https :// www . ncbi . nlm . nih . gov / pmc / articles / PMC4800688
Sickle cell disease causes acute and chronic illness , and median life expectancy is reduced by at least 30 years in all countries , with greater reductions in low-income countries . There is a wide spectrum of severity , with some patients having no symptoms and others suffering frequent , life-changing complications . Much of this variability is unexplained , despite increasingly sophisticated genetic studies . Environmental factors , including climate , air quality , socio-economics , exercise and infection , are likely to be important , as demonstrated by the stark differences in outcomes between patients in Africa and USA / Europe . The effects of weather vary with geography , although most studies show that exposure to cold or wind increases hospital attendance with acute pain . Most of the different air pollutants are closely intercorrelated , and increasing overall levels seem to correlate with increased hospital attendance , although higher concentrations of atmospheric carbon monoxide may offer some benefit for patients with sickle cell disease . Exercise causes some adverse physiological changes , although this may be off-set by improvements in cardiovascular health . Most sickle cell disease patients live in low-income countries and socioeconomic factors are undoubtedly important , but little studied beyond documenting that sickle cell disease is associated with decreases in some measures of social status . Infections cause many of the differences in outcomes seen across the world , but again these effects are relatively poorly understood . All the above factors are likely to account for much of the pathology and variability of sickle cell disease , and large prospective studies are needed to understand these effects better .
Introduction
Sickle cell disease ( SCD ) is a highly variable condition , with some patients being asymptomatic and others admitted frequently to hospital . Despite its genetic simplicity , a single base change T > A at codon 6 of the β gene , the clinical heterogeneity of the disease has long been recognized . 1 The polymerization of deoxygenated hemoglobin S ( HbS ), formation of irreversibly sickled erythrocytes and vaso-occlusion underlie the pathophysiology of SCD 2 and lead to the two hallmarks of the disease : recurrent episodes of acute pain and chronic organ damage . 3 The severe pain is ischemic in origin , and these painful episodes are the most common reason for patients seeking medical attention . Hemolysis also plays a central role in the pathophysiology , contributing significantly to anemia , vasculopathy , nitric oxide deficiency and inflammation . 4
SCD is endemic in many regions in which malaria is or was prevalent , due to the protective nature of the carrier state . It is estimated that around the world more than 312,000 infants are born with homozygous HbS ( sickle cell anaemia , SCA ) each year with the vast majority of births occurring in the developing world , and an estimated 230,000 such births annually in Sub-Saharan Africa . 5 However , migration has led to an increase in the prevalence and genetic heterogeneity of hemoglobinopathies across the world , including many European countries and other non-endemic regions , 6 with SCD accounting for many hospital episodes in some cities such as London and Paris . 7 A similar pattern is seen in the USA , where many emergency department attendances and inpatient hospitalizations are related to SCD . 8 There has been a steady improvement in the early mortality caused by SCD in high-income countries as a result of early diagnosis by newborn screening and improved clinical care . This is in contrast to low-income countries in which early mortality due to SCD is still strikingly high . 9 , 10