What is DIOS?

Patient Presentation
A 17-year-old male with cystic fibrosis came to the emergency room with acute onset of abdominal pain. The patient had started 2 hours previously in the periumbilical area. It was described as a constant pain and generally didn’t radiate. He had nausea and emesis of food and fluid but it was not bilious or bloody. He denied any bad tastes in his mouth or other reflux symptoms. His last bowel movement was 2 days previously and was described as hard stools. He said he generally was eating and drinking normally.

The past medical history showed that he was diagnosed with cystic fibrosis with his newborn screening and had meconium ileus. He generally took his medications but over the past couple of years “forgot sometimes.” He had a history of constipation and had distal intestinal obstruction syndrome 4 months previously. His appendix was in place. His lung function was monitored closely and he had needed hospitalization for aggressive pulmonary therapy a few times in his lifetime. The family history was non-contributory. The review of systems was negative for fever, chills, and urinary frequency/urgency. He denied recent sexual activity.

The pertinent physical exam showed a thin male in distress from abdominal pain. His respiratory rate was 36 with a saturation of 93%, heart rate was 96, blood pressure was 132/76, and temperature of 99°F. HEENT was normal. Heart was slightly tachycardic without murmur. He was slightly barrel chested with coarse breath sounds. His abdomen was soft with pain in the periumbilical to right lower quadrant area. He had no guarding. There was a mass in the right lower quadrant, but no hepatosplenomegaly. He did not have specific guarding at McBurney’s point, nor peritoneal signs. His genitourinary examination showed no testicular pain or masses and no hernias. Rectal examination revealed no masses and guaiac negative stool.

The work-up included a normal complete blood count, urinalysis, and complete metabolic panel. A surgeon was consulted who felt this was most likely constipation or distal intestinal obstruction syndrome and not appendicitis but imaging was necessary.
The radiologic evaluation on plain film showed dilated loops of bowel and a heavy stool burden. A computed tomographic study of the abdomen showed no appendicitis.

The diagnosis of distal intestinal obstruction syndrome was made. The patient’s clinical course was given intravenous fluids, and non-opiate pain medication. Two hyperosmotic enemas administered by radiology along with laxatives eventually improved his symptoms and he was discharged 3 days later. He was re-educated regarding the importance of taking all of his medication daily and maintaining good hydration.

Case Image

Figure 121 – Supine view of the abdomen (above) reveals multiple dilated loops of distal small bowel and a colon packed with stool. The findings were compatible with a distal small bowel obstruction due to distal intestinal obstruction syndrome. A lateral view of the abdomen (below) taken during a hyperosmolar contrast enema, shows in the center of the image multiple filling defects in the terminal ileum due to it being packed with stool, which is a classic appearance of distal intestinal obstruction syndrome. The enema flushed this stool out of the terminal ileum and the obstruction was relieved.

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane receptor (CFTR). It is found in the epithelium of the bronchi, intestine, pancreatic duct and biliary tree. It regulates chloride, bicarbonate and water secretion. The heterozygous state helps prevent against secretory diarrhea, but the homozygous state causes thickened secretions in the hollow tubes of the lungs and digestive tract. There are multiple mutations (> 2000) which have been currently classified into classes depending on their protein production and activity. CF patients generally are living longer with improved morbidity because of new treatments including lung transplantation but they also are at higher risk of having gastrointestinal problems over their lifespan. Gastrointestinal problems in patients with CF include:

  • Pancreas
    • Second most frequent organ affected after the lung
    • Concentrated pancreatic juice and thickened secretions can increase obstruction leading to acute or chronic injury and inflammation
      • Pancreatic insufficiency
        • Most (~90%) patients have exocrine pancreatic insufficiency
        • Greasy stools, abdominal bloating, flatulence, diarrhea and poor weight gain are symptoms
        • Treatment is pancreatic enzyme replacement therapy (PERT), proton pump inhibitors are used sometimes also
        • Fat soluble vitamins (A, D, E, and K) can occur and usually are also supplemented
      • Poor nutrition
        • Patients have increased nutrition needs because of the exocrine pancreatic insufficiency, potential vitamin deficiencies, increased caloric needs (additional 20-50%)
        • Patients who cannot consume the necessary nutrition orally are often treated with feeding tubes
      • Acute pancreatitis
        • Severe epigastric pain along with increased serum lipase and amylase levels
        • Affects up to 20% of CF patients
        • Occurs more often in patients with exocrine pancreatic sufficiency than those with insufficiency
      • Chronic pancreatitis
        • Pancreatic atrophy, fatty replacement, calcification and fibrosis on imaging
      • Pancreatic cysts
        • Can be single or multiple, large or small
      • Diabetes mellitis
        • Diffuse scaring causes endocrine pancreatic insufficiency and diabetes
        • Risk increases with age
  • Hepatobiliary tract
    • Hepatobiliary disease complications are some of the most serious after lung complications
      • Fatty liver disease
        • More common in children and adolescents than adults
        • Usually transient
      • Focal biliary cirrhosis
        • Thickened bile and slow flow causes inflammation and fibrosis
        • 11-70% of adults will have it but often it is not clinically discernable
        • Primary treatment is ursodoxycholic acid to increase bile flow. Liver transplantation is also a potential option
      • Large bile duct disease
        • Stasis in large bile duct causes a variety of problems including bile stones, inflammation and strictures
        • Treatment is stone removal and stricture dilatation
      • Cholelithiasis
        • The stones can be cholesterol stones or pigment stones
      • Microgallbladder
        • Found in 30% of CF patients
  • Gastrointestinal lumen
    • Appendicitis
      • The appendix itself can have an increased luminal volume because of increased mucous in asymptomatic CF patients and it is thought that this may be protective against appendicitis
      • Can be confused with Distal Intestinal Obstruction Syndrome (DIOS – see below)
    • Constipation
      • Common in CF patients (40-50%)
      • On radiographs, fecal mass throughout the colon (N.B. note location) without air fluid levels are more common with constipation in comparison to DIOS
    • Fibrosing colonopathy
      • Associated with increased amounts of PERT. It is less common today than previously with changes in PERT dosing
      • Occurs 12-15 months after starting increased amounts of PERT
      • Symptoms similar to colitis, inflammatory bowel disease or DIOS
      • Fibrosis can be in concentric rings (especially ascending colon) but can involve the entire colon
    • Gastroesophageal reflux disease (GERD)
      • Increased risk because of prolonged gastric emptying time, coughing increasing abdominal pressure, lung percussion therapy increasing abdominal pressure and various medications
      • Patients are treated aggressively because even with gastroesophageal reflux patients are at risk of refluxing into the lung and compromising respiratory function
      • GERD can cause bronchiolitis obliterans syndrome
      • In addition to usual GERD treatment, along with positioning for pulmonary toilet and judicious choices of medications, fundoplication may be necessary
    • Ulcer disease
      • Includes peptic and duodenal ulcers
    • Intussception
      • More common in CF patients than the general population
      • Ileocolic intussception is the most common with thickened secretions being the proposed lead point
      • Presents as acute abdominal pain and obstruction and can also resolve spontaneously
      • Can be confused with DIOS
      • Treatment is by enema
    • Gastrointestinal malignancy
      • There is an increased risk of gastrointestinal malignancies overall
      • There is an increased risk for those CF patients who have had a lung transplant
    • Meconium ileus
      • Thickened secretions occlude the gastrointestinal lumen in the terminal ileum (N.B. note location)
      • Affects 10-20% of newborn CF patients. If a full term infant has meconium ileus there is an 80-90% chance they have CF. Premature infants can also have meconium ileus though
      • Treatment is aggressive and can be fatal if untreated. Intravenous hydration, nasogastric decompression, antibiotics and hyperosmolar enemas
      • Classified as simple or complex
        • Simple (50% of patients)
          • Failure to pass meconium by 48 hours without complications
        • Complex (50% of patients)
          • Has one or more complications including intestinal atresia or microcolon, bowel necrosis, perforation, meconium peritonitis, pseudocyst formation, or volvulus
    • Meconium plug
      • Thickened secretions occlude the gastrointestinal lumen in the colon (N.B. note location)
      • Treatment by hyperosmolar enemas
    • Rectal prolapse
      • Occurs in toddlers (1-2.5 years)
      • Used to be a common presentation before universal newborn screening
      • Treatment is usually conservative with treatment of constipation or other ways to decrease abdominal pressure
    • Pneumotosis intestinalis
      • Usually asymptomatic with submucosal or subserosal air that appears linearly in the bowel wall
      • Usually not treated
    • Small intestine bacterial overgrowth
      • Patients can have discomfort, bloating and flatuance
      • The small intestine has decreased motility in many CF patients (but not other areas of the gastrointestinal tract) and therefore the bacterial overgrowth is seen primarily in the small intestine.
        Treatment includes antibiotics. Probiotics are also used sometimes as are prokinetic agents in children.

    Learning Point

  • Distal Intestinal Obstruction Syndrome (DIOS)
      • DIOS has thickened secretions that occlude the gastrointestinal lumen in the ileocecum (N.B. note location)
      • Has also been called meconium ileus equivalent
      • Occurs in any age after newborn period, more common in teens and adults
      • Affects 16-21% of CF patients but up to 50% of those who had meconium ileus as an infant. Risk increases with lung transplant and increased 10x with previous episode of DIOS
      • Patients have acute colicky abdominal pain that is located periumbilically to right lower quadrant with the pain usually being progressive
      • Patients also have bilious emesis or air fluid levels on radiographs
      • Palpation of a mass in the right lower abdominal occurs but this can also be palpated without ileus or obstruction
      • Plain radiographs show dilated loops of bowel with or without air fluid levels with “soap bubbles” in the intraluminal fecal material in the small intestine
      • Differential diagnosis mainly is constipation, intussception and appendicitis
      • Treatment is intravenous or oral hydration, osmotic laxatives, stool softened. Potentially hyperosmotic enemas administered radiographically or surgical intervention may be needed

    Questions for Further Discussion
    1. What are indications for lung transplantation in patients with cystic fibrosis?
    2. How is pulmonary toilet performed for patients with cystic fibrosis?
    3. What are some of the physical examination findings in patients with cystic fibrosis?

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for this topic: Cystic Fibrosis

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    To view videos related to this topic check YouTube Videos.

    Demeyer S, De Boeck K, Witters P, Cosaert K.Beyond pancreatic insufficiency and liver disease in cystic fibrosis. Eur J Pediatr. 2016 Jul;175(7):881-94.

    Assis DN, Freedman SD. Gastrointestinal Disorders in Cystic Fibrosis. Clin Chest Med. 2016 Mar;37(1):109-18.

    Kelly T, Buxbaum J. Gastrointestinal Manifestations of Cystic Fibrosis. Dig Dis Sci. 2015 Jul;60(7):1903-13.

    Classification of CFTR Mutations. CFTR.info. Available from the internet at:https://http://www.cftr.info/about-cf/cftr-mutations/the-six-classes-of-cftr-defects/ (rev. 2017, cited 10/17/18)

    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa

  • How Does Pediatric Sjögren Syndrome Present?

    Patient Presentation
    A 14-year-old female came to clinic with fever to 101.2°F and sore throat for 36 hours. She also complained of some nausea but denied emesis, rash, cough, rhinorrhea or diarrhea. She had been around people with strep throat at school. Her past medical history was positive for Sjögren Syndrome diagnosed at age 9 after she had recurrent parotitis and multiple caries. Her disease had progressed to include some arthritis and she was treated with pulse steroids and an anti-inflammatory biological agent which did not work for her. She had been off her steroids for more than 1 year. The family history was positive for systemic lupus erythematosus. The pertinent physical exam showed a tired looking female. Her eyes were normal. Tympanic membranes were also normal. Her mouth had erythema of the posterior pharynx, and pus on her tonsils and palatal petechiae. She had some shotty anterior cervical nodes. Her lungs, abdomen and heart examinations were normal. Her skin did not show any rashes.

    The laboratory evaluation of a rapid streptococcal test was positive. The diagnosis of of a patient with strep throat was made. She was prescribed penicillin. She was very knowledgeable about her disease and told the physician that “My doctor told me that as long as I am not taking the steroids then my immune system is like everyone elses.” Her mother agreed and said how they were all so glad to have her not taking the steroid medications, but they knew that her symptoms could get worse again. The girl had a followup appointment with her immunologist the following week, and so her annual influenza vaccine was deferred until that appointment.

    Sjögren Syndrome (SS) is named for Swedish ophthalmologist Henrik Sjögren who published a case series in 1933 describing patients with dry eyes and arthritis. SS is a “chronic autoimmune inflammatory exocrinopathy” that is characterized by lymphocytic infiltration of the lacrimal and salivary glands and has various degrees of systematic involvement. Keratoconjunctivitis sicca and xerostomia are the main clinical symptoms.

    Sicca is a Latin word meaning dry. Dryness of the eyes and mouth without evidence of autoimmune disease is called Sicca syndrome or Sicca complex. SS can be primary or secondary. Primary includes keratoconjunctivitis sicca and xerostomia which is the same as Sicca syndrome. Secondary includes keratoconjunctivitis sicca and xerostomia and evidence of connective tissue disease, usually rheumatoid arthritis. Many people with Sicca syndrome may have SS, but not all. SS is an autoimmune disease and therefore the cause of the Sicca syndrome symptoms needs to be established that it is caused by an autoimmune problem and not because of another reason. Symptoms may take time to develop and therefore patients can be diagnosed with Sicca syndrome before SS is diagnosed.

    SS in adults is a clinical diagnosis with various professional organizations having diagnostic criteria for making its diagnosis. Patients usually have dry eyes, dry mouth, and abnormal salivary gland biopsies and abnormal laboratory testing. Patients are usually female and between 40-50 years old. SS can be found with other autoimmune disorders such as rheumatoid arthritis or systemic lupus erythematosus.

    SS is thought to be rare or possibly underdiagnosed in children as it’s classical manifestations seen in adults are less likely to occur in children. Although dry eyes or mouth are less common, detailed history may find additional symptoms. Abnormal laboratory testing especially Anti-SS-A or Anti-SS-B or antinuclear antibodies are often positive. Recurrent parotitis is one of the first symptoms, and is the most frequent and most consistent symptom at diagnosis and followup. Causes of parotitis can be reviewed here.

    Pediatric patients with SS are usually female as well (5:1 being reported) and patients can be as young as 4 years old. Average is around 10 years in some studies.

    Learning Point
    Pediatric patients with SS may have the following:

    • Oral symptoms and signs
      • Recurrent parotitis (64%)
      • Xerostomia – (27%) may be present with detailed history
      • Caries, multiple
      • Candidiasis, erythematous
    • Ocular symptoms and signs
      • Dry eyes – (33%)
      • Negative Schirmer or Rose Bengal testing is common
    • Salivary gland involvement
      • Histopathology changes of the parotid gland on biopsy are relatively common
      • Histopathology changes of the minor salivary glands on biopsy are less common
    • Abnormal laboratory testing
      • Anti-SS-A (Ro) positivity (67%)
      • Anti-SS-B (La) positivity (62%)
      • Antinuclear antibodies positivity (82%)
      • Rheumatoid factor positivity (53%)

    Other systemic extraglandular problems include:

    • Dermatological
      • Vasculitis – can look like Henoch-Sch&oum;nlein purpura, erythema nodosum or granuloma annulare
    • Gastrointestinal
      • Hepatitis, autoimmune
      • Pancreatitis
    • Hematological
      • Anemia
      • Hypergammaglobulinemia
      • Lymphoma
    • Nervous system
      • Central nervous system
        • Cerebellar ataxia
        • Meningoencephalitis
        • Optic neuritis
        • Transverse myelitis
      • Headache
      • Peripheral neuropathy
    • Musculoskeletal
      • Arthralgia
      • Hypokalemic paralysis
      • Rheumatoid arthritis
      • Polyarthritis
      • Raynaud phenomenon
    • Pulmonary
      • Alveolitis
      • Interstitial lymphocytosis
    • Renal
      • Glomerulonephritis
      • Renal tubular acidosis

    Note: percentages are from 2012 systematic review

    Questions for Further Discussion
    1. What treatment is available for Sjögren Syndrome?
    2. What specialists should be involved in the care of patients with Sjögren Syndrome?
    3. How do you perform a Schirmer test?

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for this topic: Sj&ouml:gren’s Syndrome

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    To view videos related to this topic check YouTube Videos.

    Singer NG, Tomanova-Soltys I, Lowe R. Sjögren’s syndrome in childhood. Curr Rheumatol Rep. 2008 Apr;10(2):147-55.

    de Souza TR, Silva IH, Carvalho AT, Gomes VB, Duarte AP, Leão JC, Gueiros LA. Juvenile Sjögren syndrome: distinctive age, unique findings. Pediatr Dent. 2012 Sep-Oct;34(5):427-30.

    Maciel G, Crowson CS, Matteson EL, Cornec D. Incidence and Mortality of Physician-Diagnosed Primary Sj&ouml:gren Syndrome: Time Trends Over a 40-Year Period in a Population-Based US Cohort. Mayo Clin Proc. 2017 May;92(5):734-743.

    Olschowka N. The History of Henrich Sjögren. Association Du Syndrome De Sjögren. Available from the Internet at: http://sjogrens.ca/en/the-history-of-henrick-sjogren (rev. 2017, cited 10/10/17).

    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa

    December 11, 2017

    How Do You Perform the Adams Forward Bend Test?

    Patient Presentation
    A 12-year-old female came to clinic for her health supervision visit in June. She was doing well but her mother was concerned about her back as her aunt had noticed a “lump” on her back when she bent over at the swimming pool. The mother said that it just looks like her shoulder is a little higher on the right side. The girl denied any pain, discomfort or problems with mobility. The patient had not started her periods but had started to “develop” per her mother and was getting taller. The family history was negative for any back problems including scoliosis, but the mother said that her maternal great grandmother had lost height and became more “hunchback” when she was older. The review of systems was negative.

    The pertinent physical exam showed a cooperative female with normal vital signs and growth parameters. Her height was 75% which was slightly increased from the 50-75% she had been tracking. Her weight was 50%. Her musculoskeletal examination was negative. On Adams forward bend test she had an elevation of the right rib/scapula that improved but did not go away with proper re-positioning of the patient. Her hips and shoulder levels appeared to be normal. She was Tanner 3 for breast and Tanner 2 for pubic hair. The rest of her examination was normal including skin examination.

    The diagnosis of probable idiopathic scoliosis with a positive forward bend screening test was made in a skeletally immature female. The radiologic evaluation of a spine radiograph showed a right thoracic curve of 11°. The patient’s clinical course showed that after discussing the results with the family, they wanted a referral to an orthopaedist because she was undergoing her growth spurt. Repeat radiographs one year later showed an increase in the Cobb angle to 13° and another year later it was 15°. At this time she was postmenarchal and repeat examination 6 months and 1 year later showed no additional progression. She was clinically well over this entire followup time period.

    Scoliosis is a lateral and rotational curvature of the spine from a plumb line hanging from C7 to the floor.
    Idiopathic scoliosis is the most common form. A review of scoliosis and its differential diagnosis can be found here.

    Depending on the age, 2-4% of adolescents have a positive Adams Forward Bend Test when assessed and ~2% may have idiopathic scoliosis of > 10 degrees. Curve progression relates to the magnitude of the curve and the patient’s age. Thus increased risk of progression occurs in patients with higher curvature magnitude at diagnosis, females (earlier start of puberty and therefore possibly not identified or have great curvature to start with), younger children (same reason), being skeletally immature, symptomatic (pain or other neurological problems), underlying disease (e.g. congenital, neuromuscular, connective tissue disease, or foot deformities), and patients with excessive lordosis or kyphosis.

    Routine clinical screening is controversial but several professional organizations including the American Academy of Orthopaedic Surgeons and the American Academy of Pediatrics recommend screening. It is recommended to screen females in US in 5th and 7th grades (10-11 years and 12-13 years), and males in 8th grade (13-14 years).

    In general, idiopathic scoliosis that has a Cobb angle 50 degrees often progress at a rate of 0.75-1.00 degree/year. Those between ~30-40 degrees may or may not progress but are at risk especially if skeletally immature.

    The most common curve variation is a righted-sided thoracic curve with a compensatory left-sided lumbar curve. Some people remember this as RIGHT in the thoRax and LEFT in the Lumbar spine. If a different pattern is seen then alternative causes to idiopathic scoliosis should be considered. Treatment options depend on the magnitude of the curve and risk of progression.

    Learning Point
    Mr. William Adams (1820-1900) along with Dr. Thomas Hodgkin (1798-1866) described scoliosis in a post mortem examination of a contemporary physician in 1854. Mr. Adams later described his “Forward Bend Test” in lecture 10 in his series of Lectures on the Pathology and Treatment of Lateral and Other Forms of Curvature of the Spine.

    The primary evaluation for scoliosis is inspection looking for asymmetric laterality and the Adams Forward Bend Test.

    • The patient is inspected standing upright with feet together and knees extended/straight with arms held at the side. The head should be in an upright neutral position. The patient is inspected from the front noticing differences in shoulder or waist alignment from side-to-side or prominence of the chest.
    • The patient is again inspected from the back noticing any differences in the shoulder or waist alignment or prominence of the scapula or ribs. The location and laterality of any potential abnormalities should be noted.
    • The patient is then instructed to put both of their palms together, head down and bend forward, similar to diving. The palms should be together but arms should hang freely.
      The examiner’s eyes should be level with the spine from behind and noticing if there are any differences in the scapula, rib cage or paraspinous muscles.

    • If a scoliometer (inclinometer) is used and there is a difference in laterality, 5-7 degrees is considered the cut-off point for positive screening.

    Other areas to note on examination include dermatological examination for sign of neurofibromatosis (e.g. axillary freckling, cafe-au-lait spots, subcutaneous fibromas), joint examination for signs of connective tissue disease (e.g. joint laxity, arachnodactly), and midline spinal abnormalities such as dimpling. Leg length discrepancy may also cause a false positive Adams test.

    While inspection and the Adams Forward Bend Test seems to be a simple painless test, patients will often not understand the instructions or fail to move their body into the correct position and therefore need additional instructions. The patient may need to be reminded to stand erect during the upright part of the test with weight balanced between their feet. This should correct any positional changes that are solely caused by posture or positioning. If abnormalities do not correct then there is possible scoliosis or a leg length discrepancy. Placing the examiner’s fingers on the top of the scapula (acromium) and thumb on the inferior angle of the scapula can also help the examiner to determine if there is mild shoulder height differences or scapular prominences. The examiner’s own spatial perception of where his/her hands are in space may be more sensitive than visual inspection alone. Similarly, placement of the examiner’s hands on the iliac crests bilaterally may again also allow better visual inspection for height differences between sides, especially in obese patients. The examiner’s spatial perception may also detect small alignment differences.

    During the bending part of the test, patients will often try to keep their head up, place their hands on their knees or bend their knees. Again reminding the patient to move into the proper position and maintain it while the examination is carried out is important. Some patients will try to touch their feet and will not have enough flexibility to do this, thus they move during the examination. Reminding the patient they do not have to stretch, just bend forward often helps. Running the examiner’s hand over the entire spine from C7-L5 during the forward bend part of the examination may also help to assess alignment or rotation, especially in obese individuals.

    Indications for further evaluation include if abnormalities are noticed on physical examination, a scoliometer reading of > 5-7 degrees, abnormal curve pattern or other abnormal physical examination findings particularly in young or skeletally immature patients.

    Questions for Further Discussion
    1. What other caveats do you have for performing the Adams Forward Bend Test?
    2. How successful are non-surgical and surgical treatment for scoliosis?

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for these topics: Scoliosis and Spine Injuries and Disorders.

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    To view videos related to this topic check YouTube Videos.

    Hodgkin T, Adams W. Case of Distortion of the Spine, with observations on Rotation of the Vertebrae as a complication of Lateral Curvature. Med Chir Trans. 1854;37:167-180.5.

    Adams W. Lectures on the Pathology and Treatment of Lateral and Other Forms of Curvature of the Spine, 2nd ed. London; J & A Churchill, 1882.

    Fairbank J. Historical perspective: William Adams, the forward bending test, and the spine of Gideon Algernon Mantell. Spine (Phila Pa 1976). 2004 Sep 1;29(17):1953-5.

    Rosenberg JJ. Scoliosis. Pediatr Rev. 2011 Sep;32(9):397-8; discussion 398.

    Horne JP, Flannery R, Usman S. Adolescent idiopathic scoliosis: diagnosis and management. Am Fam Physician. 2014 Feb 1;89(3):193-8.

    Hresko MT. Clinical practice. Idiopathic scoliosis in adolescents. N Engl J Med. 2013 Feb 28;368(9):834-41.

    Hresko MT, Talwalkar V, Schwend R; AAOS, SRS, and POSNA. Early Detection of Idiopathic Scoliosis in Adolescents. J Bone Joint Surg Am. 2016 Aug 17;98(16):e67.

    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa

    December 4, 2017

    Can I Give Cholera Vaccine?

    Patient Presentation
    A 17-year-old male came to clinic for travel immunizations before a medical mission to Haiti for 2 weeks. His father was a health care provider and had traveled to Haiti on two previous trips, but this trip was to spend more time in more rural locations. His father had been to the travel clinic and had received cholera vaccine along with malaria prophylaxis. He was current with typhoid vaccine. The pertinent physical exam showed a healthy teenager with normal vital signs and growth parameters in the 75-95%. His examination was normal.

    The diagnosis of a healthy male was made. The pediatrician reviewed the Centers for Disease Control website for current immunization recommendations for Haiti. The teenager was current with his standard vaccinations and received typhoid vaccine and malaria prophylaxis along with counseling regarding using insect repellent, safe water and hygiene practices. “Unfortunately you just turned 17, and the cholera vaccine in the United States is only for those over 18 years, so I can’t give it to you. It’s really, really important that you use safe water and wash your hands well, ALL THE TIME,” the pediatrician emphasized. The father said that he had been making his son practice at home using bottled water for drinking, toothbrushing and preparing meals. “It’s a lot of work to fill up the bottles from the faucet and practice, but I don’t want to get sick so I guess its okay,” the teen obliged.

    Cholera is caused by more than 200 serogroups of Vibrio cholerae, a Gram-negative rod that is waterborne. Only two (serogroup O1 which causes about 99% of the cases, and O139) cause disease. There are biotypes of each of these serotypes. The only known hosts are humans. The organism colonizes the epithelial lining of the gut. Cholera toxin is produced by some species and if produced binds to specific receptors on host cells, activating a series of steps which cases massive loss of sodium, potassium, chloride, hydrogen carbonate, and fluids in vomitus and feces. A review of causes of diarrhea can be found here.

    More than 1 billion people are at risk for cholera in endemic countries with an estimated 2.86 million cases and ~95,000 deaths annually Cholera is endemic in sub-Saharan Africa and Asia but has areas that have become epidemic such as Haiti and Yemen in the past few years. Studies in Africa have an incidence of < 0.3/10,000 which increased to 20/10,000 during epidemics. About half of the cases and deaths are in children < 5 years of age. For travelers from non-endemic countries cholera is rare with a risk of 0.01-0.001% per month of stay in a developing country. Cholera is rare in the United States with < 25 cases/year reported with most occurring among travelers to epidemic or endemic cholera.

    Cholera is spread by direct fecal-oral and contaminated water or food routes thus the risk of cholera increases in areas where crowding, lack of access to clean water, sanitation and health care are issues. Incubation period is < 24 hours to 5 days. Only 1-25% of those exposed actually develop disease. Of those that are symptomatic, 10-20% experience severe disease. Symptomatic patients produce watery diarrhea sometimes referred to as "rice water stools." Emesis can also occur. Symptoms last 1 to a few days. Patients can have profuse fluid loss of up to 0.5 – 1.0 liters/hour and obviously severe dehydration is a major cause of morbidity and mortality if not promptly and aggressively treated. Healthy persons have been known to die within 24 hours of symptom onset because of the complications of dehydration.

    Risk factors for cholera include number of bacteria ingested, lack of immunity from prior disease or vaccination, lack of passive immunity for newborn infants because of lack of breastfeeding, pregnancy, immunocompromised state (especially HIV), malnourishment, blood group O, and decreased ability to make gastric acid which neutralizes the bacteria. High concentrations of the bacteria is found in feces, and often vomitus also. There is some data suggesting “…that passage through a human host transiently increases the infective potential of V. cholerae by creating a hyperinfectious state that is maintained soon after shedding, and which may contribute to the epidemic spread of the disease.”

    The diagnosis standard is by culture, but polymerase chain reaction testing and other rapid diagnostic testing is also available. Treatment is by rapid and aggressive administration of fluid and electrolytes. In patients with mild to moderate dehydration, oral rehydration with low osmolarity oral rehydration solution (ORS) is standard. The lower osmolarity compared to standard ORS decreases emesis. For severe dehydration, intravenous fluid administration with correction of electrolytes is imperative. Antibiotics are given to hospitalized patients during epidemics which decreases the symptom duration, stool volume, and length of time the active pathogen is excreted which reduces transmission and hospital length of stay. Doxycycline is usually the first choice, but ciprofloxacin or azithromycin are used in doxycycline-resistant areas. Unfortunately drug-resistance is common.

    Although both children and adults are able to mount antibody responses to both the organism and the toxin, they are not reliably predictive of protection against cholera.

    Learning Point
    Cholera vaccines are available for use in endemic and epidemic areas, and for travelers.

    • Dukoral® is a whole-cell, killed, monovalent vaccine again serotype O1
      • Has a cholera toxin subunit which also has some cross-reactivity with enterotoxigenic Escherichia coli and therefore it offers some protection for this entity also
      • Given orally
        • 3 doses for children given 1-6 weeks apart for ages 2-5 years
        • 2 doses are given 1-6 weeks apart for ages 6 years and up
      • Protection is 6 months for children 2-5 years, and 2 years for those 6 years and older
      • For revaccination
        • For children 2-5 years, 1 dose can be used if given within 6 months of primary immunization, otherwise re-start primary vaccination
        • For 6 years and up, 1 dose can be used if given within 2 years of primary immunization, otherwise re-start primary vaccination
      • Licensed in countries worldwide, primarily for travelers to endemic countries but has been used for epidemics
    • Shanchol™, Euvichol®, and mORCVA™ are modified whole-cell, killed, bivalent vaccine against serotypes O1 and O139
      • These 3 vaccines are based on the same strains but are available in different areas of the world.
      • Does not have cholera toxin subunit therefore is no cross-reactivity with enterotoxigenic Escerichia coli
      • Given orally
        • 2 doses given 14 days apart for ages 1 year and older
      • Protection is up to 5 years
      • Licensed in countries worldwide, for travelers and also for epidemics
    • Vaxchora® is a live-attenuated single-dose oral vaccine.
      • It is the only cholera vaccine available in the United States and is given as a single oral dose to people ages 18-64 years for those traveling to cholera-affected areas.
      • Its protection is at least 3 months according to the Centers for Disease Control, but others studies have shown efficacy for 6 months.

    The World Health Organization recommends during humanitarian emergencies where there is a risk of cholera but no current outbreak that oral cholera vaccine be considered as an additional measure for prevention. International workers and travelers should also use safe hygiene practices. Emergency/relief workers who would be likely to encounter patients with cholera or exposed to contaminated food and water should be vaccinated. “Vaccination is not generally recommended for long-term or short-term travelers to cholera-affected countries,….”

    Other vaccines are currently being developed.

    Questions for Further Discussion
    1. What are good “hygiene” practices for places with risks for fecal-oral transmission of infections?
    2. What are good malaria prevention practices?

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for these topics: Cholera and Traveler’s Health.

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    To view videos related to this topic check YouTube Videos.

    Tran NT, Taylor R, Antierens A, Staderini N. Cholera in Pregnancy: A Systematic Review and Meta-Analysis of Fetal, Neonatal, and Maternal Mortality. PLoS One. 2015 Jul 15;10(7):e0132920.

    Das JK, Ali A, Salam RA, Bhutta ZA. Antibiotics for the treatment of Cholera, Shigella and Cryptosporidium in children. BMC Public Health. 2013;13 Suppl 3:S10.

    Cabrera A, Lepage JE, Sullivan KM, Seed SM. Vaxchora: A Single-Dose Oral Cholera Vaccine. Ann Pharmacother. 2017 Jul;51(7):584-589.

    Wong KK, Burdette E, Mahon BE, Mintz ED, Ryan ET, Reingold AL. Recommendations of the Advisory Committee on Immunization Practices for Use of Cholera Vaccine. MMWR Morb Mortal Wkly Rep. 2017 May 12;66(18):482-485.

    Cholera vaccines: WHO position paper – August 2017. Wkly Epidemiol Rec. 2017 Aug 25;92(34):477-98.

    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa