December 2005

The guest columnist and contributor for this month is Mary L. Vader, DO, of Montrose, Colo. It is a southwestern, rural community of about 14,000 people with a surrounding population of about 40,000, and mostly dependant on agriculture. It serves as the regional medical referral center for the surrounding area up to an 80-mile radius.

Dr. Vader is an alumna of my medical alma mater, Texas College of Osteopathic Medicine in Fort Worth, only 10 years later (1987). She trained in pediatrics at St. Joseph’s Children’s Health Center, University of Arizona, Phoenix (1990). She is Board Certified in Pediatrics and has faculty appointments at the University of Colorado School of Medicine and Hospital and Denver Children’s Hospital. Dr. Vader is heavily involved in various community activities for children and child welfare. I would like to thank Dr. Vader for contributing this fascinating case.

A 7-year-old Mexican National male is referred for admission and evaluation of prolonged fever, hepatosplenomegaly and a transient rash. The history of the chief complaint began 10 days earlier, on the same day that he received varicella and hepatitis B vaccines. His parents treated him with Diporina – a Mexican brand of a non-steroidal anti-inflammatory drug (NSAID) – with minimal benefit. However, the fever persisted and a transient, intermittent maculopapular rash developed on his trunk and legs, as well as some dull abdominal pain and distension. He was seen in a primary care clinic earlier in the illness and treated for constipation and dehydration. When this did not help, the parents took him to a pharmacist (commonly done in Mexico) who encouraged them to travel to Montrose Memorial Hospital for care.

His past medical history is significant for being born in Central Mexico, with a normal, healthy childhood till now. He moved to the United States about one year ago. His immunizations are up to date, with the most recent as noted above.

His family and social history is significant for living in rather crowded conditions with his extended family that includes numerous siblings and cousins. He has no unusual dietary habits, recent travel, sick exposures (including tuberculosis), or unusual pet or other animal exposure. He drinks city water and attends public schools.

He has no known allergies and takes no medications on a regular basis.

Review of systems was positive for all of the above plus fatigue, poor oral intake and chronic constipation. However, he did not lose any weight during this 10-day period.

Examination on admission revealed a fever of 102º F, with mild tachycardia and tachypnea (32). His oxygen saturation was 96% on room air. He generally appeared tired, but otherwise appropriate. Pertinent positive findings included a distended, diffusely tender abdomen with the liver edge felt at the pelvic rim and the spleen felt to the mid-left abdomen. There was no rash or other positive findings.

Abnormal lab tests included a total bilirubin of 1.2, aspartate transaminase (AST) of 225, and alanine aminotransferase (ALT) of 130, an alkaline phosphatase of 603, a partial thromboplastin time (PTT) of 33.7 with an international normalized ratio (INR) of 1.3. His complete blood count (CBC) revealed mild anemia and a platelet count of 97,000. His urine analysis was normal and cultures of blood and urine are pending.

A chest radiograph is shown in figures 1 and 2. Abdominal upright and flat radiographs are shown in figure 3 & 4, and computed tomography (CT) scan is shown in figures 5 and 6.

What’s Your Diagnosis?

1. Incomplete (atypical) Kawasaki Disease
2. Reaction to immunizations
3. Brucellosis
4. Cat Scratch Disease

Answer

After five days, the blood culture taken on admission grew a gram-negative coccobacillus that was identified by polymerase chain reaction (PCR) to be a Brucella species. By then, the child was transferred to Denver Children’s Hospital for further evaluation and management. Upon learning this, he was treated with oral doxycycline and intravenous gentamicin. After 10 days he was discharged on oral trimethoprim-sulfamethoxazole and rifampin for a six-week course and recovered without difficulty. He did well in follow up.

According to the final radiology reports, the imaging revealed dilated loops of bowel with some air-fluid levels, hepatosplenomegaly with ascites and bilateral pleural effusions.

According to the 2003 Red Book, about 100 cases of brucellosis are reported each year in the United States (100-200 according to the CDC). Most cases occur in adults, with only about 10% in patients under 19 years of age. This could be partly due to the fact that most pediatric cases are mild, and may go unnoticed and undiagnosed. Since brucellosis is a zoonotic disease, children typically contract it as a result of direct contact with infected animals or consumption of unpasteurized milk or milk products, such as goat’s milk or cheese. With an incubation time of up to several months (about one month on average), one might find it difficult to remember where they came in contact with the organism. In this case, the source was never discovered, but many cases are found in rural communities, in migrant workers with agricultural jobs. Their children would likewise be at increased risk, because they are frequently in close proximity with farm animals and more likely exposed to unpasteurized milk products.

The clinical presentation of brucellosis can be either mild or severe, especially with the species B. melitensis. The patient will usually have a febrile illness with a variety of symptoms including: fatigue, malaise, night sweats, weight loss and often evidence of multi-organ disease. Any system can be involved. Children frequently present with joint pain and swelling but might initially present with a fever of unknown origin (FUO). Diagnosis is obviously confirmed with a positive culture, but in order for cultures to be held long enough – usually about one month – one must notify the lab of the possibility. Serologic tests are also available.

There are several species of Brucella that we will not go into in this column, but to read all about it, I recommend Edward Young’s chapter (133) in the new Feigin, Cherry, Demmier and Kaplan Textbook of Pediatric Infectious Diseases, 5th Edition (2004). It includes a nice historical review of the disease. The treatment of choice is doxycycline plus rifampin or doxycycline plus gentamicin. Trimethoprim-sulfamethoxazole can be substituted for the doxycycline in younger children (younger than 8 years). The recommended duration of therapy is six weeks. Relapse is possible. If left untreated, brucellosis can become chronic.

Incomplete (atypical) Kawasaki Disease is being seen more all the time. We recently saw a 9-year-old patient who had only fever and mild conjunctival erythema without discharge (figure 7). An abnormal echocardiogram confirmed the diagnosis when we noticed that her platelet count went to over 700,000. Of course, like with all vasculitities, these patients can also have multi-system abnormalities with liver, lung, renal, brain, and gastrointestinal (GI) tract abnormalities. The older child and young infants are more likely to have very incomplete presentations, but just as likely to have severe cardiac sequelae. This is a very concerning problem.

Cat Scratch Disease (CSD), caused by Bartonella henselae, can also present as an FUO; in fact, it is a common cause of prolonged fever in children. Furthermore, it is not unusual to see hepatosplenic involvement (figures 8 and 9), showing multiple hypo-echogenic lesions in the liver and spleen. But enlargement of the organs is less common. The child might present with fever and vague, persistent upper abdominal pain. It takes a high index of suspicion for CSD in these cases. Confirmation is usually by a positive serology.

A reaction to the vaccines he received at the onset would not last this long, or cause the visceral problems seen on imaging.

When I was a high school student growing up in rural Texas in the early 1960’s, with lots of farming and ranching around the area, we all took agriculture classes and belonged to the Future Farmers of America. But I cannot think of a single classmate who actually went into farming or ranching as an occupation. Regardless, as a result, we grew up knowing something about the dreaded cattle disease known as Bangs or Bang disease (brucellosis), named after the 19th century Danish physician and veterinarian, Bernhard Bang. Bang first isolated the organism from infected cattle in 1897.

There were also a lot of Mexican migrant families in the area, following the harvest seasons. Many of their children attended our school. They would be there one year and not the next, but sometimes back the following year. One of these kids was one of my best friends in fifth grade. He did not come back to school for the sixth grade, but came back a year behind, the following year, with leg braces and a crippled left arm due to polio (in the summer of 1958, polio vaccine had been available for several years by then). If these kids made it to high school, they were usually strong, healthy and very good athletes. Yet these families were at higher risk for all diseases, including vaccine-preventable diseases and contracting brucellosis, because of their close proximity to the farm animals and increased use of unpasteurized milk products.

Nowadays, this zoonotic disease is well controlled in this country, and human disease is very uncommon. As with this case, poverty conditions and Hispanic connections are likely when cases are seen.

Columnists’ Comments

You may think of this as part three in a series of commentary regarding the lethal effects of malaria on the children of Africa (primarily), where, on average, 2,000 die each day because of this preventable disease. I commented originally in the February 2005 issue of Infectious Diseases in Children that there was something out of whack when the world responded with such great zeal to the tsunami disaster while the relatively silent and much more deadly malaria catastrophe went unnoticed. Then in the September issue, I briefly commented on the work of a couple Dutch investigators (entomologists) who infected the mosquito with a fungus that prevents it from taking another blood meal, thus preventing transmission. Well, the news is getting better. At the end of October, it was announced that the Bill and Melinda Gates Foundation was donating over a quarter of a billion dollars ($258.3 million) in grants to fight this miserable disease. It will be used in three different areas: vaccine development, new medication research and vector control.

“Millions of children have died from malaria because they were not protected by an insecticide-treated bed net, or did not receive effective treatment,” Bill Gates was quoted saying. “If we expand malaria control programs, and invest what’s needed in R and D (research and development), we can stop this tragedy.” Now, that’s putting your money where your mouth is. Part four to come later.

Update

It is confirmed that the 2006 Uniformed Services Pediatric Seminar (USPS) will now be held in Portsmouth, Va., March 13 to 16. You may recall before Hurricane Katrina hit the Gulf area, it was originally scheduled in Biloxi, Miss. The information you need about this great meeting is available at the American Academy of Pediatrics Web site (www.aap.org). If you have any trouble finding it, just e-mail me at jhbrien@aol.com. I am happy to forward any information you need.

Lastly, December is always a very difficult time for soldiers, sailors, marines and airmen deployed away from their families. You do not have to be assigned to a combat zone to feel depressed. Any unaccompanied tour can be stressful and depressing and a phone call is the most cherished gift one can receive. So, if you have an opportunity to contribute to one of these military Holiday Care Package programs, think of donating a calling card. It is better than gold to a lonely soldier. From the Brien family to yours, please have a happy and safe holiday season. Peace.