What Are Potential Treatments for Irritable Bowel Syndrome?

Patient Presentation
An 11-year-old female came to clinic for evaluation of recurrent abdominal pain. She had been seen twice in the emergency room and once in the outpatient clinic for similar problems over the past two months. The episodes occurred at least once a week and would cause her to not want to go to her music lessons and she would lie down for a while. Occasionally she would take acetaminophen for the pain. She described periumbilical pain without radiation and which improved with defecation. She said that her stools were “looser” but denied any blood or mucous. The episodes were not increasing in frequency or intensity and never occurred at night. She denied any bloating, flatulance or emesis. She ate a normal, mixed diet and the pain did not appear related to meals. They had been traveling in the region where she lived for musical recitals which she enjoyed but had been drinking from municipal water supplies. She also has not been around non-domestic animals. She had not had menarche. She had not been around anyone with gastrointestinal complaints nor had taken any medications other than the acetaminophen. The past medical history revealed that she was a high achieving individual both in the classroom and in regional music competitions. The family history is remarkable for high achieving parents. The mother related that she has always had some “stomach trouble” that she watched her diet for, especially her fiber intake. There was no gastrointestinal or rheumatological diseases in the family. There was a maternal uncle with basal cell skin cancer that was treated with excision. The review of systems was negative including no weight, skin, urinary, or vision changes.

The pertinent physical exam showed a healthy female who had gained 1.5 kilograms since her well child visit several months ago and who had gained 0.5 kg since the onset of her pain. Her weight was 25% and height was 50%. Her abdominal examination showed normal bowel sounds, with no masses or splenomegaly. She had no pain with palpation and rectal examination had normal tone without masses palpable. Genitourinary examination showed a normal female with patent vaginal opening. The work-up included a complete blood count, erythrocyte sedimentation rate, electrolytes, urinalysis and stool guiac which were all negative. Because of parental concerns and the regional travel, stool cultures were also negative eventually.

The diagnosis of irritable bowel syndrome was made. The family was counseled about the etiology and natural history with an emphasis that the patient was having real pain yet there is not anything seriously wrong with her gastrointestinal tract. The family was instructed to keep consistent habits for sleep, eating, school and other activities. They were asked to keep a symptom diary. The mother said that she would especially be sure that the child had adequate fiber in her diet. “I know that this helps me, so I hope it will help her,” the mother stated. The patient’s clinical course at followup 6 weeks later showed marked improvement with only 2 episodes of pain. The diary also showed that the pain seemed to be around when she was doing more musical performances, so the family said they were try to be aware and supportive of the patient around those times.

Discussion
Abdominal pain is a common problem for children and a review can be found here.here. Functional gastrointestinal diseases are one of the most common problems not only in children but throughout the lifespan and a review can be found here.

Irritable bowel syndrome (IBS) is the most common functional gastrointestinal diseases with 10 to 15% of children suffering from IBS. The cause is unknown but it is considered a brain-gut disorder. “It is postulated that the state of disregulation exists/occurs within the enteric and the central nervous systems in patients with IBS and this results in alteration in sensation, motility, and possibly, immune system dysfunction.” It is most likely due to complex interaction between hereditary and environmental factors.

The Rome III criteria for IBS is:

  • Irritable Bowel Syndrome
    • Criteria fulfilled at least once per week for at least 2 months prior to diagnosis
    • Must include both of the following:
      • Abdominal discomfort (meaning an uncomfortable sensation not described as pain) or pain associated with two or more of the following at least 25% of the time:
        • Improvement with defecation
        • Onset associated with a change in frequency of stool
        • Onset associated with a change in form (appearance) of stool
      • No evidence of an inflammatory, anatomic, metabolic, or neoplastic process that explains the subject’s symptoms

Classically the change in bowel frequency or consistency is associated with periumbilical abdominal pain that is relieved by defecation. Symptoms will also worsen during periods of emotional distress. There are 3 non-mutually exclusive subtypes. IBSC which has constipation as a predominant symptom. IBSD which has diarrhea as a predominant symptom. And IBSA which alternates between constipation and diarrhea. Patients may have one predominant subtype and overtime have another.

A thorough history and physical examination is important to look for “red flags” possibly indicating organic disease which include:

  • Growth problems and unintentional weight loss
  • Significant GI complaints including emesis, diarrhea and blood in the stool
  • Pain that is not periumbilical (or radiates) or pain at night
  • Systemic symptoms – fever, rash, joint pain, urinary symptoms, apthous ulcers
  • Family history of gastrointestinal organic disease – inflammatory bowel disease, ulcer, celiac disease
  • Abnormal laboratory testing – elevated inflammatory markers, anemia, etc.

Basic laboratory testing are also important in excluding more serious disease and can include a basic metabolic panel, complete blood count, C-reactive protein or erythrocyte sedimentation rate, urinalysis and urine culture and stool guaiac. Additional testing may be indicated based on the patient’s history such as stool for ova and parasites with a history of travel or animal exposure, stool C. difficile after antibiotics or breath hydrogen testing for possible malabsorption.

Despite best clinical efforts, some patients with IBS will eventually be diagnosed with a more serious alternative diagnosis. A study of adults 18 to 75 years old diagnosed with IBS found that there was a small increased incidence of Crohn’s disease, inflammatory bowel disease and colorectal cancer. The greatest risk was in the first 6 months of diagnosis and the authors believe that this is due to timing of the diagnostic evaluation for the patients. This finding was true even for young adults in the 18 to 29 year range.

Learning Point
After a thorough history, physical examination and laboratory evaluation excludes evidence of organic causes or other functional abdominal pain etiologies, the diagnosis of IBS can be made based on the criteria above.
The most important step in treatment of IBS is explaining to the family and the child the diagnosis, the natural history and providing reassurance that there is no underlying serious pathology. This often provides adequate treatment for the child and family. However some children have more severe symptoms and therefore need further intervention.
Dietary interventions are one of the most common and generally accepted treatments for families. There is some evidence that fiber supplementation help patients with IBSC subtype disease. A low fiber diet could be beneficial for those with IBSD. Use of partially hydrolyzed guar gum may help patients with IBSA.
Probiotics have been used for adult patients with IBS. They are considered safe to use and may be helpful for patients whose symptoms were initiated as the result of an infectious etiology such as gastroenteritis.
Medications generally show weak evidence of benefit. Peppermint oil and trimebutine maleate can be helpful for some children with spasmotic pain. Antibiotics are usually not recommended but can be useful if bacterial overgrowth is suspected. The antidepressant amitriptyline is effective in adults.
Hypnotherapy and yoga have also shown some beneficial effects in children. Cognitive behavioral therapy is often prescribed but evidence is not strong to support it.

Questions for Further Discussion
1. What are the key signs and symptoms of Crohn’s disease and inflammatory bowel disease?
2. What are other functional abdominal pain syndromes?

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: Irritable Bowel Syndrome and Abdominal Pain.

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.

Sandhu BK, Paul SP. Irritable bowel syndrome in children: pathogenesis, diagnosis and evidence-based treatment.
World J Gastroenterol. 2014 May 28;20(20):6013-23.

Paul SP, Barnard P, Bigwood C, Candy DC. Challenges in management of irritable bowel syndrome in children.
Indian Pediatr. 2013 Dec;50(12):1137-43.

Canavan C, Card T, West J. The incidence of other gastroenterological disease following diagnosis of irritable bowel syndrome in the UK: a cohort study.
PLoS One. 2014 Sep 19;9(9):e106478.

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital

What is the Epidemiology of Adolescent E-Cigarette Use?

Patient Presentation
A 14-year-old male came to clinic for a sports physical. He played soccer and baseball and denied any significant sports injuries or concussions. He was doing well in school and had several friends that he liked to play sports or video games with. During the interview, he said that he had tried smoking with an e-cigarette that an older student had given him. He said that it was chocolate flavored and tasted “okay” but he really didn’t like it much and hasn’t tried it since. He denied any other tobacco, drugs or alcohol use. The past medical history showed a broken arm in the 2nd grade. The social history revealed maternal grandparents that smoked.

The pertinent physical exam showed a well appearing male with normal vital signs and growth parameters in the 25-75%. His physical examination had no focal findings. The diagnosis of a healthy male with what appears to be low risk, risk-taking was made. The physician reiterated that tobacco use in all forms was not healthy. “Although using e-cigarettes isn’t illegal in our state, buying them is. Plus your soccer and baseball teams have rules against using them and sports are important to you. You probably don’t want to get kicked off the team, so I would try to stay away from it if possible,” the physician said. They then discussed some ways that the teen could say no to substances if he was in a similar situation, and brainstormed who he might call to pick him up from a friend’s house or party if he wanted to get out of the situation.

Discussion
Electronic cigarettes, e-cigarettes or electronic nicotine delivery devices (ENDS) are battery-powered devices that vaporize nicotine or non-nicotine containing solutions by a heating element. They were originally introduced into the global market around 2004 and in the United States market in 2007. Their use is commonly called vaping. The vaporized solutions are called e-liquids which usually contain propylene glycol, glycerin, water, nicotine, and flavorings, but variations without different components are sold as well. The devices can also be modified to vaporize other combustible materials such as oils, wax, and dried materials such as tobacco or cannibas.

The potential risks of e-cigarettes are not fully elucidated to date, but potential risks include:

  • Nicotine addiction
  • Inhalation, ingestion, or absorption of harmful chemicals including various carcinogens, nicotine, formaldehyde and acetylaldehyde
  • Potential use of other drugs and/or alcohol
  • Burns from the heating elements
  • Long-term effects that are currently unknown

Potential benefits of e-cigarettes could be decreased risks compared to combustible cigarettes or for smoking cessation, but again data is unproven to date.

Countries worldwide are recognizing the unknown but potential effects of e-cigarettes and are increasing their regulation. The United States Food and Drug Administration is currently seeking to extend its legal authority to regulate e-cigarettes in addition to the numerous tobacco products that it already oversees and regulates. Additionally, US state legislatures and local municipalities may or may not have laws that regulate e-cigarette purchase and use, particularly for minors. The American Academy of Pediatrics recommends children not be exposed or use any tobacco products in any form and the minimum age to purchase products be consistent across the US at age 21 years.

As with all potentially hazardous materials, e-cigarettes and liquid nicotine should be kept locked up and out of the reach of children. E-cigarette users should follow the package label for appropriate disposal.

Learning Point

The use of e-cigarettes by minors in the United States is rapidly increasing. Many data sources cite ~20% use of e-cigarettes by teens with a current trend that is increasing, and a stable or decreasing trends (~10-15%) for cigarette use. A study of high school students in Hawaii with data collected in 2013 found that 17% used e-cigarettes, 12% had dual use of e-cigarette’s and conventional combustible cigarettes (cigarettes), and only 3% used combustible cigarettes. A study of high school students in California with data collected in 2014 found 24% used e-cigarettes, 3.2% reported dual use, and 18.7% used cigarettes. The National Youth Tobacco Survey found an increase in e-cigarette use from 2011 to 2014 (2011 = 1.5% and 2014 = 13.4%). Cigarette and e-cigarette use has been strongly associated but during the same time, there has been a decrease in cigarette use among teens (2011 = 15.8% and 2014 = 9.2%). A study of high school students in Connecticut with data collected in 2014 found 18% e-cigarette usage. A significent number of the teens had also used the devices to vaporize cannibas variants including hash oil (15-23%), wax fused with the cannibas’s active ingredient (10-15%) or used dry cannabis leaves (20-29%).

Questions for Further Discussion
1. What are the acute affects of nicotine overdose?
2. What are risk factors for use of e-cigarettes and other tobacco products?
3. How much do e-cigarettes devices and e-liquid cost?

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: Smoking and Youth and Smoking.

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.

Wills TA, Knight R, Williams RJ, Pagano I, Sargent JD. Risk factors for exclusive e-cigarette use and dual e-cigarette use and tobacco use in adolescents. Pediatrics. 2015 Jan;135(1):e43-51.

Pbert L, Farber H, Horn K, Lando HA, Muramoto M, O’Loughlin J, Tanski S, Wellman RJ, Winickoff JP, Klein JD; American Academy of Pediatrics, Julius B. Richmond Center of Excellence Tobacco Consortium. State-of-the-art office-based interventions to eliminate youth tobacco use: the past decade. Pediatrics. 2015 Apr;135(4):734-47.

Barrington-Trimis JL, Berhane K, Unger JB, Cruz TB, Huh J, Leventhal AM, et.al. Psychosocial Factors Associated With Adolescent Electronic Cigarette and Cigarette Use. Pediatrics. 2015 Aug;136(2):308-17.

Morean ME, Kong G, Camenga DR, Cavallo DA, Krishnan-Sarin S. High School Students’ Use of Electronic Cigarettes to Vaporize Cannabis. Pediatrics. 2015 Sep 7. pii: peds.2015-1727.

American Non Smokers Rights Foundation. States and Municipalities with Laws Regulating Use of Electronic Cigarettes. Available from the Internet at http://www.no-smoke.org/pdf/ecigslaws.pdf (rev. 6/1/15, cited 9/16/15).

National Convention of State Legislatures. Alternative Nicotine Products, Electronic Cigarettes. Available from the Internet at http://www.ncsl.org/research/health/alternative-nicotine-products-e-cigarettes.aspx (rev. 8/11/15, cited 9/16/15).

American Academy of Pediatrics. AAP Statement on New E-Cigarette Poisoning Data, Need for Government Action. Available from the Internet at https://www.aap.org/en-us/about-the-aap/aap-press-room/pages/EcigarettePoisoning.aspx (rev. no date, cited 9/16/15).

American Academy of Pediatrics. Electronic Nicotine Delivery Systems. Available from the Internet at http://www2.aap.org/richmondcenter/ENDS.html (rev. no date, cited 9/16/15).

American Academy of Pediatrics. Clinical Practice Policy to Protect Children From Tobacco, Nicotine,and Tobacco Smoke. Available from the Internet at: http://pediatrics.aappublications.org/content/early/2015/10/21/peds.2015-3108.full.pdf+html (rev. 10/26/2015, cited 10/26/2015).

Author

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

What is a Tonsillolith?

Patient Presentation
A 17-year-old male came to clinic with halitosis for the past several days. He denied any fever or pain, and was performing oral hygiene at least 2x/day. He denied any allergic or upper respiratory tract infection symptoms. He also denied any foreign bodies, medications or drug use, or eating strong foods. The past medical history was positive for 2 strep throat infections over the past 6 months.

The pertinent physical exam showed a healthy male in no distress with normal vital signs and growth parameters. His ears and nose examination was normal. His oral examination found a white/yellow lesion within the right palatine tonsil. The tonsils did not show any erythema and were not enlarged. His teeth had good oral hygiene. The diagnosis of a tonsillolith was made. As the physician described the tonsillolith to the adolescent, he got a smile on his face and said, “That’s what I thought it was because it looked like the pictures on the Internet. I also spit out a hard thing about a month ago that sort of looked like that.” He was referred to his dentist for removal as it was causing problems and appeared to be recurrent by history.

Case Image
Figure 118 – Clinical image of a giant tonsillolith. From Thaker, 2008. Creative Commons License. Other images can be seen in the To Learn More below.

Discussion
Tonsillolith or tonsil stones are calcified structures that form in the palantine tonsillar crypts. The calculi are made up of calcium and other salts, along with microorganisms and other unidentified material (oral debris), that are likely caused by chronic irritation of the tonsil. Tonsilloliths often cause no problems and are an incidental finding on physical examination, but they can cause irritation, local pain, referred pain (to the ear), foreign body sensation, abscess and halitosis. Bacterial metabolism can cause volatile sulfur compounds and gases to be produced, thus causing oral halitosis. Tonsilloliths usually self-resolve, but they can also become dislodged and swallowed, or regurgitated as in the patient above.

Tonsilloliths are generally not common in the pediatric age range, but do occur and occur more in the teenage years. This may be because of differences in the pediatric population, but it also may be because of detection. One study of 482 patients in Japan who were being evaluated for head and neck concerns, found only 6 patients with tonsilloliths of the 30 patients who were < 19 years of age. This study evaluated panoramic radiographs versus computer tomography (CT) for tonsillolith detection. CT identified tonsilloliths more often, 46.1%, vs 7.6% for radiographs, CT also identified many tonsilloliths that were of smaller sizes (59 of then were < 2 mm in size). Radiographs detected no tonsilloliths that were < 2 mm and most were 3-5 mm in size. If dental imaging is performed for children, panoramic radiographs are used more often and therefore may not detect the tonsilloliths at all, and/or the tonsilloliths in children may be smaller and therefore not identified.

Learning Point
A tonsillolith is a living biofilm. The “[m]echanism of tonsillolith formation is due to the bacteria form[ing] a three-dimensional structure [with] dormant bacteria being in the center to serve as a constant nidus of biofilm.”

Bacteria adhere to the surface of the tonsil and secretes a slimy substance that holds the bacteria together in the tonsillar crypt. The adhesive substance is a polysaccharide that protects the bacteria against the body’s immune system. “Cell to cell signaling (quorum sensing) and communication with different bacteria enhances the biofilm formation.” Matrix calcification also appears to give further protection to the bacteria biofilm.

Aerobic and anaerobic microorganisms are present in tonsilloliths, with aerobic bacteria predominating on the external surface and anaerobic bacteria on the internal area.

Questions for Further Discussion
1. What are indications for referral for dental care?
2. What are indications for tonsillectomy? See Review here
3. What causes halitosis? See Review here

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: Tonsils and Adenoids.

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.

Thakur JS, Minhas RS, Thakur A, Sharma DR, Mohindroo NK. Giant tonsillolith causing odynophagia in a child: a rare case report. Cases J. 2008 Jul 18;1(1):50.

Babu TA, Joseph NM. Persistent earache due to tonsillolith. Indian Pediatr. 2012 Feb;49(2):144-5.

Oda M, Kito S, Tanaka T, Nishida I, Awano S, Fujita Y, et.al. Prevalence and imaging characteristics of detectable tonsilloliths on 482 pairs of consecutive CT and panoramic radiographs. BMC Oral Health. 2013 Oct 14;13:54.

Yellamma Bai K, Vinod Kumar B. Tonsillolith: A polymicrobial biofilm. Med J Armed Forces India. 2015 Jul;71(Suppl 1):S95-8.

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital

What Are Treatments for Hiccups?

Patient Presentation
An 8-year-old male came to clinic for his well child care. His mother had no concerns and the patient was healthy. In the office, they were laughing because the boy had hiccups that were causing halting speech that was comical to them. The mother noted that he had intermittent hiccups that appeared to be associated with “fizzier” carbonated beverages such as some types of root beer or ginger ale. The physician inquired if they caused any problems or lasted a long time. The family said that they seemed to get better after a bit of time and never caused any problems. “He’s tried to hold his breath today, but I think all the laughing is making it worse. It’ll go away in a while after we all stop laughing,” chuckled the mother.

Discussion

Hiccups affect nearly everyone at sometime in their life but continue to be poorly understood and are usually considered a nuisance. The medical term for hiccups is singultus which comes from the Latin meaning “to be caught in the act of sobbing.” Hiccups are caused by a diaphragmatic spasm that causes a sudden inhalation that is interrupted by the spasmodic closure of the glottis that produces the characteristic hiccup sound. The ‘hic’ in hiccup occurs 4-60 times/minute and in adults has no physiological purpose, but in fetuses may help train inspiratory muscles for respiration after delivery.

A retrospective study of consecutive patients in a community hospital found 55 of 100,000 patients had hiccups. Of those, only 2 were under age 18, so it appears that although hiccups occur in the pediatric population, they are not often brought to the attention of medical personnel.

Hiccups are classified based on their duration. Acute hiccups last less than 48 hours, persistent hiccups last more than two days and intractable hiccups last more than one month. Hiccups that last more than 48 hours are more likely to be associated with an organic or anatomic problem.

Hiccups are caused by a reflex arc. The afferent component is from the vagus nerve, phrenic nerve and sympathetic nerves of the thoracic outflow tract. The central nerves are in the upper spinal cord, medulla near the respiratory center, hypothalamus and reticular formation. These areas seems to have numerous dopaminergic and GABA-ergic receptors involved. The efferent component is the phrenic nerve to the diaphragm (usually unilaterally) with intercostal muscles also being recruited. Glottis closure is through the recurrent laryngeal nerve branch of the vagus nerve.

Hiccups often seem to start and stop for no specific reason. Causes of hiccups are numerous but those affecting the gastrointestinal tract or central nervous system are common. Stomach distention and gastrointestinal/pulmonary irritants such as carbonated beverages, alcohol and smoking, or even hot chili peppers can cause hiccups. Anxiety and overbreathing or aerophagia can also cause hiccups. Central nervous system diseases that can have hiccups associated with them include epilepsy, meningitis, encephalitis and other brain injuries. Psychosomatic causes include anxiety and excitement, stress and fear. Drugs (benzodiazepines, steroids, and opiates) and also metabolic states (i.e. hyponatremia, hypokalemia, hypocapnia etc.) can cause hiccups.

Complications of hiccups include malnutrition, weight loss fatigue and insomnia.

Learning Point
Charles Mayo made the following comment, “The amount of knowledge on any subject such as hiccup can be considered as being in inverse proportion to the number of different treatments suggested for it.”

There are numerous purported treatments for hiccups. The best treatment for hiccups is directed toward underlying problems identified. Treatment for acute hiccups is usually physical maneuvers but no clinical trials have been conducted. Respiratory maneuvers such as breath-holding or rebreathing seems to help as acute hiccups seem to decrease with an increase in CO2. Using valsalva maneuvers or CPAP-respiration may also be tried. Vagal stimulation such as cold compresses to the face, single-side carotid massage or gentle eyeball massage have also had some success. Induced fright or self-induced vomiting has also been tried. Nasopharyngeal stimulation using irritants such as smelling ammonia or vinegar, or drinking ice water to stimulate the oro-pharyngeal tissues has also been used.

Treatment for persistent or intractable hiccups often involves medications with baclofen and gabapentin being recommended in a recent systematic review. Other secondary and tertiary medications are recommended also in this publication. See To Learn More below.

Questions for Further Discussion
1. When should laboratory testing or radiological imaging be considered for hiccups?
2. If medications do not work, what are other alternative treatments which may be considered for hiccups?

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: Hiccups.

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.

Mayo CW. Hiccup. Sug Gynecol Obstet. 1932;55:700-8.

Amirjamshidi A, Abbassioun K, Parsa K. Hiccup and neurosurgeons: a report of 4 rare dorsal medullary compressive pathologies and review of the literature. Surg Neurol. 2007 Apr;67(4):395-402.

Hao XT, Wang L, Yan B, Zhou HY. Intractable hiccup caused by spinal cord lesions in demyelination disease. J Spinal Cord Med. 2013 Nov;36(6):711-4.

Wallace AH, Manikkam N, Maxwell F. Seizures and a hiccup in the diagnosis. J Paediatr Child Health. 2004 Dec;40(12):707-8.

Cymet TC. Retrospective analysis of hiccups in patients at a community hospital from 1995-2000.
J Natl Med Assoc. 2002 Jun;94(6):480-3.

Steger M, Schneemann M, Fox M. Systemic review: the pathogenesis and pharmacological treatment of hiccups.
Aliment Pharmacol Ther. 2015 Aug 25. (epub ahead of publication).

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital