The Comprehensive Examination Cage S Johnson M D

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The Comprehensive Examination Cage S. Johnson, M. D. Professor Emeritus of Medicine Director, Sickle

The Comprehensive Examination Cage S. Johnson, M. D. Professor Emeritus of Medicine Director, Sickle Cell Center Keck School of Medicine University of Southern California

Adult Health Care • Preventive Health Maintenance: • Psychosocial Assessment: school achievement, occupational Hx,

Adult Health Care • Preventive Health Maintenance: • Psychosocial Assessment: school achievement, occupational Hx, depression, anxiety, financial resources • Education: tobacco, alcohol, recreational drugs, safe sex techniques, sickle cell related education – fever, dyspnea, pain management • Surveillance for complications of SCDz, as well as for disorders of adulthood • Referral network, early treatment of complications

General Internal Medicine • • Thyroid Cholesterol Diabetes Mellitus Hypertension

General Internal Medicine • • Thyroid Cholesterol Diabetes Mellitus Hypertension

General Internal Medicine • • Thyroid Cholesterol Diabetes Mellitus Hypertension

General Internal Medicine • • Thyroid Cholesterol Diabetes Mellitus Hypertension

Immunization • • • Pneumovax Hib Hepatitis B HPV Hepatitis A (confounder)

Immunization • • • Pneumovax Hib Hepatitis B HPV Hepatitis A (confounder)

Age appropriate cancer screening • • PAP smear Mammography PSA Occult blood

Age appropriate cancer screening • • PAP smear Mammography PSA Occult blood

Malignancy in SCD, No HU • Incidence of malignancy at Howard Univ. is 1.

Malignancy in SCD, No HU • Incidence of malignancy at Howard Univ. is 1. 74 per 1000 pt-yrs Vs. 3. 82 per 1000 ptyrs in the Afro-American population. Am J Hematol 55: 188, 1997 • 2 malignancies in 144 autopsies in Hb SS Br J Haematol 123: 359, 2003 • “CSSCD reported 16 malgnancies in over 4000 patients during a 15 y follow-up” Cited in Am J Hematol 74: 249, 2003

IASCNAPA: ~n= 16, 613 Am J Hematol 74: 249, 2003 • • All: 6

IASCNAPA: ~n= 16, 613 Am J Hematol 74: 249, 2003 • • All: 6 cases, 1 on HU AML: 2 cases CML: 1 case Brain, Breast, Bladder, Bone, Gall bladder, GI tract, Lymphoma – HD & NHL, Myeloma, Pancreatic, Testis

Manifestations of Sickle Cell Disease 1. 2. 3. 4. 5. Chronic Hemolysis Intermittent “crises”

Manifestations of Sickle Cell Disease 1. 2. 3. 4. 5. Chronic Hemolysis Intermittent “crises” Frequent Infections End organ dysfunction Disorders unrelated to the Hbopathy

Acute & Chronic Manifestations of Sickle Cell Disease • • Pain : Brain: Eye:

Acute & Chronic Manifestations of Sickle Cell Disease • • Pain : Brain: Eye: Bone: ischemic, neuropathic, collapsed bone TIA, ischemic Stroke, hemorrhage retinopathy remodeling by marrow hyperplasia, osteonecrosis, collapse, osteomyelitis • Lung: ACS, chronic restrictive lung disease (hypoxia) • Heart : pulmonary hypertension • Liver : gallstones, hepatitis, iron overload, sequestration • Spleen : auto-infarction, sequestration, bacterial sepsis • GU: infection, proteinuria, renal insufficiency, obstetrical, priapism • Skin: leg ulcers

Surveillance: (repeated annually) • H/O sickling related events: Pain-acute & chronic, CVA, PNA/ACS (ICU),

Surveillance: (repeated annually) • H/O sickling related events: Pain-acute & chronic, CVA, PNA/ACS (ICU), Hepatitis, Cholelithiasis, Priapism, Retinopathy, Pregnancy, Leg Ulcer, Hematuria/Infection, Bone infections/AVN, Transfusion • Lab: CBC, Bun/Creatinine, Urine protein, Iron/Ferritin, Hepatitis markers, B 12, Folate, RBC phenotype, pulse oximetry, allantibodies, EKG, additional assays based upon Hx/Px • X-ray: Chest, Hips, Shoulders, T/L Spines, etc.

Br Med J 295: 234, 1987

Br Med J 295: 234, 1987

Hepatic Diseases • Cholelithiasis • Chronic active hepatitis B/C RUQ ultrasound (biopsy) Viral load

Hepatic Diseases • Cholelithiasis • Chronic active hepatitis B/C RUQ ultrasound (biopsy) Viral load & genotype Rx: Interferon & Ribivarin • Iron overload

Pulmonary Disease (CSSCD) • N = 318, > 18 y of age (mean 31

Pulmonary Disease (CSSCD) • N = 318, > 18 y of age (mean 31 10), 41 % male • 90 % abnormal Restrictive - 74 % Obstructive - 1% Mixed O/R - 2% DLCO - 13 % • Association between lung & kidney disease Am J Resp Crit Care Med epublished 23 Oct 2005

J Clin Epidemiol 45: 893, 1992

J Clin Epidemiol 45: 893, 1992

Prevalence rates of proteinuria and renal insufficiency per decade of life Int J Artif

Prevalence rates of proteinuria and renal insufficiency per decade of life Int J Artif Organs 13: 231, 1990

Proteinuria microalbuminuria: > 20 mg/g creatinine macroalbuminuria: > 300 mg/g creatinine Histology: Progressive focal

Proteinuria microalbuminuria: > 20 mg/g creatinine macroalbuminuria: > 300 mg/g creatinine Histology: Progressive focal segmental glomerular sclerosis – – – effacement of foot processes thickening of basement membrane Fe+++ deposition Differential diagnosis: – – – post streptococcal glomerulonephiritis acute diffuse proliferative glomerulonephritis acute diffuse mesangial glomerulonephritis membranoproliferative glomerulonephritis renal vein thrombosis Treatment: – ACE inhibitor

Hematuria • Papillary necrosis • Glomerulonephritis • Medullary Carcinoma

Hematuria • Papillary necrosis • Glomerulonephritis • Medullary Carcinoma

Renal Insufficiency • Anemia: EPO + HU • Acidosis - ineffective erythropoiesis - Shohl’s

Renal Insufficiency • Anemia: EPO + HU • Acidosis - ineffective erythropoiesis - Shohl’s Solution • Blood Pressure

Management of Hypertension • Rx if BP > 130/80 • Assess for renal disease

Management of Hypertension • Rx if BP > 130/80 • Assess for renal disease • Rx if BP rises from baseline by 20 mm Hg systolic or 10 mm Hg diastolic • With proteinuria: Rx if BP > 120/75 or with > 300 mg/24 h

Management of Hypertension • ACE inhibitor – hyperkalemia (spurious) • Calcium channel blocker –

Management of Hypertension • ACE inhibitor – hyperkalemia (spurious) • Calcium channel blocker – dose adjustment in hepatic or renal disease • Beta-blocker – asthma, CHF, thrombocytopenia, bradycardia • Diuretic – dose adjustment for hyposthenuria/naturesis

Air Travel • • • Identify a source of care at the destination Oxygen

Air Travel • • • Identify a source of care at the destination Oxygen if Sp. O 2 < 88% Non-caffeinated fluids Walk every hr or more often VTE prophylaxis with h/o prior VTE

CHALLENGES in MANAGEMENT of the ADULT PATIENT: • Shorten the duration of acute complications

CHALLENGES in MANAGEMENT of the ADULT PATIENT: • Shorten the duration of acute complications • Reduce the frequency/severity of chronic complications • Improve survival • Enhance the Quality of Life

Options • Stem Cell Transplantation • Hydroxyurea, L-Glutamine • Crizanlizumab • Transfusion/Chelation • Gene

Options • Stem Cell Transplantation • Hydroxyurea, L-Glutamine • Crizanlizumab • Transfusion/Chelation • Gene Therapy

Mortality: Hydroxyurea • 40 % reduction (JAMA 290: 756, 2003) • Unclear (Blood 105:

Mortality: Hydroxyurea • 40 % reduction (JAMA 290: 756, 2003) • Unclear (Blood 105: 545, 2005)

Leukemia in SCD on HU • ALL, Ph+: 10 y F SS, 7 weeks

Leukemia in SCD on HU • ALL, Ph+: 10 y F SS, 7 weeks of Rx Arch Dis Child 81: 437, 1999; Blood 98: 2878, 2001 • • AML: 42 y F SS, 6 yrs of Rx Ann Intern Med 133: 925, 2000 AML: 2 yrs of Rx Saudi Med J 23: 1411, 2002 APL(m 3 v): 21 y F SS, 8+ yrs of Rx Br J Haematol 123: 368, 2003 ANLL: 27 y F SO-Arab, 8 yrs of Rx on a background of MDS Blood 94: 415 a, 1999

Leukemia in SCD, No HU • ALL: 4 cases Clin Pediatr 11: 183, 1972

Leukemia in SCD, No HU • ALL: 4 cases Clin Pediatr 11: 183, 1972 Cent Afr J Med 34: 158, 1988 Cancer Genet Cytogenet. 21: 267, 1986 Arch Pathol Lab Med 123: 745, 1999 • AML: 5 cases Ann Intern Med 39: 920, 1953 Am J Med 73: 268, 1982 N Engl J Med 311: 780, 1984 Am J Hematol 21: 223, 1986 Indian Pediatr 16: 453, 1979 • CML, Ph+: 6 cases (plus 1 from USC) Hum Genetik 30: 13, 1975 N Engl J Med 298: 72, 1978 Am J Med 85: 567, 1988 J Assoc Physicians India 34: 821, 1986 Am J Hematol 31: 302, 1989 Arch Pathol Lab Med 129: 423, 2005

Long Term Follow-up of SCD on HU • MSH: no malignancy at 9 yrs

Long Term Follow-up of SCD on HU • MSH: no malignancy at 9 yrs (n=156 on HU>1 y) JAMA 289: 1645, 2003 • MCG: no malignancy in 236 adults at 15 yrs Blood 195: 545, 2005 • HUG-KIDS: no malignancy in 84 children at 2+ yrs Blood 94: 1550, 1999 • France: 1 ALL in 101 children at 2+ yrs Arch Dis Child 81: 437, 1999 • Belgium: 1 AML (M 3 v) in 141 children with 598 pt-yrs of F/U Br J Haematol 123: 368, 2003

Summary: Goal of reducing morbidity & mortality • More aggressive use of Hydroxyurea: www.

Summary: Goal of reducing morbidity & mortality • More aggressive use of Hydroxyurea: www. ahrq. gov/clinic/tp/hydscdtp. htm • • Additional therapies Regular Surveillance Prompt referral Individualize therapy to the patient

Gene Therapy • Clinical Trial in 5 Hb SS & 5 Thal (Paris) •

Gene Therapy • Clinical Trial in 5 Hb SS & 5 Thal (Paris) • Self-inactivating lentiviral vector • A-T 87 Q Ann NY Acad Sci 1054: 308, 2005 ,

Gene Therapy • Blue. Bird Bio

Gene Therapy • Blue. Bird Bio