AssessmentsSystemic lupus erythematosus (SLE): Pathology review
USMLE® Step 1 style questions USMLE
A 38-year-old woman comes to the clinic complaining of pain in her hands for several months. The pain is characterized by an intermittent aching in both of the wrists and the bases of the fingers that lasts for hours at a time. The patient also feels warm at night and has not had much of an appetite recently. The patient’s temperature is 37.6 C (99.6 F), pulse is 77/min, respirations are 14/min, and blood pressure is 145/85 mmHg. Physical examination shows mild symmetric swelling of the wrists, metacarpophalangeal, and proximal interphalangeal joints bilaterally, without tenderness on palpation. There are no skin lesions. Laboratory studies show the following:
Which of the following is the most common cause of death in patients with this condition?
At the internal medicine department, a 42 year old female named Mary shows up. She complains of multiple skin lesions on the arms, chest and back. She reports having these lesions for about 3 months. In the past, she had similar lesions. She reports morning stiffness involving her fingers and knees, as well as a history of multiple miscarriages. Blood tests revealed pancytopenia as well as a very high ESR and CRP. She was positive for ANA and antiphospholipid antibodies.
Meanwhile, at the emergency department, a 25 year old man named Kyle shows up with flank pain and hematuria. He has a history of migratory arthralgias and photosensitivity. He was positive for ANA and double-stranded DNA antibodies, and also had low complement levels. Blood tests revealed very high ESR and CRP, as well as high creatinine, so a urinalysis was performed, showing proteinuria and red blood cell casts.
Both individuals actually have very different presentations of the same disease, called Systemic Lupus Erythematosus. This is a systemic, relapsing, and remitting autoimmune disease, where systemic means that essentially any tissue or organ can undergo inflammation; while relapsing and remitting, stands for periods of illness, called relapses or flares; and periods of remission during which there are few or no symptoms.
Now, lupus develops when the person’s immune system starts recognizing nuclear antigens of the body’s own cells as foreign and tries to attack them. Essentially, B cells start producing antibodies which bind to nuclear antigens in our own cells. Normally, these B cells are destroyed before they fully mature in a process called self tolerance, but in people with lupus this process is impaired. The antibodies released by these B cells form antigen-antibody complexes and these complexes drift around in the blood until they deposit or stick to the vessel wall in all sorts of different organs and tissues like the kidneys, skin, joints, heart.
Deposited complexes then initiate a local inflammatory reaction, which causes damage through the activation of the complement system, which, after a huge cascade of enzyme activation, causes the cell to burst and die. Eventually, this gets complement factors like C3 and C4 all used up. A very high yield fact to remember is that this is a kind of type III hypersensitivity reaction.
Another high-yield fact is that because early complement proteins like C1q, C2 and C4 are all involved in removing those antigen-antibody complexes, individuals that lack any of these proteins are more likely to experience lupus. Now, many patients also develop antibodies targeting other cells like red, white blood cells and platelets, leading to pancytopenia. This is considered a type II hypersensitivity reaction.
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