Rheumatic Fever : Background, Causes, Treatment, & Prevention

Rheumatic fever is a multisystem inflammatory  disease that occurs in the genetically susceptible host 2 to 4 wk after a pharyngeal infection with group A streptococci.

PHYSICAL FINDINGS & CLINICAL PRESENTATION

  • Acute streptococcal pharyngitis, which may be subclinical and not reported by the patient
  • After latent period of 2 to 4 wk (average, 19 days), acute rheumatic attack
  • Patient is febrile, with a migratory polyarthritis of knees, ankles, wrists, elbows; typically severe for 1 wk, remits by 3 to 4 wk
  • Carditis:
  1. New heart murmur
  2. Mitral regurgitation
  3. Aortic insufficiency
  4. Diastolic mitral murmur
  5. Cardiomegaly
  6. CHF
  7. Pericardial friction rub or effusion
  • Rarely, pancarditis is severe and fatal
  • Subcutaneous nodules can be palpated over extensor tendon surfaces or bony prominences, such as the skull
  • Chorea (Sydenham’s chorea) is characterized by rapid involuntary movements affecting all muscles:
  1. Muscular weakness
  2. Emotional lability
  3. Rarely seen after adolescence and almost never in adult males
  • Erythema marginatum:
  1. Evanescent, pink, well-demarcated spreading to trunk and proximal extremities
  2. Not specific
  • Arthralgias (joint pain without swelling)
  • Abdominal pain


ETIOLOGY

  • Group A streptococci not recovered from tissue lesions.
  • It does not occur in the absence of a streptococcal antibody response.
  • Immunologic cross-reactivity between certain streptococcal antigens and human tissue antigens suggests an autoimmune cause.
  • Both initial attacks and recurrences can be completely prevented by prompt treatment of streptococcal pharyngitis with penicillin.

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS

  • Rheumatoid arthritis
  • Juvenile rheumatoid arthritis (Still’s disease)
  • Bacterial endocarditis
  • Systemic lupus
  • Viral infections
  • Poststreptococcal reactive arthritis: severe arthritis but no carditis

WORKUP

  • “Jones Criteria (revised) for Guidance in the Diagnosis of Rheumatic Fever”
  • One major and two minor criteria if supported by evidence of an antecedent group A streptococcal infection
  • Major criteria:
  1. Carditis and valvulitis
  2. Migratory arthritis (predominantly involving large joints)
  3. Central nervous system involvement (e.g., chorea)
  4. Erythema marginatum
  5. Subcutaneous nodules
  • Minor criteria:
  1. Fever
  2. Arthralgia
  3. Increased acute-phase reactants
  4. ESR
  5. C-reactive protein
  6. Leukocytosis
  7. Prolonged P-R interval

LABORATORY TESTS

  • Throat cultures are usually negative at presentation of clinical manifestations of rheumatic fever.
  • Streptococcal antibody tests are more useful in establishing the diagnosis.
  1. Peak at the beginning of the attack
  2. Can document a recent streptococcal infection
  • ASO (antistreptolysin O) titers peak:
  1. 4 to 5 wk after the actual streptococcal throat infection
  2. Which coincides during the second or third wk of illness of rheumatic fever
  • Anti-DNase B (Streptozyme) can be detected for 6 to 9 mo following infection and can be tested for if ASO titer negative.
  • Other antistreptococcal antibody tests include: streptokinase and antihyaluronidase.
  • High-titer streptococcal antibodies:
  1. Are supportive of diagnosis, but not proof
  2. Should be interpreted in the context of clinical criteria

IMAGING STUDIES

  • Chest x-ray to assess heart size
  • Echocardiogram:
  1. To evaluate murmurs
  2. To rule out pericardial effusion

TREATMENT

ACUTE GENERAL Rx

  • Course of penicillin to eradicate throat carriage of group A streptococci
  • Arthralgia or arthritis without carditis: aspirin 90 to 100 mg/kg/day for 2 wk, followed by 60 to 70 mg/kg/day for the subsequent 4 to 6 wk if needed
  • Carditis and heart failure:
  1. Prednisone 40 to 60 mg/day
  2. IV corticosteroids, such as methylprednisolone, 10 to 40 mg/day for severe carditis prophylaxis

Understand About MENSTRUAL CYCLE – Read more

The menstrual cycle is the cyclical changes that occur in the female reproductive system .The hypothalamus, pituitary, ovaries, and uterus interact to allow ovulation approximately once per month (average 28 days [+/–7 days]). The following description is based on a 28-day menstrual cycle.

_ Many follicles are stimulated by follicle-stimulating hormone (FSH), but the follicle that secretes more estrogen than androgen will be released. This dominant follicle releases the most estradiol so that its positive feedback causes an LH surge.

_ Average menses = 4 days. More than 7 days is abnormal.

_ Blood loss in menstruation averages 30–50 mL and should not form clots; > 80 mL is an abnormally high amount of blood loss.

Days 1–14: Follicular Phase

_ The follicular phase begins on the fi rst day of menses. All hormone levels are low. Without any negative feedback, GnRH from the hypothalamus  causes FSH release from the pituitary.

FSH stimulates maturation of granulosa cells in the ovary. The granulosa cells secrete estradiol in response.

Estradiol inhibits luteinizing hormone (LH) and FSH due to negative feedback. In the meantime, the estradiol secretion also causes the endometrium to proliferate.

LH acts on the theca cells to  secretion of androgens (which are converted  to estradiol), prepare the cells for progesterone secretion, and cause further granulosa maturation.

Day 14: Ovulation

_ A critical level of estradiol triggers an LH surge.

_ The LH surge causes the oocyte to be released from the follicle. The ruptured follicle then becomes the corpus luteum, which secretes progesterone.

Days 14–28: Luteal Phase

_ The corpus luteum secretes progesterone for only about 11 days in the absence of human chorionic gonadotropin (hCG).

Progesterone causes the endometrium to mature in preparation for possible implantation. It becomes highly vascularized and ↑ glandular secretions .

Progesterone also causes inhibition of FSH and LH release.

_ If fertilization does not occur, the corpus luteum involutes, progesterone and estradiol levels fall, with subsequent endometrial sloughing (menses). The hypothalamic-pituitary axis is released from inhibition, and the cycle begins again.

Thyroid Nodule in Management

A thyroid nodule is an abnormality found on physical examination of the thyroid gland; nodules can be benign (70%) or malignant.

CAUSE

_ History of prior head and neck irradiation

_ Family history of pheochromocytoma, carcinoma of the thyroid, and hyperparathyroidism (medullary carcinoma of the thyroid is a component of MEN-II).

CLINICAL 

_ Palpable, firm, and nontender nodule in the thyroid area should prompt suspicion of carcinoma. Signs of metastasis are regional lymphadenopathy and inspiratory stridor.

_ Signs and symptoms of thyrotoxicosis can be found in functioning nodules.

DIFFERENTIAL DIAGNOSIS

_ Thyroid carcinoma

_ Multinodular goiter

_ Thyroglossal duct cyst

_ Epidermoid cyst

_ Laryngocele

_ Nonthyroid neck neoplasm

_ Branchial cleft cyst

WORKUP

_ Thyroid ultrasound

_ Fine-needle aspiration (FNA) biopsy

LABORATORY TESTS

_ Serum TSH should be obtained in all patients with thyroid nodules.

_ Thyroid-stimulating hormone (TSH), T4, and serum thyroglobulin levels should be obtained before thyroidectomy in patients with confirmed thyroid carcinoma on FNA biopsy.

_ Serum calcitonin

MANAGEMENT

_ Evaluation of results of FNA:

_ Normal cells: may repeat biopsy during present evaluation or reevaluate patient after 3 to 6 mo of suppressive therapy (l-thyroxine, prescribed in doses to suppress the TSH level to 0.1-0.5).

  • Failure to regress indicates increased likelihood of malignancy.
  • Reliance on repeat FNA biopsy is preferable to routine surgery for nodules not responding to thyroxine.

_ Indeterminate: use of gene expression classifier profile. If suspicious, perform surgery; if benign, monitor with subsequent repeat FNA and gene expression classifier profile.

_ Malignant cells: surgery.

Diabetic Foot Ulcer Management

DEFINITION
Diabetic foot infections (DFIs) are a common and potentially serious problem in persons with diabetes. They usually arise from either a skin ulceration that occurs secondarily to peripheral neuropathy or in a wound caused by some form of trauma. The infection usually involves one or more bacteria and can spread to contiguous tissues including bone, causing an osteomyelitis.

Diabetes mellitus (DM), a common complex metabolic disorder characterized by hyperglycemia, affects over 18 million people in the United States. The skin is one of many organ systems affected, especially the skin of the leg and foot. Microvascular disease may result in a decreased cutaneous blood fl ow; peripheral sensory neuropathy may render the skin susceptible toinjury and may blunt healing; and hyperglycemia predisposes the extremity to an increased occurrence of bacterial and fungal infections.

Associated complications in the lower limb include Charcot joint (progressive destructive arthropathy caused by
neuropathy), ulceration, infection, gangrene, and amputation. DM accounts for most nontraumatic foot and lower leg amputations, which total more than 80,000 per year.

Atherosclerosis can affect not only the coronary and cerebral vasculature but also the arteries that supply the kidneys, intestines, and lower limbs. The resulting arterial stenosis (narrowing) or occlusion in the leg leads to peripheral vascular disease (PVD), a disorder largely associated with increasing age. PVD produces symptoms of claudication, which should be a warning sign of atherosclerosis elsewhere that may produce myocardial infarction and stroke.

RISK FACTORS:
• Diabetes greater than 10 years
• Poor glucose control
• Peripheral neuropathy: altered protective sensation and altered pain response
• Diabetic angiopathy: atherosclerotic obstruction of larger vessels leading to peripheral vascular disease
• Evidence of increased local pressure: callus or erythema.

DIFFERENTIAL DIAGNOSIS
Other inflammatory conditions that can mimic diabetic foot infections include:
• Crystal-associated arthritis such as gout
• Trauma
• Acute Charcot arthropathy from long-standing diabetes
• Venous stasis ulcers
• Deep vein thrombosis

ACUTE GENERAL TREATMENT
WOUND MANAGEMENT:
• Debridement of callus and necrotic tissues by wound care specialist or surgeon and at times may require multiple debridements.
• Wound dressing: to absorb exudates and promote healing. Many products are available but none has been proven superior and include:
1. Enzymes
2. Gels
3. Hydrocolloids
4. Antiseptics containing iodine or silver salts
5. Honey
• Relieve pressure on the foot: casts or special shoes.
• Amputation or revascularization procedures such as angioplasty or bypass grafting may be necessary.

Diabetes Mellitus (DM) In Management

DEFINITION
Diabetes mellitus (DM) refers to a syndrome of hyperglycemia resulting from many different causes. It can be classified into type 1 (formerly insulin-dependent diabetes mellitus [IDDM]) and type 2 (formerly non–insulin-dependent diabetes mellitus [NIDDM]). Because insulin-dependent and non–insulindependent refer to the stage at diagnosis, when a type 2 diabetic needs insulin, he or she remains classifi ed as type 2 and does not revert to type 1.
The American Diabetes Association (ADA) defi nes DM as (1) a fasting plasma glucose 126 mg/dL, (2) a nonfasting
plasma glucose 200 mg/dL, or (3) glucose 200 mg/dL in the 2-hour sample in an oral glucose tolerance test (OGTT). Furthermore, a value of 100 mg/dL of fasting blood sugar is the upper limit of normal for glucose. A fasting glucose between 100 and 126 mg/dL is classifi ed as impaired fasting glucose (IFG).

CAUSE
Idiopathic diabetes
TYPE 1 DIABETES MELLITUS
● Hereditary factors
1. Islet cell antibodies (found in 90% of patients within the first year of diagnosis)
2. Higher incidence of HLA types DR3, DR4 3. 50% concordance in identical twins
● Environmental factors: viral infection (possibly coxsackie virus, mumps virus)
TYPE 2 DIABETES MELLITUS
● Hereditary factors: 90% concordance in identical twins
● Environmental factor: obesity

Diabetes secondary to other factors
● Hormonal excess: Cushing’s syndrome, acromegaly, glucagonoma, pheochromocytoma
● Drugs: glucocorticoids, diuretics, oral contraceptives
● Insulin receptor unavailability (with or without circulating antibodies)
● Pancreatic disease: pancreatitis, pancreatectomy, hemochromatosis
● Genetic syndromes: hyperlipidemias, myotonic dystrophy, lipoatrophy
● Gestational diabetes

DIFFERENTIAL DIAGNOSIS
● Diabetes insipidus
● Stress hyperglycemia
● Diabetes secondary to hormonal excess, drugs, pancreatic disease
PHYSICAL FINDINGS AND CLINICAL PRESENTATION
● Physical examination varies with the presence of complications and may be normal in early stages.
● Diabetic retinopathy
● Nonproliferative (background diabetic retinopathy)
1. Initially: microaneurysms (Fig. 285–1), capillary dilation, waxy or hard exudates, dot and fl ame hemorrhages , arteriovenous (AV) shunts 2. Advanced stage: microinfarcts with cotton-wool exudates, macular edema
● Proliferative retinopathy: characterized by formation of new vessels , vitreal hemorrhages, fibrous scarring,
and retinal detachment
● Cataracts and glaucoma occur with increased frequency in diabetics.
● Peripheral neuropathy: patients often complain of paresthesias of extremities (feet more than hands); the symptoms are symmetrical, bilateral, and associated with intense burning pain (particularly during the night).
● Mononeuropathies involving cranial nerves III, IV, and VI, intercostal nerves, and femoral nerves are also common.

TREATMENT
● Diet
● Calories
1. The diabetic patient can be started on 15 cal/lb of ideal body weight; this can be increased to 20 cal/lb for an active
person and 25 cal/lb if the patient does heavy physical labor.
2. The calories should be distributed as 50% to 60% carbohydrates, less than 30% fat, with saturated fat limited to less than 10% of total calories, and 15% to 20% protein.
3. The emphasis should be on complex carbohydrates rather than simple and refi ned starches and on polyunsaturated instead of saturated fats in a ratio of 2:1.
● Seven food groups
1. The exchange diet of the ADA includes protein, bread, fruit, milk, and low- and intermediate-carbohydrate vegetables.
2. The name of each exchange is meant to be all-inclusive (e.g., cereal, muffins, spaghetti, potatoes, rice are in the
bread group; meats, fish, eggs, cheese, peanut butter are in the protein group).
3. The glycemic index compares the rise in blood sugar after the ingestion of simple sugars and complex carbohydrates with the rise that occurs after the absorption of glucose.
Equal amounts of starches do not produce the same increase in plasma glucose (pasta equal in calories to a baked
potato causes less of an increase than the potato). Thus, it is helpful to know the glycemic index of a particular food
product.
4. Fiber: insoluble fi ber (bran, celery) and soluble globular fiber (pectin in fruit) delay glucose absorption and attenuate the postprandial serum glucose peak. They also appear to lower the elevated triglyceride level often present in uncontrolled diabetics. A diet high in fiber should be emphasized (20 to 35 g/day of soluble and insoluble fiber).

Cushing’s Syndrome In Management

DEFINITION
Cushing’s syndrome is the occurrence of clinical abnormalities associated with glucocorticoid excess secondary to exaggerated adrenal cortisol production or chronic glucocorticoid therapy. Cushing’s disease is Cushing’s syndrome caused by pituitary ACTH excess .
PHYSICAL FINDINGS AND CLINICAL PRESENTATION
● Hypertension
● Central obesity  with rounding of the facies (moon facies); thin extremities
● Hirsutism, menstrual irregularities, hypogonadism
● Skin fragility, ecchymoses, red-purple abdominal striae, acne, poor wound healing, hair loss, facial plethora, hyperpigmentation (when there is ACTH excess)
● Psychosis, emotional lability, paranoia
● Muscle wasting with proximal myopathy
Note: The previous characteristics are not commonly present in Cushing’s syndrome secondary to ectopic ACTH production. Many of these tumors secrete a biologically inactive ACTH that does not activate adrenal steroid synthesis. These patients may have only weight loss and weakness  .
CAUSE
● Iatrogenic from chronic glucocorticoid therapy (common)
● Pituitary ACTH excess (Cushing’s disease; 60%)
● Adrenal neoplasms (30%)
● Ectopic ACTH production (neoplasms of the lung, pancreas,
kidney, thyroid, thymus; 10%)
● Figure 271–4 illustrates the difference between ACTHdependent and ACTH-independent Cushing’s syndrome.
DIFFERENTIAL DIAGNOSIS
● Alcoholic pseudo-Cushing’s syndrome (endogenous cortisol overproduction)
● Obesity associated with diabetes mellitus
● Adrenogenital syndrome
LABORATORY TESTS
● Hypokalemia, hypochloremia, metabolic alkalosis, hyperglycemia, hypercholesterolemia
● Increased 24-hour urinary free cortisol (100 g/24 hr)
● In patients with a clinical diagnosis of Cushing’s syndrome, the initial screening test is the overnight dexamethasone suppression test:
1. Dexamethasone 1 mg PO given at 11 PM
2. Plasma cortisol level measured 9 hours later (8 AM)
3. Plasma cortisol level 5 g/100 mL excludes Cushing’s syndrome.
● Serial measurements (two or three consecutive measurements) of 24-hour urinary free cortisol and creatinine (to
ensure adequacy of collection) are undertaken if overnight dexamethasone test is suggestive of Cushing’s syndrome.
Persistent elevated cortisol excretion (300 g/24 hr) indicates Cushing’s syndrome.The low-dose (2 mg) dexamethasone suppression test is useful to exclude pseudo-Cushing’s syndrome if the previous
results are equivocal. Corticotropin-releasing hormone (CRH) stimulation after low-dose dexamethasone administration (dexamethasone-CRH test) is also used to distinguish patients with suspected Cushing’s syndrome from those who have a mildly elevated urinary free cortisol level and equivocal findings.
● The high-dose (8 mg) dexamethasone test and measurement of ACTH by radioimmunoassay (RIA) are useful to
determine the cause of Cushing’s syndrome.
1. ACTH undetectable or decreased. Lack of suppression indicates adrenal cause of Cushing’s syndrome.