What is DRESS Syndrome?

DRESS (drug reaction with eosinophilia and systemic symptoms) is a poorly understood syndrome that has an unknown prevalence in the pediatric population because it is often missed by doctors. 

Symptoms include fever, an itchy rash covering over half the body, enlarged lymph nodes, and inflammation of the liver. A blood test reveals increased white blood cells, "atypical lymphocytes" (abnormally large and irregular lymphocytes because they are infected with the virus), and elevated eosinophils. 

What causes it? There have been links to both herpesvirus (including oral and genital herpes, epstein barr virus and roseola virus) and a couple months after starting certain anti-seizure medications. Bad cases will involve >90% of the skin and affect multiple organs such as the kidneys, and there may be involvement of the mucosal lining of the mouth and lips which can mimic life threatening drug and infectious reactions known as Stevens Johnson Syndrome and Toxic Epidermal Necrolysis.

It is very difficult to avoid getting this syndrome, as it is unknown why some patients get it and others do not. It can take months to fully recover from DRESS syndrome. The treatment, if caused by a medication, is to stop that medication. Most patients get IV or topical steroids to calm the immune system. 

Most often, pediatric rashes are harmless. In rare cases such as this, however, some detective work is required to make a swift and proper diagnosis.

A Swollen Pediatric Joint

A 6 year old girl with a swollen right knee in the absence of trauma, fever, rash or lymphadenopathy. Symptoms are worse in the early morning, and improve throughout the day. She also complains of eye pain. What is the diagnosis?

Juvenile Idiopathic Arthritis (oligoarticular type)


Arthritis in children is not uncommon. When encountered by pediatricians, it is characterized into one of three subtypes: systemic, oligoarticular, and polyarticular.

• The oligoarticular type is the most common. Usually occuring around 5 years old, it is seen in the large joints (but not the hips) and is known for it's casual but unique association with uveitis (irritation of the eye) and a positive ANA (an antibody in the blood). If left untreated, this uveitis can lead to glaucoma when they are older.

• The polyarticular type is the second most common, and usually affects the large and small joints on both sides symmetrically. Older children with bloodwork that is rheumatoid factor positive are likely to progress to arthritis as adults.

• The systemic type is often easiest to recognize, as an adolescent will often present with fever, a salmon-colored rash, and lymphadenopathy. Many different joints can be affected, and treatment requires disease-modifying drugs (DMARDs). Untreated systemic JIA can progress to a dangerous condition known as macrophage activating syndrome. 

The disease is manageable when caught early, and is typically managed by a specialist known as a rheumatologist. An early step is be sure the swelling isn't the result of an athletic injury or fall. The pediatrician will be sure to rule out more serious causes such as a septic (infected) joint.

Childhood Eczema

Eczema (atopic dermatitis) is a chronic condition caused by inflammation of the skin. It's a component of the "atopic march" which includes asthma, hay fever, and food allergy. Though the exact cause is unknown, the risk of developing eczema is higher in children with dry skin (xerosis) and those with immune dysfunction. 

Additionally, possible triggers reported include:

• irritants (wool, soaps and chemicals)
• contact allergens (latex, metals, perfumes)
• food allergens (cow's milk, eggs nuts, soy, wheat and shellfish)
• house allergens (tobacco smoke, hard water, dust mites, animal dander)
• other irritants (extreme changes in humidity, pollens, molds)

Eczema is most common in children younger than 5 years old. Studies show that 66% of patients first experienced eczema before 7 years of age. The amount of children affected by eczema varies by country and, in the United States, from state to state. Numbers reported are from 1 to as high as 22% of children younger than 18. Studies also show that preterm infants (<37 weeks gestation at birth) have a higher risk of developing the condition. 

Possible risk factors include atopy (positive reaction to at least one skin prick allergen), not breast feeding, immunosuppressants and stress.

Children with eczema are at an increased risk of skin infections caused by staph, strep, herpes simplex 1 and various fungi. Chronic itching may lead to scarring and sleep disturbances. 

The pediatrician will make the diagnosis based on physical examination. It's important to rule out conditions such as parasitic infections (scabies), fungal infections (tinea), metabolic conditions (zinc deficiency), immunological deficiencies (Wiskott-Aldrich Syndrome, dermatitis herpetiformis, lupus, HIV dermatitis), systemic disease (primary biliary cirrhosis, polycythemia vera and renal failure) and other skin conditions (contact dermatitis, ichthyosis, psoriasis and seborrheic dermatitis).

Most cases of childhood eczema improve with age, and up to 70% of cases clear by teenage years. 

The secret to managing eczema lies in both controlling the dryness of the skin and minimizing any inflammation. This includes:

• Use moisturizing soap (Dove brand preferable) at very END of bath to avoid irritation
• Moisturizing cream (such as Vaseline or Eucerin) applied immediately after bath (while still damp) to affected areas 
• An anti-inflammatory (steroid cream such as triamcinolone) may be prescribed. Use twice a day.
• Avoiding irritants or triggers

Reference

Atopic dermatitis. Dynamed database. Updated January 21 2014. Accessed July 2, 2014.

Heart Attacks in Children? The Kawasaki Disease Epidemic

A recent study out of Australia published in the Journal of Pediatrics revealed that cases of the potentially deadly Kawasaki Disease are steadily increasing. Kawasaki Disease (KD) is a poorly understood condition known as vasculitis, which is the inflammation of small blood vessels. The disease is known for attacking the coronary arteries of children, the vital blood vessels supplying the heart muscle with oxygen and other nutrients. The child suffers from an acute fever and severe pain, essentially symptoms of both infection and a heart attack.

Doctors do not know the cause of KD, but they believe it may be infectious in origin because most cases occur between the winter and spring, and epidemics occur frequently.  KD most commonly affects Japanese children and those of Japanese ancestry: the incidence in Japan has been steadily increasing, from 102 per every 100,000 children <5 years old to 188 in 2006.  In the United States, it is 17.1 per 100,000 children <5 years old, but clinicians fear this number will continue to increase.

85% of children suffering from KD are <5 years old, and the median age is 2 years old. The symptoms begin with a high fever that lasts a minimum of 5 days and lasts as long as 4 weeks. The child typically experiences redness and swelling of his or her hands and feet and a morbilliform rash of the face and extremities. The lips and mouth will typically dry out, crack and blister.

Meanwhile, inside the coronary arteries, the body is attacking the vascular smooth muscle and causing inflammation that will lead to scarring and poor vessel integrity.  It is for this reason that coronary artery aneurysm (ballooning and tearing) occurs in 25% of cases, particularly if the child is less than 6 months or older than 6 years old. Other complications include myocardial infarction, cardiac arrest, heart failure, myocarditis and pericarditis. Two reports have noted children becoming insulin dependent diabetic within 4 months of the vasculitis.

When the pediatrician recognizes these harrowing symptoms, he or she will order an echocardiogram to visualize the heart.  When a blood test reveals high white blood cells (leukocytosis), high erythrocyte sedimentation rate (ESR) and high C-reactive protein (CRP), a diagnosis can be made.

The treatment for KD is intravenous immunoglobulin (IVIG), which is an injection of IgG (long-term) antibodies pooled from over 1,000 blood donors. High dose aspirin with or without corticosteroids is also administered to help reduce swelling and prevent a heart attack. The child should follow up with a cardiologist for repeated echocardiograms and long-term monitoring, since the highest risk for a heart attack is in the first year after diagnosis.

Until more is learned about KD and its origins, it will be added to a long list of autoimmune diseases that are poorly understood but well respected in the medical community.  

References

Saundankar J1, Yim D, Itotoh B, Payne R, Maslin K, Jape G, Ramsay J, Kothari D, Cheng A, Burgner D. The epidemiology and clinical features of Kawasaki disease in Australia. Pediatrics. 2014; 133(4):e1009-14.

Kawasaki Disease. Dynamed Database. Updated June 9, 2014. Accessed June 13, 2014.

The Importance of Identifying a Morbilliform Rash

The term "morbilliform" is used to describe any skin finding that resembles the measles rash. The macular lesions are typically diffuse, red and 2-10 mm in diameter. They may become confluent (come together to form clusters) in some areas. 

It is very important for doctors to know the differential diagnosis for a morbilliform rash, since some of the conditions are deadly. The process occurring within the body leading up to the rash, known as the prodrome, will help the physician narrow the diagnosis.This prodrome can be learned by ascertaining a good history. 

Some notable causes of morbilliform rash are:

• Fifth Disease (erythema infectiosum/parvovirus B19/)
• Sixth disease (roseola infantum/herpesvirus 6)
• Streptococcal infection (Groups A, C)
• Echovirus
• Adenovirus
• Kawasaki Disease
• Rubella
• Measles
• Syphilis
• Meningeal Petechiae (or Waterhouse Friedrichsen Syndorme)
• Drug hypersensitivity Reaction (especially nevirapine, abacavir, phenytoin)

A study by Ramsay et al in 2002 evaluated the laboratory samples of 93 vaccinated children in England, and noted that the most common cause of the rash was a parvovirus B19 infection (17%). Group A strep was found in 15% of cases, and sixth disease (roseola infantum or herpesvirus 6) in 11%. None of the cases were caused by measles. The use of widespread vaccination has nearly eliminated the measles infection, making way for other viruses that cause similar rashes. It is paramount that physicians discern the cause of the findings.

Reference

Ramsay M, Reacher M, O'Flynn C, Buttery R, Hadden F, Cohen B, Knowles W, Wreghitt T, Brown D. Causes of morbilliform rash in a highly immunised English population. Arch Dis Child. 2002 Sep;87(3):202-6.