Clinical manifestations of Sickle cell Disease in Children

Dr. Vinit Warthe M.D.(Pediatrics)

Assistant Professor, Dept. of Pediatrics, GMC Akola

Signs and Symptoms

Individual signs and symptoms varies. Some have mild symptoms, others have very severe symptoms and may be hospitalized for treatment 1st symptom: dactylitis and fever (6 m-2 years) Anemia: Fatigue (tiredness), pale skin and nail beds, jaundice, and shortness of breath Pain (Sickle Cell Crisis): Sudden episode of pain throughout the body. Common sites: bones, abdomen, and joints. Lack of blood flow can cause pain and organ damage.

Severity of SCD varies widely between patients

Pain ACS CVA Moderate forms Asymptomatic patients Severe forms

Penicillin, folic acid, hydration

Hydroxyurea Chronic transfusion Bone marrow transplantation
ACS = acute chest syndrome; CVA = cerebrovascular accident.

In India
Painful crisis is the commonest presentation followed by anaemia. Persistent and gross splenic enlargement are peculiarities of Indian Sickle Cell Disease patients.

EMERGENCIES

Emergencies
Fever/infection Severe Pain Acute chest syndrome Priapism Stroke Splenic sequestration

PAIN

Pain
The cardinal clinical feature of sickle cell anemia is pain from vaso-occlusive episode. The pain is characterized as unremitting discomfort that may occur in any part of the body, but most often occurs in the chest, abdomen, or extremities. These painful episodes are often abrupt and can disrupt daily life activities and cause anguish for children and their families. A patient with sickle cell anemia usually has approximately 1 painful episode per yr that requires medical attention.

Summary of the Chronology of Pain in Children with Sickle Cell Disease

PHASE PAIN CHARACTERISTICS SUGGESTED COMFORT measures used No comfort measures are used.

1 (Baseline)

No vaso-occlusive pain. Pain or complications may be present, such as that connected with avascular necrosis of the hip. No vaso-occlusive pain. Pain or complications may be present, and prodromal signs of an impending vaso-occlusive episode may appear, e.g.,yellow eyes and/or fatigue.

2 (Prepain)

Comfort measures are used. Caregivers may encourage the child to increase fluids.

3 (Pain start point)

First signs of vaso-occlusive pain appear, usually in mild form.

A mild oral analgesic is often given and fluids are increased. The child usually maintains normal activities

Summary of the Chronology of Pain in Children with Sickle Cell Disease

PHASE 4 (Pain acceleration) PAIN CHARACTERISTICS Intensity of pain increases from mild to moderate. Some children may skip this level or move quickly from phase 3 to phase 5. SUGGESTED COMFORT measures used Stronger oral analgesics are given. Rubbing, heat, or other activities are often used. Child usually stays in school until the pain becomes more severe, then stays home and limits activities. The child is usually in bed. Oral analgesics are given around the clock at home. A combination of comfort measures is used.

5 (Peak pain experience)

Pain accelerates to high moderate or severe levels and plateaus. Pain may remain elevated for an extended period. The child's appearance, behaviour, and mood are significantly different from normal.

Summary of the Chronology of Pain in Children with Sickle Cell Disease

PHASE 6 (Pain decrease start point) PAIN CHARACTERISTICS Pain finally begins to decrease in intensity from the peak pain level. SUGGESTED COMFORT measures used Family caregivers again become active in comforting the child, but not as intensely as during phases 4 and 5. Health care providers begin to wean the child from the IV analgesic. Oral opioids are given, and discharge planning is started. Children may be discharged before they are pain-free The child may receive oral analgesics.

7 (Steady pain decline)

Pain decreases more rapidly and becomes more tolerable for the child. The child and family are more relaxed.

8 (Pain resolution)

Pain intensity is at a tolerable level, and discharge is imminent. The child looks and acts like his or her normal self. Mood improves.

VASO-OCCLUSIVE CRISIS

Vaso-occlusive Events (Pain Crisis)

Precipitating factors Perceived factors
Hypoxia Acidosis Fever Infection Dehydration Exposure to cold
Exposure to cold Emotional stress Physical exertion Not identified

Sergeant, G. et al., Brit J. Haemat 1994: 87;586.

Sites of vaso-occlusive pain

Site Frequency Bilateral

Lumbar spine Abdominal pain Femur Knees Sternum Ribs Shoulder Elbows Tibia/fibula Humerus Thoracic spine Hips All over

49% 30% 21% 18% 18% 18% 17% 15% 12% 12% 11% 1%

32% 28% 68% 47% 53% 45% 57% 44%

48%

Hand Foot Syndrome - Dactylitis

Early complication of sickle cell disease Highest incidence 6 months to 2 years Painful swelling of hands and feet Treatment involves fluids and pain medication Fevers treated as medical emergency

Acute Chest Syndrome

A leading cause of death in sickle cell disease

Clinically: Acute onset of fever, respiratory symptoms, new infiltrate on chest x-ray Causes
Infection Fat emboli Lung infarct

Since you cannot distinguish between acute chest syndrome and pneumonia clinically there is no change in treatment.

Splenic Sequestration
Sudden trapping of blood within the spleen Usually occurs in infants under 2 years of age with SS as early as 5 week of age Spleen enlarged on physical exam, may not be associated with fever, pain, respiratory, or other symptoms Circulatory collapse and death can occur in less than thirty minutes Recurrence very common (50%) Associated with high mortality (20%)

Priapism
Commonly occurs in children and adolescents, an involuntary penile erection lasting for more than 30 minutes

Treatment is difficult
Opioid pain medication Intravenous fluids Aspiration and irrigation of the corpus cavernosum Surgery Blood Transfusions

Impotence with severe disease or recurrent episodes

Urethra

Corpus cavernosum

Neurologic Complications
Among children with sickle cell anaemia, approximately 11% and 20% will have either overt or silent strokes, respectively, before their 18th birthday. Functional definition is the presence of a focal neurologic deficit that lasts >24 hr and/or a lesion on the T2 weighted MRI of the brain indicative of a cerebral infarct and corresponding with the focal neurologic deficit. A silent stroke is the absence of a focal neurologic deficit lasting >24 hr in the presence of a lesion on T2 weighted MRI indicative of a cerebral infarct.

 Other neurologic complications include headaches that may or may not be related to sickle cell anaemia, seizures, cerebral venous thrombosis, and reversible posterior leukoencephalopathy syndrome (RPLS).

INFECTIONS

Infections
Functional asplenia by age of 5 years, as early as 6 months. Deficiency of alternative complement pathway. Regardless of age all patients with SCD are at increased risk of infection and death from bacterial infection particularly encasulated organism eg. Streptococcus pneumoniae and H. influenzae. Human parvovirus B19 infection limits the production of reticulocytes.

Indications for admission in febrile child with SCD

Fever > 38.5 C (101F) is an EMERGENCY . Seriously ill appearance Hypotension (systolic blood pressure of <70 mm Hg at 1 year of age or <70 mm Hg + 2 the age in year for older children) Poor perfusion (capillary refill time > 4 sec) Temperature > 40.0C (104F) A corrected white cell count >30,000 mm3 or <500 mm3 Platelet count <100,000 mm3 History of pneumococcal sepsis Severe pain

RENAL DISEASE

Renal Disease
Renal findings
Decreased ability to concentrate urine Decreased ability to excrete potassium Inability to lower urine pH normally Hematuria / papillary necrosis

Risk factors for progressive renal failure

Anemia, proteinuria, hematuria.

 Renal disease in patients with sickle cell anaemia is a major comorbid condition that can lead to premature death. Seven sickle cell anaemia nephropathies have been identified: (1) gross haematuria, (2) papillary necrosis, (3) nephrotic syndrome, (4) renal infarction, (5) hyposthenuria, (6) pyelonephritis, and (7) renal medullary carcinoma.

APLASTIC CRISIS

Aplastic Crisis
Bone marrow stops producing RBCs Seen in patients with infection or folate deficiency Usually self-limited and may follow viral infections( parvovirus B19 )

BONE INVOLEMENT

Bone Involvement
Avascular necrosis of hips and shoulders
Index of suspicion
Persistent hip or shoulder pain Plain film or MRI

Screening AVN
Avascular Necrosis
Hip Films Hip MRI Grading of AVN
Grade I: MRI Grade II: Film/MRI Grade III: Film Grade IV: Film Grade V: Film

No grade for AVN of the shoulder

CHRONIC COMPLICATIOS

Chronic Complications
Anemia/Jaundice Brain Damage/Stroke Kidney failure Decreased lung function Eye disease (bleeding, retinal detachment) Leg ulcers Chronic pain management Gall stones

Anemia Jaundice
Common and starting in the first year of life Decreased lifespan of sickle red cells
Hemolysis Anemia Hyperbilirubinemia Reticulocytosis

Leg Ulcers
Occurs in hemoglobin SS patients Predominantly males
Incidence increased with Age Decreased hemoglobin Incidence decreased with alpha thalassemia

Recurrence rate is ~ 75%

Chronic Pain
Pain lasting >3 to 6 months
Patients should receive comprehensive psychologic and clinical assessment

SCD and Surgery

Surgical preparation for children with sickle cell anaemia requires a coordinated effort between the haematologist, surgeon, and primary care provider. ACS and pain are the 2 most common postoperative complications, with the former being a significant risk factor for postoperative death. Blood transfusion before surgery for children with sickle cell anaemia designed to raise the haemoglobin level preoperatively to 10.0 g/dL is desirable.

Indian Sickle Cell Disease in comparison to other populations?

No painful crisis Pain rate AVN Cholelithiasis Hb Mortality Leg Ulcer Priapism

India 13.4% 1.30 18.3% 27% 8.2g% 4.7% 1.9% 0.3%

CSSCD/Jamaica 39% 0.8 (per year) 4-19% 31% 8g% 2.6% 10-75% 2-6%

Reference: PlattOSetal.NEnglJMed.1991;325:1116. LeikinSLetal.Pediatrics.1989Sep;84(3):500508. SergeantGRetalSickleCellDisease.OxfordUniversityPress,3rded,200 1:240-280.