Dajani AS, Ayoub E, Bierman FZ, et al. Guidelines for the diag- nosis of rheumatic fever: Jones criteria, updated 1992. Circulation 1993;87:302–307. Dajani AS, Taubert KA, Takahashi M, et al. Guidelines for long term management of patients with Kawasaki disease. Circulation 1994;89:916–922. Dajani AS, Taubert KA, Wilson W, et al. Prevention of bacterial endocarditis. Recommendations by the American Heart Association. JAMA 1997;277:1794–1801. Durack DT, Lukas AS, Bright DK. New criteria for diagnosis of infective endocarditis. Utilization of specific echocardio- graphic findings. Am J Med 1994;96:200–209. Ferrieri P. Proceedings of the Jones criteria workshop. Circulation 2002;106:2521–2523. Martin AB, Webber S, Fricker FJ, et al. Acute myocarditis: Rapid diagnosis by PCR in children. Circulation 1994;90:330–333. Minich LL, Tani LY, Dagotto LT, et al. Doppler echocardiogra- phy distinguishes between physiologic and pathologic “silent” mitral regurgitation in patients with rheumatic fever. Clin Cardiol 1997;20:924–926. Newburger JW, Takahashi M, Beiser AS, Burns JC, et al. A single intravenous infusion of gamma globulin in the treatment of acute Kawasaki disease. N Engl J Med 1991;324:1633–1639. Pinsky WW, Friedman RA. Pericarditis. In: Garson A, Jr. (ed.), The Science and Practice of Pediatric Cardiology. Philadelphia, PA: Lea and Felsinger, 1990, pp. 1590–1604. Rheuban KS. Pericardial diseases. In: Allen HD, Gutgesell HP, Clark EB, Driscall DJ (eds.), Moss and Adams Heart Disease in Infants, Children and Adolescents, Including the Fetus and Young Adult, 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2001, pp. 1287–1296. Sainer L, Prince A, Gregary WN. Pediatric infective endocarditis in the modern era. J Pediatr 1993;122:847–853. Towbin JA. Myocarditis. In: Allen HD, Gutgesell HP, Clark EB, Driscall DJ (eds.), Moss and Adams Heart Disease in Infants, Children and Adolescents, Including the Fetus and Young Adult, 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2001, 1287–1296. 58 HYPERTENSION Rae-Ellen W. Kavey • In childhood, high blood pressure (HBP) is defined as systolic and/or diastolic pressure above the 95th per- centile for age, gender, and height. •Over the last decade, normal values for blood pressure in childhood have been defined based on more than 60,000 BPs in children. These standards are available online at http://www.nhldi.nih.gov/health/prof/agart/ hbp/hbp ped.htm. • Primary and secondary hypertension can manifest at any time in childhood so measurement and correct interpretation of BP for age and body size is essential. At a minimum, blood pressure should be measured at every pediatric visit from 3 years of age and charted against norms for age/gender/height. •To be accurate, blood pressure needs to be measured using the correct size cuff for the child’s arm so a vari- ety of cuff sizes need to be available. An approximation of the correct size is a cuff whose bladder will cover 80–100% of the circumference of the arm. Blood pres- sure should be measured with the child at rest after 3–5 minutes with the arm supported at heart level. It should be taken at least twice and the average used. • Systolic BP is determined by the onset of Korotkoff sounds and diastolic blood pressure is determined by the disappearance of the Korotkoff sounds. • The National Heart Lung and Blood Institute com- missioned a series of Task Forces to define appropri- ate evaluation and management of high blood pressure in childhood. The most recent update in 1996 confirmed the use of the Second Task Force report of 1987 as the basis for the evaluation of high blood pressure in children. • From that report, the younger the child and higher the blood pressure, the more likely it is for hypertension to be secondary. A summary of the most common eti- ologies of hypertension at different ages is included in Table 58-1. • Because blood pressure variation is under multiple physiologic controls including cardiac, vascular, cen- tral nervous system (CNS), and endocrine, derange- ments in any of these systems can cause high blood pressure. • From the algorithm of the Second Task Force, evalua- tion for high blood pressure is indicated after a series of systolic and/or diastolic pressures are recorded above the 95th percentile for age/gender/height (Fig. 58-1). 244 SECTION 7 • DISEASES OF THE HEART AND GREAT VESSELS TABLE 58-1 Etiology of Hypertension: Prevalence by Age Group AGE GROUP CAUSE Newborn Abnormal renal blood flow Renal artery thrombosis (indwelling umbilical catheter) Renal artery atresia Congenital malformation of the kidney Coarctation of the aorta Infancy to 6 years Renal parenchymal disease Coarctation of the aorta Renal artery stenosis 6–10 years Renal artery stenosis Renal parenchymal disease Essential hypertension >10 years Essential hypertension Renal parenchymal disease CHAPTER 58 • HYPERTENSION 245 • Body size and blood pressure are very closely linked throughout childhood. If repeated blood pressure measurements are above the 95th percentile in a child who is overweight, few diagnostic tests are needed other than a urinalysis, blood urea nitrogen (BUN), and creatinine (Cr) to exclude renal dysfunction. •A summary of the important historic information and the relevant necessary testing for the most common diagnoses leading to hypertension in childhood is contained in Table 58-2. • In adolescents, the phenomenon of white coat hyper- tension is quite common. This is high blood pressure seen in medical care settings but not present at any other time. The best way to evaluate for white coat hypertension is the use of ambulatory monitoring which measures blood pressure using an automated cuff away from the office. Norms for wake and sleep blood pressure on ambulatory monitoring in child- hood are now available. If BPs are normal on ambula- tory monitoring, no additional evaluation is needed so this is a good first test for evaluation of potential hypertension in teenagers. • Whenever obesity is seen in conjunction with hyperten- sion, weight loss is the primary therapy. Even small amounts of weight loss often result in complete normal- ization of the blood pressure in both children and adults. • Therapy for hypertension in childhood focuses on elimination of the etiology when one is present. Drugs >95% Persistent >95% Diagnostic evaluation Appropriate treatment for cause Evaluate target organ effects. Nonpharmacologic treatment and possible drug therapy If BP persists at >95%, evaluate target organ effects, consider Dx evaluation for secondary cause and possible drug therapy Cause identified Cause not identified Monitor q 6 months Weight reduction; monitor q 6 months Institute sodium restriction; monitor BP Institute weight control; monitor BP; consider sodium restriction If child is not obese If child is obese No Ye s Persistent Determine if high BP can be explained by weight In younger patients with high BP and little family history, strongly consider secondary cause In older patients with mild to moderate BP elevation; often obese; positive family history Repeat BP over several visits 90–95% <90% Continuing heath care Repeat BP over several visits; determine BP percentile 90–95% <90% Measure height; determine height percentile; measure BP; determine BP percentile FIG. 58-1 Algorithm for identifying children with high BP. Note: Whenever BP measurement is stipulated, the average of at least two measurements should be used. S OURCE: Report of the Second Task Force on blood pressure control in children. Pediatrics 1987; 79:16–23. are used on a short-term basis while this is being accomplished or chronically when the diagnosis is essential hypertension and there is significant eleva- tion of BP plus increased left ventricular (LV) mass on echocardiography, indicating end-organ response to sustained BP elevation. In Table 58-3, antihyperten- sive drug therapy recommendations from the Second Task Force report are summarized. • There are no long-term clinical trials evaluating the risks of chronic antihypertensive therapy in children. For this reason, a very conservative approach should be taken to the initiation of drug therapy for hyperten- sion in young children. BIBLIOGRAPHY Harshfield GA, Alpert BS, Pulliam DA, Somes GW, Wilson DK. Ambulatory blood pressure monitoring in healthy and hyper- tensive children. Arch Dis Child 1994;94:180–184. Mirkin BL, Newman TJ. Efficacy and safety of captopril in the treat- ment of severe childhood hypertension: report of the International Collaborative Study Group. Pediatrics 1985;75:1091–1100. Report of the Second Task Force on blood pressure control in children—1987. Pediatrics 1987;79:1–25. Rocchini AP, Katch V, Anderson J. Blood pressure in obese ado- lescents: effect of weight loss. Pediatrics 1988;82:16–23. 246 SECTION 7 • DISEASES OF THE HEART AND GREAT VESSELS TABLE 58-2 History, Physical Examination Findings, and Targeted Workup for HBP in Childhood HISTORY PHYSICAL EXAMINATION POTENTIAL DIAGNOSIS EVALUATION ABBREVIATIONS: U/A, urinary analysis; UTI, urinary tract infection; OHCS, hydroxycorticosteroids; CT, computed tomography; MRI, magnetic resonance imaging; IVP, intravenous pyelogram. Plasma renin level, renal artery doppler flow; renal arteriogram Echocardiogram for LV mass, U/A, BUN, Cr to exclude renal disease Urinary 17-OHCS excretion, plasma cortisol Cardiac echo/doppler with evaluation of aortic arch; +/– aortic arch angiogram/CT/MRI U/A; urine culture, BUN, Cr; renal ultrasound, IVP Plasma and urine catecholamines and metabolites; abdominal CT Cardiac echocardiogram for peripheral pulmonary stenosis, supravalvar aortic stenosis; renal artery doppler flow/arteriogram, serum calcium Electrolytes, plasma aldosterone Drug withdrawal Thyroid function tests Thyroid function tests Renal artery thrombosis/stenosis Essential hypertension Cushing syndrome Coarctation of the aorta Chronic renal disease Phaeochromocytoma Williams syndrome Hyperaldosteronism Drug response Hyperthyroidism Hypothyroidism +/–Abdominal bruit High BP alone Truncal obesity, hirsution, striae, buffalo hump Upper extremity hypertension. Decreased pulses, BP in lower body. Murmur over left back. Pallor, edema Tachycardia, diaphoresis Elfin facies, small size, cardiac murmur, abdominal bruit Edema Tachycardia, cushingoid facies Tachycardia, decreased weight for height, brisk deep tendon reflexes Increased weight for height, decreased linear growth velocity Indwelling U/A catheter Family history of HBP Progressive weight gain, muscle cramps, weakness, acne Leg cramps post exertion Dysuria, frequency, UTIs Episodic flushing, diaphoresis Poor growth, developmental delay Muscle cramps, weakness, constipation, polyuria Drug use—prescription steroids, contraceptives; nonprescription stimulants, anabolic steroids Weight loss, family history of autoimmune disease Obesity, decreased linear growth, cold intolerance, constipation TABLE 58-3 Antihypertensive Drugs MAXIMUM DOSE INITIAL DOSE (MGM/KG/DAY) Converting enzyme inhibitors Captopril Neonates 0.03–0.15 2 Children 1.5 6 Enalapril 0.15 0.6 Calcium channel blockers Nifedipine 0.25 3 Diuretics Hydrochlorothiazide 1 2–3 Furosemide 1 12 Bumetadine 0.02–0.05 0.3 Metolazone 0.1 3 Spironolactone 1 3 Beta-adrenergic blockers Propanalol 1 8 Atenolol 1 8 Metoprolol 1 8 Alpha-adrenergic blockers Prazosin 0.05–0.1 0.5 Central alpha-adrenergic agonists Methyldopa 5 40 Clonidine 0.005 0.03 Vasodilators Hydralazine 0.75 7.5 Minoxidil 0.1–0.2 1 CHAPTER 59 • HYPERLIPIDEMIA 247 Soergel M, Kirschstein M, Busch C, Thomas D, et al. Oscillometric twenty-four-hour ambulatory BP values in healthy children and adolescents: a multicenter trial including 1141 subjects. J Pediatr 1997;130:178–184. Sorof JM, Poffenbarger T, Franok PR. Evaluation of white coat hypertension in children: Importance of the definitions of normal ambulatory blood pressure and the severity of casual hypertension. Am J Hypertens 2001;14:855–860. Update on the 1987 Task Force Report on high blood pressure in children and adolescents: A working group report from the National High Blood Pressure Education Program. Pediatrics 1996;98:649–658. 59 HYPERLIPIDEMIA Rae-Ellen W. Kavey •Pathologic studies have now shown that both the pres- ence and extent of atherosclerotic lesions at autopsy after unexpected death of children and young adults correlate positively and significantly with known hypercholesterolemia. This information supports rec- ommendations for early identification and manage- ment of hyperlipidemia in childhood. • Cholesterol is one of the body’s major lipids and acts as a precursor for steroids, hormones, and bile acids as well as providing an important structural component in all cell membranes. •For most individuals, control of cholesterol metabo- lism is polygenic, representing the sum of additive small effects on a number of different genes. In this setting, hypercholesterolemia will often only be expressed in childhood if there is an environmental stimulus like obesity or a high-fat diet. •A small number of individuals inherit specific single gene disorders of lipid metabolism. A classic example of this is familial hypercholesterolemia (FH) in which reduced low-density lipoprotein (LDL) receptors in the liver result in elevated cholesterol levels dating from birth. Heterozygous FH is inherited in an auto- somal recessive pattern and occurs at a frequency of 1 in 500 in the American population. In these individ- uals, symptomatic coronary heart disease develops in the forties. •Regardless of the genetic basis, management of hypercholesterolemia is based on serum lipid levels. • Researchers have shown that cholesterol levels “track” from childhood into adult life, meaning that extremely high levels in childhood will be predictive of similar elevation in adult life; however, for the majority of children, a single screening cholesterol is a relatively weak predictor of future cholesterol levels. •For this reason, the National Cholesterol Education Program (NCEP)-Pediatric Panel, recommends a “selective screening” approach to hyperlipidemia in childhood as outlined in Figs. 59-1 and 59-2. The panel recommends that lipid levels be measured in children with a positive family history of early cardio- vascular disease in an expanded first-degree pedigree or with a parental history of hypercholesterolemia. Do fasting lipid profile Positive family history Measure total blood cholesterol High blood cholesterol ≥200 mg/dL Acceptable blood cholesterol <170 mg/dL Borderline blood cholesterol 170−199 mg/dL Repeat cholesterol and average with previous measurement Parental high blood cholesterol ≥240 mg/dL Repeat cholesterol measurement within 5 years Provide education on recommended eating pattern and risk factor reduction <170 mg/dL >170 mg/dL Risk Assessment Do lipoprotein analysis FIG. 59-1 Algorithm for selective screen- ing of lipid levels in children from the National Cholesterol Education Program— Pediatric Panel Guidelines. •A positive family history means evidence for cardio- vascular disease, treated angina, angioplasty, stenting of the coronary arteries, myocardial infarction, or coronary artery bypass surgery in a male below the age of 55 or a female below the age of 60 in an expanded first-degree pedigree comprised of parents, grandparents, aunts, and uncles. •To address the second group, those children with a parental history of hypercholesterolemia, pediatric care providers should obtain lipid levels in parents where this information is needed to determine the screening status of their patients. In adults, a total cho- lesterol >240 mg/dL has been designated as abnormal. • In addition to checking lipids in children with a pos- itive family history of either hypercholesterolemia or premature coronary disease, I would add obesity, diabetes mellitus, and chronic renal disease as addi- tional reasons to obtain a lipid profile in childhood. • The best age to measure lipids in an identified child is approximately 3–5 years when the 12-hour fast neces- sary is tolerable. Total cholesterol and high-density lipoprotein (HDL) cholesterol levels can be measured accurately from a nonfasting specimen; however, determination of triglycerides requires a fasting spec- imen and triglyceride level is necessary to calculate LDL cholesterol (Friedewald equation: LDL–C = TC–HDL–(TG/5)) • Normal values for lipids in children are lower than they are in adults and are similar from 1 to 18 years of age with the 75th percentile being roughly 170 mg/dL and the 95th percentile being 200 mg/dL. • The NCEP-Pediatric Panel recommends use of the 75th percentile of the normal distribution (170 mg/dL) to designate a total cholesterol level as abnormal, sim- ilar to the adult guidelines; however, tracking studies indicate that this approach would erroneously identify many children as having elevated cholesterol levels which will not track into adult life. For this reason, most pediatric specialists use the 95th percentile to designate an abnormal level in childhood. Practically 248 SECTION 7 • DISEASES OF THE HEART AND GREAT VESSELS *If low HDL-cholesterol is detected, then patients should be counseled regarding cigarette smoking, low saturated fat diet, physical activity and weight management. **For patients 10 years old and over and with LDL-C > 190 mg/dl (or >160 mg/dL with additional risk factors), if diet does not achieve the goal, then pharmacologic intervention should be considered. Elevated LDL-cholesterol ≥130 mg/dL Borderline LDL-cholesterol 110−129 mg/dL HDL-cholesterol <35 mg/dL* Persistently high LDL-cholesterol ≥130 mg/dL Borderline LDL-cholesterol 110−129 mg/dL Risk factor advice Provide step-one diet and other risk factor intervention Reevaluate status in one year Do clinical evaluation (history, physical exam, lab tests) • Evaluate for secondary causes. • Evaluate for familial disorders Screen all family members Intensive clinical intervention Step-one, then step-two diet** Set goal LDL-cholesterol • Minimal: <130 mg/dL • Ideal: <110 mg/dL Risk assessment positive family history of parental high blood cholesterol or premature CVD Repeat lipoprotein analysis and average previous measurements Fasting lipoprotein analysis Acceptable LDL-cholesterol <110 mg/dL Repeat lipoprotein analysis within 5 years Provide education on recommended eating pattern and risk factor reduction Acceptable LDL-cholesterol <110 mg/dL FIG. 59-2 Algorithm for classification and management of children with measured LDL choles- terol from the National Cholesterol Education Program—Pediatric Panel Guidelines. CHAPTER 59 • HYPERLIPIDEMIA 249 speaking, this means that a total cholesterol >200 mg/ dL is abnormal. • Lipid levels vary from day to day; thus an average of at least two results should be reviewed before labeling a child as hypercholesterolemic. •Total cholesterol level is often used as a proxy for LDL cholesterol; however, in order to know the LDL cholesterol level, all the elements in the lipid panel need to be measured. • The two most common patterns of lipid abnormality identified in children are type 2A (FH) where there is marked elevation in total and LDL-C levels with the remainder of the profile usually normal; and type 2B, a pattern associated with obesity where there is mild elevation in cholesterol, moderate-to-severe elevation in triglycerides, and reduced HDL. The type 2B pat- tern is associated with adult onset diabetes and with premature atherosclerotic disease. This pattern is almost always seen with obesity when it appears in children. Initial management for either of these two forms of hypercholesterolemia is dietary. • Other very rare forms of hyperlipidemia exist. If a fasting lipid profile reveals an unusual pattern not consistent with 2A or 2B hypercholesterolemia, refer- ral to a lipid specialist is recommended at that time. • When a child is identified as having true hypercho- lesterolemia (i.e., an average of at least two choles- terol levels >200 mg/dL), secondary causes which include hypothyroidism, diabetes, nephrotic syn- drome, hepatic disease, and exogenous factors like steroid and oral contraceptive use must be excluded. • Once secondary hypercholesterolemia has been excluded, the first step in management of hypercho- lesterolemia is institution of the American Heart Association Step One diet. This is actually the diet recommended by the American Academy of Pediatrics for all normal children with <30% of calo- ries from fat and <10% from saturated fat, plus cho- lesterol intake below 300 mg/day. • The most effective way to implement this diet is for the hypercholesterolemic child and parent(s) to meet with a nutritionist at least twice for training. • On average, on a well-maintained low-fat and low- cholesterol diet, total and LDL cholesterol levels decrease by 10–20%. This diet has been shown to be both safe and effective in children. •For obese children, response to diet change can be very impressive. In obesity, a decrease in calorie intake needs to be associated with the shift toward lower fat and lower saturated fat and with this combination even small amounts of weight loss can be associated with complete normalization of the lipid profile. • If lipid levels do not decline significantly, the Step Two diet is recommended. This contains <30% of calories from fat and <7% from saturated fat. The low-fat, low-cholesterol diet should be maintained for at least 1 year before drug therapy is considered. • The NCEP-Pediatric Panel recommends drug therapy be considered only for children >10 years of age if LDL cholesterol remains >190 mg/dL (equivalent to a total cholesterol of >300 mg/dL); or if LDL choles- terol is greater than 160 mg/dL (equivalent to a total cholesterol of 250 mg/dL) with a positive family his- tory of premature cardiovascular disease and at least two additional risk factors. • Drug therapy should be implemented in conjunction with a specialist for lipid disorders in children. • While other lipid elements have not been addressed by guidelines, low-HDL cholesterol is known to be a strong predictor of early atherosclerotic disease in adults and can be anticipated to track in the same way as the total and LDL cholesterol levels do from child- hood. Certainly, HDL levels below 35 mg/dL should be taken into consideration in the decision to initiate drug therapy for hypercholesterolemia in childhood. • In all children with hypercholesterolemia, attention needs to be paid to optimization of all the risk factors: elimination of cigarette smoking in the home, mainte- nance of a normal weight for height proportion, nor- malization of blood pressure, and promotion of a very active lifestyle. B IBLIOGRAPHY Kavey REW, Daniels SR, Lauer RM, et al. American Heart Association guidelines for primary prevention of atherosclerotic cardiovascular disease beginning in childhood. Circulation 2003;107:1562–1566. Lauer RM, Lee J, Clarke WR. Factors affecting the relationship between childhood and adult cholesterol levels: The Muscatine study. Pediatrics 1988;82:309–318. National cholesterol education program: Report of the expert panel on blood cholesterol levels in children and adolescents. Pediatrics 1992;S9(3 Part 2):525–584. Obarzanek E, Kimm SY, Barton BA, et al. Long-term safety and efficacy of a cholesterol-lowering diet in children with elevated low-density lipoprotein cholesterol: Seven year results of the DISC study. Pediatrics 2001;107:256–264. Williams CL, Hayman CC, Daniels SR, et al. Cardiovascular health in childhood: a statement for health professionals from the committee on atherosclerosis, hypertension and obesity in the young of the American Heart Association. Circulation 2002;106:1178–1185. This page intentionally left blank. 60 BIRTHMARKS Annette M. Wagner HEMANGIOMAS EPIDEMIOLOGY AND PATHOPHYSIOLOGY • One of most common tumors of infancy. • Present in 2.5% of newborns and 10% of infants at 1 year of age. • More common in premature infants <30 weeks gesta- tion and in girls. • Eighty percent of hemangiomas are solitary and 38% occur on the head and neck. • Comprised of endothelial cell proliferation with dilated vascular channels. • Resolution occurs by apoptosis of cells. •Pathophysiology is unknown but hemangioma cells contain similar histochemical markers to maternal placental cells. DIFFERENTIAL DIAGNOSIS AND CLINICAL FEATURES • Deep lesions can be mistaken for other rapidly grow- ing infantile tumors including rhabdomyomas, infan- tile myofibromas, sarcomas, or hemangioendothelio- mas. • Early lesions may be mistaken for port-wine stains. • Hemangiomas appear in the first month of life and undergo proliferation for 8–12 months followed by involution with 50% gone by age 5, 60% by age 6, and so on. • Can be superficial, deep, or mixed in type. • Superficial hemangiomas begin as small telangiectatic papules that are surrounded by a white halo that rap- idly enlarge into a raised lobulated tumor with a “strawberry” appearance. • Deep hemangiomas are large subcutaneous masses often with an overlying blue hue or telangiectasias on the surface. • Congenital hemangiomas rarely occur and can persist without involution (NICH—noninvoluting congenital hemangioma) or undergo more rapid involution with resolution by age 2 (RICH—rapidly involuting con- genital hemangioma). • Complications of hemangiomas requiring interven- tion are ulceration, visual obstruction, disfigurement, and airway occlusion. •Patients studded with multiple hemangiomas may have hemangiomatosis with liver involvement (diffuse hemangiomatosis) and be at risk for high output heart failure. • Large segmental facial hemangiomas are associated with PHACES syndrome (posterior fossa malforma- tions, hemangioma, arterial or aortic defects, cardiac anomalies, eye anomalies, and sternal defects). TREATMENT AND PROGNOSIS • Most hemangiomas do not require treatment and have excellent prognosis. • Large facial hemangiomas or hemangiomas overlying the cervical or lumbosacral spine should be imaged by magnetic resonance imaging (MRI) for evidence of posterior fossa malformations or spinal dysraphism. • Ulcerated hemangiomas may require treatment with antibiotics, occlusive dressings, analgesics, and occa- sionally oral steroids or pulsed dye laser. • Oral steroids are the mainstay of treatment for vis- ual or airway obstruction, disfigurement or diffuse 251 Section 8 SKIN DISEASES Sarah L. Chamlin, Section Editor Copyright © 2005 by The McGraw-Hill Companies, Inc. Click here for terms of use. hemangiomatosis, and are effective during the prolif- erative phase. • Other treatments for complicated hemangiomas include interferon-a or vincristine. •After involution, skin changes of atrophy, redundancy and fibrofatty tissue deposition can be present and may require surgical correction. PORT-WINE STAINS AND STURGE-WEBER SYNDROME EPIDEMIOLOGY AND PATHOPHYSIOLOGY • Port-wine stains are congenital vascular malforma- tions comprised of dilated and ectatic capillary-like vessels. • Occur in 0.3–0.5% of infants at birth; an occasional acquired form occurs. •Five to eight percent of facial port-wine stains are associated with Sturge-Weber syndrome. •Sturge-Weber syndrome is port-wine stain involving the first branch of the trigeminal nerve associated with vascular malformation of the ipsilateral meninges and cerebral cortex. • Dysmorphogenesis of cephalic neuroectoderm due to a somatic mutation arising during development is pro- posed pathogenesis of Sturge-Weber. • No sex or race predilection is seen. DIFFERENTIAL DIAGNOSIS AND CLINICAL FEATURES • May be mistaken for early superficial hemangioma. • Stains are brightly erythematous irregular patches at birth. •Progressive deepening of color to bluish-purple occurs with time. • Hypertrophy of underlying tissue and angiomatous papules can develop within the stain. •Klippel-Trenaunay syndrome is the association of limb overgrowth, a venous or lymphatic malformation with a port-wine stain. • CMTC (cutis marmorata telangiectatica congenita) is a mottled form of vascular malformation with cuta- neous atrophy and limb hypotrophy. •Sturge-Weber syndrome is the association of V1 facial port-wine stain with ipsilateral eye abnormalities (glaucoma, buphthalmos, or choroids vascular anom- alies) in 30% of patients, and brain abnormalities (vascular anomalies, cerebral atrophy, and calcifica- tions) manifesting as seizures (80%), developmental delay (60%), or hemiplegia (30%). • Diagnosis of Sturge-Weber can be aided by MRI with gadolinium but may be nondiagnostic. TREATMENT AND PROGNOSIS • Pulsed dye laser can be used to lighten port-wine stains. • Multiple treatments at 2–3 month intervals are required for maximum improvement. • Infants affected with Sturge-Weber require regular eye examinations, treatment of glaucoma to prevent vision loss, neurologic follow-up for control of epilepsy, early developmental intervention, treatment for overgrowth of the jaw. • Cosmetic improvement of the port-wine stain can be obtained with laser treatment but some darkening of the stain with time and sun exposure is anticipated and recurrent treatment may be required. CONGENITAL AND ACQUIRED MELANOCYTIC NEVI EPIDEMIOLOGY AND PATHOPHYSIOLOGY • Small congenital nevi occur in 1–2% of infants. • Large congenital nevi occur in 0.02% of infants. • Comprised of proliferations of melanocytes in nests occurring at or shortly after birth that track along hair follicles and extend deeply into the skin. • Acquired nevi usually appear after 18 months increas- ing in number until age 30 with two peaks of acquisi- tion in the preschool years and at puberty. • Acquired nevi are less common in pigmented races. DIFFERENTIAL DIAGNOSIS AND CLINICAL FEATURES • Can be mistaken for café au lait macules, urticaria pigmentosa, smooth muscle hamartoma, mosaic hyperpigmentation, or lentigines. • All congenital nevi have an increased risk of mela- noma estimated at 1% for small lesions (<1.5 cm in adult) and as high as 12% for garment-type congeni- tal nevi (>20 cm in adult). • Congenital nevi are usually larger than acquired nevi and often have a papillated surface; many develop hypertrichosis with time. • Congenital nevi often have irregular borders and mul- tiple colors. • Acquired nevi are tan to dark brown macules that may become elevated with time. 252 SECTION 8 • SKIN DISEASES CHAPTER 60 • BIRTHMARKS 253 •Nevi with features concerning for malignancy are Asymmetric, have Border irregularity, multiple Colors, and a Diameter >6 mm (ABCDs). • Changes of rapid growth, color, or shape should be evaluated in all nevi. •Family history of melanoma in first-degree relatives increased the risk of melanoma in a child. • Atypical nevus syndrome is a familial condition asso- ciated with the development of multiple acquired nevi with atypical features and an increased risk of melanoma. • Spitz nevi are dome-shaped red-brown to pink or flat jet-black nevi that may appear suddenly and grow rap- idly; they often have a concerning histopathologic appearance. TREATMENT AND PROGNOSIS • Excision of small congenital nevi without atypical features is not recommended. • Excision of medium-sized and large congenital nevi with atypical features should be considered due to the increased risk of melanoma in these lesions. • Excision should be considered for Spitz nevi; histopathologic evaluation by an experienced der- matopathologist is suggested. • Large congenital nevi associated with neurocutaneous melanosis (a benign or malignant melanocytic infil- tration of the meninges) has a poor prognosis; infants with large congenital nevi overlying the spine or with large congenital nevi should be evaluated with an MRI to look for this finding. • Children with a family history of melanoma or atypi- cal nevus syndrome should be routinely evaluated by a dermatologist. •Melanoma is rare in children; the prognosis for melanoma in a child, like in an adult, depends on the depth of the lesion. CAFÉ AU LAIT MACULES AND NEUROFIBROMATOSIS TYPE 1 EPIDEMIOLOGY AND PATHOPHYSIOLOGY •A café au lait spot occurs in up to 18% of newborns and 36% of older children. • More common in pigmented races. • Increased epidermal melanin is present in keratinocytes and melanocytes without melanocyte proliferation. • Can be markers of genetic disease including neurofi- bromatosis (NF), McCune-Albright syndrome, or Watson syndrome. •Neurofibromatosis Type 1 (NF-1) is autosomal domi- nant, occurs in 1/3000 infants and results from a mutation in the gene for neurofibromin (17q22.2), a tumor suppressor which controls cell proliferation. DIFFERENTIAL DIAGNOSIS AND CLINICAL FEATURES • Can be mistaken for nevi, mastocytomas, lentigines. • Café au lait spots are flat, light to dark brown macules and patches with well-defined borders that occur on any body part except the palms, soles, and scalp. •New lesions can be acquired with time and lesions grow proportionately. • NF-1 is diagnosed in prepubertal children by the pres- ence of at least two of the following criteria: ≥6 café au lait macules ≥5 mm, ≥2 neurofibromas of any type or one plexiform neurofibroma, axillary or inguinal freckling, optic glioma, ≥2 Lisch nodules, bony abnormality (pseudoarthrosis or sphenoid dysplasia), or a first-degree relative with NF-1. • Other manifestations of NF-1 include learning dis- abilities, scoliosis, leukemia, and other malignancies. TREATMENT AND PROGNOSIS • Some successful treatment of café au lait spots with laser have been reported, but repigmentation after treatment occurs. • Children with neurofibromatosis Type 1 have highly variable disease expression. • Comprehensive follow-up is indicated; ideally in the context of a multidisciplinary clinic. B IBLIOGRAPHY Arbuckle HA, Morelli JG. Pigmentary disorders: Update on neu- rofibromatosis-1 and tuberous sclerosis. Curr Opin Pediatr 2000;12(4):354–358. Brown TJ, Friedman J, Levy ML. The diagnosis and treatment of common birthmarks. Clin Plast Surg 1998;25(4):509–525. Chamlin SL, Williams ML. Pigmented lesions in adolescents. Adolesc Med 2001;12(2):195–212. Drolet BA, Esterly NB, Frieden IJ. Hemangiomas in children. N Engl J Med 1999;341(3):173–181. Fishman C, Mihm MC, Jr., Sober AJ. Diagnosis and management of nevi and cutaneous melanoma in infants and children. Clin Dermatol 2002;20(1):44–50. Garzon MC, Frieden IJ. Hemangiomas: when to worry. Pediatr Ann 2000;29(1):58–67. [...]... DISORDERS OF THE ENDOCRINE SYSTEM Glycogen 3 7 Galactose 4 2 Glucose-1-phosphate 1 Glucose-6-phosphate Glucose Fructose-6-phosphate 6 Fructose-1, 6-phosphate Fructose 5 Fructose-1-phosphate Triose phosphate Glycerol Triglycerides Lactate Alanine Pyruvate Free fatty acids 1 Glucose-6-phosphatase 2 Amylo 1,6 glucosidase (debrancher enzyme) 3 Phosphorylase 4 Glycogen synthase 5 Fructose-1-phosphate aldolase... Kir6.2 gene and is regulated by the sulfonylurea receptor encoded by SUR1 Glucose—G-6-P Insulin K+ Ca+ Ca+ K+ (A) Glucose—G-6-P ATP/ADP K Insulin + Ca+ Ca+ K+ (B) FIG 6 4-1 Insulin secretion from the beta-cell (A) Resting state (B) Fed state 271 5 Closing of the K+-ATP channel depolarizes the cell 6 Leading to influx of calcium 7 Resulting in insulin secretion (Fig 6 4-1 a and b) DIAGNOSIS • At time of... glucose around 200 mg/dL for at least the first 12 hours Increase dextrose in fluids once glucose is below 250 mg/dL BEDTIME (GLUCOSE, mg/dL) 150 –200 150 –200 120–180 100–180 100–180 HgbA1c (%) . 18 years of age with the 75th percentile being roughly 170 mg/dL and the 95th percentile being 200 mg/dL. • The NCEP -Pediatric Panel recommends use of the 75th percentile of the normal distribution. 8 Alpha-adrenergic blockers Prazosin 0. 05 0.1 0 .5 Central alpha-adrenergic agonists Methyldopa 5 40 Clonidine 0.0 05 0.03 Vasodilators Hydralazine 0. 75 7 .5 Minoxidil 0.1–0.2 1 CHAPTER 59 • HYPERLIPIDEMIA 247 Soergel. indicating end-organ response to sustained BP elevation. In Table 5 8-3 , antihyperten- sive drug therapy recommendations from the Second Task Force report are summarized. • There are no long-term clinical