Risks are the same as those for MR. MECHANICAL HEART VALVES IN PREGNANCY 417 Mechanical heart valves in pregnancy The optimal management of women with prosthetic mechan ical heart valve replacements in pregnancy is controversial since the interests of the moth er and the fetus are in con \202 ict. These women require lifelong antico- agulation (see Box 10.2), and this must be continued in pregnancy because of the increased risk of thrombo sis. Warfarin is associated with warfarin embryopathy if given between 6 and 12 weeks gestation1 and with increased risks of miscarriage, stillbirth, and fetal intracerebral hemorrhage.2 There is some evidence that the adverse effects of warfarin are related to the dose require d to maintain the INR >2, with doses in excess of 5 mg being associated with higher risks o f teratogenesis, miscarriage, and stillbirth.3 Heparin and low-molecular-weight heparin, even in full anticoagulant doses, are associated with increased risks of valve thrombosis and embolic events1 \200\2234 but are not associat ed with fetal malformations and offer greater \202 exibility as delivery nears. Management There are three basic options: \200 Continue warfarin throughout pregnancy, stopping only for delivery. This is the safest opti on for the mother.1,2 Replace the warfarin with high-dose unfractionated or low-molecular- weight heparin from 6 to 12 weeks gestation to avoid warfarin embryopathy and then resume w arfarin and switch back to heparin as delivery nears. Use high-dose unfractionated or low-m olecular-weight heparin throughout pregnancy. The option is chosen will depend on several factors: \200 The type of mechanical valve. The risk of thrombosis is less with the newer bilea \202 et valves (e.g., CarboMedics) than with the \201 rst- generation ball and cage (e.g., Starr \200\223Edwards) or second-generation single tilting disc (e.g., Bjork \200\223Shiley) valv es. The position of the valve replacement. Valves in the aortic rather than the mitral posi tion are associated with a lower risk of thrombosis.4,5 The number of mechanical valves The dose of warfarin required to maintain a therapeutic INR Any previous history of embolic ev ents \200 \200 Whichever management option is chosen, warfarin should be discontin- ued and substituted wi th heparin for 10 days prior to delivery to allow 1 Chan WS, Anand S, Ginsberg JS (2000). Anticoagulation of pregnant women with mechanical h eart valves. Arch Intern Med 160:191 \200\223196. 2 Sadler L, McCowan L, White H, et al. (2 000). Pregnancy outcomes and cardiac complications in women with mechanical, bioprosthetic and homograft valves. Br J Obstet Gynaecol 107:245 \200\223253. 3 Cotrufo M, De Feo M, De S anto L, et al. (2002). Risk of warfarin during pregnancy with mechan- ical valve prostheses . Obstet Gynecol 99:35 \200\22340. 4 Meschengieser SS, Fondevilla CG, Santarelli MT, et al. (1999). Anticoagulation in pregnant women with mechanical heart valve prostheses. Heart 82 :23 \200\22326. 5 Elkayam U (1999). Pregnancy through a prosthetic heart valve. J Am Coll C ardiol 33:1642 \200\2231645. CHAPTER 10 Heart disease in pregnancy 418 clearance of warfarin from the fetal circulation. For delivery itself, heparin therapy is i nterrupted. Warfarin is recommenced postpartum. In the event of bleeding or the need for urgent deliver y in a fully anticoagulated patient, warfarin may be reversed with fresh frozen plasma (FFP ) and vitamin K, and heparin with protamine sulfate. Vitamin K should be avoided if possibl e since it renders the woman practically unable to anticoagulate with warfarin after delive ry. Women with prosthetic valve replacements all require antibiotic endo- carditis prophylaxis for delivery regardless of the mode of delivery.6,7 Urgent vaginal delivery should be avoided in a woman anticoagulated with Coumadin because of risk of fetal intracerebral hemorrhage. Box 10.2 Anticoagulation in pregnancy Unfractionated heparin \200 Often given in early and late pregnancy in patients with mechanical heart valves and valvul ar heart disease with AF. Used early in pregnancy, as it is not teratogenic. In peripartum period it is used for rapid control (and reversal) of anticoagulation in case emergency del ivery undertaken. Not as effective as other forms of anticoagulation Side effects: \200 ( monitor FBC), osteoporosis, alopecia hemorrhage (fetal and maternal), thrombocytopenia Low-molecular-weight heparin \200 Effective anticoagulant. Easier to monitor dosage schedule. Less likely to cause thrombocyt openia (but does still occur) \200 Side effects: maternal and fetal hemorrhage Warfarin \200 Effective oral anticoagulant. Studies show it to be more effective than unfractionated hepa rin at preventing valve thrombosis. \200 Side effects: avoid during this period if at all possible (use heparin). hemorrhage, teratogenic in \201 rst trimester, therefore Aspirin \200 Occasionally used in high-risk patients (AF, LV dysfunction, previous emboli) or those with previous prosthetic valve thrombosis \200 Side effects: hemorrhage, prolonged labor, low birth weight (in high doses), constriction o f ductus, fetal renal dysfunction, and hemostatis abnormalities 6 Endocarditis Working Party of the British Society for Antimicrobial Chemotherapy (1982). Lancet 2:1323 \200\2231326. 7 Dajani AS, Taubert KA, Wilson W, et al. (1997). Prevention of bacterial endocarditis. Recommendations by the American Heart Association. JAMA 277:1794 \200\2231801. ISCHEMIC HEART DISEASE 419 Ischemic heart disease The risk factors for myocardial infarction (MI) in pregnancy are the same as for the nonpregnant woman. The risk is increased in multigravid women and in those who smoke, and in women with diabetes, obesity, hyperten- sion, and hypercholesterolemia. Infarction most commonly occurs in the third trimester and affects the anterior wall of the heart.1 Maternal death rate is 20%. In pregnancy the underlying etiology is more likely to be due to nonatherosclerotic con- ditions (such as coronary artery thrombosis or dissectio n) than in the nonpregnant woman.2 Management \200 \200 Management of acute MI is as for the nonpregnant woman. Angiography should not be withheld if clinically indicated. The fetus should be shielded. Intravenous and intracoronary thromb olysis and percutaneous transluminal coronary angioplasty and stenting have all been succes sfully performed in pregnancy. B-blockers are safe in pregnancy. Both aspirin and There are less data for clopidogrel and glycoprotein IIb/IIIa inhibitors, although there are case re ports of their successful use. Statins should be discontinued for the duration of pregnancy as they are associated with an increased risk of malformations.2 ACE inhibitors and ARBs a re similarly contraindicated during pregnancy. \200 1 Roth A, Elkayam U (1996). Acute myocardial infarction associated with pregnancy. Ann Inte rn Med 125:751 \200\223757. 2 Edison RJ, Muenke M (2004). Central nervous system and limb a nomalies in case reports of \201 rst trimester statin exposure. N Engl J Med 350:1579 \200\2231582. CHAPTER 10 Heart disease in pregnancy 420 Hypertrophic obstructive cardiomyopathy (HOCM) The danger in pregnancy relates to left vent ricular out \202 ow tract obstruc- tion that may be precipitated by hypotension or hypovol emia. Provided these are avoided, pregnancy is usually well tolerated. Management B-Blockers should be continued in pregnancy or initiated for symptomatic women.1 Epidural anesthesia/analgesia carries the risk of vasodilation and hypo- tension with conse quent increased left ventricular out \202 ow tract obstruc- tion. Any hypovolemia will hav e the same effect and should be rapidly and adequately corrected. 1 Oakley GD, McGarry K, Limb DG (1979). Management of pregnancy in patients with hyper- tro phic cardiomyopathy. BMJ 1:1749 \200\2231750. PERIPARTUM CARDIOMYOPATHY 421 Peripartum cardiomyopathy This pregnancy-speci \201 c condition is de \201 ned as the dev elopment of cardiac failure between the last month of pregnancy and 5 months postpartum, in the absence of an other identi \201 able cause or recognizable heart dis- ease prior to t he last month of pregnancy, and left ventricular systolic dysfunction. The diagnosis should be suspected in the puerperal patient with short- ness of breath, tach ycardia, or signs of heart failure. It is con \201 rmed with echocardiography. Echocardiographic criteria for peripartum LV dysfunction1 \200 \200 \200 \200 Left ventricular ejection fraction <45% Fractional shortening <30% LVEDP (left ventricular end diastolic pressure) >2.7 cm/m Often, echocardiography shows that the heart is enlarged with global dilation of all four chambers and markedly reduced left ventricular function 2 Risk factors \200 \200 Multiple pregnancy Hypertension (be it pre-existing or related to pregnancy or pre-eclampsi a) Multiparity Increased age African American race \200 \200 Management Treatment is as for other causes of heart failure: \200 \200 \200 \200 \200 \200 Oxygen Diuretics Vasodilators ACE inhibitors if postpartum Inotropes if required Heart tran splantation About 50% of women make a spontaneous and full recovery. Most case fatalities occur close t o presentation. Recent data show a 5-year survival of 94%.2 Prognosis and recurrence depend on the normalization of left ventricular size and function within 6 months of delivery.3 T hose women with severe myocardial dysfunction, de \201 ned as LV end diastolic dimen- sion (cid:116)6 cm and fractional shortening (cid:100)21%, are unlikely to regain normal cardia c function on follow-up.4 Those whose LV function and size do not return to normal within 6 months and prior to a subsequent pregnancy CHAPTER 10 Heart disease in pregnancy 422 are at signi \201 cant risk of worsening heart failure (50%) and death (25%) or recurrent peripartum cardiomyopathy with a future pregnancy. They should therefore be advised against pregnancy.5 1 Pearson GD, Veille JC, Rahimtoola S, et al. (2000). Peripartum cardiomyopathy. National H eart, Lung and Blood Institute and Of \201 ce of Rare Diseases (NIH). Workshop recommendat ions and review. JAMA 283:1183 \200\2231188. 2 Felker GM, Thompson RE, Hare JM, et al. (200 0). Underlying causes and long-term survival in patients with initially unexplained cardiom yopathy. N Engl J Med 342:1077 \200\2231084. 3 Elkayam U, Tummala PP, Rao K, et al. (2001). Maternal and fetal outcomes of subsequent preg- nancies in women with peripartum cardiomyo pathy. N Engl J Med 344:1567 \200\2231571. 4 Witlin AG, Mabie WC, Sibai BM (1997). Peripart um cardiomyopathy: a longitudinal echocardio- graphic study. Am J Obstet Gynecol 177:1129 \200\2231132. 5 Shotan A, Ostrezega E, Mehra A, et al. (1997). Incidence of arrhythmias in normal pregnancy and relation to palpitations, dizziness and syncope. Am J Cardiol 79:1061 \200\2231064. ARRHYTHMIAS IN PREGNANCY 423 Arrhythmias in pregnancy Atrial and ventricular premature complexes (APC, VPC) are common i n pregnancy. Many pregnant women are symptomatic from forceful heart beats that occur follo wing a compensatory pause after a VPC or from physiological sinus tachycardia. Most women w ith symptomatic episodes of dizziness, syncope, and palpitations do not have arrhythmias.1 An unusually fast sinus tachycardia requires investigation for possible underlying pathology, such as \200 \200 \200 \200 \200 Blood loss Infection Heart failure Thyrotoxicosis Pulmonary embolus The most common arrhythmia encountered in pregnancy is supraventricu- lar tachycardia (SVT) . First onset of SVT (both accessory pathway-medi- ated and AV nodal reentrant) is rare in pregnancy, but 22% of 63 women with SVT had exacerbation of symptoms in pregnancy.2 Half of SVTs do not respond to vagal maneuvers. Management \200 Propranolol, verapamil, and adenosine have FDA approval for acute termination of SVT. Adeno sine has advantages over verapamil, including probable lack of placental transfer, and may be safely used in pregnancy for SVTs that do not respond to vagal stimulation.3,4 Flecainid e is safe and is also used in the treatment of fetal tachycardias. 5 the latter because of Propafenone and amiodarone should be avoided, interference with fetal thyroid function. Tem porary and permanent pacing, cardioversion, and implantable de \201 brillators are also sa fe in pregnancy.3 \200 1 Lee SH, Chen SA, Wu TJ, et al. (1995). Effects of pregnancy on \201 rst onset and sympt oms of paroxysmal supraventricular tachycardia. Am J Cardiol 76:675 \200\223678. 2 Page RL (1995). Treatment of arrhythmias during pregnancy Am Heart 130:871 \200\223876. 3 Mason BA, Ricci-Goodman J, Koos BJ. (1992). Adenosine in the treatment of maternal paroxysmal suprav entricular tachycardia. Obstet Gynecol 80:478 \200\223480. 4 James PR (2001). Cardiovascula r disease. In Nelson-Piercy C (Ed.), Prescribing in Pregnancy. Bailliere \200\231s Best Pra ctice and Research in Clinical Obstetrics and Gynecology 15:903 \200\223911. 5 Magee LA, Do wnar E, Sermer M, et al. (1995). Pregnancy outcome after gestational exposure to amiodarone . Am J Obstet Gynecol 172:1307 \200\2231311. CHAPTER 10 Heart disease in pregnancy 424 Cardiac arrest in pregnancy This should be managed according to the same protocols used in the nonpregnant woman, with two very important additions. Pregnant women (especially those in advanced pregnancy) should be \200\234wedged \200\235 to relieve any obstruction to venous return from pressure of the gravid uterus on the infer ior vena cava. This can be most rapidly achieved by turning the patient into the left later al position. If CPR is required, then the pelvis can be tilted while keeping the torso \202 at to allow external chest compressions. The obstetric team should be present. This is to ensure that obstet- ric causes of the coll apse are considered (e.g., amniotic \202 uid embolism, massive postpartum hemorrhage) and appropriately treated. In addition, emergency cesarean section may be required to aid mate rnal resuscita- tion and rescue the fetus if of viable age. ENDOCARDITIS PROPHYLAXIS 425 Endocarditis prophylaxis Antibiotic prophylaxis is mandatory for those with prosthetic valv es, com- plex congenital heart disease, or heart transplant and for those with a previous e pisode of endocarditis.1 Many cardiologists recommend that women with structural heart defects (e.g., VSD) also receive prophylaxis. Recommendations of the American Heart Association stratify cardiac conditions into high, mo derate, and negligible (not requiring antibiotic prophylaxis) risk (see Table 10.2).1 Fatal cases of endocarditis in pregnancy have occurred antenatally, rather than as a consequence of infection acquired at the time of delivery. The current U.S. recom mendations1 are as follows: \200 Amoxycillin 2 g po or ampicillin 2 g IV or cefazolin 1 g IV onset of labor or ruptured memb ranes or prior to cesarean section, followed by amoxycillin 500 mg po (or IM/IV depending o n patient \200\231s condition) 8 hours later. For women who are allergic to penicillin, giv e cephalexin 2 g po or clindamycin 600 mg po or azithromycin 500 mg po, for IV cefazolin or ceftriaxone 1g IV or clindamycin 600 mg IV. at the Table 10.2 Strati \201 cation of cardiac conditions according to risk of bacterial endocar ditis High risk Endocarditis prophylaxis recommended Prosthetic valves (metal, bioprosthetic and homografts) Previous bacterial endocarditis Com plex cyanotic congenital heart disease (Fallot \200\231s, transposition of great arteries) Surgical systemic/pulmonary shunts \200 \200 \200 \200 Moderate risk Endocarditis prophylaxis not recommended Other congenital cardiac malformations Acquired valvular disease Hypertrophic cardiomyopath y Mitral valve prolapse with mitral regurgitation \200 \200 \200 \200 Negligible risk Endocarditis prophylaxis not recommended Isolated secundum atrial septal defects Surgically repaired ASD, VSD, PDA Mitral valve prol apse without regurgitation Physiological heart murmurs Cardiac pacemakers 1 Nishimura RA, Carabello BA, Faxon DP, et al. (2008). ACC/AHA 2008 guideline update on val vu- lar heart disease: focused updated on infective endocarditis. Circulation 118:887 \200 \223896. 2 Endocarditis Working Party of the British Society for Antimicrobial Chemotherapy (1982). Lancet 2:1323 \200\2231326. This page intentionally left blank 427 Chapter 11 Multisystem disorders Libman \200\223Sacks endocarditis 428 Marfan \200\231s syndrome 430 Ghent criteria for Marf an \200\231s syndrome 431 Ehlers \200\223Danlos syndrome 432 Kawasaki disease 434 Takayasu arteritis 436 Polyarteritis nodosa and other systemic vasculitides 438 Ankylosing spondylit is 440 Polymyositis and dermatomyositis 442 Rheumatoid disease 443 CHAPTER 11 Multisystem disorders 428 Libman \200\223Sacks endocarditis Associations \200 \200 Systemic lupus erythematosus (SLE) Primary and secondary anti-phospholipid antibody syndrom e Epidemiology \200 Present in at least 50% of fatal SLE patients who undergo postmortem examination. Up to 43% of cases with echocardiography 6% \200\22310% of primary anti-phospholipid antibody syndro me cases with echocardiography Young, African/Caribbean women typically Pathology \200 Classically sterile, verrucous vegetations on the ventricular aspect. Diffuse lea \202 et thickening is thought to be the chronic, healed stage. Commonly mitral and aortic valves. O ther valves and endocardial surfaces are also affected. Usually valve regurgitation; stenos is is rare. It is uncertain whether the association with anti-phospholipid antibodies is ca usal. Antigens are negatively charged phospholipids in endothelial cell membranes. Prevalen ce and severity of valve disease are similar, whether antibodies are present or not. Sites of endothelial damage due to turbulence and jet impaction may act as foci for thromboses an d further damage. Valve thickening and regurgitation are more common after chronic steroid therapy and in older patients. \200 Clinical features \200 \200 Usually asymptomatic with a normal cardiovascular examination General lupus features, such as a malar rash, arthritis, sweats, and alopecia Recurrent miscarriage, arterial and venous thromboses, and thrombocytopenia suggest anti-phospholipid antibody syndrome. Symptoms and signs due to heart failure and valve disease could be present. Imaging \201 ndings in lupus \200 Valve abnormalities in 28% \200\22374% of cases. Vegetations occur in 4% \200\22343% of cas es, particularly those with anti-phospholipid antibodies. Thickening occurs in 19% \200\223 52% of cases, with associated regurgitation in 73%. Pericardial effusion or thickening, lef t ventricular hypertrophy (due to hypertension), left ventricular dilatation, left ventricu lar segmental dysfunction, left ventricular global dysfunction, and pulmonary hypertension. LIBMAN \200\223SACKS ENDOCARDITIS 429 Imaging \201 ndings in primary anti-phospholipid antibody syndrome \200 Valve abnormalities in 30% \200\22332% of cases, particularly those with peripheral arteria l thromboses. Vegetations are found in 6% \200\22310% and thickening in 10% \200\22324%. Re gurgitation occurs in 10% \200\22324% of cases. Blood tests \200 \200 Blood cultures to exclude infective endocarditis Full blood count, clotting pro \201 le, a utoantibody screen Treatment \200 \200 No speci \201 c therapy is recommended. Treat underlying conditions and complications. Prognosis in lupus \200 \200 Cardiovascular death is ranked third in lupus patients. Combined incidence of heart failure , valve replacement, thromboembolism, and infective endocarditis is 22%. CHAPTER 11 Multisystem disorders 430 Marfan \200\231s syndrome Epidemiology \200 \200 \200 Incidence is 1 in 5,000 to 1 in 10,000 persons. There are no known geographical, racial, or gender predilections. It is diagnosed prenatally through to adulthood. Pathology \200 Autosomal dominant point mutations occur in \201 brillin-1 gene on chromosome 15. Over 20 0 mutations are described. Fibrillin-1 glycoprotein is an integral component of micro \201 brils in connective tissues. Structural integrity of ocular, skeletal, cardiovascular, and other tissues is compromised. Phenotype is highly variable because of varying genotype exp ression. Ghent criteria for diagnosis \200 The index case has no contributory family or genetic history, with major criteria in at lea st two different organ systems plus involvement of a third organ system. Alternatively, the re is contributory family or genetic history, one major organ system criterion, plus involv ement of second organ system. Relative of the index case has a major criterion in family hi story, major criterion in organ system, plus involvement of a second organ system. Imaging \200 Radiographs, CT, and MRI scans are used to assess axial skeleton, hip joints, hands, and fe et. Echocardiography and MRI are used to assess the mitral and aortic valves, aortic root, and ascending aorta. Slit-lamp examination is used to look for retinal detachment, supero- lateral lens dislocation, cataracts, severe myopia, and open-angle gla- ucoma. Globe ultras ound and keratometry help in assessing the cornea. Genetic testing This has a limited role in diagnosis and is used primarily to diagnose fami ly members if a mutation is known. Linkage analysis can be applied in families with several affected relatives. Treatment B \200 Blockers (possibly calcium channel blockers) delay and attenuate aortic root dilation Antibiotic chemoprophylaxis for bacteremia-prone procedures Surgery fo r aortic root and valve disease, skeletal and ocular complications Gentle exercise Some pre liminary studies suggest that ACE inhibitors are useful and may improve outcomes \200 \200 \200 Prognosis \200 \200 Life expectancy is about two-thirds of normal. Cardiovascular death occurs in over 90% of c ases from aortic dissection or heart failure. GHENT CRITERIA FOR MARFAN \200\231S SYNDROME 431 Ghent criteria for Marfan \200\231s syndrome Table 11.1 Skeletal system involvement (2 major or 1 major and 2 minor criteria) Major criteria Minor criteria 1. Pectus carinatum 2. Pectus excavatum requiring surgery 3. Reduced upper to lower segment ratio 1. Moderately severe pectus excavatum 2. Joint hypermobility 3. High arched palate with teeth or arm span to height ratio >1.05 crowding 4. Wrist and thumb signs 5. Scoliosis exceeding 20* or 4. Facial appearance (dolichocephaly, malar hypoplasia, down-slanting palpabral \201 ssur es, retrognathia) spondylolisthesis 6. Elbow extension <170* 7. Medial displacement of medial malleolus causing pes planus 5. Enophthalmos 8. Protrusio acetabulae Ocular system involvement (1 major or 2 minor criteria) Major criteria 1. Ectopia lentis Minor criteria 1. Abnormally \202 at cornea 2. Axial globe lengthening 3. Iris or ciliary muscle hypoplasia Cardiovascular system involvement (1 major or 1 minor criterion only) Major criteria 1. Ascending aortic dilation involving at least the sinuses of Valsalva with or without aortic regurgitation and Minor criteria 1. Mitral valve prolapse with or without mitral regurgitation 2. Main pulmon ary artery dilation 3. Mitral annulus calci \201 cation 4. Descending thoracic or abdomina l 2. Ascending aortic dissection aortic dilation or dissection Pulmonary system involvement (requires 1 minor criterion) 1. Spontaneous pneumothorax or ap ical blebs Skin and integument involvement (requires one of the following): 1. Striae atrophicae witho ut marked weight change, pregnancy, or repetitive stress 2. Recurrent or incisional herniae Dural involvement (1 major criterion) 1. Lumbosacral dural ectasia A contributory family or genetic history (1 major criterion) 1. Parent, child, or sibling meeting diagnostic criteria independently 2. Known \201 bril lin-1 mutation 3. Presence of haplotype around \201 brillin-1 inherited by descendent kno wn to be associated with unequivocally diagnosed Marfan \200\231s syndrome in the family CHAPTER 11 Multisystem disorders 432 Ehlers \200\223Danlos syndrome Epidemiology \200 \200 \200 1 in 5,000 live births. Incidence is about 1 in 400,000. It typically presents between chil dhood and early adulthood. No racial or gender bias is known. Pathology \200 Inherited (autosomal dominant or recessive and X-linked recessive) defects in synthesis and metabolism of different types of collagen produce connective tissue defects. A new form re cently described shows de \201 ciency of tenascin-X (extracellular matrix protein) with no rmal collagen. Six different subtypes are described: classic, hypermobile, vascular, kyphos coliosis, arthrochalasia, and dermatosparaxis. There is much overlap between types in up to 50% cases. Increased tissue elasticity with decreased strength and poor healing. Clinical features \200 Typically there is joint hypermobility, skin hyperextensibility, tissue fragility, and poor wound healing. Classically, patients get \200\234cigarette paper \200\235 scarring over t heir knees. Mitral valve prolapse is typically seen in classic, hypermobile, and vascular f orms. A minority of patients progress to severe mitral regurgitation requiring surgery. Rec ent echocardiographic studies suggest that cardiac defects may be less frequent than previo usly thought, although coronary artery aneurysm can be devastating. Aortic root ectasia wit h dilated sinuses of Valsalva is found. This is rarely severe or progressive, and aortic ro ot replacement is exceptional. The vascular form also exhibits prominent veins, low weight, short stature, spontaneous pneumothorax and rupture of medium-sized and large arteries, an d bowel perforation. Joints are affected less frequently. The skin is fragile but not hyper extensible. Differential diagnoses include Marfan \200\231s syndrome, Menkes kinky hair dis ease, Williams syndrome, Stickler syndrome, cutis laxa, and pseudoxanthoma elasticum. Treatment \200 No speci \201 c medical therapy is indicated. High-dose vitamin C may provide some bene \201 t but there are no controlled studies. Provide patient education and preventive strate gies. Patients should avoid excess and repetitive lifting and contact sports. Avoid suturin g wounds, if possible. Regular eye and dental assessments are required. Genetic counseling is recommended. There is a limited role for genetic testing. \200 \200 EHLERS \200\223DANLOS SYNDROME 433 Prognosis \200 Increased mortality occurs in the vascular form. Median age is 50 years, with death from sp ontaneous arterial and gastrointestinal rupture. Patients with other forms usually have nor mal life expectancy with increased morbidity from recurrent dislocations, poor wound healin g, and scarring. CHAPTER 11 Multisystem disorders 434 Kawasaki disease Epidemiology More than 90% of cases are in children under 10 years of age. Peak inci- dence is at age 18 \200\22324 months in the United States and 6 \200\22312 mont hs in Japan. It is more common in males and in children of Japanese descent. Pathology \200 Etiology is unknown but likely to be infectious. Possible agents include Parvovirus B19, me ningococcus, Coxiella burnetii, bacterial toxin- mediated superantigens, HIV, Mycoplasma pn eumoniae, adenovirus, Klebsiella pneumoniae, Parain \202 uenza type 3 virus, rotavirus, me asles, and human lymphotropic virus. Other determinants may be genetic and immunological fa ctors, vectors, and passive maternal immunity. Generalized vasculitis is most severe in med ium-sized arteries affecting all layers of the wall. There is smooth muscle necrosis with s plitting of internal and external elastic laminae and aneurysm formation. Subsequent vessel \201 brosis, stenosis, thrombosis, and aneurysm rupture occur. Clinical features \200 Acute stage (days 1 \200\22311) is characterized by high fever, irritability, non- exudativ e bilateral conjunctivitis (90%), iritis (70%), perianal erythema (70%), acral erythema and edema that impede ambulation, strawberry tongue, lip \201 ssures, hepatic, renal, and ga strointestinal dysfunction, myocarditis, pericarditis, and cervical lymphadenopathy (75%). Subacute stage irritability, anorexia, conjunctival injection, decreased temperature, throm bocytosis, acral desquamation, and aneurysm formation. Convalescent/chronic phase (after 30 days) is characterized by aneurysm expansion, possible myocardial infarction, and resoluti on of smaller aneurysms (60% of cases). (days 11 \200\22330) is characterized by persistent Diagnosis requires exclusion of other illnesses with similar clinical signs, fever lasting more than 5 days, and four out of the following: polymorph- ous rash, bilateral conjunctiva l injection, mucous membrane changes (dif- fuse injection of oral and pharyngeal mucosa, er ythema or \201 ssuring of the lips, and strawberry tongue), acute, nonpurulent cervical l ymphadenop- athy (one lymph node must be >1.5 cm), and extremity changes (erythema of palms or soles, indurative edema of hands or feet, and membranous desquamation of the \201 nge rtips). Other features include heart failure, mitral regurgitation, aseptic menin- gitis, facial pa lsy, stroke, arthralgias or arthritis, pleural effusion, pulmonary in \201 ltrates, vulvit is, urethritis, extremity gangrene, pustules, and erythema multiforme \200\223like lesions. KAWASAKI DISEASE 435 Imaging \200 Echocardiogram at baseline, 3 weeks, and 1 month after blood work have normalized. Look for coronary artery aneurysms and evidence of valvulitis, myocarditis, and pericarditis. Diffu se coronary dilation is seen in 50% of cases by day 10. An alternative is magnetic resonanc e angiography. \200 Blood work \200 Normocytic anemia, granulocytosis, thrombocytosis (weeks 2 \200\2233), and thrombocytopenia (with severe coronary disease) Elevated ESR, CRP, normal) Mild transaminitis (40%) and rai sed bilirubin (10%) A 1-antitrypsin and serum complement (may be Treatment \200 \200 Intravenous gammaglobulin Aspirin (small aneurysms). Dipyridamole (large aneurysms). Consid er anticoagulation. Hospitalization until patient is afebrile and in \202 ammatory markers have normalized In \202 uenza vaccine if patient is on long-term aspirin therapy. Prognosis \200 Mortality is 0.1% \200\2232%. Cardiac complications occur in 25% of patients if untreated. Recurrence rate is 1% \200\2233%.