Lupus is an autoimmune disease where the immune system attacks healthy tissue, causing inflammation and damage to various parts of the body. The exact causes of lupus are unknown, but certain factors are thought to trigger the onset and flares of the disease. Understanding the potential triggers can help lupus patients better manage their condition. This article will explore the various environmental, genetic, hormonal, and lifestyle factors that may trigger lupus.
Environmental Triggers
Certain environmental exposures are associated with increased risk of developing lupus or triggering lupus flares in those who already have the disease. Some of the top environmental triggers include:
Sunlight Exposure
Exposure to UV rays from sunlight is one of the most common lupus triggers. Sunlight contains ultraviolet B (UVB) rays that activate the immune system and cause inflammation in people with lupus. This can lead to skin rashes in sun-exposed areas and general flares involving internal organs. Patients with discoid lupus and subacute cutaneous lupus are especially photosensitive. Limiting sun exposure, wearing protective clothing and sunscreen are important preventive measures.
Infections
Viral and bacterial infections are capable of activating the immune system and increasing autoantibody production, which can trigger lupus flares. The Epstein-Barr virus that causes mononucleosis has been strongly linked to increased lupus risk. Other viruses like parvovirus B19, cytomegalovirus, HIV, and hepatitis C can trigger episodes of disease activity. Bacterial infections like streptococcus may also stir up antibodies that target tissues and cause symptoms.
Medications
Certain prescription drugs are associated with drug-induced lupus, an autoimmune reaction that causes symptoms similar to systemic lupus. Drugs most linked to drug-induced lupus include hydralazine used for high blood pressure, quinidine used for heart arrhythmias, minocycline which is an antibiotic, and TNF inhibitors used for rheumatoid arthritis. In most cases, symptoms resolve within months after stopping the medication.
Pollution
Exposure to pollutants such as cigarette smoke, exhaust fumes, and industrial chemicals may increase the risk of developing lupus. Air pollution containing ozone and fine particulate matter is associated with more fatigue, joint pain, rashes, and internal organ involvement in lupus patients. Minimizing pollution exposure by avoiding or reducing smoking and staying indoors on high smog days may help.
Stress
High levels of emotional, physical, or occupational-related stress can overstimulate the immune system and trigger lupus flares. Stress causes increased production of immune cells and inflammation-triggering chemicals like CRP. Finding healthy ways to manage stress through good coping techniques, relaxation practices, therapy, medication, or support groups can help prevent stress-related flares.
Genetic Factors
Lupus has a strong hereditary component, indicating that genetics plays an important role. People with a family history of lupus or related autoimmune diseases are at higher risk. Specific genes linked to increased lupus risk include:
Gene mutations
Certain mutations in immune system genes can cause immune cells to be overactive and more prone to attacking the body’s own tissues. Mutations in genes like TREX1, SPP1, STAT4, IRF5, BLK and TNIP1 are associated with higher lupus risk. These mutations may be inherited or develop spontaneously.
Human leukocyte antigen (HLA) genes
Variations in HLA class II genes that regulate immune function are strongly associated with lupus. The HLA-DR2, HLA-DR3, and HLA-DR4 alleles appear to increase risk, especially in certain ethnic groups. Altered HLA genes may allow the immune system to be misdirected against normal tissue.
Interferon genes
People with lupus often have abnormal interferon levels. Variations in interferon regulatory genes lead to excess interferon activity, triggering increased autoimmunity. Changes in interferon-related genes represent a genetic predisposition for developing lupus.
While genetics set the stage, environmental factors are often needed to trigger lupus onset in those predisposed. But in those already diagnosed, flares can often be triggered by inheritable influences alone.
Hormonal Triggers
Female sex hormones, especially estrogen, affect the function of the immune system and are thought to explain the 9:1 ratio of females to males who get lupus. Changes in estrogen and progesterone may stimulate immune reactivity in lupus-prone women. Key hormonal factors that can lead to flares include:
Puberty
Lupus is rare before puberty, but the surge in estrogen levels often brings on the first symptoms. Up to 1/3 of pediatric lupus cases begin around the time of their first period in adolescent girls. Estrogen increases immune activity and autoantibody production, which may trigger disease processes.
Pregnancy
Pregnancy provokes major changes in the hormonal, immune and vascular systems, so lupus patients are at increased risk of developing preeclampsia, miscarriage, flares and other pregnancy complications. The high estrogen state can upregulate immune activity, while shifts in the balance between protective and harmful antibodies may also have negative impacts.
Postpartum Period
Many women experience lupus flares in the months following childbirth due to crashing estrogen levels. The risk of postpartum flares is up to 3 times higher compared to pregnancy rates. Hormones, complement proteins and vascular factors normalize in the postpartum period, leading to increased lupus activity.
Menopause
Reductions in estrogen during menopause can remodel the immune system and influence lupus course. Up to 20% of lupus patients report increased disease activity in the peri-menopause and menopause transition phase. Declining estrogen disrupts immune regulation, often triggering symptom flares.
Hormone Therapy
Estrogen/progesterone medications like birth control pills, hormone replacement therapy (HRT) or infertility treatments can boost immune activity and flare symptoms like rashes, joint pain and fatigue in lupus patients. Any hormonal therapies should be carefully considered and monitored.
Lifestyle Triggers
Certain lifestyle habits and conditions can trigger lupus flares by increasing inflammation or disturbing immune function. Some key lifestyle factors that provoke lupus include:
Stress
As mentioned under environmental triggers, physical and emotional stress causes hormonal and immunological changes that can aggravate lupus. High stress and poor coping abilities are associated with increased disease activity. Managing stress can help minimize its impact.
Smoking
Smoking cigarettes introduces toxins and free radicals into the body, which activate the immune system. This contributes to inflammatory chemical release and reduced red blood cells in lupus patients. Smoking causes worse general health, frequent flares, organ damage and poor response to therapy.
Alcohol Use
Drinking alcohol to excess can impair immune regulation and promote inflammation. Alcohol consumption is linked to more joint inflammation, increased risk of lupus nephritis, and interferes with medications used to treat lupus. Limiting alcohol intake can help avoid flares.
Inadequate Sleep
Not getting enough quality sleep contributes to fatigue and has negative immunologic effects in lupus patients. Lack of sleep increases pro-inflammatory cytokines while decreasing antibodies and anti-inflammatory cytokines. Maintaining good sleep hygiene helps prevent flares related to sleep debt.
Medication Non-adherence
Many lupus patients struggle to take their medications as prescribed, often due to side effects. But missing doses frequently can result in higher disease activity and flares. Good adherence to steroids, antimalarials, immunosuppressants and other drugs helps control inflammation.
Blood Transfusions
Receiving donated blood components can trigger severe lupus flares, especially in those with latent disease. Transfusions may stimulate abnormal immune activity from the mismatched blood components or the release of cytokines that drive tissue damage.
Other Potential Triggers
Aside from the main categories described above, other miscellaneous factors may act as lupus flare triggers in certain patients including:
Vitamin D deficiency
Many lupus patients are low in vitamin D which is important for a balanced immune response. This deficiency is linked to increased disease activity, so vitamin D supplements may help control flares.
Medications
In addition to drugs that induce lupus-like symptoms, certain medications like antibiotics, antifungals, anticonvulsants, and antihypertensives can also provoke flares in some people with pre-existing lupus.
Physical trauma
Accidents, falls, or other forms of physical injury involving bruising, tissue damage or bleeding can trigger localized lupus activity, vasculitis and worsening joint pain by causing acute immune activation and inflammation.
Weather changes
Some patients report more symptoms when weather fronts are moving in or atmospheric pressure is changing rapidly. The reasons for weather sensitivity are unclear but may involve factors like heat, humidity, sunlight intensity and barometric pressure affecting circulation and joint swelling.
Diet
While no specific foods are proven lupus triggers, deficiencies or eating excess fat, sugar or sodium may promote inflammation. An unhealthy diet contributes to obesity, heart disease, kidney problems and reduced exercise tolerance.
Conclusion
Lupus is a disease with complex causes and influences. While the exact pathogenesis remains unclear, various environmental, genetic, hormonal and lifestyle factors can trigger the onset and flares of lupus by stimulating the inflammatory immune responses that drive this condition. Reducing exposure to these known triggers can help stabilize the disease course. More research is needed to better understand the interactions of these different variables and develop optimal prevention strategies for susceptible individuals. But avoiding potential triggers forms a key part of managing lupus. Patients should try to limit environmental exposures, balance hormones, maintain a healthy lifestyle and follow treatment plans to prevent avoidable flares of this chronic autoimmune disorder.
