Challenges in the diagnosis and management of immune-mediated necrotising myopathy (IMNM) in a patient on long-term statins.

Immune-mediated necrotising myopathy (IMNM) is a severe and poorly understood complication of statin use. Prompt management with immunosuppressive treatment is often needed to control the condition, which differs from the management of the more commonly recognised statin-induced myopathy. We present a case report and brief review of the literature regarding the pathogenesis, diagnosis, and management of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) positive IMNM (HMGCR IMNM). There are no randomised clinical trials, but several smaller studies and cases suggest a triple therapy of corticosteroids, IVIG, and a corticosteroid-sparing immunosuppressant appears efficacious in patients with IMNM and proximal weakness. The mechanism of statin-induced IMNM is uncertain, and this is further complicated by the reports of HMGCR IMNM in statin-naïve patients, including children. We present a case of biopsy-confirmed HMGCR IMNM in a woman taking daily statins for treatment of hypercholesterolaemia for 4 years. She presented with symptoms consistent with a urinary tract infection (UTI), including muscle weakness. She was treated as an isolated case of UTI. One month later, she presented again with worsening weakness in her shoulders and hips. Creatine kinase was elevated, and MRI showed increased signal with STIR sequences in both thighs. Anti-HMGCR was positive and leg biopsy-confirmed necrotising changes. Stopping her statin prescription and a short course of prednisolone did not improve her muscle weakness. Adding methotrexate resulted in eventual resolution of her symptoms. IMNM should be considered as a differential in any patient taking statins presenting with muscle weakness, and this case suggests that immunosuppressant therapy in addition to cessation of statins is effective at treating IMNM. Clinical trials are needed to further investigate the efficacy of different combinations of immunosuppressants.

Antibodies and Immunity During Kawasaki Disease.

The cause of Kawasaki disease (KD), the leading cause of acquired heart disease in children, is currently unknown. Epidemiology studies support that an infectious disease is involved in at least starting the inflammatory cascade set off during KD. Clues from epidemiology support that humoral immunity can have a protective effect. However, the role of the immune system, particularly of B cells and antibodies, in pathogenesis of KD is still unclear. Intravenous immunoglobulin (IVIG) and other therapies targeted at modulating inflammation can prevent development of coronary aneurysms. A number of autoantibody responses have been reported in children with KD and antibodies have been generated from aneurysmal plasma cell infiltrates. Recent reports show that children with KD have similar plasmablast responses as other children with infectious diseases, further supporting an infectious starting point. As ongoing studies are attempting to identify the etiology of KD through study of antibody responses, we sought to review the role of humoral immunity in KD pathogenesis, treatment, and recovery.

Measles virus neutralizing antibodies in immunoglobulin lots produced from plasma collected in Europe or the United States.

Vaccination against measles has reduced disease, although measles virus antibody (MVAb) levels are lower after vaccination than natural infection. Immunoglobulin (IG) preparations thus contain decreasing MVAb titers. US IG lot release requires a minimum titer of MVAb, yet equivalent information is not available for other geographies. Using a measles virus neutralization assay, IG fractionated from US or EU plasma is shown to contain similar levels of MVAb always above US regulatory requirements, supportive of equivalent protection against MV infection. Thus, the dosage for post-exposure prophylaxis in the EU could be aligned with the US FDA's treatment recommendations.

Neonatal Enterovirus Infection: Case Series of Clinical Sepsis and Positive Cerebrospinal Fluid Polymerase Chain Reaction Test with Myocarditis and Cerebral White Matter Injury Complications.

Objective We describe five neonates with enteroviral (EV) infection to demonstrate central nervous system (CNS) and cardiac complications and report successful treatment of myocarditis with immunoglobulin intravenous (IVIG) in two. Study Design Case series identified during three enteroviral seasons in one neonatal intensive care unit (NICU) by cerebral spinal fluid (CSF) reverse transcriptase polymerase chain reaction (PCR) testing for EV in neonates suspected to have sepsis, but with sterile bacterial cultures. Results Cases were identified in each of three sequential years in a NICU with 800 to 900 admissions/year. Two cases were likely acquired perinatally; all were symptomatic with lethargy and poor feeding by age 5 to 10 days. All had signs of sepsis and/or meningitis; one progressed to periventricular leukomalacia and encephalomalacia. Two recovered from myocarditis after treatment that included IVIG 3 to 5 g/kg. Conclusion Neonates who appear septic without bacterial etiology may have EV CNS infections that can be diagnosed rapidly by CSF PCR testing. Cases may be underdiagnosed in the early neonatal period if specific testing is not performed. Neonates with EV infection should be investigated for evidence of periventricular leukomalacia, screened for myocarditis, and considered for IVIG treatment.

Age and duration of bleeding symptoms at diagnosis best predict resolution of childhood immune thrombocytopenia at 3, 6, and 12 months.

OBJECTIVE: To evaluate the predictive value of clinical features at diagnosis of immune thrombocytopenia (ITP) for resolution of disease. STUDY DESIGN: Hospital records of 472 consecutive children (<18 years old) with ITP cared for at 2 participating centers were reviewed retrospectively and data related to the initial presentation were recorded. Logistic regression analysis was used for calculating prediction of resolution at 3, 6, and 12 months from diagnosis. RESULTS: The most significant predictors for resolution of ITP at 3, 6, and 12 months were age at onset <10 years and abrupt onset (history of <2 weeks of bleeding). We designed a prediction rule for ITP chronicity based on these criteria. The rate of developing chronic ITP for low, intermediate, and high risk children at diagnosis of ITP was 11%, 39%, and 63%, respectively. Recovery rate at 3 months for low, intermediate, and high risk children was 72%, 43% and 30%, respectively. CONCLUSIONS: We present a simple rule to predict recovery from ITP at 3, 6, and 12 months from diagnosis. For prediction of resolution at 3 months, our rule was in agreement with the more complex, previously described Nordic score. Prediction of resolution of ITP may enable practitioners to better inform children and parents at the time of diagnosis, resulting in reduced anxiety and improved quality of life.

Encefalopatía aguda en un paciente tratado con inmunoglobulina endovenosa por un síndrome de Guillain-Barré / Acute encephalopathy associated with the use of intravenous immunoglobulin. Report of one case

Adverse reactions to intravenous immunoglobulin (ivIg) therapy, such as anaphylaxis, acute encephalopathy, aseptic meningitis, or thrombotic phenomena are uncommon. We report a 58-year-old man with hypertension presenting with muscle weakness which led to paraparesia and respiratory failure. With the diagnosis of Guillain-Barré syndrome (GBS), he was treated with ivIg. He developed an acute encephalopathy few hours after the administration of ivIg, with a decreased level of consciousness and agitation. A CT scan revealed moderate and diffuse brain edema. Encephalopathy resolved 96 hours after ivIg withdrawal and use of plasma exchange. A CT scan performed seven days after showed the resolution of brain edema.

Clinical applications of immunoglobulin: update: [review]

Human immunoglobulin is the most used blood product in the clinical practice. Immunoglobulin applications have increased quickly since the elucidation of its immunomodulatory and antiinflammatory properties which turned this blood product into a precious tool in the treatment of numerous diseases that present with humoral immune deficiency or that cause immune system dysfunction. Currently, the approved indications for Ig are: primary immunodeficiencies, secondary immunodeficiencies (multiple myeloma or chronic lymphoid leukemia), Kawasaki syndrome, immune thrombocytopenic purpura, Guillain Barré syndrome, graft-versus-host disease following bone marrow transplantation and repeat infections in HIV children. On the other hand, there are numerous "off-label" indications of immunoglobulin, which represent 20-60 percent of all clinical applications of this drug. It is important to study all these indications and, above all, the scientific evidence for its use, in order to provide patients with a new therapeutic option without burdening the health system. This review results from a wide selection of papers identified in the Pubmed and Lilacs scientific electronic databases. A group of descriptors were used from human immunoglobulin to the names of each disease that immunoglobulin is clinically applied. Our main objective is to list the numerous indications of immunoglobulin, both authorized and "off-label" and to analyze these indications in the light of the most recent scientific evidence.

Clinical applications of immunoglobulin: update.

Human immunoglobulin is the most used blood product in the clinical practice. Immunoglobulin applications have increased quickly since the elucidation of its immunomodulatory and antiinflammatory properties which turned this blood product into a precious tool in the treatment of numerous diseases that present with humoral immune deficiency or that cause immune system dysfunction. Currently, the approved indications for Ig are: primary immunodeficiencies, secondary immunodeficiencies (multiple myeloma or chronic lymphoid leukemia), Kawasaki syndrome, immune thrombocytopenic purpura, Guillain Barré syndrome, graft-versus-host disease following bone marrow transplantation and repeat infections in HIV children. On the other hand, there are numerous "off-label" indications of immunoglobulin, which represent 20-60% of all clinical applications of this drug. It is important to study all these indications and, above all, the scientific evidence for its use, in order to provide patients with a new therapeutic option without burdening the health system. This review results from a wide selection of papers identified in the Pubmed and Lilacs scientific electronic databases. A group of descriptors were used from human immunoglobulin to the names of each disease that immunoglobulin is clinically applied. Our main objective is to list the numerous indications of immunoglobulin, both authorized and "off-label" and to analyze these indications in the light of the most recent scientific evidence.

Tratamento de vasculopatia livedóide com imunoglobulina intravenosa / Treatment of Livedoid Vasculopathy with intravenous immunoglobulin

A vasculopatia livedóide apresenta-se com dor e úlceras de cicatrização lenta em membros inferiores, e fisiopatologia obscura. As estratégias terapêuticas incluem cicatrizantes, antiinflamatórios e imunossupressores, sem relatos de benefício permanente. Administrou-se imunoglobulina em paciente refratário a outras terapias e avaliou-se o comprometimento da pele antes e depois por meio de escore clínico. Houve regressão significativa das lesões. A droga foi bem tolerada, e a terapia foi finalizada.

Livedoid vasculopathy presents with pain and slowly healing ulcerations of the lower limbs, and has obscure pathophysiology. Usual therapeutics include rheologic, anti-inflammatory and immunosuppressing agents with no reports of permanent benefits. Immunoglobulin was administered to a patient who was refractory to other treatments and skin involvement was assessed by means of clinical score before and after treatment. There was a significant healing of the lesions. Imunoglobulim was well tolerated and therapy was discontinued.