Case

A pregnant mother presents with her 8 year-old son who has headache, fatigue, nasal congestion, and decreased interest in school.

A mother who is two months pregnant brings her 8-year-old son, John, to the pediatrician. He has been complaining of headache, weakness, and less interest in school this fall. His symptoms have continued for several weeks. He feels nauseous, but has no vomiting, diarrhea, abdominal pain, or fever. The headache is bifrontal and pounding. It is present in the morning when he wakes up. His teacher says he appears sleepy and does not seem to be paying attention in class, although he does begin to perk up somewhat in the afternoon. The teacher did not mention problems with classmates or adjustments to the beginning of a new year at school. Although his mother tried putting him to bed earlier, it did not seem to help. At first, she thought John’s symptoms were related to a viral syndrome or were a reaction to her pregnancy, since she has been more fatigued and irritable and therefore a bit short with him. She herself complains of considerable “morning sickness” that she describes as headache and vomiting in the morning. Her husband has been traveling more during the past month. In the last few weeks, John’s headaches have become worse. His mother has wondered if he has a medical problem like sinusitis, especially since he has been coughing at night.

John’s previous medical history is unremarkable. His birth was full-term by a normal spontaneous vaginal delivery without complications. His height and weight have been consistently in the 40th percentile for his age. He met his developmental milestones appropriately. His immunizations are up to date. He is not taking medications, dietary supplements, or herbal medicines. Although his mother is a former smoker, she stopped when she was pregnant with John. No one smokes in the house now. The family history is negative for migraine headaches. His maternal aunt has asthma and seasonal allergies. The mother denies family problems with alcohol, drugs, or domestic violence, nor are there any metabolic or genetic diseases. A review of systems and a brief assessment of family function are noncontributory. No one in the family has been traveling in a foreign country.

Physical examination reveals a somewhat tired-appearing but otherwise healthy 8-year-old boy with some mild nasal congestion. His height is 50 inches and his weight 52 lbs (both 50th percentile for age). His temperature is 98.3°F (36.8°C), blood pressure is 100/60 mmHg, and the pulse is 100. His skin and mucous membranes are normal. His neck is supple, without enlarged nodes, masses, or thyromegaly. No other adenopathy is noted. Head, eyes (including fundoscopic exam), ears, nose, and throat are within normal limits except for some mild nasal congestion. The lungs are clear to auscultation except for an occasional scattered wheeze. The heart rate is regular without murmurs. His abdomen is soft, and it is not distended or tender to palpation; there are no abdominal masses or hepatosplenomegaly. Genitourinary exam is normal. His joints have a full range of motion and no signs of inflammation. Neurologic examination reveals normal cranial nerves, sensory function, motor strength and tone, cerebellar function, gait, and deep tendon reflexes. Babinski reflexes are downgoing bilaterally. Vision screening is normal (20/20 bilaterally).

Initial Check Questions 1-4

1. What is the differential diagnosis for this patient?
2. What additional questions relevant to the environment would you gather by interview?
3. What would you include in this patient’s problem list?
4. At this point, what tests would you order to investigate the possibilities on your differential diagnosis?

Initial Check Answers 1 - 4

1. Leading diagnostic possibilities include

   • allergies and/or sinusitis,
   • migraine or tension headache,
   • social adjustment to new school and/or mom’s pregnancy and/or dad’s absence, and
   • carbon monoxide poisoning.

   Other possible diagnostic possibilities include

   • brain tumor,
   • anemia,
   • leukemia,
   • reactions to possible environmental pollutants, and
   • lead poisoning.

   More information for this answer can be found in the “Clinical Assessment—Establish a Problem List” section.

2. What additional questions relevant to environmental exposures would you ask of John and his mother?

   • John’s physical exam is normal except for mild nasal congestion and some wheezing. His findings are not consistent with a brain tumor. Because carbon monoxide (CO) poisoning is a top consideration and lead poisoning and solvent exposure also come to mind, this presentation prompts the need for more questions concerning the home environment and surroundings. Questions include
     • age and condition of the home,
     • heating sources,
     • ongoing or planned renovations,
     • water damage,
     • hobbies done at home,
     • water source,
     • nearby outdoor environment of house, school exposures, and
     • parental occupations.

     The house is a single-family dwelling built around 1960. It has old paint, but none is peeling. The family has lived here for 5 years. The heating source is forced hot air from a gas furnace installed when the house was built. There has been some ductwork repair done a few months previously, at the end of the summer. There is a fireplace in the living room, but the family has not yet used it this year. The chimneys have not been checked or cleaned since the family moved in. The family has smoke detectors but no CO detectors. There have been no current renovations, but the parents are planning to fix up a room for the new baby. There is no history of water damage, nor use of indoor or outdoor pesticides. The family drinks town water. John’s hobbies include putting together model trains, but he rarely uses glues that have solvents. He plays baseball in a nearby field. The school had no recent renovation projects, and John had been there since the preceding year. The home is in a predominately residential area. Two blocks away, a company is digging an underground parking lot. The neighbors say there are leaking chemical barrels buried there. John’s father works in a biotechnology company. Previously, he was a senior “bench” lab scientist. In the last year, he has been involved with administrative matters related to contracting with pharmaceutical companies and has been traveling, so that he has no exposures to chemical or biological agents. The child’s mother works half-time as a graphic designer at a local company, with no exposure to toxic agents. For hobbies, his mother paints with acrylics. She cleans up with soap and water, not with solvents.

   More information for this answer can be found in the “What Types of Questions Should Be Asked if an Exposure-related Illness Is Suspected?” section.

3. What would you include in the patient’s problem list?

   The problem list includes

   • John’s symptoms of:
     • headache,
     • fatigue,
     • nausea,
     • nasal congestion.
   • His mother’s symptoms of
     • headache,
     • fatigue, and
     • nausea that occur in the context of first trimester pregnancy.

   More information for this answer can be found in the “Clinical Assessment—Establish a Problem List” section.

4. At this point, what tests would you order to investigate the possibilities on your differential diagnosis?

   Laboratory testing (biological monitoring)

   • Complete blood count (CBC) with differential
   • Carboxyhemoglobin (COHb) level (A specialist in pediatric environmental health in a poison control center was consulted and suggested that the COHb level should be drawn shortly after John has spent several hours at home, such as first thing in the morning)
   • Blood lead level
   • Magnetic resonance imaging (MRI)of the brain to be considered if above testing is unremarkable, and consultation with a neurologist.

   Because of your concern for the possibility of carbon monoxide or lead exposure, you would also recommend that the mother be tested with a COHb and blood lead.

   More information for this answer can be found in the “Clinical Assessment—Characterize Exposure by Laboratory and Environmental Testing” section.

Results of Laboratory Tests

John’s CBC and differential were unremarkable. His blood lead level was 3ug/dl—which is about background for city dwellers (< 2ug/dl). His blood COHb drawn in the morning, about one hour after leaving his house, was elevated at 15% (normal = 1–3%). His mother’s COHb was 10%, and her blood lead was undetectable.

The COHb is the clinical biological monitoring test used to establish exposure. Background levels range from 1–3% in non-smokers [Ernst and Zibrak 1998]. John clearly has an elevated level, suggesting carbon monoxide poisoning (Table 1).

* Adapted from Government of Alberta Work Safe Alberta site. Available at: http://www.employment.alberta.ca/documents/WHS/WHS-PUB_ch031.pdf [PDF - 182 KB]

Medical management

Once an elevated carbon monoxide (CO) level in the home is recognized, the situation must be treated as a medical emergency. The family must be advised to leave the home immediately. The family is not to return home until the source of the problem is found and the problem is definitively remediated. Failure to act promptly can be life-threatening to John, his mother, and other family members, as well as to her fetus.

The family leaves the home and stays with relatives. The gas company is called and comes to the house. Elevated CO levels are traced to a problem with incomplete combustion in the furnace exacerbated by the design and condition of the ductwork, resulting in CO leaking into the house. The gas company immediately shuts down the furnace and works to remedy the problem. The family does not return until the problem is remedied. In some locales, the utility company is required to report an elevated CO level to the local municipality, which may order the building evacuated until the situation is remedied.

Principles of Biological Monitoring

This example illustrates several points relevant to the choice of effective biological monitoring (laboratory tests) for adverse health effects from possible environmental exposure:

• Choose a measure that most accurately reflects exposure and ideally correlates the best with symptoms.

  Although CO leads to tissue hypoxia, the arterial oxygen tension (PaO₂, a measure of the amount of oxygen dissolved in plasma) is typically normal and unaffected by CO poisoning. Thus, although easy to do, the PaO₂ is NOT a good biological monitor for CO poisoning. Carbon monoxide binds to hemoglobin (200x more tightly than oxygen), and the COHb level, although more difficult to perform, is a good measure of exposure.

• The test must occur within a timeframe that will reflect the occurrence of the exposure and take into account the half-life of the biological indicator.

  The half-life of COHb for someone breathing room air is about 4 hours. In this case, John’s COHb was drawn after he spent the night at home and within about 2 hours of leaving the home; it is therefore expected to be a good measure of home exposure. If the COHb was drawn after school, perhaps 8 hours after exposure, the level may have already declined to near background level and the diagnosis may have been missed.

• Ideally, the measured level of the biological indicator should correlate well with adverse health effects (dose-response).

  Low and moderately increased COHb levels do not necessarily correlate with the severity of the illness, and there is much individual variability [Ernst and Zibrak 1998]. In this case, John’s COHb is definitely elevated: his symptoms of headache and fatigue are consistent with a blood COHb of 15%. His level may have been higher if measured sooner after exposure.

  Pediatricians may need to use resources for guidance in choosing the best biological monitoring tests for environmental exposures in children. These include Regional Poison Control Centers (1-800-222-1222), Pediatric Environmental Health Specialty Units ( http://aoec.org/PEHSU/), toxicology documents from ATSDR (http://www.atsdr.cdc.gov/), and relevant textbooks [Lauwerys and Hoet 2000; Olson 2004].

Environmental Assessment

Environmental monitoring is often an important component in assessing exposure. Sometimes it is the major one when biological monitoring is not possible or adequate. Environmental monitoring includes air monitoring (as for CO) and monitoring such other media as water and soil when necessary. Reference ranges are available for acceptable levels of contaminants in drinking water [US Environmental Protection Agency 2003], ambient (outdoor) air (http://www.epa.gov/ttn/naaqs/), and indoor air (http://www.epa.gov/iaq/co.html). For example, EPA has an ambient air quality index chart suggesting a level of concern for CO levels of 9 parts per million (ppm) over 8 hours. There are no agreed-upon standards for indoor home air, but average levels in homes without gas stoves vary from 0.5 to 5 ppm, while levels near properly adjusted gas stoves are often 5–15ppm (http://www.epa.gov/iaq/co.html). For the work site, the US Occupational Safety and Health Administration (OSHA) set the allowable CO standard at 50 ppm for an 8-hour time-weighted average. The American Conference of Governmental Industrial Hygienists set 25 ppm as an 8-hour time-weighted average.

Diagnosis

CO poisoning is the primary diagnosis, and it is potentially life-threatening.

CO is an odorless, non-irritating, and colorless gas generated from the incomplete combustion of carbon-based fuels. It can be generated from a variety of sources, including

• forced air furnaces,
• unvented or poorly vented kerosene and gas space heaters,
• poorly ventilated natural gas stoves and gas fireplaces,
• gas water heaters,
• wood stoves, and
• automobiles with poorly functioning exhaust systems with emissions that accumulate in attached garages when a car is running.

CO poisoning is one the most common types of unintentional poisoning in the United States, accounting for thousands of emergency department visits and some 800 deaths annually [Ernst and Zibrak 1998; Piantadosi 2002].

Acute effects of mild CO exposure include non-specific flu-like symptoms (headache, dizziness, weakness, nausea, vomiting) along with dizziness and confusion. Higher and more prolonged exposure can lead to seizures, coma, and death. Delayed cognitive effects have been reported as sequelae of severe CO poisoning, accompanied by loss of consciousness and/or seizures [Kwon et al. 2004].

CO toxicity results from a combination of tissue hypoxia and direct CO-mediated damage at the tissue level [Ernst and Zibrak 1998]. CO competes with oxygen for binding to hemoglobin, and CO binds 200x more tightly than oxygen, leading to less oxygen released at the tissue level and consequently to tissue hypoxia.

Special Susceptibility of Infants and Children

Infants and children have increased susceptibility to the effects of CO because of higher metabolic rates. Children with such underlying pulmonary conditions as asthma and those with anemia are more susceptible to CO effects. The fetus is very susceptible because fetal hemoglobin has a higher affinity for CO than adult hemoglobin.

Initial Check Question 5

5. What actions would you recommend now to treat mild carbon monoxide poisoning?

Initial Check 5 Answer

5. Recommend actions now to treat mild carbon monoxide poisoning.

• Immediate removal from exposure—no return to the house until repaired.
• 100% oxygen for John and his mother, either on site or in the emergency department.
• Treatment with hyperbaric oxygen to prevent long term neurological sequelae is controversial. Most authorities would not recommend hyperbaric oxygen treatment at the levels seen in John’s case. COHb levels must reach more than 15% in pregnant women [Ernst and Zibrak 1998] and more than 25% in others [Thom 2002; Weaver et al. 2002] before hyperbaric oxygen treatment would be considered. This advice should be considered with caution because many studies excluded children under age 18 and pregnant women [Weaver et al. 2002].

More information for this answer can be found in the “How Do You Manage a Child with Known Environmental Exposures?” section.

Continuation of Case Study

After treatment with oxygen and repair of the furnace, John and his mother felt much better. John’s headache and fatigue completely resolved, but his nasal congestion persisted. He is now with some dry cough and slight breathlessness with activity.

Initial Check Question 6

6. Although the primary diagnosis was carbon monoxide poisoning, what other diagnoses need to still be considered?

Initial Check 6 Answer

6. Allergies and asthma also need to be considered once the life-threatening CO situation has been remedied.

CO explains headache and fatigue but does not explain nasal congestion and wheezing. Allergies and asthma may be additional conditions to consider. Environmental triggers of asthma include irritants and allergens found in outdoor or indoor environments (for further information, see the ATSDR CSEM “Environmental Triggers of Asthma”). Indoor allergens include dust mites, animal allergens, cockroaches, and molds [Rosenstreich et al. 1997; Etzel 2003]. Indoor irritants include second-hand smoke (SHS), wood smoke from fireplaces, nitrogen oxides from space heaters or gas-fueled cooking stoves, and volatile organic compounds (from building materials, pesticides, home solvents, and cleaners) [IOM 2000; IOM 2004]. Outdoor allergens include pollens, molds, and organic materials such as soybean dust [Anto et al. 1989; Anto, Sunyer et al., 1993]. Such ambient air pollutants as particulates, ozone, and sulfur dioxides increase asthma exacerbations and decrease exercise tolerance in children [Delfino 2002; McConnell et al. 2002; Committee on Environmental Health 2004].

More information for this answer can be found in the “What Types of Questions Should Be Asked if an Exposure-related Illness Is Suspected—Final Follow-up Questions?” section.

Initial Check Question 7

7. What recommendations would you give to prevent such environmentally related problems as carbon monoxide poisoning?

Initial Check 7 Answer

7. Steps to prevent CO poisoning.

• Advise parents to check all fuel-burning appliances once a year or as recommended by the manufacturer. This includes forced air furnaces, gas water heaters, gas stoves, gas clothes dryers, fireplaces, and wood stoves. Carbon monoxide detectors are also recommended but are not a substitute for regular inspections of appliances.
• Have parents purchase CO alarms that meet the standards of the Underwriters Laboratory (UL2034). These are the most reliable (U.S. Consumer Product Safety Commission: http://www.cpsc.gov).
• Identify and reduce environmental risk factors for asthma. With John’s symptoms noted in the fall, triggers could be dust mobilized when the heating system is used, mold on leaves spread by wind, or volatile toxicants released during household use or from such other nearby sources as a leaking underground storage tank.
• Be extremely careful concerning home renovation because of potential risks of increasing lead exposure, particularly to the mother (and fetus) and John. Given the age of the home, it probably has lead paint, so that testing of the paint is recommended before renovations begin. Efforts to de-lead or repair and contain lead paint must be done by a contractor certified to remove lead safely.

More information for this question can be found in the “How Do You Manage a Child with Known Environmental Exposures?—Public Health Reporting” section.