Acute Rheumatic Fever in Children: Diagnostic Criteria

Acute rheumatic fever (ARF) is a common diagnostic problem in developing countries. The incidence of ARF (acute rheumatic fever) in developed countries is well under control. Joint pain can be common problem in children but may rarely be symptom of serious joint disease. The physician must be able to determine whether the pain is a result of some lifestyle disorder or of some serious problem within the joints. Juvenile rheumatoid arthritis or rheumatic fever may also be a cause of joint pains and should always be ruled out. Complex and variable presentation of this devastating disorder sometimes confuse the physicians to reach at a diagnosis clinically.

Signs & symptoms and clinical history:

The spectrum of diagnoses that need to be considered can be narrowed down on the basis of clinical history. Age, sex and the acute or insidious mode of onset and development of joint pains act as pointers of the clinical history's role in diagnosis of the rheumatic fever or juvenile rheumatoid arthritis. The diagnostic workup of a child demands a history of preceding or concurrent illness presenting with sore throat or viral symptoms, or a history of recent immunization for rubella or other viral infections. The location, pattern and duration of joint pain are other important points to be taken into consideration.

Diagnostic criteria:

The diagnosis of rheumatic fever is very complicated as the disease may affect a number of organs and tissues. The fact is that no single laboratory test or clinical manifestation is enough to be diagnostic. A composite understanding of clinical manifestations and laboratory investigations is essential to reach at a diagnosis of ARF. If supported by the evidence of preceding Group-A Streptococcal infection, the presence of two major manifestations or one major and two minor manifestations is must to make a diagnosis of rheumatic fever.

1) Major manifestations: As proposed by the American Heart Association, the major manifestations of acute rheumatic fever are clinical evidences of this disease. The major manifestations are: carditis polyarthritis, chorea, erythema marginatum and
subcutaneous nodules. The arthritis/polyarthritis is the most common major manifestation found in the majority (around 75%) of patients during the acute stage of the disease and the remainder being found in relatively small proportion (around 25%) of patients. The arthritis is painful with the joints being swollen, red and warm to touch. Ankles, knees, elbows and wrists are usually involved. Rheumatic carditis is the most serious manifestation of acute rheumatic fever and may affect around 5% of patients with ARF. Chorea means rapid, purposeless involuntary movements of various body parts, generally bilateral and accompanied by muscle weakness. Around 15% of the patients with rheumatic fever may show the signs of chorea. The rash of rheumatic fever is called Erythema marginatum and is nonpruritic, nonindurated and pink rash. Lesions may vary in size and occur mainly on the trunk, buttocks and proximal extremities and occurs in around 5% of patients with rheumatic fever. Subcutaneous nodules are firm, painless nodules and may appear over some joints in about 1% of patients with rheumatic fever.

2) Minor manifestations and laboratory investigations: The minor manifestations of rheumatic fever are: history of previous rheumatic fever or rheumatic heart disease, arthralgia, fever, elevated acute phase proteins and prolonged P-R intervals on Electrocardiogram (ECG). The minor manifestations tend to be less specific than the major manifestations discussed above. The laboratory studies such as detection of elevated levels of acute phase reactants are also nonspecific. Differential count of white blood cells may show granulocytosis in patients having acute streptococcal infection. Fever is always present at the onset of an attack of rheumatic fever. The temperature is usually around 102^o F (39^o C) at the onset and may persist at around 100^o F (37.8^o C) for several weeks. Arthralgia means the presence of joint pain in one or more joints without inflammation, tenderness or limitation of range of motion of a joint. If polyarthritis has already been counted as major manifestation, arthralgia should be ignored. Elevated levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and fibrinogen are generally observed in untreated patients with rheumatic fever. These are nonspecific indicators of inflammation and neither ESR nor CRP is specific for rheumatic fever. Prolongation of P-R interval on ECG usually indicates an abnormal delay in conduction through the atrioventricular (AV) node. P-R interval prolongation on ECG is observed in around 35% of patients with rheumatic fever but may also be present in other inflammatory diseases (Myocarditis and digitalis or quinidine toxicity may also cause prolonged P-R intervals on ECG). A throat swab culture should always be done to isolate Group-A Streptococcal infection at the time of diagnosis of acute rheumatic fever. It is better if antistreptolysin-O (ASO) titers are measured in these patients. Elevated levels of antistreptolysin-O (ASO) titers are observed in approximately 80% of patients
affected by rheumatic fever. An ASO titer of over 300 units in a school-age child is an evidence of recent Group-A Streptococcal infection.

Differential diagnosis:

Non-rheumatic conditions that present with musculo-skeletal pain in children can usually be diagnosed on the basis of physical examination and history without any laboratory investigation. Such conditions could be trauma, hypermobility syndrome, overuse syndrome, benign recurrent limb pains and psychogenic rheumatism. Rheumatic fever, juvenile rheumatoid arthritis, infectious and neoplastic bone disease as causative agents of joint pains need to be evaluated in the light of major and minor manifestations discussed above.

Coronary Heart Disease and Dietary Interventions

Dyslipidemia is the main biochemical feature of coronary heart disease (CHD). Dyslipidemia refers to the elevated level of total cholesterol (TC) as well as triglycerides (TG) or a decreased level of high density lipoprotein (HDL). Dyslipidemia may result from alteration in the production of lipid components or due to abnormal catabolism or clearance as a result of environmental or genetic factors. Single or multiple gene mutations affecting the triglycerides/low density lipoprotein cholesterol are the cause of primary dyslipidemia. Sedentary life style or excessive dietary intake of saturated fat, cholesterol and trans fats can cause secondary dyslipidemia. Secondary dyslipidemia may also be caused due to certain health ailments, such as: diabetes mellitus (DM), obesity, chronic kidney disease, hypothyroidism, primary biliary cirrhosis and cholestatic liver disease. Overuse of alcohol and some drugs can also cause secondary dyslipidemia. Early identification and treatment of children with primary dyslipidemia or hyperlipidemia is important to prevent coronary heart disease. Screening is recommended for children above the age of two having positive family history of premature coronary heart disease, early heart disease. Positive family history of CHD refers to the history of angina pectoris, peripheral vascular disease, myocardial infarction, cerebrocardiac disease, coronary atherosclerosis or sudden death before the age of 55 years in parents, grand parents or first degree uncle or aunt.

Fasting cholesterol and low density lipoprotein (LDL) levels should be determined in the sera of children suspected to have dyslipidemia. Total cholesterol level <170 mg/dl and LDL <110 mg/dl are considered normal, whereas total cholesterol level >200 mg/dl and LDL >130 mg/dl are considered elevated in children. Levels between upper and lower limits could be called borderline values. Physical activity in the form of exercise and brisk walking should be encouraged to maintain weight control and endurance in insulin resistance in diabetics to prevent the risk of developing cardiovascular disease.

Dietary interventions play a vital role in the management of dyslipidemia. A diet low in saturated fat and cholesterol, high in complex carbohydrates should be encouraged for the normal growth and maintenance of desirable weight. Dietary fibre intake should be increased as it helps in reducing the blood cholesterol levels. 'Whole wheat flour bread', corn fakes and barley sattu should be preferred in addition to leafy vegetables. Regular intake of diet containing phytosterols/stanols, omega-3 fatty acid and Soya protein have been found to be effective to reduce the serum LDL cholesterol as well lowering the total cholesterol. Pharmacological treatment is recommended for managing the dyslipidemia in children at 10 years of age and adolescents with LDL>190mg/dl.

Rickets: A preventable bone disease

Rickets is a well known bone disease seen among infants and children. It causes skeletal deformities and softening of bones. An identical disorder seen amongst adults is known as osteomalacia. Rickets is a vitamin deficiency disease caused by lack of vitamin-D. Dietary intake of vitamin-D and natural conversion of pro-vitamin-D to vitamin-D through ultraviolet radiation of sunlight is must for the prevention of rickets. Inadequate exposure to sunlight may be the main biological factor responsible for the development of rickets, but inadequate intake of vitamin-D and calcium remains the number one cause of rickets. So, the main factors responsible for causing rickets are malnutrition, vegetarianism and inadequate exposure to sunlight. Rickets is very common amongst the malnourished children. Egg yolk, butter and some species of fish are the best known natural sources of vitamin-D. Lactating mothers should always take adequate diet rich in vitamin-D to prevent rickets in their infants. Growing children need food supplements fortified with vitamin-D in addition to normal diet and adequate exposure to sunlight for healthy bones and prevention of rickets.

Geriatrics: Old age and its management

The definition of old age varies in indifferent zones of the worldwith respect to the cutoff age or the age of onset of old age. Arbitrarily the attainment of the age of 65 years is said to be the knocking point of old age, but the health status of all old people is always influenced by physical and emotional stress. As a general criterion , all people above the age of 75 fall in the category of old. Generally doing all the duties of personal cleanliness and comfort, unassisted is a challenge for some old people. Since 1950 Geriatric medicine has been recognized as a specialty of medicine which focuses on the healthcare of aged citizens. Geriatricians are better trained in the care of elderly patients than the general physicians. The old generally suffer from incapacitating illness. Very few hospitals have special wards for old and the specialty of geriatrics. Many people suffer a decline in their metabolic and immune functions when they get old. The health authorities of all the countries should have comprehensive policy for the care of old people. Our cultural traditions include the respect for parents and the old. The fifth commandment directs, "to honour thy father and mother". The specialized agencies of the U.N. (including I.L.O., F.A.O., U.N.E.S.C.O. and W.H.O.) and many non-governmental organizations (NGOs) have been doing their best for the general care and medicinal needs of the elderly. NGOs should focus their attention on the vital sectors like personal hygiene, food, optimal clothing, exercise and entertainment in an effort to provide quality life to the inmates of old age homes. The elderly people need our special attention as we do in case of children. There is a need for integration of the specialty of geriatrics with other medical and paramedical services in order to provide appropriate medical expertise to elderly patients.

Type-2 Diabetes and the role of incretins

The incretins are the hormones, which are released into the blood circulation in response to nutrients we eat. These peptide hormones are generally released within minutes of eating or enteral nutrition. In humans, the major incretins are: (i) Glucagon like peptide-1 (GLP-1) and (ii) Glucose-dependent insulinotropic polypeptide (GIP). GLP-1 is secreted by L-cells in the ileum and colon, while GIP is secreted by K-cells in the duodenum of our alimentary canal. GLP-1 and GIP stimulate insulin secretion by the pancreas and also affect the gut and the brain. Their combine effect make significant contribution in glucose homoeostasis, particularly in scaling down the peak of postprandial glucose level. It has been proved through experimental studies that the GLP-1 has the major incretin effect; that is around 80% of the combine effect of GLP-1 and GIP. These incretins probably act via glycoprotein-coupled receptors.

Non-insulin dependent diabetes mellitus (NIDDM) or type-2 diabetes mellitus (Type-2 DM) is characterized by pancreatic beta-cell dysfunction and variable degree of insulin response. Complex interaction of genetics and environmental factors are responsible for metabolic disorders leading to diabetes. Taming of hyperglycemia through medicines, dietary control and regular exercise is possible. Increasing prevalence of obesity and reduced physical activity is directly related to the increasing prevalence of type-2 DM, worldwide. Oral antidiabetic agents, diet and or exercise and insulin are currently used for the treatment of patients with diabetes. Existing antihyperglycemic agents are often associated with an increased risk of adverse effects (such as weight gain and hypoglycemia) and most often become less effective due to histological/cellular variations (progressive beta cell failure) in the pancreas of the patient.

Incretins provide insulinotropic stimulus and thus lower the blood glucose level by increasing insulin secretion. However, the incretin response to a meal lasts approximately around 3 hours as the incretin molecules have very short half-life (<5 minutes) and are metabolized quickly. An enzyme known as dipeptidyl peptidase-4 (DPP4), produced by endothelial cells, disintegrate the incretin molecules within 2-3 minutes of their secretion. Poor incretin response has been observed in patients with type-2 diabetes during the glucose tolerance test as indicated by reduced level of GLP-1 as compared to normal individuals. The functional response (insulinotropic response) of GLP-1 was found to be intact in patients with type-2 diabetes and that gave new direction to the treatment regimen of diabetes. At present the incretin system has been under active study to find out the effective compounds for the treatment of type-2 diabetes. Pharmaceutical compounds like: (1) GLP-1 'analogues' or GLP-1 receptor agonists which are resistant to breakdown by DPP4 and (2) Incretin enhancers which inhibit the action of DPP4 on GLP-1 molecules, have been under active study for use in new formulations.

Exenatide is already in clinical use after its approval by US-FDA. Exenatide is a biosynthetic form of GLP-1 analogue-exendin-4. Exendin-4 is a naturally occurring GLP-1 found in the saliva of a lizard known as Gila monster. It was approved by US-FDA in 2005 for use in combination with metformin or sulfonylureas or both together. Exenatide is administered twice daily before meals by subcutaneous injections from a pre-filled pen. Incretin enhancers improve the control of glucose level in blood by inhibiting DPP4 action on incretin hormones especially GLP-1 molecules. Incretin enhancer Sitagliptin was approved by US-FDA in 2006 and Vildagliptin was approved by US-FDA in 2007, and both have been used as monotherapy or in combination with antidiabetic drugs like metformin or thiazolidinedione for glycemic control in patients affected by type-2 diabetes.

Important Note: Antihyperglycemic treatment should always be taken in consultation with a physician or specialized diabetologist.