Etiologically involved immune mechanisms, possibly associated with chronic infection of Pseudomonas aeruginosa. The onset is sudden and manifests in pain, swelling and sometimes may be accompanied by skin changes such as maculopapular rash, erythema nodular and sometimes Purpura. It can be mono – or polyarticular, involving large or small joints, most commonly the knee, ankle, hand, elbow or shoulder.
Osteopenia or osteoporosis are common symptoms in patients with cystic fibrosis and are associated with fractures and kyphosis 3 .Classically, the diagnosis of cystic fibrosis is determined on the basis of clinical-anamnestic characteristics and then confirmed by a sweat test or molecular analysis.
A diagnosis of cystic fibrosis can be made with suspicion
70% of patients are diagnosed before the age of 1 year, usually in the first months of life. However, there are patients whose diagnosis is confirmed only after 10 years of age. A diagnosis of cystic fibrosis can be made with suspicion if presented:1. one or more phenotypic characteristics of CF;i2. proof of the CFTR function anomaly:- presence of pathogenic mutations in the CFTR gene;or-2 abnormal chloride values in sweat with quantitative pilocarpine ionophoresis (>60 mEq / L);or- specific values of difference of nasal potentials.The sweat Test remains the gold standard in diagnosing disease and allows you to assess the concentration of chlorine and sodium ions in sweating.
Normal electrolytes in sweat are <40 mmol / l; positive values in children > 60 mMol / l and in adolescents and young adults > 70 mMol / l ; ambiguous values: between 40-60 mMol / l should be repeated and interpreted in a clinical context. Chloride concentrations above 60 mMol / l in sweat at two different determinations determine the diagnosis of the disease.False positive results may be associated with Hurler syndrome, and false negative results may occur with acute salt loss. If FC is suspected in a person with hyponatraemia and Hypochloremia, the sweat test should be postponed to restore the 3: 6 chemical balance.
In the following specific situations, a genetic test is a preliminary diagnostic test:- diagnosis in utero of high-risk girls (in 2002, 4% of newly diagnosed people were identified by prenatal diagnosis);- Prenatal screening of girls in low-risk groups, but with ultrasound images suggesting disease;- neonatal screening (in 2002, 12.8% of newly diagnosed people were identified through neonatal screening);- examination of symptomatic infants (with tar obstruction) who are too small to produce adequate amounts of sweat;- study of a symptomatic person who has relatives with identified CFTR 6 mutations.
Genetic testing plays an important role in detecting mutations
Because cystic fibrosis is transmitted autosomally recessive, at conception each sibling of the patient has a 25% chance of being a carrier and developing the disease, 50% of being asymptomatic and 25% of being non-carrier and healthy. Prenatal testing is performed on fetal cells taken as a result of chorionic biopsy taken around 10-12 weeks of gestation or amniocentesis, usually around 15-18 weeks of intrauterine life.
The sweat Test should be performed after delivery in all patients suspected of cystic fibrosis. Genetic testing plays an important role in detecting mutations with important implications in the determinism of certain phenotypes. The best correlation between genotype and phenotype relates to pancreatic function.
The most common mutations are divided into two categories: those that cause pancreatic failure and those that are associated with normal pancreatic function (called “sufficient pancreas”, PS). People without pancreas seizure usually have one or two mutant PS-type alleles that are dominant in terms of pancreatic phenotype.In contrast, genotype-phenotype correlation is generally poor for lung diseases in cystic fibrosis. Lung diseases in individuals with identical genotypes vary widely, and the likely explanation is the intervention of environmental factors.Heterozygotes with ΔF508 / a455e mutations have better lung function than Homozygous Individuals with ΔF508.
- The severity of lung disease in people with one or two r117h mutations depends on the length of the Poly T region at intron 8, so if a patient has variant 5T in the CIS configuration they usually develop lung disease, and those with variant 7T or 9T have an extremely variable phenotype that can range from no pulmonary symptoms to moderate forms of the disease.
- Since the a455 and R117H mutations are associated with normal pancreatic function, the less severe lung dsease seen in these individuals may therefore be a better nutritional condition in June.
A negative genetic test for targeted mutations cannot rule out the disease. As more than 1000 mutations are currently described, several diagnostic kits are available on the market that can identify the most common mutations for a specific geographic area or population group. In truly suspicious cases, complex methods of genetic analysis of DNA (sequencing) can be used.The American College of Medical Genetics recommends carrier screening using a panel that highlights 23 mutations that include most mutations that have a prevalence greater than 0.1% in the general U.S. population.
Genetic testing is available for screening of asymptomatic
However, the list of screening mutations can be supplemented with other mutations to improve detection sensitivity for certain ethnic groups. Genetic testing is available for screening of asymptomatic people who want to know if they are carriers of a defective cystic fibrosis gene and typically includes pre-screening interviews as well as advice on the possible impact of positive or negative test results. This type of genetic testing allows parents to find out if they have an increased risk of giving birth to a child with cystic fibrosis.
Screening for cystic fibrosis carriers is recommended for the following people:- adults who have relatives in a family with cystic fibrosis;- partners of people with cystic fibrosis; if one partner has cystic fibrosis and the other has a defective cystic fibrosis gene, then the child will have a 50% chance of developing the disease;- couples who want to conceive children.If studies show that a person is a carrier of a defective cystic fibrosis gene, partner tests are also needed.
For a child to develop the disease, both parents must be carriers of the mutated gene. If your partner’s test results are negative, your child’s chances of developing the disease are minimal.Sticky and adjacent mucus in the airways promotes recurrent lung infections with antibiotic-resistant microbes, while exocrine pancreatic failure and sticky mucus in the intestines lead to nutrient malabsorption, causing malnutrition.