Differentials
Atopic dermatitis
SIGNS / SYMPTOMS
Pruritic, morbilliform, or maculopapular eruptions.
INVESTIGATIONS
Selected allergens evaluated for specific IgE based on history.
Rash in the predilection sites for atopic dermatitis within 1 hour of an oral challenge.[59]
Urticaria
SIGNS / SYMPTOMS
Appearance not necessarily related to food ingestion (e.g., penicillins, sulfonamides, muscle relaxants, diuretics, non-steroidal anti-inflammatories).
Erythematous oedematous lesions on any part of the body.
Typically pruritic, although occasionally painful or burning sensation reported.
Dissipates within 24 hours leaving no residual markings.
Up to 40% of cases of urticaria have associated angio-oedema (swelling of the deeper layers of the subdermis).
Foods are not the cause of chronic urticaria (lasting >6 weeks).
INVESTIGATIONS
Lack of response to in vitro IgE testing or skin prick testing.
Foods are not the cause of chronic urticaria (lasting >6 weeks).
Auriculotemporal syndrome
SIGNS / SYMPTOMS
Recurrent episodes of facial flushing, sweating along the distribution of the auriculotemporal nerve.
Occurs in response to gustatory stimuli.[60]
INVESTIGATIONS
Diagnosis is clinical.
Acute asthma exacerbation in children
SIGNS / SYMPTOMS
Fatigue, dyspnoea, exercise intolerance, aesthete body type, and wheezing, but seldom the only symptoms and signs.[61]
INVESTIGATIONS
Pulmonary function testing with diminished FEV1.
Greater likelihood of progression to irreversible obstructive airway disease.
Acute asthma exacerbation in adults
SIGNS / SYMPTOMS
Dyspnoea; may be precipitated by allergens, cold, or exercise; wheezing reversible on administration of bronchodilators.
INVESTIGATIONS
Pulmonary function testing with diminished FEV1.
Greater likelihood of progression to irreversible obstructive airway disease.
Food-induced pulmonary haemosiderosis (Heiner's syndrome)
SIGNS / SYMPTOMS
Recurrent pneumonia associated with pulmonary infiltrates, haemosiderosis, gastrointestinal blood loss, iron deficiency anaemia, and failure to thrive.[2]
In infants, most often caused by non-IgE-mediated hypersensitivity to cows' milk.
Tracheo-oesophageal fistula
SIGNS / SYMPTOMS
Neonates.
Regurgitation of feeding.
Aspiration and pneumonia.
INVESTIGATIONS
Chest x-ray with air-distended oesophageal atretic pouch; the nasogastric tube coiled in this pouch.
Also, excessive dilation of stomach as a result of fistula communication.[62]
Pollen food syndrome (oral allergy syndrome)
SIGNS / SYMPTOMS
Oropharyngeal pruritus and angio-oedema of the lips, oral mucosa, and soft palate.[63]
Symptoms not likely to progress to systemic anaphylaxis.
INVESTIGATIONS
Double-blind placebo-controlled food challenge.
Skin prick testing or in vitro assays with suspected fresh fruit or vegetable.
Causative allergens in fruits and vegetables have homologous proteins to pollens of grasses, trees, and weeds.[63]
Food protein-induced enterocolitis syndrome
SIGNS / SYMPTOMS
Manifests in the first few months of life. Projectile vomiting, diarrhoea, and failure to thrive.[19]
Associated with ingestion of cows' milk or soya protein.
Similar syndrome presents in older infants and children as a result of egg, wheat, rice, oat, peanut, nuts, chicken, turkey, and fish sensitivity. Shellfish sensitivity may be causative in adults.
INVESTIGATIONS
Oral food challenge will lead to vomiting within 1 to 4 hours after ingestion (caution: may cause severe hypotension).
Elevation in peripheral blood neutrophils.[37]
Food protein-induced colitis
SIGNS / SYMPTOMS
Presents in first few months of life.[19]
Infants with isolated finding of blood in the stool.
INVESTIGATIONS
Stool positive for blood in infants.
Eosinophilic oesophagitis/gastroenteritis
Gastroenteritis in children
SIGNS / SYMPTOMS
Persistent diarrhoea lasting from 1 to 8 days.
Usually accompanied by fever.
INVESTIGATIONS
Presence of faecal lymphocytes.
Microscopy and stool culture positive for causative organisms.
Elevated WBC if sepsis; blood cultures positive for causative organisms.
Clostridium difficile toxin present (i.e., in patients with recent prolonged antibiotic use).
Gastroenteritis in adults
SIGNS / SYMPTOMS
Persistent diarrhoea lasting from 1 to 8 days. Usually accompanied by fever.
INVESTIGATIONS
Presence of faecal lymphocytes.
Microscopy and stool culture positive for causative organisms.
Elevated WBC if sepsis; blood cultures positive for causative organisms.
Clostridium difficile toxin present (i.e., in patients with recent prolonged antibiotic use).
Irritable bowel syndrome
SIGNS / SYMPTOMS
Recurrent abdominal pain or discomfort that is associated with a change in stool frequency or form.
Mild and poorly localised tenderness in the right lower quadrant and/or left lower quadrant.
INVESTIGATIONS
Diagnosis is clinical and by exclusion of other causes (e.g., Crohn's disease, ulcerative colitis).
Crohn's disease
SIGNS / SYMPTOMS
Family history of Crohn's disease; more common in white people than in black or Asian people; age 15 to 40 years or 60 to 80 years.
Crampy or constant abdominal pain with non-bloody, intermittent diarrhoea.
Perianal lesions (e.g., skin tags, fistulae, abscesses, scarring) may be present.
INVESTIGATIONS
Abdominal radiography with small bowel or colonic dilation; calcification; sacroiliitis; intra-abdominal abscesses.
CT and MRI with skip lesions, bowel wall thickening, surrounding inflammation, abscess, fistulae.
Bowel biopsy histology demonstrates transmural non-caseating granulomas.
Ulcerative colitis
SIGNS / SYMPTOMS
Diarrhoea and haematochezia.
Cramps, anorexia, weight loss, mild anaemia, malaise, and low-grade or intermittent fever.[64]
INVESTIGATIONS
Abdominal radiography with dilated colon, intra-abdominal free air, perforation.
Colonic biopsy histology of acute and chronic inflammation with polymorphonuclear leukocytes infiltrating the submucosa.[64]
Hiatal hernia
SIGNS / SYMPTOMS
Intolerance to spicy or acidic foods, particularly with recumbency and after retiring for the evening.
Mid-epigastric to lower thoracic discomfort relieved with prolonged sitting position or elevation of head of bed.
Specific lack of cutaneous or respiratory symptoms.
INVESTIGATIONS
Diagnosis is primarily clinical.
Upper gastrointestinal series with gastric cardia herniated 2 cm above the hiatus.
Pyloric stenosis
INVESTIGATIONS
Abdominal ultrasound with pyloric thickness >4 mm or an overall pyloric length >14 mm.[65]
Hirschsprung's disease
SIGNS / SYMPTOMS
Abdominal distension and stool retention.
Toxic megacolon, peritonitis, perforation.
INVESTIGATIONS
Barium enema demonstrates segmental narrowing with ballooning of the proximal part of the bowel.
Rectal/colon biopsy absence of ganglion cells.
Pancreatic insufficiency (e.g., cystic fibrosis)
SIGNS / SYMPTOMS
Chronic diarrhoea.
Steatorrhoea.
INVESTIGATIONS
Elevated sweat chloride levels (>60 mmol/L) in cystic fibrosis.
Gastro-oesophageal reflux disease
SIGNS / SYMPTOMS
Heartburn.
Hiatal hernia and advancing age.
Acidic reflux into oral cavity.
Absence of cutaneous or respiratory involvement.
INVESTIGATIONS
Diagnosis is clinical.
A therapeutic trial of a proton-pump inhibitor can serve for both diagnosis and initial treatment.
Cholecystitis
SIGNS / SYMPTOMS
Right upper quadrant or epigastric abdominal pain.[66] Pain may radiate to the right shoulder or back and is usually steady and severe.
Associated symptoms: nausea, vomiting, and anorexia.
Often a history of fatty food ingestion about 1 hour or more before initial onset of pain.
INVESTIGATIONS
Elevated leukocytes with a left shift on FBC.
Ultrasound or cholescintigraphy may be needed to confirm the diagnosis.[66]
Coeliac disease
SIGNS / SYMPTOMS
Persistent diarrhoea with gluten ingestion.
Presence of dermatitis herpetiformis.
INVESTIGATIONS
Low Hb and microcytic red cells on FBC.
Immunoglobulin A-tissue transglutaminase (IgA-tTG) titre above normal for laboratory.
Endomysial antibody titre elevated.
Biopsy of the small bowel helpful when positive, but a negative result does not rule out the disease.
Human leukocyte antigen DQ2DQ8 testing is highly sensitive (90% to 95%) for coeliac disease but not very specific.
Food poisoning (e.g., Clostridium botulinum, Staphylococcus aureus, Escherichia coli)
SIGNS / SYMPTOMS
Abdominal pain, nausea, vomiting.
Fever may appear from 1 to 72 hours after ingestion.[65]
INVESTIGATIONS
Faecal leukocytes present and stool culture grows organism.
Blood cultures grow organism.
Alcohol overdose
SIGNS / SYMPTOMS
In early acute intoxication, euphoria, giddiness, and loss of inhibitions.[52] Nausea, vomiting, abdominal pain, facial flushing, ataxia, and diminished reflexes.
In late acute intoxication, central nervous system depression becomes generalised, leading to ataxia, nystagmus, slurred speech, and sedation. May progress to coma, loss of protective airway reflexes, autonomic dysfunction, hypothermia, death.
INVESTIGATIONS
With acute intoxication an elevated blood alcohol level is detectable.
Lactose intolerance
Toxic reactions (e.g., scombroid poisoning, ciguatera poisoning, saxitoxin)
Accidental contamination (pesticide or antibiotics)
SIGNS / SYMPTOMS
Excessive salivation, lacrimation, bronchorrhoea, urinary and faecal incontinence, and vomiting.[68]
INVESTIGATIONS
Atropine (1 to 2 mg intravenously as a single dose) is given as a therapeutic trial in all suspected cases or when diagnosis is in doubt. Lack of anticholinergic response is a positive test.
Plasma cholinesterase and red blood cell cholinesterase used to confirm diagnosis.
Specific IgE may be present with inadvertent allergy to antibiotic ingested.
Fungal toxins (e.g., aflatoxins, trichothecenes, ergots)
SIGNS / SYMPTOMS
Fever, malaise, vomiting, and jaundice.[69]
INVESTIGATIONS
Absence of specific IgE.
Caffeine overdose
SIGNS / SYMPTOMS
Overdose may lead to agitation, vasoconstriction, tremor, and hypertension.[68]
INVESTIGATIONS
Diagnosis is clinical.
Theobromine (e.g., tea, chocolate) intoxication
SIGNS / SYMPTOMS
Nausea, vomiting, anxiety, nervousness, and insomnia are evident in mild intoxication. Seizures occur in severe poisonings.[68]
INVESTIGATIONS
Diagnosis is clinical.
Serotonin (e.g., banana, tomato) overdose
SIGNS / SYMPTOMS
Diarrhoea, headache, and fatigue if ingested in large amounts.[70]
INVESTIGATIONS
Diagnosis is clinical.
Food phobias/aversions
SIGNS / SYMPTOMS
May mimic adverse food reactions.
INVESTIGATIONS
Absence of specific IgE.
Double-blind placebo-controlled food challenge (DBPCFC).
Symptoms are not reproducible with DBPCFC.[19]
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