Respiratory symptoms in children with Ehlers-Danlos syndrome.

Ehlers-Danlos syndrome (EDS) is a connective tissue disorder characterized by hypermobility, skin laxity, and tissue fragility. EDS is classified based on clinical manifestations, inheritance pattern, and genetic defects. The 6 subtypes per the 1997 Villefranche classification include classic, hypermobility, vascular, kyphoscoliosis, arthrochalasia, and dermatosparaxis. Hypermobility type EDS is characterized by generalized joint hypermobility and the presence of minor skin involvement, including hyperextensibility and/or smooth velvety skin. This subtype remains a diagnostic challenge given the lack of biomarkers and known genetic defect. In contrast, the classic type EDS is linked to a defect in type V collagen, and the 3 major diagnostic criteria are skin hyperextensibility, widened atrophic scars, and joint hypermobility. EDS case reports discuss the increased prevalence of chest wall deformities, mild hearing impairment, dysphonia, vocal cord abnormalities, and swallowing difficulties. A recent report indicates increased atopy and asthmatic symptoms in adult patients with this syndrome. Data are lacking in the pediatric literature. We report respiratory symptoms in children with EDS that weremisdiagnosed as asthma or that accompanied this disease. Our series of 5 children with EDS presented to the allergy clinic with a previous diagnosis of asthma (Table I). All the patients underwent spirometry and assessment of albuterol response. Pulmonary function measurements included a forced expiratory volume in 1 second (FEV1) of 96%-124% predicted, and an FEV1 to forced vital capacity (FVC) ratio of 77% to 89%. Because the FEV1 was not reduced in association with a normal or increased FEV1/FVC ratio, there was no apparent restrictive component that may be related to a chest wall or skeletal deformity. For further evaluation of airway hyperreactivity, 1 patient underwent a methacholine challenge, which was negative. Only 2 patients had confirmed asthma with reversible airway obstruction with albuterol or exercise pulmonary function tests with a fall of the FEV1 by at least 10%. Patient no. 1 was a 9-year-old boy with classic EDS and with a history of gastroesophageal reflux (GER) status-post fundoplication, platelet function disorder, irritable bowel syndrome, and kyphoscoliosis who presented with dyspnea and chest tightness with exercise. He was taking a bronchodilator and an inhaled corticosteroid for asthma. This patient had normal spirometry, with no response to a bronchodilator. Airway fluoroscopy was normal, and radioallergosorbent test (RAST) for common food allergens was negative. He was diagnosed with vocal cord dysfunction after a videostroboscopy demonstrated significant paradoxical vocal fold movement. Patient no. 2 was a 10-year-old boy with hypermobility type EDS who presented with nocturnal dyspnea, intermittent stridor, and cough. His asthma was being treated with a bronchodilator and montelukast. Other medical history information included GER, failure to thrive, scoliosis, recurrent croup, and bicuspid aortic valve. Spirometry was normal, without reversibility from a bronchodilator. Allergy scratch testing was positive for several common environmental and airborne allergens. The patient also had a positive RAST to egg. The patient underwent a direct laryngoscopy and rigid bronchoscopy with bronchial alveolar lavage given the concern for anatomic abnormality. He was found to have distal tracheal compression, greater than 50% at the level of the carina, with a pulsatile appearance. A subsequent angiogram chest computed tomography demonstrated a dilated ascending aorta and right innominate vessel leading to tracheal compression (the trachea was 6 mm in diameter at the level of greatest involvement) (Figure 1). Patient no. 3 was an 11-year-old girl with hypermobility type EDS and history of failure to thrive, pancreatitis, dysautonomia, GER status-post fundoplication, and anxiety who presented with dyspnea on exertion, cough, and chronic nasal congestion. Food and drug allergies were present based on clinical history. Allergy scratch testing to common indoor and outdoor allergens was negative. Her spirometry demonstrated mild obstruction with reversibility from a bronchodilator, which confirmed a diagnosis of asthma. A flexible laryngoscopy demonstrated 100% choanal obstruction by adenoid tissue and normal vocal cord mobility. A polysomnogram was normal, without evidence of obstructive sleep apnea. She underwent an adenoidectomy without much improvement to her cough and snoring. A methacholine challenge and videostroboscopy were recommended but not done. Patient no. 4 was a 13-year-old girl with classic EDS and is the sibling of patient no. 1. She had a history of ichthyosis, GER, scoliosis, and irritable bowel syndrome, and presented to the clinic with dyspnea on exertion, cough, and “throat clearing.” Her asthma was treated with a bronchodilator and montelukast but with minimal effect on the symptoms. Her spirometry was normal, without significant change with bronchodilator administration. Skin testing was not performed due to ichthyosis, but RAST was negative for common environmental allergies. A methacholine challenge was negative, and an airway fluoroscopy was normal. A laryngoscopy was unable to confirm vocal cord dysfunction but this diagnosis was probable based on her symptoms and improvement with breathing exercises provided by speech therapy. Lastly, patient no. 5 was a 14-year-old girl with hypermobility type EDS who was taking a bronchodilator and inhaled corticosteroid for her asthma. She presented with dyspnea on exertion and cough. Her medical history included anomalous right coronary artery and attention deficit hyperactivity disorder. Asthma was confirmed with spirometry, which showed a mild obstructive pattern with clinically significant bronchodilator response in symptoms and FEV1. Allergy scratch testing to