Wounds

NEW ORLEANS – Topical dapsone is a novel and effective treatment for atrophie blanche ulcerations.

Atrophie blanche (also known as livedoid vasculopathy) is a therapeutic challenge. The etiology of this chronic and painful condition is unclear. The current standard care, which consists of low-dose aspirin, pentoxifylline, pain medications, and conservative wound dressings, has a suboptimal success rate in reducing pain and healing the ulcers, Dr. Erik Maus observed at the annual meeting of the American Academy of Dermatology.

He reported on 10 patients with biopsy-confirmed – and/or clinical findings consistent with – atrophie blanche, all of whom had failed to respond adequately to conventional measures. At the Memorial Hermann Center for Wound Healing at the University of Texas, Houston, they were placed on dapsone gel 5% (Aczone) twice daily, usually in conjunction with compression stockings or compression bandages when edema or venous stasis was present. The clinical results were impressive, according to Dr. Maus of the university.

One patient quickly discontinued topical dapsone after reporting feeling vaguely ill. Of the nine patients who continued on the drug, seven (78%) experienced rapid and steady cutaneous healing and reduced pain; their longstanding wounds closed in 6-20 weeks.

Patients described the topical therapy as easy to use. No one reported discomfort in applying dapsone gel to open wounds.

One patient relapsed when she ran out of the medication. Healing resumed when she restarted treatment.

Dapsone gel's likely mechanism of action in atrophie blanche involves inhibition of neutrophilic migration to the ulcerated sites, Dr. Maus speculated.

Atrophie blanche is characterized by painful, persistent ulcerations of the ankle and dorsal surface of the foot. The condition affects mainly young to middle-aged women. Areas of healed ulceration are marked by ivory-colored atrophic scars surrounded by sclerotic skin with hyperpigmentation and peripheral telangiectasias. Although altered local or systemic control of coagulation is believed to play a role in some cases, the etiology of atrophie blanche often remains obscure.

This study was conducted without corporate sponsorship. Dr. Maus declared having no relevant financial interests.

NEW ORLEANS – Topical dapsone is a novel and effective treatment for atrophie blanche ulcerations.

Atrophie blanche (also known as livedoid vasculopathy) is a therapeutic challenge. The etiology of this chronic and painful condition is unclear. The current standard care, which consists of low-dose aspirin, pentoxifylline, pain medications, and conservative wound dressings, has a suboptimal success rate in reducing pain and healing the ulcers, Dr. Erik Maus observed at the annual meeting of the American Academy of Dermatology.

He reported on 10 patients with biopsy-confirmed – and/or clinical findings consistent with – atrophie blanche, all of whom had failed to respond adequately to conventional measures. At the Memorial Hermann Center for Wound Healing at the University of Texas, Houston, they were placed on dapsone gel 5% (Aczone) twice daily, usually in conjunction with compression stockings or compression bandages when edema or venous stasis was present. The clinical results were impressive, according to Dr. Maus of the university.

One patient quickly discontinued topical dapsone after reporting feeling vaguely ill. Of the nine patients who continued on the drug, seven (78%) experienced rapid and steady cutaneous healing and reduced pain; their longstanding wounds closed in 6-20 weeks.

Patients described the topical therapy as easy to use. No one reported discomfort in applying dapsone gel to open wounds.

One patient relapsed when she ran out of the medication. Healing resumed when she restarted treatment.

Dapsone gel's likely mechanism of action in atrophie blanche involves inhibition of neutrophilic migration to the ulcerated sites, Dr. Maus speculated.

Atrophie blanche is characterized by painful, persistent ulcerations of the ankle and dorsal surface of the foot. The condition affects mainly young to middle-aged women. Areas of healed ulceration are marked by ivory-colored atrophic scars surrounded by sclerotic skin with hyperpigmentation and peripheral telangiectasias. Although altered local or systemic control of coagulation is believed to play a role in some cases, the etiology of atrophie blanche often remains obscure.

This study was conducted without corporate sponsorship. Dr. Maus declared having no relevant financial interests.

NEW ORLEANS – Topical dapsone is a novel and effective treatment for atrophie blanche ulcerations.

Atrophie blanche (also known as livedoid vasculopathy) is a therapeutic challenge. The etiology of this chronic and painful condition is unclear. The current standard care, which consists of low-dose aspirin, pentoxifylline, pain medications, and conservative wound dressings, has a suboptimal success rate in reducing pain and healing the ulcers, Dr. Erik Maus observed at the annual meeting of the American Academy of Dermatology.

He reported on 10 patients with biopsy-confirmed – and/or clinical findings consistent with – atrophie blanche, all of whom had failed to respond adequately to conventional measures. At the Memorial Hermann Center for Wound Healing at the University of Texas, Houston, they were placed on dapsone gel 5% (Aczone) twice daily, usually in conjunction with compression stockings or compression bandages when edema or venous stasis was present. The clinical results were impressive, according to Dr. Maus of the university.

One patient quickly discontinued topical dapsone after reporting feeling vaguely ill. Of the nine patients who continued on the drug, seven (78%) experienced rapid and steady cutaneous healing and reduced pain; their longstanding wounds closed in 6-20 weeks.

Patients described the topical therapy as easy to use. No one reported discomfort in applying dapsone gel to open wounds.

One patient relapsed when she ran out of the medication. Healing resumed when she restarted treatment.

Dapsone gel's likely mechanism of action in atrophie blanche involves inhibition of neutrophilic migration to the ulcerated sites, Dr. Maus speculated.

Atrophie blanche is characterized by painful, persistent ulcerations of the ankle and dorsal surface of the foot. The condition affects mainly young to middle-aged women. Areas of healed ulceration are marked by ivory-colored atrophic scars surrounded by sclerotic skin with hyperpigmentation and peripheral telangiectasias. Although altered local or systemic control of coagulation is believed to play a role in some cases, the etiology of atrophie blanche often remains obscure.

This study was conducted without corporate sponsorship. Dr. Maus declared having no relevant financial interests.

NEW ORLEANS - The epidemiology of occupational skin disorders may be undergoing substantial change, results of a large new study suggest.

Historically, dermatologic disorders have accounted for 10%-15% of all workplace injuries, and contact dermatitis represented more than 90% of all workers' compensation claims for occupational skin disorders. But results of a new study conducted in a large, multisite occupational medicine program contradict both of these historical findings, Dr. Nita Kohli reported at the annual meeting of the American Academy of Dermatology.

The study included approximately 147,000 patients who were seen at Kaiser Permanente occupational medicine clinics located throughout Southern California during 2004-2008. Skin disorders accounted for just 1% of all workplace injuries, not the 10%-15% previously reported by other investigators. And burns – not contact dermatitis – made up the largest category of dermatologic claims.

Indeed, burns accounted for 65% of all workers' compensation cases involving skin disorders, compared with contact dermatitis (20%), infections (9%), bites (4%), and "unspecified" (2%).

About 90% of occupational dermatologic disorders among food workers were burns. In addition, burns accounted for the majority of skin injuries in all other occupational classes (including office jobs), with the sole exception of personal care jobs, in which burns were slightly outnumbered by cases of dermatitis, according to Dr. Kohli of the University of California, Los Angeles.

The occupational skin disorders caseload consisted of equal numbers of women and men. The average time to the first clinic visit was 12.1 days. Construction and production workers averaged 4.3 clinic visits per claim, compared with transportation workers (3.5), food workers (3.4), cleaning personnel (3.2), and health care workers (2.9).

The hands were the most frequently affected body part.

Burns resulted in an average of 4.3 lost workdays, compared with infections (4.2) and contact dermatitis (2.3). On average, patients lost 3.1 workdays because of their occupational skin disorder. Construction workers missed an average of 8.1 days of work, more than twice as many as did workers in any other occupational category.

The average treatment duration for patients with an occupational skin disorder was 33.5 days; contact dermatitis entailed by far the greatest average treatment length (53 days).

Dr. Kohli declared having no relevant financial disclosures.

NEW ORLEANS - The epidemiology of occupational skin disorders may be undergoing substantial change, results of a large new study suggest.

Historically, dermatologic disorders have accounted for 10%-15% of all workplace injuries, and contact dermatitis represented more than 90% of all workers' compensation claims for occupational skin disorders. But results of a new study conducted in a large, multisite occupational medicine program contradict both of these historical findings, Dr. Nita Kohli reported at the annual meeting of the American Academy of Dermatology.

The study included approximately 147,000 patients who were seen at Kaiser Permanente occupational medicine clinics located throughout Southern California during 2004-2008. Skin disorders accounted for just 1% of all workplace injuries, not the 10%-15% previously reported by other investigators. And burns – not contact dermatitis – made up the largest category of dermatologic claims.

Indeed, burns accounted for 65% of all workers' compensation cases involving skin disorders, compared with contact dermatitis (20%), infections (9%), bites (4%), and "unspecified" (2%).

About 90% of occupational dermatologic disorders among food workers were burns. In addition, burns accounted for the majority of skin injuries in all other occupational classes (including office jobs), with the sole exception of personal care jobs, in which burns were slightly outnumbered by cases of dermatitis, according to Dr. Kohli of the University of California, Los Angeles.

The occupational skin disorders caseload consisted of equal numbers of women and men. The average time to the first clinic visit was 12.1 days. Construction and production workers averaged 4.3 clinic visits per claim, compared with transportation workers (3.5), food workers (3.4), cleaning personnel (3.2), and health care workers (2.9).

The hands were the most frequently affected body part.

Burns resulted in an average of 4.3 lost workdays, compared with infections (4.2) and contact dermatitis (2.3). On average, patients lost 3.1 workdays because of their occupational skin disorder. Construction workers missed an average of 8.1 days of work, more than twice as many as did workers in any other occupational category.

The average treatment duration for patients with an occupational skin disorder was 33.5 days; contact dermatitis entailed by far the greatest average treatment length (53 days).

Dr. Kohli declared having no relevant financial disclosures.

NEW ORLEANS - The epidemiology of occupational skin disorders may be undergoing substantial change, results of a large new study suggest.

Historically, dermatologic disorders have accounted for 10%-15% of all workplace injuries, and contact dermatitis represented more than 90% of all workers' compensation claims for occupational skin disorders. But results of a new study conducted in a large, multisite occupational medicine program contradict both of these historical findings, Dr. Nita Kohli reported at the annual meeting of the American Academy of Dermatology.

The study included approximately 147,000 patients who were seen at Kaiser Permanente occupational medicine clinics located throughout Southern California during 2004-2008. Skin disorders accounted for just 1% of all workplace injuries, not the 10%-15% previously reported by other investigators. And burns – not contact dermatitis – made up the largest category of dermatologic claims.

Indeed, burns accounted for 65% of all workers' compensation cases involving skin disorders, compared with contact dermatitis (20%), infections (9%), bites (4%), and "unspecified" (2%).

About 90% of occupational dermatologic disorders among food workers were burns. In addition, burns accounted for the majority of skin injuries in all other occupational classes (including office jobs), with the sole exception of personal care jobs, in which burns were slightly outnumbered by cases of dermatitis, according to Dr. Kohli of the University of California, Los Angeles.

The occupational skin disorders caseload consisted of equal numbers of women and men. The average time to the first clinic visit was 12.1 days. Construction and production workers averaged 4.3 clinic visits per claim, compared with transportation workers (3.5), food workers (3.4), cleaning personnel (3.2), and health care workers (2.9).

The hands were the most frequently affected body part.

Burns resulted in an average of 4.3 lost workdays, compared with infections (4.2) and contact dermatitis (2.3). On average, patients lost 3.1 workdays because of their occupational skin disorder. Construction workers missed an average of 8.1 days of work, more than twice as many as did workers in any other occupational category.

The average treatment duration for patients with an occupational skin disorder was 33.5 days; contact dermatitis entailed by far the greatest average treatment length (53 days).

Dr. Kohli declared having no relevant financial disclosures.

NEW ORLEANS - Their presentation can be alarming, even for dermatologists accustomed to seeing all kinds of adverse skin manifestations. Widespread necrosis, skin detachment, erythema, large bullae, and more are seen in patients with the life-threatening drug eruption, toxic epidermal necrolysis.

Medical management with intravenous immunoglobulin and a focus on supportive care save lives at the University of Miami, a toxic epidermal necrolysis (TEN) referral center.

Photo courtesy Dr. Carlos Ricotti

"The survival rate is extremely low for this set of patients," Dr. Carlos A. Ricotti said at the annual meeting of the American Academy of Dermatology. But "the outcome at the University of Miami is very good. We see these patients, and we have a good understanding they are going to leave the hospital well."

Medical management is swift and comprehensive. "Assume there will be fluid loss, possible infection, impaired thermal regulation, altered immunity, and increased energy expenditure," Dr. Ricotti said. "Each of these has to be addressed."

In addition, despite a clinical appearance similar to that of burns, recognize that patients with TEN differ from burn patients in important ways, said Dr. Ricotti, who is on the dermatology staff at the University of Miami Hospital. TEN patients typically feature less edema, minimal vascular damage, and less damage to regenerative tissue, leading to faster re-epithelialization, compared with burn patients. "The rate of healing is much faster."

The hospital's dermatologic medical management of TEN begins with withdrawal of offending medication. Because patients present with a burning sensation, pain control is essential to achieve comfort and to decrease their movement during recovery.

Photo courtesy Dr. Carlos Ricotti

Think in terms of "acute skin failure" when providing supportive care, Dr. Ricotti said. Consider medical ICU or a burn unit admission; an air mattress with pressure ulcer prophylaxis; nonstick sheets and heating blankets; and maintenance of room temperature at 30° C.

"We don't do debridement," Dr. Ricotti said. Pathology reveals that the entire dermis is not necrotic. The remaining viable tissue can act as a natural biologic dressing that may retake as a graft. "This speeds re-epithelialization ... and we believe this speeds recovery of the patient."

By day 6-10 of admission, most of the skin erosions re-epithelialize (as opposed to second-degree burns, which can take 14 days or longer). Because of this rapid tissue regeneration, patients require high caloric intake, which can include total parenteral nutrition or feeding via a nasogastric tube.

Strict fluid monitoring is essential, Dr. Ricotti said. "We feel very strongly about [fluid management]. We feel this plays an important role in our excellent outcomes." They typically administer IV fluids with half normal saline and 20 mEq KCl. Fluids in and out are monitored with a urine output goal of 40-80 mL/hr.

"We know that in TEN, there is potential for alveolar/epithelial barrier alteration due to the systemic nature of the disease," Dr. Ricotti said. "Our working hypothesis is that by decreasing fluid overload, we can minimize pulmonary involvement and improve outcomes." He recommended reading the results of a prospective clinical trial for more insight into the management of pulmonary complications (Intensive Care Med. 1997;23:1237-44).

Not only is intravenous immunoglobulin (IVIG) therapy important, the total dose makes a difference, Dr. Ricotti said. Survival increases significantly with each 1-g/kg increase in IVIG dose (odds ratio 4.2), according to a review article (Expert Rev. Dermatol. 2007;2:299-303).

A typical IVIG protocol at the hospital is 1 g/kg per day for 4 days, Dr. Ricotti said in response to a meeting attendee’s question. "The higher the dosage, the better the outcome." Although IVIG is essential, so is treatment at a center of excellence with special expertise in treating patients with drug eruptions.

TEN know-how also is important, he said, because "with its low incidence, it's difficult to perform large, multicenter prospective trials."

Infections can occur. Cutaneous infection, pneumonia, and subsequent life-threatening sepsis are well-recognized complications of TEN. However, "we refrain from using empiric antibiotic therapy," Dr. Ricotti said.

They do routinely provide anticoagulation prophylaxis with heparin to prevent deep vein thrombosis, gastrointestinal prophylaxis with proton pump inhibitors, and eye care with tobramycin and dexamethasone.

TEN is relatively rare, with an estimated incidence of 1 person per million per year. Even so, "we see drug eruptions all the time in inpatient units," Dr. Ricotti said.

In addition to TEN (classified as "with spots" or "without spots" by extent of skin involvement), other drug eruptions include erythema multiforme major, Stevens-Johnson syndrome (SJS), and patients who have an overlap of SJS and TEN. Consider staphylococcal scalded skin syndrome and TEN with drug hypersensitivity syndrome in your differential diagnosis, he added.

Dr. Ricotti said he had no relevant disclosures.

NEW ORLEANS - Their presentation can be alarming, even for dermatologists accustomed to seeing all kinds of adverse skin manifestations. Widespread necrosis, skin detachment, erythema, large bullae, and more are seen in patients with the life-threatening drug eruption, toxic epidermal necrolysis.

Medical management with intravenous immunoglobulin and a focus on supportive care save lives at the University of Miami, a toxic epidermal necrolysis (TEN) referral center.

Photo courtesy Dr. Carlos Ricotti

"The survival rate is extremely low for this set of patients," Dr. Carlos A. Ricotti said at the annual meeting of the American Academy of Dermatology. But "the outcome at the University of Miami is very good. We see these patients, and we have a good understanding they are going to leave the hospital well."

Medical management is swift and comprehensive. "Assume there will be fluid loss, possible infection, impaired thermal regulation, altered immunity, and increased energy expenditure," Dr. Ricotti said. "Each of these has to be addressed."

In addition, despite a clinical appearance similar to that of burns, recognize that patients with TEN differ from burn patients in important ways, said Dr. Ricotti, who is on the dermatology staff at the University of Miami Hospital. TEN patients typically feature less edema, minimal vascular damage, and less damage to regenerative tissue, leading to faster re-epithelialization, compared with burn patients. "The rate of healing is much faster."

The hospital's dermatologic medical management of TEN begins with withdrawal of offending medication. Because patients present with a burning sensation, pain control is essential to achieve comfort and to decrease their movement during recovery.

Photo courtesy Dr. Carlos Ricotti

Think in terms of "acute skin failure" when providing supportive care, Dr. Ricotti said. Consider medical ICU or a burn unit admission; an air mattress with pressure ulcer prophylaxis; nonstick sheets and heating blankets; and maintenance of room temperature at 30° C.

"We don't do debridement," Dr. Ricotti said. Pathology reveals that the entire dermis is not necrotic. The remaining viable tissue can act as a natural biologic dressing that may retake as a graft. "This speeds re-epithelialization ... and we believe this speeds recovery of the patient."

By day 6-10 of admission, most of the skin erosions re-epithelialize (as opposed to second-degree burns, which can take 14 days or longer). Because of this rapid tissue regeneration, patients require high caloric intake, which can include total parenteral nutrition or feeding via a nasogastric tube.

Strict fluid monitoring is essential, Dr. Ricotti said. "We feel very strongly about [fluid management]. We feel this plays an important role in our excellent outcomes." They typically administer IV fluids with half normal saline and 20 mEq KCl. Fluids in and out are monitored with a urine output goal of 40-80 mL/hr.

"We know that in TEN, there is potential for alveolar/epithelial barrier alteration due to the systemic nature of the disease," Dr. Ricotti said. "Our working hypothesis is that by decreasing fluid overload, we can minimize pulmonary involvement and improve outcomes." He recommended reading the results of a prospective clinical trial for more insight into the management of pulmonary complications (Intensive Care Med. 1997;23:1237-44).

Not only is intravenous immunoglobulin (IVIG) therapy important, the total dose makes a difference, Dr. Ricotti said. Survival increases significantly with each 1-g/kg increase in IVIG dose (odds ratio 4.2), according to a review article (Expert Rev. Dermatol. 2007;2:299-303).

A typical IVIG protocol at the hospital is 1 g/kg per day for 4 days, Dr. Ricotti said in response to a meeting attendee’s question. "The higher the dosage, the better the outcome." Although IVIG is essential, so is treatment at a center of excellence with special expertise in treating patients with drug eruptions.

TEN know-how also is important, he said, because "with its low incidence, it's difficult to perform large, multicenter prospective trials."

Infections can occur. Cutaneous infection, pneumonia, and subsequent life-threatening sepsis are well-recognized complications of TEN. However, "we refrain from using empiric antibiotic therapy," Dr. Ricotti said.

They do routinely provide anticoagulation prophylaxis with heparin to prevent deep vein thrombosis, gastrointestinal prophylaxis with proton pump inhibitors, and eye care with tobramycin and dexamethasone.

TEN is relatively rare, with an estimated incidence of 1 person per million per year. Even so, "we see drug eruptions all the time in inpatient units," Dr. Ricotti said.

In addition to TEN (classified as "with spots" or "without spots" by extent of skin involvement), other drug eruptions include erythema multiforme major, Stevens-Johnson syndrome (SJS), and patients who have an overlap of SJS and TEN. Consider staphylococcal scalded skin syndrome and TEN with drug hypersensitivity syndrome in your differential diagnosis, he added.

Dr. Ricotti said he had no relevant disclosures.

NEW ORLEANS - Their presentation can be alarming, even for dermatologists accustomed to seeing all kinds of adverse skin manifestations. Widespread necrosis, skin detachment, erythema, large bullae, and more are seen in patients with the life-threatening drug eruption, toxic epidermal necrolysis.

Medical management with intravenous immunoglobulin and a focus on supportive care save lives at the University of Miami, a toxic epidermal necrolysis (TEN) referral center.

Photo courtesy Dr. Carlos Ricotti

"The survival rate is extremely low for this set of patients," Dr. Carlos A. Ricotti said at the annual meeting of the American Academy of Dermatology. But "the outcome at the University of Miami is very good. We see these patients, and we have a good understanding they are going to leave the hospital well."

Medical management is swift and comprehensive. "Assume there will be fluid loss, possible infection, impaired thermal regulation, altered immunity, and increased energy expenditure," Dr. Ricotti said. "Each of these has to be addressed."

In addition, despite a clinical appearance similar to that of burns, recognize that patients with TEN differ from burn patients in important ways, said Dr. Ricotti, who is on the dermatology staff at the University of Miami Hospital. TEN patients typically feature less edema, minimal vascular damage, and less damage to regenerative tissue, leading to faster re-epithelialization, compared with burn patients. "The rate of healing is much faster."

The hospital's dermatologic medical management of TEN begins with withdrawal of offending medication. Because patients present with a burning sensation, pain control is essential to achieve comfort and to decrease their movement during recovery.

Photo courtesy Dr. Carlos Ricotti

Think in terms of "acute skin failure" when providing supportive care, Dr. Ricotti said. Consider medical ICU or a burn unit admission; an air mattress with pressure ulcer prophylaxis; nonstick sheets and heating blankets; and maintenance of room temperature at 30° C.

"We don't do debridement," Dr. Ricotti said. Pathology reveals that the entire dermis is not necrotic. The remaining viable tissue can act as a natural biologic dressing that may retake as a graft. "This speeds re-epithelialization ... and we believe this speeds recovery of the patient."

By day 6-10 of admission, most of the skin erosions re-epithelialize (as opposed to second-degree burns, which can take 14 days or longer). Because of this rapid tissue regeneration, patients require high caloric intake, which can include total parenteral nutrition or feeding via a nasogastric tube.

Strict fluid monitoring is essential, Dr. Ricotti said. "We feel very strongly about [fluid management]. We feel this plays an important role in our excellent outcomes." They typically administer IV fluids with half normal saline and 20 mEq KCl. Fluids in and out are monitored with a urine output goal of 40-80 mL/hr.

"We know that in TEN, there is potential for alveolar/epithelial barrier alteration due to the systemic nature of the disease," Dr. Ricotti said. "Our working hypothesis is that by decreasing fluid overload, we can minimize pulmonary involvement and improve outcomes." He recommended reading the results of a prospective clinical trial for more insight into the management of pulmonary complications (Intensive Care Med. 1997;23:1237-44).

Not only is intravenous immunoglobulin (IVIG) therapy important, the total dose makes a difference, Dr. Ricotti said. Survival increases significantly with each 1-g/kg increase in IVIG dose (odds ratio 4.2), according to a review article (Expert Rev. Dermatol. 2007;2:299-303).

A typical IVIG protocol at the hospital is 1 g/kg per day for 4 days, Dr. Ricotti said in response to a meeting attendee’s question. "The higher the dosage, the better the outcome." Although IVIG is essential, so is treatment at a center of excellence with special expertise in treating patients with drug eruptions.

TEN know-how also is important, he said, because "with its low incidence, it's difficult to perform large, multicenter prospective trials."

Infections can occur. Cutaneous infection, pneumonia, and subsequent life-threatening sepsis are well-recognized complications of TEN. However, "we refrain from using empiric antibiotic therapy," Dr. Ricotti said.

They do routinely provide anticoagulation prophylaxis with heparin to prevent deep vein thrombosis, gastrointestinal prophylaxis with proton pump inhibitors, and eye care with tobramycin and dexamethasone.

TEN is relatively rare, with an estimated incidence of 1 person per million per year. Even so, "we see drug eruptions all the time in inpatient units," Dr. Ricotti said.

In addition to TEN (classified as "with spots" or "without spots" by extent of skin involvement), other drug eruptions include erythema multiforme major, Stevens-Johnson syndrome (SJS), and patients who have an overlap of SJS and TEN. Consider staphylococcal scalded skin syndrome and TEN with drug hypersensitivity syndrome in your differential diagnosis, he added.

Dr. Ricotti said he had no relevant disclosures.

SAN DIEGO – Administering enoxaparin to patients with acute burn injuries at a dosage of less than 30 mg every 12 hours often leads to subtherapeutic anti-Xa levels that are associated with an increase in risk of venous thromboembolism, according to results from a single-center study.

The finding suggests that enoxaparin dosing should be individualized for this patient population, Hsin Lin, Pharm.D., said in an interview during a poster session at the annual congress of the Society of Critical Care Medicine. "Most of the published enoxaparin dosing regimens we see are not for burn patients," said Dr. Lin, a pharmacist at the University of Utah Burn Trauma Center, Salt Lake City. "Burn patients are hypermetabolic. One dose does not fit everyone."

Dr. Lin and her associates evaluated the effectiveness of a protocol for graduated enoxaparin dosing with concurrent monitoring to achieve a peak anti-Xa level of 0.2-0.4 U/mL in 84 patients with acute burn injuries who received venous thromboembolism (VTE) prophylaxis with an initial dosage of 30 mg subcutaneously twice daily. They adjusted the dosages until patients obtained therapeutic levels or until they were discharged. About 1 month later, the patients were interviewed by telephone to determine if any VTE events had occurred.

The median age of patients was 39 years, their median body mass index was 27 kg/m2, and their injuries covered a median of 15% of body surface area.

Of the 84 patients, 64 showed initial anti-Xa levels below target (0.2 U/mL), and their enoxaparin dosage was then increased. In 15 patients, the target anti-Xa level was never reached before discharge. Of 69 patients who had appropriate anti-Xa levels, 1 had a deep vein thrombosis during the hospital stay, 1 developed pulmonary embolism 1 month after discharge, 2 died of non-VTE causes, and 5 were unable to be reached by telephone.

There were no episodes of abnormal hemorrhage, thrombocytopenia, or heparin allergy documented.

Dr. Lin reported that the median final enoxaparin dosage required to achieve therapeutic anti-Xa levels was 40 mg every 12 hours, ranging from 20 to 70 mg. Linear regression analysis revealed that the final enoxaparin dosage correlated with total body surface area and weight.

"Enoxaparin dose adjustment was associated with a low incidence of VTE events, and there was no hemorrhagic bleeding–related complication," Dr. Lin said. "In patients with acute burn injury, routine monitoring of anti-Xa levels is recommended."

Dr. Lin said that she had no relevant financial disclosures to make.

SAN DIEGO – Administering enoxaparin to patients with acute burn injuries at a dosage of less than 30 mg every 12 hours often leads to subtherapeutic anti-Xa levels that are associated with an increase in risk of venous thromboembolism, according to results from a single-center study.

The finding suggests that enoxaparin dosing should be individualized for this patient population, Hsin Lin, Pharm.D., said in an interview during a poster session at the annual congress of the Society of Critical Care Medicine. "Most of the published enoxaparin dosing regimens we see are not for burn patients," said Dr. Lin, a pharmacist at the University of Utah Burn Trauma Center, Salt Lake City. "Burn patients are hypermetabolic. One dose does not fit everyone."

Dr. Lin and her associates evaluated the effectiveness of a protocol for graduated enoxaparin dosing with concurrent monitoring to achieve a peak anti-Xa level of 0.2-0.4 U/mL in 84 patients with acute burn injuries who received venous thromboembolism (VTE) prophylaxis with an initial dosage of 30 mg subcutaneously twice daily. They adjusted the dosages until patients obtained therapeutic levels or until they were discharged. About 1 month later, the patients were interviewed by telephone to determine if any VTE events had occurred.

The median age of patients was 39 years, their median body mass index was 27 kg/m2, and their injuries covered a median of 15% of body surface area.

Of the 84 patients, 64 showed initial anti-Xa levels below target (0.2 U/mL), and their enoxaparin dosage was then increased. In 15 patients, the target anti-Xa level was never reached before discharge. Of 69 patients who had appropriate anti-Xa levels, 1 had a deep vein thrombosis during the hospital stay, 1 developed pulmonary embolism 1 month after discharge, 2 died of non-VTE causes, and 5 were unable to be reached by telephone.

There were no episodes of abnormal hemorrhage, thrombocytopenia, or heparin allergy documented.

Dr. Lin reported that the median final enoxaparin dosage required to achieve therapeutic anti-Xa levels was 40 mg every 12 hours, ranging from 20 to 70 mg. Linear regression analysis revealed that the final enoxaparin dosage correlated with total body surface area and weight.

"Enoxaparin dose adjustment was associated with a low incidence of VTE events, and there was no hemorrhagic bleeding–related complication," Dr. Lin said. "In patients with acute burn injury, routine monitoring of anti-Xa levels is recommended."

Dr. Lin said that she had no relevant financial disclosures to make.

SAN DIEGO – Administering enoxaparin to patients with acute burn injuries at a dosage of less than 30 mg every 12 hours often leads to subtherapeutic anti-Xa levels that are associated with an increase in risk of venous thromboembolism, according to results from a single-center study.

The finding suggests that enoxaparin dosing should be individualized for this patient population, Hsin Lin, Pharm.D., said in an interview during a poster session at the annual congress of the Society of Critical Care Medicine. "Most of the published enoxaparin dosing regimens we see are not for burn patients," said Dr. Lin, a pharmacist at the University of Utah Burn Trauma Center, Salt Lake City. "Burn patients are hypermetabolic. One dose does not fit everyone."

Dr. Lin and her associates evaluated the effectiveness of a protocol for graduated enoxaparin dosing with concurrent monitoring to achieve a peak anti-Xa level of 0.2-0.4 U/mL in 84 patients with acute burn injuries who received venous thromboembolism (VTE) prophylaxis with an initial dosage of 30 mg subcutaneously twice daily. They adjusted the dosages until patients obtained therapeutic levels or until they were discharged. About 1 month later, the patients were interviewed by telephone to determine if any VTE events had occurred.

The median age of patients was 39 years, their median body mass index was 27 kg/m2, and their injuries covered a median of 15% of body surface area.

Of the 84 patients, 64 showed initial anti-Xa levels below target (0.2 U/mL), and their enoxaparin dosage was then increased. In 15 patients, the target anti-Xa level was never reached before discharge. Of 69 patients who had appropriate anti-Xa levels, 1 had a deep vein thrombosis during the hospital stay, 1 developed pulmonary embolism 1 month after discharge, 2 died of non-VTE causes, and 5 were unable to be reached by telephone.

There were no episodes of abnormal hemorrhage, thrombocytopenia, or heparin allergy documented.

Dr. Lin reported that the median final enoxaparin dosage required to achieve therapeutic anti-Xa levels was 40 mg every 12 hours, ranging from 20 to 70 mg. Linear regression analysis revealed that the final enoxaparin dosage correlated with total body surface area and weight.

"Enoxaparin dose adjustment was associated with a low incidence of VTE events, and there was no hemorrhagic bleeding–related complication," Dr. Lin said. "In patients with acute burn injury, routine monitoring of anti-Xa levels is recommended."

Dr. Lin said that she had no relevant financial disclosures to make.

The Infectious Diseases Society of America rolled out its first-ever guidelines for treating methicillin-resistant Staphylococcus aureus – including recommendations to battle the growing threat posed by MRSA-related skin and soft-tissue infections.

The comprehensive guidelines also outline evidence-based approaches on topics ranging from personal hygiene and wound care to antibiotic therapies for invasive MRSA, as well as options after vancomycin treatment failure.

The guidelines' primary objective is "to provide recommendations on the management of some of the most common clinical syndromes encountered by adult and pediatric clinicians who care for patients with MRSA infections," according to the executive summary, published online Jan. 5 (Clin. Infect. Dis. 2010 [doi:10.1093/cid/ciq146]).

The guidelines provide adult and pediatric clinicians with guidance on how to treat relatively uncomplicated MRSA infections, as well as more serious infections, according to Dr. Catherine Liu, the guidelines' lead author and assistant clinical professor in the division of infectious diseases, University of California, San Francisco. The recommendations cover community- and hospital-associated MRSA infections, she added.

MRSA infections account for about 60% of skin infections seen in U.S. emergency departments, and invasive MRSA infections cause about 18,000 deaths a year, according to the Infectious Diseases Society of America (IDSA).

The evidence-based guidelines, which will be published in the Feb. 1 issue of Clinical Infectious Diseases, have been endorsed by the Pediatric Infectious Diseases Society, the American College of Emergency Physicians, and the American Academy of Pediatrics.

The guidelines are voluntary and "are not intended to take the place of a doctor's judgment, but rather support the decision-making process, which must be individualized according to each patient's circumstances," according to a statement issued by IDSA, which funded the guidelines.

A 13-member expert panel reviewed hundreds of scientific studies, papers, and presentations to create the recommendations. The guidelines' sections start with a clinical question, followed by a numbered list of recommendations and a summary of the most relevant evidence to support the recommendations. In most cases, the sections include information on pediatric considerations. The guidelines also highlight areas that are controversial because of limited or conflicting data.

The first topic addressed is the management of skin and soft tissue infections due to MRSA, which have become a significant problem in the past few years, Dr. Liu said in an interview. For example, MRSA is now the predominant organism causing skin infections in patients who present to emergency departments with skin infections, she noted.

The guidelines cover multiple types of skin infections, including abscesses, cellulitis, and more complicated skin infections. The guidelines also offer recommendations on the role of antibiotics, including whether or not they need to be used, situations in which they may not be indicated, and when they definitely should be used. They also offer guidance " on specific types of antibiotic choices that clinicians should consider," Dr. Liu noted.

Other topics covered include the management of MRSA pneumonia, bacteremia, and infective endocarditis; central nervous system infections; and bone and joint infections. Additional sections review the role of adjunctive therapies in the treatment of MRSA infections, MRSA infections in neonates, and specific recommendations on vancomycin dosing and monitoring.

IDSA will update the guidelines as more information and newer antibiotics become available. However, timely updating can be difficult because of the review and publication process, Dr. Liu noted.

For example, the Food and Drug Administration approved the intravenous cephalosporin antibiotic ceftaroline in October 2010 for acute bacterial skin and soft tissue infections, including cases caused by MRSA. But approval came after the IDSA guidelines were finalized, and that information was not included. Nonetheless, the guidelines note that ceftaroline "may become available in the near future for the treatment" of complicated skin and skin structure infections, Dr. Liu said.

The guidelines do not address active surveillance testing or other strategies aimed at preventing MRSA in health care settings, topics that have been addressed in previously released guidelines.

IDSA funded the development of the guidelines. Of the expert panel's 13 members, 9 reported having potential conflicts of interest that included honoraria or research support from, or having served as a consultant or adviser to, pharmaceutical companies, including Astellas, Cubist Pharmaceutical, Forest, Merck, Ortho-McNeil, Pfizer, Sanofi-Aventis, Schering-Plough, and Theravance. The remaining authors of the guidelines, including the lead author, Dr. Catherine Liu, reported no conflicts.

The Infectious Diseases Society of America rolled out its first-ever guidelines for treating methicillin-resistant Staphylococcus aureus – including recommendations to battle the growing threat posed by MRSA-related skin and soft-tissue infections.

The comprehensive guidelines also outline evidence-based approaches on topics ranging from personal hygiene and wound care to antibiotic therapies for invasive MRSA, as well as options after vancomycin treatment failure.

The guidelines' primary objective is "to provide recommendations on the management of some of the most common clinical syndromes encountered by adult and pediatric clinicians who care for patients with MRSA infections," according to the executive summary, published online Jan. 5 (Clin. Infect. Dis. 2010 [doi:10.1093/cid/ciq146]).

The guidelines provide adult and pediatric clinicians with guidance on how to treat relatively uncomplicated MRSA infections, as well as more serious infections, according to Dr. Catherine Liu, the guidelines' lead author and assistant clinical professor in the division of infectious diseases, University of California, San Francisco. The recommendations cover community- and hospital-associated MRSA infections, she added.

MRSA infections account for about 60% of skin infections seen in U.S. emergency departments, and invasive MRSA infections cause about 18,000 deaths a year, according to the Infectious Diseases Society of America (IDSA).

The evidence-based guidelines, which will be published in the Feb. 1 issue of Clinical Infectious Diseases, have been endorsed by the Pediatric Infectious Diseases Society, the American College of Emergency Physicians, and the American Academy of Pediatrics.

The guidelines are voluntary and "are not intended to take the place of a doctor's judgment, but rather support the decision-making process, which must be individualized according to each patient's circumstances," according to a statement issued by IDSA, which funded the guidelines.

A 13-member expert panel reviewed hundreds of scientific studies, papers, and presentations to create the recommendations. The guidelines' sections start with a clinical question, followed by a numbered list of recommendations and a summary of the most relevant evidence to support the recommendations. In most cases, the sections include information on pediatric considerations. The guidelines also highlight areas that are controversial because of limited or conflicting data.

The first topic addressed is the management of skin and soft tissue infections due to MRSA, which have become a significant problem in the past few years, Dr. Liu said in an interview. For example, MRSA is now the predominant organism causing skin infections in patients who present to emergency departments with skin infections, she noted.

The guidelines cover multiple types of skin infections, including abscesses, cellulitis, and more complicated skin infections. The guidelines also offer recommendations on the role of antibiotics, including whether or not they need to be used, situations in which they may not be indicated, and when they definitely should be used. They also offer guidance " on specific types of antibiotic choices that clinicians should consider," Dr. Liu noted.

Other topics covered include the management of MRSA pneumonia, bacteremia, and infective endocarditis; central nervous system infections; and bone and joint infections. Additional sections review the role of adjunctive therapies in the treatment of MRSA infections, MRSA infections in neonates, and specific recommendations on vancomycin dosing and monitoring.

IDSA will update the guidelines as more information and newer antibiotics become available. However, timely updating can be difficult because of the review and publication process, Dr. Liu noted.

For example, the Food and Drug Administration approved the intravenous cephalosporin antibiotic ceftaroline in October 2010 for acute bacterial skin and soft tissue infections, including cases caused by MRSA. But approval came after the IDSA guidelines were finalized, and that information was not included. Nonetheless, the guidelines note that ceftaroline "may become available in the near future for the treatment" of complicated skin and skin structure infections, Dr. Liu said.

The guidelines do not address active surveillance testing or other strategies aimed at preventing MRSA in health care settings, topics that have been addressed in previously released guidelines.

IDSA funded the development of the guidelines. Of the expert panel's 13 members, 9 reported having potential conflicts of interest that included honoraria or research support from, or having served as a consultant or adviser to, pharmaceutical companies, including Astellas, Cubist Pharmaceutical, Forest, Merck, Ortho-McNeil, Pfizer, Sanofi-Aventis, Schering-Plough, and Theravance. The remaining authors of the guidelines, including the lead author, Dr. Catherine Liu, reported no conflicts.

The Infectious Diseases Society of America rolled out its first-ever guidelines for treating methicillin-resistant Staphylococcus aureus – including recommendations to battle the growing threat posed by MRSA-related skin and soft-tissue infections.

The comprehensive guidelines also outline evidence-based approaches on topics ranging from personal hygiene and wound care to antibiotic therapies for invasive MRSA, as well as options after vancomycin treatment failure.

The guidelines' primary objective is "to provide recommendations on the management of some of the most common clinical syndromes encountered by adult and pediatric clinicians who care for patients with MRSA infections," according to the executive summary, published online Jan. 5 (Clin. Infect. Dis. 2010 [doi:10.1093/cid/ciq146]).

The guidelines provide adult and pediatric clinicians with guidance on how to treat relatively uncomplicated MRSA infections, as well as more serious infections, according to Dr. Catherine Liu, the guidelines' lead author and assistant clinical professor in the division of infectious diseases, University of California, San Francisco. The recommendations cover community- and hospital-associated MRSA infections, she added.

MRSA infections account for about 60% of skin infections seen in U.S. emergency departments, and invasive MRSA infections cause about 18,000 deaths a year, according to the Infectious Diseases Society of America (IDSA).

The evidence-based guidelines, which will be published in the Feb. 1 issue of Clinical Infectious Diseases, have been endorsed by the Pediatric Infectious Diseases Society, the American College of Emergency Physicians, and the American Academy of Pediatrics.

The guidelines are voluntary and "are not intended to take the place of a doctor's judgment, but rather support the decision-making process, which must be individualized according to each patient's circumstances," according to a statement issued by IDSA, which funded the guidelines.

A 13-member expert panel reviewed hundreds of scientific studies, papers, and presentations to create the recommendations. The guidelines' sections start with a clinical question, followed by a numbered list of recommendations and a summary of the most relevant evidence to support the recommendations. In most cases, the sections include information on pediatric considerations. The guidelines also highlight areas that are controversial because of limited or conflicting data.

The first topic addressed is the management of skin and soft tissue infections due to MRSA, which have become a significant problem in the past few years, Dr. Liu said in an interview. For example, MRSA is now the predominant organism causing skin infections in patients who present to emergency departments with skin infections, she noted.

The guidelines cover multiple types of skin infections, including abscesses, cellulitis, and more complicated skin infections. The guidelines also offer recommendations on the role of antibiotics, including whether or not they need to be used, situations in which they may not be indicated, and when they definitely should be used. They also offer guidance " on specific types of antibiotic choices that clinicians should consider," Dr. Liu noted.

Other topics covered include the management of MRSA pneumonia, bacteremia, and infective endocarditis; central nervous system infections; and bone and joint infections. Additional sections review the role of adjunctive therapies in the treatment of MRSA infections, MRSA infections in neonates, and specific recommendations on vancomycin dosing and monitoring.

IDSA will update the guidelines as more information and newer antibiotics become available. However, timely updating can be difficult because of the review and publication process, Dr. Liu noted.

For example, the Food and Drug Administration approved the intravenous cephalosporin antibiotic ceftaroline in October 2010 for acute bacterial skin and soft tissue infections, including cases caused by MRSA. But approval came after the IDSA guidelines were finalized, and that information was not included. Nonetheless, the guidelines note that ceftaroline "may become available in the near future for the treatment" of complicated skin and skin structure infections, Dr. Liu said.

The guidelines do not address active surveillance testing or other strategies aimed at preventing MRSA in health care settings, topics that have been addressed in previously released guidelines.

IDSA funded the development of the guidelines. Of the expert panel's 13 members, 9 reported having potential conflicts of interest that included honoraria or research support from, or having served as a consultant or adviser to, pharmaceutical companies, including Astellas, Cubist Pharmaceutical, Forest, Merck, Ortho-McNeil, Pfizer, Sanofi-Aventis, Schering-Plough, and Theravance. The remaining authors of the guidelines, including the lead author, Dr. Catherine Liu, reported no conflicts.

CHICAGO – Want to learn more about liposuction in Indonesia? Want to teach your cryosurgery technique to dermatologists in Greece? Want to help physicians in the Philippines perform fat transfer?

You can. Dermatologic surgeons in the United States now have more opportunities to travel, teach, and learn surgical techniques from colleagues in other countries, thanks to a unique collaboration that expands the International Mentorship Program and the International Preceptorship Program.

Photo courtesy Dr. Lawrence M. Field

Earlier this year, Dr. Lawrence M. Field, traveling chair of the International Society for Dermatologic Surgery (ISDS) International Mentorship Program, donated $100,000 to the American Society for Dermatologic Surgeons (ASDS) to establish the Lawrence M. Field MD International Dermatologic Surgery Educational Exchange Fund.

"Dr. Field's donation will allow us to have two preceptorships, a fellowship here in the U.S. and [another] for what Dr. Field has been doing sending fellows to other countries," Dr. Jeffrey S. Dover, ASDS president, said at their annual meeting where the collaboration was announced.

Dr. Field is a "dermatologic surgeon, teacher, and benefactor. He has taught mostly hands-on in more than 60 countries," added ISDS president Dr. Gary J. Brauner.

The ISDS has run the mentorship program since 1986. Additional staffing and other resources provided by the ASDS will significantly expand its reach, said Dr. Field, who is in private practice in San Luis Obispo, Calif.

Photo courtesy Dr. Lawrence M. Field

According to Dr. Field, the program has about 70 mentors from 19 nations.* The program continues to expand and is actively seeking host institutions around the world to work with the faculty. The ASDS/ISDS program is for established dermatologic surgeons and not residents.

Special language skills are a plus but not mandatory, Dr. Field said. In addition, there are no ethnic, cultural, religious or any other exclusions, only mutual acceptability is required.

The ASDS/ISDS program pays the airfare. All mentors, including Dr. Field, offer their expertise free of charge. "Pick me up at the airport; take me to a reasonably nice place; provide me with food, clothing, and shelter; licensure; and surgical scrubs," Dr. Field said, describing his requests to a host institution when he travels. In exchange, "I will give you everything I can ... from me to you, for nothing. Then take me back to the airport, I'll go home, and I'll remember these things forever."

A week commitment is the minimum, Dr. Field said. "You gain knowledge, experience, enjoyment, and the respect of your peers."

Photo courtesy Dr. Lawrence M. Field

In his nearly 25 years as a traveling mentor, Dr. Field has taught and learned about scar revision in the Philippines, cryosurgery in Heraklion, Greece, and fat transfer in Saudi Arabia.**  As a consultant to the DermaClinic, Dr. Field shared his expertise to transfer fat from a patient's abdomen to treat her facial atrophy.

Dr. Field praised the accomplishments of the many dermatologic surgeons who participated as ISDS international mentors. For example, Dr. John Strasswimmer, a dermatologic surgeon in Delray Beach, Fla. has treated albino patients in Africa. "Many great things will happen from that," Dr. Field said.

Another mentor, Dr. Rhoda Narins, worked with Dr. Indah Julianto to get permission from the Minister of Health in Indonesia to perform liposuction. "This program is just forming in Jakarta, Indonesia, so some of you might go there," Dr. Field said.

Dr. Field spent 31 years as a preceptor in his private office for dermatologic surgery fellows at University of California, San Francisco. During this time, he also

hosted international surgeons who, unlike the U.S. physicians, could not participate in hands-on training because of licensure requirements. This disparity led to the genesis of the international mentorship program.

The deadline for the first round of applications is Dec. 15, 2010. To apply or find out more, visit www.asds.net/InternationalEd/.

Dr. Field said that he has no relevant disclosures.

*CORRECTION 1/10/11: The article originally stated that the program had 29 U.S. dermatologic mentors and the program is active in 18 countries. The statement was corrected to: 70 mentors from 19 countries.

**CORRECTION 1/10/11: The article originally stated that Dr. Field has taught and learned about...fat transfer in Iran. That statement was revised to state: fat transfer in Saudi Arabia.

CHICAGO – Want to learn more about liposuction in Indonesia? Want to teach your cryosurgery technique to dermatologists in Greece? Want to help physicians in the Philippines perform fat transfer?

You can. Dermatologic surgeons in the United States now have more opportunities to travel, teach, and learn surgical techniques from colleagues in other countries, thanks to a unique collaboration that expands the International Mentorship Program and the International Preceptorship Program.

Photo courtesy Dr. Lawrence M. Field

Earlier this year, Dr. Lawrence M. Field, traveling chair of the International Society for Dermatologic Surgery (ISDS) International Mentorship Program, donated $100,000 to the American Society for Dermatologic Surgeons (ASDS) to establish the Lawrence M. Field MD International Dermatologic Surgery Educational Exchange Fund.

"Dr. Field's donation will allow us to have two preceptorships, a fellowship here in the U.S. and [another] for what Dr. Field has been doing sending fellows to other countries," Dr. Jeffrey S. Dover, ASDS president, said at their annual meeting where the collaboration was announced.

Dr. Field is a "dermatologic surgeon, teacher, and benefactor. He has taught mostly hands-on in more than 60 countries," added ISDS president Dr. Gary J. Brauner.

The ISDS has run the mentorship program since 1986. Additional staffing and other resources provided by the ASDS will significantly expand its reach, said Dr. Field, who is in private practice in San Luis Obispo, Calif.

Photo courtesy Dr. Lawrence M. Field

According to Dr. Field, the program has about 70 mentors from 19 nations.* The program continues to expand and is actively seeking host institutions around the world to work with the faculty. The ASDS/ISDS program is for established dermatologic surgeons and not residents.

Special language skills are a plus but not mandatory, Dr. Field said. In addition, there are no ethnic, cultural, religious or any other exclusions, only mutual acceptability is required.

The ASDS/ISDS program pays the airfare. All mentors, including Dr. Field, offer their expertise free of charge. "Pick me up at the airport; take me to a reasonably nice place; provide me with food, clothing, and shelter; licensure; and surgical scrubs," Dr. Field said, describing his requests to a host institution when he travels. In exchange, "I will give you everything I can ... from me to you, for nothing. Then take me back to the airport, I'll go home, and I'll remember these things forever."

A week commitment is the minimum, Dr. Field said. "You gain knowledge, experience, enjoyment, and the respect of your peers."

Photo courtesy Dr. Lawrence M. Field

In his nearly 25 years as a traveling mentor, Dr. Field has taught and learned about scar revision in the Philippines, cryosurgery in Heraklion, Greece, and fat transfer in Saudi Arabia.**  As a consultant to the DermaClinic, Dr. Field shared his expertise to transfer fat from a patient's abdomen to treat her facial atrophy.

Dr. Field praised the accomplishments of the many dermatologic surgeons who participated as ISDS international mentors. For example, Dr. John Strasswimmer, a dermatologic surgeon in Delray Beach, Fla. has treated albino patients in Africa. "Many great things will happen from that," Dr. Field said.

Another mentor, Dr. Rhoda Narins, worked with Dr. Indah Julianto to get permission from the Minister of Health in Indonesia to perform liposuction. "This program is just forming in Jakarta, Indonesia, so some of you might go there," Dr. Field said.

Dr. Field spent 31 years as a preceptor in his private office for dermatologic surgery fellows at University of California, San Francisco. During this time, he also

hosted international surgeons who, unlike the U.S. physicians, could not participate in hands-on training because of licensure requirements. This disparity led to the genesis of the international mentorship program.

The deadline for the first round of applications is Dec. 15, 2010. To apply or find out more, visit www.asds.net/InternationalEd/.

Dr. Field said that he has no relevant disclosures.

*CORRECTION 1/10/11: The article originally stated that the program had 29 U.S. dermatologic mentors and the program is active in 18 countries. The statement was corrected to: 70 mentors from 19 countries.

**CORRECTION 1/10/11: The article originally stated that Dr. Field has taught and learned about...fat transfer in Iran. That statement was revised to state: fat transfer in Saudi Arabia.

CHICAGO – Want to learn more about liposuction in Indonesia? Want to teach your cryosurgery technique to dermatologists in Greece? Want to help physicians in the Philippines perform fat transfer?

You can. Dermatologic surgeons in the United States now have more opportunities to travel, teach, and learn surgical techniques from colleagues in other countries, thanks to a unique collaboration that expands the International Mentorship Program and the International Preceptorship Program.

Photo courtesy Dr. Lawrence M. Field

Earlier this year, Dr. Lawrence M. Field, traveling chair of the International Society for Dermatologic Surgery (ISDS) International Mentorship Program, donated $100,000 to the American Society for Dermatologic Surgeons (ASDS) to establish the Lawrence M. Field MD International Dermatologic Surgery Educational Exchange Fund.

"Dr. Field's donation will allow us to have two preceptorships, a fellowship here in the U.S. and [another] for what Dr. Field has been doing sending fellows to other countries," Dr. Jeffrey S. Dover, ASDS president, said at their annual meeting where the collaboration was announced.

Dr. Field is a "dermatologic surgeon, teacher, and benefactor. He has taught mostly hands-on in more than 60 countries," added ISDS president Dr. Gary J. Brauner.

The ISDS has run the mentorship program since 1986. Additional staffing and other resources provided by the ASDS will significantly expand its reach, said Dr. Field, who is in private practice in San Luis Obispo, Calif.

Photo courtesy Dr. Lawrence M. Field

According to Dr. Field, the program has about 70 mentors from 19 nations.* The program continues to expand and is actively seeking host institutions around the world to work with the faculty. The ASDS/ISDS program is for established dermatologic surgeons and not residents.

Special language skills are a plus but not mandatory, Dr. Field said. In addition, there are no ethnic, cultural, religious or any other exclusions, only mutual acceptability is required.

The ASDS/ISDS program pays the airfare. All mentors, including Dr. Field, offer their expertise free of charge. "Pick me up at the airport; take me to a reasonably nice place; provide me with food, clothing, and shelter; licensure; and surgical scrubs," Dr. Field said, describing his requests to a host institution when he travels. In exchange, "I will give you everything I can ... from me to you, for nothing. Then take me back to the airport, I'll go home, and I'll remember these things forever."

A week commitment is the minimum, Dr. Field said. "You gain knowledge, experience, enjoyment, and the respect of your peers."

Photo courtesy Dr. Lawrence M. Field

In his nearly 25 years as a traveling mentor, Dr. Field has taught and learned about scar revision in the Philippines, cryosurgery in Heraklion, Greece, and fat transfer in Saudi Arabia.**  As a consultant to the DermaClinic, Dr. Field shared his expertise to transfer fat from a patient's abdomen to treat her facial atrophy.

Dr. Field praised the accomplishments of the many dermatologic surgeons who participated as ISDS international mentors. For example, Dr. John Strasswimmer, a dermatologic surgeon in Delray Beach, Fla. has treated albino patients in Africa. "Many great things will happen from that," Dr. Field said.

Another mentor, Dr. Rhoda Narins, worked with Dr. Indah Julianto to get permission from the Minister of Health in Indonesia to perform liposuction. "This program is just forming in Jakarta, Indonesia, so some of you might go there," Dr. Field said.

Dr. Field spent 31 years as a preceptor in his private office for dermatologic surgery fellows at University of California, San Francisco. During this time, he also

hosted international surgeons who, unlike the U.S. physicians, could not participate in hands-on training because of licensure requirements. This disparity led to the genesis of the international mentorship program.

The deadline for the first round of applications is Dec. 15, 2010. To apply or find out more, visit www.asds.net/InternationalEd/.

Dr. Field said that he has no relevant disclosures.

*CORRECTION 1/10/11: The article originally stated that the program had 29 U.S. dermatologic mentors and the program is active in 18 countries. The statement was corrected to: 70 mentors from 19 countries.

**CORRECTION 1/10/11: The article originally stated that Dr. Field has taught and learned about...fat transfer in Iran. That statement was revised to state: fat transfer in Saudi Arabia.

PORTLAND, Ore. - Wounds from recessive dystrophic epidermolysis bullosa healed more rapidly following injection of their margins with donor allogeneic fibroblasts, according to early study results summarized by Dr. John A. McGrath.

In some cases, wounds caused by recessive dystrophic epidermolysis bullosa (RDEB) healed almost completely within 2 weeks, said Dr. McGrath, professor of molecular dermatology at King’s College London, who is studying the technique.

The procedure is in its earliest stages of clinical investigation, tried so far in just a handful of patients.

And it is not a cure; the healing effect may taper off after several months; reformed wounds would likely need additional injections.

Even so, initial results suggest fibroblast injections could be an “effective approach to therapy for RDEB,” said Dr. Dedee Murrell, professor and chair of the dermatology department at St. George Hospital and the University of New South Wales in Sydney. She is also studying the technique.

Patients with RDEB, which results from a genetic mutation, produce low or no amounts of type VII collagen at the dermal-epidermal junction (DEJ). As a result of the weak or absent fibrils in RDEB,

the slightest skin trauma causes the epidermal layer to blister off, resulting in recurrent wounds, pain, infection, scarring, deformity, digit loss, and failure to thrive. The condition also predisposes patients to squamous cell carcinoma.

Supportive care is the only treatment option at present; the new technique offers the hope of a truly effective intervention.

Though the injected fibroblasts disappear within 2 weeks, they appear to encourage native keratinocytes – and perhaps resident fibroblasts – to increase production of the patient’s own mutant, but partially functional, collagen VII, increasing anchoring fibrils at the junction and leading to better skin adhesion and wound repair.

Those who have a higher baseline expression collagen VII appear to benefit most from the intervention, Dr. McGrath said in an interview following the meeting.

So far, “we have injected [fibroblasts into] wounds in 12 people with RDEB and have observed more rapid skin closure in most subjects. We can show a single injection of fibroblasts increases the patient’s type VII collagen gene expression for 3-6 months, and [collagen VII] expression for 9-12 months,” he said.

Dr. McGrath’s team uses foreskin fibroblast preparations made by Intercytex Ltd. There have been no serious side-effects; antibodies to the donor fibroblasts have not been detected. Patients were 18-35 years old.

They will soon start a phase II RDEB wound-healing trial. “Thereafter, we hope to launch multicenter phase III clinical trials in Europe,” he said.

Dr. McGrath also believes his team has identified a growth factor that triggers collagen VII production at the DEJ and has filed a patent on it through his institution.

The hope is that “we don’t actually need the cells,” Dr. McGrath said.

In Australia, Dr. Murrell’s team has injected allogeneic fibroblasts into the wounds of 5 RDEB patients aged 20-25 years, she said in an interview.

Compared with untreated wounds, those injected rapidly improved; ulcer sizes were at least halved 2 weeks after injection, and continued to heal – or at least did not worsen – after 6 months.

In a surprising twist, Dr. Murrell’s group found that wounds healed equally as well when injected with the fibroblast transport solution, without the cells. Her team used the inert mineral solution Plasma-Lyte with 2% albumen as the transport medium.

“We do not know if it was the needling itself or the placebo solution, or both, that had this beneficial effect,” she said, adding that needling is known to increase skin collagen remodeling. Her team is studying the finding.

Dr. McGrath’s group also found that injecting saline, without cells, increases collagen VII in RDEB skin, probably because of minor inflammation, he said. The investigators also found that the degree and duration of response was considerably less than following fibroblast injection.

But because of Dr. Murrell’s findings, “our future clinical trials will include use of the transport medium – minus the cells – as a control,” he said.

Dr. McGrath noted that other forms of cell therapy also are being studied for RDEB, including intradermal injections of allogeneic, unmatched bone marrow cells and, most recently, whole bone marrow transplantation from matched, related donors (Cytotherapy 2010;12:429-31; N. Engl. J. Med. 2010;363:629-39).

“We should also remember that cell therapy is just one approach; a combination of gene, protein, and drug [therapies] may well be necessary for optimal patient management in the future,” he said.

PORTLAND, Ore. - Wounds from recessive dystrophic epidermolysis bullosa healed more rapidly following injection of their margins with donor allogeneic fibroblasts, according to early study results summarized by Dr. John A. McGrath.

In some cases, wounds caused by recessive dystrophic epidermolysis bullosa (RDEB) healed almost completely within 2 weeks, said Dr. McGrath, professor of molecular dermatology at King’s College London, who is studying the technique.

The procedure is in its earliest stages of clinical investigation, tried so far in just a handful of patients.

And it is not a cure; the healing effect may taper off after several months; reformed wounds would likely need additional injections.

Even so, initial results suggest fibroblast injections could be an “effective approach to therapy for RDEB,” said Dr. Dedee Murrell, professor and chair of the dermatology department at St. George Hospital and the University of New South Wales in Sydney. She is also studying the technique.

Patients with RDEB, which results from a genetic mutation, produce low or no amounts of type VII collagen at the dermal-epidermal junction (DEJ). As a result of the weak or absent fibrils in RDEB,

the slightest skin trauma causes the epidermal layer to blister off, resulting in recurrent wounds, pain, infection, scarring, deformity, digit loss, and failure to thrive. The condition also predisposes patients to squamous cell carcinoma.

Supportive care is the only treatment option at present; the new technique offers the hope of a truly effective intervention.

Though the injected fibroblasts disappear within 2 weeks, they appear to encourage native keratinocytes – and perhaps resident fibroblasts – to increase production of the patient’s own mutant, but partially functional, collagen VII, increasing anchoring fibrils at the junction and leading to better skin adhesion and wound repair.

Those who have a higher baseline expression collagen VII appear to benefit most from the intervention, Dr. McGrath said in an interview following the meeting.

So far, “we have injected [fibroblasts into] wounds in 12 people with RDEB and have observed more rapid skin closure in most subjects. We can show a single injection of fibroblasts increases the patient’s type VII collagen gene expression for 3-6 months, and [collagen VII] expression for 9-12 months,” he said.

Dr. McGrath’s team uses foreskin fibroblast preparations made by Intercytex Ltd. There have been no serious side-effects; antibodies to the donor fibroblasts have not been detected. Patients were 18-35 years old.

They will soon start a phase II RDEB wound-healing trial. “Thereafter, we hope to launch multicenter phase III clinical trials in Europe,” he said.

Dr. McGrath also believes his team has identified a growth factor that triggers collagen VII production at the DEJ and has filed a patent on it through his institution.

The hope is that “we don’t actually need the cells,” Dr. McGrath said.

In Australia, Dr. Murrell’s team has injected allogeneic fibroblasts into the wounds of 5 RDEB patients aged 20-25 years, she said in an interview.

Compared with untreated wounds, those injected rapidly improved; ulcer sizes were at least halved 2 weeks after injection, and continued to heal – or at least did not worsen – after 6 months.

In a surprising twist, Dr. Murrell’s group found that wounds healed equally as well when injected with the fibroblast transport solution, without the cells. Her team used the inert mineral solution Plasma-Lyte with 2% albumen as the transport medium.

“We do not know if it was the needling itself or the placebo solution, or both, that had this beneficial effect,” she said, adding that needling is known to increase skin collagen remodeling. Her team is studying the finding.

Dr. McGrath’s group also found that injecting saline, without cells, increases collagen VII in RDEB skin, probably because of minor inflammation, he said. The investigators also found that the degree and duration of response was considerably less than following fibroblast injection.

But because of Dr. Murrell’s findings, “our future clinical trials will include use of the transport medium – minus the cells – as a control,” he said.

Dr. McGrath noted that other forms of cell therapy also are being studied for RDEB, including intradermal injections of allogeneic, unmatched bone marrow cells and, most recently, whole bone marrow transplantation from matched, related donors (Cytotherapy 2010;12:429-31; N. Engl. J. Med. 2010;363:629-39).

“We should also remember that cell therapy is just one approach; a combination of gene, protein, and drug [therapies] may well be necessary for optimal patient management in the future,” he said.

PORTLAND, Ore. - Wounds from recessive dystrophic epidermolysis bullosa healed more rapidly following injection of their margins with donor allogeneic fibroblasts, according to early study results summarized by Dr. John A. McGrath.

In some cases, wounds caused by recessive dystrophic epidermolysis bullosa (RDEB) healed almost completely within 2 weeks, said Dr. McGrath, professor of molecular dermatology at King’s College London, who is studying the technique.

The procedure is in its earliest stages of clinical investigation, tried so far in just a handful of patients.

And it is not a cure; the healing effect may taper off after several months; reformed wounds would likely need additional injections.

Even so, initial results suggest fibroblast injections could be an “effective approach to therapy for RDEB,” said Dr. Dedee Murrell, professor and chair of the dermatology department at St. George Hospital and the University of New South Wales in Sydney. She is also studying the technique.

Patients with RDEB, which results from a genetic mutation, produce low or no amounts of type VII collagen at the dermal-epidermal junction (DEJ). As a result of the weak or absent fibrils in RDEB,

the slightest skin trauma causes the epidermal layer to blister off, resulting in recurrent wounds, pain, infection, scarring, deformity, digit loss, and failure to thrive. The condition also predisposes patients to squamous cell carcinoma.

Supportive care is the only treatment option at present; the new technique offers the hope of a truly effective intervention.

Though the injected fibroblasts disappear within 2 weeks, they appear to encourage native keratinocytes – and perhaps resident fibroblasts – to increase production of the patient’s own mutant, but partially functional, collagen VII, increasing anchoring fibrils at the junction and leading to better skin adhesion and wound repair.

Those who have a higher baseline expression collagen VII appear to benefit most from the intervention, Dr. McGrath said in an interview following the meeting.

So far, “we have injected [fibroblasts into] wounds in 12 people with RDEB and have observed more rapid skin closure in most subjects. We can show a single injection of fibroblasts increases the patient’s type VII collagen gene expression for 3-6 months, and [collagen VII] expression for 9-12 months,” he said.

Dr. McGrath’s team uses foreskin fibroblast preparations made by Intercytex Ltd. There have been no serious side-effects; antibodies to the donor fibroblasts have not been detected. Patients were 18-35 years old.

They will soon start a phase II RDEB wound-healing trial. “Thereafter, we hope to launch multicenter phase III clinical trials in Europe,” he said.

Dr. McGrath also believes his team has identified a growth factor that triggers collagen VII production at the DEJ and has filed a patent on it through his institution.

The hope is that “we don’t actually need the cells,” Dr. McGrath said.

In Australia, Dr. Murrell’s team has injected allogeneic fibroblasts into the wounds of 5 RDEB patients aged 20-25 years, she said in an interview.

Compared with untreated wounds, those injected rapidly improved; ulcer sizes were at least halved 2 weeks after injection, and continued to heal – or at least did not worsen – after 6 months.

In a surprising twist, Dr. Murrell’s group found that wounds healed equally as well when injected with the fibroblast transport solution, without the cells. Her team used the inert mineral solution Plasma-Lyte with 2% albumen as the transport medium.

“We do not know if it was the needling itself or the placebo solution, or both, that had this beneficial effect,” she said, adding that needling is known to increase skin collagen remodeling. Her team is studying the finding.

Dr. McGrath’s group also found that injecting saline, without cells, increases collagen VII in RDEB skin, probably because of minor inflammation, he said. The investigators also found that the degree and duration of response was considerably less than following fibroblast injection.

But because of Dr. Murrell’s findings, “our future clinical trials will include use of the transport medium – minus the cells – as a control,” he said.

Dr. McGrath noted that other forms of cell therapy also are being studied for RDEB, including intradermal injections of allogeneic, unmatched bone marrow cells and, most recently, whole bone marrow transplantation from matched, related donors (Cytotherapy 2010;12:429-31; N. Engl. J. Med. 2010;363:629-39).

“We should also remember that cell therapy is just one approach; a combination of gene, protein, and drug [therapies] may well be necessary for optimal patient management in the future,” he said.

CHICAGO - A multimodal approach is usually necessary to shut down the destructive progress of pyoderma gangrenosum and induce wound healing.

“The primary, No. 1 issue is shutting down the inflammation that causes the wound to continually expand,” Dr. Laura Winterfield said. “Second in importance is pain control. These patients have a very high level of pain, which is sometimes out of proportion to the size of the lesion.”

Once the inflammatory process halts and pain is under control, physicians can address any behaviors or concomitant disorders that might interfere with healing.

A long list of options is available to control inflammation, “which is usually an indication that no one treatment works in everyone all the time,” said Dr. Winterfield a dermatologist at Brigham and Women’s Hospital, Boston. “Corticosteroids and cyclosporine are usually the first lines of therapy, but there are not really any data saying that they are better than anything else.”

A small randomized controlled trial examined the use of infliximab for the treatment of pyoderma gangrenosum. Thirty patients were randomized to infliximab (13) or placebo (17). At week 2, significantly more patients in the infliximab group had improved (46% vs. 6% placebo, respectively). After 2 weeks, nonresponders in the placebo group were offered infliximab; of 29 of the 30 patients being treated with infliximab at 6 weeks, 69% reported improvement. The remission rate at 6 weeks was 21% (Gut 2006; 55:505-9).

In patients with a history of pyoderma gangrenosum, early lesions can sometimes be controlled with topical or intralesional corticosteroids, calcineurin inhibitors, topical cyclosporine in the form of ophthalmic drops, or dapsone gel.

Minocylcine is also a possibility. “We’ve had a fair amount of success in our patients. It’s fairly well-tolerated and is a good choice where immunosuppression is a concern,” she said.

Dapsone gel can also be helpful. “It can be quite useful for patients who are reluctant to use immunosuppressive agents,” said Dr. Winterfield. She cited one patient who responded so well to dapsone gel that she was later able to undergo an autologous skin graft.

Shutting down pain is also critically important. “Dermatologists don’t think about treating pain as often as other specialties, so work with your pain management colleagues on this. Send patients for consult early in therapy. Controlling pain makes them feel you are much more invested in their care.”

After wound inflammation and pain are controlled, nonstick dressings are a necessity. Dry or wet-to-dry dressings can pull on healing tissue and reactive the inflammatory process. Dressing impregnated with silver or iodine can help prevent superinfection of the lesion.

Cyclosporine ophthalmic drops can also help some. “Drip the liquid right into the wound,” she said. Topical tacrolimus and dapsone gel applied to the wound edges are often helpful. “For a wound that’s ‘stuck’ and won’t heal, you can try a topical recombinant human platelet–derived growth factor.”

Although many are hesitant to surgically debride pyoderma lesions, some patients can tolerate gentle curette debridement once inflammation and pain have stabilized. Enzymatic debridement is an option for patients with a thick wound eschar interfering with topical medications. “Collagenase can soften the eschar and help you remove it so those medicines can get in there and work better,” she said.

Skin grafting may be necessary for some wounds, but autologous grafts can set up another pyoderma lesion at the harvest site. Engineered allograft may make more sense for some patients.

Finally, she said, it’s important to address other issues that might interfere with healing—nutritional status, smoking, venous insufficiency, and poorly controlled diabetes. “Sometimes patients in a lot of pain don’t take in adequate calories and protein, which can be a problem. See what you can do about mitigating these other issues, and you may start to see some improvement.”

 Disclosures: Dr. Winterfield said she had no relevant financial conflicts.

CHICAGO - A multimodal approach is usually necessary to shut down the destructive progress of pyoderma gangrenosum and induce wound healing.

“The primary, No. 1 issue is shutting down the inflammation that causes the wound to continually expand,” Dr. Laura Winterfield said. “Second in importance is pain control. These patients have a very high level of pain, which is sometimes out of proportion to the size of the lesion.”

Once the inflammatory process halts and pain is under control, physicians can address any behaviors or concomitant disorders that might interfere with healing.

A long list of options is available to control inflammation, “which is usually an indication that no one treatment works in everyone all the time,” said Dr. Winterfield a dermatologist at Brigham and Women’s Hospital, Boston. “Corticosteroids and cyclosporine are usually the first lines of therapy, but there are not really any data saying that they are better than anything else.”

A small randomized controlled trial examined the use of infliximab for the treatment of pyoderma gangrenosum. Thirty patients were randomized to infliximab (13) or placebo (17). At week 2, significantly more patients in the infliximab group had improved (46% vs. 6% placebo, respectively). After 2 weeks, nonresponders in the placebo group were offered infliximab; of 29 of the 30 patients being treated with infliximab at 6 weeks, 69% reported improvement. The remission rate at 6 weeks was 21% (Gut 2006; 55:505-9).

In patients with a history of pyoderma gangrenosum, early lesions can sometimes be controlled with topical or intralesional corticosteroids, calcineurin inhibitors, topical cyclosporine in the form of ophthalmic drops, or dapsone gel.

Minocylcine is also a possibility. “We’ve had a fair amount of success in our patients. It’s fairly well-tolerated and is a good choice where immunosuppression is a concern,” she said.

Dapsone gel can also be helpful. “It can be quite useful for patients who are reluctant to use immunosuppressive agents,” said Dr. Winterfield. She cited one patient who responded so well to dapsone gel that she was later able to undergo an autologous skin graft.

Shutting down pain is also critically important. “Dermatologists don’t think about treating pain as often as other specialties, so work with your pain management colleagues on this. Send patients for consult early in therapy. Controlling pain makes them feel you are much more invested in their care.”

After wound inflammation and pain are controlled, nonstick dressings are a necessity. Dry or wet-to-dry dressings can pull on healing tissue and reactive the inflammatory process. Dressing impregnated with silver or iodine can help prevent superinfection of the lesion.

Cyclosporine ophthalmic drops can also help some. “Drip the liquid right into the wound,” she said. Topical tacrolimus and dapsone gel applied to the wound edges are often helpful. “For a wound that’s ‘stuck’ and won’t heal, you can try a topical recombinant human platelet–derived growth factor.”

Although many are hesitant to surgically debride pyoderma lesions, some patients can tolerate gentle curette debridement once inflammation and pain have stabilized. Enzymatic debridement is an option for patients with a thick wound eschar interfering with topical medications. “Collagenase can soften the eschar and help you remove it so those medicines can get in there and work better,” she said.

Skin grafting may be necessary for some wounds, but autologous grafts can set up another pyoderma lesion at the harvest site. Engineered allograft may make more sense for some patients.

Finally, she said, it’s important to address other issues that might interfere with healing—nutritional status, smoking, venous insufficiency, and poorly controlled diabetes. “Sometimes patients in a lot of pain don’t take in adequate calories and protein, which can be a problem. See what you can do about mitigating these other issues, and you may start to see some improvement.”

 Disclosures: Dr. Winterfield said she had no relevant financial conflicts.

CHICAGO - A multimodal approach is usually necessary to shut down the destructive progress of pyoderma gangrenosum and induce wound healing.

“The primary, No. 1 issue is shutting down the inflammation that causes the wound to continually expand,” Dr. Laura Winterfield said. “Second in importance is pain control. These patients have a very high level of pain, which is sometimes out of proportion to the size of the lesion.”

Once the inflammatory process halts and pain is under control, physicians can address any behaviors or concomitant disorders that might interfere with healing.

A long list of options is available to control inflammation, “which is usually an indication that no one treatment works in everyone all the time,” said Dr. Winterfield a dermatologist at Brigham and Women’s Hospital, Boston. “Corticosteroids and cyclosporine are usually the first lines of therapy, but there are not really any data saying that they are better than anything else.”

A small randomized controlled trial examined the use of infliximab for the treatment of pyoderma gangrenosum. Thirty patients were randomized to infliximab (13) or placebo (17). At week 2, significantly more patients in the infliximab group had improved (46% vs. 6% placebo, respectively). After 2 weeks, nonresponders in the placebo group were offered infliximab; of 29 of the 30 patients being treated with infliximab at 6 weeks, 69% reported improvement. The remission rate at 6 weeks was 21% (Gut 2006; 55:505-9).

In patients with a history of pyoderma gangrenosum, early lesions can sometimes be controlled with topical or intralesional corticosteroids, calcineurin inhibitors, topical cyclosporine in the form of ophthalmic drops, or dapsone gel.

Minocylcine is also a possibility. “We’ve had a fair amount of success in our patients. It’s fairly well-tolerated and is a good choice where immunosuppression is a concern,” she said.

Dapsone gel can also be helpful. “It can be quite useful for patients who are reluctant to use immunosuppressive agents,” said Dr. Winterfield. She cited one patient who responded so well to dapsone gel that she was later able to undergo an autologous skin graft.

Shutting down pain is also critically important. “Dermatologists don’t think about treating pain as often as other specialties, so work with your pain management colleagues on this. Send patients for consult early in therapy. Controlling pain makes them feel you are much more invested in their care.”

After wound inflammation and pain are controlled, nonstick dressings are a necessity. Dry or wet-to-dry dressings can pull on healing tissue and reactive the inflammatory process. Dressing impregnated with silver or iodine can help prevent superinfection of the lesion.

Cyclosporine ophthalmic drops can also help some. “Drip the liquid right into the wound,” she said. Topical tacrolimus and dapsone gel applied to the wound edges are often helpful. “For a wound that’s ‘stuck’ and won’t heal, you can try a topical recombinant human platelet–derived growth factor.”

Although many are hesitant to surgically debride pyoderma lesions, some patients can tolerate gentle curette debridement once inflammation and pain have stabilized. Enzymatic debridement is an option for patients with a thick wound eschar interfering with topical medications. “Collagenase can soften the eschar and help you remove it so those medicines can get in there and work better,” she said.

Skin grafting may be necessary for some wounds, but autologous grafts can set up another pyoderma lesion at the harvest site. Engineered allograft may make more sense for some patients.

Finally, she said, it’s important to address other issues that might interfere with healing—nutritional status, smoking, venous insufficiency, and poorly controlled diabetes. “Sometimes patients in a lot of pain don’t take in adequate calories and protein, which can be a problem. See what you can do about mitigating these other issues, and you may start to see some improvement.”

 Disclosures: Dr. Winterfield said she had no relevant financial conflicts.

Sensitivity analyses may help smooth the approval pathway for ceftaroline fosamil under the Food and Drug Administration's evolving efficacy requirements for skin infections and community-acquired bacterial pneumonia, even though the antibiotic's pivotal data were developed under the agency's old standards.

Ceftaroline (Forest Laboratories) was shown to be noninferior to comparator agents pursuant to the company's prespecified efficacy analyses as well as sensitivity analyses applying the FDA's new efficacy criteria, according to agency briefing materials released ahead of the agency's Anti-Infective Drugs Advisory Committee's Sept. 7 review of the beta lactam cephalosporin.

If endorsed by the committee and approved by the FDA, ceftaroline could become a poster child for how to survive the "shifting goalposts" created by the agency’s evolution in antibiotic development standards – the message being if the data are truly robust, sensitivity analyses can get you through the new efficacy hurdles.

Forest acquired ceftaroline through its January 2007 acquisition of Cerexa, which in-licensed rights from Takeda. The phase III trials for complicated skin and skin structure infections (cSSSI) and community-acquired bacterial pneumonia (CABP) began in 2007, prior to FDA-initiated public discussions about use of noninferiority trials for these indications.

New Skin Infections Guidance

In the case of the cSSSIs, the FDA issued new draft guidance on Aug. 26 that proposes changes in the nomenclature, primary efficacy end point, and study population. The draft forgoes the terms cSSSI and uncomplicated SSSI in favor of acute bacterial SSSI and milder skin infections. The document states that noninferiority trials are acceptable for acute bacterial SSSIs, although it does not set a specific margin that should be used.

During a November 2008 meeting on drug development standards for cSSSI, the Anti-Infective Drugs Advisory Committee generally recommended a 10% margin.

The guidance recommends a new primary efficacy end point based on cessation of lesion spread and resolution of fever at 48-72 hours after enrollment. This is a dramatic change from the end point that has generally been used in cSSSI studies: resolution of signs and symptoms at the test-of-cure visit 7-14 days after completion of treatment. The guidance also recommends that patients with wound infections and major cutaneous abscesses be enrolled only if they have coexisting cellulitis.

Forest's phase III studies tested ceftaroline against vancomycin plus aztreonam in adults with cSSSI requiring initial treatment with an intravenous antimicrobial agent in a hospital or urgent care setting. Cellulitis was present in about 35% of patients. Duration of therapy was 5-14 days.

The primary efficacy end point was clinical response rate at the test-of-cure visit, with clinical cure defined as total resolution of all signs and symptoms or improvement such that further antimicrobial therapy was unnecessary.

Ten Percent Noninferiority Margin Draws No Objections

The FDA's briefing documents raise no objections to the prespecified noninferiority margin of 10% in the cSSSI studies, for which the agency had asked Cerexa to provide supporting justification at the end-of-phase II meeting in October 2006.

In both studies, the 10% margin was met for both the modified intent-to-treat and clinically evaluable populations in the test-of-cure visit 8-15 days after the last dose of study drug, as well as at an end-of-therapy visit, a secondary end point.

FDA reviewers conducted a sensitivity analysis using the draft guidance's early end point of lesion spread cessation at day 3 in a study population that includes only patients with cellulitis. As a result, this reanalyzed population represented only about 56-58% of the originally randomized trial populations, reducing the statistical power to demonstrate noninferiority.

Nevertheless, in both studies the responder rate in the ceftaroline group was higher than in the comparator group. "These findings supported the noninferiority of ceftaroline to vancomycin plus aztreonam for a noninferiority margin of less than 4% for both trials," the agency said.

Additional sensitivity analyses that took into account investigator measurements of lesion size and consistency of clinical response at later timepoints also confirmed ceftaroline's noninferiority. "Overall, findings of noninferiority of ceftaroline to vancomycin plus aztreonam based on key sensitivity analyses of Day 3 responder rates in FDA-MITT [modified intention to treat] subjects appeared to be robust," the document stated.

Justifying the Margin in CABP

The noninferiority margin was the issue in the CABP indication. FDA reviewers were concerned about the absence of historical data to justify the noninferiority margin used in the two phase III trials for that indication.

In studies P903-06 and P903-09, ceftaroline was shown to be noninferior to ceftriaxone on the primary end points – clinical cure rate at the test-of-cure visit in the clinically evaluable and in the modified intent-to-treat efficacy populations – with a prespecified noninferiority margin of 10%. Patients received the study drugs for 5-7 days; the test-of-cure visit was 8-15 days after the last drug dose.

The sponsor's justification for the 10% noninferiority margin relied on historical data related to mortality and "even if such a margin was justified, this would not imply that a margin could be extrapolated for clinical response at TOC [test of cure]," the FDA’s briefing documents stated.

There are, however, historical data demonstrating dramatic improvement in patient signs and symptoms after a few days of antibiotic therapy, the agency noted. So FDA reviewers analyzed as an end point the sign and symptom measurements at Day 4 available in case report forms from the two studies, with achievement of a 10% noninferiority margin as the measure of success.

The new end point was not considered a surrogate, "but rather a direct measure of patient well-being," the FDA said.

The FDA analysis was limited to microbiologically confirmed patients. This markedly decreased the size of the study population, the agency said, but the results nevertheless "provided evidence of efficacy as ceftaroline met the 10% noninferiority margin in both studies."

While efficacy was demonstrated, the FDA reviewers noted several problems with their calculations. Investigators' recording of signs and symptoms was not standardized and their evaluation of symptom severity was subjective. Further, no algorithmic combination of the Day 4 signs and symptoms would have precisely corresponded to those discussed in the historical studies, and the measures did not necessarily capture patient feeling, function, or survival. The reviewers also suggested that changes in signs and symptoms could have been influenced by concomitant therapy.

Because the FDA analysis involved several arbitrary choices and cutoffs, the agency conducted sensitivity analyses for several modifications. Their conclusion was that the noninferiority results were relatively robust with regard to end point, timing of assessment, and analysis population, but the 10% noninferiority margin would not have been met in study P903-09 if the assessment had been at Day 3 or end-of-treatment, rather than Day 4.

To further justify a 10% noninferiority margin for a clinical response end point at test-of-cure, reviewers also looked at two recent trials comparing ceftriaxone to daptomycin, with daptomycin considered to be a substitute for a placebo arm. An ad hoc analysis "provided supportive evidence for the clinical response end point at TOC," the FDA concluded.

Much like the cSSSI program, the CABP trials moved along during a time of transition in FDA standards for the indication. The ceftaroline pneumonia clinical trials were initiated prior to discussions at a 2008 FDA/Infectious Diseases Society of America public workshop and Anti-Infective Drugs Advisory Committee meetings in 2008 and 2009 about the use of noninferiority trials for CABP, and a March 2009 draft guidance. The CABP guidance is currently undergoing revisions.

The sensitivity analyses applied by FDA reviewers to view the results in terms of the evolving regulatory requirements for CABP were based largely on discussions at the public forums, the agency said. At the December 2009 anti-infectives advisory committee meeting, members agreed that either all-cause mortality or clinical response could be used as a primary end point.

The FDA's apparent satisfaction with ceftaroline's demonstration of efficacy in skin infections and CABP could mean that the Sept. 7 advisory committee meeting will turn into a referendum on the agency’s current thinking about clinical trial requirements for these two conditions.

Skin & Allergy News Digital Network and "The Pink Sheet" are published by Elsevier.

Sensitivity analyses may help smooth the approval pathway for ceftaroline fosamil under the Food and Drug Administration's evolving efficacy requirements for skin infections and community-acquired bacterial pneumonia, even though the antibiotic's pivotal data were developed under the agency's old standards.

Ceftaroline (Forest Laboratories) was shown to be noninferior to comparator agents pursuant to the company's prespecified efficacy analyses as well as sensitivity analyses applying the FDA's new efficacy criteria, according to agency briefing materials released ahead of the agency's Anti-Infective Drugs Advisory Committee's Sept. 7 review of the beta lactam cephalosporin.

If endorsed by the committee and approved by the FDA, ceftaroline could become a poster child for how to survive the "shifting goalposts" created by the agency’s evolution in antibiotic development standards – the message being if the data are truly robust, sensitivity analyses can get you through the new efficacy hurdles.

Forest acquired ceftaroline through its January 2007 acquisition of Cerexa, which in-licensed rights from Takeda. The phase III trials for complicated skin and skin structure infections (cSSSI) and community-acquired bacterial pneumonia (CABP) began in 2007, prior to FDA-initiated public discussions about use of noninferiority trials for these indications.

New Skin Infections Guidance

In the case of the cSSSIs, the FDA issued new draft guidance on Aug. 26 that proposes changes in the nomenclature, primary efficacy end point, and study population. The draft forgoes the terms cSSSI and uncomplicated SSSI in favor of acute bacterial SSSI and milder skin infections. The document states that noninferiority trials are acceptable for acute bacterial SSSIs, although it does not set a specific margin that should be used.

During a November 2008 meeting on drug development standards for cSSSI, the Anti-Infective Drugs Advisory Committee generally recommended a 10% margin.

The guidance recommends a new primary efficacy end point based on cessation of lesion spread and resolution of fever at 48-72 hours after enrollment. This is a dramatic change from the end point that has generally been used in cSSSI studies: resolution of signs and symptoms at the test-of-cure visit 7-14 days after completion of treatment. The guidance also recommends that patients with wound infections and major cutaneous abscesses be enrolled only if they have coexisting cellulitis.

Forest's phase III studies tested ceftaroline against vancomycin plus aztreonam in adults with cSSSI requiring initial treatment with an intravenous antimicrobial agent in a hospital or urgent care setting. Cellulitis was present in about 35% of patients. Duration of therapy was 5-14 days.

The primary efficacy end point was clinical response rate at the test-of-cure visit, with clinical cure defined as total resolution of all signs and symptoms or improvement such that further antimicrobial therapy was unnecessary.

Ten Percent Noninferiority Margin Draws No Objections

The FDA's briefing documents raise no objections to the prespecified noninferiority margin of 10% in the cSSSI studies, for which the agency had asked Cerexa to provide supporting justification at the end-of-phase II meeting in October 2006.

In both studies, the 10% margin was met for both the modified intent-to-treat and clinically evaluable populations in the test-of-cure visit 8-15 days after the last dose of study drug, as well as at an end-of-therapy visit, a secondary end point.

FDA reviewers conducted a sensitivity analysis using the draft guidance's early end point of lesion spread cessation at day 3 in a study population that includes only patients with cellulitis. As a result, this reanalyzed population represented only about 56-58% of the originally randomized trial populations, reducing the statistical power to demonstrate noninferiority.

Nevertheless, in both studies the responder rate in the ceftaroline group was higher than in the comparator group. "These findings supported the noninferiority of ceftaroline to vancomycin plus aztreonam for a noninferiority margin of less than 4% for both trials," the agency said.

Additional sensitivity analyses that took into account investigator measurements of lesion size and consistency of clinical response at later timepoints also confirmed ceftaroline's noninferiority. "Overall, findings of noninferiority of ceftaroline to vancomycin plus aztreonam based on key sensitivity analyses of Day 3 responder rates in FDA-MITT [modified intention to treat] subjects appeared to be robust," the document stated.

Justifying the Margin in CABP

The noninferiority margin was the issue in the CABP indication. FDA reviewers were concerned about the absence of historical data to justify the noninferiority margin used in the two phase III trials for that indication.

In studies P903-06 and P903-09, ceftaroline was shown to be noninferior to ceftriaxone on the primary end points – clinical cure rate at the test-of-cure visit in the clinically evaluable and in the modified intent-to-treat efficacy populations – with a prespecified noninferiority margin of 10%. Patients received the study drugs for 5-7 days; the test-of-cure visit was 8-15 days after the last drug dose.

The sponsor's justification for the 10% noninferiority margin relied on historical data related to mortality and "even if such a margin was justified, this would not imply that a margin could be extrapolated for clinical response at TOC [test of cure]," the FDA’s briefing documents stated.

There are, however, historical data demonstrating dramatic improvement in patient signs and symptoms after a few days of antibiotic therapy, the agency noted. So FDA reviewers analyzed as an end point the sign and symptom measurements at Day 4 available in case report forms from the two studies, with achievement of a 10% noninferiority margin as the measure of success.

The new end point was not considered a surrogate, "but rather a direct measure of patient well-being," the FDA said.

The FDA analysis was limited to microbiologically confirmed patients. This markedly decreased the size of the study population, the agency said, but the results nevertheless "provided evidence of efficacy as ceftaroline met the 10% noninferiority margin in both studies."

While efficacy was demonstrated, the FDA reviewers noted several problems with their calculations. Investigators' recording of signs and symptoms was not standardized and their evaluation of symptom severity was subjective. Further, no algorithmic combination of the Day 4 signs and symptoms would have precisely corresponded to those discussed in the historical studies, and the measures did not necessarily capture patient feeling, function, or survival. The reviewers also suggested that changes in signs and symptoms could have been influenced by concomitant therapy.

Because the FDA analysis involved several arbitrary choices and cutoffs, the agency conducted sensitivity analyses for several modifications. Their conclusion was that the noninferiority results were relatively robust with regard to end point, timing of assessment, and analysis population, but the 10% noninferiority margin would not have been met in study P903-09 if the assessment had been at Day 3 or end-of-treatment, rather than Day 4.

To further justify a 10% noninferiority margin for a clinical response end point at test-of-cure, reviewers also looked at two recent trials comparing ceftriaxone to daptomycin, with daptomycin considered to be a substitute for a placebo arm. An ad hoc analysis "provided supportive evidence for the clinical response end point at TOC," the FDA concluded.

Much like the cSSSI program, the CABP trials moved along during a time of transition in FDA standards for the indication. The ceftaroline pneumonia clinical trials were initiated prior to discussions at a 2008 FDA/Infectious Diseases Society of America public workshop and Anti-Infective Drugs Advisory Committee meetings in 2008 and 2009 about the use of noninferiority trials for CABP, and a March 2009 draft guidance. The CABP guidance is currently undergoing revisions.

The sensitivity analyses applied by FDA reviewers to view the results in terms of the evolving regulatory requirements for CABP were based largely on discussions at the public forums, the agency said. At the December 2009 anti-infectives advisory committee meeting, members agreed that either all-cause mortality or clinical response could be used as a primary end point.

The FDA's apparent satisfaction with ceftaroline's demonstration of efficacy in skin infections and CABP could mean that the Sept. 7 advisory committee meeting will turn into a referendum on the agency’s current thinking about clinical trial requirements for these two conditions.

Skin & Allergy News Digital Network and "The Pink Sheet" are published by Elsevier.

Sensitivity analyses may help smooth the approval pathway for ceftaroline fosamil under the Food and Drug Administration's evolving efficacy requirements for skin infections and community-acquired bacterial pneumonia, even though the antibiotic's pivotal data were developed under the agency's old standards.

Ceftaroline (Forest Laboratories) was shown to be noninferior to comparator agents pursuant to the company's prespecified efficacy analyses as well as sensitivity analyses applying the FDA's new efficacy criteria, according to agency briefing materials released ahead of the agency's Anti-Infective Drugs Advisory Committee's Sept. 7 review of the beta lactam cephalosporin.

If endorsed by the committee and approved by the FDA, ceftaroline could become a poster child for how to survive the "shifting goalposts" created by the agency’s evolution in antibiotic development standards – the message being if the data are truly robust, sensitivity analyses can get you through the new efficacy hurdles.

Forest acquired ceftaroline through its January 2007 acquisition of Cerexa, which in-licensed rights from Takeda. The phase III trials for complicated skin and skin structure infections (cSSSI) and community-acquired bacterial pneumonia (CABP) began in 2007, prior to FDA-initiated public discussions about use of noninferiority trials for these indications.

New Skin Infections Guidance

In the case of the cSSSIs, the FDA issued new draft guidance on Aug. 26 that proposes changes in the nomenclature, primary efficacy end point, and study population. The draft forgoes the terms cSSSI and uncomplicated SSSI in favor of acute bacterial SSSI and milder skin infections. The document states that noninferiority trials are acceptable for acute bacterial SSSIs, although it does not set a specific margin that should be used.

During a November 2008 meeting on drug development standards for cSSSI, the Anti-Infective Drugs Advisory Committee generally recommended a 10% margin.

The guidance recommends a new primary efficacy end point based on cessation of lesion spread and resolution of fever at 48-72 hours after enrollment. This is a dramatic change from the end point that has generally been used in cSSSI studies: resolution of signs and symptoms at the test-of-cure visit 7-14 days after completion of treatment. The guidance also recommends that patients with wound infections and major cutaneous abscesses be enrolled only if they have coexisting cellulitis.

Forest's phase III studies tested ceftaroline against vancomycin plus aztreonam in adults with cSSSI requiring initial treatment with an intravenous antimicrobial agent in a hospital or urgent care setting. Cellulitis was present in about 35% of patients. Duration of therapy was 5-14 days.

The primary efficacy end point was clinical response rate at the test-of-cure visit, with clinical cure defined as total resolution of all signs and symptoms or improvement such that further antimicrobial therapy was unnecessary.

Ten Percent Noninferiority Margin Draws No Objections

The FDA's briefing documents raise no objections to the prespecified noninferiority margin of 10% in the cSSSI studies, for which the agency had asked Cerexa to provide supporting justification at the end-of-phase II meeting in October 2006.

In both studies, the 10% margin was met for both the modified intent-to-treat and clinically evaluable populations in the test-of-cure visit 8-15 days after the last dose of study drug, as well as at an end-of-therapy visit, a secondary end point.

FDA reviewers conducted a sensitivity analysis using the draft guidance's early end point of lesion spread cessation at day 3 in a study population that includes only patients with cellulitis. As a result, this reanalyzed population represented only about 56-58% of the originally randomized trial populations, reducing the statistical power to demonstrate noninferiority.

Nevertheless, in both studies the responder rate in the ceftaroline group was higher than in the comparator group. "These findings supported the noninferiority of ceftaroline to vancomycin plus aztreonam for a noninferiority margin of less than 4% for both trials," the agency said.

Additional sensitivity analyses that took into account investigator measurements of lesion size and consistency of clinical response at later timepoints also confirmed ceftaroline's noninferiority. "Overall, findings of noninferiority of ceftaroline to vancomycin plus aztreonam based on key sensitivity analyses of Day 3 responder rates in FDA-MITT [modified intention to treat] subjects appeared to be robust," the document stated.

Justifying the Margin in CABP

The noninferiority margin was the issue in the CABP indication. FDA reviewers were concerned about the absence of historical data to justify the noninferiority margin used in the two phase III trials for that indication.

In studies P903-06 and P903-09, ceftaroline was shown to be noninferior to ceftriaxone on the primary end points – clinical cure rate at the test-of-cure visit in the clinically evaluable and in the modified intent-to-treat efficacy populations – with a prespecified noninferiority margin of 10%. Patients received the study drugs for 5-7 days; the test-of-cure visit was 8-15 days after the last drug dose.

The sponsor's justification for the 10% noninferiority margin relied on historical data related to mortality and "even if such a margin was justified, this would not imply that a margin could be extrapolated for clinical response at TOC [test of cure]," the FDA’s briefing documents stated.

There are, however, historical data demonstrating dramatic improvement in patient signs and symptoms after a few days of antibiotic therapy, the agency noted. So FDA reviewers analyzed as an end point the sign and symptom measurements at Day 4 available in case report forms from the two studies, with achievement of a 10% noninferiority margin as the measure of success.

The new end point was not considered a surrogate, "but rather a direct measure of patient well-being," the FDA said.

The FDA analysis was limited to microbiologically confirmed patients. This markedly decreased the size of the study population, the agency said, but the results nevertheless "provided evidence of efficacy as ceftaroline met the 10% noninferiority margin in both studies."

While efficacy was demonstrated, the FDA reviewers noted several problems with their calculations. Investigators' recording of signs and symptoms was not standardized and their evaluation of symptom severity was subjective. Further, no algorithmic combination of the Day 4 signs and symptoms would have precisely corresponded to those discussed in the historical studies, and the measures did not necessarily capture patient feeling, function, or survival. The reviewers also suggested that changes in signs and symptoms could have been influenced by concomitant therapy.

Because the FDA analysis involved several arbitrary choices and cutoffs, the agency conducted sensitivity analyses for several modifications. Their conclusion was that the noninferiority results were relatively robust with regard to end point, timing of assessment, and analysis population, but the 10% noninferiority margin would not have been met in study P903-09 if the assessment had been at Day 3 or end-of-treatment, rather than Day 4.

To further justify a 10% noninferiority margin for a clinical response end point at test-of-cure, reviewers also looked at two recent trials comparing ceftriaxone to daptomycin, with daptomycin considered to be a substitute for a placebo arm. An ad hoc analysis "provided supportive evidence for the clinical response end point at TOC," the FDA concluded.

Much like the cSSSI program, the CABP trials moved along during a time of transition in FDA standards for the indication. The ceftaroline pneumonia clinical trials were initiated prior to discussions at a 2008 FDA/Infectious Diseases Society of America public workshop and Anti-Infective Drugs Advisory Committee meetings in 2008 and 2009 about the use of noninferiority trials for CABP, and a March 2009 draft guidance. The CABP guidance is currently undergoing revisions.

The sensitivity analyses applied by FDA reviewers to view the results in terms of the evolving regulatory requirements for CABP were based largely on discussions at the public forums, the agency said. At the December 2009 anti-infectives advisory committee meeting, members agreed that either all-cause mortality or clinical response could be used as a primary end point.

The FDA's apparent satisfaction with ceftaroline's demonstration of efficacy in skin infections and CABP could mean that the Sept. 7 advisory committee meeting will turn into a referendum on the agency’s current thinking about clinical trial requirements for these two conditions.

Skin & Allergy News Digital Network and "The Pink Sheet" are published by Elsevier.