13 minute read
Hyperpigmented scaly patch
Dermatologic Look-Alikes
Lower Leg Ulcers
BRIANA FERNANDEZ; SIDRA DEEN; CARLY DUNN, MD; TARA L. BRAUN, MD
CASE #1
A 63-year-old man presents to the dermatology clinic with a 3-month history of a nonhealing ulcer on his right lower leg. The patient notes that the ulcer has been getting bigger and is painful (including when touched by socks or pants). He has no other similar lesions on his body. He has a history of diabetes mellitus, hyperlipidemia, and 30 years of smoking. On physical examination, a hyperpigmented scaly patch is found above the right lateral malleolus with several small areas of shallow ulceration. The area is tender to palpation. His lower legs have no hair and his feet are cool to the touch.
CASE #2
A 72-year-old man presents to the dermatology clinic with a 6-month history of swelling of the lower extremities with associated painful ulcers. The ulcers are currently being managed with gentle wound care by another health care provider. His medical history includes obesity, diabetes mellitus, and hypertension. The patient reports drinking approximately 1 alcoholic drink per month and does not smoke. On physical examination, the clinician notes bilateral pitting edema of the lower extremities and ulcerations on the lateral ankle and foot with yellow exudate and red granulation tissue at the base.
Dermatologic Look-Alikes
CASE #1 Arterial Ulcers
Arterial ulcers comprise a quarter of leg ulcers and are most commonly caused by atherosclerosis and thrombosis.1 Atherosclerosis results in lower extremity peripheral arterial occlusive disease (PAOD), a subset of peripheral arterial disease (PAD), which occurs in 30% to 40% of patients older than 60 years.2 Advanced PAOD can lead to the formation of arterial ulcers and may be asymptomatic before the loss of tissue, making the condition difficult to detect.2 Other forms of ischemia and impaired arterial flow such as thrombosis or trauma also can produce arterial ulcers.3 Occlusion of arterial blood can occur in capillaries, arterioles, and large arteries.3
Risk factors for PAD and arterial ulcers include hyperviscosity, hypercoagulability, cerebrovascular disease, coronary artery disease, hyperlipidemia or dyslipidemia, hyperhomocysteinemia, diabetes mellitus, smoking, renal failure or insufficiency, hypertension, associated vasculitis, family history of arterial disease, sedentary lifestyle, and advanced age.1-3 Smoking is one of the most important factors in the progression of peripheral atherosclerosis to arterial ulcer.2 Increased number of pack years are associated with an increased risk for vascular graft occlusions, amputations, and mortality. Diabetes mellitus is
another major contributing factor that can triple or quadruple the risk for PAOD. Reduced psychosocial status as seen in patients with alcohol abuse, malnutrition, poor hygiene, and mental illness is an additional risk factor.2
A review of systems of patients with PAOD may reveal leg pain on exertion, fatigue or numbness in the legs when walking, decreased walking, and numbness and/or nighttime pain in the feet.2 Symptoms of intermittent claudication may go unnoticed if the patient does not have an active lifestyle.1 Signs of PAOD include cool, shiny, dry, or dark purple skin; dry or wet soft crusty tissue; mummified or blackened toes; thickened toenails; and hair loss which commonly occurs around the leg and/or ankle.2 If untreated, these sites could develop arterial ulcers.2
Arterial ulcers are commonly found on the distal leg, especially around the lateral malleoli, pretibial and lateral leg, toes, dorsum of the feet, and bony protuberances.1,3 These lesions vary in depth and are typically painful even if they are not large. Ischemic arterial ulcers are small and round and often have smooth, demarcated borders with a “punched-out” appearance. The base of the ulcer is usually pale but may present with wet or dry gangrene. No granulation tissue and typically no or minimal exudate are found. Local hair loss, atrophy, slow capillary refill, decreased or absent peripheral pulses, decreased temperature, and pallor may be seen around the ulcer.1,3 Ischemia of the affected leg can be noted by induced pallor when the limb is raised to greater than 30 degrees.3 Pain increases when the leg is raised and mild improvement may be observed when the leg is lowered into a dependent position.1
Diseases that mimic arterial ulcers include hypertensive ulcers, eosinophilic vasculitis, pyoderma gangrenosum, calciphylaxis, spider bites, scleroderma, venous ulcers, and trauma.3 An ankle-brachial index (ABI) measurement is one of the most common methods for confirming PAD, with a value below 0.9 signifying PAD and values below 0.5 indicating advanced arterial damage that may be unlikely to heal.1 Arterial calcification can manifest as an ABI greater than 1.2.1 Doppler waveform changes and toe-brachial-pressure-index can also help confirm PAD diagnosis.4,5 Histopathologic examination of arterial ulcers most commonly shows epidermal thinning, progressive necrosis of the epidermis, dermal sclerosis, and thrombi in dermal blood vessels; but this evaluation is not necessary for diagnosis.6
The primary treatments for arterial ulcers include pain control, conservative debridement, occlusive dressings, and measures to increase circulation.3 Compression and aggressive debridement could lead to further necrosis and should be avoided.1,3 Evidence suggests that spinal cord stimulation may reduce pain.4 To care for an ulcer bed, it is important to assess and treat the etiology and contributing factors, such as hypertension, diabetes, nutrition, smoking, and use of immunosuppressive drugs.3-4 If an ulcer becomes moist, it should be treated with foam dressings, alginates, hydrocolloids, and negative wound pressure therapy to prevent infections.4 Ulcers that are new or accompanied by increased odor, erythema, edema, exudate, temperature, or size may signify an infection and systemic antibiotics should be given if a combination of any 3 of the prior signs is noted.1
Arterial ulcers can be improved through surgery to revascularize the leg and restore blood flow and/or skin grafts to cover the ulceration.4,7 If bone or tendon becomes exposed,
free or pedicled flaps should be considered.7 Extensive arterial ulcers can be revascularized with a 1-stage multiple arterial reconstruction with an omental free flap if standard free flaps cannot be used.7 If the wound cannot be revascularized, the limb may need to be amputated or treated with prostaglandin E1 derivatives.1,4 Transcutaneous oxygen pressure (TcPO2) measurement can help identify the severity of ischemia and the appropriate level of amputation if necessary.1 In patients with end-stage renal disease or heel gangrene, amputation may be considered before surgical revascularization or skin flaps because of surgical risks and the decreased likelihood of successful perfusion.4 Hyperbaric oxygen therapy should be considered as adjuvant therapy in hypoxic ulcers responsive to oxygen if revascularization is unsuccessful, especially in patients with diabetes.1,4 Findings from a case study by Carbinatto et al showed promise for a triple-therapy approach of low-level laser therapy, photodynamic therapy, and cellulose membranes.8
The patient in this case was diagnosed clinically with arterial ulcer and referred to vascular surgery for additional management. frequently in women compared with men with an average age of onset between 70 and 79 years.9
In normal conditions, contraction of lower extremity muscles and working intraluminal valves promote the forward flow of blood within veins. In venous insufficiency, reflux and/or obstruction in the superficial, perforator, or deep veins of the legs occurs, which leads to poor venous return to the heart. This increase in blood in the venous system results in venous hypertension, which if chronic can manifest as edema, pain, varicose veins, stasis dermatitis, ulcerations, and other cutaneous changes.12,13 At the cellular level, mast cells, leukocytes, matrix
metalloproteinase inhibitors, prostacyclins, and myofibroblasts create a proinflammatory microenvironment with eventual remodeling of vessel walls.13 Chronic inflammation combined with blood pooling in the lower limbs favors thrombus formation, fibrosis, and destruction of intraluminal valves. When all of these factors are present they impair proper healing and result in ulcer formation within chronic wounds.
The following are risk factors for venous insufficiency and the subsequent development of venous ulcers: advanced age, female sex, obesity, immobility, congenitally absent or incompetent valves, and history of either deep vein thrombosis or phlebitis.10,14 A cross-sectional study that enrolled 854 men and 1580 women found that age, family history of venous disease, and ligamentous laxity were the strongest risk factors for venous disease.15 In addition, prior lower limb injury in women and smoking in men were found to be correlated with severe disease.15
Clinically, venous ulcers typically affect the gaiter area of the legs, defined as the area between the mid-calf and ankle.13 The most common location is the medial malleolus.16 The wound normally appears as a shallow, well-defined ulcer with an irregular shape and a base of fibrin and granulation tissue.13,14 It is associated with moderate to heavy exudate, leg hyperpigmentation, edema, dull pain, and lipodermatosclerosis.14,16
When a biopsy is performed, tissue should be obtained from both the wound edge and the ulcer base. Histology of the epidermis shows spongiosis, marked epidermal hyperplasia, and abrupt transition from normal epidermis to ulceration (termed “step sign”).6 Dermal changes include the presence of diffuse edema, granulation tissue, collagen-bundle degeneration, fibrin, and hemosiderin-laden macrophages.6
CASE #2 Venous Ulcers
Approximately 60% to 80% of all lower extremity ulcers are caused by venous insufficiency.9,10 These ulcers can last for several years, especially with inadequate treatment, and have a high rate of recurrence. Chronic venous ulcers have been linked to pain, disability, depression, social isolation, and decreased quality of life.11 Venous ulcers also have significant financial implications as they account for approximately 2% to 3% of total health care expenditure in developed countries.11 It is estimated that between 1.5 and 3.0 in 1000 people have active leg ulcers.12 Although the prevalence and incidence of lower extremity ulcers with venous causes continue to be contested, 1 study found that the incidence of venous ulcers ranged from 0.5 to 1.0 cases per 1000 people between 2010 and 2014.9 The incidence of venous ulcers increases with age to approximately 20 in 1000 people older than 80 years.12 With baby boomers reaching older age, an estimated 10% of the population is expected to develop a chronic wound and 1% of the population will develop a venous leg ulcer at least once in their lifetime.9 Venous ulcers occur 3 times more
Risk factors for venous ulcers include advanced age, obesity, immobility, and history of deep vein thrombosis.
Dermatologic Look-Alikes
TABLE. Arterial Ulcers vs Venous Ulcers
Arterial Ulcers1-8
Dermatologic presentation • Small and round with smooth, demarcated borders and a “punched-out” appearance • Base of the ulcer is usually pale, may be gangrenous • No granulation tissue and typically no or minimal exudate are found • May have local hair loss, atrophy, slow capillary refill, decreased or absent peripheral pulses, decreased temperature, and pallor
Characteristic location • Distal leg, especially around the lateral malleoli • Pretibial and lateral leg • Dorsum of feet, toes, and bony protuberances
Epidemiology • ~25% of leg ulcers • Advanced POAD, which can lead to formation of arterial ulcers, occurs in 30%-40% of patients older than 60 years
Potential risk factors • Advanced age >60 years • Associated vasculitis • Cerebrovascular disease • Coronary artery disease • Diabetes mellitus • Family history of arterial disease • Hypercoagulability • Hyperlipidemia or dyslipidemia • Hyperhomocysteinemia • Hypertension • Hyperviscosity • Renal failure or insufficiency • Sedentary lifestyle • Smoking
Etiology • Atherosclerosis • Other forms of ischemia and impaired arterial flow, such as thrombosis or trauma • Venous hypertension
Histology • Epidermis: thinning and progressive necrosis • Dermis: sclerosis and thrombi in blood vessels • Epidermis: spongiosis, marked epidermal hyperplasia, and “step sign” • Dermis: diffuse edema, granulation tissue, collagen-bundle degeneration, fibrin, and hemosiderin-laden macrophages
Diagnosis
Treatment • History and physical examination • Arterial-brachial pressure index, toe-brachial pressure index, Doppler waveform changes • History and physical examination • Venous duplex ultrasonography and arterial-brachial pressure index may provide additional assistance
• Conservative debridement • Occlusive dressings • Pain control • Revascularization • Treat etiology and underlying contributing factors • Antibiotics, if needed • Compression therapy • Debridement • Dressing • Pentoxifylline
PAOD, peripheral arterial occlusive disease
Venous Ulcers6,9-16
• Shallow, exudative, well-defined ulcer with an irregular shape and a base of fibrin and granulation tissue • Associated with lipodermatosclerosis, skin hyperpigmentation, and edema
• Gaiter area • Medial > lateral malleolus
• 0.5%-1.0% of the population • 3 times more common in women compared with men
• Advanced age >65 years • Congenitally absent or incompetent valves • Family history of venous disease • Female sex • History of either deep vein thrombosis or phlebitis • Obesity
Although venous ulcers are the most common type of lower extremity ulceration, the differential diagnosis should include arterial ulcer, neuropathic ulcer, pressure ulcer, pyoderma gangrenosum, and malignancy.14 Arterial ulcers are typically caused by atherosclerosis and can be differentiated from venous ulcers with the ABI. Neuropathic ulcers are often a result of diabetes mellitus and are associated with peripheral neuropathy and foot deformities. Pressure ulcers are seen in dependent areas in patients with limited mobility. Pyoderma gangrenosum and malignancy should be suspected when the ulcer is not responding to standard treatment.14
Venous ulcers are diagnosed clinically, but noninvasive venous imaging with duplex ultrasonography demonstrating reflux and/or obstruction in the veins can confirm the diagnosis.9,14 Arterial pulse examination and ABI can also help differentiate venous ulcers from other diagnoses. Further evaluation with biopsy is warranted if the ulcer is not responsive to treatment or if there is suspicion of an alternate diagnosis.
Treatment of venous ulcers consists of compression therapy and direct wound management.13,14 Compression therapy is the standard of care for initial and long-term management of venous ulcers in patients without concomitant arterial disease. Leg elevation and exercise may also be beneficial in increasing venous flow and decreasing edema. Direct wound management consists of debridement, dressings, and medications. Treatment with pentoxifylline, a hemorrheologic agent that improves microcirculation and oxygenation, has been found to improve healing with or without compression therapy.13,14 Antibiotics are indicated when there is evidence of a superimposed infection. When suspected, tissue cultures are needed to guide antimicrobial therapy. Despite adequate treatment, only 20% of venous ulcers heal in less than 3 months.9
The patient in this case was diagnosed with venous ulcer confirmed via biopsy of the edge of the ulcer. He is being managed with wound care and compression therapy. ■
Briana Fernandez and Sidra Deen are medical students at Baylor College of Medicine in Houston, Texas; Carly Dunn, MD, and Tara L. Braun, MD, are resident physicians at Baylor College of Medicine.
References
1. Abbade LPF, Frade MAC, Pegas JRP, et al. Consensus on the diagnosis and management of chronic leg ulcers - Brazilian Society of Dermatology. An Bras Dermatol. 2020;95 Suppl 1(Suppl 1):1-18. 2. Hopf HW, Ueno C, Aslam R, et al. Guidelines for the prevention of lower extremity arterial ulcers. Wound Repair Regen. 2008;16(2):175-188. 3. Hess CT. Arterial ulcer checklist. Adv Skin Wound Care. 2010;23(9):432. 4. Federman DG, Ladiiznski B, Dardik A, et al. Wound Healing Society 2014 update on guidelines for arterial ulcers. Wound Repair Regen. 2016;24(1):127-135. 5. Kavros SJ, Coronado R. Diagnostic and therapeutic ultrasound on venous and arterial ulcers: a focused review. Adv Skin Wound Care. 2018;31(2):55-65. 6. Misciali C, Dika E, Baraldi C, et al. Vascular leg ulcers: histopathologic study of 293 patients. Am J Dermatopathol. 2014;36(12):977-983. 7. Horch RE, Horbach T, Lang W. The nutrient omentum free flap: revascularization with vein bypasses and greater omentum flap in severe arterial ulcers. J Vasc Surg. 2007;45(4):837-840. 8. Carbinatto FM, de Aquino AE Jr, Coelho VHM, Bagnato VS. Photonic technology for the treatments of venous and arterial ulcers: case report. Photodiagnosis Photodyn Ther. 2018;22:39-41. 9. Berenguer Pérez M, López-Casanova P, Sarabia Lavín R, González de la Torre H, Verdú-Soriano J. Epidemiology of venous leg ulcers in primary health care: Incidence and prevalence in a health centre — a time series study (2010-2014). Int Wound J. 2019;16(1):256-265. 10. Probst S, Weller CD, Bobbink P, et al. Prevalence and incidence of venous leg ulcers — a protocol for a systematic review. Syst Rev. 2021;10(1):148. 11. Finlayson K, Wu ML, Edwards HE. Identifying risk factors and protective factors for venous leg ulcer recurrence using a theoretical approach: a longitudinal study. Int J Nurs Stud. 2015;52(6):1042-1051. 12. Nelson EA, Adderley U. Venous leg ulcers. BMJ Clin Evid. 2016;2016:1902. 13. Robles-Tenorio A, Lev-Tov H, Ocampo-Candiani J. Venous leg ulcer. In: StatPearls. StatPearls Publishing; 2022 Apr 14. 14. Bonkemeyer Millan S, Gan R, Townsend PE. Venous ulcers: diagnosis and treatment. Am Fam Physician. 2019;100(5):298-305. 15. Criqui MH, Denenberg JO, Bergan J, Langer RD, Fronek A. Risk factors for chronic venous disease: the San Diego Population Study. J Vasc Surg. 2007;46(2):331-337. 16. Abbade LP, Lastória S, Rollo Hde A. Venous ulcer: clinical characteristics and risk factors. Int J Dermatol. 2011;50(4):405-411.
