Lyme disease is a tick-borne infection caused by Borrelia burgdorferi, a spirochetal bacterial pathogen [1] [2]. In approximately 80% of cases, cutaneous manifestations of this infection appear, predominantly in the form of erythema chronicum migrans (or erythema migrans), a pathognomonic finding of Lyme disease. It is described as an erythematous papule or macule at the site of the tick bite [3] [4] [5] [6]. The incubation period is variable (3-30 days), but in the majority of cases, erythema chronicum migrans is seen after 1-2 weeks and can occur on virtually any site of the body [1] [2] [5]. However, the waist, the extremities, the groins, the back, and the head and neck in the pediatric population are most frequent sites [4]. The progression of the erythematous macule, which may be asymptomatic, painful, or pruritic, eventually leads to a "target" or "bull's eye" lesion (as a central clearing around the center of the erythematous lesion is observed), with a diameter of > 5 cm, although a diameter as large as 60 cm has been reported [7] [8]. Numerous reports have confirmed that up to 30% of lesions exhibit significant variations [3] [5] [6] [7]. Firstly, multiple lesions can develop, the reason being the dissemination of the infection [3]. Secondly, an increasing number of cases present only with profound erythema and the absence of central clearing, thus the typical "target" lesion is not a mandatory finding in Lyme disease [5] [6]. Moreover, necrosis of the lesion, central hemorrhage, and formation of bullae are less common, but still possible variants of erythema chronicum migrans [1] [8]. It must be noted that numerous symptoms of Lyme disease can accompany erythema chronicum migrans, such as neurological deficits, fever, neck stiffness (suggesting meningitis), cardiac conduction abnormalities and arthritis (a sign of disseminated disease) [1] [2] [5].

• Fatigue

  Nausea, vomiting, and diarrhea are sometimes observed along with headache and fatigue. The rash fades with time and the patient can start to develop joint problems, susceptibility to infection, extreme fatigue, and a host of other symptoms. [wisegeek.com]

  This condition is often associated with systemic symptoms such as chills, fever, headache, malaise, nausea, vomiting, fatigue, backache, and stiff neck. synonyms Erythema Chronicum Migrans UMLS ECM - Erythema chronic migrans, ECM - Erythema chronicum [dermis.net]

  This condition is often associated with systemic symptoms such as chills, fever, headache, malaise, nausea, vomiting, fatigue, backache, and stiff neck. [profiles.umassmed.edu]

• Constitutional Symptom

  - Images in Clinical Medicine: Disseminated Lyme Disease - constitutional symptoms - flu like symptoms: fatigue, headache, myalgias, and arthralgias; - neurologic symptoms - neurologic symptoms may occur early or late; - look for headache, neck stiffness [wheelessonline.com]

• Nausea

  This condition is often associated with systemic symptoms such as chills, fever, headache, malaise, nausea, vomiting, fatigue, backache, and stiff neck. synonyms Erythema Chronicum Migrans UMLS ECM - Erythema chronic migrans, ECM - Erythema chronicum [dermis.net]

  This condition is often associated with systemic symptoms such as chills, fever, headache, malaise, nausea, vomiting, fatigue, backache, and stiff neck. [profiles.umassmed.edu]

• Abnormal Pulse

  Erythema chronicum migrans is also associated with flu-like symptoms including fever, headache, fatigue, headache, sore throat, abnormal pulse, neck stiffness and pain, pain and swelling of one or more large joints, numbness or tingling sensation of hands [dermatalk.com]

• Erythema

  In approximately 80% of cases, cutaneous manifestations of this infection appear, predominantly in the form of erythema chronicum migrans (or erythema migrans), a pathognomonic finding of Lyme disease. [symptoma.com]

  Southern tick-associated rash illness (STARI) produces a similar rash pattern although it develops more quickly and is smaller. [12] This erythema is also sometimes called erythema migrans [13] or EM. [en.wikipedia.org]

  Only two of the erythema chronicum migrans patients had IgG or IgM antibodies to flagellin. However, all seven morphea lesions as well as the other lesions were polymerase chain reaction negative. [ncbi.nlm.nih.gov]

• Erythema Annulare

  It is very similar to erythema annulare centrifugum, except that the advancing edge is frequently broader, up to a centimeter of raised erythema. It is associated with an arthritis known as Lyme arthritis. [skincareguide.ca]

  Erythema annulare entstanden durch Insektenstiche. Arch Dermatol Syph. 1910; 105: 423–430 View in Article Google Scholar [jaad.org]

  Erythema Annulare Centrifugum (Overview) Erythema Annulare Centrifugum: Background, Pathophysiology, Etiology Edition: No Results No Results Please confirm that you would like to log out of Medscape. [tripdatabase.com]

  Afzelius erythema - single lesions of erythema annulare centrifugum which erupt and spread. [medical-dictionary.thefreedictionary.com]

• Larva Migrans

  Cutaneous Larva Migrans Cutaneous larva migrans is a roundworm (usually hookworm) infection.Cutaneous Larva Migrans is abbreviated CLM. [evidence.nhs.uk]

  … … Medical dictionary Erythema migrans — is a term used to describe two very different types of erythema: * Erythema chronicum migrans * Geographic tongue … Wikipedia migrans — see ERYTHEMA CHRONICUM MIGRANS, LARVAL MIGRANS, LARVA MIGRANS … Medical [medicine.academic.ru]

• Skin Lesions with Central Clearing

  A Skin lesion with central clearing, in right lower quadrant of abdomen. Raised lesion marks indicate from which area the attached tick was removed. [doi.org]

• Subcutaneous Nodule

  nodules RA *Excludes rheumatic vasculitis diseases. [tripdatabase.com]

• Headache

  General symptoms such as headache, fever, myalgia and/or arthralgia were found in about half of the patients with a disease duration of less than or equal to 3 weeks. Three patients had coexisting lymphadenosis benigna cutis. [ncbi.nlm.nih.gov]

  This condition is often associated with systemic symptoms such as chills, fever, headache, malaise, nausea, vomiting, fatigue, backache, and stiff neck. synonyms Erythema Chronicum Migrans UMLS ECM - Erythema chronic migrans, ECM - Erythema chronicum [dermis.net]

  This condition is often associated with systemic symptoms such as chills, fever, headache, malaise, nausea, vomiting, fatigue, backache, and stiff neck. [profiles.umassmed.edu]

• Neglect

  Cameron has proposed that despite the controversy surrounding persistent Lyme disease symptoms, evidence to deny care is lacking and to do so is neglectful to patient care. [dermaamin.com]

The importance of recognizing erythema chronicum migrans lies in the fact that up to 60% of patients have negative serology tests for B. burgdorferi in the first several weeks of the infection [5]. For this reason, a meticulous physical examination supported by data obtained during patient history is the pivotal step in confirming Lyme disease and observing its hallmark lesion [6]. Physicians must inquire whether patients reside in or have recently visited at-risk areas, and note the signs and symptoms that possibly suggest an infectious etiology, while the course and progression of the skin lesion should also be discussed with the patient (if the patient had noticed the lesion etc.). The entire body should be examined in order to exclude multiple erythema chronicum migrans, and a close inspection, as well as palpation of the lesion, is vital for raising clinical suspicion of Lyme disease as a potential diagnosis [1] [2] [4] [7] [8]. Physicians must be aware of the incubation period of erythema chronicum migrans, its variable presentation, and the broad differential diagnosis [4]. In all patients in whom this lesion is suspected, microbiological investigation to confirm Lyme disease is mandatory. As serologic testing may be initially negative, blood cultures, biopsy samples of the lesion and polymerase chain reaction (PCR) testing can be implemented [1] [2] [5] [6]. But because of their limited use and sensitivity/specificity in the absence of erythema chronicum migrans, clinical assessment remains the most important part of Lyme disease workup.

• Rickettsia Akari

  This indicates that ECM and related diseases are not due to an hitherto known rickettsia. 5 out of 158 tests showed, however, positive reactions in low titers against Rickettsia akari and Coxiella burnetii. [ncbi.nlm.nih.gov]

1. Murray PR, Rosenthal KS, Pfaller MA. Medical Microbiology. Seventh edition. Philadelphia: Elsevier/Saunders; 2013.
2. Mandell GL, Bennett JE, Dolin R. Mandel, Douglas and Bennett's Principles and Practice of Infectious Diseases. 8th ed. Philadelphia, Pennsylvania: Churchill Livingstone; 2015.
3. Eriksson P, Schröder MT, Niiranen K, Nevanlinna A, Panelius J, Ranki A. The many faces of solitary and multiple erythema migrans. Acta Derm Venereol. 2013;93(6):693-700.
4. Juckett G. Arthropod bites. Am Fam Physician. 2013;88(12):841-847.
5. Shapiro ED. Lyme Disease. N Engl J Med. 2014;370(18):1724-1731.
6. Aucott J, Morrison C, Munoz B, Rowe PC, Schwarzwalder A, West SK. Diagnostic challenges of early Lyme disease: Lessons from a community case series. BMC Infect Dis. 2009;9:79.
7. Schutzer SE, Berger BW, Krueger JG, Eshoo MW, Ecker DJ, Aucott JN. Atypical Erythema Migrans in Patients with PCR-Positive Lyme Disease. Emerg Infect Dis. 2013;19(5):815-817.
8. Wetter DA, Ruff CA. Erythema migrans in Lyme disease. CMAJ. 2011;183(11):1281.