Jul. 17, 2012

Seasonal Influences on Lupus Flares

Evidence that abnormally large seasonal declines in vitamin D status may trigger SLE flare in non-African Americans
Birmingham D, Hebert L, Song H, Noonan W, Rovin B, Nagaraja H, Yu C. (2012). Lupus 21:855-864.

What is the topic?

Vitamin D exerts a wide range of influences on immune functions. Low levels of vitamin D are associated with autoimmune diseases, especially lupus. Interestingly, many of vitamin D’s actions are opposite to the immunological abnormalities observed in people with lupus. Multiple studies indicate that low levels of vitamin D are associated with increased lupus disease activity. The role of vitamin D levels and their relationship to lupus flares, however, has not been thoroughly investigated.

This study took into account the seasonal effect of sunlight exposure and skin pigmentation (by inclusion of both African-American and non-African-American patients), and their relationship to vitamin D levels and lupus flares.

What did the researchers hope to learn?

The researchers hoped to learn about the temporal relationship between vitamin D levels and lupus flares in people with lupus.

Who was studied?

A total of 46 people with active lupus, who developed one or more flares out of 106, from the Ohio Systemic Lupus Erythematosus Study, were included.

How was the study conducted?

Study participants were evaluated bimonthly to assess lupus-related biomarkers and approximately yearly to assess lupus flares. Each annual visit was classified as either “flare” or “no flare.” Study visits indicative of a flare were further classified as either “renal” or “non-renal” to describe whether or not the flare involved the kidney. Most of the study participants were followed for about 44 months.

Study participants were evaluated for blood levels of vitamin D at the time of each flare, as well as two and four months before a flare (together, this period of time is hereafter referred to as a “flare interval”). Additional studies assessed the effects of seasons on vitamin D levels during flare intervals.

What did the researchers find?

The participants were mostly white women (although African-Americans and Asians were also included) with an average age of 35 years of age. Most of them had lupus nephritis and were taking prednisone (a steroid) and immune-suppressing drugs. The study included 82 flare intervals in 46 lupus patients. Age, body mass index, and race were found to be significant predictors of vitamin D levels in the blood, but use of prednisone or hydroxycholoroquine were not.

When the data were stratified by race, there was a significant decrease in blood levels of vitamin D in non-African-American patients at the time of a flare (regardless of whether this was a renal flare or not). This difference occurred mostly during low daylight months (October through March, having an average of 10.5 hours of daylight), but not during high daylight months (April through September, having an average of 13.0 hours of daylight). This difference was also specific to flare intervals, as there were no significant decreases in vitamin D in the same non-African-American patients during no-flare periods occurring in low daylight hours.

Additional analyses (in the entire Ohio Systemic Lupus Erythematosus Study cohort of 106 patients; n=201 flares) showed a trend towards higher flare (mostly renal flares) rates in non-African-Americans during low daylight months as compared to high daylight months. During high daylight months, flare rates were significantly lower for non-African-Americans than for African-Americans.

What were the limitations of the study?

Lupus disease activity per se was not reported for the patients included in this study. Thus, it is unknown whether these results are applicable to patients who have chronically low, intermediate, or high disease activity. Also, these studies need to be repeated in a larger group of patients with variable organ-related manifestations of lupus. Lastly, it is unknown to what degree these results are applicable to men with lupus, as most of the patients included were women.

What do the results mean for you?

The results of this study indicate an important role for vitamin D levels as a mechanism or biomarker for lupus flares in non-African-American patients. During low daylight months, vitamin D levels become especially low, and during this time, flare rates are increased in non-African-American patients. Clinical trials further investigating these relationships will be required to more fully understand the roles of race/ethnicity and vitamin D levels in lupus flares occurring during different seasons.

Lupus patients may be well advised to work closely with their doctors to monitor their vitamin D levels and their relationship to their lupus flares. Decisions about whether lupus patients should take vitamin D supplementation may best be made in consultation with a rheumatologist or other qualified lupus practitioner.