Chronic venous insufficiency and venous leg ulceration.

UNLABELLED: Venous ulcers are the most common form of leg ulcers. Venous disease has a significant impact on quality of life and work productivity. In addition, the costs associated with the long-term care of these chronic wounds are substantial. Although the exact pathogenic steps leading from venous hypertension to venous ulceration remain unclear, several hypotheses have been developed to explain the development of venous ulceration. A better understanding of the current pathophysiology of venous ulceration has led to the development of new approaches in its management. New types of wound dressings, topical and systemic therapeutic agents, surgical modalities, bioengineered tissue, matrix materials, and growth factors are all novel therapeutic options that may be used in addition to the "gold standard," compression therapy, for venous ulcers. This review discusses current aspects of the epidemiology, pathophysiology, clinical presentation, diagnostic assessment, and current therapeutic options for chronic venous insufficiency and venous ulceration. (J Am Acad Dermatol 2001;44:401-21.) LEARNING OBJECTIVE: At the conclusion of this learning activity, participants should be familiar with the 3 main types of lower extremity ulcers and should improve their understanding of the epidemiology, pathogenesis, risk factors, clinical presentation, diagnostic assessment, and current therapies for chronic venous insufficiency and venous ulcers.

Tissue-engineered skin (Apligraf) in the healing of patients with epidermolysis bullosa wounds.

BACKGROUND: At present, wound treatment of inherited epidermolysis bullosa (EB) is only supportive. OBJECTIVE: To determine the safety and clinical effects of tissue-engineered skin (Apligraf; Organogenesis Inc, Canton, Mass) in the healing of wounds of patients with different types of EB. DESIGN: An open-label uncontrolled study of 15 patients with EB treated with tissue-engineered skin. Each patient received tissue-engineered skin on up to 2 wounds on each of 3 clinic visits: day 1, week 6, and week 12. They were evaluated 7 (+/- 3) days and 6 weeks after each round of treatment. A quality-of-life survey was administered during week 6. SETTING: University of Miami, Miami, Fla. PATIENTS: Volunteers with EB. MAIN OUTCOME MEASURE: Safety and wound healing. RESULTS: A total of 69 different acute wounds received tissue-engineered skin at the day-1 (24 wounds), week-6 (23 wounds), and week-12 (22 wounds) visits. Overall, 63 wounds (79%) were found healed at the day-7 visit. Of the acute wounds, 82% (51/62) were healed 6 weeks after being treated, 75% (27/36) after 12 weeks, and 79% (11/14) after 18 weeks. Nine chronic wounds were also treated. Four were healed at 6 weeks; however, 7 were still open at the last clinic visit (week 18). There were no signs of rejection or clinical infection and no adverse events related to the tissue-engineered skin. The quality of life for most patients improved after treatment. Compared with patients' recollection of wounds treated with standard dressings, healing was faster and less painful. CONCLUSION: In this series of patients, tissue-engineered skin induced very rapid healing, was not clinically rejected, and was devoid of adverse effects. It was felt by the patients and families to be more effective than conventional dressings for EB wounds.

Skin grafting.

No longer an option of last resort, skin grafting has become a technique that is routinely and sometimes preferentially considered as skin replacement for burns, chronic ulcers, and skin defects after cutaneous surgical procedures. When selected as the best alternative for wound closure, autologous skin grafts are commonly considered the gold standard. Availability of autologous grafts is a major obstacle, however, and the search for a manufactured skin replacement has continued. In cases in which autologous grafts cannot be performed, skin substitutes have become an attractive alternative.

The use of tissue-engineered skin (Apligraf) to treat a newborn with epidermolysis bullosa.

BACKGROUND: Inherited epidermolysis bullosa (EB) is a mechanobullous disorder. The Dowling-Meara variant, a subtype of EB, is characterized by widespread blister formation that may include the oral cavity and nails. Many patients with the Dowling-Meara phenotype are at increased risk of sepsis and death during infancy. The treatment of EB is generally supportive. The tissue-engineered skin used (Apligraf) is a bilayered human skin equivalent developed from foreskin. It is the only Food and Drug Administration-approved skin equivalent of its kind. It is approved for the treatment of venous ulcers of the lower extremities. It has also been used to treat acute wounds, such as graft donor sites and cancer excision sites. OBSERVATION: To our knowledge, we describe the first case in which a newborn with EB, Dowling-Meara variant, was treated with bilayered tissue-engineered skin. The areas treated with the tissue-engineered skin healed faster than the areas treated with conventional therapy. Most of the areas treated with tissue-engineered skin have remained healed, without developing new blisters. These areas appear to be more resistant to trauma. CONCLUSIONS: Our early success with tissue-engineered skin in this patient may have a significant impact on the future treatment of neonates with EB simplex. Future studies are needed to determine if the beneficial effects of tissue-engineered skin are reproducible in other neonates with EB simplex and in patients of all ages with different subtypes of EB.

Eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy.

OBJECTIVE: To characterize the epidemiological, clinical, and histopathological features of patients with cancer who develop widespread polymorphic and pruritic skin lesions following radiotherapy. PATIENTS, DESIGN, AND INTERVENTIONS: During phase 1, epidemiological and clinical features of 103 patients with cancer, 83 treated with radiotherapy (71 women and 12 men) and 20 controls who did not undergo radiotherapy (16 women and 4 men), were explored during 3 months (October 1995 to January 1996). During phase 2, in 30 additional patients with cancer who were treated with telecobalt or linear accelerator, 18 with skin lesions (15 women and 3 men) and 12 without lesions (10 women and 2 men), the following were investigated: (1) hematoxylin-eosin-stained sections for routine histopathological examination and direct immunofluorescence, and lymphocytic markers; (2) blood, skin, and primary tumor eosinophilia; and (3) the presence of antiepidermal autoantibodies. Patients were examined during 5 months (February 1996 to June 1996). SETTING: A dermatology department at a university hospital. RESULTS: During phase 1, 14 (17%) of the 83 patients undergoing radiotherapy developed an eruption. Acral excoriations, erythematous papules, vesicles, and bullae were the most frequent lesions. During phase 2, in 18 patients, a superficial and deep lymphocytic perivascular infiltrate with numerous eosinophils, intraepidermal and interstitial eosinophilic infiltrates, eosinophilic panniculitis, IgM and C3 perivascular deposits, and slightly predominant CD4+ cells were observed. No antiepidermal autoantibodies were found. CONCLUSIONS: The clinical, histopathological, and immunopathologic features in patients with cancer undergoing radiotherapy are described. To our knowledge, this condition has not been well characterized. Because of its unique presentation, the denomination "eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy" is suggested.

Multicentric reticulohistiocytosis associated with recurrent breast carcinoma.

Multicentric reticulohistiocytosis (MRH) is a rare systemic disorder that most often affects women in the fourth to fifth decades of life and is characterized by widespread cutaneous papules and nodules, often associated with a destructive arthritis. The characteristic histologic feature of the skin lesions, and of other affected organs, is the presence of histiocytes and multinucleated giant cells containing abundant eosinophilic cytoplasm with a "ground glass appearance." Approximately 30% of the patients have an underlying malignancy suggesting MRH may be a paraneoplastic phenomenon. We describe a case of MRH associated with recurrent, metastatic breast carcinoma.