Systemic lupus erythematosus with acanthosis nigricans, hyperpigmentation, and insulin receptor antibody.

Acanthosis nigricans, insulin receptor antibody, and systemic lupus erythematosus are associated in the potentially lethal syndrome of type B insulin resistance. Hyperpigmentation has been reported rarely, while glucose intolerance is common in these patients. We report an adolescent girl with acanthosis nigricans, hyperpigmentation, insulin receptor antibody, and systemic lupus erythematosus without glucose intolerance. Insulin resistance may be mild or transient in some patients with type B insulin resistance. Resolution of skin lesions was noted during therapy of SLE, and was associated with disappearance of insulin receptor antibody.

Renal failure in sickle cell anemia.

ESRD is a major complication in young adults with sickle cell anemia. As more patients with sickle cell anemia reach the third and fourth decades of life, the incidence of clinically apparent renal insufficiency will increase. As we understand the pathophysiology of renal damage and the effects of various therapies on the sickle renal vasculature, we can tailor specific management without further compromising already impaired renal function. Diagnostic clues must be recognized prior to the onset of irreversible damage, with appropriate intervention initiated at each age group. Bone marrow transplantation (BMT) is the only available cure for SCA at the present time. The demonstration that several distinct haplotypes of the beta s gene cluster on chromosome 11 influence the clinical expression of sickle cell anemia may be useful in delineating children who are at high risk for severe disease, and hence candidates for such hazardous therapeutic interventions as BMT prior to onset of clinically discernable disease. Current BMT preparative regimens can produce renal cortical and pulmonary toxicity, posing a patient selection problem in those cases in which the vasculopathy of the major organs is at an early stage and might be potentially repairable. Gene therapy without toxic preparative regimens is the ultimate answer. The challenge for the near future is the development of effective early therapeutic intervention during childhood and young adulthood.

Chronic renal failure in sickle cell disease: risk factors, clinical course, and mortality.

OBJECTIVE: To determine the incidence, clinical course, and risk factors associated with the onset of chronic renal failure in sickle cell anemia and sickle C disease. DESIGN: A prospective, 25-year longitudinal demographic and clinical cohort study. A matched case-control study was conducted to determine risk factors. PATIENTS: A total of 725 patients with sickle cell anemia and 209 patients with sickle C disease who received medical care from the hematology service in a large municipal hospital. Most were observed from birth or early childhood. MEASUREMENTS: Thirty-six patients developed sickle renal failure: 4.2% of patients with sickle cell anemia and 2.4% of patients with sickle C disease. The median age of disease onset for these patients was 23.1 and 49.9 years, respectively. Survival time for patients with sickle cell anemia after the diagnosis of sickle renal failure, despite dialysis, was 4 years, and the median age at the time of death was 27 years. Relative risk for mortality was 1.42 (95% Cl, 1.12 to 1.81; P = 0.02) compared with patients who did not develop renal insufficiency. MAIN RESULTS: Histopathologic studies showed characteristic lesions of glomerular "drop out" and glomerulosclerosis. Case-control analysis showed that ineffective erythropoiesis with increasingly severe anemia, hypertension, proteinuria, the nephrotic syndrome, and microscopic hematuria were significant pre-azotemic predictors of chronic renal failure. The risk for sickle renal failure was increased in patients who had inherited the Central African Republic beta s-gene cluster haplotype. CONCLUSIONS: The pre-azotemic manifestations of hypertension, proteinuria, and increasingly severe anemia predict end-stage renal failure in patients with sickle cell disease. The rate of progression of renal insufficiency is genetically determined. Treatment of the uremic phase has been dismal, underscoring the need for the development of useful pre-azotemic therapeutic modalities.