An often overlooked cause of lower extremity ulcers is diseases of the hematopoietic system. Although ulcers due to hematologic diseases are not as common as those due to venous and arterial disorders, podiatric physicians still need to include such conditions in their differential diagnosis. Ulcers of the foot and ankle secondary to blood dyscrasias may become more common as a result of modern medicine’s ability to keep patients alive long enough to become victims of chronic diseases. Also, many pharmaceutical agents have among their side effects the ability to produce hematologic complications. The physician should not overlook hematologic disorders as being among the etiologic agents responsible for foot and ankle ulcers. Some of the conditions in which foot ulcers may occur associated with hematologic disorders are discussed.

Many severity indices for foot and leg ulcers are based on size, depth, and duration. Staging based on depth is as follows:

Sickle cell anemia is an example of a hematologic disease that may cause ulcers affecting the lower extremities. The U.S. Cooperative Study of Sickle Cell Disease (SCD) reported that about 25% of patients with the disease over age 10 years had a history of leg ulcers.¹ The disease affects 50,000 to 100,000 people in the United States.² Its geographical distribution is variable, affecting 75% of patients in Jamaica but only 8% to 10% of North American patients.³,⁴,⁵ Ulcers due to sickle cell anemia are less common in patients with α-gene deletion, high total hemoglobin level, or high levels of hemoglobin F. The pathogenesis of chronic ulcers in SCD is complex. Mechanical obstruction by dense sickled red cells, venous incompetence, bacterial infections, abnormal autonomic control with excessive vasoconstriction when in the dependent position, in situ thrombosis, anemia with decrease in oxygen carrying capacity, and decreased nitric oxide (NO) bioavailability leading to impaired endothelial function have all been proposed as potential contributing factors.⁶,⁷ Patients have a marked reduction of NO, which is an important regulator of vascular tone, cell adhesion, and blood flow. This results in the development of a vasculopathy skewing the normal balance between vasoconstriction and vasodilatation in favor of vasoconstriction. As a result, there is NO deficiency leading to tissue ischemia and ulcer formation.⁸ Ulcers are painful and often disabling complications of SCD, may affect 5% to 10% of adult patients, and may necessitate opioids. Those that are acute usually heal within a month, but those that are chronic may take 6 months. The SCD ulcers are more common in males and increase with age. Ulcers in sickle cell anemia typically occur in areas with thin skin and less subcutaneous fat, typically at the medial and lateral malleoli. However, sometimes the dorsum of the foot is affected as is the region over the Achilles tendon. These ulcers appear round and punched-out with raised margins, deep bases and necrotic slough varying in size from a few millimeters to large circumferential areas covering the entire distal lower extremity. The lesion is usually precipitated by minor trauma and spreads in size gradually.⁹,¹⁰ Sickle cell anemia ulcers frequently are colonized with Staphylococcus aureus, Pseudomonas aeruginosa, and group A Streptococci. Typically patients with these ulcers develop wound infections which may be localized super-infections or recurrent cellulitis that heal slowly with residual hyperpigmentation and chronic scarring.¹

Healing of this difficult to treat condition is reported as being 20 times slower than in similar types of refractory vascular lesions
and is often recurrent.¹¹ Prevention includes the reduction of trauma with properly fitted shoes and compression stockings supported by application of emollients along with proper hygiene. When the ulcers occur moist, supportive dressing are indicated, but when they drain, absorbent dressing could be used. Topical antibiotics such as neomycin, polymyxin B, or bacitracin can be used if superinfection occurs. When there is necrotic tissue, debridement is indicated. There are reports that oral zinc sulfate accelerates healing.¹²,¹³ The only Food and Drug Administration-approved treatment of sickle cell anemia-caused ulcers in adults is hydroxyurea, a cytotoxic, cytostatic drug also used for the prevention of the ulcers. Treatment with hydroxyurea starts with an initial dose of 15 mg per kg (10 to 20 mg per kg) once a day.¹⁴ The dose may be increased in 5 mg/kg/day increments every 12 weeks to a maximum dose of 35 mg/kg/day. However, others suggest that hydroxyurea does not cause, prevent, or speed healing in SCD. Surgical intervention for recalcitrant ulcers using split-thickness skin grafting and myocutaneous flaps to bring blood supply to the area of ulceration has been used, but results are inconsistent.