Saturday, August 16, 2008

Essentials of Diagnosis

• Acute rhinorrhea, sneezing, sore throat, burning eyes, cough, malaise, headache, anosmia.

• Usually there is no or low-grade fever in adults, higher fever in infants and children.

• Examination may demonstrate serous nasal discharge, conjunctival and/or pharyngeal congestion, and rhonchi.

• Diagnosis is made clinically, can be confirmed by serology or nasopharyngeal viral cultures in selected cases.

• Imaging is helpful if bacterial superinfective complications suspected (ie, sinusitis).

General Considerations

A "cold" is a self-limited viral infection of the upper respiratory tract presenting with a coryzal syndrome. It is the most common cause for physician visits and absenteeism in school and industry. Infection rates increase sharply during the fall through spring months with peak activity being in the winter. During these months, adults and children have an average of 2-4 and 6-8 colds per year, respectively.

Rhinoviruses are the most common cause of colds, accounting for one third of all colds (Box 9-1). Parainfluenza 1-4 viruses, coronaviruses, influenza types A and B, adenovirus, respiratory syncytial virus (RSV), and their numerous serotypes also are predominant viruses that induce colds. These viruses share a common property of frequent antigenic variation and evasion from the host humoral defense mechanisms, thereby permitting their persistent survival in the community. Other viruses can present with coldlike symptoms during the prodromal period, but their primary syndrome may be localized to another organ system(s).

Transmission is via aerosol, droplet, or direct contact with infected saliva or fomite from an infected person. The rate of infection increases in families with school-age children and in overcrowded and poorly ventilated living spaces. Cigarette smokers are more likely to develop severe disease as compared with nonsmokers.

Once the virus enters the cell, replication and subsequent shedding of the virus occur. The cytopathic effect of the virus on the epithelium varies depending on the virus, being relatively mild in rhinovirus and more marked with influenza virus infection. There is an acute inflammatory response, increased vascular permeability, tissue edema, mucus production, and serum transudation, resulting in the typical cold symptoms of rhinorrhea, nasal obstruction, and cough. After the initial neutrophilic response, there is immunoglobulin M (IgM), IgG antibody, and cytokine production such as interferon, tumor necrosis factor-a, interleukin 8, interleukin 6, and others. Cytolytic T-cell response is more marked and significant in the immune response against influenza viruses than rhinoviruses. Antibody neutralization is the predominant immune mechanism for the latter. Production of antibodies coincides with the cessation of viral replication and waning of the inflammatory response and symptoms. This period may vary depending on the infecting virus. Viral shedding may occur for a few days to weeks.

Clinical Findings

A. Signs and Symptoms. Onset of symptoms is between 24 and 72 h after the infectious contact. Symptoms include malaise, rapid progression to serous nasal discharge and obstruction, sneezing, throat irritation, and cough. There may be nasal intonation of voice with nasal obstruction or hoarseness with laryngeal involvement, or both. Patients may complain of burning of the eyes. Fever usually is low-grade or absent in adults but can be much higher in infants and children. Loss of smell and taste occurs as a result of nasal mucosal edema and obstruction. Overall, the symptoms can last for 1-2 wk.

Associated clinical findings can suggest a specific viral diagnosis; for example, the presence of conjunctivitis suggests an adenoviral upper respiratory infection; myalgias and lower respiratory symptoms such as pneumonia or bronchiolitis may suggest an influenza or RSV infection. Mild disease suggests rhinovirus or coronaviruses. Symptoms of complications such as sinusitis, otitis media, or lower respiratory tract infection may be present. Patients with previous hyperactive airways or asthma can develop exacerbations.

The patient usually appears tired, with thin serous nasal discharge, mild tenderness over the sinuses, and mildly suffused conjunctiva without frank conjunctivitis, and the skin over the nostrils may be red from recurrent blowing of the nose. Pharyngeal erythema without any exudates or lymphadenopathy may be present. Lung examination may reveal evidence of bronchitis or bronchiolitis.

B. Laboratory Findings. Most colds are diagnosed clinically and do not need any further investigations. Mild leukocytosis or leukopenia with or without thrombocytopenia may be noted. Serologies and viral cultures can make a specific viral diagnosis; however, this should be attempted only in selected cases. Rapid RSV or influenza type A antigen detection enzyme immunoassays are very sensitive for nasopharyngeal specimens. Influenza, parainfluenza, adenovirus, cytomegalovirus (CMV), and other viruses can be isolated on cell line cultures. Serologies are available for influenza, parainfluenza, RSV, adenovirus, CMV, and Epstein-Barr virus (EBV). The serologic test is considered positive for active infection if an IgM is present during acute infection or a fourfold rise in IgG in paired sera is detected. Patients with equivocal histories for colds versus group A streptococcal (GAS) pharyngitis should have a rapid antigen detection test (RADT) and bacterial cultures for group A streptococcus.

C. Imaging. No imaging is recommended for uncomplicated colds. However if bacterial or viral complications such as sinusitis or pneumonia are suspected, then appropriate radiographs should be done. A computed-tomography (CT) scan study in patients with a common cold shows frequent involvement of the sinuses.

Differential Diagnosis

A common dilemma is clinically differentiating the common cold from GAS pharyngitis and prodromal symptoms related to systemic syndromes caused by other viruses such as measles, chickenpox, EBV, or CMV. The presence of high fever, chills, severe pharyngeal congestion with exudate, and tender lymphadenopathy is more likely to suggest GAS pharyngitis. An RADT and bacterial culture may be able to confirm this. An exposure history to chickenpox or other viral disease may be a helpful clue to the correct diagnosis. A diagnosis of allergies is evident with rapid resolution and no recurrences in the absence of exposure.


A complication of the common cold is viral or bacterial sinusitis. A common cold CT scan study by Gwaltney et al (1994) showed that sinus involvement occurs in > 60% of patients with a cold, with 79% of these resolving spontaneously in 2 wk without antibiotics. However, bacterial superinfections of the sinuses, middle ear, or both are potential complications. Viral pneumonia or worsening of bronchospastic airway disease is seen, particularly in children or immunocompromised hosts.


The old idiom of "prevention is better than cure" is certainly true for the treatment of the common cold. Multiple different viruses, their many serotypes, and rapid mutations pose a considerable challenge in the development of one vaccine or drug for cold prevention or treatment. Symptomatic support is the only therapy because no effective antiviral therapy is available.

Treatment is directed to rhinorrhea, nasal obstruction, sore throat, and cough. Sneezing, rhinorrhea, and nasal blockage improve markedly with topical or systemic decongestants that decrease edema by vasoconstriction. Topical decongestants such as phenylephrine (0.5% or 0.25%) or ephedrine (1%) nasal spray or drops should be used for a short period. Rebound congestion particularly with use of decongestant sprays beyond 3-4 d can occur. Systemic decongestants include pseudoephedrine hydrochloride, ephedrine, phenylephrine hydrochloride, propylhexedrine hydrochloride, phenylpropanolamine hydrochloride, xylometazoline hydrochloride, oxymetazoline hydrochloride, naphazoline hydrochloride, and tramazoline hydrochloride. Decongestant side effects include tachycardia, elevated blood pressure, fatigue, and dizziness. These should be used cautiously in patients with hypertension and dysrhythmias.

Nasal anticholinergics are effective in inhibiting the parasympathetic activation that contributes to rhinorrhea. Ipratropium bromide nasal spray reduces rhinorrhea and sneezing in the first 3 d of the cold.

Antitussives such as codeine, dextromethorphan, hydrocodone bitartrate, and diphenhydramine hydrochloride suppress the cough reflex in the medullary cough center. Analgesics can be used to improve the myalgias, headache, and sore throat that accompany the common cold. Antihistaminics have no role in the treatment of common cold. The majority of the above mentioned drugs are available over the counter in combination with antihistaminics, analgesics, or antitussives.

Nonspecific measures such as warm saline gargles are encouraged. The role of vitamin C in the common cold is controversial. Studies with dosages of 1-30 g/d demonstrate a 5-29% decrease in severity and duration of symptoms. However, these studies had significant variations for conclusive evidence. Similarly, despite numerous studies of the role of zinc in the management of cold, zinc's role is still controversial and needs further confirmation. Antibiotics have no role in colds unless patients have evidence of bacterial superinfection of the upper respiratory tract.

Prevention & Control

Handwashing is key in the prevention of common colds. Minimizing aerosol or droplet transmission with tissues or covering the mouth should be taught to children and adults. Experimental therapies with interferon-a2 and leukocyte A interferon show some role in the prevention of cold. Producing vaccines for these viruses is difficult because of their numerous serotypes. However, active vaccination can be used for influenza types A and B along with the prophylactic use of amantadine or rimantadine.


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