Written by Shreya Bhardwaj
Edited by Anirudh Koneru
Published on 9/21/2020
In honor of September being sickle cell awareness month, this week's rare disease highlight is on sickle cell disease!
Description
Sickle cell disease is a group of inherited red blood disorders in which red blood cells become hard, sticky, and sickle shaped. This causes the cells to die early leading to a shortage of RBCs, as well as a multitude of other symptoms, including pain crises.
Out of this group of disorders, sickle cell anemia is the most common condition, with around 100,000 people in the US alone suffering from this condition. Sickle cell disease can be diagnosed as early as in utero, with being able to perform blood tests to confirm diagnosis as early as age two.
Signs and Symptoms
With symptoms appearing as quickly as five months old, there are a multitude of symptoms that are associated with this condition. The most prevalent sign of this condition is anemia, which is when sickle red blood cells end up quickly dying off and the body is not left enough time to recuperate the lost cells. This can lead to chronic fatigue overtime, considering that without an adequate amount of red blood cells, oxygen supply to the body is significantly lower.
Perhaps the most painful of all these symptoms are the sudden episodes of pain, also known as pain crises, that occur when sickle cells flow into the capillaries surrounding the chest, abdomen, joints as well as bones.
Another important effect of this condition to notice is frequent infections, of various types. Seeing as this disease can leave the spleen severely damaged, this leaves the body more prone to infections. In a means to prevent dangerous illnesses such as pneumonia, infants and children are often given vaccines and antibiotics as a prophylactic method of protection against harmful pathogens. In addition, other symptoms include swelling of the hand and feet (as a result of blocked blood flow), pale skin/nail beds, and a yellowish tint to the skin and the whites of the eyes.
There are a plethora of complications that are associated with this condition, all of which impact different areas in the body, the most serious of which is stroke. Occurring as a result of blocked blood flow to the brain, signs of stroke such as seizures, numbness in the arms/legs, speech difficulties and confusion can be present.
Another serious complication is Acute chest syndrome, in which a lung infection that is present in the body causes sickle cells to block blood vessels to the lung, resulting in chest pain, fever and difficulty breathing. This condition can potentially be fatal and requires emergency medical treatment.
Pulmonary hypertension is another such complication which impacts the lungs, in which there is high blood pressure within the lungs, possibly leading to shortness of breath and fatigue. Continuing with blood flow blockage as a result of sickle cells, organ damage is also something that can occur as a result of those areas of the body being oxygen-deprived. With a lack of oxygen-rich blood, it leads to damaged nerves and organs within the body.
In addition, blindness, leg ulcers, gallstones and priapism are all other associated complications. Regarding pregnancy, having sickle cell disease can lead to an increased risk of high blood pressure, blood clots, miscarriage, premature birth and low-weight birth.
Etiology
Sickle cell disease is caused by a mutation in a gene which instructs the body to produce hemoglobin, an iron-rich compound which makes blood the color red and enables red blood cells to carry oxygen from the lungs throughout the body. Specifically, the mutated allele of this gene results in production of abnormal hemoglobin that causes red blood cells to become rigid, sticky and misshapen.
Considering that this disease is an autosomal recessive inherited condition, both the mother and father must pass the recessive allele onto their child in order for them to have it. If only one parent ends up passing on the mutated allele, the child will still produce normal hemoglobin, but will end up being a carrier for the disease, meaning that they would be able to pass it onto their children.
Diagnosis
In terms of diagnosis, a simple blood test can check for the defective form of hemoglobin, which is directly derived from sickle cell disease, in which blood is drawn from the arm (adults) or the heel (babies) and then is sent to the lab to screen for the abnormal protein. In the US, this test is one of many routine tests that are performed on newborn babies.
If the person is diagnosed with sickle cell disease, additional tests may be performed in order to check for possible complications that are associated with the disease. Specifically in assessing stroke risk, a special, painless ultrasound machine is used in which doctors check which children have a higher risk of stroke. Additionally, sickle cell disease can be diagnosed in an unborn child by extracting some of the amniotic fluid to see whether the child has the pair of recessive alleles for the condition, and is especially given if both parents are carriers of the defective allele.
Treatments/Therapies
Most therapies for sickle cell disease are usually aimed at minimizing/avoiding pain episodes, relieving symptoms and preventing complications. Managing symptoms can be achieved through medications, prophylactic infection prevention, and blood transfusions.
In terms of medications, there are a variety of drugs out in the market that aim to reduce the frequency of pain crises and are sometimes associated with side effects. For instance, Hydroxyurea and L-glutamine oral powder are helpful in reducing the frequency of episodes of pain and reduce the need for blood transfusions and hospitalizations.
Similarly, Crizanlizumab also does the same job in the body and is given intravenously, however it is associated with side effects such as nausea, joint/back pain and fever. In addition, a doctor might prescribe general pain-relieving medications (usually narcotics) in order to relieve the pain that is felt during pain crises.
A particular medication that is used for improving anemia in sickle cell patients is Voxelotor, however this drug can be associated with headache, nausea, diarrhea, fatigue, rash and fever. As aforementioned, prophylactic use of antibiotics and vaccines are useful in preventing dangerous infections such as pneumonia.
While these are usually given to children between the ages of 2 months and 5 years old, some adults may have to take penicillin throughout their life, especially if they have had pneumonia or removed their spleen, which is vital in protecting against pathogens.
Another method of treatment that is sometimes considered is blood transfusions, such as red blood cell transfusions along with stem cell transplants. In a red blood cell transfusion, red blood cells are removed from a supply of donated blood and are given intravenously, which ultimately helps in increasing the number of normal red blood cells within the body.
The only current cures for sickle cell disease are stem cell or bone marrow transplants. However, both of these treatments are rarely done as there are many serious risks involved. A stem cell transplant involves replacing bone marrow that is affected by sickle cell disease with healthy bone marrow from a donor, and the procedure usually calls for a matched donor, such as a sibling, who does not have the disease. Considering the risks, this procedure is only recommended to people who have many complications associated with sickle cell disease.
Rarity
Sickle cell disease is considered a rare disease around the world, and in the US, it is the most common inherited blood disorder, affecting approximately a total of 100,000 Americans. Within the US, sickle cell disease most often affects black people, with 1 new case reported per 365 African American births.
Additional Resources
There is a wide variety of organizations and support groups that are available to help patients who suffer from sickle cell disease, along with their caretakers.
For a general list of resources, click HERE
Organizations:
Facebook Groups:
Clinical trials related to sickle cell disease can be found on clinicaltrials.gov, where you can apply to be a part of trials that might change the course of sickle cell disease treatment!
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Citations:
CDC. (2019, October 21). What is Sickle Cell Disease? Retrieved September 21, 2020, from https://www.cdc.gov/ncbddd/sicklecell/facts.html
Mayo Clinic Staff. (2020, January 30). Sickle Cell Anemia. Retrieved September 21, 2020, from https://www.mayoclinic.org/diseases-conditions/sickle-cell-anemia/symptoms-causes/syc-20355876
United Kingdom National Health Service. (2019, April 16). Treatment - Sickle Cell Disease. Retrieved September 21, 2020, from https://www.nhs.uk/conditions/sickle-cell-disease/treatment/