ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Lyme disease: Clinical manifestations in children

Lyme disease: Clinical manifestations in children
Literature review current through: Jan 2024.
This topic last updated: Jun 07, 2022.

INTRODUCTION — Lyme disease is a tick-borne illness primarily caused by a number of pathogenic genomospecies of the spirochete Borrelia burgdorferi sensu lato ("in the broad sense") [1]. The nomenclature of Borrelia that cause human infections is in transition and the genus name may be represented as either Borrelia or Borreliella. (See "Microbiology of Lyme disease".)

Lyme disease has a broad spectrum of clinical manifestations which vary, in part, due to differences in the infecting genomospecies. B. burgdorferi sensu stricto ("in the narrow sense") is the primary cause of Lyme disease in the United States. Another genomospecies, Borrelia mayonii, causes Lyme disease in the northern Midwestern states, with clinical manifestations and serologic changes similar to those of disease caused by B. burgdorferi [2]. B. burgdorferi sensu stricto, Borrelia afzelii, and Borrelia garinii and a number of other genomospecies may cause disease in Europe, and B. afzelii and B. garinii have been identified in Asia.

The clinical manifestations of Lyme disease in children will be reviewed here. The clinical manifestations of Lyme disease in adults and the microbiology, epidemiology, treatment, and prevention of Lyme disease are discussed separately. (See "Epidemiology of Lyme disease" and "Clinical manifestations of Lyme disease in adults" and "Diagnosis of Lyme disease" and "Treatment of Lyme disease" and "Prevention of Lyme disease".)

OVERVIEW — The clinical manifestations of Lyme disease depend on the stage of the illness [3-5]:

Early localized disease

Early disseminated disease

Late disease

The clinical manifestations of Lyme disease in children were described in a community-based prospective study of 201 Connecticut children with Lyme disease [6]. The median age was seven years (range 1 to 21 years). The presenting manifestations were as follows:

Erythema migrans – 89 percent (single erythema migrans: 66 percent; multiple erythema migrans: 23 percent)

Arthritis – 7 percent

Facial palsy – 3 percent

Aseptic meningitis – 1 percent

Carditis – 0.5 percent

The basic features of Lyme disease are similar worldwide, but there are regional variations, primarily between the illness found in the United States and that found in Europe and Asia. (See "Clinical manifestations of Lyme disease in adults", section on 'United States versus Europe'.)

EARLY LOCALIZED DISEASE

Timing and serologic response — During early localized disease (ie, within the first two to three weeks of infection), serologic testing is not sufficiently sensitive to be helpful in diagnosis [7-10]. In a community-based prospective study of 201 children with Lyme disease, only 19 percent of those with a single erythema migrans lesion had positive immunoglobulin (Ig)G serology for B. burgdorferi at the time of presentation, compared with 58 percent of those with multiple erythema migrans [6]. (See "Diagnosis of Lyme disease".)

Erythema migrans — Early localized Lyme disease is manifest by a single erythema migrans lesion (picture 1A-B). Erythema migrans is a rash that appears at the site of the tick bite, usually within 7 to 14 days after the bite (range 3 to 30 days) [11]. In the United States, erythema migrans (including multiple erythema migrans, discussed below) is the only manifestation of Lyme disease that permits clinical diagnosis without laboratory confirmation (although it may be clinically indistinguishable from the rash of Southern tick-associated rash illness) [12]. (See "Southern tick-associated rash illness (STARI)".)

Clinical features — Erythema migrans begins as a red macule at the site of attachment of the tick. The most frequent sites for a single erythema migrans lesion in children are [13]:

Head and neck (26 percent)

Arms and legs (25 percent)

Back (24 percent)

Abdomen (9 percent)

Axilla (8 percent)

Groin (5 percent)

Chest (3 percent)

The lesion is more likely to occur on the head or neck in younger children and on the extremities in older children [6].

Untreated, the rash expands over the course of days to weeks to form a large, annular, erythematous lesion that is at least 5 cm and as many as 70 cm in diameter (median 15 cm). Although the propensity for the rash to develop clearing in the center and a "bull's eye" appearance (picture 1A) is well publicized, most commonly the rash is uniformly erythematous (picture 1B). This was illustrated in a cohort of 118 adult patients with erythema migrans and B. burgdorferi infection (confirmed by culture or polymerase chain reaction) [14]. The lesion was homogeneous in 59 percent, had central erythema in 32 percent, and central clearing in only 9 percent.

Erythema migrans lesions usually are flat and without scale; they may be pruritic or burning but are rarely painful [13,15]. The lesions occasionally may have vesicular or necrotic areas in the center related to an intense inflammatory response (picture 2) [14,16]. Vesicular-appearing erythema migrans lesions usually are not pruritic; this lack of pruritus and the large area of erythema without vesicles help to distinguish vesicular erythema migrans from contact dermatitis (eg, poison ivy) [10].

Erythema migrans is annular, but the lesion can vary greatly in shape and rarely is perfectly round. A perfectly round lesion should prompt consideration of other diagnoses, such as nummular eczema or erythema multiforme. (See 'Differential diagnosis' below.)

Differential diagnosis — The differential diagnosis of erythema migrans includes a number of dermatologic conditions that usually can be differentiated from erythema migrans by clinical features, such as morphology, size, secondary changes (eg, scale, crusting), pruritus, location, and/or pain.

If there is uncertainty about whether a rash is erythema migrans, it is reasonable to observe the rash and follow the patient closely for 24 to 48 hours, provided that the patient is not severely ill. Erythema migrans will persist and increase in size. If the lesion disappears in a few days without treatment, it is unlikely to have been erythema migrans. (See "Diagnosis of Lyme disease", section on 'Serologic tests'.)

Tick bite hypersensitivity reaction – Tick bite hypersensitivity reactions typically develop while the tick is attached or within 48 hours of removal [10]. They are usually <5 cm in largest diameter and sometimes urticarial. In contrast to erythema migrans, which enlarge over time, tick bite hypersensitivity reactions usually begin to disappear within 24 to 48 hours.

Southern tick-associated rash illness – Southern tick-associated rash illness (STARI) is associated with an erythema migrans-like rash and mild flu-like symptoms. STARI was first described in patients from Missouri and the southeastern United States. It should be considered in patients with appropriate clinical features who are from non-Lyme-endemic areas. Its frequency in Lyme-endemic areas is unknown. (See "Southern tick-associated rash illness (STARI)".)

Nummular eczema – Nummular eczema is a dermatitis consisting of spontaneous eruption of one or more circular lesions (2 to 10 cm in diameter) with papules, scale, and/or crusting, typically distributed on the trunk or extremities, with sparing of the head. The lesions are intensely pruritic. (See "Nummular eczema".)

Tinea corporis – Tinea corporis (ringworm) is a dermatophyte infection that begins as a pruritic circular or oval erythematous scaling patch or plaque that spreads centrifugally. Central clearing follows, while the active advancing border, a few millimeters wide, remains red and slightly raised (picture 3). Multiple lesions may coalesce to form "flower petal" configurations. (See "Dermatophyte (tinea) infections", section on 'Tinea corporis'.)

Cellulitis – Cellulitis is an infection of the deep dermis and subcutaneous fat without an underlying suppurative focus; it manifests with erythema, edema, and warmth [10]. Erythema migrans lesions typically occur at sites that would be unusual for cellulitis (eg, axilla, popliteal fossa, abdomen). (See "Cellulitis and skin abscess: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

Granuloma annulare – Granuloma annulare is characterized by papules or nodules grouped in a circular configuration; the lesions range from 0.5 to several centimeters in diameter [17]. Granuloma annulare lesions typically have raised borders, which distinguishes them from erythema migrans. (See "Granuloma annulare: Epidemiology, clinical manifestations, and diagnosis", section on 'Clinical features'.)

Spider and other bites – (See "Diagnostic approach to the patient with a suspected spider bite: An overview".)

Erythema multiforme – Erythema multiforme is an acute eruption characterized by distinctive circular target lesions (picture 4). It has no prodrome and a typically benign clinical course. (See "Erythema multiforme: Pathogenesis, clinical features, and diagnosis".)

Associated findings — Localized erythema migrans may be accompanied by systemic findings, such as fever (24 percent), fatigue (58 percent), headache (42 percent), neck pain (26 percent), arthralgia (33 percent), or myalgia (16 percent) [6].

History of tick bite — Most cases of Lyme disease result from tick bites that are not recognized. In a community-based prospective study, only 36 percent of 132 children with Lyme disease and a single erythema migrans lesion had had a recognized tick bite in the preceding month [6]. Among these, the bite was at a site different than the lesion in 38 percent (indicating that the infection was transmitted by a different, unrecognized tick).

Thus, the absence of a recognized tick bite does not exclude Lyme disease as long as exposure to a vector tick in an endemic area is a possibility. Likewise, a history of a tick bite on a different part of the body, or in the more distant past, should be viewed as evidence of potential tick exposure rather than evidence that the lesion is not erythema migrans. (See "Epidemiology of Lyme disease" and "Evaluation of a tick bite for possible Lyme disease" and "Diagnosis of Lyme disease".)

EARLY DISSEMINATED DISEASE

Timing and serologic response — Early disseminated Lyme disease usually occurs weeks to several months after the tick bite. If Lyme disease is not recognized or treated during the early localized stage, the spirochete may enter the bloodstream and disseminate to tissues throughout the body, potentially including the central nervous system (CNS) and the heart [3-5]. The likelihood of dissemination appears to be related to the genotype of the strain of the bacteria that is causing the infection [18].

At least 90 percent of children with extracutaneous early disseminated Lyme disease have positive serology. (See "Diagnosis of Lyme disease".)

Clinical manifestations — The clinical manifestations of early disseminated Lyme disease in children include multiple erythema migrans (picture 5), cranial nerve palsy (especially facial nerve palsy), meningitis, and carditis. Meningoradiculitis (Bannwarth syndrome), which occurs in adults, is virtually never seen in children [19]. (See "Clinical manifestations of Lyme disease in adults", section on 'Neurologic manifestations'.)

Systemic signs and symptoms, such as fever (45 percent), fatigue (80 percent), headache (70 percent), and arthralgia (50 percent), are common in this stage of Lyme disease [6].

Multiple erythema migrans — Multiple erythema migrans is the most common manifestation of early disseminated Lyme disease in the United States. In a prospective cohort of 201 children with Lyme disease, it was the presenting manifestation in 23 percent [6].

Secondary erythema migrans lesions usually appear three to five weeks after the tick bite and arise through hematogenous dissemination [11,20]. They consist of multiple annular erythematous lesions similar to, but usually smaller than, the primary lesion and are more often round (picture 5).

In the United States, multiple erythema migrans is a clinical diagnosis of Lyme disease and does not require laboratory confirmation [11]. (See "Diagnosis of Lyme disease".)

Neurologic manifestations

Cranial nerve palsy

Clinical features – Cranial nerve palsies, especially of the facial nerve (cranial nerve VII) are another common manifestation of Lyme disease in children [19,21,22]. In a prospective cohort of 201 children with Lyme disease, facial nerve palsy was the presenting manifestation in 3 percent [6]. Among 313 children living in a Lyme-endemic area who presented to a pediatric emergency department with facial nerve palsy, 34 percent had Lyme disease [23]. Factors associated with Lyme disease included onset of symptoms between June and October, fever, headache, and absence of history of herpetic lesions [24]. Because the majority of patients with facial palsy attributed to Lyme disease were diagnosed with Lyme disease based solely upon a positive IgM (for which false-positive results are common), the actual proportion due to Lyme disease may have been smaller.

Bilateral palsy of the facial nerves is virtually pathognomonic of Lyme disease (though it rarely may be caused by other conditions, such as lymphoma). The palsy in Lyme disease may be a result of mononeuritis multiplex, which is a peripheral neuritis, or of basilar meningitis with involvement of the facial nerve. (See "Facial nerve palsy in children".)

Facial nerve palsy associated with Lyme disease usually resolves completely with or without antimicrobial therapy, although persistence of minor, often clinically inapparent deficits is not uncommon [25-27]. Antimicrobial therapy is necessary to prevent other manifestations of Lyme disease, including late Lyme disease [28]. (See 'Late disease' below.)

Evaluation – It can be difficult to establish the diagnosis of Lyme disease in a patient with facial nerve palsy without erythema migrans [28]. In such patients, diagnosis depends upon serology. However, serology occasionally may not be positive until days or weeks after the onset of facial nerve palsy. If Lyme disease is suspected and initial serology is negative, serology should be repeated two to three weeks later. (See "Diagnosis of Lyme disease", section on 'Serologic tests'.)

Need for lumbar puncture – Decisions about lumbar puncture in children with cranial nerve palsy are individualized. Lumbar puncture may be warranted to exclude other causes of CNS infection, to permit a definitive diagnosis of CNS neuroborreliosis or evaluation for increased intracranial pressure, and to provide baseline cell counts for monitoring therapy [11]. We suggest that children who have facial nerve palsy and Lyme disease undergo lumbar puncture only if they have clinical evidence of CNS infection (eg, nuchal rigidity, papilledema, or a very severe headache) [28]. (See "Nervous system Lyme disease" and 'Meningitis' below.)

Some abnormalities will be found in the CSF in a large proportion of children with Lyme disease-associated facial nerve palsy who undergo a lumbar puncture [29-31]. However, the clinical significance of these abnormalities is not clear [28]. There is substantial evidence that such children (and adults) who are treated with oral antimicrobial agents have excellent outcomes with no or very minor long-term sequelae, even if they have CSF pleocytosis [6,30,32-39]. (See "Treatment of Lyme disease", section on 'Acute neurologic manifestations'.)

Meningitis — Meningitis is the presenting manifestation in approximately 1 percent of children with Lyme disease [6]. The presentation of Lyme meningitis is similar to that of aseptic meningitis. In Lyme-endemic areas during the summer and fall, it can be difficult to distinguish Lyme meningitis from enteroviral and other types of aseptic meningitis unless the patient has erythema migrans. (See "Viral meningitis in children: Epidemiology, pathogenesis, and etiology" and "Viral meningitis in children: Clinical features and diagnosis", section on 'Bacterial meningitis'.)

The clinical and laboratory features of Lyme meningitis and viral meningitis have been compared in several small series of patients [40-45]. Features that may be helpful in differentiating between enteroviral and Lyme meningitis include:

Children with Lyme meningitis tend to be older (median age of 10.5 versus 5.5 years) [41]

Children with Lyme meningitis tend to have a longer duration of symptoms before diagnosis (12 versus <7 days) [41,45]

Erythema migrans (by history or examination), cranial nerve palsy, and papilledema (from increased intracranial pressure) are strongly associated with Lyme meningitis but are uncommon in viral meningitis [40,41,43-45]

The proportion of polymorphonuclear cells in the CSF of children with Lyme meningitis is usually <10 percent, significantly lower than that observed in many children with meningitis due to enterovirus [41,42,45]

In rare cases, increased intracranial pressure may persist despite treatment with antibiotics and may require specific treatment to prevent permanent damage to vision [46,47]. Optic neuritis also has been reported to be caused by Lyme disease [46].

Carditis — Carditis, manifest by complete heart block, is a rare presenting manifestation of early disseminated Lyme disease in children [6]. In a prospective cohort of 201 children with Lyme disease, carditis was the presenting manifestation in only 0.5 percent [6]. Partial heart block, an incidental finding, may be more common. (See "ECG tutorial: Atrioventricular block".)

Lyme carditis is usually self-limited, although affected children may need a temporary pacemaker [48]. Rarely, Lyme carditis may be severe and can be a cause of serious myocarditis and even of death [48-50]. (See "Lyme carditis".)

Nonspecific symptoms — Patients with early, disseminated Lyme disease rarely may have only nonspecific symptoms similar to those caused by viruses (eg, with fever, malaise, myalgia) without erythema migrans or other manifestations of Lyme disease [51].

The frequency of fever and nonspecific symptoms as a presentation of Lyme disease is not known. However, information from clinical trials of Lyme vaccine, in which subjects had routine serology performed by a reference laboratory, suggests that it is uncommon (<0.3 percent of patients in the trial) [52].

We recommend that children with only nonspecific symptoms not be routinely tested for Lyme disease. It is virtually impossible to confirm a diagnosis of Lyme disease in such patients. Nonspecific symptoms of a viral-like illness from causes other than Lyme disease are common, particularly in children. Given the low prevalence of Lyme disease in the population of patients presenting with isolated nonspecific symptoms, the positive predictive value of serologic test results is low [7,53,54]. Most of the positive results will be falsely positive (figure 1). (See "Glossary of common biostatistical and epidemiological terms", section on 'Predictive values' and "Diagnosis of Lyme disease", section on 'Ability to confirm active disease'.)

Other manifestations — There are numerous case reports of involvement of a large variety of other organ systems during disseminated Lyme disease. However, these reports often are based on a positive serologic test result in a patient with no other evidence of Lyme disease and may be a consequence of either a false-positive test result or a prior infection, rather than a causal association.

LATE DISEASE

Timing — Late Lyme disease occurs weeks to months after the initial infection if the initial infection is not recognized or is not treated effectively.

Clinical manifestations

Arthritis — Arthritis is the most common manifestation of late Lyme disease. The arthritis is usually monoarticular or oligoarticular and affects the large joints, particularly the knee, which is involved in more than 90 percent of cases [11,55-58].

There is a wide spectrum in the acuity of the presentation of Lyme arthritis, and in some instances it may be confused with acute bacterial arthritis [55,59]. (See "Bacterial arthritis: Clinical features and diagnosis in infants and children", section on 'Clinical features'.)

Clinical features that may help to distinguish Lyme arthritis from acute bacterial arthritis include [55,59-61]:

In Lyme arthritis, the affected joint usually is swollen and may be tender, but the pain is less intense than that associated with bacterial arthritis.

Most children with Lyme arthritis of the knee can walk without difficulty despite some limitation in range of motion; most children with acute bacterial arthritis of the lower extremity refuse to bear weight.

In Lyme arthritis, associated fever is uncommon, and erythema of the involved joint is less common.

In Lyme arthritis, the synovial fluid white blood cell (WBC) count usually ranges from 20,000 to 60,000 cells/microL (but it can exceed 100,000 cells/microL), whereas in acute bacterial arthritis, the synovial fluid WBC count is usually >50,000 cells/microL (often >100,000 cells/microL) with a predominance of polymorphonuclear leukocytes (PMNs). Given the potential overlap in synovial fluid WBC count and proportion of PMNs, synovial fluid results cannot be used in isolation to distinguish Lyme arthritis from septic arthritis [62,63].

Rarely, inflammation of a joint may persist despite apparently adequate antimicrobial treatment leading to so-called antibiotic-refractory (or treatment-refractory) Lyme arthritis. Evidence suggests that the persistent inflammation may be due to an unusual peptidoglycan produced by B. burgdorferi that may drive inflammation and that may persist for a prolonged time despite eradication of the organism [64].

The natural history of untreated Lyme arthritis was illustrated in long-term follow-up of 46 children included in the initial description of Lyme disease [58,65]. None of the children received antimicrobial treatment in the four years after the initial diagnosis, and many never received antimicrobial treatment. Thirty-nine of the 46 patients were contacted 10 to 15 years later. Recurrent episodes of arthritis that were not treated were common during the early years after symptoms began. However, by 10 years, recurrent episodes of arthritis had resolved. There are virtually no reports of chronic Lyme arthritis in children.

The prognosis for children with treated Lyme arthritis is excellent [56,65,66]. The long-term outcome was evaluated in a telephone survey of 90 children who were diagnosed with Lyme arthritis between 1982 and 1991 (mean age 8.3 years; range 1.9 to 16 years) [56]. All but five children were treated with antimicrobial therapy at a median of two months after onset of symptoms (range 2 days to 5.5 years). Follow-up occurred at a median of seven years (range 2 to 12 years) after diagnosis. None of the patients had evidence of active arthritis, but four reported ongoing musculoskeletal complaints with mild to moderate impairment of activity.

CONGENITAL LYME DISEASE — There is no evidence of increased risk of abnormal outcomes with Lyme disease during pregnancy. Lyme disease in pregnancy is discussed separately. (See "Clinical manifestations of Lyme disease in adults", section on 'Pregnancy and breast feeding'.)

"CHRONIC LYME DISEASE" IN CHILDREN — Although there has been a great deal of publicity about "chronic Lyme disease" as the cause of nonspecific symptoms (eg, headache, fatigue, arthralgia) in both children and adults, there is no evidence that such an entity exists [11,67-70]. Indeed, there is no accepted definition of "chronic Lyme disease" for either clinical use or scientific study. Numerous studies from different academic medical centers have found that the great majority of patients labeled as having "chronic Lyme disease" had no evidence of Lyme disease based on either the history or the results of serologic testing [11]. In long-term (median five years) follow-up of 84 children with confirmed Lyme disease of the central nervous system, the frequency of occurrence of nonspecific subjective symptoms (approximately 40 percent) was similar among cases and controls [38].

There is substantial evidence that long-term treatment with antimicrobials for "chronic Lyme disease" is not associated with benefit, but is associated with a variety of potential deleterious effects including death, substantial financial expense, and selection of antimicrobial-resistant bacteria [67,68,71,72]. Moreover, patients treated with antimicrobials for "chronic Lyme disease" often fail to receive treatment for their actual illness or for relief of their symptoms. (See "Treatment of Lyme disease", section on 'Persistent symptoms after treatment'.)

"Chronic Lyme disease" probably falls in the category of illness known as medically unexplained symptoms [73]. Caregivers and patients should be cautioned about both the lack of benefit and the risks of long-term antimicrobial therapy, as well as the large amount of misinformation about Lyme disease on the internet [74]. It is important for clinicians to realize that many caregivers who are worried about symptoms in their children feel dismissed when a clinician brushes aside their fears, simply saying that their child does not have Lyme disease. Such caregivers and patients may benefit from a supportive, long-term relationship with a caregiver who will not dismiss their concerns.

BORRELIA MIYAMOTOI INFECTION — Borrelia miyamotoi, a Borrelia species in the same taxonomic group as the agents of relapsing fever, has been found in some of the same tick vectors and rodent reservoirs as for Lyme disease agents in North America, Europe, and Asia. B. miyamotoi is discussed separately. (See "Borrelia miyamotoi infection".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)

Basics topic (see "Patient education: Lyme disease (The Basics)")

Beyond the Basics topics (see "Patient education: Lyme disease symptoms and diagnosis (Beyond the Basics)" and "Patient education: Lyme disease treatment (Beyond the Basics)" and "Patient education: Lyme disease prevention (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Early localized Lyme disease – Early localized Lyme disease is manifest by a single erythema migrans lesion (picture 1A-B). Erythema migrans usually appears at the site of the tick bite within 7 to 14 days after the bite. In the United States, erythema migrans (including multiple erythema migrans (picture 5)) is the only manifestation of Lyme disease for which diagnosis can be based on clinical manifestations without laboratory confirmation. (See 'Erythema migrans' above and "Diagnosis of Lyme disease".)

Most cases of Lyme disease result from tick bites that are not recognized. In endemic areas, the absence of a recognized tick bite does not exclude Lyme disease. (See 'History of tick bite' above.)

Early disseminated Lyme disease – The clinical manifestations of early disseminated Lyme disease in children include (see 'Early disseminated disease' above):

Multiple erythema migrans (picture 5) (see 'Multiple erythema migrans' above)

Cranial nerve palsy (especially facial nerve palsy) Bilateral facial nerve palsy is virtually pathognomonic for Lyme disease. (See 'Cranial nerve palsy' above.)

We suggest that children who have facial nerve palsy and Lyme disease undergo lumbar puncture only if they have clinical evidence of central nervous system infection (eg, nuchal rigidity, papilledema, or a very severe headache). The clinical significance of cerebrospinal fluid (CSF) abnormalities in children with Lyme disease-associated facial nerve palsy and no signs of meningitis is unclear. (See 'Cranial nerve palsy' above.)

Lyme meningitis – The presentation of Lyme meningitis is similar to that of aseptic meningitis. Clinical features suggestive of Lyme meningitis include erythema migrans, cranial nerve palsy, papilledema, increased duration of symptoms, and less than 10 percent polymorphonuclear cells in the CSF. (See 'Meningitis' above.)

Lyme carditis – Lyme carditis, manifest by complete heart block, is a rare presenting manifestation of early disseminated Lyme disease in children. Although lyme carditis is usually self-limited, affected children may need a temporary pacemaker. (See 'Carditis' above.)

Nonspecific symptoms – Nonspecific symptoms alone without concomitant specific signs are a rare presentation of Lyme disease. We recommend not testing children with only nonspecific symptoms for Lyme disease; most of the positive results will be falsely positive. (See 'Nonspecific symptoms' above.)

Lyme arthritis (late Lyme disease) – Arthritis is the most common manifestation of late Lyme disease. The arthritis is usually monoarticular or oligoarticular and affects the large joints, particularly the knee. The pain of Lyme arthritis is usually less intense than that of bacterial arthritis. The long-term prognosis of Lyme arthritis in children is excellent. (See 'Arthritis' above.)

"Chronic Lyme disease" – There is no accepted definition for "chronic Lyme disease" for either clinical use or scientific study and no evidence that such an entity exists. Long-term antibiotic therapy for "chronic Lyme disease" has no proven benefit and is associated with potential deleterious adverse effects. (See '"Chronic Lyme disease" in children' above.)

  1. Stanek G, Wormser GP, Gray J, Strle F. Lyme borreliosis. Lancet 2012; 379:461.
  2. Pritt BS, Mead PS, Johnson DK, et al. Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: a descriptive study. Lancet Infect Dis 2016; 16:556.
  3. Steere AC. Lyme disease. N Engl J Med 1989; 321:586.
  4. Shapiro ED, Gerber MA. Lyme disease. Clin Infect Dis 2000; 31:533.
  5. Nadelman RB, Wormser GP. Lyme borreliosis. Lancet 1998; 352:557.
  6. Gerber MA, Shapiro ED, Burke GS, et al. Lyme disease in children in southeastern Connecticut. Pediatric Lyme Disease Study Group. N Engl J Med 1996; 335:1270.
  7. Tugwell P, Dennis DT, Weinstein A, et al. Laboratory evaluation in the diagnosis of Lyme disease. Ann Intern Med 1997; 127:1109.
  8. Aguero-Rosenfeld ME, Wang G, Schwartz I, Wormser GP. Diagnosis of lyme borreliosis. Clin Microbiol Rev 2005; 18:484.
  9. Nowakowski J, Schwartz I, Liveris D, et al. Laboratory diagnostic techniques for patients with early Lyme disease associated with erythema migrans: a comparison of different techniques. Clin Infect Dis 2001; 33:2023.
  10. Shapiro ED. Clinical practice. Lyme disease. N Engl J Med 2014; 370:1724.
  11. Lantos PM, Rumbaugh J, Bockenstedt LK, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR): 2020 Guidelines for the Prevention, Diagnosis and Treatment of Lyme Disease. Clin Infect Dis 2021; 72:e1.
  12. Wormser GP, Masters E, Nowakowski J, et al. Prospective clinical evaluation of patients from Missouri and New York with erythema migrans-like skin lesions. Clin Infect Dis 2005; 41:958.
  13. Feder HM Jr. Lyme disease in children. Infect Dis Clin North Am 2008; 22:315.
  14. Smith RP, Schoen RT, Rahn DW, et al. Clinical characteristics and treatment outcome of early Lyme disease in patients with microbiologically confirmed erythema migrans. Ann Intern Med 2002; 136:421.
  15. Nadelman RB, Nowakowski J, Forseter G, et al. The clinical spectrum of early Lyme borreliosis in patients with culture-confirmed erythema migrans. Am J Med 1996; 100:502.
  16. Goldberg NS, Forseter G, Nadelman RB, et al. Vesicular erythema migrans. Arch Dermatol 1992; 128:1495.
  17. Cutaneous tumors and tumor syndromes. In: Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence, 3rd ed, Paller AS, Mancini AJ (Eds), WB Saunders, Philadelphia 2006. p.205.
  18. Wormser GP, Brisson D, Liveris D, et al. Borrelia burgdorferi genotype predicts the capacity for hematogenous dissemination during early Lyme disease. J Infect Dis 2008; 198:1358.
  19. Belman AL, Iyer M, Coyle PK, Dattwyler R. Neurologic manifestations in children with North American Lyme disease. Neurology 1993; 43:2609.
  20. Wormser GP, McKenna D, Carlin J, et al. Brief communication: hematogenous dissemination in early Lyme disease. Ann Intern Med 2005; 142:751.
  21. Christen HJ, Hanefeld F, Eiffert H, Thomssen R. Epidemiology and clinical manifestations of Lyme borreliosis in childhood. A prospective multicentre study with special regard to neuroborreliosis. Acta Paediatr Suppl 1993; 386:1.
  22. Christen HJ, Bartlau N, Hanefeld F, et al. Peripheral facial palsy in childhood--Lyme borreliosis to be suspected unless proven otherwise. Acta Paediatr Scand 1990; 79:1219.
  23. Nigrovic LE, Thompson AD, Fine AM, Kimia A. Clinical predictors of Lyme disease among children with a peripheral facial palsy at an emergency department in a Lyme disease-endemic area. Pediatrics 2008; 122:e1080.
  24. Guez-Barber D, Swami SK, Harrison JB, McGuire JL. Differentiating Bell's Palsy From Lyme-Related Facial Palsy. Pediatrics 2022; 149.
  25. Clark JR, Carlson RD, Sasaki CT, et al. Facial paralysis in Lyme disease. Laryngoscope 1985; 95:1341.
  26. Rahn DW, Malawista SE. Lyme disease: recommendations for diagnosis and treatment. Ann Intern Med 1991; 114:472.
  27. Skogman BH, Croner S, Odkvist L. Acute facial palsy in children--a 2-year follow-up study with focus on Lyme neuroborreliosis. Int J Pediatr Otorhinolaryngol 2003; 67:597.
  28. Shapiro ED, Gerber MA. Lyme disease and facial nerve palsy. Arch Pediatr Adolesc Med 1997; 151:1183.
  29. Belman AL, Reynolds L, Preston T, et al. Cerebrospinal fluid findings in children with Lyme disease-associated facial nerve palsy. Arch Pediatr Adolesc Med 1997; 151:1224.
  30. Skogman BH, Croner S, Nordwall M, et al. Lyme neuroborreliosis in children: a prospective study of clinical features, prognosis, and outcome. Pediatr Infect Dis J 2008; 27:1089.
  31. Paydar-Darian N, Kimia AA, Lantos PM, et al. Diagnostic Lumbar Puncture Among Children With Facial Palsy in a Lyme Disease Endemic Area. J Pediatric Infect Dis Soc 2017; 6:205.
  32. Kuiper H, de Jongh BM, van Dam AP, et al. Evaluation of central nervous system involvement in Lyme borreliosis patients with a solitary erythema migrans lesion. Eur J Clin Microbiol Infect Dis 1994; 13:379.
  33. Vázquez M, Sparrow SS, Shapiro ED. Long-term neuropsychologic and health outcomes of children with facial nerve palsy attributable to Lyme disease. Pediatrics 2003; 112:e93.
  34. Adams WV, Rose CD, Eppes SC, Klein JD. Cognitive effects of Lyme disease in children. Pediatrics 1994; 94:185.
  35. Bingham PM, Galetta SL, Athreya B, Sladky J. Neurologic manifestations in children with Lyme disease. Pediatrics 1995; 96:1053.
  36. Krbkova L, Stanek G. Therapy of Lyme borreliosis in children. Infection 1996; 24:170.
  37. Thorstrand C, Belfrage E, Bennet R, et al. Successful treatment of neuroborreliosis with ten day regimens. Pediatr Infect Dis J 2002; 21:1142.
  38. Skogman BH, Glimåker K, Nordwall M, et al. Long-term clinical outcome after Lyme neuroborreliosis in childhood. Pediatrics 2012; 130:262.
  39. Ljøstad U, Skogvoll E, Eikeland R, et al. Oral doxycycline versus intravenous ceftriaxone for European Lyme neuroborreliosis: a multicentre, non-inferiority, double-blind, randomised trial. Lancet Neurol 2008; 7:690.
  40. Avery RA, Frank G, Glutting JJ, Eppes SC. Prediction of Lyme meningitis in children from a Lyme disease-endemic region: a logistic-regression model using history, physical, and laboratory findings. Pediatrics 2006; 117:e1.
  41. Shah SS, Zaoutis TE, Turnquist J, et al. Early differentiation of Lyme from enteroviral meningitis. Pediatr Infect Dis J 2005; 24:542.
  42. Eppes SC, Nelson DK, Lewis LL, Klein JD. Characterization of Lyme meningitis and comparison with viral meningitis in children. Pediatrics 1999; 103:957.
  43. Tuerlinckx D, Bodart E, Jamart J, Glupczynski Y. Prediction of Lyme meningitis based on a logistic regression model using clinical and cerebrospinal fluid analysis: a European study. Pediatr Infect Dis J 2009; 28:394.
  44. Tveitnes D, Natås OB, Skadberg Ø, Øymar K. Lyme meningitis, the major cause of childhood meningitis in an endemic area: a population based study. Arch Dis Child 2012; 97:215.
  45. Cohn KA, Thompson AD, Shah SS, et al. Validation of a clinical prediction rule to distinguish Lyme meningitis from aseptic meningitis. Pediatrics 2012; 129:e46.
  46. Rothermel H, Hedges TR 3rd, Steere AC. Optic neuropathy in children with Lyme disease. Pediatrics 2001; 108:477.
  47. Nord JA, Karter D. Lyme disease complicated with pseudotumor cerebri. Clin Infect Dis 2003; 37:e25.
  48. Costello JM, Alexander ME, Greco KM, et al. Lyme carditis in children: presentation, predictive factors, and clinical course. Pediatrics 2009; 123:e835.
  49. Centers for Disease Control and Prevention (CDC). Three sudden cardiac deaths associated with Lyme carditis - United States, November 2012-July 2013. MMWR Morb Mortal Wkly Rep 2013; 62:993.
  50. Forrester JD, Meiman J, Mullins J, et al. Notes from the field: update on Lyme carditis, groups at high risk, and frequency of associated sudden cardiac death--United States. MMWR Morb Mortal Wkly Rep 2014; 63:982.
  51. Feder HM Jr, Gerber MA, Krause PJ, et al. Early Lyme disease: a flu-like illness without erythema migrans. Pediatrics 1993; 91:456.
  52. Steere AC, Sikand VK, Schoen RT, Nowakowski J. Asymptomatic infection with Borrelia burgdorferi. Clin Infect Dis 2003; 37:528.
  53. Seltzer EG, Shapiro ED. Misdiagnosis of Lyme disease: when not to order serologic tests. Pediatr Infect Dis J 1996; 15:762.
  54. Lantos PM, Lipsett SC, Nigrovic LE. False Positive Lyme Disease IgM Immunoblots in Children. J Pediatr 2016; 174:267.
  55. Bachman DT, Srivastava G. Emergency department presentations of Lyme disease in children. Pediatr Emerg Care 1998; 14:356.
  56. Gerber MA, Zemel LS, Shapiro ED. Lyme arthritis in children: clinical epidemiology and long-term outcomes. Pediatrics 1998; 102:905.
  57. Culp RW, Eichenfield AH, Davidson RS, et al. Lyme arthritis in children. An orthopaedic perspective. J Bone Joint Surg Am 1987; 69:96.
  58. Steere AC, Malawista SE, Snydman DR, et al. Lyme arthritis: an epidemic of oligoarticular arthritis in children and adults in three connecticut communities. Arthritis Rheum 1977; 20:7.
  59. Thompson A, Mannix R, Bachur R. Acute pediatric monoarticular arthritis: distinguishing lyme arthritis from other etiologies. Pediatrics 2009; 123:959.
  60. Cruz AI Jr, Aversano FJ, Seeley MA, et al. Pediatric Lyme Arthritis of the Hip: The Great Imitator? J Pediatr Orthop 2017; 37:355.
  61. Lyons TW, Kharbanda AB, Thompson AD, et al. A Clinical Prediction Rule for Bacterial Musculoskeletal Infections in Children with Monoarthritis in Lyme Endemic Regions. Ann Emerg Med 2022; 80:225.
  62. Deanehan JK, Nigrovic PA, Milewski MD, et al. Synovial fluid findings in children with knee monoarthritis in lyme disease endemic areas. Pediatr Emerg Care 2014; 30:16.
  63. Dart AH, Michelson KA, Aronson PL, et al. Hip Synovial Fluid Cell Counts in Children From a Lyme Disease Endemic Area. Pediatrics 2018; 141.
  64. Jutras BL, Lochhead RB, Kloos ZA, et al. Borrelia burgdorferi peptidoglycan is a persistent antigen in patients with Lyme arthritis. Proc Natl Acad Sci U S A 2019; 116:13498.
  65. Szer IS, Taylor E, Steere AC. The long-term course of Lyme arthritis in children. N Engl J Med 1991; 325:159.
  66. Shapiro ED. Long-term outcomes of persons with Lyme disease. Vector Borne Zoonotic Dis 2002; 2:279.
  67. Feder HM Jr, Johnson BJ, O'Connell S, et al. A critical appraisal of "chronic Lyme disease". N Engl J Med 2007; 357:1422.
  68. Baker PJ. Chronic Lyme disease: in defense of the scientific enterprise. FASEB J 2010; 24:4175.
  69. Baker PJ. Is It Possible to Make a Correct Diagnosis of Lyme Disease on Symptoms Alone? Review of Key Issues and Public Health Implications. Am J Med 2019; 132:1148.
  70. Zomer TP, Bruinsma RA, Vermeeren YM, et al. Nonspecific Symptoms in Children Referred to a Lyme Borreliosis Center. Pediatr Infect Dis J 2020; 39:775.
  71. Marzec NS, Nelson C, Waldron PR, et al. Serious Bacterial Infections Acquired During Treatment of Patients Given a Diagnosis of Chronic Lyme Disease - United States. MMWR Morb Mortal Wkly Rep 2017; 66:607.
  72. Goodlet KJ, Fairman KA. Adverse Events Associated With Antibiotics and Intravenous Therapies for Post-Lyme Disease Syndrome in a Commercially Insured Sample. Clin Infect Dis 2018; 67:1568.
  73. Hatcher S, Arroll B. Assessment and management of medically unexplained symptoms. BMJ 2008; 336:1124.
  74. Oliveira CR, Shapiro ED. Update on persistent symptoms associated with Lyme disease. Curr Opin Pediatr 2015; 27:100.
Topic 6038 Version 31.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟