|
 
 |
| REVIEW ARTICLE |
|
| Year : 2021 | Volume
: 2
| Issue : 2 | Page : 48-54 |
|
Systemic complications and imaging challenges of sickle cell disease in sub-saharan Africa
Grace B Inah1, Emmanuel E Ekanem2, Christiana I Obiora1, Godwin I Ogbole3
1 Department of Radiology, University of Calabar Teaching Hospital, Calabar, Cross River State, Nigeria
2 Department of Pediatrics, University of Calabar Teaching Hospital, Calabar, Cross River State, Nigeria
3 Department of Radiology, University of Ibadan, Ibadan, Nigeria
| Date of Submission | 08-Jul-2021 |
| Date of Decision | 10-Sep-2021 |
| Date of Acceptance | 27-Sep-2021 |
| Date of Web Publication | 30-Nov-2021 |
Correspondence Address:
Grace B Inah
Department of Radiology, University of Calabar Teaching Hospital, Calabar, Cross River State
Nigeria
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/jrmt.jrmt_12_21
With improved life expectancy of people living with sickle cell disease (SCD) as a result of modern interventions, chronic problems such as pulmonary, abdominal, cardiovascular, musculoskeletal, and obstetric challenges are more often encountered. The need for radiological examination is, therefore, growing for the early diagnosis of these complications and improved prognosis. The emphasis, therefore, should be toward safer diagnostic options such as ultrasonography, transcranial Doppler ultrasound, and echocardiography as repeated radiation is counterproductive. This review is aimed at highlighting the imaging challenges encountered in the management of SCD in sub-Saharan Africa and possible ways of mitigating them. We reviewed available electronic literature in the last 20 years, especially articles from Google Scholar and PubMed with search keywords of imaging challenges, sickle cell disease, and sub-Saharan Africa. The challenges identified in this review include lack of institutional infrastructure, poor equipment availability, weak health and imaging personnel capacity, treatment affordability, service accessibility, and poor research and training facilities. With the increasing longevity of SCD individuals in sub-Saharan Africa, imaging requirements are rising. Repeated exposure to radiation should be minimized as much as possible. Engagement of the private sector through public-private partnership in equipping health institutions with radiological equipment, as well as training of appropriate personnel for their deployment is strongly recommended to enhance care, prevent complications, and improve outcomes for SCD in sub-Saharan Africa.
Keywords: Challenges, complications, imaging, sub-Saharan Africa, sickle cell disease
How to cite this article:
Inah GB, Ekanem EE, Obiora CI, Ogbole GI. Systemic complications and imaging challenges of sickle cell disease in sub-saharan Africa. J Radiat Med Trop 2021;2:48-54 |
How to cite this URL:
Inah GB, Ekanem EE, Obiora CI, Ogbole GI. Systemic complications and imaging challenges of sickle cell disease in sub-saharan Africa. J Radiat Med Trop [serial online] 2021 [cited 2023 Jun 3];2:48-54. Available from: http://www.jrmt.org/text.asp?2021/2/2/48/331521 |
| Introduction | |  |
Sickle cell disease (SCD) is the most common genetic disease in the world.[1],[2] It is predominant in people from the Middle East, Mediterranean regions, South Asia, and sub-Saharan Africa, especially Nigeria affecting about 3% of births.[3],[4] SCD is also found in the other parts of the world, including the USA and Europe due to migration and interracial marriages.[1] It is an inherited autosomal-recessive disorder of the blood resulting from the inheritance of sickle cell gene either homozygously or as a double heterozygous with another interacting gene. The most common cause of the (SS disease) being the homozygosity for B-globin S gene mutation, which is consistent with early mortality of 50%–90% among children born with the disease in sub-Saharan Africa[4],[5] The hallmarks of SCD include chronic hemolysis, anemia, and ischemia leading to a variety of pains and other complications.[1]
A sudy done by Flemings et al.[4] in Nigeria showed that 92% of children with SCD have excess mortality past age of 5 years. McAuley et al.[6] in Kenya have 90% excess mortality by the age of 13 years, and Danquah et al.[7] in Ghana had excess mortality past age of 5 years.
With the increasing population of older SCD patients, chronic problems such as chronic abdominal pain, gallbladder stones, sexual problems including priapism, sub-fertility, and obstetric challenges such as intrauterine growth restriction, spontaneous abortion, and preeclampsia are escalating.[8] There is a greater need for imaging for the early diagnosis and treatment of these complications to ensure the improved prognosis. This review describes the imaging challenges in sub-Saharan Africa in the management of SCD patients in the context of their increasing longevity.[9]
| Methodology | | |
A search was conducted in Google Scholar and PubMed with various combinations of the following keywords: Sickle cell disease, increasing longevity, imaging, ultrasonography, Transcranial Doppler scan, radiological findings, magnetic resonance imaging (MRI), and computed tomography (CT) scan. The articles on the subject of imaging challenges in people living with SCD in sub-Saharan Africa were identified. Selected articles were arranged into sub-sections for appropriate sequence and clarity. The key imaging challenges that mitigate adequate management of SCD in sub-Saharan Africa were identified and extracted for discussion.
| Systemic Complications and Imaging Challenges of Sickle Cell Disease in Africa: Musculoskeletal Complications | | |
Conventional radiography using plain X-ray films has played a major role in the imaging of musculoskeletal complications of SCD.[10] It is not only more readily and widely available in most radiological centers in Africa but is also relatively affordable. However, caution is no doubt critical as it uses potentially harmful X-rays which are ionizing radiation. This constitutes a hazard that may compound its repeated use in SCD patients needing multiple X-rays for chronic bone pains encountered in the course of the disease, which are essential to monitor disease progression in the patients. The radiographic features resulting from musculoskeletal indications are often nonspecific, and the earliest changes may not be evident until after 7–10 days.[10] Repeated X-ray exposures at an early age and as these patients become older may be deleterious as a result of the cumulative effects of radiation nevertheless, X-rays still remain an important component in diagnosing most skeletal complications in SCD.[11]
The musculoskeletal system represents one of the most commonly affected systems in SCD patients. The skeletal involvement in SCD is mediated through different pathophysiological mechanisms. These include excessive intramedullary and extramedullary hematopoiesis, ischemic osteonecrosis, and increased susceptibility to osteomyelitis.[11],[12] Widening of osseous medullary spaces leads to osteopenia and thinning of cortical bone, making the bone vulnerable to pathologic fractures which are easily seen on radiographs. The skull diploic space is widened and together with some trabecular thickening produces the X-ray “hair-on-end” appearance of the skull, which is pathognomonic for hemolytic anemia.[12],[13] The vertebral osteopenic texture can result in central vertebral body compression giving a typical appearance of multiple H-shaped vertebrae that are commonly seen in the dorsal spine.[13]
Avascular necrosis (AVN) due to ischemia is one of the most frequently encountered complications of SCD. Ischemia and consequent infarcts mainly involve the medullary cavities of the shafts and epiphyses of long bones, the body of spinal vertebrae, and pelvic bones. It may also involve small tubular bones of hands or feet, which is known as sickle cell dactylitis or hand-foot syndrome.[14] This syndrome usually presents before the peripheral skeleton of affected hands or feet can show soft-tissue swelling with periosteal reaction 7–10 days after the onset of severe pain. Later on, it shows medullary expansion, cortical thinning, and osseous lucent patches. It mainly involves the metacarpal/metatarsal bones and proximal phalanges.[11],[14] Usually, it is self-limiting with spontaneous resolution in few weeks; however, bone destruction and resultant deformity may be seen on X-rays of AVN in long bones. The bone shafts show relatively delayed findings of mixed lucent and sclerotic patches, sometimes associated with periostitis and periosteal reaction if the cortex is involved. AVN of long bones epiphysis is considered one of the common features of SCD. The femoral head is the most common site, followed by the humeral head. It can occur in single or several bones at the same or different times. X-ray is usually normal in the early stage of the disease or may show regional osteopenia. Afterward, it usually shows mixed lucent and sclerotic patches, crescent-shaped subchondral lucency, collapse, fragmentation and eventually, secondary osteoarthritis.[10],[12]
Osteomyelitis and septic arthritis are also common complications in patients with SCD. This may be due to the immune-compromised status of these patients and the presence of osteonecrotic lesions. Osteomyelitis and septic arthritis were reported to be 18% and 7% in SCD patients, respectively, than non-SCD.[15] Sometimes, differentiating acute osteomyelitis from osteonecrosis in SCD patients is difficult. Plain X-ray and CT have limited roles in such differentiation, as the major positive signs could be seen in both pathologies, such as periosteal reaction and bone destruction. Effective alternatives to X-rays such as ultrasonography, magnetic resonant imaging, and nuclear imaging may be employed as these patients grow older and could require repeated imaging.[15],[16] Very few countries have adequate access to MRI in sub-Saharan Africa. In West Africa, Ghana seems to have highest supply of MRI with 0.48 units/million population seconded by Nigeria with 0.30 units/million population. These may be attributed to cost limitations as well/lack of insurance and level of poverty as 70% of Africans live on <$2/day.[17] Ultrasound is easily accessible, cheap, and can be used for follow-up while nuclear imaging is good for the diagnosis of osteomyelitis although expensive. MRI is the most sensitive investigative modality for diagnosing AVN in the long bone shaft and long bone epiphysis. First, it shows bone marrow oedema as medullary T2w hyperintense and T1w hypo-intense signal. Shortly afterward it shows a serpentine geographic medullary patch of different sizes according to the severity of insult, with T1 low signal and T2w hyperintense ring. This can be explained by the formation of central serpentine granulation tissue surrounded by a sclerotic ring. Furthermore, this granulation tissue may show enhancement in postcontrast scans.[18],[19]
MRI facilitates a better response to treatment because it helps early correct therapeutic application, avoiding complications of delayed diagnosis. MRI may also help and guide interventional procedures such as core decompression as well as judge and check the therapeutic response.[20],[21]
| Neurological Complications | | |
The neurological complications of SCD are quite common and protean. Some can go undetected and can be a major cause of morbidity and mortality. They include silent brain infarcts (39%) by the age of 18 years, acute and chronic headache (36% in children), neurological impairment (25%), seizures (7%–10%), ischemic stroke (1%) in children with effective screening, but occurs in about 11% in children without effective screening.[22],[23] Hemorrhagic stroke occurs in 3% of children and 10% of adults.[23],[24] These complications are lower in non-African countries contrasting with higher vulnerability of patients in African countries.[24] This difference is due to the lack of standard up-to-date equipment, lack of public awareness, accessibility to adequate diagnostic tools (neuroimaging, trans-cranial Doppler [TCD], EEG, neurophysiological evaluation, preventive, and therapeutic) as well as evaluation of trained care persons.[24],[25]
Cerebrovascular accidents are the most common cerebral insults reported in SCD patients, accounting for about 12% of deaths in these patients.[26] Stroke is more prevalent in children between the age group of 2 and 20 years, and its prevention has become a major effort in the management of SCD.[26],[27] The identification of the child with SCD at increased risk of stroke using TCD ultrasonography, followed by preventive, chronic transfusion therapy, as practiced in developed countries, is not a common practice in most developing countries.[23],[24],[25],[27] This gap needs to be promptly addressed in sub-Saharan Africa to help reverse the poor health indices for SCD patients.
Modern medical interventions have allowed the childhood mortality rate of SCD to decrease and life expectancy to increase, especially in developed countries in the West even where these conditions are not prevalent. However, cerebrovascular events in childhood are relatively common and can significantly limit the full potential of a developing child, adolescent or adult. Improved diagnosis of these neurological conditions can be achieved using cross-sectional imaging tools for the brain and spinal evaluations such as CT scans or MRI equipment. MRI is a safe, noninvasive, useful technique for the diagnosis and management of SCD-related cerebral infarction, CVD, and other neurological abnormalities.[28] MRI studies have shown that most strokes occur from the distribution of the internal carotid artery. Pathologies are frequently observed in tissue within the anterior cerebral and middle cerebral arterial distribution.[27],[28],[29] Stenosis of these vessels with relative sparing of the posterior circulation has been reported.[18],[29] The high cost and poor availability of MRI consistently limit the use of this imaging modality in the developing countries due to poor resources and competent personnel to man the systems.
| Cardiovascular/Vascular Complications | | |
Previously, owing to a short life span of SCA patients, there were no considerable recognized cardiovascular complications.[25] However, currently because of the relatively increased longevity of these patients, cardiovascular complications are more pronounced which include pulmonary hypertension (PHT), myocardial infarct, heart failure, left ventricular dysfunction, cardiopulmonary vasculopathy, renal vasculopathy, cerebral vasculopathy, iron overload, and sudden death.[30]
The diagnostic hallmark of PHT is dilation of the central pulmonary arteries with rapid tapering and right ventricular hypertrophy, which is easily seen in plain chest X-ray. It can also be clearly identified in CT or CT angiography (CTA) scans, in which accurate measurements of the diameter of the main pulmonary artery can be done.[5],[30],[31] CT or CTA scans should, therefore, be preferred in this situation. However, both modalities are lacking in this region.
Chronic anemia in SCD patients causes cardiac chamber dilation and a compensatory increase in left ventricular mass, which can be accurately estimated by echocardiography. Children with SCD may have electrocardiography ischemic changes with reported cases of myocardial infarcts and ventricular aneurysms.[31],[32] This may be one of the possible etiologies of sudden death, which is an increasingly recognized problem among SCA patients; thus, cardiac investigations are mandatory to recognize and treat high-risk patients.[30],[31],[32] Perhaps echocardiography not usually done should be included as a routine screening protocol in the investigation of patients with SCD in steady-state and in crises, since is widely available.
Extra medullary haematopoiesis, though not a common feature of SCD, and more commonly seen in thalassemia, is still reported in a considerable percentage of SCD patients.[11],[19] It may involve liver, spleen or paravertebral spaces; less likely kidneys, adrenal glands, and skin. Sectional imaging by CT scan or MRI can perfectly diagnose these masses. They usually show CT isodensity and intermediate signal intensity or both TI-weighted and T2-weighted MR images, with no or minimal postcontract enhan × cement.[20],[21] CTA or magnetic resonant angiography or conventional digital subtraction angiography show this cerebral vasculopathy as arterial tortuosity, stenosis, or occlusion. CT or CTA scans can clearly identify PHT; an accurate measurement of the diameter of the main pulmonary artery can be done.
Multi-detector CT scan is the most sensitive tool for the diagnosis of liver infarction. Noncontract CT scan shows homogenously increased liver density 75–135 Hu (normal 45–65HU). As sicklers live longer in our environment and chances of these complications presenting become higher, more facilities in sub-Saharan Africa should acquire ultrasound machines, CT and MRI.
| Pulmonary Complications | | |
Pulmonary complications are one of the medical emergencies among the SCD patients and include the following acute chest syndrome (ACS), restrictive lung disease, asthma/reactive airways disease, PHT, and pulmonary embolism.[33],[34] ACS is one of the most common causes of hospitalization and even death of SCD patients. ACS is defined as a new lung infiltrate on chest radiograph, associated with fever, cough, wheezes, dyspnea, and tachypnea.[34],[35],[36] There is no clear single pathogenesis of this syndrome; however multiple different factors (separate or combined) may be incriminated, for example, pulmonary fat embolism, hypoxemia, and atelectasis due to shallow breath secondary to painful rib infarction, as well as a pulmonary vascular obstruction. X-ray film may show single or multiple areas of pulmonary infiltrate, mainly involving the middle and lower lobe air space.[34],[35],[36] Pleural effusion may be seen. Noninfectious infiltrate will clear more rapidly than infectious ones, so follow up chest X-rays are recommended to monitor the resolution of the disease. Unavailability of most of the imaging modalities become a major limitation in the diagnosis, therapeutic management, and follow-up of patients in rural areas.
| Splenic/Gallbladder Complications | | |
Ischemic vascular occlusion frequently affects different parts of the abdominal vascular structures. The commonly involved organ is the spleen, which is affected in most patients with SCD.[37] Repeated splenic infarctions start within the first 18–36 months of life, corresponding to the dates of the disappearance of protective Hb F, resulting in hyposplenism or even autosplenectomy.[8],[38] Splenic atrophy is a major etiology of the compromised immune status of these patients and increased susceptibility to infections.[39] Imaging appearance of splenic infarction depends on the timing of imaging and the size of the infarcts. In well-established cases, both ultrasound and CT are almost equally sensitive; however, in the early acute stage, contrast-enhanced CT scan is the most sensitive tool of imaging. Ultrasonography can detect splenomegaly, infarctions, splenic fibrosis, and autosplenectomy.[8],[39] The typical infarct is seen as a hypodense nonor poorly enhancing wedge, with the apex pointing toward the hilum. Later on, these infarcts may resolve completely or leave a permanent scar seen as a contracted segment, or liquefy with possible abscess formation.[38],[39] Furthermore, multiple small infarcts or global infarcts of the whole spleen are reported in imaging findings. Here again, because of availability, cost-effectiveness, and safety, ultrasound should be the preferred imaging modality in sub-Saharan Africa.
A high incidence of gall bladder stones is reported among SCA patients.[40] Ultrasound is sufficient for the diagnosis of these stones, except if complicated by the biliary tree or CBD obstruction, then magnetic resonance cholangiopancreatography is recommended for the diagnosis.[28],[40],[41]
In a case report, it has been observed that with increased longevity of SCD patients in Nigeria, gall bladder stones should be considered a possible cause of acute and recurrent abdominal pain among these children.[38] Ultrasound with a deliberate search for gall bladder stones should perhaps also be routine in SCD patients and certainly indicated in acute recurrent abdominal pain in them.
| Renal Complications | | |
Sickle cell nephropathy is another major complication of SCD, which develops as a result of vasoocclusion in the renal circulation.[33],[42] Ultrasonography may be regarded as the fastest means of assessing nephropathic changes. It shows cortical echogenicity accentuation, loss of cortico-medullary differentiation. Increased resistive index on Doppler examination as well as size and morphology changes.[42] The management of end organ manage is the key challenge in the management of patients with SCD of which most of them survive till adulthood. The prevention of kidney complication is the focus as this guidelines, accepted in first November 2019,[43] which the American society of hematology addressed specific question relating to screening, diagnosis, and management of these complication.[43],[44]
| Sexual, Fertility and Obstetric Complications | | |
Infertility is another worrisome complication seen among the SCD patients. Infertility in these group of individuals appears more frequently in males than females.[45] Their clinical presentations may include hypogonadism, sperm abnormality, and erectile dysfunction from several causes including priapism. There may be relative delay in sexual maturation in young adolescents with SCD, in up to 24%[45],[46] compared to persons without the disease. In females, menses could be delayed but menstrual flow may be normal.[45],[47]
Pregnancy in SCD is considered a very high risk condition due to the development of conditions such as preeclampsia, stillbirth, preterm deliveries, and small-for-gestational-age newborns. Ultrasonography is the mainstay for the diagnosis and useful in the early detection of most obstetrics conditions and complications.[47] However, accessing expert imaging care is limited as the number of subspecialty sonographers and sonologists within the region are few and only in tertiary centers.
| Major Imaging Challenges/Limitations in Management of Sickle Cell Disease | | |
SCD is recognized as one of the most common cause of morbidity and mortality among adolescent worldwide.[48] Although the recent advances in its management, have result in better outcomes; however, a lot still remains to be put in place and into consideration to reduce mortality. In resource-poor countries, basic facilities for the diagnosis and management are lacking, systemic screening is not a common exercise and diagnosis is commonly made late. Common morbidities associated with SCD are often not managed properly due to lack of proper infrastructure, expertise, economic burdens, and inadequate laboratory facilities. There is a need to develop tailored guidelines in the radiological management and follow up of SCD patients in major public practice[3],[48] Ultrasonography is readily available, relatively cheap, safe, with no radiation hazards, and does not require much expertise to interpret.[49] Many of the morbid changes during crises and chronic pathologies can be more easily, safely, and cost-effectively assessed by ultrasonography.[50] Mobile operated units can easily be used in a remote environment, thus removing the need to transport these very ill children through long distances and addressing the problem supply in these environments.[49],[50] There is also an added advantage of telesonography as the images acquired in the remote centers can be shared with the radiologist in the cities but that is not the case in the most part of sub-Saharan Africa. Lack of improved trained clinician insight into the current trend of SCD management.[51],[52],[53]
Present need should be centered around provision of good road/transport facility to inaccessible areas, proper financial, and technical availability of radiological equipment which usually preclude the proper diagnosis of SCD in most prevalent areas.[51],[54] Lack of standard equipment, maintenance culture, and training of adequate workforce limits the management of SCD in most prevalent areas.[52],[54]
Infrastructure
The effective management of SCD and its complications invariably depends on the availability of functional radiological facilities. The absence of most imaging modalities in most of these health facilities in the developing countries is a major setback to the care of these patients. Where available, power outages and inadequate water supply usually hinder the use of this equipment and their life span.[55],[56]
Battery operated mobile X-ray machines and digitally obtained X-ray films are yet to be accessible in the many parts of the developing world where the majority of people with SCD are located.[48],[55],[56] This then means that patients who require regular X-rays during a crisis are put through the added stress of being transported to bigger centres where these facilities are available.
Competence and capacity
Manpower development is crucial to quality health-care delivery. It is required to be a continuous process to effectively deal with the constantly evolving health-care needs of the people. Most radiologists and radiographers reside in the urban areas and very few if any, practice in the rural communities where the majority of these patients reside.[49],[50],[57] Emphasis should be laid on the in-house training of nurses and midwives who practice in the rural areas to identify sickle cell complications and refer promptly. Improved clinician insight to the management of the disease will herald management of the disease.[58] Genetic counseling in the rural areas is advocated. Private partnership between potential stakeholders and design sustainable financing scheme with availability of standard health care in rural area is needed.[58],[59]
One of the limitations of this work, was finding citations and having access to nononline materials and articles on SCD published in Africa as most of the African papers do not have on-line platforms
| Conclusion | | |
There is a large population of SCD patients in sub-Saharan Africa and with the improvements in care these individual are tending to live longer, which result in a greater incidence of chronic complications in them. Repeated and multiple radiological investigation using of radiation may be counterproductive in their care. Emphasis should be placed on the use of ultrasonography, Transcranial Doppler scan, Echocardiography, and MRI. Leveraging on the capacity of the private sector through Public-Private Partnership Programs could contribute in equipping hospitals and health institutions with the needed capital intensive radiological equipment to ease access to radiological services. Training of nurses and midwives on the use of mobile ultrasound units for identifying sickle cell complications in rural areas is imperative. Furthermore, the application of teleradiology technologies would greatly transform the landscape of imaging SCD in sub-Saharan Africa once the power and internet connectivity problems are addressed sufficiently.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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