Diagnosis
Other Symptoms Affected by CF
Meconium Ileus
The first sign of CF appears in 15% to 20% of children at birth in the form of meconium ileus. The CFTR mutations affect the viscosity of meconium during fetal development, so that instead of clearing normally, it builds up into a hardened obstruction that the infant cannot pass.
Abdominal distention is usually present at birth. Without attention, the distension increases, and the infant may vomit bile-stained material.1,27,31
Distal Ileal Obstruction Syndrome (DIOS)
Older children and young adult patients present with a similar condition due to thickened intestinal secretions and poor intestinal motility. Because meconium is not present beyond infancy, the condition has been named DIOS in older children and young adults.
DIOS presents with intermittent lower-right quadrant pain, loss of appetite, occasional vomiting, and often a palpable mass. Contrast enemas and radiography are utilized to confirm diagnosis of both meconium ileus and DIOS. DIOS may sometimes be confused with appendicitis. However, even though the appendix may be distended with thickened secretions, the incidence of acute appendicitis in CF patients is lower than in the general population.1,32
Patients with CF often fail to thrive and grow normally. As both DIOS and meconium ileus occur early in life, they provide for early diagnosis and management of patients with CF. Clinical experience and research have suggested that the earlier the patient is diagnosed and treatment is begun, the better the prognosis.27,32,33
Pancreatic Disease
More than 90% of all patients with CF have pancreatic insufficiency; that is, they lack the enzymes to help digest fats.1
The signs of pancreatic insufficiency are frequent, bulky, foul-smelling stools; meconium ileus; and symptoms of fat-soluble vitamin deficiency (vitamins A, D, E, and K). It left untreated, patients fail to thrive and grow, and are malnourished. In fact, weight loss and failure to thrive often lead to a diagnosis of CF.3,1
Long-term treatment of pancreatic insufficiency can cause fibrosing colonopathy. Ingestion of very high doses of pancreatic enzymes can cause inflammation leading to scarring and constriction of the right colon. This has been reported in adults, but it occurs more frequently in pediatric patients. Because of this, high doses of enzymes have been restricted.18
Exocrine pancreatic secretions help the body process protein, fat, and fat-soluble vitamins. Exocrine secretion is a function of the pancreas separate from the islets of Langerhans, which are responsible for producing insulin (an endocrine function). Although the islets of Langerhans are usually spared in C F, some patients (approximately 7%) will develop hyperglycemia (diabetes) or cystic fibrosis-related diabetes (CFRD) as teens and adults.
CFRD is unlike type 1 or type 1 diabetes; often the patients are able to produce some insulin, but will require supplemental insulin with meals. CFRD can be intermittent with illness. Oral diabetic agents have shown to be ineffective in this population.3
Hepatobiliary Disease
The hepatobiliary system is affected in many patients with CF. Some patients do not exhibit overt signs of liver damage; they present only with slightly elevated liver enzymes in the blood.
In some patients with CF, thickened secretions result in the obstruction of ducts, and often progress to the development of gallstones. The retention of secretions also causes inflammation–fatty deposits build up in liver tissue until enlargement of the organ is observed. Esophageal varices are often the first sign that there is serious hepatobiliary disease; this may be a sign of portal hypertension.
Eventually tissue damage leads to irreversible scarring (cirrhosis) of the liver and liver failure. In a few patients liver transplantation is an option, but only when lung function is still viable.1,3,28
Infertility
Late onset of puberty is common in both male and female patients with CF. More than 95% of males with CF are azoospermic, meaning an absence of live sperm in the semen. This may result from an absence of the bas deferens or a blockage in the vas deferens from thickened secretions. In actuality, sperm do develop, and viable sperm have been retrieved from patients with CF and used for in vitro fertilization.
Roughly 20% of women with CF are infertile, possibly due to the effects of chronic lung disease on the menstrual cycle, thick cervical mucus that can block sperm migration, or abnormalities in liquid transport at the uterine wall or fallopian tubes. Additionally, the condition of women with comprised lung function and nutritional status may deteriorate at a faster rate during pregnancy. However, more than 90% of completed pregnancies in women with CF do produce viable infants.3,1
Musculoskeletal Disorders
Digital clubbing is often considered a manifestation of hypertrophic osteoarthropathy. This condition also affects the long bones in patients with CF. There is an abnormal disposition of bone developed directly from beneath the periosteum that is thought to be caused by immunologic processes.18 This is easily visible on x-rays.
Bones and joints may also be affected by malabsorption, which increases the risk of osteoporosis. Some patients also complain of arthritic pain, which may be due to high circulating immunity substances.5,18,28
Other Abnormalities
Sweat gland dysfunction is a hallmark of the disease and manifests as noticeable salty sweat. This feature also can lead to fluid depletion by the body, especially with heat stress.
Another feature of CF is that the glands under the jaw and under the tongue are often enlarged and can be observed on physical examination.3,5,28
References:
1. Boucher RC. Cystic Fibrosis. In: Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL et al., editors. Harrison's Internal Medicine. 16th ed. New York: McGraw-Hill; 2005. p. 1-9.
3. Welsh M. Cystic Fibrosis. In: Goldman L, Ausiello D, eds. Cecil Textbook of Medicine. 22nd ed. Philadelphia: WB Saunders; 2004. p. 1-22.
5. Mason P. Cystic fibrosis-the disease. Hospital Pharmacist 2005;12:201-7.
18. Yankaskas JR, Marshall BC, Sufian B, Simon RH, Rodman D. Cystic fibrosis adult care: consensus conference report. Chest 2004 January;125(1 Suppl):1S-39S.
27. Centers for Disease Control and Prevention. Newborn Screening for Cystic Fibrosis. Atlanta, GA: U.S Department of Health and Human Services; 2004 Oct 15. Report No.: MMWR/53/RR-13.
28. Smyth RL. Diagnosis and management of cystic fibrosis. Arch Dis Child Ed Pract 2005;90:1-6.
31. Loening-Baucke V, Kimura K. Failure to pass meconium: diagnosing neonatal intestinal obstruction. Am Fam Physician. 1999:60;7;1-11.
32. Agrons GA, Corse WR, Markowitz RI, Suarez ES, Perry DR. Gastrointestinal manifestations of cystic fibrosis: radiologic-pathologic correlation. RadioGraphics 1996;16(4):871-93.
33. Lai HC, Kosorok MR, Laxova A, Davis LA, FitzSimmon SC, Farrell PM. Nutritional status of patients with cystic fibrosis with meconium ileus: a comparison with patients without meconium ileus and diagnosed early through neonatal screening. Pediatrics 2000 January;105(1):53-61.