Multisystem Imaging Findings of Cystic Fibrosis in Adults: PDF

S p e c i a l A r t i c l e s R ev i ew Averill et al....

S p e c i a l A r t i c l e s R ev i ew Averill et al. Typical and Atypical Patterns of Cystic Fibrosis Special Articles Review Multisystem Imaging Findings Downloaded from ajronline.org by 203.192.239.182 on 06/15/24 from IP address 203.192.239.182. Copyright ARRS. For personal use only; all rights reserved of Cystic Fibrosis in Adults: Recognizing Typical and Atypical Patterns of Disease Sarah Averill1 OBJECTIVE. There is an expanding and increasingly heterogeneous population of adult Meghan G. Lubner 1 patients with cystic fibrosis (CF). Although CF is usually diagnosed in children with progres- Christine O. Menias 2 sive multisystem involvement, up to 7% of CF cases are currently diagnosed de novo in adults Sanjeev Bhalla3 with subtle manifestations distinct from the typical features of classic CF. The purpose of this Vincent M. Mellnick 3 article is to present the wide spectrum of CF in adults, including both classic and nonclassic variants, with an emphasis on the nonclassic imaging findings. Tabassum A. Kennedy 1 CONCLUSION. Recurrent pancreatitis, chronic sinusitis, and congenital bilateral ab- Perry J. Pickhardt 1 sence of the vas deferens (CBAVD) are several of the ways in which CF is identified in adult Averill S, Lubner MG, Menias CO, et al. patients with relatively rare mutations and with overall milder manifestations. It is important for radiologists to recognize the wide spectrum of CF to optimally monitor disease progres- sion and response to therapeutic interventions in distinct adult patient populations. n 1938, cystic fibrosis (CF) was pulmonary disease and the establishment of CF I first established as a distinct entity from celiac disease based on the thick mucus secretions found at treatment centers in the 1950s providing com- prehensive care, including maintenance of good nutritional status, are considered major con- autopsy within the exocrine ducts of infants tributing factors [1, 2]. Currently, 40–50% of who died of malnutrition. The secretions were CF patients are adults, with a life expectancy Keywords: adults, cystic fibrosis, multisystem the basis of its early classification as a “muco- of between 35 and 40 years in countries with DOI:10.2214/AJR.16.17462 viscidosis”. CF is the most common lethal well-developed CF programs and projected to inherited disease among whites, with an inci- be 50 years for those born after the year 2000 Received September 29, 2016; accepted after revision dence of 1 in 2500 live births [2, 3]. CF is inher- [3, 4, 7, 8, 10]. Because adult medical and imag- January 12, 2017. ited in an autosomal recessive pattern, most ing services are dealing with a rising number M. G. Lubner received grant funding from Philips commonly among whites who are carriers of and complexity of multisystem complications, Healthcare and Ethicon. P. J. Pickhardt is cofounder disease-causing CFTR gene mutations at a rate many authorities now regard CF to be as much of VirtuoCTC and owns shares in Cellectar, Elucent, of approximately 1 in 20. The disease is a disease of adulthood as one of childhood [9, and SHINE. characterized by dysfunctional chloride chan- 11–13]. Thus, it is important for radiologists to 1 nel ion transport in all exocrine tissues. World- recognize the spectrum of imaging manifesta- Department of Radiology, University of Wisconsin School of Medicine & Public Health, 600 Highland Ave, wide, approximately 70,000 people are affect- tions in adults with CF. This article emphasizes E3/311 Clinical Science Center, Madison, WI 53792-3252. ed with CF, 30,000 of whom are in the United the shifting age and changing pattern of disease Address correspondence to M. G. ­L ubner States. Populations of African, Asian, and in adult patients with CF; it will only briefly re- ([email protected]). Hispanic descent are rarely affected [5, 6]. view some of the more well-known imaging 2 Department of Radiology, Mayo Clinic Arizona, Over the past few decades, marked improve- findings of CF and will contrast these findings Scottsdale, AZ. ments in the effective medical management of to other less severe or less typical presentations. CF, particularly of pulmonary disease, have improved life expectancy among patients with 3 Mallinckrodt Institute of Radiology, Washington Diagnosis of Cystic Fibrosis University in St. Louis, St. Louis, MO. CF [7–9]. In 1938, most children born with CF In most cases the diagnosis of CF is un- This article is available for credit. would die before their first birthday. By 1970, equivocal. Patients present with classic clinical mean survival had improved to 14 years, and symptoms of CF in childhood, and results from AJR 2017; 209:3–18 in the late 1990s, mean survival had climbed to standard genetic assays and biochemical tests 0361–803X/17/2091–3 29 years. Although all the factors contribut- are confirmatory. The sweat test remains ing to survival are not well understood to our the reference standard for CF diagnosis con- © American Roentgen Ray Society knowledge, improved aggressive treatments for firmation, with a chloride level threshold of 60 AJR:209, July 2017 3  Averill et al. mEq/L, above which is considered abnormal ble 1); a history of CF in a sibling; or a positive infertility study of patients with CBAVD re- Before the discovery of the CF gene, a small screening test result in a neonate and laborato- ported that CF was subsequently diagnosed in proportion of CF patients had clinical symp- ry tests showing cystic fibrosis transmembrane 21% of patients. Between 70% and 75% of toms of CF but had equivocal sweat chloride conductance regulator (CFTR) dysfunction as male subjects with CBAVD carry mutations in test results. It was hoped that the advent of ge- evidenced by an abnormal CFTR gene, abnor- each CFTR gene [13, 17]. Heterozygous patients netic testing would lead to more diagnostic cer- mal sweat chloride level, or abnormal nasal po- who carry a single copy of the ΔF508 mutation tainty. Instead, the number of nonclassic cases tential difference. have been shown to have an increased risk for Downloaded from ajronline.org by 203.192.239.182 on 06/15/24 from IP address 203.192.239.182. Copyright ARRS. For personal use only; all rights reserved of CF has grown, and the development of more Up to 7% of CF cases are now diagnosed sinus disease (33% [15/46] of patients), recur- sophisticated biochemical tests, such as the na- in patients over the age of 16 years. In patients rent pancreatitis (≈ 9%), pancreatic insufficien- sal potential difference, a test that measures presenting de novo as adults, borderline sweat cy (≈ 15%), and allergic bronchopulmonary epithelial ion fluxes and their resulting voltage chloride test results (30–60 mmol/L) are rela- aspergillosis (≈ 2–10%) [1, 10, 18]. Given this potential at the mucosal surface, has helped in tively common, and the test can be repeated variability, a high clinical and imaging index of many cases but has not always resolved the di- when clinical suspicion remains high. If the suspicion must be maintained when assessing agnostic dilemma in atypical cases. sweat chloride level is normal (< 30 mmol/L), adults who present later in life or who present Classic CF can be diagnosed prenatally at the diagnosis of CF requires the identification with nonclassical symptoms and patterns of or- routine screening of high-risk white popula- of at least one CF-causing mutation allele on gan involvement [10, 19] (Figs. 1 and 2). tions through the identification of two mutant each CFTR gene or direct quantification of In 1989, the CF gene was localized to chro- alleles, but CF is diagnosed most often in the CFTR with bioassays, such as the nasal po- mosome 7 by positional cloning. It encodes first year of life. Genetic testing can be per- tential difference [1, 10, 16]. a large protein of 1480 amino acids and lo- formed in neonates and infants with symptoms Patients presenting in adulthood often have calizes to the apical membrane of secretory suspicious for the disease, including meconi- at least one so-called “mild” CF mutation and and absorptive epithelial cells within the air- um ileus at birth, failure to thrive, or recurrent have retained some chloride channel activity ways, pancreas, liver, intestine, sweat glands, sinopulmonary infections. An abnormal sweat. With as little as 10% of the normal lev- and vas deferens. Many of the manifesta- chloride result of greater than 60 mmol/L is els of CFTR messenger RNA present, patients tions of CF are caused by glandular duct plug- confirmatory of the CF diagnosis [14, 15]. can have normal lung and pancreatic function, ging from macromolecules, which are inade- As our understanding of the spectrum of which is a marked difference from the classic quately hydrated. Organ-specific involvement disorders associated with alterations of the pattern seen in CF diagnosed in childhood. is related in part to the ductal anatomy in each CFTR gene has grown, it is not always clear Patients with nonclassic CF may have few exocrine tissue type, including the diameter, when to apply a diagnosis of CF, particularly symptoms of CF and often have fewer organ length, and degree of tortuosity. in very mild variants of the phenotypic spec- systems involved. Male patients with nonclas- In the 25 years since the CFTR gene was trum. Consensus guidelines from the Cystic Fi- sic CF have a markedly high risk for congenital identified, more than 2000 mutations in the brosis Foundation define CF as the presence of bilateral absence of the vas deferens (CBAVD) CFTR gene have been identified [3, 20] and one or more characteristic clinical features (Ta- and resultant azoospermia. For example, a male have been grouped into six subclasses to help in TABLE 1: Phenotypic Features Consistent With a Diagnosis of Cystic Fibrosis (CF) in Adults and Children Phenotypic Features Consistent With CF Diagnosis 1. Chronic sinopulmonary disease manifested by the following: a. Persistent colonization and infection with typical CF pathogens, including Staphylococcus aureus, nontypeable Haemophilus influenza, mucoid and nonmucoid Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Burkholderia cepacia b. Chronic cough and sputum production c. Persistent chest radiograph abnormalities (e.g., bronchiectasis, atelectasis, pneumonia or air-space disease, and hyperinflation) d. Airway obstruction manifested by wheezing and air-trapping e. Nasal polyps; radiographic or CT abnormalities of the paranasal sinuses f. Digital clubbing 2. Gastrointestinal and nutritional abnormalities including the following: a. Intestinal abnormalities: meconium ileus, distal intestinal obstruction syndrome, rectal prolapse b. Pancreatic abnormalities: recurrent acute pancreatitis, chronic pancreatitis, pancreatic abnormalities on imaging c. Hepatic abnormalities: prolonged neonatal jaundice, chronic hepatic disease manifested by clinical or histologic evidence of focal biliary cirrhosis or multilobular cirrhosis d. Nutritional abnormalities: failure to thrive (protein-calorie malnutrition), hypoproteinemia and edema, complications secondary to fat-soluble vitamin deficiencies 3. Salt loss syndromes: acute salt depletion, chronic metabolic alkalosis 4. Genital abnormalities in male patients that result in obstructive azoospermia Note—Adapted from (Journal of Pediatrics; volume 153; Farrell PM, Rosenstein BJ, White TB, et al.; Cystic Fibrosis Foundation; “Cystic Fibrosis Foundation. Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation consensus report”; pages S4–S14; 2008) with permission from Elsevier. 4 AJR:209, July 2017  Typical and Atypical Patterns of Cystic Fibrosis TABLE 2: Classification of CFTR Gene Mutations serve as a bacterial reservoir even after lung transplant (Fig. 3). Classification Abnormality Result of Abnormality Class I Abnormal protein biosynthesis Absent CFTR Pancreatic Manifestations Class II Abnormal protein folding Degraded CFTR protein The pancreatic manifestations of classic CF Class III Abnormal channel activation Poor response to ATP are diverse, ranging from recurrent pancreati- tis to progressive, complete fatty replacement, Downloaded from ajronline.org by 203.192.239.182 on 06/15/24 from IP address 203.192.239.182. Copyright ARRS. For personal use only; all rights reserved Class IV Impaired anion conductance Decreased chloride ion flow which represents end-stage disease of the pan- Class V Abnormal splicing and promoter mutations Less abundant CFTR creas. Complete fatty atrophy is seen at an Class VI Truncation of C-terminus Functional but unstable protein earlier age in patients with more severe forms Note—CFTR = cystic fibrosis transmembrane conductance regulator, ATP = adenosine triphosphate. of CF, with complete fatty replacement seen at a mean age of 17 years [11, 26, 27]. Calcifi- the process of correlating genotype with pheno- pertrophy and hemorrhage. In cases of mas- cations and cysts can also sometimes be seen type (Table 2). The ΔF508 mutation is the most sive hemoptysis (> 240 mL), bronchial artery at imaging. Low water content in secretions common mutation seen in CF patients in the embolization is a definitive treatment [3, 18]. from defective transmembrane ion transport United States, accounting for 66% of cases [9, Despite advances in treatment, respiratory leads to viscous ductal pancreatic contents, 15]. The ΔF508 mutation is a class II mutation problems continue to dominate the clinical which over time cause ductal ectasia and ul- with a single deletion of phenylalanine creating features of patients with CF and account for timately acinar tissue atrophy. a misfolded CFTR protein preventing traffick- 95% of morbidity and mortality [3, 6]. Between 85% and 90% of adult patients ing into the cell’s apical membrane. How- Lung transplant remains the only definitive with CF diagnosed in childhood have defi- ever, patients with CF presenting in adulthood treatment of pulmonary disease due to CF, cient pancreatic enzyme production and pan- are more likely to have mutations not common- which is the third most common indication creatic exocrine insufficiency, which lead to ly seen in patients with CF diagnosed in child- for lung transplant after chronic obstructive fat malabsorption, causing steatorrhea, mal- hood. In one series, 10 of 46 patients with CF pulmonary disease and idiopathic pulmonary nutrition, and a deficiency of fat-soluble vita- diagnosed as adults had rare mutations not in- fibrosis. Transplant can be complicated mins including vitamin D. Endocrine gland cluded in the 31-mutation screening panel. by atypical infections related to immunosup- insufficiency affects a relatively smaller per- pression and increased risk of osteoporosis centage of patients (30–50%), but a substan- Pulmonary Manifestations from chronic steroid use (Fig. 4). tial proportion of patients still experience Although the lungs of CF patients are nor- By comparison, adults presenting with non- glucose intolerance; glucose intolerance can mal at birth, by adulthood, patients with classic classic CF later in life can have very subtle to progress to CF-related diabetes mellitus, CF typically have advanced pulmonary mani- near-absent pulmonary manifestations or can which is a unique combination of type 1 and festations visible on CT. Defective mucociliary have very mild versions of the typical advanced type 2 diabetes. clearance with resultant retention of mucus and findings (e.g., mild bronchiectasis) (Fig. 5). Patients diagnosed with nonclassic CF de inflammatory debris remains the clinical hall- novo as adults typically have overall milder mark of classic CF. The airways of CF patients Head and Neck Manifestations disease and are more likely to retain pancre- are colonized early and are frequently infected Nearly 100% of patients with CF develop atic sufficiency in adulthood [10, 11, 28]. The with alternating periods of relative quiescence chronic rhinosinusitis, with opacified parana- severity of pancreatic disease is one of the and intense inflammatory and immune acti- sal sinuses starting after the age of 8 months principal features distinguishing between the vation, which can manifest clinically with in-. At CT, characteristic findings include si- classic and nonclassic variants of CF. creased mucus production and change in spu- nus obstruction, polyposis, mucocele forma- Pancreatic cystosis is a relatively rare pan- tum color as well as fever, cough, dyspnea, and tion, and bony sclerosis from chronic inflam- creatic manifestation of CF. Mild cystosis re- weight loss. By adulthood, upper lobe–pre- mation in adult patients with CF. Frontal sinus sults in a few cysts, and more severe cystosis dominant bronchiectasis is an almost univer- hypoplasia has been reported in 44–66% results in complete cystic replacement of the sal finding in patients with classic CF. Super- of adult CF patients [24, 25]. Together with pancreas [27, 29]. Macroscopic cysts have an imposed recurrent infections seen in children opacification of the maxillary and ethmoidal epithelial lining that is characteristic of true with classic CF continue to substantially affect sinuses in more than three-quarters of patients cysts, which result from preserved exocrine them in adulthood. Mucoid impaction is a com- with CF, hypoplastic frontal sinuses have been function in the presence of ductal obstruc- mon finding and can be associated with both proposed as criteria that are pathognomonic tion. The cysts form from progressive dila- typical and atypical bacterial colonization with for CF. In one series up to 71% of patients tation proximal to ducts obstructed with in- Burkholderia cepacia and resistant Pseudomo- with CF had prior surgery for chronic sinusitis spissated proteinaceous secretions. nas species, both of which can herald a precip-. The most common bacterial pathogens Ultrasound (US), CT, and MRI play a role itous decline. Allergic bronchopulmonary as- causing sinusitis are Staphylococcus aureus in the assessment of pancreatic involvement pergillosis, which manifests as central varicose and P. aeruginosa. More than 40% of adult in patients with CF. US is noninvasive and bronchiectasis with high-attenuation mucus CF patients are also colonized by nonbacteri- fast and avoids the use of ionizing radiation plugging at CT, develops in 10–20% of patients al pathogens such as Aspergillus species. Be- but can be limited by overlying bowel gas. with CF [3, 18] (Fig. 3). cause the bacteria colonizing the paranasal Classic US findings include increased pan- Advanced pulmonary disease in a patient sinuses and the lower airway are identical in creatic echogenicity resembling that of ret- with CF often leads to bronchial artery hy- CF patients, infection of the upper airway can roperitoneal fat, small size of the pancreas, AJR:209, July 2017 5  Averill et al. and the loss of the lobular border of the pan- CF and is considered a characteristic lesion adherent to bowel wall and crypts making it dif- creas [27, 29]. Fatty replacement can be seen in classic CF [31, 32]. ficult to remove (Fig. 8). at both CT and MRI as an enlarged pancre- Gallbladder anomalies are also reported In addition to reduced chloride and fluid se- as which is fat density on CT images and is in patients with CF; the gallbladder may be cretion from defective CFTR function, abnor- generally fat signal intensity on T1- and T2- absent or small, the so-called “micro gall- malities in bile acid absorption, which are ac- weighted sequences. Fibrosis at CT mani- bladder,” and may be nonfunctioning. Cho- tively reabsorbed in the terminal ileum, may fests as areas of low attenuation with de- lelithiasis occurs in up to one-quarter of CF help explain the location of the obstructive pro- Downloaded from ajronline.org by 203.192.239.182 on 06/15/24 from IP address 203.192.239.182. Copyright ARRS. For personal use only; all rights reserved creased enhancement on contrast-enhanced patients and is influenced by pancreatic in- cess. Risk factors for DIOS include severe images. At MRI, fibrosis is low signal inten- sufficiency and fat malabsorption. phenotype, such as ΔF508 mutation, history of sity on both T1- and T2-weighted sequences. The onset of liver disease is generally in the meconium ileus at birth, and pancreatic insuffi- The imaging appearance of pancreatic cysto- 2nd decade of life or later. However, in one se- ciency. A history of DIOS increases the risk for sis is similar to that found in association with ries, half of the cases of cirrhosis were in chil- subsequent episodes by 10-fold. von Hippel–Lindau syndrome and is occa- dren under the age of 10 years, which high- Patients with complete DIOS and those with sionally in autosomal-dominant polycystic lights that the progression of liver disease is incomplete DIOS can present with acute onset disease. The distinct clinical context of CF, unpredictable in this population. Com- of symptoms with periumbilical or right low- however, obviates the need to invoke these mon findings in patients with CF include fat- er quadrant pain. Differential considerations in alternative diagnoses (Fig. 6). ty liver, which has been reported at imaging in a CF patient include intussusception, appendi- 30–50% of CF patients and at autopsy in up to citis, mucoid appendix, and constipation, the Hepatobiliary Manifestations 60%. Cirrhosis develops in more than 10% latter of which is the most common finding. The hepatobiliary and gastrointestinal sys- of CF patients, and cirrhosis will progress to In most cases, clinical history together with tems are affected in CF patients prenatally, portal hypertension in a smaller percentage of clinical findings of a palpable mass and char- and by adulthood, most CF patients with clas- these patients. Hepatocellular carcinoma is acteristic abdominal radiographic findings are sic disease have some degree of hepatobiliary rare but has been reported in CF patients with adequate to establish the diagnosis. The dif- involvement. Often hepatobiliary involve- long-standing cirrhosis, and cholangiocarcino- ferentiation of severe constipation from DIOS ment is of no clinical consequence , but in ma has been reported in CF patients with long- based on history, physical examination find- a minority of cases it is severe and constitutes standing biliary fibrosis. Because CF pa- ings, and imaging findings is not always pos- the second leading cause of death in CF pa- tients now live longer into adulthood, advanced sible, although the distribution of feces on ra- tients (3–5%) after respiratory and transplant liver disease has become increasingly impor- diographs can be helpful in some cases [6, 34]. complications [1, 2, 11, 30]. Hepatocytes do tant in their medical management. The initial approach to treatment is empiri- not express CFTR and are therefore not the cal, with most patients responding to oral rehy- proximal cause of hepatobiliary disease in Gastrointestinal Manifestations dration and osmotic laxatives containing poly- CF patients. Rather, hepatocyte dysfunction Up to 90% of patients with classic CF have ethylene glycol, in cases of both constipation is the result of CFTR expressed in the apical gastrointestinal complications. Meconium and incomplete DIOS. In cases of moder- cells of cholangiocytes. This loss of protein ileus in the neonatal period is often the first clin- ate DIOS, a similar approach can be used ini- function in cholangiocytes reduces the hydra- ical indication of CF in patients with classic dis- tially if the patient is not vomiting. In severe tion and alkalization of bile secretions lead- ease and is a clinical rarity in patients with non- cases of DIOS when the symptom of bilious ing to increased biliary secretion viscosity, classic disease. In adults with classic disease, vomiting is present, hospitalization is recom- which can cause periodic blockage of the bile distal intestinal obstruction syndrome (DIOS), mended, and serial water-soluble enemas can ducts. These secretions coupled with their first called “meconium ileus equivalent” by be performed over several days if necessary. toxic action on the biliary epithelium result in Jensen in 1962, is a common manifestation of CT can be performed when DIOS symptoms chronic focal periductal inflammation, steno- CF, affecting approximately 35 per 1000 adult are protracted and uncharacteristic. CT can sis, strictures, and fibrosis. Biliary stasis and patients per year, and up to 15% overall [5, 34]. show dilated loops of proximal small bowel, infection can lead to lithogenesis. Now referred to as “distal intestinal obstruction often with fecalized contents from slow transit, US can show prominent periportal echo- syndrome” or “DIOS,” DIOS is characterized and inspissated fecal material in the cecum and genicity, which is frequently described in by the accumulation of abnormally viscous fe- distal ileum, often with a masslike appearance. patients with CF, corresponding to the in- cal contents within the distal small bowel. In Early aggressive therapy can usually obviate creased periportal thickness that is caused contradistinction to constipation, which is also surgery. Although the evidence for treatment by proliferation of bile ducts with or without common in CF patients, in which the fecal and management of DIOS remains empirical biliary stasis, inflammatory changes, edema, contents are distributed throughout the bowel, in the absence of randomized control trials to and fibrosis. US also depicts biliary calculi. in DIOS impacted stool is concentrated in the guide therapy, given the elevated risk for recur- Because of high soft-tissue contrast resolu- terminal ileum and cecum. Presenting clinical rence in patients who experience an episode tion, MRI or MRCP is superior to US in the symptoms range from subacute or chronic ab- of DIOS, maintenance laxative therapy can be evaluation of biliary strictures and calculi dominal pain from fecal impaction to complete considered in this patient population. (Fig. 7). The cholangiopathy related to intestinal obstruction with signs and symptoms Intussusception is more common in pa- CF simulates the imaging findings of prima- of small-bowel obstruction. The impacted stool tients with CF diagnosed in childhood, with ry sclerosing cholangitis and those of recur- can sometimes be palpated as a cecal mass and an average age of presentation of 10 years, rent pyogenic cholangitis. Focal biliary fibro- may be visualized on abdominal radiographs but also occurs in approximately 1% of adult sis is present in the majority of patients with [6, 7, 34]. The fecal mass can become strongly CF patients [6, 34]. The lead mass is thought 6 AJR:209, July 2017  Typical and Atypical Patterns of Cystic Fibrosis to be due to the inspissated stool. Clinical- glucocorticoid therapy, and inactivity. Vi- compressible tubular structure medial to the ly significant intussusception in adults is un- tamin D deficiency from gut malabsorption seminal vesicles. common and often spontaneously resolves; and resultant decreased absorption of calcium The pathogenesis of CBAVD is thought to however, in patients presenting with obstruc- also contribute to bone disease. be related to abnormal secretions during ear- tion, intussusception is identified as the un- There is emerging evidence that an insulin- ly embryogenesis from faulty CFTR with re- derlying cause in 20% of cases. Sometimes deficient state from reduced pancreatic func- sultant trapping of debris in the developing intussusception is found in combination with tion in patients with CF may contribute to re- wolffian duct. Scrotal abnormalities can also Downloaded from ajronline.org by 203.192.239.182 on 06/15/24 from IP address 203.192.239.182. Copyright ARRS. For personal use only; all rights reserved DIOS. At both US and CT, intussusception duced osteoblast activity [22, 39]. As awareness be seen at US as obstructive azoospermia and has the classic targetlike appearance (Fig. 9). has grown, increased attention has been given can result in tubular ectasia in the epididymal Transient intussusception involving only the to the reduction of modifiable risk factors, such head and dilatation of the rete testes within small bowel can also be seen. as poor nutrition, and to performance of bone the testicles (Fig. 11). The appendix in patients with CF is com- density screening. The recommendations monly enlarged from mucoid impaction and proposed by the Cystic Fibrosis Foundation in Conclusion can simulate features of acute appendicitis at 2005 and 2011 include dual-energy x-ray ab- There is a diverse and growing population imaging. Although the reported incidence sorptiometry (DEXA) scanning of CF patients of adult patients with CF. Up to 7% of CF cases of acute appendicitis is lower in patients with beginning at the age or 18 years or earlier if are now diagnosed de novo in adults. Recurrent CF than in the general population, the diag- substantial risk factors for bone disease exist pancreatitis, chronic sinusitis, and CBAVD are nosis of acute appendicitis can sometimes be. Bisphosphonate therapy is indicated in pa- several of the ways in which CF is identified delayed in CF patients. Patients with CF ex- tients with a Z score of less than –2 on DEXA in adult patients with relatively rare mutations perience an increased rate of perforation and scanning (Fig. 4). and with overall milder manifestations. It is im- abscess formation, in part because of the over- portant for radiologists to recognize the wide lapping appearance and possibly because of Reproductive System–Related spectrum of CF to optimally monitor disease masking of acute symptoms due to chronic an- Manifestations progression and response to therapeutic inter- tibiotic and steroid use [2, 34]. As the life expectancy of patients with CF ventions in distinct adult patient populations. Almost all adult CF patients have nonspe- improves, the issue of infertility is increas- cific colonic wall thickening and pericolon- ingly raised by both women and men seen at References ic infiltration, which can be identified at CT, adult CF clinics; however, the impact of CF 1. Davis PB. Cystic fibrosis since 1938. Am J Respir most commonly involving the ascending co- on the fertility of women is less clear than it Crit Care Med 2006; 173:475–482 lon [33, 35]. Acute colitis can be seen as a is on the fertility of men. Although CFTR is 2. Wilschanski M. Patterns of gastrointestinal dis- complication of chronic antibiotic therapy expressed in the cervical mucosa and the cer- ease associated with mutations of CFTR. Curr for respiratory infections due to C. difficile vical mucus is abnormally thickened and te- Gastroenterol Rep 2008; 10:316–323 and can present in the absence of the clin- nacious throughout the menstrual cycle, with 3. Morrissey BM, Schock BC, Marelich GP, Cross ical symptom of diarrhea given the role of potential to significantly impact the fertility CE. Cystic fibrosis in adults: current and future the CFTR gene in chloride secretion into the of women with CF, from an imaging stand- management strategies. Clin Rev Allergy I­ mmunol intestinal lumen; in rare cases, acute colitis point, there are no anatomic abnormalities or 2003; 25:275–287 can lead to total colectomy (Fig. 10). Positive specific imaging findings in the female repro- 4. 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