Sickle cell disease in Adult
Alerts and Notices
SynopsisSickle cell disease is a life-threatening autosomal recessive genetic disease that results in an abnormal β-globin chain of hemoglobin A (hemoglobin S). Sickle cell trait or hemoglobin S trait (heterozygote for mutation) rarely results in significant chronic symptoms. Hemoglobin S homozygotes (sickle cell disease) manifests in infancy and progresses to a chronic disabling disease.
Current thinking suggests that the causative mutation in sickle cell disease primarily arose on the African continent due to the protective effect of the carrier state against malaria, so, globally, most patients share an African ancestry. The disease is most prevalent in Nigeria, where nearly 150 000 children are born with sickle cell disease annually. Additionally, there is a high incidence of sickle cell disease in individuals of Caribbean descent and those from Mediterranean countries such as Turkey, Greece, and Italy. In the United States, about 100 000 people have sickle cell disease.
In the United States, sickle cell disease is the most frequently detected condition in newborn-screening programs, regardless of ethnicity. Originally as a result of the transatlantic slave trade from Africa, nearly all sickle cell disease patients in the United States are Black.
Hemoglobin S has diminished solubility, especially when there is low oxygen tension. This diminished solubility results in the characteristic sickle shape of the affected red blood cells, leading to hemolysis and adherence to vascular endothelium, which leads to vascular occlusion, coagulation activation, and subsequent ischemia and tissue necrosis.
Acute presentations include vaso-occlusive crises (painful episodes of microvascular occlusion that involve joints, bones, and internal organs such as the spleen, liver, kidneys, and central nervous system; see sickle cell acute pain crisis and acute chest syndrome), hematologic crises (due to pooling of blood in the enlarged spleen), and infectious crises (result from functional asplenia, predisposing to infections from encapsulated organisms).
These painful crises cause significant suffering and stigmatization for sickle cell patients, who are often unjustly described as drug seekers and accused of faking their pain. This results in inadequate treatment, as well as added stress and suffering, leading many patients to avoid care altogether. Without adequate treatment, sickle cell disease can affect any organ and is associated with decreased quality of life and a shortened life span.
Chronic clinical manifestations of disease include hemolytic anemia and a variety of systemic symptoms and signs that occur as a result of microvascular occlusion (eg, ischemia, necrosis, splenic autoinfarction).
Leg ulcers, which can be extremely painful, are considered a marker of disease severity. The shins, dorsal feet, Achilles tendon, or ankles are frequent sites of involvement, as these are areas with little subcutaneous tissue and thin overlying skin with decreased blood flow. Ulcer formation may be spontaneous or may result from local trauma. Sickle cell ulcers are more common in males.
Factors that predispose to ulcer formation are:
- Vessel obstruction by sickle cells.
- Increased venous and capillary pressure.
- Secondary bacterial infection.
- Decreased oxygen carrying capacity of the blood, leading to peripheral ischemic changes in the skin.
D57.819 – Other sickle-cell disorders with crisis, unspecified
127040003 – Sickle cell anemia
Differential Diagnosis & Pitfalls
- Parvovirus B19 infection
- Bone infarcts
- Gout / septic arthritis
- Alpha and beta thalassemia
- Glucose-6-phosphate dehydrogenase deficiency (G6PD)
- Systemic lupus erythematosus
- Drug-related hemolytic anemia
- Disseminated intravascular coagulation
- Hemolytic uremic syndrome
- Thrombotic thrombocytopenic purpura
- Arterial ulcers (ischemic ulcers) are typically painful.
- Venous ulcers are associated with peripheral edema.
- Martorell ulcer
- Diabetic skin ulcers (neurogenic ulcers) are associated with neuropathy.
- Leukocytoclastic vasculitis – Related ulcers typically have associated purpura.
- Pyoderma gangrenosum usually occurs in association with inflammatory bowel disease, and ulcers are deeper with an undermined ulcer edge.
- Cholesterol emboli
- Coumadin necrosis
- Purpura fulminans
- Cocaine levamisole toxicity
- Klinefelter syndrome
- Pressure injury
- Squamous cell carcinoma / Marjolin ulcer
Patient Information for Sickle cell disease in Adult
OverviewThis summary discusses sickle cell ulcers. A sickle cell disease (SCD) ulcer is a breakdown of the top layer of skin that exposes underlying tissue. The ulcers can be very painful and can increase your risk of infection.
SCD ulcers occur most frequently on the legs and feet. It is not known exactly why individuals develop these ulcers, but it is thought to be due to blockage of small blood vessels and inadequate amounts of oxygen in the skin. Secondary bacterial infection can occur, causing fever, chills, swelling, redness, and draining of the ulcer. These ulcers can be challenging to manage and treat. Prevention is key in those with SCD and includes trying to minimize trauma on the lower legs and improving circulation in the legs. Due to the tendency of these ulcers to come back as well as the pain associated with SCD ulcers, this condition can have a significant psychological impact. It is important to notify your doctor of any psychologic stress or feelings of depression if they are present.
Who’s At RiskPatients with SCD are at an increased risk of developing ulcers. They are most common in patients aged 10 years and older.
There is an increased risk of ulcers with certain common treatments, such as hydroxyurea.
Signs & Symptoms
- Ulcers are most commonly seen on the lower legs and feet, specifically the sides of the foot as well as on the shins and tops of the feet. They can occur spontaneously or after trauma (eg, scratches, insect bites).
- Ulcers appear as a "punched-out" area of skin with distinct borders, raised edges, and surrounding darkening of skin (hyperpigmentation).
- The most common symptom is pain, which can be severe and debilitating.
- Regularly check skin on the lower legs to look for small ulcers.
- Use insect repellant to prevent bug bites.
- Wear properly fitting shoes.
- Treat any injury on the lower legs early.
- Use compression socks to help with circulation.
- Frequently elevate the legs.
When to Seek Medical CareIf an ulcer develops and you have SCD, it is important to see your doctor.
- Testing of involved skin (biopsy) might be necessary to confirm diagnosis and/or identify bacteria if there is a suspected infection.
- Most treatments are focused on decreasing pain, promoting wound healing, and preventing and/or treating any complicating bacterial infection. Some therapies used are:
- Specialized wound care dressings.
- Deep cleaning of the ulcer by a medical professional.
- Pain management.
- Oral zinc supplements to help with wound healing.
- Antibiotics for infection, if present.
- Your physician will also want to ensure your overall health with respect to the SCD.
Sickle cell disease in Adult