Meconium ileus cystic fibrosis

Meconium ileus cystic fibrosis is the most common lethal genetic disease in white populations. It is autosomal recessive, with a median survival of approximately 30 years. Nearly 35% of persons with Cystic Fibrosis are 18 years old or older.

I. Meconium ileus cystic fibrosis Diagnosis

Diagnosis of Meconium ileus cystic fibrosis is confirmed when a person has either typical pulmonary or GI manifestations or a history of CF in the immediate family and an elevated sweat chloride (>60 mEq/L in children and >80 mEq/L in adults) using the pilocarpine iontophoresis method. Measurement of nasal potential difference and Cystic Fibrosis gene mutation analysis (Cystic Fibrosis transmembrane conductance regulator gene) are useful adjuncts to diagnosis in atypical cases, and their use may become more widespread in the future.

II. Meconium ileus cystic fibrosis Symptoms and Signs

Clinical manifestations of Meconium ileus cystic fibrosis reflect the abnormal composition of exocrine secretions, resulting in excessively thick and tenacious mucus, obstruction of the pancreatic ducts with inspissated secretions, and elevated sweat chloride and sodium concentrations.

A.  Pulmonary disease is characterized by chronic airway infection and the development of bronchiectasis and chronic obstructive lung disease and accounts for most of the morbidity and mortality associated with Meconium ileus cystic fibrosis. The presenting symptoms of cough, purulent sputum, wheezing, and dyspnea are variable and depend on the extent of superimposed infection. Its course is chronic and progressive, with superimposed acute pulmonary exacerbations. Allergic bronchopulmonary aspergillosis may be present in up to 10% of patients with Meconium ileus cystic fibrosis, with massive hemoptysis and pneumothorax being more common in the adult population.

B. The most important extrapulmonary manifestation of Meconium ileus cystic fibrosis is pancreatic insufficiency, which affects approximately 90% of persons with Meconium ileus cystic fibrosis and results in fat malabsorption, steatorrhea, and malnutrition. Other extrapulmonary systems affected by Cystic Fibrosis are GI (constipation, intussusception, distal intestinal obstruction syndrome, rectal prolapse), endocrine (diabetes mellitus, affecting »10% of adults), hepatobiliary (cholelithiasis, cholecystitis, focal biliary cirrhosis, portal hypertension), skeletal (hypertrophic osteoarthropathy, retardation of growth and bone age, demineralization), upper respiratory tract (nasal polyps, chronic sinusitis), and genitourinary (sterility and infertility in men secondary to bilateral absence of the vas deferens). Although fertility may be decreased in women with Meconium ileus cystic fibrosis secondary to thickened cervical mucus, many women with Meconium ileus cystic fibrosis have tolerated pregnancy well.

C. Laboratory studies

1. Chest radiograph usually reveals increased interstitial reticular markings, bronchiectasis, and hilar adenopathy. Generally, the upper lobes are more involved than are the lower lobes.

2. PFTs typically are consistent with an obstructive abnormality. Patients also may exhibit bronchial hyperreactivity. Later in the disease, hypoxemia and progressive hypercapnia develop.

3. Cultures and sensitivities of the sputum are mandatory during exacerbations. Early in life, the most characteristic organisms associated with Meconium ileus cystic fibrosis are Staphylococcus aureus and H. influenzae. By adulthood, infection with mucoid strains of Pseudomonas aeruginosa predominate. Infection with Burkholderia cepacia has been associated with a rapid deterioration in some patients and may preclude transplantation at some centers.

III. Cystic Fibrosis Therapy

The goals of therapy for the pulmonary disease in Meconium ileus cystic fibrosis are to decrease the burden of infection, to provide bronchopulmonary hygiene, to aid in the clearance of secretions, and to maintain adequate nutrition. As the disease progresses, supplemental oxygen may be required, and referral for lung transplantation is appropriate for many patients.

A. Antibiotics. IV antibiotics are the treatment of choice for acute exacerbations of Meconium ileus cystic fibrosis. Because P. aeruginosa is the pathogen encountered most frequently in adults, a combination of a semisynthetic penicillin or a cephalosporin with antipseudomonal activity (ceftazidime, 2 g IV q8h, or cefepime, 2 g IV q12h) and an aminoglycoside, such as tobramycin (3 mg/kg q8h), usually is selected, pending results from sputum cultures and sensitivities. The use of chronic prophylactic and suppressive oral antibiotics remains controversial. Inhaled tobramycin (300 mg bid) in patients with clinically stable disease has been shown to improve pulmonary function, decrease the density of P. aeruginosa, and reduce the need for IV antibiotics and hospitalizations. Voice alteration (13%) and tinnitus (3%) are potential adverse events associated with long-term inhaled tobramycin.

B. Bronchial hygiene

1. Chest physiotherapy consisting of postural drainage with percussion, autogenic drainage, forced expiratory techniques (e.g., huffing), and participation in an exercise program has been shown to have short-term clinical utility in the clearance of mucous secretions and improvement of physical performance. Chest compression with an inflatable vest and such devices as positive expiratory pressure valves, intrapulmonary percussive ventilation devices, and airway oscillators (i.e., flutter valve) offer patients greater independence. One should be alert to the possibility of oxygen desaturation and exercise-induced bronchospasm when using these techniques.

2. Bronchodilators are used for patients with bronchial hyperreactivity and may facilitate adequate respiratory toilet.

3. Dornase alfa

C. Anti-inflammatory therapy. Because some of the lung damage in CF is attributable to an excessive inflammatory response to chronic infection, it has been proposed that the natural history of the disease can be moderated if the inflammatory response can be controlled. Short-term courses of corticosteroid therapy may be useful in some patients; however, adverse effects preclude their long-term use. In one trial with high-dose ibuprofen, the rate of decline in FEV1 was slowed, being most pronounced in children with mild lung disease.

D. Oxygen therapy is indicated in patients with hypoxemia at rest, at night, during exercise, or with evidence of pulmonary hypertension.

E. Nutritional support. An important component of any CF management program is nutritional support, including pancreatic enzyme replacement (500–2000 units of lipase per kilogram per meal), nutritional supplements, and supplementation of fat-soluble vitamins.

F. Lung transplantation. The majority of patients with Meconium ileus cystic fibrosis die from pulmonary disease. Referral for lung transplantation should be considered when the FEV1 has decreased to approximately 30% of the predicted value. Sequential bilateral lung transplantation is the procedure of choice because of the risk of spill over infection from the remaining native lung. The actuarial 1-, 2-, and 3-year survival for Meconium ileus cystic fibrosis patients after lung transplantation is 81%, 58%, and 49%, respectively.

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