Part 4 • Infectious Uveitic Conditions

Chapter 10 Spirochetal Diseases

Box 10-4  Relapsing fever – key features

•Caused by spirochetes of the genus Borrelia

•Two epidemiologic types: epidemic (louse-borne) and endemic (tick-borne)

•Characterized by recurrent bouts of fever separated by relatively asymptomatic periods

•Eye pain, blurred vision, and photophobia are often seen with disease onset

•Diagnosis is usually based on finding Borrelia on thick smear of blood during a febrile episode

•Mortality reported in 2–5% of treated patients and up to 40% of untreated patients

Transmission to humans occurs when infected saliva from the tick contaminates the site of the bite. In the United States, tick-borne relapsing fever occurs mostly in western states, usually between May and September.117

Clinical Manifestations

After inoculation, the spirochetes multiply in the blood and invade most tissues of the body. Onset of the disease occurs 3–12 days after infection and is marked by fever (temperature up to 39–40°C), chills, severe headache,113 and commonly eye pain, blurred vision, and photophobia. Other symptoms include myalgias and joint pain, meningismus, anorexia, abdominal pain, nonproductive cough, and neurologic symptoms, including facial paralysis and altered mental status. Hepatosplenomegaly, jaundice, myocarditis, and heart failure sometimes occur late in the disease. The course of louse-borne relapsing fever tends to be more severe than that of tick-borne relapsing fever. Bleeding is common in both forms of the disease and often manifests as purpura, petechiae, or epistaxis.118 Subconjunctival and retinal hemorrhages have been described. In more severe cases of relapsing fever, gastrointestinal or cerebral hemorrhage and disseminated intravascular coagulation may result in death.

The initial attack of relapsing fever lasts 3–6 days and is followed by an afebrile period of 6–9 days. Defervescence may be accompanied by hypotension. Relapses tend to become shorter and less severe as the disease progresses. Mortality in relapsing fever ranges between 2 and 5% in treated cases and as high as 40% in untreated cases.113

Eye pain and photophobia are common, and conjunctivitis and iridocyclitis have both been reported in approximately 15% of cases of relapsing fever, usually after several relapses.119 Cases of more severe uveitis with vitritis have been reported, but they apparently respond well to therapy.120 Neuroophthalmic manifestations of relapsing fever are mostly limited to ptosis caused by paralysis of the facial nerve, but pupillary dilatation and optic neuritis have also been documented. Retinal venous occlusion with retinal hemorrhage and exudate has been documented in one case.112

Ocular Manifestations

The ocular manifestations of relapsing fever are listed in

Table 10-8.

Diagnosis

Definitive diagnosis of relapsing fever is based on the presence of Borrelia on a thick smear of peripheral blood obtained

Table 10-8  Ocular manifestations of relapsing fever

Conjunctivitis

Subconjunctival and retinal hemorrhages

Iridocyclitis (usually after several relapses of the disease)

Vitritis

Ptosis (secondary to facial nerve paralysis)

Mydriasis

Optic neuritis

Retinal venous occlusion

during a febrile episode. Borrelia species are best seen with Giemsa’s or Wright’s stain.113 Repeated smears or use of an acridine orange fluorescent stain increases the sensitivity of the smears.113,121 If direct methods of diagnosis fail, blood from the patient may be injected into mice or rats, and the blood from these animals may then be examined for spirochetes.

Immunofluorescence assays and ELISAs are being developed, but serologic findings are not yet useful in diagnosing relapsing fever.115 The description of a specific antigen may facilitate the serologic detection of Borrelia responsible for relapsing fever, in contrast to the B. burgdorferi of Lyme disease.122 Nonspecific laboratory abnormalities include anemia, elevated erythrocyte sedimentation rate, platelet count <150 000/mm3, and prolonged bleeding time. Serologic results for syphilis may be positive in as many as 10% of patients tested. In patients with CNS involvement, analysis of the CSF usually reveals a pleocytosis with an elevated protein concentration but a normal glucose level.113

Prognosis

Ninety-five percent of patients with relapsing fever recover with therapy, but if untreated, louse-borne relapsing fever is often fatal. Rare complications include respiratory disease, nephritis, endocarditis, neurologic disease, and bleeding diatheses. Uveitis may lead to permanent visual disability.

Treatment

The treatment of choice for tick-borne relapsing fever in adults is tetracycline, 500 mg orally, every 6 hours for 7–10 days. Penicillin, erythromycin, and chloramphenicol are also effective. In louse-borne relapsing fever the treatment of choice in adults is one 500 mg dose of erythromycin, given orally or intravenously. Ceftriaxone is effective against Borrelia species and may be used intravenously to treat relapsing fever. Vancomycin may or may not be of value because of the possible persistence of organisms in the CNS.123 Therapy should be given during the early part of a febrile episode to diminish the possibility of a Jarisch– Herxheimer reaction,124 which is caused by the release of a nonendotoxin pyrogen as Borrelia species are killed, and is characterized by rigors, fever, and elevated blood pressure, followed by hypotension and possible shock.

Leptospirosis

Etiology and Epidemiology

Leptospirosis is a zoonosis caused by spirochetes of the genus Leptospira whose natural reservoir is wild animals, mostly rodents. Weil125 first recognized a severe form of leptospirosis as a distinct clinical entity in 1886, and the