History
As previously discussed, six clinical forms of tularemia have been described (ie, ulceroglandular, glandular, oculoglandular, oropharyngeal, pneumonic, and typhoidal). These forms are not necessarily distinct entities and may have overlapping features. [50]
As with many other tick-borne diseases, tularemia may, early in its course, have a nonspecific presentation. Moreover, many individuals may be unaware of or may not recall having been bitten by a tick or fly. These factors illustrate the importance of routinely including queries regarding travel, work, and animal and arthropod exposure in the history when presented with a patient who potentially has tularemia.
Delayed diagnosis and late administration of effective antibiotic therapy may result in increased morbidity and a greater risk for mortality in patients with the disease. Atypical or particularly severe presentations of common illnesses may provide clues to the presence of relatively rare diseases. [51, 52, 53, 54]
Children infected with tularemia typically have a clinical presentation similar to that of adults. However, children have been reported to have fever, pharyngitis, hepatosplenomegaly, and constitutional symptoms more often than do adult patients.
The following are common findings in the various clinical forms of tularemia:
-
Abrupt onset of fever and chills - These symptoms typically last for several days, remit for a brief interval, and then recur
-
Pulse-temperature disassociation [2]
-
Headache
-
Anorexia
-
Malaise and fatigue or prostration
-
Myalgias
-
Cough
-
Vomiting
-
Pharyngitis
-
Abdominal pain
-
Secondary pneumonitis - May occur in 45-83% of patients with the typhoidal form
As many as 20% of patients with tularemia have a rash, which may begin as blotchy, macular, or maculopapular and progress to pustular. Erythema nodosum and erythema multiforme are rare.
Ulceroglandular tularemia
In this form of tularemia, F tularensis usually enters the body via a scratch or abrasion and then spreads lymphatically, typically causing painful regional lymphadenopathy and an ulcerated skin lesion.
In most cases, 2-5 days after exposure to the disease bacterium (but with a range of 1-10 days) a small, erythematous, tender, or pruritic papule occurs at the site of inoculation; the papule enlarges and becomes ulcerated 2-3 days later. Gradually, the tender necrotic base develops with a black eschar, often concomitantly with tender regional adenopathy.
Eschar on thumb and under thumbnail at the site of a rabbit bite in a patient with tularemia.
The tick-borne form usually involves inguinal or femoral adenopathy, whereas the rabbit (animal)-associated form usually involves axillary or epitrochlear adenopathy.
Systemic adenopathy also may occur. Some patients will exhibit a sporotrichoid picture of ascending, tender subcutaneous nodules. Lymphadenopathy, lymphadenitis, or both may occur, with tender, suppurative, local enlargement reflecting the site of entry. More than 20% of lymph nodes will suppurate if left untreated or treatment is delayed longer than 2 weeks. [2, 55]
The ulcer, which has raised edges and a jagged floor, is located on a finger or hand in more than 90% of patients with rabbit-associated disease. In tick-borne tularemia, the ulcer is found on a lower extremity or the perineal area in 50% of patients, on the trunk in 30% of cases, and on the head in 5-10% of patients.
Glandular tularemia
In the glandular form of tularemia, tender lymphadenopathy occurs without evidence of local cutaneous lesions. The bacterium presumably gains entry via microscopic abrasions or potentially through intact skin. It then spreads lymphatically or via the bloodstream.
Oculoglandular tularemia
In this form, F tularensis enters via the conjunctivae after the patient is either splashed with blood or rubs their eyes following contact with contaminated tissue fluids. Clinical manifestations usually are unilateral; they include the following:
-
Unilateral conjunctivitis - Painful, purulent conjunctivitis; some patients experience chemosis, periorbital edema, and small, nodular or ulcerative lesions of the palpebral conjunctivae
-
Corneal ulceration
-
Lymphadenopathy - Most commonly cervical, but preauricular and submandibular also are observed
-
Photophobia
-
Lacrimation
-
Lid edema
-
Vision loss (rare)
Oropharyngeal tularemia
This is a rare form that may occur after consumption of infected, undercooked meat or contaminated water. Manifestations of oropharyngeal tularemia include the following:
-
Stomatitis and exudative pharyngitis or tonsillitis - The patient may occasionally develop a yellow-white pseudomembrane resembling diphtheria
-
Abdominal pain (due to mesenteric lymphadenopathy), nausea, and vomiting
-
Cervical lymphadenopathy, including deep neck infection [56]
-
Diarrhea
-
Gastrointestinal bleeding - Occasionally; caused by intestinal ulcerations
Pneumonic tularemia
Primary tularemia pneumonia, an uncommon condition, occurs after inhalation of F tularensis. [57] Rarely acquired naturally, pneumonic tularemia may develop in laboratory workers.
Secondary pneumonic tularemia may result from hematogenous spread and may complicate any form of tularemia, but is most common with the ulceroglandular or typhoidal forms. [2, 58]
Patients with pneumonic tularemia usually report a dry cough, dyspnea, and pleuritic-type chest pain. Chest radiography may reveal patchy, ill-defined infiltrates in one or more lobes. Frank lobar pneumonia also may develop, and bilateral hilar adenopathy may be present. Bloody pleural effusions are characteristic and demonstrate a mononuclear cellular response. ARDS develops in some patients. [57, 59]
Typhoidal tularemia
This form of tularemia is particularly severe; it probably represents F tularensis bacteremia. Patients with this disease present with the following:
-
Fever
-
Chills
-
Myalgias
-
Malaise
-
Weight loss
Patients often have pneumonia. Diagnosis is difficult because ulcers and lymphadenopathy usually are absent.
Additional manifestations
Rare manifestations of tularemia include the following:
-
Osteomyelitis
-
Pericarditis
-
Peritonitis
-
Endocarditis
Other possible manifestations include acute renal failure, hepatomegaly, abnormal liver function, and rhabdomyolysis.
Physical Examination
Patients with tularemia have fever and possibly tender hepatosplenomegaly. As many as 20% of patients have a rash, which may begin as blotchy, macular, or maculopapular and progress to pustular. Erythema nodosum and erythema multiforme rarely occur.
Ulceroglandular tularemia
This form is characterized by an ulcer at the site of F tularensis entry through the skin. The ulcer varies with the vector. It usually begins as a tender papule that eventually ulcerates and has a sharply demarcated border with a yellowish exudate. Initially, the base of the ulcer also has a yellowish exudate, but this subsequently turns black.
Regional lymphadenopathy develops, and the lymph nodes usually are edematous and tender. They can become fluctuant and may drain spontaneously.
Oculoglandular tularemia
Ocular findings usually are unilateral. Clinical presentation includes the following:
-
Painful conjunctivitis with purulent exudate may be present
-
Nodules or ulcerations may develop on the palpebral conjunctivae
-
Submandibular, preauricular, and cervical adenopathy are common
-
Corneal ulcerations may develop
Oropharyngeal tularemia
Exudative or membranous pharyngotonsillitis with regional adenopathy may be observed.
Pneumonic tularemia
Chest examination findings may be normal in tularemic pneumonia, or rales may be present in the affected lung fields.
-
Eschar on thumb and under thumbnail at the site of a rabbit bite in a patient with tularemia.
-
Axillary bubo in a patient with tularemia.
-
Ulceroglandular type of tularemia on the face. Courtesy of Dr Hon Pak.
-
Ulceroglandular tularemia on an extremity. Courtesy of Dr Hon Pak.
-
Ulceroglandular type of tularemia on the hand. Courtesy of Dr Hon Pak.
