Dr Lindsay Farrant on Sickle Cell Disease

Sickle cell disease (SCD) is the most common severe inherited disease in Africa.

Sickle cell disease (SCD) is the most common severe inherited disease in Africa as a whole, but not in South Africa.1 The incidence in South Africa is 1%, while in West Africa the incidence is highest, at 30-40%.1  The inheritance of the disease is autosomal recessive, meaning that it occurs in persons with two copies of the sickle cell gene – one from each parent (homozygous for the sickle cell gene, Hb SS).  Carriers have the sickle cell trait (Hb AS), meaning they only have one sickle cell gene and one ‘normal’ gene. In sickle cell disease the resultant haemoglobin (Hb SS) causes a distortion of the red blood cell shape – creating the ‘sickle cell’. SCD is one of the haemolytic anaemias where there is 1) increased red blood cell destruction, causing anaemia and jaundice; and 2) a compensatory increase in bone marrow erythropoiesis (red blood cell formation) and resultant bone and joint damage in the long term.1  Erythropoiesis can also occur in the liver and spleen, causing these organs to enlarge.¹ In addition to these features, painful sickle cell ‘crises’ (vaso-occlusive crises) occur when blood vessels are blocked by the ‘sickle cells’ when they interact in a specific manner with the lining of the blood vessels and the blood plasma.² These blockages can occur in any blood vessels, with the symptoms reflecting the area/s that are receiving insufficient blood supply.1 Some of the complications resulting from these vaso-occlusive crises are: pain syndromes, stroke, leg ulcers or kidney dysfunction.² These crises may be precipitated by factors such as dehydration, infections or exposure to cold.1,2

There is no curative treatment for SCD.1 A sickle cell crisis requires prompt supportive treatment to correct dehydration and acidosis, treat infections, and to relieve the underlying pain.1 This may be done at home or in hospital, depending on the severity of the attack. The acute pain in a crisis is caused by ischaemic (lack of blood supply) tissue injury. 2 Chronic pain is the result of repeated destruction of bones, joints and organs.2 The acute pain of unpredictable and recurrent crises interacts on a background of chronic pain over the lifetime of the person.2

The framework for management of pain in this disease should include treating acute pain crises effectively and promptly, preventing crises in the long term, and treating the chronic pain and related complications that can result from repeated crises.2 Adequate treatment of pain requires a comprehensive assessment of the patient’s pain. A brief assessment involves predominantly the physical aspects of the pain to enable prompt and adequate pain control in a crisis.3 This is followed up by a more comprehensive assessment involving the assessment of the multidimensional nature of the pain and is important for forward planning of the management of the patient’s pain.3

A comment on the mechanisms of pain is important. Nociceptive pain is a result of the damage to the tissue. Neuropathic pain is a result of damage to nerve fibres in the area of tissue damage, often, but not only, as a part of the chronic pain picture. Nociceptive and neuropathic pain are treated differently and as such it is important to identify the specific nature of the pain. Mixed pain refers to pain of mixed type (acute and chronic) and mixed mechanism (nociceptive and neuropathic). Mixed pain is not uncommon in SCD and should always be considered.4 The totality of the pain experience for the patient makes the comprehensive pain assessment a vital part of the pain assessment and enables adequate patient support. Psychological, social, cultural and spiritual support is important in the long term management plan for SCD patients. Acute admissions for crises should always been seen in the context of a chronic disease, with possible chronic pain.  The NICE guideline: Sickle cell disease: Managing acute painful episodes in hospital (CG143) is very helpful in the acute setting.5

(https://www.nice.org.uk/guidance/cg143/resources/sickle-cell-disease-managing-acute-painful-episodes-in-hospital-pdf-35109569155525 ) The American Pain Society guideline recommends that patients have a detailed clinical assessment of their pain, at least once per year, but more often if their pain is frequent or chronic.3 Pharmacological management of acute and chronic pain in SCD follows standard pain management guidelines. This includes the use of non-opioids, opioids and neuropathic pain agents for acute and chronic pain. Not infrequently, according to a number of studies, have doctors incorrectly label patients with SCD as being addicted to opioids,.6 Preboth writes “Opioid tolerance and physical dependence are expected with long term opioid treatment and should not be confused with psychologic dependence”.3 It is important that all pain be adequately treated with appropriate dosing of all analgesia. Specialist opinion and involvement may be required at times for some patients or more regularly for patients with particularly complicated pain.

Patients with SCD as children, grow to become young adults.  Transition of care between paediatric and adult services is an important part of care. The NICE guidelines point to the importance of adult and paediatric services working together for patient-centred care to ensure continuity of care.5
Life expectancy in persons with sickle cell disease is reduced. Death may be due to pulmonary complications, strokes, infection and its sequelae, acute splenic sequestration and chronic organ damage and failure.6 Acute death in a crisis, particularly a pain crisis, acute chest syndrome or a stroke occurs in around one third of patients, indicating the unpredictability of timing of death.6 This points to another key part of the holistic care of patients with SCD – the discussion of and preparation for the end of life. The WHO endorses palliative care for adults and children, as “an approach that improves the quality of life of patients and their families facing the problems associated with life threatening illness”.7 This is done “through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual.”7 According to this approach, many patients with SCD would derive benefit from a palliative care approach, while a smaller number of patients with SCD will require specialist palliative care for pain and symptom control and quality of life support. Quality of life is important throughout life, including at the end of life, and as such, for patients with a chronic, life-long disease, support and management aimed at the best possible quality of life is imperative for the entirety of that person’s life. While there is a need for more research into the specific palliative care needs of patients with SCD6, impeccable pain control in a crisis and at all other times should be an integral part of the aims of any care package offered to patients with SCD.

References:
Paediatrics and Child Health. A Manual for Health Professionals in the Third World. 4th Ed. Ed. Coovadia HM, Wittenberg DF. Ch 23. Disorders of the blood. Hesseling PB. P416-419. Oxford University Press.
Yale SH, Nagib N, Guthrie T. Approach to the vaso-occlusive crisis in adults with sickle-cell disease. Am Fam Physician. 2000 Mar 1;61(5):1349-1356. http://www.aafp.org/afp/2000/0301/p1349.html# (accessed 19 May 2017, 22.00)
Preboth M. Management of pain in sickle cell disease. Am Fam Physician 2000 Mar 1;61(5):1544-1550. http://www.aafp.org/afp/2000/0301/p1544.html# (Accessed 19  May 2017,  22.20)
The Management of Sickle Cell Disease. NIH. National Heart Lung and Blood Institute. Division of Blood Diseases and Resources. NIH Publication No. 02/2117. 4th Ed. 2002. P 60. https://www.nhlbi.nih.gov/files/docs/guidelines/sc_mngt.pdf (accessed 22 May 2017, 22.40)
NICE. 2012. Sickle cell disease: Managing acute painful episodes in hospital  (CG143) https://www.nice.org.uk/guidance/cg143/resources/sickle-cell-disease-managing-acute-painful-episodes-in-hospital-pdf-35109569155525 (accessed 22 May 2017, 22.55)
Fallon M. Introduction: Palliative medicine in non-malignant disease. In: Doyle D, Hanks G, Cherny N, Calman K. Oxford Textbook of Palliative Medicine. 3rd Ed. Oxford University Press 2005. P. 845-6.
Sepúlveda C et al. Palliative Care: The World Health Organization’s Global Perspective. JPSM 24(2) 2002 p91-96. DOI: http://dxdoi.org/10.1016/SO885-3924(02)00440-2 (accessed 29 May 2017, 22.0