SAN FRANCISCO—At the May 17 California Rheumatology Alliance 10th Annual Medical and Scientific Meeting, Bevra H. Hahn, MD, professor emeritus of medicine, David Geffen School of Medicine, University of California Los Angeles (UCLA), gave a comprehensive talk titled, 2014: An Update on Pathogenesis, Diagnosis and Treatment of SLE.
She discussed two important new clinical concepts in systemic lupus erythematosus (SLE). First was the 2012 publication of the Systemic Lupus International Collaborating Clinics (SLICC) criteria,1 which have “definite advantages,” said Dr. Hahn, due to expansion of dermatologic, neurologic and immunologic disease classification indicators. The SLICC criteria, she said, have been validated in a cohort of more than 1,700 patients with lupus and shown to have 93% specificity and 92% sensitivity. Dr. Hahn has been encouraging pharmaceutical companies to incorporate these criteria along with the older ACR SLE criteria in clinical studies going forward.
The second clinical concept is the current international movement to incorporate treat-to-target (T2T) principles into management of people with lupus. “In my opinion,” she stated, “we need to do a better job [of treating patients]. That’s why we’re trying to introduce ‘treat to target.’ We should first treat to low level disease activity [LL-DAS, a concept introduced by the Asia Pacific League of Associations for Rheumatology and a EULAR committee] and then treat to prevent flares.” The goals of therapy should be to induce and maintain improvement, prevent damage and address pain, fatigue and depression, “which are major drivers of quality of life.” In conversation following the meeting, Dr. Hahn said she currently incorporates discussion of T2T in all her lupus talks and hopes that the U.S. rheumatology community will soon embrace the principles, which have been used successfully in rheumatoid arthritis.
Disease Pathways
Dr. Hahn described the SLE disease process, which begins with autoantibodies and immune complexes fixing to tissue and causing damage by activating the complement system (a component of the innate immune system). The resultant inflammatory response takes on “a domino effect.” Recent research has revealed that neutrophils in the process of netosis cast out nets of protein studded with DNA, which present to the immune system, activating additional inflammatory response. Dendritic cells also sense the neutrophil nets and react by releasing interferon alpha. “We never thought neutrophils were major players in SLE, but they are,” Dr. Hahn stated.
Researchers now know of 50–55 genes that predispose people to SLE; and environmental factors, such as Epstein-Barr virus and cigarette smoking, are now well validated as possible triggers for lupus. Female gender is also important. Dr. Hahn also noted, “If lupus begins when the patient is younger than 25, it’s far more severe.”
Treat Nephritis Early
A heterogeneous disease, lupus has many organ manifestations. The kidneys are susceptible to damage, and the extent of involvement determines treatment strategies. It’s critical to recognize and treat nephritis early, said Dr. Hahn. “Delay of treatment more than six months increases mortality fourfold; and data from Chan et al in Hong Kong suggest that a delay of three months before initiating treatment doubles mortality.”
