Sickle Cell Disease in Social Security Disability Evaluations (2025)
Chapter: 6 Effects of Sickle Cell Disease on Body Systems Other Than the Central Nervous System
6
Effects of Sickle Cell Disease on Body Systems Other Than the Central Nervous System
Sickle cell disease (SCD) causes organ damage resulting from the abnormal adhesion and sickling of affected red blood cells (RBCs) after they release oxygen within capillary beds. This sickling causes vaso-occlusion of these blood vessels and ischemia of surrounding tissues. In addition, abnormal RBCs are rapidly destroyed—a process known as hemolysis—causing inflammation and dysfunction of blood vessels in addition to significant anemia (Kavanagh et al., 2022). The sickling and hemolysis seen in SCD triggers chronic inflammation and blood vessel dysfunction, leading to acute and chronic organ damage throughout the body.
This chapter describes complications resulting from SCD that occur outside the central nervous system (CNS), which is covered in Chapter 5, and is organized into sections consistent with the Social Security Administration (SSA) disability listings. People with SCD may have a myriad of complications for which there are individual SSA listings in various organ systems, although many complications listed below do not have a specific listing. Often, a person with SCD might be under the threshold for an individual listing but may have multiple complications that collectively can impair functioning and an individual’s ability to maintain a job or consistently attend school. In addition, many SSA listings allow an individual to meet medically determinable impairments via a certain number of visits, treatments, interventions, required testing, and symptoms. In people with SCD, the same number of visits, treatments, and tests may be accumulated through multiple different organ complications.
CNS complications are also mentioned throughout this chapter since many with serious organ damage have concomitant CNS issues, such as
neurocognitive decline and depression in those with heart failure and kidney disease. In addition, this chapter discusses the use of chronic transfusion therapy in SCD and compares that with the use of the same therapy in those with beta-thalassemia.
Annex Tables 6-1 through 6-7 at the end of the chapter list selected non-CNS conditions associated with SCD. The tables include a summary of the potential functional implications of each of the conditions and, for children, the potential functional equivalence domains affected. Where applicable, they also include potentially relevant SSA listings. For functional implications, the committee chose to focus on the kind of information that SSA considers about functioning in children and adults, which comes from a variety of sources, including the applicant, medical providers, educators, employers, and other third parties with knowledge of the applicant. In the previous chapter, Annex Table 5-2 lists the six functional equivalence domains considered by SSA when evaluating children for disability, and Annex Table 5-3 lists the physical activities; vision, hearing, and speaking activities; and mental activities the committee considered in populating the tables, along with their definitions. For Annex Tables 6-1 through 6-7, the committee members populated the columns on potential functional limitations and potential functional equivalence domains affected based on their collective expertise.
SPECIAL SENSES
Retinopathy
Sickle cell retinopathy (SCR) is a unique sickle cell complication that can cause vision loss. Vaso-occlusion causes hypoxia and inflammation, resulting in endothelial activation and infarction. This may be nonproliferative, which is characterized by varying degrees of hemorrhage and infarct, or proliferative, a more severe type with infarction, fibrosis, and the growth of abnormal and fragile blood vessels that are prone to bleeding and can cause vitreous hemorrhage and retinal detachment (Sourla, 2024). Some patients may also have macular infarction and central retinal vein thrombosis.
Pathogenesis and Risk Factors
SCR occurs in all genotypes of SCD but is more prevalent in those with HbSC disease, affecting up to 33 percent of adults with this genotype (Sourla, 2024). It is slightly less common in other genotypes, such as HbSS. Vessel changes may begin during adolescence and are progressive during adulthood, with older age being one of the main risk factors for SCR. Male
sex, increased hemoglobin, and low fetal hemoglobin are additional risk factors (Scott, 2016; Sourla, 2024).
Functional Implications
Initially, patients may be asymptomatic. In more severe cases, SCR can cause visual impairment, including blind spots, floaters, blurred vision, loss of peripheral vision, and irreversible vision loss. People with SCD are recommended to undergo routine SCR screenings starting around 10 years of age, with dilated eye exams and occasionally through angiography by a retinal specialist to identify damage early. People living with SCD report inadequate counseling about the risks of SCR and early warning signs. One study evaluated online educational content about SCR, concluding that it is often difficult to understand and of substandard quality (Gbedemah et al., 2024; Sourla, 2024; Taylor et al., 2024).
Treatment options range from intraocular injections of medications to inhibit endothelial proliferation (vascular endothelial growth factor inhibitors) to laser ablation. Injections can result in blurred vision and light sensitivity up to 48 hours from the injection and may be required weekly in severe cases. Chronic blood transfusions and hydroxyurea treatment are disease-modifying therapies for SCD that may also decrease the severity of SCR (Menaa et al., 2017). While there is no specific listing for SCR, the listings for a loss of visual acuity (2.02 and 102.02), contraction of the visual field (2.03 and 102.03), or overall loss of visual efficiency accounting for effects on both visual acuity and visual field (2.04 and 102.04) may apply.
Hearing and Vestibular Function
Sensorineural hearing loss, or hearing loss from inner ear damage, is a common form of hearing loss in individuals with SCD (Speller-Brown et al., 2022).
Pathogenesis and Risk Factors
Repetitive damage secondary to SCD and related vaso-occlusion is thought to present most commonly as sensorineural hearing loss (Kiser et al., 2019). Vaso-occlusion may lead to decreased flow through the labyrinthine artery that supplies the inner ear. This may lead to hypoxia of the organ of Corti and the stria vascularis within the cochlea and cause the death of outer hair cells that amplify sound (Abdelmahmuod et al., 2020). This results in permanent inner ear damage and hearing loss. Hearing loss may also occur as a negative side effect from iron chelation therapy, which is used in cases of iron overload from chronic transfusions (Farrell et al., 2019).
Functional Implications
Hearing loss in children has a documented negative effect on speech and language development, academic performance, and self-image (Kiser et al., 2019). Hearing loss for adults can have a significant effect on career choices, effective communication in the workplace, and employment. The SSA listing criteria should be similar to those with loss of hearing or disturbance of labyrinthine-vestibular function (Listings 2.07, 2.10, 102.10), as there is no specific listing for SCD-related hearing loss.
CARDIOVASCULAR COMPLICATIONS
Cardiomyopathy
Cardiomyopathy in patients with SCD is common, with prevalence estimates unknown (Kaur et al., 2020; Sachdev et al., 2021). An enlarged cardiac silhouette on routine chest radiograph is a common finding.
Pathogenesis and Risk Factors
Chronic anemia results in a high cardiac output state that over time may lead to ventricular hypertrophy from increased workload. In fact, SCD is associated with a somewhat unique cardiomyopathy characterized by cardiac muscle hypertrophy, myocardial fibrosis, and inflammation, leading to ventricular dilation, increased filling pressures (diastolic dysfunction), and increased propensity for arrhythmias (Kaur et al., 2020; Sachdev et al., 2007). The pathogenesis may involve repeated ischemia–reperfusion injury (Federti et al., 2025). Myocardial fibrosis may result in ventricular stiffness and diastolic dysfunction in the absence of hypertrophy. The left atrium can also become enlarged because of SCD; this enlargement is associated with more severe diastolic dysfunction, anemia, and volume overload (Sachdev et al., 2021). Indeed, many clinicians have experienced inducing pulmonary edema after administration of intravenous fluids and blood products even in young patients with SCD who do not have signs of cardiac enlargement on chest radiograph or electrocardiogram (EKG).
Thus, heart failure with preserved ejection fraction is more common than heart failure with reduced ejection fraction, though the latter can develop at later stages. Patients with SCD and heart failure may present with left ventricular dilatation and/or hypertrophy, but these features may also be absent in those with significant diastolic dysfunction caused by myocardial fibrosis. Elevated right-sided heart pressures and eventual right-sided heart failure from SCD-related pulmonary arterial hypertension may also result from left-sided heart failure. For unknown reasons, cardiac iron
loading is not as prevalent in patients with SCD as in similarly transfused patients with thalassemia major.
Functional Implications
Similar to the case with patients with heart failure of any etiology, function may be impaired by dyspnea (shortness of breath on exertion), orthopnea (difficulty breathing when lying flat), and peripheral edema. Fatigue is also a common manifestation of heart failure and may be exacerbated by baseline anemia in patients with SCD. As noted, clinicians must exercise caution in delivering intravenous fluids and blood products as patients with subclinical systolic or diastolic dysfunction may develop congestive heart failure with relatively small volumes of fluid. Other potential functional limitations can include neurocognitive deficits, as discussed in Chapter 5. Neurocognitive deficits have been associated with SCD and heart failure independently (Shore et al., 2025), but no data currently exist on the effect of heart failure on cognitive function in people with SCD.
Implications for SSA Listings
SSA Listing 4.02 states that patients must have evidence of ventricular hypertrophy (i.e., left ventricular posterior wall plus septal thickness totaling ≥ 2.5 cm on imaging) to fulfill the criteria for disability resulting from heart failure with preserved ejection fraction. However, this may not be present in those with SCD with heart failure with preserved ejection fraction. For children, the associated SSA listing may be 104.02.
Arrhythmias
Abnormal heart rhythms, or arrhythmias, are also common in patients with SCD. As with people in general, arrhythmias may be asymptomatic and harmless. However, they can be symptomatic in the form of fatigue, syncope (fainting or a temporary loss of consciousness), embolic stroke (stroke caused by a blood clot), and sudden death.
Pathogenesis and Risk Factors
The processes that contribute to heart failure also predispose people with SCD to arrhythmias. One study of 100 patients found that the prevalence of ventricular arrhythmias was 22 percent, with nine of these patients having nonsustained ventricular tachycardia (D’Humières et al., 2023). These data may help explain the relatively high risk of sudden death in SCD patients. This same group later documented a 26 percent prevalence
of atrial arrhythmias in 130 SCD patients, and this was associated with a history of stroke without underlying vasculopathy. Eight percent had a history of paroxysmal or atrial fibrillation, and four percent had a history of permanent or persistent atrial fibrillation (D’Humières et al., 2024.) Because atrial fibrillation may cause embolic stroke, these data highlight the need to look for etiologies of stroke as one would in the general adult stroke population without SCD and not assume that SCD-associated damage, disease, or dysfunction of blood vessels is the cause.
Functional Implications
To suppress symptomatic arrhythmias, individuals may require medication, mechanical ablation, placement of implantable defibrillators, or combinations of these therapies, just like those without SCD. The SSA criteria should be similar to those for individuals with cardiac arrhythmias (4.05, 104.05) as there is no specific SCD listing.
Other Cardiac Complications
Classical coronary artery disease and myocardial infarction from atherosclerosis in epicardial vessels are uncommon in patients with SCD (Chacko et al., 2013). In the past this was likely the result of a low prevalence of classic risk factors, such as hyperlipidemia and hypertension, and of the short lifespan of people with SCD, who often did not live long enough to develop atherosclerotic lesions. Chest pain is a common concern in patients with SCD but often with atypical characteristics, such as sharp rather than pressure-like pain, and absence of EKG changes typical of ischemia. However, elevation of cardiac injury biomarkers is not uncommon, and cardiac magnetic resonance imaging (MRI) demonstrates evidence of cardiac microvascular disease in about one-third of patients in one study during the study period (Kaur et al., 2021). In addition, some patients do manifest a more typical course of acute coronary syndromes with EKG changes and cardiac injury biomarkers despite the absence of epicardial vessel disease. It is presumed that these events are caused by acute reverse microvascular occlusion. There is no evidence-based management approach for SCD, and case series have described a combination of disease-modifying therapies, including hydroxyurea and RBC exchange, in addition to those used for large vessel disease, such as aspirin, beta-blockers, and statins.
Pathogenesis and Risk Factors
It is presumed that these events result from acute reverse microvascular occlusion.
Functional Implications
Chest pain is common but not generally attributable to cardiac ischemia. The criteria should be similar to those for coronary artery disease (4.04) for the rare patient with SCD who has coronary artery disease.
RESPIRATORY COMPLICATIONS
Pulmonary disease and pulmonary complications are major contributors to disability, morbidity, and mortality in SCD (Miller and Gladwin, 2012). The causes of pulmonary manifestations of SCD include chronic, direct injury to the lungs from sickled RBCs that results in vaso-occlusion and hemolysis. The presence of vaso-occlusion and hemolysis in the lungs can lead to intrinsic restrictive lung disease, asthma and other obstructive lung diseases, and pulmonary arterial hypertension.
Intrinsic Restrictive Lung Disease
Also called sickle cell chronic lung disease, intrinsic restrictive lung disease is a direct manifestation of SCD that is associated with dramatically shortened lifespan and functional limitations (Greenough, 2016). Sickle cell chronic lung disease causes fibrosis of the lung and is thought to result from chronic inflammation, repeated vaso-occlusion, and repeated injury from infection and acute chest syndrome.
Functional Implications
Restrictive lung diseases are associated with decreased exercise tolerance and, when more advanced, cause weight loss, medical frailty, reduced quality of life, and limited ability to carry out activities of daily living. The associated SSA listings include 3.02 for chronic respiratory disorders in adults and 103.02 for chronic respiratory disorders in children.
Asthma and Other Obstructive Lung Diseases
In addition to asthma, individuals with SCD often develop an asthma-like syndrome marked by cough and wheeze, with obstruction on pulmonary function testing. Asthma has disproportionately high rates in urban populations owing to such factors as indoor and outdoor air pollution and other environmental allergens (Grant and Wood, 2022). As discussed in Chapter 1, individuals living with SCD often live in urban or highly urban areas (Olaniran et al., 2024), leaving children living with SCD at an increased risk for asthma and asthma-like syndrome (George et al., 2023). Chronic inflammation of blood vessels in individuals with SCD is thought
to contribute to higher rates of obstructive asthma-like symptoms above rates that would be expected in the general population (Gomez and Morris, 2013).
Functional Implications
Obstructive lung diseases are also associated with decreased exercise tolerance and, when more advanced, cause weight loss, medical frailty, reduced quality of life, and limited ability to carry out activities of daily living. The associated SSA listings include 3.02 and 103.02 for chronic respiratory disorders in adults and children, respectively, and 3.03 and 103.03 for asthma in adults and children, respectively.
Pulmonary Arterial Hypertension
Pulmonary arterial hypertension is a complication associated with many hemolytic anemias, leading to the hypothesis that chronic hemolysis may be a direct cause of pulmonary arterial hypertension. Pulmonary arterial hypertension caused directly by SCD is treated by the optimization and escalation of SCD therapy (hydroxyurea, chronic transfusion, curative therapy), whereas pulmonary hypertension resulting from repeated pulmonary emboli is treated as chronic thromboembolic pulmonary hypertension, similar to the case with the general population (Chong et al., 2021; Machado and Gladwin, 2005). Pulmonary hypertension in SCD may also be caused by left-sided heart failure. Individuals with SCD often also have sleep apnea, which can exacerbate pulmonary hypertension.
Functional Implications
Pulmonary hypertension is associated with limitations in exercise tolerance in its early stages. In more advanced disease, patients become dependent on supplemental oxygen and develop right-sided heart failure. Chronic hypoxemia further exacerbates symptoms of SCD by increasing systemic sickling. The applicable SSA listing is 3.09, chronic pulmonary hypertension resulting from any cause.
Acute Pulmonary Injury
Individuals with SCD develop acute lung complications, including
- Pneumonia—Individuals with SCD often develop pneumonia, thought to result in part from increased susceptibility to infections with encapsulated organism infections such as Streptococcus
- pneumoniae. Some sources view pneumonia that responds to antibiotics as a mild form of acute chest syndrome (Vichinsky et al., 2000), while others view the pathophysiologies as distinct with acute chest syndrome being caused by by-products of hemolysis triggering a capillary leak syndrome (Ghosh et al., 2013).
- Acute chest syndrome—Acute chest syndrome is marked by lung infiltrates and other symptoms of pneumonia that, if untreated, often rapidly progress to respiratory failure. The initial presentations of acute chest syndrome are indistinguishable from pneumonia. Failure to respond to antibiotics, progression of symptoms, and improvement with blood transfusion increase the likelihood that the patient has acute chest syndrome rather than simple pneumonia, though the two are often indistinguishable. Causes of acute chest syndrome include infection, pulmonary embolism, fat embolism, and other direct injuries to lung tissue (Vichinsky et al., 2000).
- Acute lung infarcts—While it is rare, individuals with SCD can present with acute infarcts of a portion of their lung resulting from large vessel occlusion.
Functional Implications
Acute pulmonary injury events can lead to short-term disability with each episode, caused by hospitalization and deconditioning. With recurrent events, chronic lung disease typically develops. The SSA listings relevant to acute lung complications include 14.07 and 114.07 for pneumonia and 7.05 and 107.05, listed for hemolytic anemias, including SCD, thalassemia, and their variants, which may apply to acute chest syndrome and acute lung infarcts.
Pulmonary Embolism
SCD is associated with a predisposition to clotting, deep venous thrombosis, and pulmonary embolism. Studies have suggested that these complications are found at elevated rates compared with the general population (Novelli et al., 2012). Pulmonary embolism is common in SCD and should be treated the same as it is in the general population (Shet and Wun, 2018). Acute pulmonary embolism may trigger SCD pain and can result in extended hospitalization as well as functional limitation resulting from decreased cardiopulmonary reserve. Chronic repeated pulmonary emboli can cause chronic thromboembolic pulmonary hypertension, which has high morbidity and functional limitation and is treated the same as in the general population.
Functional Consequences of Acute and Chronic SCD Lung Manifestations
Acute Deoxygenation of hemoglobin causes sickling in individuals with SCD, which leads to many of the disease’s downstream manifestations. Since lung dysfunction can lead to hypoxemia and therefore increased sickling, acute episodes that involve the lung often trigger other manifestations of SCD, especially pain. Hospitalizations for acute pulmonary issues often result in multifactorial, extended disability owing to decreased cardiopulmonary reserves, anemia, pain, and deconditioning from hospitalization.
Chronic Given the combination of decreased cardiopulmonary reserve and hemolytic anemia, chronic lung manifestations often result in permanent functional limitation and an increased frequency of acute complications. Chronic hypoxemia with intermittent worsening increases the likelihood of more frequent and severe SCD crises as lung function declines. The SSA listings for chronic respiratory disorders are 3.02 and 103.02.
Sleep Apnea
Sleep-disordered breathing (SDB) refers to a family of sleep-related disorders including sleep apnea and other interruptions of breathing that occur during sleep. In the general population, SDB occurs most commonly in obese individuals as a result of a compression of the airway by facial and neck structures (Leinum et al., 2009). In children with SCD, SDB occurs more commonly from obstruction by enlarged tonsillar or adenoid tissue (Sharma et al., 2015). In adults with SCD, increased levels of oxygen desaturation are linked to SDB. Similarly, chronic use of opioids may be a risk factor for central sleep apnea (Sharma et al., 2015). Central sleep apnea, though less well described in people with SCD, is associated with cerebral ischemia (Kepplinger et al., 2014).
Epidemiology and Pathophysiology
Estimates of the prevalence of SDB in SCD range from 30 to 70 percent of patients (Raghunathan et al., 2017). SDB, even when mild, can result in nocturnal hypoxemia, diastolic cardiac dysfunction, and eventually pulmonary hypertension. As individuals with SCD are already predisposed to cardiac abnormalities and pulmonary hypertension, even mild to moderate SDB can have substantial consequences.
Functional Implications
Primary symptoms of SDB include fatigue, low sleep latency, and neurocognitive dysfunction. Individuals with SCD experience the same symptoms as a result of chronic anemia and SCD cerebrovascular manifestations, including decreased cerebral perfusion and silent and overt strokes. Because the underlying etiology of symptoms is often multifactorial, mild anemia combined with mild cerebrovascular damage and mild SDB can result in symptoms that are severe enough to be disabling. There is no specific SSA listing for sleep apnea, and sleep-related breathing disorders are evaluated under their specific affected body system.
GENITOURINARY COMPLICATIONS
Chronic Kidney Disease
Chronic kidney disease is defined as the presence of kidney damage, as evidenced by urinary albumin excretion of more than 30 milligrams per day or the equivalent or an estimated glomerular filtration rate (eGFR) of less than 60 milliliters per minute per 1.73 meters-squared (ml/min/per 1.73 m2) of body surface area for at least 3 months (Kidney International Supplements, 2012). Among individuals with SCD, one study suggests that 20 percent of adults with SCD will develop chronic kidney disease (Derebail et al., 2019). A population surveillance study estimated the prevalence of chronic kidney disease among adults with SCD in California to be 24.4 percent, with the highest prevalence in males aged 50 to 59 years at 48.4 percent (Valle et al., 2024). Chronic kidney disease is often preceded by changes in the amount of protein excreted in the urine, which in individuals with SCD increases with age, affecting more than 50 percent of patients with SCD who are over 40 years of age (Guasch et al., 2006). In addition, 4 to 18 percent will progress to end-stage kidney disease (Airy and Eknoyan, 2017). Using data from the U.S. Renal Data System, researchers found that over 2,000 individuals with SCD developed end-stage kidney disease over a 20-year period ending in 2017, with 20 percent of the cases occurring before age 30 years (Winer et al., 2022).
Pathogenesis and Risk Factors
The pathophysiology of chronic kidney disease in SCD is incompletely understood, but research has identified vaso-occlusion and associated ischemia–reperfusion injury, hemolysis, oxidative stress, and hyperfiltration as contributing factors (Ataga et al., 2022). In SCD, chronic medullary ischemia in the inner part of the kidney results in vasodilation and increased
renal blood flow, resulting in glomerular hyperfiltration (Ataga et al., 2022). A study of infants with SCD revealed that glomerular hyperfiltration is one of the earliest complications seen in SCD, observed in infancy and early childhood (Ware et al., 2010). As individuals with SCD age, the eGFR appears to return to normal, but this represents a loss of kidney function rather than an improvement in hyperfiltration (Derebail et al., 2021). In addition, the common formula for estimating glomerular filtration rates using creatinine is inaccurate in SCD because of lower muscle mass and increased renal tubular secretion of creatinine (Afangbedji and Jerebtsova, 2022; Sharpe and Thein, 2014). Risk factors for chronic kidney disease include male gender, increasing age, and lower hemoglobin levels.
Functional Implications
The functional effects of chronic kidney disease and end-stage kidney disease among individuals with SCD are similar to those among the general population and include fatigue from worsening anemia, cognitive dysfunction, depression and anxiety, and decreased quality of life (Kittiskulnam et al., 2016). All of these significantly affect physical and emotional functioning and may limit the ability to work. In addition, the burden of maintenance dialysis is significant and includes managing the symptoms associated with the procedure, such as fatigue, itching, and nausea; common complications associated with dialysis, including electrolyte abnormalities, muscle cramps, bone pain, and chest pain; mental health effects including anxiety and depression; and the time commitment required (Mehrotra et al., 2023), all of which affect one’s ability to work. Individuals with SCD with end-stage kidney disease have almost a three times higher mortality rate than individuals with end-stage kidney disease who do not have SCD (McClellan et al., 2012). Moreover, people with SCD and end-stage kidney disease in the United States who qualify for kidney transplant have longer wait times for transplant than age-matched comparators and are therefore likely to be on dialysis longer (Zahr et al., 2024).
Implications for SSA Listings
SSA Listings 6.05 and 106.5, chronic kidney disease with impairment of kidney function, may underestimate the degree of impairment in people with SCD, as they state that children and adults must have serum creatinine levels of at least 3 milligrams per deciliter or greater, creatinine clearance of at most 30 ml/min/1.73m2, or eGFR of 30 ml/min/1.73m2 or less to fulfill the criteria for disability resulting from chronic kidney disease. However, individuals with SCD can have higher eGFRs because of hyperfiltration and
lower creatinine levels because of decreased muscle mass and renal secretion and thus can have clinically significant chronic kidney disease without meeting SSA criteria for disability.
The associated SSA listings for adults include 6.03, chronic kidney disease with chronic hemodialysis or peritoneal dialysis; 6.04, chronic kidney disease with kidney transplant; 6.05, chronic kidney disease with impairment of kidney function; and 6.09, complications of chronic kidney disease. The associated SSA listings for children include 106.03, chronic kidney disease with chronic hemodialysis or peritoneal dialysis; 106.04, chronic kidney disease with kidney transplant; and 106.05, chronic kidney disease with impairment of kidney function.
Priapism
Priapism, a persistent painful erection, is a common complication of SCD that occurs at least once in approximately one-third of adolescents and adults (Idris et al., 2020). Priapism is classified as stuttering, lasting 4 hours or less, or major, lasting more than 4 hours. It is often recurrent, but most episodes resolve without medical intervention. The pain associated with priapism in SCD is caused by ischemia resulting from compartment syndrome. Given the lack of knowledge, shame, and embarrassment regarding priapism, up to 50 percent of individuals may not seek treatment or disclose this condition to their family or SCD provider (Idris et al., 2020).
Pathogenesis and Risk Factors
Nitric oxide is a key molecule in normal erectile functioning, activating the process that leads to blood vessel dilation and penile smooth muscle relaxation and later terminating the erection (Idris et al., 2022b). Chronic hemolysis, or the breakdown of RBCs, in SCD depletes nitric oxide, which in turn leads to low levels of phosphodiesterase type 5, the primary enzyme responsible for the termination of an erection (Musicki and Burnett, 2020). Priapism is often seen in individuals with SCD who have other forms of vascular disorders, including leg ulcers (Minniti et al., 2010), pulmonary hypertension, and kidney disease. In addition, use of antidepressants, anti-psychotics, anticoagulants, alcohol, and cocaine have been associated with priapism (Pucci et al., 2020).
Functional Implications
While there are sparse data on the effects of priapism on function in the workplace and school, focus groups have found that priapism is detrimental to psychological, physical, and sexual well-being (Idris et al.,
2022a). One could imagine that a painful and prolonged erection may impair one’s ability to remain at work or school, and people with this complication frequently report shame and embarrassment (Nellesen et al., 2019). Priapism is also associated with depression, suicidal ideation, and anxiety (Idris et al., 2022b). Erectile dysfunction is a common sequela of priapism, with individuals with SCD having a two-fold increase compared to those without SCD (Anele and Burnett, 2015). There is no specific SSA listing for priapism.
Nocturnal Enuresis and Frequent Daytime Urination
Nocturnal enuresis, or recurrent nighttime bed-wetting in children older than 5 years of age at least twice per week, affects up to half of individuals with SCD at some point in childhood (Esezobor et al., 2018; Porter et al., 2022). Frequent daytime urination is a common feature of SCD, as children are instructed to drink approximately 2 liters of fluids each day to maintain hydration and prevent complications, especially pain crises.
Pathogenesis and Risk Factors
The etiology of nocturnal enuresis is not well understood, but it is thought to result from kidney impairment in concentrating urine plus a lower functional bladder capacity in those with SCD (Becker, 2011). These factors also contribute to frequent daytime urination. Nocturnal enuresis is more prevalent in males, in younger children, and in those with a family history (Esezobor et al., 2018; Porter et al., 2022).
Functional Implications
Nocturnal enuresis is associated with increased fatigue and diminished sleep and higher externalizing behaviors such as aggression and impulsivity, internalizing behaviors such as mood disorders and anxiety, and attention problems (Jordan et al., 2005; Porter et al., 2022). There is no specific SSA listing for nocturnal enuresis or frequent daytime urination.
MUSCULOSKELETAL COMPLICATIONS
Osteonecrosis
Osteonecrosis, also known as avascular, aseptic, or ischemic necrosis, is a prevalent skeletal complication of SCD attributed to repeated ischemia–reperfusion injury of susceptible articular surfaces. Recurrent and painful vaso-occlusive events, the hallmark of SCD, compromise blood flow to all
joints and increase the likelihood of multifocal osteonecrosis. Because the head of the femur lacks collateral blood flow, it is particularly vulnerable to microvascular insults. Osteonecrosis of the femoral head typically affects both hips and often coexists with osteonecrosis in the shoulders, knees, and other joints. A large cohort study found that 22 percent of patients will develop symptomatic osteonecrosis of the femoral head at a median age of 27 (Adesina et al., 2017). Chronic joint pain, stiffness, and a limited range of motion are symptoms and signs of osteonecrosis. The presence of osteonecrosis of the femoral head is associated with chronic pain and the use of opioids. Management includes pain mitigation, physical therapy, and surgical options such as core decompression or joint replacement in severe cases.
Pathogenesis and Risk Factors
As noted, osteonecrosis is attributed to repeated episodes of ischemia–reperfusion with damage from repeated infarction and chronic inflammation with abnormal bone repair in this situation.
Functional Implications
Osteonecrosis of the femoral head may lead to chronic, debilitating pain and ambulatory impediments. There is no specific SSA listing for osteonecrosis, though some adults may qualify under Listing 7.18. In addition, some applicants may qualify under one of the 1.00 listings (e.g., 1.17, 1.18, 1.19, or 1.22) as applicable or the equivalent 101.00 listings for children.1
Osteomyelitis and Bone Infarctions
Osteomyelitis, an inflammation or infection of the bone, is also more common in patients with SCD. Impaired immune function and bone infarction are thought to play a role in this increased risk. Salmonella species are particularly common in osteomyelitis in individuals with SCD, unlike in the general population where infection by Staphylococcus aureus is more frequent. Patients present with localized pain, edema, and systemic symptoms, and there may be an overlying nonhealing leg ulcer. As with other forms of osteomyelitis, treatment may require prolonged antibiotic therapy because Salmonella and other Gram-negative bacteria are common causes of osteomyelitis in people with SCD (Burnett et al., 1998).
Bone infarctions are seen in all individuals with SCD. Dactylitis, a condition characterized by swelling of the fingers and toes and also known as hand–foot syndrome, predominantly affects young children and occurs in
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1 This sentence was added after release of the report to include additional examples of SSA listings that some claimants may qualify under.
the small bones of the hands and feet. It results from acute vaso-occlusion in these bones with resultant painful swelling. Analgesics are used for management of symptoms. Acute bone infarcts occur in children and young adults, with vascular occlusion causing areas of infarction without infection, although redness and swelling may be present. Patients may present with aching bone pain that may worsen during sickle cell crises, and the spine, distal femur, and tibia are common sites. Diagnosis is now commonly made by MRI. Repeated infarctions may lead to scoliosis and short stature in some patients. Though it is not common to have small joint involvement, individuals with SCD have an increased incidence of gout (Gupta et al., 2015), likely caused by high cellular turnover.
Pathogenesis and Risk Factors
Impaired immune function and bone infarction are thought to play a role in this increased risk of osteomyelitis. Dactylitis and bone infarction result from acute ischemic injury.
Functional Implications
Depending on the course of infection and location, patients may have chronic pain and functional impairment from osteomyelitis. There are no specific SSA listings for osteomyelitis, though some may qualify under Listing 7.05 or Listing 107.05. As with osteonecrosis, some applicants with osteomyelitis may qualify under one of the 1.00 listings (e.g., 1.17, 1.18, 1.19, or 1.22) as applicable or the equivalent 101.00 listings for children.2 Children with dactylitis generally recover full function, though their hands and feet may be smaller than normal. Bone infarctions typically heal without significant functional impairment.
DIGESTIVE AND OTHER ABDOMINAL COMPLICATIONS
Splenic Infarction or Sequestration
The spleen is almost always affected in individuals with SCD. Most individuals with SCD, particularly with HbSS or HbSC disease, will have microinfarcts within the first 36 months of life, resulting in splenic atrophy (Ebert et al., 2010). Splenic atrophy increases an individual’s susceptibility to certain types of bacterial infections. The prevalence and severity of splenic complications can differ depending on SCD genotype, and those
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2 This sentence was added after release of the report to include additional examples of SSA listings that some claimants may qualify under.
with HbSS and HbSβ0-thalassemia have the most severe complications in the pediatric population (George et al., 2024).
Splenic sequestration is a life-threatening emergency where blood rapidly pools in the spleen. It can result in hypovolemic shock caused by a severe loss of blood or fluid and death if not addressed with transfusions and possible splenectomy. Depending on the SCD phenotype, sequestration might occur at any age (Ebert et al., 2010).
Pathogenesis and Risk Factors
Splenic infarcts and sequestration are both results of microinfarction. Splenic sequestration is thought to occur as microinfarcts accumulate and result in splenic fibrosis. This then impedes the ability of the spleen to appropriately sequester blood.
Functional Implications
Short-term functional limitations are related to recovery after surgery. In addition, individuals with SCD are functionally asplenic because of splenic infarcts, putting them at increased risk of infection and sepsis beginning in infancy. SCD complications related to splenic infarct or sequestration are not currently tied to any current SSA listings, though some may qualify under Listing 7.05 for adults and 107.05 for children.
Gallstones
The majority of individuals with SCD will have evidence of gallstones (cholelithiasis) on imaging. However, not everyone goes on to have symptoms or develop inflammation of the gallbladder or gallstones in the common bile duct. Gallbladder removal is the most frequent surgery in patients with SCD, making up almost 40 percent of the procedures on SCD patients (Ebert et al., 2010). There is uncertainty in the field about whether individuals with SCD should have their gallbladders removed early before onset of symptoms or only if there are symptoms. Individuals with SCD may have higher rates of choledocholithiasis (blockage of the biliary drainage system) than the general population with gallstones.
Pathogenesis and Risk Factors
The increased breakdown of RBCs raises circulating levels of bilirubin, increasing the accumulation of bile in the biliary system and resulting in gallstone formation. The presence of gallstones increases the risk of
developing inflammation of the gallbladder and blockage of the biliary drainage system caused by gallstones in the common bile duct.
Functional Implications
There may be a need for recovery after surgery that can affect daily function. The SSA listings associated with gallstones are 5.06 and 105.06.
Chronic Liver Disease
There is a wide clinical spectrum of how liver disease may present in an individual with SCD. It may range from mild abnormalities of liver function in asymptomatic patients to acute crises associated with acute liver failure to cirrhosis with chronic progressive liver failure.
Pathogenesis and Risk Factors
Chronic liver disease in SCD might result from iron overload associated with chronic transfusions, hepatitis, or both (Theocharidou and Suddle, 2019). Hepatitis is thought to occur from inflammation resulting from repeated small, clinically silent microvascular occlusions occurring throughout the life of an SCD patient. This may eventually lead to liver fibrosis superimposed on other causes of chronic liver disease. Given the increased need for transfusions, individuals with SCD have higher rates of hepatitis B and C prior to viral screening of blood products.
Functional Implications
Chronic liver disease may cause weakness and fatigue, limiting endurance for work, and progressive liver disease may result in altered mental status and decreased cognition to the point of not being able to work. The same criteria for hepatic failure in the general population apply for hepatic failure in SCD, as noted in Listing 5.05 for adults and 105.05 for children.
Malnutrition
Malnutrition can affect an individual with SCD in multiple ways. Malnutrition can weaken the immune system, making individuals with SCD more susceptible to infections and respiratory complications (Agda Dos Santos et al., 2018). It may also reduce the pain threshold, which can lead to an increased frequency of pain crises. Nutrient deficiencies may decrease the body’s ability to heal and repair damaged tissues. As discussed in Chapter 1, individuals with SCD may disproportionately experience food insecurity,
leading to poorer health outcomes from inadequate nutrition intake (Khan et al., 2023). Malnourished individuals with SCD may experience extended hospital stays because of longer recovery times. Malnutrition can also impede the growth and development of children with SCD.
Pathogenesis and Risk Factors
The causes of malnutrition in individuals with SCD are multifactorial (Obeagu and Obeagu, 2024). The effects of RBC breakdown, the resulting turnover of RBCs, and chronic anemia are all associated with an increased demand for nutrients. Individuals with SCD are also affected by chronic inflammation, and inflammatory processes can lead to increased energy expenditure and protein turnover, further elevating nutritional requirements (Obeagu and Obeagu, 2024). During a pain crisis, individuals with SCD may experience anorexia and have an associated reduction in food intake.
Functional Implications
The increased risk of infections stemming from malnutrition may result in health complications and lead to more frequent hospitalizations. The delay or inability to heal with acute illness or injury may also have long-term implications for functioning. Faltering growth and delayed sexual maturation are common consequences of malnutrition, affecting the long-term health and quality of life of these individuals. There is no SSA listing for malnutrition.
Pica
Pica is defined as the ingestion of nonnutritive substances for at least 1 month at an age that is considered developmentally inappropriate (APA, 2013). The consequences of consuming nonfood substances include intestinal obstruction; gastric bezoars, or solid masses of indigestible items that accumulate in the digestive tract; lead poisoning; dental injury; and electrolyte imbalance (Cleveland Clinic, 2022). Items ingested include clay, soil, sand, stones, grass, hair, lead, paper, ice, string, starch, foam, and cigarette butts (Khan and Tisman, 2010). It is more commonly seen in children, pregnant women, and individuals with learning disabilities (Danford and Huber, 1982; Horner et al., 1991). Patients with SCD with pica ingest paper, fabric, Styrofoam or cushion foam, and dirt (Ivascu et al., 2001). Research has found the prevalence of pica in SCD ranges from 33 to 56 percent (Ahmed, 2015; Aloni et al., 2015; Ivascu et al., 2001).
Pathogenesis and Risk Factors
The etiology of pica is not clear, but there is evidence for deficiency of minerals such as iron and zinc, lead poisoning, malnutrition, family history, low socioeconomic status, family stress, and dysfunctional eating patterns as a coping mechanism to stress associated with chronic and recurrent pain (Ahmed, 2015; Hackworth and Williams, 2003; Issaivanan et al., 2009; Ivascu et al., 2001; Lemanek et al., 2002; Rose et al., 2000). There is also evidence that individuals who engage in pica behaviors also have family members with a pica history (Ivascu et al., 2001). More recent research suggests that obsessive compulsive disorder is linked to pica (Herguner et al., 2008). Patients with SCD with pica have lower hemoglobin levels, have higher reticulocyte counts, are younger in age, weigh less, and are more anemic than patients without pica (Ahmed, 2015; Aloni et al., 2015; Ivascu et al., 2001). In addition, research has found that the prevalence of pica is higher in patients with HbSS than in those with other SCD genotypes (Ivascu et al., 2001).
Functional Implications
Pica behaviors are frequently carried out secretly, contributing to underreporting and limiting the ability to assess functional impairment. These behaviors can result in significant medical complications, and individuals may experience associated shame or embarrassment, further hindering disclosure and intervention. The SSA listing applicable for pica is 112.00.
SKIN DISORDERS
Leg Ulcers
Chronic leg ulcers are a common and debilitating complication of SCD, estimated to occur in half of individuals at some point in their lifetime (Minniti and Kato, 2016). Incidence and prevalence estimates vary widely, from 1 to 30 percent (Minniti and Kato, 2016; Spira et al., 2022), with the true incidence and prevalence unknown because of a lack of prospective surveillance data. Individuals with SCD who have leg ulcers often first experience localized pain, followed by hardening or thickening of the skin, hyperpigmentation, formation of blisters, and destruction of the dermis (Catella et al., 2024). One study conducted in Brazil found that over half of individuals with SCD had their first ulcer between ages 10 and 20 years and that the median time to healing of the leg ulcer was 3 years (Spira et al., 2022). Individuals with SCD who develop leg ulcers tend to have less frequent hospitalizations for pain crises but are prone to developing kidney
disease and pulmonary hypertension (Minniti et al., 2011). Among individuals with SCD, only 75 to 80 percent will experience leg ulcer healing with treatment (Minniti and Kato, 2016).
Pathogenesis and Risk Factors
Leg ulcers are likely caused by a local vaso-occlusive crisis in the skin, typically without preceding trauma, resulting in ischemia (Minniti and Kato, 2016). The proposed pathogenesis of leg ulcers is venostasis and capillary stasis, which may cause further sickling resulting from hypoxia and the localized vaso-occlusion. Risk factors for developing leg ulcers include an increased rate of RBC destruction, male gender, older age, and malnutrition (Catella et al., 2024; Minniti et al., 2011).
Functional Implications
The functional implications of leg ulcers stem from limited mobility, including difficulty walking, because of pain, which can be severe. It is estimated that up to 1 percent of the total SCD population living in the United States, and up to 25 percent of those with leg ulcers, suffer from chronic pain and disability from a leg ulcer (Minniti and Kato, 2016). In addition, leg ulcers significantly decrease quality of life. In a study of 72 adults with SCD and leg ulcers, over one-third avoided social events because of embarrassment or stigma, and 16 percent were unable to work because of pain (Spira et al., 2022). The SSA listings for leg ulcers are 8.09 and 108.09, chronic conditions of the skin or mucous membrane.
GROWTH FALTERING
Growth in children with specific genotypes of SCD, particularly HbSS and HbSβ0-thalassemia, may be impaired. Changes in growth patterns can be first seen at 6 months of age (Soliman et al., 2017). One large retrospective cohort study demonstrated that 7-year-old female children with SCD who were on chronic transfusion therapy were significantly taller than those on hydroxyurea or not on treatment. In male children aged 10 to 12 years, those on transfusion therapy were taller than those on hydroxyurea or no treatment (Nagalapuram et al., 2019). These growth differences persisted through ages 8 to 12 for both female and male children. These findings were also seen in a large randomized trial using chronic transfusion therapy for stroke prevention (Wang et al., 2005). Suboptimal growth is also present in puberty, with a prospective cohort study demonstrating delays in puberty by 1 to 2 years in individuals with SCD (Zemel et al., 2007) and a case–control study finding that adolescents with SCD demonstrated slower
progression through puberty than their peers (Rhodes et al., 2009). Notably, studies have consistently shown that hydroxyurea does not affect growth patterns compared to those with SCD who are not on therapy (Nagalapuram et al., 2019; Wang et al., 2002, 2011).
Pathogenesis and Risk Factors
The pathophysiology of growth faltering for children with sickle cell anemia is poorly understood. Factors that may affect growth include hypoxic–vascular effects on the hypothalamus–pituitary axis, resulting in decreased growth hormone release and lower levels of insulin-like growth factor; malnutrition; and the hypermetabolic state induced by the hemolytic process (Soliman et al., 2017).
Functional Implications
Individuals with SCD may be stigmatized for growth delay and short stature, interfering with relationships with peers and partners (Bulgin et al., 2018). The SSA listing for growth faltering that may be applicable in some cases is 105.08, growth failure due to any digestive disorder.
CHRONIC TRANSFUSION IN SICKLE CELL DISEASE
RBC Transfusion in SCD and Beta-Thalassemia
How and Why Are Regular RBC Transfusions Used Differently in the Treatment of SCD and Beta-Thalassemia?
Beta-thalassemia major is an inherited condition in which the affected person does not make an adequate amount of RBCs, resulting in severe anemia and failure to thrive. Regular RBC transfusion is required for normal growth and development in childhood and subsequently to maintain hemoglobin within a range that allows for adequate function as an adult. Transfusions for beta-thalassemia are simple transfusions (outlined in greater detail below), meaning that RBCs are infused with the goal of raising hemoglobin levels. Transfusions are also used to prevent chronic organ dysfunction, such as heart failure and hepatosplenomegaly, and bone deformities that can result from ineffective erythropoiesis (Pennell et al., 2013; Shah et al., 2019). Without RBC transfusion, the degree of anemia is worse in beta-thalassemia major than in most patients with SCD.
For patients with SCD, RBC transfusion is indicated for treatment or prevention of complications such as ischemic stroke and acute chest syndrome and may be “simple,” as previously described, or may require
exchange transfusion (i.e., the removal of blood with replacement of non-sickled RBCs). The goal in SCD is not only to lessen anemia but also to keep the HbS percentage low, typically less than 30 percent, to decrease the complications that result from sickled cells.
Indicators for RBC Transfusions for SCD
Transfusion support is a critical intervention in the management of many individuals with SCD. Indications for transfusion support are often dichotomized between acute and chronic (Howard, 2016). Indications for acute transfusion include severe, worsening anemia often resulting from an aplastic crisis, splenic sequestration, acute stroke, acute chest syndrome, and multi-organ failure. Transfusions are given with caution in men with priapism refractory to analgesia and local procedures because of reports of acute neurological deterioration if the posttransfusion hemoglobin level is high (Siegel et al., 1993). RBC transfusions are also indicated before surgical procedures (Oyedeji and Welsby, 2021). A high frequency of acute, unplanned transfusions may be an indicator of SCD disease burden but is unlikely to be a reliable one as transfusion practices and thresholds may vary between providers and hospital systems. The use of transfusions may also be limited by a patient’s prior complications, particularly RBC alloimmunization, in which case matched blood can be challenging to find. In addition, transfusions are administered sparingly regardless of the person’s disease severity.
Guidelines recommend chronic transfusion therapy for children at high risk for ischemic stroke based on screening transcranial Doppler examination and for those with a history of ischemic stroke for secondary prevention (Chou et al., 2020; Yawn et al., 2014). Other indications, for which there is less evidence and agreement, include
- prevention of acute chest syndrome in those who have experienced two or more episodes;
- secondary prevention of hemorrhagic stroke;
- patients having silent cerebral ischemia on MRI, especially if tests show cognitive impairment;
- pulmonary arterial hypertension;
- after solid organ transplant;
- nonhealing leg ulcers;
- recurrent priapism;
- women with pregnancy-related complications; and
- chronic pain refractory to other modalities.
Each of these complications may be disabling in itself, and many can ultimately be fatal.
Transfusions are not without complications, however. Risks with any transfusion include acute complications such as hemolytic transfusion reactions, febrile nonhemolytic transfusion reactions, allergic transfusion reactions, transfusion-associated circulatory overload, and transfusion-related acute lung injury (Abdallah et al., 2021).
Comparison of the Burden of Transfusions for Thalassemia and SCD
Transfusions may be delivered in different forms, from a simple transfusion to manual or automated exchange transfusion. Simple transfusions are given in order to increase the level of hemoglobin and can be administered in a variety of settings over 2 to 4 hours and often only require one peripheral intravenous catheter. People with beta-thalassemia or SCD may receive simple transfusions, but because blood is being added without any removal, there is an increased risk of iron overload. After a simple transfusion, most people report improved energy and less fatigue.
Exchange transfusions are a manual or automated process in which the patient’s blood is removed and donated blood is added. This is done in people with SCD to remove the abnormal hemoglobin, but it is not done in those with beta-thalassemia. Exchange transfusions require two intravenous lumens, one of which must have a large bore for blood removal. Patients often have implantable central venous catheters, or ports, or arterio-venous fistulas placed if they require monthly exchange transfusions. Exchange transfusions have the benefits of removing the sickled blood and result in less iron loading, but they require a significantly longer time of up to 8 hours, and can be associated with hypocalcemia resulting from the anticoagulant commonly used. They also are often followed by fatigue, nausea, and lightheadedness the following day resulting from the major fluid shifts associated with the removal of a large portion of the patient’s own blood. Exchange transfusions require specialized equipment and oversight by specialized nurses. In addition, they are not available at all hospitals or infusion centers, so patients may need to travel farther to receive this therapy.
Overall, chronic long-term transfusion therapy for those with SCD or beta-thalassemia is burdensome. It requires a time commitment, including often up to a full day at the hospital or infusion center every month, especially for SCD patients receiving exchange transfusions. Given limited venous access, patients often require an implanted central venous catheter that carries the risk of infection and venous thromboembolism. Patients may develop iron overload and require iron chelation therapy to prevent iron-mediated organ damage. There is also an increased risk of alloimmunization to RBC antigens, which makes it more difficult—and sometimes
nearly impossible and time consuming—to find compatible RBCs for subsequent transfusions (Chou et al., 2020).
The applicable SSA listings include 7.05D—“Beta-thalassemia major requiring life-long RBC transfusions at least once every 6 weeks to maintain life (see 7.00C4).” The equivalent listing for children (107.05D) includes the same criteria.
SUMMARY AND CONCLUSIONS
The breadth of issues discussed throughout this chapter further illustrates the frequency, severity, and accumulation of complications resulting from SCD and their disabling effects on daily functioning. Individuals with SCD may experience complications in nearly all body systems, including musculoskeletal, special senses, respiratory, cardiovascular, digestive, genitourinary, hematological, skin, neurological, and behavioral. Although some SCD complications do have associated SSA listings, many complications do not. Similarly, a person with SCD may not reach the needed threshold to qualify for individual listings but may have a cumulative impact of multi-organ involvement that can collectively impair their ability to work. Many SSA listings permit individuals to qualify for medically determinable impairments based on a specified number of medical visits, treatments, interventions, tests, and symptoms. For individuals with SCD, this same threshold may be reached through a combination of different organ-related complications.
The complications associated with SCD may manifest as disabling functional impairments, often affecting an individual’s ability to participate in school or work. There are a few complications specific to SCD, including SCR, cardiomyopathy, chronic kidney disease, and intrinsic restrictive lung disease or sickle cell chronic lung disease. However, many complications have unique characteristics specific to SCD. For example, SCD is associated with unique cardiomyopathy characterized by cardiac muscle hypertrophy, myocardial fibrosis, and inflammation. Similarly, many complications occur more frequently in those with SCD and can be characteristic of specific SCD genotypes. For example, many individuals with HbSS disease will have microinfarcts within the first 36 months of life resulting in splenic atrophy. This is also seen in growth faltering, with children with HbSS and HbSβ0thalassemia often experiencing impairment with growth.
Based on its review of the literature and its expert assessment, the committee reached the following conclusions:
Conclusion 6-1: There is a cumulative effect of multi-organ involvement in sickle cell disease (SCD). One may not meet disability criteria
within an organ system or specific complication, but the cumulative damage of SCD may affect overall functioning.
Conclusion 6-2: While people with SCD may qualify under listing criteria not specific to SCD in the same way as people without SCD, there are unique considerations in applying some of the listings to people with SCD, such as with cardiac and renal disease. These complications are associated with the same functional burden but may not meet one specific part of the criteria.
Conclusion 6-3: Although some people with SCD do not have significant complications, most do and have them in combination, including associated neurocognitive and mental health and behavioral disorders.
- Some studies suggest that there are clinical sub-phenotypes of SCD with clustering of end-organ complications in different individuals with SCD. For example, pulmonary hypertension, stroke, priapism, and leg ulcers tend to occur in the same patient, while others may experience frequent vaso-occlusive episodes, osteonecrosis, and acute chest syndrome (Gladwin and Vichinsky, 2008).
Although RBC transfusions are used differently in the treatment of SCD and beta-thalassemia, both are used to lessen anemia and decrease complications overall. RBC transfusions for beta-thalassemia are required for normal growth and development in children and to maintain the hemoglobin levels needed for functioning. In SCD, RBC transfusions are a critical intervention for the management of SCD for many individuals, used as both treatment and for the prevention of complications. Although acute and chronic transfusion support is common for those living with SCD, a higher frequency of transfusions is not the most reliable indicator of SCD disease burden as transfusion practice and thresholds vary depending on provider practices and patient complications. Regardless of whether someone has SCD or beta-thalassemia, chronic long-term transfusion therapy can be burdensome, given the lengthy time commitments, limited venous access leading to implanted central venous catheters that increase the risk of infection and venous thromboembolism, and the risk of developing iron overload.
Based on its review of the literature and its expert assessment, the committee reached the following conclusion:
Conclusion 6-4: People with SCD receiving chronic transfusions are at least as severely burdened as someone with beta-thalassemia receiving chronic simple transfusions. The burden may be higher for individuals with SCD requiring exchange transfusions, which are not used in
beta-thalassemia, as they take significantly more time; require specialized expertise and equipment, such as double lumen central venous access and apheresis machines; and are more likely to be followed by fatigue, nausea, and lightheadedness.
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ANNEX TABLE 6-1 Selected Special Senses and Speech Conditions Associated with SCD
| Health Effects | Potential Functional Limitations | Potential Functional Equivalence Domains Affected | Potential SSA Listings |
|---|---|---|---|
| Retinopathy | Near visual acuity, far visual acuity, peripheral vision | Acquiring and using information, attending and completing tasks, moving about and manipulating objects, and health and physical well-being | 2.02, 102.02 |
| Hearing loss and related loss of balance/dizziness | Hearing, speaking | Acquiring and using information, attending and completing tasks, moving about and manipulating objects, and health and physical well-being | 2.07, 2.10, 102.10 |
ANNEX TABLE 6-2 Selected Cardiovascular Conditions Associated with SCD
| Health Effects | Potential Functional Limitations | Potential Functional Equivalence Domains Affected | Potential SSA Listings |
|---|---|---|---|
| Heart failure | Standing; walking; strenuous physical activity; lifting; carrying; pushing/pulling; reaching; gross and fine manipulation; foot/leg controls; climbing; low work; speaking; understanding, remembering, and applying information; concentrating, persisting, or maintaining pace | Acquiring and using information, attending and completing tasks, moving about and manipulating objects, health and physical well-being | 4.02, 104.02 |
| Health Effects | Potential Functional Limitations | Potential Functional Equivalence Domains Affected | Potential SSA Listings |
|---|---|---|---|
| Coronary artery disease | Standing, walking, strenuous physical activity, lifting, carrying, pushing/pulling, reaching, gross and fine manipulation, foot/leg controls, climbing, low work, speaking | Acquiring and using information, attending and completing tasks, moving about and manipulating objects, health and physical well-being | 4.04 |
| Arrhythmias | Standing, walking, strenuous physical activity, lifting, carrying, pushing/pulling, reaching, gross and fine manipulation, foot/leg controls, climbing, low work, speaking | Acquiring and using information, attending and completing tasks, moving about and manipulating objects, health and physical well-being | 4.05, 104.05 |
| Cardiomyopathy | Standing, walking, strenuous physical activity, lifting, carrying, pushing/pulling, reaching, gross and fine manipulation, foot/leg controls, climbing, low work, speaking | Acquiring and using information, attending and completing tasks, moving about and manipulating objects, health and physical well-being | 4.02, 104.02 |
ANNEX TABLE 6-3 Selected Respiratory Conditions Associated with SCD
| Health Effects | Potential Functional Limitations | Potential Functional Equivalence Domains Affected | Potential SSA Listings |
|---|---|---|---|
| Intrinsic restrictive lung disease | Standing, walking, strenuous physical activity, lifting, carrying, pushing/pulling, overhead reaching, climbing, low work | Acquiring and using information, attending and completing tasks, moving about and manipulating objects, and health and physical well-being | 3.02, 103.02 |
| Pneumonia | Standing; walking; strenuous physical activity; lifting; carrying; pushing/pulling; overhead reaching; climbing; low work; understanding, remembering, and applying information; concentrating, persisting, or maintaining pace | Acquiring and using information, attending and completing tasks, moving about and manipulating objects, and health and physical well-being | 14.07, 114.07 |
| Chronic pulmonary hypertension | Standing, walking, strenuous physical activity, lifting, carrying, pushing/pulling, overhead reaching, climbing, low work | Acquiring and using information, attending and completing tasks, moving about and manipulating objects, and health and physical well-being | 3.09 |
| Asthma | Standing, walking, strenuous physical activity, lifting, carrying, pushing/pulling, overhead reaching, climbing, low work | Acquiring and using information, attending and completing tasks, moving about and manipulating objects, and health and physical well-being | 3.03, 103.03 |
| Acute chest syndrome | Standing, walking, strenuous physical activity, lifting, carrying, pushing/pulling, overhead reaching, climbing, low work | Acquiring and using information, attending and completing tasks, moving about and manipulating objects, and health and physical well-being | 7.05, 107.05 |
| Health Effects | Potential Functional Limitations | Potential Functional Equivalence Domains Affected | Potential SSA Listings |
|---|---|---|---|
| Acute lung infarcts | Standing, walking, strenuous physical activity, lifting, carrying, pushing/pulling, overhead reaching, climbing, low work | Attending and completing tasks, moving about and manipulating objects, and health and physical well-being | 7.05, 107.05 |
| Pulmonary embolism | Standing, walking, strenuous physical activity, lifting, carrying, pushing/pulling, overhead reaching, climbing, low work | Attending and completing tasks, moving about and manipulating objects, and health and physical well-being | 3.02, 103.02 |
| Sleep apnea | Understanding, remembering, and applying information; concentrating, persisting, or maintaining pace | Attending and completing tasks | None |
ANNEX TABLE 6-4 Selected Genitourinary Conditions Associated with SCD
| Health Effects | Potential Functional Limitations | Potential Functional Equivalence Domains Affected | Potential SSA Listings |
|---|---|---|---|
| Chronic kidney disease (> 12 months) | Standing; walking; strenuous physical activity; lifting; carrying; pushing/pulling; climbing; low work; understanding, remembering, and applying information; concentrating, persisting, or maintaining pace | Acquiring and using information, attending and completing tasks, moving about and manipulating objects, health and physical well-being | 6.03, 6.05, 106.03, 106.05 |
| Priapism | Concentrating, persisting, or maintaining pace | Health and physical well-being | None |
ANNEX TABLE 6-5 Selected Musculoskeletal Conditions Associated with SCD
| Health Effects | Potential Functional Limitations | Potential Functional Equivalence Domains Affected | Potential SSA Listings |
|---|---|---|---|
| Osteonecrosis | Sitting, standing, walking, strenuous physical activity, lifting, carrying, pushing/pulling, reaching, gross and fine manipulation, foot/leg controls, climbing, low work | Acquiring and using information, attending and completing tasks, moving about and manipulating objects, health and physical well-being | 7.18, 1.17, 1.18, 1.19, 1.22, 101.17, 101.18, 101.19, 101.221 |
| Osteomyelitis | Sitting, standing, walking, strenuous physical activity, lifting, carrying, pushing/pulling, reaching, gross and fine manipulation, foot/leg controls, climbing, low work | Acquiring and using information, attending and completing tasks, moving about and manipulating objects, health and physical well-being | 7.05, 107.05, 1.17, 1.18, 1.19, 1.22, 101.17, 101.18, 101.19, 101.222 |
1 The 1.00 and 101.00 listings were added after release of the report to provide additional examples of SSA listings that some claimants may qualify under.
2 The 1.00 and 101.00 listings were added after release of the report to provide additional examples of SSA listings that some claimants may qualify under.
ANNEX TABLE 6-6 Selected Digestive and Other Abdominal Conditions Associated with SCD
| Health Effects | Potential Functional Limitations | Potential Functional Equivalence Domains Affected | Potential SSA Listings |
|---|---|---|---|
| Splenic infarction | Standing, walking, strenuous physical activity, lifting, carrying, pushing/pulling, climbing, low work | Acquiring and using information, attending and completing tasks, moving about and manipulating objects, health and physical well-being | 7.05, 107.05 |
| Gallstones | Standing; walking; strenuous physical activity; lifting; carrying; pushing/pulling; climbing; low work; understanding, remembering, and applying information; concentrating, persisting, or maintaining pace | Acquiring and using information, attending and completing tasks, moving about and manipulating objects, health and physical well-being | 5.06, 105.06 |
| Chronic liver disease | Standing; walking; strenuous physical activity; lifting; carrying; pushing/pulling; climbing; low work; understanding, remembering, and applying information; concentrating, persisting, or maintaining pace | Acquiring and using information, attending and completing tasks, moving about and manipulating objects, health and physical well-being | 5.05, 105.05 |
| Malnutrition | Standing; walking; strenuous physical activity; lifting; carrying; pushing/pulling; climbing; low work; understanding, remembering, and applying information; concentrating, persisting, or maintaining pace | Acquiring and using information, attending and completing tasks, moving about and manipulating objects, health and physical well-being | None |
| Health Effects | Potential Functional Limitations | Potential Functional Equivalence Domains Affected | Potential SSA Listings |
|---|---|---|---|
| Pica | Understanding, remembering, and applying information; concentrating, persisting, or maintaining pace | Acquiring and using information, attending and completing tasks, moving about and manipulating objects, health and physical well-being | 112.00 |
ANNEX TABLE 6-7 Selected Skin Condition Associated with SCD
| Health Effects | Potential Functional Limitations | Potential Functional Equivalence Domains Affected | Potential SSA Listings |
|---|---|---|---|
| Leg ulcers | Standing, walking, strenuous physical activity, pushing/pulling, foot/leg controls, climbing, low work | Acquiring and using information, attending and completing tasks, moving about and manipulating objects, health and physical well-being | 8.09, 108.09 |
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