Patient Presentation
A 10-year-old female came to clinic for her health maintenance visit. There were no concerns and she was playing youth soccer and softball. The past medical history showed a history of Kawasaki disease as a 7 month old, and had been treated with intravenous gamma globulin and aspirin. Her initial and followup echocardiogram were normal.

The pertinent physical exam revealed growth parameters in the 10-25% and normal vital signs. Her examination was normal including her cardiac exam.

The diagnosis of a healthy female was made. The pediatrician knew that the natural history of Kawasaki disease was that if the echocardiogram was negative at followup that the patients did well and generally did not need lots of long-term followup. He pondered that it was funny how different coronary artery disease was in children versus adults; almost like it was two different diseases. “I really haven’t thought about this much and if I have some time at lunch, I think I’ll look this up,” he thought to himself.

Discussion
Coronary artery disease in children and young adults is overall rare fortunately. It can be symptomatic with chest pain, fatigue, palpitations or syncope, or can be asymptomatic. In children it is hard to image the coronary arteries through an echocardiogram. Arteries are small and superficial while the corresponding veins are larger. Children often move and therefore need sedation to even accomplish the procedure. Because of the potential risk for sudden death there has been much discussion about using screening electrocardiograms and echocardiograms for athletes with arguments for identifying potential disease, but also the cost and risk of false positives.

Learning Point
Common causes of coronary artery disease include:

• Aberrant coronary arteries – overall rare incidence of 0.6-1.3%
  • Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) – most common
  • Aberrant origin of the coronary artery from incorrect sinus of Valsalva
  • Single coronary artery
• Coronary artery fistula – generally rare and asymptomatic but can cause heart failure
• Kawasaki disease
  • Causes ectasias (arterial dilatation without vessel lumen irregularity) and aneurysms most commonly at the left anterior descending but other locations as well
• Multisystem inflammatory syndrome in children (MIS-C) due to COVID-19
• Ischemia
• Iatrogenic from congenital heart surgery

Although coronary artery bypass surgery is overall rare, it has become more common as part of its role in treatment for congenital heart disease.
One review found the five main indications for bypass surgery were:

• ALCAPA
• Left main coronary trunk atresia
• Transposition of the great arteries, acute and late coronary events
• Ross operation for congenital aortic stenosis especially when complicated by infective endocarditis
• Inadvertent acute injury during surgery

One study reviewing sudden cardiac death in individuals < 35 years of age, found that coronary artery disease of some type was relatively common.

Problem	Athlete	Non-Athlete	United States	Europe
Anomalous origin of coronary artery	9.7%	4.4%	14%	5.5%
Ischemic heart disease	9.1%	19.1%	8.7%	12%

Questions for Further Discussion
1. What are the recommendations for electrocardiograms or echocardiograms for athletes in your location?
2. Can Kawasaki disease recur? A review can be found here
3. How common is syncope? A review can be found here
4. What patient education and screening tests are recommended to prevent adult coronary artery disease?

Related Cases

Disease: Coronary Disease

Symptom/Presentation: Health Maintenance and Disease Prevention

Specialty: Cardiology / Cardiovascular-Thoracic Surgery

Age:School Ager

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: Coronary Artery Disease

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.

Brown LM, Duffy CE, Mitchell C, Young L. A Practical Guide to Pediatric Coronary Artery Imaging with Echocardiography. Journal of the American Society of Echocardiography. 2015;28(4):379-391. doi:10.1016/j.echo.2015.01.008

Kitamura S. Pediatric Coronary Artery Bypass Surgery for Congenital Heart Disease. The Annals of Thoracic Surgery. 2018;106(5):1570-1577. doi:10.1016/j.athoracsur.2018.04.085

D’Ascenzi F, Valentini F, Pistoresi S, et al. Causes of sudden cardiac death in young athletes and non-athletes: systematic review and meta-analysis. Trends in Cardiovascular Medicine. 2022;32(5):299-308. doi:10.1016/j.tcm.2021.06.001

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

Patient Presentation
A 9-year-old male came to clinic for his well child examination. His mother was slightly worried about his weight as she had noted that he seemed to be eating more and was not being as active. She said he came home from school and would play videogames mainly. He did play soccer 2 times per week and had recess and gym class at school. She herself noted that she was overweight. The family history was positive for heart disease, type 2 diabetes and obesity. The review of systems was negative including no sleep disturbances, headache, abdominal pain, joint pain, excessive tiredness, or vision complaints.

The pertinent physical exam revealed a blood pressure = 104/70 (normal for age and gender), respiratory rate of 24 per minute, weight = 46.1 kilograms (>90%, equivalent of 13 year old, which was increased from 90% the previous year), height = 138 cm (75% which was consistent from the past several years), BMI = 23.4 (97%, 110% of 95th percentile). Vision screening was 20/30 bilaterally. Skin exam showed no acanthosis nigricans, but he did have some pink-white abdominal striae. His heart, lungs, and abdomen were normal. Genitourinary exam showed that he was Tanner I for gonads and hair. His neurological and extremity exams were normal.

The diagnosis of of healthy male with obesity was made. The patient and mother were counseled regarding ways to improve his nutrition and increase his activity. “I highly recommend family walks. It gets everyone out of the house and people can laugh and talk. You have a dog too, so it would be great to walk the dog then,” he recommended. Obesity screening labs were also added to the routine lipid screening for this visit as well.

Afterwards, the medical student asked how the pediatrician didn’t think the obesity wasn’t due to something else like Cushing syndrome. “That’s always a good question. First I’ve only seen Cushing’s one time. It’s not very common and obesity is very common especially after COVID. He mainly didn’t have other problems like his height was normal, the striae were a pink-white color and not purple which I’ve seen in pictures. He didn’t look overall fat and round with thinner extremities and he had normal blood pressure, plus he didn’t complain of other problems like a headache. Cushing’s is due to elevated cortisol as you know. So it is an endocrine problem. If it is a real endocrine problem then kids usually will have two or more of their growth parameters that are abnormal. Cushing’s I know has children that are overweight and not growing. His growth was consistent but he was gaining in weight. Polycystic ovarian syndrome in girls has some overlap too with general obesity and metabolic syndrome as well as Cushing syndrome. He’s male so we don’t have to worry about PCOS. We’ll follow him up in 6 months to check on his weight. It’s always good though to think about broad differential diagnoses.”

Discussion
Cushing’s syndrome (CS) is caused by prolonged, excessive cortisol exposure which causes disruption of the hypothalamic-pituitary-axis. Normally the hypothalamus secretes corticotropin-releasing hormone (CRH), which stimulates the anterior pituitary to release ACTH (adrenocorticotropic hormone, also called corticotropin). Increased ACTH causes the adrenal gland to secrete cortisol. Increased cortisol then feeds back to down regulate the hypothalamus and anterior pituitary from releasing their respective hormones.

The most common cause of CS is exogeneous glucorticoid such as the medications prednisone or dexamethasone. Endogeneous CS is rare in the pediatric population. Endogeneous causes are due to tumors of the pituitary, adrenal gland or rarely some other type of tumors which secretes CRH or ACTH. Adrenal hyperplasia is also a potential cause.

Cushing’s disease (CD) is CS due to a pituitary adenoma secreting excess ACTH. This is even rarer than CS overall. CD has a male predisposition. The adenomas usually are sporadic but can be part of recognized genetic patterns including Multiple Endocrine Neoplasia 1 (MEN1)

Diagnosis of hypercortisolism can be done by several tests each of which have their pros and cons and multiple tests may be needed to confirm the hypercortisolism. Treatment depends on the cause and often surgery is needed to remove pituitary or adrenal masses, along with medical therapy to suppress adrenal steroidogenesis such as ketoconazole or mitotane. Other therapy to address side effects also includes treatment for hypertension, glucose management, bone fractures and psychological treatment. Even with treatment children can have long-term health problems including growth and pubertal development (adult height is often shorter than expected), metabolic problems and especially behavioral problems. Cognitive and emotional regulation has been disrupted by the CS, and therefore it can take a long time for the brain to resolve it (cerebral atrophy has been documented in pediatric patients). It is not uncommon for at least 1 year of continued academic and other problems before there may be some resolution. Complete resolution may also not occur and there is an increased risk of suicidal ideation after treatment.

Learning Point
Clinical manifestations of CS include:

• Growth and body habitus
  • **Weight gain with simultaneous linear growth deceleration (accelerated weight gain is often not recognized)
  • **Central obesity
  • **Dorsocervical fat pads
  • **Facial plethora (Moon facies)
  • Muscle wasting and general weakness
• Skin
  • **Striae that are violaceous
  • Hyperpigmentation
  • Skin atrophy
  • Acanthosis nigricans
  • Hirsutism with fine downy hair especially on cheeks, arms, and legs
  • Acne
  • Easy bruising
  • Fungal infections
• Behavior/Psychological
  • **Irritability
  • Anxiety
  • Depression
  • Mood swings
  • Fatigue
  • Academic problems
• Cardiac
  • **Hypertension
  • Hypertrophic cardiomyopathy
• Genitourinary
  • Puberty disruption
  • Amenorrhea – primary or secondary
  • Gynecomastia
  • Virilization
• Hematologic
  • Easy bruising
  • Hypercoagulability
• Metabolic
  • Glucose intolerance
  • Insulin resistance / suppression
  • Osteopenia or osteoporosis
  • Bone pain or fracture
• Neurological
  • Headaches

** are common presentations

Questions for Further Discussion
1. What is Addison’s disease?
2. What is Cushing’s triad?
3. What causes short stature? A review can be found here.
4. What clinical signs are seen in PCOS? A review can be found here.

Related Cases

Disease: Obesity | Cushing’s Syndrome

Symptom/Presentation: Obesity

Specialty: Endocrinology

Age: School Ager

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: Cushing’s Syndrome and Obesity in Children.

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.

Ferrigno R, Hasenmajer V, Caiulo S, et al. Paediatric Cushing’s disease: Epidemiology, pathogenesis, clinical management and outcome. Rev Endocr Metab Disord. 2021;22(4):817-835. doi:10.1007/s11154-021-09626-4.

Stratakis CA. Cushing’s disease in children: unique features and update on genetics. Pituitary. 2022;25(5):764-767. doi:10.1007/s11102-022-01237-9.

Parish A, Cheung C, Ryabets-Lienhard A, Zamiara P, Kim MS. Cushing Syndrome in Childhood. Pediatric in Review. 2024:45(1);14-24.

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

Patient Presentation
An 8-year-old male came to clinic with his parents because of uncontrolled asthma symptoms. They had moved into a rented home that was about 50 years old in August, when they moved to the area from another country. Since that time he had increased runny nose and coughing and used his albuterol only intermittently. He was coughing several times per day and his parents said he “coughed all night” but it didn’t wake up the patient. They denied that he was excessively sleepy, had problems with activity or keeping up with other children. The family had noticed some mold growing in the bathroom and had talked with the landlord. The landlord had changed out the bathroom ventilation filter and replaced the caulking. He had professionally cleaned the carpets in the unit before they had moved in. The parents said that the boy still was not getting better and they felt it was due to mold in the house and wanted the pediatrician to write a letter to the City to have the landlord take additional mitigation changes.

The past medical history showed that he had atopic dermatitis as an infant and was diagnosed with asthma at 2 years of age.
He used albuterol intermittently and used steroids for exacerbations about 2 times per year. The family denied any seasonal variation to his symptoms and had never used a steroid inhaler. He had not been hospitalized but had been in the emergency room for a couple of exacerbations within his lifetime but none recently. The family history was positive for several others who had asthma and allergies. No others had any increase in symptoms with moving into the new home.

The pertinent physical exam showed a patient with normal vital signs and growth parameters in the 90%. He had allergic shiners and boggy nasal mucosa with some clear rhinorrhea. His lungs were clear but had a slightly prolonged expiratory phase. His skin had general xerosis with patchy areas on extensor surfaces with some lichenification.

The diagnosis of atopy and asthma that was not controlled was made. The pediatrician recommended that they start using some long-acting antihistamine and nasal steroid daily to help with his rhinitis. He also recommended that they use his albuterol on a more regular basis for coughing and increased work of breathing, along with keeping a symptoms diary of how often they were using it. “He may also need to start a daily steroid medicine too, but I would like to see how he does with these medicines before starting that one,” he recommended. “I’m also going to go over some things you can do at home to help such as vacuuming his room and cleaning the bath more regularly and I think that should help as well.” The family was quite insistent upon having a letter that said that the boy’s symptoms were due to the mold they had found, and that the landlord was not responsive. “I don’t think I can write that letter now, but what I will do is have our social worker talk with you and give you some resources. I do want to see you back in about 2-3 weeks to see how he is doing though,” the pediatrician counseled. The social worker provided phone numbers to the local housing commission, and local contractors who could do evaluation and mitigation services. She also explained how the housing commission and landlord dispute system worked in the local area. The family asked for a list of lawyers they could contact if they continued to be not satisfied with their housing problem. At followup, the boy’s symptoms had improved but an inhaled steroid was prescribed. The family had contacted the local housing commission but had not heard back from them at that time.

Discussion
Fungi are ubiquitous and adaptive to all environments including buildings. They can be viewed as potential contaminants but mainly as environmental companions. Fungi are important for biodegrating and nutrient cycles and are commensal with other organisms such as bacteria and viruses. We use fungi to make food (e.g. beer, wine, bread) and assist with decomposition making compost. When there is a balance between the fungi and other systems, then there generally are not problems. It is when there is too much fungi for a particular time frame or location that fungi cause problems.

Fungi can also cause or exacerbate other problems such as increased respiratory problems, allergies or asthma. Examples of allergenic fungi include …Alternaria alternata, Aspergillus fumigatus and Clasosporium herbarum.” There is evidence to support health risks from fungi, but the exact mechanisms are not well understood.

“The endemic mycoses are a group of infections caused by fungi with distinct geographic distribution, determined by environment niche in which the causative pathogen can persist and sporulate.” These are divided into two groups. Those that are systemic and caused by inhalation or cutaneous caused by inoculation of the skin. Contaminated soil or vegetation are the most common reservoirs for these mycoses. For immunocompetent patients, many of the systemic mycoses produce asymptomatic infections or have relatively common self-limited symptoms such as cough, lethargy, fever, chest pain and mild acute weight loss. Therefore if patients have insidious, persistent or unexplained illness patterns, then systemic mycoses certainly should be considered. Cutaneous infections often will cause rashes and/or lymphadenopathy. The evaluation depends on the suspected fungal infection with culturing of body fluids, tissue or skin being common with treatment usually being systemic anti-fungal medications for prolonged periods of time.

Learning Point
Indoors, the most common source of fungi are airborne outdoor fungi. Thus the content of indoor fungi varies based on location and seasonality. Farming areas have a large number of species and counts overall, but interestingly have fewer allergies and asthma problems. Other sources of indoor fungi are handling of biological materials (e.g. fruits, root vegetables, blue cheese) including spoiled material (e.g. moldy vegetables or bread), houseplants and potting soil, and firewood. Clothing and shoes brought inside are also sources. Humans can also bring it into the home though contamination of skin, hair and nails, and similarly animals can bring it in on their fur and nails.

Flooring is an important source of fungi location. Fungal levels are driven by house dust levels. Smooth flooring has less dust, yet can more easily have this dust and fungi re-aerosolized. Carpeting acts more like a filter in that house dust and fungi can be trapped in it. However there is more of it within the carpet and significant build up of the house dust and fungi can then cause re-aerosolization of the dust and fungi as well.

Dampness and moisture are wonderful environments for fungi to grow and therefore can cause enough mold to form that is visible to the naked eye. This occurs often in humid environments such as bathrooms, kitchens and laundry. It can occur in other areas as well such as when condensation forms on cold machinery in a humid environment or systems that are designed for it such as drip pans. Mold growth is not considered a normal source indoors and can be more of ahealth issue.

How to help mitigate over accumulation of fungi is always a question. Any of these methods may increase exposure and therefore individuals who are more affected should be out of the immediate environment if possible, or if doing the cleaning themselves should wear protective equipment to help reduce exposure.

Ventilation helps. Although ventilation can bring in outdoor air, it also serves to remove contaminants (including particles and gaseous chemicals) and moisture. It also can speed up the drying of areas that are intermittently moist. Ventilation systems filters can help to trap indoor air contaminants but need to be cleaned often. Air ducting requires deep cleaning and is often not cleaned regularly. These ducts can accumulate years of dust and debris. If moisture is added into this environment it is a wonderful medium for growing organisms including fungi. Similarly any air filters for ventilation systems, or even the vents themselves should be cleaned frequently. Frequent vacuuming of surfaces can stir up the dust, but eliminates the dust and decreases fungal counts.

For mold, increasing ventilation, and eliminating infected items that can be changed (e.g. kitchen sponges, shower curtains, bathroom filters) regularly can help prevent problems. Regular wet cleaning with household bleach of bathroom tile and similar surfaces usually can help mitigate the problem.

Extensive damp and wetness problems within the building structure due to ongoing moisture issues needs to be mitigated professionally. Cleanup from weather related events such as severe storms, tornados, hurricanes or flooding require more extensive mitigation but the principles are similar in eliminating infected materials, cleaning remaining materials and increasing ventilation.

Questions for Further Discussion
1. What do you recommend for environmental changes for asthma?
2. What systemic and cutaneous mycoses are endemic to your area?
3. What community resource assistance do you have in your local area for housing and legal resources?
4. What causes indoor air pollution?

Related Cases

Disease: Asthma | Molds | Fungal Infections

Symptom/Presentation: Cough | Rhinitis

Specialty: Allergy / Pulmonary Diseases | Preventive Medicine and Health Maintenance | Social Services

Age: School Ager

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: Molds, Indoor Air Pollution, 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.

Nevalainen A, Taubel M, Hyvarinen A. Indoor fungi: companions and contaminants. Indoor Air. 2015;25(2):125-156. doi:10.1111/ina.12182

Adams RI, Lymperopoulou DS, Misztal PK, et al. Microbes and associated soluble and volatile chemicals on periodically wet household surfaces. Microbiome. 2017;5(1):128. doi:10.1186/s40168-017-0347-6

Yeah DK, Butters C, Curtis N. Endemic Mycoses in Children. Ped Inf Dis J. 2019:38(6S); S52-59.

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

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