Celiac Disease

Celiac Disease

Key points

·         Celiac disease is an immune-mediated enteropathy that results from increased sensitivity to and intolerance of gluten proteins. The immunologic reaction to gluten proteins promotes injury to the intestinal mucosa, resulting in diarrhea, steatorrhea, bloating, flatulence, and fatigue in adults. In children, the condition presents as irritability and failure to thrive. Enteropathy is its most common presentation, though celiac disease can affect other organ systems

·         Celiac disease is genetically transmitted and affects 0.5% to 1% of the people in the western hemisphere and Europe

·         Presence of class II human leukocyte antigen DQ2 and DQ8 confers an increased risk of developing celiac disease

·         Serologic detection of immunoglobulin A (IgA) anti-endomysial antibodies during a gluten–non-deprived diet is a useful screening test in suspected individuals

·         The sine qua non of diagnosis in celiac disease is small intestinal biopsy obtained during a gluten–non-deprived diet

·         A gluten-free diet is the mainstay of treatment

Background

Description

·         Celiac disease is a lifelong intolerance to gluten, causing autoimmune injury to the mucosa of the upper small intestine. Damaged intestinal epithelium subsequently impairs digestion and absorption of nutrients, producing the clinical signs and symptoms of the disease

·         The condition may be classified as asymptomatic, classic, and atypical:

o    Asymptomatic patients present with no clinical disease manifestations

o    Classic presentation symptoms include diarrhea, steatorrhea, bloating, flatulence, and ensuing nutrient and mineral deficiencies.

o    Atypical patients present with predominantly extraintestinal manifestations with absent or minimal gastrointestinal manifestations. Extraintestinal manifestations include anemia, dermatitis herpetiformis, aphthous stomatitis, neurologic dysfunction, osteopathy, and diabetes mellitus

·         Synonyms include gluten-sensitive enteropathy and nontropical sprue

Epidemiology

·         Celiac disease affects 0.5% to 1% of the population

·         Its prevalence is decreased among blacks and those of Hispanic or Asian ethnicity

·         The incidence of symptomatic celiac disease in adults is estimated at 2 to 13 per 100,000 per year

Causes and risk factors

·         Gliadins and glutenins in the presence of CD4+ T cells with HLA-DQ2 and HLA-DQ8 activate cytokine production and clonal expansion of antibody-producing B cells, which lead to lymphocyte-mediated destruction of the epithelium and mucosa. This is termed the adaptive response. The resulting injury impairs villous function and absorption of nutrients, producing the clinical signs and symptoms of celiac disease. In addition, there is an innate response, which involves interleukin-15 expressed by enterocytes

·         Celiac disease affects predominantly the mucosa of the proximal small intestine, which receives the majority of dietary gluten. Distal parts of the small intestine are less affected because gluten has generally been absorbed by the time the enteric bolus reaches these areas

Risk factors

Geographic:

·         The highest incidence of celiac disease is found in western Europe and the U.S.

Age:

·         Peaks in diagnosis occur in childhood (when approximately 6% of the cases are diagnosed) and between the fifth and seventh decades of life

Female gender:

·         The female-to-male ratio in celiac disease is about 2:1

Heredity:

·         Celiac disease is an inherited condition with a concordance rate of 70% to 100% between monozygotic twins

·         The concordance rate among siblings is 7% to 30%. The rate increases up to 40% if the sibling has the same HLA risk haplotype as the index case

·         Risk is higher among first-degree relatives of those with the condition, with a 1:22 ratio, compared with the risk among second-degree relatives (1:29)

·         At lease 11% of first-degree relatives of index cases have celiac disease

Infant diet:

·         If gluten-containing foods are brought into the diet within the first 3 months or after 7 months of life, the risk of developing celiac disease increases five-fold

·         The risk is higher in the first 3 months because of the infant's underdeveloped intestinal mucosal barrier, which allows immunogenic peptides to cross the epithelium

Absent breastfeeding:

·         Breastfeeding protects against the development of celiac disease in childhood. Gradual introduction of gluten-containing foods while breastfeeding decreases the risk by 48%. Its benefit in preventing the disease later in adulthood, however, is unknown

·         Breastfeeding may have the following protective effects:

o    Continuation of breastfeeding limits the amount of gluten a child receives

o    Breast milk protects against gastrointestinal infections that increase the permeability of the intestinal mucosa to gluten

o    IgA in breast milk agglutinates with antigen, preventing the antigen's uptake to the mucosa

o    Breast milk has T-cell–specific suppressive effects

Inflammatory bowel disease:

·         A few studies have shown an increased prevalence of celiac disease in patients with Crohn disease and, to a lesser extent, ulcerative colitis

Comorbid risk factors:

·         Lymphocytic colitis (increases risk of celiac disease 15%-27%)

·         Down syndrome (increases risk 12%)

·         Type 1 diabetes mellitus (increases risk 5%-6%)

·         Autoimmune thyroid disease (increases risk 5%)

·         Chronic fatigue syndrome (increases risk 2%)

Screening

Summary approach

Screening for celiac disease is essential to avoid unnecessary loss of growth potential in children at risk for the disease (eg, those children with a family history) and untreated progression of disease or complications in adults similarly at risk (eg, those with autoimmune disease). In these instances, testing for the disease even in asymptomatic patients should be strongly considered.

Population at risk

·         Screening for celiac disease is recommended for individuals with certain autoimmune and comorbid disorders (eg, lymphocytic colitis, Down syndrome, type 1 diabetes mellitus, autoimmune thyroid disease, and chronic fatigue syndrome) who are at increased risk for celiac disease. Screening is also recommended for first-degree relatives of patients with celiac disease. Screening of the general population for celiac disease is not recommended

·         Screening for celiac disease is also advised for patients with the following conditions:

o    Unexplained iron-deficiency anemia

o    Early-onset or unexplained osteopenia or osteoporosis

o    Unexplained elevated hepatic transaminases

o    Dermatitis herpetiformis

o    Unexplained epilepsy

o    Failure to thrive, developmental delay, growth retardation, and other unexplained nutritional problems (pediatric patients)

o    Poor glucose control, lactose intolerance, diarrhea, and bloating (diabetic patients)

o    Recurrent pancreatitis and no clear etiology

o    Unexplained infertility, recurrent spontaneous abortion, stillbirth, perinatal death, and intrauterine growth retardation in women

o    Unexplained chronic diarrhea

Evidence

·         According to a population-based cohort study of 111 index cases and their family members from southeast Minnesota, the prevalence of celiac disease in family members was estimated to be 11%. All affected family members carried the at-risk HLA-DQ genotype. Occult intestinal villous atrophy was present in more than half of the cases. High risk factors for celiac disease include carrying HLA-DQ2 (OR = 16.1) and being a sibling (OR = 2.5).[1]Level of evidence: 3

·         A multicenter, prospective study was conducted from 2002 to 2004 on 976 adult subjects who attended a participating primary care practice. Those with symptoms or conditions known to be associated with celiac disease were tested. Of these, 30 (3.07%) had a positive anti-tTG test, and celiac disease was diagnosed in 22 patients (18 women). Prevalence of celiac disease in the serologically screened sample was 2.25%. Diagnostic rate was 0.27 cases/1000 visits at baseline and 11.6/1000 after active screening.[2]Level of evidence: 3

References

Screening modalities

·         Serologic testing for the detection of IgA antiendomysial antibodies is the preferred method of screening for individuals suspected of having celiac disease because it has high sensitivity and specificity (approaching 100%)

·         A total serum IgA level is preferred as patients deficient in IgA may be unable to produce the antibodies on which further screening tests depend

Prevention

Summary approach

Celiac disease in susceptible individuals can only be successfully prevented by strict avoidance of all gluten-containing foods.

Population at risk

Infants with a family history of celiac disease are at increased risk and may benefit from delayed introduction of gluten in the diet and prolonged breastfeeding.

Preventive measures

·         Introduction of gluten-containing food within the first 3 months of life increases the risk of celiac disease. At the time of weaning, gluten-containing food products should not be introduced in large amounts

·         Breastfeeding is encouraged to decrease the risk of celiac disease; however, the optimum duration of breastfeeding is not known

Bronchiolitis

Bronchiolitis

Summary

Description

·         Viral inflammation of the bronchioles usually seen in young children and occasionally in high-risk adults

·         The most common serious respiratory infection in infancy

·         Seasonal occurrence often in epidemics

·         May lead to respiratory distress requiring in-hospital care

·         Treatment is largely supportive

·         Respiratory syncytial virus (RSV) is the pathogen in 70% to 80% of cases

Synonyms

Capillary pneumonia.

Immediate action

·         Assess for signs of respiratory distress and admit if baby is tired or compromised

·         Recognize risk factors for severe disease, including severe prematurity, bronchopulmonary dysplasia, and congenital heart disease

·         Look for intercostal retraction, pyrexia, and tachypnea, which predict need for hospital care

·         Tired babies who are unable to maintain fluid balance or feed adequately require hospital assessment

·         The higher the respiratory rate, the lower the arterial oxygen tension

·         Hypercapnia does not usually occur until respirations exceed 60 breaths/minute; it then increases in proportion to the tachypnea

·         Consider admission in young infants if respirations exceed 60 breaths/minute, as feeding is likely to be severely compromised

·         Signs of severe, life-threatening illness are central cyanosis, tachypnea of more than 70 breaths/minute, listlessness, and apneic spells

·         At this stage, the chest may be greatly hyperexpanded and almost silent to auscultation because of poor air exchange

Urgent action

·         Assess respiratory effort and hydration status

·         Assess parental level of concern about the severity of child's illness, and ability to care for the child

Key points

·         Bronchiolitis is a viral, self-limited respiratory illness that resolves without long-term complications in most previously well children

·         The management of bronchiolitis is largely supportive; few medical therapies have demonstrated effectiveness in reducing clinical symptoms and hospitalizations

·         The single most effective means of preventing nosocomial spread of RSV bronchiolitis is hand decontamination with alcohol hand rubs or soap and water washes prior to and after each patient contact

Background

Cardinal features

Pathology:

·         Virus-induced inflammation of the bronchiolar epithelium, with hypersecretion of mucus and edema of the surrounding submucosa

·         These changes result in formation of mucous plugs obstructing bronchioles with consequent hyperinflation or collapse of the distal lung tissue

·         Infants are particularly apt to experience small airway obstruction because of the small size of the normal bronchioles; even minor thickening of the bronchiolar wall in infants may profoundly affect airflow

·         Resistance in small air passages is increased during inspiration and expiration, but because airway radius is smaller during expiration, resultant ball valve respiratory obstruction leads to early air trapping and overinflation

·         Atelectasis may occur when obstruction becomes complete and trapped air is absorbed

Presentation:

·         Most affected infants have history of exposure to older children or adults with minor respiratory diseases within the week preceding onset of illness

·         Mild upper respiratory tract infection with serous nasal discharge and sneezing usually precedes

·         These symptoms usually last several days and may be accompanied by diminished appetite and fever of 101 to 102ºF (38.5-39ºC)

·         Gradual development of respiratory distress is characterized by paroxysmal wheezy cough, dyspnea, tachypnea, and irritability

·         In mild cases, symptoms disappear in 1 to 3 days

·         In more severely affected patients, symptoms may develop within several hours, and the course is protracted

·         Breast- or bottle-feeding may be difficult because the rapid respiratory rate may not permit time for sucking and swallowing

·         Other systemic manifestations, such as vomiting and diarrhea, are usually absent

·         Hypoxemia is frequent and tends to be more marked than anticipated on the basis of the clinical findings. When severe, it is frequently accompanied by hypercapnia and acidosis

·         Second and third severe attacks are uncommon, although infection does not grant long-term immunity

Causes

Common causes

·         Respiratory syncytial virus (RSV) (70% to 80%)

·         Parainfluenza

·         Adenovirus

·         Human metapneumovirus

·         Rhinovirus (tends to cause upper respiratory tract illness more than lower)

·         Influenza virus

·         Chlamydial pneumonia

·         Source of viral infection is usually a family member with minor respiratory illness

·         Older children and adults tolerate bronchiolar edema better than infants and do not acquire the clinical picture of bronchiolitis, even when the smaller airways of the respiratory tract are infected

RSV:

·         Medium-sized, membrane-bound, RNA paramyxovirus

·         Incubation period from exposure to first symptoms is about 4 days

·         Virus is excreted for variable periods, probably depending on severity of illness and immunologic status

·         Most infants with lower respiratory tract illness shed virus for 5 to 12 days after hospital admission

·         Excretion for 3 weeks and longer has been documented

·         Spread of infection occurs when large, infected droplets, either airborne or conveyed on hands, are inoculated in the nose or conjunctiva of a susceptible subject

·         RSV is probably introduced into most families by schoolchildren undergoing reinfection

·         Nosocomial infection during RSV epidemics is an important concern. Virus is usually spread from child to child on the hands of caregivers

·         Adults undergoing reinfection have also been implicated in spread of the virus

Serious causes

Adenoviral bronchiolitis may be associated with a higher incidence of complications, including need for hospital admission and for supplemental oxygen.

Contributory or predisposing factors

·         Contact with infected person

·         Children in daycare environment

·         Heart-lung transplantation patient

·         Children with bronchopulmonary dysplasia

·         Adults: exposure to toxic fumes, connective tissue disease, immunocompromised state

·         Diminished lung function may play a role in determining which infants with viral infection acquire bronchiolitis

·         Infants whose mothers smoke cigarettes are more likely to get bronchiolitis than are infants of nonsmoking mothers

·         Despite risks of respiratory infections in children who attend childcare, bronchiolitis is more likely in infants who stay at home with mothers who are heavy smokers than in infants who attend daycare centers

·         Premature infants, especially those born at <30 to 32 weeks' gestation, and those with chronic lung disease, such as bronchopulmonary dysplasia, are at greatest risk for severe episodes of RSV-linked disease

·         Infants with congenital heart disease also are more prone to severe RSV-related illness

Epidemiology

Incidence and prevalence

Incidence

·         The incidence is highest during the winter and early spring

·         Medical care is provided to 1000 to 1500/100,000 annually in U.S.; estimated incidence is higher

·         In the U.S. and Britain, 1% to 3% of infants with bronchiolitis are admitted to hospital with the condition each winter

·         Of those admitted, about 2% to 5% will require mechanical ventilation; this is more likely in premature babies and babies with existing lung disease. The mortality rate is <1% for all infants overall, but ranges from 3% to 10% for infants with chronic lung disease or congential heart disease

Prevalence

·         It is estimated that in an urban setting about half of the susceptible infants undergo primary infection in each epidemic; virtually all are symptomatic

·         More than 90% of children are infected with RSV in the first 2 years of life

Demographics

Age

·         Newborn to 2 years (peak age 2-6 months), though can occur in adults

·         Placentally transmitted anti-RSV antibody has some protective effect

·         This may account for the low frequency of severe infections during the first 4 to 6 weeks of life, except in infants born prematurely

·         Serum antibody is not fully protective, and the age at which an infant undergoes first infection depends also on the opportunities for exposure

Gender

·         1:1 male to female as outpatients

·         2:1 male to female in hospital

Geography

·         RSV is distributed worldwide and appears in yearly epidemics

·         In temperate climates, these epidemics occur each winter and last 4 to 5 months

·         During the remainder of the year, infections are sporadic and uncommon

·         In the northern hemisphere, epidemics usually peak in January, February, or March, but peaks have been recognized as early as December and as late as June. At these times, hospital admissions for bronchiolitis and pneumonia of children younger than 1 year increase and decrease in proportion to the number of RSV infections in the community

·         In the tropics, the epidemic pattern is less clear

Socioeconomic status

·         Bronchiolitis occurs most commonly in male infants between 3 and 6 months of age who have not been breast-fed and who live in crowded conditions

·         Infants whose mothers smoke cigarettes are more likely to acquire bronchiolitis than are infants of nonsmoking mothers

·         Bronchiolitis is more likely to develop in infants who stay at home with mothers who are heavy smokers than in infants who attend daycare centers

·         Lower respiratory tract involvement occurs more often and earlier in life in lower socioeconomic groups and in crowded living conditions

·         American Indians and native Alaskans have high incidences of bronchiolitis

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