1. This lecture was conducted during the Nephrology Unit Grand Ground by Medical Student under Nephrology Division under the supervision and administration of Prof. Jamal Al Wakeel, Head of Nephrology Unit, Department of Medicine and Dr. Abdulkareem Al Suwaida, Chairman of Department of Medicine and Nephrology Consultant. Nephrology Division is not responsible for the content of the presentation for it is intended for learning and /or education purpose only.

2. Presented By: Dr. Majed Abaalkhail Medical Student 2009

3.  Systemic lupus erythematosus is an autoimmune rheumatic disorder of unknown cause that typically strikes young women  The word lupus, meaning wolf, derives from this characteristic rash that was thought to resemble wolf's markings; erythematosus is derived from the Latin word for redness

4.  The damage of lupus occurs when the immune system produce antibodies that attack the body's own tissues.  Abnormalities of the immune system also make people with lupus vulnerable to infections

5.  the reported prevalence of systemic lupus erythematosus (SLE) world wide is 40 to 50 cases per 100,000.  Due to improved detection of mild disease, the incidence has nearly tripled in the last 40 years.

6.  Sixty-five percent of patients with SLE have disease onset between the ages of 16 and 55. Of the remaining cases, 20 percent present before age 16, and 15 percent after age 55.

7.  The specific cause of SLE is unknown.  Research suggests that many factors contribute to the immune dysregulation observed in SLE. These factors are : 1) Genetic factors 2) Environmental factors (UV light, stress.. ) 3) Hormonal factors ( Estrogen.. ) 4) Drugs

8.  Drug-induced lupus erythematosus is a reversible condition.  Drug-induced lupus mimics systemic lupus, however, symptoms of drug-induced lupus generally disappear once a patient is taken off the medication which triggered the episode.  There are about 400 medications currently in use that can cause this condition & most common drugs are procainamide, quinidine (antiarrhythmic), hydralazine (vasodilator) and isoniazid (anti-TB).

9.  Lupus disease can be divided according to symptoms and site of body involved into two main categories: cutaneous & systemic.

10.  Cutaneous LE usually provoked by sunlight  Types: discoid lupus, subacute lupus, lupus profundus, cutanous lupus mucinosis &neonatal lupus.

11.  Discoid lupus: Is the most common type of cutanous lupus.

12.  Subacute lupus:  Chracteristics: a non-itchy dry rash appears on the upper back and chest, often following sun exposure.

13.  SLE may begin suddenly or develop slowly over months or years. Chronic fatigue, unexplained fever, weight loss & loss of appetite are common systemic complaints.

14.  Muscle aches.  Joint pain.

15.  The most common skin presentation in SLE is butterfly rash (specific feature).  Features:

16.  In SLE, deposits of antibodies accumulate in the glomeruli which causes persistent inflammation of kidneys called lupus nephritis.  The World Health Organization has divided lupus nephritis into six classes based on biopsy findings

17.  Class I is minimal mesangial glomerulonepphritis.  Class II is based on a finding of mesangial proliferative lupus nephritis.  Class III is focal proliferative nephritis.  Class IV is diffuse proliferative nephritis.  Class V is membranous nephritis.  Class VI Glomerulosclerosis.

18.  Blood disorders can affect up to 85% of patients with SLE. These disorders are:  Anemia: The most common hematological abnormality in SLE is anemia.  Thrombocytopenia.  Granulocytopenia and Lymphocytopenia: increasing susceptibility to infections

19.  Nerve disorders can affect up to 25% of those with SLE.  CNS Vasculitis is the most serious form of systemic lupus  Other symptoms include headache, seizures, memory impairment, cognitive dysfunction ……..

20.  Inflammation of various parts of heart may occur as pericarditis, endocarditis or myocarditis. Chest pain & arrhythmias may result from these conditions.  SLE can increase risk of atherosclerosis which can lead to coronary artery disease.

21.  Chronic diffuse interstitial lung disease  pluritis  SLE can cause other manifestation as pulmonary hypertention, pleural effusion, pulmonary hemorrhage (rare fatal complication).

22.  In 1971 The American College of Rheumatology (ACR) established a criteria to diagnose SLE witch consist of 11 items.  4 of these items are enough to establish a diagnosis.

23. - Items :  1- Malar rash  2- Discoid rash  3-Photosensetivity  4-Oral ulcer  5-Non- erosive arthritis  6-Pleuritis or pericarditis  7-Renal disorder  8- Seizures or phsychosis  9- Hematolgical disorder  10-Immunological disorder  11- Positive ANA

25.  NSAIDs (e.g. ibuprofen..) are useful for patients with mild disease and arthralgia.  Chloroquine and hydroxychloroquine are also used in mild disease when symptoms cannot be controlled with NSAIDs, or for cutaneous disease.  Topical steroids are used for discoid lupus.

26.  Corticosteroids form the mainstay of treatment, particularly in moderate to severe disease.  Imuunosuppressives (e.g. Azathioprine, cyclophosphamide), Usually in combination with steroids are used for patients with severe manifestations ( e.g. renal or cerebral disease)

27. Infections remain a major cause of morbidity and mortality in patients with SLE throughout the world, Almost two decades ago, the Lupus Survival Study Group examined the causes of death of 1103 patients with SLE. Infections accounted for 33% of the deaths, whereas active disease for 31% WHY? 1- leukopenia 2- Drugs

29.  The Institute of Molecular and Cell Biology in Strasbourg - France - has discovered a protein fragment, the P140 peptide, that is capable of treating lupus-affected mice. The initial results of phase II studies in patients with the disease were published on November 26 2008 on the website of the journal Arthritis & Rheumatism.

30.  When treated with the P140 peptide, lupus- affected mice exhibited a lifespan similar to that of unaffected animals. Their renal disease was significantly diminished and they presented with much less severe inflammatory and joint symptoms.  The phase IIa clinical study was carried out in two centers in Bulgaria on 20 lupus patients who received three subcutaneous injections of the P140 peptide at 15-day intervals.

31.  It was shown that this peptide did not generate any adverse effects (side effects) in the patients, apart from minor redness at the injection site that rapidly regressed.  The efficacy of P140 was demonstrated by a reduction in the anti-DNA auto-antibodies. Immune globulin levels, which are elevated in lupus patients, were also regulated.

32.  It was shown in animals that repeated doses of P140 peptide did not affect their ability to resist viral infection, unlike immunosuppressants in general. Thus P140 peptide constitutes the first potential candidate for the specific treatment of lupus.  A phase IIb clinical study involving some 200 patients is currently under way in South America and Europe.