Sickle cell disease presenting with chronic lower extremity ulcers Free

Introduction Lower extremity ulcerations (LEU), usually caused by peripheral neuropathy, venous insufficiency, peripheral artery disease, and diabetes mellitus, are common in clinical practice. Less frequent causes include vasculitis, neoplasia, metabolic disorders, and hematological diseases like Sickle cell disease (SCD). SCD, an autosomal codominant genetic disorder, alters the morphology of red blood cells (RBCs), favoring their hemolysis and long-term organ damage due to vaso-occlusive crisis (VOC). VOC events lead to several acute and chronic complications due to ischemia, including dactylitis, acute stroke, priapism, central retinal artery occlusion, or even chronic LEU. In this article, we report a case of SCD that presented as bilateral LEU, underscoring the importance of considering SCD in the differential diagnosis when evaluating patients with LEU.

Case Presentation A 31-year-old male with no known past medical history presented with a chief complaint of bilateral painless LEU for 3-4 months. He denied any fevers, chills, or purulent discharge from the ulcerations. He complained of dark colored urine for several months. On arrival, he was found to be hypoxic. Physical examination showed icteric sclera, pale skin, 6 cm well-defined painless ulcerations on the bilateral lower extremities, and no skin discoloration. Peripheral pulses and capillary refill were normal. Labs were remarkable for normocytic normochromic anemia (hemoglobin 7.9 g/dL), indirect hyperbilirubinemia, increased reticulocyte count, elevated lactic dehydrogenase, and reduced haptoglobin levels. Coombs testing and agglutinins were negative. Urinalysis showed increased urobilinogen and positive urinary hemosiderin, suggesting intravascular non-autoimmune hemolysis. Blood smear was remarkable for the presence of a high number of sickle cells. Hemoglobin electrophoresis showed a predominant hemoglobin S peak (90% expression, normal range <2%), consistent with homozygous SCD. Extensive workup for LEU, including for infections, arterial and venous doppler, was unremarkable. The patient received wound care with debridement, one unit of red blood cell transfusion, and he did not require any more supplementary oxygen at the time of discharge.

Discussion LEU in SCD typically occurs in the second to fifth decade of life, frequently appearing in the peri-malleolar area. Individuals with homozygous forms of SCD, over 20 years old, and males are at increased risk. Its prevalence is variable, being as high as 75% of homozygous patients in Jamaica, but only 8–10% in North American patients. It can be spontaneous or secondary to local trauma and is associated with priapism and pulmonary hypertension. Coexisting venous valve incompetence and genetic polymorphisms like BMP6, TGFBR3, Klotho genes, and glutathione-s-transferase predispose to ulcer development and delayed wound healing. Additionally, therapies for SCD, like hydroxyurea, can lead to ulcers by causing epidermal toxicity, altering microcirculation, and inducing tissue anoxia. Comorbid conditions like venous insufficiency, peripheral arterial disease, diabetes, nutritional deficiencies, autoimmune diseases (cryoglobulinemia and vasculitides), and infective etiology should be evaluated, as they can contribute to poor wound healing and recurrence. Biopsy of the ulcer is considered in atypical presentations or nonresponse to conventional treatment. Histopathology of the ulcer reveals sickled blood cells, dilated blood vessels, and cell proliferation with atrophic borders.

Adequate wound care with debridement is the cornerstone of treatment of SCD ulcers. Topical antibiotics (bacitracin, neomycin, and polymyxin B) may significantly improve the healing of ulcers. Newer modalities of treatment, like glycosaminoglycans, growth factors, skin grafting, zinc, L-carnitine, and pentoxifylline, are mostly anecdotal and lack robust evidence. Finally, these patients require close follow-up due to the risk of recurrence, poor wound healing, and complications.

Conclusions Managing LEU in patients with SCD requires a multidisciplinary approach with meticulous wound care, appropriate pharmacotherapy, and addressing comorbid conditions to prevent recurrence, delayed wound healing, and profound impact on quality of life. Further research is necessary to establish more effective treatment protocols and reduce the burden of this debilitating complication.