Lupus

What is lupus?

Lupus is a long term condition where a person’s body forms antibodies against different parts of itself. Lupus may cause the body to attack  the skin, joints, kidneys, lungs, heart, or brain.  Lupus is a type of vasculitis. This means that there is swelling of the blood vessels. In lupus, this swelling is caused by the immune system attacking itself.

What is vasculitis?

Vasculitis is inflammation (“-itis”) of blood vessels (vasculum = vessel). Inflammation is caused by white blood cells attacking something in a tissue. When “-itis” is at the end of a diagnosis, it means that swelling is involved in the disease. . There are many different causes of vasculitis.  Some vasculitis is caused by infection of vessels (as in Rocky Mountain spotted fever). Another cause of vasculitis is autoimmunity. Learn more about ANCA vasculitis here.

Who gets lupus?

Lupus affects an estimated 1.5 million Americans.  This disease is  found more often in women with a ratio of 9:1.  Lupus tends to affect more African Americans and Hispanics than Caucasians. Severe disease symptoms are more often seen in non-Caucasian patients.  

What causes lupus?

The causes of SLE are unknown. Many factors may play a role, including

  • gender—SLE is more common in women than men
  • heredity—a gene passed down by a parent
  • infections
  • viruses
  • environmental causes

What is lupus nephritis?

Lupus nephritis is a complication of lupus disease. It happens when lupus causes kidney damage. This damage is caused by swelling in the small blood vessels and small filtering units of the kidney.

How is lupus diagnosed?

Lupus nephritis is suspected when blood or protein is found in the urine. Another test that can indicate a problem is when the serum creatinine level in your blood is abnormally high. This  can result in a decreased Glomerular Filtration Rate (GFR).  Doctors estimate how well your kidneys are functioning using this test. Your doctor then might refer you to a nephrologist for a kidney biopsy. A biopsy is the only test which can diagnose lupus nephritis.

Once you have a biopsy, the sample is then identified based upon the degree and pattern of swelling and damage. This is shown in the table below. There are six classes of the disease. The severity of your disease is used by your kidney doctor or rheumatologist to make decisions with you about treatment options.

Table 1: The 2003 International Society of Nephrology and International Pathology Society Classification of lupus nephritis

  • Class I: Minimal mesangial lupus glomerulonephritis (LGN)
  • Class II: Mesangial proliferative LGN
  • Class III: Focal LGN (< 50% glomeruli)
  • Class IV: Diffuse LGN (> 50% glomeruli)
    • Class IV-S: Predominantly segmental
    • Class IV-G: Predominantly global
  • Class V: Membranous LGN
  • Class VI: Advanced sclerotic LGN (> 90% sclerotic  glomeruli)

Lupus classes 

Why are these classes important?

There are several treatment choices for people with lupus nephritis. Some of these treatment options are considered “aggressive.” They also have side effects which may not be appropriate for individuals with certain forms of lupus nephritis. The classes were based on several factors that help doctors discuss the best treatment options and outlook for people with lupus nephritis.

  • Class I: Mild disease with small amount of swelling
  • Class II: Still fairly mild disease but more swelling than Class I
  • Class III : Moderate degree of swelling with less than 50% of the filtering units (glomeruli) affected
  • Class IV : Severe degree of swelling with greater than 50% filtering units affected
    • Class IV-S: Of the affected filtering unit, less than ½ of it is affected by swelling
    • Class IV-G: Of the affected filtering unit, most of it is affected by inflammation
  • Class V: Most of the swelling is confined to the outer layer surrounding the filter unit
  • Class VI : Most of the filter units show scarring

What does lupus look like in a biopsy?

The kidney filter of a patient with lupus will show deposits in the kidney tissue. The deposits are made up of proteins turned on to help the kidney protect itself. In this image, these deposits are pointed out with arrows and are dark gray here. There are many of them in this image collecting along the walls of the inner layer of the filter.

Lupus deposits
Deposits in the kidney tissue of a patient with lupus

How is lupus treated?

The treatment of lupus can be complex, and should always involve specialists for each affected body system.

Doctors use a combination of approaches to try to reduce the symptoms of the disease without causing negative side effects from the treatment. The goal of the treatment is to reduce the swelling to protect organs from damage without harming the immune system and allowing other infections to spread.

Exact treatment depends on:

  • The type of blood vessel swelling
  • The severity of the disease
  • How many organ systems are affected                                          

Treatment options may include a combination of some of the following:

  • Corticosteroids: (prednisone, methyl prednisone, or Medrol®) is provided to reduce swelling and slow down the autoimmune response in vasculitis. To date, these are the only medicines that have been approved by the US Federal Drug Administration for the treatment of lupus disease.  
    • How do they work? Corticosteroids block the production of substances that trigger allergic and inflammatory actions in the immune system. By doing this, however, they cause white blood cells which protect the body from infections to not work as well. 
    • How is it given? Can be given either by mouth as a pill or liquid or supplied intravenously (IV). 
    • What are the possible side effects? This class of medication is very effective and usually necessary to control active disease symptoms.  There are several side effects. It is important to make sure patients are taking the lowest doses possible to keep their disease in control.  Some of these side effects include:
      • High blood pressure
      • High blood sugar (diabetes)
      • Osteoporosis (weakened bones)
      • Weight gain
      • Stretch marks
      • Cataracts
      • Severe mood swings/psychosis (more common in young children)
      • Infections (from weakening of the immune system)
  • Hydroxychloroquine (Plaquenil®) A drug that helps reduce swelling in lupus patients
    • How does it work? The way this medicine works is not entirely clear.  It is a medicine which has historically been used to treat malaria but has been found to have effects on cells of the immune system responsible for causing swelling.  Your doctor may refer to this medicine as a DMARD. This stands for Disease-ModifyingAnti-Rheumatic Drugs. It has been shown to be an important medicine in maintaining remission and treating lupus symptoms outside of lupus nephritis. However, it may not be enough if used alone for the treatment of advanced forms of lupus nephritis.
    • How is it given? It is given by mouth as a pill
    • What are the possible side effects? This medication in general is well-tolerated but there are several possible side effects.
      • Vision problems: It is important for patients taking this medication to undergo yearly eye exams
      • Severe anemia (low blood count): Individuals should be tested for a condition called G-6-PD deficiency before starting this medicine. If a person with this condition takes this medicine, it can cause a reaction that results in a massive breakdown of red blood cells.
      • GI: abdominal cramps and/or diarrhea
      • Liver problems:  Rare: your doctor should do  liver function tests at least twice a year
  • Immunosuppressive Drugs: (cyclophosphamide, cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, or Rituximab) Drugs that reduce the immune system's tendency to attack itself. These drugs are typically reserved for individuals with lupus and severe organ involvement.  Lupus that involves the kidney, brain, or significant arthritis may require this drug.
  • Cyclophosphamide (Cytoxan®)
    • How does it work? Cyclophosphamide reduces the ability of the immune system to make the white blood cells responsible for causing swelling. It is considered a type of chemotherapy.
    • How is it given? It can be given by mouth as a pill daily for several months or by IV once or twice monthly for 3-6 months. There is good data to support that it is just as effective if given by mouth as by IV. If given orally however, the overall exposure to this medicine is much greater.  Therefore it could possibly be associated with more side effects.
    • What are the possible side effects?
      • Having too few white blood cells-important to fight infections
      •  Low blood count
      • Low platelets (needed to help stop and prevent bleeding)
      • Blood in the urine caused by swelling in the bladder
      • Serious Infections
      • Increased risk of cancer in the future
  • Cyclosporine/tacrolimus (Gengraf®, Sandimmune®, Prograf®)
    • How does it work? These drugs block the effect of T-cells which are an important type of white blood cell in the immune system.
    • How is it given?  It is given orally as a pill or liquid
    • What are the possible side effects?
      • Having too few white blood cells-important to fight infections
      • Low blood count
      • Nervous system: Some individuals can experience headaches, tingling or numbness in the fingers or toes. In severe cases, seizures can occur if there is too much medicine in the body. All of these symptoms should be reported immediately to the doctor. 
      • Dental: Some individuals may notice swelling of the gums. This may be more common in people who are taking a specific type of blood pressure medicine called a calcium channel blocker at the same time.
      • Hair growth: This medicine can cause excessive hair growth on different parts of the body
  • Azathioprine/mycophenolate mofetil [MMF] (Imuran®, Cellcept®, Myfortic®)
    • How does it work? These drugs weaken the production of white blood cell in the immune system.
    • How is it given?  It is given orally as a pill or liquid
    • What are the possible side effects?
      • Having too few white blood cells-important to fight infections
      • Low blood count
      • GI upset: mostly with MMF (diarrhea and stomach cramps)
      • Birth Defects: MMF taken during pregnancy may cause some birth defects. Azathioprine on the other hand is relatively safe in pregnancy
      • Infections
  • Rituximab (Rituxan®)
    • How does it work? This drug blocks the production of B-cells which are important type of white blood cell of the immune system.
    • How is it given?  It is given through an IV 
    • What are the possible side effects? This treatment has only been around for about 10 years now and so there is little information about long-term effects.
      • Anaphylaxis: This is a severe allergic reaction that may happen at the time of infusion
      • Severe infection 
  • Other important treatments: The following treatments do not specifically treat lupus disease itself. But they are important for protecting the overall health of the kidneys. These treatments may help slow the progression of advanced kidney disease or kidney failure.
    • Controlling blood pressure to reduce increased damage to the kidneys
    • ACE inhibitors: A class of blood pressure medications that  helps slow down the formation of scars in the kidney


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