August 2006

A 6-year-old girl is transferred from a community hospital for evaluation and treatment of fever without a focus. She was admitted four days earlier with a one-week history of fever. Evaluation at the referring hospital included a chest radiograph, blood and urine cultures and a bone scan; all were negative and no positive findings were found upon exam. She eventually had an abdominal CT scan, which revealed hypodense lesions in her liver and spleen (figures 1-2). Her past medical history is unremarkable. She did not travel recently, nor did she have any insect/tick bites or medications prior to the onset of fever. There has been some recent cat exposure, but no other close animal contact.

Examination revealed a well-developed, well-nourished 6-year-old female in no acute distress, but appeared moderately ill during her febrile episodes. She has had documented fevers higher than 102° F one to two times per day. Her other vital signs were normal. The only positive finding upon physical examination was several discrete papular lesions with some central umbilication on small erythematous bases (figures 3-5). There was no significant adenopathy. However, soon after admission, she began having some ill-defined pain in the area of her right hip. She had an MRI of her pelvis, as shown in figure 6.

The only pending laboratory tests from the referring hospital were cat scratch titers (IgG & IgM). Laboratory tests obtained soon after arrival included a normal CBC, an erythrocyte sedimentation rate of 180 and a C-reactive protein of 42. Numerous other tests are pending, including an HIV antibody and other immunodeficiency tests.

What’s Your Diagnosis?

1. Cat scratch disease
2. HIV infection
3. Juvenile Rheumatoid Arthritis
4. Staphylococcal osteomyelitis

Answer

The most likely diagnosis is A, Cat scratch disease (CSD). The Bartonella henselae immunofluorescent antibody (IFA) titers sent from the referring hospital returned significantly elevated for both IgG and IgM. Based on the existing anecdotal data in the literature, intravenous gentamicin was started. Her symptoms of right-sided hip/leg pain rapidly improved, but her fevers continued. Therefore, rifampin was added to her regimen, again based on very limited published data.

Her abdominal CT scan was read as being positive for both liver and splenic lesions. I have seen hepatosplenic cat scratch disease, and I’ve seen cat scratch bone lesions, but I’ve never seen both in the same patient. Her pelvic MRI revealed right iliac crest enhancement, consistent with osteomyelitis, which has been described in patients with CSD. Initially, she was treated with clindamycin for the possibility of bacterial (staphylococcal) osteomyelitis, but this was discontinued within a few days when it became clearer that she had CSD. After 12 days in our hospital on IV gentamicin and rifampin, she was sent home on oral rifampin, still having occasional fevers, but feeling well. She ended up having about six weeks of fever in all. Interestingly, she never developed adenopathy.

Her immune work up and an oncology consult were normal. However, an acquired immune deficiency, like HIV may present in a similar fashion, but would likely be due to an opportunistic invader, such as candida species, zoster or common bacteria, such as staph, pseudomonas, etc., often in multi-focal locations. Certain metastatic cancers could also have a similar presentation, but she had no weight loss and the appearance of the lesions on imaging did not resemble cancerous changes.

Staphylococcal osteomyelitis would certainly cause pain and fever, but would be more acute and would not explain the liver and splenic lesions or the apparent cutaneous cat scratch granulomas seen in figures 3-5. On further history, these lesions correlated with where she had been scratched or pricked by the kitten’s claws. When CSD presents with the typical chronic lymph node enhancement, these skin lesions are often resolved by the time the patient is brought to the primary provider. In my experience, when CSD has a more rapid, febrile systemic presentation, these skin lesions are usually still present.

Lastly, juvenile rheumatoid arthritis (JRA [which is now being referred to as juvenile idiopathic arthritis]) may present with a painful joint, prolonged fever and a rash. However, the rash would be more of a diffuse maculopapular, erythematous, salmon-pink rash (figure 7) and not the discrete lesions this patient had.

This case supports the growing recognition that CSD is one of, if not the leading cause of fevers of unknown origin in children. This is especially true of CSD that has more systemic manifestations at presentation. After almost two years of follow up, the patient remains well.

Commentary

My very first column in this publication featured a case of CSD in April 1989 (Holy cow, that was more than 17 years ago). I have since written about CSD on several occasions: one case with an update in January 1994; another case regarding the etiology in May 1996; in February 1999, another case describing a chronically draining cervical node that had been subjected to surgical incision and drainage; and lastly, a case in March 2002, of hepatosplenic CSD.

The case presented in this issue, of course, relates to CSD osteomyelitis and hepatosplenic involvement with cutaneous lesions and presenting as a fever of unknown origin. She almost had it all. She just needed encephalitis, oculoglandular disease and a suppurative node to run the spectrum of manifestations. Perhaps in a few years, I’ll feature a composite of all these cases into one complete review of CSD.

An excellent resource for information about Cat Scratch Disease, and a wide variety of other infectious diseases is the Red Book. As a matter of fact, the 2006 Red Book (Report of the Committee on Infectious Diseases of the American Academy of Pediatrics) was recently released. The Red Book continues to grow in size and importance. This edition is just under 1,000 pages; the last edition (2003) was a whopping 926 pages. The visual Red Book on CD-ROM contains a wealth of supportive images as well as all the contents of the hard copy of the Red Book.

Another good reference is “The Expanded Spectrum of Bartonellosis in Children” by Massei, et al., in the September 2005 issue of Infectious Disease Clinics of North America.

The hard work of many good people comes together to produce this invaluable resource under the editorial leadership of Larry K. Pickering, MD. This edition is dedicated to Caroline Breese Hall, MD, FAAP, of the University of Rochester School of Medicine, who was a member and committee chair from 1984-1995. In the dedication, she is referred to as an academic “triple threat:” a clinician, teacher and investigator.

Indeed, Dr. Hall is widely accomplished in all three areas. I first heard of Dr. Hall when I was a brand new infectious disease fellow under Jim Bass in 1982. Caroline’s father, Burtis Burr Breese, who died at the age of 93 in May 1998, was an outstanding pediatrician who served in the Navy during World War II. It was there he developed an interest in group A streptococcal disease (GAS), its complications and its effects on recruits; it often resulted in closing down entire camps.

Dr. Burtis Breese helped pioneer office-based research and during his career, he conducted ample research on GAS out of his office, publishing around 150 papers. Jim Bass often admiringly referred to Dr. Breese’s work when discussing strep with us fellows and the discussion usually included flattering comments about his rising-star daughter, Caroline. That was 22 years ago and her star is still shining bright. Congratulations, Caren.

By the way, the Pediatric Infectious Diseases Society established an award in the memory of Burtis Breese after his death. Jim Bass received the very first Burtis Burr Breese Award in 1999 for outstanding research, teaching and practice of pediatric infectious diseases, specifically for his paper on the treatment of cat scratch disease with azithromycin (Zithromax, Pfizer); which, by the way, did not show much benefit compared to placebo for treating uncomplicated CSD lymphadenitis.

As of this writing (early July), there have been 2,543 American military deaths and 18,786 wounded in Iraq and 315 killed and 797 wounded in Afghanistan (www.cnn.com).

Have a great summer and keep your children safe and out of the sun without protection.