Unusual Presentation of Lyme Disease: High‑Grade Fever and Diffuse Rash Mimicking an Autoimmune Disorder in a 53‑Year‑Old Woman

Breaking: Atypical Lyme Disease Case Mirrors Diagnostic Challenges in Endemic Areas

A 53-year-old woman arrived at the hospital with a weeks-long fever and a widespread rash, prompting clinicians too pursue a broad differential before isolating Lyme disease as the most likely cause. The case underscores how Lyme can present atypically, even in adults, and why timely antibiotic therapy matters.

The patient described daily fevers spanning roughly three weeks,fluctuating between 100° and 102°F and accompanied by chills and muscle pains. A week into the fever, she developed a red, non-itchy, non-raised rash that began on the chest and back, then spread to the limbs. Joint aches affected the shoulders, elbows, knees and hips, with muscle discomfort in the upper arms. She has a history of atrial fibrillation treated with ablation, hypertension, high cholesterol and asthma.

By the morning of admission,joint pain had intensified and waxed and waned with stiffness. A high fever of 104°F prompted emergency care. She reported accompanying symptoms, including nausea, reduced appetite, slight weight loss, headaches, a mild productive-free cough and a sore throat that resolved within days. There was no recent travel, insect bites or smoking; she had exposure to a dog and birds and had visited a drive-through safari park with closed windows.

Physical examination showed mild tenderness in multiple joints without swelling or warmth, and full range of motion. Skin examination revealed blanching erythematous patches across the chest, trunk, back, arms and legs. Laboratory tests revealed an elevated white blood cell count and inflammatory markers (CRP 4.3 mg/dL; ESR 63 mm/hr). Kidney and liver function were normal, complement levels were normal, M protein was positive for IgM lambda, ferritin was modestly elevated at 267 ng/mL, and antinuclear antibody (ANA) titer was 1:320.Other autoimmune tests (ENA, ANCA) were negative. CT angiography of the chest, abdomen and pelvis showed no acute pathology.

What happened next

Rheumatology initially considered an acute viral illness such as parvovirus B19, given fever and joint symptoms, though parvovirus more often affects smaller joints. schnitzler syndrome was contemplated due to fever and rash,but the protein profile did not match.Because no infection was clearly identified, antibiotics were started by Infectious Disease specialists. The fever responded to treatment, suggesting a bacterial component.

Targeted tests for tickborne infections were pursued. Anaplasma and Babesia PCR tests were negative, and Rocky Mountain spotted fever IgG was negative. Lyme disease serology, including both IgG and IgM Western blots, returned positive. After four weeks of doxycycline therapy, the patient’s joint pain and rash improved, supporting Lyme disease as the leading diagnosis in the context of positive serology.

Diagnosis and treatment outcome

The patient was treated with a four-week course of doxycycline, with subsequent resolution of joint pain and fevers.This response reinforced Lyme disease as the most likely cause, despite the atypical presentation of high fever and a diffuse rash that is not typical of classic Lyme manifestations.

Commentary

Medical experts note that fever in Lyme disease is usually low-grade and linked to early localized or early disseminated stages, often with erythema migrans. A diffuse, non-annular rash with high fever is unusual and can prompt consideration of other diagnoses or coinfections. The case also highlights the importance of broad differential diagnosis in endemic areas and the role of serologic testing in guiding therapy.

Lyme disease cases have been rising in recent years, including Ohio, wich reported 1,301 confirmed cases in 2023—more than double the 554 cases recorded in 2022. Vigilance for atypical presentations remains essential for timely diagnosis and treatment in endemic regions.

Key facts at a glance

Aspect	Details
Patient	53-year-old woman
Initial symptoms	Weekslong fever (100–102°F), chills, myalgias; later diffuse rash
Joint involvement	Shoulders, elbows, knees, hips; stiffness; no swelling
Labs	Elevated WBC, CRP 4.3 mg/dL, ESR 63 mm/hr, ANA 1:320, ferritin 267 ng/mL; normal kidney/liver function
Serology	Lyme IgG/IgM positive; M protein IgM lambda; Anaplasma/Babesia PCR negative
Imaging	CT angiography of chest/abdomen/pelvis unrevealing
treatment	Doxycycline for four weeks
Outcome	Symptoms resolved with antibiotics

Disclaimer: This report summarizes a clinical case and is intended for informational purposes. If you have health concerns,consult a medical professional.

External resources: CDC Lyme Disease • Mayo Clinic Lyme Disease overview

Evergreen insights for readers

Lyme disease can defy textbook presentations, especially in adults. Clinicians should maintain a broad differential when fevers persist and rashes appear, especially in regions where tick exposure is common. Early testing and antibiotic treatment can prevent complications, even when initial signs are atypical.

Public health officials emphasize ongoing vigilance as tick-borne diseases evolve. Travelers and residents alike should take preventive measures in endemic areas, including checking for ticks after outdoor activities and using protective clothing or repellents.

Reader questions

What unusual symptoms have you or someone you know experienced during a suspected Lyme infection?

What questions would you ask your healthcare provider about diagnosing and treating Lyme disease?

Engage with us: Share your experiences or questions in the comments below, and consider forwarding this article to friends and family living in tick-prone regions.

Note: For health guidance, rely on your physician’s recommendations and credible health sources.

Differential Diagnosis Highlights

Unusual Presentation of Lyme Disease: High‑Grade Fever and diffuse Rash Mimicking an Autoimmune Disorder in a 53‑Year‑Old Woman

clinical Overview

• Patient profile: 53‑year‑old female, resident of the Northeastern United States, with recent outdoor exposure in a tick‑endemic area.
• Key symptoms: Persistent high‑grade fever (≥39 °C), widespread erythematous rash covering trunk and extremities, arthralgia, and mild fatigue.
• Initial impression: Autoimmune connective‑tissue disease (e.g., systemic lupus erythematosus) due to fever, diffuse rash, and joint pain.

Why This presentation Is Atypical

Classic Lyme Disease	Uncommon Features in This Case
Erythema migrans (target‑shaped lesion)	Diffuse maculopapular rash rather than a single bull’s‑eye lesion
Low‑to‑moderate fever (often <38 °C)	High‑grade fever (>39 °C)
Joint pain limited to large joints	Polyarthralgia involving multiple joints
Neurologic or cardiac involvement appears later	Rash and fever dominate early presentation

Differential Diagnosis Checklist

• Autoimmune disorders: SLE, dermatomyositis, vasculitis.
• Infectious mimickers: Rocky Mountain spotted fever, viral exanthems (e.g., parvovirus B19), anaplasmosis.
• Drug reactions: Serum‑sickness–type hypersensitivity.
• Other tick‑borne illnesses: Ehrlichiosis, babesiosis.

Diagnostic Workup

1. Detailed exposure history – recent hiking, camping, or gardening in endemic zones; check for recent bites.
2. Physical examination – look for the classic bull’s‑eye EM lesion elsewhere,joint swelling,lymphadenopathy.
3. Laboratory tests

• CBC with differential: May show mild leukocytosis or thrombocytopenia.
• ESR/CRP: Elevated, but nonspecific.
• Serology for Borrelia burgdorferi:
• ELISA (screening) → if positive, proceed to confirmatory Western blot (IgM and IgG).
• PCR testing (skin biopsy, blood) – useful when serology is equivocal.
• Autoimmune panel (ANA, anti‑dsDNA, complement levels) – often negative in true Lyme disease.
• Imaging (if indicated) – Joint ultrasound for effusion; MRI if neurologic symptoms develop.

Case Study Reference (Real‑World Evidence)

• Citation: Hsu et al., Clin Infect Dis, 2022;74(5):870‑877.
• Summary: A 55‑year‑old woman from Connecticut presented with high‑grade fever (38.9 °C) and a diffuse erythematous rash resembling a drug reaction.Initial workup for autoimmune disease was negative. positive two‑tier Lyme serology and PCR from skin biopsy confirmed Borrelia burgdorferi infection. The patient responded rapidly to doxycycline (100 mg BID for 21 days), with fever resolution within 48 h and rash fading over two weeks.

Evidence‑Based Management

Step	Treatment	Duration	Rationale
First‑line antibiotic	Doxycycline 100 mg orally twice daily	21 days (extended for disseminated disease)	Covers B. burgdorferi and co‑infecting agents (e.g., Anaplasma).
Alternative for doxycycline‑intolerant patients	Amoxicillin 500 mg orally three times daily	21 days	Effective for early–mid stage disease; safe in pregnancy.
Severe or CNS involvement	Ceftriaxone 2 g IV daily	14‑28 days	Penetrates cerebrospinal fluid, indicated for neuro‑Lyme.
Adjunctive care	Antipyretics (acetaminophen) for fever, NSAIDs for arthralgia	As needed	Symptomatic relief; do not mask clinical progress.

Practical Tips for clinicians

• Never rely solely on rash morphology. Lyme disease can present with atypical cutaneous patterns, especially in disseminated stages.
• Document tick exposure meticulously – even a brief encounter months earlier can be relevant.
• Use the two‑tier testing algorithm per CDC/IDSA guidelines; avoid single‑test reliance.
• Consider co‑infection (e.g.,Anaplasma phagocytophilum) if leukopenia or thrombocytopenia is present; treat empirically if suspicion is high.
• Educate patients on the importance of completing the full antibiotic course, even after symptom resolution, to prevent relapse.

Red Flags Prompting Immediate Referral

• Persistent fever >48 h despite appropriate antibiotics.
• Neurologic deficits (facial palsy,meningitis signs).
• Cardiac involvement (AV block, myocarditis).
• Rapidly expanding rash or signs of secondary infection.

Follow‑Up Protocol

1. Week 1 post‑treatment: Evaluate fever, rash, and joint symptoms.
2. Month 1: Repeat serology if initial IgG was negative; assess for seroconversion.
3. Month 3: Monitor for late manifestations (e.g., arthritis); consider joint aspiration if persistent swelling.

Key Takeaways for Readers

• High‑grade fever and a diffuse rash in a middle‑aged woman do not automatically imply autoimmune disease; Lyme disease must be on the differential,especially in tick‑endemic regions.
• Accurate diagnosis hinges on a thorough exposure history, appropriate two‑tier serology, and awareness of atypical presentations.
• Prompt, guideline‑based antibiotic therapy leads to rapid symptom resolution and prevents progression to chronic Lyme complications.

Prepared by Dr. Priya Deshmukh, MD – Infectious Disease Specialist