Infectious Disease

Patients with greater alpha-gal IgE levels report higher rates of knee pain, stiffness

January 24, 2024

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Key takeaways:

  • In a study of tick-borne diseases, alpha-gal IgE was associated with knee pain severity, particularly at high levels.
  • Two tick-borne pathogens, Ehrlichia and spotted fever group Rickettsia, had no link to symptomatic, radiographic knee osteoarthritis.

Among patients with Ehrlichia IgG, Rickettsia IgG or alpha-gal IgE following a tick bite, only those with heightened levels of alpha-gal IgE demonstrated musculoskeletal symptoms, specifically higher rates of knee pain, according to data.

“While Lyme disease accounts for the majority of reported [tick-borne disease (TBD)] cases, spotted fever group rickettsiosis and ehrlichiosis remain important public health issues, particularly in southeastern states,” Diana L. Zychowski, MD, MPH, of the University of North Carolina at Chapel Hill, and colleagues wrote in JAMA Network Open. “For example, cases of ehrlichiosis, transmitted by the lone star tick (Amblyomma americanum), have increased more than 10-fold since 2000.

A tick sits on someone's skin.

Among patients with Ehrlichia IgG, Rickettsia IgG or alpha-gal IgE following a tick bite, only those with heightened levels of alpha-gal IgE demonstrated musculoskeletal symptoms, according to data. Image: Adobe Stock

“Despite the lack of evidence that infection with Rickettsia or Ehrlichia is associated with persistent symptoms after treatment, many patients attribute nonspecific symptoms, especially musculoskeletal symptoms, to a prior infection,” they added. “… In addition to tick-borne infections, lone star tick bites are also associated with the development of IgE to galactose–1,3-galactose (-gal).”

According to the researchers, some of the “more subtle manifestations” of elevated alpha-gal IgE levels have included persistent induration and erythema around tick bites, gastrointestinal distress and arthralgia, which can be “diffuse, migratory, and improved by an appropriate avoidance diet,” they wrote.

To analyze the association between tick-borne illness and chronic musculoskeletal symptoms, Zychowski and colleagues conducted a cross-sectional study of serum samples from 488 participants (median age, 72 years; 68.9% women) enrolled in the Johnston County Osteoarthritis project. According to the researchers, the Johnston County Osteoarthritis project is an ongoing longitudinal, population-based study based on data collected in Johnston County, North Carolina.

The researchers screened samples for IgG antibodies specific to Ehrlichia chaffeensis and spotted fever group Rickettsia, as well as alpha-gal IgE antibodies at levels greater than 0.1 IU/mL. Participants reported their severity of pain, aching and stiffness through questionnaires, and an expert radiologist reviewed images for radiographic knee OA. Multivariable logistic regression models examined the relationship between joint symptoms and antibodies.

Although just 84 participants reported having a tick bite in the past 5 years, 178 demonstrated evidence of prior tick-borne exposure, according to the researchers. Among the 488 participants with available serum samples, the overall weighted point prevalences for Ehrlichia IgG, Rickettsia IgG or alpha-gal IgE greater than 0.1 IU/mL were 8.6% (95% CI, 5.9% to 11.3%), 17.1% (95% CI, 12.6% to 21.5%) and 19.6% (95% CI, 15.3% to 23.8%), respectively.

According to the researchers, only elevated alpha-gal IgE was associated with self-reported symptoms in the knees (mean ratio = 1.3; 95% CI, 1.09-1.56), particularly at levels greater than 0.35 IU/mL (MR = 1.49; 95% CI, 1.19-1.85). Detectable IgG for Ehrlichia and spotted fever group Rickettsia demonstrated no associations with symptoms in any joint, and alpha-gal IgE had no association with pain, aching or stiffness in the hands or hips.

Meanwhile, eisk factors for alpha-gal IgE greater than 0.1 IU/mL included male sex (OR = 2.63; 95% CI, 1.55-4.47), current smoker status (OR = 3.55; 95% CI, 1.38-9.18) and a tick bite in the past 5 years (OR =3.99; 95% CI, 2.22-7.15).

“In this cross-sectional study of a population with high levels of tick exposure and osteoarthritis, there was no association between musculoskeletal symptoms and [spotted fever group Rickettsia] and Ehrlichia antibodies,” Zychowski and colleagues wrote. “However, -gal IgE was associated with knee pain, aching, or stiffness. These findings suggest that substantial investment is required to examine the pathogenesis of these TBDs and interventions to reduce human-tick interactions.”

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Sources/Disclosures

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Disclosures:
Zychowski reports receiving a T32 grant from the National Institute of Allergy and Infectious Diseases during the study. Please see the study for all other authors’ relevant financial disclosures.

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