International Journal of Behavioral Medicine 2005, Vol. 12, No. 3, 171–179

Copyright © 2005 by Lawrence Erlbaum Associates, Inc.

A Brief Review of the Pathophysiology, Associated Pain, and Psychosocial Issues in Sickle Cell Disease Christopher L. Edwards, Mischca T. Scales, Charles Loughlin, Gary G. Bennett, Shani Harris-Peterson, Laura M. De Castro, Elaine Whitworth, Mary Abrams, Miriam Feliu, Stephanie Johnson, Mary Wood, Ojinga Harrison, and Alvin Killough Sickle cell disease (SCD) is the most common genetic disorder of the blood. The disease produces significantly abnormal hemoglobin (Hgb) molecules in red blood cells (RBCs). The sickling of RBCs occurs when partially or totally deoxygenated Hgb molecules distort their normal disk shape, producing stiff, sticky, sickle-shaped cells that obstruct small blood vessels and produce vasoocclusion as well as the disruption of oxygen to body tissues. Because tissue damage can occur at multiple foci, patients with SCD are at risk for other medical complications including, but not limited to, delayed growth and sexual maturation; acute and chronic pulmonary dysfunction; stroke; aseptic necrosis of the hip, shoulders, or both; sickle cell retinopathy; dermal ulcers; and severe chronic pain. The chronicity of the illness combined with frequent hospitalizations for pain and other medical management can contribute significantly to impaired psychosocial functioning, altered intra- and interpersonal relationships, and reduced quality of life. Unlike previous qualitative reviews of SCD, this article describes the relevant clinical and research data on the relation between psychosocial functioning and SCD in adult and child populations. The authors discuss the significant role of psychosocial issues in the trajectory and management of the disease and conclude that understanding the pathophysiology of SCD without thoroughly understanding the equally important psychosocial influences is misunderstanding SCD. Key words: sickle cell disease, psychosocial functioning, chronic pain, pain is seen in approximately 1 in 10 African Americans. However, when both parents have the sickle cell trait, there is a one in four chance with each pregnancy that the child will have sickle cell anemia. A major public health issue, SCD affects 1 in 375 African Americans in the United States and, although less common, also affects people of Hispanic, Native American, East Indian, Greek, Italian, and Eastern Asian ancestry (Charache, Lubin, & Reid, 1989; Embury, Hebbel, Mohandas, & Steinburg, 1996; Rodgers, 1997).

Sickle Cell Disease Pathophysiology Sickle cell disease (SCD) is the most common genetic disorder of the blood. The term sickle cell disease refers to several diseases, all associated with the presence of abnormal hemoglobin (Hgb) S. SCD is characterized by a predominance of abnormal Hgb molecules in red blood cells (RBCs; see Figure 1A and 1B for view of normal and sickled RBCs). Sickle cell trait (AS), the heterozygote carrier state, is not a disease and

Christopher L. Edwards, Department of Psychiatry and Behavioral Sciences, Pain and Palliative Care Center, Department of Medicine, Division of Hematology, Duke University Medical Center, Department of Psychology, North Carolina Central University; Mischca T. Scales, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center; Charles Loughlin, Department of Psychiatry and Behavioral Sciences, Pain and Palliative Care Center, Duke University Medical Center; Gary G. Bennett, Harvard School of Public Health; Shani Harris-Peterson, Johns Hopkins Bloomberg School of Public Health; Laura M. De Castro, Department of Medicine, Division of Hematology, Duke University Medical Center; Elaine Whitworth, Department of Medicine, Division of Hematology, Duke University Medical Center; Mary Abrams, Department of Medicine, Division of Hematology, Duke University Medical Center; Miriam Feliu, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Pain and Palliative Care Center, Duke University Medical Center; Stephanie Johnson, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Pain and Palliative Care Center, Duke University Medical Center; Mary Wood, Department of Psychology, North Carolina Central University, Pain and Palliative Care Center, Duke University Medical Center; Ojinga Harrison, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center; Alvin Killough, Department of Library and Information Sciences, North Carolina Central University Correspondence concerning this article should be addressed to Christopher L. Edwards, Medical Director, Biofeedback Laboratory and Pediatric Neuropsychology Service, Director, Chronic Pain Management Program, Duke University Medical Center, 932 Morreene Rd., Rm 170, Durham, N.C. 27705. E-mail: [email protected]

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Figure 1. Blood smear at 60× magnification from a patient with sickle cell disease. Picture shows normal red blood cells (RBCs) and multiple sickled RBC’s (arrows) as well as target cells as evidence of a significant hemolytic process. Source: Duke University Medical Center.

Sicklemia, or the sickling of red cells, is caused when partially or totally deoxygenated Hgb molecules distort the shape of normal RBCs producing stiff, sticky, and sickle-shaped cells. These sickled cells occlude small blood vessels and disrupt the supply of oxygen to body tissues. Such vasoocclusion often causes significant tissue damage and is the source of the intense episodes of pain and physical dysfunction that primarily characterize the disease. Because tissue damage can occur all over the body, patients with SCD are at risk for other medical complications including, but not limited to, delayed growth and sexual maturation; acute and chronic pulmonary dysfunction; stroke; aseptic necrosis of the hip, shoulders, or both; sickle cell retinopathy; dermal ulcers; severe and chronic pain; and psychosocial dysfunction (Abiodun, 1993; Abrams, Phillips, & Whitworth, 1994; Adedoyin, 1992; Schaeffer et al., 1999). The clinical course of SCD includes periods of acute and chronic hematological crises that often result in marked psychosocial and physical morbidity and even early death. Although most SCD variants can be diagnosed prenatally, symptoms of the disease usually do not appear for months after birth due to increased levels of fetal Hgb that tends to suppress symptom expression (Huntsman, 1987). The characteristic symptoms of SCD tend to vary with age and often appear progressive. For example, in infants and children with SCD, the most common problems tend to be related to recurrent infections and stroke, whereas in adolescents and adults, symptoms usually involve more severe organ damage such as renal and hepatic failure. Of the sickled cell disease syndromes, sickle cell anemia (SS hemoglobinopathy) is the most common. Other Hgb S related hemoglobinopathies include the double heterozygous states (sickle β-thalassemia; SC disease; SD disease), Hgb C, Hgb SOarab, and Hereditary Persistance of Fetal Hemoglobin (HPFH). The mean life expectancy of patients with sickle cell anemia is 42 years for men and 48 for women, almost 28 172

and 27 years below the asymptomatic population, respectively (Platt et al., 1994). This high morbidity and mortality is influenced by medical and psychosocial processes. However, relative to the body of literature on the disease, the influence of psychosocial factors are not well understood or thoroughly explored. This article reviews the select but representative clinical and research data on the relation between psychosocial factors and SCD. More specifically, this article explores the relations among pain, peer, family and interpersonal relations, and psychological adjustment as they relate to SCD. Lastly, we discuss issues of the future direction of research and clinical practice in the management of SCD.

Pain and SCD Patients with SCD can encounter multiple physical complications associated with their disease including delayed growth, fatigue, headaches, and cerebral vascular damage (Anderson & Rehm, 1984; Cozzi, Tryon, & Sedlacek, 1987; Gil, Phillips, Edens, Martin, & Abrams, 1994; Gil, Williams, Thompson, & Kinney, 1991; Maxwell & Streetly, 1998; Salman, 1996; Stefanantou & Bowler, 1996; Waters & Thomas, 1995). However, the most frequent complication associated with SCD is pain. Pain precipitates more presentations for medical care than any other symptom. In children, for example, pain accounts for approximately one fourth of hospital service visits independent of age, sex, the number of SCD complications, and Hgb levels. Pain is also recognized as the predominant reason for presentations for medical care by adults with SCD (Rees et al., 2003). The precipitants of SCD-related pain, its frequency, and duration are often variable, unpredictable, and not always well understood (Cozzi et al., 1987; Gil et al., 1991; Selman, 1996). Precipitants of painful crises may include, but are not limited to, increases in the ra-

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tio of sickled cells to normal blood cells, increased barometric pressure, nutritional factors, and stress (Waters & Thomas, 1995). The resulting pain these precipitants cause contributes substantially to depression, anxiety, and other psychiatric disturbances (Grant, Gil, Floyd, & Abrams, 2000; Leavell & Ford, 1983; Molock & Belgrave, 1994). Reciprocally, such psychiatric disturbances are almost always associated with a diminished ability to cope with pain; they help perpetuate the cycle of intensifying pain with significant life dysfunctions and functional disabilities that marks the disease. Thus, like many other illnesses that possess a substantial chronic pain component, SCD is better conceptualized as a disease with psychosocial as well as physiological complications. For many clinicians, then, SCD-related pain is the most complicated issue to manage (Gil, Wilson, & Edens, et al., 1997; Waters & Thomas, 1995). The selection of appropriate interventions can pose a difficult challenge.

Pain, SCD, and Psychosocial Issues There is growing evidence that psychological and social factors contribute substantially to complaints of pain (C. L. Edwards, Fillingim, & Keefe, 2001). Sociodemographic factors such as race, gender, age, education, and socioeconomic status as an index of attained wealth, as well as general psychological factors such as coping style (Anie et al., 2002), coping capacity, and social support, have been used to explain differences in disability associated with pain intensity, pain threshold, and pain tolerance, both clinically and in research settings (Bates, 1996; C. L. Edwards et al., 2001; Thompson, Gil, Burbach, Keith, & Kinney, 1993). For example, African Americans have been found to report higher levels of pain in clinical and research settings (R. R. Edwards, Doleys, Fillingim, & Lowery, 2001), whereas demographic and psychosocial variables have been found to influence pain associated with disease (Creamer, Lethbridge-Cejku, & Hochber, 1999). Several studies demonstrate the efficacy and cost effectiveness of cognitive, behavioral, and cognitive-behavioral interventions, which address psychosocial issues, for the treatment of chronic pain disorders (C. L. Edwards et al., 2000; Hyman, Feldman, Harris, Levin, & Malloy, 1989; Keefe, Jacobs, & Edwards, 1997; Logue & Edwards, 1998; Thomas, Dixon, & Milligan, 1999; Thomas, Gruen, & Shu, 2001; Thomas, Wilson-Barnett, & Goodhart, 1998). Like many other diseases with a substantial chronic pain component, SCD may now be conceptualized as existing reciprocally with psychosocial factors. Many of these sociodemographic and psychological factors have also been used to explain comorbid

diseases and common reactions such as anxiety, anger, frustration, and depression that often occur in response to unremitting pain (Cepeda, Yang, Price, & Shah, 1997). Although it is not known whether depressive symptoms result from the psychosocial versus the somatic features of SCD (Belgrave & Molock, 1991; Damlouji, 1982), the functional consequences of depression and affective disturbance are negative and well known. Among patients with SCD, depression is the most common psychiatric reaction to unremitting pain (Cepeda, et al., 1997).The acknowledgment of strong psychosocial influences on the manifestation and management of SCD-related pain has lead to the development and application of several behavioral models for treatment (Gil et al., 2000; Gil et al., 1994; Gil et al., 1991). Nadel and Portadin (1977) found that 27% of patients with SCD reported depressive symptoms such as sadness, guilt, hopelessness, and helplessness. Twenty-three percent of these patients were deemed chronically depressed and had been so for up to 3 years prior to the time of assessment. More recently, Cepeda et al. (1997) administered diagnostic clinical interviews to 39 patients (ages 6–19) with SCD and found that depression was the most frequently reported symptom (13%) followed closely by anxiety (10%) and behavioral problems (8%). The interconnection between depression and pain is possibly best illustrated by studies that evaluated how the treatment of depression affected the perception of pain in chronic pain patients. Morin and Warin (1981) found that the health condition of patients with SCD, including pain, significantly improved when antidepressant and psychotherapeutic interventions were applied. In total, these studies and many others suggest an intimate and reciprocal relation between affect and pain.

Developmental Context The integration of psychosocial factors into treatment is based on gathering appropriate information in a fashion that has utility for clinicians and patients. The most effective techniques for assessment of patients with SCD pain and psychosocial issues vary as a function of the patient’s age and developmental stage. For example, structured interviews, rating scales, and clinical observation are commonly used to assess pain and psychosocial functioning in adults with SCD. In contrast, pain drawings (Stephanatou & Bowler, 1997) and health diaries, techniques that have been demonstrated reliable and valid for this population (Gil, Edens, Wilson, et al., 1997), are most often used to assess psychosocial functioning in children and adolescents with SCD. Information gained during the assessment of pain often increases the skilled clinician’s ability to 173

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predict crises in advance of patient’s reports and gauge which patients are at higher risk of experiencing difficulty managing painful episodes. For example, Gil et al. (1993) found that patients who experienced negative thinking during formal assessments utilized the health care system more than patients with positive thinking patterns. In addition, patients who reported the most intense negative thinking patterns experienced the lowest tolerance for pain (Gil et al., 1991). Similar results have been found in children and adolescents (Gil, Edens, Wilson, et al., 1997). Interestingly, psychosocial factors are intimately integrated in and appear to exert differential impact on the experience of pain and pain on psychosocial functioning. As patients with SCD encounter multiple stressors related to their disease process, psychosocial outcomes and the influence of psychosocial factors appear to vary as a function of the patient’s age and developmental stage (children, adolescents, and adults; Anderson & Rehm, 1984; Gil et al., 1994; Gil et al., 1991; Salman, 1996; Stefanantou & Bowler, 1997; Waters & Thomas, 1995). Consequently, the assessment strategy and the psychosocial issues pursued must also vary based on developmental stage.

Childhood and Adolescence Among children suffering from SCD several indicators of poor psychological adjustment including emotional and behavioral problems, disturbed or altered sexuality, poor body image and self-concept, poor social and interpersonal functioning, and social withdrawal may be observed. Poor psychological adjustment in children with SCD may also manifest as poor academic performance and low levels of achievement (Morgan & Jackson, 1986; Eaton et al., 1995; Schaeffer et al., 1999; Thompson et al., 1993). These factors are most problematic when they appear as distinct changes from premorbid levels of functioning. Traditionally, many of these indicators have been incorrectly attributed to a lack of effort on the part of the patient, a side effect of addiction to opioid medications, a personality disorder, or a biologically based propensity toward low achievement. In recent years, these indicators of poor adjustment have been more accurately understood as effects of social deprivation; a deficit of interpersonal skills; and a lack of academic exposure during sensitive periods of cognitive, emotional, and social development due to prolonged periods of hospitalization and illness (Fowler et al., 1988; Schaeffer et al., 1999; Thompson et al., 1993). Most importantly, by choosing to understand these indicators as psychosocial problems, not mere personal flaws, investigators have found them to be amenable to intervention and alteration unlike the older, traditional explanations. 174

Adolescence In adolescents with and without chronic disease, the task of identity formation, which is most characterized by a growing sense of “self,” is influenced by an emphasis on physical and sexual competence and development (Schaeffer et al., 1999). A disruption of the formation of a cohesive identity (strong sense of self) may significantly and negatively influence a patient’s ability to appreciate their self-worth and effectively and confidently engage in interpersonal relationships (Hurtig & Park, 1991). For many children with SCD, “turbulent” is an appropriate description of their adolescent development and psychosocial struggles (Burlew, Telfair, Colangelo, & Wright, 2000). Adolescents with SCD often experience difficulty forming substantive and fulfilling peer relationships and exhibit behavioral and academic problems (Hurtig & Park, 1991; Schaeffer et al., 1999) due to an interruption in their development that can result in a weakened sense of self. Long periods of hospitalization and illness exacerbate these personal and interpersonal difficulties. The common, secondary biological effects of SCD, which include delayed growth and sexual development, also contribute to a diminished sense of self and poor interpersonal functioning. Developmental delays may lead to maladjustment for the adolescent suffering from SCD, particularly among boys. Hurtig and Park (1991) found boys with SCD to be at higher risk for maladjustment than girls during adolescence. Interestingly, there is also evidence that adolescents with SCD have fewer concerns about social and family relations and more concerns about slow body development, self-confidence, the burden their illness causes their families and friends, and ultimately death (Schaeffer et al., 1999).

Adulthood Research on psychosocial functioning among adults with SCD is limited. In general, studies have yielded mixed evidence for differences in the social adjustment of adult patients with SCD as compared to non-SCD controls. Small sample sizes, cross-sectional methodology, and inadequate control groups plague many of the studies we reviewed. What is clearly evident is that some adults with SCD appear more resilient, remaining psychologically and socially unaffected by their disease process, whereas others experience significant distress. Several factors appear to influence resiliency including age, gender, and socioeconomic status. Interpersonal support from family and friends, the effective use of coping strategies, and daily stressors are also salient predictors of resiliency

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in adults (Leavell & Ford, 1983; Rosse, 1983; Schaeffer et al., 1999). Adults and children differ in their ability to cope with disease-related pain over time. Adults are often more entrenched in their coping patterns, whereas children were more flexible and may ultimately be more open to a wider variety of interventions including therapy (Gil, Edens, Wilson, et al., 1997). Other studies have found that negative thinking (cognitive distortions), particularly in adults, and passive coping strategies are most related to poor health in patients with SCD (McCrae & Lumley, 1998). Ultimately, interventions to modify coping should be implemented as early as possible and preferably before children develop maladaptive patterns. Several interesting psychosocially oriented relationships have been observed in adult patients with SCD. Poor psychosocial adjustment is related to increased depression, employment difficulties, and psychiatric morbidity (Schaeffer et al., 1999). Increased levels of hope are associated with decreased levels of anxiety and are moderated by the patient’s use of active coping strategies (Lewis & Kliewer, 1996). Low levels of daily illness-related stress, positive thinking about pain, and palliative methods of coping with stress are most associated with adequate levels of psychosocial adjustment (Thompson et al., 1996). Lastly, increased levels of religiousity and spirituality are associated with reports of SCD-related pains (Harrison et al., 2005).

Interpersonal Context Peer Relations Peer relationships are a salient factor in the social and emotional development of children and are considered particularly important in the social and emotional well-being of children with SCD (Noll, Vannatta, Koontz, Kalinyak, et al., 1996; Noll, Ris, Davies, Bukowski, & Koontz, 1992). Unfortunately, little research has been conducted to examine the role of peer relationships in chronically ill populations or in children with SCD. A few studies indicate that children with SCD are at higher risk for problematic peer relationships (Hurtig & Park, 1991; Luthar, 1991; Morgan & Jackson, 1986; Schaeffer et al., 1999). For example, young girls with SCD report having fewer best friends and being less well liked than their race-, gender-, and age-matched peers (Hurtig & Park, 1991; Noll et al., 1996). Boys with SCD experience more difficulties with social acceptance but receive fewer nominations for aggressive or disruptive behaviors than their nondiseased peers (Hurtig, Koepke, & Park, 1989; Noll et al., 1996).

Some children with SCD may behave more cautiously due to the secondary physical consequences of their disease and may therefore set in motion a cascade of events that circularly lead to increased affective distress and limited social interactions. For example, avoidance of confrontation and a more cautious interpersonal style can protect the patient with SCD from verbal abuse, insult, or physical harm but at the significant risk of increased social isolation and limited peer interactions. Over many years of relative social isolation, brought about by illness and frequent hospitalizations, patients with SCD often develop more slowly, interpersonally, as compared to their peers, and may lack the experience with problem resolution skills needed for effective interactions. This skills deficit may increase the propensity for negative affect and social withdrawal, which ultimately exacerbates poor peer relations. Peer relationships, consequently, are intimately associated with a patient’s affect, disease state, and social context. Family Relations Typically, parent–child relationships are not effected negatively by SCD, but marital relationships between the adult patient and a spouse or the patient’s parents do tend to suffer as a result of this chronic illness. The primary caretaker, typically the mother, has significantly reduced opportunities to socialize outside of the family network and often feels hopeless, helpless, frustrated, and not well supported by family and friends during the child’s painful crises (Midence, Fuggle, & Davies, 1993). Mothers of children with SCD report fewer social contacts and less effective social networks as compared to mothers of children without SCD (Schuman et al., 1993). Poor psychological adjustment of mothers with children who have SCD is most influenced by a nonpalliative coping style, ineffective family support systems, and stress from daily hassles (Thompson et al., 1993, 1994). By inference, the mechanisms of healthy maternal adjustment in parents of children with SCD may be most related to decreasing daily stress; increasing a palliative coping style; and expanding the frequency, quality, and utilization of social and family support systems. Interestingly, few studies have evaluated the effectiveness of targeting these factors in psychosocial interventions.

Intervention and Treatment Several cognitive- and behavioral-based interventions have demonstrated efficacy and effectiveness for the treatment of chronic pain and related psychosocial disorders. These interventions include (a) activity rest cycling, (b) pain coping skills training, (c) pain distrac175

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tion techniques, (d) increased social support, (e) hypnosis, (f) reinforcement strategies, (g) electromyographic biofeedback, (h) traditional cognitive and cognitive behavioral therapies, (i) progressive muscle relaxation, and (j) breathing retraining (C. L. Edwards et al., 2000; Midence & Elander, 1996; Keefe, Jacobs, & Edwards, 1997; Logue & Edwards, 1998). Although negative affect, ineffective or deficient coping, and other cognitive behavioral factors have been shown to independently predict increased reports of pain and psychosocial dysfunction among patients with SCD (Fisher, Haythornthwaite, Heinberg, Clark, & Reed, 2001; Hassett, Cone, Patella, & Sigal, 2000; Martin & Teoh, 1999; Schaeffer et al., 1999), few studies have explored the previous techniques for the management of symptoms in this population. Although many patients often utilize medications as the first line of response during SCD-related pain crises, behaviorally based psychosocial approaches can be used effectively and adjunctively to standard medical treatments for pain and its related dysfunctions (Conner-Warren, 1996). Dinges et al. (1997) found that patients’ use of self-hypnosis resulted in significant reductions in both sleep disturbance and requirements for pain medications. Similarly, Gil et al. (1996) instituted a cognitive coping skills training program designed to decrease negative affect and improve pain coping and sensitivity among patients at a regional SCD center. Participants were randomized to either the cognitive coping skills treatment or a disease-education condition and were subject to a pretest–posttest design comprised of pain sensitivity task and structured interview. Individuals in the intervention condition participated in six individual sessions, which included relaxation and distraction strategies (breathing relaxation, pleasant imagery, counting backwards slowly, focusing on physical surroundings, reinterpreting pain sensations, and repeating calming self-statements). Patients in the cognitive coping skills treatment condition were found to make significantly more coping attempts and demonstrated lower levels of negative affect than those in the education-only condition. Furthermore, those receiving the intervention were less likely to report pain during stimulation in the laboratory.

Summary and Discussion In conclusion, although bone marrow transplant and gene therapies may be promising future cures for SCD, due to several obstacles in developing and implementing these technological advancements (Iannone, Ohene-Frempong, Fuchs, Casella, & Chen, 2005: Walters et al., 1996), clinicians and researchers must continue to focus on the management of symptoms in the context of the continued existence of the disease 176

(Burdick, 1994). Traditionally, SCD has been characterized as a complex of hematological disorders typically with sicklemia, recurrent episodes of intense pain requiring hospitalization, and long periods of physical disability that may even cause death. Consequently, traditional interventional strategies have addressed only these issues, often with inadequate attention to psychological, social, and interpersonal functioning. This presented evidence of the dynamic relationship in patients with SCD between psychological dysfunctions and the pathophysiology of the disease. Indeed, it views this relationship as integral to the conceptualization of SCD. Effective management of the illness requires a full utilization of intervention and prevention strategies including prophylactic opioid use (chronic pain management with long-acting preparations), awareness and effective management of acute pain crises within the context of a chronic pain disorder (management of break-through pain with shorter acting preparations), antiinflammatory medications, adjuvant medications, patient education (King, Tang, Ferguson, DeBaun, 2005), and cognitive behavioral and psychosocially oriented therapies. This review also emphasizes the tremendous opportunities that exist to intervene early on at an educational, psychosocial, and psychiatric level with patients, parents, and other caregivers who may be at risk for future psychosocial complications. Such interventions hinge on early detection and monitoring as well as early mental health screenings and testing. These processes and supports must also be extended to caregivers in a systematic and coherent manner. Certainly, many other chronic conditions—such as cancer and Alzheimer’s disease in adults and chronic pain in children—provide a model of how to effectively integrate the needs and concerns of caregivers as a salient focus in the clinical management of SCD. At a minimum, all caregivers and parents of children with SCD should be provided a comprehensive didactic education about potential avenues through which they could obtain mental health support and interventions as well as information related to their role in the effective management of the disease. In the context of increased federal attention to health care spending and decreased funding from state SCD programs, there is a need for comprehensive and effective approaches to the management of SCD that include both medical and psychosocial interventions (Koshy & Dorn, 1996; Lesi, 1982). Although several models have been proposed to accomplish this goal (Vavasseur, 1977), to date, empirical investigations of such interventions have been limited. Research, which begins to quantify the impact of adding psychosocial prevention and interventional strategies to reduce the incidence of SCD as well as more effectively treat those patients with the disease, is needed. Further re-

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search is needed to explore the impact of sociodemographic and cultural factors on SCD manifestation and progress. For example, there is increasing evidence that chronic pain is manifest, coped with, and even managed and treated, differentially, as a function of race and ethnicity, gender (C. L. Edwards et al., 2001), and other demographic factors. How do these sociodemographic factors influence the manifestation and treatment of pain in patients with SCD, a population in the United States that tends to be primarily African American? How do social support, coping style, depression, religiosity, spirituality, and other psychosocial factors influence health care utilization in patients with SCD? Are patients with insurance and affluence treated the same as patients without such means in the health care system? Would the use of transdermal and other technologically advanced medication modalities reduce physician worries about opioid medication abuse and consequently increase the overall effectiveness of pharmacologic treatment? Would such advanced delivery systems have an impact on the quality life of patients with SCD? What is the role of political advocacy in the care of patients with SCD? These and many other questions need to be answered as part of the development of effective treatments for SCD. Variability, too often based on prescriber’s misconceptions of patients’ propensity for medication misuse, can result in inappropriately low doses of opioids for the treatment of chronic pain and SCD crises. Misconceptions can also result in the suboptimal treatment and inappropriate management of acute pain crises in patients with SCD who have a history of chronic pain. Even more pervasive, increased access to information from the Internet and an increased prevalence of patient support groups have lead to greatly empowered and informed patients who actively request specific doses and types of medications and, too often, reinforce clinician misconceptions about inappropriate medication usage (Jacob, The American Pain Society, 2001). Yet other studies suggest that African Americans may be less tolerant of both laboratory (R. R. Edwards & Fillingim, 1999; R. R. Edwards et al., 2001) and clinical pain (Faucett, Gordon, & Levine, 1994; Janal, Glusman, Kuhl, & Clark, 1994; Lautenbacher & Rollman, 1997) as compared to their White counterparts. These differences are thought due to several factors including (a) comorbid diseases that affect the nervous system, (b) unfamiliarity with the research process, and (c) a healthy level of skepticism associated with participation in research and clinical trials. Addressing these many issues through psychoeducation and by encouraging the utilization of active cognitive and behavioral coping while assisting patients to correct maladaptive cognitions are a major focus of psychological interventions in the manage-

ment of SCD-related pain (C. L. Edwards et al., 2001). Ultimately, standards of hematological practice must move toward the systematic inclusion of interventions for adults and children (Brown, Armstrong, & Eckman, 1993) that address their psychosocial needs. The basic definition of “adequate care” must be elevated and modified to include the full range of pharmacologic and nonpharmacologic interventional and prevention strategies with the goal of increasing the quality of life of patients with SCD. We can no longer afford to see psychosocial issues as anything other than primary, and most importantly, we must recognize that understanding the pathophysiology of SCD in the absence of a thorough understanding of the psychological, psychiatric, cultural, and social influences is really misunderstanding SCD.

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