When 'Normal Labs' Don't Match How You Feel: Investigating Unexplained Pain, Fatigue, and Inflammation
There is nothing more frustrating than feeling unwell—dealing with fatigue, joint pain, or brain fog—only to be told by a doctor that "everything looks normal." For many patients, this leads to a cycle of dismissal, anxiety, and silent suffering.
At Whole Health Rheumatology, we specialize in investigating unexplained pain, fatigue, and inflammation, looking beyond "normal labs" to identify what's actually causing your symptoms and create a personalized plan for relief.
The Limits of Standard Blood Work
Standard rheumatologic testing—including inflammatory markers like ESR and CRP, rheumatoid factor, and antinuclear antibodies—can be invaluable when positive. But here's what many patients don't realize: normal results don't always mean nothing is wrong.
Approximately 30% of patients with established rheumatoid arthritis test negative for rheumatoid factor. This is called seronegative rheumatoid arthritis—a condition where patients have the joint inflammation and destruction of RA but without the typical blood markers. A 2023 review in The New England Journal of Medicine describes seronegative RA as "a separate entity marked by polyarthritis but with poorly defined pathogenetic mechanisms." These patients can still experience significant joint damage and require the same aggressive treatment as seropositive patients.
Similarly, low-titer antinuclear antibodies (1:40) are present in approximately 30% of healthy people, while some patients with genuine autoimmune disease may have negative or borderline results early in their disease course. Autoantibodies can precede symptoms by years in conditions like lupus, Sjögren syndrome, and systemic sclerosis—meaning a negative test today doesn't rule out a developing condition.
Conditions That Hide Behind "Normal" Results
Several rheumatologic and related conditions frequently present with normal or near-normal standard blood work:
Seronegative Inflammatory Arthritis: Both seronegative rheumatoid arthritis and the spondyloarthropathies (including psoriatic arthritis and axial spondyloarthritis) can cause significant joint inflammation without positive autoantibodies. Axial spondyloarthritis should be considered in patients with chronic low back pain that started before age 45 with inflammatory features—pain that improves with activity but not rest, prolonged morning stiffness, and good response to anti-inflammatory medications. There is no diagnostic blood test; diagnosis requires careful clinical evaluation and often imaging.
Fibromyalgia and Central Sensitization: Fibromyalgia is characterized by chronic widespread musculoskeletal pain, fatigue, sleep disturbances, and cognitive difficulties—all with completely normal inflammatory markers and imaging. This is not because "nothing is wrong," but because fibromyalgia is a disorder of how the nervous system processes pain. Brain imaging studies reveal measurable structural, functional, and neurochemical changes in patients with fibromyalgia. The condition affects 2-8% of the population and is the third most common musculoskeletal condition.
Hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum Disorders: These connective tissue conditions cause chronic pain, joint instability, and fatigue—but there is no blood test for hEDS. Diagnosis is entirely clinical, based on the 2017 International Classification criteria requiring generalized joint hypermobility, musculoskeletal and systemic manifestations, and exclusion of alternative diagnoses. Patients with hEDS wait an average of 22 years for a correct diagnosis, often being told their symptoms are "just anxiety."
Sjögren Syndrome: This autoimmune condition causes dry eyes, dry mouth, fatigue, and joint pain—symptoms that overlap significantly with fibromyalgia and other pain syndromes. While specific antibodies (anti-SSA/Ro and anti-SSB/La) can confirm the diagnosis, the classic triad of dryness, fatigue, and pain is very common in the general population, making diagnosis challenging. Sjögren syndrome can also cause peripheral neuropathy, contributing to pain that standard tests won't explain.
Small Fiber Neuropathy: Patients with small fiber neuropathy experience burning pain, numbness, tingling, and autonomic symptoms—but standard nerve conduction studies are normal because they only test large nerve fibers. Diagnosis requires specialized testing such as skin punch biopsy to assess intraepidermal nerve fiber density. Small fiber neuropathy can be associated with diabetes, autoimmune conditions, and sometimes occurs without an identifiable cause.
Menopause Musculoskeletal Syndrome: More than 70% of women experience musculoskeletal symptoms during the menopause transition, and 25% will be disabled by them. Research shows that joint pain and stiffness are significantly more likely in postmenopausal women compared to premenopausal women—and this association is with hormonal status, not chronological age. These symptoms can closely mimic inflammatory arthritis, with morning stiffness, hand pain, and even frozen shoulder, yet all inflammatory markers remain normal.
The Detective Work of Rheumatology
Autoimmune and inflammatory conditions are often episodic or develop gradually over years. Standard 15-minute appointments rarely provide enough time to connect the dots between seemingly unrelated issues like rashes, digestive problems, fatigue, and joint stiffness.
Dr. Olga Pinkston approaches these cases like a detective. By dedicating 60–75 minutes to your initial evaluation, she reviews your full history and prior workups to catch early signs of disease that others might miss. We don't just treat the labs; we treat the patient.
As a board-certified, Mayo Clinic-trained rheumatologist, Dr. Pinkston has the expertise to:
- Distinguish between inflammatory arthritis and conditions that mimic it
- Recognize seronegative autoimmune disease before it causes permanent damage
- Identify fibromyalgia and central sensitization, which require a completely different treatment approach than inflammatory conditions
- Evaluate for hypermobility syndromes through careful physical examination, including the Beighton score
- Assess whether hormonal changes are contributing to musculoskeletal symptoms
- Determine when specialized testing—such as MRI of the sacroiliac joints or skin biopsy for small fiber neuropathy—is warranted
Why a Rheumatologist for "Normal Labs"?
Many patients with unexplained pain bounce between specialists, never finding answers. A rheumatologist is uniquely positioned to evaluate these complex cases because we are trained to recognize patterns across multiple organ systems and to understand when "normal" tests don't tell the whole story.
At Whole Health Rheumatology, we believe that if your labs say you are fine but you cannot function normally, the evaluation is incomplete—not you.
Our Approach
We take a comprehensive approach to unexplained symptoms:
Thorough History: We listen to your full story, including symptoms that may seem unrelated—digestive issues, skin changes, fatigue patterns, sleep quality, and how your symptoms have evolved over time.
Detailed Physical Examination: Many conditions—including hEDS, early inflammatory arthritis, and Sjögren syndrome—are diagnosed primarily through careful examination, not blood tests.
Targeted Testing: Rather than ordering every test available, we use clinical reasoning to determine which additional investigations will actually change your diagnosis or treatment.
Addressing Overlapping Conditions: Many patients have more than one condition contributing to their symptoms. Fibromyalgia commonly coexists with inflammatory arthritis, and when unrecognized, can lead to overtreatment of the inflammatory condition. We identify and address each contributing factor.
A Clear Path Forward: Whether we identify a specific diagnosis or determine that your symptoms are best explained by central sensitization or hormonal changes, you will leave with a clear understanding of what's happening and a concrete treatment plan.
You Shouldn't Have to Wait for Answers
You shouldn't have to wait until your condition becomes severe—or until you finally test positive for something—to get help. Our goal is to validate your experience and provide a clear, actionable plan to reduce your symptoms and protect your future health.
If you are dealing with symptoms that are affecting your life and still don't have answers, schedule your evaluation to start your journey toward clarity and relief.
