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

2. 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

3. General Internal Medicine
Thyroid
Cholesterol
Diabetes Mellitus
Hypertension

4. General Internal Medicine
Thyroid
Cholesterol
Diabetes Mellitus
Hypertension

5. Immunization
Pneumovax
Hib
Hepatitis B
HPV
Hepatitis A (confounder)

6. Age appropriate cancer screening
PAP smear
Mammography
PSA
Occult blood

7. Malignancy in SCD, No HU
Incidence of malignancy at Howard Univ. is 1.74 per 1000 pt-yrs Vs per 1000 pt-yrs 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

8. 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

9. Manifestations of Sickle Cell Disease
Chronic Hemolysis
Intermittent “crises”
Frequent Infections
End organ dysfunction
Disorders unrelated to the Hbopathy

10. Acute & Chronic Manifestations of Sickle Cell Disease
Pain : ischemic, neuropathic, collapsed bone
Brain: TIA, ischemic Stroke, hemorrhage
Eye: retinopathy
Bone: 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

11. 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, B12, Folate, RBC phenotype, pulse oximetry, allantibodies, EKG, additional assays based upon Hx/Px
X-ray: Chest, Hips, Shoulders, T/L Spines, etc.

12. Br Med J 295:234, 1987

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

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

16. J Clin Epidemiol 45:893, 1992

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

18. Proteinuria
microalbuminuria: > 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

19. Hematuria
Papillary necrosis
Glomerulonephritis
Medullary Carcinoma

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

21. 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

22. 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

24. Air Travel Identify a source of care at the destination
Oxygen if SpO2 < 88%
Non-caffeinated fluids
Walk every hr or more often
VTE prophylaxis with h/o prior VTE

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

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

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

29. 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(m3v): 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 94:415a, 1999

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

31. 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 (M3v) in 141 children with 598 pt-yrs of F/U Br J Haematol 123:368, 2003

32. Summary: Goal of reducing morbidity & mortality
More aggressive use of Hydroxyurea:
Additional therapies
Regular Surveillance
Prompt referral
Individualize therapy to the patient

33. Gene Therapy Clinical Trial in 5 Hb SS & 5  Thal (Paris)
Self-inactivating lentiviral vector
A-T87Q
Ann NY Acad Sci 1054:308, 2005 ,

34. Gene Therapy
BlueBird Bio