scholarly journals Transcriptome Assessment of Erythema Migrans Skin Lesions in Patients With Early Lyme Disease Reveals Predominant Interferon Signaling

2017 ◽  
Vol 217 (1) ◽  
pp. 158-167 ◽  
Author(s):  
Adriana Marques ◽  
Ira Schwartz ◽  
Gary P Wormser ◽  
Yanmei Wang ◽  
Ronald L Hornung ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Cell Activation ◽  
Critical Role ◽  
Erythema Migrans ◽  
Transcriptional Response ◽  
Skin Lesions ◽  
Microbial Pathogens ◽  
Activation Markers ◽  
Transcriptional Pattern ◽  
Transcriptional Alterations

Abstract Background The most common clinical manifestation of early Lyme disease is the erythema migrans (EM) skin lesion that develops at the tick bite site typically between 7 and 14 days after infection with Borreliella burgdorferi. The host-pathogen interactions that occur in the skin may have a critical role in determining outcome of infection. Methods Gene arrays were used to characterize the global transcriptional alterations in skin biopsy samples of EM lesions from untreated adult patients with Lyme disease in comparison to controls. Results The transcriptional pattern in EM biopsies consisted of 254 differentially regulated genes (180 induced and 74 repressed) characterized by the induction of chemokines, cytokines, Toll-like receptors, antimicrobial peptides, monocytoid cell activation markers, and numerous genes annotated as interferon (IFN)-inducible. The IFN-inducible genes included 3 transcripts involved in tryptophan catabolism (IDO1, KMO, KYNU) that play a pivotal role in immune evasion by certain other microbial pathogens by driving the differentiation of regulatory T cells. Conclusions This is the first study to globally assess the human skin transcriptional response during early Lyme disease. Borreliella burgdorferi elicits a predominant IFN signature in the EM lesion, suggesting a potential mechanism for spirochetal dissemination via IDO1-mediated localized immunosuppression.

scholarly journals Serologic Evaluation of Patients from Missouri with Erythema Migrans-Like Skin Lesions with the C6 Lyme Test

2006 ◽  
Vol 13 (10) ◽  
pp. 1170-1171 ◽  
Author(s):  
Mario T. Philipp ◽  
Edwin Masters ◽  
Gary P. Wormser ◽  
Wayne Hogrefe ◽  
Dale Martin
Keyword(s):  
New York ◽  
Lyme Disease ◽  
Erythema Migrans ◽  
New York State ◽  
Skin Lesions ◽  
Etiologic Agent ◽  
Acute Stage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Convalescent Phase ◽  
South Central

ABSTRACT Southern tick-associated rash illness (STARI), also known as Masters disease, affects people predominantly in the Southeast and South Central United States. These patients exhibit skin lesions that resemble erythema migrans (EM), the characteristic skin lesion in early Lyme disease. The etiology of STARI remains unknown, and no serologic test is available to aid in its diagnosis. The C6 Lyme enzyme-linked immunosorbent assay was used to evaluate coded serum specimens from patients with STARI at two laboratory sites. The specimens tested at one site consisted of acute- and convalescent-phase samples that were obtained from nine STARI patients from Missouri and from one patient with documented Borrelia lonestari infection who acquired this infection in either North Carolina or Maryland. All of these samples were C6 negative. Seventy acute- or convalescent-phase specimens from 63 STARI patients from Missouri were C6 tested at the second site. All but one of these STARI specimens were also negative. In contrast, of nine acute- and nine convalescent-phase serum specimens obtained from culture-confirmed Lyme disease patients with EM from New York state, seven were C6 positive at the acute stage, and eight were positive at convalescence. The C6 test is negative in patients with STARI, providing further evidence that B. burgdorferi is not the etiologic agent of this disease.

scholarly journals Bull’s-Eye and Nontarget Skin Lesions of Lyme Disease: An Internet Survey of Identification of Erythema Migrans

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
John N. Aucott ◽  
Lauren A. Crowder ◽  
Victoria Yedlin ◽  
Kathleen B. Kortte
Keyword(s):  
Infectious Disease ◽  
Lyme Disease ◽  
Early Recognition ◽  
Erythema Migrans ◽  
Skin Lesions ◽  
Disease Diagnosis ◽  
Internet Survey ◽  
Appropriate Use ◽  
Bull's Eye ◽  
Use Of Medical Services

Introduction. Lyme disease is an emerging worldwide infectious disease with major foci of endemicity in North America and regions of temperate Eurasia. The erythema migrans rash associated with early infection is found in approximately 80% of patients and can have a range of appearances including the classic target bull’s-eye lesion and nontarget appearing lesions.Methods. A survey was designed to assess the ability of the general public to distinguish various appearances of erythema migrans from non-Lyme rashes. Participants were solicited from individuals who visited an educational website about Lyme disease.Results. Of 3,104 people who accessed a rash identification survey, 72.7% of participants correctly identified the classic target erythema migrans commonly associated with Lyme disease. A mean of 20.5% of participants was able to correctly identify the four nonclassic erythema migrans. 24.2% of participants incorrectly identified a tick bite reaction in the skin as erythema migrans.Conclusions. Participants were most familiar with the classic target erythema migrans of Lyme disease but were unlikely to correctly identify the nonclassic erythema migrans. These results identify an opportunity for educational intervention to improve early recognition of Lyme disease and to increase the patient’s appropriate use of medical services for early Lyme disease diagnosis.

scholarly journals Impact of Clinical Variables on Borrelia burgdorferi-Specific Antibody Seropositivity in Acute-Phase Sera from Patients in North America with Culture-Confirmed Early Lyme Disease

2008 ◽  
Vol 15 (10) ◽  
pp. 1519-1522 ◽  
Author(s):  
Gary P. Wormser ◽  
John Nowakowski ◽  
Robert B. Nadelman ◽  
Paul Visintainer ◽  
Andrew Levin ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Acute Phase ◽  
Erythema Migrans ◽  
Skin Lesions ◽  
Enzyme Linked Immunosorbent Assay ◽  
Clinical Variables ◽  
Gender And Age ◽  
Serologic Assay ◽  
Single Lesion

ABSTRACT Erythema migrans, the most common manifestation of Lyme disease, has been associated with highly variable rates of seropositivity for antibodies to Borrelia burgdorferi. Differences in the sensitivities of serologic assays for the detection of these antibodies, however, may not be the only or even the primary explanation for this observation. We investigated the impacts of four clinical variables on seropositivity—the duration of erythema migrans, the presence of single versus multiple skin lesions, and the gender and age of the patient. In this analysis, three different serologic tests were performed on acute-phase sera from 175 untreated patients with culture-confirmed erythema migrans: the C6 single-peptide enzyme-linked immunosorbent assay (ELISA), a commercially available ELISA in which a whole-cell sonicate of B. burgdorferi was the antigen, and a two-tier procedure. Irrespective of the serologic test performed, the results showed that seropositivity rates increased with the duration of the erythema migrans for patients with single lesions (P < 0.001) but not for those with multiple skin lesions. The variability in seropositivity rates was greatest for the two-tier testing strategy, with a >6-fold-higher rate of seropositivity among patients with a single lesion of 22- to 30-day duration than among those whose skin lesion was of 1- to 7-day duration (85.7 versus 14.1%; P < 0.001). Rates of seropositivity by each of the testing methods were also significantly higher for patients with multiple skin lesions than for those with single lesions (P < 0.001). In contrast, seropositivity rates were not affected by either the gender or the age of the patient. Thus, in patients with erythema migrans, certain clinical variables such as the duration and number of skin lesions had a profound impact on seropositivity rates, irrespective of the serologic assay performed.

scholarly journals Misdiagnosis of early Lyme disease as the summer flu

2011 ◽  
Vol 3 (2) ◽  
pp. 14 ◽  
Author(s):  
John N. Aucott ◽  
Ari Seifter
Keyword(s):  
West Nile Virus ◽  
Lyme Disease ◽  
Physical Examination ◽  
Influenza A ◽  
Influenza Season ◽  
Erythema Migrans ◽  
Skin Lesions ◽  
Specific Diagnosis ◽  
Seasonal Peak ◽  
Diagnostic Importance

Lyme disease is often identified by the hallmark erythema migrans rash, but not all early cases present with a rash. In other cases the rash may be unseen or unrecognized by a physician. In these situations, Lyme disease is difficult to diagnose because it masquerades as a non-specific viral-like illness. The seasonal peak of Lyme disease ranging from May through September overlaps with that of viral illnesses such as enteroviral infections, West Nile virus, and in rare years such as 2009, early influenza season. We present a case of a patient with Lyme disease who was initially misdiagnosed with influenza A during the summer of 2009. Because of the diagnostic importance of recognizing the erythema migrans rash, physicians in endemic regions should always ask about new rashes or skin lesions and perform a thorough physical examination when patients present over the summer with viral-like symptoms. Even when no rash is evident, Lyme disease should be considered if these symptoms persist or worsen without a specific diagnosis.

scholarly journals Selective Up‐Regulation of Matrix Metalloproteinase–9 Expression in Human Erythema Migrans Skin Lesions of Acute Lyme Disease

2003 ◽  
Vol 188 (8) ◽  
pp. 1098-1104 ◽  
Author(s):  
Zhihui Zhao ◽  
Hernan Chang ◽  
Richard P. Trevino ◽  
Kara Whren ◽  
Jag Bhawan ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Matrix Metalloproteinase ◽  
Erythema Migrans ◽  
Skin Lesions ◽  
Matrix Metalloproteinase 9 ◽  
Metalloproteinase 9

scholarly journals Geographical and genospecies distribution of Borrelia burgdorferi sensu lato DNA detected in humans in the USA

2014 ◽  
Vol 63 (5) ◽  
pp. 674-684 ◽  
Author(s):  
Kerry L. Clark ◽  
Brian F. Leydet ◽  
Clifford Threlkeld
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Skin Biopsy ◽  
Lyme Borreliosis ◽  
Erythema Migrans ◽  
Skin Lesions ◽  
Sensu Stricto ◽  
Borrelia Burgdorferi Sensu Lato ◽  
Southern States ◽  
The Usa

The present study investigated the cause of illness in human patients primarily in the southern USA with suspected Lyme disease based on erythema migrans-like skin lesions and/or symptoms consistent with early localized or late disseminated Lyme borreliosis. The study also included some patients from other states throughout the USA. Several PCR assays specific for either members of the genus Borrelia or only for Lyme group Borrelia spp. (Borrelia burgdorferi sensu lato), and DNA sequence analysis, were used to identify Borrelia spp. DNA in blood and skin biopsy samples from human patients. B. burgdorferi sensu lato DNA was found in both blood and skin biopsy samples from patients residing in the southern states and elsewhere in the USA, but no evidence of DNA from other Borrelia spp. was detected. Based on phylogenetic analysis of partial flagellin (flaB) gene sequences, strains that clustered separately with B. burgdorferi sensu stricto, Borrelia americana or Borrelia andersonii were associated with Lyme disease-like signs and symptoms in patients from the southern states, as well as from some other areas of the country. Strains most similar to B. burgdorferi sensu stricto and B. americana were found most commonly and appeared to be widely distributed among patients residing throughout the USA. The study findings suggest that human cases of Lyme disease in the southern USA may be more common than previously recognized and may also be caused by more than one species of B. burgdorferi sensu lato. This study provides further evidence that B. burgdorferi sensu stricto is not the only species associated with signs and/or symptoms consistent with Lyme borreliosis in the USA.

Cytokine profiles in the erythema migrans skin lesions of Lyme disease

Cytokine ◽  
1994 ◽  
Vol 6 (5) ◽  
pp. 568
Author(s):  
EV Granowitz ◽  
T Kamradt ◽  
S Luger ◽  
CA Dinarello ◽  
AC Steere
Keyword(s):  
Lyme Disease ◽  
Erythema Migrans ◽  
Skin Lesions ◽  
Cytokine Profiles

scholarly journals Purinergic Signaling and Inflammasome Activation in Psoriasis Pathogenesis

2021 ◽  
Vol 22 (17) ◽  
pp. 9449
Author(s):  
Davide Ferrari ◽  
Fabio Casciano ◽  
Paola Secchiero ◽  
Eva Reali
Keyword(s):  
T Cell Activation ◽  
Cell Activation ◽  
Purinergic Signaling ◽  
Critical Role ◽  
Clinical Manifestations ◽  
Skin Lesions ◽  
Psoriatic Skin ◽  
Inflammasome Activation ◽  
Increased Risk

Psoriasis is a chronic inflammatory disease of the skin associated with systemic and joint manifestations and accompanied by comorbidities, such as metabolic syndrome and increased risk of cardiovascular disease. Psoriasis has a strong genetic basis, but exacerbation requires additional signals that are still largely unknown. The clinical manifestations involve the interplay between dendritic and T cells in the dermis to generate a self-sustaining inflammatory loop around the TNFα/IL-23/IL-17 axis that forms the psoriatic plaque. In addition, in recent years, a critical role of keratinocytes in establishing the interplay that leads to psoriatic plaques’ formation has re-emerged. In this review, we analyze the most recent evidence of the role of keratinocytes and danger associates molecular patterns, such as extracellular ATP in the generation of psoriatic skin lesions. Particular attention will be given to purinergic signaling in inflammasome activation and in the initiation of psoriasis. In this phase, keratinocytes’ inflammasome may trigger early inflammatory pathways involving IL-1β production, to elicit the subsequent cascade of events that leads to dendritic and T cell activation. Since psoriasis is likely triggered by skin-damaging events and trauma, we can envisage that intracellular ATP, released by damaged cells, may play a role in triggering the inflammatory response underlying the pathogenesis of the disease by activating the inflammasome. Therefore, purinergic signaling in the skin could represent a new and early step of psoriasis; thus, opening the possibility to target single molecular actors of the purinome to develop new psoriasis treatments.

scholarly journals SEVERE COVID-19 IS MARKED BY DYSREGULATED SERUM LEVELS OF CARBOXYPEPTIDASE A3 AND SEROTONIN

2021 ◽  
Author(s):  
Rodolfo Soria-Castro ◽  
Yatsiri G. Meneses-Preza ◽  
Gloria M. Rodríguez López ◽  
Sandra Romero-Ramírez ◽  
Víctor A. Sosa-Hernandez ◽  
...  
Keyword(s):  
Immune Response ◽  
Mast Cells ◽  
Tissue Damage ◽  
Cell Activation ◽  
Viral Infections ◽  
Critical Role ◽  
Serum Levels ◽  
Mast Cell Activation ◽  
Activation Markers ◽  
Reactive Protein

AbstractThe immune response plays a critical role in the pathophysiology of SARS-CoV-2 infection ranging from protection to tissue damage. This is observed in the development of acute respiratory distress syndrome when elevated levels of inflammatory cytokines are detected. Several cells of the immune response are implied in this dysregulated immune response including innate immune cells and T and B cell lymphocytes. Mast cells are abundant resident cells of the respiratory tract, able to rapidly release different inflammatory mediators following stimulation. Recently, mast cells have been associated with tissue damage during viral infections, but little is known about their role in SARS-CoV-2 infection. In this study we examined the profile of mast cell activation markers in the serum of COVID-19 patients. We noticed that SARS-CoV-2 infected patients showed increased carboxypeptidase A3 (CPA3), and decreased serotonin levels in their serum. CPA3 levels correlated with C-reactive protein, the number of circulating neutrophils and quick SOFA. CPA3 in serum was a good biomarker for identifying severe COVID-19 patients, while serotonin was a good predictor of SARS-CoV-2 infection. In summary, our results show that serum CPA3 and serotonin levels are relevant biomarkers during SARS-CoV-2 infection, suggesting that mast cells are relevant players in the inflammatory response in COVID-19, might represent targets for therapeutic intervention.

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