It’s full medical name is Systemic Lupus Erythematosus, or SLE for short. Most people just call it Lupus. That’s much easier to say and remember. It’s a complex disease that physicians often suspect, but infrequently diagnose. Actually diagnosing it is a process that can take months or years and requires testing, re-testing, biopsy, and a host of clinical acumen. Most cases are diagnosed and treated by rheumatologists because it is an autoimmune disease, and autoimmune disorders are their area of expertise.
Lupus is a multi-system disease meaning it can potentially involve any organ in the body, and thus can present with a variety of symptoms. It is estimated there are 200,000 cases of Lupus in the U.S. for an incidence of 1 in every 1660 people. Women of childbearing age (15-45 yrs.) are 10 times more likely to have lupus than men. Cases vary from mild, with symptoms of a rash, arthritis, and fatigue, to severe with involvement of the kidneys, central nervous system, and bloodstream. The symptoms a patient has are directly related to the extent of involvement of the body’s organ systems.
A simplified explanation of what happens in Lupus is that the patient produces antibodies against components of the nuclei of its own cells. The nucleus, or center, of a cell, contains structures called nucleosomes, histones, and the DNA of the cell. These harmful antibodies attack and damage the structures in the nucleus, particularly the DNA, resulting in inflammation and blood vessel abnormalities in the targeted organ. If antibodies target the skin, patients have a typical rash. If they target the kidneys, nephritis and kidney failure ensue. If they target the joints, arthritis develops. If it’s the blood, anemia, low white blood cell and platelet counts are the results.
The diagnosis of SLE is made by measuring antibody levels in the blood, biopsying the affected organ (eg. kidney biopsy, skin biopsy), and correlating the results with the symptoms experienced by the patient. The test done most often is an ANA, or Antinuclear Antibody, level. The level is called the titre (tight-er) of antibody present in the blood. The higher the titre, or level, of antibody, the greater the likelihood the patient has lupus. Titres are expressed as dilutions, or “watering down,” of the blood. Negative means, of course, no antibodies were present. A dilution of 1:80 (1 to 80) means significant antibody is present to diagnose lupus. Higher antibody titres, such as 1:160, 1:640, or higher, increase the possibility of the diagnosis. I once had a patient with an ANA of 1:1280, but she was diagnosed with a different autoimmune disorder.
Therein lies the problem with ANA testing—It is not specific for Lupus. Other autoimmune diseases can have a positive ANA. To help diagnose SLE accurately, Anti-DNA Antibody levels in the blood are also measured. These results are also expressed as the titre, or dilution; the higher the titre, the greater the chance Lupus is present. These results, plus the ANA titre, and a biopsy of the targeted tissue correlated with symptoms will pin down the diagnosis. In a biopsy, the pathologist looks for blood vessel inflammation (vasculitis) and damage to the cells of the organ. As you can see, diagnosing Lupus takes patience, persistence, and clinical suspicion. For forty years I suspected a lot of patients had lupus. I tested patients for it, but never proved it once. My patients with positive ANA’s always turned out to have something else. The woman whose ANA was 1:1280 has CREST syndrome (Calcinosis, Raynaud’s phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasias).
Mild cases of Lupus involve only the skin and/or joints causing a rash, joint pain and swelling. and fatigue. Severe cases cause kidney failure, neurologic symptoms such as headache, seizures, neuropathy, and psychiatric symptoms(depression, psychosis), plus pleuritis (inflammation of the lining of the lungs and chest wall). Pleuritis causes chest pain, cough, shortness of breath, and in severe cases, free fluid to collect in the chest cavity (pleural effusion). Deaths from Lupus do occur with the cause determined by duration of the illness. Kidney failure takes younger, sicker patients while the elderly are felled by widespread vascular (circulatory) disease.
Treatment involves potent, expensive drugs. The foundation of therapy is a combination of corticosteroids (prednisone, solumedrol, etc.) and immunosuppressives such as hydroxychloroquine, methotrexate, cyclophosphamide, and azathioprine. These are the rheumatologists aspirin and penicillin and have been used for decades. These drugs suppress the entire immune system and do not target the specific areas involved with Lupus. Thus they often have untoward effects that are more harmful than desired.
To circumvent this lack of specific focus, scientists have developed a host of biologicals called monoclonal antibodies that are used as “add-on” therapy. These drugs are developed specifically to target the abnormality causing the symptoms the Lupus patient experiences and supplement the immunosuppressive regimen. Studies using belimumab, anifrolumab, ustekinumab, and baricitinib have been successful in relieving symptoms from the organ affected by the abnormal antibodies. Scientists anticipate further developments and improvements in monoclonal antibody drugs in the future. Very gratifying is the lack of adverse effects from these drugs because of their targeted specificity.
The negative about these drugs is they’re expensive and must be given parenterally, meaning either as a shot or through an intravenous infusion. I don’t have specific numbers, but belimumab out of pocket can run $15,000 a year. So at that price you want to be sure it’s the right drug for you. If you enroll in a clinical trial you get the drug free if you’re in the treatment arm, but you may not be. You don’t know.
Systemic Lupus Erythematosus is one of those enigmatic diagnoses that draws the attention of physicians because it is complex, interesting, and intellectually challenging. Lupus is often the unknown diagnosis in a clinicopathologic conference (CPC) or the topic of a grand rounds seminar. Physicians like to speculate on the diagnosis and pathologic findings when given a smattering of information. Lupus fits that profile. If you’re a patient with Lupus, however, it’s still an enigma because you’re constantly hoping someone will find a treatment that will end your discomfort and bring about a remission.
References: Manson JJ, Rahman A. Systemic Lupus Erythematosus. Orphanet J of Rare Dis 2006;1(6):1-6.
Tanaka Y. State-of-the-art treatment of systemic lupus erythematosus. Int J Rheum Dis. 2020 ;23: 465-471.
Srivastasa A. Belimumab in Systemic Lupus Erythematosus Indian J Dermatol 2016 Sep-Oct;61(5) 550-553.
https://www.Medline plus.gov/druginfo/meds/a611027.html.
Dubey AK, Handu SS, Dubey S, Sharma P, Sharma KK, Ahmed QM. Belimumab: First targeted biological treatment for Systemic Lupus Erythematosus. J Pharmacol and Pharmacother. Oct-Dec 2011;2(4):317-319.
