HISTORY OF PRESENT ILLNESS
The patient is a 17-year-old boy who was in good health until 3 days prior to his admission. At that time, he fell while playing basketball and noted some pain in his right thigh. He also complained of shortness of breath and chest discomfort when lying flat. He denied fever, rash, joint pains, and cough.
Bilateral inguinal hernia repairs were performed in infancy, but he has no history of other hospitalizations. He was not taking any medications. A paternal uncle required a renal transplant at 43 years of age for an unknown diagnosis. A maternal grandmother has systemic lupus erythematosus.
T 37.2°C; HR 92 bpm; RR 20/min; BP 151/66 mmHg; SpO2 100% in room air
Weight 50th percentile; Height 75th percentile
Initial examination revealed a teenage boy who was awake and alert and in no respiratory distress. A rash was distributed across his nose and cheeks. The rash consisted of erythematous patches with keratotic scaling (Figure 14-1). His chest examination demonstrated decreased breath sounds at the right base. No wheezes or rales were noted. His cardiac examination was significant for slightly diminished heart sounds but no murmurs or rubs. His right thigh was swollen with a circumference 6 cm greater than the left thigh. He also had swelling of his right calf, which was 2 cm greater than the left calf. Flexion of the right knee was limited and there was mild calf pain with dorsiflexion of the right foot. The remainder of his physical examination was normal.
FIGURE 14-1. Rash on the face.
Laboratory analysis revealed a peripheral blood count with 6000 WBCs/mm3 with 79% segmented neutrophils and 14% lymphocytes. Hemoglobin was 12.9 g/dL and the platelet count was 156 000/mm3. An erythrocyte sedimentation rate was elevated at 101 mm/h. Prothrombin and partial thromboplastin times were 13.6 and 31.9 seconds, respectively. Urinalysis revealed large blood and 3+ protein. A Doppler ultrasound of the right lower extremity revealed a thrombus extending from the superficial femoral vein to the calf vein.
COURSE OF ILLNESS
The patient was admitted and treated with intravenous heparin at 20 units/kg/h for his deep vein thrombosis (DVT) and with furosemide for his hypertension. A chest roentgenogram in conjunction with further laboratory work suggested an underlying condition that predisposed to this presentation (Figure 14-2).
FIGURE 14-2. Chest radiograph.
DISCUSSION CASE 14-1
Chest pain in children and adolescents is rarely life-threatening. The majority of cases of chest pain in these age groups are classified as idiopathic. Among adolescents, the most common nonidiopathic etiologies include psychogenic, cough, asthma, pneumonia, and musculoskeletal pain. Less common etiologies include trauma, drug use or abuse, gastroesophageal reflux, and pneumothorax. Cardiac etiologies are exceedingly uncommon, but should be considered in certain clinical situations, such as patients with syncope and exertional or positional symptoms.
This patient has many physical and laboratory findings that warrant further evaluation. The two most worrisome findings include his chest pain when supine and his deep venous thrombosis. Shortness of breath and chest pain that worsens while lying supine suggests possible pericardial disease. The development of deep venous thrombosis in an otherwise healthy adolescent is extremely uncommon. In this situation one should suspect underlying hypercoagulable disorders. Finally, this DVT in conjunction with shortness of breath and chest pain suggest a pulmonary embolus as a possible diagnosis.
The chest roentgenogram revealed blunting of the right costophrenic angle, suggesting a small right pleural effusion, and cardiomegaly (Figure 14-1). An echocardiogram demonstrated a small-to-moderate-sized pericardial effusion that accounted for the finding of cardiomegaly on the chest radiograph. A ventilation-perfusion (VQ) scan suggested a low probability of pulmonary embolus.
As his hospitalization progressed, his hemoglobin dropped acutely to 10.3 g/dL and Coombs positive warm antibodies were demonstrated. A 24-hour urine collection demonstrated 8.5 g protein/day. Antinuclear antibody titer was elevated at 1:1280 and complement C3 and C4 were decreased. Autoantibody studies were positive including anti-Smith, anti-RNP, anti-SSA, anti-SSB, anti-SCL 70, and anti-JO 30. As part of his hypercoagulable work up, he was found to have anticardiolipin antibodies and antiphospholipid antibodies.
These laboratory values along with his clinical picture, including the rash, suggested the underlying diagnosis of systemic lupus erythematosus (SLE). He was treated with prednisone for his nephritis. After a period of time, his anticoagulation was changed to low-molecular weight heparin and he was discharged home on the tenth day of hospitalization.
INCIDENCE AND EPIDEMIOLOGY
SLE is a multisystemic autoimmune disorder that can present in children and adolescents. Determining the incidence of SLE in children is difficult with minimal data. However, national registries in Canada and Finland have suggested a mean annual incidence of 0.36/100 000 and 0.37/100 000, respectively. Studies in the United States have suggested an annual incidence of 0.53-0.60/100 000.
SLE rarely develops before the age of 5, and most commonly has its onset during adolescence. Girls are more commonly affected than boys with a ratio of approximately 5:1. There is a suggestion of a higher incidence in African-Americans followed by Hispanic children/adolescents.
SLE has a quite variable presentation, with children often having more severe presentations than adults. The most common presenting signs and symptoms overall include fever, arthralgias or arthritis, rashes, lymphadenopathy, hepatosplenomegaly, malaise, and weight loss. However, almost all organ systems have the potential for involvement.
Constitutional symptoms are common at diagnosis and with disease flares. Cutaneous findings may include the classic butterfly rash, discoid rash, or even mucosal ulcerations. Arthralgias and arthritis as well as aseptic necrosis of the femoral head may occur. Classic cardiac findings may include pericarditis, pericardial effusions, myocarditis, and Libman-Sacks endocarditis. Pulmonary manifestations occur in approximately 50% of patients. Both pleural and parenchymal involvement can occur with pleuritis and pneumonitis most often seen. Neurologic findings include seizures, psychosis, cerebrovascular accidents, peripheral neuropathies, and pseudotumor cerebri. Ocular findings includes papilledema and retinopathy. From a hematologic standpoint, patients with SLE are at a higher risk for the development of the antiphospholipid syndrome placing them at high risk of thromboembolic events. Finally, renal disease is also common with the development of glomerulonephritis, nephrotic syndrome and hypertension. These renal manifestations are probably the major prognostic factors in patients with SLE.
With such a variable presentation, attempts have been made to provide criteria for the diagnosis of SLE. The American College of Rheumatology updated the criteria for the diagnosis of SLE in 1997 (Table 14-4).
TABLE 14-4. American College of Rheumatology diagnostic criteria for systemic lupus erythematosus. 4
*Diagnostic for systemic lupus erythematosus if four or more criteria are present
In general, patients with a minimum of 4 of the 11 criteria are diagnosed with SLE. The criteria can present serially or simultaneously and during any interval of observation. In childhood, this has a sensitivity of 96% and a specificity of 100%.
Acute-phase reactants. Most acute-phase reactants will be elevated in lupus exacerbations, including erythrocyte sedimentation rate, serum ferritin levels, and a hypergammaglobulinemia.
Hematologic studies. Approximately 50% of children with SLE will have anemia of chronic disease.
Other findings include an acute hemolytic anemia, leukopenia and thrombocytopenia. As mentioned previously, a high proportion of SLE patients will have a hypercoagulable state with the presence of antiphospholipid antibodies.
Autoantibodies. The majority of SLE patients will have detectable antinuclear antibodies. Those antinuclear antibodies that can be seen in SLE include anti-dsDNA, anti-DNP, anti-Ro (SS/A), anti-La (SS/B), anti-Sm and anti-histone antibodies. Various other autoantibodies include antierythrocyte, antilymphocytotoxic, antitissue specific, antiphospholipid antibodies as well as rheumatoid factors. In terms of diagnosis, antibodies against dsDNA are considered pathognomonic of SLE.
Complement levels. Decreased complement levels are particular indicators of active disease in SLE. One can measure either complement components C3 and C4 or total hemolytic complement, as measured by CH50 (ability of a test sample to hemolyze 50% of antibody coated erythrocytes).
Urinalysis. The most common abnormality on a urinalysis in SLE is proteinuria. Hematuria and RBC casts also occur. Further tests to evaluate for lupus nephritis include creatinine clearance, glomerular filtration rate studies, renal ultrasonography, and biopsy.
There is no standard protocol to treat patients with SLE, as each child has a variable presentation. The primary goal is to prevent exacerbations, rather than treat each flare episodically. Certain recommendations are universal including the need to avoid exposure to excessive sunlight.
A variety of pharmacologic agents are available to treat symptoms of SLE. Nonsteroidal antiinflammatory agents are typically used for the treatment of musculoskeletal complaints. Patients with anticardiolipin antibodies often receive low-dose aspirin to decrease the risk of thromboembolisms. Hydroxychloroquine can be very effective in conjunction with glucocorticoids to minimize disease exacerbations. However, these agents may not always be effective in controlling the disease and other immunosuppressive agents such as azathioprine, cyclophosphamide, and methotrexate may be needed.
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