Babies can`t say they experience a pain and run the risk of many diseases. If you notice that your baby has some strange symptoms and you are not sure if this can mean a disease. Don`t wait to ask our pediatrician for advice if you think that your baby has some health problems. The treatment of a baby should be done in time.
Sickle cell disease is an inherited disorder of hemoglobin synthesis. The resulting abnormality produces a normocytic, hemolytic anemia with multiple diversely shaped RBCs that are susceptible to morphologically changing into a sickle shape. The sickle cells produce thrombosis and obstruction in small vessels, leading to ischemia and necrosis of distal tissue.
Pathophysiology:
Sickle cell disease results from a single amino acid substitution (valine for glutamate) in position 6 of the beta-globin chain of hemoglobin. This genetic alteration yields an unstable RBC with a shortened survival that under stress becomes sickle shaped.
Frequency:
In the US : Approximately 8-10% of African Americans carry the gene (S) in the population. Homozygous (SS) sickle disease occurs in about 0.15% of African American newborns.
Internationally: Other sickle syndromes also may be present in individuals from India , the Middle East, and the Mediterranean .
Mortality/Morbidity: The clinical course of sickle cell disease is one of chronic illness precipitated by multiple acute exacerbations that can become life threatening at any time.
Today, approximately 50% of patients survive beyond the fifth decade.
A third of deaths during an acute crisis occur in patients who are clinically free of organ failure.
Infection is the leading cause of death in affected children aged 1-3 years.
Strokes and trauma are the leading causes of death in patients aged 10-20 years. Children in this age range also succumb to acute chest syndrome, splenic sequestration crisis, and aplastic crisis.
Race: Sickle hemoglobinopathy syndromes are a genetically predetermined group of hemolytic anemias found predominantly in individuals of Central African descent. In Latin America, high frequencies are observed in the Caribbean , Guyanese, Panamanian, and Brazilian populations.
Age:
Hematologic changes indicative of the disorder become evident as early as age 10 weeks, although symptoms usually are delayed until age 6-12 months because of high levels of circulating fetal hemoglobin. Beta-chain (adult) hemoglobulin usually is not prominent until age 3 months.
After infancy, erythrocytes of patients with sickle cell anemia contain approximately 90% hemoglobin S (HbS), 2-10% hemoglobin F (HbF), a normal amount of minor fraction of adult hemoglobin (HbA2), and no hemoglobin A (HbA).
History:
Patients with sickle cell disease, at some point in their lifetime, may experience exacerbations in their clinical course. Children at different ages are susceptible to differing types of crisis, which each may occur in a given child at some point.
A painful vaso-occlusive crisis is the most frequent clinical symptom of sickle cell disease.
In infants, painful symmetrical swelling of the hands and feet (dactylitis or hand-foot syndrome) caused by infarctions of the small bones may be the initial manifestation of sickle cell anemia.
Most bony vaso-occlusive events occur primarily within the bone marrow cavity. Most are multifocal and associated with mild tenderness and localized edema.
As the child matures, these painful episodes usually occur in the joints, especially the hips, knees, chest wall, and back. Document the frequency, precipitants, and similarity of painful episodes on each visit to exclude more serious causes such as infection.
Promptly evaluate older patients who complain of chest pain, cough, dyspnea, or tachypnea to exclude acute chest syndrome.
This acute febrile pneumonic process is associated with new infiltrates on chest radiographs. The radiographic findings may be preceded by chest pain, or they may occur in conjunction with the onset of pain. Although initial chest radiograph findings may be normal, subsequent radiographs will reveal an infiltrate, which may rapidly extend to involve one or more lobes as well as the pleura.
The etiology may be infectious (eg, pneumonia), vaso-occlusive, or both. This syndrome often results in hypoxia and, occasionally, death.
Abdominal pain may be present, often as excruciating pain with diffuse tenderness, distension, and abdominal wall muscular rigidity.
The pain often is caused by small infarcts of the mesentery and viscera, usually without peritoneal signs.
A thorough history, obtained from the patient or parents, is crucial because recognition of the nature of the pain by either the patient or parents helps distinguish vaso-occlusive pain from other etiologies such as cholecystitis, perforated viscus, or appendicitis.
Sequestration crisis is a distinct form of acute hypersplenism unique to infants and young children.
Vascular occlusion occurs within the splenic sinusoids, resulting in large volumes of blood trapped within the substance of the spleen.
If these events occur gradually, the patient may present with progressive pallor, fatigue, left-sided abdominal pain, and increasing splenomegaly.
This event may occur before or after auto-infarction of the spleen transpires. If splenic sequestration occurs more abruptly, patients may present in extremis, manifesting severe hypovolemic shock.
If vascular occlusion occurs in large or small cerebral vessels, a neurological event may occur. Patients may experience gait disturbances, hemipareses, paresthesias, aphasias, alterations in consciousness, or seizures. Recent studies have shown that MRI findings or high flow values on transcranial Doppler ultrasound examinations of "silent" lesions are associated with a high risk of stroke.
Often, the older male patient may present with priapism (ie, a prolonged, acute, painful erection due to venous occlusion). Priapism may recur often.
Infants and children are susceptible to an aplastic anemia crisis.
During these episodes, the degree of anemia worsens, and jaundice decreases due to a profound reticulocytopenia, resulting in no erythrocyte precursors in the bone marrow.
The patient appears acutely ill, tachycardic, and pale, yet nonicteric. Occasionally, recovery occurs in several days. These symptoms usually are due to an infection by the parvovirus B19 prototype.
Patients with sickle trait have erythrocytes that contain only 30-40% HbS. Heterozygosity for the sickle gene has a benign clinical course. Sickling does not occur under physiologic conditions.
Rarely, patients may experience hypoxia or shock when flying at high altitudes in an unpressurized aircraft, causing vaso-occlusive phenomena.
Spontaneous hematuria, usually from the left kidney, has also occurred in patients with the sickle trait as well. The bleeding most often is mild but may often necessitate a blood transfusion.
Patients with sickle cell disease and trait often have a high incidence of enuresis because their bodies are unable to concentrate the urine appropriately.
Physical:
In evaluating the patient with sickle cell disease, it is important to consider the pattern of past events, baseline laboratory values, and current status of disease.
Patients most often present with pain complaints; but younger children, who cannot communicate well, must be observed for irritability, poor feeding, or fussiness.
Vital signs must be evaluated for fever, tachycardia, and tachypnea, which may be present due to pain or infection.
As the patient matures, he or she may exhibit icteric sclera and pallor of the conjunctiva and mucous membranes. Funduscopic examination may reveal retinopathy.
Dental malocclusion may be present secondary to maxillary hyperplasia due to expansion of the bone marrow space.
Perform a cardiac examination to determine presence of a murmur.
Breath sounds may elicit rales or may be decreased bilaterally due to extensive pulmonary consolidation. Infarction is difficult to distinguish from pneumonia.
The presence of active bowel sounds, absence of emesis, and patient recognition of pain helps distinguish vaso-occlusive pain from other etiologies.
The abdomen of the young child may reveal splenomegaly if sequestration is occurring. Otherwise, the spleen recedes and should not be palpable by age 3-4 years as a result of auto-infarction.
Patients with milder variants of sickle disease may have persistent splenomegaly into adulthood.
Note the size of the liver and conduct an examination for evidence of gallstones, since these can form in patients as young as age 3 years.
Inspect genitalia for priapism if the patient complains of pain.
The most dramatic physical finding often is observed in the extremities.
The younger infant may have recurrent edema of the dorsum of the hands and feet.
Infarction of the cortex of the long bones may lead to prominent signs of local inflammation, including tenderness, edema, and erythema.
As the child grows, repetitive infarctions in the joints of large and small bones may produce abnormally angled digits and enlarged, malformed, and, occasionally, frozen joints, particularly at the knees and ankles.
Chronic leg ulcers are also common in the adolescent patient.
Thoroughly examine any patient who complains of mental status changes, paresis, or other symptoms compatible with a stroke because strokes are prominent in this age group.
By mid childhood, most patients are noted to be underweight compared to children of the same age and height.
Causes:
The sickling process that frequently occurs with sickle cell anemia may be precipitated by multiple factors.
A crisis may be induced by local tissue hypoxia, dehydration secondary to a viral illness, or nausea and vomiting, all of which lead to hypertonicity of the plasma.
Any process that can lead to acidosis, such as infection or extreme dehydration, can cause sickling.
More benign factors and environmental changes, such as fatigue, exposure to cold, and psychosocial stress, can elicit the sickling process that prompts a crisis.
Lab Studies:
Newborn screening for sickle hemoglobinopathies is currently mandatory in 43 states. Most patients presenting to the ED, therefore, have a known diagnosis.
Specific diagnosis is confirmed with hemoglobin electrophoresis performed in specialized reference laboratories.
The patient with homozygous sickle cell disease normally has a hemoglobin level between 5-9 g/dL, with a hematocrit level decreased to 17-29%.
The total leukocyte count is elevated to 12,000-20,000 with a predominance of neutrophils.
The platelet count is increased, and the sedimentation rate is low.
The reticulocyte count usually is elevated but may be variable, depending on the extent of baseline hemolysis.
Examination of the peripheral blood smear demonstrates target cells, elongated cells, and characteristic sickle erythrocytes.
The hemoglobin solubility test result is positive, but it does not distinguish between sickle cell disease and sickle cell trait.
Perform the following laboratory studies for a patient younger than 5 years who presents with a temperature higher than 38.5°C:
Liver enzymes
Electrolytes
Complete blood count (CBC) with differential
Reticulocyte count
Urinalysis
Blood, urine, and throat cultures
During bacterial infection, elevations of the absolute band count to more than 1000/mm 3 are common compared to moderate elevations during the painful crisis.
Laboratory studies for the patient presenting with a painful crisis should routinely include a CBC and reticulocyte count for comparison to previous episodes.
During the vaso-occlusive crisis, the reticulocyte count may rise to 30%.
Obtain a blood gas analysis if pulmonary symptoms exist.
Imaging Studies:
The patient complaining of cough or chest pain warrants a prompt chest x-ray to exclude pneumonia versus acute chest syndrome.
If an ill-appearing patient presents with pain in the extremities that differs from the usual painful episodes, a radiograph and/or MRI of the affected extremity is necessary to exclude osteomyelitis.
Evaluate any new onset of neurological changes with a head CT scan or MRI of the brain to exclude a stroke.
Other Tests:
Use a pulse oximeter on the patient complaining of chest pain to assess hypoxia related to acute chest syndrome.
Procedures:
Consider a lumbar puncture in the pediatric patient with altered mental status, meningeal signs, and fever to exclude meningitis. Also, perform this procedure if a subarachnoid hemorrhage is suspected after a head CT scan reveals no evidence of increased intracranial pressure or mass lesion.
Emergency Department Care: The emergency physician must weigh all etiologies of possible precipitants when evaluating the presumed painful crisis.
In the ED, the mainstay of therapy for vaso-occlusive crises is hydration and analgesia.
Hydration should replace ongoing losses and meet maintenance needs as well as correct preexisting deficits. Administer IV isotonic sodium chloride solution at a rate of 1-1.5 times the maintenance rate if oral hydration cannot be sustained.
Base analgesia on the severity of symptoms and the response to therapy at home prior to ED presentation. Mild pain can be controlled by ibuprofen, acetaminophen (with or without codeine), or ketorolac. If more severe pain exists, patients can be given morphine, meperidine, hydromorphone, or oxycodone. Some pediatric patients have actually benefited from high-dose IV methylprednisolone.
Patients presenting with variable signs of respiratory distress suggestive of acute chest syndrome should have early and aggressive therapy. Fluids should be monitored judiciously to avoid pulmonary edema. An incentive spirometer may prove helpful.
Direct antibiotic therapy at covering Pneumococcus species, Haemophilus influenzae type b, and Mycoplasma pneumoniae with cefuroxime, ceftriaxone, and erythromycin, respectively.
Provide oxygen and respiratory support to relieve hypoxemia.
When respiratory distress is moderate to severe, especially in conjunction with progressive anemia, transfusion therapy is appropriate to increase the oxygen-carrying capacity and to decrease the percentage of sickle hemoglobin, thereby diminishing the tendency toward further intrapulmonary vaso-occlusion.
For the patient with acute splenic sequestration, therapy is directed primarily toward the repletion of intravascular volume with appropriate isotonic fluids. Severe anemia requires transfusion therapy. Spleen size tends to return to the baseline state with an associated increase in hemoglobin concentration over several days.
Patients who are suspected of having a stroke require immediate exchange transfusion sufficient to decrease the percent of sickle hemoglobin to less than approximately 25%. A single volume-exchange transfusion using packed red blood cells (PRBCs) reconstituted with fresh frozen plasma (FFP) to a hematocrit level of approximately 40% is an appropriate emergency measure. If the patient has large vessel occlusive disease, long-term transfusion therapy is required to prevent recurrent stroke. If signs of increased intracranial pressure develop, hyperventilation is warranted as well as anticonvulsants for seizure activity.
Treat priapism with analgesia, hydration, and transfusion therapy sufficient to decrease the sickle hemoglobin level to less than 30%. The choice between a simple RBC transfusion and exchange transfusion depends upon the initial hematocrit level. This level should not be raised above 35% to avoid hyperviscosity and an increased tendency toward sickling.
Transfusions may be necessary for the patient with aplastic crisis, although spontaneous resolution within 5-10 days generally occurs. Caution should be exercised to isolate the child at the time of aplasia, because the human parvovirus B19 is responsible for more than 80% of crises and is very contagious. The patient should be isolated from all vulnerable groups such as immunocompromised children, children with hemolytic anemias, and pregnant women.
Consultations:
Always call the patient's primary pediatrician if the patient presents with severe complications of his or her sickle cell disease.
Consult a pediatric hematologist for any patient requiring an exchange transfusion as therapy for their disease process.
If the patient presents with neurological deficits, a pediatric neurologist may be consulted after the initial evaluation and workup.
Multiple pediatric tertiary care centers equipped with specialized sickle cell services have emerged over the last few years. Children with sickle cell disease who become acutely ill may best be served by these facilities.
Further Inpatient Care:
The primary care team should reevaluate the medication plan every day for patients admitted for pain control. Taper IV drug doses when acute pain subsides, but do not change the dosing interval. Once the patient tolerates a 50% decrease, consider oral analgesics and discontinue parenteral therapy.
If patients were started on IV antibiotics in the ED, continue therapy until appropriate culture results suggest a possible change in antibiotic choice.
Patients who required emergent transfusion should have their hematocrit levels checked to ensure adequacy of the transfusion amount.
The primary care team should review the patient's immunization schedule and prophylactic antibiotic use.
Further Outpatient Care:
The patient's pediatrician should examine the patient every 3-4 months to review acute illnesses and possible precipitants, crisis frequencies, hospitalizations, and blood transfusion requirements. The patient's CBC, reticulocyte count, liver function, and renal function also should be monitored during these visits.
In addition to the currently recommended American Academy of Pediatrics' immunization schedule, pediatric sickle cell patients require pneumococcal, meningococcal, and influenzal vaccines.
The pneumococcal vaccine should be administered at age 2 years with subsequent boosters determined by the patient's hematologist.
Meningococcal prophylaxis is administered as a single quadrivalent vaccine when the child is older than 2 years.
The influenza vaccine is administered annually.
In/Out Patient Meds:
Penicillin prophylaxis for encapsulated organisms is instituted as soon as the diagnosis of sickle cell disease is established, preferably by age 2 months.
An initial dose of 125 mg of penicillin V or G bid is recommended.
The dose is increased to 250 mg bid by age 3 years.
If the patient is allergic to penicillin, erythromycin may be substituted.
The pediatrician initiates folic acid therapy.
For patients younger than 6 months, the usual dose is 0.1 mg/d.
For infants aged 6 months to 1 year, the usual dose is 0.25 mg/d.
For children aged 1-2 years, the usual dose is 0.5 mg/d.
For patients older than 2 years, the dose is 1 mg/d.
Hydroxyurea, which increases fetal hemoglobin production, reduces the incidence of pain episodes and acute chest syndromes in some patients who are severely affected. The patient's hematologist determines doses based on frequent laboratory determinations.
Complications:
The patient with sickle cell disease is susceptible to a multitude of complications during this life-long disease. Patients may experience any or all entities at some time.
Susceptibility to infection, mainly to encapsulated organisms secondary to splenic dysfunction, begins in infants aged 4-6 months. Overwhelming sepsis can occur at any time.
Osteomyelitis, particularly due to Salmonella and Staphylococcus species, occurs more commonly in patients with sickle cell disease than in the general population.
Avascular necrosis of the femoral head occurs in 10% of patients and may require hip arthroplasty.
The severity of anemia may induce high output failure, cardiomegaly, and flow murmurs.
Retinopathy, secondary to sequestration of blood in the conjunctival vessels, is marked by dilated and tortuous retinal vessels, microaneurysms, and retinal hemorrhage.
Patients who sustain trauma to the eye resulting in hyphema are at risk for glaucoma due to a physical obstruction of the trabecular meshwork by sickled blood inside the anterior chamber.
Cholelithiasis, particularly in patients older than 6 years, can occur due to chronic hemolysis.
Irreversible renal damage causing hyposthenuria is present in almost all patients by age 3 years and may progress to renal failure requiring transplant.
Hematuria, as a result of sickling in the vas recta or renal papillary necrosis, is common. Refractory hematuria may require hospitalization for bedrest, hydration, and a trial of epsilon aminocaproic acid (2-8 g/d PO). Patients with the sickle cell trait later may develop hyposthenuria or hematuria.
Prognosis:
At any time, the patient with sickle cell disease can be faced with a myriad of potentially life-threatening and unpredictable complications.
Most patients and families with a good understanding of the disease process have good outcomes due to compliance with medication regimes and an overall healthy attitude that promotes well-being.
Patient Education:
Patient's families should have genetic counseling and education regarding clinical manifestations associated with the disorder and its complications.
Reinforcement should occur incrementally during the course of ongoing care.
Families should be educated on the importance of hydration, diet, outpatient medications, and immunization protocol.
Patients should be instructed on proper splenic palpation and observation of pallor, jaundice, and fever.
Families should be encouraged to contact community sickle cell agencies for follow-up information, new drug protocols, and psychosocial support. Families should also follow the advances of gene therapy, bone marrow transplantation, and the usage of cord blood stem cells.
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