What Are the Long-term Sequelae of Dermatomyositis?

Patient Presentation
A 10-year-old female was admitted to the hospital for an evaluation of possible dermatomyositis.
She first had symptoms 6 months prior to admission when she developed a scaly, red rash on her hands, elbows, knees, bilateral cheeks and eyelids.
Shortly after this rash appeared she began having stiffness in her hands. She had no fevers, weight loss or other systemic problems.
She was seen by an adult dermatologist who diagnosed psoriasis. Since that time, despite dermatological treatment, she has not had improvement.
She needed assistance with activities of daily living at home and at school because of pain and generalized weakness felt to be secondary to deconditioning.
She was referred to a pediatric rheumatologist who believed the differential diagnosis included psoriatic arthritis, dermatomyositis or an overlapping syndrome with another similar disease process.
She was begun on prednisone with improvement of the arthritis, however 4 weeks later, her rash was now progressing on her arms, legs and feet and was violaceous around her eyes and upper cheeks.
She also complained of increasing pain in her right elbow and had difficulty moving it. She said that she also felt weaker.

The family history is negative for joint, muscular, neurological, kidney or small vessel abnormalities.
There is a maternal aunt with migraine headaches, another maternal aunt with psoriasis and other family members have eczema.
Some family members are allergic to penicillin.

The review of systems is positive for 3 days of abdominal pain that was diffuse and intermittent. She had not had a bowel movement for 3 days and had pebbly stools at baseline.
She denied blood per rectum. She also has occasional nausea, but no vomiting or acid reflux in her mouth. She has no fever or urinary complaints.
The pertinent physical exam showed a cooperative girl who had mild pain in her right elbow and no abdominal pain.
She had growth parameters at ~75%. She as afebrile and had a blood pressure of 115/68.
She had mild bilateral yellow-white discharge on her eyelids with mild conjunctival injection. Her lips were dry with mild cracking without bleeding.
Lungs are clear. Cardiac examination is normal with no rubs or murmurs.
Abdomen was slightly distended but soft with normal bowel sounds. She had stool palpable throughout the colon. She had mild tenderness with deep palpation and no rebound. Stool guaiac was negative.
There was no organomegaly.
Skin examination showed a violaceous rash around the eyes and cheeks with mild edema. She also had erythematous, maculopapular patches with mild scaling on the face, arms, legs, chest, abdomen, back and inguinal area. She had golden yellow crusting on some areas of her lower legs.
Extremity examination showed her right elbow was contracted, red and warm. Additionally, she had full flexion but limited extension of the elbow. She had swollen fingers.
Neurological evaluation showed cranial nerves and deep tendon reflexes to be normal. She had decreased strength in her neck (4/5), trunk (3/5) and extremities (3/5). She had a normal gait but needed assistance secondary to her generalized weakness.
An extensive laboratory evaluation was done including a complete blood count showing mild anemia, and increased aldolase, transaminases, lactate dehydrogenase and creatine phosphokinase.
She had a normal C-reactive protein. All other testing was negative
The radiologic evaluation included an right elbow radiograph which was normal and a right elbow magnetic resonance that showed mild subcutaneous edema but no effusion.
Abdominal radiograph showed stool present throughout the colon.
She also had a magnetic resonance imaging of her pelvis which showed findings within the pelvic musculature consistent with dermatomyositis.
After the pelvic imaging the rheumatologists felt that diagnosis of dermatomyositis was probable and felt that a muscle biopsy or electromyographic abnormalities was not needed to further confirm the diagnosis.
The patient’s clinical course was that she was begun on pulse steroid therapy with Solu-Medrol for 3 days by IV infusion for 3 days. Etanercept to be given weekly. She was not started on methotrexate because of her elevated liver function tests.
She was evaluated by physical and occupational therapy who prescribed range of motion exercises and some accommodations for activities of daily living.
Her abdominal pain improved after treatment with Miralax® and subsequent bowel movement. the Miralax was continued as prophylaxis for her constipation.
She was also given lansoprazole and ranitidine for ulcer prophylaxis secondary to her steroids.
for her impetigo she was treated with clindamycin IV and then changed to oral medication with resolution.
Ophthalmology consult confirmed conjunctivitis and recommended gentamicin ophthalmic drops because of her immunosuppression and risk of infection. A more comprehensive ophthalmologic evaluation was recommended as an outpatient.
Her anemia was felt to be secondary to chronic disease.
Her blood pressure remained normal during admission and did not require treatment.
At follow-up 10 days later, her rash is slowly resolving and she is having some increased range of motion in her elbow. She continued to be weak however. Her liver function tests were returning to normal and she was to begin methotrexate soon.
Other laboratory testing for disease monitoring was being completed.

Figure 57 – Axial T2-weighted (above) and post-contrast T1-weighted (below) MRI images through the level of the hips demonstrate small patchy areas of increased T2 signal and mild enhancement bilaterally and symmetrically in the gluteus muscles and in the subcutaneous tissues of the lateral and posterior thighs. These findings were felt to be compatible with mild dermatomyositis.

Discussion
Juvenile dermatomyositis (JDM) is a disease causing inflammation of small vessels in multiple organs. Its etiology is unknown, but possibly is autoimmune in origin. Overall incidence is 2-3/million with females more affected than males.
Over the past 40 years, there has been a marked improvement in survival (mortality is < 3%) and functionality.

In one prospective study of JDM patients presenting symptoms, they had: rash (100%, i.e. heliotrope, Groton papules or malar/facial rashes often), weakness (100%), muscle pain (73%), fever (65%), dysphagia (44%), hoarseness (43%), abdominal pain (37%) and arthritis (35%).
Another study found that JDM patients presenting symptoms had: rash (42-91%), fever (16%), dysphonia (24%), pulmonary problems (11%), arthritis (6%), and gastrointestinal problems (5%).

Learning Point
Patients with JDM can have many long-term sequelae.

  • Calcinosis – seen in 22-40% of patients – usually in sites of trauma late in the disease.
  • Gastrointestinal abnormalities – seen in 22-37% of patients – vasculopathy may cause hemorrhage, perforation or ulceration. Esophageal dysmotility, malabsorption and pneumatosis intestinalis have occurred.
  • Growth problems – seen in approximately 30% of patients – these patients were at least 1 standard deviation below their predicted height.
  • Lipodystrophy and metabolic problems – seen in 14-25% of patients – slow, progressive symmetrical loss of subcutaneous fatty tissue that may be generalized, partial or localized. There may be associated metabolic problems including
    acanthosis nigricans, clitoral enlargement, hirsutism, hepatomegaly, insulin resistance, menstrual abnormalities, and hypertriglyceridemia.

  • Nailfold capillary changes – seen in 80-100% of patients – The total number of capillaries may predict overall disease outcome.

Some patients continue to have long-term problems including weakness (15%), rash (85%), and need for medications (35%). Luckily
most, if not all, appear to have good educational and vocational outcome with patients attending and finishing school and working.

Questions for Further Discussion
1. What medications are available for treatment of dermatomyositis?
2. What are the diagnostic criteria for dermatomyositis?
3. What consultants may be necessary for comprehensive care of a child with JDM?

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: Myositis and Muscle Disorders.

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

To view images related to this topic check Google Images.

Pachman LM, Hayford JR, Chung A, et. al. Juvenile Dermatomyositis At Diagnosis Clinical Characeristics of 79 Children. J Rheumatology. 1998:25;1198-1204.

Huber AM, Lang B, LeBlanc CM, et. al. Medium- and Long-term Functional Outcomes in a Multicenter Cohort of Children with Juvenile Dermatomyositis. Arthritis Rheumatology 2000;43:541-49.

Ramanan AV, Feldman BM. Clinical Outcomes in Juvenile Dermatomyositis. Current Opinion in Rheumatology. 2002;14;658-662.

Rudolph CD, et.al. Rudolph’s Pediatrics. 21st edit. McGraw-Hill, New York, NY. 2003:854-856.

Lindsley CB. Juvenile Dermatomyositis Update. Current Rheumatology Reports. 2006:8;174-77.

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.

  • Systems Based Practice
    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

    Date
    January 7, 2008

  • How Long Does Immunity Last After Routine Childhood Immunization with Pertussis Vaccine?

    Patient Presentation
    A 2.5 month-old male came to clinic with persistent cough of 2 weeks duration.
    He started with a runny nose and then began coughing. The cough has been getting worse especially in the past 2-3 days where he is now having post-tussive emesis of his feeds.
    Since last night his parents have noticed more rapid breathing and he is slower feeding also. They have not noticed any apnea, color changes, tracheal tugging or intercostal retractions. They state that “his belly keeps going up and down more though.”The coughing seems to be all the time and not in groups of coughs.
    He has not had a fever, rash, or diarrhea. He did have sneezing intermittently.
    The past medical history showed that he was born full-term and went home on time. He has not had his two month health maintenance visit.
    The social history showed that he lives with his parents, two preschool age siblings who are immunized, and a high-school age cousin who was immunized in 2004. The cousin has been coughing for about 4 weeks and there is known pertussis in his high school.
    The pertinent physical exam shows a tachypneic infant with a respiratory rate of 70 breaths/minute. He is afebrile, his oxygen saturation is 89% on room air and decreases with coughing episodes.
    He has moderate subcostal retractions and minor nasal flaring and tracheal tugging. He is not cyanotic and is well-perfused.
    HEENT shows no rhinorrhea. Lung examination has no rubs, rales or rhonchi. He seems to have generalized decreased breath sounds.
    The rest of his examination was normal.
    The differential diagnosis of his respiratory distress includes pertussis, pneumonia, sepsis, late onset perinatally acquired infections, and various viral syndromes.
    It was less likely that this is congenital abnormality because of the onset and lack of previous symptoms.
    The patient’s clinical course was that he was admitted to the hospital with a diagnosis of presumed pertussis.
    The laboratory evaluation showed a white blood cell count of 10.3 with 70% lymphocytes.
    Blood cultures, and a nasal swab for respiratory pathogens including pertussis antigen detection were sent.
    The radiologic evaluation was normal.
    He was given supplemental oxygen and monitored for apnea. He was also given occasional albuterol for respiratory distress and wheezing which gave some relief.
    His cousin also had a nasal swab sent for pertussis antigen detection and was begun on azithromycin for presumed pertussis. He had received Td for his 11-12 year vaccinations but as 5 years had not elapsed since that time and he was not in contact with other high risk individuals, he was not re-immunized with Tdap that was currently available.
    His family members were given antibiotics as well to treat unrecognized disease and to limit transmission. Public health was contacted for community disease management once pertussis was confirmed.
    On day 2 of admission, the pertussis antigen testing was positive and the other cultures remained negative throughout the admission.
    He slowly weaned off of his oxygen by day 4 and he had no apneic episodes in the hospital.
    He received his 2 month vaccinations including DTaP prior to leaving the hospital.

    Figure 56 – PA and lateral radiographs of the chest show the heart size and pulmonary vasculature to be unremarkable and the lungs to be clear from infiltrates and effusions. There is no evidence of the classic “shaggy heart” appearance of interstial infiltrates classically described in pertussis pneumonia.

    Discussion
    Bordetella pertussis is pleomorphic gram-negative bacillus that is transmitted by aerosolized droplets between humans which are the only known host.
    The incubation period is from 5-21 days with an average of 7-10 days. It is most contagious during the catarrhal stage and first 2 weeks of cough. .
    Isolation is for 5 days after treatment is started or until 3 weeks after cough has started that has not received treatment.
    It occurs cyclically within communities with 3-5 year cycling but because of travel may occur in any community at any time.

    The catarrhal stage occurs from the beginning of symptoms up to 2-3 weeks of coughing and has symptoms of rhinorrhea, low grade fever, cough, sore throat, headache and fatigue.
    The paroxysmal stage occurs from after the catarrhal stage to weeks later and has progressive proxysmalcough that may be preceeded by an inspiratory whoop. Emesis is common.
    Infants often do not have the whoop sound and may have apnea, gagging or gasping. The whooping sound may or may not be present at any age.
    The convalescent stage occurs from weeks to months and has a gradual improvement of symptoms. Duration of classic pertussis is 6-10 weeks.

    Complications include encephalopathy (0.5%), incontinence, pneumonia (22%), rib fractures, seizures (2%), syncope, sleep disturbance, and death. Particularly in infants < 2 months there is a 1% risk of death. This is markedly decreased after 2 months.
    Diagnostic testing is available for pertussis by culturing on special culture mediums. Unfortunately this takes 10-14 days for results. DNA polymerase chain reaction testing or IgG antibody testing is also available.

    Prolonged cough can also be seen with Mycoplasma pneumoniae, Chlamydia trachomatis, Chlamydophila pneumoniae, Bordetella bronchiseptica, Bordetella parapertussis, Bordetella holmseii , adenovirus, respiratory syncytial virus and some other respiratory viruses.

    Infants less than 6 months are often hospitalized because of the risk of apnea. The infants also need to have their ability to self-rescue after the paroxysms of cough, and ability to remain hydrated.
    Antibiotics if given during the catarrhal phase may improve the disease. After the paroxysmal stage, they are used to prevent the spread of the organism but have no effect on the disease.
    Persons who are unimmunized or underimmunized should receive vaccination as soon as possible.
    Penicillins and cephalosporins are not effective against pertussis.
    Recommended treatment or prophylaxis is with erythromycin, azithromycin or clarithromycin. Trimethoprim-sulfa is used as an alternative.
    Because of the risk of idiopathic hypertrophic pyloric stenosis associated with erythromycin, azithromycin is the preferred drug for infants < 6 months.

    Learning Point
    It is highly infectious with ~80% of household contacts acquiring infection regardless of immunization status.
    Infection itself nor immunization provides life-long immunity. Immunity after receiving early childhood immunization (e.g. infant, preschool, kindergarten) wanes after ~ 10 years.

    Tdap became available for persons 11-64 years of age since the spring of 2005.
    Boosterix® by GlaxoSmithKline Biologicals is recommended for routine immunization for ages 11-18 years (preferrably at the 11-12 year vaccines).
    Adacel® by Sanofi Pasteur is recommended for routine immunization for one dose in persons ages 11-64 years.

    Questions for Further Discussion
    1. What are the differences in the side effect profile for accelular or whole-cell pertussis vaccine?
    2. What other diseases besides pertussis should be reported to the Department of Public Health?

    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: Whooping Cough and Immunization.

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

    To view images related to this topic check Google Images.

    American Academy of Pediatrics. Pertussis, 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;498-520.

    Centers for Disease Control. Guidelines for the Control of Pertussis Outbreaks.
    Available from the Internet at http://www.cdc.gov/vaccines/pubs/pertussis-guide/guide.htm (rev. 2006, cited 11/16/07).

    Altunaiji S, Kukuruzovic R, Curtis N, Massie J. Antibiotics for whooping cough (pertussis).Cochrane Database Syst Rev. 2007 Jul 18;(3):CD004404.
    Available from the Internet at http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD004404/frame.html (rev. 7/18/2007, cited 11/16/2007).

    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.
    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.

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

    Date
    December 31, 2007

  • How Can We Improve Patient Safety?

    Patient Presentation
    A 3-week-old premature male neonate was transferred because of a medication overdose.
    The neonate had been admitted locally after a septic work-up because of a fever to 38.5° Centigrade.
    He was initially treated with ampicillin and cefotaxime but the coverage was expanded 12 hours later to include vancomycin because of a high rate of methicillin-resistant staphylococcus aureus (MRSA) in the local community and hospital.
    After the vancomycin infusion was completed 36 hours after admission, he was noted to be extremely flushed, sleepy and fussy, and it was determined that he had received 12 times the appropriate amount of vancomycin for his weight.
    His parents reported that the antibiotic infusion bag was labeled with another patient’s name.
    Laboratory studies were drawn while awaiting the transport team, which showed a vancomycin level of 242 mcg/ml and blood urea nitrogen of 8.0 mg/dl and creatinine of 0.6 mg/dl.
    The past medical history revealed a 35.5 week premature infant who needed some supplemental oxygen for 12 hours for tachypnea that resolved. He had no difficulties feeding and was discharged at 3 days of life.
    He was followed closely and regained his birth weight by 10 days of age.
    The family history was negative for any kidney disease or hearing problems.
    The pertinent physical exam on arrival showed normal vital signs. His weight was 3.2 kilograms (50%) and length and head circumferences were 50-75%.
    He was alert with very flushed skin. He had a 1 cm lesion on right foot where an IV had infiltrated and now appeared to be healing.
    The work-up included monitoring of electrolytes which were all normal.
    Vancomycin levels were 105.9 mcg/dl on admission and were < 5 mcg/dl at 36 hours after the overdose.
    The blood urea nitrogen was 7 mg/dl on discharge and never was higher than 11 mg/dl.
    The creatinine slowly decreased and was 0.3 mg/dl at discharge.
    Blood, urine and cerebrospinal fluid cultures locally all remained negative.
    A hearing test on day 3 of admission was negative.
    The diagnosis of fever in a neonate with vancomycin overdose was made.
    The patient’s clinical course improved over the 6 total days of admission, and he was discharged to followup with his local healthcare provider and audiology in 4-6 weeks for repeated testing.
    The local hospital was evaluating their medication administration system to find out why their system had failed and how they could effect change and respond to this critical incident.

    Discussion
    Vancomycin is an antibiotic that has known ototoxicity and nephrotoxicity. “Red man syndrome” of severe flushing can be seen with rapid administration of the drug.
    Vancomycin should be used for treatment of serious infections known to be caused by beta-lactam-resistant gram-positive organisms (like MRSA), in patients with serious allergy to beta-lactam antibiotics, antimicrobial-associated colitis (e.g. Clostridium difficile) that is severe and potentially life-threatening or fails to respond to metronidazole, endocarditis prophylaxis for certain high-risk patients, and for anti-microbial prophylaxis in major surgical procedures involving implantation of prosthetic materials or devices at institutions with a high rate of MRSA.
    Vancomycin is also indicated for febrile, neutropenic patients (like a neonate) in an institution with a high prevalence of MRSA such as the local hospital in this case.

    Vancomycin levels need to be checked during administration. A peak level of 25-40 mg/L and a trough of 5-10 mg/L are usually recommended. For central nervous system infections a higher peak (>35 mg/L) is recommended.
    Peak and trough measurements are usually done around the time of the third vancomycin dosing.
    As neonates have changing nephrogenic function, dosing is based upon patient weight and post-natal age.

    Learning Point
    Patient safety is an important issue for everyone. Errors of commission and omission occur inside hospitals and clinics and have been well-outlined by studies from the Institute of Medicine.
    Errors occur because human beings have limitations, medicine is a highly complex system that changes continually, and because the barriers that are put into place to stop or mitigate an error fail for some reason.
    For hospitalized children, medication errors are some of the most common errors and often they occur in infants and adolescents.

    Systems to improve patient safety need approaches that include improving the overall system, improving human factors (i.e. limiting their limitations) and developing a safety culture.

    Ideas for improved patient safety through systems:

    • Computer physician order entry (CPOE) – helps assure proper drug and dosage is ordered, transcription errors and errors because of poor handwriting are decreased or eliminated, CPOE can also “force” use of standard dosing and medications.
    • Computerized clinical decision support systems – helps assure drug is being used for the proper indication or reason, checks the drug ordered against allergies and other medications to make sure all drugs administered are compatible.
    • Barcode scanning of patients and medicine – helps assure that the proper medication is being given to the proper patient at the proper time.
    • Smart medication infusion pumps – only allows a certain volume of medication over a prescribed rate, i.e. is pre-set .
    • Streamline and simplify the process so opportunity for errors are decreased – fewer, simpler steps makes the process less likely to have an error.
    • Standardize medications – use the same medication, e.g. have available only 1 concentration of an intravenous medication and not multiple ones so the wrong dilution is used inadvertently.

    Ideas for improved patient safety through human factors:

      • Limit prolonged work hours – fatigue and sleep deprivation are known causes of increased errors so methods to limit total hours worked and protect sleep are important
      • Protect sleep recovery periods
      • Employ strategic napping and judicious use of caffeine
      • Improve communications through decreased patient handoffs, decrease cross-coverage of patients by healthcare providers (i.e. increase continuity of healthcare providers and the patient)
      • Improve communications through improved information transfer during handoffs and feedback – e.g. use a computerized sign-out program to assure all pertinent information is communicated verbally and in written form

      Ideas for improved patient safety through developing a safety culture:

      • Develop methods for error reporting that is non-punitive
      • Develop methods for anonymous error reporting to a central registry
      • Conduct audits of patient safety with non-punitive feedback given to healthcare providers and the institution
      • Analysis by the institution of critical incidents that occur, along with the authority of the analyzing body to change the system to improve it
      • Educate healthcare personnel and the public

      Questions for Further Discussion
      1. What patient safety efforts are ongoing in your own institution?
      2. How can you report a patient safety problem in your own institution?

      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: Drug Safety and Poisoning.

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

    To view images related to this topic check Google Images.

    Committee on Quality of Health Care in America.
    To Err is Human. Institute of Medicine, National Academy Press.
    Washington, D.C..
    Available from the Internet at http://www.nap.edu/catalog.php?record_id=9728#toc (rev. 11/1/1999, cited 11/12/07).

    Committee on Quality of Health Care in America.
    Crossing the Quality Chasm:
    A New Health System for the 21st Century. Institute of Medicine, National Academy Press.
    Washington, D.C..
    Available from the Internet at http://www.nap.edu/catalog.php?record_id=10027#toc (rev. 3/1/2001, cited 11/12/07).

    Committee on Quality of Health Care in America.
    Patient Safety:
    Achieving a New Standard for Care. Institute of Medicine, National Academy Press.
    Washington, D.C..
    Available from the Internet at http://www.nap.edu/catalog.php?record_id=10863#toc (rev. 11/20/2003, cited 11/12/07).

    Robertson J, Shilkofski N. The Harriet Lane Handbook. 17th. Edit. Mosby Publications: St. Louis. 2005:996-997.

    Committee on Quality of Health Care in America.
    Preventing Medication Errors: Quality Chasm Series. Institute of Medicine, National Academy Press.
    Washington, D.C..
    Available from the Internet at http://www.nap.edu/catalog.php?record_id=11623#toc (rev. 7/20/2006, cited 11/12/07).

    American Academy of Pediatrics. Appropriate Use of Antimicrobial Agents, 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;740-741.

    Morriss, FW. Patient Safety in Pediatrics. Presentation at the Department of Pediatrics’ Societal, Professional and Ethical Issues Conference. University of Iowa Children’s Hospital, 11/8/2007.

    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.

  • 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.
    14. Knowledge of study designs and statistical methods to appraisal clinical studies and other information on diagnostic and therapeutic effectiveness is applied.

    16. Learning of students and other health care professionals is facilitated.

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

    Date
    December 17, 2007

  • Which Vaccines Contain Preservatives?

    Patient Presentation
    A 3-year-old female came to clinic for her health supervision visit. The resident physician noted that the preschooler was due for her second Hepatitis A and Influenza vaccines.
    Her mother said, “I know that most of the thimerosal has been taken out of the vaccines, but do they still have preservatives in them?” The resident stated that he wasn’t sure but would find out for the mother before ordering the vaccines.
    When discussing the healthy child with his attending physician, the resident said that he wasn’t sure where to find the preservative information.
    The attending physician offered several suggestions including checking the American Academy of Pediatrics RedBook®, looking at the package inserts that the nursing staff kept easily available where they prepared the vaccines, and also looking at the U.S. Food and Drug Administration’s website.
    Together the resident and attending physician looked up information about thimerosal and also the other preservatives in currently licensed vaccines.
    The Hepatitis A vaccine (Havrix®) contained 2-phenoxyethanol but the Influenza vaccine (FluMist®) did not. Both did not contain thimerosal.
    The diagnosis of a healthy preschooler was confirmed by the attending physician. During the discussion about the preservatives, the mother decided to have her daughter receive both vaccines.

    Discussion
    Preservatives in vaccines and other biological products are used to prevent growth or kill microorganisms especially bacteria and fungi that could accidentally contaminate the product prior to administration.
    While preservatives can decrease the risk of contamination, especially in multi-dose vials, they cannot completely eliminate the risk.

    Thimerosal has been used as a preservative for many years and is approximately 50% mercury by weight. It is metabolized into ethyl mercury and thiosalicylate. Ethyl mercury is an organomercurial that is related, but distinctive from, methylmercury.
    Methylmercury is a known neurotoxin and most exposure comes through food.

    Because of potential concerns about thimerosal as a preservative, especially neurocognitive concerns, manufacturers have decreased or eliminated thimerosal as a preservative in many vaccines and other biological agents.
    The Institute of Medicine Immunization Safety Review Committee issued a report in 2004 which concluded that the evidence “??? favors rejection of a causal relationship between thimerosal-containing vaccines and autism, and that hypotheses generated to date concerning a biological mechanism for such causality are theoretical only. The committee also stated “???that the benefits of vaccination are proven and the hypothesis of susceptible populations is presently speculative, and that widespread rejection of vaccines would lead to increase in incidence of serious infectious diseases like measles, whooping cough and Hib bacterial meningitis.”

    Learning Point
    Preservatives used in vaccines licensed in the U.S.

    • 2- Phenoxyethanol
      • DTaP – Infranix by GlaxoSmithKline Biologicals
      • Hepatitis A – Havrix by GlaxoSmithKline Biologicals
      • Hepatitis A/Hepatitis B – Twinrix by GlaxoSmithKline Biologicals
    • 2 -Phenoxyethanol and formaldehyde
      • DTaP – Daptacel by Sanofi Pasteur, Ltd
    • Inactivated Poliovirus – IPOL by Sanofi Pasteur, SA
    • Benzethonium chloride (Phemerol)
      • Anthrax – Biothrax by BioPort Corporation
    • Phenol
      • Pneumococcal Polysaccaride – Pneumovax 23 by Merck and Co., Inc.
      • Typhoid Vi Polysaccaride – Typhim Vi by Sanofi Pasteur, SA
    • Thimerosal
      • DT
      • Td – several manufacturers
      • TT – several manufacturers
      • Influenza – several manufacturers


    Thimerosal-free vaccines
    for vaccines routinely recommended for children under 6 years of age

    • DTaP
      • Infanrix by GlaxoSmithKline Biologicals, thimerosal free since 9/29/2000
      • Daptacel by Sanofi Pasteur, Ltd, never contained thimerosal
    • DTaP-HepB-IPV – Pediarix by GlaxoSmithKline Biologicals, thimerosal free since 1/29/2007
    • Hepatitis B
      • Recombivax HB by Merck and Co, Inc., thimerosal free since 8/27/99
      • Engerix B by GlaxoSmithKline Biologicals, thimerosal free since 1/30/2007
    • Haemophilus influenza type b conjugate (HIB)
      • ActHIB by Sanofi Pasteur, SA, never contained thimerosal
      • OmniHIB by GlaxoSmithKline Biologicals, never contained thimerosal
      • PedvaxHIB by Merck and Co, Inc., thimerosal free since 8/99
      • HibTITER (single dose) by Wyeth Pharmaceutical Inc., never contained thimerosal
    • Hib/Hepatitis B combination – Comvax by Merck and Co, Inc., never contained thimerosal
    • Inactivated Poliovirus – IPOL by Sanofi Pasteur, SA, never contained thimerosal
    • Influenza (inactivated)- Fluzone by Sanofi Pasteur, inc, thimerosal free since 12/23/2004
    • Influenza (live) – FluMist by MedImmune Vaccines, Inc., never contained thimerosal
    • Measles-Mumps-Rubella – M-M-R-II by Merck and Co, Inc., never contained thimerosal
    • Pneumococcal conjugate – Prevnar by Wyeth Pharmaceutical Inc., never contained thimerosal
    • Rotavirus – Rotateq by Merck and Co, Inc., never contained thimerosal
    • Varicella – Varivax by Merck and Co, Inc., never contained thimerosal

    Questions for Further Discussion
    1. What other biological agents contain mercury as a preservative?

    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: Childhood Immunization and Immunization

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

    To view images related to this topic check Google Images.

    U.S. Food and Drug Administration. Thimerosal in Vaccines.
    Available from the Internet at http://www.fda.gov/cber/vaccine/thimerosal.htm#t1 (rev. 9/6/2007, cited 11/8/2007).

    Immunization Action Coalition. Thimerosal in Vaccines.
    Available from the Internet at http://www.vaccineinformation.org/thimerosal.asp (rev. 7/6/2007, cited 11/8/2007).

    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.
    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
    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.
    14. Knowledge of study designs and statistical methods to appraisal clinical studies and other information on diagnostic and therapeutic effectiveness is applied.
    15. Information technology to manage information, access on-line medical information and support the healthcare professional’s own education is used.
    16. Learning of students and other health care professionals is facilitated.

  • 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.

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

    Date
    December 10, 2007