Digoxin is useful as a symptomatic treatment (it is a positive inotropic) in heart failure, although it does not improve survival. Carvedilol is a very well tolerated aß-blocker (due to its anti-a1 effect) that is associated with symptomatic and survival improvement. Acenocoumarol (Sintrom) would be indicated in this patient with chronic AF to avoid thromboembolic events. Enalapril and ACE inhibitors in general, by inhibiting the renin-angiotensin-aldosterone axis, suppress part of the neurohormonal effects that occur in heart failure; they improve survival in patients with systolic dysfunction. Ibuprofen and NSAIDs in general are contraindicated in patients with heart failure because they inhibit prostaglandin synthesis at the renal level, causing an increase in systemic vascular resistance, reduced renal perfusion, and inhibition of sodium and water excretion, which can precipitate decompensation of heart failure.

A 78-year-old patient diagnosed with idiopathic dilated cardiomyopathy with mild left ventricular dysfunction (ejection fraction 48%) and chronic atrial fibrillation. Which of the following drugs should be avoided in his treatment?

[The effects of mid- and long-term administration (3-4 years) of carvedilol in patients with idiopathic dilated cardiomyopathy].

Carvedilol has been shown to determine a significant improvement in left ventricular function, symptoms, clinical course and prognosis of patients with chronic heart failure. However, these results were obtained in medium-term studies of < 1 year duration. We report the results obtained with long-term (3-4 years) carvedilol administration to 40 patients with idiopathic dilated cardiomyopathy who were initially recruited in a 4-month double-blind placebo-controlled trial. In the initial 4-month double-blind trial, 20 patients were randomized to placebo and 20 to carvedilol treatment. All patients, except one who was not on ACE-inhibitors, were on digoxin, furosemide and ACE-inhibitors. Carvedilol or placebo doses were progressively titrated, at weekly intervals, up to the maximal doses of 25 mg bid. After the initial 4-month double-blind phase, all patients were followed long term. Mean follow-up duration was 52 +/- 12 months (range 48-61). Among the 20 patients initially randomized to carvedilol administration, 4 died (3 for cardiac and 1 for extracardiac causes) and 2 underwent heart transplant. Among the 20 patients initially randomized to placebo, 5 died for cardiac causes, 3 underwent heart transplant and 4 were started on carvedilol because of progressive heart failure during the initial 4 months of the study. The remaining 8 patients, who were kept on digoxin, furosemide and ACE-inhibitors, were used as control group. Each patient underwent an assessment of clinical conditions (NYHA functional classification and Minnesota Living with Heart Failure questionnaire), equilibrium radionuclide ventriculography, and maximal cardiopulmonary bicycle exercise testing. Exams were performed before treatment, after 4 and 12 months, and at the end of the follow-up period. No significant difference between the carvedilol and control group was present at baseline. Compared with baseline, patients in the control group presented a significant increase in left ventricular end-diastolic volume after long-term follow-up (from 126 +/- 62 to 138 +/- 43 and 158 +/- 52 ml/m2 after 12 and 48 months, respectively). No significant difference, compared to baseline values, was noted. Patients on carvedilol presented a persistent improvement in left ventricular function. This was shown by the progressive increment in left ventricular ejection fraction from 22 +/- 6 to 34 +/- 11, 37 +/- 11 and 37 +/- 13%, after 4, 12 and 48 months, respectively (p < 0.001) with a concomitant reduction in left ventricular end-diastolic volume from 147 +/- 54 to 101 +/- 44 ml/m2 at the end of the follow-up (p < 0.05). NYHA functional class remained significantly improved, in comparison with baseline (2.6 +/- 0.5 to 1.9 +/- 0.3, 1.9 +/- 0.8 and 2.0 +/- 1.0 after 4, 12 and 48 months, respectively; p < 0.01). Maximal functional capacity, assessed as peak VO2 was not significantly changed after 4 months (from 15.2 +/- 3.6 to 16.4 +/- 4.0 ml/kg/min) and showed a tendency towards a further improvement after 12 months and at the end of the follow-up (17.3 +/- 5.6 and 17.2 +/- 5.3 ml/kg/min, respectively). These results show that the favorable effects of carvedilol administration on left ventricular function and clinical symptoms are maintained also after long-term treatment.

[Arrhythmogenic right ventricular cardiomyopathy associated with arrhythmia-induced cardiomyopathy: A case report].

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a kind of inherited cardio-myopathy, which is characterized by fibro-fatty replacement of right ventricular myocardium, leading to ventricular arrhythmia. However, rapid atrial arrhythmias are also common, including atrial fibrillation, atrial flutter and atrial tachycardia. Long term rapid atrial arrhythmia can lead to further deterioration of cardiac function. This case is a 51-year-old male. He was admitted to Department of Cardiology, Peking University Third Hospital with palpitation and fatigue after exercise. Electrocardiogram showed incessant atrial tachycardia. Echocardiography revealed dilation of all his four chambers, especially the right ventricle, with the left ventricular ejection fraction of 40% and the right ventricular hypokinesis. Cardiac magnetic resonance imaging found that the right ventricle was significantly enlarged, and the right ventricular aneurysm had formed; the right ventricular ejection fraction was as low as 8%, and the left ventricular ejection fraction was 35%. The patients met the diagnostic criteria of ARVC, and both left and right ventricles were involved. His physical activities were restricted, and metoprolol, digoxin, spironolactone and ramipril were given. Rivaroxaban was also given because atrial tachycardia could cause left atrial thrombosis and embolism. His atrial tachycardia converted spontaneously to normal sinus rhythm after these treatments. Since the patient had severe right ventricular dysfunction, frequent premature ventricular beats and non-sustained ventricular tachycardia on Holter monitoring, indicating a high risk of sudden death, implantable cardioverter defibrillator (ICD) was implanted. After discharge from hospital, physical activity restriction and the above medicines were continued. As rapid atrial arrhythmia could lead to inappropriate ICD shocks, amiodarone was added to prevent the recurrence of atrial tachycardia, and also control ventricular arrhythmia. After 6 months, echocardiography was repeated and showed that the left ventricle diameter was reduced significantly, and the left ventricular ejection fraction increased to 60%, while the size of right ventricle and right atrium decreased slightly. According to the clinical manifestations and outcomes, he was diagnosed with ARVC associated with arrhythmia induced cardiomyopathy. According to the results of his cardiac magnetic resonance imaging, the patient had left ventricular involvement caused by ARVC, and the persistent atrial tachycardia led to left ventricular systolic dysfunction.

Beneficial effect of carvedilol on heart rate response to exercise in digitalised patients with heart failure in atrial fibrillation due to idiopathic dilated cardiomyopathy.

Fourteen digitalised patients diagnosed with heart failure (NYHA Functional class II) with idiopathic dilated cardiomyopathy in chronic established atrial fibrillation were administered carvedilol in addition to their anti-heart failure medications in an attempt to improve their heart rate control. Fourteen matched patients who did not receive carvedilol acted as control subjects. Patients treated with carvedilol showed significantly reduced resting heart rates (10-36%), maximal heart rates on exercise (5-20%) and an increased exercise time (2-30%) on treadmill stress tests (all P=0.001). Ventricular ectopic activity was also diminished. This was associated with symptomatic improvement in effort intolerance and palpitations. NYHA functional class, left ventricular dimensions and ejection fractions did not improve during the study period of 3 months. Thus, addition of carvedilol to digoxin had a beneficial effect on exercise tolerance in patients with idiopathic dilated cardiomyopathy in atrial fibrillation by virtue of an improved heart rate control both at rest and on exercise. Carvedilol was well tolerated despite impaired myocardial function.

ECG of the month. Irregular rhythm in a 25-year-old man with three prior cardiac operations. Coarse atrial fibrillation with a rapid ventricular response, left anterior fascicular block, left ventricular hypertrophy with repolarization abnormality.

The patient underwent closure of an atrial septal defect at age 3, had a leaking "mitral" valve repaired at age 9, and at age 13 had a "mitral" valve replacement. He began taking warfarin sodium at that time and remained symptom-free until 10 days before his initial visit here when he presented to another hospital with dyspnea and palpitations. Treatment there consisted of lisinopril 10 mg qd, carvedilol 6.25 mg bid, aldactone 25 mg qd, furosemide 40 mg qd, digoxin 0.25 mg qd, and a continuation of warfarin sodium 7.5 mg qd. An echocardiogram showed a left ventricular ejection fraction of 20%. After diuresis, he was referred to our cardiology clinic. On his initial visit here, his heart rate was an irregular 120 beats/min, his blood pressure was 106/77 mmHg, and closing and opening snaps of a normally functioning mechanical mitral valvular prosthesis were heard. He was obese (height, 5' 9"; weight, 272 lbs). An electrocardiogram was recorded (Figure 1).

The management of heart failure--an overview.

National and international societies have issued guidelines on the management of heart failure: The European Society of Cardiology, WHO, ACC/AHA Task Force Report, US Department of Health and Human Services, German Society of Cardiology. The therapeutic approaches to heart failure have undergone considerable changes during the last few years. The guidelines have to be updated almost yearly due to new results from prospective randomized studies. Although an agreement could be reached with respect to general measures and drug treatment, no agreement on mechanical devices, pacemakers and surgical interventions has been reached. The basis for medical treatment of chronic heart failure depends on diuretics, digitalis, ACE inhibitors, and beta-blockers. Calcium antagonists and other positive inotropic drugs, other than digitalis, should be avoided as far as possible. Thiazides, loop diuretics and aldosterone antagonists are needed for acute and chronic treatment of heart failure, alone or in combination (diuretic resistant heart failure!). Digitalis glycosides are needed in patients with atrial fibrillation with a fast ventricular rate or atrial flutter and in patients with systolic dysfunction, large hearts and symptomatic failure class NYHA III and IV. However, digitalis does not convert atrial fibrillation to sinus rhythm. Today there is no question that ACE inhibitors improve the prognosis of all patients with heart failure in all stages, if ejection fraction is reduced. Therefore, most patients after myocardial infarction or after having experienced pump failure due to myocarditis or cardiomyopathy are treated with ACE inhibitors and diuretics. The beneficial effects of ACE inhibitors seem to be most pronounced the worse the situation is. Relative risk reductions (mortality!) between 10% and 40% have been published depending on the severity of symptomatic left ventricular dysfunction. Those patients with high absolute risk have more to gain than those with low risk for any given "risk reduction", of course. Recent studies also indicate that most high risk cardiac patients profit from ACE inhibitors even if pump function is normal (i.e., patients with coronary heart disease, diabetes mellitus, cerebral vascular disease, hypertension) (15). AT1 antagonists can substitute for ACE inhibitors, if the latter are not tolerated due to cough. Up to now, beta-blocking agents apart from diuretics seem to be the best investigated drugs in heart failure. Large controlled studies with bisoprolol, carvedilol and metoprolol in addition to diuretics, digitalis and ACE inhibitors convincingly yielded positive results in chronic left ventricular failure patients. Reduction of mortality by 35% and even of sudden cardiac deaths by 40% have been proven beyond doubt. Thus, heart failure patients today should also receive beta-blocking agents in all stages of the disease. In the era of controlled prospective studies (evidence-based medicine), physicians are well advised to use only drugs that have been proven beneficial in large controlled studies.

Effects of carvedilol on ventriculo-arterial coupling in patients with heart failure.

Ventriculo-arterial coupling, defined as the ratio of the effective afterload (Ea) to contractility (Ees), reflects the mechano-energetic performance of the heart and is increased in chronic heart failure (CHF); the aim of treatment is to reduce its value. We studied the effect of carvedilol on the Ea/Ees ratio in patients with CHF treated with ACE-inhibitors, diuretics, and digoxin. Between November 1999 and October 2001, 36 consecutive ambulatory patients (aged 31 to 76 years) with stable CHF and idiopathic or hypertensive cardiomyopathy, in sinus rhythm and with a left ventricular ejection fraction < or = 40%, were started on carvedilol and the dose was increased to the maximum tolerated. Ees was calculated as the left ventricular systolic pressure--taken as the systolic arterial pressure measured using the cuff manometer simultaneously with two-dimensional echocardiographic recordings--divided by the left ventricular end-systolic volume. Ea was measured as the ratio of the left ventricular systolic pressure to the stroke volume. All patients were investigated prospectively after 6 and 12 months of treatment. Out of 36 patients, 4 did not tolerate the drug and were dropped out. At 6.35 +/- 1 months, the daily dosage of carvedilol was 49.7 +/- 21 mg. The NYHA functional class improved from 1.52 +/- 0.67 to 1.29 +/- 0.53 (p = 0.017), the heart rate markedly diminished from 73.6 +/- 13.3 to 60.8 +/- 10.8 b/min (p < 0.001) and so did Ea (3.35 +/- 0.91 to 2.84 +/- 0.93, p = 0.001). Peripheral resistances and Ees did not change. Therefore, the decrease in the Ea/Ees ratio (2.61 +/- 0.78 vs 2.19 +/- 0.89, p = 0.004) and the related increase in left ventricular ejection fraction (28.8 +/- 5.68 vs 33.3 +/- 7.5%, p < 0.001) were due to the decrease in Ea, while Ees did not vary significantly. Moreover, the Ea reduction was related linearly to the decrease in heart rate (r = 0.46, p = 0.001). There was no change in diuretic or ACE-inhibitor dosing during carvedilol titration. At 14.7 +/- 2 months of follow-up, no further variation occurred, short of a trend toward a slight increase in Ees (1.38 +/- 0.49 to 1.58 +/- 0.65, p = 0.07). Carvedilol, added to the conventional therapy of CHF, improves left ventricular performance and reduces the Ea/Ees ratio by decreasing Ea, mainly through a reduction in heart rate. This effect is already evident at 6 months and persists later on, while only after 12 months does Ees tend to increase slightly.

Pharmacology_Katzung

Enalapril Generic, Vasotec, Vasotec I.V. Fosinopril Generic, Monopril Lisinopril Generic, Prinivil, Zestril Quinapril Generic, Accupril Ramipril Generic, Altace Trandolapril Generic, Mavik Eprosartan Generic, Teveten Irbesartan Generic, Avapro Losartan Generic, Cozaar Telmisartan Generic, Micardis Bisoprolol Generic, Zebeta Carvedilol Generic, Coreg Metoprolol Generic, Lopressor, Toprol XL Eplerenone Generic, Inspra Isosorbide dinitrate Generic, Isordil Milrinone Generic, Primacor Ahmed A et al: Effectiveness of digoxin in reducing one-year mortality in chronic heart failure in the Digitalis Investigation Group trial. Am J Cardiol 2009;103:82. Borlaug BA, Colucci WS: Treatment and prognosis of heart failure with preserved ejection fraction. UpToDate, 2016. http://www.UpToDate.com. Bourge RC et al: Digoxin reduces 30-day all-cause hospital admission in older patients with chronic systolic heart failure. Am J Med 2013;126:701.

Carvedilol alone or in combination with digoxin for the management of atrial fibrillation in patients with heart failure?

This study examined the relative merits of digoxin, carvedilol, and their combination for the management of patients with atrial fibrillation (AF) and heart failure (HF). In patients with AF and HF, both digoxin and beta-blockers reduce the ventricular rate, and both may improve symptoms, but only beta-blockers have been shown to improve prognosis. If combined therapy is not superior to beta-blockers alone, treatment of patients with HF and AF could be simplified by stopping digoxin. We enrolled 47 patients (29 males; mean age 68 years) with persistent AF and HF (mean left ventricular ejection fraction [LVEF] 24%) in a randomized, double-blinded, placebo-controlled study. In the first phase of the study, digoxin was compared with the combination of digoxin and carvedilol (four months). In the second phase, digoxin was withdrawn in a double-blinded manner in the carvedilol-treated arm, thus allowing a comparison between digoxin and carvedilol (six months). Investigations were undertaken at baseline and at the end of each phase. Compared with digoxin alone, combination therapy lowered the ventricular rate on 24-h ambulatory electrocardiographic monitoring (p < 0.0001) and during submaximal exercise (p < 0.05), whereas LVEF (p < 0.05) and symptom score (p < 0.05) improved. In phase 2, there was no significant difference between digoxin alone and carvedilol alone in any variable. The mean ventricular rate rose and LVEF fell when patients switched from combination therapy to carvedilol alone. Six-minute walk distance was not significantly influenced by any therapy. The combination of carvedilol and digoxin appears generally superior to either carvedilol or digoxin alone in the management of AF in patients with HF.

Paroxysmal Atrial Fibrillation -- Treatment / Management -- Rate Control

Rate control is the preferred strategy for all asymptomatic AF patients. Guidelines on target heart rate in patients selected for rate control are lacking. A previously conducted randomized trial (RACE II) to assess heart rate goal in patients with AF showed no outcome difference between lenient and strict heart rate control; however, sufficient evidence to assess the impact on all-cause mortality was lacking. Physicians usually attempt to control heart rate control with agents such as beta-blockers (metoprolol, esmolol, propranolol), nondihydropyridine calcium-channel blockers (verapamil, diltiazem), or digoxin. All 3 classes of drugs are given intravenously (IV) for acute rate control and can be switched to oral therapy for chronic management. In patients with chronic heart failure with reduced ejection fraction, carvedilol therapy has shown significant improvement in left ventricular ejection fraction. Due to the negative inotropic properties of calcium channel blockers, physicians do not use these not preferred in such patients. Digoxin is usually reserved for patients who do not achieve rate control with beta-blockers or calcium channel blockers alone. Amiodarone can be used as second-line therapy when treatment with other agents has failed. [23] In patients refractory to medical therapy, AV node ablation with a permanent pacemaker placement can effectively control and regularize ventricular heart rate. Low doses of magnesium have shown synergistic effects on rate control. [24]

Management of atrial fibrillation in the elderly.

Atrial fibrillation (AF) is associated with a higher incidence of mortality, stroke, and coronary events than is sinus rhythm. AF with a rapid ventricular rate may cause a tachycardia-related cardiomyopathy. Immediate direct-current (DC) cardioversion should be performed in patients with AF and acute myocardial infarction, chest pain due to myocardial ischemia, hypotension, severe heart failure, or syncope. Intravenous beta blockers, diltiazem, or verapamil may be administered to slow immediately a very rapid ventricular rate in AF. An oral beta blocker, verapamil, or diltiazem should be used in persons with AF if a fast ventricular rate occurs at rest or during exercise despite digoxin. Amiodarone may be used in selected patients with symptomatic life-threatening AF refractory to other drugs. Digoxin should not be used to treat patients with paroxysmal AF. Nondrug therapies should be performed in patients with symptomatic AF in whom a rapid ventricular rate cannot be slowed by drugs. Paroxysmal AF associated with the tachycardia-bradycardia syndrome should be treated with a permanent pacemaker in combination with drugs. A permanent pacemaker should be implanted in patients with AF and symptoms such as dizziness or syncope associated with ventricular pauses greater than 3 seconds which are not drug-induced. Elective DC cardioversion has a higher success rate and a lower incidence of cardiac adverse effects than does medical cardioversion in converting AF to sinus rhythm. Unless transesophageal echocardiography has shown no thrombus in the left atrial appendage before cardioversion, oral warfarin should be given for 3 weeks before elective DC or drug cardioversion of AF and continued for at least 4 weeks after maintenance of sinus rhythm. Many cardiologists prefer, especially in older patients, ventricular rate control plus warfarin rather than maintaining sinus rhythm with antiar-rhythmic drugs. Patients with chronic or paroxysmal AF at high risk for stroke should be treated with long-term warfarin to achieve an International Normalized Ratio of 2.0 to 3.0. Patients with AF at low risk for stroke or with contraindications to warfarin should be treated with aspirin 325 mg daily.

Peripartum cardiomyopathy

Peripartum cardiomyopathy (PPCM) is a form of dilated cardiomyopathy that is defined as a deterioration in cardiac function presenting typically between the last month of pregnancy and up to six months postpartum. As with other forms of dilated cardiomyopathy, PPCM involves systolic dysfunction of the heart with a decrease of the left ventricular ejection fraction (EF) with associated congestive heart failure and an increased risk of atrial and ventricular arrhythmias, thromboembolism (blockage of a blood vessel by a blood clot), and even sudden cardiac death. In essence, the heart muscle cannot contract forcefully enough to pump adequate amounts of blood for the needs of the body's vital organs. PPCM is a diagnosis of exclusion, wherein patients have no prior history of heart disease and there are no other known possible causes of heart failure. Echocardiogram is used to both diagnose and monitor the effectiveness of treatment for PPCM.

Management of the older person with atrial fibrillation.

Atrial fibrillation (AF) is associated with a higher incidence of mortality, stroke, and coronary events than is sinus rhythm. AF with a rapid ventricular rate may cause a tachycardia-related cardiomyopathy. Immediate direct-current (DC) cardioversion should be performed in patients with AF and acute myocardial infarction, chest pain due to myocardial ischemia, hypotension, severe heart failure, or syncope. Intravenous beta blockers, verapamil, or diltiazem may be given to slow immediately a very rapid ventricular rate in AF. An oral beta blocker, verapamil, or diltiazem should be used in persons with AF if a fast ventricular rate occurs at rest or during exercise despite digoxin. Amiodarone may be used in selected patients with symptomatic life-threatening AF refractory to other drugs. Nondrug therapies should be performed in patients with symptomatic AF in whom a rapid ventricular rate cannot be slowed by drugs. Paroxysmal AF associated with the tachycardia-bradycardia syndrome should be treated with a permanent pacemaker in combination with drugs. A permanent pacemaker should be implanted in patients with AF and with symptoms such as dizziness or syncope associated with ventricular pauses greater than 3 seconds that are not drug-induced. Elective DC cardioversion has a higher success rate and a lower incidence of cardiac adverse effects than does medical cardioversion in converting AF to sinus rhythm. Unless transesophageal echocardiography has shown no thrombus in the left atrial appendage before cardioversion, oral warfarin should be given for 3 weeks before elective DC or drug cardioversion of AF and should be continued for at least 4 weeks after maintenance of sinus rhythm. Many cardiologists prefer, especially in older persons, ventricular rate control plus warfarin rather than maintaining sinus rhythm with antiarrhythmic drugs. Digoxin should not be used to treat patients with paroxysmal AF. Patients with chronic or paroxysmal AF at high risk for stroke should be treated with long-term warfarin to achieve an International Normalized Ratio of 2.0 to 3.0. Patients with AF at low risk for stroke or with contraindications to warfarin should receive 325 mg of aspirin daily.

[Effect of long-term treatment with enalapril, losartan and their combination on the quality of life of patients with congestive heart failure].

To study the effect a combination of enalapril and losartan on life quality in patients with congestive heart failure (HF). One hundred and eighty six patients with NYHA functional classes II to IV HF were examined. The study inclusion criteria were as follows: a left ventricular (LV) end-diastolic volume of > 160 ml, a LV ejection fraction of < 35%, sinus rhythm, a cardiothoracic index of > 0.55, no history data on prior treatment with an angiotensin-converting enzyme inhibitor (ACEI) and/or an AT1-antagonist, a patient's written free-will consent to participate in the study. The exclusion criteria were as follows: pacemaker migration, an artificial pacemaker, high-degree block, atrial fibrillation, cerebral circulatory disorders. All the patients were divided into 4 groups and received basic therapy with cardicet, 60-120 mg/day, aspirin, 250 mg/day, furosemide, 80-440 mg/week, and digoxin, 0.25-0.5 mg/day. Group 1 comprised 60 patients who refused therapy with ACEI and/or AT1-antagonist despite that they had indications for their use and they had been convinced many times. In Group 2 (n = 82) enalapril, an ACEI, was added to the basic therapy. Its initial dose of 2.5 mg/day was given once and slowly incremented to the therapeutical one (10-20 mg/day). Group 3 patients (n = 56) on the basic therapy were additionally treated with the AT1-antagonist losartan in a daily dose of 25-50 mg. They were started on 12.5 mg a day. In group 4 the basic therapy was added by a combination of enalapril and losartan in the same doses. The follow-up was 48 weeks. The efficiency of the treatments was controlled by the personal questionnaires SF-36, Life with Heart Failure, by evaluating the magnitude of clinical HF manifestations and by estimating the total life quality inxed. The data were analyzed by assuming that all the patients received the treatments. As compared with the conventional therapy and the use of each drug alone, a combination of the ACEI enalapril and the AT1-antagonist losartan promotes a more significant increase in the satisfaction of the patients with their vital activity, in the critical rate of their self-assessment of the "internal picture" of disease, and leads to a greater improvement of the quality of their life as a whole. The ICAE-AT1-antagonist combination exerts a positive impact on life quality in patients with heart failure.

Atrial Fibrillation: The New Epidemic of the Ageing World.

The prevalence of atrial fibrillation (AF) increases with age. As the population ages, the burden of AF increases. AF is associated with an increased incidence of mortality, stroke, and coronary events compared to sinus rhythm. AF with a rapid ventricular rate may cause a tachycardia-related cardiomyopathy. Immediate direct-current (DC) cardioversion should be performed in patients with AF and acute myocardial infarction, chest pain due to myocardial ischemia, hypotension, severe heart failure, or syncope. Intravenous beta blockers, diltiazem, or verapamil may be administered to reduce immediately a very rapid ventricular rate in AF. An oral beta blocker, verapamil, or diltiazem should be used in persons with AF if a fast ventricular rate occurs at rest or during exercise despite digoxin. Amiodarone may be used in selected patients with symptomatic life-threatening AF refractory to other drugs. Digoxin should not be used to treat patients with paroxysmal AF. Nondrug therapies should be performed in patients with symptomatic AF in whom a rapid ventricular rate cannot be slowed by drugs. Paroxysmal AF associated with the tachycardia-bradycardia syndrome should be treated with a permanent pacemaker in combination with drugs. A permanent pacemaker should be implanted in patients with AF and symptoms such as dizziness or syncope associated with ventricular pauses greater than 3 seconds which are not drug-induced. Elective DC cardioversion has a higher success rate and a lower incidence of cardiac adverse effects than does medical cardioversion in converting AF to sinus rhythm. Unless transesophageal echocardiography has shown no thrombus in the left atrial appendage before cardioversion, oral warfarin should be given for 3 weeks before elective DC or drug cardioversion of AF and continued for at least 4 weeks after maintenance of sinus rhythm. Many cardiologists prefer, especially in elderly patients , ventricular rate control plus warfarin rather than maintaining sinus rhythm with antiarrhythmic drugs. Patients with chronic or paroxysmal AF at high risk for stroke should be treated with long-term warfarin to achieve an International Normalized Ratio of 2.0 to 3.0. Patients with AF at low risk for stroke or with contraindications to warfarin should be treated with aspirin 325 mg daily.

Beneficial effects of pentoxifylline in patients with idiopathic dilated cardiomyopathy treated with angiotensin-converting enzyme inhibitors and carvedilol: results of a randomized study.

We previously reported beneficial effects of pentoxifylline, a xanthine-derived agent known to inhibit the production of tumor necrosis factor-alpha, in patients with idiopathic dilated cardiomyopathy treated with diuretics, digoxin, and ACE inhibitors. Since then, 3 large clinical trials showed important clinical benefits of beta-blockers in this population. Therefore, we designed the present study to establish whether in patients with heart failure already receiving treatment with ACE inhibitors and beta-blockers, the addition of pentoxifylline would have an additive beneficial effect. In a single-center, prospective, double-blind, randomized, placebo-controlled study, 39 patients with idiopathic dilated cardiomyopathy were randomized to pentoxifylline 400 mg TID (n=20) or placebo (n=19) if they had a left ventricular ejection fraction <40% after 3 months of therapy with digoxin, ACE inhibitors, and carvedilol. Primary end points were New York Heart Association functional class, exercise tolerance, and left ventricular function. Patients were followed up for 6 months. Five patients died (3 in the placebo group). Patients treated with pentoxifylline had a significant improvement in functional class compared with the placebo group (P:=0.01), with an increment in exercise time from 9.5+/-5 to 12.3+/-6 minutes (P:=0.1). Left ventricular ejection fraction improved from 24+/-9% to 31+/-13%, P:=0.03, in the treatment group. In patients with idiopathic dilated cardiomyopathy, the addition of pentoxifylline to treatment with digoxin, ACE inhibitors, and carvedilol is associated with a significant improvement in symptoms and left ventricular function.

Optimal management of older patients with atrial fibrillation.

Long term oral warfarin should be administered to elderly patients with atrial fibrillation who are at high risk for developing thromboembolic stroke and who have no contraindications to anticoagulant therapy. Oral aspirin (acetylsalicylic acid) 325mg daily may be given to elderly patients with chronic atrial fibrillation who have contraindications to anticoagulant therapy or who are not at high risk for developing thromboembolic stroke. Management of atrial fibrillation includes treatment of the underlying disease and precipitating factors. If patients have paroxysmal atrial fibrillation with a very rapid ventricular rate associated with hypotension, severe left ventricular failure or chest pain due to myocardial ischaemia, immediate direct-current cardioversion should be performed. Intravenous verapamil, diltiazem or a beta-blocker should be used for immediate slowing of a very rapid ventricular rate associated with atrial fibrillation. If a rapid ventricular rate associated with atrial fibrillation persists at rest or during exercise despite digoxin, then oral verapamil, diltiazem or a beta-blocker should be added. Low dosages of oral amiodarone (200 to 400 mg/day) may be used in selected patients with symptomatic life-threatening atrial fibrillation refractory to other therapy. No medication which depresses atrioventricular conduction should be given to patients with atrial fibrillation and a slow ventricular rate. Cardioversion should not be performed in asymptomatic elderly patients with chronic atrial fibrillation. This author would use a beta-blocker for control of ventricular arrhythmias and following conversion of atrial fibrillation to sinus rhythm. Should atrial fibrillation recur, beta-blockers have the additional advantage of slowing the ventricular rate.

Valvular heart disease

Mitral regurgitation Surgery is recommended for chronic severe mitral regurgitation in symptomatic patients with left ventricular ejection fraction (LVEF) of greater than 30%, and asymptomatic patients with LVEF of 30-60% or left ventricular end diastolic volume (LVEDV) > 40%. Surgical repair of the leaflets is preferred to mitral valve replacement as long as the repair is feasible. Mitral regurgitation may be treated medically with vasodilators, diuretics, digoxin, antiarrhythmics, and chronic anticoagulation. Mild to moderate mitral regurgitation should be followed with echocardiography and cardiac stress test every 1–3 years. Severe mitral regurgitation should be followed with echocardiography every 3–6 months.

[Drugs prescribed for chronic heart failure. Current data on their effectiveness].

VARIABLE EFFICACY: Prognosis in patients with chronic heart failure remains poor. Certain drugs can lower mortality and improve quality of life. DRUGS WITH PROVEN EFFICACY: Converting enzyme inhibitors (CEI) have proven efficacy and should be used in all stages of heart failure outside contraindications. High-dose regimens are recommended when tolerated. Certain beta-blockers have also been added to the list of effective drugs for heart failure. Positive data have been reported for metroprolol, bisoprolol and carvedilol. Improved function has been demonstrated only with carvedilol allowing a clear reduction in mortality; it is currently indicated in combination with CEI and diuretics for patients with symptomatic heart failure. DRUGS WITH INSUFFICIENTLY PROVEN EFFICACY: Certain drugs which have been used for many years can improve heart function but data clearly proving lower mortality are lacking. These include diuretics and nitrate derivatives for symptomatic patients and digitalics which are useful not only for patients with complete arrhythmia due to atrial fibrillation but also for symptomatic patients with sinus rhythm. According to preliminary studies, aldosterone antagonists appear to have a positive effect on mortality due to heart failure. DRUGS WITH LIMITED INDICATIONS: Other drugs have been found to have no effect on mortality. Amiodarone, amlodipine and felodipine can thus be used for patients with associated diseases. Finally anticoagulant therapy should be reserved for patients with atrial fibrillation or a history of thromboembolism.

Left ventricular dysfunction due to atrial fibrillation in patients initially believed to have idiopathic dilated cardiomyopathy.

Ten patients aged 22 to 80 years (median 57) with severe left ventricular (LV) dysfunction and atrial fibrillation (AF) with rapid ventricular response were evaluated after therapy. Because most patients were unaware of their arrhythmia, duration was usually unknown. All patients had heart failure symptoms; 9 presented with New York Heart Association class III or IV disability, and 1 with class II disability. Initial LV ejection fraction ranged from 12 to 30% (median 25). No patient had symptomatic coronary artery disease (4 underwent angiography). Myocarditis and infiltrative processes were excluded by biopsy in 5 patients. All patients were considered initially to have idiopathic dilated cardiomyopathy with secondary AF. Ventricular rate was controlled in all patients, with sinus rhythm restored in 5. At follow-up (median 30 months, range 3 to 56), all patients were asymptomatic. LV ejection fraction after treatment ranged from 40 to 64% (median 52). It is concluded that in some patients initially considered to have idiopathic dilated cardiomyopathy, AF with rapid ventricular response may be the primary cause rather than the consequence of severe LV dysfunction. LV dysfunction may be completely reversible with ventricular rate control.

[Pharmacotherapy of chronic heart failure in clinical practice].

Chronic heart failure affects between 1-5% of the population and rise steeply with age. Most patients with chronic heart failure should be routinely managed with a combination of 4 types of drugs: a diuretic, an angiotensin converting enzyme inhibitors (ACE-I), beta-blocker and usually digitalis. Diuretics are essential for symptomatic treatment when fluid overload is present, and should always be administrated in combination with ACE-I if possible. ACE-I improves survival and symptoms and reduces hospitalization in patients with moderate to severe ventricular systolic dysfunction, and in the absence of fluid retention should be given first. Angiotensin II receptor antagonist could be considered in patients who not tolerate ACE-I. beta-blocking agents are recommended for treatment of patients with stable, mild, moderate and severe heart failure unless there is a contraindication. Bisoprolol, metoprolol and carvedilol have been associated with reduction in total mortality, cardiovascular mortality and sudden death. Cardiac glycosides are indicated in atrial fibrillation and any degree of symptomatic heart failure in order slow ventricular rate. Indications for antiarrhythmic drug therapy include atrial fibrillation, non-sustained or sustained ventricular tachycardia. Oral anticoagulation reduces the risk of stroke in patients with atrial fibrillation, and there is a lack of evidence to support the use of antithrombotic therapy in patients in sinus rhythm.

Effects of short- and long-term carvedilol administration on rest and exercise hemodynamic variables, exercise capacity and clinical conditions in patients with idiopathic dilated cardiomyopathy.

The study evaluated the effects of short- and long-term administration of carvedilol in patients with idiopathic dilated cardiomyopathy. Carvedilol is a beta-adrenergic blocking agent with vasodilator activity that might be well tolerated in patients with heart failure. Forty patients with idiopathic dilated cardiomyopathy treated with digoxin, furosemide and angiotensin-converting enzyme inhibitors were randomized in a double-blind manner to receive either placebo or carvedilol. Right heart hemodynamic variables were evaluated up to 8 h after short-term drug administration and, on the next day, during cardiopulmonary exercise testing before and 3 h after drug ingestion. Placebo or carvedilol was added to standard therapy, starting with a dose of 6.25 mg twice a day with weekly increments up to the maximum of 25 mg twice a day. Patients were reevaluated after 4 months by cardiopulmonary exercise testing and measurement of right heart hemodynamic variables 12 h after last drug ingestion and 3 h after drug readministration. Left ventricular ejection fraction and volume, measured by equilibrium radionuclide ventriculography, quality of life and submaximal exercise duration were assessed before and after long-term therapy. Compared with placebo, carvedilol produced a short-term reduction in heart rate and pulmonary artery and pulmonary wedge pressures and, after long-term administration, increased both rest and peak exercise cardiac, stroke volume and stroke work indexes, with a further reduction in right atrial, pulmonary artery and pulmonary wedge pressures. Long-term carvedilol administration also improved rest left ventricular ejection fraction (from 20 +/- 7% to 30 +/- 12%, p < 0.001), submaximal exercise capacity, quality of life and New York Heart Association functional class. No baseline variable was predictive of the response to therapy. Short-term carvedilol administration reduces heart rate and mean pulmonary artery and pulmonary wedge pressures, whereas it improves both long-term rest and exercise left ventricular systolic function, reduces heart failure symptoms and improves submaximal exercise tolerance in patients with idiopathic cardiomyopathy.

Left ventricular diastolic heart failure with normal left ventricular systolic function in older persons.

Underlying causes and precipitating causes of congestive heart failure (CHF) should be treated when possible. Older persons with CHF and normal left ventricular (LV) ejection fraction should have maintenance of sinus rhythm, treatment of hypertension and myocardial ischemia, slowing of the ventricular rate below 90 beats/minute, and reduction of salt overload. First-line drug treatment in the management of these persons is the use of loop diuretics combined with beta blockers as tolerated. Angiotensin-converting enzyme (ACE) inhibitors should be administered if CHF persists despite diuretics and beta blockers. If persons are unable to tolerate ACE inhibitors because of cough, rash, or altered taste sensation, angiotensin II type 1 receptor antagonists should be given. If CHF persists despite diuretics, beta blockers, and ACE inhibitors or the person is unable to tolerate beta blockers, ACE inhibitors, and angiotensin II type 1 receptor antagonists, isosorbide dinitrate plus hydralazine should be administered. Calcium channel blockers should be used if CHF persists despite administration of diuretics and the person is unable to tolerate beta blockers, ACE inhibitors, angiotensin II type 1 receptor antagonists, and isosorbide dinitrate plus hydralazine. Digoxin, beta blockers, verapamil, and diltiazem may be used to slow a rapid ventricular rate in persons with supraventricular tachyarrhythmias. Digoxin should not be used in persons with CHF in sinus rhythm with normal LV ejection fraction.

Digitalis

under current regulations by the Food and Drug Administration on the basis of prospective, randomized study and clinical trials. It was also approved for the control of ventricular response rate for patients with atrial fibrillation. American College of Cardiology/American Heart Association guidelines recommend digoxin for symptomatic chronic heart failure for patients with reduced systolic function, preservation of systolic function, and/or rate control for atrial fibrillation with a rapid ventricular response. Heart Failure Society of America guidelines for heart failure provide similar recommendations. Despite its relatively recent approval by the Food and Drug Administration and the guideline recommendations, the therapeutic use of digoxin is declining in patients with heart failure—likely the result of several factors. The main factor is the more recent introduction of several drugs shown in randomised controlled studies to improve outcomes in heart failure. Safety concerns

Arrhythmogenic cardiomyopathy

Minor criteria Right ventricular dysfunction Mild global RV dilatation and/or reduced ejection fraction with normal LV. Mild segmental dilatation of the RV Regional RV hypokinesis Tissue characterization Electrocardiographical abnormalities Late potentials on signal averaged EKG. Ventricular tachycardia with a left bundle branch block (LBBB) morphology, with inferior or unknown axis Frequent PVCs (> 500 PVCs / 24 hours) Management The goal of management of ACM is to decrease the incidence of sudden cardiac death. This raises a clinical dilemma: How to prophylactically treat the asymptomatic patient who was diagnosed during family screening.

Pharmacologic therapy for patients with chronic heart failure and reduced systolic function: review of trials and practical considerations.

Heart failure (HF) is a complex clinical syndrome resulting from any structural or functional cardiac disorder impairing the ability of the ventricles to fill with or eject blood. The approach to pharmacologic treatment has become a combined preventive and symptomatic management strategy. Ideally, treatment should be initiated in patients at risk, preventing disease progression. In patients who have progressed to symptomatic left ventricular dysfunction, certain therapies have been demonstrated to improve survival, decrease hospitalizations, and reduce symptoms. The mainstay therapies are angiotensin-converting enzyme (ACE) inhibitors and beta-blockers (bisoprolol, carvedilol, and metoprolol XL/CR), with diuretics to control fluid balance. In patients who cannot tolerate ACE inhibitors because of angioedema or severe cough, valsartan can be substituted. Valsartan should not be added in patients already taking an ACE inhibitor and a beta-blocker. Spironolactone is recommended in patients who have New York Heart Association (NYHA) class III to IV symptoms despite maximal therapies with ACE inhibitors, beta-blockers, diuretics, and digoxin. Low-dose digoxin, yielding a serum concentration <1 ng/mL can be added to improve symptoms and, possibly, mortality. The combination of hydralazine and isosorbide dinitrate might be useful in patients (especially in African Americans) who cannot tolerate ACE inhibitors or valsartan because of hypotension or renal dysfunction. Calcium antagonists, with the exception of amlodipine, oral or intravenous inotropes, and vasodilators, should be avoided in HF with reduced systolic function. Amiodarone should be used only if patients have a history of sudden death, or a history of ventricular fibrillation or sustained ventricular tachycardia, and should be used in conjunction with an implantable defibrillator [corrected]. Finally, anticoagulation is recommended only in patients who have concomitant atrial fibrillation or a previous history of cerebral or systemic emboli.

Heart failure

Anemia is an independent factor in mortality in people with chronic heart failure. Treatment of anemia significantly improves quality of life for those with heart failure, often with a reduction in severity of the NYHA classification, and also improves mortality rates. The European Society of Cardiology guideline in 2016 recommend screening for iron-deficiency anemia and treating with intravenous iron if deficiency is found. The decision to anticoagulate people with HF, typically with left ventricular ejection fractions <35% is debated, but generally, people with coexisting atrial fibrillation, a prior embolic event, or conditions that increase the risk of an embolic event such as amyloidosis, left ventricular noncompaction, familial dilated cardiomyopathy, or a thromboembolic event in a first-degree relative.

Atrial fibrillation.

The prevalence and incidence of atrial fibrillation increase with age. Atrial fibrillation is associated with a higher incidence of coronary events, stroke, and mortality than sinus rhythm. A fast ventricular rate associated with atrial fibrillation may cause tachycardia-related cardiomyopathy. Management of atrial fibrillation includes treatment of underlying causes and precipitating factors. Immediate direct-current cardioversion should be performed in persons with atrial fibrillation associated with acute myocardial infarction, chest pain due to myocardial ischemia, hypotension, severe heart failure, or syncope. Intravenous beta-blockers, verapamil, or diltiazem may be used to immediately slow a fast ventricular rate associated with atrial fibrillation. An oral beta-blocker, verapamil, or diltiazem should be given to persons with atrial fibrillation if a rapid ventricular rate occurs a rest or during exercise despite digoxin. Amiodarone may be used in selected persons with symptomatic life-threatening atrial fibrillation refractory to other drug therapy. Nondrug therapies should be performed in persons with symptomatic atrial fibrillation in whom a rapid ventricular rate cannot be slowed by drug therapy. Paroxysmal atrial fibrillation associated with the tachycardia-bradycardia syndrome should be managed with a permanent pacemaker in combination with drugs. A permanent pacemaker should be implanted in persons with atrial fibrillation in whom symptoms such as dizziness or syncope associated with non-drug-induced ventricular pauses longer than 3 seconds develop. Elective direct-current cardioversion has a higher success rate and a lower incidence of cardiac adverse effects than medical cardioversion in converting atrial fibrillation to sinus rhythm. Unless transesophageal echocardiography shows no thrombus in the left atrial appendage before cardioversion, oral warfarin should be given for 3 weeks before elective direct-current or drug cardioversion of atrial fibrillation and continued for at least 4 weeks after maintenance of sinus rhythm. Many cardiologists prefer the treatment strategy of ventricular rate control plus warfarin rather than to maintain sinus rhythm with antiarrhythmic drugs, especially in older patients. Digoxin should not be used in persons with paroxysmal atrial fibrillation. Patients with chronic or paroxysmal atrial fibrillation who are at high risk for stroke should be treated with long-term warfarin to achieve an International Normalized Ratio (INR) of 2.0 to 3.0. Persons with atrial fibrillation who are at low risk for stroke or who have contraindications to warfarin should receive 325 mg aspirin daily.

List of dog diseases

Dilated cardiomyopathy (DCM) is a disease of heart muscle resulting in decreased myocardial contractility. The left ventricle compensates for this disease by growing larger (eccentric or volume overload hypertrophy; AKA dilation). The left atrial is also dilated when the disease is severe. It is seen in large/giant dog breeds such as Boxers, Great Danes, and Doberman Pinschers. It is usually idiopathic, but can also be caused by taurine deficiency in American Cocker Spaniels or doxorubicin use. A mutation in the gene that encodes for pyruvate dehydrogenase kinase 4 is associated with DCM in Doberman Pinschers in the USA. Dilated cardiomyopathy usually ultimately results in congestive heart failure. Atrial fibrillation is common in giant breed dogs with DCM. Doberman Pinschers more commonly have ventricular arrhythmias (e.g., premature ventricular complexes; ventricular tachycardia) that predispose them to sudden death (i.e., ventricular fibrillation).

Dilated cardiomyopathy

Diagnosis Generalized enlargement of the heart is seen upon normal chest X-ray. Pleural effusion may also be noticed, which is due to pulmonary venous hypertension. The electrocardiogram often shows sinus tachycardia or atrial fibrillation, ventricular arrhythmias, left atrial enlargement, and sometimes intraventricular conduction defects and low voltage. When left bundle-branch block (LBBB) is accompanied by right axis deviation (RAD), the rare combination is considered to be highly suggestive of dilated or congestive cardiomyopathy. Echocardiogram shows left ventricular dilatation with normal or thinned walls and reduced ejection fraction. Cardiac catheterization and coronary angiography are often performed to exclude ischemic heart disease.

[The therapy of chronic heart failure].

A rational therapy of the chronic cardiac insufficiency should be performed according to a certain scheme, in which case the knowledge of the basic disease is necessary for the causal treatment. Apart from the general measures the medicamentous therapy is of particular significance. Hereby up to now the digitalis glycosides remained the remedy of primary choice. They are without doubt indicated in the latent and manifest cardiac insufficiency, consequently from the transition of the NYHA stage II into stage III, in tachycardiac disturbances of rhythm also without cardiac insufficiency in form of auricular fibrillation and auricular flutter as well as in the paroxysmal supraventricular tachycardia. Prophylactic, preoperative applications of glycosides and such ones which are performed only for reasons of age are not justified. Also a maintenance therapy is in most cases no more necessary after removal of the cause of the cardiac insufficiency. - Diuretics are to be used in an insufficiency which continues existing despite application of glycosides. Their application must be performed as protracted as possible. - The therapies with vasodilators, such as prazosin, hydralazine and nitrates, which were performed during the last years, showed, indeed, initial success, but no long-term effect. Another fact it is, however, with the angiotensin-converting enzyme (ACE) inhibitors captopril and enalapril, which are to be regarded as second grade medicaments in combination with glycosides and diuretics. Whether or not they will supersede the glycosides, is at present still an open question. Other positively inotropic medicaments which in comparison to the glycosides show a larger therapeutic breadth are still being developed.(ABSTRACT TRUNCATED AT 250 WORDS)

Tachycardia-induced cardiomyopathy

Diagnosis There are no specific diagnostic criteria for TIC, and it can be difficult to diagnose for a number of reasons. First, in patients presenting with both tachycardia and cardiomyopathy, it can be difficult to distinguish which is the causative agent. Additionally, it can occur in patients with or without underlying structural heart disease. Previously normal left ventricular ejection fraction or left ventricular systolic dysfunction out of proportion to a patient’s underlying cardiac disease can be important clues to possible TIC. The diagnosis of TIC is made after excluding other causes of cardiomyopathy and observing resolution of the left ventricular systolic dysfunction with treatment of the tachycardia.

[Atrial fibrillation].

Atrial fibrilation is the most frequent arrhythmia, the occurrence increasing with age and associated diseases. The incidence at the age below 60 years is markedly lower than one per cent, whereas in persons above 80 years of age it exceeds six per cent. The occurrence in patients with heart failure is from 10% (NYHA II) up to 50% (NYHA IV). Atrial fibrillation is classified into that observed for the first time and permanent, respectively, while transient forms include paroxyzmal and persistent atrial fibrillation. The diagnosis is based on ECG recording, while echocardiography is most significant. The therapy includes two basic questions--anticoagulant or anti-aggregation treatment and the control of rhythm or frequency. The anticoagulant therapy should be introduced in all patients, where contraindications are not present, being necessary before every cardioversion, provided atrial fibrillation lasts more than two days. In patients without any heart disease and with a physiological echocardiogram it is possible to administer only anti-aggregation treatment. Cardioversion (the control of rhythm) is recommended to all symptomatic patients, in other cases and especially in older persons the control of frequency is safer and of more advantage. Electrical cardioversion is more effective that a pharmacological treatment, the sinus rhythm is preferably controlled by dofetilid, ibutilid, propafenon and amiodaron. For the control of heart rate beta-blockers, diltiazem, verapamil and digitalis are recommended.


The question of exanthematous diseases that pediatricians and MIR exam takers like so much. By the picture of high fever of several days that suddenly subsides with the appearance of a rash, we have a sudden exanthem, caused by Herpes virus type 6 (remember the mnemonic rule of "sudden Hexanthem"). Parvovirus B19 is the cause of erythema infectiosum or "fifth disease", whose characteristic rash is on the cheeks, giving the appearance of a slapped face. Coxackie A16 causes herpangina and also boca-mano-pie disease, which presents an initially macular rash, which does not respect palms or soles and evolves into bursting vesicles. Finally, EBV infection produces a mononucleosis syndrome with high fever lasting several days, with pharyngeal erythema and grayish exudates on the tonsils. It can present if penicillins are given to treat it (when confused with a streptococcal pharyngotonsillitis) a generalized exanthema. In addition, it also presents with fatigue, hepatic inflammation with increased transaminases and splenomegaly.

The question of exanthematous diseases that pediatricians and MIR exam takers like so much. By the picture of high fever of several days that suddenly subsides with the appearance of a rash, we have a sudden exanthem, caused by Herpes virus type 6 (remember the mnemonic rule of "sudden Hexanthem"). Parvovirus B19 is the cause of erythema infectiosum or "fifth disease", whose characteristic rash is on the cheeks, giving the appearance of a slapped face. Coxsackie A16 causes herpangina and also boca-mano-pie disease, which presents an initially macular rash, which does not respect palms or soles and evolves into bursting vesicles. Finally, EBV infection produces a mononucleosis syndrome with high fever lasting several days, with pharyngeal erythema and grayish exudates on the tonsils. It can present if penicillins are given to treat it (when confused with a streptococcal pharyngotonsillitis) a generalized exanthema. In addition, it also presents with fatigue, hepatic inflammation with increased transaminases and splenomegaly.

The appearance of a high fever of 39°C in a 10-month-old infant that abruptly subsides after 3-5 days, followed by a cephalocaudal morbilliform exanthema with enanthema consisting of reddish papules on the palate, and resolving within a week, associated with good general condition, is usually caused by:

Spontaneous resolution of hemophagocytic syndrome associated with acute parvovirus B19 infection and concomitant Epstein-Barr virus reactivation in an otherwise healthy adult.

Reported here is the case of a patient who spontaneously recovered from hemophagocytic syndrome associated with acute B19 infection and concomitant Epstein-Barr virus reactivation. The previously healthy 37-year-old-man was hospitalized after 10 days of high fever, arthralgia and arthritis and was determined to have hemophagocytic syndrome. Immunoglobulin (Ig) M antibodies to Epstein-Barr virus (EBV) capsid antigen, early antigen and parvovirus B19 (B19) were found. B19 DNA and low-level EBV DNA were detected in bone marrow, serum and peripheral blood mononuclear cells. The patient recovered spontaneously without any treatment. Two months later anti-B19 IgG antibodies were detected, while at 9-month follow-up, anti-B19 IgM antibodies were no longer detectable and B19 DNA had disappeared from serum. To the best of our knowledge, this is the first report of spontaneous resolution of hemophagocytic syndrome associated with acute B19 infection and concomitant EBV reactivation in an otherwise healthy adult.

Herpesviral encephalitis

Earlier treatment (within 48 hours of symptom onset) improves the chances of a good recovery. Rarely, treated individuals can have relapse of infection weeks to months later. There is evidence that aberrant inflammation triggered by herpes simplex can result in granulomatous inflammation in the brain, which responds to steroids. While the herpes virus can be spread, encephalitis itself is not infectious. Other viruses can cause similar symptoms of encephalitis, though usually milder (Herpesvirus 6, varicella zoster virus, Epstein-Barr, cytomegalovirus, coxsackievirus, etc.). References External links Herpes Viral encephalitis Pediatrics Herpes simplex virus-associated diseases

InternalMed_Harrison

Hand-foot-and-moUtH disease (Fig. 228-1) After an incubation period of 4–6 days, patients with hand-foot-and-mouth disease present with fever, anorexia, and malaise; these manifestations are followed by the development of sore throat and vesicles (see Fig. 25e-23) on the buccal mucosa and often on the tongue and then by the appearance of tender vesicular lesions on the dorsum of the hands, sometimes with involvement of the palms. The vesicles may form bullae and quickly ulcerate. About one-third of patients also have lesions on the palate, uvula, or tonsillar pillars, and one-third have a rash on the feet (including the soles) or on the buttocks. The disease is highly infectious, with attack rates of close to 100% among young children. The lesions usually resolve in 1 week. Most cases are due to coxsackievirus A16 or enterovirus 71.

InternalMed_Harrison

PART 2 Cardinal Manifestations and Presentation of Diseases CAuSES of ExAnTHEMS I. Morbilliform A. Drugs B. Viral 1. 2. 3. Erythema infectiosum (erythema of cheeks; reticulated on extremities) 4. Epstein-Barr virus, echovirus, coxsackievirus, CMV, adenovirus, HHV-6/ HHV-7a, dengue virus, and West Nile virus infections 5. C. Bacterial 1. 2. 3. 4. 5. D. Acute graft-versus-host disease E. Kawasaki disease II. A. B. C. D. Early staphylococcal scalded-skin syndrome aPrimary infection in infants and reactivation in the setting of immunosuppression. Abbreviations: CMV, cytomegalovirus; HHV, human herpesvirus; HIV, human immunodeficiency virus.

Etiologies of rash and fever illnesses in Campinas, Brazil.

Few population-based studies of infectious etiologies of fever-rash illnesses have been conducted. This study reports on enhanced febrile-rash illness surveillance in Campinas, Brazil, a setting of low measles and rubella virus transmission. Cases of febrile-rash illnesses in individuals aged <40 years that occurred during the period 1 May 2003-30 May 2004 were reported. Blood samples were collected for laboratory diagnostic confirmation, which included testing for adenovirus, dengue virus, Epstein-Barr virus (EBV), enterovirus, human herpes virus 6 (HHV6), measles virus, parvovirus-B19, Rickettsia rickettsii, rubella virus, and group A streptococci (GAS) infections. Notification rates were compared with the prestudy period. A total of 1248 cases were notified, of which 519 (42%) had laboratory diagnosis. Of these, HHV-6 (312 cases), EBV (66 cases), parvovirus (30 cases), rubella virus (30 cases), and GAS (30 cases) were the most frequent causes of infection. Only 10 rubella cases met the rubella clinical case definition currently in use. Notification rates were higher during the study than in the prestudy period (181 vs 52.3 cases per 100,000 population aged <40 years). Stimulating a passive surveillance system enhanced its sensitivity and resulted in additional rubella cases detected. In settings with rubella elimination goals, rubella testing may be considered for all cases of febrile-rash illness, regardless of suspected clinical diagnosis.

Eosinophilic myocarditis

The DRESS syndrome is a severe immunological drug reaction. It differs from other drug reactions in that it: a) is caused by a particular set of drugs; b) typically occurs after a delay of 2 to 8 weeks following intake of an offending drug; c) presents with a specific set of signs and symptoms (i.e. modest or extreme elevations in blood eosinophil and atypical lymphocyte counts; acute onset of a skin rash; lymphadenopathy; fever; neuralgia; and involvement of at least one internal organ such as the liver, lung, or heart; d) develops in individuals with particular genetic predispositions; and e) involves reactivation of latent viruses, most commonly human herpesvirus 6 or more rarely human herpes virus 5 (i.e. human cytomegalovirus), human herpesvirus 7, and human herpesvirus 4 (i.e. Epstein–Barr virus). These viruses usually become dormant after infecting humans but under special circumstances, such as drug intake, are reactivated and may contribute to serious diseases such as the

Eastern equine encephalitis

Signs and symptoms The incubation period for Eastern equine encephalitis virus (EEEV) disease ranges from 4 to 10 days. The illness can progress either systematically or encephalitically, depending on the person's age. Encephalitic disease involves swelling of the brain and can be asymptomatic, while the systemic illness occurs very abruptly. Those with the systemic illness usually recover within 1–2 weeks. While the encephalitis is more common among infants, in adults and children, it usually manifests after experiencing the systemic illness. Symptoms include high fever, muscle pain, altered mental status, headache, meningeal irritation, photophobia, and seizures, which occur 3–10 days after the bite of an infected mosquito. Due to the virus's effect on the brain, patients who survive can be left with mental and physical impairments, such as personality disorders, paralysis, seizures, and intellectual impairment. Cause Virus

Human herpesvirus 6

HHV-6 has also been demonstrated to transactivate Epstein–Barr virus. Epidemiology Age Humans acquire the virus at an early age, some as early as less than one month of age. HHV-6 primary infections account for up to 20% of infant emergency room visits for fever in the United States and are associated with several more severe complications, such as encephalitis, lymphadenopathy, myocarditis and myelosuppression. The prevalence of the virus in the body increases with age (rates of infection are highest among infant between 6 and 12 months old) and it is hypothesized that this is due to the loss of maternal antibodies in a child that protect him or her from infections.

Cephalhematoma and petechial rashes associated with acute parvovirus B19 infection: a case report.

Parvovirus B19 can cause petechial rashes in the acute phase of illness as well as erythema infectiosum (fifth disease) during convalescence. This petechial rash is often called "gloves and socks" syndrome because of the typical distribution of the eruption. However, involvement of other sites (e.g., intertriginous area) and generalized involvement have been recently recognized. We report here a patient with parvovirus-associated petechiae and cephalhematoma. The patient was a previously healthy 10-year-old boy. There was a family history of fatal bleeding; his sister died of intracranial bleeding with an uncertain cause at the age of 5 months. The patient was admitted to our hospital because of sudden onset of cephalhematoma associated with fever. He reported that he had no recent head trauma but that he massaged his scalp on the day before admission. On admission, his temperature was 38.8°C; otherwise, he was in a stable condition. Besides cephalhematoma, petechial rashes were present on his trunk and limbs. The initial laboratory tests were essentially normal, including platelet count and coagulation tests. Expanded laboratory tests were repeated to explore the etiology of his skin hemorrhage, all of which indicated that hematological disorders were unlikely. His symptoms subsided spontaneously over the next few days and he was discharged uneventfully. Anti-parvovirus IgM titer was elevated during hospitalization and typical erythema infectiosum was seen approximately 1 week after discharge. During 6 months follow-up, he remained stable without recurrence of a hemorrhagic episode. Finally, we concluded that his cephalhematoma was responsible for acute parvoviral infection. This is believed to be the first report describing a possible association between parvovirus B19 infection and cephalhematoma. Parvovirus B19 infection should be considered in the differential diagnosis of children who present with unexplained hemorrhage such as cephalhematoma or petechiae.

Eczema herpeticum

Eczema herpeticum is a rare but severe disseminated infection that generally occurs at sites of skin damage produced by, for example, atopic dermatitis, burns, long-term usage of topical steroids or eczema. It is also known as Kaposi varicelliform eruption, Pustulosis varioliformis acute and Kaposi-Juliusberg dermatitis. Some sources reserve the term "eczema herpeticum" when the cause is due to human herpes simplex virus, and the term "Kaposi varicelliform eruption" to describe the general presentation without specifying the virus. This condition is most commonly caused by herpes simplex virus type 1 or 2, but may also be caused by coxsackievirus A16, or vaccinia virus. It appears as numerous umbilicated vesicles superimposed on healing atopic dermatitis. it is often accompanied by fever and lymphadenopathy. Eczema herpeticum can be life-threatening in babies.

Eruptive pseudoangiomatosis

Eruptive pseudoangiomatosis is a cutaneous condition characterized by the sudden appearance of 2- to 4-mm blanchable red papules. It can appear in children or adults.The papules appear similar to hemangiomas Viruses found in patients include Echovirus 25 and 32, coxsackie B, Epstein-Barr virus, and cytomegalovirus. See also Boston exanthem disease Skin lesion References Virus-related cutaneous conditions

Viral hepatitis

Other viruses The virus first known to cause hepatitis was the yellow fever virus, a mosquito-borne flavivirus. Other viruses than can cause hepatitis include: Adenoviruses Arenaviruses: Guanarito virus, Junín virus, Lassa fever virus, Lujo virus, Machupo virus, and Sabiá virus Bunyaviruses: Crimean–Congo hemorrhagic fever virus, Dobrava virus, Hantaan virus, Puumala virus, Rift Valley fever virus, and Seoul virus Coronavirus: severe acute respiratory syndrome virus Erythrovirus: Parvovirus B19 Filoviruses: Ebola virus and Marburg virus Flaviviruses: dengue, Kyasanur Forest disease virus, Omsk hemorrhagic fever virus, and yellow fever virus Herpesviruses: cytomegalovirus, Epstein–Barr virus, varicella-zoster virus, human herpesvirus 6, human herpesvirus 7, and human herpesvirus 8 Orthomyxoviruses: influenza Picornaviruses: echovirus Reovirus: Colorado tick fever virus, reovirus 3

[The blood picture in exanthema subitum (Zahorsky)/ critical 3-day fever-exanthema in young children].

Exanthema subitum was described in 1910 by John Zahorsky/USA; in 1986 and 1988 the human herpesvirus 6 (HHV 6) was discovered as the causative agent of the disease and serologic tests were established for diagnostics (specific IgM and IgG antibodies). Up to this time the diagnosis was based on the typical clinical course: the prodromal febrile stage (3 days) followed by the onset of a (more or less characteristic) rash closely connected with the normalisation of the body temperature. Usually a typical white blood cell count was described for diagnostics on the first day of exanthema: leukocytopenia with eosino- and granulocytopenia associated with consequent lymphocytosis. We analysed the hematologic data for children with a serologically documented HHV6 infection including exanthema (group 1: n = 9), without exanthema (group 2: n = 11) or with a serologically unexplained febrile rash (group 3: n = 13). In children with exanthematous HHV6 infection (exanthema subitum) granulocytopenia and a decreased thrombocyte count (mean values) is the rule. But the total white blood cell count and the mean values for eosinophils did not differ between the groups studied.

Scarlet fever associated with hepatitis in pediatrics. A case report.

Scarlet fever is a common illness in pediatrics caused by group A beta-hemolytic strep tococcus (GABHS), which usually occurs after an episode of pharyngitis, and has an overall excellent prognosis. Hepatitis secondary to scarlet fever is a rare complication described in adults and even less frequently in children. Our objective was to describe a case of hepatitis secondary to scarlet fever in a pediatric patient. A 12-year-old male with scarlet fever presented with a 4-day history of jaundice, dark urine, and decreased appetite. Laboratory tests revealed elevated liver enzy mes and total and direct bilirubin levels, and negative studies for hepatitis A, B and C, Epstein Barr virus, parvovirus B19, adenovirus, cytomegalovirus, human herpes virus-6, and herpes simplex virus 1 and 2. Abdominal ultrasound examination was normal. The pathogenesis of scarlet fever associated hepatitis remains unclear. Streptococcal pyrogenic exotoxin mediated cellular injury via cytokine production has been proposed as a possible mechanism of hepatotoxicity in GABHS infections. Hepatitis secondary to scarlet fever remains a rare but benign entity, with complete recovery expected over weeks to months.

[3-day fever: agreement between clinical diagnosis and seroconversion of type 6 human herpesvirus (HHV-6)].

The aim of this study was to investigate the correlation between clinical diagnosis of exanthema subitum and seroconversion of herpes virus type 6 (HHV-6). 90 children with fever of unknown origin were investigated by 11 pediatricians in the Canton of Zürich, Switzerland, between October 1989 and June 1990. Antibodies against HHV-6 were determined at the first consultation and 2-3 weeks later. History and clinical findings were investigated and the clinical probability of the diagnosis exanthema subitum was estimated. 82 of the 90 children could be evaluated. 33 of them already had HHV-6 antibodies in their first blood sample although their history was negative concerning exanthema subitum. In 24 children exanthema subitum was proven by seroconversion. The clinical diagnosis was much more reliable at the second consultation compared to the first one. The clinical course of the disease was highly variable. Duration of fever differed widely and in some children the exanthema was atypical or even absent.

Herpes virus

Herpes virus may refer to: Any member of the large family of DNA viruses known as Herpesviridae Human herpesviruses, nine types of herpesviruses that can cause diseases in humans Herpes simplex virus 1 and 2, responsible for herpes simplex infections Human alphaherpesvirus 3, also called varicella-zoster virus, responsible for chickenpox and shingles Human gammaherpesvirus 4, or Epstein–Barr virus, one of the most common viruses which can cause various diseases Human betaherpesvirus 5 Roseolovirus, a genus that includes three human herpesviruses: Human herpesvirus 6, the collective name for Human betaherpesvirus 6A and Human betaherpesvirus 6B Human betaherpesvirus 7 Human gammaherpesvirus 8, or Kaposi's sarcoma-associated herpesvirus

[Viral exanthem].

The most frequent cause of exanthematous diseases are viral infections, which provoke skin alterations either directly or via the reaction of the immune system. In many distinct parainfectious clinical pictures, several viruses from quite different groups are able to produce a specific exanthem. Dominant pathogens for exanthematous diseases include non-polio enteroviruses, respiratory viruses, Epstein-Barr virus, HHV-6 and HHV-7 viruses as well as parvovirus B19. In many cases exanthemata present with maculate or maculopapular features in disseminated distribution. Some exanthematous diseases exhibit typical predilection sites. In addition to the clinical picture, diagnosis is based on the patient's history, observation of the patient's general condition, awareness of the season in the year, and physical examination. In uncertain cases and for scientific studies, blood analysis, smear tests, and histological investigation confirm the diagnosis. Knowledge of exanthematous disease, which usually run harmless course, is essential for differentiation of life-threatening disorders. This article presents exanthematous viral diseases depending on age at primary manifestation.

Herpes Virus Type 6 -- History and Physical

HHV-6B is the causative agent in exanthema subitum (also known as roseola infantum), a childhood disease characterized by high fever and a mild skin rash, and accounts for up to 10 to 17% of acute febrile Emergency department visits in children up to 36 months of age. [9] Primary HHV-6 infection accounts for over 36% of all cases of acute fever in children between 12 and 15 months old and is almost exclusively caused by HHV-6B, not HHV-6A. [9] [8] [10]

[Round Table: Urticaria in relation to infections].

1) To study the clinical and analytic features of infectious disease associated to urticaria in children. 2) To look into the probable etiology of the infectious disease. 3) To determine atopic predisposition and previous urticarial episodes and to rule out the involvement of antibiotics. Transversal and observational study. Pediatric Allergy Outpatient Clinic of a tertiary Hospital. Forty-four children, aged 1 to 12 years with acute urticaria associated to clinically infectious or febrile illness attending an Emergency Pediatric Department. Symptoms evaluation and physical examination in the seventh first days and follow over 3-6 weeks by the same physician. Clinical features of urticaria (duration, angioedema associated); Clinic diagnosis of illness infectious (acute respiratory infection, gastroenteritis, febrile syndrome); white blood cells count, C-reactive protein, aminotransferases (AST, ALT), L-Y-glutamyl transferase; viral culture and antigen detection: enterovirus (EV), adenovirus, respiratory syncytial virus (RSV), parainfluenza 1, 2 and 3, influenza A y B and cytomegalovirus (CMV); serological assay: CMV, enterovirus, mycoplasma pneumoniae, Epstein-Barr, parvovirus B19. 22 children (50%) are between 1-2 years old. 40 patients (90,9%) had symptoms of respiratory tract infection and only four patients had a pneumonia. The other 4 children had a gastroenteritis. The analytic was suggestive of viral infection in 35 (79.5%) and unknown on seven patients. In 20 children (45.4%) was identified a probable infection. The viral detection was positive in 3 patients: CMV, herpes simplex 1 and influenza A. Twenty microbiological findings for seventeen patients was found by serological criterion of probable infection: enterovirus (10); parvovirus B19 (4); Epstein-Barr (3) y mycoplasma (3). Evidence of a double serologic infection was found in three patients. In comparison with a serological control group encountered that acute urticaria during a infectious disease is significantly associated (p = 0.0054) to high titer to enterovirus by complement-fixation. The urticaria was associated with angioedema in 38.6% and 9 children (20.4%) related an previous similar episode. Twenty-one (47.7%) had been treated with antibiotics before development the urticaria. All patients was given the suspected antibiotic and no patient developed any adverse reaction. The clinically infectious associated to urticarial rash in children, usually is a viral respiratory infections. Is more frequent at infant. In spite of antibiotic therapy is often related to development the urticaria, the subsequent challenge with the same antibiotic is good tolerated.

[Parvovirus B19 primo-infection and cold agglutinins].

Parvovirus B19 infection is frequent. Primary infection leads to diverse skin manifestations including the recently described gloves-and-socks papulopurpura. A patient presented with a papulopurpuric eruption on the nose, hands, feet and perineum with cheilitis and high-grade fever. Parvovirus B19 serology showed characteristic IgG on the 15th day after the initial eruption demonstrating the seroconversion. Cold agglutinins were positive during the eruption and negative after regression. The gloves-and-socks papulopurpura syndrome was initially described in 1990. Since that time 20 cases have been reported. In 7 cases, primary parvovirus B19 infection was proven and viral infections were suspected in the others (measles, coxsackie B6, hepatitis B, Epstein-Barr virus). Our case evidenced here to undescribed skin manifestations and the development of cold agglutinins. The presence of cold agglutinins at eruption could explain the acral localizations observed in this syndrome.

Systemic vasculitis

Vasculitis secondary to viral infection. Usually due to hepatitis B and C, human immunodeficiency virus, cytomegalovirus, Epstein–Barr virus, and parvovirus B19. Signs and symptoms Patients usually present with systemic symptoms with single or multiorgan dysfunction. Common (and nonspecific) complaints include fatigue, weakness, fever, joint pains, abdominal pain, hypertension, chronic kidney disease, and neurologic dysfunction. The following symptoms should raise a strong suspicion of a vasculitis:

[Infections with herpesvirus 6--really only "exanthema subitum"? Part 1: More frequent disease pictures].

The human herpes virus 6 (HHV6) is the causal agent of exanthem subitum (rose rash of infants). In addition, however, a wide range of other clinical manifestations are possible, the more common of these include: Untypical exanthem or uncharacteristic rash (with and without fever), acute respiratory disease (ARD) acute gastroenteritis and febrile convulsions (with and without exanthem). More uncommon, and in part unknown, clinical manifestations associated with HHV6 infection are discussed in Part 2 of this paper. In common with other herpes viruses, HHV6 also tends to show persistence and intermittent or chronic shedding in the normal population, making the unusually early infection of children (seroconversion in the first year of life in up to 80% of all children) understandable. This means that HHV6 infections manifesting in close temporal association with recommended vaccinations may be misinterpreted as complications of the vaccination. Today, the situation can be clarified by employing special virological-serological laboratory tests, which are available throughout the country.

Acute cerebellar ataxia of childhood

Acute cerebellar ataxia of childhood is a childhood condition characterized by an unsteady gait, most likely secondary to an autoimmune response to infection, drug induced or paraneoplastic. Most common virus causing acute cerebellar ataxia are Chickenpox virus and Epstein Barr Virus, leading to a childhood form of post viral cerebellar ataxia. It is a diagnosis of exclusion. Signs and symptoms Acute cerebellar ataxia usually follows 2–3 weeks after an infection. Onset is abrupt. Vomiting may be present at the onset but fever and nuchal rigidity characteristically are absent. Horizontal nystagmus is present is approximately 50% of cases. Truncal ataxia with deterioration of gait Slurred speech and nystagmus Afebrile Cause Possible causes of acute cerebellar ataxia include varicella infection, as well as infection with influenza, Epstein-Barr virus, Coxsackie virus, Echo virus or mycoplasma.

[The relationship of clinical manifestations and age distribution in enterovirus infections--viral isolation and seroepidemiology in Aichi Prefecture].

We studied the epidemiology of enterovirus infection in Aichi Prefecture from 1985 to 1989. We examined the age distribution of aseptic meningitis patients (AM) and exanthematous disease patients (Ex) and a seroepidemiological study of echovirus type 7 (E7), E9, E18 and group A coxsackievirus type 9 (CA9), was performed. The results is as follows: 1) E7, E9, E18 and CA9 were isolated from AM and Ex but E6, E11 and group B Coxsackie viruses (CB) were isolated in fewer cases from Ex. 2) The AM was consistently increased from June to August. Whereas the Ex was seen in all seasons but a slight increase was noted between June to July, and enteroviruses (EV) isolation was increased in this season. 3) The AM occurred in 0 year olds and 4 year olds whereas the Ex was seen in 0 to 1 years. EV was mainly isolated from 0-1 year olds. 4) The relationship of clinical manifestations and age was very clear in E9 and E18, a higher proportion of children at 1 years or under were those of the Ex and most children of the latter part of 4 years were those of the AM. The Ex had the same results with E7 and CA9 but AM was increased in 0 years and 4 year olds. 5) We studied the age distributions of neutralizing antibodies against E7, E9, E18 and CA9. The positive rate of neutralizing antibody after prevalence rose between 2-5 years of age. There were few patients among the 2 to 3 year olds but the neutralizing antibody was raised in this age. I considered that reason the enteroviruses infected mainly the 2 to 6 year olds showing no clinical symptoms where as some of the 3 year olds had aseptic meningitis and some under 1 year had symptoms of exanthematous diseases.

Acute necrotizing encephalopathy associated with human herpesvirus-6 infection.

An extremely rare case of acute necrotizing encephalopathy caused by human herpesvirus-6 variant type B infection is reported. The patient, a 14-month-old previously healthy female, presented with high fever and generalized tonic convulsion followed by rapid deterioration of consciousness. On the second day of the illness, the protein level of the cerebrospinal fluid increased without pleocytosis. On the third day, magnetic resonance images demonstrated symmetric, abnormal signal intensity lesions in the bilateral thalamus, cerebellum, and brainstem. On the fourth day, characteristic maculopapular rash of exanthema subitum appeared on the trunk. Human herpesvirus-6 deoxyribonucleic acid was detected by the polymerase chain reaction in the serum, and immunoglobulin G and immunoglobulin M of serum human herpesvirus-6 were positive. On the twelfth day of illness, the patient died as a result of severe brain damage. Acute necrotizing encephalopathy should be included in the differential diagnosis when examining infants and young children with fulminating consciousness disturbance and intractable convulsion. In addition, as a causative virus, human herpesvirus-6 has to be considered at the pre-eruptive stage of exanthema subitum. Magnetic resonance images are useful because they reveal the characteristic distribution of lesions specific to acute necrotizing encephalopathy.

[Macrophage activation syndrome in primary human herpes virus-6 infection: a rare condition after liver transplantation in infants].

Human herpes virus-6 primary infection generally occurs during the first three years of childhood and is generally asymptomatic. The virus has been identified as the causal agent of exanthemum subitum in children or mononucleosis-like disease in adults, and may also cause several disorders in immunocompromised patients. We report a clinical case of acute rejection observed 29 days after orthotopic liver transplantation in a 22-month-old child associated with acute hepatitis and a hemophagocytic syndrome on day 38. Human herpes virus-6 primary infection was identified based on several virological tests: seroconversion, detection of viral DNA in bone marrow and peripheral blood after polymerase chain reaction, and detection of viral replication in peripheral blood. Tests for Epstein-Barr virus, cytomegalovirus or Parvovirus B19 infections were negative. After treatment by ganciclovir (Cymévan(R)), clinical status improved.

[Clinical manifestations of infectious erythema in adults].

The infectious erythema is usually childhood disease associated with rash and caused by parvovirus B19. At the beginning of 1993., at the Clinic for infectious and tropical diseases of the Military Medical Academy 36 patients were treated for this disease, the average age 21 years. The prodromal phase of illness lasted approximately 2.9 days, the elevated temperature 5.2 days, and 17 patients had temperature above 39 degrees C. The rash was usually maculo-papullous and lasted about 6 days. Four patients had the recurrence of rash. The polyarthralgia appeared for short in six patients and in one patient lasted longer than 4 months. The mild anemia during infectious erythema was observed in 18 patients. IgM antiparvo B19 antibodies were proven in serum in 91.7%, and IgG antibodies in 58.3% of patients.

[THE FEATURES OF THE COURSE OF INFECTIOUS MONONUKLEOSIS OF DIFFERENT ETIOLOGY IN CHILDREN].

Aim - to study the effect of different pathogens (EBV, CMV, HHV-6, and MIXT) on the severity of clinical-paraclinical manifestations of infectious mononucleosis in children. The clinical and laboratory study performed for 410 children aged from 10 months up to 12 years with infectious mononucleosis. The association of herpes viruses, mainly EBV, CMV and HHV type 6, takes part in the formation of the clinical picture of IM in (52,9%) of cases. The sole participation of EBV in the development of IM was observed only in (34,1%), CMV (9,02%) and HHV-6 in (3,17%) patients. The etiology of infectious mononucleosis in children affects the acuity, severity, and intensity of the clinical and paraclinical signs of the disease. Infectious mononucleosis VEB etiology is manifested by acute onset (79,5%), intoxication (70,5%), subfebrile and febrile fever up to 7 days (61,03%), lacunar tonsillitis (85,8%), hepatomegaly ( 88,2%), splenomegaly (63,8%), mostly moderate (81,7%) with lymphocytosis (62,9%) and monocytosis (20,5%). For CMV mononucleosis - acute onset (89,9%), severe course (29,8%), febrile and high fever for up to 7 (56,7%) or more days, neutrophilic leukocytosis (73,55) with atypical mononuclear cells (64,7%) and anemia (29,7%). Severe (33,3%), with prolonged high fever (50%), exanthema syndrome (33,3%), pharyngitis without tonsillitis (66,7%), leukocytosis (66,7%) with accelerated ESR (66,7%) and monocytosis (33,3%) are characteristic of HHV-6 infection. For MIXT - acute onset (78,3%), intoxication (79,7%), lacunar tonsillitis (92,9%), hepatomegaly (84,1%) and splenomegaly (67%), low-grade and febrile fever from 3- x (27,1%) up to 7 days (35,05%), lymphocytosis (55,3%) with neutropenia (57,4%), atypical mononuclear cells (48,2%) and hypochromic anemia (17,29 %).

Infectious mononucleosis

Incubation period The exact length of time between infection and symptoms is unclear. A review of the literature made an estimate of 33–49 days. In adolescents and young adults, symptoms are thought to appear around 4–6 weeks after initial infection. Onset is often gradual, though it can be abrupt. The main symptoms may be preceded by 1–2 weeks of fatigue, feeling unwell and body aches. Cause Epstein–Barr virus About 90% of cases of infectious mononucleosis are caused by the Epstein–Barr virus, a member of the Herpesviridae family of DNA viruses. It is one of the most commonly found viruses throughout the world. Contrary to common belief, the Epstein–Barr virus is not highly contagious. It can only be contracted through direct contact with an infected person's saliva, such as through kissing or sharing toothbrushes. About 95% of the population has been exposed to this virus by the age of 40, but only 15–20% of teenagers and about 40% of exposed adults actually become infected.

Vertically transmitted infection

T – toxoplasmosis from Toxoplasma gondii O – other infections (see below) R – rubella C – cytomegalovirus H – herpes simplex virus-2 or neonatal herpes simplex Other infections include: Parvovirus B19 Coxsackievirus Chickenpox (caused by varicella zoster virus) Chlamydia HIV Human T-lymphotropic virus Syphilis Zika fever, caused by Zika virus, can cause microcephaly and other brain defects in the child. Hepatitis B may also be classified as a vertically transmitted infection. The hepatitis B virus is large and does not cross the placenta. Hence, it cannot infect the fetus unless breaks in the maternal-fetal barrier have occurred, but such breaks can occur in bleeding during childbirth or amniocentesis.

[Febrile eruptions and herpesviruses].

There are 2 types of febrile skin eruptions due to herpesviruses: rashes (human herpesvirus 6 and 7. Epstein-Barr virus and cytomegalovirus), and vesicular eruptions (varicella and herpes zoster, primary and recurrent herpetic infections). Clinical diagnosis is often easy, based on the features of the eruption: characteristic sudden exanthem, clinical signs of infectious mononucleosis, or early vesicular trunk lesions characteristic of varicella or herpes. However, it must be stressed that exanthematic viroses can be highly variable. In some cases, and based on the background on which these eruptions occur, laboratory investigations will be necessary, according to the suspected virus.

Severe atypical hand-foot-and-mouth disease in adults due to coxsackievirus A6: Clinical presentation and phylogenesis of CV-A6 strains.

Typically, hand-foot-and-mouth disease (HFMD) is a mild childhood illness associated with coxsackievirus (CV)-A16, CV-A6, enterovirus (EV)-A71. To identify the viral agents associated with severe cases of atypical HFMD in Italy. Epidemiologically unrelated cases of severe atypical HFMD admitted to the Emergency Room (ER) of IRCCS San Martino IST (Genoa, Italy) in 2014-2016 were investigated. Serologic screening for viral positivity was performed against exanthem-inducing agents. Ten cases with serology indicative of recent EV infection were selected. Molecular assays were used to detect viral genomes in blood [EVs, Parvovirus B19 (PVB19), herpesviruses (CMV; EBV, HHV-6, -7, -8)]. CV-A6 was detected in 10 cases of severe atypical HFMD. Two cases were also infected with PVB19. Herpesviruses were not detected. Phylogenetic analysis mapped the CV-A6 strains into a single cluster related to two recent isolates from a German and an Asian child. Fever, systemic symptoms, severe vasculitis-like rash, and enanthem were predominant at presentation. Spontaneous recovery occurred in 1-3 weeks. CV-A6 is emerging as a frequent cause of severe atypical HFMD in Italian adults. This viral agent is disseminating worldwide. Dermatologists must identify the manifold alterations caused by EVs and understand the diagnostic power of current virology methods.