Girl develops lump in axillary area, fever

A previously healthy 6-year-old female presents to your clinic for evaluation of a left axillary lump and subjective fever.

History reveals that her left axillary area began having mild pain about 1 week earlier while visiting her grandmother. Upon returning home, her mother noted the lump, prompting a visit that day (about 7 to 10 days after the discomfort was first noted). A 1.5-cm left axillary node is felt, with mild tenderness. Her exam at that time was otherwise unremarkable except for a healing scratch on her left wrist. She otherwise denies any injury anywhere along her left arm. Further history reveals that while visiting her grandmother, the patient had frequently played with some kittens.

At that first clinic visit, she has a normal chest radiograph to look for any mediastinal adenopathy, a normal CBC and cat scratch titers pending. She is clinically diagnosed with cat scratch disease at that visit and given a prescription for azithromycin for 5 days. She returns to the clinic at the end of her 5-day course for follow up, with no significant change, except the node is a bit larger at 2 cm. The next day (6 days after the first visit), she returns with acute fever of 102°F (38.9°C), with loss of appetite but still minimal pain of the node. Another normal CBC is done with an erythrocyte sedimentation rate of 41 mm per hour (< 20 mm per hour). Two days later, she returns for follow-up with no more fever and improving appetite, but the node is now 3 cm in diameter, but still with minimal to no pain.

Examination on the day of this visit reveals normal vital signs and only a mildly tender left axillary node that measured 3 cm using clippers (Figures 1 and 2), as well as a healed scratch on the left wrist with a firm papule in the mid-part of the old scratch (Figures 3 and 4). The patient now feels better.

Her past medical history and review of systems is otherwise unremarkable, and her immunizations are up to date. Her family history is positive for all family members being ill over the last several days with fever and influenza-like complaints. She has had no other travel or animal exposure.

The cat scratch titers done at the first visit 1 week earlier return negative for both IgG and IgM.

In summary:

• The patient experiences an onset of left axillary pain while visiting her grandmother, who had some kittens.

• One week later, the patient is seen in the clinic with low-grade subjective fever, a 1.5-cm lymph node and a small papule on the left wrist. She has an otherwise normal exam; normal CBC and chest radiograph; cat scratch disease titers are sent; cat scratch disease is diagnosed; and the patient is sent home with a prescription for azithromycin.

• Five days later, the patient returns for follow-up with more subjective low-grade fever; cat scratch disease remains the diagnosis.

• The patient returns the next day with fever of 102°F and loss of appetite with “influenza-like” illness. Other family members reported fever as well a few days earlier.

• Two days later, the cat scratch disease titers return negative for both IgG and IgM, and the node is now 3 cm in diameter, but the fever has resolved, and the patient feels better.

What's Your Diagnosis?

A. Cat scratch disease
B. Pyogenic lymphadenitis
C. Influenza-like viral illness
D. Both A and C

The best answer is D — both cat scratch disease and an influenza-like viral illness. The fact that the cat scratch titers were negative should not distract you from the classic cat scratch history and presentation. The titers may have been drawn before an antibody reaction had risen to positive levels. Additionally, the sensitivity of the antibody testing is around 80% to 90%, so some obvious cases may test negative. The name “cat scratch disease” was adopted around the mid-1980s. It had previously been known as cat scratch fever (not to be confused with the famous Ted Nugent 1979 hit by the same name), but fever was a relatively uncommon part of the infection, therefore the name change. When seen, fever would more likely occur in the early phase, and certainly not likely to make an appearance after a course of azithromycin, which is still the only antibiotic subjected to a prospective, double-blinded, placebo-controlled study (Bass and colleagues). However, just to confuse things more, on occasion, cat scratch disease can be a cause of a fever of unknown origin (FUO). Nonetheless, given the family history of all members being ill with an influenza-like illness recently, it is highly likely that the fever, loss of appetite and influenza-like symptoms the patient had were from the same cause. Score another one for the almighty HISTORY; in this case, family history.

Now, the healed and somewhat depigmented scratch, with the classic cat scratch disease papule right in the mid-point on the wrist of the same side as the axillary adenopathy, makes cat scratch disease a near “slam dunk,” although one needs to keep in mind the possibility of lymphocutaneous sporotrichosis as well, but that is statistically much less likely to occur. The lesion of sporotrichosis will typically evolve into a chronic ulcerative lesion (Figure 5).

As in this case, the diagnosis of cat scratch disease is usually made on the grounds of the history and clinical findings. However, when the IgM and IgG titers are positive, in the presence of a compatible illness, they can be highly supportive, especially in cases of systemic cat scratch disease, such as FUO, hepatosplenic involvement, encephalitis, bone involvement, etc. Some labs offer a PCR test for cat scratch disease, but it is rarely needed. Lastly, if tissue is obtained, a Warthin-Starry silver stain may reveal the bacilli; however, this is usually not done these days because there is less need for surgical intervention. In the 1960s, a commonly used but somewhat crude skin test was employed to support the diagnosis (see more below). In those days, etiology was unknown.

Pyogenic or bacterial lymphadenitis is almost always acute in onset (days rather than weeks), accompanied by pain and fever and usually caused by Staphylococcus aureus or Streptococcus pyogenes. In the axillary area, a node can grow to a fairly large size before being noticed by parents, simply due to the depth of the space in which it resides. This may mislead or delay diagnosis (see Figure 4 from my June 2020 column showing a suppurative axillary node that hid from detection for several days in the hospital).

A special tribute to Andy Margileth, MD

Over the years, I have written numerous memorial tributes to individuals who had achieved greatness in medicine as educators, clinicians and researchers. I have never featured a living legend, until now. The venerable physician, Andrew M. Margileth, MD, turned 100 years of age on Friday, July 17. After taking a week off to travel and celebrate, he went back to work on Monday, July 27, as usual at the pediatric dermatology clinic at the University of Miami Miller School of Medicine. This is in the face of COVID-19, which is heavily affecting the state of Florida. At 100 years of age, Andy would certainly be in a high-risk category, should he contract this deadly virus. Therefore, one could say that he is literally risking his life to continue seeing patients and teaching students and residents his knowledge of pediatrics, dermatology and infectious diseases.

Dr. Margileth received his BA from Washington & Jefferson College in 1942, his BS from MIT in 1943, and his MD from the University of Cincinnati in 1947. He then went on active duty with the U.S. Navy and did a rotating internship and his first year of pediatric residency at the Naval Medical Center in Bethesda, Maryland, from 1947 to 1949. He finished his pediatric residency at Johns Hopkins Hospital in Baltimore in 1950. Andy spent 24 years on active duty with the Nany, retiring in 1967 at the rank of Captain (equivalent to full Colonel in the Army or Air Force). During those years, he honed his teaching and research skills, with assignments ranging from the Washington, D.C., area to Hawaii.

While never fellowship trained, Dr. Margileth became a recognized expert in the field of pediatric infectious diseases as well as dermatology, publishing across a wide range of topics from bacteriology to virology. Early on, he published some of the landmark work on cat scratch disease, and he was considered to be one of the world’s leading experts on the subject. He was among the first to recognize the association of cat scratch disease with Parinaud oculoglandular syndrome (Margileth, 1957), like that seen in Figures 6 and 7. In the mid-20th century, cat scratch fever (as it was known then) had no test to give reassurance to the diagnosis and to distinguish it from other subacute and chronic forms of lymphadenopathy. Dr. Margileth championed the development of a cat scratch skin test, which was widely used until the 1980s. Some older infectious diseases textbooks have detailed instructions on making one’s own skin test material for cat scratch disease, much of which came from Andy’s early research on the topic (Hoeprich, 1977). My first AAP Red Book was the 1982 edition. In that copy, the skin test is the only diagnostic test mentioned, along with a disclaimer that it is not approved and may carry some risk for transmission of hepatitis and other infectious diseases. The 1986 Red Book had essentially the same statement. In the 1991 edition, the same paragraph was included, but with additional information on using the Warthin-Starry silver stain on biopsy tissue to see the organism. By the 1994 edition, the indirect immunofluorescent antibody test was added. By 1997, the skin test option was reduced to one sentence, and in the 2000, 2003 and 2006 editions, it is only mentioned as no longer recommended. In the 2009 Red Book, the skin test no longer appears. In retrospect, the skin test was useful in confirming cases before the availability of newer modalities, and no infectious disease was ever shown to be a result of the skin test antigen. This is also supported by Dr. Margileth’s own records of about 2,000 patients with whom he followed up over a period of about 20 years, with none having any diagnosed infection related to the skin test (personal history). Considering part of Dr. Margileth’s landmark work on cat scratch disease, it seemed appropriate to use a new case of cat scratch disease to lead into this tribute. While I have never presented two of the same cases, the subject of cat scratch disease is the most common subject matter of the cases featured in this column (10 of the 357 columns, written since April 1989).

Due to his extraordinary dedication to teaching, Andy has won numerous teaching awards over his obviously long and ongoing career. I first heard of Dr. Margileth as being a preeminent pediatrician and educator when I entered active duty in the Army as a new pediatric resident at Fitzsimons Army Medical Center in Denver in 1977. In fact, that same year, the Uniformed Services Section of the AAP established an award in his honor, The Margileth Award (Figure 8), which is still given today for the best clinical research paper. The Margileth Award originally came with a monetary prize for first-, second- and third-place finishers. Several years ago, budgetary constraints led to the discontinuation of monetary prizes by the AAP. Therefore, Andy stepped up and donated the money to continue this tradition. He attends all the meetings and personally hands out the award plaques and checks to the winners, which continues still today. I saw Andy at meetings in subsequent years and got to know him better when I photographed him, along with the other two military pediatric award namesakes of that time — Ogden Bruton and Howard Johnson — at the 1992 Uniformed Services Pediatric Seminar in Washington, D.C. (Figure 9). Andy was a mere 72 years old that time. Since then, he continues to attend ALL the Uniformed Services Pediatric Seminars, which run concurrently with the AAP National Conference & Exhibition (Figures 10 to 13). In 2016, the AAP published a 50-page oral history of Dr. Margileth as part of their Oral History Project (Figure 14), which can be found online here.

In recent years, my wife Ellen and I have joined Andy and his wife, Catherine, on educational vacations. Last year, when Andy was 99 years of age, we ventured off for a 2-week tour of the Euro-Mediterranean coast, from Spain to Italy, ending in Venice, where Andy demonstrated his ability to keep pace and enjoy the gay life of the tourist (Figures 15 and 16). One year later, he celebrated his 100th Birthday in Florida (Figure 17), where he once again dawned his Navy Sword, standing ready to defend the country, or at least keep rowdy students in line (Figure 18). I am glad to say that as of this writing, Dr. Margileth is still busy. While writing this tribute, I called Andy to clarify a question I had. He told me that he would have to call back later, as he was driving somewhere to do something more important. Perhaps that’s the secret to becoming a centenarian.

References:

• Bass JW, et al. Pediatr Infect Dis J. 1998;doi:10.1097/00006454-199806000-00002.

• Margileth AM. Pediatrics. 1957;20:1000-1005.

• Cramblett HG. Cat Scratch Fever. In: Hoeprich PD, ed. Infectious Diseases, A Modern Treatise of Infectious Processes. 2nd ed. Lippincott Williams & Wilkins; 1977:1194-1198.