For Lupus Patients, a Day in the Sun?
By Julia Hess
Image: Dr. John A. Hardin (Rheumatology)
Vitamin D is well known for its essential role in maintaining bone density. A growing body of knowledge indicates that it may help prevent cancer, hypertension, and diabetes as well as improve muscle function in older individuals. Vitamin D may also have important immunological consequences for patients with autoimmune diseases such as lupus, according to Dr. John A. Hardin, Professor of Medicine (Rheumatology) and Microbiology and Immunology at Albert Einstein College of Medicine, Professor of Orthopedic Surgery at Montefiore Medical Center, and Chief Scientific Officer of the Arthritis Foundation.
Systemic lupus erythematosus (SLE, or lupus) is a chronic, potentially fatal disease in which the body’s immune system attacks healthy cells, resulting in complications ranging from skin rashes and joint pain to seizures and kidney failure. Severe vitamin D deficiency is prevalent among patients with lupus, particularly African Americans, who are most commonly and severely affected by the disease. “Replacing patients’ vitamin D levels as part of treatment may improve the clinical outcome of SLE and significantly affect the health of people living in the Bronx,” said Hardin during a recent Medicine Grand Rounds on the topic.
Target blood levels of vitamin D are currently thought to be 30–40 ng/ml. Daily doses of 1000–2000 IU achieve this level in most patients, and 2000 IU/day is considered safe. The average American diet provides only 140–280 IU of vitamin D daily (the best sources are oily fishes like salmon and mackerel and D-fortified milk and cereals); as much as 90% is manufactured by the skin in response to UV exposure. A day in the sun produces about 10,000 IU, but after about 20,000 IU the sun destroys vitamin D in the skin, a self-regulating mechanism that prevents toxicity.
Vitamin D deficiency is particularly prevalent and profound in racial groups with higher levels of melanocytes (pigment-producing cells that help block UV photons). About 12% of apparently healthy African Americans have been found to have severe vitamin D deficiency (defined as levels at or below 10 ng/ml). Vitamin D levels within this range are associated with the bone disease osteomalacia. Severe vitamin D deficiency is also common among Hispanic populations. Medical advice to avoid sun exposure, medications such as corticosteroids (commonly prescribed for lupus), and inflammation, which augments the catabolism (enzymatic breakdown) of vitamin D, may contribute to its deficiency. In a recent study of patients in the Bronx and in South Carolina, Hardin and colleagues found that almost 30% of African Americans and 12% of Hispanics with SLE have severe vitamin D deficiency.
Vitamin D deficiency is likely to be a particular problem for people with SLE. Patients are usually advised to avoid sun exposure, known to trigger disease flares in some individuals. During SLE’s immune response, dendritic cells (DCs, which are the body’s sentinels against infection) respond to activating factors such as interferon alpha present in lupus plasma. Activated DCs are thought to stimulate autoreactive responses by T and B lymphocytes. Additionally, patients with active lupus often have an enhanced interferon (IFN) signature, characterized by higher levels of expression of interferon alpha regulated genes.
In an ongoing study, Hardin and colleagues are examining whether correcting vitamin D levels can reverse the vitamin D signature of patients with SLE. They reason that vitamin D could enable DCs to resist the activating effects of interferon alpha. If the study confirms this, vitamin D supplementation could provide a safe, effective means to improve treatment outcomes for lupus patients. Reducing the DC response and reversing the IFN signature could lessen the severity of SLE-associated complications including kidney disease, blood disorders, and central nervous system issues such as seizure and stroke.
Race is one factor that influences patients’ vitamin D requirements and response to supplementation. Others include age, sex, BMI, and amount of sun exposure. Despite its variability, vitamin D, a relatively benign treatment approach, has significant immunologic potential. Hardin recommends that physicians in the Bronx be particularly vigilant in determining patients’ blood levels of 25-hydroxy vitamin D and recommending appropriate amounts of vitamin D supplements. “Vitamin D can improve immune regulation and may even reverse features of established autoimmunity,” he said. “This has a pervasive impact on many different processes that are integral to our musculoskeletal health and our immunity.”