What Causes Hypocomplementemic Glomerulonephritis?

Patient Presentation
A 10-year-old female was admitted to a regional children’s hospital because of headache and hypertension. The headaches had been present intermittently for 1 week but were not increasing in intensity. They were relieved with rest and ibuprofen. She complained of some intermittent leg pains also. About 3 days prior to admission, her mother noted increased puffiness of her face and abdomen. She had no changes in urination. On the day of admission, the headache returned with increased intensity and she had emesis x 3. Her primary care provider noted a blood pressure of 156/108 and periorbital edema. Urine dipstick in his office showed marked protein and blood. She was then referred. The past medical history was negative. The family history was positive for several family members with lupus, but no other autoimmune, nephrology or gastrointestinal problems. The review of systems showed at least a 10 pound weight gain per mother’s estimate, but no fever, chills, rashes, eye changes, or mucous membrane changes. She denied recent illnesses or travel.

The pertinent physical exam showed a child with moderate pain secondary to headache. Blood pressure was 131/85, pulse of 90, and respiratory rate of 32. She had periorbital and peripheral edema. Lungs had mild crackles at the bases. Heart was tachycardic with a flow murmur. Abdomen was soft and slightly tender throughout, but the abdomen was not tense. A fluid wave was inconsistently present. The rest of her examination was negative. The laboratory evaluation included a urinalysis which showed a specific gravity of 1.030, pH = 6, with +1 ketones and bilirubin, and +3 blood and protein. The microanalysis showed numerous red blood cells but no white blood cells. There were some red blood cell casts. Electrolytes showed a sodium of 143 mEq/l, potassium of 4.4 mEq/l, BUN of 44 mg/dl and creatinine of 1.7 mg/dl. Total cholesterol was 126, high density lipoprotein of 36 and low density lipoprotein of 79. C-reactive protein was < 0.5 mg/dl. C3, C4 and CH50 were significantly low. CBC and bleeding profile laboratories were normal. Her antistreptolysin O titer was 738 IU/ml (normal 0-240).

The diagnosis of presumed acute post-infectious glomerulonephritis was made. Additional history revealed treatment for streptococcal pharyngitis 3 weeks before admission. The patient’s clinical course showed that she was treated with fluid restriction, diuretics and anti-hypertensive medications. Within 3 days, the BUN and creatinine began to decrease toward normal. She had no oliguria. Because of the strong lupus family history, additional rheumatological testing was done which was all negative. The patient was discharged on day 4 still on antihypertensive medications. At followup 6 weeks later, she was reported to be back to her normal self including no edema, headache and was her normal weight. She still had slightly high, intermittent blood pressures but her electrolytes and urine were normal with a creatinine of 0.6 mg/dl. She was to stop her anti-hypertensive medication and monitor blood pressures at home with telephone followup in 1 week.

Discussion
Post-infectious glomerulonephritis (GN) is very common and 80-90% of cases are caused by acute poststreptococcal glomerulonephritis (APSGN) which is an immune-complex mediated problem.
Typically:

  • Infection precedes the nephritis generally by a few weeks and may be difficult to identify. It can be caused by nephritogenic strains of Group A, Beta-hemolytic Streptococcus from both pharyngitis and dermatological infections, other bacteria, viruses and parasites. Interestingly, usually acute rheumatic fever and APSGN do not occur together.
  • Abrupt onset of edema, hematuria, usually hypertension, with usually mild renal failure.
  • Patients begin recovering usually starting within 1 week for edema and 2-3 weeks for hypertension. Urinalysis may be abnormal for several years though, especially microscopic hematuria.

Lab testing:

  • C3 level low (< 50% normal) and generally returns to normal in 3-6 weeks
  • C4 levels usually are normal (if low, consider other causes)
  • Antistreptolysin O titre is positive in ~80% of children
  • Other tests are often ordered to eliminate other disease causes and to help treatment

Supportive care is the mainstay of treatment with careful fluid management including fluid restriction and diuretics, electrolyte management (including sodium restriction) as necessary, antihypertensive medications to control hypertension, and antibiotics only if an infection is identified.
If the clinical presentation does not support an initial diagnosis or clinical course consistent with the diagnosis of APSGN such as having increasing hematuria or anemia, uncontrollable hypertension, progressive renal insufficiency such as oliguria, azotemia or worsening laboratory tests, then renal biopsy may be necessary to identify other potential causes of GN.

Learning Point
Hypocomplementemic glomerulonephritis is caused by one of 4 diseases:

  • Acute post-infectious GN (usually APSGN)
  • GN associated with chronic infections such as shunt nephritis or bacterial endocarditis
  • Membranoproliferative GN
  • Lupus GN

Questions for Further Discussion
1. What are indications for a renal biopsy?
2. What are indications for renal dialysis? Review a previous case here.
3. What are the components of nephrotic syndrome?

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: Kidney Diseases and Streptococcal Infections.

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

To view images related to this topic check Google Images.

Rudolph CD, et.al. Rudolph’s Pediatrics. 21st edit. McGraw-Hill, New York, NY. 2003:1677-1681.

Singh GR. Glomerulonephritis and managing the risks of chronic renal disease. Pediatr Clin North Am. 2009 Dec;56(6):1363-82.

Bhimma R. Acute Poststreptococcal Glomerulonephritis. eMedicine.
Available from the Internet at http://emedicine.medscape.com/article/980685-overview (rev. 1/7/10, cited 10/11/10).

ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    6. Information technology to support patient care decisions and patient education is used.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Systems Based Practice
    24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.

    Author

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

  • What Are Causes of Diarrhea?

    Patient Presentation
    A 3-year-old male came to clinic with a 6-week history of large, unformed stools at least 4 times/week. Occasionally he will have a formed stool though. The family denies blood, mucous, constipation, excessive juice or fluid intake, or recent antibiotic use. The past medical history showed Clostridium difficile infection 6 months previously after several antibiotic courses, and it was successfully treated with Flagyl®. The family history was positive for an aunt with irritable bowel syndrome. The review of systems was negative.

    The pertinent physical exam showed a smiling male with appropriate weight gain since last visit and growth parameters in the 50-90%. The physical examination was negative including all mucous membranes and skin. The diagnosis of chronic diarrhea was made. Stool ova and parasites, bacterial culture, shiga and clostridium toxins were performed and were negative. The patient’s clinical course showed at one week the diarrhea continued and an evaluation for inflammatory bowel disease was begun. At two weeks, the inflammatory bowel disease evaluation was negative and the diarrhea had resolved. The clinician suspected Toddler’s diarrhea despite the negative history.

    Discussion
    Diarrhea is increased stool volume, usually with looser consistency and increased frequency than normal. Frequency may not change however. These qualitative attributes are relative to the person’s normal bowel pattern. Acute viral gastroenteritis, one of the most common causes, usually resolves in 2-5 days. Chronic diarrhea is defined as diarrhea lasting more than 2 weeks. With chronic diarrhea there is often a cycle of infection, malabsorption and malnutrition which propagates the diarrhea.

    Osmotic diarrhea usually will cease once the offending agent is stopped such as juice (Toddler’s diarrhea) or dairy products (Lactose intolerance). It has a low stool electrolyte content. Weight loss and failure to thrive may be seen. Secretory diarrhea will continue even when taking nothing by mouth. It has a high stool electrolyte content. Infectious diarrhea often is accompanied by fever, nausea, emesis, prior antibiotic use and possibly bloody stools. More commonly it is an acute problem. Inflammatory diarrhea is generally chronic with other signs of disease such as failure to thrive, arthritis, perianal lesions, and/or rash.

    Diarrhea prevention includes high standards of hygiene include water, food and personal hygiene. Vaccination against Rotavirus is available in many countries. Treatment for acute diarrhea includes oral rehydration solutions, intravenous isotonic fluids, and early refeeding. Antimicrobials for identified microorganisms depends on the organism and presenting problems. Treatment for chronic diarrhea includes removal of the offending agent (e.g. cow’s milk, laxative, juice, etc.), and appropriate evaluation to identify the disease process and its treatment.

    Learning Point
    Common causes of diarrhea include:

      Acute
      • Allergic enteritis – cow’s milk allergy, soy allergy
      • Brush border deficiency – Fructose, Isomaltose, Lactose, Sucrose
      • Infectious
        • Bacteria – common organisms include Aeromonas, Campylobacter, Clostridium, E. coli, Klebsiella, Plesiomonas, Salmonella, Shigella, Vibrio cholera, Yersinia
        • Parasite – common organisms include Amoeba, Cryptosporidium, Giardia, Strongyloides
        • Viral – common organisms include Adenovirus, Astrovirus, Calcivirus, Norovirus, Rotavirus
      • Medications – laxative use or abuse, Magnesium-containing antacids, opioid withdrawal, medication colorants and flavorings such as sorbitol
      • Methylxanthines – caffeine, theophylline
      • Surgical problems – Ascites, Appendicitis, Intussception, Malrotation, Necrotizing enterocolitis, Peritonitis
    • Chronic
      • Abetalipoproteinemia
      • Allergic enteritis – cow’s milk allergy, soy allergy, eosinophilic enteritis
      • Bile salt malabsorption
      • Brush border deficiency – Fructose, Isomaltose, Lactose, Sucrose
      • Celiac disease
      • Congenital chloride diarrhea
      • Endocrine – Addison’s disease, diabetes, hypoparathyroidism, pancreatic insufficiency (Cystic fibrosis, Schwachman-Diamond syndrome), thyrotoxicosis
      • Fecal impaction – including Hirshsprung disease
      • Infectious
        • Parasites – common organisms include Cryptosporidium, Giardia, Tuberculosis
        • Viruses – common organisms include HIV
      • Intestinal lymphangectasia
      • Inflammatory bowel syndrome
      • Immunodeficiency – Common variable immunodeficiency, Graft-vs-Host Disease
      • Irritable bowel syndrome
      • Liver disease, advanced
      • Malnutrition – failure to thrive, acrodermatitis entropathica
      • Medications – alcohol, laxative use or abuse, medication colorants and flavorings such as sorbitol, NSAID enteritis
      • Oncological – primary tumors (including lymphoma), radiation enteritis
      • Psychological – secondary to stress
      • Protein losing enteropathy
      • Surgical problems – short gut syndrome, feeding tube problems
      • Toddler’s diarrhea – excessive intake of clear, sweet liquids
      • Tropical sprue
      • Vitamin
        • Deficiency – Folate, Niacin
        • Toxicity – Niacin

    A differential diagnosis of gastrointestinal bleeding can be found here, and one of different colored stools can be found here.

    Questions for Further Discussion
    1. What is the mathematical formula for determining secretory versus osmotic diarrhea?
    2. How common are pediatric diarrheal deaths in the world? In your own country?
    3. What is your approach to evaluating chronic diarrhea?

    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: Diarrhea
    and at Pediatric Common Questions, Quick Answers for this topic: Chronic Diarrhea

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

    To view images related to this topic check Google Images.

    Lo CW, Walker WA. Chronic Protracted Diarrhea of Infancy: A Nutritional Disease. Pediatrics 1983; 72: 786-800.

    Illingworth RS. Common Symptoms of Disease in Children. Blackwell Scientific Publications: Oxford. 1988:90-94.

    Woodhead JC. Pediatric Clerkship Guide. Mosby. St. Louis MO, 2003:226-229.

    Berkowitz CD. Diarrhea. Pediatrics A Primary Care Approach. W.B. Saunders Company, Philadelphia PA. 1996;344-348.

    Grimwood K, Forbes DA. Acute and persistent diarrhea. Pediatr Clin North Am. 2009 Dec;56(6):1343-61.

    Guandalini S. Frye RE, Tamer MA. Diarrhea. eMedicine.
    Available from the Internet at http://emedicine.medscape.com/article/928598-overview (rev. 4/8/10, cited 10/5/10).

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.

  • Systems Based Practice
    23. Differing types of medical practice and delivery systems including methods of controlling health care costs and allocating resources are known.
    24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.

    Author

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

  • What Are the Classification of Genetic Disorders?

    Patient Presentation
    A pediatrician was telling her partner about a good conversation that she had that day with a parent. She had followed an 8-year old female who had facial hemi-hypertrophy. Over time, several evaluations including consultations with genetics, neurology and imaging. did not reveal a diagnosis. The mother was a strong advocate but wanted to continue to pursue “reasonable” evaluations. The pediatrician would review the medical literature about hemi-hypertrophy and the mother looked at the Internet and found other local services to help support her child and family. During a routine visit, her dentist noticed an unusual lip lesion. The mother agreed to have a picture taken and it was sent to a dental pathologist, who said that it was classic for the diagnosis of Parry-Romberg syndrome which is hemifacial atrophy. (A geneticist later confirmed the diagnosis.) The mother called the pediatrician to let her know the diagnosis and stated that it certainly didn’t change her love of her child, but now she had a diagnosis and she would have a better idea of what the future may hold for her daughter and family. The pediatrician commented that she herself was pleased that the mother felt supported by her efforts to continue to evaluate the child, and that this family made her carefully look at parent desires for testing and to have honest conversations with families about testing and necessity of procedures. She said “…genetics is such a rapidly advancing field that it is always a good thing to have follow-up of your undiagnosed cases.”

    Discussion
    Parry-Romberg syndrome is a rare disorder with atrophy of the soft tissues and skin of the face (usually left-sided) called hemifacial atrophy. External tissues are more affected but also eye, oral, and neck structures. Skin hypo- or hyperpigmentation and whitening of the hair and/or alopecia may occur. Trigeminal neuralgia and seizures can also be seen. Onset is usually between 5-15 years and is more common in females. The atrophy usually lasts 2-10 years and then seems to enter a stable phase. There appears to be a genetic basis for this disease but the exact mechanism is unknown. In the classification below, it would be a miscellaneous disorder.

    Learning Point
    As the tools, techniques and knowledge in the exploding field of genetics continues into the future, many of the disorders and syndromes that are currently classified into one category will necessarily be reclassified because of new knowledge. The field of epigenetics is ripe for expanding classifications and better understanding the natural history of these problems.

    Genetic disorder categories include:

    • Chromosomal disorders
      • Whole or part of a chromosome is missing or duplicated. These are large enough to be seen on a standard karyotype.
      • Examples: Trisomy 21, Cri-du-chat, Turner, Kleinfelter
      • Testing: karyotype
    • Microdeletion or microduplication
      • Part of a chromosome is missing or duplicated. These are often too small to be seen on a standard karyotype
      • Examples: DiGeorge syndrome, Prader-Willi syndrome (deletion type), Smith-Magenis syndrome, Williams syndrome
      • Testing: FISH – fluorescent in situ hybridization, aCHG – array comparative hybridization
    • Single gene disorders
      • A mutation on a single gene. May be autosomomal dominant, autosomal recessive, X-linked.
      • Examples: Cystic fibrosis, Duchenne muscular dystrophy, Marfan syndrome, Sickle cell anemia
      • Testing: DNA sequencing, mutation analysis, deletion testing
    • Triplet repeat disorders
      • Exceeding the number of normal trinucleotide repeats in genes. The normal number varies depending on the gene.
      • Examples: Fragile X, Huntington’s disease
      • Testing: DNA testing for number of repeats
    • Epigenetic disorders
      • The genetic sequence is not changed, but the expression of the DNA is altered
      • Examples: Angleman, Beckwith-Wiedemann syndrome, Prader-Willi (methylation or isodisomy type)
      • Testing: Methylation testing
    • Multifactorial disorders
      • Combination of genetics and environment
      • Examples: isolated congenital heart defects, cleft lip and palate, pyloric stenosis
      • Testing: may be available if part of a syndrome, but usually no testing is available
    • Miscellaneous
      • Not otherwise categorized, and also includes:
        • Associations or non-random association of anomies without a known genetic basis, example is CHARGE association
        • Disruptions or morphological defect of a previously normal organ, example is amniotic bands
        • Sequences or one malformation leads to other malformation, example is Pierre-Robin sequence

    Questions for Further Discussion
    1. What types of disorders can be identified on newborn screening using tandem mass spectrometry?
    2. What tests do your state/country perform as part of newborn screening?

    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.

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

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

    To view images related to this topic check Google Images.

    NINDS Parry-Romberg Information Page. National Institute of Neurological Disorders and Stroke.
    Available from the Internet at http://www.ninds.nih.gov/disorders/parry_romberg/parry_romberg.htm (rev. 2/2007, cited 10/4/10).

    Shur N, Abulo D. Genetic Syndromes: From Clinical Suspicion to Referral to Diagnosis. Pediatric Annals. 2009;38;419-425.

    Online Mendelian Inheritance in Man. Hemifacial atrophy, progressive; HFA.
    Available from the Internet at http://www.ncbi.nlm.nih.gov/omim (rev. 4/30/2010, cited 10/4/2010).

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    6. Information technology to support patient care decisions and patient education is used.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    12. Evidence from scientific studies related to the patients’ health problems is located, appraised and assimilated.
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.

  • Interpersonal and Communication Skills
    17. A therapeutic and ethically sound relationship with patients is created and sustained.
    18. Using effective nonverbal, explanatory, questioning, and writing skills, the healthcare professional uses effective listening skills and elicits and provides information.
    19. The health professional works effectively with others as a member or leader of a health care team or other professional group.

  • Professionalism
    22. Sensitivity and responsiveness to patients’ culture, age, gender, and disabilities are demonstrated.

  • Systems Based Practice
    24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.
    25. Quality patient care and assisting patients in dealing with system complexities is advocated.

    Author

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

    Stacy McConkey, M.D.
    Associate Professor of Pediatrics, University of Iowa Children’s Hospital

  • What Are Common Toxidromes?

    Patient Presentation
    A 30-month-old male was transferred to the inpatient unit at a regional children’s hospital for worsening clinical condition. The night before admission, the father said the patient fell off the back of a couch hitting his head on a chair and/or floor. The child then went limp and was lethargic. While emergency medical services was enroute, the child began to flutter his eyes and have several episodes of emesis. At the local emergency room, his initial laboratory tests were normal except for a glucose of 200 mg/dl and potassium of 2.8 mg/dl. A computed tomography examination of the head was negative. He was admitted locally but began to have more gagging and was not coherent or consistently arousable. The past medical history included croup. The family history included a sister with seizures and other family members with asthma and diabetes The review of systems was negative.

    The pertinent physical exam showed a lethargic appearing male who became somewhat agitated with handling. He had normal growth parameters and vital signs. HEENT showed intermittent eye opening without direct gaze or tracking. Pupils were 3 mm and reactive. Abdomen revealed decreased bowel sounds. Neurological examination showed he was unable to hold his head without support and had marked truncal ataxia. There was decreased tone and normal deep tendon reflexes. Repeat laboratory evaluation was normal. When the family arrived, they mentioned that they had been unable to find the sister’s Tegretol®. The patient’s Tegretol level was drawn about 8 hours after arrival at the local emergency room and was found to be 17.4 mg/L. (normal = 4-12 mg/L.) and diagnosis of a Tegretol overdose was made. The patient was treated with close monitoring and hydration. The patient’s clinical course showed that he was back to his normal baseline at 36 hours. The outside hospital and children’s hospital urine toxicology testing was negative. As there was a complicated social history and other children in the home with injuries (e.g. accidental broken bones and another overdose in other children), the Department of Human Services was contacted and agreed with discharge home but they were planning on investigating the home situation within 48 hours.

    Discussion
    Treatment for toxicologic emergencies initially includes the traditional ABC’s of airway, breathing and circulation management. “D” includes drugs such as glucose, naloxone, thiamine, hydration and oxygen, and disability treatment (or neurological status, some say “Da Brain”) such as fluid management, hyperventilation, etc. “D” in toxicological emergencies also includes decontamination including gastric lavage, syrup of ipecac, activated charcoal, and bowel cathartics. Although antidotes do exist, there are relatively few for the plethora of potential toxic substances. Supportive treatment is a mainstay including fluid management (i.e. hydration, acidification/alkalinazation, diuresis, and dialysis), electrolyte management (i.e. glucose, calcium and potassium management), respiratory management, and an antidote if available.

    The social history is important in all toxicologic emergencies. Accidental overdose is usually the most common reason for a toxicologic emergency in young children and brings up the issue of possible child neglect. Older children and teens may attempt suicide necessitating psychiatric consultation and social service implementation. Forced ingestion may reveal issues of coercion, and even attempted battery, rape or murder. Occupational or recreational exposure may bring to light general safety standards.

    Carbamazepine (Tegretol®) is a common anti-epileptic medication. Peak plasma levels occur 6-24 hours after ingestion.

    • Carbamazepine overdose
      • Most Common Presentation
        • Mental Status – altered
        • Neuromuscular – seizure, dystonia
        • Lung – depression or apnea
        • Eyes – ophthamoplegia
        • Skin – hypo- or hyperthermia
      • Other Common Problems
        • Lung – edema
        • Skin – idiosyncratic reactions
        • GI/GU – decreased bowel sounds, decreased bowel emptying
        • Other – SIADH
      • Agent – carmamazepine
      • Treatment – support, hemodialysis

    Learning Point
    Toxidromes are poisoning patterns or constellations of physical examination findings that are found because of a toxic dose of a medication, drug or toxin. Common toxidromes include:

    • Anticholinergic
      • Most Common Presentation
        • Mental Status – altered
        • Eyes – midriasis
        • Skin – dry, flushed, hyperthermia, dry mucous membranes
        • GI/GU – decreased bowel sounds, urinary retension
      • Other Common Problems
        • Mental Status – seizures
        • Neuromuscular – rhabdomyolysis
        • Heart – dysrhythmias
      • Agent – antihistamines, atropine, scopolamine, tricyclic antidepressants
      • Treatment – physostigmine, sedation, cooling
    • Cholinergic
      • Most Common Presentation
        • Neuromuscular – muscle fasciculations, weakness
        • Lung – respiratory secretions
        • Skin – lacrimination, salivation
        • GI/GU – nausea, emesis, increased stooling and urination
      • Other Common Problems
        • Mental Status – seizures
        • Neuromuscular – paralysis
        • Heart – bradycardia
        • Lung – respiratory failure
        • Eyes – miosis, mydriasis
      • Agent – insecticides including carbamate, organophosphate, mushrooms
      • Treatment – atropine, pralidoxime, airway management and ventilatory support
    • Sympathomimetic
      • Most Common Presentation
        • Mental Status – agitation
        • Heart – tachycardia, hypertension
        • Eyes – mydriasis
        • Skin – diaphoresis, hyperthermia
      • Other Common Problems
        • Mental Status – seizures
        • Neuromuscular – rhabdomyolysis
        • Heart – cardiac arrest, myocardial infarction
      • Agent – amphetamine, cocaine
      • Treatment – sedation, cooling, hydration
    • Hypoglycemic
      • Most Common Presentation
        • Mental Status – altered
        • Heart – tachycardia, hypertension
        • Skin – diaphoresis
      • Other Common Problems
        • Mental Status – abnormal behavior, slurred speech, seizures
        • Neuromuscular – paralysis
        • GI/GU – hypoglycemia
      • Agent – insulin, sulfonylureas
      • Treatment – glucose solutions intravenously or orally
    • Opioid
      • Most Common Presentation
        • Mental Status – depressed
        • Lung – respiratory depression
        • Eyes – miosis
      • Other Common Problems
        • Lung – edema
        • Skin – hypothermia
      • Agent – clonidine, heroin, morphine
      • Treatment – naloxone, respiratory support
    • Salicylates
      • Most Common Presentation
        • Mental Status – altered
        • Heart – tachycardia
        • Lung – hyperpnea, respiratory alkalosis
        • Skin – diaphoresis
        • GI/GU – nausea, emesis
        • Other – metabolic acidosis, tinnitus
      • Other Common Problems
        • Heart – cardiorespiratory arrest
        • Lung – edema
        • GI/GU – ketonuria
        • Other – fever (low grade)
      • Agent – aspirin, wintergreen oil
      • Treatment – hydration, urine alkalinization, hemodialysis
    • Serotonin
      • Most Common Presentation
        • Mental Status – altered especially agitation, hallucination
        • Neuromuscular – increased tone, hyperreflexia
        • Skin – hyperthermia
      • Other Common Problems
        • Mental Status
        • Neuromuscular – whole body tremors
      • Agent – SSRI, SSRI with other medications such as MAOI and TCAs, drugs of abuse including ectasy, LSD
      • Treatment – cooling, sedation, possibly cyproheptadine

    Acetaminophen is not a toxidrome but a common poisoning so it included it here for comparison.

    • Acetaminophen
      • Most Common Presentation
        • Skin – diaphoresis
        • GI/GU – anorexia, nausea, emesis
      • Other Common Problems
        • Mental Status – altered, agitated
        • Heart – dysrhythmia
        • Skin – jaundice
        • GI/GU – hypoglycemia, hepatitis, pancreatitis, renal failure
      • Agent – acetaminophen
      • Treatment – N-acetyl choline

    Questions for Further Discussion
    1. What is the telephone number for the American Association of Poison Control Centers where 24 hour information can be obtained?
    2. What substances are tested for in your local urine toxicology screening test?
    3. What are indications for activated charcoal?
    4. Under what circumstances is Syrup of Ipecac used?
    5. What are some measures parents can take at home to prevent an accidental overdose?

    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: Poisoning

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

    To view images related to this topic check Google Images.

    Fleisher GR, Ludwig S. Synopsis of Pediatric Emergency Medicine. Williams and Wilkins. Baltimore, MD. 1996:405-415.

    RxList. Tegretol.
    Available from the Internet at http://www.rxlist.com/tegretol-drug.htm (rev. 1/3/2008, cited 9/27/2010).

    Waseem W, Gernsheimer JR. Toxicity, Carbemazepine. eMedicine.
    Available from the Internet at http://emedicine.medscape.com/article/1011240-overview (rev. 10/27/2009, cited 9/27/2010).

    Defendi GL, Tucker JR. Toxicity, Acetaminophen. eMedicine.
    Available from the Internet at http://emedicine.medscape.com/article/1008683-overview (rev. 4/16/2010, cited 9/27/10).

    Emergency Central. Table 98.1 Toxidromes.
    Available from the Internet at http://emergency.unboundmedicine.com/emergency/ub/view/Emergency-Medicine-Manual/410204/0/Toxidromes (rev. 2010, cited 9/27/2010).

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.

  • Interpersonal and Communication Skills
    19. The health professional works effectively with others as a member or leader of a health care team or other professional group.

  • Professionalism
    21. A commitment to ethical principles pertaining to provision or withholding of clinical care, confidentiality of patient information, informed consent, and business practices are demonstrated.

    Author

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