Sickle Cell Disease: Other Aspects to consider Erika Heard, PGY5 Internal Medicine & Psychiatry Emory University October 30, 2015 Objectives: Inspect the impact of psychological distress on thefunctioning of patients with sickle cell disease (SCD) Identify the common the psychiatric co-morbidities inSCD Demonstrate an understanding of the role ofinflammation in SCD Appreciate the effects of physician attitudes onclinician-patient interactions Overview: Sickle Cell Disease (SCD)
Background Role of inflammation Mental Health Co-morbidities Utility of Cognitive Behavioral Therapy Substance Use Physician Attitudes Background: SCD is a common autosomal recessive genetic disorder 1
1/375 African Americans are affected by SCD 1 Caused by a mutation on the 6th codon of the globin geneleading to a valine substituting for glutamic acid 2 Causes altered form of hemoglobin: HbSS, HbSC, HbS-thalssemia 1 Primarily in those of African decent but also inMediterranean, Middle Eastern, and Asian decent 1 Average life span of sickle red blood cell is dayswhile normally it is 120 days 3 Complications of SCD leads to multiple hospitalizations with>$450 million dollars in healthcare expenses each year 4 Inflammation in SCD: SCD is considered a chronic inflammatory condition 2 Increased levels of inflammatory markers due torepeated vaso-occlusive episodes and endothelial cellactivation Bandeira et al, conducted a cross-sectional study of 62patients with HbSS looking at the level of inflammatorymarkers in their blood 2 - levels of IL-6 and TNF- were significantly moreelevated and IL-7 was elevated when comparing thestudy and control groups Consistent with past studies, even when not having avaso-occlusive crisis (in steady state), there isinflammation 2 --increased levels of inflammatory cytokines, decreased nitric oxide, and oxidative stress causes the continued tissue damage Inflammation in SCD: Changes in the red blood cellcauses the cells to have a greater affinity for the vessel walls This activates the endothelial cells of the cell wall When the endothelial cells become activated they release cytokines Monocytes undergo extravasation More inflammatory cells are released and surround the nociceptor terminals These terminals release substance P Feeling of pain is detected 4 --vaso-occlusive event causes pain in SCD --pain is mainly nocioceptive type pain Lutz, B., Meiler, S., Bekker, A., et al. Updated mechanisms of sickle cell disease-associated chronic pain. Transl Perioper Pain Med. 2015; 2(2):8-17. Complications of SCD: Repeated microvascular insults lead to organ damageaffecting most systems: 1 - CVA - Acute chest syndrome - Avascular necrosis - Sickle cell retinopathy - Splenic sequestration - Vaso-occulsive crisis - Chronic pain - Nephropathy - Increased risk of infection Co-morbid Mental Illness in SCD:
PiSCES study looked at the health related quality of life(HRQOL) of those with SCD compared to those who sufferfrom cystic fibrosis, asthma, and on hemodialysis 5 -SCD had similar HRQOL to those with other chronicdiseases even compared to chronically debilitating illnessessuch as being on hemodialysis The negative impact on the quality of life of those with SCDis likely related to the chronicity of illness, chronic pain,frequent hospitalizations, and the unpredictable nature ofthe illness 5 Often symptoms such as fatigue, poor sleep, depressedmood, etc are due to pain and these symptoms overlap withsymptoms of depression 5 --Pain in SCD epidemiology study Co-morbid Mental Illness in SCD:
Rates of depression in this population vary between 18-44% 6 In the PiSCES study, the rate of depression was 27.6% (13.8% met criteriafor MDD) and 6.5% had anxiety 5 - In this patient population, patients with depression were significantly older,poor, and suffered from more frequent days of pain than those who werenot depressed - Depressed patients had significantly worse functioning on all short formhealth survey (SF-36) subscales than those who were non-depressed Depressed patients used more opioids and received less relief from thesemedications6 Some studies found depressed and anxious patients had greater healthcareutilization while others did not 6 In addition to social factors such as social isolation, decreased physicalfunctioning, and financial hardship, there are also biological factors thatcontribute to depression 6 --Depressive and anxiety sxs were measured using the PH-Q9 --interestingly, they found that depression was a greater predictor on functionality than genotype --Used the short form (SF-36) to measure health related to functional well-being; the lower the score the worse the functioning --it has 8 dimensions: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social functioning, mental health --they found significant differences among all the cohorts for all subscales except mental health; they had similarly reported quality of life as asthma patients in physical function and emotional function; compared to patients on HD, pt with SCD had low score for physical, emotional, and social functioning --in fact SCD functioning in the SF-36 domains was most similar to those on HD Inflammation and Depression:
Increasing amount of research exists that connectspsychological stress to increased inflammation leading tobehavioral changes 7 - These changes have been described as sicknessbehaviors Studies show that chronic inflammation may play a role indiseases such as asthma, rheumatoid arthritis, coronaryartery disease, diabetes, inflammatory bowel disease, andAlzheimer's 7 In these studies, there are increased rates of depression 7 - A study on rheumatoid arthritis and inflammatory boweldisease rates of depression were 2-3 times greater than inthe general population --sickness behaviors: sxs consistent with depressionpoor mood, anhdeonia, fatigue, psychomotor retardation, and social withdrawal --early life stressors have been shown to lead to increased levels of pro-inflammatory markers seen in adult patients with MDD Inflammation and Depression:
Stress-induced activation of the inflammatory response. Psychosocial stressors activate central nervous system stress circuitry, including CRH and ultimately sympathetic nervous system outflow pathways via the locus coeruleus. Acting through alpha and beta adrenergic receptors, catecholamines released from sympathetic nerve endings can increase NF-B DNA binding in relevant immune cell types, including macrophages, resulting in the release of inflammatory mediators that promote inflammation. Proinflammatory cytokines, in turn, can access the brain, induce inflammatory signaling pathways including NF-B, and ultimately contribute to altered monoamine metabolism, increased excitotoxicity, and decreased production of relevant trophic factors. Cytokine-induced activation of CRH and the hypothalamic-pituitary-adrenal axis, in turn, leads to the release of cortisol, which along with efferent parasympathetic nervous system pathways (e.g., the vagus nerve) serve to inhibit NF-B activation and decrease the inflammatory response. In the context of chronic stress and the influence of cytokines on glucocorticoid receptor function, activation of inflammatory pathways may become less sensitive to the inhibitory effects of cortisol, and the relative balance between the proinflammatory and anti-inflammatory actions of the sympathetic and parasympathetic nervous systems, respectively, may play an increasingly important role in the neural regulation of inflammation. CRH, corticotropin-releasing hormone; NF-B, nuclear factor kappa B. Miller, A., Maletic, V., and Raison, C. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry. 2009; 65(9): Inflammation and Depression:
--cytokines are released by monocytes, macrophages, dendritic cells, and neutrophiles--- they alter the neurochemical and neuroendocrine processes leading to both increased and decreased inflammation Singhal, G., Jaehne, E., Corrigan, F., et al. Inflammasomes in neuroinflammation and changes in brain function: a focused review. Front Neurosci. 2014; 8(315): 1-13. Inflammation and Depression:
Weinstein et al, showed that depressed patientsplasma levels of pro-inflammatory cytokines TNF- alpha, IL-6, and CRP are elevated 7 Another study, Dowlati et al, found that these pro- inflammatory markers were elevated in the brains ofpatients with MDD leading to neuroinflammation 7 Inflammation and depression in SCD:
No studies found looking at how chronicinflammation from SCD may affect mood - However, many previous studies regarding chronicinflammatory diseases show that this inflammationcan modulate mood and likely has an impact ondepressive symptomatology Future studies may focus on specifically whether thechronic inflammation in SCD correlates withdepression Neurocognitive Effects of SCD:
Many SCD patients are affected cognitively bychronic anemia, pain events, and frequent use ofopioid medications 10 In addition to these factors, 10-15% of patientswith HbSS have overt strokes and 20-25% havesilent strokes 10 Thus, many patients with SCD have unrecognizedneurocognitive issues Cognitive impairment influences ones ability totransition to adulthood due to compromised executivefunctioning affecting social abilities and problemsolving skills --these factors should be taken into account when working with SCD patients. --not only are there psychological issues but also cognitive impairment which might impede processing skills, social interactions, and may lead to social discord Psychological Distress:
SCD is a chronic disease beginning from birth Dealing with frequent, disruptive pain episodes greatly impactsthe growth and development of children with SCD leading to 11: - Social isolation - Difficulty developing fulfilling peer relationships - Academic difficulties - Difficulty developing a cohesive identity These difficulties in childhood can carry over to adulthood 11 - Limited studies comparing psychologically and sociallysturdiness in those with SCD compared to those without SCD Edwards et al, found that resiliency is a factor that leads to thedifference in those with SCD who are less affected vs those whoare more affected 11 --we all know that there are those patients with SCD who well adjusted socially and psychologically while others who are greatly affected --resiliency is influenced by age, gender, SES, interpersonal support from family/friends, and effective coping strategies --resiliency is ones ability to properly adapt to stress and adversity Psychological Distress:
Many patients with SCD have significant psychologicaldistress 12 Maladaptive behaviors develop from this psychologicaldistress 12 Most patients with SCD are dealing with emotions ofanger, frustration, and fear 12 Previous studies have shown that negative mood andstress are related to pain, psychosocial, and functionaloutcomes 12 Similarly, Edward et al, demonstrated a relationshipbetween negative emotional reactions to pain andpsychological outcomes in SCD 11 --Edwards et al, found that pt with SCD may develop negative thinking pattern better known as cognitive distortions and develop passive coping strategies which is correlated with poorer health outcomes in SCD patients --fear related to dying from disease and knowing others who have --Edwards found that negative emotional reactions to pain were significantly associated withsomatic symptoms, anxiety, phobic anxiety, and general severity index --Kofi also reported that multiple studies showed that negative thinking/passive adherence were shown to be positively associated with pain severity and health care utilization Cognitive Behavioral Therapy (CBT):
Goal is to help those recognize the relationship between thoughts, emotions, and actions Understanding these relationships and catching automatic thoughts helps to change ones emotions and ones reactions to situations 13 --this hopefully helps one to identify and correct these maladaptive behaviors https://growwiseyoga.wordpress.com/ CBT in SCD: With SCD, the goal is to recognize ones thoughtsregarding his/her pain and how this influencesactions Improve coping skills Reduce psychological distress Reduce fear avoidance to allow one to becomemore active in life Recognize and correct maladaptive behaviors 14 CBT in SCD: When treating patients with SCD, little focus has beenplaced on the psychological and social cultural aspects ofpain Studies have shown the efficacy and cost effectiveness ofcognitive behavioral interventions in addressing psychosocialaspects of chronic pain (ie reduction in hospital admission,analgesics intake, and decreased ER visits) Cognitive based therapies can provide alternative copingmechanisms leading to greater empowerment and fostergreater self-reliant 14 --these therapies fall into the category as probably efficacious Grady CBT for SCD Group:
Occurs on Wednesday afternoons in InternationalClinic Referrals accepted by Dr. Clearo by Epic messagingher Accepting all patients with SCD, especially highutilizers Will receive initial psychiatric assessment anddetermine whether interested and appropriate forthe group A Patient Perspective:
More times than not, when I am finally seen by aphysician or nurse, I am met with a callous, rude,disdainful attitude{Why are there no physicianswilling to accept new adult sickle cell patients?} Someof the reasons that I have been given are that sicklecell patients tend to be narcotics seekers and addicts,that most are on welfare, that they take up aninordinate amount of doctors time, and that theytend to be difficult patients Glinda Dames- Fincher 15 Transitions In Care: Previously not a chronic illness Transitioning from pediatric care to adult care can be difficult Limitations in care transitions 16: - Limited adult providers - Poor communication between pediatric and adult care centers - Family and patient unpreparedness for transition - Limited financial independence Transitions In Care: Telfair et al, found that adolescents,young adults, andprimary caregivers endorse concerns about this transition 17 Primary concerns included: - How they would pay for medical care - Providers being able to understand who sickle cell affects a person with this disease - Staff not believing their pain - Leaving the pediatric center - Primary Caretaker endorsed concern that child would be able to handle responsibility --Telifair found that primary emotions associated with transfer of care being anxiety, fear, and uncertainty Substance Use in SCD: in this population?
Why do you think there is this perception of opioid addiction in this population? What is the rate of opioid addiction in patients with SCD? - Actual rates are 3-10% which is no higher than thegeneral population18 Multiple studies have shown that healthcare professionals overestimaterates of opioid abuse by patients with sickle cell disease 19 - One study found that of ED doctors and of hematologist believethat ~20% of sickle cell patients they encounter have a problem withopioid abuse - Another study found that 63% of nurses believed that opioidaddiction frequently develops in sickle cell patients Pseudoaddiction: Common for those on long term opioids to developtolerance and physiological dependence 19 Due to the development of tolerance anddependence, MDs can be uncomfortable to dosethese medications 18 Does anyone know about psudoaddiction? - Manifestation of certain behaviors (exaggerated or manipulative) based on under treatment of pain 19 Pseudoaddiction vs Dependence:
Examples of Patients Descriptions of DSM-IV Symptoms of Substance Dependence Classified as Pain-Related and Non-Pain Related 19 Pain-Related Symptoms Non-Pain-Related Symptoms I found I needed more and more medication [to manage pain at home and avoid going into hospital] (Tolerance) I couldnt sleep without them [pain killers] I was restless at night walking up and down and feeling depressed (Withdrawal symptoms) Sometimes I am tempted to take it more frequently than prescribed, say when I am still in pain after two hours (Greater use than intended) I have taken an excess amount, because of my psychological state; I was stressed and thinking of killing myself (Greater than intended use) I have done that before [taking more painkillers] thinking the more I take the faster the pain would go (Greater use than intended) I look two, three, or even four, I was like high (Greater use than intended) It makes my skin itch and makes me feel drowsybut nothing else works. I try not to take it again but the pain always comes back (Attempt to cut down) I knew I was becoming dependent and I weaned myself off (Attempted to cut down) If the pain is really severe and I take a high dose. The tablets make me sleepy and I have to go to bed, so I am not able to go out (Social impairment) I was going through problemsdepression I was staying indoors and not working and being awake all night (Social impairment) A Common Grady patient:
Ms. H is a 27 y/o AAF with pmh sig for HbSS with complicationsof acute chest, stroke, and multiple hospitalizations for vaso- occlusive crisis (7 in the past year) presents for pain typical ofher sickle cell pain. At home she is on MS contin 60mg BID and10mg IR q4H. She has tried to alleviate the pain at home buthas returned to your service for the second time this month. Youremember her always talking on the phone, laughing, watchingmovies, doing things that you feel was atypical for someonewho claims they have severe pain. You dread going down tothe ER having to face her because you know she requires dilaudid4mg IV q4 hours and you feel uncomfortable giving her thisdose. Your resident snickers that you have the unfortunate luck totake care of the sickler again. You just hope to get her out assoon as possible so you dont have to deal with her constantrequest. She really only wants the narcotics anyway. --even though this is common at Grady this occurs at most institutions where patients with SCD are treated Physician Attitudes: Reflecting on the previous patient, when you have had a patient like this admitted, what is usually your first thought? How do you think these thoughts negatively or positively affect your interaction with patients with SCD? What is the culture that our program promotes when caring for SCD patients? What would be helpful for you as a resident to better care for patients with SCD? Physician Perceptions Toward SCD:
Health disparities are prevalent 20 Factors that may influence these disparities 20: - Provider bias/prejudice - Clinical uncertainty when interacting with minoritypopulations - Stereotypes about minority populations held byproviders Using the term sickler dehumanizes an individual anddevalues them to just their illness 21 - Glassberg et al, found that there was a correlationbetween negative attitudes towards patients with SCDand the use of the term sickler by ED phyicians Physician Perceptions toward SCD:
Patients recognize these negative beliefs heldtoward them and feel stigmatized 22 Effects of physician perceptions 22 Negative view toward healthcare system Feeds pseudoaddiction Breakdown of the therapeutic alliance Patient feels devalued Poor pain control Improving Care of Patients with SCD:
Platt et al, based at the GA Comprehensive Sickle CellCenter published guidelines regarding patient careduring a vaso-occlusive episode 3 A- Assessment of the pain (use a pain assessment tool) B- Believe the patients level of pain C- Complications or cause of pain D- Drugs and distractions (opioids and NSAIDS/distract with music, TV, relaxation techniques) E- Environment (quite area for rest) F- Fluids --many patients have both acute and chronic pain; failure to treat acute pain aggressively can lead to chronic intractable pain (Ballas) --alternative non-pharmacologic treatment of pain: heat pads, relaxation, music, massage, vibration,prayer, therapeutic exercises, menthol cream rub, self-hypnosis, acupuncture, TENS, biofeedback Improving Care of Patients with SCD:
In future encounters with SCD patients, rememberthat there are social, psychological, cultural factorsthat influence the current interaction between youand patient Gaining better context of all these factors and whatyour patient brings to the interaction will help indealing with frustrations related to care of thispopulation QUESTIONS??? --important to recognize counter-transferrence References: 1. Levenson,J. Psychiatric issues in adults with sickle cell disease. Primary Psychiatry 2008; 15(5):45-49. 2. Bandeira, I., Rocha, L., Barbosa, M., et al. Chronic inflammatory state in sickle cell anemia patients isassociated with HBB*S haplotype. Cytokine. 2014; 65(2): 3. Platt, A., Eckman, J., Beasley, J., et al. Treating sickle cell pain: an update from the Georgiacomprehensive sickle cell center. J Emerg Nurs 2002; 28: 4. Lutz, B., Meiler, S., Bekker, A., et al. Updated mechanisms of sickle cell disease-associated chronic pain.Transl Perioper Pain Med. 2015; 2(2):8-17. 5. McClish, D., Penberthy, L, Bovbjerg, V, et al. Health related quality of life in sickle cell patients: thePiSCES project. Health and Qual Life Outcomes. 2005; 3(1): 1-7. 6. Levenson, J., McClish, D., Dahman, B., et al. Depression and anxiety in adults with sickle cell disease: thePiSCES project. Psychosom Med. 2008; 70(2): 7. Slavich, G. and Irwin, R. From stress to inflammation and major depressive disorder: a social signaltransduction theory of depression. Psychol Pull. 2014; 140(3): 8. Miller, A., Maletic, V., and Raison, C. Inflammation and its discontents: the role of cytokines in thepathophysiology of major depression. Biol Psychiatry. 2009; 65(9): 9. Singhal, G., Jaehne, E., Corrigan, F., et al. Inflammasomes in neuroinflammation and changes in brainfunction: a focused review. Front Neurosci. 2014; 8(315): 1-13. 10. Wills, K., Nelson, S., Hennessy, J., et al. Transition planning for youth with sickle cell disease embeddingneuropsychological assessment into comprehensive care. Pediatrics. 2010; 126 (suppl 3): S151-S159. 11. Edwards, C., Mischca, T., loughlin, G., et al. A brief review of the pathophysiology, associatedpain, and psychosocial issues in sickle cell disease. Int J Behav Med. 2005; 12(3): References: 12. Edwards, C., OGaro, K., Killough, A., et al. Emotional reactions to pain predict psychological distress in adult patientswith sickle cell disease. Intl J Psychiatry Medicine. 2014; 47(1): 1-16. 13. Beck, Judith. Cognitive Therapy. John Wiley and Sons, Inc., 1979. 14. Chen, E., Coles, S., and Koto, P. A review of empirically supported psychosocial interventions for pain and adherenceoutcomes in sickle cell disease. J Pediatr Psychol. 2004; 29(3): 15. Dames-Fincher, G. A patient perspective on sickle cell disease treatment. JNMA. 1992; 84(9): 739. 16. Treadwell, M., Telfair, J., Gibson, R. W., Johnson, S. and Osunkwo, I. Transition from pediatric to adult care in sicklecell disease: Establishing evidence-based practice and directions for research. Am. J. Hematol. 2011;86: 116120. 17. Telfair, J., Myers, J., and Drezner, S. Transfer as a component of the transition of adolescents with sickle cell diseaseto adult care: adolescent, adult and parent perspectives. Journal of Adolescent Health. 1994; 15(11): 18. Feliu, M., Wellington, C., Crawford, R., et al. Opioid management and dependency among adult patients with sicklecell disease. Hemoglobin. 2011; 35(5-6): 19. Elander, J., Lusher, J., Bevan, D., et al. Understanding the causes of problematic pain management in sickle celldisease: evidence that pseudoaddiction plays a more important role than genuine analgesic dependence. J PainSymptom Manage. 2004; 27(2): 20. Freiermuth, C., Haywood, C., Silva. S., et al. Attitudes toward patients with sickle cell disease in a multicenter sampleof emergency department providers. Adv Emerg Nurs J. 2014; 36(4): 21. Glassberg, J., Tanabe, P., Richardson, L., et al. Among emergency physicians, use of the term sickler is associatedwith negative attitudes towards people with sickle cell disease. Am J Hematol. 2013; 86(6): 22. Chen, E., Cole, Steve, and Kato, Pamela. A review of empirically supported psychosocial interventions for pain andadherence outcomes in sickle cell disease. J Ped Psychol. 2004; 29(3):