literature. DESIGN: Case series. SETTING: Patients referred to a European multicenter SCLS registry between January 1997 and July 2010. PATIENTS: 28 patients with SCLS. MEASUREMENTS: Frequency, severity of attacks, and vital status were assessed every 6 months, from diagnosis to the end of the study. RESULTS: 13 men and 15 women referred to the registry who were not previously reported in the literature had 252 attacks. Median age at disease onset was 49.1 years (range, 5.4 to 77.7 years), and median annual frequency of attacks was 1.23 (range, 0.13 to 21.18) per patient. Monoclonal IgG gammopathy was observed in 25 patients (89%). Preventive treatment included intravenous immunoglobulin (n = 18), terbutaline (n = 9), and aminophylline (n = 10). Eight patients died (29%); 1-year survival was 89%, and 5-year survival was 73%. Death was directly related to SCLS attacks in 6 of 8 cases (75%). In 10 patients with a prediagnosis period greater than 6 months who received preventive treatment, the annual frequency of attacks after diagnosis decreased by a median of 1.55 (range, 0.14 to 8.84) per patient. Five years after diagnosis, survival was 85% in 23 patients who had received prophylactic treatment and 20% in 5 patients who had not. LIMITATION: The benefits of preventive treatment could not be precisely ascertained because of the small sample size and because most patients received several treatments. CONCLUSION: Clinical experience with these 28 patients with SCLS suggests that prophylactic treatment with ß(2)-agonists or intravenous immunoglobulin may reduce the frequency and severity of attacks and may improve survival. PRIMARY FUNDING SOURCE: Université Pierre et Marie Curie, Paris, France.

F-18 FDG-PET/CT in aseptic abscesses with recurrent febrile abdominal pain.

OBJECTIVE: Mendelian and complex autoinflammatory disorders frequently manifest as recurrent abdominal pain and fever. Diagnosis may be difficult and scant data are available about the interest of 2-deoxy-2-[18F]fluoro-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in such conditions, particularly aseptic abscesses (AA). MATERIAL AND METHODS: We analyzed five cases of AA in which FDG-PET/CT was performed at diagnosis (n = 2) and after a suspected relapse (n = 5). Follow-up FDG-PET/CT was performed in two patients 9 days and 6 weeks after the initiation of oral corticosteroids. RESULTS: FDG-PET/CT showed intense uptake foci in the abdominal lymph nodes (n = 4), liver (n = 2) and spleen (n = 4) before treatment. A marked metabolic response was observed while patients were being treated. In a relapsing patient with abdominal pain but no raised CRP, although CT scan was unchanged, abnormal uptake of FDG was observed. By contrast, some lesions previously observed on CT scan displayed no fixation on new FDG-PET/CT and were suggestive of sequelae in three patients. CONCLUSION: Although nonspecific, FDG-PET/CT may be an interesting tool for the diagnosis and management of recurrent and febrile abdominal pain in AA. At the time of relapse, it can differentiate between a sequela of previous flares and a new localization. It can be used for whole-body screening to look for other asymptomatic disease localizations.

Reactive hemophagocytic syndrome in adult-onset Still disease: clinical features and long-term outcome: a case-control study of 8 patients.

Reactive hemophagocytic syndrome (RHS) is a rare, life-threatening, and little-known complication of rheumatic diseases. This disorder is characterized by fever, pancytopenia, liver failure, coagulopathy, and neurologic symptoms. RHS may develop in patents who have lymphoma, organ transplantation, serious infection, and rheumatic diseases, most notably systemic lupus erythematosus and adult-onset Still disease (AOSD). Observations of specific cases of RHS in AOSD remain rare, and the significance of this syndrome during the course of AOSD remains unknown. We retrospectively studied 16 episodes of AOSD-associated RHS in 8 patients. To determine whether RHS is associated with a particular phenotype of AOSD, we conducted a case-control study from the cohort of AOSD patients seen during the same period. The estimated frequency of RHS in AOSD patients from our cohort was 15.3% (8/52). The median age at RHS diagnosis was 44.5 years. We collected clinical and laboratory data. RHS was the first manifestation of AOSD in 7 cases. The main symptoms were fever (n = 8), salmon rash (n = 6), arthralgia (n = 7), lymphadenopathy (n = 6), and shock (n = 4). Serum ferritin concentration was consistently elevated (>1000 microg/L in 8 cases), and the level of glycosylated ferritin was low in all cases (<5% in 7 cases, 15% in 1 case). Six patients presented with coagulopathy; hypertriglyceridemia was found in 6 cases. Admission to the intensive care unit was required in 4 cases. Treatment included corticosteroids (n = 8) and intravenous immunoglobulin (n = 6), cyclophosphamide in 2 cases, infliximab in the same 2 cases, and cyclosporine in 1 case. With a follow-up ranging from 2 to 15 years, the patients were in remission with prednisone plus methotrexate (n = 4), prednisone plus infliximab (n = 2), and low-dose prednisone alone (n = 2). We compared the 8 patients included in this study with 44 control patients with AOSD without RHS. Low haptoglobin levels, very high ferritin levels (>10,000 microg/L), and a normal or low neutrophil count seem to be predictive factors of the occurrence of RHS in AOSD.

Yield of bone marrow examination in diagnosing the source of fever of unknown origin.

BACKGROUND: Fever of unknown origin (FUO) still remains a diagnostic challenge, while diagnosis may remain obscure for several weeks or months. The role of tissue biopsy is crucial in the diagnostic approach. We report a series of 130 consecutive patients with FUO who had undergone a bone marrow biopsy (BMB). METHODS: Among 280 consecutive nonimmunocompromised patients hospitalized between 1995 and 2005 for a febrile illness of uncertain cause, lasting at least 3 weeks, with no diagnosis after an appropriate minimal diagnostic workup, 130 underwent BMB. RESULTS: Overall, a specific diagnosis was achieved by BMB and histological examination in 31 cases (diagnostic yield, 23.7%). Three types of diseases were found: hematological malignant diseases in 25 cases, including 19 patients with malignant lymphoma, 4 with acute leukemia, 1 with hairy cell leukemia, and 1 with multiple myeloma; infectious diseases in 3 cases; systemic mastocytosis in 2 cases; and disseminated granulomatosis in 1 case. Thrombocytopenia (odds ratio, 4.9; 95% confidence interval, 1.04-9.30) and anemia (odds ratio, 3.24; 95% CI, 1.13-9.34) were the most reliable predictive factors regarding the usefulness of BMB. Bone marrow cultures had very limited value in our cohort. Finally, corticosteroid use did not seem to affect the yield of BMB. CONCLUSIONS: Bone marrow biopsy is a useful technique for the diagnosis of prolonged fever in immunocompetent patients. Thrombocytopenia and anemia seem to be correlated with the value of this test.