Doug Brunk

Alaser system for skin rejuvenation that delivers ablative fractional resurfacing technology made its official debut at the annual meeting of the American Academy of Dermatology.

Manufactured by Mountain View, Calif.-based Reliant Technologies, the 10,600-nm CO₂ Fraxel re:pair laser uses a continuous motion handpiece to create microscopic "zones of treatment" evenly across the surface of the skin. Clinical studies have demonstrated that it can treat up to 6 g of dermal tissue in a single treatment session with depths that range from 300 mcm to 1.6 mm, according to the manufacturer.

In May of 2007 the device was cleared by the Food and Drug Administration for ablation, coagulation, and skin resurfacing. In December of 2007 it received FDA 510(k) clearance for the treatment of wrinkles, rhytids, furrows, fine lines, textural irregularities, pigmented lesions, and vascular dyschromia. The current retail price of the Fraxel re:pair system is $129,000.

Studies of the device have included about 500 treatments over the last 2.5 years. In one recent study of its use on the forearm skin of 24 subjects with Fitzpatrick skin types II-IV, researchers tested pulse energies that ranged from 5 to 40 mJ and used hematoxylin and eosin to assess the legions histologically (Lasers Surg. Med. 2007;39:96–107). They found that changing the pulse energy from 5 to 30 mJ created a threefold increase in lesion depth and a twofold increase in width.

"Interestingly, ablative fractional resurfacing demonstrated much more rapid reepithelialization when compared to its nonfractional predecessors, whether powered by erbium or CO₂ lasers," reported the researchers (some of whom were employed by Reliant), led by Dr. Basil M. Hantash of Stanford (Calif.) University. "By 48 hours, most subjects demonstrated complete reepithelialization."

Subsequent studies of the system have used pulse energies that reach 70 mJ.

In an interview, one of the other study authors, Dr. Christopher Zachary, chair of the department of dermatology, University of California, Irvine, said that as long as physicians work within the recommended parameters, the Fraxel re:pair system "is going to give you a very predictable and reliable result and it's going to be much safer than the traditional carbon dioxide or erbium YAG lasers, which were associated with persistent redness, loss of pigmentation—which is delayed and permanent—scarring, and so forth."

In most cases, one treatment is sufficient and downtime is 2–4 days depending on the parameters used. "On day 5 you have redness and swelling," said Dr. Zachary, an unpaid consultant to Reliant Technologies.

Dr. Zachary said that he has limited experience using the device in dark-skinned patients, but "I absolutely intend to use it [on dark-skinned patients] on a regular basis," he said. "Darker skin types are going to have problems with skin pigmentation. To prevent it, we are pretreating for at least 2 weeks with a bleaching agent such as hydroquinone 4% cream, which will reside within the normal untreated skin after you have treated a fraction of the skin. That area that you do not treat will have a reservoir of hydroquinone which tends to prevent increased postinflammatory hyperpigmentation."

Trials are currently underway to study the use of the Fraxel re:pair system for treating acne scars, surgical scars, and striae. Dr. Zachary said that patients with severe acne scarring "are probably going to have two to three treatments separated by about a month each."

Dr. Robert A. Weiss, president-elect of the American Society for Dermatologic Surgery, called the Fraxel re:pair system an "elegant device" and noted that ablative fractional technology "is the next phase of fractional. It really does give a lot more improvement."

Dr. Weiss, who practices in Hunt Valley, Md., said that he currently uses a competing fractional laser procedure from Lumenis Ltd. called ActiveFX, which is delivered by the company's UltraCool Encore CO₂ system. Dr. Weiss is a member of the medical advisory board for Lumenis Ltd.

Dr. Zachary disclosed that he has received equipment and honoraria from Reliant Technologies and that he serves as a consultant for other laser companies.

A patient is shown before (left) and 1 month after treatment with the Fraxel re:pair laser, which is said to demonstrate "more rapid reepithelialization." Photos courtesy Dr. Zakia Rahman

Alaser system for skin rejuvenation that delivers ablative fractional resurfacing technology made its official debut at the annual meeting of the American Academy of Dermatology.

Manufactured by Mountain View, Calif.-based Reliant Technologies, the 10,600-nm CO₂ Fraxel re:pair laser uses a continuous motion handpiece to create microscopic "zones of treatment" evenly across the surface of the skin. Clinical studies have demonstrated that it can treat up to 6 g of dermal tissue in a single treatment session with depths that range from 300 mcm to 1.6 mm, according to the manufacturer.

In May of 2007 the device was cleared by the Food and Drug Administration for ablation, coagulation, and skin resurfacing. In December of 2007 it received FDA 510(k) clearance for the treatment of wrinkles, rhytids, furrows, fine lines, textural irregularities, pigmented lesions, and vascular dyschromia. The current retail price of the Fraxel re:pair system is $129,000.

Studies of the device have included about 500 treatments over the last 2.5 years. In one recent study of its use on the forearm skin of 24 subjects with Fitzpatrick skin types II-IV, researchers tested pulse energies that ranged from 5 to 40 mJ and used hematoxylin and eosin to assess the legions histologically (Lasers Surg. Med. 2007;39:96–107). They found that changing the pulse energy from 5 to 30 mJ created a threefold increase in lesion depth and a twofold increase in width.

"Interestingly, ablative fractional resurfacing demonstrated much more rapid reepithelialization when compared to its nonfractional predecessors, whether powered by erbium or CO₂ lasers," reported the researchers (some of whom were employed by Reliant), led by Dr. Basil M. Hantash of Stanford (Calif.) University. "By 48 hours, most subjects demonstrated complete reepithelialization."

Subsequent studies of the system have used pulse energies that reach 70 mJ.

In an interview, one of the other study authors, Dr. Christopher Zachary, chair of the department of dermatology, University of California, Irvine, said that as long as physicians work within the recommended parameters, the Fraxel re:pair system "is going to give you a very predictable and reliable result and it's going to be much safer than the traditional carbon dioxide or erbium YAG lasers, which were associated with persistent redness, loss of pigmentation—which is delayed and permanent—scarring, and so forth."

In most cases, one treatment is sufficient and downtime is 2–4 days depending on the parameters used. "On day 5 you have redness and swelling," said Dr. Zachary, an unpaid consultant to Reliant Technologies.

Dr. Zachary said that he has limited experience using the device in dark-skinned patients, but "I absolutely intend to use it [on dark-skinned patients] on a regular basis," he said. "Darker skin types are going to have problems with skin pigmentation. To prevent it, we are pretreating for at least 2 weeks with a bleaching agent such as hydroquinone 4% cream, which will reside within the normal untreated skin after you have treated a fraction of the skin. That area that you do not treat will have a reservoir of hydroquinone which tends to prevent increased postinflammatory hyperpigmentation."

Trials are currently underway to study the use of the Fraxel re:pair system for treating acne scars, surgical scars, and striae. Dr. Zachary said that patients with severe acne scarring "are probably going to have two to three treatments separated by about a month each."

Dr. Robert A. Weiss, president-elect of the American Society for Dermatologic Surgery, called the Fraxel re:pair system an "elegant device" and noted that ablative fractional technology "is the next phase of fractional. It really does give a lot more improvement."

Dr. Weiss, who practices in Hunt Valley, Md., said that he currently uses a competing fractional laser procedure from Lumenis Ltd. called ActiveFX, which is delivered by the company's UltraCool Encore CO₂ system. Dr. Weiss is a member of the medical advisory board for Lumenis Ltd.

Dr. Zachary disclosed that he has received equipment and honoraria from Reliant Technologies and that he serves as a consultant for other laser companies.

A patient is shown before (left) and 1 month after treatment with the Fraxel re:pair laser, which is said to demonstrate "more rapid reepithelialization." Photos courtesy Dr. Zakia Rahman

Alaser system for skin rejuvenation that delivers ablative fractional resurfacing technology made its official debut at the annual meeting of the American Academy of Dermatology.

Manufactured by Mountain View, Calif.-based Reliant Technologies, the 10,600-nm CO₂ Fraxel re:pair laser uses a continuous motion handpiece to create microscopic "zones of treatment" evenly across the surface of the skin. Clinical studies have demonstrated that it can treat up to 6 g of dermal tissue in a single treatment session with depths that range from 300 mcm to 1.6 mm, according to the manufacturer.

In May of 2007 the device was cleared by the Food and Drug Administration for ablation, coagulation, and skin resurfacing. In December of 2007 it received FDA 510(k) clearance for the treatment of wrinkles, rhytids, furrows, fine lines, textural irregularities, pigmented lesions, and vascular dyschromia. The current retail price of the Fraxel re:pair system is $129,000.

Studies of the device have included about 500 treatments over the last 2.5 years. In one recent study of its use on the forearm skin of 24 subjects with Fitzpatrick skin types II-IV, researchers tested pulse energies that ranged from 5 to 40 mJ and used hematoxylin and eosin to assess the legions histologically (Lasers Surg. Med. 2007;39:96–107). They found that changing the pulse energy from 5 to 30 mJ created a threefold increase in lesion depth and a twofold increase in width.

"Interestingly, ablative fractional resurfacing demonstrated much more rapid reepithelialization when compared to its nonfractional predecessors, whether powered by erbium or CO₂ lasers," reported the researchers (some of whom were employed by Reliant), led by Dr. Basil M. Hantash of Stanford (Calif.) University. "By 48 hours, most subjects demonstrated complete reepithelialization."

Subsequent studies of the system have used pulse energies that reach 70 mJ.

In an interview, one of the other study authors, Dr. Christopher Zachary, chair of the department of dermatology, University of California, Irvine, said that as long as physicians work within the recommended parameters, the Fraxel re:pair system "is going to give you a very predictable and reliable result and it's going to be much safer than the traditional carbon dioxide or erbium YAG lasers, which were associated with persistent redness, loss of pigmentation—which is delayed and permanent—scarring, and so forth."

In most cases, one treatment is sufficient and downtime is 2–4 days depending on the parameters used. "On day 5 you have redness and swelling," said Dr. Zachary, an unpaid consultant to Reliant Technologies.

Dr. Zachary said that he has limited experience using the device in dark-skinned patients, but "I absolutely intend to use it [on dark-skinned patients] on a regular basis," he said. "Darker skin types are going to have problems with skin pigmentation. To prevent it, we are pretreating for at least 2 weeks with a bleaching agent such as hydroquinone 4% cream, which will reside within the normal untreated skin after you have treated a fraction of the skin. That area that you do not treat will have a reservoir of hydroquinone which tends to prevent increased postinflammatory hyperpigmentation."

Trials are currently underway to study the use of the Fraxel re:pair system for treating acne scars, surgical scars, and striae. Dr. Zachary said that patients with severe acne scarring "are probably going to have two to three treatments separated by about a month each."

Dr. Robert A. Weiss, president-elect of the American Society for Dermatologic Surgery, called the Fraxel re:pair system an "elegant device" and noted that ablative fractional technology "is the next phase of fractional. It really does give a lot more improvement."

Dr. Weiss, who practices in Hunt Valley, Md., said that he currently uses a competing fractional laser procedure from Lumenis Ltd. called ActiveFX, which is delivered by the company's UltraCool Encore CO₂ system. Dr. Weiss is a member of the medical advisory board for Lumenis Ltd.

Dr. Zachary disclosed that he has received equipment and honoraria from Reliant Technologies and that he serves as a consultant for other laser companies.

A patient is shown before (left) and 1 month after treatment with the Fraxel re:pair laser, which is said to demonstrate "more rapid reepithelialization." Photos courtesy Dr. Zakia Rahman

SAN DIEGO — When Dr. Michael Swann advises patients to apply sunscreen to protect against melanoma, the suggestion sometimes falls on deaf ears.

"Patients who don't want to wear sunscreen will say, 'I don't wear sunscreen because it's never been shown to protect against melanoma,'" he said in an update on melanoma sponsored by the Scripps Clinic. "There are a lot of arguments against using it. People will believe what they want to believe."

He acknowledges that retrospective studies have not shown a clear benefit or detriment to using sunscreen to reduce the risk of melanoma but points his patients to other evidence. In Hawaii, where residents apply more sunscreen regularly than in other states, melanoma rates are declining.

The same goes for Australia, where an estimated 74% of residents use sunscreen regularly.

He goes on to tell them that the sunscreens studied over the past 20 years lacked any appreciable UVA protection, which may be important in melanoma. In recent years, though, sunscreens have hit the market with effective protection against UVA. For everyday protection, Dr. Swann recommends Anthelios SX by L'Oréal La Roche-Possay, which contains the sun filter Mexoryl SX.

"At this point, it is only approved as an SPF 15, so it's not really a good one for being on the golf course all day," said Dr. Swann of the Scripps Clinic, La Jolla, Calif.

For periods of longer exposure, he recommends Neutrogena sunscreens with Helioplex, which contain stable avobenzone.

He said that he has no conflict of interest with either manufacturer.

SAN DIEGO — When Dr. Michael Swann advises patients to apply sunscreen to protect against melanoma, the suggestion sometimes falls on deaf ears.

"Patients who don't want to wear sunscreen will say, 'I don't wear sunscreen because it's never been shown to protect against melanoma,'" he said in an update on melanoma sponsored by the Scripps Clinic. "There are a lot of arguments against using it. People will believe what they want to believe."

He acknowledges that retrospective studies have not shown a clear benefit or detriment to using sunscreen to reduce the risk of melanoma but points his patients to other evidence. In Hawaii, where residents apply more sunscreen regularly than in other states, melanoma rates are declining.

The same goes for Australia, where an estimated 74% of residents use sunscreen regularly.

He goes on to tell them that the sunscreens studied over the past 20 years lacked any appreciable UVA protection, which may be important in melanoma. In recent years, though, sunscreens have hit the market with effective protection against UVA. For everyday protection, Dr. Swann recommends Anthelios SX by L'Oréal La Roche-Possay, which contains the sun filter Mexoryl SX.

"At this point, it is only approved as an SPF 15, so it's not really a good one for being on the golf course all day," said Dr. Swann of the Scripps Clinic, La Jolla, Calif.

For periods of longer exposure, he recommends Neutrogena sunscreens with Helioplex, which contain stable avobenzone.

He said that he has no conflict of interest with either manufacturer.

SAN DIEGO — When Dr. Michael Swann advises patients to apply sunscreen to protect against melanoma, the suggestion sometimes falls on deaf ears.

"Patients who don't want to wear sunscreen will say, 'I don't wear sunscreen because it's never been shown to protect against melanoma,'" he said in an update on melanoma sponsored by the Scripps Clinic. "There are a lot of arguments against using it. People will believe what they want to believe."

He acknowledges that retrospective studies have not shown a clear benefit or detriment to using sunscreen to reduce the risk of melanoma but points his patients to other evidence. In Hawaii, where residents apply more sunscreen regularly than in other states, melanoma rates are declining.

The same goes for Australia, where an estimated 74% of residents use sunscreen regularly.

He goes on to tell them that the sunscreens studied over the past 20 years lacked any appreciable UVA protection, which may be important in melanoma. In recent years, though, sunscreens have hit the market with effective protection against UVA. For everyday protection, Dr. Swann recommends Anthelios SX by L'Oréal La Roche-Possay, which contains the sun filter Mexoryl SX.

"At this point, it is only approved as an SPF 15, so it's not really a good one for being on the golf course all day," said Dr. Swann of the Scripps Clinic, La Jolla, Calif.

For periods of longer exposure, he recommends Neutrogena sunscreens with Helioplex, which contain stable avobenzone.

He said that he has no conflict of interest with either manufacturer.

SAN DIEGO — When it comes to follow-up surveillance of melanoma patients, history and physical examination remain the cornerstone of good care, with little solid evidence to support anything else.

"The literature on this aspect of melanoma management is incomplete, mainly because there are very few prospective studies," Dr. Peter R. Shumaker said at a melanoma update sponsored by the Scripps Clinic.

He discussed several goals for the postoperative follow-up of melanoma patients:

▸ Earliest possible detection of treatable recurrence. About one-quarter of patients with local disease and 60%–70% of patients with in-transit [and] nodal disease will develop recurrence, said Dr. Shumaker, clinical fellow in procedural dermatology at the Scripps Clinic in La Jolla, Calif.

One study that reviewed the rate of first recurrence after treatment for malignant melanoma among 250 Australian patients found that 52% of recurrences were in the regional lymph nodes, 17% were local, 8% were in-transit, and 23% were visceral (Plast. Reconstr. Surg. 1993;91:94–8).

"The majority of recurrences occur within the first couple of years," Dr. Shumaker said.

▸ Detection of other primary skin cancers. "These patients are at high risk for a second primary melanoma," he said.

▸ Patient education, emotional support, and reassurance. Most studies report that at least half of recurrences are found by the patients themselves, despite being in a structured follow-up program. "So these follow-ups, in addition to providing an opportunity to inspect and palpate lesions, also provide an opportunity to educate patients," Dr. Shumaker said.

▸ Quality assurance. By this Dr. Shumaker meant the collection of data to improve future treatment and surveillance, such as blood tests and imaging techniques.

Chest x-rays and blood tests are frequently used in the routine follow-up of melanoma patients, "but they offer little benefit in terms of cost effectiveness," Dr. Shumaker said. They generally provide low sensitivity and a high rate of false positives.

Dr. Shumaker considers

Ultrasound "appears to be more sensitive than physical exam in detecting tumor recurrence in in-transit routes and regional nodal basins," he said. "There is an increased likelihood of survival benefit from asymptomatic detection in these areas."

He noted that ultrasound can be combined with fine-needle aspiration to diagnose recurrent or metastatic disease, but there appears to be no role for abdominal ultrasound in routine follow-up.

At Scripps, Dr. Shumaker and his associates perform a comprehensive history and physical exam in melanoma patients every 3 months for 3 years, then every 6 months for life. "This includes baseline and an annual chest x-ray and lab tests," he said.

Most studies report that at least half of recurrences are found bythe patients themselves. DR. SHUMAKER

SAN DIEGO — When it comes to follow-up surveillance of melanoma patients, history and physical examination remain the cornerstone of good care, with little solid evidence to support anything else.

"The literature on this aspect of melanoma management is incomplete, mainly because there are very few prospective studies," Dr. Peter R. Shumaker said at a melanoma update sponsored by the Scripps Clinic.

He discussed several goals for the postoperative follow-up of melanoma patients:

▸ Earliest possible detection of treatable recurrence. About one-quarter of patients with local disease and 60%–70% of patients with in-transit [and] nodal disease will develop recurrence, said Dr. Shumaker, clinical fellow in procedural dermatology at the Scripps Clinic in La Jolla, Calif.

One study that reviewed the rate of first recurrence after treatment for malignant melanoma among 250 Australian patients found that 52% of recurrences were in the regional lymph nodes, 17% were local, 8% were in-transit, and 23% were visceral (Plast. Reconstr. Surg. 1993;91:94–8).

"The majority of recurrences occur within the first couple of years," Dr. Shumaker said.

▸ Detection of other primary skin cancers. "These patients are at high risk for a second primary melanoma," he said.

▸ Patient education, emotional support, and reassurance. Most studies report that at least half of recurrences are found by the patients themselves, despite being in a structured follow-up program. "So these follow-ups, in addition to providing an opportunity to inspect and palpate lesions, also provide an opportunity to educate patients," Dr. Shumaker said.

▸ Quality assurance. By this Dr. Shumaker meant the collection of data to improve future treatment and surveillance, such as blood tests and imaging techniques.

Chest x-rays and blood tests are frequently used in the routine follow-up of melanoma patients, "but they offer little benefit in terms of cost effectiveness," Dr. Shumaker said. They generally provide low sensitivity and a high rate of false positives.

Dr. Shumaker considers

Ultrasound "appears to be more sensitive than physical exam in detecting tumor recurrence in in-transit routes and regional nodal basins," he said. "There is an increased likelihood of survival benefit from asymptomatic detection in these areas."

He noted that ultrasound can be combined with fine-needle aspiration to diagnose recurrent or metastatic disease, but there appears to be no role for abdominal ultrasound in routine follow-up.

At Scripps, Dr. Shumaker and his associates perform a comprehensive history and physical exam in melanoma patients every 3 months for 3 years, then every 6 months for life. "This includes baseline and an annual chest x-ray and lab tests," he said.

Most studies report that at least half of recurrences are found bythe patients themselves. DR. SHUMAKER

SAN DIEGO — When it comes to follow-up surveillance of melanoma patients, history and physical examination remain the cornerstone of good care, with little solid evidence to support anything else.

"The literature on this aspect of melanoma management is incomplete, mainly because there are very few prospective studies," Dr. Peter R. Shumaker said at a melanoma update sponsored by the Scripps Clinic.

He discussed several goals for the postoperative follow-up of melanoma patients:

▸ Earliest possible detection of treatable recurrence. About one-quarter of patients with local disease and 60%–70% of patients with in-transit [and] nodal disease will develop recurrence, said Dr. Shumaker, clinical fellow in procedural dermatology at the Scripps Clinic in La Jolla, Calif.

One study that reviewed the rate of first recurrence after treatment for malignant melanoma among 250 Australian patients found that 52% of recurrences were in the regional lymph nodes, 17% were local, 8% were in-transit, and 23% were visceral (Plast. Reconstr. Surg. 1993;91:94–8).

"The majority of recurrences occur within the first couple of years," Dr. Shumaker said.

▸ Detection of other primary skin cancers. "These patients are at high risk for a second primary melanoma," he said.

▸ Patient education, emotional support, and reassurance. Most studies report that at least half of recurrences are found by the patients themselves, despite being in a structured follow-up program. "So these follow-ups, in addition to providing an opportunity to inspect and palpate lesions, also provide an opportunity to educate patients," Dr. Shumaker said.

▸ Quality assurance. By this Dr. Shumaker meant the collection of data to improve future treatment and surveillance, such as blood tests and imaging techniques.

Chest x-rays and blood tests are frequently used in the routine follow-up of melanoma patients, "but they offer little benefit in terms of cost effectiveness," Dr. Shumaker said. They generally provide low sensitivity and a high rate of false positives.

Dr. Shumaker considers

Ultrasound "appears to be more sensitive than physical exam in detecting tumor recurrence in in-transit routes and regional nodal basins," he said. "There is an increased likelihood of survival benefit from asymptomatic detection in these areas."

He noted that ultrasound can be combined with fine-needle aspiration to diagnose recurrent or metastatic disease, but there appears to be no role for abdominal ultrasound in routine follow-up.

At Scripps, Dr. Shumaker and his associates perform a comprehensive history and physical exam in melanoma patients every 3 months for 3 years, then every 6 months for life. "This includes baseline and an annual chest x-ray and lab tests," he said.

Most studies report that at least half of recurrences are found bythe patients themselves. DR. SHUMAKER

SAN DIEGO — If you're confident that a primary lesion is melanoma, do an excisional biopsy and send the entire specimen to a pathologist.

If you're less certain about the diagnosis, you can do an incisional biopsy of the primary lesion and send the specimen for evaluation, Dr. Avis B. Yount said at an update on melanoma sponsored by the Scripps Clinic. "The goals of biopsy are to establish the diagnosis, determine the best treatment and prognosis for the patient, and determine the type of melanoma, accurate tumor thickness, and information on ulceration and regression," said Dr. Yount of the department of dermatology at the Medical College of Georgia, Augusta.

She defined excisional biopsy as a full thickness biopsy that conservatively excises the entire lesion; its margin is 2–3 mm around the lesion and includes subcutaneous fat. "I try to orient the excision to facilitate future wide excision while maintaining optimal cosmetic and functional results," she said.

Wide excision is not initially recommended because "the lesion may be benign, the excision may be insufficient because of the tumor thickness, and it may interfere with further treatment such as sentinel node biopsy," she said.

If the lesion is located where complete removal would cause substantial disfigurement or a skin graft or flap would be needed for repair, consider proceeding with incisional biopsy. "You can do an elliptical incision through part of the lesion, giving the pathologist the part that will give the best diagnosis, or you can do a punch biopsy or a saucerization-type biopsy," she said. Recent studies have suggested that saucerization might be the most effective approach (J. Am. Acad. Dermatol. 2005;52:798–802).

For incisional biopsy, "you want to biopsy the most nodular or deeply pigmented area into the subcutaneous fat," said Dr. Yount, who also practices in Augusta and Evans, Ga. "Biopsy by shaving, scissor excision, or curettage is not recommended."

She pointed out that there is no evidence that an incisional biopsy has a detrimental influence on the survival of the patient or on the rate of metastases.

When Dr. Yount detects a suspicious lesion on the nail, she removes the entire plate and submits it to the pathologist. "You want to do a transverse biopsy in the nail matrix and a longitudinal biopsy in the nail bed," she said. "Before I remove the nail plate I mark the area of pigment, so that I don't lose the lesion after the nail plate is removed."

Biopsies that are too small create certain challenges. "They may compromise histological assessment, including the accurate assessment of Breslow depth," she said. "You may see a dysplastic or congenital nevus but not the melanoma. I've had seborrheic keratoses abut against a melanoma."

Another problem of small biopsies is that in situ melanoma might coexist with an unidentified invasive component.

"After you've done the biopsy then you need to proceed with excision," Dr. Yount said. "The goals of excision are to cure the patient with low-risk disease, provide local control in patients with probably incurable disease, minimize functional impairment, and minimize cosmetic disfigurement."

Treatment is based primarily on the Breslow depth. "Use judgment in determining margins according to tumor thickness, anatomic location, and skin laxity," Dr. Yount said. She had no relevant conflicts of interest to disclose.

SAN DIEGO — If you're confident that a primary lesion is melanoma, do an excisional biopsy and send the entire specimen to a pathologist.

If you're less certain about the diagnosis, you can do an incisional biopsy of the primary lesion and send the specimen for evaluation, Dr. Avis B. Yount said at an update on melanoma sponsored by the Scripps Clinic. "The goals of biopsy are to establish the diagnosis, determine the best treatment and prognosis for the patient, and determine the type of melanoma, accurate tumor thickness, and information on ulceration and regression," said Dr. Yount of the department of dermatology at the Medical College of Georgia, Augusta.

She defined excisional biopsy as a full thickness biopsy that conservatively excises the entire lesion; its margin is 2–3 mm around the lesion and includes subcutaneous fat. "I try to orient the excision to facilitate future wide excision while maintaining optimal cosmetic and functional results," she said.

Wide excision is not initially recommended because "the lesion may be benign, the excision may be insufficient because of the tumor thickness, and it may interfere with further treatment such as sentinel node biopsy," she said.

If the lesion is located where complete removal would cause substantial disfigurement or a skin graft or flap would be needed for repair, consider proceeding with incisional biopsy. "You can do an elliptical incision through part of the lesion, giving the pathologist the part that will give the best diagnosis, or you can do a punch biopsy or a saucerization-type biopsy," she said. Recent studies have suggested that saucerization might be the most effective approach (J. Am. Acad. Dermatol. 2005;52:798–802).

For incisional biopsy, "you want to biopsy the most nodular or deeply pigmented area into the subcutaneous fat," said Dr. Yount, who also practices in Augusta and Evans, Ga. "Biopsy by shaving, scissor excision, or curettage is not recommended."

She pointed out that there is no evidence that an incisional biopsy has a detrimental influence on the survival of the patient or on the rate of metastases.

When Dr. Yount detects a suspicious lesion on the nail, she removes the entire plate and submits it to the pathologist. "You want to do a transverse biopsy in the nail matrix and a longitudinal biopsy in the nail bed," she said. "Before I remove the nail plate I mark the area of pigment, so that I don't lose the lesion after the nail plate is removed."

Biopsies that are too small create certain challenges. "They may compromise histological assessment, including the accurate assessment of Breslow depth," she said. "You may see a dysplastic or congenital nevus but not the melanoma. I've had seborrheic keratoses abut against a melanoma."

Another problem of small biopsies is that in situ melanoma might coexist with an unidentified invasive component.

"After you've done the biopsy then you need to proceed with excision," Dr. Yount said. "The goals of excision are to cure the patient with low-risk disease, provide local control in patients with probably incurable disease, minimize functional impairment, and minimize cosmetic disfigurement."

Treatment is based primarily on the Breslow depth. "Use judgment in determining margins according to tumor thickness, anatomic location, and skin laxity," Dr. Yount said. She had no relevant conflicts of interest to disclose.

SAN DIEGO — If you're confident that a primary lesion is melanoma, do an excisional biopsy and send the entire specimen to a pathologist.

If you're less certain about the diagnosis, you can do an incisional biopsy of the primary lesion and send the specimen for evaluation, Dr. Avis B. Yount said at an update on melanoma sponsored by the Scripps Clinic. "The goals of biopsy are to establish the diagnosis, determine the best treatment and prognosis for the patient, and determine the type of melanoma, accurate tumor thickness, and information on ulceration and regression," said Dr. Yount of the department of dermatology at the Medical College of Georgia, Augusta.

She defined excisional biopsy as a full thickness biopsy that conservatively excises the entire lesion; its margin is 2–3 mm around the lesion and includes subcutaneous fat. "I try to orient the excision to facilitate future wide excision while maintaining optimal cosmetic and functional results," she said.

Wide excision is not initially recommended because "the lesion may be benign, the excision may be insufficient because of the tumor thickness, and it may interfere with further treatment such as sentinel node biopsy," she said.

If the lesion is located where complete removal would cause substantial disfigurement or a skin graft or flap would be needed for repair, consider proceeding with incisional biopsy. "You can do an elliptical incision through part of the lesion, giving the pathologist the part that will give the best diagnosis, or you can do a punch biopsy or a saucerization-type biopsy," she said. Recent studies have suggested that saucerization might be the most effective approach (J. Am. Acad. Dermatol. 2005;52:798–802).

For incisional biopsy, "you want to biopsy the most nodular or deeply pigmented area into the subcutaneous fat," said Dr. Yount, who also practices in Augusta and Evans, Ga. "Biopsy by shaving, scissor excision, or curettage is not recommended."

She pointed out that there is no evidence that an incisional biopsy has a detrimental influence on the survival of the patient or on the rate of metastases.

When Dr. Yount detects a suspicious lesion on the nail, she removes the entire plate and submits it to the pathologist. "You want to do a transverse biopsy in the nail matrix and a longitudinal biopsy in the nail bed," she said. "Before I remove the nail plate I mark the area of pigment, so that I don't lose the lesion after the nail plate is removed."

Biopsies that are too small create certain challenges. "They may compromise histological assessment, including the accurate assessment of Breslow depth," she said. "You may see a dysplastic or congenital nevus but not the melanoma. I've had seborrheic keratoses abut against a melanoma."

Another problem of small biopsies is that in situ melanoma might coexist with an unidentified invasive component.

"After you've done the biopsy then you need to proceed with excision," Dr. Yount said. "The goals of excision are to cure the patient with low-risk disease, provide local control in patients with probably incurable disease, minimize functional impairment, and minimize cosmetic disfigurement."

Treatment is based primarily on the Breslow depth. "Use judgment in determining margins according to tumor thickness, anatomic location, and skin laxity," Dr. Yount said. She had no relevant conflicts of interest to disclose.

SAN DIEGO — What is an adequate margin for surgical excision of melanoma?

Beyond a clear margin, "we really don't know," Dr. Duane C. Whitaker said at a melanoma update sponsored by the Scripps Clinic.

That's why there's a place for Mohs surgery in the treatment of melanoma.

"Mohs for melanoma has not caught on terribly widely, but on the other hand I don't believe it will ever disappear because there are times when you simply need Mohs surgery to be able to treat the primary melanoma in a reasonable way," said Dr. Whitaker, a dermatologist and Mohs surgeon who practices in Tucson, Ariz.

He described Mohs surgery as "the best method we have to establish tumor-free margins when we remove any type of visible tumor. Any time that we don't truly know what margin beyond clear should be achieved to help the patient, then probably there is some role for Mohs surgery."

The best studies to date have demonstrated that the cure rate with Mohs surgery in stage I and stage II melanomas is at least equivalent to local excision with a predetermined margin, he said.

Mohs surgery has several traditional advantages. It spares tissue in the ear, nose, and other critical anatomic sites; determines margins precisely; allows for immediate reconstruction; allows minimum wound and repair; and allows physicians to start additional and adjunctive therapies right away.

The technique is especially useful for neurotrophic and desmoplastic melanomas since "they're often deeper and wider than you would anticipate," he said.

A key factor when deciding whether to perform Mohs or not "is your comfort with following [the patients], talking about the issues involved, and being ready for that patient who may come back with a lump that you didn't expect," continued Dr. Whitaker, who is the current vice president of the American College of Mohs Surgery.

Beyond the realm of melanoma, Mohs surgery seems to have applications as the method to establish free margins of a primary tumor when evidence does not support a survival benefit achieved by more radical surgery. "If all melanomas occurred in the trunk or proximal extremities where we can do a wider local excision with 3-cm margins, they wouldn't be so difficult to treat," he said, "but when they occur on the digits, the nose, or the periocular areas," that adds complexity.

Mohs surgery seems to be the most reliable method to obtain local free margins at the time of surgery. "It is considered one component of treatment for those tumors which have substantial metastatic risk," Dr. Whitaker said. "Assessment of the host and tumor characteristics will help you determine the full therapeutic plan."

Mohs is 'the best method we have to establish tumor-free margins when we remove any type of visible tumor.' DR. WHITAKER

A melanoma lesion on a patient's nose is shown before Mohs surgery.

The same patient is shown after Mohs was performed to remove the lesion. Photos courtesy Dr. Duane C. Whitaker

SAN DIEGO — What is an adequate margin for surgical excision of melanoma?

Beyond a clear margin, "we really don't know," Dr. Duane C. Whitaker said at a melanoma update sponsored by the Scripps Clinic.

That's why there's a place for Mohs surgery in the treatment of melanoma.

"Mohs for melanoma has not caught on terribly widely, but on the other hand I don't believe it will ever disappear because there are times when you simply need Mohs surgery to be able to treat the primary melanoma in a reasonable way," said Dr. Whitaker, a dermatologist and Mohs surgeon who practices in Tucson, Ariz.

He described Mohs surgery as "the best method we have to establish tumor-free margins when we remove any type of visible tumor. Any time that we don't truly know what margin beyond clear should be achieved to help the patient, then probably there is some role for Mohs surgery."

The best studies to date have demonstrated that the cure rate with Mohs surgery in stage I and stage II melanomas is at least equivalent to local excision with a predetermined margin, he said.

Mohs surgery has several traditional advantages. It spares tissue in the ear, nose, and other critical anatomic sites; determines margins precisely; allows for immediate reconstruction; allows minimum wound and repair; and allows physicians to start additional and adjunctive therapies right away.

The technique is especially useful for neurotrophic and desmoplastic melanomas since "they're often deeper and wider than you would anticipate," he said.

A key factor when deciding whether to perform Mohs or not "is your comfort with following [the patients], talking about the issues involved, and being ready for that patient who may come back with a lump that you didn't expect," continued Dr. Whitaker, who is the current vice president of the American College of Mohs Surgery.

Beyond the realm of melanoma, Mohs surgery seems to have applications as the method to establish free margins of a primary tumor when evidence does not support a survival benefit achieved by more radical surgery. "If all melanomas occurred in the trunk or proximal extremities where we can do a wider local excision with 3-cm margins, they wouldn't be so difficult to treat," he said, "but when they occur on the digits, the nose, or the periocular areas," that adds complexity.

Mohs surgery seems to be the most reliable method to obtain local free margins at the time of surgery. "It is considered one component of treatment for those tumors which have substantial metastatic risk," Dr. Whitaker said. "Assessment of the host and tumor characteristics will help you determine the full therapeutic plan."

Mohs is 'the best method we have to establish tumor-free margins when we remove any type of visible tumor.' DR. WHITAKER

A melanoma lesion on a patient's nose is shown before Mohs surgery.

The same patient is shown after Mohs was performed to remove the lesion. Photos courtesy Dr. Duane C. Whitaker

SAN DIEGO — What is an adequate margin for surgical excision of melanoma?

Beyond a clear margin, "we really don't know," Dr. Duane C. Whitaker said at a melanoma update sponsored by the Scripps Clinic.

That's why there's a place for Mohs surgery in the treatment of melanoma.

"Mohs for melanoma has not caught on terribly widely, but on the other hand I don't believe it will ever disappear because there are times when you simply need Mohs surgery to be able to treat the primary melanoma in a reasonable way," said Dr. Whitaker, a dermatologist and Mohs surgeon who practices in Tucson, Ariz.

He described Mohs surgery as "the best method we have to establish tumor-free margins when we remove any type of visible tumor. Any time that we don't truly know what margin beyond clear should be achieved to help the patient, then probably there is some role for Mohs surgery."

The best studies to date have demonstrated that the cure rate with Mohs surgery in stage I and stage II melanomas is at least equivalent to local excision with a predetermined margin, he said.

Mohs surgery has several traditional advantages. It spares tissue in the ear, nose, and other critical anatomic sites; determines margins precisely; allows for immediate reconstruction; allows minimum wound and repair; and allows physicians to start additional and adjunctive therapies right away.

The technique is especially useful for neurotrophic and desmoplastic melanomas since "they're often deeper and wider than you would anticipate," he said.

A key factor when deciding whether to perform Mohs or not "is your comfort with following [the patients], talking about the issues involved, and being ready for that patient who may come back with a lump that you didn't expect," continued Dr. Whitaker, who is the current vice president of the American College of Mohs Surgery.

Beyond the realm of melanoma, Mohs surgery seems to have applications as the method to establish free margins of a primary tumor when evidence does not support a survival benefit achieved by more radical surgery. "If all melanomas occurred in the trunk or proximal extremities where we can do a wider local excision with 3-cm margins, they wouldn't be so difficult to treat," he said, "but when they occur on the digits, the nose, or the periocular areas," that adds complexity.

Mohs surgery seems to be the most reliable method to obtain local free margins at the time of surgery. "It is considered one component of treatment for those tumors which have substantial metastatic risk," Dr. Whitaker said. "Assessment of the host and tumor characteristics will help you determine the full therapeutic plan."

Mohs is 'the best method we have to establish tumor-free margins when we remove any type of visible tumor.' DR. WHITAKER

A melanoma lesion on a patient's nose is shown before Mohs surgery.

The same patient is shown after Mohs was performed to remove the lesion. Photos courtesy Dr. Duane C. Whitaker

SAN DIEGO — There's no need to grade the level of architectural disorder when assessing dysplastic nevi. Just acknowledge if it's present or not.

"It doesn't matter how much architectural disorder is there; it only matters that it's present or absent," Dr. Terry L. Barrett said at an update on melanoma sponsored by the Scripps Clinic. "It's like being pregnant. Every single person in the world can be divided into one of two categories: You're either pregnant or you're not."

His minimal criterion for defining the presence of architectural disorder in a lesion is a well-defined junctional nevus with nests at the base of the rete and lentiginous proliferation. Concentric eosinophilic fibroplasia and lamellar fibroplasia are commonly seen.

In addition to architectural disorder, dysplastic nevi may or may not have cytologic atypia, which may include large nuclei with variation of nuclear size; irregular nuclear membrane; variably staining chromatin; large eosinophilic nucleoli; and fine dusty melanin pigment in cytoplasm.

Some experts recommend that cytologic atypia be graded as mild, moderate, or severe, but Dr. Barrett does not use the term moderate. "If there's none there's none, but if there's some cytologic atypia it's either mild or severe," said Dr. Barrett of the departments of pathology and dermatology at the University of Texas, Dallas.

He favors a modified version of Dr. Arthur R. Rhodes' atypia grading system (Mod. Pathol. 1989;2:306–19). Cytologic atypia is considered mild if the size of the nucleus of the melanocyte is 1.5–2 times the size of the nucleus of the keratinocyte and if nucleoli are not present; if they are present, there should be no more than one per cell, he explained.

"I can tell that in 2 microseconds," Dr. Barrett said. "It's very easy."

Cytologic atypia is severe if there are multiple nucleoli per cell, or if the nucleus is more than two times the size of the basal keratinocyte nucleus, or if there is chromatin clumping or nuclear membrane notching.

"I can tell that very quickly," said Dr. Barrett, who also directs an outpatient pathology group in Dallas.

"More importantly, it's reproducible. I'll grant you that it's arbitrary. But the important thing is, no matter which one of the dermatopathologists who works with me signs this case out, it's going to be the same. For the dermatologist who gets the report, it's always going to be the same. If they ask me to review the case later because they want to know what I think, it's going to be the same because it's easy to do and it's reproducible."

Common acquired nevi begin to appear in childhood and increase in number from approximately 6 months of age until the third decade. At that point, they begin to decline in number. "They usually stabilize at 3–5 mm and rarely develop in patients over age 40," said Dr. Barrett, who had no relevant conflicts of interest to disclose.

In contrast, dysplastic nevi begin to appear near puberty and continue to develop throughout adulthood. "If you do serial photography of these lesions, they will increase and decrease in atypicality," he said. "They are usually greater than 5 mm."

Dysplastic nevi were originally classified as familial dysplastic nevi syndrome and sporadic nevus syndrome. Current concepts include the familial atypical mole/melanoma syndrome, which came out of the 1992 National Institutes of Health consensus statement on the diagnosis and treatment of early melanoma, and the abnormal mole phenotype. The latter definition was developed by researchers who proposed a spectrum approach that considers both the number and atypicality of nevi (West. J. Med. 1994;160:343–50). Melanoma risk increases along this continuum.

Initially, that theory "went nowhere because people didn't believe that you could have large numbers of common acquired nevi and no dysplastic nevi, and you [would nevertheless be] at increased risk for melanoma. But we now know that is absolutely true, and a number of studies have shown that patients who have large numbers of common acquired nevi have an increased risk of developing melanoma," Dr. Barrett said.

Melanoma risk also appears to increase in the presence of dysplastic nevi. A significant factor is the presence or absence of family history of either condition.

Intermittent sun exposure correlates with the risk of developing malignant melanoma and with the risk of developing multiple nevi. "Whether melanoma arises from nevi or not is unclear, but it appears that the stimulus for formation of both is the same," he said.

The risk of melanoma in a patient who has "one dysplastic nevus and nothing else" is the about the same as someone who has red or blond hair. "Not everybody with red or blond hair is going to get melanoma, but they are at an increased risk," he said.

Dr. Barrett likened dysplastic lesions to amoebae. These lesions "go through quiescent phases and they go through active phases," he said. "If we do serial photographs, we can document this change. If the lesion is quiescent and you biopsy it, you see no atypia because there is minimal cellular activity. If you biopsy it in an active phase, it's going to have some degree of atypia. That doesn't mean that atypia equates with dysplasia or premalignancy. That's what I think is happening."

No cytologic atypia can be seen in this slide from a patient with dysplastic nevi, per Dr. Terry L. Barrett.

The atypia seen above is considered mild according to Dr. Barrett's modified dysplastic nevi grading system.

This patient has severe cytologic atypia. Dr. Barrett avoids the term moderate when assessing atypia. Photos courtesy Dr. Terry L. Barrett

SAN DIEGO — There's no need to grade the level of architectural disorder when assessing dysplastic nevi. Just acknowledge if it's present or not.

"It doesn't matter how much architectural disorder is there; it only matters that it's present or absent," Dr. Terry L. Barrett said at an update on melanoma sponsored by the Scripps Clinic. "It's like being pregnant. Every single person in the world can be divided into one of two categories: You're either pregnant or you're not."

His minimal criterion for defining the presence of architectural disorder in a lesion is a well-defined junctional nevus with nests at the base of the rete and lentiginous proliferation. Concentric eosinophilic fibroplasia and lamellar fibroplasia are commonly seen.

In addition to architectural disorder, dysplastic nevi may or may not have cytologic atypia, which may include large nuclei with variation of nuclear size; irregular nuclear membrane; variably staining chromatin; large eosinophilic nucleoli; and fine dusty melanin pigment in cytoplasm.

Some experts recommend that cytologic atypia be graded as mild, moderate, or severe, but Dr. Barrett does not use the term moderate. "If there's none there's none, but if there's some cytologic atypia it's either mild or severe," said Dr. Barrett of the departments of pathology and dermatology at the University of Texas, Dallas.

He favors a modified version of Dr. Arthur R. Rhodes' atypia grading system (Mod. Pathol. 1989;2:306–19). Cytologic atypia is considered mild if the size of the nucleus of the melanocyte is 1.5–2 times the size of the nucleus of the keratinocyte and if nucleoli are not present; if they are present, there should be no more than one per cell, he explained.

"I can tell that in 2 microseconds," Dr. Barrett said. "It's very easy."

Cytologic atypia is severe if there are multiple nucleoli per cell, or if the nucleus is more than two times the size of the basal keratinocyte nucleus, or if there is chromatin clumping or nuclear membrane notching.

"I can tell that very quickly," said Dr. Barrett, who also directs an outpatient pathology group in Dallas.

"More importantly, it's reproducible. I'll grant you that it's arbitrary. But the important thing is, no matter which one of the dermatopathologists who works with me signs this case out, it's going to be the same. For the dermatologist who gets the report, it's always going to be the same. If they ask me to review the case later because they want to know what I think, it's going to be the same because it's easy to do and it's reproducible."

Common acquired nevi begin to appear in childhood and increase in number from approximately 6 months of age until the third decade. At that point, they begin to decline in number. "They usually stabilize at 3–5 mm and rarely develop in patients over age 40," said Dr. Barrett, who had no relevant conflicts of interest to disclose.

In contrast, dysplastic nevi begin to appear near puberty and continue to develop throughout adulthood. "If you do serial photography of these lesions, they will increase and decrease in atypicality," he said. "They are usually greater than 5 mm."

Dysplastic nevi were originally classified as familial dysplastic nevi syndrome and sporadic nevus syndrome. Current concepts include the familial atypical mole/melanoma syndrome, which came out of the 1992 National Institutes of Health consensus statement on the diagnosis and treatment of early melanoma, and the abnormal mole phenotype. The latter definition was developed by researchers who proposed a spectrum approach that considers both the number and atypicality of nevi (West. J. Med. 1994;160:343–50). Melanoma risk increases along this continuum.

Initially, that theory "went nowhere because people didn't believe that you could have large numbers of common acquired nevi and no dysplastic nevi, and you [would nevertheless be] at increased risk for melanoma. But we now know that is absolutely true, and a number of studies have shown that patients who have large numbers of common acquired nevi have an increased risk of developing melanoma," Dr. Barrett said.

Melanoma risk also appears to increase in the presence of dysplastic nevi. A significant factor is the presence or absence of family history of either condition.

Intermittent sun exposure correlates with the risk of developing malignant melanoma and with the risk of developing multiple nevi. "Whether melanoma arises from nevi or not is unclear, but it appears that the stimulus for formation of both is the same," he said.

The risk of melanoma in a patient who has "one dysplastic nevus and nothing else" is the about the same as someone who has red or blond hair. "Not everybody with red or blond hair is going to get melanoma, but they are at an increased risk," he said.

Dr. Barrett likened dysplastic lesions to amoebae. These lesions "go through quiescent phases and they go through active phases," he said. "If we do serial photographs, we can document this change. If the lesion is quiescent and you biopsy it, you see no atypia because there is minimal cellular activity. If you biopsy it in an active phase, it's going to have some degree of atypia. That doesn't mean that atypia equates with dysplasia or premalignancy. That's what I think is happening."

No cytologic atypia can be seen in this slide from a patient with dysplastic nevi, per Dr. Terry L. Barrett.

The atypia seen above is considered mild according to Dr. Barrett's modified dysplastic nevi grading system.

This patient has severe cytologic atypia. Dr. Barrett avoids the term moderate when assessing atypia. Photos courtesy Dr. Terry L. Barrett

SAN DIEGO — There's no need to grade the level of architectural disorder when assessing dysplastic nevi. Just acknowledge if it's present or not.

"It doesn't matter how much architectural disorder is there; it only matters that it's present or absent," Dr. Terry L. Barrett said at an update on melanoma sponsored by the Scripps Clinic. "It's like being pregnant. Every single person in the world can be divided into one of two categories: You're either pregnant or you're not."

His minimal criterion for defining the presence of architectural disorder in a lesion is a well-defined junctional nevus with nests at the base of the rete and lentiginous proliferation. Concentric eosinophilic fibroplasia and lamellar fibroplasia are commonly seen.

In addition to architectural disorder, dysplastic nevi may or may not have cytologic atypia, which may include large nuclei with variation of nuclear size; irregular nuclear membrane; variably staining chromatin; large eosinophilic nucleoli; and fine dusty melanin pigment in cytoplasm.

Some experts recommend that cytologic atypia be graded as mild, moderate, or severe, but Dr. Barrett does not use the term moderate. "If there's none there's none, but if there's some cytologic atypia it's either mild or severe," said Dr. Barrett of the departments of pathology and dermatology at the University of Texas, Dallas.

He favors a modified version of Dr. Arthur R. Rhodes' atypia grading system (Mod. Pathol. 1989;2:306–19). Cytologic atypia is considered mild if the size of the nucleus of the melanocyte is 1.5–2 times the size of the nucleus of the keratinocyte and if nucleoli are not present; if they are present, there should be no more than one per cell, he explained.

"I can tell that in 2 microseconds," Dr. Barrett said. "It's very easy."

Cytologic atypia is severe if there are multiple nucleoli per cell, or if the nucleus is more than two times the size of the basal keratinocyte nucleus, or if there is chromatin clumping or nuclear membrane notching.

"I can tell that very quickly," said Dr. Barrett, who also directs an outpatient pathology group in Dallas.

"More importantly, it's reproducible. I'll grant you that it's arbitrary. But the important thing is, no matter which one of the dermatopathologists who works with me signs this case out, it's going to be the same. For the dermatologist who gets the report, it's always going to be the same. If they ask me to review the case later because they want to know what I think, it's going to be the same because it's easy to do and it's reproducible."

Common acquired nevi begin to appear in childhood and increase in number from approximately 6 months of age until the third decade. At that point, they begin to decline in number. "They usually stabilize at 3–5 mm and rarely develop in patients over age 40," said Dr. Barrett, who had no relevant conflicts of interest to disclose.

In contrast, dysplastic nevi begin to appear near puberty and continue to develop throughout adulthood. "If you do serial photography of these lesions, they will increase and decrease in atypicality," he said. "They are usually greater than 5 mm."

Dysplastic nevi were originally classified as familial dysplastic nevi syndrome and sporadic nevus syndrome. Current concepts include the familial atypical mole/melanoma syndrome, which came out of the 1992 National Institutes of Health consensus statement on the diagnosis and treatment of early melanoma, and the abnormal mole phenotype. The latter definition was developed by researchers who proposed a spectrum approach that considers both the number and atypicality of nevi (West. J. Med. 1994;160:343–50). Melanoma risk increases along this continuum.

Initially, that theory "went nowhere because people didn't believe that you could have large numbers of common acquired nevi and no dysplastic nevi, and you [would nevertheless be] at increased risk for melanoma. But we now know that is absolutely true, and a number of studies have shown that patients who have large numbers of common acquired nevi have an increased risk of developing melanoma," Dr. Barrett said.

Melanoma risk also appears to increase in the presence of dysplastic nevi. A significant factor is the presence or absence of family history of either condition.

Intermittent sun exposure correlates with the risk of developing malignant melanoma and with the risk of developing multiple nevi. "Whether melanoma arises from nevi or not is unclear, but it appears that the stimulus for formation of both is the same," he said.

The risk of melanoma in a patient who has "one dysplastic nevus and nothing else" is the about the same as someone who has red or blond hair. "Not everybody with red or blond hair is going to get melanoma, but they are at an increased risk," he said.

Dr. Barrett likened dysplastic lesions to amoebae. These lesions "go through quiescent phases and they go through active phases," he said. "If we do serial photographs, we can document this change. If the lesion is quiescent and you biopsy it, you see no atypia because there is minimal cellular activity. If you biopsy it in an active phase, it's going to have some degree of atypia. That doesn't mean that atypia equates with dysplasia or premalignancy. That's what I think is happening."

No cytologic atypia can be seen in this slide from a patient with dysplastic nevi, per Dr. Terry L. Barrett.

The atypia seen above is considered mild according to Dr. Barrett's modified dysplastic nevi grading system.

This patient has severe cytologic atypia. Dr. Barrett avoids the term moderate when assessing atypia. Photos courtesy Dr. Terry L. Barrett

SAN DIEGO — For patients with regionally advanced melanoma, the current standard of care is high-dose interferon.

"It's an imperfect standard, but nonetheless it is the standard," Dr. Michael P. Kosty said at a melanoma update sponsored by the Scripps Clinic.

To date, five randomized trials of high-dose interferon have shown a recurrence-free survival advantage, but an overall survival advantage "has been harder to demonstrate," said Dr. Kosty, program director of the hematology/oncology fellowship training program at the Scripps Clinic.

"One of the things about survival as an end point is that if you have a patient population and you treat them with your experimental therapy and they progress or recur, a lot of patients will go on standard therapy, which will impact your ability to assess their survival," he said.

Two studies have shown a survival advantage for high-dose interferon. In one study, patients were randomized to either 52 weeks of observation or to an induction phase of 20 megaunits/m

A more recent study assessed the impact of low-dose and high-dose interferon on overall survival compared with no treatment. It found that only high-dose interferon conferred a survival advantage: a median of 20 months, compared with a median of 9.6 months among those who did not receive treatment (J. Clin. Oncol. 2000; 18: 2444–58). A similar association was seen in the rates of recurrence-free survival.

"There is a dose-response relationship between the higher doses of interferon and the higher likelihood of recurrence-free benefit," said Dr. Kosty, who had no relevant conflicts of interest to disclose.

At this time, patients with stage III or stage IV disease are ideal candidates for systemic therapy. "If you look at the current data, there is no evidence in stage II disease of efficacy of adjuvant therapy, either in terms of progression free or overall survival," he noted.

The most common adverse events from high-dose interferon treatment include fatigue and depressive symptoms. Despite aggressive antidepressive therapy, "this impacts the function of many patients. Some are unable to work, particularly if they have physically demanding jobs or mentally challenging jobs," said Dr. Kosty.

In an effort to find a better alternative, a trial of 400 patients to compare standard high-dose interferon treatment to a chemoimmunotherapy combination has completed accrual. Results are expected in the coming year.

So far, no vaccine trial has shown improvement in overall survival, although some trials have shown an improvement in relapse-free survival. "There is about a 20% reduction in relapse rate and perhaps as high as a 10% reduction in death rate, although that 10% is probably the most optimistic number," he said. "Vaccines will probably have their ultimate utility in patients who have a very high risk of either developing melanoma or developing recurrence from their surgically treated melanoma, as opposed to patients with more advanced disease."

Effective treatment options for metastatic melanoma remain a challenge for researchers. Current therapies have little impact on median survival, although the combination of chemotherapy, interleukin-2, and interferon has "a fairly high response rate," Dr. Kosty said.

"That therapy might be useful if you have somebody with metastatic disease that is significantly symptomatic from the disease, such as somebody with bony metastasis and pain or somebody with liver metastasis and diminished appetite. They may benefit symptomatically but will not benefit from that therapy in terms of survival," he noted.

Recurrence-free survival has been shown, but overall survival 'has been harder to demonstrate.' DR. KOSTY

SAN DIEGO — For patients with regionally advanced melanoma, the current standard of care is high-dose interferon.

"It's an imperfect standard, but nonetheless it is the standard," Dr. Michael P. Kosty said at a melanoma update sponsored by the Scripps Clinic.

To date, five randomized trials of high-dose interferon have shown a recurrence-free survival advantage, but an overall survival advantage "has been harder to demonstrate," said Dr. Kosty, program director of the hematology/oncology fellowship training program at the Scripps Clinic.

"One of the things about survival as an end point is that if you have a patient population and you treat them with your experimental therapy and they progress or recur, a lot of patients will go on standard therapy, which will impact your ability to assess their survival," he said.

Two studies have shown a survival advantage for high-dose interferon. In one study, patients were randomized to either 52 weeks of observation or to an induction phase of 20 megaunits/m

A more recent study assessed the impact of low-dose and high-dose interferon on overall survival compared with no treatment. It found that only high-dose interferon conferred a survival advantage: a median of 20 months, compared with a median of 9.6 months among those who did not receive treatment (J. Clin. Oncol. 2000; 18: 2444–58). A similar association was seen in the rates of recurrence-free survival.

"There is a dose-response relationship between the higher doses of interferon and the higher likelihood of recurrence-free benefit," said Dr. Kosty, who had no relevant conflicts of interest to disclose.

At this time, patients with stage III or stage IV disease are ideal candidates for systemic therapy. "If you look at the current data, there is no evidence in stage II disease of efficacy of adjuvant therapy, either in terms of progression free or overall survival," he noted.

The most common adverse events from high-dose interferon treatment include fatigue and depressive symptoms. Despite aggressive antidepressive therapy, "this impacts the function of many patients. Some are unable to work, particularly if they have physically demanding jobs or mentally challenging jobs," said Dr. Kosty.

In an effort to find a better alternative, a trial of 400 patients to compare standard high-dose interferon treatment to a chemoimmunotherapy combination has completed accrual. Results are expected in the coming year.

So far, no vaccine trial has shown improvement in overall survival, although some trials have shown an improvement in relapse-free survival. "There is about a 20% reduction in relapse rate and perhaps as high as a 10% reduction in death rate, although that 10% is probably the most optimistic number," he said. "Vaccines will probably have their ultimate utility in patients who have a very high risk of either developing melanoma or developing recurrence from their surgically treated melanoma, as opposed to patients with more advanced disease."

Effective treatment options for metastatic melanoma remain a challenge for researchers. Current therapies have little impact on median survival, although the combination of chemotherapy, interleukin-2, and interferon has "a fairly high response rate," Dr. Kosty said.

"That therapy might be useful if you have somebody with metastatic disease that is significantly symptomatic from the disease, such as somebody with bony metastasis and pain or somebody with liver metastasis and diminished appetite. They may benefit symptomatically but will not benefit from that therapy in terms of survival," he noted.

Recurrence-free survival has been shown, but overall survival 'has been harder to demonstrate.' DR. KOSTY

SAN DIEGO — For patients with regionally advanced melanoma, the current standard of care is high-dose interferon.

"It's an imperfect standard, but nonetheless it is the standard," Dr. Michael P. Kosty said at a melanoma update sponsored by the Scripps Clinic.

To date, five randomized trials of high-dose interferon have shown a recurrence-free survival advantage, but an overall survival advantage "has been harder to demonstrate," said Dr. Kosty, program director of the hematology/oncology fellowship training program at the Scripps Clinic.

"One of the things about survival as an end point is that if you have a patient population and you treat them with your experimental therapy and they progress or recur, a lot of patients will go on standard therapy, which will impact your ability to assess their survival," he said.

Two studies have shown a survival advantage for high-dose interferon. In one study, patients were randomized to either 52 weeks of observation or to an induction phase of 20 megaunits/m

A more recent study assessed the impact of low-dose and high-dose interferon on overall survival compared with no treatment. It found that only high-dose interferon conferred a survival advantage: a median of 20 months, compared with a median of 9.6 months among those who did not receive treatment (J. Clin. Oncol. 2000; 18: 2444–58). A similar association was seen in the rates of recurrence-free survival.

"There is a dose-response relationship between the higher doses of interferon and the higher likelihood of recurrence-free benefit," said Dr. Kosty, who had no relevant conflicts of interest to disclose.

At this time, patients with stage III or stage IV disease are ideal candidates for systemic therapy. "If you look at the current data, there is no evidence in stage II disease of efficacy of adjuvant therapy, either in terms of progression free or overall survival," he noted.

The most common adverse events from high-dose interferon treatment include fatigue and depressive symptoms. Despite aggressive antidepressive therapy, "this impacts the function of many patients. Some are unable to work, particularly if they have physically demanding jobs or mentally challenging jobs," said Dr. Kosty.

In an effort to find a better alternative, a trial of 400 patients to compare standard high-dose interferon treatment to a chemoimmunotherapy combination has completed accrual. Results are expected in the coming year.

So far, no vaccine trial has shown improvement in overall survival, although some trials have shown an improvement in relapse-free survival. "There is about a 20% reduction in relapse rate and perhaps as high as a 10% reduction in death rate, although that 10% is probably the most optimistic number," he said. "Vaccines will probably have their ultimate utility in patients who have a very high risk of either developing melanoma or developing recurrence from their surgically treated melanoma, as opposed to patients with more advanced disease."

Effective treatment options for metastatic melanoma remain a challenge for researchers. Current therapies have little impact on median survival, although the combination of chemotherapy, interleukin-2, and interferon has "a fairly high response rate," Dr. Kosty said.

"That therapy might be useful if you have somebody with metastatic disease that is significantly symptomatic from the disease, such as somebody with bony metastasis and pain or somebody with liver metastasis and diminished appetite. They may benefit symptomatically but will not benefit from that therapy in terms of survival," he noted.

Recurrence-free survival has been shown, but overall survival 'has been harder to demonstrate.' DR. KOSTY

The American Contact Dermatitis Society has proclaimed nickel as its 2008 Allergen of the Year because of its rise as a cause of significant contact dermatitis in the United States, particularly among children.

“To dismiss nickel's importance and relevance to public health and skin disease, would be a mistake,” said Dr. Kathryn A. Zug in an article scheduled for publication in the Jan./Feb. issue of Dermatitis.

The metal can be found in coins, jewelry, buckles, pant snaps, tools, and other products, noted Dr. Zug of the of the department of dermatology at Dartmouth Hitchcock Medical Center, Lebanon, N.H.

Data from the North American Contact Dermatitis Group (NACDG) have shown that the number of patients who patch-tested positive for nickel grew from 11% in 1985-1990 to 19% in 2003-2004. Of 391 children who were patch-tested by the group from 2001 to 2004, 28% had a positive patch test to nickel, and 26% were thought to have a nickel allergy of either current or past relevance.

“NACDG data [also] show that as in adult females, nickel sensitization in girls is on the rise,” wrote Dr. Zug, the immediate past president of the American Contact Dermatitis Society, who cowrote the article with Rachel Kornik, a fourth-year medical student at Dartmouth.

The prevalence of nickel allergy in girls and women is probably mostly due to ear piercing and sensitization from some jewelry, Dr. Zug said in an interview. Sensitization is higher in men with pierced ears.

Health providers should also consider:

▸ Complications related to biomedical devices. Although reactions to medical-grade stainless steel is uncommon in nickel-sensitized patients, orthopedic surgeons and orthodontists still consult dermatologists about the safety of metal medical devices, the authors wrote. In addition, in patients who undergo endovascular stenting, evidence that nickel allergy is associated with stent restenosis “remains in question.”

▸ Ingestion of dietary nickel. Nickel is found in foods such as legumes, nuts, grains, chocolate, and fish, as well as medications and vitamins.

▸ Prevention of contact allergy to nickel is challenging. The best approach is to find ways to reduce sensitization. Regulation of nickel release from consumer goods “would be a challenging but potentially successful solution,” wrote the authors, who reported no conflicts of interest.

The American Contact Dermatitis Society has proclaimed nickel as its 2008 Allergen of the Year because of its rise as a cause of significant contact dermatitis in the United States, particularly among children.

“To dismiss nickel's importance and relevance to public health and skin disease, would be a mistake,” said Dr. Kathryn A. Zug in an article scheduled for publication in the Jan./Feb. issue of Dermatitis.

The metal can be found in coins, jewelry, buckles, pant snaps, tools, and other products, noted Dr. Zug of the of the department of dermatology at Dartmouth Hitchcock Medical Center, Lebanon, N.H.

Data from the North American Contact Dermatitis Group (NACDG) have shown that the number of patients who patch-tested positive for nickel grew from 11% in 1985-1990 to 19% in 2003-2004. Of 391 children who were patch-tested by the group from 2001 to 2004, 28% had a positive patch test to nickel, and 26% were thought to have a nickel allergy of either current or past relevance.

“NACDG data [also] show that as in adult females, nickel sensitization in girls is on the rise,” wrote Dr. Zug, the immediate past president of the American Contact Dermatitis Society, who cowrote the article with Rachel Kornik, a fourth-year medical student at Dartmouth.

The prevalence of nickel allergy in girls and women is probably mostly due to ear piercing and sensitization from some jewelry, Dr. Zug said in an interview. Sensitization is higher in men with pierced ears.

Health providers should also consider:

▸ Complications related to biomedical devices. Although reactions to medical-grade stainless steel is uncommon in nickel-sensitized patients, orthopedic surgeons and orthodontists still consult dermatologists about the safety of metal medical devices, the authors wrote. In addition, in patients who undergo endovascular stenting, evidence that nickel allergy is associated with stent restenosis “remains in question.”

▸ Ingestion of dietary nickel. Nickel is found in foods such as legumes, nuts, grains, chocolate, and fish, as well as medications and vitamins.

▸ Prevention of contact allergy to nickel is challenging. The best approach is to find ways to reduce sensitization. Regulation of nickel release from consumer goods “would be a challenging but potentially successful solution,” wrote the authors, who reported no conflicts of interest.

The American Contact Dermatitis Society has proclaimed nickel as its 2008 Allergen of the Year because of its rise as a cause of significant contact dermatitis in the United States, particularly among children.

“To dismiss nickel's importance and relevance to public health and skin disease, would be a mistake,” said Dr. Kathryn A. Zug in an article scheduled for publication in the Jan./Feb. issue of Dermatitis.

The metal can be found in coins, jewelry, buckles, pant snaps, tools, and other products, noted Dr. Zug of the of the department of dermatology at Dartmouth Hitchcock Medical Center, Lebanon, N.H.

Data from the North American Contact Dermatitis Group (NACDG) have shown that the number of patients who patch-tested positive for nickel grew from 11% in 1985-1990 to 19% in 2003-2004. Of 391 children who were patch-tested by the group from 2001 to 2004, 28% had a positive patch test to nickel, and 26% were thought to have a nickel allergy of either current or past relevance.

“NACDG data [also] show that as in adult females, nickel sensitization in girls is on the rise,” wrote Dr. Zug, the immediate past president of the American Contact Dermatitis Society, who cowrote the article with Rachel Kornik, a fourth-year medical student at Dartmouth.

The prevalence of nickel allergy in girls and women is probably mostly due to ear piercing and sensitization from some jewelry, Dr. Zug said in an interview. Sensitization is higher in men with pierced ears.

Health providers should also consider:

▸ Complications related to biomedical devices. Although reactions to medical-grade stainless steel is uncommon in nickel-sensitized patients, orthopedic surgeons and orthodontists still consult dermatologists about the safety of metal medical devices, the authors wrote. In addition, in patients who undergo endovascular stenting, evidence that nickel allergy is associated with stent restenosis “remains in question.”

▸ Ingestion of dietary nickel. Nickel is found in foods such as legumes, nuts, grains, chocolate, and fish, as well as medications and vitamins.

▸ Prevention of contact allergy to nickel is challenging. The best approach is to find ways to reduce sensitization. Regulation of nickel release from consumer goods “would be a challenging but potentially successful solution,” wrote the authors, who reported no conflicts of interest.

SAN DIEGO — The number of adolescents with asthma and other high-risk conditions who received the influenza vaccine increased between 1992 and 2002, but the coverage remains poor at about 15% overall, results from a large HMO study showed.

“About 85% of these kids who should have been getting the vaccine weren't getting it,” Dr. Mari M. Nakamura said in an interview during a poster session at the annual meeting of the Infectious Diseases Society of America. “A risk-based approach to vaccination isn't working in this population. Universal vaccination in this age group may be warranted instead.”

She and her mentor, Dr. Grace M. Lee, reviewed the medical records of 18,703 patients aged 11–17 years with high-risk conditions who were enrolled in Harvard Pilgrim Health Care for at least one influenza season and the preceding 1-year period, from 1992 to 2002.

High-risk conditions were indicated by ICD-9 diagnoses, and included asthma or other chronic pulmonary disease, chronic cardiac disease, immunosuppressive disorders or therapy, sickle cell anemia or other hemoglobinopathy, chronic renal dysfunction, or chronic metabolic disease.

“The burden of influenza is especially high in children and adolescents with high-risk conditions, accounting for excess hospitalizations, outpatient visits, and antibiotic courses,” the researchers wrote.

They evaluated the changes in influenza vaccination rates over the time period, as well as the number of missed opportunities for vaccination (defined as office visits during the first 4 months of influenza season at which an unvaccinated adolescent was not vaccinated).

The mean age of patients was 14 years, and 48% were female, reported Dr. Nakamura, a Harvard pediatric health services research fellow at Children's Hospital Boston. The majority of patients (90%) had asthma or other chronic pulmonary disease, whereas 2% had more than one high-risk condition.

Influenza vaccination rates improved significantly from 1992 to 1993 (from 8.3% to 12.8%), and then again from 1993 to 2002 (from 12.8% to 15.4%).

The researchers also noted that between 1992 and 2002, about half of all unvaccinated patients had at least one missed opportunity for vaccination.

“The main reasons that they came in included preventive care and the need for other vaccinations,” she said. “This tells us that providers are a group to target, to remind them that these patients should be getting flu vaccine every year.”

The study was funded by Harvard Pilgrim Health Care and by the Agency for Healthcare Research and Quality. The researchers disclosed that they had no conflicts of interest.

SAN DIEGO — The number of adolescents with asthma and other high-risk conditions who received the influenza vaccine increased between 1992 and 2002, but the coverage remains poor at about 15% overall, results from a large HMO study showed.

“About 85% of these kids who should have been getting the vaccine weren't getting it,” Dr. Mari M. Nakamura said in an interview during a poster session at the annual meeting of the Infectious Diseases Society of America. “A risk-based approach to vaccination isn't working in this population. Universal vaccination in this age group may be warranted instead.”

She and her mentor, Dr. Grace M. Lee, reviewed the medical records of 18,703 patients aged 11–17 years with high-risk conditions who were enrolled in Harvard Pilgrim Health Care for at least one influenza season and the preceding 1-year period, from 1992 to 2002.

High-risk conditions were indicated by ICD-9 diagnoses, and included asthma or other chronic pulmonary disease, chronic cardiac disease, immunosuppressive disorders or therapy, sickle cell anemia or other hemoglobinopathy, chronic renal dysfunction, or chronic metabolic disease.

“The burden of influenza is especially high in children and adolescents with high-risk conditions, accounting for excess hospitalizations, outpatient visits, and antibiotic courses,” the researchers wrote.

They evaluated the changes in influenza vaccination rates over the time period, as well as the number of missed opportunities for vaccination (defined as office visits during the first 4 months of influenza season at which an unvaccinated adolescent was not vaccinated).

The mean age of patients was 14 years, and 48% were female, reported Dr. Nakamura, a Harvard pediatric health services research fellow at Children's Hospital Boston. The majority of patients (90%) had asthma or other chronic pulmonary disease, whereas 2% had more than one high-risk condition.

Influenza vaccination rates improved significantly from 1992 to 1993 (from 8.3% to 12.8%), and then again from 1993 to 2002 (from 12.8% to 15.4%).

The researchers also noted that between 1992 and 2002, about half of all unvaccinated patients had at least one missed opportunity for vaccination.

“The main reasons that they came in included preventive care and the need for other vaccinations,” she said. “This tells us that providers are a group to target, to remind them that these patients should be getting flu vaccine every year.”

The study was funded by Harvard Pilgrim Health Care and by the Agency for Healthcare Research and Quality. The researchers disclosed that they had no conflicts of interest.

SAN DIEGO — The number of adolescents with asthma and other high-risk conditions who received the influenza vaccine increased between 1992 and 2002, but the coverage remains poor at about 15% overall, results from a large HMO study showed.

“About 85% of these kids who should have been getting the vaccine weren't getting it,” Dr. Mari M. Nakamura said in an interview during a poster session at the annual meeting of the Infectious Diseases Society of America. “A risk-based approach to vaccination isn't working in this population. Universal vaccination in this age group may be warranted instead.”

She and her mentor, Dr. Grace M. Lee, reviewed the medical records of 18,703 patients aged 11–17 years with high-risk conditions who were enrolled in Harvard Pilgrim Health Care for at least one influenza season and the preceding 1-year period, from 1992 to 2002.

High-risk conditions were indicated by ICD-9 diagnoses, and included asthma or other chronic pulmonary disease, chronic cardiac disease, immunosuppressive disorders or therapy, sickle cell anemia or other hemoglobinopathy, chronic renal dysfunction, or chronic metabolic disease.

“The burden of influenza is especially high in children and adolescents with high-risk conditions, accounting for excess hospitalizations, outpatient visits, and antibiotic courses,” the researchers wrote.

They evaluated the changes in influenza vaccination rates over the time period, as well as the number of missed opportunities for vaccination (defined as office visits during the first 4 months of influenza season at which an unvaccinated adolescent was not vaccinated).

The mean age of patients was 14 years, and 48% were female, reported Dr. Nakamura, a Harvard pediatric health services research fellow at Children's Hospital Boston. The majority of patients (90%) had asthma or other chronic pulmonary disease, whereas 2% had more than one high-risk condition.

Influenza vaccination rates improved significantly from 1992 to 1993 (from 8.3% to 12.8%), and then again from 1993 to 2002 (from 12.8% to 15.4%).

The researchers also noted that between 1992 and 2002, about half of all unvaccinated patients had at least one missed opportunity for vaccination.

“The main reasons that they came in included preventive care and the need for other vaccinations,” she said. “This tells us that providers are a group to target, to remind them that these patients should be getting flu vaccine every year.”

The study was funded by Harvard Pilgrim Health Care and by the Agency for Healthcare Research and Quality. The researchers disclosed that they had no conflicts of interest.

“Evidence is insufficient to draw firm conclusions.”

“We did not find any head-to-head randomized controlled trials.”

Those are phrases that commonly appear in a 151-page report, based on a literature review and released by the Agency for Healthcare Research and Quality, titled “Comparative Effectiveness of Drug Therapy for Rheumatoid Arthritis and Psoriatic Arthritis in Adults.”

“The gaps in information for specific [rheumatoid arthritis] therapies are substantial,” wrote the researchers of the RTI International-University of North Carolina Evidence-Based Practice Center, under contract to AHRQ, a part of the U.S. Department of Health and Human Services.

Despite the paucity of data, the researchers draw some conclusions from the best available medical literature about the benefits and harms of three classes of medications for rheumatoid arthritis (RA) and psoriatic arthritis: synthetic formulations of disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and corticosteroids.

For example, they found that combining the synthetic DMARD methotrexate with one of the biologic DMARDs (abatacept, adalimumab, anakinra, etanercept, infliximab, or rituximab) works better to lessen joint damage than does using methotrexate or one of the biologic DMARDs alone.

In addition, they found that methotrexate works as effectively as adalimumab and etanercept for patients with early RA. “Radiographic outcomes, however, were statistically significantly better in patients treated with biologic DMARDs than [in] patients treated with methotrexate,” the researchers wrote.

“How such intermediate outcomes translate to the long-term clinical progression of the disease remains unclear.”

Dr. Steven B. Abramson, director of the division of rheumatology at New York University Medical Center, called the report “very comprehensive and useful” and “reflective of what I think is our common practice. It tries not to tilt toward one therapy or another. It's a good summation of several years of literature.”

Dr. Craig Leonardi, a dermatologist in private practice in St. Louis, Mo., called the report a “good start” and acknowledged the challenge researchers faced in assembling a document “when there is such precious little data comparing therapies directly.

“That's always a limitation of any of these studies, yet clinicians are forced to make these comparisons all the time,” according to Dr. Leonardi.

The team of researchers, led by Dr. Katrina E. Donahue of the department of family medicine at the University of North Carolina at Chapel Hill, reviewed 156 articles in the medical literature based on 103 studies of synthetic DMARDs, biologic DMARDs, and corticosteroids. Of these, 50% were supported by pharmaceutical companies, 20% were supported by government or independent funds, 11% had a combination of pharmaceutical and government funding, and the source of funding could not be determined in the remaining 19% of studies.

Most of the studies were found to be of fair quality, which was defined as susceptible to some bias but probably not sufficient to invalidate their results. Only one-quarter of the studies were rated good quality, which was defined as having the least bias and results that are considered to be valid.

Based on their literature review, the researchers found that combining prednisone with hydroxychloroquine, methotrexate, or sulfasalazine works better than using only a synthetic DMARD to reduce joint swelling and tenderness and to improve function. They also determined that there are no meaningful clinical differences between methotrexate and either leflunomide or sulfasalazine.

Other findings in the report include the following:

▸ There is not enough evidence to conclude that combining two biologic DMARDs is better than using one biologic DMARD.

▸ An estimated 17 out of every 1,000 people who take a biologic DMARD for 3-12 months develop serious infection. Combining biologic DMARDs increases this risk.

▸ Painful injection-site reactions occur more often among patients who take anakinra (67%), compared with those who take etanercept (22%) or adalimumab (18%).

Dr. Leonardi, who has helped run clinical trials of biologic DMARDs for psoriasis patients, said that while the current data on comparative treatments for RA and psoriatic RA might be limited, dermatologists “have a long way to go” in comparing biologic DMARDs for psoriasis. “We're left to try our own meta-analysis based on safety and efficacy and looking at the types of patients that come into the trials, [asking] how well did things perform? What were the comparable end points at 12, or 14, or 16 weeks? We try to make our own assessments as best as we can without those head-to-head trials. We just don't have that degree of sophistication yet.”

In the report's conclusion, the researchers emphasized the need for long-term studies of arthritis medications, including head-to-head trials “assessing combination therapies involving synthetic DMARDs in comparison with those involving biologic DMARDs,” they wrote. “Adequately powered, long-term [randomized clinical trials] must also examine different treatment strategies with and without corticosteroids, synthetic DMARDs, and biologic DMARDs to determine the best therapy to prevent or minimize debilitating joint damage in patients with RA. Additionally, no head-to-head [randomized clinical trials] have compared one biologic DMARD with another; this is a significant hole in the literature that future research should fill. However, this is less likely to occur because of the expense of biologic DMARDs.”

Dr. Abramson, who is also vice dean for education, faculty and academic affairs at New York University, New York, called the lack of head-to-head trials of biologic DMARDs “a weakness of this field. These are the studies that do need to get done, particularly with respect to x-ray progression.”

To access the full report online, visit www.effectivehealthcare.ahrq.gov/reports/final.cfm

“Evidence is insufficient to draw firm conclusions.”

“We did not find any head-to-head randomized controlled trials.”

Those are phrases that commonly appear in a 151-page report, based on a literature review and released by the Agency for Healthcare Research and Quality, titled “Comparative Effectiveness of Drug Therapy for Rheumatoid Arthritis and Psoriatic Arthritis in Adults.”

“The gaps in information for specific [rheumatoid arthritis] therapies are substantial,” wrote the researchers of the RTI International-University of North Carolina Evidence-Based Practice Center, under contract to AHRQ, a part of the U.S. Department of Health and Human Services.

Despite the paucity of data, the researchers draw some conclusions from the best available medical literature about the benefits and harms of three classes of medications for rheumatoid arthritis (RA) and psoriatic arthritis: synthetic formulations of disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and corticosteroids.

For example, they found that combining the synthetic DMARD methotrexate with one of the biologic DMARDs (abatacept, adalimumab, anakinra, etanercept, infliximab, or rituximab) works better to lessen joint damage than does using methotrexate or one of the biologic DMARDs alone.

In addition, they found that methotrexate works as effectively as adalimumab and etanercept for patients with early RA. “Radiographic outcomes, however, were statistically significantly better in patients treated with biologic DMARDs than [in] patients treated with methotrexate,” the researchers wrote.

“How such intermediate outcomes translate to the long-term clinical progression of the disease remains unclear.”

Dr. Steven B. Abramson, director of the division of rheumatology at New York University Medical Center, called the report “very comprehensive and useful” and “reflective of what I think is our common practice. It tries not to tilt toward one therapy or another. It's a good summation of several years of literature.”

Dr. Craig Leonardi, a dermatologist in private practice in St. Louis, Mo., called the report a “good start” and acknowledged the challenge researchers faced in assembling a document “when there is such precious little data comparing therapies directly.

“That's always a limitation of any of these studies, yet clinicians are forced to make these comparisons all the time,” according to Dr. Leonardi.

The team of researchers, led by Dr. Katrina E. Donahue of the department of family medicine at the University of North Carolina at Chapel Hill, reviewed 156 articles in the medical literature based on 103 studies of synthetic DMARDs, biologic DMARDs, and corticosteroids. Of these, 50% were supported by pharmaceutical companies, 20% were supported by government or independent funds, 11% had a combination of pharmaceutical and government funding, and the source of funding could not be determined in the remaining 19% of studies.

Most of the studies were found to be of fair quality, which was defined as susceptible to some bias but probably not sufficient to invalidate their results. Only one-quarter of the studies were rated good quality, which was defined as having the least bias and results that are considered to be valid.

Based on their literature review, the researchers found that combining prednisone with hydroxychloroquine, methotrexate, or sulfasalazine works better than using only a synthetic DMARD to reduce joint swelling and tenderness and to improve function. They also determined that there are no meaningful clinical differences between methotrexate and either leflunomide or sulfasalazine.

Other findings in the report include the following:

▸ There is not enough evidence to conclude that combining two biologic DMARDs is better than using one biologic DMARD.

▸ An estimated 17 out of every 1,000 people who take a biologic DMARD for 3-12 months develop serious infection. Combining biologic DMARDs increases this risk.

▸ Painful injection-site reactions occur more often among patients who take anakinra (67%), compared with those who take etanercept (22%) or adalimumab (18%).

Dr. Leonardi, who has helped run clinical trials of biologic DMARDs for psoriasis patients, said that while the current data on comparative treatments for RA and psoriatic RA might be limited, dermatologists “have a long way to go” in comparing biologic DMARDs for psoriasis. “We're left to try our own meta-analysis based on safety and efficacy and looking at the types of patients that come into the trials, [asking] how well did things perform? What were the comparable end points at 12, or 14, or 16 weeks? We try to make our own assessments as best as we can without those head-to-head trials. We just don't have that degree of sophistication yet.”

In the report's conclusion, the researchers emphasized the need for long-term studies of arthritis medications, including head-to-head trials “assessing combination therapies involving synthetic DMARDs in comparison with those involving biologic DMARDs,” they wrote. “Adequately powered, long-term [randomized clinical trials] must also examine different treatment strategies with and without corticosteroids, synthetic DMARDs, and biologic DMARDs to determine the best therapy to prevent or minimize debilitating joint damage in patients with RA. Additionally, no head-to-head [randomized clinical trials] have compared one biologic DMARD with another; this is a significant hole in the literature that future research should fill. However, this is less likely to occur because of the expense of biologic DMARDs.”

Dr. Abramson, who is also vice dean for education, faculty and academic affairs at New York University, New York, called the lack of head-to-head trials of biologic DMARDs “a weakness of this field. These are the studies that do need to get done, particularly with respect to x-ray progression.”

To access the full report online, visit www.effectivehealthcare.ahrq.gov/reports/final.cfm

“Evidence is insufficient to draw firm conclusions.”

“We did not find any head-to-head randomized controlled trials.”

Those are phrases that commonly appear in a 151-page report, based on a literature review and released by the Agency for Healthcare Research and Quality, titled “Comparative Effectiveness of Drug Therapy for Rheumatoid Arthritis and Psoriatic Arthritis in Adults.”

“The gaps in information for specific [rheumatoid arthritis] therapies are substantial,” wrote the researchers of the RTI International-University of North Carolina Evidence-Based Practice Center, under contract to AHRQ, a part of the U.S. Department of Health and Human Services.

Despite the paucity of data, the researchers draw some conclusions from the best available medical literature about the benefits and harms of three classes of medications for rheumatoid arthritis (RA) and psoriatic arthritis: synthetic formulations of disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and corticosteroids.

For example, they found that combining the synthetic DMARD methotrexate with one of the biologic DMARDs (abatacept, adalimumab, anakinra, etanercept, infliximab, or rituximab) works better to lessen joint damage than does using methotrexate or one of the biologic DMARDs alone.

In addition, they found that methotrexate works as effectively as adalimumab and etanercept for patients with early RA. “Radiographic outcomes, however, were statistically significantly better in patients treated with biologic DMARDs than [in] patients treated with methotrexate,” the researchers wrote.

“How such intermediate outcomes translate to the long-term clinical progression of the disease remains unclear.”

Dr. Steven B. Abramson, director of the division of rheumatology at New York University Medical Center, called the report “very comprehensive and useful” and “reflective of what I think is our common practice. It tries not to tilt toward one therapy or another. It's a good summation of several years of literature.”

Dr. Craig Leonardi, a dermatologist in private practice in St. Louis, Mo., called the report a “good start” and acknowledged the challenge researchers faced in assembling a document “when there is such precious little data comparing therapies directly.

“That's always a limitation of any of these studies, yet clinicians are forced to make these comparisons all the time,” according to Dr. Leonardi.

The team of researchers, led by Dr. Katrina E. Donahue of the department of family medicine at the University of North Carolina at Chapel Hill, reviewed 156 articles in the medical literature based on 103 studies of synthetic DMARDs, biologic DMARDs, and corticosteroids. Of these, 50% were supported by pharmaceutical companies, 20% were supported by government or independent funds, 11% had a combination of pharmaceutical and government funding, and the source of funding could not be determined in the remaining 19% of studies.

Most of the studies were found to be of fair quality, which was defined as susceptible to some bias but probably not sufficient to invalidate their results. Only one-quarter of the studies were rated good quality, which was defined as having the least bias and results that are considered to be valid.

Based on their literature review, the researchers found that combining prednisone with hydroxychloroquine, methotrexate, or sulfasalazine works better than using only a synthetic DMARD to reduce joint swelling and tenderness and to improve function. They also determined that there are no meaningful clinical differences between methotrexate and either leflunomide or sulfasalazine.

Other findings in the report include the following:

▸ There is not enough evidence to conclude that combining two biologic DMARDs is better than using one biologic DMARD.

▸ An estimated 17 out of every 1,000 people who take a biologic DMARD for 3-12 months develop serious infection. Combining biologic DMARDs increases this risk.

▸ Painful injection-site reactions occur more often among patients who take anakinra (67%), compared with those who take etanercept (22%) or adalimumab (18%).

Dr. Leonardi, who has helped run clinical trials of biologic DMARDs for psoriasis patients, said that while the current data on comparative treatments for RA and psoriatic RA might be limited, dermatologists “have a long way to go” in comparing biologic DMARDs for psoriasis. “We're left to try our own meta-analysis based on safety and efficacy and looking at the types of patients that come into the trials, [asking] how well did things perform? What were the comparable end points at 12, or 14, or 16 weeks? We try to make our own assessments as best as we can without those head-to-head trials. We just don't have that degree of sophistication yet.”

In the report's conclusion, the researchers emphasized the need for long-term studies of arthritis medications, including head-to-head trials “assessing combination therapies involving synthetic DMARDs in comparison with those involving biologic DMARDs,” they wrote. “Adequately powered, long-term [randomized clinical trials] must also examine different treatment strategies with and without corticosteroids, synthetic DMARDs, and biologic DMARDs to determine the best therapy to prevent or minimize debilitating joint damage in patients with RA. Additionally, no head-to-head [randomized clinical trials] have compared one biologic DMARD with another; this is a significant hole in the literature that future research should fill. However, this is less likely to occur because of the expense of biologic DMARDs.”

Dr. Abramson, who is also vice dean for education, faculty and academic affairs at New York University, New York, called the lack of head-to-head trials of biologic DMARDs “a weakness of this field. These are the studies that do need to get done, particularly with respect to x-ray progression.”

To access the full report online, visit www.effectivehealthcare.ahrq.gov/reports/final.cfm