Mycoplasma pneumoniae infects only humans and isa common bacterial cause of respiratory infections in pediatric patients. M pneumoniae spreads via airborne droplets after close contact with an infected person. Infections are more common during summer and early fall.¹ Although M pneumoniae infection often presents as a mild, limited respiratory illness, more severe diseases, such as severe pneumonia, polyarthritis, glomerulonephritis, hemolytic anemia, hemophagocytic syndrome, erythema multiforme, Stevens-Johnson syndrome, and encephalitis have been reported.²

M pneumoniae infection is not a reportable disease, and testing is often not performed in the outpatient setting, limiting estimates of clinical prevalence and delaying recognition of community epidemics.³ Through evaluation of International Statistical Classification of Diseases, Tenth Revision, diagnostic codes from emergency departments (ED) and urgent care centers, an increase in the incidence of cases has been identified in the US and worldwide since the fall of 2023.⁴ Locally, our institution has observed an increase in the number of M pneumoniae detected in respiratory panel multiplex polymerase chain reaction (PCR) since then. Amid this local outbreak, we have encountered, in a short time, pediatric patients with unusual clinical presentations due to M pneumoniae.

Below, we describe 3 pediatric cases of M pneumoniae infection with more severe and atypical presentations. We aim to raise awareness of and suspicion of M pneumoniae in children with similar symptomatology.

Cases

Patient 1

A fully vaccinated boy aged 11 years with autism spectrum disorder, attention-deficit/hyperactivity disorder, allergies, and a remote history of asthma presented to the pediatric ED with 1 week of intermittent fever, barky cough, hoarseness, stridor, and several days of increased work of breathing. A 3-day course of steroids provided only minimal improvement. On the day of presentation, he had acute shortness of breath unresponsive to inhaled albuterol.

In the ED, he was afebrile, tachycardic, and tachypneic, with an oxygen saturation of 90% in room air. His examination was remarkable for subcostal and intercostal retractions, head bobbing, and diminished air movement with faint expiratory wheezes. He was treated for severe asthma exacerbation and placed on bilevel-positive airway pressure (BiPAP). The chest x-ray results were normal. Neck x-ray noted enlarged adenoids and tonsils. No tonsillar hypertrophy was present on physical examination. The complete blood count and comprehensive metabolic panel were unremarkable.

He was admitted to the pediatric intensive care unit (PICU). On BiPAP, his lungs had good bilateral air entry, but disproportionate tachypnea with tracheal tugging was present. Racemic epinephrine improved the tracheal tugging. Initiation of heliox normalized his respiratory effort.

A CT scan of the soft tissue of the neck identified diffuse circumferential swelling of the false and true cords with airway narrowing and mild subglottic edema (Figure 1). Broad-spectrum antibiotics were started. The subsequent day, the patient was weaned off respiratory support with no significant work of breathing and only a slight barking quality to his cough. His multiplex respiratory PCR returned positive for M pneumoniae. He was discharged home to complete 3 days of azithromycin and 5 days of prednisolone. On follow-up 2 days after discharge, he was at his baseline state of health and activity with a residual, intermittent, nonbarky cough.

Patient 2

A previously healthy and fully vaccinated adolescent boy aged 13 years presented in the outpatient setting for evaluation of a vesicular rash. He had returned from a weeklong summer camp 3 days before the visit. After arriving home, he noted a vesicular rash, mostly on his upper extremities, that became bullous a few days later (Figure 2). Lesions had an erythematous base and appeared to have central umbilication. More lesions developed over the next 1 to 2 days. He had no fever, malaise, oral ulcers, or conjunctivitis. He and his siblings reported having a cough for the past 3 weeks, attributed to allergies.

Routine bacterial culture, herpes simplex virus, and varicella zoster virus PCR testing were all negative. The child’s throat M pneumoniae PCR was detected. The rash resolved after azithromycin treatment was initiated.

Patient 3

A fully vaccinated boy aged 9 years with a history of intermittent albuterol use presented to the ED with 1 week of fever and fatigue and 2 days of cough, posttussive emesis, and headache. He completed 3 doses of high-dose amoxicillin for treatment of community-acquired pneumonia. His fever persisted, and his breathing became more labored.

In the ED, he was febrile, tachycardic, and hypoxemic. His examination was notable for decreased breath sounds, worse over the left lower lobe, without wheezing or increased work of breathing. Lab workup was remarkable only for a C-reactive protein of 4 mg/dL. The chest x-ray showed focal left lower lobe and left lingular lobe airspace disease (Figure 3).

He was started on ampicillin-sulbactam intravenously and oxygen by nasal cannula. Over the next 24 hours, respiratory support was escalated to high-flow nasal cannula for increasing work of breathing and worsening hypoxemia. The chest x-ray was unchanged, and the chest ultrasound demonstrated a focal left lower lobe consolidation and trace left pleural effusion. Due to increasing oxygen needs and work of breathing, he was transferred to the PICU.

His physical examination on arrival at the PICU remained mostly focal to the left lower lobe but some rhonchi were noted bilaterally. Azithromycin was initiated, given the known high community prevalence. Multiplex respiratory PCR results were positive for M pneumoniae. On day 3 of azithromycin treatment, he had an exacerbation of his underlying reactive airways requiring albuterol and steroids; however, the subsequent day, he was weaned off respiratory support.

Discussion

M pneumoniae is a respiratory pathogen causing mild disease in most pediatric patients. Serious and atypical clinical presentations are possible. In this case series, we describe 3 pediatric patients with unusual presentations of M pneumoniae infection seen within a 6-week period. These cases presented during increased numbers of positive diagnostic respiratory multiplex PCR testing. Following the 2020 COVID-19 pandemic, there has been a shift in the incidence and timing of respiratory infections.^5,6

As with other infections, the increased incidence of M pneumonia infections appears related to infection control measures used during the pandemic and changes in herd immunity.⁷ Before the pandemic, the incidence of M pneumoniae worldwide was 8.6%, decreasing to 1.7% during the pandemic and followed by a resurgence in fall 2023.^8-10

It is possible, as with other respiratory viruses, that the increased number of cases could be related in part to increased use of multiplex respiratory PCR.¹¹ Regardless, the cases reported here had no other positive etiology, and clinical presentation resolved with macrolide treatment.

Figure 4 shows increased positive tests for M pneumoniae by multiplex respiratory PCR in our community. Among these cases, we saw an increase in atypical and more severe diseases. Our cases illustrate this trend.

M pneumoniae is not a common cause of laryngitis. There are case reports in the literature of pseudomembranous necrotizing laryngotracheobronchitis due to M pneumoniae.

These patients may have a similar presentation of cough, shortness of breath, and hoarseness but with high fevers. In reported cases, M pneumoniae is identified on PCR examination from a bronchial aspirate.¹² Given the degree of swelling and airway narrowing in patient 1 described above, a laryngoscopy was deemed unsafe, so direct infectious studies from the larynx were not obtained.

Rashes have been described in cases of M pneumoniae infection. More recently, in 2015, M pneumoniae–induced rash and mucositis (MIRM) was described as a clinical entity.¹³ Patient 2 had a bullous rash compatible with the vesiculobullous rash described in MIRM. However, he lacked mucosal involvement. Bullous rash secondary to M pneumoniae has been rarely reported,¹⁴ but lack of mucosal involvement can lead to underdiagnosis. Severe cases of rash and mucositis require admission, and treatment modalities usually include steroids and intravenous immunoglobulin. Our patient was clinically stable, appeared well, and did not require hospital admission or treatment with immune modulators. He was treated only with an oral macrolide.

M pneumoniae pneumonia (MPP) is commonly associated with atypical pneumonia, with diffuse, peribronchial, and perivascular interstitial infiltrates on chest x-ray. One-third of patients with MPP present with airspace consolidation. Other patterns include reticulonodular opacities or masslike opacities.¹⁵ Although MPP is often a mild and self-limited disease, approximately 12% of children with it progress to more severe lung disease, including pleural effusions, pulmonary embolism, and/or necrotizing pneumonia, as well as serious extrapulmonary complications.¹⁶ Macrolides are the first-line treatment for this pathogen and are appropriate for treating children with more severe diseases. Although macrolide-resistant M pneumoniae and refractory MPP (persistent symptoms despite an appropriate antibiotic treatment course) have been reported, recent publications estimate resistance in the US is less than 10%.^17-19

Conclusion

This pediatric case series describes 3 atypical clinical presentations of M pneumoniae and highlights the importance of maintaining a high index of suspicion for M pneumoniae, especially in the context of increased community incidence. In many cases, identification and appropriate treatment can decrease progression to more severe disease. Continued vigilance is necessary given the changing patterns of M pneumoniae and other respiratory pathogens in the aftermath of the COVID-19 pandemic.

Click here for more from the January/February, 2025 issue of Contemporary Pediatrics.

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