Clinical signssymptoms

The most typical, although non-specific, symptoms of esophageal dysfunction are GER, regurgitation and vomiting. While reflux does occur physiologically at all ages, there is a continuum between physiological GER and GERD leading to significant symptoms and complications. GERD is a spectrum of diseases that can best be defined as the symptoms and/or signs of esophageal or adjacent organ injury secondary to the reflux of gastric contents into the esophagus or, beyond, into the oral cavity or airways.

Presentation may be with decreased food intake and aversive behavior around feeds. There is often clearly abnormal sucking and swallowing. Not surprisingly, the mother-child interaction is affected, making the situation less easily treated.57 There may be poor weight gain. These infants have no apparent malformations, and may be diagnosed as 'non-organic failure to thrive' (NOFTT),58 a 'disorder' that is sometimes attributed to social/sensory deprivation, socioeconomic or primary maternal-child problems. Primary GERD is but one root cause of 'feeding problems' in infancy, others being structural abnormalities of the mouth/pharynx/upper gastrointestinal tract, neurological conditions, primary behavior disorders, cardiorespiratory problems, or metabolic dysfunction. However, no matter what the cause, so-called 'feeding problems' are bio-behavioral conditions, i.e. disorders in which biological and behavioral causes interact.59

A wide spectrum of clinical presentations of GERD exists, with relevant differences within ages (Table 4.2). Regurgitation is the most common presentation of infantile GER, with occasional projectile vomiting.7,60 In infants and young children, verbal expression of symptoms is often vague or impossible, and persistent crying, irritability, feeding and sleeping difficulties have been proposed as equivalents for heartburn in adults. Nevertheless, the descriptions for infants are non-specific and even functional. Therefore, poor weight gain, feeding refusal, back-arching, irritability and sleep disturbances have also been reported to be unrelated to GERD.61,62 Esophageal pain and behaviors perceived by the caregiver (usually the mother) to represent pain (e.g. crying and retching) potentially affect the response of the infant to visceral stimuli and the ability to cope with these sensations, either painful or non-painful.63 In addition, cow's milk allergy (CMA) may overlap with many symptoms of GER, and may coexist or complicate GERD in up to 40% of infants.64-66

Table 4.2 Spectrum of gastroesophageal reflux disease manifestations according to different ages

Symptoms and signs

Infants

Children

Adults

Vomiting

++

++

+

Regurgitation

+++

++

++

Heartburn/pyrosis

?

++

+++

Epigastric pain

?

+

++

Chest pain

?

+

++

Dysphagia

?

+

++

Excessive crying/irritability

+++

+

-

Anemia/melena/hematemesis

+

+

+

Food refusal/feeding disturbancies/anorexia

++

+

+

Failure to thrive/poor growth

++

+

-

Abnormal posturing/Sandifer's syndrome

++

+

-

Persisting hiccups

++

+

+

Dental erosions/halitosis/water brush

-

+

+

Hoarseness/globus pharyngeus

-

+

+

Persistent cough/aspiration pneumonia/wheezing

+

+

+

Laryngitis/ear problems

+

+

+

Laryngomalacia/stridor/croup

+

+

-

Laryngostenosis/resistant asthma/chronic sinusitis

-

+

+

Vocal nodule problems

-

-

+

ALTE/SIDS/apnea/desaturation

+

-

-

Bradycardia

+

?

?

Sleeping disturbancies

+

+

+

Impaired quality of life

?

?

+++

Esophagitis

+

+

++

Stenosis

-

(+)

+

Barrett's esophagus/esophageal adenocarcinoma

-

(+)

+

ALTE, apparent life-threatening events; SIDS, sudden infant death syndrome +++ very common; ++ common; + possible; (+) rare; - absent; ? unknown

Compared to adults, children report more regurgitation and emesis and less heartburn, dysphagia and chest pain.13,23,67 The younger the children are, the more difficult it is to describe and perceive these 'unpleasant sensations'. In 69 children with GERD, regurgitation and vomiting occurred in 72%, symptoms attributed to the esophagus (epigastric/abdominal pain, feeding difficulties, irritability and Sandifer-Sutcliffe syndrome) in 68%, failure to thrive in 28%, chronic respiratory symptoms in 13% and recurrent apnea in 12%, with more feeding difficulties in toddlers and more irritability in infants.21 Clinical distinction is, however, not simple, as GERD may be occult or masquerade as respiratory or other manifestations co-existing at different ages.

GERD in adolescents is more adult-like. Heartburn is the predominant GER symptom, occurring weekly in 15-20%15,68 and daily in 5-10% of subjects.16 Atypical symptoms such as epigastric pain, nausea, flatulence, hiccups, chronic cough, asthma, chest pain, hoarseness and earache, account for 30-60% of presentations of GERD.1,16 GERD is diagnosed in 50% of the adult patients with chest pain and in 80% presenting with chronic hoarseness and asthma.69 The incidence of GERD in this group with atypical symptoms is determined by the selection (bias) of the patients.

Recent evidence has shown that GERD affects the quality of life significantly in adults, and probably also in children (and their parents), although quality of life is more difficult to evaluate in infants and young children. The developing nervous system of infants exposed to acid seems susceptible to pain hypersensitivity despite the absence of tissue damage.70 The role of hypersensitivity to dietary allergens, both in exclusively breast-fed and formula-fed infants, is likely to be underestimated at present. The 'hygiene hypothesis' suggests that the Th2-predominant immune response at birth in the industrialized world is insufficiently skewed towards a well-balanced Th1/Th2 response.71 Lack of controlled chronic or repetitive inflammation of the mucosa during the first months of life may account for the dramatic increase in atopic disease during infancy and childhood (which is a Th2 response) and the increase in autoimmune diseases such as diabetes and Crohn's disease in adolescents and adults

(which are a Th1 response).72 This hypothesis fits well with the observations that atopy is inversely related to family income and early attendance at a day-care center, and positively related to number of siblings and living on a farm. Repeated contacts with certain infectious organisms and endotoxins decrease the incidence of atopic disease. Infant distress and colic are now recognized as manifestations of food hypersensitivity during early childhood. Histology of the duodenal, gastric and esophageal mucosa reveals eosinophilic infiltration, characteristic of a Th2 type and thus allergic response, in many although not all infants.

Infants with GERD learn to associate eating with discomfort and thus subsequently tend to avoid eating, although behavioral feeding difficulties are common even in control toddlers.11 In adults, impaired quality of life, notably regarding pain, mental health and social function, has been demonstrated in patients with GERD, regardless of the presence of esophagitis.17 In an unselected population, 28% of the adults reported heartburn, almost half of them weekly, with a significant impact on the quality of life in 76%, especially if the symptoms were frequent and long-lasting. Despite that, only half of heartburn complainers sought medical help, although 60% were taking medications.73 Thus, some adults 'learn to live with their symptoms', and acquire tolerance to long-lasting symptoms, while others accept living with an impaired quality of life.

The reason for the differences in presentation of GERD according to age remains unclear. The persistence of symptoms and progression to complications are unpredictable for a group of patients and for an individual patient. Alarm symptoms are similar in adults and children: weight loss, dysphagia, bleeding, anemia, chest pain and choking.16,69 Additional alarm symptoms in children are failure to thrive, irritability/crying and feeding or sleeping difficulties.74

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