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Mayo Clin Proc. 2010 April; 85(4): e13–e16.
PMCID: PMC2848428

31-Year-Old Man With Fever, Palpitations, and Generalized Rash

A previously healthy 31-year-old man without a history of cardiac disease presented to the emergency department with a 5-day history of a sore throat, neck stiffness, progressive dyspnea, transient confusion, fever, palpitations, and a generalized rash. His medical history was unremarkable. He reported no recent local or foreign travel, sick contacts, vaccinations, new medications, or exposure to human immunodeficiency virus or hepatitis. He had not been on any recent camping trips and had had no tick or rodent exposure. Of note, he lived in northwestern Wisconsin.

Physical examination revealed a heart rate of 113 beats/min, a blood pressure of 104/55 mm Hg, and a temperature of 36.7°C. His oxygen saturation was 100% on room air.

Cardiopulmonary examination revealed inspiratory wheezes in both lung bases and 1/6 systolic murmur consistent with tricuspid regurgitation. Abdominal examination revealed hepatomegaly; the abdomen was otherwise nontender and soft with positive bowel sounds. Skin examination revealed extensive tattooing covering the entire body (done in the distant past), with multiple, diffuse, raised, well-circumscribed, nonblanching, nonpurpuric, nontender, nonpruritic erythematous plaques approximately 5 to 10 cm in diameter involving his back, neck, trunk, and all extremities but sparing his palms and soles. The patient stated that he had never had such lesions before.

Initial laboratory studies yielded the following results (reference ranges provided parenthetically): hemoglobin, 13.0 g/dL (13.5-17.5 g/dL); leukocytes, 10.2 × 109/L (3.5-10.5 × 109/L); sedimentation rate, 34 mm/1 h (0-22 mm/1 h); C-reactive protein, 34.7 mg/L (<8.0 mg/L); alkaline phosphatase, 294 U/L (45-115 U/L); aspartate aminotransferase, 165 U/L (8-48 U/L); alanine aminotransferase, 277 U/L (7-55 U/L); γ-glutamyltransferase, 216 U/L (9-31 U/L), troponin, <0.01 ng/mL times 2 (<0.01 ng/mL), and creatine kinase–MB, 2.4 ng/mL (≤6.2 ng/mL). Blood cultures were obtained.

Electrocardiography showed the following: sinus tachycardia (atrial rate, 108 beats/min), absent PR depression, a ventricular rate of 118 beats/min, third-degree or complete heart block with atrioventricular dissociation and capture beats, low anterior forces, and nonspecific ST- and T-wave abnormalities.

  1. Which one of the following should be the next step in the evaluation and management of this patient?
    1. Send patient home from the emergency department
    2. Observe the patient overnight
    3. Discharge home, with outpatient dermatology follow-up for the rash
    4. Discharge home, with outpatient infectious disease (ID) follow-up for the fever
    5. Admit to the cardiology service for telemetry monitoring and further management
    It would not be safe to send this 38-year-old patient with a fever, rash, and third-degree heart block home without an appropriate work-up. Overnight observation would not be appropriate because the underlying etiology needs to be investigated in a young patient with complete heart block. Discharging this patient with outpatient dermatology or ID follow-up is also inappropriate because of his cardiac symptoms. This patient needs to be admitted to a monitored bed on the cardiology floor. Complete heart block can present with or progress to dizziness, presyncope, and syncope; therefore, it would not be safe to send this patient home.
  2. Which one of the following best explains this patient's rash?
    1. Cellulitis
    2. Syphilis
    3. Contact dermatitis
    4. Erythema migrans (EM)
    5. Hypersensitivity vasculitis
    In cellulitis, the involved site is warm, erythematous, hot, tender, and swollen. The borders are not elevated or sharply demarcated, and overlying skin necrosis may occur. In syphilis, the rash tends to be rough and characterized by red or reddish brown spots on both the palms of the hands and the bottoms of the feet, as well as on mucosal surfaces. Contact dermatitis, which tends to present with papular, erythematous dermatitis with indistinct margins distributed in areas of exposure, is associated with pruritus. The most reasonable explanation for the patient's rash is EM, a nonpruritic cutaneous lesion that develops after a tick bite and that can appear uniformly red or have a complex bull's eye appearance because of central clearing. Although central clearing is considered classic for EM, it often requires considerable expansion of the lesion and is usually not yet present in the first days of illness. It is normally found in or near the axilla, the inguinal region, behind the knees, or at the belt line because ticks take their meals in warm, moist regions of the body.1 Hypersensitivity vasculitis is characterized by inflammation of the small vessels of the skin with resultant ischemia of distally supplied areas. Palpable petechiae or purpura is a major finding in hypersensitivity vasculitis. It may be secondary to medications (antibiotics, loop and thiazide diuretics, sulfonamides, allopurinol, and phenytoin), infections (human immunodeficiency virus, hepatitis B and C), malignancy, connective tissue disease (systemic lupus erythematosus [SLE], rheumatoid arthritis), and autoimmune disease.2
    A dermatology consultation was sought for the rash, and a skin biopsy was performed.
  3. Which one of the following is the most likely differential diagnosis based on this patient's constellation of symptoms?
    1. Viral myocarditis
    2. Bacterial endocarditis
    3. Lyme disease
    4. Meningitis
    5. SLE
    Conduction delays including second-degree AV and complete AV block are rarely seen in myocarditis, but the precise incidence is unknown.3 Bacterial endocarditis may present with nonspecific constitutional symptoms and is associated with the appearance of a new cardiac murmur, Janeway lesions, Osler nodes, petechiae, clubbing, or splinter hemorrhage, but these were not present in our patient. Lyme disease is the most likely diagnosis and should be considered in young patients with heart block who present with a rash, especially if they are from endemic regions. The classic triad of symptoms of acute bacterial meningitis consists of fever, nuchal rigidity, and a change in mental status, although an appreciable number of patients do not have all 3 features (one-third in one series).4 On the basis of some of this patient's symptoms, such as confusion, neck stiffness, and fever, this patient may have meningitis. However, our patient's rash did not resemble the classic petechial rash in meningitis. The petechial rash in meningitis typically appears as discrete lesions that are 1 to 2 mm in diameter, are most frequently found on the trunk and lower portions of the body, and can coalesce into larger purpuric and ecchymotic lesions. Fifty percent of patients will have the rash on presentation.5 A chronic inflammatory disease of unknown cause, SLE can affect the skin, joints, heart, kidneys, lungs, nervous system, serous membranes, and/or other organs of the body. Commonly reported conduction disturbances include first- and second-degree blocks and intraventricular conduction defects such as bundle branch blocks. Complete or third-degree heart block has been rarely reported.6
    With the presumptive diagnosis of Lyme disease, confirmatory testing was performed. Skin biopsy revealed nonspecific dermal inflammation and mild dermal edema.
  4. Which one of the following would be the best initial test for confirming the diagnosis of Lyme disease?
    1. Erythrocyte sedimentation rate
    2. Lyme serology
    3. Skin biopsy
    4. Liver biopsy
    5. Antinuclear antibody assay
    The erythrocyte sedimentation rate, an indirect measurement of plasma acute phase protein concentration, is a nonspecific disease marker of many inflammatory states and is not very contributory by itself. In patients with early disseminated disease and late disease, the diagnosis of Lyme disease is based on the presence of clinical symptoms in a patient who resides in or has visited an endemic region, evidence of clinical inflammation at the site, and confirmatory serologic findings. A 2-test approach is recommended for the confirmatory diagnosis of Lyme disease: an enzyme-linked immunofluorescent assay followed by Western immunoblot.7 Although skin biopsy results may provide some pathological information about inflammation, they would not confirm the diagnosis. Liver biopsy may provide insight into liver function abnormalities; however, it is not indicated in this case. The antinuclear antibody assay is the most commonly performed screening test for patients with suspected systemic rheumatic disease. Antinuclear antibodies occur in patients with a variety of autoimmune diseases, both systemic and organ-specific. They are particularly common in the systemic rheumatic diseases, which include SLE, discoid SLE, drug-induced SLE, mixed connective tissue disease, Sjögren syndrome, scleroderma (systemic sclerosis), CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) syndrome, polymyositis/dermatomyositis, and rheumatoid arthritis.
    Because of the patient's transient confusion, a lumbar puncture was performed. Analysis of the cerebrospinal fluid showed normal protein and glucose levels and no evidence of xanthochromia. Lyme serology results revealed positive findings on enzyme-linked immunofluorescent assays for Lyme IgG and IgM, with confirmatory Western immunoblots for each. Blood cultures were negative.
    Echocardiographic findings for the patient showed a mild to moderate decrease in left ventricular systolic function, mild to moderate generalized left ventricular hypokinesis, an ejection fraction of 42%, mild right ventricular enlargement, and no pericardial effusion.
  5. Which one of the following is the most appropriate initial treatment for this patient?
    1. Intravenous ceftriaxone
    2. Oral doxycycline
    3. Intravenous vancomycin
    4. Aspirin
    5. Transcutaneous pacing
    The Infectious Diseases Society of America guidelines recommend 2 g of ceftriaxone intravenously every 8 hours or 18 to 24 million U/d of penicillin G for initial treatment of Lyme disease in patients with normal renal function. Hospitalization and continuous monitoring are advisable for symptomatic patients as well as for those with first-, second-, and/or third-degree AV block. An oral antibiotic treatment regimen (eg, 100 mg of doxycycline) should complete in-hospital therapy and should be continued on an outpatient basis.8
    Vancomycin is a tricyclic glycopeptide antibiotic that primarily inhibits bacterial cell wall synthesis. It is bactericidal against a number of aerobic and anaerobic gram-positive microorganisms but is not typically used in the treatment of Lyme disease. Aspirin is not appropriate because this patient does not have an acute coronary syndrome. Transcutaneous pacing is required in up to one-third of cases with Lyme carditis; however, our patient was hemodynamically stable throughout his hospital course, with a normal blood pressure on admission and tachycardia rather than bradycardia.
    Although this patient presented with complete heart block, he was clinically stable. Within 12 hours of presentation, the complete heart block resolved. Initially, the patient received intravenous ceftriaxone and was observed for 48 hours, after which time he was discharged from the hospital with oral doxycycline and recommendations to follow up with the cardiology and ID services as an outpatient. Unfortunately, he was lost to follow-up.

DISCUSSION

Lyme disease is an arthropod-borne disease known to affect primarily the skin, heart, and nervous system. It is caused by the spirochete Borrelia burgdorferi, introduced to the host by the bite of ticks of the Ixodes species. Lyme disease is endemic in the areas in which Ixodes ticks and the vector-competent animal hosts are found. From 2003 through 2005, approximately 93% of cases in the United States were reported from 10 states: Massachusetts, Connecticut, Rhode Island, New York, New Jersey, Pennsylvania, Delaware, Maryland, Minnesota, and Wisconsin.9 B burgdorferi organisms are present in the midgut of the unfed nymphal ticks. On attachment of the ticks to the host, the bacteria multiply quickly, with a doubling time close to 4 hours, and reach a maximum number after 72 hours of attachment.10 During the initial 15-hour period, the spirochetes appear restricted to the tick gut, but after 48 hours they disseminate to the salivary glands, supporting previous data showing a low risk of infection before 36 hours of tick attachment.10,11

Clinical features of Lyme disease vary during the course of the infection and are divided into stages: early localized disease, early disseminated disease, and late disease.

Early localized disease usually occurs between a few days to one month after the tick bite and is manifested by the presence of skin lesions (EM), which occur in 50% to 70% of patients. During the first few days, EM lesions may be uniformly red; as they expand, however, some central clearing often develops, and they may have a more complex target or bull's eye appearance. In an observational cohort study of 118 cases of EM in which B burgdorferi infection was confirmed by culture or polymerase chain reaction, the EM lesion was homogeneous in 59%, had central erythema in 32%, and had central clearing in 9%.12 Constitutional symptoms that may occur include fatigue, malaise, lethargy, headache, stiff neck, myalgia, arthralgias, and lymphadenopathy. Early disseminated disease, which occurs between a few days to 10 months after the tick bite, may be characterized by carditis, which may present as conduction defects, cardiomyopathy, or myopericarditis. It may also present with neurologic disease manifesting as lymphocytic meningitis, encephalitis, cranial and peripheral neuropathy, myelitis, or even liver disease (eg, liver function abnormalities, hepatitis). Late disease can appear months to years after the tick bite, presenting as arthralgia, chronic monoarthritis, or neurologic disease manifesting as encephalopathy, peripheral neuropathy, or ataxia.1

Lyme carditis is a rare manifestation of the disease.13 It is estimated that only 4% to 10% of patients with untreated Lyme disease develop Lyme carditis.14 Cardiovascular manifestations of Lyme disease often occur within 21 days of exposure. The most frequent cardiac symptom is AV block (first-, second-, and/or third-degree or even an alternating variant of them). Patients with high-degree AV block are often symptomatic with palpitations, dyspnea, chest pain, and dizziness, whereas patients with first-degree block are generally asymptomatic. Other cardiac manifestations include myopericarditis, bundle branch block, and chronic heart failure.15 It has been suggested that the mechanism by which Lyme disease affects the conduction system is the result of the direct dissemination of spirochetes into cardiac tissues, the inflammatory response associated with the infection, or a combination of both.13 The overall prognosis of patients with Lyme carditis is very good; however, delayed recovery and late manifestations (eg, dilated cardiomyopathy) have been described.15

Patients with minor cardiac disease (first-degree AV block with a PR interval <300 ms) could be treated with oral doxycycline, tetracycline, or amoxicillin. Administration of doxycycline is preferred because of the higher efficacy in other tick-borne diseases (babesiosis, ehrlichiosis, and anaplasmosis) that could be cotransmitted with Lyme disease. Patients with more severe conduction system disturbances (first-degree AV block with a PR interval >300 ms, second- or third-degree AV block) should be observed in a telemetry unit and given intravenous ceftriaxone or high-dose intravenous penicillin G according to Infectious Diseases Society of America guidelines. Transcutaneous pacing is required in up to one-third of cases with Lyme carditis. Insertion of a temporary pacemaker may be required if warranted by the specific case. Implantation of a permanent pacemaker is not usually required.13

Notes

See end of article for correct answers to questions.

Correct answers: 1. e, 2. d, 3. c, 4. b, 5. a

REFERENCES

1. Sigal LH. Clinical manifestations of Lyme disease. N J Med. 1990;87:549-555 [PubMed]
2. Blanco R, Martinez-Taboada VM, Rodriguez-Valverde V, Garcia-Fuentes M. Cutaneous vasculitis in children and adults: associated diseases and etiologic factors in 303 patients. Medicine (Baltimore) 1998;77:403-418 [PubMed]
3. Kang TJ, Wu CC, Lu CW, Jean WH, Yang MH, Lin TY. Acute myocarditis-related complete atrioventricular block–an accidental finding in an acute appendicitis patient. Acta Anaesthesiol Taiwan 2008;46(3):138-141 [PubMed]
4. Aronin SI, Peduzzi P, Quagliarello VJ. Community-acquired bacterial meningitis: risk stratification for adverse clinical outcome and effect of antibiotic timing. Ann Intern Med. 1998;129:862-869 [PubMed]
5. Milonovich LM. Meningococcemia: epidemiology, pathophysiology, and management. J Pediatr Health Care 2007;21:75-80 [PubMed]
6. Liautaud S, Khan AJ, Nalamasu SR, Tan IJ, Onwuanyi AE. Variable atrioventricular block in systemic lupus erythematosus. Clin Rheumatol. 2005;24:162-165 [PubMed]
7. Centers for Disease Control and Prevention (CDC) Recommendations for test performance and interpretation from the Second National Conference on Serologic Diagnosis of Lyme Disease. MMWR Morb Mortal Wkly Rep. 1995;44(31):590-591 [PubMed]
8. Wormser GP, Dattwyler RJ, Shapiro ED, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006;43:1089-1134 [PubMed]
9. Bacon RM, Kugeler KJ, Mead PS. Surveillance for Lyme disease–United States, 1992-2006. MMWR Surveill Summ. 2008;57:1-9 [PubMed]
10. De Silva AM, Fikrig E. Growth and migration of Borrelia burgdorferi in Ixodes ticks during blood feeding. Am J Trop Med Hyg. 1995;53:397-404 [PubMed]
11. Piesman J. Dynamics of Borrelia burgdorferi transmission by nymphal Ixodes dammini ticks. J Infect Dis. 1993;167:1082-1085 [PubMed]
12. 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;136:421-428 [PubMed]
13. Xanthos T, Lelovas P, Kantsos H, Dontas I, Perrea D, Kouskouni E. Lyme carditis: complete atrioventricular dissociation with need for temporary pacing. Hellenic J Cardiol. 2006;47:313-316 [PubMed]
14. Sigal LH. Diagnosis of Lyme disease. JAMA 1995;274:1427-1428 [PubMed]
15. Lo R, Menzies DJ, Archer H, Cohen TJ. Complete heart block due to Lyme carditis. J Invasive Cardiol. 2003;15:367-369 [PubMed]

Articles from Mayo Clinic Proceedings are provided here courtesy of The Mayo Foundation for Medical Education and Research