What Organisms Cause Osteomyelitis?

Patient Presentation
A 5 week-old white male came to the emergency room with a 1 day history of fever to 39.4 degree Celsius and crying.
He had some loose stools for the past several days but they had no blood, mucous or color change. His brother attended a day care and has had some loose stools for a few days.
There have been no recent day care illnesses or with anyone else the patient has been in contact with.
He had been well with no rashes, emesis, cold symptoms, or coughing. He had been growing well with breastmilk and formula.
There was no history of trauma, including birth injuries.
The past medical history revealed an uncomplicated pregnancy and delivery. He had been seen by his local physician at 1 and 2 weeks of age and was growing well.
The family history was non-contributory.
The pertinent physical exam showed a fussy infant with a temperature of 39.2 degrees Celsius, respiratory rate of 40 respirations/minute, heart rate of 150 beats/minutes, blood pressure of 90/55 mm Hg, weight was 4100 g (50%), height 56 cm (50%) and head circumference 37 cm (25-50%).
The head showed a non-bulging anterior fontanelle. HEENT were normal. Lungs were clear. Heart showed a regular rate and rhythm with no murmurs. There were strong symmetrical peripheral pulses.
Abdomen and GU examinations were normal. Extremity examination showed increased fussiness with general movement of the right leg. There was no redness, warmth or distention to the skin or the leg itself. There was no point tenderness. There was full range of motion in the hips, knees, ankles and toes of both extremities.
The neurological and skin examinations were normal.
The laboratory evaluation and work-up included a complete blood count with a hemoglobin of 13.5 g/dL, hematocrit of 40%, and a white blood cell count of 22,400 x 1000/mm2 with a differential of 50% neutrophils, 20% bands, and 30% lymphocytes.
A C-reactive protein was 1 mg/L (normal 0.08-3.1 mg/L) and the erythrocyte sedimentation rate was 45 mg/hr (normal 1-25 mm/hr).
Cerebrospinal fluid (CSF) examination revealed 2 mononuclear white cells and 5 red blood cells with normal protein and glucose.
Blood, CSF and stool were sent for cultures.
The radiologic evaluation of plain radiographs of the right lower extremity and hip were normal.
During the patient’s clinical course he was begun on Vancomycin and Gentamicin for coverage of common neonatal infections.
Two days after admission the patient’s blood culture grew Salmonella serotype Enteriditis.
The patient continued with fevers and general fussiness for 6 days and then he had increased tenderness to palpation in the right femur. The repeat plain radiographs of the right femr showed an osteolytic lesion in the metaphysis consistent with osteomyelitis on day 6. He was changed to ceftriaxone only after the organism’s sensitivities were finalized on day 7. He became afebrile on day 9. Final cultures of the CSF were negative. Initial stool culture grew Salmonella serotype Enteriditis, but repeated ones were negative. Repeated blood cultures from day 1 and 2 grew the same organism but repeated ones were negative.
Stool cultures for family members were negative and the day care facility was being investigated by the local health department as a potential source. A total of 5 weeks of antibiotics for the diagnosis of salmonella bacteremia with osteomyelitis was planned at discharge.

Discussion
Salmonella is a gram-negative bacilli belonging to the Enterobacteriaceae family.
There are more than 2460 serotypes that are classified by O-antigen groups (A-E).
The most common serotypes were Typhimurium, Enteritidis and Newport.
Main reservoirs for non-typhoidal Salmonella include livestock, poultry, reptiles and pets.
Transmission is mainly by contaminated food but also contaminated water, medicines, medical equipment, and through animal contacts.
Non-typhoidal Salmonella infections cause gastroenteritis (most common), asymptomatic carriage, bacteremia and focal infections such as osteomyelitis and meningitis.
Intermittent or sustained bacteremia can occur and up to 10% of patients with bacteremia develop focal infections.

Salmonella typhi (serotype group D) is only found in humans and is spread by direct contact or contaminated items. It is uncommon in the US (i.e. ~400 cases/year) but endemic in many other countries.
It causes a protracted bacteremic illness that can include fever, abdominal pain, hepatosplenomegaly, skin changes and mental status changes.
Diarrhea and constipation can occur.

Risks of invasive Salmonella infection and mortality are higher in infants, the elderly, hemoglobinopathies (especially sickle cell anemia) and immunosuppressive conditions.
Children < 5 years excrete the organisms for a longer time than older children and adults. Antibiotic therapy also prolongs the excretion. Chronic carriers (1%) are those who excrete for more than 1 year.
Treatment for localized invasive disease such as osteomyelitis is recommended for 4 or more weeks (6 for meningitis) with ampicillin, ceftriaxone or cefotaxime once organism susceptibilities are known.

Osteomyelitis is an infection of the bone whose exact cause is not well understood but main mechanisms include bacteremia, trauma or local invasion. It can affect any bone but most commonly affects the long bones.
Diagnosis can be difficult as it can present insidiously in children with fever, pain, difficulty walking or bearing weight. Laboratory and radiographic testing may be negative early on and therefore should be re-checked. Radiographic changes on plain radiograph are often not apparent until 10-14 days after illness onset.
Bone scans or magnetic resonance imaging are often used for diagnosis. Empiric treatments should be begun for the clinical situation but should include treatment for S. aureus.
For methicillin-susceptable S. aureus, nafcillin, oxacillin or clindamycin are often used. Vancomycin for methicilin-resistance S. aureus is the usual standard.

Surgical drainage of osteomyelitis can be helpful if a subperiosteal or intraosseous abscess is present. If there is direct extension of an infection, direct inoculation or chronic osteomyelitis, then surgical debridement is necessary. Hyperbaric oxygen can also be helpful with chronic osteomyelitis.

Learning Point
In up to 50% of children, a bacterial organism for osteomyelitis is not identified.

Most common causes of acute osteomyelitis include:

  • Staphylococcus aureus – including an increasing amount of methicillin-resistant organisms
  • Streptococcus pneumoniae
  • Streptococcus pyogenes

Other causes include:

  • Anaerobes – including Bacteroides, Clostridium, Fusobacterium, and Peptostreptococcus
  • Bartonella henselae
  • Kingella kingae – associated with osteoarticular infections
  • Gram-negative enteric organisms – seen in neonates
  • Group B Streptococcus – seen in neonates
  • Pseudomonas aeruginosa – can be associated with puncture wounds to the feet
  • Salmonella species

Haemophilus influenzae used to be a common organism but is less common due to vaccination.

Chronic osteomyelitis is commonly caused by S. aureus and gram-negative enteric bacteria.

Questions for Further Discussion
1. When can a child with Salmonella return to childcare?
2. What type of Salmonella typhi vaccines are available and at what ages can they be given?

Related Cases

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

Information prescriptions for patients can be found at MedlinePlus for these topics: Bone Diseases and Salmonella Infections
and at Pediatric Common Questions, Quick Answers for this topic: Salmonella

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

Kaplan SL. Osteomyelitis in Children. Infect Dis Clin North Am. 2005;19(4):787-97.

American Academy of Pediatrics. Salmonella Infections, In Pickering LD, Baker CJ, Long SS, McMillan JA, eds. Red Book: 2006 Report of the Committee on Infectious Diseases. 27th edit. Elk Grove Village, IL: American Academy of Pediatrics; 2006;59-584.

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 competency performed.
    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.

  • 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.
    26. Partnering with health care managers and health care providers to assess, coordinate, and improve health care and how these activities can affect system performance are known.

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

    Date
    October 30, 2006

  • How is Elemental Iron and Lead Related to Heme Synthesis?

    Patient Presentation
    A 14 month old female came to a specialty clinic for a second opinion requested by her mother about anemia and positive lead tests.
    At the 12 month health maintenance visit she was found to have a hematocrit of 30% and a lead level of 21 mcg/dL (normal <10).
    The patient could not be found and followed-up with until 2 months later, when the patient was retested and found to have a hemoglobin = 12.3 mg/dL, total iron = 35 mcg/dL (normal = 40-100), ferritin = 17 ng/mL (normal = 7-142), total iron binding capacity = 421mcg/dL, (normal = 225-450), iron saturation = 8% (normal = 20-50%) and lead level = 24 mcg/dL.
    A wrist radiograph and abdominal radiograph showed no paint chips or lead lines. The patient was placed on treatment doses of oral iron and the health department was contacted to evaluate her home. The parents had an altercation with the health department and so the evaluation was not completed.
    The past medical history revealed a full-term infant with normal developmental milestones to date.
    Her home was built in the 1920s and her mother stated that it is painted with non-leaded paint currently and that it is in good repair with no peeling paint. The mother stated that she plays often on a painted porch and eats dirt from around the house’s foundation.
    She does not go to daycare or spend significant time at other homes. The mother assumed that there is lead piping in the home, but there was no occupational or recreational exposure to lead by family members.
    They also have not used any unglazed ceramics or eaten candy or medicines from other countries.
    Mother continued to exclusively breastfeed the patient but also offers solid foods including some red meat and chicken but states that she doesn’t eat much of it. The patient did receive rice and oatmeal cereal as an infant for an uncertain amount of time. No vitamins have been given.
    The review of systems showed no vomiting, diarrhea, constipation, changes in mental status or development.
    The pertinent physical exam showed a developmentally appropriate toddler with growth parameters in the 10-25%. HEENT showed her to be atraumatic and normocephalic. Abdomen was soft, non-tender with no masses and normal bowel sounds. The rest of the examination was normal.
    The diagnosis of iron deficiency anemia and lead poisoning were confirmed.
    The laboratory evaluation was deferred as the patient had only been on the iron for a few days. The mother was counseled to offer red meat and other iron rich foods first and then if she wanted to continue the breastfeeding for emotional support to offer this afterwards. She was also instructed to give the iron with an acidic fluid such as orange juice (<4 ounces) and that introduction of a cup with whole cow’s milk would be advised.
    The cow’s milk would also provide an excellent protein and calcium source in her diet.
    The mother was extensively re-counseled about the need to identify the lead source which was most likely the dirt around the foundation and/or dust/paint in the home. Handouts from the health department were given and the mother agreed to implementing the dietary changes and allowing the health department to come to her home.
    The patient will be re-assessed in 3-4 weeks.

    Discussion

    Iron deficiency anemia is a hypochromic, microcytic anemia and is the most common cause of anemia in children in the United States, especially in infants and toddlers. It is defined as a hemoglobin level more than 2 standard deviations below the mean reference value for age. It is commonly caused by inadequate stores (e.g. premature infants), inadequate intake (e.g. poor nutrition) or blood loss (e.g. menses). The fetus increases its total iron body stores mainly in the last trimester of pregnancy and if the fetus is born prematurely, it does not have the opportunity to build up its iron stores.
    Fetal iron stores last approximately 6 months, therefore dietary iron intake after birth is very important. Breastmilk contains iron that is bioavailable to infants, but after 6 months breastmilk does not supply enough total iron overall. Formula contains more total iron but this iron is only ~10% bioavailable to the infant. Iron containing cereals are often introduced into the infants diet at ~6 months of age for this reason.
    Infants with poor nutrition often may not receive enough total iron. High milk intake may also cause a microscopic blood loss in the gastrointestinal tract, thereby exacerbating the problem.

    Anemia screening is recommended at age 9-12 months, and for adolescent males and females during routine health examinations. As iron deficiency is the most common cause of anemias, often an empiric trial of therapeutic iron (2-6 mg/kg/day of elemental iron) is often started and then a complete blood count and reticulocyte count is rechecked ~ 1 month later.
    If iron deficiency is the cause, then there should be an increase in hemoglobin 1-2 g/dL. Reticulocytosis can be seen as early as 3 days and peaks at 7-10 days. If appropriate increases are not seen then other causes must be sought. Parental education and possible enrollment in food supplement programs such a WIC (i.e. Women, Infants and Children) program or food stamps may help families dealing with food shortage, although families of all socioeconomic backgrounds can have iron deficiency anemia.

    Other markers of iron deficiency anemia include iron stores (absent), transferrin saturation (&lt;16%), free erythrocyte protoporphyrin (>35 ng/dL), hemoglobin (&lt;11 g/dL) and mean corpuscular volume (<70 fL)

    Lead poisoning is caused most often by environmental lead exposure as it is a ubiquitous heavy metal in the earth’s surface. It can permanently affect intelligence, hearing, growth and is associated with increased developmental deficits, learning disorders and possibly behavioral disorders. Studies have estimated that the intelligence quotient will drop 1-3 points for every 10 mcg/dL of blood lead level.
    Children at highest risk are infants and toddlers because they are close to the ground where contaminated dirt and dust occurs and because they have frequent mouthing behaviors. Children also have a higher absorbency of lead from the gastrointestinal tract than adults (40 vs 10%).

    The local health department can be helpful in identifying the cause of the lead exposure. Lead poisoning is often asymptomatic.
    Common places that children are exposed include:

    • Lead based paint – from older housing especially before 1978 in the United States. Paint chips or dust are ingested. This can be increased during renovation or remodeling.
      Lead paint has a slightly sweet taste and children often like to eat the chips. It is important to remember that children often are in other environments such as a daycare center, relatives’ or friends’ homes which may also have lead. Lead abatement may actually raise lead levels. Families are often counseled to repaint the house with a non-lead based paint and to keep it in good repair.
      Additionally, frequent vacuuming to clean up dust and/or frequent washing/wiping of surfaces with a non-phosphate containing detergent can help decrease dust exposure.

    • Contaminated dirt – often found near older housing or near highways. Lead based paint may have been removed or painted over, however the dirt near the house has a high lead concentration. Lead based gasoline was previously used in the US and the emissions often contaminated soil near heavily traveled roads.
    • Lead piping and solder – Home water supplies that contain lead piping or that use lead solder are common in older homes. Lead can leach into standing or warm water. It is recommended before using water for drinking or food preparation for the first time in the morning, to run cold water for 2 minutes before using it.
    • Occupational exposure – parents working as a painter, welder, foundry worker, home renovator, battery plant, sheet or scrap metal or plumber or other occupations may have contaminated clothing that the child is exposed to.
    • Recreational exposure – parents working with leaded glass or ceramics may expose their children.
    • Unglazed ceramics and lead crystalware – certain ceramics and crystalware may contain lead and it can leach into the food and liquids placed into these containers. The child then eats or drinks the food and liquids and is exposed. The leaching of the lead is increased if acidic food is placed into them (e.g. orange juice) or the food item remains in the container for a long time.
    • Candy and medications – candy, medications or folk remedies purchased in other countries, often Mexico, may contain lead.
    • Art supplies – all art supplies in the US must be certified as non-toxic to be sold. Supplies purchased in other countries may not be non-toxic.

    Low risk children are usually screened for lead at 12 and 24 months. High risk children are usually screened for lead at 12, 18, 24 months and at 3, 4, and 5 years or age. Fingerstick blood samples are often used but can be contaminated. Venous blood levels are used for confirmation and to monitor the child. The FDA has recently certified a new portable, easy-to-use, finger-stick test which gives results in 3 minutes and is comparable to a full laboratory testing.

    Iron deficiency anemia and lead poisoning can occur separately but often occur concomitantly.

    Learning Point

    Normal hemoglobin has 3 components: iron (Fe+2, an element), heme (an organic molecule), and globin (a protein molecule).
    Problems in any of these 3 components can lead to a variety of disease states including porphyrias and thalassemias.
    Lead interferes with early steps in heme synthesis leading elevations of erythrocyte protoporphyrin, zinc protoporphyrin (ZPP), and d-aminolevulinate (which is neurotoxic). ZPP is sometimes used as a screening test for lead.
    The final step in heme synthesis is the addition of Fe+2 to the finished heme molecule.

    Questions for Further Discussion
    1. What are the recommended treatments for lead and at what level should they be instituted?
    2. What is the recommended treatment for iron deficiency anemia?

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed for Lead Poisoning
    and PubMed for Iron Deficiency Anemia.

    Information prescriptions for patients can be found at MedlinePlus for these topics: Lead Poisoning and Anemia
    and at Pediatric Common Questions, Quick Answers for these topics: Lead Poisoning and Iron Deficiency Anemia

    To view current news articles on this topic check Google News for Lead Poisoning
    and Google News for Iron Deficiency Anemia.

    Rudolph CD, et.al. Rudolph’s Pediatrics. 21st edit. McGraw-Hill, New York, NY. 2003:368-371,1525-1528.

    Diwan JJ. Molecular Biochemistry II. Synthesis of Heme. Rensselaer Polytechnic Institute. Available from the Internet at: http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb2/part1/heme.htm(rev. 2005, cited 9/21/06).

    Early and Periodic Screening Diagnosis and Treatment (EPSDT) Care for Kids Newsletter. The Effects of Lead Exposure on School Performance. 2006;13(2). http://64.233.167.104/u/IowaEPSDT?q=cache:KNnzTCz5RYAJ:iowaepsdt.org/EPSDTNews/2006/Spring06/spring06.pdf+lead&hl=en&gl=us&ct=clnk&cd=4&ie=UTF-8 (rev. Spring 2006, cited 9/21/06).

    U.S. Food and Drug Administration Press Release. FDA Broadens Access to Lead Screening Test That Gives Immediate Results. Available from the Internet at: http://www.fda.gov/bbs/topics/NEWS/2006/NEW01456.html (rev. 9/18/06, cited 9/21/06).

    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.
    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
    17. A therapeutic and ethically sound relationship with patients is created and sustained.

  • Professionalism
    20. Respect, compassion, and integrity; a responsiveness to the needs of patients and society that supercedes self-interest; accountability to patients, society, and the profession; and a commitment to excellence and on-going professional development are demonstrated.

  • 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.
    25. Quality patient care and assisting patients in dealing with system complexities is advocated.
    26. Partnering with health care managers and health care providers to assess, coordinate, and improve health care and how these activities can affect system performance are known.

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

    Date
    October 23, 2006

  • How Does Gastroesophageal Reflux Present?

    Patient Presentation
    A 4-month-old female came to clinic because her parents were concerned about frequent spitting up.
    They reported spitting up of at least 1/4 of her formula with feeding that was associated with her arching or crying. She seemed eager to eat, but part way through or after the feeding she would become fussy, have some spitting up of formula only, and arch her body. She would finish her formula and was fussy for a period of time after the feeding.
    This pattern occurred at least 2-4 times/day. The spitting up was never projectile. She was taking about 30 ounces of formula per day (5-6 ounces every 4 hours). Frequent burping and a change from a cows milk-based formula to a soy-based formula did not improve the symptoms.
    During the interview her mother did feed her and the infant was noted to be fussy and effortlessly spit up at least 1 ounce of formula but did not arch.
    The past medical history revealed a full-term infant with no prenatal or natal complications.
    The family history was positive for her mother having severe heartburn that she is followed for by a specialist. The father was described as having a sensitive stomach.
    The review of systems was negative for choking, coughing, apnea or gastrointestinal complaints including blood in the stool or vomitus. She had normal growth and development to date.
    The pertinent physical exam showed an infant that interactively smiled initially. Her growth parameters were 10-50% for height, weight and head circumference and were tracking correctly on the growth charts.
    Her gastrointestinal examination revealed a soft abdomen with no tenderness, hepatosplenomegaly or masses.
    The clinical diagnosis of gastroesophageal reflux disease was made and the patient was begun on lansoprazole (off-label use of a gastric acid pump inhibitor) empirically.
    The patient’s clinical course showed that within a few days the episodes had stopped and the infant continued to be evaluated by telephone and electronic mail. The lansoprazole was continued and at ~ 7 months of age, the mother called because the symptoms had re-appeared.
    The dosage was increased based upon a more recent weight and the symptoms again went away. At the 9 month visit, the physician and parents agreed to an empirical trial off the medication to see if it was still needed.

    Discussion
    Gastroesophageal reflux (GER) is the normal physiological process of gastric contents passing into the esophagus throughout the day that is caused by transient relaxation of the lower esophageal sphincter.
    This is usually cleared by gravity, peristasis and neutralization of the acid by saliva. These protective mechanisms decrease during sleep.
    This process can sometimes lead to gastroesophageal reflux disease (GERD).
    Since GER is normal, it can be difficult sometimes to determine if there is GERD. There is no gold standard for GERD diagnostic testing, but common tests include:

    • Upper gastrointestinal radiography (UGI) is useful to determine anatomical abnormalities and other causes of nonbilious emesis such as pyloric stenosis and achalasia. Reflux of radiographic contrast occurs in many normal individuals and therefore UGI is not useful for GERD.
    • Esophageal pH monitoring. Monitoring records the frequency and duration of reflux episodes into the esophagus. Certain standard measurements (11% mucosal exposure for infants and 6% for older children) determine the risk for esophagitis.
    • Upper endoscopy with biopsy – is useful to evaluate for esophagitis, stricture, etc. Also allows diagnosis of other diseases (e.g. Crohn’s disease).
    • Nuclear scintigraphy – monitors the distribution of radiolabeled food, but reflux of the food can occur in normal individuals.

    Warning signs and symptoms of disorders other than GERD include:

    • Abdominal distension or tenderness
    • Bilious or forceful emesis
    • Constipation
    • Diarrhea
    • Fever
    • Fontanelle bulging
    • Hepatosplenomegaly
    • GI bleeding
    • Lethargy
    • Macro- or microcephaly
    • Onset of emesis after 6 months of age
    • Seizures

    Learning Point
    Common presentations of gastroesophageal reflux include:

    • General
      • Arching of the body or posturing (i.e. Sandifer syndrome)
      • Fussiness, irritability, inconsolable crying
      • Halitosis
      • Poor dentitia
      • Weight loss, failure to gain adequate weight, or failure to thrive
    • Gastrointestinal
      • Chest pain or abdominal pain (heartburn)
      • Dysphagia
      • Non-forceful, non-bilious emesis
      • Melena, anemia
      • Sore throat
    • Pulmonary
      • Apnea, sudden infant death syndrome, acute life threatening event
      • Bronchospasm, wheezing, asthma
      • Cough
      • Hoarseness
      • Laryngitis
      • Stridor
      • Recurrent pneumonia or pulmonary fibrosis

    Questions for Further Discussion
    1. What does off-label use of a drug mean?
    2. What are the potential legal implications of using a drug off-label?
    3. What treatments are used for GERD?

    Related Cases

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

    Information prescriptions for patients can be found at MedlinePlus for these topics: GERD and Heartburn
    and at Pediatric Common Questions, Quick Answers for this topic: Heartburn

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

    Liburd JDA, Hebra A. Gastroesophageal Reflux. eMedicine.
    Available from the Internet at http://www.emedicine.com/ped/topic1177.htm (rev. 02/15/2005, cited 9/19/2006).

    Rudolph CD, et.al. Rudolph’s Pediatrics. 21st edit. McGraw-Hill, New York, NY. 2003:1389-1394.

    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.
    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.
    15. Information technology to manage information, access on-line medical information and support the healthcare professional’s own education is used.

  • 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
    Associate Professor of Pediatrics, Children’s Hospital of Iowa

    Date
    October 16, 2006

  • What Tests Are Available to Diagnose Cystic Fibrosis?

    Patient Presentation
    A 2-year-old caucasian male came to clinic with his mother for his health maintenance visit.
    She had no concerns about him, but she was 8 weeks pregnant and had just learned that her sister’s new baby was diagnosed with cystic fibrosis (CF).
    The mother said her niece was 2 months old, healthy, was diagnosed by a blood test and was going to see the specialists soon.
    She said that the families were shocked because no one in her family nor the father’s family had CF.
    She says that she has already made her first prenatal appointment but it is scheduled in 2 weeks and she has lots of questions about testing her unborn child.
    The family history is negative for fetal, infant, or unexpected deaths. There were no gastrointestinal or pulmonary diseases. The father had seasonal allergic rhinitis.
    The pertinent physical exam of the 2 year old male is unremarkable.
    The diagnosis of a healthy 2 year old male is made. The physician told the mother that prenatal testing of the parents and the fetus were available, but
    that without more information about the niece he could be more specific about the overall risk of CF for the fetus. The physician also recommended that the mother obtain as much specific information about the niece as possible as this would help increase the accuracy in determining the risk for the fetus.
    The physician gave an information prescription to the mother with Internet resources about CF that she could consult.
    She was also told to consider contacting her obstetrician for a possible earlier appointment.
    The mother’s clinical course was that she had blood DNA testing for CF at her prenatal appointment and was found to be a carrier of the ΔF508 CF mutation. The father then was tested and found to be negative.
    Therefore they were counseled that the fetus should not have CF and should either be normal or be a carrier. Carrier testing could be offered when the child was older.

    Discussion
    Cystic fibrosis (CF) is a common autosomal recessive genetic disease. It occurs worldwide in all ethnic groups. In northern European ethnicity it has an incidence of 1:3200 live births. In African-Americans it is 1:15,000 births and occurs less commonly in Asian populations.
    The carrier risk in Caucasians is ~4%.

    The mutation is on the long arm of chromosome 7. The most common mutation is a 3 base pair deletion causing loss of a phenylalanine at the 508 position of the protein molecule. This ΔF508 causes 70-80% of the mutations, and at least 850 other mutations have been identified.

    CF is a disease of ion channel regulation. There is an impermeability of chloride ions in epithelial cells, leading to dysregulation of ions (including sodium) and fluid. This simplistically leads to increased viscosity of secretions and blockage of ducts and airways.
    The average life span is ~35 years currently.

    Any organ with an epithelial surface can be affected, but major clinical manifestations include:

    • General – malnutrition, growth failure, delayed puberty
    • Pancreas – mainly exocrine dysfunction but also secondary endocrine dysfunction
    • Intestine – intestinal obstruction, meconium ileus
    • Liver – cholelithiasis, cholestasis and cirrhosis
    • Pulmonary – chronic bronchopulmonary infection especially with Pseudomonas aeruginosa, emphysema
    • Skin – high sweat electrolyte with depletion in a hot environment
    • Genitourinary – infertility

    Learning Point
    Tests that are currently available for CF include:

    • Sweat testing – a sweat chloride concentration >60 meq/L on at least 2 samples that are properly collected with an adequate amount of sweat (>100 mg) is diagnostic. Borderline tests (i.e. 40-60 meq/L) need to be re-tested. Because it is almost impossible to test for all the possible mutations, a person usually is not diagnosed with CF unless the sweat test is positive.
      The sweat test can be difficult to perform properly and therefore a patient may need to be sent to a CF center or other large institution that regularly performs the test.

    • DNA testing – is usually done for the ΔF508 mutation plus other common local mutations. It is becoming easier to test for more mutations. DNA testing can be done on blood, buccal brushings, chorionic villous or amniocentesis samples.
    • Immunoreactive trypsinogen – infants with CF have abnormally high levels of immunoreactive trypsinogen (IRT) in their serum and this is the basis for its use in newborn screening programs. The blood spots on Guthrie cards can be screened, and if abnormal, followup tests conducted.
      These tests include DNA analysis and/or repeated IRT testing depending on the local circumstances.

    • Nasal potential differences or nasal PD – can be performed at some CF centers by measuring the electric voltage difference across the nasal epithelium.

    Questions for Further Discussion
    1. What are the current treatments for CF?
    2. Why is Pseudomonas aeruginosa more common in patients with CF?

    Related Cases

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

    Information prescriptions for patients can be found at MedlinePlus for these topics: Cystic Fibrosis and Newborn Screening
    and at Pediatric Common Questions, Quick Answers for this topic: Birth Defects

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

    Rudolph CD, et.al. Rudolph’s Pediatrics. 21st edit. McGraw-Hill, New York, NY. 2003:1967-1980.

    Gross SD, Boyle CA, Botkin JR, Comeau AM, Kharrazi M, Rosenfeld M, Wilfond BS. Newborn Screening for Cystic Fibrosis. Evaluation of Benefits and Risks and Recommendations for State Newborn Screening Programs.
    MMWR. 2004;53(RR13);1-36. Available from the Internet at: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5313a1.htm (cited 9/11/06).

    J Massie, L Curnow, N Tzanakos, I Francis, C F Robertson. Markedly elevated neonatal immunoreactive trypsinogen levels in the absence of cystic fibrosis gene mutations is not an indication for further testing.
    Arch. Dis. Child. 2006;91:222-225. Available from the Internet at: http://adc.bmjjournals.com/cgi/content/abstract/91/3/222?lookupType=volpage&vol=91&fp=222&view=short (cited 9/11/06).

    Price JF. Newborn screening for cystic fibrosis: do we need a second IRT? Arch Dis Child. 2006;91(3):209-10. Available from the Internet at: http://adc.bmjjournals.com/cgi/content/full/91/3/209 (cited 9/11/06).

    Online Mendelian Inheritance in Man. Cystic Fibrosis. National Institutes of Health and Johns Hopkins University. Available from the Internet at: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=219700 (rev. cited 9/14/06).

    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.
    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 competency 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.
    15. Information technology to manage information, access on-line medical information and support the healthcare professional’s own education is used.

  • Interpersonal and Communication Skills

    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.

  • 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.
    25. Quality patient care and assisting patients in dealing with system complexities is advocated.
    26. Partnering with health care managers and health care providers to assess, coordinate, and improve health care and how these activities can affect system performance are known.

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

    Date
    October 9, 2006