Heparin-induced thrombocytopenia (HIT) is a relatively infrequent complication of heparin administration. HIT can cause devastating thrombosis, making it one of the most serious adverse drug reactions encountered in clinical practice. We successfully treated a case of severe HIT presenting with thrombosis and life-threatening bleeding complications with intravenous immunoglobulin (IVIG), platelet transfusion and oral anticoagulant Rivaroxaban. In this case, we considered that IVIG played the most important role by preventing further thrombosis, increasing the platelet count, and ensuring the efficacy of Rivaroxaban. We therefore suggest that IVIG might be the optimal treatment for patients with this urgent condition.
Aged, 80 and over ; Female ; Heparin ; administration & dosage ; adverse effects ; Humans ; Immunoglobulins, Intravenous ; administration & dosage ; Platelet Transfusion ; Rivaroxaban ; administration & dosage ; Thrombocytopenia ; chemically induced ; therapy

PURPOSE: Intravenous immunoglobulin (IVIG) is the standard treatment for Kawasaki disease (KD). However, there is still no standard treatment for IVIG-resistant KD. This study aimed to evaluate the efficacy of low-dose methotrexate (MTX) as a treatment for IVIG-resistant KD. MATERIALS AND METHODS: We retrospectively analyzed 10-year data for patients with IVIG-resistant KD who were administered MTX at Severance Children's Hospital. RESULTS: The subjects included 75 patients with KD aged 5 months to 9.2 years who had been administered MTX. Their maximum body temperatures decreased significantly within 24 h of therapy. The patients' C-reactive protein levels were significantly lower 1 week after administering the first dose of MTX than those before treatment. No adverse effect for MTX was observed. CONCLUSION: MTX treatment of IVIG-resistant KD resulted in rapid defervescence, improvement of clinical symptoms, and normalization of acute-phase reactants in all patients. Thus, MTX could be a candidate treatment for IVIG-resistant KD.
C-Reactive Protein/analysis ; Child ; Child, Preschool ; Coronary Vessels/pathology ; Demography ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Female ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Infant ; Male ; Methotrexate/administration & dosage ; Methotrexate/therapeutic use ; Mucocutaneous Lymph Node Syndrome/blood ; Mucocutaneous Lymph Node Syndrome/drug therapy ; Retrospective Studies ; Steroids/therapeutic use ; Treatment Outcome

Acute hemorrhagic leukoencephalitis (AHLE) is an acute, rapidly progressing, fulminant demyelinating disease. It is a rare disease of the central nervous system with high mortality; survivors commonly present with significant neurological deficit. We report the case of a 16-month-old girl who survived AHLE and presented with the associated neurologic deficit. The patient came into the emergency department with febrile seizure. She showed bilateral pinpoint-sized pupils and hyperactive deep tendon reflexes. Her mental status was initially drowsy and rapidly progressed to stupor. Extensive demyelination and microbleeds were found in the cerebral white matter, thalamus and left cerebellum on Magnetic resonance imaging (MRI) scans. Her mental status was improved by intravenous administration of immunoglobulin and methylprednisolone. Five months after being discharged, increased white matter connectivity was found on color-coded follow-up MR diffusion tensor imaging (DTI) as compared to previous MRI. We therefore suggest adding the DTI technique when a follow-up MRI is performed in patients with AHLE. It could be useful to visualize the status of axonal injury and to encourage patients and their parents to continue the rehabilitation program.
Administration, Intravenous ; Axons ; Central Nervous System ; Cerebellum ; Child ; Demyelinating Diseases ; Diffusion Tensor Imaging* ; Diffusion* ; Emergency Service, Hospital ; Female ; Follow-Up Studies* ; Humans ; Immunoglobulins ; Infant ; Leukoencephalitis, Acute Hemorrhagic* ; Magnetic Resonance Imaging ; Methylprednisolone ; Mortality ; Neurologic Manifestations ; Parents ; Pupil ; Rare Diseases ; Reflex, Stretch ; Rehabilitation ; Seizures ; Seizures, Febrile ; Stupor ; Survivors ; Thalamus ; White Matter

Acute hemorrhagic leukoencephalitis (AHLE) is an acute, rapidly progressing, fulminant demyelinating disease. It is a rare disease of the central nervous system with high mortality; survivors commonly present with significant neurological deficit. We report the case of a 16-month-old girl who survived AHLE and presented with the associated neurologic deficit. The patient came into the emergency department with febrile seizure. She showed bilateral pinpoint-sized pupils and hyperactive deep tendon reflexes. Her mental status was initially drowsy and rapidly progressed to stupor. Extensive demyelination and microbleeds were found in the cerebral white matter, thalamus and left cerebellum on Magnetic resonance imaging (MRI) scans. Her mental status was improved by intravenous administration of immunoglobulin and methylprednisolone. Five months after being discharged, increased white matter connectivity was found on color-coded follow-up MR diffusion tensor imaging (DTI) as compared to previous MRI. We therefore suggest adding the DTI technique when a follow-up MRI is performed in patients with AHLE. It could be useful to visualize the status of axonal injury and to encourage patients and their parents to continue the rehabilitation program.
Administration, Intravenous ; Axons ; Central Nervous System ; Cerebellum ; Child ; Demyelinating Diseases ; Diffusion Tensor Imaging* ; Diffusion* ; Emergency Service, Hospital ; Female ; Follow-Up Studies* ; Humans ; Immunoglobulins ; Infant ; Leukoencephalitis, Acute Hemorrhagic* ; Magnetic Resonance Imaging ; Methylprednisolone ; Mortality ; Neurologic Manifestations ; Parents ; Pupil ; Rare Diseases ; Reflex, Stretch ; Rehabilitation ; Seizures ; Seizures, Febrile ; Stupor ; Survivors ; Thalamus ; White Matter

Enterovirus 71 frequently involves the central nervous system and may present with a variety of neurologic manifestations. Here, we aimed to describe the clinical features, magnetic resonance imaging (MRI) findings, and cerebrospinal fluid (CSF) profiles of patients presenting with neurologic complications of enterovirus 71 infection. We retrospectively reviewed the records of 31 pediatric patients hospitalized with acute neurologic manifestations accompanied by confirmed enterovirus 71 infection at Ulsan University Hospital between 2010 and 2014. The patients' mean age was 2.9 ± 5.5 years (range, 18 days to 12 years), and 80.6% of patients were less than 4 years old. Based on their clinical features, the patients were classified into 4 clinical groups: brainstem encephalitis (n = 21), meningitis (n = 7), encephalitis (n = 2), and acute flaccid paralysis (n = 1). The common neurologic symptoms included myoclonus (58.1%), lethargy (54.8%), irritability (54.8%), vomiting (48.4%), ataxia (38.7%), and tremor (35.5%). Twenty-five patients underwent an MRI scan; of these, 14 (56.0%) revealed the characteristic increased T2 signal intensity in the posterior region of the brainstem and bilateral cerebellar dentate nuclei. Twenty-six of 30 patients (86.7%) showed CSF pleocytosis. Thirty patients (96.8%) recovered completely without any neurologic deficits; one patient (3.2%) died due to pulmonary hemorrhage and shock. In the present study, brainstem encephalitis was the most common neurologic manifestation of enterovirus 71 infection. The characteristic clinical symptoms such as myoclonus, ataxia, and tremor in conjunction with CSF pleocytosis and brainstem lesions on MR images are pathognomonic for diagnosis of neurologic involvement by enterovirus 71 infection.
Acute Disease ; Brain/diagnostic imaging ; Central Nervous System Diseases/etiology/*pathology ; Child ; Child, Preschool ; Encephalitis/pathology ; Enterovirus A, Human/genetics/*isolation & purification ; Enterovirus Infections/drug therapy/*pathology/virology ; Feces/virology ; Female ; Humans ; Immunoglobulins/administration & dosage ; Infant ; Injections, Intravenous ; Leukocytes/cytology ; Leukocytosis/cerebrospinal fluid/pathology ; Magnetic Resonance Imaging ; Male ; RNA, Viral/genetics/metabolism ; Real-Time Polymerase Chain Reaction ; Republic of Korea ; Retrospective Studies ; Seasons

OBJECTIVETo systematically investigate the efficacy and safety of glucocorticoids (GCs) combined with intravenous injection of immunoglobulin (IVIG) in the initial treatment of Kawasaki disease (KD).

METHODSEDLINE Database, PubMed Database, CNKI, Wanfang Data, and VIP Database were searched to collect prospective or retrospective controlled studies on the combination of GCs and IVIG as the initial treatment of KD, which were published up to March 2016. Two investigators independently screened the literature, extracted data, and assessed the quality of the articles included. Then, a Meta analysis was performed using RevMan 5.2 software.

RESULTSA total of 11 articles in English were included, with 7 prospective studies and 4 retrospective studies. The results of the Meta analysis showed that compared with the group using IVIG alone, the combination group had a significantly lower incidence rate of coronary artery lesion (CAL) (OR=0.44, 95%CI 0.23-0.86, P=0.02) and a significantly shorter duration of fever (MD=-1.66, 95%CI -2.32 to -1.01, P<0.00001). The combination group had a significantly lower rate of no response to initial treatment than the IVIG alone group (OR=0.37, 95%CI 0.27-0.51, P<0.00001). The recurrence rate of KD and the incidence rate of adverse events showed no significant differences between the two groups.

CONCLUSIONSGCs combined with IVIG as the initial treatment for KD can reduce the incidence rate of CAL and the rate of no response to initial treatment and shorten the duration of fever, and does not increase the recurrence rate of KD and the incidence rate of adverse events.

Coronary Artery Disease ; prevention & control ; Drug Therapy, Combination ; Glucocorticoids ; administration & dosage ; Humans ; Immunoglobulins, Intravenous ; administration & dosage ; Mucocutaneous Lymph Node Syndrome ; drug therapy ; Recurrence

PURPOSE: Recently, bortezomib has been used to treat antibody-mediated rejection (AMR) refractory to conventional treatment such as plasmapheresis, intravenous immunoglobulin, and rituximab. The authors aimed to describe their experiences when bortezomib was used to treat refractory AMR. MATERIALS AND METHODS: Eleven refractory AMR episodes treated with bortezomib were included in this study. The patients received one or two cycles of bortezomib (1.3 mg/m2) on days 1, 4, 8, and 11. RESULTS: Bortezomib effectively reduced antibodies against various targets, including human leukocyte antigen (HLA) class I and II, ABO blood group antigen, and angiotensin II type 1 receptor. Antibodies were depleted or reduced significantly in eight AMR episodes. Overall, there was a significant improvement in the mean estimated glomerular filtration rate (eGFR) at 3 months after therapy (36.91+/-22.15 mL/min/1.73 m2) versus eGFR at time of AMR diagnosis (17.00+/-9.25 mL/min/1.73 m2; p=0.007). All six early-onset AMR episodes (within 6 months post-transplantation) showed full recovery of allograft function. Additionally, three of the five late-onset AMR episodes (>6 months post-transplantation) showed improved allograft function. CONCLUSION: Anti-humoral treatment based on bortezomib might be an effective strategy against refractory AMR caused by various types of antibodies. Notably, this treatment could be more effective in early-onset AMR than in late-onset AMR.
Adolescent ; Adult ; Antibodies, Monoclonal/therapeutic use ; Antineoplastic Agents/*therapeutic use ; Boronic Acids/therapeutic use ; Bortezomib/*therapeutic use ; Female ; Graft Rejection/*drug therapy/*prevention & control ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Immunologic Factors/therapeutic use ; Isoantibodies ; Kidney Failure, Chronic/*surgery ; *Kidney Transplantation ; Male ; Middle Aged ; Plasmapheresis ; Pyrazines/administration & dosage ; Transplantation, Homologous

PURPOSE: To investigate the clinical effects of a single high dose intravenous immunoglobulin (IVIG) combined with initial dexamethasone as a primary treatment on Kawasaki disease (KD). MATERIALS AND METHODS: Between January 2008 and December 2010, we reviewed the medical records of 216 patients with complete KD patients that were admitted to a single medical center. 106 patients were treated with a single high dose of IVIG (2 g/kg) alone and 110 patients received IVIG and dexamethasone (0.3 mg/kg per day for three days). RESULTS: The combined IVIG plus dexamethasone patient group had a significantly shorter febrile period and duration of hospital stay (1.4+/-0.7 days vs. 2.0+/-1.2 days, p<0.001; 5.8+/-1.7 days vs. 6.9+/-2.5 days, p<0.001, respectively) than the IVIG alone group. The combined IVIG plus dexamethasone group required IVIG retreatment significantly less than the IVIG only group (12.7% vs. 32%, p=0.003). After completion of the initial IVIG, C-reactive protein levels in the combined IVIG plus dexamethasone group were significantly lower than those in the IVIG only group (2.7+/-4.0 mg/dL vs. 4.6+/-8.7 mg/dL, p=0.03). In the combined IVIG plus dexamethasone group, the incidence of coronary artery lesions tended to be lower without worse outcomes at admission after initial infusion of IVIG and in follow-up at two months; however, the differences were not significant (8.2% vs. 11.3%, p=0.22; 0.9% vs. 2.8%, p=0.29). CONCLUSION: Initial combined therapy with dexamethasone and a single high-dose of IVIG resulted in an improved clinical course, in particular a shorter febrile period, less IVIG retreatment, and shorter hospital stay without worse coronary outcomes.
Child, Preschool ; Dexamethasone/administration & dosage/adverse effects/*therapeutic use ; Female ; Fever/drug therapy ; Glucocorticoids/administration & dosage/adverse effects/*therapeutic use ; Humans ; Immunoglobulins, Intravenous/administration & dosage/adverse effects/therapeutic use ; Immunologic Factors/administration & dosage/adverse effects/*therapeutic use ; Infant ; Length of Stay ; Male ; Mucocutaneous Lymph Node Syndrome/*drug therapy ; Treatment Outcome

OBJECTIVETo analyze the clinical and molecular characteristics of patients with X-linked thrombocytopenia (XLT) and their responsiveness to treatment with various doses of corticosteroids or intravenous immunoglobulin (IVIG) separately.

METHODData from 15 XLT patients who were hospitalized in Children's Hospital Affiliated to Chongqing Medical University from March 2010 to July 2014 were analyzed retrospectively, including clinical manifestations, scores, peripheral blood, immunological functions, responses to IVIG and steroid treatment with various doses and duration.

RESULTAll 15 XLT patients met the inclusion criteria and showed microthrombocytopenia with or without mild-to-moderate eczema or minor infections. Platelet counts ranged from (8-80) × 10⁹/L. The platelet volume value ranged between 5.6 and 10.9 fl (normal range: 9.4-12.5 fl). Raised serum IgG was found in 5 cases, while low serum IgG was found in 2 cases. WAS gene analysis revealed missense mutations in 14 patients, including 4 hotspots (V75M, R86C, R86H, R86L) and 1 novel mutation (Y107C). Flow cytometer analysis of 13 patients showed various amounts of WAS protein (WASP) expression, 2 patients had normal amounts of WASP expression, 5 had reduced amounts, and 6 had absent WASP expression. Their responses to individual steroid and IVIG treatment with various doses and duration were also reviewed. Fourteen patients who were misdiagnosed as immune thrombocytopenic purpura at first received 28 courses of steroids and (or) 47 courses of IVIG treatment. The post-treatment platelet counts of 1 000-2 000 mg/(kg × d) IVIG(25 courses) at 2-7 d and 8-14 d time points were (60 ± 10) × 10⁹/L and (41 ± 7) × 10⁹/L, which indicate a significantly better responsiveness than those by [(31 ± 7) × 10⁹/L, (21 ± 2) × 10⁹/L] of 400-500 mg/(kg·d) IVIG(22 courses) (Z = -4.419, -1.592;P = 0.002,0.011). However, there were no significant differences between the responsiveness of 3 doses [1-2 mg/(kg·d)(8 courses), 3-6 mg/(kg·d) (11 courses) and 20-30 mg/(kg × d)(9 courses)] of steroids (F = 0.387,0.252;P = 0.980,0.761) at 2-7 d and 8-14 d time points. The platelet counts gradually decreased to the primary level at 15-30 d after any doses of steroids and (or) IVIG treatment. The effective rate of 1 000-2 000 mg/(kg × d) IVIG treatment was 18/25, which was significantly higher than that (2/22) of 400-500 mg/(kg × d) (χ² = 9.836, P = 0.008). The effective rate of 20-30 mg/(kg × d) steroids treatment (7/9) was relatively higher than 1-2 mg/(kg × d) (4/8) and 3-6 mg/(kg × d) (6/11) with no significant difference (χ⁹ = 3.235, P = 0.581). After the treatment with steroids and /or IVIG 14 cases with hemorrhage were all improved.

CONCLUSIONThe clinical characteristics of X-linked thrombocytopenia were microthrombocytopenia with or without mild-to-moderate eczema or minor infections. WAS gene and WASP analysis were diagnostic methods. There were no significant differences between the responsiveness of 3 doses of steroids; 1 000-2 000 mg/(kg·d) IVIG had a significantly better responsiveness. However, IVIG and steroids with any dose and duration may only transiently increase peripheral platelet level of XLT patients.

Adrenal Cortex Hormones ; administration & dosage ; Child ; Genetic Diseases, X-Linked ; drug therapy ; Humans ; Immunoglobulins, Intravenous ; administration & dosage ; Platelet Count ; statistics & numerical data ; Retrospective Studies ; Thrombocytopenia ; drug therapy ; Treatment Outcome

PURPOSE: This retrospective observational case series of fifty-one consecutive patients referred to the eye clinic with acute-stage Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) from 1995 to 2011 examines the effect of early treatment with a systemic corticosteroid or intravenous immunoglobulin (IVIG) on the ocular outcomes in patients with SJS or TEN. METHODS: All patients were classified by age (< or =18 years vs. >18 years) and analyzed by treatment modality and early intervention with systemic corticosteroids (< or =5 days), IVIG (< or =6 days), or amniotic membrane graft transplantation (AMT) (< or =15 days). The main outcomes were best-corrected visual acuity (BCVA) in logarithm of the minimum angle of resolution (logMAR) and ocular involvement scores (OIS, 0-12), which were calculated based on the presence of superficial punctate keratitis, epithelial defect, conjunctivalization, neovascularization, corneal opacity, keratinization, hyperemia, symblepharon, trichiasis, mucocutaneous junction involvement, meibomian gland involvement, and punctal damage. RESULTS: The mean logMAR and OIS scores at the initial visit were not significantly different in the pediatric group (logMAR = 0.44, OIS = 2.76, n = 17) or the adult group (logMAR = 0.60, OIS = 2.21, n = 34). At the final follow-up, the logMAR and OIS had improved significantly in the adult group (p = 0.0002, p = 0.023, respectively), but not in the pediatric group. Early intervention with IVIG or corticosteroids significantly improved the mean BCVA and OIS in the adult group (p = 0.043 and p = 0.024, respectively for IVIG; p = 0.002 and p = 0.034, respectively for corticosteroid). AMT was found to be associated with a significantly improved BCVA or OIS in the late treatment group or the group with a better initial OIS (p = 0.043 and p = 0.043, respectively for BCVA; p = 0.042 and p = 0.041, respectively for OIS). CONCLUSIONS: Our findings suggest that patients with SJS or TEN who are aged 18 years or less have poorer ocular outcomes than older patients and that early treatment with steroid or immunoglobulin therapy improves ocular outcomes.
Acute Disease ; Adolescent ; Age Factors ; Amnion/*transplantation ; Biopsy ; Child ; Child, Preschool ; Corneal Diseases/etiology/pathology/*therapy ; Female ; Follow-Up Studies ; Glucocorticoids/*administration & dosage ; Humans ; Immunoglobulins, Intravenous/*administration & dosage ; Infant ; Male ; Retrospective Studies ; Stevens-Johnson Syndrome/complications/pathology/*therapy ; Time Factors ; Treatment Outcome ; *Visual Acuity