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Cystic fibrosis: Clinical manifestations and diagnosis

INTRODUCTION

Cystic fibrosis (CF) is the most common life-shortening autosomal recessive disease among Caucasian populations, with a frequency of 1 in 2000 to 3000 live births. The median predicted survival for CF patients in the United States was 36.8 years (95% CI, 34.7-40.3) according to the Cystic Fibrosis Foundation 2011 Registry Report [1]. The usual presenting symptoms and signs include persistent pulmonary infection, pancreatic insufficiency, and elevated sweat chloride levels. However, many patients demonstrate mild or atypical symptoms, and clinicians should remain alert to the possibility of CF even when only a few of the usual features are present [2].

An overview of the clinical manifestations and diagnosis of CF will be presented here. The genetics, pathogenesis, and treatment of CF are reviewed separately. (See "Cystic fibrosis: Genetics and pathogenesis" and "Cystic fibrosis: Overview of the treatment of lung disease" and "Cystic fibrosis: Antibiotic therapy for lung disease" and "Cystic fibrosis: Overview of gastrointestinal disease".)

EPIDEMIOLOGY

In the United States, cystic fibrosis (CF) occurs in approximately 1:3000 Caucasians, 1:9200 Hispanics, 1:10,900 Native Americans, 1:15,000 African Americans, and 1:30,000 Asian Americans [3]. CF is increasingly recognized in nonwhite populations, not only in regions familiar with CF but also in South and East Asia, Africa, and Latin America. Prevalence estimates are likely to rise with increasing use of newborn screening and increasing recognition of individuals with mild disease or disease limited to one organ system.

DEFINITIONS

Classic CF — The classic or typical form of cystic fibrosis (CF) is diagnosed if a patient demonstrates clinical disease in one or more organ systems (as described below) and has elevated sweat chloride (≥60 mmol/L). Most of these patients have disease manifestations in multiple organ systems (pancreas, upper and lower respiratory tract, and male reproductive tract). (See 'Overview of clinical features' below.)

Nonclassic CF — About 2 percent of patients fulfill diagnostic criteria for CF but have a normal or intermediate sweat chloride result. In these patients, the diagnosis of CF depends upon DNA analysis (two copies of a disease-causing mutation in the cystic fibrosis transmembrane conductance regulator [CFTR] gene on each parental allele [ie, in trans]) or on measurement of nasal potential difference. This disease pattern has often been termed "nonclassic" CF [4,5]. However, current guidelines emphasize that there is a wide spectrum of severity in CF and that there is no clear distinction between "classic" and "nonclassic" types [6]. The estimated prevalence and disease manifestations of nonclassic CF may change in the future, as diagnostic methods for CFTR mutations and dysfunction become more sensitive and are more broadly applied.

                               

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Literature review current through: Oct 2014. | This topic last updated: Jun 25, 2014.
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