Ear disease is not a common complication in cystic fibrosis

Although upper respiratory tract involvement is a common finding in cystic fibrosis (CF), there is no agreement on whether hearing is affected in these patients. We studied 75 CF subjects and 50 healthy agematched children with the same audiological protocol. An original scoring system was used to quantify the degree of hearing involvement (normal, mild, moderate and severe) in each subject. Prevalence of ear involvement in children with CF was similar to that in agematched control subjects (25.4% and 18% respectively,P>0.05). Ear disease in CF was not related to pulmonary disease, radiological sinusitis, nasal polyposis, or use of parenteral aminoglycosides. These data showed that the risk of ear disease in CF was not increased even if patients with severe audiological involvement were described only in the CF group.     

Dopamine-beta-hydroxylase in patients with cystic fibrosis

The enzymatic activity of plasma dopamine-beta-hydroxylase (DBH) was determined in 92 children/adolescents with cystic fibrosis, in 25 parents (heterozygotes) of these patients and in 68 healthy controls. Statistically significant (P<0.01) lower DBH levels were found in cystic fibrosis patients (17.9±1.4 mol/min per 1, SEM) compared to the controls (25.5±2.1 mol/min per 1). In 37 patients plasma norepinephrine and dopamine levels were compared to the enzymatic activity, no significant correlation between these variables being shown (r=-0.134 for norepinephrine; r=0.159 for dopamine). However, due to the large variability of DBH within the groups and due to the lack of relationship of this enzymatic activity to plasma catecholamines, it is concluded that these differences may neither account for the observed elevation of plasma dopamine in cystic fibrosis patients (0.94–6.73 nmol/l vs. 0.01–0.986 nmol/l for controls) nor for their putative autonomic dysfunction.Abbreviations DBH dopamine-beta-hydroxylase - CF cystic fibrosis - NE norepinephrine - DA dopamine - HZ heterozygote - COMT catechol-O-methyltransferase     

Myocardial fibrosis — a rare complication in patients with cystic fibrosis

We report a 10-month-old male infant who was admitted to our hospital with a history of failure to thrive and bulky stools. On examination, he was dystrophic and had a protruding abdomen, but he was well oxygenated and his lungs were clear on auscultation. A tachycardia of 145 beats per min and radiological evidence of cardiomegaly indicated involvement of the heart, but an ECG failed to show signs of myocarditis or cardiac hypertrophy. An elevated sweat chloride concentration of 141 mEq/l confirmed the diagnosis of cystic fibrosis (CF). Molecular analysis revealed heterozygosity for the common mutation delta F₅₀₈. He died unexpectedly of a sudden cardiac arrest 2 days later. Autopsy revealed scattered myocardial necrosis and fibrosis. Some 50 documented cases of myocardial fibrosis in infants with CF have been reported. Suggested causes such as malnourishment and hypovitaminosis remain speculative as systematic studies have yet to be done.     

Protein-energy malnutrition in cystic fibrosis patients

Protein-energy malnutrition with associated specific nutrient deficiencies is an important feature of cystic fibrosis and has been recognized as a poor prognostic factor. Therefore, the nutritional status of cystic fibrosis patients has to be evaluated regularly by diet diaries, clinical evaluation, anthropometry and more sophisticated methods, such as bioelectrical impedance analysis. Nutritional management, including nutritional rehabilitation programmes, of cystic fibrosis patients is well established today. Consequently, protein-energy malnutrition is no longer acceptable in cystic fibrosis patients, except perhaps in end-stage disease when lung transplantation is not considered.     

Calcification of the pancreas in cystic fibrosis

Using the gastric insufflation method, 5 cases of pancreatic calcification have been detected in a series of 60 patients with cystic fibrosis. All patients were over 5 years of age. Four of them showed a diabetic curve at glucose tolerance test and 2 have recently developed frank diabetes mellitus. The value of gastric distension by gas in the radiological detection of pancreatic calcification and the relatively high frequency of such calcification in cystic fibrosis are emphasized. The pathogenesis of the calcific change and its clinical significance are briefly discussed.     

Radiographic reduction of intussusception in patients with cystic fibrosis

Cystic fibrosis (CF) is a genetic disorder affecting approximately one in 2,500 births in the United States. Nearly 1% of patients with CF will develop intussusception, which is commonly ileocecal and felt to be secondary to inspissated feces. These patients generally present before the age of ten. Once the diagnosis of intussusception is confirmed on ultrasound or CT, surgery has been the mainstay of treatment in this patient group. We propose the use of air and contrast enemas as effective and beneficial non-operative approach in these patients. Clinical and imaging findings in four children with known CF who presented with intestinal intussusception, average age 13.25 +/- 5.3 years (range 8-18 years) were reviewed. Patients were diagnosed using ultrasound (n = 3) or abdominal CT (n = 1). All patients suffered from an ileocolic intussusception. Air and Gastrografin(R) enemas were used in an attempt to reduce the intussusception. There were six separate successful intussusception reductions in four patients. Three patients required multiple attempts (2.3 +/- 0.6). Air enemas were used initially in all cases. Gastrografin(R) was used successfully following the failure of air enema in one patient. One patient suffered three separate intussusceptions over a period of 18 months, which were all successfully reduced using air. There were no complications and the patients tolerated the procedure well. Intussusception is an uncommon but serious complication in children with CF. While surgical reduction has been the mainstay of treatment for these patients, we demonstrated that reduction of an intussusception using air or contrast can be accomplished safely, without anesthesia, and should be the initial treatment option.     

Sputum penetration of fusidic acid in patients with cystic fibrosis

We report the sputum penetration and efficacy of fusidic acid in 16 children with cystic fibrosis (CF) who were hospitalized because of acute respiratory tract infection due to Staphylococcus aureus. Penetration into sputum and response to therapy were evaluated after intravenous and oral drug administration. Oral fusidic acid therapy (approximately 1,000 mg/m²/day) achieved highly satisfactory serum (10–50 g/ml) and sputum (0.6–4.0 g/ml) concentrations which were several fold greater than the MIC of the infecting S. aureus strains. The average percentage penetration into sputum during the steady state phase of the concentration-time curve was between 5 and 10%. The efficacy of treatment is reflected by improvement in clinical findings and laboratory data. Eradication of S. aureus from the sputum was documented in 14 of the 16 patients, although 6 months later this was shown to be transient in half of them (7 of 14 patients). No staphylococci resistant to fusidic acid were found. Nine of the 14 children with documented staphylococcal eradication from the sputum had received gentamicin in addition to fusidic acid therapy which could have added antistaphylococcal efficacy. Further investigations are needed to formulate the definitive role of fusidic acid in the antistaphylococcal therapy of patients with CF.     

Identification of novel mutations in Arabs with cystic fibrosis and their impact on the cystic fibrosis transmembrane regulator mutation detection rate in Arab populations

The cystic fibrosis transmembrane regulator (CFTR) gene in Arab patients with cystic fibrosis (CF) (sweat chloride >60 mmol/l) from 61 unrelated families was screened for mutations in exons 3, 4, 5, 7, 10, 11, 16 and 19 and for mutations W1282X, N1303K and 3849 + 10kbC → T. Eight novel mutations were identified. These are: in exon 4: a) 425del42 (an in-frame 42 bp deletion that removes 14 amino acids and causes Gln₉₈ → His at the point of deletion), b) 475G → T (Glu₁₁₅ → Stop) and c) 548A → T (His₁₃₉ → Leu); in intron 5, 711 + 1G → A (splice site mutation); in exon 10, 1548delG (deletion of a “G” nucleotide causing a frameshift mutation that alters the amino acid sequence at residue 473 and results in translation termination at residue 526); in exon 11, a) 1729T → C (Ph₅₃₃E → Leu) and b) 1811 + 2 (splice site mutation) and finally in exon 19, 3361A → T (Lys₁₁₇₇ → Stop). All mutations were detected by heteroduplex analysis and identified by sequencing. Of more than 850 known CFTR mutations, only 9 were encountered. The comparative frequencies of the most common mutations are: 1548delG> I123V=ΔF508=3120 + 1G → A > H139L. Screening for these five mutations identifies 60% of the CF alleles in Arab populations. The novel mutation 1548delG is the most frequent (17%) among Arabs. Conclusion Novel Arab-specific mutations were identified in the CFTR gene underlying cystic fibrosis. As a result of this study, the CFTR mutation detection rate among Arabs with cystic fibrosis is now comparable to that of other populations. Received: 18 December 1998 / Accepted: 14 May 1999     

Appendico-cutaneous fistula in cystic fibrosis

Appendico-cutaneous fistulae are rare. We describe a 12-year-old girl with cystic fibrosis (CF) and a chronically draining sinus in the right iliac fossa, found to be a primary appendico-cutaneous fistula. Misdiagnosis of right iliac fossa pain in patients with CF and the preponderance of complicated disease frequently lead to manifestations of appendicitis rarely seen in usual clinical practice.     

HL-A antigens in cystic fibrosis

HL-A frequencies of 28 patients with cystic fibrosis and of 240 unrelated controls were compared. No statistically significant difference of HL-A frequencies could be observed for both groups. A slightly increased HL-A 2 frequency is considered a chance phenomenon. In accordance with a previously demonstrated lacking association of the ABH blood group substances no correlation with certain HL-A antigens was demonstrable.     

Sodium chloride deficiency in cystic fibrosis patients

Sodium chloride deficiency (SCD) was observed within the 1st year of life in 12 of 46 cystic fibrosis (CF) patients between July 1989 and September 1992. All patients showed sweating, loss of appetite, fever, vomiting, irritation, dehydration, weakness, and cyanosis during an attack. Mean plasma sodium, potassium and chloride levels were 122.9 (range 106–135), 2.5 (range 1.6–3.5), and 73.3 (range 60–90) mEq/l respectively. Alkalosis and elevated plasma renin activity were detected in all patients. Of the patients, 50% showed microscopic haematuria, and hypercalciuria was detected in two out of four patients. Low urinary sodium and high urinary potassium were observed in the four examined patients. Increased creatinine, BUN and uric acid values returned to normal with treatment. All the patients were treated initially with intravenous fluids and electrolyte solutions. All patients were less than 7 months of age during the first attack, five received only breast milk and the others breast milk with formula milk. Their oral salt supplement was 2–4 mEq/kg per day, which is recommended for CF patients, but could be deficient in excessively sweating infants. The genotype of these patients might be cause of high salt losses. F508 is the most common mutation with the frequency of 38% in our CF patients with SCD, but the frequency of unknown mutations is high (54%).     

Secular changes in anthropometric data in cystic fibrosis patients

The aim of this study was to study the secular changes in anthropometric data over calendar time in patients with cystic fibrosis (CF). Growth curves were constructed for 270 patients based on height and weight registrations from the medical files. Height, body mass index (BMI), magnitude of pubertal peak height velocity (PHV) and age at PHV were analysed for possible secular changes from the 1960s to the 1990s. There was a significant change in height over calendar time in only 1 of 12 age groups. BMI showed a significant increase in 10- and 15-y-old boys and girls and in 5-y-old girls. The magnitude of PHV changed significantly over time, whereas age at PHV was constant. No significant changes in height and age at PHV over calendar time were observed; this was probably due to a selection bias since the oldest patients, who survived to be part of the present investigation, represented milder forms of the disease. The increase in BMI and change in magnitude of PHV over calendar time may reflect the improvement in treatment leading to a better survival and clinical status through puberty. The increase in BMI and change in magnitude of PHV were sufficient to overcome the selection bias from older patients with milder disease.     

Granulomatous appendiceal disease in cystic fibrosis

Abdominal pain due to acute appendicitis in patients with cystic fibrosis is uncommon. A review of 572 patients with cystic fibrosis from the cystic fibrosis clinic of the Children's Hospital of Pittsburgh from 1959 to 1983 disclosed only 4 in whom the diagnosis of acute appendicitis lead to appendectomy. In 3 of these the diagnosis was confirmed at operation. In 1 child, laparotomy for a persistent asymptomatic abdominal mass disclosed a huge cecal fecaloma originating in the appendiceal lumen. Histological examination of the appendix established the diagnosis of cystic fibrosis. Large, symptomatic appendiceal granulomas were noted in 6 other children; these simulated abdominal tumors in 2. In 3 others there was smoldering infection and abscess with sepsis and in 1 a colocystic fistula. Such chronic granulomas, acute appendicitis, meconium ileus, and nonsurgical abdominal pain in cystic fibrosis can best be differentiated by careful clinical examination before and after treatment for meconium ileus equivalent. The granulomas involve not only the appendix but also the cecum and ascending colon. Contrast X-ray studies are of little value in diagnosis. The appendix in cystic fibrosis undergoes changes that are diagnostic even in the newborn; the granulomas described here appear to represent a progression of these changes.Offprint requests to: W. K. Sieber     

Abdominal manifestations of cystic fibrosis in children

Pulmonary complications remain the main cause of mortality in cystic fibrosis, but the presenting symptoms in children are often related to gastrointestinal or pancreaticobiliary disease. Furthermore, abdominal manifestations are now seen throughout childhood, from infancy to adolescence. The child might present in the neonatal period with meconium ileus or its attendant complications. The older child might present with distal intestinal obstruction syndrome or colonic stricture secondary to high doses of pancreatic enzyme replacement. Less-common gastrointestinal manifestations include intussusception, duodenitis and fecal impaction of the appendix. Most children also show evidence of exocrine pancreatic deficiency. Radiologically, the combination of fat deposition and pancreatic fibrosis leads to varying CT and MR appearances. A higher than normal incidence of pancreatic cysts and calcification is also seen. Decreased transport of water and chloride also increases the viscosity of bile, with subsequent obstruction of the biliary ductules. If extensive, this can progress to obstructive cirrhosis, portal hypertension and esophageal varices. Diffuse fatty infiltration, hypersplenism and gallstones are also commonly seen in these patients. We present a pictorial review of the radiological appearance of these abdominal manifestations. The conditions are dealt with individually, together with typical appearances in various imaging modalities.     

Abnormal fatty acid pattern of the plasma cholesterol ester fraction in cystic fibrosis patients with and without pancreatic insufficiency

In our previous work it was found that in cystic fibrosis patients with and without pancreatic insufficiency, the fatty acid pattern of the plasma long chain, non-esterified fatty acid fraction is strikingly abnormal in comparison with the corresponding pattern of healthy subjects. However, other investigators have shown abnormal fatty acid patterns only in patients with pancreatic insufficiency. Therefore, we studied the plasma cholesterol ester fraction in cystic fibrosis patients of both types by gas liquid chromatography. It was found that the absolute total concentration of the plasma cholesterol esters in cystic fibrosis patients with and also without pancreatic insufficiency is significantly lower than in healthy subjects.Furthermore, the fatty acid pattern of this lipid fraction is significantly abnormal in both groups of patients, although to a lesser extent in patients without pancreatic insufficiency.     

Chronic metabolic alkalosis in an infant with cystic fibrosis

A 6-month-old infant suffering from cystic fibrosis is reported. In spite of an apparently appropriate treatment and in absence of respiratory infection, the patient showed progressive anorexia, intermittent vomiting and weight loss. These non-specific signs and symptoms could all be explained by metabolic alkalosis and disappeared immediately after oral supplementation with sodium and potassium chloride. This unusual metabolic complication should be searched for in every cystic fibrosis infant with unexplained anorexia and failure to thrive.     

Bronchial mucous glands in the newborn with cystic fibrosis

The size of bronchial mucous glands in 21 patients who presented with meconium ileus and dieds at less than three weeks of age were compared quantitatively with that of 28 control patients. There were no significant differences by most methods of comparison. However, pulmonary infection was seen in a higher percentage of cystic fibrosis patients. The absence of mucous gland hyperplasia at birth suggests that mucous obstruction of airways may not be primarily responsible for the increased susceptibility to respiratory tract infection in cystic fibrosis, but when present later in life may aggravate the infection. Offprint requests to: Department of Anatomical Pathology, Royal Children's Hospital, Flemington Road, Parkville, Victoria, 3052, Australia     

Encephalopathy in cystic fibrosis

Cystic fibrosis liver disease (CFLD) affects a large proportion of cystic fibrosis (CF) patients; however encephalopathy is a rare complication. While classical hepatic encephalopathy can be a feature of end-stage liver disease, “hyperammonemic encephalopathy” can be precipitated in previously stable CFLD by various triggers including systemic corticosteroids. We describe one such case and review the relevant literature.     

Mucocele of paranasal sinuses in a young infant with cystic fibrosis

We report the case of an infant who developed severe nasal obstruction as an unusual first presentation of cystic fibrosis (CF). Computed tomography (CT) showed homogeneous opacification of the symmetrically enlarged paranasal sinuses that gave the clue for the final diagnosis.