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Background: Systematic assessments of the presence and severity of particular symptoms over time are relatively uncommon for Lyme disease patients in the United States, and especially for Lyme disease patients with extracutaneous manifestations (ECLD)., Methods: Symptoms and symptom severity of 12 particular symptoms were evaluated in a prospective study at baseline and at 12 months for 35 adult Lyme disease patients with ECLD, 91.4% of whom were already started on antibiotic therapy, and compared with 52 adult Lyme disease patients with erythema migrans, who were untreated at study entry., Results: No significant difference in the frequency of having at least 1 symptom of the 12 evaluated was found between the 2 groups at either the baseline visit or the 12-month evaluation. Demographic variables were also similar between the 2 study groups, except that the ECLD patients were significantly less likely to be Caucasian: 24/35 (68.6%) of the ECLD cases vs 48/52 (92.3%) of the erythema migrans cases; P = .008., Conclusion: Lyme disease patients with ECLD had a similar frequency of symptoms at baseline compared with patients with erythema migrans. ECLD subjects, however, were significantly less likely to be Caucasian, raising the question of whether a preceding erythema migrans skin lesion may have been missed in persons with a darker skin color. An important limitation of our study, however, is that we did not record skin color per se, which should be considered for future studies., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Erythema migrans is the most common clinical manifestation of Lyme disease, with concomitant subjective symptoms occurring in ∼65% of cases in the United States. We evaluated the impact of having been started on antibiotic treatment before study enrollment on 12 particular symptoms for 38 subjects with erythema migrans versus 52 untreated subjects. There were no significant differences in the frequency of having at least one symptom or in the symptom severity score on study entry. However, the frequency of having at least one symptom was significantly greater for those who had received <7 days of antibiotic treatment than for those who had been treated for ≥7 days (23/24 [95.8%] versus 8/14 [57.1%], P  = 0.006). In addition, the percentage of subjects who were males was significantly lower among the group on treatment than among the untreated study subjects (13/38 [34.2%] versus 34/52 [65.4%], P  = 0.005). In conclusion, based on these findings, combining untreated and treated groups of patients with erythema migrans for research study analyses may have limitations and, depending on the study objectives, might not be preferred. Additional studies are warranted to better understand the day-to-day impact of antibiotic treatment on the presence, type, and severity of symptoms in patients with early Lyme disease., (Copyright © 2020 American Society for Microbiology.)

Background: Erythema migrans is the most common clinical manifestation of Lyme disease. Despite antibiotic therapy, typically at least 10% of adult patients with erythema migrans experience persistence of at least 1 subjective symptom for ≥6 months (posttreatment Lyme disease symptoms [PTLDS])., Methods: This study was designed to determine whether the frequency and severity (based on a visual analogue scale) of 12 particular symptoms in patients with erythema migrans (n = 52) differed from matched control subjects (n = 104) followed prospectively for 12 months., Results: At baseline, patients with Lyme disease were more likely than controls to have at least 1 symptom (P = .006). Among symptomatic subjects, Lyme disease patients had a higher mean number of symptoms (P < .001) and a higher mean total symptom severity score (P < .001). At both 6 and 12 months, however, there were no significant differences for these variables and no significant differences in the frequency or severity of any of the 12 individual symptoms assessed. However, 10 patients were clinically assessed as having possible PTLDS., Conclusions: Patients with erythema migrans were more likely than matched control subjects to be symptomatic at baseline with a greater symptom severity score, but this was not found at ≥6 months. Use of symptom survey data alone, however, was less likely to identify patients with possible PTLDS compared with individual clinical assessments. Because it is very challenging to be certain that the presence of long-term symptoms in a particular patient is correctly attributable to having had Lyme disease, an objective biomarker would be highly desirable., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Although a 14-day treatment course with amoxicillin is in wide clinical usage to treat early Lyme disease, only a few published studies exist to validate its efficacy and safety, with none in the United States. In this study, we reviewed the records of 24 prospectively followed adult patients with erythema migrans who were prescribed a 14-day course of amoxicillin, 500 mg 3 times daily. Treatment with amoxicillin was well tolerated and uniformly successful in resolving the erythema migrans skin lesion and in preventing the development of an objective neurologic, cardiac, or rheumatologic manifestation. Although the study was relatively small and only involved a single center, the findings provide additional evidence that a 14-day course of 500 mg amoxicillin given 3 times per day is highly effective therapy for patients with early Lyme disease., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The Beck Depression Inventory (BDI-II) may be used to evaluate individuals for symptoms of depression., Methods: In a 1-year prospective study, 52 adult Lyme disease patients with erythema migrans and 104 matched control subjects were clinically assessed and completed the BDI-II at study entry and approximately 6 and 12 months later following antibiotic treatment., Results: The mean BDI-II score was significantly higher at the baseline visit among Lyme disease patients compared with controls (P = .002), but no significant differences between the groups were observed at either the 6- or 12-month study visits. Over the course of the study, the mean BDI-II scores decreased an average of approximately 0.22 points per month (P < .0005) for Lyme disease patients, whereas the mean scores changed very little for controls (mean change = -0.02 per month, P = .50). The total number of somatic symptoms, of the 12 symptoms evaluated, strongly and directly correlated with the BDI-II scores at the baseline visit for the Lyme disease patients., Conclusions: The mean BDI-II scores of patients with early Lyme disease significantly exceeded that of matched controls at study entry, but by 6 months the values did not differ significantly. There was a good-to-excellent direct correlation between the BDI-II score and the total number of symptoms, suggesting that the BDI-II scores were reflecting somatic rather than affective depressive symptoms. When using the BDI-II as an assessment tool of patients with Lyme disease, infection-related somatic symptoms per se need to be considered in the interpretation of the results., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The most common and most recognizable feature of Borrelia burgdorferi infection (Lyme disease) is the skin lesion erythema migrans (EM). An illness associated with an EM-like skin lesion, but which is not caused by B. burgdorferi, occurs in many southern states in the United States (southern tick-associated rash illness [STARI], also known as Masters disease)., Methods: Clinical features of 21 cases of EM-like skin lesions in 21 patients from Missouri were compared in a prospective study with those of 101 cases in 97 patients with EM-like skin lesions from New York., Results: Among Missouri cases, the peak incidence of EM-like skin lesions occurred earlier in the year than it did among New York cases (P<.001). Case patients from Missouri were more likely to recall a tick bite than were case patients from New York (85.7% and 19.8%, respectively; P<.001), and the time period from tick bite to onset of the skin lesion was shorter among Missouri case patients (6.1+/-4.2 days and 10.4+/-6.1 days, respectively; P=.011). Missouri case patients were less likely to be symptomatic than were New York case patients (19.0% and 76.2%, respectively; P<.001), and Missouri case patients were less likely to have multiple skin lesions (4.8% and 26.7%, respectively; P=.042). EM-like lesions in Missouri cases were smaller in size than those in New York cases (8.3+/-2.2 cm and 16.4+/-11.5 cm, respectively; P<.001), more circular in shape (P=.004), and more likely to have central clearing (76.2% and 21.6%, respectively; P<.001). After antibiotic treatment, Missouri case patients recovered more rapidly than did New York case patients (P=.037)., Conclusion: Cases of EM-like skin lesion in patients from Missouri and New York have distinct clinical presentations.

Variability of disease manifestations has been noted in patients with Lyme disease. A contributing factor to this variation may be the number of spirochetes present in infected patients. We evaluated clinical and laboratory findings for patients with erythema migrans with regard to the number of Borrelia burgdorferi organisms detected by quantitative PCR (qPCR) in 2-mm skin biopsy specimens. B. burgdorferi was detected in 80% (40 of 50) of the specimens tested; the mean number of spirochetes in these specimens ranged over 3 orders of magnitude (10 to 11,000 spirochetes per 2-mm biopsy specimen). Larger numbers of spirochetes were significantly associated with a shorter duration of the erythema migrans skin lesion (P = 0.020), smaller skin lesions (P = 0.020), and infection with a specific genotype of B. burgdorferi (P = 0.008) but not with the number or severity of symptoms. Skin culture positivity was significantly associated with skin lesions containing larger numbers of spirochetes (P = 0.019).

Recently, a number of refinements in diagnostic modalities for detection of Borrelia burgdorferi infection have been developed. These include large-volume blood cultures, quantitative polymerase chain reaction (PCR) techniques, and 2-stage serologic testing. In the present study, we compared 6 diagnostic modalities in 47 adult patients who had a clinical diagnosis of erythema migrans. Quantitative PCR on skin biopsy-derived material was the most sensitive diagnostic method (80.9%), followed by 2-stage serologic testing of convalescent-phase samples (66.0%), conventional nested PCR (63.8%), skin culture (51.1%), blood culture (44.7%), and serologic testing of acute-phase samples (40.4%). Results of all assays were negative for 3 patients (6.4%). We conclude that the clinical diagnosis of erythema migrans is highly accurate in an area where B. burgdorferi is endemic if it is made by experienced health care personnel, but some patients with this diagnosis may not have B. burgdorferi infection. No single diagnostic modality is suitable for detection of B. burgdorferi in every patient with erythema migrans.

Genetic diversity among Borrelia burgdorferi isolates recovered from the skin of Lyme disease patients was assessed by ribosomal DNA (rDNA) spacer restriction fragment length polymorphism analysis, genomic restriction site polymorphism analysis, and plasmid content analysis. There was a significant association between the three rDNA spacer types, the six pulsed-field gel types, and plasmid content (P < 0.001). The association between distinct chromosomal and plasmid markers implies a clonal origin for each genotype.

To investigate whether genetic diversity of Borrelia burgdorferi sensu stricto may affect the occurrence of hematogenous dissemination, 104 untreated adults with erythema migrans from a Lyme disease diagnostic center in Westchester County, New York, were studied. Cultured skin isolates were classified into 3 groups by a polymerase chain reaction amplification and restriction fragment length polymorphism (RFLP) method. A highly significant association between infecting RFLP type in skin and the presence of spirochetemia was found (P<.001). The same association existed for the presence of multiple erythema migrans lesions (P=.045), providing clinical corroboration that hematogenous dissemination is related to the genetic subtype of B. burgdorferi sensu stricto. There were no significant associations between RFLP type and seropositivity or clinical symptoms and signs except for a history of fever and chills (P=.033). These results suggest that specific genetic subtypes of B. burgdorferi sensu stricto influence disease pathogenesis. Infection with different subtypes of B. burgdorferi sensu stricto may help to explain differences in the clinical presentation of patients with Lyme disease.

Understanding the role that nymphal and female ticks, Ixodes scapularis, have in the epidemiology of Lyme disease is essential to the development of successful prevention programs. In this study, the authors sought to evaluate the seasonal and annual relations between tick densities and patients > or = 16 years of age diagnosed with erythema migrans (EM), the rash associated with early Lyme disease. Ticks were collected weekly by drag sampling throughout most of the year from 1991 to 1996 in Westchester County, New York. The number of EM cases was based on patients diagnosed at the Westchester County Medical Center using Centers for Disease Control and Prevention (CDC) criteria. No patients with EM were diagnosed from January through April, when only adult ticks were active. Correlation analysis between monthly tick densities and EM incidence was significant for nymphs (r = 0.87, p < 0.01), but not for adult ticks (r = -0.57, p > 0.05). There was a strong, although not significant, correlation between peak annual number of patients with EM and peak nymphal tick abundance (r = 0.76, p = 0.08). These data indicate that bites from adult I. scapularis only rarely result in Lyme disease, and that annual nymphal tick abundance determines exposure. This suggests that annual fluctuations in Lyme disease case numbers are largely due to natural changes in tick abundance and, therefore, that control of nymphal I. scapularis should be a major component of Lyme disease prevention efforts.

Background: Doxycycline is widely used to treat Lyme disease associated with erythema migrans. Whether it is comparable to tetracycline is unknown., Objective: We conducted a two-part retrospective analysis of (1) the safety and efficacy of doxycycline compared with tetracycline and (2) the safety and efficacy of a 14-day versus a 20-day course of doxycycline., Methods: Twenty-seven patients given tetracycline (500 mg four times a day for 14 days [group 1]) were compared retrospectively with 21 patients who received doxycycline (100 mg two or three times a day for 14 days [group 2]). The results for group 2 were also compared with that of 38 patients who received doxycycline for 20 days (100 mg three times daily) in a prospective treatment trial (group 3)., Results: There was no significant difference in the incidence of adverse drug effects or in efficacy at 1 month, but at 1 year there was a trend toward a better outcome in the group treated with tetracycline (p = 0.08). A 14-day course of doxycycline was comparable to a 20-day course in the incidence of adverse drug effects and in clinical outcome., Conclusion: The principal advantage of doxycycline over tetracycline for the treatment of Lyme disease associated with erythema migrans is the convenience of less frequent dosing, not enhanced efficacy or safety. There appears to be no advantage in extending treatment with doxycycline from 14 to 20 days.

Background: Borrelia burgdorferi, the etiologic agent of Lyme borreliosis, has occasionally been isolated from tissues or body fluids of patients after antimicrobial treatment. A prospective study of patients with Lyme borreliosis associated with erythema migrans (EM) was initiated in Westchester County, New York, to determine: (1) the clinical and laboratory parameters associated with culture positivity, and (2) the microbiologic response to treatment., Methods: Skin biopsies were performed in patients with EM and cultured for B. burgdorferi in modified Barbour-Stoenner-Kelly medium at 33 degrees C. Subsequent biopsies for culture were performed adjacent to the original biopsy site for culture-positive patients after the completion of antimicrobial therapy., Results: Initial biopsy cultures were performed for 44 patients; 6 were unevaluable due to culture contamination with other bacteria. Cultures were positive in 21 of 29 patients prior to treatment (72%), but in none of 9 patients during treatment (p < 0.001). The only other identified factor associated with successful recovery of B. burgdorferi was shorter duration of EM. When patients who had received prior antimicrobial therapy were excluded, the mean duration of the EM lesion for those with positive cultures was 5.0 +/- 5.2 days compared with 14.6 +/- 9.9 days for those with negative cultures (p < 0.01). B. burgdorferi could not be reisolated from any of 18 evaluable subsequent biopsies of skin from 13 culture-positive patients 4 to 209 days after completion of a course of antimicrobial therapy. Five patients had negative subsequent biopsy cultures on two separate occasions 3 to 5 months apart., Conclusions: After brief courses of antibiotics, B. burgdorferi appears to be rapidly eliminated from the skin at EM sites. The ability to recover B. burgdorferi from skin biopsy cultures of untreated patients with EM lesions wanes with increasing duration of EM, suggesting that this organism may also be spontaneously cleared from skin over time.

Background: Lyme disease is the most common vector-borne disease in the United States. The characteristic rash, erythema migrans, is an early sign of the disease. Clinical criteria remain the "gold standard" for diagnosis at this stage of illness., Observations: Five (8%) of 65 patients with erythema migrans seen in a Lyme disease diagnostic center in Westchester County, New York, had a lesion with vesicles. Borrelia burgdorferi was cultured from two of five. In one case the positive culture came from a swab of the blister fluid., Conclusions: Recognition of erythema migrans and its variants is important, since early treatment of Lyme disease may prevent late complications. Vesicular erythema migrans should be added to the differential diagnosis of inflammatory vesicular rashes in the appropriate clinical setting.