Clinician toolkit: Evaluating for other medical diagnoses

It is important to keep an open mind. A complete history and physical examination, medical record review and devising a broad differential is essential to ensure diagnosable conditions are ruled out.

• Outline a comprehensive diagnostic work-up, as indicated. This might include:
  • Age- and risk-appropriate cancer screening
  • Two-tiered testing for Lyme disease, deciding whether to test and how to interpret test results, based on patient’s pre-test probability
  • Considering autoimmune conditions with directed diagnostic testing tailored to symptomatology
  • Screening for obstructive sleep apnea (e.g., STOP-Bang)
  • Cognitive evaluations (with video instructions)
  • Screening for mental health diagnoses: Anxiety (GAD-7) | Depression (PHQ-9)
  • Objective Activity tools like Duke Activity Status Index can help patients measure their abilities
• Acknowledge that multiple visits will be required
• Provide a thorough medical record review, which may take longer than the allotted visit time
• Consider billing for prolonged services and determine if you can use add-on codes like G2211 for complex visits, which Medicare and some commercial insurance companies recognize

It is important to review prior laboratory testing and imaging results–including non-FDA-cleared tests (i.e., laboratory-developed [PDF] or in-house tests). Some patients may have active Lyme disease or be experiencing prolonged symptoms after an acute episode of treated Lyme disease, called Post-Treatment Lyme Disease Syndrome. If the clinical presentation and epidemiologic risk factors suggest acute Lyme disease, clinicians should provide a course of recommended antibiotic treatment.

If a patient with evidence of prior Lyme disease has already received recommended treatment, it is important to provide counseling that additional antibiotics have not been shown to provide sustained symptom improvement and to acknowledge that for some patients, it may take months to feel better. There is some research looking at different biomarkers that might help distinguish patients with PTLDS from those with other diagnoses; however, at this time there is no commercial test available.

For patients with prolonged symptoms without evidence of acute Lyme disease, it is important to consider and evaluate other possible medical issues. Research indicates that more than half of patients experiencing such symptoms have a diagnosis other than Lyme disease as the cause of their prolonged symptoms.

After a thorough work up, some patients may obtain a diagnosis; some will not (Chen A, Felt-Lisk S. Unpublished data. August 11, 2022). It is important to evaluate and address mental health for all patients, as depression and anxiety may be common in this population, given their long health care journey and prolonged symptoms (Chen A, Felt-Lisk S. Unpublished data. August 11, 2022). There is also some research indicating that post-infection cytokine damage to part of the brain (e.g., the ventral striatum) can cause a decrease in the motivation/reward pathway, which may manifest as depressive symptoms or fatigue. In short, chemical pathways can be disrupted after an infection, leading to more fatigue and depression. Psychiatrists can recommend medications that might restore these pathways.

Obtaining a complete history and reviewing records can require long office visits, which can be difficult for health care professionals to manage financially (Chen A, Felt-Lisk S. Unpublished data. August 11, 2022). Early in the initial visit, set the expectation that because patients have been living with these symptoms for a while, it can take several visits to thoroughly evaluate their symptoms.

It is important to do a thorough physical exam and consider possible diagnoses based on patient symptoms (e.g., fatigue) . There are several cognitive assessments for clinicians to use–some examples are available on paper and some are digital. Patients should have age- and risk-appropriate cancer screenings, plus a targeted workup for specific cancers if there are any concerning findings on history and physical.  Clinicians should also consider ME/CFS (evaluation, diagnostic criteria, using the diagnostic criteria, diagnosis and management*), endocrinopathies (such as diabetes, hypothyroidism) and rheumatologic diseases (such as polymyalgia rheumatica, fibromyalgia, rheumatoid arthritis and lupus) when appropriate. Screening for sleep disorders can be helpful.  Multiple medical societies and the United States Preventive Services Task Force recommend routine screening for depression and anxiety disorders.  Primary care clinicians can use a standardized mental health screening tool such as PHQ-9 and GAD-7 for patients with prolonged symptoms.

*Used with permission of Mayo Foundation for Medical Education and Research, all rights reserved.

This effort is supported through a cooperative agreement (grant number NU50CK000597). The U.S. Centers for Disease Control and Prevention is an agency within the Department of Health and Human Services (HHS). The contents of this course do not necessarily represent the policy of CDC or HHS and should not be considered an endorsement by the Federal Government.

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