Young girl presents with 3-week intermittent fever, worsening cough

A previously healthy 5-year-old female presented for evaluation after 3 weeks of intermittent fever and worsening cough. The history of this illness began 23 days earlier.

Lisa Forman

James H. Brien

She was seen in the local ED with a 1-day history of fever of 102°F, rhinorrhea, sore throat and abdominal discomfort. She was diagnosed with strep throat with a positive rapid strep screen and was prescribed amoxicillin for 10 days.

Her past medical history was unremarkable, and her immunizations are up to date, including the annual influenza immunization. Her family and social history reveals no known sick contacts and no recent travel or animal contact.

Figure 1. Urticarial rash on the face. Source: Lisa Forman, MD

The amoxicillin produced no significant change, but she noted that her fever seemed to resolve on day 9 of treatment. However, her cough persisted, and her fever returned 1 week later with some post-tussive emesis. She was seen again in the ED, where her examination revealed a temperature of 102.7°F, with some mild tachycardia and an oxygen saturation of 97% on room air. Examination at that time revealed clear breath sounds and a normal respiratory rate but with a prolonged expiratory phase. Additionally, her eyes were injected without exudate. She was diagnosed with an upper respiratory tract infection and prescribed an albuterol metered-dose inhaler (MDI) to use every 4 to 6 hours and polymyxin B plus trimethoprim ophthalmic drops for her conjunctivitis.

Figure 2. Urticarial rash of the lower back. Source: Lisa Forman, MD

Figure 3. Urticarial rash of the upper thighs. Source: Lisa Forman, MD

Four days later (today), she presents to her primary pediatrician who verifies the previous exam findings noted earlier (specifically, clear lungs without tachypnea or retractions). Additionally, she is now complaining of a waxing and waning rash on her face, lower back and upper thighs (Figures 1, 2 and 3), along with erythematous, bulging tympanic membranes. Her general appearance was that of a tired, mildly ill child. At this time, the following tests were performed:

• Lab tests with a CBC showing a WBC count of 17.7 and 80% neutrophils; complete metabolic profile was normal.
• Pending blood tests, including blood culture and Mycoplasma immunoglobulin G and immunoglobulin M titers.
• Chest radiograph, with a final reading as bilateral lingular infiltrates (Figures 4 and 5).

Figure 4. Chest radiograph showing bilateral lingular infiltrates. Source: Lisa Forman, MD

Figure 5. Lateral chest radiograph showing lingular infiltrates. Source: Lisa Forman, MD

Summary:

1. Previously healthy 5-year-old female with prolonged illness, spanning 3 weeks of fever, cough, sore throat, otitis media, conjunctivitis, bronchospasm and an urticaria-type rash.
2. Previous treatment included 10 days of amoxicillin and albuterol by MDI without apparent benefit.
3. Lab findings reveal an elevated WBC count with 80% neutrophils and chest radiograph with a bilateral infiltrates.

What’s your treatment?

A. Supportive care pending lab results
B. Continue albuterol and observe
C. High-dose amoxicillin-clavulanate
D. Azithromycin

Case discussion:

The best answer is not straightforward, but we feel it is D, azithromycin. The Mycoplasma pneumoniae IgG was subsequently found to be positive (equivocal range) and the IgM titer was very high. M. pneumoniae infections have a great capacity for presenting in mysterious ways, from common, atypical pneumonia to atypical Stevens-Johnson syndrome (Figures 6 and 7, showing severe mucous membrane manifestation without significant skin involvement). Any organ system can be affected and produce a confusing myriad of chronic, recurring symptoms. Every finding that this patient had can be explained by M. pneumoniae as a single cause.

Figure 6. Conjunctival inflammation of atypical Stevens-Johnson syndrome. Source: James H. Brien, DO

Figure 7. Severe lip and mouth inflammation of atypical Stevens-Johnson syndrome. Source: James H. Brien, DO

The question of treatment is not as simple. While scientific data supporting the benefit of treating outpatient Mycoplasma infections are lacking, it would seem reasonable to treat this patient in light of her multiple extrapulmonary manifestations and prolonged illness. Of note, her pulmonary exam was entirely normal, and she did not appear very ill despite the presence of infiltrates on chest X-ray and the prolonged respiratory symptoms. This scenario is found in Mycoplasma pneumonias and differs from the typical physical exam you might expect with a pneumococcal pneumonia. Treatment with a macrolide such as azithromycin is the recommended choice. As acellular organisms, one would not expect any beta-lactam to work against any Mycoplasma species. However, a macrolide, which works by inhibiting protein synthesis by binding at the 50S ribosome, would have a bacteriostatic effect.

Regarding the other choices, since the trial of albuterol was not thought to be beneficial, continuing it would not seem necessary. And using high-dose amoxicillin-clavulanate would not help for the reasons noted earlier, unless there was evidence of a bacterial coinfection. Continuing to watch without treatment would be a judgement call, but that is when clinical judgement based on experience and common sense comes in.

It is likely that the rapid strep was a false-positive consistent with the lack of an apparent response of the fever to amoxicillin until day 9, and when the whole picture is in the same frame, it makes Mycoplasma the most likely cause for that symptom as well.

Acknowledgement: I want to thank Lisa Forman, MD, a pediatric attending physician at Elmhurst Hospital in New York, for contributing this interesting case. She can be reached at formanl@nychhc.org with any questions.