Sickle-cell disease natural history, complications, and prognosis: Difference between revisions

Jump to navigation Jump to search
No edit summary
mNo edit summary
 
(3 intermediate revisions by 2 users not shown)
Line 1: Line 1:
__NOTOC__
{{Sickle-cell disease}}
{{Sickle-cell disease}}
{{CMG}}; {{AE}} {{AN}} {{shyam}}
{{CMG}}; {{AE}} {{AN}}, {{shyam}}


==Overview==
==Overview==
Line 6: Line 7:


==Natural History==
==Natural History==
The natural history of sickle cell disease involves manifestations that begin shortly after birth. Once gamma-globin chains (from fetal hemoglobin) are replaced by the defective beta-globin chains, patients can experience symptoms. This usually occurs at 8-10 weeks of life.<ref name="pmid23813607">{{cite journal| author=Serjeant GR| title=The natural history of sickle cell disease. | journal=Cold Spring Harb Perspect Med | year= 2013 | volume= 3 | issue= 10 | pages= a011783 | pmid=23813607 | doi=10.1101/cshperspect.a011783 | pmc=3784812 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23813607  }} </ref>  
The natural history of sickle cell disease involves manifestations that begin shortly after birth. If left untreated, the following is a general timeline of the effects of sickle-cell disease:<ref name="pmid23813607">{{cite journal| author=Serjeant GR| title=The natural history of sickle cell disease. | journal=Cold Spring Harb Perspect Med | year= 2013 | volume= 3 | issue= 10 | pages= a011783 | pmid=23813607 | doi=10.1101/cshperspect.a011783 | pmc=3784812 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23813607  }} </ref>  


By 2 months of life, infants can be affected by [[dactylitis]] (vaso-occlusive episodes in the hands and feet), or other complications. Dactylitis episodes typically resolve after 5-7 days with conservative measures. The reason is that bone marrow is present in the small extremity bones during the early weeks of life.
*By 2 months of life, infants can be affected by [[dactylitis]] (vaso-occlusive episodes in the hands and feet), or other complications. Dactylitis episodes typically resolve after 5-7 days with conservative measures. The reason is that bone marrow is present in the small extremity bones during the early weeks of life.
*By 3 months of life, splenic sequestration can occur.<ref name="pmid22924029">{{cite journal| author=Ballas SK, Kesen MR, Goldberg MF, Lutty GA, Dampier C, Osunkwo I et al.| title=Beyond the definitions of the phenotypic complications of sickle cell disease: an update on management. | journal=ScientificWorldJournal | year= 2012 | volume= 2012 | issue=  | pages= 949535 | pmid=22924029 | doi=10.1100/2012/949535 | pmc=3415156 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22924029  }} </ref> This is the age at which routine spleen size examination is important. If a person has 2 episodes of splenic sequestration, [[splenectomy]] should be considered. Symptoms include tachycardia, tachypnea, abdominal pain, and abdominal fullness, which are reflective of trapping of sickled [[red blood cells]] in splenic sinuses.<ref name="pmid22924029">{{cite journal| author=Ballas SK, Kesen MR, Goldberg MF, Lutty GA, Dampier C, Osunkwo I et al.| title=Beyond the definitions of the phenotypic complications of sickle cell disease: an update on management. | journal=ScientificWorldJournal | year= 2012 | volume= 2012 | issue=  | pages= 949535 | pmid=22924029 | doi=10.1100/2012/949535 | pmc=3415156 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22924029  }} </ref>
*By 6-12 months of life, death has been observed but can generally occur at any age after 1 year. One of the causes of death is [[acute chest syndrome]]. Other reasons for death in sickle cell anemia include [[sepsis]] and aplastic crises.<ref name="pmid23813607">{{cite journal| author=Serjeant GR| title=The natural history of sickle cell disease. | journal=Cold Spring Harb Perspect Med | year= 2013 | volume= 3 | issue= 10 | pages= a011783 | pmid=23813607 | doi=10.1101/cshperspect.a011783 | pmc=3784812 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23813607  }} </ref> Splenic dysfunction can occur by the first year of life.<ref name="pmid22924029">{{cite journal| author=Ballas SK, Kesen MR, Goldberg MF, Lutty GA, Dampier C, Osunkwo I et al.| title=Beyond the definitions of the phenotypic complications of sickle cell disease: an update on management. | journal=ScientificWorldJournal | year= 2012 | volume= 2012 | issue=  | pages= 949535 | pmid=22924029 | doi=10.1100/2012/949535 | pmc=3415156 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22924029  }} </ref>
*By 24 months of life, [[stroke]] can occur from vaso-occlusive episodes in the brain.<ref name="pmid23813607">{{cite journal| author=Serjeant GR| title=The natural history of sickle cell disease. | journal=Cold Spring Harb Perspect Med | year= 2013 | volume= 3 | issue= 10 | pages= a011783 | pmid=23813607 | doi=10.1101/cshperspect.a011783 | pmc=3784812 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23813607  }} </ref> Within 3 years of the first stroke, recurrent strokes are known to occur, which can pose significant morbidity.
*By 5 years of age, [[dactylitis]] usually does not occur, since the [[bone marrow]] is no longer present in small bones of the extremities by age 5.
*By late childhood, bone pain crises and [[avascular necrosis]] of the femoral head can occur. If sickled red blood cells become lodged in the penis, [[priapism]] can occur. Chronic leg ulceration is also a common problem in late adolescence.
*By adult age, patients can develop [[subarachnoid hemorrhage]], [[berry aneurysm]]s, and direct [[Intracranial hemorrhage|intracerebral bleeding]].  


By 3 months of life, splenic sequestration can occur.<ref name="pmid22924029">{{cite journal| author=Ballas SK, Kesen MR, Goldberg MF, Lutty GA, Dampier C, Osunkwo I et al.| title=Beyond the definitions of the phenotypic complications of sickle cell disease: an update on management. | journal=ScientificWorldJournal | year= 2012 | volume= 2012 | issue= | pages= 949535 | pmid=22924029 | doi=10.1100/2012/949535 | pmc=3415156 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22924029 }} </ref> This is the age at which routine spleen size examination is important. If a person has 2 episodes of splenic sequestration, [[splenectomy]] should be considered. Symptoms include tachycardia, tachypnea, abdominal pain, and abdominal fullness, which are reflective of trapping of sickled [[red blood cells]] in splenic sinuses.<ref name="pmid22924029">{{cite journal| author=Ballas SK, Kesen MR, Goldberg MF, Lutty GA, Dampier C, Osunkwo I et al.| title=Beyond the definitions of the phenotypic complications of sickle cell disease: an update on management. | journal=ScientificWorldJournal | year= 2012 | volume= 2012 | issue= | pages= 949535 | pmid=22924029 | doi=10.1100/2012/949535 | pmc=3415156 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22924029 }} </ref>
==Complications==
 
Sickle-cell anemia can lead to various complications, including:<ref name="pmid19610078">{{cite journal| author=Kato GJ, Hebbel RP, Steinberg MH, Gladwin MT| title=Vasculopathy in sickle cell disease: Biology, pathophysiology, genetics, translational medicine, and new research directions. | journal=Am J Hematol | year= 2009 | volume= 84 | issue= 9 | pages= 618-25 | pmid=19610078 | doi=10.1002/ajh.21475 | pmc=3209715 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19610078 }} </ref><ref name="pmid21554552">{{cite journal| author=Kato GJ| title=Priapism in sickle-cell disease: a hematologist's perspective. | journal=J Sex Med | year= 2012 | volume= 9 | issue= 1 | pages= 70-8 | pmid=21554552 | doi=10.1111/j.1743-6109.2011.02287.x | pmc=3253142 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21554552 }} </ref><ref name="pmid12911250">{{cite journal| author=Hasan SP, Hashmi S, Alhassen M, Lawson W, Castro O| title=Depression in sickle cell disease. | journal=J Natl Med Assoc | year= 2003 | volume= 95 | issue= 7 | pages= 533-7 | pmid=12911250 | doi= | pmc=2594635 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12911250 }} </ref><ref name="pmid19610078">{{cite journal| author=Kato GJ, Hebbel RP, Steinberg MH, Gladwin MT| title=Vasculopathy in sickle cell disease: Biology, pathophysiology, genetics, translational medicine, and new research directions. | journal=Am J Hematol | year= 2009 | volume= 84 | issue= 9 | pages= 618-25 | pmid=19610078 | doi=10.1002/ajh.21475 | pmc=3209715 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19610078 }} </ref><ref name="pmid19610078">{{cite journal| author=Kato GJ, Hebbel RP, Steinberg MH, Gladwin MT| title=Vasculopathy in sickle cell disease: Biology, pathophysiology, genetics, translational medicine, and new research directions. | journal=Am J Hematol | year= 2009 | volume= 84 | issue= 9 | pages= 618-25 | pmid=19610078 | doi=10.1002/ajh.21475 | pmc=3209715 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19610078 }} </ref><ref name="pmid22924029">{{cite journal| author=Ballas SK, Kesen MR, Goldberg MF, Lutty GA, Dampier C, Osunkwo I et al.| title=Beyond the definitions of the phenotypic complications of sickle cell disease: an update on management. | journal=ScientificWorldJournal | year= 2012 | volume= 2012 | issue=  | pages= 949535 | pmid=22924029 | doi=10.1100/2012/949535 | pmc=3415156 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22924029  }} </ref>
By 6-12 months of life, death has been observed but can generally occur at any age after 1 year. One of the causes of death is acute chest syndrome. Other reasons for death in sickle cell anemia include sepsis and aplastic crises.<ref name="pmid23813607">{{cite journal| author=Serjeant GR| title=The natural history of sickle cell disease. | journal=Cold Spring Harb Perspect Med | year= 2013 | volume= 3 | issue= 10 | pages= a011783 | pmid=23813607 | doi=10.1101/cshperspect.a011783 | pmc=3784812 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23813607 }} </ref> Splenic dysfunction can occur by the first year of life.<ref name="pmid22924029">{{cite journal| author=Ballas SK, Kesen MR, Goldberg MF, Lutty GA, Dampier C, Osunkwo I et al.| title=Beyond the definitions of the phenotypic complications of sickle cell disease: an update on management. | journal=ScientificWorldJournal | year= 2012 | volume= 2012 | issue= | pages= 949535 | pmid=22924029 | doi=10.1100/2012/949535 | pmc=3415156 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22924029 }} </ref>
 
By 24 months of life, stroke can occur from vaso-occlusive episodes in the brain.<ref name="pmid23813607">{{cite journal| author=Serjeant GR| title=The natural history of sickle cell disease. | journal=Cold Spring Harb Perspect Med | year= 2013 | volume= 3 | issue= 10 | pages= a011783 | pmid=23813607 | doi=10.1101/cshperspect.a011783 | pmc=3784812 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23813607 }} </ref> Within 3 years of the first stroke, recurrent strokes are known to occur, which can pose significant morbidity.
 
By 5 years of age, [[dactylitis]] usually does not occur, since the bone marrow is no longer present in small bones of the extremities by age 5.
 
By late childhood, bone pain crises and [[avascular necrosis]] of the femoral head can occur. If sickled red blood cells become lodged in the penis, priapism can occur. Chronic leg ulceration is also a common problem in late adolescence.
 
By adult age, patients can develop subarachnoid hemorrhage, berry aneurysms, and direct intracerebral bleeding.  


==Complications==
* Vaso-occlusive crisis
Sickle-cell anemia can lead to various complications, including:
* [[Acute chest syndrome]]  
* Vaso-occlusive crisis (otherwise known as painful crisis): Most patients with sickle-cell disease have periodic intensely painful episodes called vaso-occlusive crises. The frequency, severity, and duration of these crises vary tremendously. Painful crises are treated with hydration and analgesics; pain management requires [[opiate|opioid]] administration at regular intervals until the crisis has settled. For milder crises a subgroup of patients manage on [[NSAID]]s (such as [[diclofenac]] or [[naproxen]]). For more severe crises most patients require inpatient management for intravenous opioids; patient-controlled analgesia (PCA) devices are commonly used in this setting. [[Diphenhydramine]] is effective for the itching associated with the opioid use.  Incentive spirometry, a technique to encourage deep breathing to minimise the development of [[atelectasis]], is recommended.
* [[Overwhelming post-splenectomy infection|Overwhelming post-(auto)splenectomy infection]]  
* [[Acute chest syndrome]] is a life-threatening condition characterised by chest pain, shortness of breath, fever, hypoxaemia and pulmonary infiltrates on chest X-ray. It can be triggered by pain crisis, respiratory infection, bone-marrow embolization, or possibly by [[atelectasis]], such as can be caused by opiate administration, or surgery.
* [[Cerebrovascular accident|Stroke]]  
* [[Overwhelming post-splenectomy infection|Overwhelming post-(auto)splenectomy infection]] is due to functional asplenia, caused by encapsulated organisms such as ''[[Streptococcus pneumoniae]]'' and ''[[Haemophilus influenzae]]''. Daily [[penicillin]] prophylaxis is the most commonly used treatment during childhood with some haematologists continuing treatment indefinitely.  Patients benefit today from routine vaccination for ''H. influenzae'', ''S. pneumoniae'' and ''Neisseria meningitidis''.
* [[Cholelithiasis]] and [[cholecystitis]] ([[gallstone]]s)  
* [[Cerebrovascular accident|Stroke]] can result from a progressive vascular narrowing of blood vessels, preventing oxygen from reaching the [[human brain|brain]]. Cerebral infarction occurs in children with peak incidence at age 7, and cerebral hemorrhage in adults. The etiology is hyperplasia of the tunica intima and tunic media of cerebral microvasculature, which causes thrombosis.<ref name="pmid19610078">{{cite journal| author=Kato GJ, Hebbel RP, Steinberg MH, Gladwin MT| title=Vasculopathy in sickle cell disease: Biology, pathophysiology, genetics, translational medicine, and new research directions. | journal=Am J Hematol | year= 2009 | volume= 84 | issue= 9 | pages= 618-25 | pmid=19610078 | doi=10.1002/ajh.21475 | pmc=3209715 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19610078  }} </ref>
* [[Cholelithiasis]] and [[cholecystitis]] ([[gallstone]]s) may result from excessive [[bilirubin]] production and precipitation due to prolonged [[haemolysis]].
* Avascular necrosis ([[aseptic bone necrosis]]) of the hip may occur as a result of ischemia.
* Decreased [[immune system|immune reactions]] due to [[hyposplenism]] (malfunctioning of the spleen)
* Decreased [[immune system|immune reactions]] due to [[hyposplenism]] (malfunctioning of the spleen)
* [[Priapism]] and [[infarction]] of the penis.<ref name="pmid21554552">{{cite journal| author=Kato GJ| title=Priapism in sickle-cell disease: a hematologist's perspective. | journal=J Sex Med | year= 2012 | volume= 9 | issue= 1 | pages= 70-8 | pmid=21554552 | doi=10.1111/j.1743-6109.2011.02287.x | pmc=3253142 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21554552  }} </ref> There is some role of various agents to help prevent priapism. These include hydroxyurea, which increases fetal hemoglobin production, leuprolide, and sildenafil, which is a PD5 inhibitor that improves blood flow to the penis.<ref name="pmid21554552">{{cite journal| author=Kato GJ| title=Priapism in sickle-cell disease: a hematologist's perspective. | journal=J Sex Med | year= 2012 | volume= 9 | issue= 1 | pages= 70-8 | pmid=21554552 | doi=10.1111/j.1743-6109.2011.02287.x | pmc=3253142 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21554552  }} </ref>
* [[Priapism]] and [[infarction]] of the penis
* [[Osteomyelitis]] (bacterial bone infection) - ''[[Salmonella]]'' is noted much more commonly than in the general population, although ''[[Staphylococcus]]'' is still the most common.
* [[Osteomyelitis]]  
* [[Opioid]] tolerance can occur as a normal, physiologic response to the therapeutic use of opiates. Addiction to opiates occurs no more commonly among individuals with sickle cell disease than among other individuals treated with opiates for other reasons.
* [[Opioid]] tolerance
* Acute papillary necrosis in the kidneys.
* Acute [[papillary necrosis]] in the kidneys
* Leg ulcers
* Leg [[ulcer]]s
* Ocular manifestations such as orbital infarcts or central retinal artery occlusion can occur. In the eyes, there can be background retinopathy, proliferative retinopathy, vitreous hemorrhages and retinal detachments can occur. Regular annual eye checks are required.
* [[Orbital]] [[infarct]]
*During [[pregnancy]], [[intrauterine growth retardation]], spontaneous [[abortion]] and [[pre-eclampsia]] are the possibilities.
* Central retinal artery occlusion  
* [[Pulmonary hypertension]], which is defined as mean pulmonary arterial pressure > 25 mmHg on right heart catheterization.<ref name="pmid19610078">{{cite journal| author=Kato GJ, Hebbel RP, Steinberg MH, Gladwin MT| title=Vasculopathy in sickle cell disease: Biology, pathophysiology, genetics, translational medicine, and new research directions. | journal=Am J Hematol | year= 2009 | volume= 84 | issue= 9 | pages= 618-25 | pmid=19610078 | doi=10.1002/ajh.21475 | pmc=3209715 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19610078  }} </ref> Patients with sickle cell disease should be screened for pulmonary hypertension via transthoracic echocardiogram.
* [[Retinopathy]]
* Left-sided heart disease is caused by diastolic dysfunction induced the sickled rec blood cells.<ref name="pmid19610078">{{cite journal| author=Kato GJ, Hebbel RP, Steinberg MH, Gladwin MT| title=Vasculopathy in sickle cell disease: Biology, pathophysiology, genetics, translational medicine, and new research directions. | journal=Am J Hematol | year= 2009 | volume= 84 | issue= 9 | pages= 618-25 | pmid=19610078 | doi=10.1002/ajh.21475 | pmc=3209715 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19610078  }} </ref>
* [[Vitreous hemorrhage]]
* Neurocognitive impairment can occur in some patients and is not related to vaso-occlusion.<ref name="pmid22924029">{{cite journal| author=Ballas SK, Kesen MR, Goldberg MF, Lutty GA, Dampier C, Osunkwo I et al.| title=Beyond the definitions of the phenotypic complications of sickle cell disease: an update on management. | journal=ScientificWorldJournal | year= 2012 | volume= 2012 | issue=  | pages= 949535 | pmid=22924029 | doi=10.1100/2012/949535 | pmc=3415156 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22924029  }} </ref> Imaging cannot detect or diagnose neurocognitive impairment. Depression is also common.<ref name="pmid12911250">{{cite journal| author=Hasan SP, Hashmi S, Alhassen M, Lawson W, Castro O| title=Depression in sickle cell disease. | journal=J Natl Med Assoc | year= 2003 | volume= 95 | issue= 7 | pages= 533-7 | pmid=12911250 | doi= | pmc=2594635 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12911250  }} </ref>
* [[Retinal detachment]]
*During [[pregnancy]]:
**[[Intrauterine growth retardation]]
**[[Spontaneous abortion]]
**[[Pre-eclampsia]]
* [[Pulmonary hypertension]]
* Left-sided heart disease
* Neurocognitive impairment (unrelated to vaso-occlusion)
* [[Depression]]


==Prognosis==
==Prognosis==
The prognosis of patients varies. There are plenty of patients who live into adulthood and survival with supportive measures. However, in the event of severe sickling and vaso-occlusive crises in vital organs, such as the brain, the prognosis can be dismal.
The prognosis of patients varies based on degree of sickling and vaso-occlusive crises in vital organs. Sickle-cell heterozygosity has a protective advantage in infection with ''Plasmodium falciparum'', one of the causative agents of [[malaria]].<ref name="pmid26139766">{{cite journal| author=Colah RB, Mukherjee MB, Martin S, Ghosh K| title=Sickle cell disease in tribal populations in India. | journal=Indian J Med Res | year= 2015 | volume= 141 | issue= 5 | pages= 509-15 | pmid=26139766 | doi= | pmc=4510747 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26139766  }} </ref>
Importantly, sickle cell heterozygosity has a protective advantage in infection with Plasmodium falciparum, one of the causative agents of malaria.<ref name="pmid26139766">{{cite journal| author=Colah RB, Mukherjee MB, Martin S, Ghosh K| title=Sickle cell disease in tribal populations in India. | journal=Indian J Med Res | year= 2015 | volume= 141 | issue= 5 | pages= 509-15 | pmid=26139766 | doi= | pmc=4510747 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26139766  }} </ref>


The median survival of patients with sickle cell disease in the USA is 45-55 years.<ref name="pmid23813607">{{cite journal| author=Serjeant GR| title=The natural history of sickle cell disease. | journal=Cold Spring Harb Perspect Med | year= 2013 | volume= 3 | issue= 10 | pages= a011783 | pmid=23813607 | doi=10.1101/cshperspect.a011783 | pmc=3784812 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23813607  }} </ref> With improvement in treatment modalities, the median survival is likely to improve. The prognosis of sickle cell disease is better in geographic areas where there is a lower burden of infections, such as malaria or other blood-born pathogens. For example, HbSS in the USA has a better prognosis than HbSS in Africa.
The median survival of patients with sickle cell disease in the USA is 45-55 years.<ref name="pmid23813607">{{cite journal| author=Serjeant GR| title=The natural history of sickle cell disease. | journal=Cold Spring Harb Perspect Med | year= 2013 | volume= 3 | issue= 10 | pages= a011783 | pmid=23813607 | doi=10.1101/cshperspect.a011783 | pmc=3784812 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23813607  }} </ref> The prognosis of sickle cell disease is better in geographic areas where there is a lower burden of infections, such as malaria or other blood-borne pathogens.  


==References==
==References==
{{reflist|2}}
{{reflist|2}}
{{WH}}
{{WS}}

Latest revision as of 20:03, 19 October 2016

Sickle-cell disease Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Sickle-cell disease from other Diseases

Epidemiology & Demographics

Risk Factors

Screening

Natural History, Complications & Prognosis

Diagnosis

History & Symptoms

Physical Examination

Laboratory Findings

X Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Future or Investigational Therapies

Case Studies

Case #1

Sickle-cell disease natural history, complications, and prognosis On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Sickle-cell disease natural history, complications, and prognosis

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

National Guidelines Clearinghouse

NICE Guidance

FDA on Sickle-cell disease natural history, complications, and prognosis

CDC on Sickle-cell disease natural history, complications, and prognosis

Sickle-cell disease natural history, complications, and prognosis in the news

Blogs onSickle-cell disease natural history, complications, and prognosis

Directions to Hospitals Treating Sickle-cell disease

Risk calculators and risk factors for Sickle-cell disease natural history, complications, and prognosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2], Shyam Patel [3]

Overview

The natural history of sickle cell disease is characterized by various vascular phenomenon that begin at variable ages, and these vascular complications include, but are not limited to, the extremities and the brain. The complications of sickle cell disease involve various tissues and organs, including the chest, bones, and GI tract. The prognosis of sickle cell disease is variable, with a median survival of age 50 years. Of note, the prognosis of patients with malaria who have sickle cell disease is better than patients without sickle cell, since there a protective advantage.

Natural History

The natural history of sickle cell disease involves manifestations that begin shortly after birth. If left untreated, the following is a general timeline of the effects of sickle-cell disease:[1]

  • By 2 months of life, infants can be affected by dactylitis (vaso-occlusive episodes in the hands and feet), or other complications. Dactylitis episodes typically resolve after 5-7 days with conservative measures. The reason is that bone marrow is present in the small extremity bones during the early weeks of life.
  • By 3 months of life, splenic sequestration can occur.[2] This is the age at which routine spleen size examination is important. If a person has 2 episodes of splenic sequestration, splenectomy should be considered. Symptoms include tachycardia, tachypnea, abdominal pain, and abdominal fullness, which are reflective of trapping of sickled red blood cells in splenic sinuses.[2]
  • By 6-12 months of life, death has been observed but can generally occur at any age after 1 year. One of the causes of death is acute chest syndrome. Other reasons for death in sickle cell anemia include sepsis and aplastic crises.[1] Splenic dysfunction can occur by the first year of life.[2]
  • By 24 months of life, stroke can occur from vaso-occlusive episodes in the brain.[1] Within 3 years of the first stroke, recurrent strokes are known to occur, which can pose significant morbidity.
  • By 5 years of age, dactylitis usually does not occur, since the bone marrow is no longer present in small bones of the extremities by age 5.
  • By late childhood, bone pain crises and avascular necrosis of the femoral head can occur. If sickled red blood cells become lodged in the penis, priapism can occur. Chronic leg ulceration is also a common problem in late adolescence.
  • By adult age, patients can develop subarachnoid hemorrhage, berry aneurysms, and direct intracerebral bleeding.

Complications

Sickle-cell anemia can lead to various complications, including:[3][4][5][3][3][2]

Prognosis

The prognosis of patients varies based on degree of sickling and vaso-occlusive crises in vital organs. Sickle-cell heterozygosity has a protective advantage in infection with Plasmodium falciparum, one of the causative agents of malaria.[6]

The median survival of patients with sickle cell disease in the USA is 45-55 years.[1] The prognosis of sickle cell disease is better in geographic areas where there is a lower burden of infections, such as malaria or other blood-borne pathogens.

References

  1. 1.0 1.1 1.2 1.3 Serjeant GR (2013). "The natural history of sickle cell disease". Cold Spring Harb Perspect Med. 3 (10): a011783. doi:10.1101/cshperspect.a011783. PMC 3784812. PMID 23813607.
  2. 2.0 2.1 2.2 2.3 Ballas SK, Kesen MR, Goldberg MF, Lutty GA, Dampier C, Osunkwo I; et al. (2012). "Beyond the definitions of the phenotypic complications of sickle cell disease: an update on management". ScientificWorldJournal. 2012: 949535. doi:10.1100/2012/949535. PMC 3415156. PMID 22924029.
  3. 3.0 3.1 3.2 Kato GJ, Hebbel RP, Steinberg MH, Gladwin MT (2009). "Vasculopathy in sickle cell disease: Biology, pathophysiology, genetics, translational medicine, and new research directions". Am J Hematol. 84 (9): 618–25. doi:10.1002/ajh.21475. PMC 3209715. PMID 19610078.
  4. Kato GJ (2012). "Priapism in sickle-cell disease: a hematologist's perspective". J Sex Med. 9 (1): 70–8. doi:10.1111/j.1743-6109.2011.02287.x. PMC 3253142. PMID 21554552.
  5. Hasan SP, Hashmi S, Alhassen M, Lawson W, Castro O (2003). "Depression in sickle cell disease". J Natl Med Assoc. 95 (7): 533–7. PMC 2594635. PMID 12911250.
  6. Colah RB, Mukherjee MB, Martin S, Ghosh K (2015). "Sickle cell disease in tribal populations in India". Indian J Med Res. 141 (5): 509–15. PMC 4510747. PMID 26139766.