Lyme Disease Clinical Presentation
- Author: John O Meyerhoff, MD; Chief Editor: Burke A Cunha, MD more...
History
Because only approximately 25-30% of US patients with early Lyme disease recall the tick bite, the history must be directed by the clinician towards the possibility of a tick bite (in Europe, 64% do not remember being bitten). Patients are generally unaware of a tick bite because these ticks are extremely small and their bites are often painless.
Epidemiologic context is extremely important. Determining where the patient lives, works, and vacations is important, as is asking about specific activities in which the patient participates at those locales. The likelihood of Lyme disease increases as the probability of a tick bite increases in a geographically endemic area (particularly wooded, brushy, or grassy habitats). Endemic areas can be defined as those with established populations of vector ticks and evidence of enzootic transmission of B burgdorferi between the tick and the resident animal population.
The season is important, especially in patients with early disease. Most cases of erythema migrans occurs from May through September, because the nymphal stage of the tick is responsible for most cases. For patients presenting with later cutaneous manifestations, especially acrodermatitis chronica atrophicans, questions must be directed at assessing the risk of tick bite (or previous manifestations of Lyme disease) from many years in the past.
Because people who engage in activities that put them in risk for tick bites tend to continue those activities, reinfection is not uncommon. Patients who have previously had erythema migrans can be reinfected (meaning that the first infection has been successfully treated, and they have a new infection with B burgdorferi). This has been clearly demonstrated in reinfected patients who were culture positive and had different serotypes isolated in the first and second infections. Reinfection shows similar manifestations as first infections, although a tendency towards less hematogenous spread is noted. In contrast, relapse (as opposed to reinfection) is very unusual in patients who have been treated with appropriate antimicrobials.[20]
Certain manifestations of Lyme disease are related to the particular strain of Borrelia involved. In the United States, isolates from the East Coast are known as B burgdorferi sensu stricto, and infection with this organism has a particular predilection to affect joints, whereas other strains are more common in Europe, such as B burgdorferi afzelii, which is associated with acrodermatitis chronica atrophicans.
Similar to syphilis, the manifestations of Lyme disease have been divided into 3 stages: localized, disseminated, and persistent. However, in individual patients, no rigid cutoffs exist between stages. The first 2 stages are part of the early infection, whereas persistent disease is considered late infection. Unlike syphilis, stage 3 disease may occur within 1 year of infection, not many years later.
Stage 1 - Early localized infection (1-30 d after the bite)
Early localized Lyme disease refers to isolated erythema migrans and patients who present with an undifferentiated febrile illness.
Erythema migrans may be asymptomatic or it may itch or burn. It often occurs at or near the site of the tick bite, which may be an area not normally visualized by individuals, such as the axilla, groin, or popliteal areas. Most patients present with a characteristic expanding rash at the site of the tick bite 7-14 days after the tick is removed. The rash may not be observed until it is already full size. See the images below.
Erythema migrans, the characteristic rash of early Lyme disease. 
Photo of the left side of the neck of a patient who had pulled a tick from this region 7 days previously. Note the raised vesicular center, which is a variant of erythema migrans. The patient had a Jarisch-Herxheimer reaction approximately 18 hours after the first dose of doxycycline. 
Photo of the torso of a young man who had been working outdoors in northern New Jersey in late June. He was under treatment for a spider bite, although he did not have a history of a bite and had no pain, as is typical in a spider bite. The location, size, and epidemiologic context favor a diagnosis of erythema migrans. Examination was remarkable for a palpable right axillary lymph node. His symptoms resolved within 48 hours of initiating doxycycline. Note that although many patients present with erythema migrans, others first present with extracutaneous symptoms, either because erythema migrans never occurred or because it was not recognized by the patient or correctly diagnosed by the physician.
Untreated, the rash may persist for 2-3 weeks. Eighty percent of patients with Lyme disease have only one episode of erythema migrans, whereas 20% may have recurrent episodes. Multiple lesions may occur in 40% of patients with Lyme disease and are not the result of multiple tick bites (see the following image).
Multiple lesions of erythema migrans occur in approximately 20% of patients. A carpenter from Nantucket who worked predominantly outside had been treated with Lotrisone for 1 week before presenting to the emergency department with the rashes seen in this photo. The patient had no fever and only mild systemic symptoms. He was treated with a 3-week course of oral antibiotics. Approximately 50% of patients describe flulike symptoms (nonspecific febrile illness) within days to 1 week of infection, although a paucity of respiratory and gastrointestinal tract symptoms may be present. Another diagnostic clue is prompt resolution using antiborrelial therapy. Other symptoms include fatigue and myalgia (80% of patients with Lyme disease in the US but < 35% in Europe), as well as arthralgia, headache, fever, chills, and neck stiffness, which may resolve spontaneously even if specific therapy is not initiated.
Approximately one third of all patients with erythema migrans develop no further manifestations of Lyme disease, whereas two thirds of patients develop further symptoms (stages 2 and 3).
It is also important to consider co-infection by other organisms transmitted by the same tick bite. Co-infection by ehrlichial species and Babesia microti are reported with increased frequency; in some studies, co-infection is in as many as 10-15% of patients with Lyme disease. When Lyme disease is strongly suggested but some of the manifestations are atypical (eg, a high fever, especially if accompanied by rigors or a toxic appearance) these other tick-borne infections or an alternative diagnosis must be considered.
Stage 2 - Early disseminated LD (weeks to months after the bite)
Early disseminated disease refers to the secondary (usually hematogenously spread) skin lesions and to the extracutaneous manifestations that occur during the initial weeks to months of infection. Symptoms related to this stage occur in at least 50% of all untreated patients.
One or more organ systems become involved as hematologic or lymphatic spread disseminates spirochetes to distant sites. Musculoskeletal and neurologic symptoms are the most common; less common symptoms are cardiac disturbances such as dizziness, syncope, dyspnea, chest pain, and palpitations. The most common cardiac abnormality is atrioventricular block. Fibrinous pericarditis has also been described.
Intermittent inflammatory arthritis often begins as a migratory polyarticular process involving bursae, tendons, and joints, which evolves over 1-2 days into a monoarticular process involving the knee, ankle, and wrist, in decreasing frequency. When asked about their symptoms after they have resolved, patients with Lyme disease are less likely to remember those symptoms that occurred before the monoarthritis. Polyarticular episodes may also occur.
In two thirds of patients, the first episode occurs within 6 months of the erythema migrans lesion. Untreated, the episodes last approximately 1 week. Two thirds of patients have 3 recurrences approximately 2.5 months apart. The recurrences are more likely to involve more than one joint than the initial event. With time, these episodes become less frequent and severe and involve fewer joints. Even without treatment, the recurrent episodes usually resolve over a 10-year period.
Some patients may present with intermittent joint pain without inflammatory findings. This is more common in Europe, where arthritis was not recognized as a manifestation of Lyme disease until the early reports from the United States.
Patients with borrelial lymphocytoma report a bluish red nodular swelling that is almost always on the lobe of the ear or the areola of the nipple (see the following image). Occasionally, borrelial lymphocytoma lesions occur on the scrotum, nose, and extremities. Nipple lesions tend to be painful, possibly because of rubbing against clothing. Erythema migrans may occur simultaneously with borrelial lymphocytoma, which indicates that borrelial lymphocytoma can occur very early in the disease course.
Borrelial lymphocytoma of the earlobe, which shows a bluish red discoloration. The location is typical in children, as opposed to the nipple in adults. This manifestation of Lyme disease is uncommon and occurs only in Europe. Courtesy of Lyme Disease Foundation, Hartford, Conn. Neurologic involvement, also known as Lyme neuroborreliosis, is reported in 5-20% of cases. In the United States, cranial neuropathy (usually of cranial nerve 7) is the most common manifestation of early neurologic Lyme disease. When meningitis is involved, symptoms usually occur 2-10 weeks following infection. Headache, neck pain or stiffness, and photophobia typically indicate meningeal irritation.
Borrelia encephalopathy most commonly manifests as a mild confusional state accompanied by disturbances in memory, concentration, mood, sleep, personality, and/or language occurring months to years after the infection. Depression and irritability are also common.
Stage 3 - Chronic Lyme disease (months to years after infection and may occur after a period of latency)
Late or chronic Lyme disease refers to manifestations, primarily rheumatologic and neurologic, that occur months to years after the initial infection. The neurologic abnormalities are apparent in both the central (CNS) and peripheral (PNS) nervous systems. Typical presentations of late-stage neurologic Lyme disease include subacute encephalopathy, chronic progressive encephalomyelitis, and late axonal neuropathies, as well as symptoms consistent with fibromyalgia.
Borrelia encephalomyelitis is a rare but severe and slowly progressive syndrome that occurs in late disseminated disease. Symptoms can progress gradually or in a relapsing-remitting pattern, with partial improvement after the attacks. The most common clinical manifestations of Borrelia encephalomyelitis are hemiparesis, ataxia, seizures, cognitive impairment, bladder dysfunction, and hearing loss. Myelitis is present in 50% of patients with late neuroborreliosis. Progressive spastic paraparesis or quadriparesis is common.
Acrodermatitis chronica atrophicans also develops during this phase (see the image below and females, especially older patients, tend to be more commonly affected. Unlike erythema migrans, acrodermatitis chronica atrophicans tends to occur acrally, especially on the dorsal surfaces of the hands, feet, knees, and elbows. Early on, a minimally symptomatic erythema tends to occur in these locations. Initially, there is discoloration and inflammation; later, severe atrophy is noted.
Acrodermatitis chronica atrophicans is found almost exclusively in European patients and comprises an early inflammatory phase and a later atrophic phase. As the term suggests, the lesion occurs acrally and ultimately results in skin described as being like cigarette paper. Courtesy of Lyme Disease Foundation, Hartford, Conn. Other manifestations of the disease may coexist or may have occurred in the past. Thus, a history of Bell palsy, aseptic meningitis, arthritis, acral paresthesias or dysesthesias (from peripheral neuropathy), or cognitive dysfunction (from CNS involvement) may be diagnostically useful.
Physical Examination
In many patients with early Lyme disease, physical examination alone is sufficient to establish the diagnosis of erythema migrans. Careful attention to the details often makes the difference between the need to proceed with further confirmatory tests and an empiric course of antibiotics. In particular, the examination must be interpreted in the epidemiologic context; this cannot be overemphasized. The season, geography, and a patient's activities in those areas can be important diagnostic clues.
Regional lymphadenopathy may be seen, and a low-grade fever is not uncommon. High fever suggests another co-infecting tick-borne organism such as Ehrlichia or Babesia species or some other diagnosis altogether, such as streptococcal cellulitis.
Erythema migrans
As many as 90% of infected patients have a characteristic expanding rash at the site of the tick bite. Classic erythema migrans begins as an erythematous macule or papule at the site of the tick bite (within 1-33 d; median is 7-10 d).[21] Often a central punctum is seen at the site of the bite. The eruption gradually expands over days to weeks (not hours or months).
The entire lesion may be uniform in color or central clearing may be present (one third of US cases and two thirds of European cases). Although most lesions are flat erythemas, several variations are important to recognize, in particular, vesicular and centrally necrotic lesions. More proximal to the clearing may be additional erythema leading to a so-called "bull's eye" or “target” appearance (see the following images); however, this phenomenon, emphasized in the earlier literature, occurs only in a minority of patients (37% in one North American study). The center may be scaly or discolored. Single lesions may achieve a diameter of approximately 5-6 inches (approximately 16 cm). Without therapy, erythema migrans typically fades within 3-4 weeks.
Classic target lesion with concentric rings of erythema, which often show central clearing. Although this morphology was emphasized in earlier North American literature, it only represents approximately 40% of erythema migrans lesions in the United States. This pattern is more common in Europe. Courtesy of Lyme Disease Foundation, Hartford, Conn. 
Typical appearance of erythema migrans, the bull's-eye rash of Lyme disease. 
Bulls-eye rash. 
rash. Courtesy of M. Fergione, B. Tucker, and L. Zernel; Pfizer Laboratories Secondary erythema migrans lesions tend to be more uniform in morphology than the primary lesion. Necrosis and vesicles do not occur, nor does a central punctum. Because, they are spread hematogenously, the locations of secondary lesions are not as restricted as in the primary lesion (see the image below).
Multiple lesions of erythema migrans occur in approximately 20% of patients. A carpenter from Nantucket who worked predominantly outside had been treated with Lotrisone for 1 week before presenting to the emergency department with the rashes seen in this photo. The patient had no fever and only mild systemic symptoms. He was treated with a 3-week course of oral antibiotics. Note that rashes very similar to erythema migrans have been reported in the southern United States from which B burgdorferi cannot be cultured. This disease is called southern tick-associated rash illness (STARI), or Master disease. As a group, distinctions can be made between classic erythema migrans and this illness, but significant overlaps exist such that the differences are not useful in diagnosing individual patients.
An erythematous skin lesion present while an Ixodes tick is still attached is most likely a hypersensitivity reaction rather than erythema migrans. Hypersensitivity reactions also tend produce smaller (< 5 cm) lesions, which typically begin to disappear in the first 2 days. In contrast, erythema migrans starts as a flat to slightly raised erythematous lesion at the site of the tick bite within days to weeks.
Borrelial lymphocytoma
In less than 1% of patients, Borrelia lymphocytoma, described as a small, bluish-red nodule or plaque may develop on the earlobe or nipple; the earlobe and scrotum are the typical location in children (see the image below), whereas the nipple location is more commonly seen in adults. Borrelial lymphocytoma tends to occur in areas of previous (or concurrent) erythema migrans and may be up to a few centimeters in size. Regional lymphadenopathy may be present. Other terms used to describe borrelial lymphocytoma include lymphadenosis benigna cutis, lymphocytoma cutis, cutaneous lymphoid hyperplasia, and Spiegler-Fendt lymphoid hyperplasia.
Borrelial lymphocytoma of the earlobe, which shows a bluish red discoloration. The location is typical in children, as opposed to the nipple in adults. This manifestation of Lyme disease is uncommon and occurs only in Europe. Courtesy of Lyme Disease Foundation, Hartford, Conn. Other skin lesions have been associated with B burgdorferi infection, but whether they are part of the syndrome of Lyme disease is controversial. The lesion for which the most evidence of causality has been reported is morphea (localized scleroderma), which develops in roughly 10% of European patients with borrelial lymphocytoma and acrodermatitis chronica atrophicans. B burgdorferi has been isolated from these lesions but not from North American patients with morphea. Other European reports less commonly link lichen sclerosis et atrophicans, progressive facial hemiatrophy (Parry-Romberg syndrome), and eosinophilic fasciitis with B burgdorferi infection.
Acrodermatitis chronica atrophicans
Acrodermatitis chronica atrophicans is a relatively uncommon physical manifestation of chronic Lyme disease that begins as an inflammatory phase marked by edema and erythema, usually on the distal extremities; at times, a faint bluish discoloration is found predominantly on extensor surfaces. The lesions have a predilection for the posterior heels and dorsal (extensor) surfaces of the hands, feet, elbows, and knees. The lesions also tend to become symmetric. The buttocks often become involved.
Later, atrophy supervenes and thin cigarette-paper skin is seen, as shown in the following image, with an appearance similar to scleroderma. Because of the loss of subcutaneous fat, underlying venous structures are more visible, and the skin becomes thin, atrophic, and dry. Fibrous juxtaarticular nodules or bands may be seen on the extensor surfaces of the elbows and knees. One third of patients with acrodermatitis chronicum have an associated sensory polyneuropathy.
Acrodermatitis chronica atrophicans is found almost exclusively in European patients and comprises an early inflammatory phase and a later atrophic phase. As the term suggests, the lesion occurs acrally and ultimately results in skin described as being like cigarette paper. Courtesy of Lyme Disease Foundation, Hartford, Conn. Lyme arthritis
Approximately 60% of all patients develop symptoms of intermittent migratory monoarthritis. Episodes last a mean of 3 months and very often affect the knee or temporomandibular joints, although not universally. Joint symptoms develop in approximately 80% of all untreated patients within 2 years of infection.
The severity of joint involvement can range from intermittent episodes of subjective pain to frank arthritis to chronic erosive synovitis. The knee joints are commonly affected, although migratory oligoarthritis involving the small or large joints can occur. During the attacks, the joints are swollen, hot, and painful, but they are not usually red or as severe as in a septic joint. Effusions may be large and generally recur following aspiration, as is often seen in spondyloarthropathies.
Less than 10% of patients with arthritic sequelae develop pannus or erosion of cartilage and bone.
Neurologic involvement
Approximately 5-10% of untreated patient with Lyme disease have signs of cranial neuropathies, and up to 60% of patients with early neuroborreliosis develop cranial neuritis. Seventh nerve palsy is by far the most common. Bilateral facial palsy can be seen in 35% of patients and is a unique characteristic that is useful for distinguishing it from idiopathic Bell palsy and other disorders. Typical associated findings depend on the nerve affected and can include visual or auditory disturbances, facial paresthesia, and/or vertigo. Other neurologic manifestations include diffuse or focal mononeuropathy multiplex (multifocal involvement of anatomically unrelated nerves), plexopathy, and/or radiculoneuropathy (more common in Europe). Less common presentations include myositis, pseudotumor cerebri, and cerebellitis.
Lyme meningitis is relatively common, occurring in as many as 15% of untreated patients bitten by the Ixodes tick and in 30% of Lyme disease cases, and does not manifest as the usual signs of bacterial meningitis (boardlike rigidity, Kernig and Brudzinski signs). Meningitis may be accompanied by cranial or peripheral radiculoneuropathy.
Acute radiculoneuritis is reported in 50-85% of cases. Acute onset of motor deficits, severe radicular pain, and sensory loss are commonly seen after 2-4 weeks of infection. Multifocal asymmetric weakness is a common presentation. Although the presentation of inflammatory radiculoneuropathy is often indistinguishable from that of spinal-root compression, involvement of the thorax of multiple dermatomes and a lack of a precipitating injury can aid in diagnosis.
For peripheral neuropathy, patients usually report intermittent paresthesias. The most frequent finding upon examination is decreased vibratory sensation of the distal lower extremities. A "stocking glove" distribution of epicritic sensory deficits is also a common finding.
Chronic radicular paresthesias are usually not associated with motor or sensory deficits, and the physical examination results are normal.
With late axonal neuropathy, patients can report intermittent distal limb paresthesias months to years after infection. It is distinct from the neuropathy of early Lyme disease, because the symptoms are less severe. Acrodermatitis chronica atrophicans–associated neuropathy is common in Europe and manifests as neuropathic pain, paresthesias, and muscle cramps.
In Europe, common manifestations of Garin-Boujadoux-Bannwarth syndrome (Bannwarth syndrome) include neuritic pain, cranial neuritis without headache, and lymphocytic pleocytosis. Bannwarth syndrome has also been called tick-borne meningopolyneuritis, lymphocytic meningoradiculitis, and chronic lymphocytic meningitis.
Neuropsychiatric findings are controversial and include manifestations of late-stage disease or post-Lyme disease syndrome, including depression, anxiety, schizophrenialike psychosis, bipolar disorder, and dementia.
Cardiac involvement
Cardiac involvement ranges from atrial or ventricular arrhythmias to transient heart block or myopericarditis. Approximately 8% of untreated patients have acute-onset atrioventricular conduction abnormalities. Most cardiac episodes are isolated and transient, lasting less than a week. In rare instances, patients with heart block require electrical pacing.
Ophthalmic involvement
Less than 5% of untreated patients have ophthalmic manifestations such as iritis, keratitis, retinal vasculitis, or optic neuritis.
Go to Ophthalmic Aspects of Lyme Disease for complete information on this topic.
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