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INTRODUCTION

KEY POINTS

  • Sickle cell disease (SCD) is prevalent in sub-Saharan Africa, the Middle East, India, and most tropical climates where malaria is present.

  • The SCD group of disorders can include all genotypes (eg, HbSS, HbSC, and HbSβ-thalassemia), unlike sickle cell anemia which occurs only with the HbSS genotype. SCD is characterized by recurrent vaso-occlusive crises, anemia, and a predisposition for infections.

  • Patients with SCD commonly present with jaundice and/or pallor.

  • A physical examination of the patient should include nonpathognomonic skin findings, stroke, pectus excavatum, body habitus, and an enlarged spleen, as well as the cutaneous symptoms of renal failure (see Chapter 73, Renal Disease).

  • Leg ulcers are a common cutaneous manifestation of SCD.

  • In children, hand-foot syndrome (dactylitis) is typically the first cutaneous marker of this condition.

Although it likely occurred for many years before it was first identified, sickle cell disease (SCD) was initially described by Dr. James Herrik in 1910.1 Dr. Herrik was a cardiologist in Chicago who came across SCD while evaluating a West Indian patient, Walter Noel. His intern described Noel’s blood smear as having “many pear-shaped and elongated forms - some small.”1 SCD has a unique set of cutaneous manifestations with which dermatologists should be familiar. These symptoms include leg ulcers and skin infections; however, the first manifestation of SCD is often hand-foot syndrome. This syndrome usually presents in early childhood.

ETIOLOGY AND GENETICS

SCD is a commonly inherited hemoglobinopathy. It is caused by a mutation in the gene that encodes for the β chain of hemoglobin (hemoglobin S) on chromosome 11. This mutation replaces a hydrophilic amino acid (glutamic acid) with a hydrophobic amino acid (valine). Consequently, noncovalent polymerization of hemoglobin occurs and distorts the red blood cells. The result is an abnormally rigid and sickle-shaped erythrocyte, especially when the oxygen tension is low. Problems occur because the sickle-shaped erythrocytes cannot easily navigate through small capillaries. This leads to vaso-occlusion, ischemia, hemolysis, and anemia. As a result, patients can suffer from a number of complications including strokes, infections, dactylitis, leg ulcerations and, most notably, pain crises.2 Sickle cell anemia refers to the condition caused by a homozygous mutation (HbSS), whereas SCD characterizes all of the genotypes. This includes carriers of the trait (HbAS) and other abnormal forms of hemoglobin in combination with hemoglobin S (ie, C, D, E, and β-thalassemia).3

EPIDEMIOLOGY

SCD is widespread in tropical regions, including sub-Saharan Africa, India, and the southern coast of the Arabian Peninsula. Studies show that the sickle cell trait is a protective factor against malaria, and therefore, it presents with high frequency in endemic regions due to genetic selection. However, migration has increased the prevalence of this disease across Europe and the Americas.2,4,5

Africa

Africa has by far the highest prevalence of SCD. Epidemiologic analysis ...

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