Volume 5, Case 20
Loren G. Yamamoto, MD, MPH
Kapiolani Medical Center For Women And Children
University of Hawaii John A. Burns School of Medicine
This is a 2-1/2 year old male who presents to an acute care clinic with a chief complaint of coughing and fever. He began coughing three days ago. His cough is now sounding worse. It sounds harsh and on further inquiry, it sounds like a barking seal. He was noted to be warm yesterday, but his temperature was not measured.
His past history is largely negative, but his immunization status is incomplete. He immigrated from Asia two weeks ago. He is known to have been immunized, at least partially, against typhoid and polio. He had a negative TB skin test at 12 months of age. He probably has not received any MMR or DPT immunizations.
Exam: T38.3 (rectal), P100, R24, BP 109/73, oxygen saturation 95% to 99% in room air. He is alert, but is noted to be drooling. He has stridor at rest with mild retractions. An occasional croupy cough is noted. He does not appear to be toxic. Head normocephalic. Eyes clear and moist. No pallor. Nose clear mucus. Oral mucosa pink and moist. Thick yellow and white exudates are noted on the tonsils, the uvula, and the posterior pharynx. The epiglottis is not visualized. Neck supple, with several 1 cm nodes. Heart regular, no murmurs or gallops. Lungs with inspiratory stridor at rest. Aeration is good. No wheezes or rales. Abdomen negative. Normal genitalia. Color, perfusion, pulses and turgor are good. Strength and movement good. Sensation intact. He is able to ambulate.
A lateral neck and chest radiographs are obtained.
View lateral neck radiograph.
View chest radiograph.
This lateral neck radiograph shows a normal epiglottis and no pre-vertebral soft tissue widening. There is significant subglottic narrowing. While this is radiographically consistent with croup, this patient clinically may have more than just croup. The oral exam in croup is most often normal. The epiglottis can often be visualized if the patient is cooperative and can open widely enough. In other instances, the epiglottis can be visualized by depressing the tongue with a tongue blade. In this patient's case, his exam reveals extensive exudates over his tonsils. Additionally, exudates are noted on the posterior pharynx and uvula.
Because of his lack of DPT immunization, diphtheria is suspected. He is hospitalized in an intensive care unit. He is treated with IV penicillin and diphtheria anti-toxin. A cardiac work-up is negative. During hospitalization, his stridor worsens and he requires intubation. During intubation, his larynx and epiglottis are noted to be edematous. Following intubation, his condition improves. He is eventually extubated and is subsequently discharged in good condition. Throat cultures for diphtheria are positive. Nasopharyngeal cultures for diphtheria are negative. Group A streptococcal cultures are negative.
Discussion
Corynebacterium diphtheriae are gram positive pleomorphic rods. However, they stain irregularly and their morphology depends on the media that they are grown on.
C. diphtheriae causes clinical disease by infection of tissues and/or through the elaboration of toxin. The clinical signs and symptoms of diphtheria depend on the site of infection, the immunization status of the patient, and whether or not toxin is being produced by C. diphtheriae.
C. diphtheriae generally infects mucosal surfaces. While the eyes and genital mucosal surfaces are occasionally involved, C. diphtheriae, most often infects nasal, tonsillar, pharyngeal, laryngeal, and tracheal mucosal surfaces.
Nasal diphtheria presents as a mild upper respiratory infection progressing to serosanguinous and mucopurulent nasal discharge with nasal excoriation. A white membrane may be visible on the nasal septum and a foul odor may be present.
Tonsillar and pharyngeal diphtheria have symptoms similar to a severe tonsillitis. A white membrane is visible covering the tissues including the uvula, palate, tonsils, and pharynx. The membrane may extend down into the larynx and trachea (visible on laryngoscopy and/or bronchoscopy). Attempts to remove this membrane, result in bleeding. Lymphadenopathy and/or generalized edema of the neck may be evident.
Partially immunized patients may have incomplete presentations such that the white membrane does not form.
Laryngeal diphtheria results from downward extension of pharyngeal diphtheria. Laryngeal involvement is characterized by croup-like symptoms such as stridor, drooling, hoarseness and a barking cough. Airway obstruction is more likely to progress to a severe degree. The trachea and bronchi may also be involved. Radiologic features of laryngeal diphtheria may be identical to viral croup (i.e., mild to moderate subglottic edema). However, the clinical features, especially the appearance of the pharynx is usually different. In severe cases of laryngeal diphtheria, a membrane may be visible on the lateral neck radiograph and the degree of subglottic edema seen radiographically is more severe. This radiographic appearance is termed, "membranous croup".
View membranous croup radiograph.
This radiograph shows subglottic narrowing. The black arrow points to a distortion within the airway resembling a membrane. To appreciate this, you must turn down the room lights and step back away from the monitor. Hopefully, you can now appreciate some distortion in the airway.
The differential of membranous croup is not limited to diphtheria. It also includes bacterial tracheitis (also called bacterial croup or bacterial laryngotracheobronchitis) and anatomic laryngeal anomalies such as laryngeal/tracheal webs. The presence of the membrane cannot be relied upon to make the diagnosis since it is only rarely visible. The diagnosis of diphtheria, bacterial tracheitis, and laryngotracheal anomalies must often be made clinically and later confirmed by CT, fluoroscopy, laryngoscopy or bronchoscopy. Patients with bacterial tracheitis will usually appear toxic. They may have high fever and a leukocytosis. Their airway symptoms are generally more severe and they may rapidly worsen. Laryngotracheal anomalies usually have a prolonged or recurrent course of airway difficulty.
Systemic complications of Diphtheria
Toxin elaborated by C. diphtheriae is cardiotoxic and neurotoxic. Not all C. diphtheria infections result in toxin production since toxin production depends upon the strain of the bacteria and often whether a phage virus is present. Early administration of antitoxin can prevent the toxin mediated complications.
Myocarditis may develop during the second week of illness. Signs and symptoms of myocarditis include congestive heart failure, tachycardia, muffled heart tones, murmurs, and dysrhythmia. Myocardial complications are generally reversible following antibiotic treatment, anti-toxin administration, and eradication of the C. diphtheriae infection.
Neurologic complications appear after varying latent intervals. Examples include paralysis of the soft palate, oculomotor paresis, dysphagia, diaphragmatic weakness, peripheral neuropathy, etc. Since these complications are largely motor and CSF protein is elevated, these findings are difficult to distinguish from Guillain-Barre syndrome.
Rare complications include vascular instability, gastritis, hepatitis, nephritis and hemolytic uremic syndrome.
The diagnosis of diphtheria should be made clinically. Waiting for cultures to confirm the diagnosis may result in a delay in anti-toxin administration and toxin-mediated complications. Material from beneath the white membrane or the membrane itself should be sent for gram stain and culture. Fluorescent antibody and other rapid immunologic methods may be able to confirm the identification of the organism right away. A "Schick" test may be used to determine diphtheria susceptibility, however, its interpretation is not simple and it cannot be read for 3 to 5 days (refer to other references for more discussion on the Schick test).
Diphtheria toxoid immunization and antitoxin
Diphtheria vaccine is a toxoid which results in immunity against the C. diphtheriae toxin. Note that while the vaccine is directed at the toxin and NOT at the bacteria, a well-immunized individual is protected from the toxin and the non-toxin mediated complications of diphtheria. Diphtheria vaccine does not fully immunize against infection since carrier states and mild infections are still possible in immunized individuals. However, vaccine does prevent severe infection.
While most children in the U.S. are fully immunized against diphtheria, many adults are not routinely immunized. While tetanus toxoid is commonly administered in emergency departments for tetanus wound prophylaxis, there is no routine for diphtheria vaccine. For this reason, most emergency departments administer diphtheria-tetanus toxoid (combined dT) instead of plain tetanus toxoid when tetanus prophylaxis is indicated. Pregnancy and known diphtheria toxoid hypersensitivity are indications for plain tetanus toxoid (without diphtheria toxoid) when tetanus prophylaxis is indicated.
The patient in this case had probably not received any DPT vaccines. Being susceptible, he developed a severe pharyngeal and laryngotracheal diphtheria infection. Since antitoxin was administered early, he sustained no toxin mediated complications.
Diphtheria anti-toxin is of horse serum origin, therefore horse serum hypersensitivity may occur. Antibiotics (penicillins and erythromycin) shorten the course of illness by limiting infection. However, antibiotics may not be effective in preventing toxin-mediated complications.
References