Chapter 58
Rickettsial Organisms in Ocular Disease
Main Menu   Table Of Contents



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.
Back to Top
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

Disease Spotted Fever GroupOrganismGeographic AreaAnthropodsVertebratesClinical Findings
RMSFR. rickettsiiWestern hemisphereTickWild rodent, dogsRash extremities, trunk
BoutonneuseR. conoriiAfrica, India, MediterreanTickWild rodents, dogsRash extremities, face
Queensland tick typhusR. australisAustraliaTickWild rodents, marsupialsRash extremities, face
North Asian tick typhusR. sibiricaSiberia, MongoliaTickWild rodentsRash trunk, extremities, face
RickettsialpoxR. akariUS, USSR, Korea, AfricaMiteMouseVesicules, trunk, extremities, face
Typhus Group     
Epidemic typhusR. prowazekiiHighland areas of South America, Africa, Asia;?USBody louseHumans, flying squirrelRash trunk to extremities
Brill-ZinsserR. prowazekiiWorldwide based on immigrationNoneHumans (recurrence years after primary attack)Rash trunk to extremities (may be absent)
Murine typhusR. typhiWorldwide in pocketsFleaSmall rodentsRash trunk to extremities
Scrub typhusR. tsutsugamushiSouth Pacific, Asia, AustraliaMiteWild rodentsRash trunk to extremities
Q feverC. burnetiiWorldwide cats?TicksCattle, sheep, goats (immigration of organism)None
Trench feverRoch. quintanaHighly localLiceHumansTransient or none
Cat-scratch feverRoch. henselaeUS, ?worldwide?LiceCatsPreauricular adenopathy
Bacillary angiomatosisRoch. henselaeUS, ?worldwide?LiceCatsSmall nodules

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).

Back to Top
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.

Back to Top


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, 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 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 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.

Back to Top
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.
Back to Top
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.

Back to Top

1. Saah AJ: Rickettsiosis. In Mandell GL, Douglas RG, Bennett JE et al (eds): Principles and Practice of Infectious Diseases: Antimicrobial Therapy 1995/1996, p 1719. New York, Churchill-Livingstone, 1995

2. Woodward TE: Rickettsial disease in the United States. Med Clin North Am 40:197, 1959

3. Raoult D, Roux V: Rickettsioses as paradigms of new or emerging infectious diseases. Clin Microbiol Review 10: 694, 1997

4. Tomkins DC, Steigbigel RT: Rochalimaea's role in cat-scratch disease and bacillary angiomatosis. Ann Intern Med 118:388, 1993

5. Vinson JW: In vitro cultivation of the rickettsial agent of trench fever. Bull WHO 35:155, 1966

6. Regnery RL, Olson JG, Perkins BA et al: Serological response to Rochalimaea henselae antigen in suspected cat-scratch disease. Lancet 339:1443, 1992

7. Carithers HA: Cat-scratch disease: An overview based on a study of 1200 patients. Am J Dis Child 139:1124, 1985

8. Shinall EA. Cat-scratch disease: A review of the literature. Pediatr Dermatol 7:11, 1990

9. Golnik KC, Marotto ME, Fanous MM et al: Ophthalmic manifestations of Rochalimaea species. Am J Ophthalmol 118:145, 1994

10. Fish RH, Hogan RN, Nightingale SD et al: Peripapillary angiomatosis associated with cat-scratch neuroretinitis. Arch Ophthalmol 110:323, 1992

11. Lee WR, Chawla JC, Reid R: Bacillary angiomatosis of the conjunctiva. Am J Ophthalmol 118:152, 1994

12. Avias-Stella, Liberman PH, Erlandson RA et al: Histology, immunocytochemistry, and ultrastructure of the verruga in carrion's disease. Am J Pathol 136:1125, 1990

13. Strong RP (ed): Trench fever. Report of Commission, Medical Research Committee American Red Cross, p 40. Oxford University Press, 1918

14. Debre R, Lamy M, Jammet ML, Costil L, Mozziconacci P: La maladie des griftes de chat. Sem Hop Paris 26:1895, 1950

15. Wear DJ, Margileth AM, Hadfield TL, Fischer GW, Schlagel CJ, King FM: Cat-scratch disease: A bacterial infection. Science 221:1403, 1983

16. English CK, Wear DJ, Margileth AM, Lissner CR, Walsh GP: Cat-scratch disease isolation and culture of the bacterial agent. JAMA 259:1347, 1988

17. Brenner DJ, Hollis DG, Moss CW et al: Proposal of Afipia gen. nov. with Afipia felis sp nov. (formerly the Cleveland Clinic Foundation strain), Afipia broomege sp nov., and three unnamed genospecies. J Clin Microbiol 27:2450, 1991

18. Stoler MH, Bonfiglio TA, Steibigel RT, Pereira M: An atypical subcutaneous infection associated with acquired immune deficiency syndrome. Am J Clin Pathol 80:714, 1983

19. Cockerell CJ, Whitlow MA, Webster GF, Friedman-Kien AE: Epithelioid angiomatosis: A distinct vascular disorder in patients with the acquired immunodeficiency syndrome or AIDS-related complex. Lancet 2:654, 1987

20. Cockerell CJ, LeBoit PE: Bacillary angiomatosis: A newly characterized pseudoneoplastic, infectious, cutaneous, vascular disorder. J Am Acad Derm 22:501, 1990

21. Slater LN, Welch DF, Hensel D, Coody DW: A newly recognized fastidious gram-negative pathogen as a cause of fever and bacteremia. N Engl J Med 323:1587, 1990

22. Welch DF, Pickett DA, Slater LN, Steigerwalt AG, Brenner DJ: Rochalimaea henselae sp nov., a cause of septicemia, bacillary angiomatosis, and parenchymal bacillary peliosis. J Clin Microbiol 30:275, 1991

23. LeBoit PE, Berger TG, Egbert BM: Epithelioid haemangioma-like vascular proliferation in AIDS. Manifestation of cat-scratch disease in bacillus infection? Lancet 1:960, 1988

24. Regentry RL, Olson JG, Perkins BA, Bibb W: Serologic response to Rochalimaea henselae in suspected cat-scratch disease. Lancet 339:1443, 1992

25. Anderson B, Kelly C, Threlkel R, Edwards K: Detection of Rochalimaea henselae in cat-scratch disease skin test antigens. J Infect Dis 168:1034, 1993

26. Anderson B, Sims K, Regenry R et al: Detection of Rochalimaea henselae DNA in specimens from cat-scratch disease by PCR. J Clin Microbiol 32:942, 1994

27. Tappero JW, Mohle-Boetani J, Koehler JE et al: The epidemiology of bacillary angiomatosis and bacillary peliosis. JAMA 269:770, 1993

28. Koehler JE, Glaser CA, Tappero JW: Rochalimaea henselae infection: An new zoonosis with the domestic cats as reservoir. JAMA 271:531, 1994

29. Golnik KC, Marotto ME, Fanous MM et al: Ophthalmic manifestations of Rochalimaea species. Am J Ophthalmol 118:145, 1994

30. Le H, Palay D, Anderson B, Steinberg JP: Conjunctival swab to demonstrate ocular cat-scratch disease. Am J Ophthalmol 118:249, 1994

31. Grossniklaus HE: The cat-scratch disease bacillary angiomatosis puzzle [editorial]. Am J Ophthalmol 118:246, 1994

32. Davidson MG, Breitschwerdt EB, Nasisse MP et al: Ocular manifestations of Rocky Mountain spotted fever in dogs. J Am Vet Med Assoc 194:777, 1989

33. Alio J, Ruiz-Beltram R, Herrera I et al: Rickettsial keratitis in a case of Mediterranean spotted fever. Eur J Ophthalmol 2:41, 1992

34. Walker DH, Dumler JS: Emerging and re-emerging rickettsial diseases [editorial]. N Engl J Med 331:1651, 1994

35. Saah AJ: Rickettsia akari. In Mandell GL, Douglas RG, Bennett JE et al (eds): Principles and Practice of Infectious Diseases: Antimicrobial Therapy 1995/1996, p 1727. New York, Churchill-Livingstone, 1995

36. Dolan MJ, Wong MT, Regnery RL et al: Syndrome of Rochalimaea henselae adenitis suggesting cat-scratch disease. Ann Intern Med 118:331, 1993

37. Lacey D, Dolan MJ, Moss CW et al: Relapsing illness due to Rochalimaea henselae in immunocompetent hosts. Implication for therapy and new epidemiological associations. Clin Infect Dis 14:683, 1992

38. Relman DA, Loutit JS, Schmidt TM, Fallow S, Tompkins LS: The agent of bacillary angiomatosis: An approach to the identification on uncultured pathogens. N Engl J Med 323:1537, 1990

39. Koehler JE, Quinn FD, Berger TG, LeBoit PE, Tappero JW: Isolation of Rochalimaea species from cutaneous and osseous lesions of bacillary angiomatosis. N Engl J Med 327:1625, 1992

40. Tappero JW, Koehler JE, Berger TG et al: Bacillary angiomatosis and bacillary splenitis in immunocompetent adults. Ann Intern Med 118:363, 1993

41. Welch DF, Pickett DA, Slater LN, Steigerwalt AG, Brenner DJ: Rochalimaea henselae sp nov.: A cause of septicemia, bacillary angiomatosis, and parenchymal bacillary peliosis. J Clin Microbiol 30:2;7, 1992

Back to Top