廉状细胞贫血多系统影像学表现

April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD Sickle Cell Disease:Sickle Cell Disease: Multisystem Radiographic Multisystem Radiographic manifestationsmanifestations Alaina Kipps, Harvard Medical School Year III Gillian Lieberman, MD April 2002 2 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD AgendaAgenda • Sickle cell disease (SCD) basics • A tour of sickle cell complications and their radiographic manifestations. • Patient presentation – RH, a 14 year old boy with SCD and RUQ pain • A closer look at Osteonecrosis and Osteomyelitis – Menu of radiographic tests. – Can we differentiate these two disease processes? • Patient presentations – WB, a 43 year old man with SCD and L knee pain – LF, a 42 year old woman with SCD and L hip pain • Summary • References • Acknowledgements 3 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD Sickle Cell BasicsSickle Cell Basics • The rope like polymer of deoxy Hemoglobin S leads to sickling of red blood cells. • Hypoxia, acidosis, dehydration, and blood flow stasis promote sickling • Repeated sickling causes rbc dehydration and membrane distortion • There is increased rbc “stickiness” and adherence to vascular endothelium • These altered red cells cause the primary pathophysiologic themes in SCD: –– HemolysisHemolysis and and VasoVaso--occlusionocclusion • This leads to complications in every organ system... Courtesy of Orah Platt 4 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD Sickle Cell Basics IISickle Cell Basics II – CNS: CVA with large and small vessel vaso-occlusion; risk of meningitis. – Ocular: Retinopathy – Pulmonary: Acute chest syndrome, pneumonia; chronic pulmonary disease with fibrosis, restrictive lung disease – Cardiac: Heart failure secondary to fibrosis, MI, cor pulmonale – Renal: Hematuria, papillary necrosis, nephropathy – Spleen: Sequestration crisis with massive splenomegaly; auto-splenectomy – Liver/Biliary: Bilirubin cholelithiasis; cholecystitis – Skin: Leg ulcers – Skeletal: Osteopenia, dactylitis, osteonecrosis, premature OA, growth failure, risk of osteomyelitis – Heme: Chronic anemia with HCT 18-26%; aplastic crisis with Parvovirus B19 – Immune system: Functional asplenia, intrinsic defects in immune system. 5 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD Neurologic ComplicationsNeurologic Complications • CNS: 25% of patients with SCD have neurologic complications: – TIA – Infarctive stroke – Intracerebral hemorrhage – Spinal cord infarction or compression • New role for Doppler ultrasound for prevention of CVA in SCD. BIDMC PACS L MCA filling defect on MR- angiogram High signal in L insula: Acute stroke 6 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD Cardiac ComplicationsCardiac Complications • Anemia need increased cardiac output – Chronic chamber enlargement/cardiomegaly • Increased risk of acute myocardial infarction – In absence of atherosclerosis – Cardiac muscle has increased demand (high C.O.) – Decreased oxygen carrying capacity – Microcirculatory disease • On Chest radiograph look for enlarged cardiac silhouette and upper zone redistribution with high cardiac output state. 7 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD Renal ComplicationsRenal Complications • Occlusion of vasa recta in the medulla – Medulla has low oxygen tension, and high osmolality that promote sickling • Papillary infarcts lead to papillary necrosis and renal failure • Renal osteodystrophy (with 2 hyperparathyroidism) can contribute to osteoporosis • Renal disease can also lead to decreased erythropoietin production, exacerbating the anemia Papillary necrosis causing bilateral clubbed calyces o American College of Radiology. Teaching cases: Urogenital case 506. 8 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD Pulmonary ComplicationsPulmonary Complications • Acute & chronic pulmonary manifestations are the most common cause of death • Acute Chest Syndrome: – Pulmonary vaso-occlusion: • In situ infarction • Fat embolus – Pneumonia – Hypoventilation/Atelectasis • Abdominal pain • Thorax bone pain – Pulmonary edema • Over-vigorous intravenous fluids Courtesy of Orah Platt 9 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD Pulmonary Complications IIPulmonary Complications II • Acute Chest Syndrome – Presence of new pulmonary infiltrate • Must involve at least ONE lung segment • More than simple atelectasis • Setting of chest pain, temp>38.5, tachypnea, cough or wheezing • Chronic Lung disease from repeated ACS – Restrictive lung disease – Pulmonary hypertension can cause cor pulmonale – Very poor prognosis (most die within 7 years) Courtesy of Orah Platt 10 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD Chest RadiographyChest Radiography • Acute chest syndrome (ACS) – On admission, 30% of patients have a normal Chest radiograph – Lobar distribution, frequently middle or lower lobes – Usually confluent and alveolar in location – 25% of patients also get pleural effusions. – Pneumonia is more likely in children under 5 y.o. with upper lobe infiltrates. • Chronic Lung disease from repeated ACS – CT scan: chronic interstitial fibrosis 11 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD Abdominal Complications IAbdominal Complications I • Cholelithiasis – Pigmented gallstones from chronic hemolysis – Occur as young as 3-4 years of age, 30% by age 18, and eventually in 70% of SCD patients. – Most are asymptomatic, but the stones can cause RUQ pain or lead to cholecystitis. Children’s Hospital Hyperechoic stones with posterior acoustic shadowing 12 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD Abdominal Complications IIAbdominal Complications II • Splenic sequestration – Cause of acute severe anemia. – 10-15% Mortality rate – Occurs in young children, before fibrosis of the spleen • As high as 30% incidence • In 20% of patients this is initial symptom – Vaso-occlusion and splenic pooling of red blood cells causes rapidly enlarging spleen – Risk of hypovolemic shock • Auto-splenectomy – Vaso-occlusion of spleen leads to dysfunction and infarction by 2-4 years of age – Spleen tissue undergoes fibrosis. – Leads to immunocompromised state 2 year old boy with sequestration African figurine displaying splenomegaly Courtesy Orah Platt 13 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD Patient Presentation: Mr. RHPatient Presentation: Mr. RH • Patient RH is a 14 year old male with SCD • CC: Pain in both legs, and a cough for 3 days • PMH: Sickle cell anemia, complicated by: – Dactylitis at 7 months of age – Multiple admissions for vaso occlusive (pain) crisis – History of acute chest syndrome twice in 1995, requiring exchange transfusions • Admitted for vaso-occlusive crisis • Plain films of knees were negative. • On HD#3 developed RUQ pain… 14 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD Mr. Mr. RH’sRH’s RUQ Ultrasound:RUQ Ultrasound: These findings are consistent with cholelithiasis. He had a semi- elective laparscopic cholecystectomy due to prior episodes of RUQ pain. One day later he had dyspenia and rales… Children’s Hospital Gallstone in neck of GB The common hepatic duct was measured to be 5 mm. Multiple hyperechoic rounded structures in the GB (moved to dependent side during the study) No GB distension, wall thickening, or pericholescystic fluid Duodenum with air and posterior shadowing 15 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD Mr. Mr. RH’sRH’s Chest Radiograph:Chest Radiograph: Remember, to diagnose an Acute Chest Syndrome there needs to be a NEW pulmonary infiltrate… “Can I see his baseline film?”… Children’s Hospital 16 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD Mr. Mr. RH’sRH’s Chest Radiograph:Chest Radiograph: Normal C:T ratio Clear Lungs Poor inspiration Portable AP of the Chest EKG leads This was labeled post-op atelectasis. The next day he was well enough to have an upright PA and lateral chest radiograph… Children’s Hospital Baseline film Silhouetted out Left diaphragm, suggesting L basilar atelectasis 16 17 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD Mr. RH, Post op Day #2Mr. RH, Post op Day #2 Children’s hospital Pleural Effusion Cholecystectomy clips Post-Op ileus Vertebral H RH’s respiratory symptoms resolved over the next 3 days, and he was discharged home on post- op day six. 17 18 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD Skeletal ManifestationsSkeletal Manifestations • Bone is affected in various ways by SCD: – Marrow Hyperplasia -- a response to the severe chronic anemia • Marrow space increases • Trabecular and Cortical bone thinning – Vaso-occlusion • Painful Crisis • Dactylitis • Osteonecrosis – High risk of Osteomyelitis • Immunocompromised state • Nidus for infection: osteonecrotic areas. • Salmonella and S. aureus infection most common 19 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD Marrow expansionMarrow expansion • Radiologic findings include: – Tower skull – Hair-on-end, or Crew-cut appearance of skull – Forehead bossing – Squaring of the metacarpals – Diffuse osteopenia – course trabecular pattern • thicker trabeculae stand out in radiolucent bone –– HH--shapedshaped or Codor Cod--vertebraevertebrae • central cupping of the vertebral endplates • Usually involves several contiguous vertebrae • 50% of SCD patients Diggs LW, Pulliam HN, King JC: The bone changes in sickle AJR Am J Roetology 1979 Mar; 132 (3): 373-7 This finding is VERY RARE, and is more associated with Thalasemia major than Sickle cell disease! (at least in the literature…) 20 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD HH--shaped vertebraeshaped vertebrae States,L. Imaging of Metabolic Bone disease and Marrow disorders in children. Pediatric Musculoskelatal Radiology. Radiology Clinics of N. America 39 (4): 767. flat central end plate depressions Vertebral H • Characteristic feature of sickle cell disease, best seen on lateral chest radiograph. • Can also be seen in Gaucher’s disease, Thalassemia major, and Homocystinuria Mechanism: Recurrent vaso-occlusion and ischemia of the end- arterioles serving the central portion of the growth plate impairs endochondral bone formation. There is gradual development of a flat, central end plate depression of both the superior and inferior end plates. 21 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD OsteonecrosisOsteonecrosis • Patients present with pain and swelling at the area of bone infarction • Femoral and Humeral heads most common area • Proximal tibia, vertebrae, and small bones of hand and feet also at risk (dactylitis) • Complications: – Fat and bone marrow embolism – Osteomyelitis (secondary seeding of dead bone) – Premature osteoarthritis 22 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD DactylitisDactylitis • The most common initial symptom in Sickle cell disease Courtesy of Orah Platt Swelling of the hands… …and the feet. from vascular necrosis of the metacarpal and metatarsal bones 23 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD DactylitisDactylitis moth-eaten pattern A thick layer of periosteal new bone growth recovery line ? • Typical between 6 to 18 months of age, while red cells with HbSS replace those with HbF in the bone marrow in the hands and feet • Example: Ischemic dactylitis in 10 month old boy: States,L. Imaging of Metabolic Bone disease and Marrow disorders in children. Pediatric Musculoskelatal Radiology. Radiology Clinics of N. America 39 (4): 767. 24 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD OsteomyelitisOsteomyelitis • An infection of the bone and bone marrow. • Typical symptoms: – Pain with passive motion, tenderness, warmth, pseudoparalysis • Can be acute, subacute, or chronic. • Incidence in SCD: 0.36% per year • Humerus, femur, and tibia most commonly affected • In most children osteomyelitis affects the metaphysis; in SCD patients, it often affects the diaphysis. • Very difficult to differentiate from osteonecrosis in SCD. • Radiology plays central role in evaluation… – Imaging findings of osteomyelitis are the same as those found in children without SCD. – Suspect osteomyelitis when the symptoms of acute vaso-occlusive crisis persists despite medical management, or with new onset unifocal bone pain. 25 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD Musculoskeletal imaging: Menu of TestsMusculoskeletal imaging: Menu of Tests • Plain film – Always first step; may provide clues for other disease processes – 30-50% of bone calcium must be lost before density change is seen • Sonography – Quick look at soft tissues, guides aspiration • Scintigraphy – Great for initial assessment of osteonecrosis and osteomyelitis – Total body scan: detect multiple areas of involvement • CT – See bone changes well (destruction, periosteal reaction, sequestrum or involucrum). • MRI – See full extent of local disease process (bone, muscle and soft tissue) Courtesy of Orah Platt 26 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD Plain FilmsPlain Films • Osteonecrosis: – During a Pain crisis: • Soft tissue swelling • Evidence of old infarcts – At 10-21 days: • Osteopenia in a permeative pattern, as osteoclasts dissolve dead bone • Periosteal new bone formation – Later: cortical thickening, sclerotic areas – The Crescent sign (subchondral lucency) is pathognomonic • Osteomyelitis: – 2-3 weeks required for bony changes to appear – Order of plain film manifestations: soft tissue swelling, demineralization, periosteal reaction, and cortical disruption Kothari NA, Pelchovitz DJ, and Meyer JS. Imaging of MSK Infections. Pediatric Musculoskelatal Radiology. Radiology Clinics of N. America 39 (4): 656. 27 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD OsteonecrosisOsteonecrosis of the Femoral headof the Femoral head Lucent regions with associated sclerotic rims After many insults, the weight-bearing femoral heads can collapse, or secondary osteoarthritis may lead to a need for hip replacement. Donohue, JP Osteonecrosis. (Courtsey of Jonathan Kruskal) 2002 UpToDate. (www.uptodate.com). 28 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD ScintigraphyScintigraphy • High sensitivity, low specificity • Three phase bone scan – Tc-99m bound to methylene diphosphonate accumulates in areas of increased osteoblast activity • Immediate blood flow • Blood pool imaging • Delayed bone imaging – 1.5-2 hours after initial injection • Bone Marrow scan – 99-Tc labeled sulfur colloid goes to RE system -- bone marrow, liver, and spleen • WBC labeled with Tc 99m or indium go to inflamed areas. • Gallium 67 also goes to inflamed areas (binds to degranulated WBC lactoferrin). • Dual tracer scans compare images from: 1. Physiologic/Anatomic tracer scan: Tc99-MDP or Tc99-colloid 2. Inflammation tracer scan: WBC-Tc99 or gallium 67 Cellulitis Increased uptake in osteomyelitis 29 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD OsteonecrosisOsteonecrosis vs. vs. OsteomyelitisOsteomyelitis in Sickle cell diseasein Sickle cell disease Bone scan (Tc-99 MDP) Bone Marrow (Tc-99 - colloid) Bone scan with Gallium 67 Osteonecrosis Doughnut sign: Increased turnover around cold spot Decreased uptake (cold spot) Early: decreased uptake With repair: Increased uptake around cold spot Osteomyelitis Three phase: Increased uptake on ALL 3 phases Not increased or decreased uptake Very increased uptake (more than marrow or bone scan) Osteonecrosis is 50x more common than osteomyelitis in Sickle cell disease. 30 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD ScintigraphyScintigraphy for acute for acute osteomyelitisosteomyelitis Blood Pool Phase Delayed bone scan Gallium scan The scans demonstrate increased uptake in the distal metaphysis of the right tibia. The blood pool and delayed bone scans suggest osteomyelitis; the gallium shows a large, associated area of inflammation -- evidence that this is not just bone repair. Plain radiographs were negative. Turpin,S and Lambert, R. Role of Scintigraphy in Musculoskeletal and Spinal infections. Imaging of the MSK and spinal infections. Radiologic clinics of N. Amer 39(2). 31 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD OsteomyelitisOsteomyelitis: Bone Scan and Plain Film: Bone Scan and Plain Film Oudjhane K, Azouz EM. Imaging of Osteomyelitis in Children. Imaging of the MSK and spinal infections. Radiologic clinics of N. Amer 39(2). Follow-up radiograph, 5 weeks following antibiotic therapy. Salmonella osteomyelitis of the right fifth proximal phalanx in a 4-year-old girl. Initial Gallium scan: 24 hours after symptoms started focal bone destruction & proximal sclerosis focal increase of radioisotope uptake 32 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD UltrasoundUltrasound • Convenient, practical, and cost-effective • No need for sedation in children • Increasing use for pediatric MSK evaluation • Cartilage, bone, and soft tissue distinguished • Cons: Very operator dependent • Osteomyelitis: – Soft tissue disturbance – Subperiosteal abscess: thin layer of fluid contiguous with the bone – Doppler: for monitoring the course of the disease • Prolonged increased Doppler signal may indicate need for surgery – Useful for guiding needle aspiration 33 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD MRI for MRI for OsteonecrosisOsteonecrosis and and OsteomyelitisOsteomyelitis • Most sensitive, most specific – Shows changes early in course of disease when plain films and bone scans are negative – Cons: high cost, lower availability, and need for sedation in young children • Osteonecrosis: – Pathognomonic double line: • Early: T-1 images show single density line • T-2: second high intensity line – Represents hypervascular granulation • Osteomyelitis: – Clearly demonstrates extent of soft tissue changes and medullary edema before cortical destruction occurs. – Especially good for vertebrae and feet – Can distinguish acute from chronic infections. 34 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD OsteonecrosisOsteonecrosis on MRIon MRI Double Line Sign: Concentric high and low signal at the periphery Donohue, JP Osteonecrosis. 2002 UpToDate. (www.uptodate.com). Fat suppression MRI sequence: Serpentine intramedually pattern of decreased signal intensity 35 April 2002Alaina Kipps, HMS 3Gillian Lieberman, MD Comparison of Studies for Comparison of Studies for OsteomyelitisOsteomyelitis Sensitivity Specificity Plain film (at 7-10 days after onset of symptoms) 43-75% 75-83% Three-phase bone scan