Atypical pneumonia.

The term "atypical pneumonia" is applied to non-lobar patchy or interstitial infiltrates on chest x-ray where the causative organism is not
identified on gram stain or culture of sputum.

Often they are not toxic, do not have shivers and do not seek medical attention. "Walking Pneumonia"

Differential diagnosis of atypical pneumonia

The pathogens causing atypical pneumonia include 

Mycoplasma pneumoniae
Chlamydia psittaci
Chlamydia pneumoniae 
Coxiella burnetii
Francisella tularensis
Legionella pneumophila
viruses including influenza A and B, parainfluenza, adenovirus and respiratory syncytial virus.

Mycoplasma pneumoniae

Many of the agents listed above could be responsible for this patient’s pneumonia. Features pointing to Mycoplasma include her 

age (commonly between 5-15 years)
scratchy throat (tracheitis) and 
bullae in tympanic membrane (bullous myringitis)
Mycoplasma pneumoniae is one of the smallest free-living microorganisms. 
It lacks a cell wall, and hence stains poorly on usual bacterial stains. 
It grows aerobically and produces tiny colonies on special agar that have an "inverted fried egg" appearance. 
Hemadsorption of red blood cells on the surface of agar plates is a feature of Mycoplasma pneumoniae.

Pathogenesis 

Mycoplasma pneumoniae attaches to the cilia and microvilli of cells lining the bronchial epithelium. 
Attachment is mediated by a surface adhesion, the P1 protein, which binds to oligosaccharides containing sialic acid in the bronchial
epithelial cells.
Ciliary action is stopped followed by loss of cilia and desquamation of epithelial cells into the lumen.
Oligosaccharide receptors (1-F1) are not found in non-ciliated cells or mucus; hence mycoplasma pneumoniae does not for some of the
damage produced. 
Sloughing of cells into the lumen is responsible or the cough that defines the clinical presentation.
The inflammation conspicuously involves the interstitial space or alveolar wall with mono-nuclear cells. 
The inflammatory process involves the trachea, bronchioles, and peribronchial tissues.
The lumen is filled with purulent exudate containing polymorphonuclear leukocytes. 
Bronchial and bronchiolar walls are infiltrated with monocytes and plasma cells. 
There is widening of peribronchial septae and hyperplasia of type II pneumocytes. 
Organisms are shed in respiratory secretions for 2-8 days after onset of symptoms, and shedding can continue for as long as 14 weeks
after infection.

Other pathogens producing atypical pneumonia produce similar pathologic changes.

Immunity to Mycoplasma pneumonias 

Local and systemic specific immune responses occur. 
IgA antibody wanes 2-4 weeks after onset of infection. 
Complement-fixing serum antibodies peak at 2-4 weeks and disappear in 6 to 12 months. 
Nonspecific immune response to the outer membrane also develop e.g., cold hemagglutinins (IgM antibodies that react with I antigen of
human RBC’s).
Immune mediated mechanisms play a role in M. pneumoniae infection.
Reinfections is associated with quicker development of inflammatory changes in experimental animals. 
High levels of IgG immune complex are found in the acute phase of illness and correlate with degree of pulmonary involvement. 
M. pneumonia can stimulate B and T lymphocyte mitogenic activity.
Immunity to M. pneumoniae is not complete, and re-infection is common. 
Clinical disease is more severe in older children, suggesting that many clinical manifestations are due to cellular immune responses.

Diagnosis 

Definitive diagnosis is made by isolation of the organism or demonstration of an antibody response. 

Isolation of M. pneumoniae on SP-4 medium takes 2-3 weeks and is too expensive and time consuming. 
Detection of M. pneumoniae antigens or nucleotide sequences in clinical specimens by enzyme immunoassay or per DNA hybridization
is under development.
The compliment fixation test detects specific antibody and is commonly used. Antibody rises 7-9 days after infection, peaks at 3-4
weeks and lasts for 6-12 months. A four-fold rise or decline in titer is necessary for diagnosis.
Two thirds of patients with symptomatic M. pneumoniae pneumonia will develop high titers of cold agglutinins. These are not specific
and are seen in other viral infections (adenovirus, EBV). This test is simple and can be performed at the bedside.
New assays include indirect immunofluorescence and ELISA and detect IgM as well as IgG. An ELISA using adhesion PI protein is
being developed.

Antigen detection and culture of sputum for specific pathogens helps establish the diagnosis in other cases of atypical pneumonia. Serology is
useful but acute convalescent titers are needed. 

Therapeutic strategy

Erythromycin and tetracycline are equally effective in treatment of M. pneumoniae infection. 
They shorten the course of infection but do not eliminate the carrier state.
Clarithromycin and azithromycin are also effective but much more expensive. 
Quinolones such as ciprofloxacin have in vitro efficacy against mycoplasma, but are expensive and contra-indicated in children.
Since mycoplasmas lack a cell wall, beta-lactam antibiotics are ineffective for treatment. 
Therapy is generally continued for 2-3 weeks, as relapses can occur in up to 10% cases.

Drug interaction 

Elevations of terfenadine and astemizole serum concentrations have been associated with concomitant use of erythromycin (and
clarithromycin). 
Erythromycin interferes with the hepatic metabolism of these drugs through the cytochrome P-450 system.
Erythromycin metabolites form inactive complexes with cytochrome P-450 enzymes.
Elevated levels of these antihistamines have led to serious ventricular arrhythmias.