Is dysautonomia the reason for fatigue, dizziness, and palpitations in lupus?

Systemic lupus erythematosus (SLE), more commonly known as lupus, is a complex autoimmune condition that can affect nearly every organ system in the body.[1] Most discussions about lupus focus on inflammation involving the skin, joints, kidneys, or brain. However, research indicates that the autonomic nervous system (ANS), which controls automatic bodily functions, can also be disrupted in people living with SLE.[2] This disturbance is known as dysautonomia, and it may help explain numerous symptoms that are frequently described as “non-specific,” persistent, or difficult to treat for people with lupus.

Understanding dysautonomia is important because it can significantly affect the quality of life of people with lupus, even when their lupus activity appears stable.

What is the autonomic nervous system?

The ANS plays an important role in keeping the internal environment of the body stable.[2] It regulates involuntary functions such as heart rate, blood pressure, respiration, digestion, temperature, and communication between the immune and nervous systems.[3] Unlike voluntary movements, these processes occur automatically without conscious control.[3]

The ANS consists of two complementary branches:[2]

· The sympathetic nervous system activates the body for action, increasing heart rate and blood pressure in response to stress or activity.[3]

· The parasympathetic nervous system supports recovery of the body and conserves energy, slowing the heart rate and promoting rest.[3]

In healthy individuals, these systems work together to adapt to physical activity, stress, diet, and environmental conditions. When this balance is disturbed, the body may have difficulty regulating circulation and other involuntary processes, leading to a condition known as dysautonomia.[2]

What causes autonomic dysfunction in lupus?

The mechanisms that cause autonomic dysfunction in lupus are not fully understood. It has been observed that autonomic impairment does not coincide with the classical SLE activity markers, organ damage, or with anti-dsDNA or antiphospholipid antibodies, which are lupus-specific.[2] This highlights the possibility that dysautonomia could function as a distinct condition within SLE.[2] Researchers are exploring several interconnected pathways that support this idea.[2]

Peripheral nervous system involvement in lupus is thought to be mediated by inflammatory cytokines. Nerve biopsies in people with widespread peripheral nerve damage have shown elevated levels of pro-inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α).[4,5] These inflammatory mediators may disrupt nerve signalling and contribute to damage to autonomic nerves, as they are thin and vulnerable to chronic immune-mediated injury.[4,5]

In addition to cytokine-mediated inflammation, humoral immune mechanisms may also contribute to autonomic dysfunction.[2] Some people with SLE have demonstrated antibodies directed against gangliosides, acetylcholine receptors, components of the cervical ganglion, and the vagus nerve, supporting the role of antibody-mediated interference with autonomic nerve signalling.[6,7]

Recent emerging evidence also suggests that small fibre neuropathy may play an important role. Damage to the small nerve fibres responsible for transmitting pain, temperature, and autonomic signals can lead to burning or tingling sensations, along with autonomic manifestations such as orthostatic intolerance (dizziness while standing up), abnormal sweating, and gastrointestinal dysmotility.[8]

Other than immune-related nerve injury, changes in the blood vessels may also contribute to autonomic dysfunction in lupus. Lupus is linked to endothelial dysfunction, where chronic systemic inflammation damages the inner lining of blood vessels. Consequently, cardiovascular responses to postural changes, such as standing from a sitting or lying position may be affected, causing orthostatic hypotension (low blood pressure upon standing), dizziness, or light-headedness.[9]

Endothelial dysfunction can also overlap with QT interval prolongation, which refers to an abnormally extended period for the heart’s electrical system to reset between beats.[10] This observation in some SLE patients can be due to autonomic dysfunction, particularly increased sympathetic activity or impaired parasympathetic responses.[10]

Some conditions, such as fibromyalgia and diabetes may also amplify autonomic symptoms, making it difficult to determine the contribution of lupus itself.[2,11,12] Therefore, proper evaluation and careful clinical judgment of dysautonomia in lupus is required to distinguish primary autonomic involvement from secondary or overlapping conditions.

Unfortunately, no specific biomarker has yet been identified that reliably predicts the presence of autonomic dysfunction in SLE. This lack of a diagnostic antibody marker remains a major gap in research.

How does dysautonomia present in people with lupus?

While the pathophysiology of dysautonomia may be complex, the resulting clinical symptoms can be grouped by system. This can help clinicians to recognise and manage these often-subtle manifestations.

1. Cardiovascular symptoms

The cardiovascular system is commonly affected in lupus-related dysautonomia, causing orthostatic hypotension, dizziness, or light-headedness when standing.[2] Palpitations or an irregular heartbeat may also occur.[9] All these symptoms can be attributed to impaired vascular responses and autonomic regulation.[9,13,14]

2. Fatigue and exercise intolerance

Persistent fatigue and exercise intolerance are also among the most common symptoms in lupus.[1,15] This may be due to cardiovascular and autonomic limitations affecting heart rate, blood pressure, and coexisting problems like fibromyalgia.[15]

3. Gastrointestinal symptoms

Autonomic dysfunction can affect normal gastrointestinal movement.[16] Symptoms like nausea, bloating, constipation, diarrhoea, or delayed gastric emptying (gastroparesis) may occur. These symptoms are chronic and often mistaken for medication side effects or primary gastrointestinal disorders, highlighting the need to consider autonomic involvement in SLE.[16]

4. Genitourinary symptoms

Autonomic impairment may also affect bladder function, leading to increased frequency of urination, nocturia (frequently waking up at night to urinate), urgency, or a sensation of incomplete emptying, along with recurrent urinary tract infections.[2] Although neurogenic bladder secondary to autonomic dysfunction has been infrequently reported in SLE, it should be considered in patients with persistent or unexplained urinary symptoms.[17]

5. Ocular symptoms

Autonomic dysfunction may also cause changes in pupil size or reactivity, dry eyes, or blurred vision.[18] These symptoms are similar to Sjögren’s disease, an autoimmune disease commonly seen in people with SLE.[19]

Dysautonomia in lupus often presents in a very subtle way and can be mistaken for other lupus symptoms or for conditions such as fibromyalgia or diabetes. One of the major challenges in recognising dysautonomia in lupus is that symptoms may not correlate clearly with traditional markers. Additionally, most of these symptoms are common and non-specific. Usually, they are often attributed to stress, anxiety, medication side effects, or simply “living with lupus”.

However, recent research suggests that autonomic dysfunction is a measurable and clinically relevant feature in SLE. Hence, clinicians should consider that these symptoms are not purely psychological but reflect real physiological changes.

How is dysautonomia diagnosed?

The diagnosis of autonomic dysfunction can be incredibly difficult. It begins with a review of medical history and symptoms using autonomic questionnaires such as COMPASS-31, APS, or SCOPA-AUT. Further, medications and other conditions that contribute to similar autonomic symptoms may be considered.[20,21]

Lupus activity is also assessed using laboratory tests for traditional markers. This helps to determine whether the patient’s symptoms are due to a systemic flare or another lupus-related complication.[1] This step is essential before linking the symptoms to autonomic dysfunction, which often occurs independently of traditional lupus activity markers.[1]

If the clinician suspects dysautonomia, the patient can be referred to a specialist with knowledge in treating dysautonomia, such as a neurologist or cardiologist. Non-invasive autonomic testing can provide evidence of dysfunction. These include cardiovascular assessments such as orthostatic blood pressure measurements and heart rate variability testing, Valsalva manoeuvre responses, electrocardiography (ECG) to detect QT interval prolongation, and sudomotor tests to evaluate sweat gland function.[22,23] When small fibre neuropathy is suspected, quantitative sensory testing or a skin biopsy may also be considered.[24]

Finally, clinicians collate findings from history, questionnaires, and tests to confirm a diagnosis of dysautonomia. An accurate diagnosis of dysautonomia is incredibly complicated, and assessment by an autonomic dysfunction specialist is best.

How is dysautonomia managed?

Once confirmed, management of dysautonomia in lupus requires a comprehensive, individualised approach. The fundamental goal is to control lupus, as any active inflammation may worsen autonomic symptoms.

When lupus appears stable, non-pharmacological measures like increasing fluid intake, ensuring adequate salt consumption, and wearing compression stockings daily can help to reduce the orthostatic symptoms.[2,25] Exercises such as cycling or swimming can help improve cardiovascular conditioning gradually without triggering severe symptoms.

Further, lifestyle adjustments can also be made. Rising slowly from sitting or lying positions, avoiding prolonged standing, minimising heat exposure, and staying hydrated may reduce symptoms. Smaller, more frequent meals can help limit post-meal blood pressure drops.

Where symptoms persist despite non-pharmacological measures, pharmacological therapy may be considered. Options include medications that expand blood volume, support blood pressure, and regulate heart rate.[2] There is growing evidence that treatment with intravenous immunoglobulin may also help patients with autonomic disorders.[26]

Why early recognition matters

Recognition of dysautonomia is an important step toward improving the quality of life for people living with lupus. These symptoms are real, measurable, and treatable. Validating patient experiences and offering structured evaluation can reduce uncertainty and frustration. Early detection and an appropriate management plan can make a meaningful difference in daily functioning and overall well-being.

References:

1. Justiz Vaillant AA, et al., 2022. Systemic Lupus Erythematosus. Stat Pearls Publishing: Treasure Island.
2. Frazatto CFC, et al., 2025. Dysautonomia in systemic lupus erythematosus: when to suspect and how to investigate. Expert Review of Clinical Immunology, 21(6):701–710.
3. McCorry LK. 2007. Physiology of the autonomic nervous system. Am J Pharm Educ. 71(4):78.
4. Lindenlaub T, Sommer C. 2003. Cytokines in sural nerve biopsies from inflammatory and non-inflammatory neuropathies. Acta Neuropathol (Berl). 105(6):593–602.
5. Florica B, et al., 2011. Peripheral neuropathy in patients with systemic lupus erythematosus. Semin Arthritis Rheum. 41(2):203–221.
6. Azuma N, et al., 2024. Autonomic disorder in systemic lupus erythematosus: autoimmune autonomic ganglionopathy. Immunol Med. 47(4):285–288.
7. Imamura M, et al., 2020. Ganglionic acetylcholine receptor antibodies and autonomic dysfunction in autoimmune rheumatic diseases. Int J Mol Sci. 21(4):1332.
8. Galosi E, et al., 2024. Clinical, histologic, and immunologic signatures of small fiber neuropathy in systemic lupus erythematosus. J Peripher Nerv Syst JPNS. 29(3):315–328.
9. Hussein DA, et al., 2020. Cardiovascular autonomic nervous system dysfunction in patients with systemic lupus erythematosus. QJM: An Int J Med. 113(1).
10. Bienias P, et al., 2019. Comparison of non-invasive assessment of arrhythmias, conduction disturbances and cardiac autonomic tone in systemic sclerosis and systemic lupus erythematosus. Rheumatol Int. 39(2):301–310.
11. Agashe S, et al., 2018. Cardiac autonomic neuropathy in diabetes mellitus. Methodist Debakey Cardiovasc J. 14(4):251–256.
12. Monteiro JAM, et al. 2024. Fibromyalgia comorbidity in systemic lupus erythematosus patients: assessing impact on quality of life. Adv Rheumatol. 64:90.
13. Milovanović B, et al., 2010. Cardiac autonomic dysfunction in patients with systemic lupus, rheumatoid arthritis and sudden death risk. Srp Arh Celok Lek. 138(1–2):26–32.
14. Kim MJ, et al., 2022. Orthostatic hypotension: a practical approach. Am Fam Physician. 105(1):39–46.
15. Kawka L, et al., 2021. Fatigue in systemic lupus erythematosus: an update on its impact, determinants and therapeutic management. J Clin Med. 10(17):3996.
16. Daruwala C, et al., 2009. Gastrointestinal manifestations of systemic lupus erythematosus and scleroderma. Clin Med Gastroenterol. 2: CGast.S2264.
17. Wada T, et al., 1992. Neurogenic bladder due to peripheral neuropathy and a visual disturbance in an elderly man with systemic lupus erythematosus. Ann Rheum Dis. 51(4):547–549.
18. Bremner F, et al., 2006. Pupil findings in a consecutive series of 150 patients with generalised autonomic neuropathy. J Neurol Neurosurg Psychiatry. 77(10):1163–1168.
19. Gianordoli APE, et al., 2023. Prevalence of Sjögren’s syndrome according to 2016 ACR-EULAR classification criteria in patients with systemic lupus erythematosus. Adv Rheumatol. 63(1):11.
20. Zilliox L, et al., 2011. Assessing autonomic dysfunction in early diabetic neuropathy: the survey of autonomic symptoms. Neurology. 76(12):1099–1105.
21. Sletten DM, et al., 2012. COMPASS 31: a refined and abbreviated composite autonomic symptom score. Mayo Clin Proc. 87(12):1196–1201.
22. Ewing DJ, et al., 1986. Autonomic neuropathy: its diagnosis and prognosis. Clin Endocrinol Metab. 15:855–888.
23. Baun WB, et al., 1981. Comparison of heart rate measurement protocols used during autonomic function tests. J Appl Physiol. 51:516–519.
24. Omdal R, et al., 2002. Small nerve fiber involvement in systemic lupus erythematosus: a controlled study. Arthritis Rheum. 46:1228–1232.
25. Raj SR, 2013. Postural tachycardia syndrome (POTS). Circulation. 127(23):2336–2342.
26. Schofield JR, et al., 2019. Intravenous immunoglobulin therapy in refractory autoimmune dysautonomias: a retrospective analysis of 38 patients. Am J Ther. 26(5):570–582.

Author

Dr. Jyothsna Rao Prahallada is a medical writer and science communicator with a Ph.D. in Biotechnology and a passion for translating complex medical research into accessible insights. She volunteers with Emerge Australia, Lupus Foundation Australasia, and WHEN, contributing to awareness and advocacy efforts for chronic illnesses. With experience in research, teaching, and clinical content creation, she is committed to empowering patients and supporting evidence-based health education.

Reviewer

Dr. Thomas is a rheumatologist in private practice specializing in lupus in Maryland, USA and is a Clinical Associate Professor of Medicine at the Uniformed Services University, Bethesda, Maryland. He has authored the top-rated patient education book, The Lupus Encyclopedia, from Johns Hopkins Press (2nd edition), and runs a lupus educational website and Facebook Page called “The Lupus Encyclopedia” with over 32,000 followers worldwide.

Editor

Paula De Paoli is the Principal Editor and Content Lead at The Lupus Foundation of Australasia. She is a senior medical writer and communications consultant with over a decade of experience across clinical practice, university education, and national health regulation. She has held risk advisory roles at Ahpra and currently supports healthcare organisations across education and marketing projects at Medwire. She holds postgraduate qualifications in public health from the University of Sydney and Harvard University.