Mycoplasma Pneumonia

Etiology

Mycoplasma species are the smallest living organisms that can survive alone in nature. There are over 120 Mycoplasma species; only 13 have been isolated from humans, and only four are known to cause disease in humans. M pneumoniae is the pathogen most commonly associated with disease in humans. It is a short rod with no cell wall; therefore, it is not visible on the Gram stain. It can be isolated on media supplemented with serum. However, it is fastidious, and isolation is not usually performed in clinical laboratories.[4] It requires special culture media and also takes a long time for growth. Due to these reasons, it is not routinely cultured. It is excreted from the respiratory tract after many weeks of acute infection; therefore, isolation of the organism is not specific to acute infection at that particular time.

Epidemiology

M pneumoniae is now considered a common cause of community-acquired pneumonia and is transmitted from person to person via respiratory droplets during close contact. It has an incubation period that ranges between 2 to 3 weeks. Like most respiratory pathogens, infection usually occurs during the winter months but can happen year-round. Estimates show that around 1% of the population of the United States is infected annually. Incidence may be much higher since infection can be subclinical or cause milder disease that does not require hospitalization. Outbreaks of mycoplasma infection occur in military recruits, hospitals, nursing homes, and other long-term care facilities.[5][4] Only 5 to 10% of people infected with mycoplasma develop pneumonia. It causes upper and lower respiratory tract infections in all age groups.

Pathophysiology

M pneumoniae has adherence proteins that can attach to epithelial membranes, particularly the respiratory tract epithelium. Once attached, M pneumoniae produces hydrogen peroxide and superoxide, causing injury to epithelial cells and their associated cilia. Antibodies produced against M pneumoniae may act as autoantibodies since they crossreact with human brain cells and red blood cells. The pathogenesis of M pneumoniae includes the activation of inflammatory cytokines.

M pneumoniae has a gliding movement and specific tip organelles that help in burrowing between cilia in the respiratory epithelium, leading to the sloughing of the respiratory epithelial cells. The prolonged refractory cough is considered to be due to inhibition of the ciliary movement. M pneumoniae causes extrapulmonary illnesses and respiratory tract infections, including immune thrombocytopenic purpura, acute hepatitis, autoimmune hemolytic anemia, arthritis, and transverse myelitis.

History and Physical

Many M pneumoniae infections are asymptomatic. Patient symptoms are typically more significant than objective findings on physical exams. Disease onset is gradual, and patients can initially complain of headaches, malaise, and low-grade fever. A nagging cough is usually the most prominent respiratory feature. Chest soreness from coughing is common. Wheezing can also occur. Other respiratory symptoms include pharyngitis, rhinorrhea, and ear pain. Pleural effusion occurs in 15% to 20% of patients who develop pneumonia and may predict increased morbidity and mortality.  Most cases of pneumonia are mild and self-limited. However, a more fulminant course can occur. Extrapulmonary features may help suggest the diagnosis and include hemolysis, skin rash, joint pain, gastrointestinal symptoms, and heart disease. These occur in less than 5% to 10% of patients. Hemolysis occurs due to IgM antibodies producing a cold agglutinin reaction. Cardiac involvement includes conduction abnormalities on electrocardiogram, congestive heart failure, and chest pain.

Physical examination findings are often minimal. Chest auscultation can be normal even if pneumonia is present. Scattered rales and wheezes can present later in the course of the disease. Sinus tenderness and mild erythema of the posterior pharynx may also be found on physical examination. A mild erythematous maculopapular or vesicular rash may also be found. Bullous myringitis, the presence of vesicles or bulls on the tympanic membrane, can be seen in some cases.

Evaluation

There are no specific clinical or radiological findings of mycoplasma pneumonia that can differentiate it from other causes of atypical pneumonia. However, patients tend to have a more gradual onset of disease, more multisystem involvement, and a normal white blood cell count. Patients usually present in an outpatient setting, and microbial diagnosis is not usually performed for outpatients with community-acquired pneumonia since empiric treatment is usually successful. When available, PCR can be done rapidly and is the test of choice. Testing for cold agglutinins can sometimes support a clinical diagnosis when a rapid diagnosis must be made. M pneumoniae lacks a cell wall and is fastidious; therefore, Gram stain and cultures are not useful for the diagnosis of these organisms.[6][7] Mycoplasma pneumoniae is difficult to culture; a special culture media and 7 to 21 days must culture it. Serologic tests like complement fixation, enzyme-linked immunoassay, immunochromatography, and hemagglutination have acceptable sensitivity and specificity. Those serologic tests that show a four-fold greater increase or decrease in paired sera titers or a single tire of more than 1: 32 are diagnostic of Mycoplasma pneumoniae.

Hemolysis is found in most patients with pneumonia and causes a positive Coomb test and an elevated reticulocyte count. Cold agglutinin titers are elevated in more than 50% of patients with mycoplasma disease. However, this is not specific to mycoplasma infections and can be found in patients with viral pneumonia or infectious mononucleosis due to the Epstein-Barr virus or cytomegalovirus. White blood cell count is normal in 75% to 90% of cases. The most common chest x-ray findings are a reticulonodular pattern or patchy areas of consolidation; these can be unilateral or bilateral and are more prominent in the lower lobes.[8][9] Eosinophil cationic protein is elevated in patients with mycoplasma infection and asthma. It is believed that this protein damages the epithelium in the airways and induces hypersensitivity of the bronchial smooth muscle. However, more studies are required before its use as a diagnostic marker becomes universal.[10]

Treatment / Management

Gradual onset of symptoms combined with extrapulmonary involvement and a normal white blood cel count points to atypical pneumonia. Most patients with M pneumoniae pneumonia present in outpatient settings, and treatment is often with empiric antibiotics for atypical pneumonia. Note that many patients may undergo a period of symptomatic management before seeking medical attention and/or receiving antibiotic treatment.

Treatment of M pneumoniae includes macrolides, doxycycline, or fluoroquinolones. Azithromycin is the most frequently used antibiotic and is usually prescribed for 5 days (500 mg for the first dose, followed by 250 mg daily for 4 days). Patients receiving doxycycline or fluoroquinolones should be given 7 to 14 days of treatment.[11][12] Macrolide resistance continues to emerge, so if a patient is not responding to macrolides, other antibiotics can be given. Routine antibiotic prophylaxis is not required for the exposed contacts except for those prone to serious mycoplasmal infection, like patients with sickle cell disease or antibody deficiency. For prophylaxis, doxycycline or macrolides are used.

Differential Diagnosis

Diagnostic Considerations

M pneumoniae is a prevalent cause of community-acquired pneumonia in healthy individuals younger than 40. Large outbreaks are known to occur in the late summer months and early fall. The infection is also more common in populations that live in close quarters like prisoners and military personnel. Unlike other viral pneumonia, the incubation period for mycoplasma is 14 to 21 days. The key feature of the diagnosis is the absence of a wet cough. Other diagnoses that can be confused with mycoplasma pneumonia include the following:

• Aspiration pneumonitis and pneumonia
• Bacterial pneumonia
• Chlamydia pneumoniae
• Coxiella burnetii infection
• Empyema
• Legionella pneumophila
• Lung abscess
• Pediatric pneumonia
• Q fever
• Viral pneumonia

Prognosis

In most patients who receive prompt treatment, the prognosis is excellent, and patients are expected to make a full recovery. The symptoms and signs of pneumonia usually resolve within a few days without any complications. However, in young children, the infection can be associated with severe pneumonia, and in patients with sickle cell anemia, it may be associated with acute chest syndrome. The immunity after an M pneumoniae infection is short-lived.

Complications

Even though mycoplasma pneumonia in most people is a benign infection, it can lead to several complications, especially in children and the elderly. The list of complications includes the following:

• ARDS
• Bronchiolitis obliterans
• Lobar consolidation
• Lung abscess
• Necrotizing pneumonitis
• Pleural effusion (15% to 20%), empyema (rare)
• Respiratory failure

Extrapulmonary Complications

Mycoplasma can also be associated with severe extrapulmonary complications. These complications may be due to the organism itself; they may be triggered by the resulting immunological response to the bacteria. The list of extrapulmonary complications includes:

• Myocardium problems: Conduction abnormalities, heart blocks, or rhythm disturbances. Both pericarditis and congestive heart failure have been reported in young people.
• The central nervous system: Rare but can include encephalitis, transverse myelitis, aseptic meningitis, and cerebellar ataxia. These central nervous system complications are more common in children.
• Hematologic problems: Hemolytic anemia due to cross-reactivity of antibodies to M Pneumoniae antigens to red blood cells. The hemolysis is mild.
• Dermatology: M Pneumoniae infection may be associated with urticaria, erythema nodosum, or Steven Johnson syndrome. The skin lesions are seen in about one-third of patients.
• Musculoskeletal problems include myalgia and arthralgia. Septic arthritis is very rare. Rare cases of rhabdomyolysis have been reported.
• Gastrointestinal dysfunctions include pancreatitis or hepatitis and are linked to the circulating immunoglobulin M antibodies.
• Ophthalmologic problems include conjunctivitis, optic papillitis, anterior uveitis, and cranial neuropathies.
• Kidney problems are rare and may result in glomerulonephritis due to immune complex precipitation in the glomeruli.