What Does the General Pediatrician Do When There Are Concerns for a Rare Disease?

Patient Presentation

An 8-year-old male came to clinic for his health supervision visit. He was doing well overall including school where he got special help for some reading problems. His mother also complained that he still had nocturnal enuresis about once per week. It was not bothering him but she didn’t like doing all the extra laundry. The family history was positive for his father who had nocturnal enuresis until about 10 years old. His mother had just recently found out she was a carrier for Bardet-Biedl syndrome. She said she didn’t have any personal problems including normal eyesight but that she knew there were renal problems associated with it and wondered if he needed to see a urologist because of the enuresis and possible Bardet-Biedl syndrome. The review of systems was negative.

The pertinent physical exam showed a happy male with growth parameters at 95% for weight and 50% for height. He had normal vital signs including blood pressure and vision screening of 20/20 bilaterally. His physical examination was normal including his eye, genital, and neurological examination.

The diagnosis of a healthy male with probably primary nocturnal enuresis was made. The laboratory evaluation showed a normal urinalysis. The pediatrician also made a referral to a urologist because of the mother’s concern about Bardet-Biedl syndrome after discussing with her that this was an autosomal recessive disorder and was unlikely. However the child did also have some learning problems and was at 95% for weight both of which could be signs of the syndrome. The urologist ordered a renal ultrasound which was normal and started the child on a bedwetting alarm.

Bardet-Biedl syndrome (BBS) is a rare disorder. It is usually considered an autosomal recessive disorder but there is significant intra-familial variability. There are multiple genes (~20 currently) involved and it is believed that the phenotypic variability is due to “…differences in the total mutational load across different BBS associated genes….” It is a ciliopathy where mutation changes in proteins in the cilias causes problems in the cilia’s functioning particularly signaling. Cilia are important in signaling to maintain tissue and cellular homeostasis. Obviously screening of affected family members would be important, particularly siblings as they would have ~25% chance of being affected. Genetic counseling for future pregnancies is also important.

BBS is usually diagnosed with a patient having 4 primary features or 3 primary and 2 secondary features. Polydactyly will be present at birth but the other problems usually develop over the first 2 decades.

  • Primary features
    • Rod-cone dystrophy -> 90% affected, usually before adulthood and is usually the reason for most morbidity
    • Obesity (central) – 72-92% affected, less severe in childhood but increases with age
    • Polydactly – 63-81% affected
    • Learning problems/Mental retardation – 50-61% affected with various learning problems, speech, intellectual disabilities and behavior problems
    • Hypogonadism – 59-98% affected, males generally have micropenis and/or small testes and often are infertile, females have various forms of hypoplasia
    • Renal abnormalities – 20-53% affected, renal concentrating defects without other functional or structural abnormalities are the most common problem, dysplasia and glomerular disease also occur
  • Secondary
    • Atopy
    • Diabetes – 6-48% affected
    • Hepatic fibrosis

    • Brachyactyly/syndactyly
    • Dental abnormalities
    • Facial dysmorphism
    • Anosmia/hyposmia

    • Behavior problems
    • Neuro-motor problems – 46-86% affected
    • Speech deficits – 54-81% affected
    • Hearing loss – 11-12% affected

    • Cardiac problems
    • Hypertension – 30-60% affected
    • Respiratory problems

    • Hypothyroidism

Differential diagnosis includes several syndromes that have obesity as a presentation including:

  • Alstrom syndrome
  • Biemond syndrome type II
  • Joubert syndrome
  • Laurence-Moon syndrome
  • McKusick-Kauyman syndrome
  • Meckel syndrome
  • Prader-Willi syndrome
  • Senior-Loken syndrome

A review of primary nocturnal enuresis can be found here.

A review of diurnal enuresis can be found here.

A review of common causes of blindness in children can be found here.

Learning Point
The patient and family will almost always know more about the specific uncommon disease than the pediatrician. However, general pediatricians’ know about human bodies, physiology and treatment principles. They know how to monitor patients, how to evaluate other family members, interpretate medical vocabulary and the medical literature, and how to help families understand legitimate differences of opinion as to evaluation, management and treatment. General pediatricians may need help from medical specialists to work with the family to meet all of these needs. General pediatricians can also be helpful in supporting the family with a new diagnosis or ongoing chronic disease. This could include referrals to community services, school services and mental health services. The general pediatrician often treats the other siblings and parents often have many concerns about the potential problems for other family members. Being available for families to ask questions, and navigate multiple systems are important aspects of what a general pediatrician can do for families. The general pediatrician can also be a sounding board regarding “how far” to go with the evaluation or trying a new treatment regime as they often have an ongoing relationship and understand the families’ values regarding health care and what may be functional to do in their own home.

Questions for Further Discussion
1. How would the potential management change for an autosomal dominant or variable penetrance genetic disorder?
2. What is the pediatrician’s role in genetic testing?

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: Retinal Disorders, Kidney Diseases and Birth Defects.

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.

Novas R, Cardenas-Rodriguez M, Irigoín F, Badano JL. Bardet-Biedl syndrome: Is it only cilia dysfunction? FEBS Lett. 2015 Nov 14;589(22):3479-91.

Khan SA, Muhammad N, Khan MA, Kamal A, Rehman ZU, Khan S. Genetics of human Bardet-Biedl syndrome, an updates. Clin Genet. 2016 Jul;90(1):3-15.

Agrawal H, Dokania G, Allen HD. Visual Diagnosis: Visual Impairment, Polydactyly, and Obesity: Red Flags in a Child. Pediatr Rev. 2018 May;39(5):e21-e23.

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Donna D’Alessandro and Michael D’Alessandro, curators.

The Dengue Dance?

Patient Presentation
“My friend Usha, finally came back to school today,” began the dinner conversation with a pediatrician’s daughter.
“She went to India to visit her family, and got some disease. It made her really sick with a fever and they had to stay with their family until she got better,” the girl went on.
“Do you know what it was?” asked the pediatrician.
“I don’t know but she had a bad fever and it sounds like the name of a dance,” she replied.
The pediatrician offered, “We’ll it could be many things. Was it malaria?”
“No that doesn’t sound right,” she answered.
“Maybe Dengue?” said the pediatrician.
“That sounds right! It sounds funny to me like some type of music or dance,” the daughter said.
“I think you are thinking of Merengue,” she parleyed.
“Yeah. Merengue – Dengue, they sound like something you should move to,” the daughter laughed.
“Merengue is great Caribbean music, but Dengue could be really bad. I’m really glad that Usha is much better,” the pediatrician commented.

Dengue is an important arboviral infection that affects about 40% of the world population. It is found mainly in topical and subtropical areas of the world mainly in developing countries but it range is spreading including the United States. A review of common arboviruses can be found here. It is a flaviavirus with 4 distinct serotypes named DENV-1 through DENV-4 and is spread by A. aegypti a day biting mosquito. Infection with one serotype confers immunity to that serotype but not the others. It does offer some protection for cross-infection but this only lasts a few months. Incubation period is 3-14 days with an average of 7 after exposure.

A primary infection is usually benign. A second infection with another serotype or multiple infections with different serotypes can cause severe infections.
Dengue fever (DF) presents with skin flushing and abrupt high fever (often biphasic 39.4-40.5C) but could also usually be lower that lasts for 5-7 days. Myalgia and pain especially headache or retroorbital pain is generally constant but remits in a few days. Anorexia, nausea, emesis or abdominal pain occur. Fatigue, lethargy or restlessness are also common. A maculopapular, blanching rash over the body occurs often on day 3-4 of fever and fades with time. DF is sometimes referred to as break-bone fever because of the intense fever.

Dengue hemorrhagic fever or Dengue shock syndrome (DHF/DSS) are different in that patients have the same symptoms but start to have signs of underlying serious infection particularly plasma leakage. Laboratory testing start to show leukopenia, shifting from neutrophils to lymphocytes, and thrombocytopenia which can be severe. Increased hematocrit, hypoalbuminemia and increased liver function tests occur which are part of the plasma leak. Patients will show increased abdominal tenderness, emesis, fluid accumulation including pleural effusions or ascites, mucosal bleeding, mental status changes including lethargy or restlessness, and hepatomegaly. Other signs of plasma leakage and hemorrhage occur with more severe disease including petechiae (e.g. positive tourniquet test), mucosal bleeding, and menorrhagia.

Viral antigen detection testing is available for diagnosis.

Tropical diseases associated with fever include:

  • Anthrax
  • Brucellosis
  • Carrion’s disease/Oroya fever
  • Chikungunya
  • Ebola
  • Human immunodeficiency virus
  • Japanese encephalitis
  • Lassa fever and other arenaviral infections
  • Leptospirosis
  • Lyme disease
  • Murray Valley encephalitis
  • Plague
  • Poliomyelitis
  • Q fever
  • Rabies
  • Rat lungworm
  • Relapsing fever/Borrelia
  • Rickettsioses
  • Riff Valley fever and other bunyaviral infections
  • Rubella
  • Scrub typhus
  • Typhus, endemic and epidemic
  • Sleeping sickness
  • Tetanus
  • Tick-born encephalitis
  • Toxoplasmosis
  • Yellow fever
  • Zika

A review of health affects of climate change can be found here.

Learning Point
There are 3 infection phases for Dengue:
1. Febrile
2. Critical – where patients will deteriorate and have symptoms of plasma leak and hemorrhage occurring for about 24-48 hours often (but not always) as the fever starts to subside (often day 3-7 but not always)
3. Convalescent – when patients improve with resolution of laboratory values and generally without health problems but they may have post-viral fatigue syndrome.

Most patients recover and mortality is 0.8-2.5% with children at increased risk especially those <5 years of age.

There is no specific treatment for Dengue. Treatment is only supportive. Patients who are overall well, able to maintain hydration and have no warning signs of impending hemorrhage are usually treated outpatient. Authors note that oral rehydration fluids work well but fluids that are red or brown in color should not be used as these could be mistaken for gastric hemorrhage. For patients with underlying health problems they are monitored in the hospital and treated accordingly. For patients with DHF/DSS they are treated aggressively for hemorrhage with fluid resuscitation and other measures meant to maintain organ function. Also non-steroid anti-inflammatory drugs should be avoided as they can increase the risk of bleeding.

Mosquito bite prevention is the primary prevention. Dengvaxia® vaccine was approved for use in the United States in May 2019 for persons living in endemic areas such as the US Territories of American Samoa, Puerto Rico and US Virgin Islands. Vaccines can be given to children 9-16 years. The dosing schedule is 3 doses each given 6 months apart. In other countries this vaccine can be given from ages 9-45 years.

Questions for Further Discussion
1. What are good travel health resources to find current information about specific destinations?
2. What are some health affects due to climate change? A review can be found here.
3. What patient education information do you provide to patients traveling internationally?

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 this topic: Dengue

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.

Kularatne SA. Dengue fever. BMJ. 2015 Sep 15;351:h4661.

Khetarpal N, Khanna I. Dengue Fever: Causes, Complications, and Vaccine Strategies. J Immunol Res. 2016;2016:6803098.

Scaggs Huang FA, Schlaudecker E. Fever in the Returning Traveler. Infect Dis Clin North Am. 2018 Mar;32(1):163-188.

Centers for Disease Control. Dengue Fever. Available from the Internet at https://www.cdc.gov/dengue/ (rev. 5/3/19, cited 5/16/19).

Centers for Disease Control. Dengue Vaccine. Available from the Internet at https://www.cdc.gov/dengue/prevention/dengue-vaccine.html (rev. 5/3/19, cited 5/16/19).

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

What Can You Do To Prevent Tinea Infections and Why?

Patient Presentation
A 16-year-old male came to clinic because of a groin rash that had been present for a week. It was only slightly bothersome because of the location and was slightly pruritic. He had tried some powder and also lotion but this did not help. The rash was now spreading circumferentially. He was a multi-sport athlete. The past medical history was positive for tinea pedis a few weeks previously that he had used anti-fungal cream for with resolution. He also had a history of tinea pedis more than 1 year ago. The family history was positive for a younger sister who was being treated for ringworm.
The review of systems was negative.

The pertinent physical exam showed a healthy appearing male with normal vital signs and growth parameters. His skin examination showed a 7 cm round-oval lesion in the left inguinal fold with lighter coloring in the center and a raised edge. It was difficult to tell if there was scale as he had just showered. There was a 3 cm lesion above the gluteal cleft that appeared similarly but had some scale present. All other areas of the skin appeared uninfected including his feet.

The diagnosis of tinea cruris was made. The pediatrician recommended over-the-counter antifungal cream to be used twice a day for at least 14 days. “Sounds like you are re-infecting yourself or you are getting infected from your sibling or all the sports you do.
I have some ideas about how you can prevent this from occurring again,” she said.

Superficial fungal infections are very common. “Dermatophytes are molds that can invade the stratum corneum of the skin or other keratinized tissues derived from the epidermis, such as hair and nails. Organisms most commonly affect the scalp, feet, groin and nails.”

Dermatophytes can be anthropophilic (human to human transmission), zoophilic (animal to human transmission) or geophilic (fomite to human transmission). Zoophilic dermatophytes are usually uncommon sources of human infection. Microsporum canis is the most common zoophilic dermatophyte and it can infect humans with close contact but this is less common than anthropophilic organisms. A common example of a geophilic dermatophyte is Microsporum gypseum and again it is not very commonly spread. Human to human or self-inoculation is the most common way tinea infections are spread. Anthropophilic organisms commonly encountered include Trichophyton rubrum, Triphophyton mentagrophytes, Trichophyton tonsurans, and Epidermophyton floccosum.

A review of common tinea infections and presentations can be found here

Learning Point
Tinea tends to affect the glabrous skin or skin without prominent hair. The primary method of transmission between people is contact with infected desquamated skin scales and also infected hair. Molds tend to grow in warm humid environments, so it is not surprising that areas of the bodies with these characteristics are commonly affected. Similarly, environmental exposure such as public shower rooms where large numbers of people congregate may also increase the risk of acquiring or spreading some tinea infections especially tinea pedis. Other areas where infected scale or hair could be contacted would be shared combs, brushes, hats or other clothing.

Prevention of tinea includes not sharing personal items such as combs, brushes, worn and unwashed clothing, towels or bedding. Additionally, frequent clothes changes and washing of potentially infected clothing and towels/bedding should decrease the amount of potential infected material on the clothing, etc. thereby decreasing transmission. Affected body areas should be covered when around others or in venues where people could become infected (e.g. sports practices and competitions, etc.). However, increasing the airflow by wearing loose-fitting garments can decrease the humidity and temperature thereby potentially decreasing dermatophyte growth. Wearing shower shoes in communal bathing facilities is a good practice.

Some authors note that there is an increased risk of tinea cruris after an episodes of tinea pedis. They suspect that during clothing changes and/or grooming, the affected foot or feet is placed near the genital area in a semi-crossed legged position thereby increasing transmission risk. They recommend covering the feet with socks prior to dressing other areas of the body.
Treatment of tinea infections includes antifungal medication and mechanical debridement if appropriate such as nail hygiene.

Questions for Further Discussion
1. How do you treat fungal nail infections? A review can be found here
2. Why do you treat some fungal infections with topical medication and others with oral medication?

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: Tinea Infections 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.

Gupta AK, Chaudhry M, Elewski B. Tinea corporis, tinea cruris, tinea nigra, and piedra. Dermatol Clin. 2003 Jul;21(3):395-400, v.

Panackal AA, Halpern EF, Watson AJ. Cutaneous fungal infections in the United States: Analysis of the National Ambulatory Medical Care Survey (NAMCS) and National Hospital Ambulatory Medical Care Survey (NHAMCS), 1995-2004. Int J Dermatol. 2009 Jul;48(7):704-12.

Bhadauria S, Kumar P. Broad spectrum antidermatophytic drug for the control of tinea infection in human beings. Mycoses. 2012 Jul;55(4):339-43.

Alter SJ, McDonald MB, Schloemer J, Simon R, Trevino J. Common Child and Adolescent Cutaneous Infestations and Fungal Infections. Curr Probl Pediatr Adolesc Health Care. 2018 Jan;48(1):3-25.

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