STARI or Masters disease: More like Lyme than Lyme?

A tick-borne illness has been masquerading as Lyme disease in the southern United States over the past two decades. Victims first notice the expanding "bulls-eye" skin rash that is similar in appearance to the erythema migrans (EM) of Lyme disease. However, the tick that feeds on the victim is not the Ixodes tick that causes Lyme disease but the Lone Star tick Amblyomma americanum. Moreover, Borrelia burgdorferi, the Lyme disease spirochete, is not the infectious agent. B. burgdorferi has never been successfully cultured from a southern case of the EM-like rash, and sera from most of these patients test negative for Lyme disease by CDC criteria. Lyme disease itself is uncommon in the south as the resident Ixodes ticks rarely feed on humans; most ticks found attached to humans residing in the south are the Lone Star tick, which is unlikely to harbor or transmit B. burgdorferi.

The name bestowed upon the condition, "southern tick-associated rash illness" or STARI, is misleading because the territory of the Lone Star tick has been creeping into the northeastern and northern U.S., where Lyme disease is hyperendemic. The illness has also been dubbed "Masters disease" to honor Dr. Edwin Masters, who passed away last month. Dr. Masters' observations of skin rash patients in his private practice in Cape Girardeau, Missouri sparked the contentious CDC investigation that led to the first detailed description of STARI 14 years ago. You can read about his battles with the CDC in a series of blog posts by Pamela Weintraub, author of the book Cure Unknown, Inside the Lyme Epidemic (a book I hope to read some day).

Fig. 1 from Masters et al., 2008. Lone Star tick territory in green.

Contrary to popular belief, the erythema migrans of most Lyme disease patients does not present as a bull's-eye. In fact, in one study the EM-like rashes in Masters' STARI patients were much more likely to appear as a bull's-eye than the EM of Lyme disease patients from New York. In addition, the STARI patients were less likely than those with Lyme disease to suffer from accompanying symptoms such as joint and muscle aches, fatigue, headache, and stiff neck. A question that remains unresolved is whether arthritic, neurologic, or cardiac symptoms can crop up later, as they do in those afflicted with Lyme disease.

Figure 2 from Masters et al., 2008. EM-like skin lesions in Missouri STARI patients

The agent of STARI has eluded scientists. Borrelia lonestari was suspected at one time when it was detected by PCR in one patient and the Lone Star tick attached to his skin. (The spirochete could not be cultured since it does not grow in Borrelia culture medium.) However, B. lonestari could not be detected in a later study of a series of Masters' STARI patients. Thus, B. lonestari is unlikely to bring about most cases of STARI. The failure to identify the infectious agent of STARI has led some to question whether STARI has an infectious cause.

Masters was convinced that a spirochete, perhaps one closely related to Borrelia burgdorferi, was the agent of STARI. He has offered the following observations as evidence:

• Spirochetes have been observed in Lone Star ticks.
  
• Forms resembling spirochetes have been observed by silver staining of the EM-like skin lesions from Masters' STARI patients (see figure below).
• Extracts of B. burgdorferi reacted with sera from some STARI patients in ELISA tests, although the sera were Western blot negative according to CDC criteria. This observation indicates that antibodies were elicited against proteins closely related to those found in B. burgdorferi.
  Figure 8 from Masters et al., 1998. Silver stain of skin biopsy of an EM-like rash from a Missouri patient showing an apparent spirochete.
  

Of course these observations are far from definitive proof. Nevertheless, it is possible that a Borrelia spirochete is the culprit of EM-like lesions in the southern U.S. Like B. lonestari, some of these strains may not grow in the standard Borrelia medium used to cultivate B. burgdorferi from the skin rashes of Lyme disease patients. This would account for the inability of investigators to culture the spirochete from the skin rash of STARI patients.

Finally, how is STARI treated? Although the cause of STARI remains unknown, Edwin Masters declared that Lyme-like illness deserves Lyme-like treatment. That is, he recommended that antibiotics be administered to STARI patients according to Lyme treatment guidelines. Establishing whether antibiotics truly help will require a randomized placebo-controlled study.

Featured article

MASTERS, E.J., GRIGERY, C.N., & MASTERS, R.W. (2008). STARI, or Masters Disease: Lone Star Tick–Vectored Lyme-like Illness Infectious Disease Clinics of North America, 22 (2), 361-376 DOI: 10.1016/j.idc.2007.12.010

Other references

Masters, E., Granter, S., Duray, P., and Cordes P. (1998). Physician-diagnosed erythema migrans and erythema migrans-like rashes following Lone Star tick bites. Archives of Dermatology 134(8):955-960.

Wormser G.P., Masters, E., Liveris, D., Nowakowski, J., Nadelman, R. B., Holmgren, D., Bittker, S., Cooper, D., Wang, G., and Schwartz, I. (2005). Microbiologic evaluation of patients from Missouri with erythema migrans. Clinical Infectious Diseases 40(3):423-428. DOI: 10.1086/427289

Wormser G.P., Masters, E., Nowakowski, J., McKenna, D., Holmgren D., Ma, K., Ihde, L., Cavaliere, L.F., and Nadelman, R.B. (2005). Prospective clinical evaluation of patients from Missouri and New York with erythema migrans-like skin lesions. Clinical Infectious Diseases 41(7):958-965. DOI: 10.1086/432935