What Are Toxin-Mediated Diseases?

Patient Presentation
A pediatrician’s daughter was talking at dinner about her biology class. “The teacher said different germs can make toxins. I thought that toxins were things like cleaning supplies and chemicals,” she said. “Once the germ like a bacteria gets into your body, how do you think it can make you sick?” her father asked. He explained different ways that organisms can enter the body and affect it, including using her previous knowledge of intracellular structure. “Do you remember the endoplasmic reticulum? It makes the cell’s proteins. It manufactures them. If a toxin stops the manufacturing then the cell dies and the whole organism could die too. I’d have to look it up but I think that is how Shiga toxin works,” he explained.

Discussion
A poison is a generic term for “a substance with an inherent property that tends to destroy life or impair health.” A toxin is more specific and is “any poison produced by an organism, characterized by antigenicity in certain animals and high molecular weight, and including the bacterial toxins that are the causative agents of tetanus, diphtheria, etc., and such plant and animal toxins as ricin and snake venom.” A toxin does not include those substances that are made synthetically produced. Venom is also a toxin that is used by animals and insects for predation or defense which can cause disease in humans such as snake venom, bee venom, etc.

Toxins can be cell associated (i.e. endotoxin) or secreted (i.e. exotoxin). Other terminology describes the action of the toxin such as leukocidin, enterotoxin or neurotoxin. Some toxins enter cells directly or some are receptor-mediated. Exposure to a toxin does not necessarily cause disease as the exposure may not allow penetration into the body, the concentration of the toxin is not high enough, or the body’s defense systems counteract/neutralize the threat. Vaccines can help the immune system prevent some toxin-mediated diseases.

Learning Point
Common toxin-mediated diseases in humans include:

  • Bacteria
    • Anthrax – Bacillus anthracis, enters body through inhalation, disrupts cellular defense
    • Bacillus fragilis – is part of gut microbiome, enters through gut, can cause sepsis or other organ damage
    • Clostridium
      • Botulism – Clostridium botulinum, caused by eating contaminated food or wounds, causes muscle paralysis
      • Clostridium difficile – caused usually by bacterial overgrowth after antibiotics, causes diarrhea and colitis
      • Clostridium perfingens – makes Shiga toxin, caused by eating contaminated food, causes vomiting and diarrhea
      • Tetanus – Clostridium tetani – caused by contaminated wounds, causes paralysis
    • Diphtheria – Corynebacterium diphtheriae, caused by inhalation and wounds, causes respiratory problems, heart failure, paralysis
    • Escherichia – Escherichia coli O157:H7 or non O157:H7, makes Shiga toxin (i.e. STEC or Shiga toxin E. coli), caused by eating contaminated food, causes vomiting and diarrhea, hemolytic uremia syndrome
    • Pertussis – Bordetella pertussis, enters body through inhalation, causes whooping cough
    • Pseudomonas – Pseudomonas aeroginosa, enters through inhalation or contact with contaminated soil or water, causes severe pneumonia
    • Staphylococcus – Staphylococcus aureus caused by eating contaminated food, wounds, and inhalation, can cause toxic shock syndrome, osteomyelitis, endocarditis, other organ system disease
    • Shigella – Shigella dysenteriae makes Shiga toxin, caused by eating contaminated food or water, severe vomiting and diarrhea
    • Vibriosis – Vibrio cholerae strains O1 and O139 make toxin, caused by eating contaminated food or water, causes severe vomiting, diarrhea, liver disease, sepsis
  • Fungi and Algae
    • Aflatoxin – Aspergillus fungus, contaminates corn but also peanuts, causes acute and chronic liver damage or liver cancer
    • Amanitin – Amanita phalloides, caused by eating this harmful mushroom, causes kidney and liver failure
    • Mycotoxins – various types that affect grain supply
    • Neosaxitoxin and Saxitoxin – cyanobacteria, caused by eating contaminated shellfish
  • Plants
    • Abrin – rosary pea seeds, caused by eating contaminated food, causes cellular protein production malfunction
    • Ricin – castor beans, caused by eating contaminated food, causes cellular protein production malfunction

Questions for Further Discussion
1. What are common poisonings?
2. List other toxins?
3. How common are toxin-mediated diseases in your practice and during what time of year?

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 and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Botulism and C. diff infections.

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.

Definition of poison, Dictionary.com. http://www.dictionary.com. Accessed January 19, 2021. https://www.dictionary.com/browse/poison

Definition of toxin, Dictionary.com. http://www.dictionary.com. Accessed January 19, 2021. https://www.dictionary.com/browse/toxin

Bacterial Protein Toxins. Accessed January 19, 2021. http://textbookofbacteriology.net/proteintoxins.html

Toxins, National Biomonitoring Program, CDC. Published April 3, 2019. Accessed January 19, 2021. https://www.cdc.gov/biomonitoring/toxins.html

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

What Are Recommendations for Using Portable Listening Devices?

A 17-year-old female came to clinic for her health examination visit. Her mother basically didn’t have any concerns except that she seemed to not be listening to her as much. “I can’t tell if it’s typical teenager, she’s paying too much attention to all the stuff she’s doing online, or she’s having a hearing problem,” the mother said. The teenager disagreed with her mother and said that she was paying attention to her mother. The teen said she didn’t have any hearing problems, could hear noises and voices just fine, and had no tinnitus or dizziness. The pertinent physical exam showed a healthy female with growth parameters in the 75-90% with normal vital signs.

The diagnosis of a healthy teenager was made. The teenager said that she turned her computer or phone on before putting her earbuds into her ears. “I’ve had a couple of times where I put them in and then got blasted because the volume was turned up. That hurt,” she said. She also said she usually didn’t listen to the radio when she was driving or if she did it was turned to a low volume because she needed to pay attention to the traffic. The pediatrician recommended that the teen did take frequent breaks from the earphones or earbuds in addition to what she was already doing. He also recommended that if the mother wanted to get her daughter’s attention to make sure the teen could see her and not just hear her. “She may not be able to hear you over the earbuds so make sure she can see you. That way both of you won’t be frustrated,” he offered.

Discussion
Hearing loss due to occupational or recreational exposure are problems in our current society. The increased ambient noise in many locations is above recommended thresholds such as street noise, inside communal activities such as sports/music practice or events, or even lunch in a noisy cafeteria, etc. Equipment can be sources of unrecognized exposure including air compressors, gardening tools such as leaf blowers, trimmers, lawn mowers, and snow blowers, and even loud home appliances such as vacuum cleaners, washers/dryers, and dishwashers. This can be worsened by the concurrent need to increase the volume of other appliances such as a TV or stereo to overcome the dishwasher noise in the background.

Additionally, with the increased use of portal listening devices (PLDs) including mobile phones, and the increase of time spent online, there is an increased use of amplified sound through earphones and ear buds. Harmful sound depends on the volume/intensity and the duration. Overall, “…a sound level above 75 dBA can potentially harm hearing, and a sound level above 85 dbA can induce hearing damage if the daily exposure duration is more than 45 min.” Studies of youth using PLDs have found that these devices are often used daily, for multiple hours/day and “… that PLDs can easily reach sound pressure levels … that are considered to impair hearing.” A “maximum exposure to noise of 85 dB(A) for 8 h per day for a 40-h working week and are commonly [cited] when assessing risky leisure noise exposure.”

Increased risk is due to increased exposure. A longitudinal study of German youth over 5 years found that auditory noise exposure did not change over time and that up to 73% of students exceeded these noise levels at one or more sampled time periods. Using PLDs increased the exposure compared to listening to music via a loudspeaker. The type of music also made a difference with listening to “charts, rock, and pop” more likely to exceed thresholds than “oldies and jazz” or “classic” music. In this study listening to audiobooks, movies, or playing videogames was less likely to exceed the threshold. However the use of PLDs has increased overtime, particularly with the need for online educational activities due the COVID-19 pandemic. Use of PLDs particularly in the setting of other ambient noise and the duration of the activities may have changed since this and other studies were published.

Problems associated with increased noise aren’t just hearing loss but other aural problems including tinnitus, sound distortion, difficulty understanding speech, dizziness, and earache. Other “extra-auditive damage, [includes] sleep disorders, cardiovascular disorders, stress, fatigue, tension, irritability, inattention, tiredness, nervousness, headache and arterial hypertension.”

Noise canceling headphones and ear buds can help by reducing unwanted ambient noise and helping to increase the listening experience. Active noise canceling devices work by creating sound waves in the opposite phase of the incoming noise waves thus canceling the noise waves. Additionally, the actual device also offers physical protection and thus is a passive noise reducer. Even well-fitting over-the-ear or in the ear noise canceling headphones block less noise than noise canceling headphones with a circumaural cushion (i.e. ear-muff style).

As a comparison, water dripping is 0 dB of sound and this is normal hearing. A clock ticking is 20 dB of sound, and a person with this hearing loss may miss some speech consonants. A whisper is 30 dB of sound and a person with this hearing loss may hear only louder noises or have mild speech problems. Conversational speech is 40 dB and a person with a loss may hear speech only as a whisper. A baby crying is 55 dB and a person may only be able to hear loud speech at a few feet with this degree of loss. Other common environmental sounds are telephone ringing (90 dB), lawn mower (100 dB) and an airplane (110 dB). Deafness is defined as a hearing loss > 90 dB. The person will not be able to distinguish between different speech elements. Hearing aids are often recommended for losses > 25 dB. They may also be useful for certain patients with less loss.

Learning Point
Some recommendations for use of PLDs include:

  • Decrease overall use of PLDs as much as possible – frequent aural breaks (at least hourly), use of other auditory devices such as the built-in computer speaker set at a low or normal volume, foregoing using PLDs during various activities such as exercise, cleaning etc. Longer breaks after longer use, such as school work, are also recommended.
  • Properly fitted headphones and ear buds – check fitting when initially purchased and over time
  • Use PLDs with the lowest volume setting or purchase ones that have volume limitations. Some of the volume limiting products may still exceed recommended thresholds though.
  • Keeping the volume at half of the maximum setting is a good general rule but the volume need may change over a day’s use and need to be readjusted downward if it was adjusted upward for a particular reason.
  • Turn the device on first, and then put on the headphones or ear buds – this decreases the chance the initial volume is too loud, and makes the person adjust the level needed for the current listening session.
  • There may be “parental” controls for some devices that can be set.
  • Use of active noise canceling headphones and ear buds can also help

The American Speech-Language-Hearing Association also recommends youth and parents are aware of hearing damage symptoms which can be subtle such as hearing discomfort, difficulty hearing soft or faint sounds, or tinnitus.

Questions for Further Discussion
1. What are causes of sensorineural and conductive hearing loss? A review can be found here
2. How much time do you use a portable listening device daily or weekly and what volume is it set to?
3. What loud noise is in your and your patient’s daily environment?

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 and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Hearing Disorders and Deafness, Hearing Problems in Children and Noise.

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.

Liang M, Zhao F, French D, Zheng Y. Characteristics of noise-canceling headphones to reduce the hearing hazard for MP3 users. J Acoust Soc Am. 2012;131(6):4526-4534. doi:10.1121/1.4707457

Herrera S, Lacerda ABM de, Lurdes D, Rocha F, Alcaras PA, Ribeiro LH. Amplified music with headphones and its implications on hearing health in teens. Int Tinnitus J. 2016;20(1):42-47. doi:10.5935/0946-5448.20160008

Widen SE, Moller C, Kahari K. Headphone listening habits, hearing thresholds and listening levels in Swedish adolescents with severe to profound HL and adolescents with normal hearing. Int J Audiol. 2018;57(10):730-736. doi:10.1080/14992027.2018.1461938

Dreher A, Weilnhammer V, Gerstner D, et al. Longitudinal analysis of leisure noise exposure among adolescents with special focus on portable listening devices: the OHRKAN cohort study. International Journal of Audiology. 2018;57(12):889-897. doi:10.1080/14992027.2018.1510187

Giving the Gift of Hearing Protection: ASHA Offers Tips for Smart Shopping, Safe Listening When Headphones Are on a Child’s Holiday Wish List. Accessed January 11, 2021. https://www.asha.org/news/2020/giving-the-gift-of-hearing-protection-asha-offers-tips-for-smart-shopping-safe-listening-when-headphones-are-on-a-childs-holiday-wish-list/

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

What Are Indications for a Ileostomy?

Patient Presentation
A 19-year-old male with a history of ulcerative colitis, who had an ileostomy after a partial colectomy was presented at the pediatric resident teaching conference. The ostomy had become high output and he was admitted for fluid and electrolyte management to the surgical service. The presenting resident had done a consultation for the surgical service for the concern of sexually transmitted infection treatment. “We took care of the STI issues, but it was very interesting to read his chart and see the ostomy because we usually don’t see these patients. Surgery takes care of them or the GI specialty nurses. It was interesting to see the two ends of the ileum in the one hole, and see how the ostomy bags are managed. Unfortunately with the high-out problem he’s also having a lot of skin irritation too.”

Discussion
There are three types of inflammatory bowel disease (IBD):

  • Crohn’s disease (CD) – can affect entire gastrointestinal tract but often is discontinuous (i.e., has skipped areas), has transmural inflammation and disease, has granulomas
  • Ulcerative colitis (UC) – affects the colon, is continuous (i.e., has no skipped areas) and has superficial mucosal ulcerations
  • Unclassified IBD – has chronic colitis but not specific features of CD or UC

The specific pathogenesis appears to be multifactorial with having a genetic predisposition (1.6 – 30% risk of developing UC if patient has first degree relative), the gut microbiome, the body’s inflammatory response and the overall external environment as factors. Patients can have malnutrition (more common in CD), linear growth impairment and have an increased risk of cancer (including colorectal, lymphoma and non-melanoma skin cancer). Patients have an increased risk of depression, anxiety, and feeling of lack of control in their lives. In some studies, patients with IBD have higher academic achievement and higher annual incomes. There has been an increased incidence of pediatric IBD and especially CD over the last few decades. There also seems to be a latitudinal gradient with more patients in northern latitudes than southern ones.

Ulcerative colitis often presents with increased bowel movements (including at night), stooling urgency, mucousy or bloody stools and abdominal pain. Patients may also have fatigue. Unlike CD they generally will not have malnutrition. Treatment goals are to induce and maintain disease remission, minimize disease or treatment complications, prevent surgery if possible, maintain nutrition, and optimize overall growth, health and normal lifestyle as much as possible. Treatment usually uses anti-inflammatory medications to induce and maintain remission. Unfortunately many patients with IBD become steroid dependent (10-50% for UC patients), but biological therapies have decreased steroid-complications for many patients. UC can be “cured” with colectomy as if there is no colon and rectum then there is no UC, but this also means a patient is then ileostomy dependent for the rest of their lives. Unfortunately, the older the pediatric patient is when diagnosed with UC the more likely they are to need a colectomy at some point in their life (~20% for patients diagnosed after age 10 years). More patients may need surgery at some point in their life (up to 45%). Surgery can be an emergency because of colonic perforation, severe bleeding or toxic megacolon. Non-emergent reasons may be poorly controlled colitis despite medical treatment, patient desire, and nutritional status. There are many different types of proctocolectomies but if maintaining intestinal continuity is a goal, then the anus is maintained and an anastomosis with or without a “pouch” acting as a stool reservoir is created. Complication rates for these surgeries are high (20-50%) and include anastomotic leak, dehiscence, pouchitis, deep venous thrombosis, mesenteric venous thrombosis, increased risk of pouch dysplasia and cancer. A diverting ileostomy may be created as part of these surgeries.

Learning Point
An ileostomy is a surgical diverting procedure where the ileum of the small bowel is brought through a surgical opening in the abdominal wall.
The ileostomy can be temporary or permanent.
Ileostomy indications include:

  • To permanently evacuate the stool when a permanent protocolectomy is performed and a direct anastomosis from the ileum to the abdominal wall is made. This is a single lumen ileostomy.
  • To defunction the distal bowel temporarily to protect a distal surgical anastomosis allowing that anastomosis time to heal. Often a dual opening on the abdominal wall is made where ileum is severed and the proximal ileal lumen attached to the abdomen evacuates the stool and the distal ileum lumen also attached to the abdomen evacuates mucous from the colon. The two lumens lie next to each other through one opening on the abdominal wall.
  • To relieve a bowel obstruction. This is usually a temporary ileostomy.

Ileostomy contraindications are relative and basically due to anatomic problems such as a short mesentary not allowing enough mobilization of the ileum to reach the abdominal wall.
There are some surgical differences depending on the patient’s particular anatomy, size, reason for the ileostomy, etc. Retention of the distal ileum and ileocecal valve is preferred as they are important for nutrition and management of gut mechanics.

Potential problems of ileostomies include infection/abscess, ischemia/necrosis, hemorrhage, retraction/prolapse/hernia formation, stenosis or obstruction, fistula formation and skin irritation.
There can also be electrolyte or dehydration problems if there is high output stool flow. Normal ileostomy output is 200-700 ml/day for adults.

Questions for Further Discussion
1. How is Crohn’s disease different or the same from ulcerative colitis?
2. What is irritable bowel syndrome? A review can be found here
3. What are common skin problems and how are they managed for a patient with an ostomy?

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 and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Ostomy and Ulcerative Colitis.

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.

Wilson DC, Russell RK. Overview of paediatric IBD. Semin Pediatr Surg. 2017;26(6):344-348. doi:10.1053/j.sempedsurg.2017.10.002


Ryan DP, Doody DP. Surgical options in the treatment of ulcerative colitis. Semin Pediatr Surg. 2017;26(6):379-383. doi:10.1053/j.sempedsurg.2017.10.001


Nasiri S, Kuenzig ME, Benchimol EI. Long-term outcomes of pediatric inflammatory bowel disease. Semin Pediatr Surg. 2017;26(6):398-404. doi:10.1053/j.sempedsurg.2017.10.010


Rajaretnam N, Lieske B. Ileostomy. In: StatPearls. StatPearls Publishing; 2020. Accessed January 4, 2021. http://www.ncbi.nlm.nih.gov/books/NBK519003/


Overview of Ulcerative Colitis | Crohn’s & Colitis Foundation. Accessed January 4, 2021. https://www.crohnscolitisfoundation.org/what-is-ulcerative-colitis/overview

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

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