“A growing number of urban patients present to clinics with vague, persistent complaints—tiredness that will not lift, unexplained joint aches, intermittent rashes, or dry eyes and mouth—yet standard tests often return near normal,” said Dr Aruna S Malipeddi, Senior Consultant – Rheumatology, Arete Hospitals, Hyderabad.
Clinicians increasingly recognise a pattern: the early, incomplete, or subtle forms of autoimmunity that do not yet fit textbook diagnostic boxes. Population studies and narrative reviews suggest that autoimmune conditions are overall on the rise, and that the gap between symptom onset and a clear diagnosis is widening. In this article, we explain the causes of unexplained autoimmune symptoms in the body.
Causes of Unexplained Autoimmune Symptoms
The Role of Genes and Environment
“The answer lies in an interplay of genes and environment, with modern urban living amplifying triggers that tip immune regulation off balance. Genetic susceptibility remains the foundation—familial clustering and specific genetic markers explain part of the story, but exposure patterns that have shifted dramatically over recent decades appear to matter at least as much,” said Dr Malipeddi.
Reduced contact with environmental biodiversity, altered diets, chronic psychological stress, modern lifestyle and increasing exposure to novel chemicals each shape immune responses in ways that can favour auto-reactivity.
The Gut Microbiome: A Key Player in Autoimmunity
The gut microbiome has emerged as a central mediator between environment and immunity. Multiple reviews link microbiome compositional and functional changes to autoimmunity through mechanisms, such as dysbiosis and antigenic mimicry.
“Certain microbial patterns appear to promote inflammation or molecular mimicry, mechanisms by which normal immune responses cross-react with host tissues, raising the risk of systemic autoimmunity in susceptible individuals. Dysbiosis can be triggered by antibiotics, ultra-processed diets, low fibre intake, and even air pollution, placing urban populations at particular risk,” added Dr Malipeddi.
Also Read: The Cardiac Impact Of Autoimmune Diseases: What Lupus, RA, And Psoriasis Can Do To The Heart
Environmental Triggers: Toxins, Chemicals and Lifestyle Factors
Environmental toxicants and lifestyle exposures add further pressure. Persistent organic pollutants, solvents, heavy metals and endocrine-disrupting chemicals have been associated with altered immune signalling, chronic inflammation and, where studied, higher rates of autoimmune disease.
Tobacco smoke remains a well-established environmental risk for conditions, such as rheumatoid arthritis and systemic lupus erythematosus, while emerging evidence links air pollution and climate-related exposures with increased autoimmune risk in some cohorts. Meta-analyses show smoking increases RA risk (~40% higher in ever-smokers) and occupational silica exposure is also linked to higher RA incidence.
Recognising Early Clinical Clues
Clinically, early autoimmune presentations are often protean. Patients may report:
Fatigue
- Arthralgia (joint pain) without inflammatory swelling
- Photosensitive rashes
- Dry mouth or dry eyes
- Nonspecific gastrointestinal symptoms
- Episodic numbness or pins-and-needles sensation
- Raynaud’s phenomenon (fingers change colour in cold)
Laboratory testing may show isolated autoantibodies—antinuclear antibodies (ANA) or others—raised inflammatory markers or subtle cytopenias, without fulfilling classification criteria for a single defined connective tissue disease. This cluster is sometimes labelled “undifferentiated connective tissue disease” (UCTD) or described as seropositivity with nonspecific symptoms; many patients remain stable, some remit, and others evolve into a defined autoimmune disorder over months to years.
Also Read: Autoimmune Diseases That May Trigger Hair Loss: What You Need to Know
How Do Doctors Approach These Cases?
Approach to evaluation should be measured and problem-focused. “A thorough history (including occupational and chemical exposures, infection history, lifestyle history and family autoimmune disease), careful physical examination, and targeted baseline tests which may include CBC, ESR/CRP, ANA, thyroid function, and basic metabolic panels—help triage patients,” explained Dr Malipeddi.
Referral to a rheumatologist or relevant specialist is warranted when signs of organ involvement appear (persistent proteinuria, neurologic deficits, cytopenias, or progressive serology). Over-testing can create noise; clinical judgement in repeating evaluations and monitoring evolution over time remains essential.
Managing Unexplained Autoimmune Symptoms
Management in early or unexplained presentations balances symptom control with minimising unnecessary immunosuppression.
Addressing modifiable contributors is a practical first step:
- Optimise sleep and stress management
- Encourage inclusion of whole-foods, fibre-rich diet that supports microbial diversity
- Avoid exposure to tobacco and unnecessary chemical exposures where possible
“Vaccination and prompt treatment of infections protect against immune dysregulation triggered by pathogens. Where diagnostic uncertainty persists, a shared care plan with clear follow-up intervals and thresholds for re-evaluation prevents delayed recognition of progressive disease. Emerging research explores microbiome-directed therapies and environmental remediation as preventive strategies, but robust clinical applications are still evolving,” explained Dr Malipeddi.
Bottomline
Dr Malipeddi concluded, “The rise in unexplained autoimmune symptoms isn’t a single-issue epidemic but a sign of complex changes in modern living interacting with genetic risk. For doctors, the key is to stay alert without over-treating minor complaints. For patients, it means getting checked for persistent or multi-system symptoms and reducing modifiable risks like poor diet, smoking, pollutants, and unnecessary antibiotics. Early recognition, careful testing, and lifestyle adjustments offer the best chance to stop the disease from progressing when the body starts turning on itself.”
[Disclaimer: This article contains information provided by an expert and is for informational purposes only. Hence, we advise you to consult your professional if you are dealing with any health issue to avoid complications.]