Wounds

Michael Migden, MD,*,† Arianne Chavez-Frazier, MD,* and Tri Nguyen, MD*

The use of video in the informed consent process has been well documented in the literature to improve patient satisfaction, understanding, comprehension, and to decrease anxiety. At the MD Anderson Mohs Surgery Unit, we use high-definition (HD) audiovisual (AV) modules to assist with the delivery of informed consent and to educate patients on the subject of postoperative wound care. The purpose of this work was to develop HD-AV media to inform patients of the risks, benefits, and alternatives of Mohs surgery before they are asked to sign the consent form and to educate patients on basic wound care after Mohs Surgery. The use of a HD virtual surgeon and nurse in the videos educates the patient, allowing the surgeon and nursing staff to attend to other patients within the Mohs Surgery Unit. Using HD digital recording equipment, we captured real-time HD-AV media to explain the risks, alternatives, and benefits of Mohs surgery (surgeon explanation) and to give detailed instructions for postoperative wound care (nurse explanation). Once captured, HD modules were created and stored on a central University of Texas–MD Anderson Cancer Center server in the Texas Medical Center approximately 1 mile from the Mohs Surgery Unit. The full-screen HD modules are accessed on demand at the point of need with the use of standard institutional computers within any of the Mohs’s center’s examination/surgical suites. An early evaluation of this quality improvement initiative was performed to measure patient satisfaction, efficiency, and efficacy of the videos followed by physician/nurse discussion compared with physician/nurse discussion alone. Early evaluation of HD-AV modules used for the delivery of informed consent and postoperative wound care in the MD Anderson Mohs surgery Unit revealed that patient satisfaction was maintained and that this medium was preferred by patients in the video group over physician/nurse discussion alone. The HD modules allowed increased efficiency and patient comprehension, which improved patient education in the Mohs Surgery Unit.

*For a PDF of the full article, click on the link to the left of this introduction.

Michael Migden, MD,*,† Arianne Chavez-Frazier, MD,* and Tri Nguyen, MD*

The use of video in the informed consent process has been well documented in the literature to improve patient satisfaction, understanding, comprehension, and to decrease anxiety. At the MD Anderson Mohs Surgery Unit, we use high-definition (HD) audiovisual (AV) modules to assist with the delivery of informed consent and to educate patients on the subject of postoperative wound care. The purpose of this work was to develop HD-AV media to inform patients of the risks, benefits, and alternatives of Mohs surgery before they are asked to sign the consent form and to educate patients on basic wound care after Mohs Surgery. The use of a HD virtual surgeon and nurse in the videos educates the patient, allowing the surgeon and nursing staff to attend to other patients within the Mohs Surgery Unit. Using HD digital recording equipment, we captured real-time HD-AV media to explain the risks, alternatives, and benefits of Mohs surgery (surgeon explanation) and to give detailed instructions for postoperative wound care (nurse explanation). Once captured, HD modules were created and stored on a central University of Texas–MD Anderson Cancer Center server in the Texas Medical Center approximately 1 mile from the Mohs Surgery Unit. The full-screen HD modules are accessed on demand at the point of need with the use of standard institutional computers within any of the Mohs’s center’s examination/surgical suites. An early evaluation of this quality improvement initiative was performed to measure patient satisfaction, efficiency, and efficacy of the videos followed by physician/nurse discussion compared with physician/nurse discussion alone. Early evaluation of HD-AV modules used for the delivery of informed consent and postoperative wound care in the MD Anderson Mohs surgery Unit revealed that patient satisfaction was maintained and that this medium was preferred by patients in the video group over physician/nurse discussion alone. The HD modules allowed increased efficiency and patient comprehension, which improved patient education in the Mohs Surgery Unit.

*For a PDF of the full article, click on the link to the left of this introduction.

Michael Migden, MD,*,† Arianne Chavez-Frazier, MD,* and Tri Nguyen, MD*

The use of video in the informed consent process has been well documented in the literature to improve patient satisfaction, understanding, comprehension, and to decrease anxiety. At the MD Anderson Mohs Surgery Unit, we use high-definition (HD) audiovisual (AV) modules to assist with the delivery of informed consent and to educate patients on the subject of postoperative wound care. The purpose of this work was to develop HD-AV media to inform patients of the risks, benefits, and alternatives of Mohs surgery before they are asked to sign the consent form and to educate patients on basic wound care after Mohs Surgery. The use of a HD virtual surgeon and nurse in the videos educates the patient, allowing the surgeon and nursing staff to attend to other patients within the Mohs Surgery Unit. Using HD digital recording equipment, we captured real-time HD-AV media to explain the risks, alternatives, and benefits of Mohs surgery (surgeon explanation) and to give detailed instructions for postoperative wound care (nurse explanation). Once captured, HD modules were created and stored on a central University of Texas–MD Anderson Cancer Center server in the Texas Medical Center approximately 1 mile from the Mohs Surgery Unit. The full-screen HD modules are accessed on demand at the point of need with the use of standard institutional computers within any of the Mohs’s center’s examination/surgical suites. An early evaluation of this quality improvement initiative was performed to measure patient satisfaction, efficiency, and efficacy of the videos followed by physician/nurse discussion compared with physician/nurse discussion alone. Early evaluation of HD-AV modules used for the delivery of informed consent and postoperative wound care in the MD Anderson Mohs surgery Unit revealed that patient satisfaction was maintained and that this medium was preferred by patients in the video group over physician/nurse discussion alone. The HD modules allowed increased efficiency and patient comprehension, which improved patient education in the Mohs Surgery Unit.

*For a PDF of the full article, click on the link to the left of this introduction.

BALTIMORE — The cutaneous adhesive Dermabond can be applied to the margins of a wound to buttress atrophied, thin skin enough to achieve adequate primary closure with sutures, Dr. Michael Bain reported at the annual meeting of the American Society of Plastic Surgeons.

Physicians have always had a difficult time suturing lacerations or defects created from the removal of cancer because sutures tear the skin of older patients with steroid-induced skin atrophy or genetically thin skin, said Dr. Bain, a plastic surgeon in private practice in Newport Beach, Calif.

"There are so many patients out there who in the past have needed skin grafting when they got a bad laceration," he said in an interview. "You could also use this technique in infants who have very thin skin."

After a standard wound preparation, Dermabond is applied 3 mm from the wound margins. Simple sutures placed either through or behind the Dermabond close the wound without tearing the skin. "You have to make certain that you don't get any Dermabond into the incision or into the wound because that will prevent healing," he said.

Dr. Bain has used the technique on about 15–20 patients without any problems. He said that his colleagues, as well as trauma surgeons, also have begun using the technique successfully.

By allowing the closure of wounds in thin skin, the technique may prevent the need for prolonged wound care, according to Dr. Bain, who presented the method on a poster. He and his coinvestigators have no conflicts of interest with regard to Ethicon Inc., the manufacturer of Dermabond.

The cutaneous adhesive, Dermabond, is applied 3 mm from the wound margins.

The healing wound is shown 3 weeks after the graft-sparing procedure. Photos courtesy Dr. Michael Bain

BALTIMORE — The cutaneous adhesive Dermabond can be applied to the margins of a wound to buttress atrophied, thin skin enough to achieve adequate primary closure with sutures, Dr. Michael Bain reported at the annual meeting of the American Society of Plastic Surgeons.

Physicians have always had a difficult time suturing lacerations or defects created from the removal of cancer because sutures tear the skin of older patients with steroid-induced skin atrophy or genetically thin skin, said Dr. Bain, a plastic surgeon in private practice in Newport Beach, Calif.

"There are so many patients out there who in the past have needed skin grafting when they got a bad laceration," he said in an interview. "You could also use this technique in infants who have very thin skin."

After a standard wound preparation, Dermabond is applied 3 mm from the wound margins. Simple sutures placed either through or behind the Dermabond close the wound without tearing the skin. "You have to make certain that you don't get any Dermabond into the incision or into the wound because that will prevent healing," he said.

Dr. Bain has used the technique on about 15–20 patients without any problems. He said that his colleagues, as well as trauma surgeons, also have begun using the technique successfully.

By allowing the closure of wounds in thin skin, the technique may prevent the need for prolonged wound care, according to Dr. Bain, who presented the method on a poster. He and his coinvestigators have no conflicts of interest with regard to Ethicon Inc., the manufacturer of Dermabond.

The cutaneous adhesive, Dermabond, is applied 3 mm from the wound margins.

The healing wound is shown 3 weeks after the graft-sparing procedure. Photos courtesy Dr. Michael Bain

BALTIMORE — The cutaneous adhesive Dermabond can be applied to the margins of a wound to buttress atrophied, thin skin enough to achieve adequate primary closure with sutures, Dr. Michael Bain reported at the annual meeting of the American Society of Plastic Surgeons.

Physicians have always had a difficult time suturing lacerations or defects created from the removal of cancer because sutures tear the skin of older patients with steroid-induced skin atrophy or genetically thin skin, said Dr. Bain, a plastic surgeon in private practice in Newport Beach, Calif.

"There are so many patients out there who in the past have needed skin grafting when they got a bad laceration," he said in an interview. "You could also use this technique in infants who have very thin skin."

After a standard wound preparation, Dermabond is applied 3 mm from the wound margins. Simple sutures placed either through or behind the Dermabond close the wound without tearing the skin. "You have to make certain that you don't get any Dermabond into the incision or into the wound because that will prevent healing," he said.

Dr. Bain has used the technique on about 15–20 patients without any problems. He said that his colleagues, as well as trauma surgeons, also have begun using the technique successfully.

By allowing the closure of wounds in thin skin, the technique may prevent the need for prolonged wound care, according to Dr. Bain, who presented the method on a poster. He and his coinvestigators have no conflicts of interest with regard to Ethicon Inc., the manufacturer of Dermabond.

The cutaneous adhesive, Dermabond, is applied 3 mm from the wound margins.

The healing wound is shown 3 weeks after the graft-sparing procedure. Photos courtesy Dr. Michael Bain

BALTIMORE — Oasis wound matrix provides a low-maintenance scaffold for split-thickness skin graft donor sites to grow new epidermis over several weeks without significant pain for the patient, Dr. James C. Yuen said in a poster presented at the annual meeting of the American Society of Plastic Surgeons.

Since Oasis was approved by the Food and Drug Administration in 2000, few articles have been published on its use, none of which describes using it for dressing split-thickness skin graft donor sites, according to Dr. Yuen of the division of plastic and reconstructive surgery at the University of Arkansas, Little Rock.

Oasis is derived from porcine intestinal mucosa and acts as an extracellular matrix to support cell adherence, he said.

The material contains key components of the dermal extracellular matrix (collagen, elastin, glycosaminoglycans, glycoproteins, proteoglycans, and growth hormones) to promote rapid cellular proliferation and capillary ingrowth.

During 2003–2006, Dr. Yuen and his colleague, Dr. Julio Hochberg, also of the university, used Oasis to reepithelialize split-thickness skin graft donor sites on the thighs of 131 patients.

Epithelialization was complete after 1–3 weeks in all but two patients who had delayed healing beyond 1 month. Few patients experienced significant pain at the donor site because the material protects nerve endings, the investigators suggested.

Once Oasis is placed directly over the wound, Xeroform (Kendall Inc.) is placed to cover the matrix, followed by nonadherent Telfa gauze (Kendall), 4-by-4-inch dry gauze pads, and then Tegaderm tape (3M Health Care) for smaller donor sites or a circumferential wrap with Kerlix (Kendall) for larger sites. Dr. Yuen said that neither he nor Dr. Hochberg has any conflicts of interest with the manufacturers of any the products used in the procedure.

The investigators typically changed the dressing 4–6 days after surgery, but it was done earlier if there was excessive drainage soaking through the dressing.

Subsequent dressing changes occurred every 2–3 days, leaving the Oasis wound matrix and Xeroform in place each time.

The scab-like wound matrix peels off easily after reepithelialization is complete, Dr. Yuen said.

BALTIMORE — Oasis wound matrix provides a low-maintenance scaffold for split-thickness skin graft donor sites to grow new epidermis over several weeks without significant pain for the patient, Dr. James C. Yuen said in a poster presented at the annual meeting of the American Society of Plastic Surgeons.

Since Oasis was approved by the Food and Drug Administration in 2000, few articles have been published on its use, none of which describes using it for dressing split-thickness skin graft donor sites, according to Dr. Yuen of the division of plastic and reconstructive surgery at the University of Arkansas, Little Rock.

Oasis is derived from porcine intestinal mucosa and acts as an extracellular matrix to support cell adherence, he said.

The material contains key components of the dermal extracellular matrix (collagen, elastin, glycosaminoglycans, glycoproteins, proteoglycans, and growth hormones) to promote rapid cellular proliferation and capillary ingrowth.

During 2003–2006, Dr. Yuen and his colleague, Dr. Julio Hochberg, also of the university, used Oasis to reepithelialize split-thickness skin graft donor sites on the thighs of 131 patients.

Epithelialization was complete after 1–3 weeks in all but two patients who had delayed healing beyond 1 month. Few patients experienced significant pain at the donor site because the material protects nerve endings, the investigators suggested.

Once Oasis is placed directly over the wound, Xeroform (Kendall Inc.) is placed to cover the matrix, followed by nonadherent Telfa gauze (Kendall), 4-by-4-inch dry gauze pads, and then Tegaderm tape (3M Health Care) for smaller donor sites or a circumferential wrap with Kerlix (Kendall) for larger sites. Dr. Yuen said that neither he nor Dr. Hochberg has any conflicts of interest with the manufacturers of any the products used in the procedure.

The investigators typically changed the dressing 4–6 days after surgery, but it was done earlier if there was excessive drainage soaking through the dressing.

Subsequent dressing changes occurred every 2–3 days, leaving the Oasis wound matrix and Xeroform in place each time.

The scab-like wound matrix peels off easily after reepithelialization is complete, Dr. Yuen said.

BALTIMORE — Oasis wound matrix provides a low-maintenance scaffold for split-thickness skin graft donor sites to grow new epidermis over several weeks without significant pain for the patient, Dr. James C. Yuen said in a poster presented at the annual meeting of the American Society of Plastic Surgeons.

Since Oasis was approved by the Food and Drug Administration in 2000, few articles have been published on its use, none of which describes using it for dressing split-thickness skin graft donor sites, according to Dr. Yuen of the division of plastic and reconstructive surgery at the University of Arkansas, Little Rock.

Oasis is derived from porcine intestinal mucosa and acts as an extracellular matrix to support cell adherence, he said.

The material contains key components of the dermal extracellular matrix (collagen, elastin, glycosaminoglycans, glycoproteins, proteoglycans, and growth hormones) to promote rapid cellular proliferation and capillary ingrowth.

During 2003–2006, Dr. Yuen and his colleague, Dr. Julio Hochberg, also of the university, used Oasis to reepithelialize split-thickness skin graft donor sites on the thighs of 131 patients.

Epithelialization was complete after 1–3 weeks in all but two patients who had delayed healing beyond 1 month. Few patients experienced significant pain at the donor site because the material protects nerve endings, the investigators suggested.

Once Oasis is placed directly over the wound, Xeroform (Kendall Inc.) is placed to cover the matrix, followed by nonadherent Telfa gauze (Kendall), 4-by-4-inch dry gauze pads, and then Tegaderm tape (3M Health Care) for smaller donor sites or a circumferential wrap with Kerlix (Kendall) for larger sites. Dr. Yuen said that neither he nor Dr. Hochberg has any conflicts of interest with the manufacturers of any the products used in the procedure.

The investigators typically changed the dressing 4–6 days after surgery, but it was done earlier if there was excessive drainage soaking through the dressing.

Subsequent dressing changes occurred every 2–3 days, leaving the Oasis wound matrix and Xeroform in place each time.

The scab-like wound matrix peels off easily after reepithelialization is complete, Dr. Yuen said.

WASHINGTON — Monotherapy may not be enough in the treatment of diabetic wound infections.

These infections are not caused by the planktonic or individual cellular form of mainly single-species bacteria proliferating in the wound, but rather are caused by a complex, multicell vegetative mixed-bacterial state known as a biofilm, which has to be treated as a unique and dangerous organism in its own right, if treatment is to prove effective, according to Dr. Randall Wolcott, of the department of microbiology and immunology at Texas Tech University, Lubbock.

The medical biofilm concept of infection is a fairly new one, and a recent review noted that almost every bodily system is affected by a biofilm disease, said Dr. Wolcott at a meeting sponsored by George Washington University Hospital.

He estimated that every year, more than 10 million people come down with biofilm diseases, from endocarditis to necrotizing fasciitis, which translates to more than 500,000 people a year who die from the disease.

And if all these infections are really biofilms, then the next therapeutic step is to move from antibiotic monotherapies to include the use of antibiofilm agents and aggressive treatments, Dr. Wolcott said.

His recommended combined treatment is only in its infancy, but it involves frequent, very aggressive debridement, coupled with biocide treatments that include heavy metal agents such as silver, gallium, and selenium. It is important to rotate treatments in order to prevent selective adaptation of the biofilm, which can happen not in weeks or months, but in days.

It is also critical to include the use of specific antibiofilm agents such as lactoferrin and xylitol, which are approved by the Food and Drug Administration for other purposes. He has even experimentally used predatory bacteriophages and various plant extracts known for their antibiofilm properties. Ultimately, "once you suppress the biofilm below a certain level … the wound starts contracting" and normal host healing can begin, he said.

This understanding is very new, and few people are being trained enough to understand it as yet. "I just got a [2007] medical microbiology text and it does not mention biofilms," he said.

However, physicians see biofilms in diabetic foot wounds every day without realizing it: the so-called slough that physicians routinely remove, or not, said Dr. Wolcott. Many physicians believe slough is merely a mixture of white blood cells, protein, and deteriorated host tissue, but it is actually part of a complex biofilm—and one that will return, if even "one cell remains" still virulent, exactly as before without proper treatment.

Once bacteria attach to a wounded surface, "they form a microcolony. Once they reach a critical density, they start form-sensing, and they rise up above the surface and they start forming all these complex structures. One of those structures infests itself around the vasculature and they invade the host down through the vascular system. [They also] rise up over the surface for community defenses," he said.

This vegetative state behaves like a single organism "made of billions of billions of cells" including multiple bacterial species. A large portion of this "organism"—and he stressed treating it as such—includes gluey, sugar-protein matrices formed within the first 5 minutes of biofilm development. These protect the bacteria from harm by walling them off—not only from the host immune system, but also from many of the treatments that are used, Dr. Wolcott said.

Within 30 minutes, the biofilm is rising from the surface. It is controlled centrally by various intercellular communication molecules that act almost like hormones, and it reproduces by vegetative breaking and single-cell "seeds."

The biofilm components summon white blood cells, with their phagocytic enzymes, which actually can provide nutrients for the biofilm; this explains much of the biochemistry we see, according to Dr. Wolcott.

The bacteria give up their individuality and live for the colony, with different regions producing different proteins. One clinically important factor is that there are portions of the biofilm where the cells upregulate gene transfer to create phenotypic and genotypic diversity to survive. This includes the potential for transferring antibiotic resistance across species.

Dr. Wolcott had no disclosures other than the use of materials that are not FDA approved for these indications.

WASHINGTON — Monotherapy may not be enough in the treatment of diabetic wound infections.

These infections are not caused by the planktonic or individual cellular form of mainly single-species bacteria proliferating in the wound, but rather are caused by a complex, multicell vegetative mixed-bacterial state known as a biofilm, which has to be treated as a unique and dangerous organism in its own right, if treatment is to prove effective, according to Dr. Randall Wolcott, of the department of microbiology and immunology at Texas Tech University, Lubbock.

The medical biofilm concept of infection is a fairly new one, and a recent review noted that almost every bodily system is affected by a biofilm disease, said Dr. Wolcott at a meeting sponsored by George Washington University Hospital.

He estimated that every year, more than 10 million people come down with biofilm diseases, from endocarditis to necrotizing fasciitis, which translates to more than 500,000 people a year who die from the disease.

And if all these infections are really biofilms, then the next therapeutic step is to move from antibiotic monotherapies to include the use of antibiofilm agents and aggressive treatments, Dr. Wolcott said.

His recommended combined treatment is only in its infancy, but it involves frequent, very aggressive debridement, coupled with biocide treatments that include heavy metal agents such as silver, gallium, and selenium. It is important to rotate treatments in order to prevent selective adaptation of the biofilm, which can happen not in weeks or months, but in days.

It is also critical to include the use of specific antibiofilm agents such as lactoferrin and xylitol, which are approved by the Food and Drug Administration for other purposes. He has even experimentally used predatory bacteriophages and various plant extracts known for their antibiofilm properties. Ultimately, "once you suppress the biofilm below a certain level … the wound starts contracting" and normal host healing can begin, he said.

This understanding is very new, and few people are being trained enough to understand it as yet. "I just got a [2007] medical microbiology text and it does not mention biofilms," he said.

However, physicians see biofilms in diabetic foot wounds every day without realizing it: the so-called slough that physicians routinely remove, or not, said Dr. Wolcott. Many physicians believe slough is merely a mixture of white blood cells, protein, and deteriorated host tissue, but it is actually part of a complex biofilm—and one that will return, if even "one cell remains" still virulent, exactly as before without proper treatment.

Once bacteria attach to a wounded surface, "they form a microcolony. Once they reach a critical density, they start form-sensing, and they rise up above the surface and they start forming all these complex structures. One of those structures infests itself around the vasculature and they invade the host down through the vascular system. [They also] rise up over the surface for community defenses," he said.

This vegetative state behaves like a single organism "made of billions of billions of cells" including multiple bacterial species. A large portion of this "organism"—and he stressed treating it as such—includes gluey, sugar-protein matrices formed within the first 5 minutes of biofilm development. These protect the bacteria from harm by walling them off—not only from the host immune system, but also from many of the treatments that are used, Dr. Wolcott said.

Within 30 minutes, the biofilm is rising from the surface. It is controlled centrally by various intercellular communication molecules that act almost like hormones, and it reproduces by vegetative breaking and single-cell "seeds."

The biofilm components summon white blood cells, with their phagocytic enzymes, which actually can provide nutrients for the biofilm; this explains much of the biochemistry we see, according to Dr. Wolcott.

The bacteria give up their individuality and live for the colony, with different regions producing different proteins. One clinically important factor is that there are portions of the biofilm where the cells upregulate gene transfer to create phenotypic and genotypic diversity to survive. This includes the potential for transferring antibiotic resistance across species.

Dr. Wolcott had no disclosures other than the use of materials that are not FDA approved for these indications.

WASHINGTON — Monotherapy may not be enough in the treatment of diabetic wound infections.

These infections are not caused by the planktonic or individual cellular form of mainly single-species bacteria proliferating in the wound, but rather are caused by a complex, multicell vegetative mixed-bacterial state known as a biofilm, which has to be treated as a unique and dangerous organism in its own right, if treatment is to prove effective, according to Dr. Randall Wolcott, of the department of microbiology and immunology at Texas Tech University, Lubbock.

The medical biofilm concept of infection is a fairly new one, and a recent review noted that almost every bodily system is affected by a biofilm disease, said Dr. Wolcott at a meeting sponsored by George Washington University Hospital.

He estimated that every year, more than 10 million people come down with biofilm diseases, from endocarditis to necrotizing fasciitis, which translates to more than 500,000 people a year who die from the disease.

And if all these infections are really biofilms, then the next therapeutic step is to move from antibiotic monotherapies to include the use of antibiofilm agents and aggressive treatments, Dr. Wolcott said.

His recommended combined treatment is only in its infancy, but it involves frequent, very aggressive debridement, coupled with biocide treatments that include heavy metal agents such as silver, gallium, and selenium. It is important to rotate treatments in order to prevent selective adaptation of the biofilm, which can happen not in weeks or months, but in days.

It is also critical to include the use of specific antibiofilm agents such as lactoferrin and xylitol, which are approved by the Food and Drug Administration for other purposes. He has even experimentally used predatory bacteriophages and various plant extracts known for their antibiofilm properties. Ultimately, "once you suppress the biofilm below a certain level … the wound starts contracting" and normal host healing can begin, he said.

This understanding is very new, and few people are being trained enough to understand it as yet. "I just got a [2007] medical microbiology text and it does not mention biofilms," he said.

However, physicians see biofilms in diabetic foot wounds every day without realizing it: the so-called slough that physicians routinely remove, or not, said Dr. Wolcott. Many physicians believe slough is merely a mixture of white blood cells, protein, and deteriorated host tissue, but it is actually part of a complex biofilm—and one that will return, if even "one cell remains" still virulent, exactly as before without proper treatment.

Once bacteria attach to a wounded surface, "they form a microcolony. Once they reach a critical density, they start form-sensing, and they rise up above the surface and they start forming all these complex structures. One of those structures infests itself around the vasculature and they invade the host down through the vascular system. [They also] rise up over the surface for community defenses," he said.

This vegetative state behaves like a single organism "made of billions of billions of cells" including multiple bacterial species. A large portion of this "organism"—and he stressed treating it as such—includes gluey, sugar-protein matrices formed within the first 5 minutes of biofilm development. These protect the bacteria from harm by walling them off—not only from the host immune system, but also from many of the treatments that are used, Dr. Wolcott said.

Within 30 minutes, the biofilm is rising from the surface. It is controlled centrally by various intercellular communication molecules that act almost like hormones, and it reproduces by vegetative breaking and single-cell "seeds."

The biofilm components summon white blood cells, with their phagocytic enzymes, which actually can provide nutrients for the biofilm; this explains much of the biochemistry we see, according to Dr. Wolcott.

The bacteria give up their individuality and live for the colony, with different regions producing different proteins. One clinically important factor is that there are portions of the biofilm where the cells upregulate gene transfer to create phenotypic and genotypic diversity to survive. This includes the potential for transferring antibiotic resistance across species.

Dr. Wolcott had no disclosures other than the use of materials that are not FDA approved for these indications.

The multibillion dollar wound-care industry has brought a myriad of new support surface options as well as dressings and wound treatments, but nothing works like a "back-to-basics" approach, experts say.

Has optimal practice changed in any significant way since the Agency for Health Care Policy and Research (AHCPR) guidelines for pressure ulcer prevention and treatment came out in 1992 and 1994, asked Rita A. Franz, Ph.D. "I don't think so."

Experts are excited by the potential of ultrasound technology that is being pilot tested in nursing homes for early detection of pressure ulcers.

But at this point, most of the advancements made since the early ′90s have been "advancements in the absence of science," or the absence of scientific evidence for efficacy, said Dr. Franz, Kelting dean and professor in the University of Iowa's College of Nursing in Iowa City

Data suggest, for instance, that patients likely to develop a pressure ulcer should be treated with a pressure-reducing surface or device. A 2004 Cochrane review, in fact, showed that compared with standard hospital mattresses, a variety of devices can lower the incidence of pressure ulcers by about 60%—but experts have been largely unsuccessful in comparing support surfaces based on meaningful functional characteristics, leaving no one device or type of device scientifically superior.

The science of pressure ulcers—etiology, causes, and classification—is still evolving, as is the science of quality measurement. But, despite the change and uncertainties, the vigilance with which nursing homes are attempting to bring the "basics" more consistently and successfully into everyday practice is increasing, and providers are beginning to see results of their efforts.

Certified nursing assistants (CNAs) check patients at Virtua Health and Rehabilitation Centers every day, looking for changes in the skin and reporting such changes immediately to nurses. Nurses also perform head-to-toe skin checks weekly on each patient. In addition, every resident who leaves for a diagnostic test, appointment, or family visit for at least 2 hours receives a full skin check upon returning to a nursing home unit.

Pressure reduction is also thorough: In addition to mattress replacements and overlays for at-risk residents, all residents who cannot reposition themselves have their calves and heels floated on pillows at night, for example. All wheelchairs and geriatric chairs have cushions.

Bed-bound residents are turned every 2 hours, and residents in wheelchairs and geriatric chairs are repositioned every hour. Moisture barriers are used routinely for incontinent patients.

The 2-hour turning/repositioning schedule that is commonly accepted as a standard goal was never subjected to a randomized trial, Dr. Franz notes, but evolved from the results of an observational study done years ago in London on the relationship between amounts of spontaneous nighttime movement and pressure ulcer incidence.

Even without evidence of a casual relationship between good nutrition and pressure ulcer prevention—and with disappointing results of nutritional intervention trials—it still seems only logical to promote good nutrition "on the front lines."

Dr. Jeffrey M. Levine of the Cabrini Wound Healing Center and St. Vincent's Medical Center in New York, encourages physicians to "relearn" the art of wound care that physicians used to study and practice. "Unfortunately, wound care has fallen by the wayside for contemporary doctors." He said he hopes to see new standards and techniques both for pressure relief and for the early detection and assessment of skin breakdown that can lead to the development of advanced stages of pressure ulcers.

With Medicare's upcoming reimbursement changes for hospital-acquired pressure ulcers, hospitals will turn to nursing homes for advice as they revamp their skin assessment programs and educate physicians, he said.

"Acute care has a lot to learn from the long-term care environment," he said. "The long-term care community has been far advanced in their skin care" and advanced in the application of basic processes. The back-to-basics approach that Dr. Levine teaches extends well beyond prevention and into management. "We need to evaluate the wound, keep it clean and moist, remove debris, feed the patient, and treat infections," he said.

The multibillion dollar wound-care industry has brought a myriad of new support surface options as well as dressings and wound treatments, but nothing works like a "back-to-basics" approach, experts say.

Has optimal practice changed in any significant way since the Agency for Health Care Policy and Research (AHCPR) guidelines for pressure ulcer prevention and treatment came out in 1992 and 1994, asked Rita A. Franz, Ph.D. "I don't think so."

Experts are excited by the potential of ultrasound technology that is being pilot tested in nursing homes for early detection of pressure ulcers.

But at this point, most of the advancements made since the early ′90s have been "advancements in the absence of science," or the absence of scientific evidence for efficacy, said Dr. Franz, Kelting dean and professor in the University of Iowa's College of Nursing in Iowa City

Data suggest, for instance, that patients likely to develop a pressure ulcer should be treated with a pressure-reducing surface or device. A 2004 Cochrane review, in fact, showed that compared with standard hospital mattresses, a variety of devices can lower the incidence of pressure ulcers by about 60%—but experts have been largely unsuccessful in comparing support surfaces based on meaningful functional characteristics, leaving no one device or type of device scientifically superior.

The science of pressure ulcers—etiology, causes, and classification—is still evolving, as is the science of quality measurement. But, despite the change and uncertainties, the vigilance with which nursing homes are attempting to bring the "basics" more consistently and successfully into everyday practice is increasing, and providers are beginning to see results of their efforts.

Certified nursing assistants (CNAs) check patients at Virtua Health and Rehabilitation Centers every day, looking for changes in the skin and reporting such changes immediately to nurses. Nurses also perform head-to-toe skin checks weekly on each patient. In addition, every resident who leaves for a diagnostic test, appointment, or family visit for at least 2 hours receives a full skin check upon returning to a nursing home unit.

Pressure reduction is also thorough: In addition to mattress replacements and overlays for at-risk residents, all residents who cannot reposition themselves have their calves and heels floated on pillows at night, for example. All wheelchairs and geriatric chairs have cushions.

Bed-bound residents are turned every 2 hours, and residents in wheelchairs and geriatric chairs are repositioned every hour. Moisture barriers are used routinely for incontinent patients.

The 2-hour turning/repositioning schedule that is commonly accepted as a standard goal was never subjected to a randomized trial, Dr. Franz notes, but evolved from the results of an observational study done years ago in London on the relationship between amounts of spontaneous nighttime movement and pressure ulcer incidence.

Even without evidence of a casual relationship between good nutrition and pressure ulcer prevention—and with disappointing results of nutritional intervention trials—it still seems only logical to promote good nutrition "on the front lines."

Dr. Jeffrey M. Levine of the Cabrini Wound Healing Center and St. Vincent's Medical Center in New York, encourages physicians to "relearn" the art of wound care that physicians used to study and practice. "Unfortunately, wound care has fallen by the wayside for contemporary doctors." He said he hopes to see new standards and techniques both for pressure relief and for the early detection and assessment of skin breakdown that can lead to the development of advanced stages of pressure ulcers.

With Medicare's upcoming reimbursement changes for hospital-acquired pressure ulcers, hospitals will turn to nursing homes for advice as they revamp their skin assessment programs and educate physicians, he said.

"Acute care has a lot to learn from the long-term care environment," he said. "The long-term care community has been far advanced in their skin care" and advanced in the application of basic processes. The back-to-basics approach that Dr. Levine teaches extends well beyond prevention and into management. "We need to evaluate the wound, keep it clean and moist, remove debris, feed the patient, and treat infections," he said.

The multibillion dollar wound-care industry has brought a myriad of new support surface options as well as dressings and wound treatments, but nothing works like a "back-to-basics" approach, experts say.

Has optimal practice changed in any significant way since the Agency for Health Care Policy and Research (AHCPR) guidelines for pressure ulcer prevention and treatment came out in 1992 and 1994, asked Rita A. Franz, Ph.D. "I don't think so."

Experts are excited by the potential of ultrasound technology that is being pilot tested in nursing homes for early detection of pressure ulcers.

But at this point, most of the advancements made since the early ′90s have been "advancements in the absence of science," or the absence of scientific evidence for efficacy, said Dr. Franz, Kelting dean and professor in the University of Iowa's College of Nursing in Iowa City

Data suggest, for instance, that patients likely to develop a pressure ulcer should be treated with a pressure-reducing surface or device. A 2004 Cochrane review, in fact, showed that compared with standard hospital mattresses, a variety of devices can lower the incidence of pressure ulcers by about 60%—but experts have been largely unsuccessful in comparing support surfaces based on meaningful functional characteristics, leaving no one device or type of device scientifically superior.

The science of pressure ulcers—etiology, causes, and classification—is still evolving, as is the science of quality measurement. But, despite the change and uncertainties, the vigilance with which nursing homes are attempting to bring the "basics" more consistently and successfully into everyday practice is increasing, and providers are beginning to see results of their efforts.

Certified nursing assistants (CNAs) check patients at Virtua Health and Rehabilitation Centers every day, looking for changes in the skin and reporting such changes immediately to nurses. Nurses also perform head-to-toe skin checks weekly on each patient. In addition, every resident who leaves for a diagnostic test, appointment, or family visit for at least 2 hours receives a full skin check upon returning to a nursing home unit.

Pressure reduction is also thorough: In addition to mattress replacements and overlays for at-risk residents, all residents who cannot reposition themselves have their calves and heels floated on pillows at night, for example. All wheelchairs and geriatric chairs have cushions.

Bed-bound residents are turned every 2 hours, and residents in wheelchairs and geriatric chairs are repositioned every hour. Moisture barriers are used routinely for incontinent patients.

The 2-hour turning/repositioning schedule that is commonly accepted as a standard goal was never subjected to a randomized trial, Dr. Franz notes, but evolved from the results of an observational study done years ago in London on the relationship between amounts of spontaneous nighttime movement and pressure ulcer incidence.

Even without evidence of a casual relationship between good nutrition and pressure ulcer prevention—and with disappointing results of nutritional intervention trials—it still seems only logical to promote good nutrition "on the front lines."

Dr. Jeffrey M. Levine of the Cabrini Wound Healing Center and St. Vincent's Medical Center in New York, encourages physicians to "relearn" the art of wound care that physicians used to study and practice. "Unfortunately, wound care has fallen by the wayside for contemporary doctors." He said he hopes to see new standards and techniques both for pressure relief and for the early detection and assessment of skin breakdown that can lead to the development of advanced stages of pressure ulcers.

With Medicare's upcoming reimbursement changes for hospital-acquired pressure ulcers, hospitals will turn to nursing homes for advice as they revamp their skin assessment programs and educate physicians, he said.

"Acute care has a lot to learn from the long-term care environment," he said. "The long-term care community has been far advanced in their skin care" and advanced in the application of basic processes. The back-to-basics approach that Dr. Levine teaches extends well beyond prevention and into management. "We need to evaluate the wound, keep it clean and moist, remove debris, feed the patient, and treat infections," he said.

Bromelain is a designation referring to the family of sulfhydryl-containing proteolytic enzymes derived from the stem of the pineapple plant, Ananas comosus (Altern. Med. Rev. 2003;8:359–77).

Pineapple has been used as a folk medicine in tropical regions such as Hawaii, as well as in Japan and Taiwan, for centuries.

It continues to be used to clean wounds and burns in those regions. As an oral supplement, bromelain is typically administered to aid digestion. It also is considered a natural blood thinner, and has long been part of traditional tropical health regimens for its range of anti-inflammatory properties (Skin Therapy Lett. 2000;5:1–2, 5). Bromelain is considered by some to be as effective as some of the popular NSAIDs.

The most common use of bromelain is for the treatment of inflammation and soft tissue injuries.

Therapeutic Effects

The pharmacologic properties of pineapple's constituent bromelain have been gradually uncovered by Western medicine during the last 4 decades. Bromelain inhibits platelet aggregation, exhibits fibrinolytic activity, has anti-inflammatory action, promotes skin debridement, and interferes with the growth of malignant cells (J. Ethnopharmacol. 1988;22:191–203).

Studies performed 40 years ago showed that the oral administration of bromelain reduced edema, bruising, pain, and healing time after dental surgery. Although postsurgical administration was seen as effective, a combination of pre- and postoperative administration was recommended (J. Dent. Med. 1965;20:51–4; J. Dent. Med. 1964;19:73–7).

Studies performed since the 1960s have confirmed bromelain's beneficial effects after surgery or trauma (Altern. Med. Rev. 2003;8:359–77; Obstet. Gynecol. 1967;29:275–8; Eye Ear Nose Throat Mon. 1968;47:634–9; J. Obstet. Gynaecol. Br. Commonw. 1972;79:951–3; Skin Therapy Lett. 2000;5:1–2, 5; Altern. Med. Rev. 1998;3:302–5).

In a study of patients undergoing rhinoplasty, 53 patients were randomized to one of two bromelain treatment groups or placebo. Edema and ecchymosis lasted for 7 days in the placebo group but only 2 days in both bromelain groups (Eye Ear Nose Throat Mon. 1962;41:813–7). A few years later, a randomized study of 154 facial plastic surgery patients showed no significant differences in edema between bromelain and a placebo (Acta Chir. Scand. 1966;131:193–6).

An uncontrolled trial performed a decade ago suggested that bromelain reduces edema, tenderness, and pain, at rest and in motion, in patients with blunt trauma to the musculoskeletal system (Fortschr. Med. 1995;113:303–6). In a more recent study of a proteolytic enzyme formulation containing bromelain, patients with long bone fractures given the botanical exhibited significantly less postoperative edema than the placebo group (Acta Chir. Orthop. Traumatol. Cech. 2001;68:45–9).

These effects are largely ascribed to the anti-inflammatory capacity of the plant enzyme (Altern. Med. Rev. 2003;8:359–77). In vitro and in vivo studies have shown that the various proteinases contained in bromelain have antiedematous, anti-inflammatory, antithrombotic, and fibrinolytic activities (Cell. Mol. Life Sci. 2001;58:1234–45).

The topical application of a bromelain cream (35% bromelain in a lipid base) has been shown to confer specific benefits, including eliminating burn debris and accelerating wound healing. Escharase, a nonpro-teolytic constituent, is credited with imparting these effects (Altern. Med. Rev. 1998;3:302–5).

Bromelain has been demonstrated to enhance the potentiation of antibiotics (Altern. Med. Rev. 1998;3:302–5), and to confer benefits in the treatment of angina pectoris, bronchitis, sinusitis, thrombophlebitis, pyelonephritis, and wounds (Cell. Mol. Life Sci. 2001;58:1234–45).

In animal experiments, bromelain has been found to inhibit coagulation, primarily by the stimulation of serum fibrinolytic activity, disruption of fibrinogen synthesis, and the related degradation of fibrin and fibrinogen.

Bromelain has also been shown to inhibit experimentally induced tumors in animals, predominantly dose dependently, and exhibit antiedematous and anti-inflammatory activity (Planta Med. 1990;56:249–53).

Recent studies suggest the usefulness of oral bromelain as an immunomodulatory tumor therapy, as it shows a time- and dose-dependent capacity to enhance, in vivo, the immunocytotoxicity of monocytes against tumor cells and to induce production of cytokines, including tumor necrosis factor-α, interleukin-1 β, Il-6, and Il-8 (Cell. Mol. Life Sci. 2001;58:1234–45).

Renewed interest in bromelain, after a drop-off for several years, has resulted in a spate of recent studies and evidence of oral efficacy. Such results, coupled with bromelain's positive safety profile, have brought increasing acceptance of this botanical among consumers and some practitioners (Cell. Mol. Life Sci. 2001;58:1234–45).

The discovery of oral efficacy helped to surmount earlier uncertainty about the bioavailability of bromelain. A study of 19 healthy human males found that small levels of undegraded bromelain traveled intact through the gastrointestinal tract (Am. J. Physiol. 1997;273:G139–46).

While the primary component of bromelain is the sulfhydryl proteolytic fraction, it also contains a peroxidase, acid phosphatase, several protease inhibitors, and organically bound calcium. Bromelain's pharmacologic activities, although often ascribed to the proteolytic fraction, cannot be wholly attributed to that portion as there is evidence that several of its constituents have beneficial properties (Altern. Med. Rev. 1998;3:302–5). Bromelain's mechanism of action has been ascribed partly to its modulation of the arachidonic acid cascade (J. Ethnopharmacol. 1988;22:191–203).

The pineapple enzyme is believed to inhibit the production of proinflammatory prostaglandins, initiate the production of anti-inflammatory series 1 prostaglandins, and reduce capillary permeability (Med. Hypotheses 1980;6:99–104).

A study of a commercial polyenzyme preparation containing bromelain showed that it induced cytokine production in vitro in peripheral blood mononuclear cells. This capacity to induce cytokine production has been cited as a reason for the antitumor effects of such bromelain-containing enzyme formulations (Oncology 1993;50:403–7).

On the Market

Bromelain has been approved by the German Commission E for postsurgical and/or posttraumatic edema, particularly of the nasal and paranasal sinuses characteristic of some plastic surgery. A patented cutaneous tape containing bromelain is also available in Europe for debriding scar tissue.

Although it is no longer commercially available, Ananase, used for healing wounds and resolving certain hematomas, contained bromelain as the main active ingredient and was included in the Physicians' Desk Reference in the early 1960s. Taken orally 1 hour before or 2 hours after meals, bromelain supplements are absorbed by white blood cells and enhance their enzymatic activity (Dermatol. Ther. 2003;16:106–13).

Bromelain has been known to cause allergic reactions such as asthma, rhinitis, and gastrointestinal symptoms (Clin. Allergy 1979;9:443–50). Such occurrences are rare, however.

The botanical is contraindicated in children, people with allergies to pineapple or bee stings, individuals with a history of heart palpitations, and patients taking blood thinners.

In My Practice

We began using bromelain supplements in our patients about a year ago, with spectacular results. We have them take 500 mg twice a day for 3 days after botulinum toxin injections, dermal fillers, surgeries, or other procedures that may result in bruising. We do not have patients take the supplements prior to the procedure because it seems to increase bruising. (Arnica tablets can be used prior to the procedure.)

I have seen bruising resolve much more rapidly when patients take these supplements. One of my patients had a facelift and ate pineapple three times a day, and her lack of bruising was amazing.

I had a basal cell carcinoma removed from my lid margin, which required a 1-cm-by-7-mm excision. I took bromelain supplements (even though the surgeon told me not to), and he was amazed at my lack of bruising. I have not seen any allergic reactions or complications.

I have not had time to do a formal study of this botanical, but I wanted to share my experience with you. Please send me your recommendations for preventing and treating bruising. I plan to do a future column on bruising and its treatment and prevention. Thanks to you all for your continued letters, suggestions, and input. Keep it coming!

Bromelain, a family of sulfhydryl-containing proteolytic enzymes derived from the stems of pineapples, is used to treat inflammation and soft tissue injuries. Donna Franki/Elsevier Global Medical News

Bromelain is a designation referring to the family of sulfhydryl-containing proteolytic enzymes derived from the stem of the pineapple plant, Ananas comosus (Altern. Med. Rev. 2003;8:359–77).

Pineapple has been used as a folk medicine in tropical regions such as Hawaii, as well as in Japan and Taiwan, for centuries.

It continues to be used to clean wounds and burns in those regions. As an oral supplement, bromelain is typically administered to aid digestion. It also is considered a natural blood thinner, and has long been part of traditional tropical health regimens for its range of anti-inflammatory properties (Skin Therapy Lett. 2000;5:1–2, 5). Bromelain is considered by some to be as effective as some of the popular NSAIDs.

The most common use of bromelain is for the treatment of inflammation and soft tissue injuries.

Therapeutic Effects

The pharmacologic properties of pineapple's constituent bromelain have been gradually uncovered by Western medicine during the last 4 decades. Bromelain inhibits platelet aggregation, exhibits fibrinolytic activity, has anti-inflammatory action, promotes skin debridement, and interferes with the growth of malignant cells (J. Ethnopharmacol. 1988;22:191–203).

Studies performed 40 years ago showed that the oral administration of bromelain reduced edema, bruising, pain, and healing time after dental surgery. Although postsurgical administration was seen as effective, a combination of pre- and postoperative administration was recommended (J. Dent. Med. 1965;20:51–4; J. Dent. Med. 1964;19:73–7).

Studies performed since the 1960s have confirmed bromelain's beneficial effects after surgery or trauma (Altern. Med. Rev. 2003;8:359–77; Obstet. Gynecol. 1967;29:275–8; Eye Ear Nose Throat Mon. 1968;47:634–9; J. Obstet. Gynaecol. Br. Commonw. 1972;79:951–3; Skin Therapy Lett. 2000;5:1–2, 5; Altern. Med. Rev. 1998;3:302–5).

In a study of patients undergoing rhinoplasty, 53 patients were randomized to one of two bromelain treatment groups or placebo. Edema and ecchymosis lasted for 7 days in the placebo group but only 2 days in both bromelain groups (Eye Ear Nose Throat Mon. 1962;41:813–7). A few years later, a randomized study of 154 facial plastic surgery patients showed no significant differences in edema between bromelain and a placebo (Acta Chir. Scand. 1966;131:193–6).

An uncontrolled trial performed a decade ago suggested that bromelain reduces edema, tenderness, and pain, at rest and in motion, in patients with blunt trauma to the musculoskeletal system (Fortschr. Med. 1995;113:303–6). In a more recent study of a proteolytic enzyme formulation containing bromelain, patients with long bone fractures given the botanical exhibited significantly less postoperative edema than the placebo group (Acta Chir. Orthop. Traumatol. Cech. 2001;68:45–9).

These effects are largely ascribed to the anti-inflammatory capacity of the plant enzyme (Altern. Med. Rev. 2003;8:359–77). In vitro and in vivo studies have shown that the various proteinases contained in bromelain have antiedematous, anti-inflammatory, antithrombotic, and fibrinolytic activities (Cell. Mol. Life Sci. 2001;58:1234–45).

The topical application of a bromelain cream (35% bromelain in a lipid base) has been shown to confer specific benefits, including eliminating burn debris and accelerating wound healing. Escharase, a nonpro-teolytic constituent, is credited with imparting these effects (Altern. Med. Rev. 1998;3:302–5).

Bromelain has been demonstrated to enhance the potentiation of antibiotics (Altern. Med. Rev. 1998;3:302–5), and to confer benefits in the treatment of angina pectoris, bronchitis, sinusitis, thrombophlebitis, pyelonephritis, and wounds (Cell. Mol. Life Sci. 2001;58:1234–45).

In animal experiments, bromelain has been found to inhibit coagulation, primarily by the stimulation of serum fibrinolytic activity, disruption of fibrinogen synthesis, and the related degradation of fibrin and fibrinogen.

Bromelain has also been shown to inhibit experimentally induced tumors in animals, predominantly dose dependently, and exhibit antiedematous and anti-inflammatory activity (Planta Med. 1990;56:249–53).

Recent studies suggest the usefulness of oral bromelain as an immunomodulatory tumor therapy, as it shows a time- and dose-dependent capacity to enhance, in vivo, the immunocytotoxicity of monocytes against tumor cells and to induce production of cytokines, including tumor necrosis factor-α, interleukin-1 β, Il-6, and Il-8 (Cell. Mol. Life Sci. 2001;58:1234–45).

Renewed interest in bromelain, after a drop-off for several years, has resulted in a spate of recent studies and evidence of oral efficacy. Such results, coupled with bromelain's positive safety profile, have brought increasing acceptance of this botanical among consumers and some practitioners (Cell. Mol. Life Sci. 2001;58:1234–45).

The discovery of oral efficacy helped to surmount earlier uncertainty about the bioavailability of bromelain. A study of 19 healthy human males found that small levels of undegraded bromelain traveled intact through the gastrointestinal tract (Am. J. Physiol. 1997;273:G139–46).

While the primary component of bromelain is the sulfhydryl proteolytic fraction, it also contains a peroxidase, acid phosphatase, several protease inhibitors, and organically bound calcium. Bromelain's pharmacologic activities, although often ascribed to the proteolytic fraction, cannot be wholly attributed to that portion as there is evidence that several of its constituents have beneficial properties (Altern. Med. Rev. 1998;3:302–5). Bromelain's mechanism of action has been ascribed partly to its modulation of the arachidonic acid cascade (J. Ethnopharmacol. 1988;22:191–203).

The pineapple enzyme is believed to inhibit the production of proinflammatory prostaglandins, initiate the production of anti-inflammatory series 1 prostaglandins, and reduce capillary permeability (Med. Hypotheses 1980;6:99–104).

A study of a commercial polyenzyme preparation containing bromelain showed that it induced cytokine production in vitro in peripheral blood mononuclear cells. This capacity to induce cytokine production has been cited as a reason for the antitumor effects of such bromelain-containing enzyme formulations (Oncology 1993;50:403–7).

On the Market

Bromelain has been approved by the German Commission E for postsurgical and/or posttraumatic edema, particularly of the nasal and paranasal sinuses characteristic of some plastic surgery. A patented cutaneous tape containing bromelain is also available in Europe for debriding scar tissue.

Although it is no longer commercially available, Ananase, used for healing wounds and resolving certain hematomas, contained bromelain as the main active ingredient and was included in the Physicians' Desk Reference in the early 1960s. Taken orally 1 hour before or 2 hours after meals, bromelain supplements are absorbed by white blood cells and enhance their enzymatic activity (Dermatol. Ther. 2003;16:106–13).

Bromelain has been known to cause allergic reactions such as asthma, rhinitis, and gastrointestinal symptoms (Clin. Allergy 1979;9:443–50). Such occurrences are rare, however.

The botanical is contraindicated in children, people with allergies to pineapple or bee stings, individuals with a history of heart palpitations, and patients taking blood thinners.

In My Practice

We began using bromelain supplements in our patients about a year ago, with spectacular results. We have them take 500 mg twice a day for 3 days after botulinum toxin injections, dermal fillers, surgeries, or other procedures that may result in bruising. We do not have patients take the supplements prior to the procedure because it seems to increase bruising. (Arnica tablets can be used prior to the procedure.)

I have seen bruising resolve much more rapidly when patients take these supplements. One of my patients had a facelift and ate pineapple three times a day, and her lack of bruising was amazing.

I had a basal cell carcinoma removed from my lid margin, which required a 1-cm-by-7-mm excision. I took bromelain supplements (even though the surgeon told me not to), and he was amazed at my lack of bruising. I have not seen any allergic reactions or complications.

I have not had time to do a formal study of this botanical, but I wanted to share my experience with you. Please send me your recommendations for preventing and treating bruising. I plan to do a future column on bruising and its treatment and prevention. Thanks to you all for your continued letters, suggestions, and input. Keep it coming!

Bromelain, a family of sulfhydryl-containing proteolytic enzymes derived from the stems of pineapples, is used to treat inflammation and soft tissue injuries. Donna Franki/Elsevier Global Medical News

Bromelain is a designation referring to the family of sulfhydryl-containing proteolytic enzymes derived from the stem of the pineapple plant, Ananas comosus (Altern. Med. Rev. 2003;8:359–77).

Pineapple has been used as a folk medicine in tropical regions such as Hawaii, as well as in Japan and Taiwan, for centuries.

It continues to be used to clean wounds and burns in those regions. As an oral supplement, bromelain is typically administered to aid digestion. It also is considered a natural blood thinner, and has long been part of traditional tropical health regimens for its range of anti-inflammatory properties (Skin Therapy Lett. 2000;5:1–2, 5). Bromelain is considered by some to be as effective as some of the popular NSAIDs.

The most common use of bromelain is for the treatment of inflammation and soft tissue injuries.

Therapeutic Effects

The pharmacologic properties of pineapple's constituent bromelain have been gradually uncovered by Western medicine during the last 4 decades. Bromelain inhibits platelet aggregation, exhibits fibrinolytic activity, has anti-inflammatory action, promotes skin debridement, and interferes with the growth of malignant cells (J. Ethnopharmacol. 1988;22:191–203).

Studies performed 40 years ago showed that the oral administration of bromelain reduced edema, bruising, pain, and healing time after dental surgery. Although postsurgical administration was seen as effective, a combination of pre- and postoperative administration was recommended (J. Dent. Med. 1965;20:51–4; J. Dent. Med. 1964;19:73–7).

Studies performed since the 1960s have confirmed bromelain's beneficial effects after surgery or trauma (Altern. Med. Rev. 2003;8:359–77; Obstet. Gynecol. 1967;29:275–8; Eye Ear Nose Throat Mon. 1968;47:634–9; J. Obstet. Gynaecol. Br. Commonw. 1972;79:951–3; Skin Therapy Lett. 2000;5:1–2, 5; Altern. Med. Rev. 1998;3:302–5).

In a study of patients undergoing rhinoplasty, 53 patients were randomized to one of two bromelain treatment groups or placebo. Edema and ecchymosis lasted for 7 days in the placebo group but only 2 days in both bromelain groups (Eye Ear Nose Throat Mon. 1962;41:813–7). A few years later, a randomized study of 154 facial plastic surgery patients showed no significant differences in edema between bromelain and a placebo (Acta Chir. Scand. 1966;131:193–6).

An uncontrolled trial performed a decade ago suggested that bromelain reduces edema, tenderness, and pain, at rest and in motion, in patients with blunt trauma to the musculoskeletal system (Fortschr. Med. 1995;113:303–6). In a more recent study of a proteolytic enzyme formulation containing bromelain, patients with long bone fractures given the botanical exhibited significantly less postoperative edema than the placebo group (Acta Chir. Orthop. Traumatol. Cech. 2001;68:45–9).

These effects are largely ascribed to the anti-inflammatory capacity of the plant enzyme (Altern. Med. Rev. 2003;8:359–77). In vitro and in vivo studies have shown that the various proteinases contained in bromelain have antiedematous, anti-inflammatory, antithrombotic, and fibrinolytic activities (Cell. Mol. Life Sci. 2001;58:1234–45).

The topical application of a bromelain cream (35% bromelain in a lipid base) has been shown to confer specific benefits, including eliminating burn debris and accelerating wound healing. Escharase, a nonpro-teolytic constituent, is credited with imparting these effects (Altern. Med. Rev. 1998;3:302–5).

Bromelain has been demonstrated to enhance the potentiation of antibiotics (Altern. Med. Rev. 1998;3:302–5), and to confer benefits in the treatment of angina pectoris, bronchitis, sinusitis, thrombophlebitis, pyelonephritis, and wounds (Cell. Mol. Life Sci. 2001;58:1234–45).

In animal experiments, bromelain has been found to inhibit coagulation, primarily by the stimulation of serum fibrinolytic activity, disruption of fibrinogen synthesis, and the related degradation of fibrin and fibrinogen.

Bromelain has also been shown to inhibit experimentally induced tumors in animals, predominantly dose dependently, and exhibit antiedematous and anti-inflammatory activity (Planta Med. 1990;56:249–53).

Recent studies suggest the usefulness of oral bromelain as an immunomodulatory tumor therapy, as it shows a time- and dose-dependent capacity to enhance, in vivo, the immunocytotoxicity of monocytes against tumor cells and to induce production of cytokines, including tumor necrosis factor-α, interleukin-1 β, Il-6, and Il-8 (Cell. Mol. Life Sci. 2001;58:1234–45).

Renewed interest in bromelain, after a drop-off for several years, has resulted in a spate of recent studies and evidence of oral efficacy. Such results, coupled with bromelain's positive safety profile, have brought increasing acceptance of this botanical among consumers and some practitioners (Cell. Mol. Life Sci. 2001;58:1234–45).

The discovery of oral efficacy helped to surmount earlier uncertainty about the bioavailability of bromelain. A study of 19 healthy human males found that small levels of undegraded bromelain traveled intact through the gastrointestinal tract (Am. J. Physiol. 1997;273:G139–46).

While the primary component of bromelain is the sulfhydryl proteolytic fraction, it also contains a peroxidase, acid phosphatase, several protease inhibitors, and organically bound calcium. Bromelain's pharmacologic activities, although often ascribed to the proteolytic fraction, cannot be wholly attributed to that portion as there is evidence that several of its constituents have beneficial properties (Altern. Med. Rev. 1998;3:302–5). Bromelain's mechanism of action has been ascribed partly to its modulation of the arachidonic acid cascade (J. Ethnopharmacol. 1988;22:191–203).

The pineapple enzyme is believed to inhibit the production of proinflammatory prostaglandins, initiate the production of anti-inflammatory series 1 prostaglandins, and reduce capillary permeability (Med. Hypotheses 1980;6:99–104).

A study of a commercial polyenzyme preparation containing bromelain showed that it induced cytokine production in vitro in peripheral blood mononuclear cells. This capacity to induce cytokine production has been cited as a reason for the antitumor effects of such bromelain-containing enzyme formulations (Oncology 1993;50:403–7).

On the Market

Bromelain has been approved by the German Commission E for postsurgical and/or posttraumatic edema, particularly of the nasal and paranasal sinuses characteristic of some plastic surgery. A patented cutaneous tape containing bromelain is also available in Europe for debriding scar tissue.

Although it is no longer commercially available, Ananase, used for healing wounds and resolving certain hematomas, contained bromelain as the main active ingredient and was included in the Physicians' Desk Reference in the early 1960s. Taken orally 1 hour before or 2 hours after meals, bromelain supplements are absorbed by white blood cells and enhance their enzymatic activity (Dermatol. Ther. 2003;16:106–13).

Bromelain has been known to cause allergic reactions such as asthma, rhinitis, and gastrointestinal symptoms (Clin. Allergy 1979;9:443–50). Such occurrences are rare, however.

The botanical is contraindicated in children, people with allergies to pineapple or bee stings, individuals with a history of heart palpitations, and patients taking blood thinners.

In My Practice

We began using bromelain supplements in our patients about a year ago, with spectacular results. We have them take 500 mg twice a day for 3 days after botulinum toxin injections, dermal fillers, surgeries, or other procedures that may result in bruising. We do not have patients take the supplements prior to the procedure because it seems to increase bruising. (Arnica tablets can be used prior to the procedure.)

I have seen bruising resolve much more rapidly when patients take these supplements. One of my patients had a facelift and ate pineapple three times a day, and her lack of bruising was amazing.

I had a basal cell carcinoma removed from my lid margin, which required a 1-cm-by-7-mm excision. I took bromelain supplements (even though the surgeon told me not to), and he was amazed at my lack of bruising. I have not seen any allergic reactions or complications.

I have not had time to do a formal study of this botanical, but I wanted to share my experience with you. Please send me your recommendations for preventing and treating bruising. I plan to do a future column on bruising and its treatment and prevention. Thanks to you all for your continued letters, suggestions, and input. Keep it coming!

Bromelain, a family of sulfhydryl-containing proteolytic enzymes derived from the stems of pineapples, is used to treat inflammation and soft tissue injuries. Donna Franki/Elsevier Global Medical News

Sarcoidosis initially was described by Sir Jonathan Hutchinson in 1875, and cutaneous sarcoidosis (lupus pernio) was described by Besnier 1 in 1899. Sarcoidosis is a multisystem disease that may involve almost any organ system and, therefore, may present with various clinical manifestations.2 Cutaneous sarcoidosis occurs in up to one third of patients with systemic sarcoidosis. Recognition of cutaneous lesions is important because the lesions provide a visible clue to the diagnosis and are an easily accessible source of tissue for histologic examination.3 Because lesions can exhibit many different morphologies, cutaneous sarcoidosis is known as one of the "great imitators" in dermatology.4 Lesions of cutaneous sarcoidosis also can appear in preexisting scars, a condition known as scar sarcoidosis.5 The latter condition may be caused by mechanical trauma such as venipuncture, scars caused by infection such as herpes zoster,6 and tattoos.7 Treatment of cutaneous lesions can be frustrating. For patients with widespread disease, the most effective treatment is systemic glucocorticoids. The prognosis of sarcoidosis usually is good, in particular, if the condition predominantly or solely affects the skin.8 

Case Report
A 34-year-old man presented with a progressively enlarging lesion on his left calf. He reported that about 3 months prior he had developed a small ulceration at this location following a fall. With local wound care, the ulceration healed with a scar. The scar, however, continued to grow beyond the borders of the previous ulceration and became raised with violaceous discoloration. The patient denied any history of excessive scarring or keloid formation after skin surgeries or trauma. There were no personal or family histories of granulomatous diseases. Results of a physical examination showed an erythematous-to-dusky plaque measuring approximately 4X3 cm (Figure 1) on the left calf with well-defined irregular borders and discrete papules on the internal aspect of the knee. No tender nodules on the shins were noticed, and no lymphadenopathy was present. Results from a review of systems and a routine chest x-ray were unremarkable. Results of a punch biopsy revealed changes consistent with sarcoid naked granulomas (Figure 2). The patient was started on topical potent corticosteroid tapes and experienced marked improvement.

Comment

Sarcoidosis occurs more frequently in females than in males, with reported ratios as high as 5:1. In the United States, black individuals are affected 3 to 4 times more often than white individuals.9 Sarcoidosis is found worldwide and in every race, though the incidence varies dramatically. In Europe, the disease affects white individuals more commonly than other races, and it affects Western Europeans more than Eastern Europeans. People from Scandinavia have one of the highest incidence rates at 64 cases per 100,000 population; in Poland, the incidence is 3 cases per 100,000 population. The disease is rare in Eskimos, Southeast Asians, New Zealand Maoris, and native Canadian populations.10,11 The difference in prevalence among certain populations in varying geographic locations suggests that ethnic susceptibility factors, as well as environmental factors, contribute to the etiology of sarcoidosis.11 Sarcoidosis is a multisystem disorder characterized by noncaseating, naked, epithelioid granulomas and commonly involves the hilar lymph nodes, lungs, skin, and eyes. The frequency of skin involvement in sarcoidosis is 10% to 30% of all cases, but the prevalence of particular types of cutaneous lesions varies among races, as well as among individual cases.12 Clinically, there is spontaneous development of livid or reddish-brown plaques on scars that were previously and mostly atrophic; this phenomenon occurs at varying intervals. Therefore, sarcoidosis should be considered in the differential diagnosis of an enlarging previously inactive scar. Lesions can develop in scars caused by mechanical trauma, such as in Kveim test sites, tuberculin test sites,5 sites that have received hyaluronic acid injection for wrinkles,13 sites of cosmetic tattoos,¹⁴ sites of previous laser surgery,15 and sites used for desensitization injections.16 Scar sarcoidosis has been reported following herpes zoster infection.17 Correctly diagnosing sarcoidosis may be a challenge. Unfortunately, no single test can lead to diagnosis of the condition. Patients are diagnosed with sarcoidosis when a compatible clinical or radiologic picture is present, along with histologic evidence of noncaseating granulomas, and when other potential causes, such as infections, are excluded. Cutaneous sarcoidosis varies greatly in its clinical presentation and has been labeled as one of the great dermatologic masqueraders.4,18 Maculopapular lesions can appear as xanthelasma, acne rosea, lupus erythematosus, or adenoma sebaceum. The differential diagnoses of plaques include lupus vulgaris, necrobiosis lipoidica, leprosy, leishmaniasis, psoriasis, and discoid lupus.4,18 The etiology of sarcoidosis is unknown, but several immune aberrations have been noted and are thought to play a role in its pathogenesis.19 Immune dysregulation has been theorized to result from a persistent antigen of low virulence that is poorly cleared by the immune system, leading to a chronic T cell of the TH1 subtype response and causing granuloma formation. Proposed antigens fall into 3 categories that include infectious, environmental, and autoantigens.20 The most common infectious agents implicated are Mycobacterium tuberculosis, Mycoplasma species, Corynebacterium species, spirochetes, atypical mycobacteria, Propionibacterium acnes, Borrelia burgdorferi, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, coxsackievirus, rubella virus, Histoplasma species, Cryptococcus species, coccidioidomycosis, and sporotrichosis.21 Environmental antigens implicated include metals (eg, zirconium, aluminum, beryllium), organic dusts (eg, pine, pollen), inorganic dusts (eg, clay, soil, talc), and autoantigens (AV 2S3+ and HLA-DR17+).22 Genetic factors also are thought to play a role in the disease process.23 Familial clustering of cases has been reported. Monozygotic twins are 2 to 4 times more likely to have the disease than dizygotic twins.23 Certain HLA associations have been demonstrated; the most common allele found in sarcoidosis is HLA-B8. Other associated alleles include HLA-A1 and HLA-DR3.24 Most authors divide cutaneous lesions into specific and nonspecific categories.25 Specific skin lesions display noncaseating granulomas on biopsy. Nonspecific skin lesions display no granulomas on biopsy. Scar sarcoidosis is a specific form of cutaneous sarcoidosis in which old scars become infiltrated with noncaseating epithelioid cell granulomas. Typical sarcoid lesions are characterized by the presence of circumscribed granulomas of epithelioid cells with little or no necrosis. Granulomas usually are in the superficial dermis but may involve the full thickness of the dermis and extend to the subcutaneous tissue. Islands of epithelioid cells may have a few Langerhans giant cells.25 Giant cells may contain asteroid or Schaumann bodies; asteroid bodies are star-shaped eosinophilic structures; and Schaumann bodies are round or oval laminated structures that usually are calcified at the periphery.26 Granulomas are referred to as naked because they have only a sparse lymphocytic infiltrate at the margins of the granulomas. Fibrosis, if present, usually starts at the periphery and advances toward the center.26 The treatment of cutaneous sarcoidosis often is frustrating, and the condition often is refractory to therapy or recurs following successful treatment. Therapeutic approaches range from topical, intralesional, and systemic use of corticosteroids to systemic medications such as cytostatic drugs, chloroquine,27 allopurinol (300 mg/d),28 and thalidomide.29 For localized involvement of cutaneous sarcoidosis, topical or intralesional steroids are used. Physicians frequently use superpotent topical corticosteroids because the drugs occasionally are effective.30-32 However, the corticosteroid often does not adequately penetrate the skin lesion. Intralesional corticosteroids (eg, triamcinolone acetonide in a dose of 5 mg/mL) typically are more effective, with injections repeated at 2- to 3-week intervals.30,31 Alternative therapies include oral psoralen plus UVA, surgical excision, and laser treatment.32 The Q-switched ruby laser appears to be a rapid and effective means of treating scar sarcoidosis in traumatic tattoos without adverse effects.33 Surgical excision of small lesions or excision of larger lesions with skin grafting can be attempted but may cause the recurrence of hypertrophic and keloidal scarring.34 Systemic agents are reserved for widespread progressive lesions or for lesions that impair function. Systemic glucocorticoids are the most effective agents and are commonly used at slow tapering dosages, starting at 20 to 60 mg/d of oral prednisone for 4 to 5 weeks. However, there are many drawbacks to this therapy. Aside from the well-known complications of chronic steroid use, not all patients respond to systemic steroids.35 Patients who do respond frequently experience disease flare-ups after cessation of therapy. Many other medications may be used in refractory cases, including agents such as hydroxychloroquine sulfate,36 methotrexate,37 and thalidomide.29 Although randomized controlled trials are lacking, multiple anecdotal reports suggest the efficacy of these agents. The course and prognosis of sarcoidosis correlates with the mode of onset of the disease, the patient's race, and the presenting stage. In general, the prognosis of cutaneous sarcoidosis depends on systemic involvement. The course is variable, ranging from self-limited acute episodes to a chronic debilitating disease that may result in death.³⁸ Spontaneous remissions occur in nearly two thirds of patients, but 10% to 30% of patients have a more chronic or progressive course. The mortality rate is 1% to 6%. Sarcoidosis can lead to death either from severe involvement of lung parenchyma, which leads to pulmonary fibrosis and respiratory failure,38,39 or from myocardial involvement, which leads to arrhythmias and cardiac failure.39 Other causes of significant morbidity and mortality include central nervous system involvement, blindness, pulmonary hemorrhage, renal insufficiency, hypopituitarism, and liver disease.35 Cutaneous sarcoidosis usually has a prolonged course. Papules and nodules tend to resolve over months or years, though plaques may be more resistant.19 As treatment is withdrawn, relapses are frequent, especially in black patients who tend to have more severe and prolonged symptoms.11 

Sarcoidosis initially was described by Sir Jonathan Hutchinson in 1875, and cutaneous sarcoidosis (lupus pernio) was described by Besnier 1 in 1899. Sarcoidosis is a multisystem disease that may involve almost any organ system and, therefore, may present with various clinical manifestations.2 Cutaneous sarcoidosis occurs in up to one third of patients with systemic sarcoidosis. Recognition of cutaneous lesions is important because the lesions provide a visible clue to the diagnosis and are an easily accessible source of tissue for histologic examination.3 Because lesions can exhibit many different morphologies, cutaneous sarcoidosis is known as one of the "great imitators" in dermatology.4 Lesions of cutaneous sarcoidosis also can appear in preexisting scars, a condition known as scar sarcoidosis.5 The latter condition may be caused by mechanical trauma such as venipuncture, scars caused by infection such as herpes zoster,6 and tattoos.7 Treatment of cutaneous lesions can be frustrating. For patients with widespread disease, the most effective treatment is systemic glucocorticoids. The prognosis of sarcoidosis usually is good, in particular, if the condition predominantly or solely affects the skin.8 

Case Report
A 34-year-old man presented with a progressively enlarging lesion on his left calf. He reported that about 3 months prior he had developed a small ulceration at this location following a fall. With local wound care, the ulceration healed with a scar. The scar, however, continued to grow beyond the borders of the previous ulceration and became raised with violaceous discoloration. The patient denied any history of excessive scarring or keloid formation after skin surgeries or trauma. There were no personal or family histories of granulomatous diseases. Results of a physical examination showed an erythematous-to-dusky plaque measuring approximately 4X3 cm (Figure 1) on the left calf with well-defined irregular borders and discrete papules on the internal aspect of the knee. No tender nodules on the shins were noticed, and no lymphadenopathy was present. Results from a review of systems and a routine chest x-ray were unremarkable. Results of a punch biopsy revealed changes consistent with sarcoid naked granulomas (Figure 2). The patient was started on topical potent corticosteroid tapes and experienced marked improvement.

Comment

Sarcoidosis occurs more frequently in females than in males, with reported ratios as high as 5:1. In the United States, black individuals are affected 3 to 4 times more often than white individuals.9 Sarcoidosis is found worldwide and in every race, though the incidence varies dramatically. In Europe, the disease affects white individuals more commonly than other races, and it affects Western Europeans more than Eastern Europeans. People from Scandinavia have one of the highest incidence rates at 64 cases per 100,000 population; in Poland, the incidence is 3 cases per 100,000 population. The disease is rare in Eskimos, Southeast Asians, New Zealand Maoris, and native Canadian populations.10,11 The difference in prevalence among certain populations in varying geographic locations suggests that ethnic susceptibility factors, as well as environmental factors, contribute to the etiology of sarcoidosis.11 Sarcoidosis is a multisystem disorder characterized by noncaseating, naked, epithelioid granulomas and commonly involves the hilar lymph nodes, lungs, skin, and eyes. The frequency of skin involvement in sarcoidosis is 10% to 30% of all cases, but the prevalence of particular types of cutaneous lesions varies among races, as well as among individual cases.12 Clinically, there is spontaneous development of livid or reddish-brown plaques on scars that were previously and mostly atrophic; this phenomenon occurs at varying intervals. Therefore, sarcoidosis should be considered in the differential diagnosis of an enlarging previously inactive scar. Lesions can develop in scars caused by mechanical trauma, such as in Kveim test sites, tuberculin test sites,5 sites that have received hyaluronic acid injection for wrinkles,13 sites of cosmetic tattoos,¹⁴ sites of previous laser surgery,15 and sites used for desensitization injections.16 Scar sarcoidosis has been reported following herpes zoster infection.17 Correctly diagnosing sarcoidosis may be a challenge. Unfortunately, no single test can lead to diagnosis of the condition. Patients are diagnosed with sarcoidosis when a compatible clinical or radiologic picture is present, along with histologic evidence of noncaseating granulomas, and when other potential causes, such as infections, are excluded. Cutaneous sarcoidosis varies greatly in its clinical presentation and has been labeled as one of the great dermatologic masqueraders.4,18 Maculopapular lesions can appear as xanthelasma, acne rosea, lupus erythematosus, or adenoma sebaceum. The differential diagnoses of plaques include lupus vulgaris, necrobiosis lipoidica, leprosy, leishmaniasis, psoriasis, and discoid lupus.4,18 The etiology of sarcoidosis is unknown, but several immune aberrations have been noted and are thought to play a role in its pathogenesis.19 Immune dysregulation has been theorized to result from a persistent antigen of low virulence that is poorly cleared by the immune system, leading to a chronic T cell of the TH1 subtype response and causing granuloma formation. Proposed antigens fall into 3 categories that include infectious, environmental, and autoantigens.20 The most common infectious agents implicated are Mycobacterium tuberculosis, Mycoplasma species, Corynebacterium species, spirochetes, atypical mycobacteria, Propionibacterium acnes, Borrelia burgdorferi, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, coxsackievirus, rubella virus, Histoplasma species, Cryptococcus species, coccidioidomycosis, and sporotrichosis.21 Environmental antigens implicated include metals (eg, zirconium, aluminum, beryllium), organic dusts (eg, pine, pollen), inorganic dusts (eg, clay, soil, talc), and autoantigens (AV 2S3+ and HLA-DR17+).22 Genetic factors also are thought to play a role in the disease process.23 Familial clustering of cases has been reported. Monozygotic twins are 2 to 4 times more likely to have the disease than dizygotic twins.23 Certain HLA associations have been demonstrated; the most common allele found in sarcoidosis is HLA-B8. Other associated alleles include HLA-A1 and HLA-DR3.24 Most authors divide cutaneous lesions into specific and nonspecific categories.25 Specific skin lesions display noncaseating granulomas on biopsy. Nonspecific skin lesions display no granulomas on biopsy. Scar sarcoidosis is a specific form of cutaneous sarcoidosis in which old scars become infiltrated with noncaseating epithelioid cell granulomas. Typical sarcoid lesions are characterized by the presence of circumscribed granulomas of epithelioid cells with little or no necrosis. Granulomas usually are in the superficial dermis but may involve the full thickness of the dermis and extend to the subcutaneous tissue. Islands of epithelioid cells may have a few Langerhans giant cells.25 Giant cells may contain asteroid or Schaumann bodies; asteroid bodies are star-shaped eosinophilic structures; and Schaumann bodies are round or oval laminated structures that usually are calcified at the periphery.26 Granulomas are referred to as naked because they have only a sparse lymphocytic infiltrate at the margins of the granulomas. Fibrosis, if present, usually starts at the periphery and advances toward the center.26 The treatment of cutaneous sarcoidosis often is frustrating, and the condition often is refractory to therapy or recurs following successful treatment. Therapeutic approaches range from topical, intralesional, and systemic use of corticosteroids to systemic medications such as cytostatic drugs, chloroquine,27 allopurinol (300 mg/d),28 and thalidomide.29 For localized involvement of cutaneous sarcoidosis, topical or intralesional steroids are used. Physicians frequently use superpotent topical corticosteroids because the drugs occasionally are effective.30-32 However, the corticosteroid often does not adequately penetrate the skin lesion. Intralesional corticosteroids (eg, triamcinolone acetonide in a dose of 5 mg/mL) typically are more effective, with injections repeated at 2- to 3-week intervals.30,31 Alternative therapies include oral psoralen plus UVA, surgical excision, and laser treatment.32 The Q-switched ruby laser appears to be a rapid and effective means of treating scar sarcoidosis in traumatic tattoos without adverse effects.33 Surgical excision of small lesions or excision of larger lesions with skin grafting can be attempted but may cause the recurrence of hypertrophic and keloidal scarring.34 Systemic agents are reserved for widespread progressive lesions or for lesions that impair function. Systemic glucocorticoids are the most effective agents and are commonly used at slow tapering dosages, starting at 20 to 60 mg/d of oral prednisone for 4 to 5 weeks. However, there are many drawbacks to this therapy. Aside from the well-known complications of chronic steroid use, not all patients respond to systemic steroids.35 Patients who do respond frequently experience disease flare-ups after cessation of therapy. Many other medications may be used in refractory cases, including agents such as hydroxychloroquine sulfate,36 methotrexate,37 and thalidomide.29 Although randomized controlled trials are lacking, multiple anecdotal reports suggest the efficacy of these agents. The course and prognosis of sarcoidosis correlates with the mode of onset of the disease, the patient's race, and the presenting stage. In general, the prognosis of cutaneous sarcoidosis depends on systemic involvement. The course is variable, ranging from self-limited acute episodes to a chronic debilitating disease that may result in death.³⁸ Spontaneous remissions occur in nearly two thirds of patients, but 10% to 30% of patients have a more chronic or progressive course. The mortality rate is 1% to 6%. Sarcoidosis can lead to death either from severe involvement of lung parenchyma, which leads to pulmonary fibrosis and respiratory failure,38,39 or from myocardial involvement, which leads to arrhythmias and cardiac failure.39 Other causes of significant morbidity and mortality include central nervous system involvement, blindness, pulmonary hemorrhage, renal insufficiency, hypopituitarism, and liver disease.35 Cutaneous sarcoidosis usually has a prolonged course. Papules and nodules tend to resolve over months or years, though plaques may be more resistant.19 As treatment is withdrawn, relapses are frequent, especially in black patients who tend to have more severe and prolonged symptoms.11 

Sarcoidosis initially was described by Sir Jonathan Hutchinson in 1875, and cutaneous sarcoidosis (lupus pernio) was described by Besnier 1 in 1899. Sarcoidosis is a multisystem disease that may involve almost any organ system and, therefore, may present with various clinical manifestations.2 Cutaneous sarcoidosis occurs in up to one third of patients with systemic sarcoidosis. Recognition of cutaneous lesions is important because the lesions provide a visible clue to the diagnosis and are an easily accessible source of tissue for histologic examination.3 Because lesions can exhibit many different morphologies, cutaneous sarcoidosis is known as one of the "great imitators" in dermatology.4 Lesions of cutaneous sarcoidosis also can appear in preexisting scars, a condition known as scar sarcoidosis.5 The latter condition may be caused by mechanical trauma such as venipuncture, scars caused by infection such as herpes zoster,6 and tattoos.7 Treatment of cutaneous lesions can be frustrating. For patients with widespread disease, the most effective treatment is systemic glucocorticoids. The prognosis of sarcoidosis usually is good, in particular, if the condition predominantly or solely affects the skin.8 

Case Report
A 34-year-old man presented with a progressively enlarging lesion on his left calf. He reported that about 3 months prior he had developed a small ulceration at this location following a fall. With local wound care, the ulceration healed with a scar. The scar, however, continued to grow beyond the borders of the previous ulceration and became raised with violaceous discoloration. The patient denied any history of excessive scarring or keloid formation after skin surgeries or trauma. There were no personal or family histories of granulomatous diseases. Results of a physical examination showed an erythematous-to-dusky plaque measuring approximately 4X3 cm (Figure 1) on the left calf with well-defined irregular borders and discrete papules on the internal aspect of the knee. No tender nodules on the shins were noticed, and no lymphadenopathy was present. Results from a review of systems and a routine chest x-ray were unremarkable. Results of a punch biopsy revealed changes consistent with sarcoid naked granulomas (Figure 2). The patient was started on topical potent corticosteroid tapes and experienced marked improvement.

Comment

Sarcoidosis occurs more frequently in females than in males, with reported ratios as high as 5:1. In the United States, black individuals are affected 3 to 4 times more often than white individuals.9 Sarcoidosis is found worldwide and in every race, though the incidence varies dramatically. In Europe, the disease affects white individuals more commonly than other races, and it affects Western Europeans more than Eastern Europeans. People from Scandinavia have one of the highest incidence rates at 64 cases per 100,000 population; in Poland, the incidence is 3 cases per 100,000 population. The disease is rare in Eskimos, Southeast Asians, New Zealand Maoris, and native Canadian populations.10,11 The difference in prevalence among certain populations in varying geographic locations suggests that ethnic susceptibility factors, as well as environmental factors, contribute to the etiology of sarcoidosis.11 Sarcoidosis is a multisystem disorder characterized by noncaseating, naked, epithelioid granulomas and commonly involves the hilar lymph nodes, lungs, skin, and eyes. The frequency of skin involvement in sarcoidosis is 10% to 30% of all cases, but the prevalence of particular types of cutaneous lesions varies among races, as well as among individual cases.12 Clinically, there is spontaneous development of livid or reddish-brown plaques on scars that were previously and mostly atrophic; this phenomenon occurs at varying intervals. Therefore, sarcoidosis should be considered in the differential diagnosis of an enlarging previously inactive scar. Lesions can develop in scars caused by mechanical trauma, such as in Kveim test sites, tuberculin test sites,5 sites that have received hyaluronic acid injection for wrinkles,13 sites of cosmetic tattoos,¹⁴ sites of previous laser surgery,15 and sites used for desensitization injections.16 Scar sarcoidosis has been reported following herpes zoster infection.17 Correctly diagnosing sarcoidosis may be a challenge. Unfortunately, no single test can lead to diagnosis of the condition. Patients are diagnosed with sarcoidosis when a compatible clinical or radiologic picture is present, along with histologic evidence of noncaseating granulomas, and when other potential causes, such as infections, are excluded. Cutaneous sarcoidosis varies greatly in its clinical presentation and has been labeled as one of the great dermatologic masqueraders.4,18 Maculopapular lesions can appear as xanthelasma, acne rosea, lupus erythematosus, or adenoma sebaceum. The differential diagnoses of plaques include lupus vulgaris, necrobiosis lipoidica, leprosy, leishmaniasis, psoriasis, and discoid lupus.4,18 The etiology of sarcoidosis is unknown, but several immune aberrations have been noted and are thought to play a role in its pathogenesis.19 Immune dysregulation has been theorized to result from a persistent antigen of low virulence that is poorly cleared by the immune system, leading to a chronic T cell of the TH1 subtype response and causing granuloma formation. Proposed antigens fall into 3 categories that include infectious, environmental, and autoantigens.20 The most common infectious agents implicated are Mycobacterium tuberculosis, Mycoplasma species, Corynebacterium species, spirochetes, atypical mycobacteria, Propionibacterium acnes, Borrelia burgdorferi, herpes simplex virus, Epstein-Barr virus, cytomegalovirus, coxsackievirus, rubella virus, Histoplasma species, Cryptococcus species, coccidioidomycosis, and sporotrichosis.21 Environmental antigens implicated include metals (eg, zirconium, aluminum, beryllium), organic dusts (eg, pine, pollen), inorganic dusts (eg, clay, soil, talc), and autoantigens (AV 2S3+ and HLA-DR17+).22 Genetic factors also are thought to play a role in the disease process.23 Familial clustering of cases has been reported. Monozygotic twins are 2 to 4 times more likely to have the disease than dizygotic twins.23 Certain HLA associations have been demonstrated; the most common allele found in sarcoidosis is HLA-B8. Other associated alleles include HLA-A1 and HLA-DR3.24 Most authors divide cutaneous lesions into specific and nonspecific categories.25 Specific skin lesions display noncaseating granulomas on biopsy. Nonspecific skin lesions display no granulomas on biopsy. Scar sarcoidosis is a specific form of cutaneous sarcoidosis in which old scars become infiltrated with noncaseating epithelioid cell granulomas. Typical sarcoid lesions are characterized by the presence of circumscribed granulomas of epithelioid cells with little or no necrosis. Granulomas usually are in the superficial dermis but may involve the full thickness of the dermis and extend to the subcutaneous tissue. Islands of epithelioid cells may have a few Langerhans giant cells.25 Giant cells may contain asteroid or Schaumann bodies; asteroid bodies are star-shaped eosinophilic structures; and Schaumann bodies are round or oval laminated structures that usually are calcified at the periphery.26 Granulomas are referred to as naked because they have only a sparse lymphocytic infiltrate at the margins of the granulomas. Fibrosis, if present, usually starts at the periphery and advances toward the center.26 The treatment of cutaneous sarcoidosis often is frustrating, and the condition often is refractory to therapy or recurs following successful treatment. Therapeutic approaches range from topical, intralesional, and systemic use of corticosteroids to systemic medications such as cytostatic drugs, chloroquine,27 allopurinol (300 mg/d),28 and thalidomide.29 For localized involvement of cutaneous sarcoidosis, topical or intralesional steroids are used. Physicians frequently use superpotent topical corticosteroids because the drugs occasionally are effective.30-32 However, the corticosteroid often does not adequately penetrate the skin lesion. Intralesional corticosteroids (eg, triamcinolone acetonide in a dose of 5 mg/mL) typically are more effective, with injections repeated at 2- to 3-week intervals.30,31 Alternative therapies include oral psoralen plus UVA, surgical excision, and laser treatment.32 The Q-switched ruby laser appears to be a rapid and effective means of treating scar sarcoidosis in traumatic tattoos without adverse effects.33 Surgical excision of small lesions or excision of larger lesions with skin grafting can be attempted but may cause the recurrence of hypertrophic and keloidal scarring.34 Systemic agents are reserved for widespread progressive lesions or for lesions that impair function. Systemic glucocorticoids are the most effective agents and are commonly used at slow tapering dosages, starting at 20 to 60 mg/d of oral prednisone for 4 to 5 weeks. However, there are many drawbacks to this therapy. Aside from the well-known complications of chronic steroid use, not all patients respond to systemic steroids.35 Patients who do respond frequently experience disease flare-ups after cessation of therapy. Many other medications may be used in refractory cases, including agents such as hydroxychloroquine sulfate,36 methotrexate,37 and thalidomide.29 Although randomized controlled trials are lacking, multiple anecdotal reports suggest the efficacy of these agents. The course and prognosis of sarcoidosis correlates with the mode of onset of the disease, the patient's race, and the presenting stage. In general, the prognosis of cutaneous sarcoidosis depends on systemic involvement. The course is variable, ranging from self-limited acute episodes to a chronic debilitating disease that may result in death.³⁸ Spontaneous remissions occur in nearly two thirds of patients, but 10% to 30% of patients have a more chronic or progressive course. The mortality rate is 1% to 6%. Sarcoidosis can lead to death either from severe involvement of lung parenchyma, which leads to pulmonary fibrosis and respiratory failure,38,39 or from myocardial involvement, which leads to arrhythmias and cardiac failure.39 Other causes of significant morbidity and mortality include central nervous system involvement, blindness, pulmonary hemorrhage, renal insufficiency, hypopituitarism, and liver disease.35 Cutaneous sarcoidosis usually has a prolonged course. Papules and nodules tend to resolve over months or years, though plaques may be more resistant.19 As treatment is withdrawn, relapses are frequent, especially in black patients who tend to have more severe and prolonged symptoms.11