Management of chronic complications of sickle cell disease

• chronic pain
  • often caused by orthopaedic conditions such as avascular necrosis, vertebral collapse, or chronic arthritis (1)
  • chronic pain is difficult to eradicate and the goal should be to minimise the suffering as much as possible
    • medium- to long-acting opiates (orally or transdermally) should be used
    • prescribe an alternative analgesia for "breakthrough" pain
    • if NSAID's are used, should be limited to standard doses and defined periods and if given for longer periods, monitor renal function every 3 months
    • non pharmacological therapies such as massage, psychological coping strategies, including distraction techniques should be encouraged in children
  • yearly (or more frequently in special cases) assessment, medication review, and health education should be provided to the patient
    • career/vocational and employment advice
    • occupational, psychological therapy
    • inform about the importance of avoiding factors that may exacerbate pain e.g. - cold weather, high-impact exercise or sports, weight management and dehydration
      
      
• nutrition and growth (2)
  • height and weight should be measured at each visit
  • if the child is hospitalized for frequent and long periods, consider referral to a dietician for extra calorie input
  • zinc supplementation in case of growth retardation and vitamin D deficiencies should be treated (3)
  • folic acid supplementation is recommended for all patients with SCD (although it may mask megaloblastic anaemia caused by cobalamin deficiency) (2)
  • refer children with no physical signs of puberty at 14 years in a girl and 14.5 years in a boy to a paediatric endocrinologist
    
    
• nocturnal enuresis
  • inform the parents that nocturnal enuresis is common in SCD (specially in boys with HbSS) and most will resolve spontaneously
  • advice on techniques to achieve continence e.g - intermittent alarms and parental waking to achieve continence
  • if children do not respond to routine advice, consider oral or nasal desmopressin
  • refer to
    • an ENT specialist if the history is suggestive of obstructive apnoea and snoring
    • a specialist management (e.g. an enuresis clinic) if there is no response to basic measures after the age of 7 years (3)
      
      
• cerebrovascular disease (4)
  • all children with SCD aged over 2 years should undergo annual transcranial Doppler imaging
  • parents/carers should be educated about symptoms and signs of stroke and what action should be taken if a child develops neurological symptoms
  • a first episode of acute severe headache, or a significant change in the type of headache may indicate intracranial haemorrhage or venous sinus thrombosis and these patients should be admitted for urgent assessment
  • the mean blood pressure in SCD patients is lower when compared to age and sex matched controls hence more aggressive management of systemic hypertension is required on detection
  • regular blood transfusion should be offered throughout childhood for secondary prevention of stroke
    
    
• eye complications (5)
  • prevention of developing complications is the most effective therapy
  • all SCD patients must be evaluated by an ophthalmologist annually
  • patients with acute loss of vision (due to occlusion of the central retinal artery) should be treated with immediate blood transfusion and referral to an ophthalmologist
    
    
• leg ulcers (2)
  • should be managed by a multidisciplinary team with expertise in leg ulcer management
  • could be treated with frequent dressing, support bandages, physiotherapy and antibiotics if infected (Topical antibiotics should be avoided)
  • blood transfusion could be considered in patients who fail to respond
    
    
• priapism (6)
  • boys and their parents/carers should be educated that priapism is a complication of SCD and to seek treatment early and should attend hospital as an emergency if priapism persists for more than 2 hours
  • for minor events (occurring for less than 3 hours) - bladder emptying, exercise such as jogging, warm baths and analgesia may be useful
  • for stuttering priapism oral etilefrine may be beneficial
    
    
• chronic lung disease (7)
  • in patients with chronic lung disease advice about smoking cessation, vaccinations (should be kept up to date), avoiding, or getting early treatment for chest infections
  • Trans-thoracic echocardiography should be done to screen for pulmonary hypertension every 1-2 years
  • refer patients with suspected pulmonary hypertension to a specialist
    
    
• liver disease (8)
  • an ultrasound of liver and biliary tree should be carried out in patients with recurrent abdominal pain
  • in symptomatic biliary disease, consider elective cholecystectomy

Reference:

1. Martí-Carvajal AJ, Solà I, Agreda-Pérez LH. Treatment for avascular necrosis of bone in people with sickle cell disease. Cochrane Database Syst Rev. 2019 Dec 5;(12):CD004344.
2. National Heart, Lung, and Blood Institute. Evidence-based management of sickle cell disease: expert panel report, 2014. Sep 2014 [internet publication].
3. NHS Sickle Cell and Thalassaemia Screening Programme 2009. Sickle cell and Thalassaemia. Handbook for laboratories
4. DeBaun MR, Jordan LC, King AA, et al. American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults. Blood Adv. 2020 Apr 28;4(8):1554-88.
5. Leitão Guerra RL, Leitão Guerra CL, Bastos MG, et al. Sickle cell retinopathy: What we now understand using optical coherence tomography angiography. A systematic review. Blood Rev. 2019 May;35:32-42.
6. Arduini GAO, Trovó de Marqui AB. Prevalence and characteristics of priapism in sickle cell disease. Hemoglobin. 2018 Mar;42(2):73-77.
7. Castro O, Gladwin MT. Pulmonary hypertension in sickle cell disease: mechanisms, diagnosis, and management. Hematol Oncol Clin North Am. 2005 Oct;19(5):881-96.
8. Krauss JS, Freant LJ, Lee JR. Gastrointestinal pathology in sickle cell disease. Ann Clin Lab Sci. 1998 Jan-Feb;28(1):19-23.