| Chapter 58 Rickettsial Organisms in Ocular Disease WOODFORD S. VAN METER Table Of Contents |
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EPIDEMIOLOGY CLINICAL DIAGNOSIS RICKETTSIAL DISEASES LABORATORY DIAGNOSIS TREATMENT REFERENCES |
| Rickettsial disease historically has not been considered a major ocular pathogen, although the incidence and severity of the ophthalmic manifestations of rickettsial disease are becoming increasingly understood. The most common rickettsial diseases seen in general medicine are Rocky Mountain spotted fever (RMSF) and typhus, but the ophthalmologist is most likely to be confronted with cat scratch disease. The inflammatory manifestations of rickettsial disease are nonspecific and are generally related to inflammation in the eye caused by proliferation of the organism. Because of the nonspecific nature of the ocular manifestations of the disease, ophthalmologists should be aware of the possibility of rickettsial disease when localized and systemic symptoms of inflammation and vasculitis present in a patient at risk. |
| EPIDEMIOLOGY | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Rickettsiae are small pleomorphic gram-negative bacilli that are obligate
intracellular parasites. They can in general survive only briefly outside
the host; the exception, Coxiella burnetii, which causes Q fever, is a hearty organism that resists desiccation, heat, and
sunlight and is transmitted mainly by airborne spread.1 Rickettsial organisms have been broadly divided into spotted fever and
typhus groups based on antigenic similarities and intracellular growth
characteristics.1 An overview of common rickettsial diseases and organisms is given in Table 1.
TABLE 58-1. Characteristics of Selected Rickettsioses
RMSF, Rocky Mountain spotted fever. (Adapted from Saah AJ: Rickettsiosis. in Mandell GL, Douglas RG, Bennett JE et al [eds]: Principles and Practice of Infectious Diseases: Antimicrobial Therapy 1995/1996, p 1720. New York: Churchill Livingstone, 1995.)
Rickettsial organisms are maintained in nature through a cycle involving reservoirs in mammals and vectors in insects. Humans are incidental hosts, and in general humans are not useful in propagating the organism in nature.1 Rampant outbreaks of potentially fatal disease, such as typhus or trench fever in humans, have occurred when people are crowded together in conditions of poor hygiene. Most rickettsial disease in the United States today occurs when humans have incidental contact with insect vectors in the organism life cycle. Rickettsial organisms exist in a classical commensal fashion with their insect vectors. One exception is Rickettsia prowazekii, which causes murine typhus; this organism causes the death of its vector, the human body louse, in 1 to 3 weeks. The mammalian reservoirs of Rickettsiae are many and varied but are generally composed of small animals and livestock. Rickettsial diseases endemic in the United States are RMSF (tick), Q fever (tick), and murine typhus (flea).2 Sporadically occurring in the United States are rickettsialpox (mite), epidemic typhus (body louse), and Brill-Zinsser disease (recrudescent louseborne typhus) in immigrants who lived in Europe during World War II (see Table 1). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CLINICAL DIAGNOSIS |
| The triad of fever, headaches, and rash in the appropriate season (usually
spring and summer) should alert the physician to consider rickettsial
etiology. A careful clinical history with attention to possible vector
exposure (e.g., camping, hiking, tick or flea exposure) can identify patients who may
be at risk. The pathogenesis of rickettsial disease is vasculitis that
manifests as a cutaneous rash caused by the proliferation of organisms
on the endothelial lining of small arteries, veins, and capillaries; Q
fever, however, produces no rash.1 Organisms can be found in the cytoplasm in histopathologic specimens in
most cases, but organisms can be found in the nuclei of cells in RMSF. Intracellular
organisms transmitted by tick bites can also be identified
by immunofluorescence, which aids in early diagnosis using skin
biopsy specimens during the skin rash stage. Rickettsial species are difficult to cultivate in vitro and exhibit strong serologic cross-reactivity.3 For this reason, cat scratch disease has only recently been attributed to a specific rickettsial organism, Rochalimaea (or Bartonella) henselae. Molecular biology-based identification has increased the number of recognized rickettsioses from 8 in 1986 to 14 in 1996. Specific rickettsial diseases are described below. |
| RICKETTSIAL DISEASES |
CAT-SCRATCH DISEASE R. henselae is the etiologic agent of both bacillary angiomatosis and cat-scratch disease. Cat-scratch disease (benign reticuloendotheliosis) is characterized by regional lymphadenitis that may be suppurative, secondary to skin lesions attributed to a cat scratch. A scratch or close contact with a cat is followed in 3 to 4 days by unilateral regional lymphadenopathy, which is usually benign4,5 but may progress to more severe systemic manifestations.6 The most common ophthalmic manifestation of cat-scratch disease is Parinaud's oculoglandular syndrome, or granulomatous conjunctivitis with preauricular adenopathy.7,8 Decreased vision in patients with cat-scratch disease can be caused by neuroretinitis or Leber's stellate neuroretinitis (optic nerve head swelling with a macular star of exudate).9 Peripapillary angiomatosis can be seen on retina examination.10 Bacillary angiomatosis presents as small nodules in the conjunctiva11 or on the skin.12 The nodules contain proliferating endothelial cells and bacteria. R. henselae and Rochalimaea quintana are closely related serologically. R. quintana is the agent responsible for the epidemic outbreak of trench fever among the Allied forces in France in World War I.13 Cat-Scratch Disease-Bacillary Angiomatosis Spectrum Cat-scratch disease was first reported as a distinct ophthalmic entity in 1950.14 Wear and associates15 identified bacilli in the lymph node of a patient with cat-scratch disease in 1983. This organism was successfully cultured in 1988 in 52% of patients with clinical evidence of cat-scratch disease16 and was classified in 1991 as Afipia felis.17 Stoler and associates18 in 1983 described a triad of vascular proliferation, inflammation, and Warthin-Starry-staining bacteria in a patient with AIDS. These lesions of vascular proliferation were later called bacillary angiomatosis.19,20 In 1990, an organism from the spleen of a patient with bacillary angiomatosis was identified as R. henselae.21,22 Similarity between the organisms found in cat-scratch disease and bacillary angiomatosis was established in 1988.23 Although initially it was thought that cat-scratch disease and bacillary angiomatosis were both caused by A. felis, R. henselae is now thought to be the causative agent of both diseases.24–29 Rochalimaea is also the etiologic agent for the ophthalmic manifestations of cat-scratch disease. Serum titers for R. henselae and R. quintana were greater than 1:256 in patients with intraocular inflammation, macular exudates, retinal lesions, optic nerve head swelling, and exposure to cats.29 A DNA sequence of R. henselae has been identified by polymerase chain reaction in a conjunctival swab of an AIDS patient with Parinaud's oculoglandular syndrome.30 The Rochalimaea genus is now also called Bartonella. Questions relating to R. henselae and cat-scratch disease remain.31 It is unknown how cats become infected initially and how R. henselae is transmitted from cats to humans. It is unknown why some humans develop cat-scratch disease and others develop angiomatosis. Finally, it is unknown why bacillary angiomatosis is more responsive to antibiotics than cat-scratch disease. ROCKY MOUNTAIN SPOTTED FEVER Rocky Mountain spotted fever, transmitted by tick bites, appears mainly between May and Labor Day, when adult ticks are active and likely to be encountered by hikers or campers. After a 1-week inoculation period, victims experience chills, fever to 104°F, and muscle pain. On the fourth day of fever, a rash appears on the ankles, wrists, and palms and moves to the trunk. RMSF is not known to cause ocular disease in humans. Seventy-eight percent of dogs with serologically confirmed disease had one or more ocular components, including anterior uveitis, hyphema, iris hemorrhage, retinal edema, and retinal infiltrate.32 Ameboid corneal ulcers have been reported in humans with Mediterranean spotted fever (Rochalimaea conorii).33 TYPHUS Typhus is a potentially fatal disease caused by R. prowazekii, which is transmitted to humans from lice. Two weeks after infection the patient suffers a severe headache and high fever; after 3 to 4 days, a pinkish rash spreads over the body. Typhus is not known to cause eye disease. RICKETTSIALPOX Rickettsialpox is caused by Rickettsia akari, which is transmitted from house mice to humans via blood-sucking mites that are small and colorless and have painless bites. An outbreak occurred in New York in the early 1980s.34 Nine to 14 days after infection, sudden chills, fever, headache, and myalgia occur with fever. Two or three days after the onset of symptoms, a generalized papulovesicular rash appears.35 Rickettsialpox is not known to cause ocular disease. |
| LABORATORY DIAGNOSIS |
| Patients with Rochalimaea infection should have the diagnosis confirmed with serum indirect fluorescent antibody titer to R. henselae and R. quintana. Patients with cat-scratch disease have a ratio of more than 1:256. Electrolytes, complete blood count, antinuclear antibodies, and chest x-ray are generally normal after infection by R. henselae. However, a purified protein derivative test for tuberculosis, HIV, Lyme antibody, toxoplasmosis antibody, antinuclear antibodies, and other blood tests are appropriate to exclude other diseases in the differential diagnosis. |
| TREATMENT |
| Ciprofloxacin 750 mg orally two times a day (or doxycycline 100 mg orally
two times a day) is the drug of choice for Rochalimaea, but there are favorable minimum inhibitory concentrations for multiple
antibiotics, including ampicillin, second- and third-generation cephalosporins, tetracycline, chloramphenicol, aminoglycosides, rifampin, and
cizithromycin.21,36,37 The optimal treatment of Rochalimaea has yet to be resolved.8 Eradication of infection has been reported after the use of ciprofloxacin,21 doxycycline,36,38,39 erythromycin,21,39,40 norfloxacin,41 and tetracycline.21,39 Clinical failures have been reported with doxycycline,37 erythromycin,21 and tetracycline.41 The recommended systemic treatment of Rickettsiae causing spotted fever
is doxycycline (or erythromycin). Prednisone (20 to 60 mg/day orally) can be used with antibiotics to reduce inflammation and minimize potential ophthalmic complications related to inflammation. Systemic cases of Rochalimaea may require the assistance of an infectious diseases colleague. In general, appropriate use of antibiotics with systemic steroids leads to rapid resolution of the cutaneous rash and improvement of ocular function. |