Myocardial ischemia in a 13-year-old female with progressive systemic sclerosis

Introduction: Progressive systemic sclerosis (PSS) is an autoimmune disorder with multi system involvement of undefined etiology. The main manifestations are usually dermal but involvement of the vasculature and other organ systems are the major determinants of morbidity and mortality of this disease process. Myocardial fibrosis, angina pectoris and myocardial ischemia have been recognized as cardiac manifestations of PSS. The peculiarity of the myocardial dysfunction in PSS is the usual absence of coronary artery abnormalities, raising questions as to the mechanism of injury. We present a case of progressive systemic sclerosis with severe myocarditis. Case Presentation: A 13 year old Hispanic female was diagnosed with PSS 8 months prior to admission. Penicillamine was started but was stopped a few weeks prior to admission due to abnormalities in renal function. Diagnosed with acute gastroenteritis and 5% dehydration, she was admitted to the hospital for rehydration therapy. Her vital signs showed a heart rate (HR)=137 bpm, blood pressure (BP)=119/69 mm Hg, respiratory rate (RR)=20 and temperature (T)=37.3°C. Significant physical findings were tight shiny skin, dry mucous membranes, several ulcerated lesions over the left 3^rd and 5^th fingers and cool hands and feet. Initial laboratory tests showed a normal WBC and hematocrit: normal renal and liver function: chemistries remarkable for a bicarbonate of 15 meq/l and a CPK of 632 U/l. She was given 2 liters of fluid with some improvement. She then developed an oxygen requirement and hypothermia and on the following day dropped her HR to 30 with poor peripheral perfusion. She was given atropine, intubated and transferred to the pediatric intensive care unit (PCCU). Physical examination revealed a HR=178, RR=18, T=36°C, BP=115/ 81. The skin was tense and tight with a bluish discoloration of the distal extremities, the ulceration of the fingers were still noted, pupils were reactive to light, mucous membranes were moist, breath sounds were equal bilaterally with diffuse rhonchi, (-) wheezing; there was no jugular venous distension, heart sounds were distant, S₁S₂ were appreciated with a grade 2/6 systolic murmur over the LSB, (-) pericardial rub. Abdominal skin was tight, but there was no tenderness on deep palpation, (+) hypoactive bowel sounds, (-) organomegaly. The extremities were cold and capillary refill was 4 seconds with poor peripheral pulses. Initial ABG on mechanical ventilation was pH=6.9, PaCO₂=39, PaO₂=93 with a base deficit of -23 mmol/l. The patient was resuscitated with 5% albumin and started on dobutamine at 5 μg/kg/min. ECG showed sinus tachycardia with low voltage and ST segment changes in leads V₄-V₆. CPK=3639 U/l, CK-MB=122 ng/ml and CK-MB percentage 3.4%. Serum electrolytes demonstrated a severe metabolic acidosis, normal renal function, hypocalcemia, LDH=521 U/l, SGOT=128 U/l SGPT=45 U/l. WBC=15.3, hematocrit=36, platelets=170, PT/PTT=13/30, fibrinogen=256, D-dimer=0.5. A pulmonary artery catheter was placed: initial measurement showed a CVP=10, PAP=50/21, PCWP=11, CI=2.83 l/min/m², SVRI=1665 dyne-sec/cm⁵/m², PVRI=254, LVSWI=12.5 gm-M/m² and RVSWI=2.15. Echocardiogram revealed normal LV dimensions with a decreased shortening fraction (SF=13%), marked LV dyskinesis and trace mitral regurgitation. No pericardial fluid or coronary artery abnormalities were seen. Dobutamine was increased to 10 μg/kg/min, nitroprusside was started at 1 μg/kg/min and digoxin was begun. A bicarbonate infusion was begun to correct the metabolic acidosis and steroids were started. Blood, tracheal, urine and viral cultures were obtained and Ceftriaxone was given. Nitroglycerin cream was placed over the distal extremities to help improve perfusion. Overnight, the CI improved to 4.82 and the SVRI dropped to 1200. The patient remained on inotropic, vasodilator and base therapy for the next 24 hours with improved cardiac function and resolution of the metabolic acidosis. On the 3^rd PCCU day, the ECG remained with low voltage but the ST segment changes had resolved. She was extubated without difficulty. CPK level peaked at 7203 with the highest CK-MB of 199 and a fraction of 4.3%. Dobutamine and nitroprusside were discontinued and she was maintained on digoxin, furosemide and steroids. Viral and bacterial cultures were negative. The echocardiogram prior to discharge demonstrated mild concentric LV hypertrophy with normal function (SF=35%) and no evidence of LV dyskinesis. She is being followed by a rheumatologist and although she has had progression of her disease, no repeat episodes of myocardial ischemia have occurred. Discussion: There are two patterns of myopathic disease associated with progressive systemic sclerosis: non progressive myopathy with mild elevations of CPK, and fulminant myositis with marked elevation of CPK. Patients with PSS and CPK elevation are at increased risk for myocardial involvement including congestive heart failure and sudden death. Fulminant myocarditis is frequently accompanied by skeletal myositis early in the course of the disease. Although skeletal muscle myositis responds well to steroid therapy, myocardial damage and LV dysfunction is often irreversible. The presence of normal coronary artery anatomy associated with PSS and myocardial dysfunction leads to a variety of hypotheses as to the mechanism of disease. Autopsy studies demonstrate that the myocardium has extensive focal fibrosis involving both the right and left ventricles with the presence of contraction band necrosis. This type of necrosis represents reperfusion injury and is usually seen following cardio-pulmonary bypass. In the setting of PSS, one hypothesis is that the coronary and intra myocardial arteries of the heart undergo a Raynaud's phenomenon. Another potential explanation is intermittent vascular spasm of the microcirculation with recurrent ischemia accounting for the contraction band necrosis. Immunosuppressive agents, if initiated early, may be of benefit. Prompt recognition of this entity is essential to potentially prevent severe LV dysfunction and its associated mortality. The optimal regimen for this complication of PSS has yet to be defined. Conclusion: This case illustrates a life threatening complication of PSS - myocardial ischemia, LV dyskinesis and cardiogenic shock. With vigorous resuscitation and early steroid use, the usual grave outcome associated with this complication was avoided in this patient. Our patient demonstrated improved myocardial function, disappearance of LV dyskinesis and normalization of the ECG. Awareness of myocardial dysfunction in PSS can facilitate timely diagnosis and therapy for this devastating complication of progressive systemic sclerosis.