Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Paroxysmal nocturnal hemoglobinuria (PNH) is a progressive, life-threatening disorder characterized by chronic intravascular hemolysis caused by uncontrolled complement activation. Hepatic vein thrombosis (Budd-Chiari syndrome) is common in PNH patients. This case report describes the response to eculizumab (a humanized monoclonal antibody that inhibits terminal complement activation) in a 25-year-old male with progressive liver function deterioration despite standard anticoagulation therapy and transjugular intrahepatic porto-systemic shunt. The patient presented with anemia, severe thrombocytopenia, headache, abdominal pain, and distention. He was diagnosed with PNH, cerebral vein thrombosis, and Budd-Chiari syndrome. Despite adequate anticoagulation, diuretic administration, and placement of a transjugular shunt, additional thrombotic events and progressive liver damage were observed. Eculizumab therapy was initiated, resulting in rapid blockade of intravascular hemolysis, increased platelet counts, ascites resolution, and liver function recovery, all of which are presently sustained. Since starting eculizumab the patient has had no further thrombotic events and his quality of life has dramatically improved. This is the first report to confirm the role of complement-mediated injury in the progression of Budd-Chiari syndrome in a patient with PNH. This case shows that terminal complement blockade with eculizumab can reverse progressive thromboses and hepatic failure that is unresponsive to anticoagulation therapy and suggests that early initiation of eculizumab should be included in the therapeutic regimen of patients with PNH-related Budd-Chiari syndrome.
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PMID:Eculizumab in paroxysmal nocturnal hemoglobinuria with Budd-Chiari syndrome progressing despite anticoagulation. 2321 Apr 33

A 25-year-old woman presented with acute bilateral blurred vision and history of headache, dizziness, and syncope for three days. Her visual acuity was 20/60 in both eyes. Fundoscopy revealed multiple bilateral peripapillary yellow-white patches like cotton wool spots, intraretinal hemorrhages and macular edema. The patient was diagnosed with Purtscher-like retinopathy based on the retinal findings and lack of trauma history. She was urgently admitted to the nephrology clinic due to thrombotic microangiopathy findings (hemoglobinemia, thrombocytopenia, and acute renal failure). After excluding thrombotic microangiopathy, the patient was diagnosed with atypical hemolytic uremic syndrome (aHUS) with the clinical and laboratory findings. Eculizumab treatment was added to hemodialysis and plasmapheresis therapy. Three months after starting treatment, retinal lesions regressed and visual acuity increased to 20/20 in both eyes. To the best of our knowledge, this is the first reported case of Purtscher-like retinopathy associated with aHUS.
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PMID:Purtscher-Like Retinopathy Associated with Atypical Hemolytic Uremic Syndrome. 2932 53

Bevacizumab (Avastin) is a recombinant humanized monoclonal antibody used for the management of various solid malignancies including colorectal, lung, brain, renal, and ovarian cancers as well as age-related macular degeneration of the eye. It is a vascular endothelial growth factor inhibitor which exhibits its action by blocking the growth of blood vessels in cancerous tissue. Common side effects include hypertension, fatigue, headaches, and increased risk of infections. Atypical hemolytic uremic syndrome is a serious side effect associated with bevacizumab due to its anti-angiogenic effect. It encompasses the clinical triad of thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure, without any association with Shiga toxins. Eculizumab is a terminal complement inhibitor used in the treatment of atypical hemolytic uremic syndrome. Herein, we present three cases of bevacizumab-induced atypical hemolytic syndrome treated successfully with eculizumab.
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PMID:Bevacizumab-induced atypical hemolytic uremic syndrome and treatment with eculizumab. 2976 58

Ravulizumab, a new complement component C5 inhibitor administered every 8 weeks, was noninferior to eculizumab administered every 2 weeks in complement-inhibitor-naive patients with paroxysmal nocturnal hemoglobinuria (PNH). This study assessed noninferiority of ravulizumab to eculizumab in clinically stable PNH patients during previous eculizumab therapy. In this phase 3, open-label, multicenter study, 195 PNH patients on labeled-dose (900 mg every 2 weeks) eculizumab for >6 months were randomly assigned 1:1 to switch to ravulizumab (n = 97) or continue eculizumab (n = 98). Primary efficacy end point was percentage change in lactate dehydrogenase (LDH) from baseline to day 183. Key secondary end points included proportion of patients with breakthrough hemolysis, change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score, transfusion avoidance, and stabilized hemoglobin. In 191 patients completing 183 days of treatment, ravulizumab was noninferior to eculizumab (P inf < .0006 for all end points), including percentage change in LDH (difference, 9.21% [95% confidence interval (CI), -0.42 to 18.84], P = .058 for superiority), breakthrough hemolysis (difference, 5.1 [95% CI, -8.89 to 18.99]), change in FACIT-Fatigue score (difference, 1.47 [95% CI, -0.21 to 3.15]), transfusion avoidance (difference, 5.5 [95% CI, -4.27 to 15.68]), and stabilized hemoglobin (difference, 1.4 [95% CI, -10.41 to 13.31]). The most frequently reported adverse event was headache (26.8%, ravulizumab; 17.3%, eculizumab). No meningococcal infections or discontinuations due to adverse events occurred. Patients with PNH may be safely and effectively switched from labeled-dose eculizumab administered every 2 weeks to ravulizumab administered every 8 weeks. This trial was funded by Alexion Pharmaceuticals, Inc., and is registered at www.clinicaltrials.gov as #NCT03056040.
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PMID:Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study. 3073 1

Eculizumab has been developed as a breakthrough treatment for paroxysmal nocturnal hemoglobinuria (PNH). Not only for breakthroughs, eculizumab therapy is also known to increase the risk of invasive meningococcal infection. It has also been recently reported that, although rarely, administration of eculizumab may result in disseminated gonococcal infection (DGI). We report here a case in which a young patient who had used eculizumab for PNH developed DGI. A 22-year-old Japanese male with PNH who had been treated with eculizumab complained of high fever, mild nausea, headache and right knee joint pain. The patient was admitted and suspected to have sepsis due to meningococcal infection and began to receive ceftriaxone (CTRX). Gonococci were detected in a venous blood culture a few days later, and this case was diagnosed as DGI. CTRX was effective, and the patient was discharged. However, four weeks later, he complained of the same subjective symptoms as at the beginning and was hospitalized again. The presence of gonococcus was proven by venous blood culture, CTRX was re-administered and the patient responded. After discharge, he was counseled on safer sexual activity, including accurate and consistent use of condoms, by urologists. He has not relapsed with DGI for more than one year. When serious signs of infection occur in patients receiving eculizumab, it is recommended to consider DGI as well as invasive meningococcal infection, and CTRX should be given.
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PMID:Disseminated Gonococcal Infection Associated with Eculizumab Therapy for Paroxysmal Nocturnal Hemoglobinuria: A Case Report and Literature Review. 3276 45