Indications

 

FDA Approved Indications:
    venous ulcers
    diabetic foot ulcers
other indications:
   Healing excised burn wounds
   Healing acute excisional wounds from Mohs Micrographic Surgery
   Healing acute excisional wounds from squamous cell carcinoma removal
   Healing epidermolysis bullosa wounds:
   Treatment of ulcerated necrobiosis lipoidica:

 

FDA Approved Indications:

Apligraf is indicated for use along with standard compression therapy in the treatment of venous ulcers of at least 1 month in duration that have not adequately responded to conventional ulcer therapy. The bi-layered living skin equivalent is also indicated for for the treatment of full-thickness neuropathic diabetic foot ulcers of greater than three weeks duration, which extend through the dermis but without tendon, muscle, capsule or bone exposure.

Venous ulcers:

These ulcers occur as a direct consequence of a patient exhibiting venous disease of the leg. Venous ulcers also arise in a subset of those members of the population with varicose veins and chronic venous insufficiency (CVI). Nearly 7 million people in the United States suffer from chronic venous insufficiency, which can progress to venous leg ulceration. CVI arises from a variety of causes including deep vein thrombosis and same vein valve incompetence. The condition leads to venous hypertension, accumulation of fluid in pen-capillary tissues of the lower limb and diverse symptoms such as swelling, night cramps and paraesthesia. The unfortunate end consequence of these processes  is a venous ulcer of the leg. According to Dr. Glenn Davis, a plastic surgeon at Rex Healthcare, "such wounds often appear resistant to healing, produce copious amounts of exudate and require regular dressing changes." It is well documented that compression therapy utilizing bandages that give a graduated pressure from heel to knee is essential for healing to occur. Even with compression therapy, complete healing may take many weeks or months. 

For more information regarding venous leg ulcers and its pathophysiology, clinical features, and clinical management, please view this website: http://www.apligraf.com/content/woundfact_woundove r_aboutvlu.htm 

 

Diabetic foot ulcers:

These ulcers are a common complication for many patients suffering from diabetes. More hospital beds are occupied by patients with foot ulceration, than all other complications of diabetics combined. Diabetic foot ulceration is frequently the cause of amputation, and in some cases can prove life threatening due to infection or gangrene. Following ulceration, the incidence of amputation is 15 times higher in people with diabetes than non-diabetic individuals. Of those diabetic patients suffering from foot ulcers, approximately 10% require amputation. Two predisposing features contribute to the high incidence of amputation, namely - neuropathy and ischemia, both of which can lead to localized tissue trauma, subsequent breakdown, necrosis and infection. Diabetes itself is and increasing problem in all developed countries, and the incidence of diabetic ulcers is increasing on an annual basis. The incidence of diabetic ulcers per year is estimated at 800,000 in the United States. An effective treatment able to induce or augment tissue repair in non-healing wounds would contribute greatly to reducing complications, and improving quality of life in patients with diabetic ulcers and other dermal lesions.  

For more information regarding diabetic foot ulcers, please view this website: http://www.apligraf.com/content/woundfact_woundove r_aboutdfu.htm

 

Other Indications

Healing excised burn wounds:

In the United States alone, there are 100,000 hospital-treated burns per year and 600,000 cases of surgical skin excision, together costing an estimated $70 million per year. In light of the need for new biological agents for obtaining wound closure in burn patients, a trial evaluating the effectiveness of meshed Apligraf in burn patients was conducted (Waymack, Duff, et. al. Burn 26 (7): 2000. pp609-619). The objective of this trial was to determine the safety and effectiveness of Apligraf for providing overlay coverage of widely meshed autograft. Experimental treatment sites had Apligraf placed over meshed autograft while control sites were treated with meshed autograft covered with meshed allograft, or meshed autograft not covered by a biologic dressing. Forty patients were entered into this study of which 38 were evaluated. At the completion of the study 58% of the Apligraf sites were rated superior to the control sites by the investigators, 26% were rated equivalent to the control and 16% were rated worse than control (p=0.0037). In the Apligraf group, pigmentation was significantly better than control and by month 24, (45% Apligraf sites had normal pigmentation compared with 13% of control sites (p=0.0005). Similarly, by month 24, 47% of patients had normal vascularity at the Apligraf site compared with 16% of patients at the control site.

Vancouver Burn Scar Assessment. Vancouver burn scar assessment scores were based on clinical evaluations of graft pigmentation, vascularity, pliability, and height. Normal assessment of graft appearance resulted in a score of zero and the highest possible score when readings were a maximum on all four markers was 13 points. The results comparing Apligraf vs. control were analyzed by the paired t-test.

 

Healing acute excisional wounds from Mohs Micrographic Surgery:

Mohs micrographic surgery is now universally recognized as a precise method for treating skin cancers. It is especially effective in cancers of the face and other sensitive areas because it can eliminate virtually all the cancer cells while causing minimal damage to the surrounding normal skin. Mohs micrographic surgery is also ideal for the removal of recurrent skin cancers -- tumors that reappear after treatment and can plague a patient repeatedly. As a study by Eaglstein, Alvarez et. al. indicates, this surgery creates relatively deep skin wounds, which can be effectively treated with Apligraf (Eaglstein, Alvarez et. al. Dermatol Surg. 25:3:1999) . One hundred and seven patients participated in this study. The tissue-engineered skin was applied once, immediately after excisional surgery and patients were followed for up to one year. One such patient who underwent Mohs Micrographic surgery and subsequent Apligraf treatment is presented below.

Excision site immediately after surgery Day 7 after Apligraf application
3 months after Apligraf application

 

Healing acute excisional wounds from squamous cell carinoma removal:

Squamous cell carcinoma (SCC) is a malignant neoplasm of keratinocytes with many features, one of which is the production of keratin. Etiology, histology, and clinical presentations vary. SCC can be categorized histologically into in situ (intraepidermal) or invasive (penetrating the dermal-epidermal junction). Some examples of in situ SCC include Bowen's disease and erythroplasia of Queyrat (legion of the genitalia). SCC of the lip is one example of invasive carcinoma. Squamous cell carcinoma is the second most common skin cancer after basal cell carcinoma. It typically occurs on sun-exposed areas of the body and is more common in light-skinned men greater than 55 years. The incidence of SCC increases closer to the equator. Predisposing factors for SCC include a family history of skin cancer, precursor lip lesions from smoking, actinic keratosis, old burn scars, immunosuppression, ultraviolet radiation, radiation therapy, and chemical carcinogens such as soot and arsenic. The lesions progressively increase in size either rapidly over months or slowly over years. They typically are firm, skin-colored, occasionally red or yellow, papules, nodules, or plaques, that are smooth, verrucous, crusted, ulcerated, or hyperkeratotic, occurring in skin or on mucous membranes. Lesions on the lower lip, or in a scar, have up to a 20% probability of metastasizing. Lesions on sun-damaged skin have a 2% tendency to metastasize. Metastasis is primarily by way of the lymphatics, generally first to regional lymph nodes. Metastasis by hematogenous spread to distant sites can occur, most commonly to the brain, lungs, liver, bone, or skin. In situ Squamous Cell Carcinoma (Bowen's Disease): an intraepidermal or in situ squamous cell carcinoma. It appears as a slowly enlarging erythematous, well defined plaque usually slightly scaly and crusted. These lesions vary in size from a few millimeters to several centimeters. They are generally solitary and occur on either sun-exposed or sun-protected areas. As with other excisional wounds, these lesions can be healing using treatment with Apligraf ( Eaglstein, Alvarez et. al. Dermatol Surg. 25:3:1999). One such patient who had a squamous cell carcinoma removed and received Apligraf treatment is captured below

Day 0: Immediately after excision 1 week
3 months

 

Healing epidermolysis bullosa wounds:

Epidermolysis bullosa (EB) comprises a group of genetically determined skin fragility disorders characterized by blistering of the skin and mucosae following mild mechanical trauma (Pearson. Arch Dermatol.1988;124:718-725). Most forms of inherited EB are characterized by a lifetime of blister and wound formation. Although some forms of inherited EB are associated with normal longevity, several forms of severe inherited EB are associated with significant morbidity and increased mortality as either a direct or indirect result of the EB. Death may occur from the first days of life to the first 3 decades in severely affected patients. Death usually occurs because of infections in patients who are nutritionally compromised and anemic. There is no specific treatment for any form of EB, and the mainstay of clinical management is based on protection and avoidance of provoking factors. At present, wound treatment of inherited EB is only supportive. Unfortunately, these wounds tend to heal slowly and on some occasions fail to heal, becoming chronic wounds. There is a pressing need for an effective means to halt and possibly reverse the relentless progression toward chronic wound formation in some forms of the disease. A recent study conducted by Falabella and associates has revealed the efficacy of Apligraf in treating EB (Falabella, Valencia, et. al. Arch Dermatol. 26 (10): 2000). In this study, tissue-engineered skin was applied to the wounds of patients with EB. The tissue-engineered skin was not clinically rejected, has proven very safe, and most often induced rapid healing, indicating a potential role in the management of EB wounds.

Day 0: Two acute wounds on the foot of a patient with the Weber-Cockayne variant of epidermolysis bullosa simplex. Day 5: after treatment with Apligraf, there is apparent uniform graft take throughout both lesions. Week 6: the treated sites are outlined. They remained healed at the last clinic visit (week 18).

 

Treatment of ulcerated necrobiosis lipoidica:

"Necrobiosis lipoidica is a rare cutaneous complication of diabetes mellitus. The etiology is probably multifactorial with microangiopathy, immune complex formation, abnormal collagen synthesis and breakdown all thought to play a part." (Owen, Murphy, et. al. Clin Exper Derm. 26 (2): 2001. pp176-178). Unfortunately, necrobiosis lipoidica often proves very resistant to treatment. Nevertheless, Owen, Murphy et. al.  report a case of a 44-year-old woman with ulcerated necrobiosis lipoidica that healed following grafting with a tissue-engineered living skin tissue.

Presentation of ulcerated necrobiosis lipoidica Eighteen weeks after initial treatment with a living skin equivalent