How Common is Recurrent Kawasaki Disease?

Patient Presentation
A 3.5-year-old female came to clinic with a 2-day history fever up to 101°F. The evening before she had complained of a sore throat but had no rhinorrhea, cough or rash. She was drinking reasonably well and was urinating frequently. She had been to a birthday party where an older child had had strep throat. The past medical history was positive for Kawasaki Disease diagnosed at 17 months of age and treated with intravenous immunoglobulin (IVIG) on day 6 of fever. Her echocardiograms had been negative and she was being appropriately monitored by cardiology. The family history was positive for heart disease and hypertension in grandparents in the 70s. The review of systems was otherwise negative.

The pertinent physical exam showed a preschooler who was febrile to 39.3°C, heart rate of 104 beats/minute, and respiratory rate of 24. Capillary refill was brisk and her mucous membranes were moist. She had palatal petechiae but no exudates in her throat. She had a few shotty anterior cervical and inguinal nodes that were all < 0.5 cm and freely mobile. Her ears were normal. Cardiac examination showed no murmurs with normal S1 and S2. Her abdominal and lung examination were negative and her skin examination showed no rashes.

The diagnosis of possible strep throat was made. The laboratory evaluation of a rapid strep test confirmed the diagnosis and the parents were educated regarding giving her the penicillin and reasons to call if she was not improving. “Oh we’ll call all right. After her having Kawasaki Disease we’re probably always a little worried about any fever and it coming back. We know that it’s rare to begin with and even less likely to come back, but yet we know it can. I’m not glad she’s sick but glad it is something that we know what it is and can treat it,” her father explained.

Discussion
Kawasaki Disease (KD) was first described in 1967 by Dr. Tomisaku Kawasaki, and since has been identified world-wide. It is an acute, self-limited, febrile illness seen usually in children < 5 years. In North America the incidence is ~25/100,000 children < 5 years. Highest prevalence is seen in Asian children, particularly those of Japanese ancestry. Males are more common than females (~1.5:1). In Japan, case fatality rate is < 0.1%.

The cause is not identified although strong data suggests an interaction between infectious agents and genetic susceptibility. KD is a clinical diagnosis as is recurrent KD. Without treatment at the initial episode, 15-25% of pediatric KD patients may develop cardiac aneurysms but this is decreased to 4% with IVIG treatment. It is the most common reason for acquired heart disease in developed countries.

Treatment for KD changed in 2004, and was updated by the American Heart Association in 2017 (See To Learn More for review).
Primary treatment for initial KD is IVIG (2 mg/kg x 1 infusion) within 10 days of symptoms onset but may be given later also. Aspirin can also be given until the patient is afebrile (moderate dose = 30-50 mg/kg/day to high dose = 80 mg/kg/day). Corticosteroids are sometimes used if patients do not respond to initial therapy.

KD is defined as:

  • Fever of at least 5 days (often > 39-40°C, can last 1-3 weeks without treatment)
  • Plus 4 or more principal clinical features following:
    • Changes in lips and oral cavity – erythema, cracked lips, strawberry tongue, diffuse injection
    • Bilateral bulbar conjunctival injection without exudate
    • Polymorphous exantham – maculopapular, diffuse erythroderma or erythema multiforme-like
    • Cervical lymphadenopathy – more than 1.5 cm, usually unilateral, and in the anterior cervical triangle but may be in other locations

    Note: Patients with 4 or more of the 5 principal features, especially extremity changes, can have the diagnosis made on day 4 of fever.

Laboratory findings associated with KD include:

    During acute phase

    • Leukocytosis with neutrophilia and immature forms
    • Elevated C-reactive protein
    • Elevated erythrocyte sedimentation rate
    • May also be present: sterile pyuria, hyponatremia and hypoalbuminemia

    During 2nd week after fever onset

    • Thrombocytosis

Evaluation for other possible diseases with clinical findings includes:

  • Viral infections – especially adenovirus, enterovirus, Epstein-Barr virus and measles
  • Scarlet fever
  • Staphylococcal scalded skin syndrome
  • Toxic Shock Syndrome
  • Bacterial cervical lymphadenitis
  • Drug hypersensitivity reactions
  • Stevens-Johnson syndrome
  • Juvenile rheumatoid arthritis, systemic onset
  • Rocky Mountain spotted fever
  • Leptospirosis

Learning Point
Recurrent KD is rare with the incidence rate basically unchanging over the last 30 years in Japan. Overall the incidence rate for patients reviewed between 2003-2012 in Japan, was 3.89 /1000 person-years. The authors also note that all deaths in the cohort (N=17) occurred in nonrecurrent KD patients. Risk factors in this study were age < 3 years, male gender and being resistant to initial IVIG therapy. Cardiac problems during the initial event was not a risk factor. Other studies have found other risk factors but these vary by study.

Overall, recurrent KD occurs in ~2-3% of all patients who developed initial KD. Recurrent KD is even rarer in adult patients with a 4th case being described in 2016 in a 23-year-old male who had initial KD at age 4 years.

Questions for Further Discussion
1. What is the clinical definition of incomplete KD and its treatment?
2. What are indications for a cardiology consultation?

Related Cases

What is the Interval For Non-simultaneous Administration of Live Virus Vaccines?

Patient Presentation
A 1-year-old female came to clinic for her health supervision visit. She was healthy and developing well, and her family was going for an extended stay in China for the next few months. The mother had always been concerned about giving “so many vaccines at one time” but had always given all recommended vaccines on schedule. The mother was asking about spreading out the vaccine schedule again. The pertinent physical exam showed a smiling toddler who was just starting to walk. She had normal vital signs and growth parameters were in the 75-90%. The examination was normal.

The diagnosis of a healthy toddler was made. The pediatrician discussed which vaccines were recommended at the time. She noted that, “Especially as you are leaving for China, we can keep her current on her vaccines and you won’t need to receive any there. If we start to split them up, then you have to wait a few weeks between the vaccines and you will have to get more of them in China.” The mother agreed that it would be better to keep the child on the recommended schedule and also easier because of the travel. “Even if she doesn’t need vaccines in China, it still is important that she has her well child checks on time. Otherwise we will see you back when she is 15 months old,” the pediatrician reminded the mother.

Discussion
Vaccines are a mainstay of infectious disease prevention and health promotion. Infants, children and adults benefit from vaccines the most when they are given on the recommended schedules. However there are times when this is not possible as children come to the physician a little early, or a little late, or had unavailable records and so received addition vaccine, etc. There are many questions that arise because of these timing issues such as the one above.

Standard vaccine schedules can be reviewed here.

Commonly administered vaccines includes:

  • Live-attenuated vaccines
    • Cholera
    • Measles, mumps, rubella (MMR combined vaccine)
    • Polio, oral
    • Rotavirus
    • Smallpox
    • Typhoid, oral
    • Varicella
    • Yellow fever
  • Inactivated vaccines
    • Hepatitis A
    • Influenza, injectable
    • Polio, injectable
    • Rabies
    • Typhoid, injectable
  • Subunit, recombinant, polysaccharide, and conjugate vaccines
    • Haemophilus influenzae type b (HIB) disease
    • Hepatitis B
    • Human papillomavirus (HPV)
    • Pertussis (part of the DTaP combined vaccine)
    • Pneumococcal disease
    • Meningococcal disease
    • Varicella zoster
  • Toxoid vaccines
    • Diphtheria
    • Tetanus

Simultaneous vaccine administration

  • Children can receive as many vaccines as needed at one time, so called simultaneous administration. There is no upper limit to the number of vaccines that can be given simultaneously. All vaccines that are indicated can be given simultaneously. There are no contraindications to this practice with 2 exceptions: 1) a patient needing both PCV13 (pneumococcal conjugate vaccine, recommended to be given first) and PPSV23 (pneumococcal polysaccharide vaccine, recommended to be given second) should be separated by at least 8 weeks, and 2) for patients with anatomic or functional asplenia, PCV13 and meningococcal conjugate vaccines may be given or not given together and have particular instructions depending on the vaccine brands being used. Combination vaccines with equivalent components are generally preferred over separate component vaccines.
    Simultaneous means given in the same clinic visit or same clinic day.

Minimum Intervals and Vaccine Deficiency

    Vaccines schedules have recommended intervals between vaccine administrations which provides the best timing for the vaccine to be effective. “A “minimum interval” is shorter than the recommended interval between doses, and is the shortest time between two doses of a vaccine series in which an adequate response to the second dose can be expected.” Minimal interval should not be used for scheduling routine vaccines, recommended intervals should be used instead. Minimal intervals are used for accelerating a vaccine schedule usually for children with immunization deficiency (i.e. the child is behind on their vaccines and needs to catch-up). Minimal intervals are also sometimes used because of unusual time restraints or circumstances such as international travel. Minimal intervals provide valid and effective immunizations, but are not as optimal and therefore following recommended schedules are best.


    An accelerated schedule should be used for any patient who is > 1 month or 1 dose behind the recommended dosing schedule. Minimal intervals can be used as many times as necessary until the patient is back on schedule.


    The Advisory Committee on Immunization Practice (ACIP) says “[f]or intervals of 3 months or less, you should use 28 days (4 weeks) as a “month.” For intervals of 4 months or longer, you should consider a month a “calendar month”: the interval from one calendar date to the next a month later.”

Vaccination Too Early

    When reviewing immunization records, there is a 4-day grace period instituted by the ACIP. If a vaccine was administered ≤ 4 days before the minimum age or minimum interval, it may be counted as a valid dose. The 4 day grace period is not for scheduling of vaccines but for reviewing records only. Vaccine administration even in this grace period window can cause problems with people who are less experienced or knowledgeable about vaccine timing. They can see vaccines given early and may believe them to be invalid. Documentation from a health care provider acknowledging vaccine validity may be needed or institutions may mistakenly insist on vaccine readministration even if given within the 4 day grace period. Therefore it is always best to not give vaccines early but on schedule.

Vaccination Too Late

    Do not start a vaccine series over. As long as the minimum interval and minimum age requirements have been met, then the patient usually can receive the vaccine. For some vaccines there are upper ages after which a vaccine should not be given. (e.g. HIB vaccine after 60 months of age) Oral typhoid may need to be restarted if the total doses are not completed in the recommended time frame.

Extra Vaccine Doses

    Complete vaccine records should be obtained and reviewed if possible. Unfortunately because of incomplete records, some children receive additional doses of vaccine which may be valid or invalid doses. The total number of valid vaccine doses should be determined (including review of the minimum intervals and ages). Doses that are not valid should be disregarded. If the valid doses still show the patient to be deficient, the patient should receive all indicated vaccine doses.

Learning Point
Dosing interval for non-simultaneous vaccine administration

    For 2 or more different, live viral, injectable vaccines not administered simultaneously, a minimum interval of 4 weeks should separate the vaccines. This is because the injectable, live virus vaccines may interfere with each other, decreasing the efficacy of the vaccines.
    MMR and Varicella administration specifically falls under this rule: do them all at one time or separate their administration by at least 4 weeks. If two different live virus injectable vaccines are given < 4 weeks, then the second vaccine given is considered invalid and should be repeated ≥ 28 days after the first vaccine was given. Serological testing can be obtained to determine immunity but this is costly and has other problems associated with it.


    Oral live virus vaccines including cholera, typhoid, and rotavirus can be given simultaneously with other vaccines (inactivated, or live virus injectable vaccines) and if not given simultaneously there is no minimal interval between administrations. One exception is that oral cholera should be given at least 8 hours before oral typhoid.


    Inactivated vaccines can be given simultaneously, and if not administered simultaneously, there is no minimum time intervals between administrations.

Questions for Further Discussion
1. List 2-3 references to obtain evidence-based scientific vaccine information?
2. Where can you find good evidence-based travel health information?

Related Cases

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

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Immunization and Childhood Immunization.

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

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Centers for Disease Control. General Recommendations. Epidemiology and Prevention of Vaccine-Preventable Diseases. Pink Book.
Available from the Internet at https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/genrec.pdf (2015, cited 5/16/18).

US Department of Health and Human Services. Vaccine Types.
Available from the Internet at https://www.vaccines.gov/basics/types/index.html (rev. 12/2017, cited 5/16/18).

Immunization Action Coalition. Scheduling Vaccines.
Available from the Internet at http://www.immunize.org/askexperts/scheduling-vaccines.asp (rev. 2/1/2018, cited 5/16/18).

Immunization Action Coalition. Administering Vaccines.
Available from the Internet at http://www.immunize.org/askexperts/administering-vaccines.asp (rev. 3/9/2018, cited 5/16/18).

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

No Plant Oils for Cradle Cap?

Patient Presentation
A 4-month-old male came to clinic for his health supervision visit. His mother was concerned about his continued seborrhea. She had tried corn oil and olive oil without improvement and sometimes noted that it actually got worse. “Do you think we need to see dermatology?” she asked. The past medical history was negative. The pertinent physical exam showed a healthy smiling infant with normal growth parameters. His skin examination showed mild waxy-yellow thick scale in two areas of the scalp. There was no redness or excoriations. There was no extension to the ears, face or eyebrows. The rest of his examination was negative.

The diagnosis of a healthy male with very mild seborrheic dermatitis was made. The resident discussed that this was quite mild and that dermatological consultation was not warranted at this time. He told the mother that she had several options including doing nothing as it did not appear to be bothering the infant, she could use a small amount of a steroid cream on the affected areas or could use a petroleum-based oil such as mineral oil to soften and loosen the scale. “I had this problem with my son and found out that there is a yeast on the skin that can eat the olive oil or other plant-based oils. That makes the yeast grow and the seborrhea got worse. We switched to mineral oil and it was better. I usually forgot to use the oil though,” he said laughing.

Discussion
During growth, plants first store their energy as carbohydrates but during ripening switch over to carbon-rich triglycerides. Triglycerides also occur in yeasts, molds and animal fats.

A few higher plants store lipids in other forms. One example is the Jojoba which stores its oil as a lipid wax. Simmondsia chinensis (Jojoba) is a specialty-cultivated plant found mainly in the American Southwest and Mexican Northwest. Jojoba seed oil has > 50% of its weight as liquid wax esters that are used in personal care products and lubricants. Jojoba oil is naturally extracted from the seed or synthetically produced. Natural Jojoba oil is known to contain a very small amount of triglyceride, only 0.4% by weight.

Malassezia sp. are lipid-dependent yeasts that are usually commensal organisms inhabiting the skin and mucous membranes of mammalian organisms including humans. Malassezia are major components of the mycobiome of the skin (50-80%). They can cause pathology including blood stream infections (especially preterm infants or immunocompromised patients), but are more commonly associated with dermatologic disorders including seborrheic dermatitis/dandruff, pityriasis versicolor, atopic dermatitis, psoriasis, and Malassezia folliculitis. Species predominance depends on the skin location but most common species are M. globosa, M. restricta and M. sympodialis. Treatment with topical antifungals with or without corticosteroids is the recommended treatment for Malassezia species and seborrheic dermatitis that is problematic.

Learning Point
Malassezia digests sebum into saturated and unsaturated fatty acids. Only the saturated molecules are essential while the unsaturated fatty acids are a byproduct. Organic oils (such as olive oil) contain both saturated and unsaturated lipids and may be counter productive to treat a condition whose etiology is linked to Malassezia. In fact, olive oil is a standard in vitro culture media for Malassezia. Saturated fatty acids likely encourage Malassezia overgrowth and excess unsaturated fatty acids may induce inflammation and scaling. As non-digestible oil, mineral oil may provide a triglyceride-free alternative to organic oils.” [Bolding per the author.]

Some families do not wish to use an animal-based or petroleum-based product. An alternative plant product could be recommended that contains a low amount of triglyceride such as Jojoba oil.

Questions for Further Discussion
1. What treatment do you recommend for seborrheic dermatitis?
2. What are indications for dermatology consultation for seborrheic dermatitis?

Related Cases

    Symptom/Presentation: Rash

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

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, and the Cochrane Database of Systematic Reviews.
Information prescriptions for patients can be found at MedlinePlus for these topics: Dandruff, Cradle Cap and Other Scalp Conditions and Fungal Infections.

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

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Van Boven, M., Holser, R.A., Cokelaere, M. et al. J Amer Oil Chem Soc (2000) 77: 1325.

Siegfried E, Glenn E. Use of olive oil for the treatment of seborrheic dermatitis in children. Arch Pediatr Adolesc Med. 2012 Oct;166(10):967.

Dawson TL Jr. Malassezia ecology, pathophysiology, and treatment.
Theelen B, Cafarchia C, Gaitanis G, Bassukas ID, Boekhout T,
Med Mycol. 2018 Apr 1;56(suppl_1):10-25.

Cyberlipid.org. Plant Oils and Fats. Cyberlipid.org. Available from the Internet at: http://www.cyberlipid.org/glycer/glyc0005.htm (cited 5/14/18).

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

What is the Prevalence of Somnambulism?

Patient Presentation
A 12-year-old male came to clinic for his health supervision visit. He was well but over the past month had had 3 episodes of sleepwalking into his parents’ bedroom at night. His mother noted that his eyes were open, he would mumble and didn’t seem to know what was going on. She would take him back to his bed and he would remain there the rest of the night. The next morning he did not remember the episodes. He slept in a regular bed, in a 1-story home with no open stairwells. The mother denied that he tried to leave the home by a door or window. The mother said he did not snore, nor thrashed or moved around in the bed, nor had daytime sleepiness. He did have night terrors as a young infant. She also denied any seizure-like activity or headaches currently. The past medical history was non-contributory. He had no seizures, attention deficit disorder and took no medications. He had been getting less sleep overall because of school and extra curricular activities for the past 2 months. The family history was negative for any sleep problems.

The pertinent physical exam showed a well-appearing male with normal vital signs and growth parameters in the 10-50%. His examination was normal including his neurological examination. The diagnosis of a healthy male with sleepwalking was made. The doctor counseled that this was a common problem and may or may not continue. He strongly encouraged good sleep hygiene including regular bedtimes and morning awakenings. He also counseled about a safe sleeping environment including having items picked up from the floor in the bedroom to avoid tripping. The family was to monitor the behavior and report if it was increasing or if dangerous behaviors were occurring.

Discussion
Sleep disorders are common in all ages particularly sleep deprivation in our increasingly busy world. A review of health problems caused by inadequate sleep can be found here. Sleep problems are more common in patients with attention deficit hyperactivity disorder, epilepsy, headache and visual impairments. Sleep problems can cause cognitive and behavioral impairments including emotional regulation problems, increased seizures or headaches, and impaired attention and has been known to prolong recovery from various acquired brain injuries.

Somnambulism or sleepwalking is a parasomnia (which include confusional arousals, sleep terrors, nightmares, sleep paralysis, restless legs, etc.). It is a non-rapid eye movement (non-REM) sleep arousal disorder that occurs during slow wave sleep. Slow wave sleep predominates in the early part of sleeping (usually within 1-3 hours) and children have more slow wave sleep than adults which may be part of the reason it is seen more often in children. Patients with one parasomnia are at increased risk for others. The episodes can last from a few minutes to up to 30-40 minutes and the patient has amnesia for the event. Patients have ambulation or other complex behaviors after getting out of bed and appear confused/dazed (occasionally have agitation), might talk, mumble or give inappropriate answers, and eyes are open. They may have behaviors that are inappropriate such as urinating in the wrong place.

It is very uncommon for people to have significant problems due to somnambulism, however the biggest risk is injury. The true risk is unknown because sleepwalking is a difficult diagnosis to make and injuries are often minor or are not reported. Obviously patients can have more significant injuries if they were to accidentally fall from a height such as a bed, window or down stairs. An emergency room study of patients > 15 years of age, found only 11 trauma admissions were associated with somnambulism. Two patients were 16 years of age with one having a contusion and the other having several contusions and superficial cuts. Four patients required admission and none died.

Treatment is using appropriate safety measures such as gates, locking doors and windows while sleeping etc. For patients with known sleepwalking, avoiding sleep deprivation and medications that disturb sleep arousal such as alcohol, hypnotic and psychotropic medications is also advised. Avoiding sleeping environments which may arouse the patient from sleep such as loud, sudden noises is appropriate. Scheduled sleep awakening can be used for patients with nightly somnambulism. Overall outcome is difficult to determine. For many patients, it resolves, but for others it continues intermittently or more consistently.

Learning Point
Somnambulism has been noted as early as age 2 years. The most common age for somnambulism is ~10 years of age, with 14% experiencing it at some point by this age, and 29% experiencing it at least once during childhood.

According to a 2016 meta-analysis and systematic review of the medical literature, the prevalence rate within the last year of somnambulism is 5% in children and 1.5% in adults. The estimated life-time risk is 6.9%.

There is difficulty in diagnosing somnambulism. The sleepwalking may not be observable by others (parents, significant others) and they may not be sure what is going on nor can they actually confirm the neurological arousal state the patient is in. A sleep study can confirm the sleep state. Self-report obviously has problems as people report what they have been told by others, rely on observed minor injuries such as bruises/cuts and believe they have occurred because of somnambulism, or they observe the environment has been disordered (movement of items including furniture during the night) and they believe is due to somnambulism.

Questions for Further Discussion
1. How is insomnia or narcolepsy treated?
2. How do you counsel families about common infant sleeping problems?

Related Cases

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

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.
Information prescriptions for patients can be found at MedlinePlus for this topic: Sleep Disorders

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

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Moreno MA. Sleep Terrors and Sleepwalking: Common Parasomnias of Childhood. JAMA Pediatr. 2015 Jul;169(7):704.

Maski K, Owens JA. Insomnia, parasomnias, and narcolepsy in children: clinical features, diagnosis, and management. Lancet Neurol. 2016 Oct;15(11):1170-81.

Stallman HM, Kohler M, Wilson A, Biggs S, Dollman J, Martin J, Kennedy D, Lushington K. Self-reported sleepwalking in Australian senior secondary school students. Sleep Med. 2016 Sep;25:1-3.


Sauter TC, Veerakatty S, Haider DG, Geiser T, Ricklin ME, Exadaktylos AK. Somnambulism: Emergency Department Admissions Due to Sleepwalking-Related Trauma. West J Emerg Med. 2016 Nov;17(6):709-712.

Stallman HM, Kohler M. Prevalence of Sleepwalking: A Systematic Review and Meta-Analysis. PLoS One. 2016 Nov 10;11(11):e0164769.

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