What Caused These Leg Ulcers?
Patient Presentation
A middle-aged female presented for evaluation with a chief complaint of leg ulcers of 6 months duration. Her prior treatment included local wound care and topical antibiotic and antifungal agents. Physical examination revealed an overweight female with multiple ulcerations with erythematous borders and adjacent porcelain-white scars on the medial ankles bilaterally. Two-plus pitting edema of bilateral lower extremities was also present. Serologic evaluation did not reveal any laboratory abnormalities.
Diagnosis: Atrophie Blanche (Livedoid Vasculopathy)
In 1929, French physician Milian coined the term atrophie blanche when he used it to describe ivory-white stellate scars in syphilis patients. It was later introduced in English literature by Wilson and Nelson in the 1950s.1 Since then, the lack of standard terminology has caused significant confusion among dermatologists.1 Atrophie blanche is often used interchangeably with livedoid vasculitis, as well as livedo reticularis, segmental hyalinizing vasculitis, livedo vasculopathy, capillaritis alba, and PURPLE (painful purpuric ulcers with reticular pattern of the lower extremities).1
Clinical Features
Atrophie blanche (AB) is a clinical term used to describe smooth, ivory-white, round or stellate scars or plaques with peripheral telangiectasias that are usually found bilaterally on the legs, ankles, and dorsal feet.2 These atrophic scars are often preceded by purpuric macules and papules with surrounding livedoid reticularis as well as persistent, painful, punched-out ulcers.3 The prevalence of AB in the general population is between 1% and 5%,1 with a male-to-female ratio of 1:44,5 and peak incidence between 30 and 60 years.1 Approximately 9% to 38% of patients with chronic venous insufficiency were diagnosed with AB.1 Of the patients with atrophie blanche, 99% have chronic venous insufficiency.1 The lesions are more common during summer months and often undergo spontaneous remission during the winter.6
Differential Diagnosis
In atrophie blanche, the diagnosis is usually based on history and physical exam, although a biopsy can confirm clinical findings.7 The differential diagnosis is extensive and should include antiphospholipid syndrome, lichen sclerosis, malignant atrophic papulosis, scleroderma, pseudo-Kaposi syndrome, scar formation,8 sickle cell anemia ulcers, hydroxyurea-related ulceration and cutaneous polyarteritis nodosa.2 It is important to confirm a clinical history of the characteristic ulcers of AB to distinguish this condition from other disorders that can result in similar atrophic scarring.9
Disease Associations
Atrophie blanche has been associated with various medical conditions including venous insufficiency, deep venous thrombosis, rheumatoid arthritis, scleroderma, mixed connective tissues diseases, solid organ carcinomas (colon, pancreas, prostate), multiple myeloma, B-cell lymphoproliferative disease, cerebrovascular accidents,10 systemic lupus erythematosus;11 arterial insufficiency, polyarteritis nodosa, cryoglobulinemia, and chronic myelogenous leukemia.12
Pathogenesis
The pathogenesis of atrophie blanche is controversial and ambiguous. Most research suggests a combination of coagulation and fibrinolytic disruption related to venous insufficiency, although the cause of the initial insult is unknown.13
Multiple hypotheses have been proposed to explain the mechanism of AB, including fibrin-cuffs, white-cell trapping, and microthrombi.1 Browse’s “fibrin-cuff” theory14 suggests that as a result of chronic venous insufficiency, a fibrin-cuff is formed from leakage of fibrinogen from the capillaries. This fibrin-cuff serves as a barrier to oxygen and nutrients, as demonstrated by decreased transcutaneous oxygen measurements.15,16
The “white-cell trapping” theory implicates endothelium-adherent white cells in the presence of venous hypertension, which stimulates the release of destructive proteolytic enzymes and superoxide metabolites. Thirdly, Bollinger’s microthrombosis hypothesis17 proposes that AB is caused by minor skin infarctions due to microthrombi in the capillaries.14 This theory is based on microscopic evaluations of capillaries and an underlying dysfunctional coagulation and/or fibrinolytic cascade.
Other theories of AB pathogenesis include irregular endothelial function, platelet aggregation, enhanced fibrin formation, autoantibodies, infection, and vasculitis.1
Histology
A biopsy from an atrophie blanche scar may show an atrophic epidermis with local parakeratosis, focal spongiosis, and varying levels of melanocytes depending on the degree of hypopigmentation.5,18 The dermis appears sclerotic with dilated, swollen capillaries with torturous loops and thickened walls in the upper layer of the dermis.17 Fibrinoid deposits causing occlusion, pericapillary fibrin cuffing, and erythrocyte extravasation with hemosiderin deposition can also be present in AB, especially in the upper and middle layers of the dermis.17 Few polymorphonuclear leukocytes are present, helping distinguish AB from PMN-rich vasculitides.1
Treatment
Many treatments for atrophie blanche have been explored, beginning with anti-syphilis therapy, radiographs, fasciotomy, sympathectomy, acyclovir, and corticosteroids.1 Today, the cornerstone of treatment is compression therapy consisting of medical compression stockings, which have been shown to partially reverse the lesions of AB by providing elastic support.
Because 99% of AB patients have chronic venous insufficiency, reducing edema is an essential step toward recovery.1 In addition, three main categories of pharmaceutical treatment have also shown improvement: fibrinolytics, antiplatelet/ anticoagulants, and vasodilators.1
Fibrinolytics
Phenformin and ethylestrenol were initially shown to be effective by stimulating fibrinolysis and endogenous t-PA release.18 These drugs have since been replaced by tissue plasminogen activators (t-PA), which are being studied for their ability to lyse thrombi.19
Antiplatelets/Anticoagulants
Aside from compression therapy, this class of drugs have yielded the best results in the treatment of atrophie blanche. Varying levels of improvement have been demonstrated with the use of aspirin and dipyridamole in clinical trials.1 Administration of intravenous prostaglandin E1 to vasodilate and inhibit platelet aggregation or adding pentoxifylline to decrease blood viscosity has also been found to be helpful in the treatment of AB.1 Finally, heparin has been shown to inactivate the clotting cascade, lower the blood viscosity, and increase fibrinolytic activity, making it a desirable option.20
Vasodilators
The use of nifedipine and sulfasalazine have also been shown to provide clinical improvement in AB lesions through their dilatory effects.21
Intravenous Immunoglobulins
A study by Kreuter et al in 20046 examined the efficacy and safety of IVIg in patients with AB who were resistant to other treatment methods. IVIg was shown to improve erythema, pain, and help heal areas with active ulcerations. The mechanism is not completely understood but may work by altering cytokine production, inhibiting thromboxane synthetase and increasing in prostacyclin secretion.6,22 Unfortunately, IVIg is a very expensive treatment.
Lipoprostaglandin E1
In individuals with livedoid vasculitis and underlying essential cryoglobulin-emia, lipo-PGE1 in combination with low-dose oral corticosteroids has been found to provide rapid recovery in these patients.23 This treatment employs lectin liposome protection to prevent rapid destruction of PGE1.24
Hyperbaric Oxygen
Outpatient hyperbaric oxygen treatment has also been shown to be effective in treating various ischemic wound injuries and diabetic foot ulcers.1,25,26 By a similar mechanism of stimulating angiogenesis and fibrinolysis, inhibiting collagen formation, and reducing reperfusion injury, hyperbaric oxygen has also been successful in the treatment of refractory atrophie blanche.25
Other Treatment Options
Systemic psoralen plus ultraviolet A (PUVA) with methoxsalen was successful in two patients with atrophie blanche.27 Also, a clinical trial with the synthetic androgen, Danazol, was effective in seven patients most likely because of the drug’s fibrinolytic mechanism.28
Planned Treatment
Our patient was treated with topical Silvadene 1% cream applied to ulcerations twice daily and Grade II support hose (30 mm to 40 mm Hg). On follow-up her ulcerations healed and her pitting edema improved.
What Caused These Leg Ulcers?
Patient Presentation
A middle-aged female presented for evaluation with a chief complaint of leg ulcers of 6 months duration. Her prior treatment included local wound care and topical antibiotic and antifungal agents. Physical examination revealed an overweight female with multiple ulcerations with erythematous borders and adjacent porcelain-white scars on the medial ankles bilaterally. Two-plus pitting edema of bilateral lower extremities was also present. Serologic evaluation did not reveal any laboratory abnormalities.
Diagnosis: Atrophie Blanche (Livedoid Vasculopathy)
In 1929, French physician Milian coined the term atrophie blanche when he used it to describe ivory-white stellate scars in syphilis patients. It was later introduced in English literature by Wilson and Nelson in the 1950s.1 Since then, the lack of standard terminology has caused significant confusion among dermatologists.1 Atrophie blanche is often used interchangeably with livedoid vasculitis, as well as livedo reticularis, segmental hyalinizing vasculitis, livedo vasculopathy, capillaritis alba, and PURPLE (painful purpuric ulcers with reticular pattern of the lower extremities).1
Clinical Features
Atrophie blanche (AB) is a clinical term used to describe smooth, ivory-white, round or stellate scars or plaques with peripheral telangiectasias that are usually found bilaterally on the legs, ankles, and dorsal feet.2 These atrophic scars are often preceded by purpuric macules and papules with surrounding livedoid reticularis as well as persistent, painful, punched-out ulcers.3 The prevalence of AB in the general population is between 1% and 5%,1 with a male-to-female ratio of 1:44,5 and peak incidence between 30 and 60 years.1 Approximately 9% to 38% of patients with chronic venous insufficiency were diagnosed with AB.1 Of the patients with atrophie blanche, 99% have chronic venous insufficiency.1 The lesions are more common during summer months and often undergo spontaneous remission during the winter.6
Differential Diagnosis
In atrophie blanche, the diagnosis is usually based on history and physical exam, although a biopsy can confirm clinical findings.7 The differential diagnosis is extensive and should include antiphospholipid syndrome, lichen sclerosis, malignant atrophic papulosis, scleroderma, pseudo-Kaposi syndrome, scar formation,8 sickle cell anemia ulcers, hydroxyurea-related ulceration and cutaneous polyarteritis nodosa.2 It is important to confirm a clinical history of the characteristic ulcers of AB to distinguish this condition from other disorders that can result in similar atrophic scarring.9
Disease Associations
Atrophie blanche has been associated with various medical conditions including venous insufficiency, deep venous thrombosis, rheumatoid arthritis, scleroderma, mixed connective tissues diseases, solid organ carcinomas (colon, pancreas, prostate), multiple myeloma, B-cell lymphoproliferative disease, cerebrovascular accidents,10 systemic lupus erythematosus;11 arterial insufficiency, polyarteritis nodosa, cryoglobulinemia, and chronic myelogenous leukemia.12
Pathogenesis
The pathogenesis of atrophie blanche is controversial and ambiguous. Most research suggests a combination of coagulation and fibrinolytic disruption related to venous insufficiency, although the cause of the initial insult is unknown.13
Multiple hypotheses have been proposed to explain the mechanism of AB, including fibrin-cuffs, white-cell trapping, and microthrombi.1 Browse’s “fibrin-cuff” theory14 suggests that as a result of chronic venous insufficiency, a fibrin-cuff is formed from leakage of fibrinogen from the capillaries. This fibrin-cuff serves as a barrier to oxygen and nutrients, as demonstrated by decreased transcutaneous oxygen measurements.15,16
The “white-cell trapping” theory implicates endothelium-adherent white cells in the presence of venous hypertension, which stimulates the release of destructive proteolytic enzymes and superoxide metabolites. Thirdly, Bollinger’s microthrombosis hypothesis17 proposes that AB is caused by minor skin infarctions due to microthrombi in the capillaries.14 This theory is based on microscopic evaluations of capillaries and an underlying dysfunctional coagulation and/or fibrinolytic cascade.
Other theories of AB pathogenesis include irregular endothelial function, platelet aggregation, enhanced fibrin formation, autoantibodies, infection, and vasculitis.1
Histology
A biopsy from an atrophie blanche scar may show an atrophic epidermis with local parakeratosis, focal spongiosis, and varying levels of melanocytes depending on the degree of hypopigmentation.5,18 The dermis appears sclerotic with dilated, swollen capillaries with torturous loops and thickened walls in the upper layer of the dermis.17 Fibrinoid deposits causing occlusion, pericapillary fibrin cuffing, and erythrocyte extravasation with hemosiderin deposition can also be present in AB, especially in the upper and middle layers of the dermis.17 Few polymorphonuclear leukocytes are present, helping distinguish AB from PMN-rich vasculitides.1
Treatment
Many treatments for atrophie blanche have been explored, beginning with anti-syphilis therapy, radiographs, fasciotomy, sympathectomy, acyclovir, and corticosteroids.1 Today, the cornerstone of treatment is compression therapy consisting of medical compression stockings, which have been shown to partially reverse the lesions of AB by providing elastic support.
Because 99% of AB patients have chronic venous insufficiency, reducing edema is an essential step toward recovery.1 In addition, three main categories of pharmaceutical treatment have also shown improvement: fibrinolytics, antiplatelet/ anticoagulants, and vasodilators.1
Fibrinolytics
Phenformin and ethylestrenol were initially shown to be effective by stimulating fibrinolysis and endogenous t-PA release.18 These drugs have since been replaced by tissue plasminogen activators (t-PA), which are being studied for their ability to lyse thrombi.19
Antiplatelets/Anticoagulants
Aside from compression therapy, this class of drugs have yielded the best results in the treatment of atrophie blanche. Varying levels of improvement have been demonstrated with the use of aspirin and dipyridamole in clinical trials.1 Administration of intravenous prostaglandin E1 to vasodilate and inhibit platelet aggregation or adding pentoxifylline to decrease blood viscosity has also been found to be helpful in the treatment of AB.1 Finally, heparin has been shown to inactivate the clotting cascade, lower the blood viscosity, and increase fibrinolytic activity, making it a desirable option.20
Vasodilators
The use of nifedipine and sulfasalazine have also been shown to provide clinical improvement in AB lesions through their dilatory effects.21
Intravenous Immunoglobulins
A study by Kreuter et al in 20046 examined the efficacy and safety of IVIg in patients with AB who were resistant to other treatment methods. IVIg was shown to improve erythema, pain, and help heal areas with active ulcerations. The mechanism is not completely understood but may work by altering cytokine production, inhibiting thromboxane synthetase and increasing in prostacyclin secretion.6,22 Unfortunately, IVIg is a very expensive treatment.
Lipoprostaglandin E1
In individuals with livedoid vasculitis and underlying essential cryoglobulin-emia, lipo-PGE1 in combination with low-dose oral corticosteroids has been found to provide rapid recovery in these patients.23 This treatment employs lectin liposome protection to prevent rapid destruction of PGE1.24
Hyperbaric Oxygen
Outpatient hyperbaric oxygen treatment has also been shown to be effective in treating various ischemic wound injuries and diabetic foot ulcers.1,25,26 By a similar mechanism of stimulating angiogenesis and fibrinolysis, inhibiting collagen formation, and reducing reperfusion injury, hyperbaric oxygen has also been successful in the treatment of refractory atrophie blanche.25
Other Treatment Options
Systemic psoralen plus ultraviolet A (PUVA) with methoxsalen was successful in two patients with atrophie blanche.27 Also, a clinical trial with the synthetic androgen, Danazol, was effective in seven patients most likely because of the drug’s fibrinolytic mechanism.28
Planned Treatment
Our patient was treated with topical Silvadene 1% cream applied to ulcerations twice daily and Grade II support hose (30 mm to 40 mm Hg). On follow-up her ulcerations healed and her pitting edema improved.
What Caused These Leg Ulcers?
Patient Presentation
A middle-aged female presented for evaluation with a chief complaint of leg ulcers of 6 months duration. Her prior treatment included local wound care and topical antibiotic and antifungal agents. Physical examination revealed an overweight female with multiple ulcerations with erythematous borders and adjacent porcelain-white scars on the medial ankles bilaterally. Two-plus pitting edema of bilateral lower extremities was also present. Serologic evaluation did not reveal any laboratory abnormalities.
Diagnosis: Atrophie Blanche (Livedoid Vasculopathy)
In 1929, French physician Milian coined the term atrophie blanche when he used it to describe ivory-white stellate scars in syphilis patients. It was later introduced in English literature by Wilson and Nelson in the 1950s.1 Since then, the lack of standard terminology has caused significant confusion among dermatologists.1 Atrophie blanche is often used interchangeably with livedoid vasculitis, as well as livedo reticularis, segmental hyalinizing vasculitis, livedo vasculopathy, capillaritis alba, and PURPLE (painful purpuric ulcers with reticular pattern of the lower extremities).1
Clinical Features
Atrophie blanche (AB) is a clinical term used to describe smooth, ivory-white, round or stellate scars or plaques with peripheral telangiectasias that are usually found bilaterally on the legs, ankles, and dorsal feet.2 These atrophic scars are often preceded by purpuric macules and papules with surrounding livedoid reticularis as well as persistent, painful, punched-out ulcers.3 The prevalence of AB in the general population is between 1% and 5%,1 with a male-to-female ratio of 1:44,5 and peak incidence between 30 and 60 years.1 Approximately 9% to 38% of patients with chronic venous insufficiency were diagnosed with AB.1 Of the patients with atrophie blanche, 99% have chronic venous insufficiency.1 The lesions are more common during summer months and often undergo spontaneous remission during the winter.6
Differential Diagnosis
In atrophie blanche, the diagnosis is usually based on history and physical exam, although a biopsy can confirm clinical findings.7 The differential diagnosis is extensive and should include antiphospholipid syndrome, lichen sclerosis, malignant atrophic papulosis, scleroderma, pseudo-Kaposi syndrome, scar formation,8 sickle cell anemia ulcers, hydroxyurea-related ulceration and cutaneous polyarteritis nodosa.2 It is important to confirm a clinical history of the characteristic ulcers of AB to distinguish this condition from other disorders that can result in similar atrophic scarring.9
Disease Associations
Atrophie blanche has been associated with various medical conditions including venous insufficiency, deep venous thrombosis, rheumatoid arthritis, scleroderma, mixed connective tissues diseases, solid organ carcinomas (colon, pancreas, prostate), multiple myeloma, B-cell lymphoproliferative disease, cerebrovascular accidents,10 systemic lupus erythematosus;11 arterial insufficiency, polyarteritis nodosa, cryoglobulinemia, and chronic myelogenous leukemia.12
Pathogenesis
The pathogenesis of atrophie blanche is controversial and ambiguous. Most research suggests a combination of coagulation and fibrinolytic disruption related to venous insufficiency, although the cause of the initial insult is unknown.13
Multiple hypotheses have been proposed to explain the mechanism of AB, including fibrin-cuffs, white-cell trapping, and microthrombi.1 Browse’s “fibrin-cuff” theory14 suggests that as a result of chronic venous insufficiency, a fibrin-cuff is formed from leakage of fibrinogen from the capillaries. This fibrin-cuff serves as a barrier to oxygen and nutrients, as demonstrated by decreased transcutaneous oxygen measurements.15,16
The “white-cell trapping” theory implicates endothelium-adherent white cells in the presence of venous hypertension, which stimulates the release of destructive proteolytic enzymes and superoxide metabolites. Thirdly, Bollinger’s microthrombosis hypothesis17 proposes that AB is caused by minor skin infarctions due to microthrombi in the capillaries.14 This theory is based on microscopic evaluations of capillaries and an underlying dysfunctional coagulation and/or fibrinolytic cascade.
Other theories of AB pathogenesis include irregular endothelial function, platelet aggregation, enhanced fibrin formation, autoantibodies, infection, and vasculitis.1
Histology
A biopsy from an atrophie blanche scar may show an atrophic epidermis with local parakeratosis, focal spongiosis, and varying levels of melanocytes depending on the degree of hypopigmentation.5,18 The dermis appears sclerotic with dilated, swollen capillaries with torturous loops and thickened walls in the upper layer of the dermis.17 Fibrinoid deposits causing occlusion, pericapillary fibrin cuffing, and erythrocyte extravasation with hemosiderin deposition can also be present in AB, especially in the upper and middle layers of the dermis.17 Few polymorphonuclear leukocytes are present, helping distinguish AB from PMN-rich vasculitides.1
Treatment
Many treatments for atrophie blanche have been explored, beginning with anti-syphilis therapy, radiographs, fasciotomy, sympathectomy, acyclovir, and corticosteroids.1 Today, the cornerstone of treatment is compression therapy consisting of medical compression stockings, which have been shown to partially reverse the lesions of AB by providing elastic support.
Because 99% of AB patients have chronic venous insufficiency, reducing edema is an essential step toward recovery.1 In addition, three main categories of pharmaceutical treatment have also shown improvement: fibrinolytics, antiplatelet/ anticoagulants, and vasodilators.1
Fibrinolytics
Phenformin and ethylestrenol were initially shown to be effective by stimulating fibrinolysis and endogenous t-PA release.18 These drugs have since been replaced by tissue plasminogen activators (t-PA), which are being studied for their ability to lyse thrombi.19
Antiplatelets/Anticoagulants
Aside from compression therapy, this class of drugs have yielded the best results in the treatment of atrophie blanche. Varying levels of improvement have been demonstrated with the use of aspirin and dipyridamole in clinical trials.1 Administration of intravenous prostaglandin E1 to vasodilate and inhibit platelet aggregation or adding pentoxifylline to decrease blood viscosity has also been found to be helpful in the treatment of AB.1 Finally, heparin has been shown to inactivate the clotting cascade, lower the blood viscosity, and increase fibrinolytic activity, making it a desirable option.20
Vasodilators
The use of nifedipine and sulfasalazine have also been shown to provide clinical improvement in AB lesions through their dilatory effects.21
Intravenous Immunoglobulins
A study by Kreuter et al in 20046 examined the efficacy and safety of IVIg in patients with AB who were resistant to other treatment methods. IVIg was shown to improve erythema, pain, and help heal areas with active ulcerations. The mechanism is not completely understood but may work by altering cytokine production, inhibiting thromboxane synthetase and increasing in prostacyclin secretion.6,22 Unfortunately, IVIg is a very expensive treatment.
Lipoprostaglandin E1
In individuals with livedoid vasculitis and underlying essential cryoglobulin-emia, lipo-PGE1 in combination with low-dose oral corticosteroids has been found to provide rapid recovery in these patients.23 This treatment employs lectin liposome protection to prevent rapid destruction of PGE1.24
Hyperbaric Oxygen
Outpatient hyperbaric oxygen treatment has also been shown to be effective in treating various ischemic wound injuries and diabetic foot ulcers.1,25,26 By a similar mechanism of stimulating angiogenesis and fibrinolysis, inhibiting collagen formation, and reducing reperfusion injury, hyperbaric oxygen has also been successful in the treatment of refractory atrophie blanche.25
Other Treatment Options
Systemic psoralen plus ultraviolet A (PUVA) with methoxsalen was successful in two patients with atrophie blanche.27 Also, a clinical trial with the synthetic androgen, Danazol, was effective in seven patients most likely because of the drug’s fibrinolytic mechanism.28
Planned Treatment
Our patient was treated with topical Silvadene 1% cream applied to ulcerations twice daily and Grade II support hose (30 mm to 40 mm Hg). On follow-up her ulcerations healed and her pitting edema improved.
