CHRONIC ACTIVE EPSTEIN-BARR VIRUS INFECTION MIMICKING HENOCH-SCHONLEIN PURPURA

Introduction: Chronic active Epstein-Barr virus (CAEBV) infection is characterized by chronic or recurrent symptoms for at least 3 months, such as fever, hepatosplenomegaly and lymphadenopathy. The diagnosis is established due to the presence of anti-EBV antibodies or isolation of this infectious agent in affected tissues. Three cases of CAEBV infection mimicking Henoch-Schonlein purpura (HSP) were described. Case 1: Female 3-year old patient with cervical adenomegaly, anemia and fever developed palpable purpura, haematuria and arthritis. CAEBV infection was established by serology test. She received methylprednisolone and acyclovir. She had generalized lymphadenopathy, hepatomegaly, splenomegaly, disseminated intravascular coagulation and deceased. Case 2: Male 12-year old patient with persistent anemia, lymphadenopathy, hepatomegaly and splenomegaly had CAEBV infection diagnosis by serology test. He developed purpura and arthritis and received methylprednisolone. Case 3: Male 13-year old patient had purpura, abdominal pain, haematuria, hepatomegaly, splenomegaly, lymphadenopathy, anemia and elevated liver enzymes. The cervical lymph node biopsy was positive to EBV infection. He received methylprednisolone and acyclovir, developing acute fulminant hepatitis and death. Discussion: CAEBV infection mimicking HSP was rarely observed in our population

Fatal gemcitabine-induced pulmonary toxicity in metastatic gallbladder adenocarcinoma

Gemcitabine is a chemotherapy agent that may cause unpredictable side effects. In this report, we describe a fatal gemcitabine-induced pulmonary toxicity in a patient with gallbladder metastatic adenocarcinoma. A 72-year-old patient was submitted to an elective laparoscopic cholecystectomy, and a tubular adenocarcinoma in the gallbladder was incidentally diagnosed. CT scan and ultrasound before the surgery did not show any tumor. After the surgery a Pet scan was positive for a hot-spot in the left colon. The colonic lesion was conveniently removed and the histology evaluation confirmed the diagnosis of adenocarcinoma tubular. The patient was then submitted to three sections of 1,600 mg/m(2) of gemcitabine with intervals of 1 week. Three weeks later he developed severe respiratory distress. A helicoidal CT scan showed diffuse and severe interstitial pneumonitis, and lung biopsy confirmed accelerated usual interstitial pneumonia consistent with drug-induced toxicity. The patient presented unfavorable evolution with progressive worsening of respiratory function, hypotension, and renal failure. He died 1 month later in spite of methylprednisolone pulse therapy, large spectrum antimicrobial therapy, and full support of respiratory, hemodynamic and renal systems. Gemcitabine-induced pulmonary toxicity is usually a dramatic condition. Physicians should suspect pulmonary toxicity in patients with respiratory distress after gemcitabine chemotherapy, mainly in elderly patients.

Acute pancreatitis in juvenile systemic lupus erythematosus: a manifestation of macrophage activation syndrome?

Acute pancreatitis (AP) is a rare and life-threatening manifestation of juvenile systemic lupus erythematosus (JSLE). The objective of this study was to evaluate the prevalence and clinical features of AP in our JSLE population. AP was defined according to the presence of abdominal pain or vomiting associated to an increase of pancreatic enzymes and/or pancreatic radiological abnormalities. Of note, in the last 26 years, 5367 patients were followed up at our Pediatric Rheumatology Unit and 263 (4.9%) of them had JSLE diagnosis (ACR criteria). AP was observed in 4.2% (11/263) of JSLE patients. The median of age of the JSLE patients at AP diagnosis was 12.4 years (8.8-17.9). All of them had lupus disease activity at AP onset. Three patients were receiving corticosteroids before AP diagnosis. Interestingly, 10/11 JSLE patients fulfilled preliminary guidelines for macrophage activation syndrome, three of them with macrophage hemophagocytosis in bone marrow aspirate and hyperferritinemia. The hallmark of this syndrome is excessive activation and proliferation of T lymphocytes and macrophages with massive hypersecretion of proinflammatory cytokines and clinically it is characterized by the occurrence of unexplained fever, cytopenia and hyperferritinemia. AP treatment was mainly based on intravenous methylprednisolone. Four JSLE patients with AP died and two developed diabetes mellitus. In conclusion, AP was a rare and severe manifestation in active pediatric lupus. The association between AP and macrophage activation syndrome suggests that the pancreas could be a target organ of this syndrome and that pancreatic enzyme evaluation should also be carried out in all patients. Lupus (2010) 19, 1654 1658.

Comparison of clinical features and drug therapies among European and Latin American patients with juvenile dermatomyositis

Objective To compare the demographic features, presenting manifestations, diagnostic investigations, disease course, and drug therapies of children with juvenile dermatomyositis (JDM) followed in Europe and Latin America. Methods Patients were inception cohorts seen between 1980 and 2004 in 27 paediatric rheumatology centres. The following information was collected through the review of patient charts: sex; age at disease onset; date of disease onset and diagnosis; onset type; presenting clinical features; diagnostic investigations; course type; and medications received during disease course. Results Four hundred and ninety patients (65.5% females, mean onset age 7.0 years, mean disease duration 7.7 years) were included. Disease presentation was acute or insidious in 57.1% and 42.9% of the patients, respectively. The course type was monophasic in 41.3% of patients and chronic polycyclic or continuous in 58.6% of patients. The more common presenting manifestations were muscle weakness (84.9%), Gottron`s papules (72.9%), heliotrope rash (62%), and malar rash (56.7%). Overall, the demographic and clinical features of the 2 continental cohorts were comparable. European patients received more frequently high-dose intravenous methylprednisolone, cyclosporine, cyclophosphamide, and azathioprine, while methotrexate and antimalarials medications were used more commonly by Latin American physicians. Conclusion The demographic and clinical characteristics of JDM are similar in European and Latin American patients. We found, however, several differences in the use of medications between European and Latin American paediatric rheumatologists.

Treatment of lupus nephritis: art or science? [Editorial]

No Abstract

Methadone Intoxication in a Child: Toxic Encephalopathy?

Methadone is used in the treatment of opioid addiction. Acute intoxication can lead to severe consequences and can even be lethal. In several case reports and small series, a presumably toxic leukoencephalopathy is described resulting from inhalation of heroin. We present the case of a 3-year-old boy who ingested methadone accidentally. In a coma with acute obstructive hydrocephalus owing to massive cerebellar edema and supratentorial lesions, he was successfully treated with methylprednisolone and cerebrospinal fluid external drainage. To our knowledge, this is the first report of an encephalopathy associated with synthetic opioid intoxication.

Postmalaria neurological syndrome: a case report

Described here is a case of postmalaria neurological syndrome in a patient who presented infection by Plasmodium falciparum two months earlier. The patient received empiric use of acyclovir for herpetic meningoencephalitis, but neuropsychiatric symptoms improved only after administration of methylprednisolone.

Acute disseminated encephalomyelitis following inactivated influenza vaccination in the Brazilian Amazon: a case report

AbstractHere, we describe a case of acute disseminated encephalomyelitis (ADEM) that occurred during a plausible risk interval following inactivated influenza vaccination in a previously healthy 27-year-old man from Manaus, Brazil. He was treated with intravenous methylprednisolone and immunoglobulin. One-month follow-up revealed resolution of the brain lesions, but not of the spinal cord lesions. No recurrence or progression of the main neurological symptoms was observed. After two years of monitoring, the patient continues to experience weak lower limbs and urinary retention. Thus, we recommend that ADEM should be considered in a patient presenting with neurological symptoms after influenza vaccination.

Pulmonary hemorrhage as a manifestation of systemic lupus erythematosus

The authors report a case of a 19-year-old woman admitted for the investigation of fever and hemolytic anemia for the previous 2 months. As an inpatient, she had convulsions and sudden loss of consciousness, developing hemoptysis, hypoxia, and respiratory insufficiency. Examination showed pericardial effusions on the echocardiogram and bilateral alveolar condensations on the thoracic radiograph. A hypothetical diagnosis of systemic lupus erythematosus was made, and measurement of the antinuclear factor was requested along with daily pulse therapy methylprednisolone, in spite of which the outcome was fatal. Afterwards, the result of the antinuclear factor test was positive, with a titer of 1:5120, showing a fine punctiform pattern, fulfilling the criteria for systemic lupus erythematosus according to the American College of Rheumatology. Secondary pulmonary hemorrhage in this connective tissue disease is an uncommon but serious complication that involves a high level of mortality in spite of intensive treatment, as is also reported in the literature.

Short-course thymoglobulin induction and steroid-free immunosuppressive regimen in renal transplantation

Purpose: Optimal induction and maintenance immunosuppressive therapies in renal transplantation are still a matter of debate.Chronic corticosteroid usage is a major cause of morbidity but steroid-free immunosuppression (SF) can result in unacceptably high rates of acute rejection and even graft loss. Methods and materials: We have conducted a prospective openlabelled clinical trial in the Geneva-Lausanne Transplant Network from March 2005 to May 2008. 20 low immunological risk (<20% PRA, no DSA) adult recipients of a primary kidney allograft received a 4-day course of thymoglobulin (1.5 mg/kg/d) with methylprednisolone and maintenance based immunosuppression of tacrolimus and entericcoated mycophenolic acid (MPA). The control arm consisted of 16 matched recipients treated with basiliximab induction, tacrolimus, mycophenolate mofetil and corticosteroids. Primary endpoints were the percentage of recipients not taking steroids and the percentage of rejection-free recipients at 12 months.Secondary end points were allograft survival at 12 months and significant thymoglobulin and/or other drugs side effects. Results: In the SF group, 85% of the kidney recipients remained steroid-free at 12 months. The 3 cases of steroids introduction were due to one acute tubulo-interstitial rejection occurring at day 11, one tacrolimus withdrawal due to thrombotic microangiopathy and one MPA withdrawal because of multiple sinusitis and CMV reactivations. No BK viremia was detected nor CMV disease. The 6 CMV negative patients who received a positive CMV allograft had a symptomatic primoinfection after their 6-month course valgancyclovir prophylaxis. In the steroid-based group, 3 acute rejection episodes (acute humoral rejection, acute tubulointerstitial Banff IA and vascular Banff IIA) occurred in 2 recipients, 3 BK virus nephropathies were diagnosed between 45 and 135 days post transplant No side effects were associated with thymoglobulin infusion.In the SF group, 4 recipients presented severe leukopenia or agranulocytosis and one recipient had febrile hepatitis leading to transient MPA withdrawal. Discontinuation of MPA was needed in 2 patients for recurrent sinusitis and CMV reactivations. Patient and graft survival was 100% in both groups at 12 month follow-up. Conclusion: Steroid-free with short-course thymoglobulin induction therapy was a safe protocol in low-risk renal transplant recipients. Lower rates of acute rejection and BK virus infections episodes were seen compared to the steroid-based control group. A longer follow-up will be needed to determine whether this SF immunosuppressive regimen will result in higher graft and patient survival.

Association between IL-18 gene polymorphisms and biopsy-proven giant cell

INTRODUCTION: The objective was to investigate the potential implication of the IL18 gene promoter polymorphisms in the susceptibility to giant-cell arteritis GCA). METHODS: In total, 212 patients diagnosed with biopsy-proven GCA were included in this study. DNA from patients and matched controls was obtained from peripheral blood. Samples were genotyped for the IL18-137 G>C (rs187238), the IL18-607 C>A (rs1946518), and the IL18-1297 T>C (rs360719) gene polymorphisms with polymerase chain reaction, by using a predesigned TaqMan allele discrimination assay. RESULTS: No significant association between the IL18-137 G>C polymorphism and GCA was found. However, the IL18 -607 allele A was significantly increased in GCA patients compared with controls (47.8% versus 40.9% in patients and controls respectively; P = 0.02; OR, 1.32; 95% CI, 1.04 to 1.69). It was due to an increased frequency of homozygosity for the IL18 -607 A/A genotype in patients with GCA (20.4%) compared with controls (13.4%) (IL18 -607 A/A versus IL18 -607 A/C plus IL18 -607 C/C genotypes: P = 0.04; OR, 1.59; 95% CI, 1.02 to 2.46). Also, the IL18-1297 allele C was significantly increased in GCA patients (30.7%) compared with controls (23.0%) (P = 0.003; OR, 1.48; 95% CI, 1.13 to 1.95). In this regard, an increased susceptibility to GCA was observed in individuals carrying the IL18-1297 C/C or the IL18-1297 C/T genotypes compared with those carrying the IL18-1297 T/T genotype (IL18-1297 C/C plus IL18-1297 T/C versus IL18-1297 T/T genotype in GCA patients compared with controls: P = 0.005; OR, 1.61; 95% CI, 1.15 to 2.25). We also found an additive effect of the IL18 -1297 and -607 polymorphisms with TLR4 Asp299Gly polymorphism. The OR for GCA was 1.95 for combinations of genotypes with one or two risk alleles, whereas carriers of three or more risk alleles have an OR of 3.7. CONCLUSIONS: Our results show for the first time an implication of IL18 gene-promoter polymorphisms in the susceptibility to biopsy-proven GCA. In addition, an additive effect between the associated IL18 and TLR4 genetic variants was observed.

R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study.

BACKGROUND The role of re-treatment with rituximab in aggressive B-cell lymphomas still needs to be defined. This study evaluated the influence of prior exposure to rituximab on response rates and survival in patients with diffuse large B-cell lymphoma treated with rituximab plus etoposide, cytarabine, cisplatinum and methylprednisolone (R-ESHAP). DESIGN AND METHODS We retrospectively analyzed 163 patients with relapsed or refractory diffuse large B-cell lymphoma who received R-ESHAP as salvage therapy with a curative purpose. Patients were divided into two groups according to whether rituximab had been administered (n=94, "R+" group) or not (n=69, "R-" group) prior to R-ESHAP. RESULTS Response rates were significantly higher in the R- group in the univariate but not in the multivariate analysis. In the analysis restricted to the R+ group, we observed very low complete remission and overall response rates in patients with primary refractory disease (8% and 33%, respectively), as compared to those in patients who were in first partial remission (41% and 86%) or who had relapsed disease (50% and 75%) (p<0.01 in both cases). Overall, 60% and 65% of patients in the R+ and R- groups, respectively, underwent stem-cell transplantation after the salvage therapy. With a median follow-up of 29 months (range, 6-84), patients in the R+ group had significantly worse progression-free survival (17% vs. 57% at 3 years, p<0.0001) and overall survival (38% v 67% at 3 years, p=0.0005) than patients in the R- group. Prior exposure to rituximab was also an independent adverse prognostic factor for both progression-free survival (RR: 2.0; 95% CI: 1.2-3.3, p=0.008) and overall survival (RR: 2.2; 95% CI: 1.3-3.9, p=0.004). CONCLUSIONS R-ESHAP was associated with a high response rate in patients who were not refractory to upfront rituximab-based chemotherapy. However, the survival outcome was poor for patients previously exposed to rituximab, as compared to in those who had not previously been treated with rituximab.

Rejet de greffe et iontophorèse de corticoïdes: à propos de 3 cas [Corneal graft rejection and corticoid iontophoresis: 3 case reports].

This is the first report of three cases of severe acute corneal graft rejection, treated by transscleral methylprednisolone (Solumédrol) iontophoresis. The efficacy of the treatment was evaluated by corneal transparency, visual acuity and corneal inflammation parameters. The patient was treated with Solumédrol iontophoresis once a day for 3 days with a topical corticotherapy reduced to three drops of dexamethasone per day. Iontophoresis was performed, under topical anesthesia, and lasted 3 minutes with a 1.5-mA current. The subjective and objective tolerance of iontophoresis was good. No side-effect was observed. Corneal transparency and visual acuity improved rapidly after the second iontophoresis procedure. These observations show that Solumédrol iontophoresis might be an alternative to pulse therapy in the treatment of corneal graft rejection. Further comparative studies are necessary to confirm these preliminary observations.

Impairment of JCV-specific T-cell response by corticotherapy: Effect on PML-IRIS management?

OBJECTIVE: To investigate the impact of corticosteroids (CS) on the viral-specific T-cell response, in particular the JC virus (JCV)-specific one, in an attempt to determine the optimal timing of CS in the management of progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome (PML-IRIS). METHODS: A blood draw was performed before and 7 days after the administration of IV CS to 24 patients with relapsing multiple sclerosis (MS). The phenotypic pattern of T cells was determined by CCR7 and CD45RA. To assess the impact of CS treatment on proliferative response of JCV-, influenza-, and Epstein-Barr virus (EBV)-specific T cells, a thymidine incorporation proliferation assay was performed. An intracellular cytokine staining assay was performed to determine the effect of CS treatment on the production of cytokine by virus-specific T cells. JCV T-cell assays were performed only in JCV-infected patients with MS as detected by serologies (Stratify) or detection of JCV DNA in the urine by PCR. RESULTS: CS led T cells, CD4+ and CD8+, toward a less differentiated phenotype. There was a significant decrease of EBV-, influenza-, and JCV-specific T-cell proliferative response upon CS treatment. There was a significant decrease in the frequency of interferon (IFN) γ- and tumor necrosis factor (TNF) α-producing JCV-specific CD8+ T cells, but not EBV- or influenza-specific CD4+ or CD8+ T cells. CONCLUSIONS: CS have a profound impact on the virus-specific T-cell response, especially on JCV, suggesting that when CS are considered, they should not be given before the onset of clinical or radiologic signs of IRIS. Studies addressing directly patients with MS with natalizumab-caused PML are warranted. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that methylprednisolone treatment decreases the frequency of JCV-specific CD8+ T cells producing IFN-γ and TNFα, impairing control of JCV, suggesting this should be used to treat but not to prevent PML-IRIS. No clinical outcomes were measured.

Thrombose veineuse cérébrale après ponction lombaire et stéroïdes intraveineux chez deux patients souffrant d'une sclérose en plaques [Cerebral venous thrombosis after lumbar puncture and intravenous steroids in two patients with multiple sclerosis]

Two patients affected with a multiple sclerosis developed cerebral venous thrombosis after lumbar puncture and treatment with intravenous methylprednisolone. In one case, the course was favorable. The second patient died in spite of intracerebral thrombolysis. The autopsy confirmed the diagnosis of cerebral venous thrombosis and multiple sclerosis. We discuss the relationship between lumbar puncture, steroid treatment and cerebral venous thrombosis.