Lupus Now Research Update Issue #6

Lupus Patients with Potential for Kidney Disease Need to be Monitored Carefully
Allen, E.; Farewell, V.; Isenberg, D.; Gordon, C., Rheumatology 2006; 45(3): 308-313

Researchers have long attempted to develop some framework to sort patients into subgroups so predictions could be made about who might do better with one treatment approach versus another.  A study conducted in the United Kingdom has provided some statistical verification that subsets of lupus exist, with kidney involvement (renal disease) occurring frequently on its own, while skin (mucocutaneous) and joint and muscle (musculoskeletal) diseases may represent a possible subset by flaring together. In addition, the study also shows that a history of previous lupus flares and the involvement of other organ systems affect a patient’s chance of developing additional flares.

The researchers studied the symptoms and test results of 440 lupus patients over 10 years who had a history of active mucocutaneous, musculoskeletal, or renal disease. Lupus disease activity was evaluated every three months and the side effects of lupus or its treatments (damage to joints or organs) were assessed about every six months.

The researchers found that patients who had previous history of active disease in a given part of the body were at greater risk for having future disease activity of the same type. The higher the number of previous visits in which patients reported active disease of a given type, the greater the likelihood of having new reports of active disease of that type as well. This was true for mucocutaneous, musculoskeletal, and renal system involvement.

A history of renal disease appeared to decrease a patient’s chances of developing active mucocutaneous and musculoskeletal disease. However, it should be pointed out that people with a history of renal disease likely are taking immunosuppressive medications for longer periods of time than people without any threat to the kidney, and this might keep rashes and joint pain/swelling from flaring. On the other hand, patients in the study with previous active musculoskeletal disease were less likely to present with renal disease activity. Patients with a history of mucocutaneous activity and musculoskeletal damage had an increased risk of presenting with musculoskeletal disease, as did those who had a history of severe mucocutaneous and musculoskeletal disease.

These findings lead the researchers to suggest that mucocutaneous disease and musculoskeletal disease may represent one subset of lupus, and renal disease another subset. The most important finding in this study is regarding past damage to the kidney and renal disease. A patient’s chance of developing active renal disease was increased if there was evidence of renal damage. That, the researchers point out, may be a result of renal disease activity being “clinically silent” — which means it is occurring, but without being detected by the patient or a doctor. As a result, the patient may already have encountered significant permanent damage to the kidney before an obvious flare is discovered. This finding points to the need for lupus patients with potential for kidney disease to be monitored carefully, in order to uncover disease activity that is “under the radar” but nonetheless capable of producing significant harm.  Click here to read the complete abstract.

TNF-a Protein May Contribute to Lupus Skin Rashes

Zampieri, S.; Alaibac, M.; Laccarino, L.; et. al., Annals of Rheumatic Diseases 2006; 65:545-548

Tumor necrosis factor alpha (TNF-a) is an immune-regulating protein (cytokine) that is manufactured and released by cells to act in the bloodstream. Increased amounts of this protein can be found in many inflammatory diseases, and also can be produced by the body in response to toxic substances in bacteria. Tumor necrosis factor is important because it stimulates another regulating protein called interleukin (IL)-1, which regulates other immune responses, such as activating white blood cells, called lymphocytes, and helping to trigger fever. TNF-a increases tissue damage by IL-1, stimulates immune cells to make destructive proteins (collagenases) which degrade tissues, and plays a role in how the immune system recognizes specific triggering agents.

In this study researchers examined tissue biopsy samples taken from patients with lupus skin rashes (called subacute cutaneous lupus) that had not responded to the usual treatments, such as antimalarial drugs, immunosuppressive drugs, and thalidomide.  The researchers compared what was found in these skin samples with biopsies from patients with other inflammatory and cancerous skin diseases. The skin rash samples from patients with lupus showed a strong presence of TNF-a particularly in the skin’s outer layer (the epidermis). However, TNF-a was not seen in healthy skin samples from the same group of lupus patients, or in skin biopsies from the non-lupus group.

These findings suggest that TNF-a is produced by the surface region (epidermal layer) of skin in this kind of lupus rash, and might have a role in causing of this kind of rash. This finding might help to develop superficial skin treatments for this rash that might work better and/or be less toxic than medicine which is taken by mouth or put directly into the bloodstream.  Click here to read the complete abstract.