KARA N. SHAH
HISTORY OF PRESENT ILLNESS
A 14-year-old boy presented to the emergency department complaining of a facial rash. Seven days prior to admission he had developed low-grade fevers, sore throat, myalgias, and malaise. He was evaluated by his primary pediatrician, who diagnosed him with influenza. His symptoms gradually improved until the day of admission when he developed fever to 39.0°C, a rapidly worsening cough, and rash on his face. In the emergency department he had an episode of hemoptysis (approximately 250 mL) and subsequently became hypotensive, requiring treatment with multiple normal saline boluses and a packed red blood cell transfusion. He did not have a history of abdominal or chest pain. The patient recalled striking his head in the shower while coughing, a fact that he had not mentioned to his parents.
The patient had a history of recurrent rectal prolapse at 4 years of age that resolved without sequelae. His mother noted that he had a tendency to bruise easily and often had gingival bleeding after brushing his teeth. He had not undergone any surgical procedures. He had no allergies and his immunizations were up-to-date. He was adopted at the age of 4 weeks. His biologic mother died after delivery due to complications of uterine rupture. Additional details of the family history were not known.
T 38.5°C; RR 50/min; HR 130 bpm; BP 100/55 mmHg
Height 50th percentile; Weight 25th percentile
Physical examination revealed an ill-appearing but alert boy. He had a very thin and narrow face. His sclerae were mildly injected. There was no blood in the nares and no hemotympanum. His neck was supple. He had mild suprasternal retractions with dullness to percussion approximately half way up the back on the right. There were rales in the region of the right lower and middle lobes. Cardiac examination was notable for thread femoral pulses that improved after fluid resuscitation; no murmur was appreciated. He had mild tenderness to palpation at the right costal margin but the remainder of the abdominal examination was normal. Examination of the skin was remarkable for a large ecchymoses on the patient’s forehead (3 cm) that was tender to palpation. There were numerous thin, atrophic scars on his extremities, especially overlying the joints.
Arterial blood gas demonstrated the following: pH, 7.35; PCO2, 26 mmHg; and PO2, 60 mmHg in room air. The WBC count was 1600/mm3 (26% band forms; 26% segmented neutrophils; 44% lymphocytes); hemoglobin, 9.8 g/dL; and platelets, 270 000/mm3. Erythrocyte sedimentation rate was 35 mm/h. The prothrombin and partial thromboplastin times were 13.1 seconds and 35.7 seconds, respectively. The fibrinogen was 749 mg/dL and fibrin split products were 20 mcg/mL. The creatinine kinase was 120 U/L. Serum electrolytes were as follows: sodium, 136 mmol/L; potassium, 3.6 mmol/L; chloride, 104 mmol/L; bicarbonate, 18 mmol/L; blood urea nitrogen, 16 mg/dL; creatinine, 1.0 mg/dL; and glucose, 169 mg/dL. Serum aminotransferases and total bilirubin were normal. Urinalysis was normal. A blood culture was obtained. The chest radiograph revealed areas of consolidation in the right lower and right middle lobes with a moderate right-sided pleural effusion.
COURSE OF ILLNESS
The patient received empiric vancomycin and gentamicin for presumed bacterial sepsis. Computed tomography of the chest revealed extensive consolidation involving the entire right lower lobe and part of the left lower lobe with moderate pleural effusions. A chest tube was placed, draining approximately 500 mL of pleural fluid. The pleural fluid contained 7350 WBCs/mm3 and 650 RBCs/mm3. His chest tube was removed on the third day of hospitalization. Initial blood cultures grew Staphylococcus aureus, while cultures of the pleural fluid were negative. Antibiotic coverage was changed to oxacillin and he recovered uneventfully, completing a 4-week course of antibiotics. The patient was diagnosed with influenza complicated by S. aureus pneumonia and bacteremia. A detailed cutaneous examination suggested an underlying diagnosis that predisposed the patient to bruising, hemoptysis, and poor wound healing. The diagnosis was confirmed by skin biopsy.
DISCUSSION CASE 9-4
In this case, the bruising, atrophic scars, and bleeding indicated increased vascular permeability or weakness. The use of corticosteroids or Cushing syndrome could result in the development of atrophic scars as well as easy bruising and bleeding, but there was no history of corticosteroid use nor did the patient demonstrate Cushingoid features. Scurvy, secondary to a dietary lack of vitamin C, may present with bruising, bleeding, and poor wound healing, but is unlikely in a patient in the United States with a normal diet and no history of malnutrition.
Thrombocytopenia, especially due to immune thrombocytopenic purpura or sepsis, may occur in patients with a history of recent illness and fever, but can be excluded based on the normal platelet count. Von Willebrand disease is a relatively common disorder involving a deficiency of a circulating plasma protein related to factor VIII. This results in decreased platelet aggregation and a prolonged bleeding time. There is usually a history of mild to moderate bleeding involving the mucous membranes, including epistaxis and prolonged bleeding after dental procedures. This patient had a history of gingival bleeding with routine dental care, nosebleeds, and easy bruising, but von Willebrand disease does not explain the presence of atrophic scars.
Osteogenesis imperfecta (OI) is a congenital abnormality of quality or quantity of Type I collagen synthesis. Of the four subtypes of OI, Type I is associated with easy bruising. However, this child did not display the other signs of OI, which include frequent fractures, blue sclera, hearing impairment, osteopenia, bony deformities, or excessive laxity of his joints. Ehlers-Danlos syndrome (EDS) is also a congenital defect in collagen synthesis. There are multiple forms of EDS, identified by clinical features (major and minor criteria) and biochemical and molecular findings (Table 9-6). Most of the forms of EDS are associated with skin hyperextensibility and joint hypermobility.
TABLE 9-6. The Ehlers-Danlos syndromes: clinical subtypes and associated defects.
Close examination of the patient’s skin revealed dramatic hyperextensibility. Numerous atrophic, cigarette paper-like (papyraceous) scars most prominently overlying the large joints of the extremities were also present. Additional history revealed that the patient had a history of wound dehiscence after suture placement for a skin laceration. These findings together with the history of easy bruising, history of rectal prolapse, and mother’s death from uterine rupture suggest a diagnosis of Ehlers-Danlos syndrome. The diagnosis was confirmed by skin biopsy with fibroblast culture, which revealed decreased secretion of Type III procollagen consistent with the diagnosis of Ehlers-Danlos, vascular type (previously classified as EDS Type IV).
INCIDENCE AND EPIDEMIOLOGY OF EHLERS-DANLOS SYNDROME
Ehlers-Danlos syndrome, vascular type is the most severe form of the Ehlers-Danlos syndromes. It occurs as a result of mutations on the COL3A1 gene which encodes Type III collagen. Type III collagen is found in highly vascular structures such as liver and blood vessels. EDS, vascular type is inherited as an autosomal dominant condition. This is a very rare condition with a prevalence of less than 1 per 100 000. Possibly as a result of its rarity, the diagnosis is often made only after catastrophic or fatal complication.
CLINICAL PRESENTATION OF EHLERS-DANLOS SYNDROME
The clinical diagnosis of EDS, vascular type is made on the basis having at least two of four major clinical criteria: easy bruising, thin skin with visible veins, characteristic facial features (thin faces, pinched nose, large eyes), and fragility or rupture of arteries, uterus, or intestines (Table 9-6). Minor features include acrogeria, hypermobility of small joints, tendon or muscle rupture, congenital club-foot, early onset varicose veins, and pneumothorax (Figure 9-4). Because EDS, vascular type is a heterogeneous genetic disorder, various clinical presentations may be seen. Diagnosis is often delayed until the second or third decade of life in the absence of a known family history, as vascular complications typically present during the third decade of life. The median age of survival is 48 years, with death most commonly occurring as a result of an arterial dissection or rupture; spontaneous bowel perforation and organ rupture (heart, uterus, spleen, or liver) are the other leading cause of catastrophic death. Although present in this patient, the hypermobility of the large joints and hyperextensibility of the skin, characteristic of the more common forms of EDS, are only occasionally seen in the vascular type.
FIGURE 9-4. Chest radiograph showing pneumothorax in the anterior-posterior projection with images of the A. Entire chest radiograph. B. A close-up image.
In addition to the clinical criteria noted above, diagnosis may be confirmed by the demonstration of abnormal Type III procollagen molecules in cultured fibroblasts or by the identification of a mutation in the gene for Type III procollagen (COL3A1).
Unfortunately, the prognosis in patients with EDS, vascular type is poor. In a study of 220 patients with vascular EDS, more than 80% of affected patients suffered a complication (arterial dissection or rupture, spontaneous bowel perforation, or organ rupture) by age 40 years, and 12% died after the first event. Women have a significant risk of death with each pregnancy due to uterine or vascular rupture, with a reported 11.5% mortality rate.
Genetic evaluation and counseling is crucial for patients diagnosed with this disorder. It is transmitted in an autosomal dominant pattern; thus patients and families need to be informed of the 50% risk of transmission to an affected individual’s offspring. Although management is limited to symptomatic treatment and precautionary measures, use of celiprolol, a beta(1)-adrenoceptor antagonist/beta(2)-adrenoceptor agonist has been associated with a reduction in arterial events in adults (rupture or dissection). Knowledge of the diagnostic features of vascular EDS is critical in the recognition and management of emergency, surgical, and obstetrical issues.
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