XXXX UNIVERSITY OF HEALTH AND ALLIED SCIENCES

LOGOSCHOOL OF MEDICINE

DEPARTMENT OF PEDIATRICS AND CHILD HEALTH

CASE REPORT

SCA WITH AVASCULAR NECROSIS OF THE HIP

LUTFI ABDALLAH

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TABLE OF CONTENTS;

1. Table of contents ………………..……………………………………………...2

2. Acknowledgement …………………………………………………………...…3

3. Abbreviations …………..……,……………………………………………….....4

4. Executive Summary ………………..…………………………………………...5

5. Introduction and Literature review ………………………………….…..5

6. Case presentation ………………………………………………………………….9

7. Discussion ………………………………………………………………..………...13

8. Conclusion and Recommendations ……….………………………..……14

9. References ………..………………………………………………..………...…….15

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ACKNOWLEDGEMENT

The development of this case report has not been an easy task but its success has been made a reality come true due to the help rendered to me by different parties.

I would like to extend my special gratification to my supervisor XXX for having accepted to supervise me in the course of the development of this report. To her I say Thank you a lot for all the support. I attribute my thanks also to the members of the department of Pediatrics and Child Health for having offered me the offer of developing my own case report which without them, I doubt whether I would have ever had this chance of doing my own personal work.

I cannot forget extending my sincere gratitude to my patient and his parents for having consented to participate in this report of which without them, this report would have been just a dream.

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LIST OF ABBREVIATIONS;

ANC – Antenatal Clinic

AVN – Avascular Necrosis

EPI – Extended Program of Immunization

GA – Gestation Age

ROM – Range of Motion

HIV – Human Immunodeficiency Virus

HB – Hemoglobin

HPLC – High-performance liquid chromatography

VDRL – Venereal Disease Research Laboratory

MUAC – Mid Upper Arm Circumference

LFA – Length for Age

WFA – Weight for Age

LFW – Length for Weight

SCD – Sickle Cell Disease

SCA – Sickle Cell Anemia

TCD – Transcranial Doppler

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SUMMARY.

Z A, 12 years old female child from Tanga, was admitted at MNH ward B with chief complaints of left hip & knee joint pain.

On examination she was Alert, afebrile (T 36.5˚ C), some palmar pallor, not jaundiced, spleen and liver not palpable, the joints are not swollen, of the same warmth as other part of the body and not tender by touching. The left and knee joints can’t be moved in either direction because of the unbearable pain. Diagnosis was SCD with severe avascular necrosis of left hip and knee joint secondary to vaso-occlusive crisis.

INTRODUCTION AND LITERATURE REVIEW

Sickle cell disease is the most common type of hemoglobinopathies. Mode of inheritance is autosomal co-dominant. It ranks the 9 th of the hospital Admission at MNH pediatrics general wards. It is a result of substitution of glutamic acid in the 6th amino acid position of the beta polypeptide chain with either valine (sickle cell anemia) or with lysine (sickle cell trait).[1]

Sickle cell anemia is a homozygous state for the sickle cell gene (HbSS) while sickle cell trait is a heterozygous carrier state for the sickle cell trait (HbAS). Sickle cell anemia (SCA) is a hemolytic anemia characterized by abnormally shaped (sickled) red blood cells which are destroyed and removed from the circulation at an increase rate. The sickle RBCs also can cause vascular occlusion and lead to tissue ischemia and infarction. The abnormal sickle cell hemoglobin (HbS) when deoxygenated, becomes insoluble, and forms aggregates which deform the RBCs and impair the flow through blood vessels. The red blood cells life span is reduced from 120 to about 30 to 40 days.[1]

In Africa the incidence of the disease is highest in West Africa (30% to 40%) and lowest in South Africa (1%). The gene is also prevalent in certain people of Mediterranean, Saudi Arabia and Asia. The geographical distribution tends to go parallel to that of falciparum malaria. Other rare types of hemoglobinopathies are Hb E, C and thalasemia.

The greatest burden of sickle cell anemia (SCA) is in sub-Saharan Africa (SSA), where 75% of the 300,000 global births of affected children live and estimates suggest that 50–80% of these patients will die before adulthood.[2] The frequency of the sickle heterozygous carrier state (AS) in Tanzania is 13% with an estimated annual births of 8,000 homozygous SS children.[3]

Clinical manifestation can be linked directly or indirectly with the tendency of deoxygenated HbS to polymerize. The symptoms and signs of sickle cell disease were related to hemolytic anemia and to tissue ischaemia caused by vaso-occlusive crisis.

Essential features for diagnosis are: -severe anemia with elevated reticulocyte count or jaundice, recurrent episodes of musculoskeletal or abdominal pain, splenomegally and overwhelming recurrent bacterial infection.[1]

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A child with sickle cell anemia is vulnerable to life-threatening infection by 4 months of age. By that time, splenic dysfunction is caused by sickling of the RBCs within the spleen, resulting in an inability to filter microorganisms from the bloodstream. Splenic dysfunction is followed eventually by splenic infarction, usually by 2 to 4 years of age. In the absence of normal splenic function, the patient is susceptible to overwhelming infection by encapsulated organisms, especially S. pneumoniae and H. influenzae. The hallmark of infection is fever.[1]

Vaso-occlusive crisis was found to be precipitated by Infections, Low oxygen saturation, Dehydration, Acidosis, Extreme physical exercise, Physical or psychologic stress, Alcohol, Pregnancy, Cold weather. [4,5]

Acute complications include; Chronic hemolytic anemia, Dactylitis (hand-foot

syndrome) where there is painful non-erythematous often-symmetrical swelling of the hands and feet, Fulminant bacterial infection in <5 years. Acute chest syndrome presenting with fever, tachypnoea and chest pain, Splenic sequestration syndrome presenting with severe anemia, massive splenomegally and death may occur due to hypovolemic shock, Painful crisis of joints of all four limbs and back, Acute central nervous system events following occlusion of intracranial vessels (seizures, hemiparesis, speech defect), Bone marrow infarction, chronic leg ulcers, priapism and Osteomylitis due to bacterial infection (Salmonella, Staphylococcus Aureus and Gram-negative enteric bacilli).[6]

Vaso-occlusive crises affect virtually all patients with sickle cell disease, often beginning in late infancy and recurring throughout life. The pathogenesis of the microvascular occlusion, the hallmark of the painful sickle cell crisis, is complex involving activation and adhesion of leucocytes, platelets and endothelial cells as well as haemoglobin S-containing erythrocytes[7]. While this process can occur in virtually any organ, it is particularly common in the bone marrow, resulting in bone marrow infarction typically in the medullary cavity or epiphyses[8,9] The reasons for the vulnerability of the bone marrow to microvascular occlusion are unclear but may be partly because of marrow hypercellularity leading to impaired blood flow and regional hypoxia [10].

Clinically, patients complain of intense pain localized to one or more areas of their skeleton. This may be accompanied by localized tenderness, swelling and erythema over the site of infarction; fever and leucocytosis are also common.[10] Most patients recover from vaso-occlusive crises with no further complications. However, when marrow infarction involves the epiphyses, this may give rise to joint effusions that are clinically similar to septic arthritis,[9,10] or where there is infarction of vertebral bone marrow, to collapse of the vertebrae with a typical ‘fish mouth’ appearance. [8] Osteonecrosis occurs when vaso-occlusion results in the infarction of the articular surfaces and heads of the long bones[10].

The prevalence of osteonecrosis in the epiphyses is 41% in adults and 27% in children with sickle cell disease using MRI [11], which is much higher frequency compared to the previously reported in studies based on plain X-rays where the prevalence was 9.8% of osteonecrosis of the femoral head in patients with sickle cell disease, with the highest frequency in adults, in those with homozygous sickle cell disease and in those with co-existing alpha-thalassaemia trait.[12] The difference in prevalence using radiologic investigation is because of the sensitivity, as the MRI can detect AVN at the early stages.

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The pathophysiology of osteonecrosis in sickle cell disease seems to differ from osteonecrosis because of other aetiologies. When MRI is used to quantify lesions in AVN of the femoral head, the lesions seen in sickle cell disease are larger than those seen in osteonecrosis because of other aetiologies [13]. Whereas in osteonecrosis not because of sickle cell disease, the localization and size of the lesions is directly related to the mechanical stresses on the femoral head, the larger size and wider distribution of the lesion in sickle cell disease point to the fact that a much larger variety of independent factors result in vascular occlusion in sickle arthropathy.The most common sites of osteonecrosis are the femoral heads followed by the head of the humerus, knee and small joints of the hands and feet [15,8]

The Ficat classification is used for AVN of the hip. and uses a combination on pain film, MRI and clinical features is as follows: Stage 0 (X-ray: normal, MRI: normal, clinical symptoms: nil); Stage I ( X-ray : normal or minor osteopaenia, MRI: oedema, bone scan: increased uptake, clinical symptoms: pain typically in the groin); stage II (X-ray: mixed osteopaena & / or sclerosis, MRI: geographic defect, bone scan: increased uptake, clinical symptoms: pain and stiffness); Stage III (X-ray: crescent sign & eventual cortical collapse, MRI: same as X-ray, clinical symptoms: pain and stiffness + or/ - radiation to knee and limp); stage IV (X-ray : end stage with evidence of secondary degenerative change, MRI : same as X-ray, clinical symptoms: pain and limp).[16]

Symptomatic patients complain of painful, limited motion of the affected joint, occasionally with pain at rest. Advanced disease may be easily diagnosed with plain radiographs, which show mottled attenuation of the epiphysis, subchondral lucent areas and flattening/collapse of the articular surfaces. This may be followed by narrowing of the joint space, articular sclerosis and osteophyte formation [8].

Early disease is best diagnosed by MRI, plain X-rays may not detect early disease [12,

15].Untreated, 87% of affected femoral heads will collapse within 5 years of diagnosis [17]

One of the most effective methods of preventing progression of joint damage is bed rest, in order to avoid weight bearing [17], however, this has such drastic implications for patients’ lives that it is usually an unacceptable option. In addition, the long-term symptomatic treatment is ineffective and the majority of joints require surgery for pain relief and functional improvement. Early disease may improve with coring and osteotomy [18], however, failure rates in some studies are as high as 50% at 5 years (19,20,13] and a randomized controlled trial is currently in progress to determine whether decompression coring procedures can prevent progression of AVN [21]. Late disease requires joint replacement.

Investigation include: CBC count and differential cell count, Hemoglobin electrophoresis, high-performance liquid chromatography (HPLC), Lactic dehydrogenase and haptoglobin, X-ray of the chest, bones and joints, TCD which detect abnormal blood flow velocity in the large intracranial vessels of the circle of Willis, CT- scan, MRI and Abdominal ultrasound. [1] In patients with chronic transfusion Serum ferritin, Hepatitis panel A, B and C, HIV status, Liver enzymes has to be part in diagnostic evaluation.[25]

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Oxygen therapy: Oxygen therapy is indicated for hypoxemia, tachycardia, and tachypnea. Oxygen therapy is provided to maintain oxygen saturation ≥ 94% (or enough to keep at baseline oxygen saturation percentage). Oxygen delivery has to be adjusted as needed for the patient’s comfort and cardiovascular stability. [25]

Blood transfusion: A hemoglobin value less than < 6–7g/dl and < 4–5g/dl is used as a guide for considering simple transfusion therapy in patients with Stroke/or Acute neurologic event and splenic sequestration respectively. The measurable goal is to achieve a level of hemoglobin S < 30% with hemoglobin of 10–12g/dl to patients with Stroke or/ Acute Neurologic event and not exceeding Hb of 8g/dl of Hb Splenic sequestration (autotransfusion can occur as the spleen decreases in size, resulting in a hemoglobin value higher than expected). Keeping the hemoglobin ≤ 12g/dl avoids complications of hyperviscosity. Patients are transfused to their baseline hemoglobin level since a higher hematocrit may make the blood more viscous and further increase sickling. It is also used when there is Aplastic crisis, Acute chest syndrome and priapism.[25]

Treatment of painful vaso-occlusive episodes includes the maintenance of adequate hydration (with avoidance of over hydration), correction of acidosis if present, administration of adequate analgesia. Morphine is considered the treatment of choice for moderate to severe pain in vaso-occlusive crises.[1,2]

Folic Acid is given to enhance production of red cells associated with hemolytic anaemia. Folate deficiency in sickle cell disease develops as the requirement for folic acid by an enhanced erythropoietic activity exceeds dietary intake. The Sickle cell patients with folate deficiency can impair erythropoiesis with a consequent worsening of the anaemia.[10]

Hydroxyurea increases the production of hemoglobin F and thereby reduces the severity of sickle cell disease by preventing the formation of hemoglobin S polymers.Hydroxyurea is initiated in a dosage of 500 mg per day. The dosage is increased to 1,000 mg per day after six to eight weeks, with the patient monitored for a decline in granulocyte or platelet counts. The maintenance dosage is between 1,000 and 2,000 mg per day, depending on the balance between hematologic toxicity and increases in hemoglobin F values. Blood counts should be followed every four to six weeks to detect longer term hematologic toxicities.[20]

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 12 hourly is recommended. The dose is increased to 250 mg 12 hourly by age 3 years. If the patient is allergic to penicillin, erythromycin may be substituted.[25]

Pneumococcal conjugate, Haemophilus influenzae and Hepatitis B vaccine should be administered to all children who have sickle cell disease and if splenectomy is planned, meningococcal vaccine has to be considered. [25]

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THE PATIENT .

Z.A 12 years old female child from Tanga, known sickler since 2009 when her father took her privately to India when she had yellowish discoloration of the eyes, abdominal distension and looks weak where she was diagnosed having Sickle cell. At the age of 3 years (year 2004) the child developed yellowish discoloration of the eyes, excessive crying of no specific period, refusal to eat and abdominal distension, the Hb was 3.8g/dl where she was transfused with Blood. In Tanga, 7 weeks before admission the child developed fever, cough and difficulty in breathing for 4 days where she was diagnosed with severe pneumonia, treated and discharged. One weeks later the child developed hip joint pain where she sought a medical advice where diclofenac was prescribed. At that time, she had a pelvis X-ray which was normal.

The child is not attending any sickle cell clinic, wasn’t in any medication and doesn’t have any document proving the illness claimed. She was admitted at MNH ward B with chief complaints of left hip & knee joint pain for 6 weeks before admission.

The pain was of gradual onset, wasn't proceeded by trauma. It started with a mild pain in the hip joint, aggravated by standing and walking and relieved by sitting/or lying and resting. After two weeks she was unable to move the hip joint. The knee joint started in the same manner 4 weeks before admission and attained the same state of pain?. The Pain was localized at the joints, and was so intense when she moves the joint and worsens at night when she failed to sleep.

The patient did not report numbness or unusual sensation on the skin (tingling, burning sensation) in the lower extremities. There is no bowel and bladder dysfunction. The patient did not complain of any night sweats, fever or chills.

Perinatal, Natal and Post Natal: Not extracted since father doesn't know

Immunization History: The father doesn’t know about the vaccines but he reported that his wife was attending clinic to the age of 15 months. The child has a BCG scar on the right shoulder.

Developmental milestone: The past developmental history was not extracted since the father doesn’t know. Child is in standard 6, plays with friends, can help home activities after school and during the weekend and take care of pets, able to handle many tasks on her own with little supervision. Can participate in sports with friends and can ride a bicycle, can draw, read and write but not do simple calculation such as 6 X 5

Family and Socio History: The only child to the mother. The father has 2 more wives of which the first wife had 1 daughter who died at labor at the age of 33 years, the second wife has 3 children who are well.Maternal side: No information about history of Sickle cell.Paternal side: No history of sickle cell anemia. The parents are not related by blood or by tribe.

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On Examination: -

She was Alert, Afebrile (36.5°C), some palmar pallor, wasted, not jaundiced, not cyanosed, no edema, no sign of respiratory distress.

She weighed 24kg, MUAC was 15.5cm, and Length was 138cm,W/L = -1SD to -2SD, W/A= -1SD to -2 SD and MUAC = Mean to -1SDHFA = -1SD to -2SD

Conclusion: moderate wasted and moderate underweight and moderately stunted.

Respiratory System Examination; The chest was symmetrical and moving with respiration. The RR was 28 breath/minute, the trachea was centrally located. The chest was resonant and normal breath sounds (Vesicular sounds) were heard with no added sounds i.e. the chest was clear. The vocal resonance was normal.

Abdominal Examination; Abdomen was of normal contour and moves with respiration, umbilicus is inverted, no surgical marks, no therapeutic marks, Liver, spleen and kidneys not palpable, normal bowel sound.

Cardiovascular System Examination; PR was 98 pulse/min, normal pulse volume, rhythm and was synchronous to other pulses, it was not collapsing. Thrills and parasternal heave not present. Apex beat felt at the midline of the 5th intercostal space. S1 S2 heard no murmur.

Central Nervous System: The child was well groomed, conscious, cooperative, oriented to time, people and place. She was able to memorize the events and type of meal taken in the past 24 hours which was proved by the father.

Was able to see, symmetrically move the eye following the object in all direction, direct and indirect light reflex were normal, normal corneal reflex, able to chew and swallow, symmetrical face when ordered to smile, have symmetrical shoulders, moved the shoulder and neck against resistance, able to hear, can talk and has normal voice tone and loudness, gag reflex was positive.

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She had tender non swollen right hip and knee joint and has the same warmth as other parts of the body, child has limping gait, muscle atrophy of both left thigh and leg (26.5cm and 19.5cm respectively) as compared to the right thigh and leg (30cm and 21.5 cm respectively) and there was length discrepancy between the right and the left limb (74cm and 72cm).

ROM of the joint: Right Hip; Flexion/Extension 120 – 0 – 15Abduction/Adduction 25 – 0 – 25Right Knee; NormalLeft Hip and knee; Unable to assess because of severe pain.

Dermatomal testing for pain and light touch using finger was done in Shoulders, Inner and outer aspects of the forearms, Thumbs and little fingers, Front of both thighs, Medial and lateral aspect of both calves, Little toes which was normal.

Biceps, triceps, brachioradialis, ankle right knee reflexes were normal. The left knee reflex was not done because of the refusal of the patient.

Babinski was Negative

PROVISIONAL DIAGNOSIS.

1. Osteonecrosis of the left hip and knee joint secondary to SCA

Ddx: Osteomyelitis Osteoarthritis

2. Moderate Anemia

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Investigations:

1. Sickling test was Positive2. HPLC: HbF was 4.7% and HbSS was 87.7%3. Pelvis AP X-ray:

Interpretation: Reduced joint space of the left hip, no subchondral lucency and no crescent sign. There was increased radiolucency of the left femur with cortical thinning. Right side - Normal

4. The left knee joint X-ray AP and Lateral were all normal.5. FBP revealed Leucocytosis, and hemoglobin concentration of 8mg/dl, normocytic

normochromic anemia with reticulocytosis. ESR was raised (45mm/hour) 6. Liver function test: Liver enzymes, Bilirubin (conjugated and unconjugated), were

normal.7. Serum electrolyte: the level of phosphorus was high (2.07mmol/L), Ca (2.56mmol/L),

Cl (105mmol/L), K (4.3mmol/L), Mg (0.98mmol/L) and Na (140mmol/L) were normal.

Final diagnosis:

1. Avascular necrosis Ficat stage II of the left hip joint secondary to SCA with a referred left knee pain.

2. Osteopenia of the left femur.3. Moderate Anemia

Treatment:1. IV DNS 2litres / 24hrs IV 1/7 2. Syrup Morphine 10mls 4 hourly 1/523. IV Ampicillin 1 g 6 hourly 11/74. IV Cloxacillin 1g 6 hourly 11/75. Tabs Folic acid 5mg 24hourly for 2/126. Tabs Hydroxyurea 500mg 24 hourly 6/52 7. Skin traction8. Head-preserving operation of core decompression of the left hip.

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Discussion:

It is common to have multiple joints affected: >50% of patients with an affected hip have bilateral disease and 74% of those with an affected shoulder will also have AVN of the femoral head. The prevalence of the AVN of the hip in Sickle cell disease is 5.8% in HbSS patients at the age of 12 – 14 years and 4.6% of all hemoglobin genotype group (SS, Sβ0, SC, Sβ+) of the same age [10].

This patient presented with avascular necrosis of the left hip with pain referred to the left knee. The possible causes in this case is blockage of the blood supply at the femoral head, since the head has limited collateral circulation it caused the ischemia of the subchondral area of the head. The AVN to this patient presented at the expected age as documented from the previous studies which showed low prevalence at the age of 12.

Early findings in plain radiographs are lucency and sclerosis involving the epiphysis and subsequent development of crescent shape, subchondral lucency and eventually depression of articular surface, collapse and fragmentation of femoral capital epiphysis. Changes may be seen involving the acetabulum with osteophyte formation [9].

This patient's radiographs demonstrated the presence of reduced joint space and increased radiolucency of the left femur with cortical thinning and absence of crescent sign and subchondral lucency indicating the early stage of the pathology.

After collapse, most patients will require a standard total hip arthroplasty. However, because of the young age of many of these patients, a hip replacement cannot be expected to last the patient's lifetime and therefore, when feasible, attempts should be made to save the femoral head prior to collapse with use of less invasive treatment modalities. The efficacy of these procedures has been variable, with reported success rates ranging between 60% and 80% at the time of short-term and midterm follow-up. Current treatments range from pharmacotherapies to surgical interventions that include core decompression, vascularized or nonvascularized bone-grafting, and osteotomy.[21]

In this case the core decompression was chosen over total hip arthroplasty since the child was only 12 years old diagnosed with the early stage osteonecrosis where the limited amount of dead bone from the ball of the hip was removed relieving pressure within the femoral head and allowing the body to restore its own blood supply overtime. Hip replacement surgery was not done since ideally it last about 20 years and the patient was very young where she would anticipate two, or possibly three or even more revision hip replacement surgeries over her lifetime.

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CONCLUSION AND RECOMMENDATIONS.

Whenever a patient with sickle cell anemia presents with hip pain, the clinician must include avascular necrosis as a differential. The diagnosis is confirmed by imaging procedures. The patient should be referred to pediatric orthopedic surgeon if there is a clinical evidence/ or a radiological evidence of AVN of the head of the long bones (joints with limited collateral circulation)The patient with sickle cell anemia, should immediately start sickle cell clinic or if is not accessible should be given penicillin V and Folic acid at the same time counsel the parents on the disease, importance of the medicines and mosquito treated net use for malaria prevention.

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