Lyme Disease

Am J Clin Pathol. 2007 Feb;127(2):213-22. Abstract quote

Borrelia burgdorferi is difficult to detect in routine biopsy material from patients with skin lesions of borreliosis. In this study, a new immunohistochemical method, focus floating microscopy (FFM), was developed to detect B burgdorferi in tissue sections and was compared with polymerase chain reaction (PCR).

By using standard histologic equipment, tissue sections stained with a polyclonal B burgdorferi antibody were simultaneously scanned through 2 planes: horizontally in serpentines and vertically by focusing through the thickness of the section.Borrelia were detected in 47 of 71 ticks, 34 of 66 tick bites, 30 of 32 erythema chronicum migrans cases, 41 of 43 borrelial lymphocytomas, and 50 of 51 acrodermatitis chronica atrophicans cases. FFM proved to be more sensitive than PCR (96.0% vs 45.2%) and nearly equally specific (99.4% vs 100%).

All 169 control cases, except 1 false-positive case of secondary syphilis, were negative with FFM. FFM is an easy, quick, and inexpensive method to reliably detect Borrelia in cutaneous tissue sections.

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Treatment
Commonly Used Terms
Internet Links

PATHOGENESIS	CHARACTERIZATION
Borrelia burgdorferi	Ticks carry the bacteria
Tick Species	Geographic Location
Ixodes scapularis (Deer tick) aka I. dammini	Mid-Atlantic and North Central US
I. pacificus (Western black legged tick)	West Coast US
I. ricinus (sheep tick)	Europe and Asia
I. persulcatus	Eastern Europe and Asia

LABORATORY/ RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
Laboratory Markers
EIA or IFA	Initial evaluation includes an enzyme immunoassay (EIA) or immunofluorescent antibody assay (IFA) If there is an initial negative test, a follow-up convalescent sample can be obtained within 4-6 weeks If the initial EIA/IFA is positive or equivocal, confirmation by Western blot (WB) can be obtained If it is less than 4 weeks of onset, IgM and IgG WB should be performed If more than 4 weeks after onset, IgG WB should be used It should be noted that antibodies may persist for months to years following exposure and/or treatment and thus cannot be used to indicate active disease Furthermore, it does not provide protective immunity.
Culture	Culture has a limited role and requires specialized media (modified Barbour-Stoenner-Kelly)
PCR	PCR can detect it in some skin biopsies as well as other bodily sites such as joint fluid.
Western Blot
IgM Western Blot bands (2 of 3 positive)	24kd (Osp C) 39kd, 41kd
IgG Western Blot bands (5 of 10 positive)	18kd, 21 kd (Osp C), 28kd, 30kd, 39kd, 41kd, 45kd, 58kd, 66kd, 93kd

HISTOLOGICAL TYPES	CHARACTERIZATION
SKIN	Early cases of the skin may show a sparse superficial perivascular lymphocytic infiltrate with moderate to marked mucin Plasma cells are not common In the center of acute lesions, there may be an intense neutrophilic and eosinophilic infiltrate In the later phases of the disease, the biopsy may have a diffuse interstitial dermatitis
Focus floating microscopy: "gold standard" for cutaneous borreliosis? Eisendle K, Grabner T, Zelger B. Department of Dermatology and Venerology, Innsbruck Medical University, Innsbruck, Austria.	Am J Clin Pathol. 2007 Feb;127(2):213-22. Abstract quote Borrelia burgdorferi is difficult to detect in routine biopsy material from patients with skin lesions of borreliosis. In this study, a new immunohistochemical method, focus floating microscopy (FFM), was developed to detect B burgdorferi in tissue sections and was compared with polymerase chain reaction (PCR). By using standard histologic equipment, tissue sections stained with a polyclonal B burgdorferi antibody were simultaneously scanned through 2 planes: horizontally in serpentines and vertically by focusing through the thickness of the section.Borrelia were detected in 47 of 71 ticks, 34 of 66 tick bites, 30 of 32 erythema chronicum migrans cases, 41 of 43 borrelial lymphocytomas, and 50 of 51 acrodermatitis chronica atrophicans cases. FFM proved to be more sensitive than PCR (96.0% vs 45.2%) and nearly equally specific (99.4% vs 100%). All 169 control cases, except 1 false-positive case of secondary syphilis, were negative with FFM. FFM is an easy, quick, and inexpensive method to reliably detect Borrelia in cutaneous tissue sections.
VARIANTS
ACRODERMATITIS CHRONICA ATROPHICANS (ACA)	Superficial and deep perivascular and interstitial infiltrate of plasma cells, lymphocytes, and histiocytes Later lesions show sclerosis with loss of adnexa and elastic fibers
INTERSTITIAL GRANULOMATOUS DERMATITIS
Interstitial granulomatous dermatitis with histiocytic pseudorosettes: a new histopathologic pattern in cutaneous borreliosis. Detection of Borrelia burgdorferi DNA sequences by a highly sensitive PCR-ELISA. Moreno C, Kutzner H, Palmedo G, Goerttler E, Carrasco L, Requena L. Department of Pathology, Fundacion Jimenez Diaz, Universidad Autonoma, Madrid, Spain.	J Am Acad Dermatol 2003 Mar;48(3):376-84 Abstract quote BACKGROUND: The cutaneous manifestations of Borrelia burgdorferi infection include an early phase of erythema chronicum migrans and a late stage of acrodermatitis chronica atrophicans lesions. OBJECTIVE: We describe 11 patients with peculiar cutaneous manifestations and distinctive histopathologic findings as the result of B burgdorferi infection. METHODS: Eleven patients with B burgdorferi detected by polymerase chain reaction or polymerase chain reaction enzyme-linked immunosorbent assay in their cutaneous lesions were included in this study. We analyzed clinical data and histopathologic findings in all patients. The inflammatory infiltrate was also immunohistochemically investigated. RESULTS: Most patients showed a peculiar clinical setting of morphea, and a few cases presented the characteristic appearance of erythema chronicum migrans instead of acrodermatitis chronica atrophicans, as would be expected in a late phase of B burgdorferi infection. The histopathologic findings were similar in all cases and consisted of an interstitial inflammatory infiltrate mostly composed of histiocytes dispersed among the collagen bundles of the dermis and focal areas of small pseudorosette formation, characterized by small histiocytes radially disposed around thick collagen bundles. In some cases there were also a few plasma cells intermingled with the histiocytes. CONCLUSION: Cutaneous lesions with clinical appearance similar to that of morphea and histopathologic features closely resembling those of the interstitial type of granuloma annular may be seen in intermediate-stage cutaneous lesions of B burgdorferi infection. These clinical and histopathologic findings represent a constellation of findings that have not been previously characterized as a cutaneous manifestation of B burgdorferi infection.

TREATMENT	CHARACTERIZATION
GENERAL
ANTIBIOTICS
Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. Nadelman RB, Nowakowski J, Fish D, Falco RC, Freeman K, McKenna D, Welch P, Marcus R, Aguero-Rosenfeld ME, Dennis DT, Wormser GP; Tick Bite Study Group. Department of Medicine, New York Medical College, Valhalla 10595, USA.	N Engl J Med 2001 Jul 12;345(2):79-84 Abstract quote BACKGROUND: It is unclear whether antimicrobial treatment after an Ixodes scapularis tick bite will prevent Lyme disease. METHODS: In an area of New York where Lyme disease is hyperendemic we conducted a randomized, double-blind, placebo-controlled trial of treatment with a single 200-mg dose of doxycycline in 482 subjects who had removed attached I. scapularis ticks from their bodies within the previous 72 hours. At base line, three weeks, and six weeks, subjects were interviewed and examined, and serum antibody tests were performed, along with blood cultures for Borrelia burgdorferi. Entomologists confirmed the species of the ticks and classified them according to sex, stage, and degree of engorgement. RESULTS: Erythema migrans developed at the site of the tick bite in a significantly smaller proportion of the subjects in the doxycycline group than of those in the placebo group (1 of 235 subjects [0.4 percent] vs. 8 of 247 subjects [3.2 percent], P<0.04). The efficacy of treatment was 87 percent (95 percent confidence interval, 25 to 98 percent). Objective extracutaneous signs of Lyme disease did not develop in any subject, and there were no asymptomatic seroconversions. Treatment with doxycycline was associated with more frequent adverse effects (in 30.1 percent of subjects, as compared with 11.1 percent of those assigned to placebo; P<0.001), primarily nausea (15.4 percent vs. 2.6 percent) and vomiting (5.8 percent vs. 1.3 percent). Erythema migrans developed more frequently after untreated bites from nymphal ticks than after bites from adult female ticks (8 of 142 bites [5.6 percent] vs. 0 of 97 bites [0 percent], P=0.02) and particularly after bites from nymphal ticks that were at least partially engorged with blood (8 of 81 bites [9.9 percent], as compared with 0 of 59 bites from unfed, or flat, nymphal ticks [0 percent]; P=0.02). CONCLUSIONS: A single 200-mg dose of doxycycline given within 72 hours after an I. scapularis tick bite can prevent the development of Lyme disease.