Diana Mahoney

BOSTON — The immediate initiation of depot medroxyprogesterone acetate to adolescent and young adult women seeking the contraceptive injection resulted in higher continuation rates and substantially diminished unintended pregnancy rates at 6 months, compared with the use of alternative, short-term hormonal methods meant to bridge the period between initial request and injection at a later date, Vaughn I. Rickert, Psy.D., said at the annual meeting of the Society for Adolescent Medicine.

In a study of 334 young women ages 14–26 years who asked for depot medroxyprogesterone (DMPA) during a reproductive health visit at an urban family planning clinic, 101 women were randomized to receive their first DMPA (Depo Provera) injection at the conclusion of the visit, and 233 were randomized to an alternative “quick start” bridge condition whereby they were offered their choice of either oral contraceptive pills, the transdermal patch, or the vaginal ring, said Dr. Rickert of the Mailman School of Public Health at Columbia University in New York.

In a previous study, the Columbia investigators determined that patients who immediately initiated oral contraception at the time of their clinic visit (after a negative urine pregnancy test) were significantly more likely to continue the oral contraceptive than a control group of women who were provided with conventional instructions to wait until their menses began before starting oral contraception (Contraception 2002;66:141–5).

Historically, the rationale for waiting to initiate hormonal contraception “was to be sure the patient was not pregnant and to keep from altering the bleeding pattern,” said Dr. Rickert. “Unfortunately, with the delayed initiation, many women don't take their first pill, and their motivation wanes.” Similarly, asking women to return to the clinic at a later date for a DMPA injection means that some won't come back for it, thus increasing the likelihood for unintended pregnancies.

The immediate contraception protocol was designed to avoid this outcome, according to Dr. Rickert. While the earlier study looked specifically at the efficacy of the approach with respect to oral contraceptives, the current study sought to determine whether immediate access to DMPA would lead to greater method continuation—and thus pregnancy prevention—over a 6-month period, compared with delaying the injection and providing alternative contraceptive options for the interim period.

All of the women enrolled in the study had a negative urine pregnancy test at the time of their initial clinic visit, and none were breast-feeding or currently using other forms of hormonal contraception. In addition, none of the women had received a DMPA injection within the previous 14 weeks nor had any medical contraindications to hormonal contraception, said Dr. Rickert.

All of the subjects in both conditions underwent a history, physical, pregnancy test, and structured interview at the initial visit. All were instructed to return to the clinic in 21 days for a repeat urine pregnancy test and, for those assigned to the alternative condition, to receive their first DMPA injection, said Dr. Rickert. In addition, the women were followed through two subsequent appointments for DMPA injections and structured interviews.

The DMPA injections were discontinued in women in whom pregnancy was detected at any visit, in those who refused injection at any visit, or in those for whom more than 98 days had passed since their previous injection, said Dr. Rickert.

Of the 233 women randomized to the quick start bridge condition, 95 chose oral contraceptive pills, 100 chose the transdermal patch, and 38 chose the vaginal ring. Emergency contraception was provided to 41% of the entire cohort—31 patients in the Depo group and 83 in the bridge group—at the initial visit. Of women who received immediate injection of DMPA, 7 never returned for a follow-up visit, compared with 11 in the bridge group who never returned for a follow-up visit.

As of February 2006, 278 of the women had completed the study. Of this population, 54 were between the ages of 14 and 17 years, 118 were between the ages of 18 and 21, and 106 were between 22 and 26. The sample was more than 90% Latino and approximately 7% African American. “No significant differences were found in baseline demographic or reproductive characteristics,” Dr. Rickert reported.

Bivariate analysis showed no statistically significant difference in the 21-day return rates among those who began DMPA immediately and those who were randomized to use a bridge method prior to the first injection. In addition, “rates of patient satisfaction [with the respective contraceptive protocols] between the two groups were not different at the second and third injections,” said Dr. Rickert.

However, “continuation rates were statistically higher at 6 months in the Depo group compared to the bridge group, meaning that more women in the Depo group received their third injection,” he said. “Also, the Depo group had significantly fewer pregnancies [2, compared with 23 in the bridge group] across the study period.” Other factors independently associated with 6-month DMPA continuation rates included partners' awareness of DMPA use, returning for the pregnancy test visit, and history of emergency contraceptive pill use, “suggesting continuation is also affected by behaviors consistent with intentions not to become pregnant,” said Dr. Rickert.

ELSEVIER GLOBAL MEDICAL NEWS

BOSTON — The immediate initiation of depot medroxyprogesterone acetate to adolescent and young adult women seeking the contraceptive injection resulted in higher continuation rates and substantially diminished unintended pregnancy rates at 6 months, compared with the use of alternative, short-term hormonal methods meant to bridge the period between initial request and injection at a later date, Vaughn I. Rickert, Psy.D., said at the annual meeting of the Society for Adolescent Medicine.

In a study of 334 young women ages 14–26 years who asked for depot medroxyprogesterone (DMPA) during a reproductive health visit at an urban family planning clinic, 101 women were randomized to receive their first DMPA (Depo Provera) injection at the conclusion of the visit, and 233 were randomized to an alternative “quick start” bridge condition whereby they were offered their choice of either oral contraceptive pills, the transdermal patch, or the vaginal ring, said Dr. Rickert of the Mailman School of Public Health at Columbia University in New York.

In a previous study, the Columbia investigators determined that patients who immediately initiated oral contraception at the time of their clinic visit (after a negative urine pregnancy test) were significantly more likely to continue the oral contraceptive than a control group of women who were provided with conventional instructions to wait until their menses began before starting oral contraception (Contraception 2002;66:141–5).

Historically, the rationale for waiting to initiate hormonal contraception “was to be sure the patient was not pregnant and to keep from altering the bleeding pattern,” said Dr. Rickert. “Unfortunately, with the delayed initiation, many women don't take their first pill, and their motivation wanes.” Similarly, asking women to return to the clinic at a later date for a DMPA injection means that some won't come back for it, thus increasing the likelihood for unintended pregnancies.

The immediate contraception protocol was designed to avoid this outcome, according to Dr. Rickert. While the earlier study looked specifically at the efficacy of the approach with respect to oral contraceptives, the current study sought to determine whether immediate access to DMPA would lead to greater method continuation—and thus pregnancy prevention—over a 6-month period, compared with delaying the injection and providing alternative contraceptive options for the interim period.

All of the women enrolled in the study had a negative urine pregnancy test at the time of their initial clinic visit, and none were breast-feeding or currently using other forms of hormonal contraception. In addition, none of the women had received a DMPA injection within the previous 14 weeks nor had any medical contraindications to hormonal contraception, said Dr. Rickert.

All of the subjects in both conditions underwent a history, physical, pregnancy test, and structured interview at the initial visit. All were instructed to return to the clinic in 21 days for a repeat urine pregnancy test and, for those assigned to the alternative condition, to receive their first DMPA injection, said Dr. Rickert. In addition, the women were followed through two subsequent appointments for DMPA injections and structured interviews.

The DMPA injections were discontinued in women in whom pregnancy was detected at any visit, in those who refused injection at any visit, or in those for whom more than 98 days had passed since their previous injection, said Dr. Rickert.

Of the 233 women randomized to the quick start bridge condition, 95 chose oral contraceptive pills, 100 chose the transdermal patch, and 38 chose the vaginal ring. Emergency contraception was provided to 41% of the entire cohort—31 patients in the Depo group and 83 in the bridge group—at the initial visit. Of women who received immediate injection of DMPA, 7 never returned for a follow-up visit, compared with 11 in the bridge group who never returned for a follow-up visit.

As of February 2006, 278 of the women had completed the study. Of this population, 54 were between the ages of 14 and 17 years, 118 were between the ages of 18 and 21, and 106 were between 22 and 26. The sample was more than 90% Latino and approximately 7% African American. “No significant differences were found in baseline demographic or reproductive characteristics,” Dr. Rickert reported.

Bivariate analysis showed no statistically significant difference in the 21-day return rates among those who began DMPA immediately and those who were randomized to use a bridge method prior to the first injection. In addition, “rates of patient satisfaction [with the respective contraceptive protocols] between the two groups were not different at the second and third injections,” said Dr. Rickert.

However, “continuation rates were statistically higher at 6 months in the Depo group compared to the bridge group, meaning that more women in the Depo group received their third injection,” he said. “Also, the Depo group had significantly fewer pregnancies [2, compared with 23 in the bridge group] across the study period.” Other factors independently associated with 6-month DMPA continuation rates included partners' awareness of DMPA use, returning for the pregnancy test visit, and history of emergency contraceptive pill use, “suggesting continuation is also affected by behaviors consistent with intentions not to become pregnant,” said Dr. Rickert.

ELSEVIER GLOBAL MEDICAL NEWS

BOSTON — The immediate initiation of depot medroxyprogesterone acetate to adolescent and young adult women seeking the contraceptive injection resulted in higher continuation rates and substantially diminished unintended pregnancy rates at 6 months, compared with the use of alternative, short-term hormonal methods meant to bridge the period between initial request and injection at a later date, Vaughn I. Rickert, Psy.D., said at the annual meeting of the Society for Adolescent Medicine.

In a study of 334 young women ages 14–26 years who asked for depot medroxyprogesterone (DMPA) during a reproductive health visit at an urban family planning clinic, 101 women were randomized to receive their first DMPA (Depo Provera) injection at the conclusion of the visit, and 233 were randomized to an alternative “quick start” bridge condition whereby they were offered their choice of either oral contraceptive pills, the transdermal patch, or the vaginal ring, said Dr. Rickert of the Mailman School of Public Health at Columbia University in New York.

In a previous study, the Columbia investigators determined that patients who immediately initiated oral contraception at the time of their clinic visit (after a negative urine pregnancy test) were significantly more likely to continue the oral contraceptive than a control group of women who were provided with conventional instructions to wait until their menses began before starting oral contraception (Contraception 2002;66:141–5).

Historically, the rationale for waiting to initiate hormonal contraception “was to be sure the patient was not pregnant and to keep from altering the bleeding pattern,” said Dr. Rickert. “Unfortunately, with the delayed initiation, many women don't take their first pill, and their motivation wanes.” Similarly, asking women to return to the clinic at a later date for a DMPA injection means that some won't come back for it, thus increasing the likelihood for unintended pregnancies.

The immediate contraception protocol was designed to avoid this outcome, according to Dr. Rickert. While the earlier study looked specifically at the efficacy of the approach with respect to oral contraceptives, the current study sought to determine whether immediate access to DMPA would lead to greater method continuation—and thus pregnancy prevention—over a 6-month period, compared with delaying the injection and providing alternative contraceptive options for the interim period.

All of the women enrolled in the study had a negative urine pregnancy test at the time of their initial clinic visit, and none were breast-feeding or currently using other forms of hormonal contraception. In addition, none of the women had received a DMPA injection within the previous 14 weeks nor had any medical contraindications to hormonal contraception, said Dr. Rickert.

All of the subjects in both conditions underwent a history, physical, pregnancy test, and structured interview at the initial visit. All were instructed to return to the clinic in 21 days for a repeat urine pregnancy test and, for those assigned to the alternative condition, to receive their first DMPA injection, said Dr. Rickert. In addition, the women were followed through two subsequent appointments for DMPA injections and structured interviews.

The DMPA injections were discontinued in women in whom pregnancy was detected at any visit, in those who refused injection at any visit, or in those for whom more than 98 days had passed since their previous injection, said Dr. Rickert.

Of the 233 women randomized to the quick start bridge condition, 95 chose oral contraceptive pills, 100 chose the transdermal patch, and 38 chose the vaginal ring. Emergency contraception was provided to 41% of the entire cohort—31 patients in the Depo group and 83 in the bridge group—at the initial visit. Of women who received immediate injection of DMPA, 7 never returned for a follow-up visit, compared with 11 in the bridge group who never returned for a follow-up visit.

As of February 2006, 278 of the women had completed the study. Of this population, 54 were between the ages of 14 and 17 years, 118 were between the ages of 18 and 21, and 106 were between 22 and 26. The sample was more than 90% Latino and approximately 7% African American. “No significant differences were found in baseline demographic or reproductive characteristics,” Dr. Rickert reported.

Bivariate analysis showed no statistically significant difference in the 21-day return rates among those who began DMPA immediately and those who were randomized to use a bridge method prior to the first injection. In addition, “rates of patient satisfaction [with the respective contraceptive protocols] between the two groups were not different at the second and third injections,” said Dr. Rickert.

However, “continuation rates were statistically higher at 6 months in the Depo group compared to the bridge group, meaning that more women in the Depo group received their third injection,” he said. “Also, the Depo group had significantly fewer pregnancies [2, compared with 23 in the bridge group] across the study period.” Other factors independently associated with 6-month DMPA continuation rates included partners' awareness of DMPA use, returning for the pregnancy test visit, and history of emergency contraceptive pill use, “suggesting continuation is also affected by behaviors consistent with intentions not to become pregnant,” said Dr. Rickert.

ELSEVIER GLOBAL MEDICAL NEWS

STOWE, VT. — Skin involvement is one of the most frequent manifestations of lupus erythematosus, yet the cutaneous signs of the disease are not always recognized as such, Dr. Victoria P. Werth said at a dermatology conference sponsored by the University of Vermont.

Although systemic lupus erythematosus (SLE) is estimated to occur in 17–48 per 100,000 individuals, the cutaneous variants are thought to be two to three times more prevalent, said Dr. Werth of the University of Pennsylvania, Philadelphia.

Skin findings in cutaneous lupus are generally categorized into lupus-specific and lupus-nonspecific diseases, based on biopsy findings. “Lupus-specific lesions show histology that is specific to lupus erythematosus, while nonspecific lesions are not histopathologically distinct for the disease and may be seen as a feature of another disease process,” she said. Some of the more common nonspecific skin findings include alopecia, vasculitis, and Raynaud's phenomenon.

Although skin disease is the second-most frequent clinical manifestation of SLE, cutaneous lupus does not always meet all the diagnostic criteria for SLE. Rheumatologists need to keep in mind that the diagnosis of lupus erythematosus can be confirmed whether or not the [American College of Rheumatology] criteria for SLE have been met,” Dr. Werth said.

Rheumatologists may doubt the diagnosis of lupus in an antinuclear antibody-negative patient with skin manifestations. They have a hard time believing these patients really have lupus. Dermatrologists look at these patients differently. “We know they have lupus because we see it all the time,” explained Dr. Werth, a dermatologist.

Lupus-specific cutaneous lesions are further subdivided into three categories: acute, subacute, and chronic. “The most recognizable acute presentation is the butterfly rash, which comes on abruptly and heals within hours or days, usually without scarring,” Dr. Werth said. Some variations of this rash include bullous formations or blisters.

Subacute manifestations can include annular and/or psoriasiform rashes that are usually highly photosensitive. Chronic cutaneous lupus is “the wastebasket category” for many of the other lupus-specific skin presentations, she said.

The most common chronic cutaneous form is discoid lupus erythematosus, which begins with well-defined scaly lesions that evolve into scarring plaques and often includes follicular involvement that can lead to hair loss. “Early, aggressive treatment for these patients is important in order to prevent permanent, disfiguring scarring and permanent hair loss,” said Dr. Werth.

She also discussed several of the following less prevalent manifestations of chronic cutaneous lupus:

▸ Chilblain lupus. Associated with itching, cold, and painful swelling of the extremities and toes.

▸ Hypertrophic lupus. Characterized by wartlike bumps.

▸ Lupus profundus. Causes deep dermal nodules on the upper arms and sometimes on the head, chest, or legs.

▸ Lupus tumidus. Presents as broad, indurated plaques.

Although management for the various lupus subsets does not differ substantially, the clinical distinctions are important because they relate to the likelihood that an individual patient will develop systemic disease, Dr. Werth pointed out.

Nearly all patients with acute cutaneous lupus, and half of those with subacute disease, will meet American College of Rheumatology criteria for SLE. With respect to chronic cutaneous lupus, those with generalized discoid lesions have a 20% chance of developing SLE, those with lupus profundus are estimated to have a 10% chance, those with localized discoid lesions have a 5% chance, and those with lupus tumidus have virtually no chance. “Patients whose skin conditions put them at higher risk should be followed more closely for evidence of systemic disease,” she said.

Once a diagnosis of cutaneous lupus has been made, the next step is to evaluate the patient for signs of systemic disease. The initial evaluation should include history, physical examination, CBC, sedimentation rate, antinuclear antibody (ANA) testing, and urinalysis. For ANA-positive patients or ANA-negative patients in whom there is suspicion of SLE, Dr. Werth suggests a panel that includes anti-Sjögren's syndrome A, anti-Sjögren's syndrome B, anti-ribonucleoprotein, anti-double-stranded DNA, and anti-Smith antibodies, as well as complement studies.

Patients with positive findings warrant closer monitoring, “especially those with high titre, anti-double-stranded DNA antibody because of an increased risk for renal problems,” she said.

In terms of management, “the first order of business is advising patients to avoid precipitating factors such as heat, certain medications, and sunlight,” Dr. Werth said. “I tell my patients they should not go outside without a sunscreen that has a UVB of 30 or more, as well as a UVA blocker, like Parsol 1789.”

STOWE, VT. — Skin involvement is one of the most frequent manifestations of lupus erythematosus, yet the cutaneous signs of the disease are not always recognized as such, Dr. Victoria P. Werth said at a dermatology conference sponsored by the University of Vermont.

Although systemic lupus erythematosus (SLE) is estimated to occur in 17–48 per 100,000 individuals, the cutaneous variants are thought to be two to three times more prevalent, said Dr. Werth of the University of Pennsylvania, Philadelphia.

Skin findings in cutaneous lupus are generally categorized into lupus-specific and lupus-nonspecific diseases, based on biopsy findings. “Lupus-specific lesions show histology that is specific to lupus erythematosus, while nonspecific lesions are not histopathologically distinct for the disease and may be seen as a feature of another disease process,” she said. Some of the more common nonspecific skin findings include alopecia, vasculitis, and Raynaud's phenomenon.

Although skin disease is the second-most frequent clinical manifestation of SLE, cutaneous lupus does not always meet all the diagnostic criteria for SLE. Rheumatologists need to keep in mind that the diagnosis of lupus erythematosus can be confirmed whether or not the [American College of Rheumatology] criteria for SLE have been met,” Dr. Werth said.

Rheumatologists may doubt the diagnosis of lupus in an antinuclear antibody-negative patient with skin manifestations. They have a hard time believing these patients really have lupus. Dermatrologists look at these patients differently. “We know they have lupus because we see it all the time,” explained Dr. Werth, a dermatologist.

Lupus-specific cutaneous lesions are further subdivided into three categories: acute, subacute, and chronic. “The most recognizable acute presentation is the butterfly rash, which comes on abruptly and heals within hours or days, usually without scarring,” Dr. Werth said. Some variations of this rash include bullous formations or blisters.

Subacute manifestations can include annular and/or psoriasiform rashes that are usually highly photosensitive. Chronic cutaneous lupus is “the wastebasket category” for many of the other lupus-specific skin presentations, she said.

The most common chronic cutaneous form is discoid lupus erythematosus, which begins with well-defined scaly lesions that evolve into scarring plaques and often includes follicular involvement that can lead to hair loss. “Early, aggressive treatment for these patients is important in order to prevent permanent, disfiguring scarring and permanent hair loss,” said Dr. Werth.

She also discussed several of the following less prevalent manifestations of chronic cutaneous lupus:

▸ Chilblain lupus. Associated with itching, cold, and painful swelling of the extremities and toes.

▸ Hypertrophic lupus. Characterized by wartlike bumps.

▸ Lupus profundus. Causes deep dermal nodules on the upper arms and sometimes on the head, chest, or legs.

▸ Lupus tumidus. Presents as broad, indurated plaques.

Although management for the various lupus subsets does not differ substantially, the clinical distinctions are important because they relate to the likelihood that an individual patient will develop systemic disease, Dr. Werth pointed out.

Nearly all patients with acute cutaneous lupus, and half of those with subacute disease, will meet American College of Rheumatology criteria for SLE. With respect to chronic cutaneous lupus, those with generalized discoid lesions have a 20% chance of developing SLE, those with lupus profundus are estimated to have a 10% chance, those with localized discoid lesions have a 5% chance, and those with lupus tumidus have virtually no chance. “Patients whose skin conditions put them at higher risk should be followed more closely for evidence of systemic disease,” she said.

Once a diagnosis of cutaneous lupus has been made, the next step is to evaluate the patient for signs of systemic disease. The initial evaluation should include history, physical examination, CBC, sedimentation rate, antinuclear antibody (ANA) testing, and urinalysis. For ANA-positive patients or ANA-negative patients in whom there is suspicion of SLE, Dr. Werth suggests a panel that includes anti-Sjögren's syndrome A, anti-Sjögren's syndrome B, anti-ribonucleoprotein, anti-double-stranded DNA, and anti-Smith antibodies, as well as complement studies.

Patients with positive findings warrant closer monitoring, “especially those with high titre, anti-double-stranded DNA antibody because of an increased risk for renal problems,” she said.

In terms of management, “the first order of business is advising patients to avoid precipitating factors such as heat, certain medications, and sunlight,” Dr. Werth said. “I tell my patients they should not go outside without a sunscreen that has a UVB of 30 or more, as well as a UVA blocker, like Parsol 1789.”

STOWE, VT. — Skin involvement is one of the most frequent manifestations of lupus erythematosus, yet the cutaneous signs of the disease are not always recognized as such, Dr. Victoria P. Werth said at a dermatology conference sponsored by the University of Vermont.

Although systemic lupus erythematosus (SLE) is estimated to occur in 17–48 per 100,000 individuals, the cutaneous variants are thought to be two to three times more prevalent, said Dr. Werth of the University of Pennsylvania, Philadelphia.

Skin findings in cutaneous lupus are generally categorized into lupus-specific and lupus-nonspecific diseases, based on biopsy findings. “Lupus-specific lesions show histology that is specific to lupus erythematosus, while nonspecific lesions are not histopathologically distinct for the disease and may be seen as a feature of another disease process,” she said. Some of the more common nonspecific skin findings include alopecia, vasculitis, and Raynaud's phenomenon.

Although skin disease is the second-most frequent clinical manifestation of SLE, cutaneous lupus does not always meet all the diagnostic criteria for SLE. Rheumatologists need to keep in mind that the diagnosis of lupus erythematosus can be confirmed whether or not the [American College of Rheumatology] criteria for SLE have been met,” Dr. Werth said.

Rheumatologists may doubt the diagnosis of lupus in an antinuclear antibody-negative patient with skin manifestations. They have a hard time believing these patients really have lupus. Dermatrologists look at these patients differently. “We know they have lupus because we see it all the time,” explained Dr. Werth, a dermatologist.

Lupus-specific cutaneous lesions are further subdivided into three categories: acute, subacute, and chronic. “The most recognizable acute presentation is the butterfly rash, which comes on abruptly and heals within hours or days, usually without scarring,” Dr. Werth said. Some variations of this rash include bullous formations or blisters.

Subacute manifestations can include annular and/or psoriasiform rashes that are usually highly photosensitive. Chronic cutaneous lupus is “the wastebasket category” for many of the other lupus-specific skin presentations, she said.

The most common chronic cutaneous form is discoid lupus erythematosus, which begins with well-defined scaly lesions that evolve into scarring plaques and often includes follicular involvement that can lead to hair loss. “Early, aggressive treatment for these patients is important in order to prevent permanent, disfiguring scarring and permanent hair loss,” said Dr. Werth.

She also discussed several of the following less prevalent manifestations of chronic cutaneous lupus:

▸ Chilblain lupus. Associated with itching, cold, and painful swelling of the extremities and toes.

▸ Hypertrophic lupus. Characterized by wartlike bumps.

▸ Lupus profundus. Causes deep dermal nodules on the upper arms and sometimes on the head, chest, or legs.

▸ Lupus tumidus. Presents as broad, indurated plaques.

Although management for the various lupus subsets does not differ substantially, the clinical distinctions are important because they relate to the likelihood that an individual patient will develop systemic disease, Dr. Werth pointed out.

Nearly all patients with acute cutaneous lupus, and half of those with subacute disease, will meet American College of Rheumatology criteria for SLE. With respect to chronic cutaneous lupus, those with generalized discoid lesions have a 20% chance of developing SLE, those with lupus profundus are estimated to have a 10% chance, those with localized discoid lesions have a 5% chance, and those with lupus tumidus have virtually no chance. “Patients whose skin conditions put them at higher risk should be followed more closely for evidence of systemic disease,” she said.

Once a diagnosis of cutaneous lupus has been made, the next step is to evaluate the patient for signs of systemic disease. The initial evaluation should include history, physical examination, CBC, sedimentation rate, antinuclear antibody (ANA) testing, and urinalysis. For ANA-positive patients or ANA-negative patients in whom there is suspicion of SLE, Dr. Werth suggests a panel that includes anti-Sjögren's syndrome A, anti-Sjögren's syndrome B, anti-ribonucleoprotein, anti-double-stranded DNA, and anti-Smith antibodies, as well as complement studies.

Patients with positive findings warrant closer monitoring, “especially those with high titre, anti-double-stranded DNA antibody because of an increased risk for renal problems,” she said.

In terms of management, “the first order of business is advising patients to avoid precipitating factors such as heat, certain medications, and sunlight,” Dr. Werth said. “I tell my patients they should not go outside without a sunscreen that has a UVB of 30 or more, as well as a UVA blocker, like Parsol 1789.”

STOWE, VT. — Use of several agents prescribed for the management of arthritis and other diseases seen by rheumatologists can induce cutaneous reactions that require referral to a dermatologist, said Dr. Peter W. Heald at a dermatology conference sponsored by the University of Vermont.

Because these drug-aggravated conditions often present as known diseases but frequently have different underlying mechanisms and treatment responses, diagnosis and management can be problematic, according to Dr. Heald, professor of dermatology at Yale University, New Haven, Conn. Also, the condition the suspect drug is prescribed to treat may make it inadvisable to discontinue the medication. To help unmask some of the dermatologic impostors, Dr. Heald presented a series of clinical cases from his own practice along with management pearls gleaned from personal experience and recent literature.

Interferon-Induced Cytokine Psoriasis

Cytokine psoriasis—a subset of psoriasis with a unique clinical appearance and therapy profile—started appearing with some frequency around 1990, not coincidentally around the time treatment with interferon for hepatitis C became more common, Dr. Heald said. “Over the past decade, we've started seeing tons of patients who are 1–2 months into interferon therapy coming in with psoriasis that's just gone crazy. They have acute, irritated, oozing lesions, sometimes with pruritus and often associated with palmar lesions and acral dermatitis,” he said. Of interest, the psoriatic lesions are not local to the interferon injection sites, but rather are all over the body and, if the patient has or is prone to psoriatic arthritis, that will be induced or aggravated as well.

Although the exact underlying mechanism for this is not fully understood, psoriasis is thought to be an immune-mediated disease with a cytokine profile predominantly of the T helper cell, type 1 (TH1) subset. Presumably, interferon-α triggers psoriasis by activating dendritic cells and T cells involved in the pathogenesis of the condition, according to Dr. Heald. “I'm not a big believer in interferon inducing new cases;” it is more likely that interferon causes problems in people who are prone to psoriasis or who have a mild case, he said. “If you've got a condition where you've already got a TH1-mediated process going on in the skin, and you feed that interferon, it's going to cause problems.”

The plan for managing this type of psoriasis is to treat the patients while they are completing their course of interferon therapy. “The usual regimen is etanercept—I start them on 50 mg twice a week—with or without prednisone for rapid onset of relief,” Dr. Heald said. “In my experience, the response to etanercept for this type of psoriasis is even better than [it is for] regular psoriasis.” At the end of the interferon course, patients can be safely tapered off of the etanercept, he said.

An important consideration in the management of these patients, said Dr. Heald, is to involve the treating physician in the decision process. “Let them know that you are going to start treatment and that you're comfortable using the anti-tumor necrosis factor therapy.”

Antimalarial Psoriasis

“I recently saw a patient who started on an antimalarial medication to treat symmetric polyarthritis with psoriasis. Within 2 weeks of starting the drug, he began to develop what I call a 'fill in the gap' type of psoriasis, in which erythema develops in between preexisting plaques,” Dr. Heald said. “We've seen a bunch of these cases because for a while at our Veterans [Affairs] hospital a patient had to fail an antimalarial before getting approval for treatment with a biologic for psoriatic arthritis.” To manage this condition, “we stop the drug immediately and switch over to something that can treat both [psoriasis and psoriatic arthritis] and possibly a prednisone taper,” Dr. Heald said. “I don't think psoriasis patients should ever be put on antimalarials. Hydroxychloroquine inhibits epidermal transglutaminase activity, which leads to irregular keratinization and dermoepidermal detachment and cleft formation. In psoriatics, this leads to an erythrodermic form of the disease.”

Efalizumab-Interruption Psoriasis

Most dermatologists have legions of happy psoriasis patients thanks to the efficacy of biologics for continuous control of their conditions, “but there is one little side to this that has not been published enough: the possibility of psoriasis exacerbation when treatment is interrupted,” said Dr. Heald, who has had patients weeks and even months into successful therapy whose psoriasis returns with a vengeance following two or three missed doses. “One of my patients went on a trip and forgot his medication for 3 days. He experienced an unbelievably quick, abrupt aggravation with lots of very pruritic new lesions and oozing lesions.” It's unclear what's behind this, he said, but it's possible that with an interruption in therapy “all those cells go barreling back into the skin and create this abrupt syndrome.”

To manage the reaction, “I have sometimes tried getting prednisone or cyclosporine in there right away just to get immediate control because these patients get so bad so quickly, and then [I] start another form of therapy.”

Interferon: Pyoderma Gangrenosum

Although not common, the development of virulent pyoderma gangrenosum-type ulcers at the interferon injection sites of some patients receiving the drug for multiple sclerosis or hepatitis C, “appears to be the result of interferon aggravating one of the TH1 types of inflammatory processes that typically occurs within 3 months of starting the therapy,” Dr. Heald said. Biopsies of the affected areas may show neutrophil infiltrates of vasculitis.

“Because patients and their neurologists love the drug, they're not going to stop it, so they will want you to help manage them through it,” Dr. Heald said. This is particularly true for patients with multiple sclerosis. “Patients who are staying on interferon for MS can be taught how to do interlesional triamcinolone injections, which I've had the most success with.”

Vitiligo and Imiquimod

Topical imiquimod can induce local interferon-α release and vitiligo hypopigmentation. “In patients prone to vitiligo, the imiquimod triggers an immunomodulating event that may enhance a latent cell-mediated process,” Dr. Heald said. “In the patients I've treated with this condition, nobody has developed vitiligo all over. It's been localized to the area of imiquimod application.” Use one of the other topical immunomodulator drugs, he said.

Infliximab and Lupus Erythematosus

Four months on infliximab appears to bring out subclinical lupus in a small percentage of patients with preexisting antinuclear antibodies.

“I've had about a half-dozen patients who are on infliximab for rheumatoid arthritis coming in with a lupus-like syndrome of anular, flat, scaly skin lesions that tend to be mostly on the face and arms,” Dr. Heald said.

“The mechanism for the condition is a little bit murky, but what's clear is that in some systems with an ongoing autoimmune process, the anti-TNF action can exacerbate disease,” Dr. Heald said. “In these instances, you have to stop the drug. You can't treat through this.”

Alternative treatment options include methotrexate or thiopurines. “You want to stay away from the anti-TNF family in general,” he said, noting that once infliximab therapy is withdrawn, the skin lesions tend to clear in 2–3 months.

STOWE, VT. — Use of several agents prescribed for the management of arthritis and other diseases seen by rheumatologists can induce cutaneous reactions that require referral to a dermatologist, said Dr. Peter W. Heald at a dermatology conference sponsored by the University of Vermont.

Because these drug-aggravated conditions often present as known diseases but frequently have different underlying mechanisms and treatment responses, diagnosis and management can be problematic, according to Dr. Heald, professor of dermatology at Yale University, New Haven, Conn. Also, the condition the suspect drug is prescribed to treat may make it inadvisable to discontinue the medication. To help unmask some of the dermatologic impostors, Dr. Heald presented a series of clinical cases from his own practice along with management pearls gleaned from personal experience and recent literature.

Interferon-Induced Cytokine Psoriasis

Cytokine psoriasis—a subset of psoriasis with a unique clinical appearance and therapy profile—started appearing with some frequency around 1990, not coincidentally around the time treatment with interferon for hepatitis C became more common, Dr. Heald said. “Over the past decade, we've started seeing tons of patients who are 1–2 months into interferon therapy coming in with psoriasis that's just gone crazy. They have acute, irritated, oozing lesions, sometimes with pruritus and often associated with palmar lesions and acral dermatitis,” he said. Of interest, the psoriatic lesions are not local to the interferon injection sites, but rather are all over the body and, if the patient has or is prone to psoriatic arthritis, that will be induced or aggravated as well.

Although the exact underlying mechanism for this is not fully understood, psoriasis is thought to be an immune-mediated disease with a cytokine profile predominantly of the T helper cell, type 1 (TH1) subset. Presumably, interferon-α triggers psoriasis by activating dendritic cells and T cells involved in the pathogenesis of the condition, according to Dr. Heald. “I'm not a big believer in interferon inducing new cases;” it is more likely that interferon causes problems in people who are prone to psoriasis or who have a mild case, he said. “If you've got a condition where you've already got a TH1-mediated process going on in the skin, and you feed that interferon, it's going to cause problems.”

The plan for managing this type of psoriasis is to treat the patients while they are completing their course of interferon therapy. “The usual regimen is etanercept—I start them on 50 mg twice a week—with or without prednisone for rapid onset of relief,” Dr. Heald said. “In my experience, the response to etanercept for this type of psoriasis is even better than [it is for] regular psoriasis.” At the end of the interferon course, patients can be safely tapered off of the etanercept, he said.

An important consideration in the management of these patients, said Dr. Heald, is to involve the treating physician in the decision process. “Let them know that you are going to start treatment and that you're comfortable using the anti-tumor necrosis factor therapy.”

Antimalarial Psoriasis

“I recently saw a patient who started on an antimalarial medication to treat symmetric polyarthritis with psoriasis. Within 2 weeks of starting the drug, he began to develop what I call a 'fill in the gap' type of psoriasis, in which erythema develops in between preexisting plaques,” Dr. Heald said. “We've seen a bunch of these cases because for a while at our Veterans [Affairs] hospital a patient had to fail an antimalarial before getting approval for treatment with a biologic for psoriatic arthritis.” To manage this condition, “we stop the drug immediately and switch over to something that can treat both [psoriasis and psoriatic arthritis] and possibly a prednisone taper,” Dr. Heald said. “I don't think psoriasis patients should ever be put on antimalarials. Hydroxychloroquine inhibits epidermal transglutaminase activity, which leads to irregular keratinization and dermoepidermal detachment and cleft formation. In psoriatics, this leads to an erythrodermic form of the disease.”

Efalizumab-Interruption Psoriasis

Most dermatologists have legions of happy psoriasis patients thanks to the efficacy of biologics for continuous control of their conditions, “but there is one little side to this that has not been published enough: the possibility of psoriasis exacerbation when treatment is interrupted,” said Dr. Heald, who has had patients weeks and even months into successful therapy whose psoriasis returns with a vengeance following two or three missed doses. “One of my patients went on a trip and forgot his medication for 3 days. He experienced an unbelievably quick, abrupt aggravation with lots of very pruritic new lesions and oozing lesions.” It's unclear what's behind this, he said, but it's possible that with an interruption in therapy “all those cells go barreling back into the skin and create this abrupt syndrome.”

To manage the reaction, “I have sometimes tried getting prednisone or cyclosporine in there right away just to get immediate control because these patients get so bad so quickly, and then [I] start another form of therapy.”

Interferon: Pyoderma Gangrenosum

Although not common, the development of virulent pyoderma gangrenosum-type ulcers at the interferon injection sites of some patients receiving the drug for multiple sclerosis or hepatitis C, “appears to be the result of interferon aggravating one of the TH1 types of inflammatory processes that typically occurs within 3 months of starting the therapy,” Dr. Heald said. Biopsies of the affected areas may show neutrophil infiltrates of vasculitis.

“Because patients and their neurologists love the drug, they're not going to stop it, so they will want you to help manage them through it,” Dr. Heald said. This is particularly true for patients with multiple sclerosis. “Patients who are staying on interferon for MS can be taught how to do interlesional triamcinolone injections, which I've had the most success with.”

Vitiligo and Imiquimod

Topical imiquimod can induce local interferon-α release and vitiligo hypopigmentation. “In patients prone to vitiligo, the imiquimod triggers an immunomodulating event that may enhance a latent cell-mediated process,” Dr. Heald said. “In the patients I've treated with this condition, nobody has developed vitiligo all over. It's been localized to the area of imiquimod application.” Use one of the other topical immunomodulator drugs, he said.

Infliximab and Lupus Erythematosus

Four months on infliximab appears to bring out subclinical lupus in a small percentage of patients with preexisting antinuclear antibodies.

“I've had about a half-dozen patients who are on infliximab for rheumatoid arthritis coming in with a lupus-like syndrome of anular, flat, scaly skin lesions that tend to be mostly on the face and arms,” Dr. Heald said.

“The mechanism for the condition is a little bit murky, but what's clear is that in some systems with an ongoing autoimmune process, the anti-TNF action can exacerbate disease,” Dr. Heald said. “In these instances, you have to stop the drug. You can't treat through this.”

Alternative treatment options include methotrexate or thiopurines. “You want to stay away from the anti-TNF family in general,” he said, noting that once infliximab therapy is withdrawn, the skin lesions tend to clear in 2–3 months.

STOWE, VT. — Use of several agents prescribed for the management of arthritis and other diseases seen by rheumatologists can induce cutaneous reactions that require referral to a dermatologist, said Dr. Peter W. Heald at a dermatology conference sponsored by the University of Vermont.

Because these drug-aggravated conditions often present as known diseases but frequently have different underlying mechanisms and treatment responses, diagnosis and management can be problematic, according to Dr. Heald, professor of dermatology at Yale University, New Haven, Conn. Also, the condition the suspect drug is prescribed to treat may make it inadvisable to discontinue the medication. To help unmask some of the dermatologic impostors, Dr. Heald presented a series of clinical cases from his own practice along with management pearls gleaned from personal experience and recent literature.

Interferon-Induced Cytokine Psoriasis

Cytokine psoriasis—a subset of psoriasis with a unique clinical appearance and therapy profile—started appearing with some frequency around 1990, not coincidentally around the time treatment with interferon for hepatitis C became more common, Dr. Heald said. “Over the past decade, we've started seeing tons of patients who are 1–2 months into interferon therapy coming in with psoriasis that's just gone crazy. They have acute, irritated, oozing lesions, sometimes with pruritus and often associated with palmar lesions and acral dermatitis,” he said. Of interest, the psoriatic lesions are not local to the interferon injection sites, but rather are all over the body and, if the patient has or is prone to psoriatic arthritis, that will be induced or aggravated as well.

Although the exact underlying mechanism for this is not fully understood, psoriasis is thought to be an immune-mediated disease with a cytokine profile predominantly of the T helper cell, type 1 (TH1) subset. Presumably, interferon-α triggers psoriasis by activating dendritic cells and T cells involved in the pathogenesis of the condition, according to Dr. Heald. “I'm not a big believer in interferon inducing new cases;” it is more likely that interferon causes problems in people who are prone to psoriasis or who have a mild case, he said. “If you've got a condition where you've already got a TH1-mediated process going on in the skin, and you feed that interferon, it's going to cause problems.”

The plan for managing this type of psoriasis is to treat the patients while they are completing their course of interferon therapy. “The usual regimen is etanercept—I start them on 50 mg twice a week—with or without prednisone for rapid onset of relief,” Dr. Heald said. “In my experience, the response to etanercept for this type of psoriasis is even better than [it is for] regular psoriasis.” At the end of the interferon course, patients can be safely tapered off of the etanercept, he said.

An important consideration in the management of these patients, said Dr. Heald, is to involve the treating physician in the decision process. “Let them know that you are going to start treatment and that you're comfortable using the anti-tumor necrosis factor therapy.”

Antimalarial Psoriasis

“I recently saw a patient who started on an antimalarial medication to treat symmetric polyarthritis with psoriasis. Within 2 weeks of starting the drug, he began to develop what I call a 'fill in the gap' type of psoriasis, in which erythema develops in between preexisting plaques,” Dr. Heald said. “We've seen a bunch of these cases because for a while at our Veterans [Affairs] hospital a patient had to fail an antimalarial before getting approval for treatment with a biologic for psoriatic arthritis.” To manage this condition, “we stop the drug immediately and switch over to something that can treat both [psoriasis and psoriatic arthritis] and possibly a prednisone taper,” Dr. Heald said. “I don't think psoriasis patients should ever be put on antimalarials. Hydroxychloroquine inhibits epidermal transglutaminase activity, which leads to irregular keratinization and dermoepidermal detachment and cleft formation. In psoriatics, this leads to an erythrodermic form of the disease.”

Efalizumab-Interruption Psoriasis

Most dermatologists have legions of happy psoriasis patients thanks to the efficacy of biologics for continuous control of their conditions, “but there is one little side to this that has not been published enough: the possibility of psoriasis exacerbation when treatment is interrupted,” said Dr. Heald, who has had patients weeks and even months into successful therapy whose psoriasis returns with a vengeance following two or three missed doses. “One of my patients went on a trip and forgot his medication for 3 days. He experienced an unbelievably quick, abrupt aggravation with lots of very pruritic new lesions and oozing lesions.” It's unclear what's behind this, he said, but it's possible that with an interruption in therapy “all those cells go barreling back into the skin and create this abrupt syndrome.”

To manage the reaction, “I have sometimes tried getting prednisone or cyclosporine in there right away just to get immediate control because these patients get so bad so quickly, and then [I] start another form of therapy.”

Interferon: Pyoderma Gangrenosum

Although not common, the development of virulent pyoderma gangrenosum-type ulcers at the interferon injection sites of some patients receiving the drug for multiple sclerosis or hepatitis C, “appears to be the result of interferon aggravating one of the TH1 types of inflammatory processes that typically occurs within 3 months of starting the therapy,” Dr. Heald said. Biopsies of the affected areas may show neutrophil infiltrates of vasculitis.

“Because patients and their neurologists love the drug, they're not going to stop it, so they will want you to help manage them through it,” Dr. Heald said. This is particularly true for patients with multiple sclerosis. “Patients who are staying on interferon for MS can be taught how to do interlesional triamcinolone injections, which I've had the most success with.”

Vitiligo and Imiquimod

Topical imiquimod can induce local interferon-α release and vitiligo hypopigmentation. “In patients prone to vitiligo, the imiquimod triggers an immunomodulating event that may enhance a latent cell-mediated process,” Dr. Heald said. “In the patients I've treated with this condition, nobody has developed vitiligo all over. It's been localized to the area of imiquimod application.” Use one of the other topical immunomodulator drugs, he said.

Infliximab and Lupus Erythematosus

Four months on infliximab appears to bring out subclinical lupus in a small percentage of patients with preexisting antinuclear antibodies.

“I've had about a half-dozen patients who are on infliximab for rheumatoid arthritis coming in with a lupus-like syndrome of anular, flat, scaly skin lesions that tend to be mostly on the face and arms,” Dr. Heald said.

“The mechanism for the condition is a little bit murky, but what's clear is that in some systems with an ongoing autoimmune process, the anti-TNF action can exacerbate disease,” Dr. Heald said. “In these instances, you have to stop the drug. You can't treat through this.”

Alternative treatment options include methotrexate or thiopurines. “You want to stay away from the anti-TNF family in general,” he said, noting that once infliximab therapy is withdrawn, the skin lesions tend to clear in 2–3 months.

The recent identification of novel gene mutations in seven Saudi Arabian children with camptodactyly-arthropathy-coxa vara-pericarditis syndrome has implications beyond the rare autosomal recessive joint condition, as it provides researchers with more pieces to fit into the genetic puzzle of pediatric rheumatic disease, Dr. Matthew Warman of Case Western Reserve University, in Cleveland, said in an interview.

Currently, because camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome mimics juvenile idiopathic arthritis, it is often mistakenly diagnosed and treated as such. However, “the management of the two conditions is very different,” said Amaka C. Offiah, Ph.D., of the Great Ormond Street Hospital for Children in London in an interview. While juvenile idiopathic arthritis is treated with anti-inflammatory medications, often in association with corticosteroids and methotrexate, “CACP does not respond to those therapies because it is not an inflammatory disorder,” she said. The estimated incidence of the syndrome is one case per 1–2 million individuals.

Previously, Dr. Warman and colleagues identified the CACP gene as proteoglycan, or PRG4, which maps to human chromosome 1. The PRG4 gene is switched on in human synovial cells and encodes for lubricin, which is a large, highly glycosylated secreted protein that has been identified as a key joint lubricant.

“Our studies have shown that most patients with CACP syndrome are missing lubricin from their synovial fluid,” said Dr. Warman. The PRG4 mutations in CACP patients suggest not only that inherited lubricin defects could lead to joint damage, he said, “but also that lubricin has an important role in healthy joints.”

In the aforementioned Saudi Arabian study, Anas M. Alazami, Ph.D., and colleagues at the King Faisal Specialist Hospital and Research Centre in Riyadh discovered five novel PRG4 mutations in seven children from four unrelated families (Human Mutation 2006;27:213). The new findings confirm Dr. Warman's observation that CACP may result from a loss of lubricin function.

In addition, “our paper suggests that PRG4 mutations are not uncommon, and that there may be a mutation hot spot within the gene, because each of the four families we examined in this fairly consanguineous population had a distinct mutation,” Dr. Alazami said in an interview.

Perhaps the most important conclusion from the new data “is that CACP syndrome is most likely based on a null phenotype, in other words, no synthesis of PRG4 protein at all,” said Dr. Alazami. This is because all of the mutations published thus far “predict a prematurely truncated protein and because the PRG4 gene appears to be under the control of the nonsense mediated mRNA decay pathway,” he said. “This suggests strongly that missense mutations, or in-frame deletions, may be associated with a less severe phenotype, perhaps one of the more common forms of arthropathy.”

Given that the disorder is associated with a null phenotype, “the obvious potential treatment target would be the injection of active PRG4 protein, or a synthetic substitute, into affected joints,” said Dr. Alazami. “But, from a genetic standpoint, the data are concerned more closely with prevention—in other words, the ability to identify carriers and offer genetic counseling—rather than treatment” at this juncture.

Toward this end, antibodies against lubricin could potentially be used to test synovial fluid from individuals suspected of having the disease for the protein's presence, said Dr. Warman. “The data also suggest that antibodies could be used to look for transient deficiency of lubricin, as might occur when an individual sustains a joint injury that abrades the cartilage surface or has inflammation in the joint that results in degradation of lubricin.”

Because the mounting evidence of the genetic deficiency of lubricin in CACP points to this protein's importance in maintaining human joint function, said Dr. Warman, “we can now ask specific questions about how this protein works within the joint. For example, what other proteins does it interact with? What leads to its synthesis and degradation? What happens if we find a way to replace the protein, for example, through gene therapy or protein replacement therapy? When do we need to give lubricin back to a joint? Can lubricin reverse damage that may have already occurred in the presence of other joint-damaging diseases such as rheumatoid arthritis?”

To begin answering these questions, Dr. Warman and colleagues have genetically engineered mice that lack lubricin and are studying the consequences of this deficiency on joint development. While the joints of the genetically altered mice appear normal in the newborn period, abnormal protein deposits appear on the cartilage surface and underlying superficial zone chondrocytes disappear as the mice age, leading to joint damage.

“In addition to cartilage surface changes and subsequent cartilage deterioration, intimal cells in the synovium surrounding the joint space became hyperplastic, which further contributes to joint failure,” said Dr. Warman. The investigators hypothesize that, in the absence of lubricin, the synovial cells become much more aggressive, potentially invading the cartilage surface, in a process similar to that seen in rheumatoid arthritis, he said.

To determine whether it is feasible to prevent or slow joint disease by stimulating lubricin production within the joint, “we have also just recently developed a mouse in which we can turn lubricin expression on and off using doxycycline,” said Dr. Warman. The investigators are also conducting in vitro studies of different forms of lubricin to assess the effect of each different form on cell growth, tissue localization, and surface lubrication, with the ultimate goal being to replace protein function in humans, he said.

Dr. Warman's team is hoping to apply the research findings to more common joint diseases as well. To determine whether lubricin replacement therapy could also be useful for patients with osteoarthritis and rheumatoid arthritis, Dr. Warman and his colleagues are investigating lubricin changes in the cartilage and synovial fluid of patients with those conditions. “If we identify acquired changes in CACP protein among these patients, then therapies aimed at increasing endogenous protein synthesis or diminishing protein degradation may become valuable therapeutic adjuncts,” he said.

Although molecular testing to diagnose CACP or to identify unaffected characters is not yet available, the identification of the basic molecular components involved in the development of CACP is heading in this direction. Such tests will be especially useful for differentiating CACP from other conditions with which it shares many clinical features, such as polyarthritic and systemic juvenile idiopathic arthritis, in which pericarditis occasionally occurs. The ability to identify the genetic cause of a constellation of symptoms can help direct appropriate treatment and avoid the use of ineffective agents and their potential side effects.

In the absence of definitive molecular testing, CACP is best differentiated from other conditions by the presence of certain clinical, laboratory, and radiologic features. Particularly important, according to Dr. Offiah, is the lack of clinical signs of inflammation. “[CACP syndrome] is not associated with inflammatory changes in the synovium. Also, erythrocyte sedimentation rate, C-reactive protein, and complete blood count are normal,” she said. In addition, autoantibodies, including antinuclear antibodies and rheumatoid factor, are negative.

Among the distinguishing radiologic features of CACP are nonerosive arthropathies with smooth flattening of the affected joint surfaces, squaring of the metacarpal and phalangeal heads, coxa vara, short femoral neck, osteopenia, and large acetabular cysts that can be seen on pelvic X-ray.

To date, no effective treatment has been developed for CACP. However, recognition of the condition is important in order to prevent the use of inappropriate and potentially dangerous medications, said Dr. Warman, as well as offer insight into optimal treatment strategies for more common joint conditions.

The recent identification of novel gene mutations in seven Saudi Arabian children with camptodactyly-arthropathy-coxa vara-pericarditis syndrome has implications beyond the rare autosomal recessive joint condition, as it provides researchers with more pieces to fit into the genetic puzzle of pediatric rheumatic disease, Dr. Matthew Warman of Case Western Reserve University, in Cleveland, said in an interview.

Currently, because camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome mimics juvenile idiopathic arthritis, it is often mistakenly diagnosed and treated as such. However, “the management of the two conditions is very different,” said Amaka C. Offiah, Ph.D., of the Great Ormond Street Hospital for Children in London in an interview. While juvenile idiopathic arthritis is treated with anti-inflammatory medications, often in association with corticosteroids and methotrexate, “CACP does not respond to those therapies because it is not an inflammatory disorder,” she said. The estimated incidence of the syndrome is one case per 1–2 million individuals.

Previously, Dr. Warman and colleagues identified the CACP gene as proteoglycan, or PRG4, which maps to human chromosome 1. The PRG4 gene is switched on in human synovial cells and encodes for lubricin, which is a large, highly glycosylated secreted protein that has been identified as a key joint lubricant.

“Our studies have shown that most patients with CACP syndrome are missing lubricin from their synovial fluid,” said Dr. Warman. The PRG4 mutations in CACP patients suggest not only that inherited lubricin defects could lead to joint damage, he said, “but also that lubricin has an important role in healthy joints.”

In the aforementioned Saudi Arabian study, Anas M. Alazami, Ph.D., and colleagues at the King Faisal Specialist Hospital and Research Centre in Riyadh discovered five novel PRG4 mutations in seven children from four unrelated families (Human Mutation 2006;27:213). The new findings confirm Dr. Warman's observation that CACP may result from a loss of lubricin function.

In addition, “our paper suggests that PRG4 mutations are not uncommon, and that there may be a mutation hot spot within the gene, because each of the four families we examined in this fairly consanguineous population had a distinct mutation,” Dr. Alazami said in an interview.

Perhaps the most important conclusion from the new data “is that CACP syndrome is most likely based on a null phenotype, in other words, no synthesis of PRG4 protein at all,” said Dr. Alazami. This is because all of the mutations published thus far “predict a prematurely truncated protein and because the PRG4 gene appears to be under the control of the nonsense mediated mRNA decay pathway,” he said. “This suggests strongly that missense mutations, or in-frame deletions, may be associated with a less severe phenotype, perhaps one of the more common forms of arthropathy.”

Given that the disorder is associated with a null phenotype, “the obvious potential treatment target would be the injection of active PRG4 protein, or a synthetic substitute, into affected joints,” said Dr. Alazami. “But, from a genetic standpoint, the data are concerned more closely with prevention—in other words, the ability to identify carriers and offer genetic counseling—rather than treatment” at this juncture.

Toward this end, antibodies against lubricin could potentially be used to test synovial fluid from individuals suspected of having the disease for the protein's presence, said Dr. Warman. “The data also suggest that antibodies could be used to look for transient deficiency of lubricin, as might occur when an individual sustains a joint injury that abrades the cartilage surface or has inflammation in the joint that results in degradation of lubricin.”

Because the mounting evidence of the genetic deficiency of lubricin in CACP points to this protein's importance in maintaining human joint function, said Dr. Warman, “we can now ask specific questions about how this protein works within the joint. For example, what other proteins does it interact with? What leads to its synthesis and degradation? What happens if we find a way to replace the protein, for example, through gene therapy or protein replacement therapy? When do we need to give lubricin back to a joint? Can lubricin reverse damage that may have already occurred in the presence of other joint-damaging diseases such as rheumatoid arthritis?”

To begin answering these questions, Dr. Warman and colleagues have genetically engineered mice that lack lubricin and are studying the consequences of this deficiency on joint development. While the joints of the genetically altered mice appear normal in the newborn period, abnormal protein deposits appear on the cartilage surface and underlying superficial zone chondrocytes disappear as the mice age, leading to joint damage.

“In addition to cartilage surface changes and subsequent cartilage deterioration, intimal cells in the synovium surrounding the joint space became hyperplastic, which further contributes to joint failure,” said Dr. Warman. The investigators hypothesize that, in the absence of lubricin, the synovial cells become much more aggressive, potentially invading the cartilage surface, in a process similar to that seen in rheumatoid arthritis, he said.

To determine whether it is feasible to prevent or slow joint disease by stimulating lubricin production within the joint, “we have also just recently developed a mouse in which we can turn lubricin expression on and off using doxycycline,” said Dr. Warman. The investigators are also conducting in vitro studies of different forms of lubricin to assess the effect of each different form on cell growth, tissue localization, and surface lubrication, with the ultimate goal being to replace protein function in humans, he said.

Dr. Warman's team is hoping to apply the research findings to more common joint diseases as well. To determine whether lubricin replacement therapy could also be useful for patients with osteoarthritis and rheumatoid arthritis, Dr. Warman and his colleagues are investigating lubricin changes in the cartilage and synovial fluid of patients with those conditions. “If we identify acquired changes in CACP protein among these patients, then therapies aimed at increasing endogenous protein synthesis or diminishing protein degradation may become valuable therapeutic adjuncts,” he said.

Although molecular testing to diagnose CACP or to identify unaffected characters is not yet available, the identification of the basic molecular components involved in the development of CACP is heading in this direction. Such tests will be especially useful for differentiating CACP from other conditions with which it shares many clinical features, such as polyarthritic and systemic juvenile idiopathic arthritis, in which pericarditis occasionally occurs. The ability to identify the genetic cause of a constellation of symptoms can help direct appropriate treatment and avoid the use of ineffective agents and their potential side effects.

In the absence of definitive molecular testing, CACP is best differentiated from other conditions by the presence of certain clinical, laboratory, and radiologic features. Particularly important, according to Dr. Offiah, is the lack of clinical signs of inflammation. “[CACP syndrome] is not associated with inflammatory changes in the synovium. Also, erythrocyte sedimentation rate, C-reactive protein, and complete blood count are normal,” she said. In addition, autoantibodies, including antinuclear antibodies and rheumatoid factor, are negative.

Among the distinguishing radiologic features of CACP are nonerosive arthropathies with smooth flattening of the affected joint surfaces, squaring of the metacarpal and phalangeal heads, coxa vara, short femoral neck, osteopenia, and large acetabular cysts that can be seen on pelvic X-ray.

To date, no effective treatment has been developed for CACP. However, recognition of the condition is important in order to prevent the use of inappropriate and potentially dangerous medications, said Dr. Warman, as well as offer insight into optimal treatment strategies for more common joint conditions.

The recent identification of novel gene mutations in seven Saudi Arabian children with camptodactyly-arthropathy-coxa vara-pericarditis syndrome has implications beyond the rare autosomal recessive joint condition, as it provides researchers with more pieces to fit into the genetic puzzle of pediatric rheumatic disease, Dr. Matthew Warman of Case Western Reserve University, in Cleveland, said in an interview.

Currently, because camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome mimics juvenile idiopathic arthritis, it is often mistakenly diagnosed and treated as such. However, “the management of the two conditions is very different,” said Amaka C. Offiah, Ph.D., of the Great Ormond Street Hospital for Children in London in an interview. While juvenile idiopathic arthritis is treated with anti-inflammatory medications, often in association with corticosteroids and methotrexate, “CACP does not respond to those therapies because it is not an inflammatory disorder,” she said. The estimated incidence of the syndrome is one case per 1–2 million individuals.

Previously, Dr. Warman and colleagues identified the CACP gene as proteoglycan, or PRG4, which maps to human chromosome 1. The PRG4 gene is switched on in human synovial cells and encodes for lubricin, which is a large, highly glycosylated secreted protein that has been identified as a key joint lubricant.

“Our studies have shown that most patients with CACP syndrome are missing lubricin from their synovial fluid,” said Dr. Warman. The PRG4 mutations in CACP patients suggest not only that inherited lubricin defects could lead to joint damage, he said, “but also that lubricin has an important role in healthy joints.”

In the aforementioned Saudi Arabian study, Anas M. Alazami, Ph.D., and colleagues at the King Faisal Specialist Hospital and Research Centre in Riyadh discovered five novel PRG4 mutations in seven children from four unrelated families (Human Mutation 2006;27:213). The new findings confirm Dr. Warman's observation that CACP may result from a loss of lubricin function.

In addition, “our paper suggests that PRG4 mutations are not uncommon, and that there may be a mutation hot spot within the gene, because each of the four families we examined in this fairly consanguineous population had a distinct mutation,” Dr. Alazami said in an interview.

Perhaps the most important conclusion from the new data “is that CACP syndrome is most likely based on a null phenotype, in other words, no synthesis of PRG4 protein at all,” said Dr. Alazami. This is because all of the mutations published thus far “predict a prematurely truncated protein and because the PRG4 gene appears to be under the control of the nonsense mediated mRNA decay pathway,” he said. “This suggests strongly that missense mutations, or in-frame deletions, may be associated with a less severe phenotype, perhaps one of the more common forms of arthropathy.”

Given that the disorder is associated with a null phenotype, “the obvious potential treatment target would be the injection of active PRG4 protein, or a synthetic substitute, into affected joints,” said Dr. Alazami. “But, from a genetic standpoint, the data are concerned more closely with prevention—in other words, the ability to identify carriers and offer genetic counseling—rather than treatment” at this juncture.

Toward this end, antibodies against lubricin could potentially be used to test synovial fluid from individuals suspected of having the disease for the protein's presence, said Dr. Warman. “The data also suggest that antibodies could be used to look for transient deficiency of lubricin, as might occur when an individual sustains a joint injury that abrades the cartilage surface or has inflammation in the joint that results in degradation of lubricin.”

Because the mounting evidence of the genetic deficiency of lubricin in CACP points to this protein's importance in maintaining human joint function, said Dr. Warman, “we can now ask specific questions about how this protein works within the joint. For example, what other proteins does it interact with? What leads to its synthesis and degradation? What happens if we find a way to replace the protein, for example, through gene therapy or protein replacement therapy? When do we need to give lubricin back to a joint? Can lubricin reverse damage that may have already occurred in the presence of other joint-damaging diseases such as rheumatoid arthritis?”

To begin answering these questions, Dr. Warman and colleagues have genetically engineered mice that lack lubricin and are studying the consequences of this deficiency on joint development. While the joints of the genetically altered mice appear normal in the newborn period, abnormal protein deposits appear on the cartilage surface and underlying superficial zone chondrocytes disappear as the mice age, leading to joint damage.

“In addition to cartilage surface changes and subsequent cartilage deterioration, intimal cells in the synovium surrounding the joint space became hyperplastic, which further contributes to joint failure,” said Dr. Warman. The investigators hypothesize that, in the absence of lubricin, the synovial cells become much more aggressive, potentially invading the cartilage surface, in a process similar to that seen in rheumatoid arthritis, he said.

To determine whether it is feasible to prevent or slow joint disease by stimulating lubricin production within the joint, “we have also just recently developed a mouse in which we can turn lubricin expression on and off using doxycycline,” said Dr. Warman. The investigators are also conducting in vitro studies of different forms of lubricin to assess the effect of each different form on cell growth, tissue localization, and surface lubrication, with the ultimate goal being to replace protein function in humans, he said.

Dr. Warman's team is hoping to apply the research findings to more common joint diseases as well. To determine whether lubricin replacement therapy could also be useful for patients with osteoarthritis and rheumatoid arthritis, Dr. Warman and his colleagues are investigating lubricin changes in the cartilage and synovial fluid of patients with those conditions. “If we identify acquired changes in CACP protein among these patients, then therapies aimed at increasing endogenous protein synthesis or diminishing protein degradation may become valuable therapeutic adjuncts,” he said.

Although molecular testing to diagnose CACP or to identify unaffected characters is not yet available, the identification of the basic molecular components involved in the development of CACP is heading in this direction. Such tests will be especially useful for differentiating CACP from other conditions with which it shares many clinical features, such as polyarthritic and systemic juvenile idiopathic arthritis, in which pericarditis occasionally occurs. The ability to identify the genetic cause of a constellation of symptoms can help direct appropriate treatment and avoid the use of ineffective agents and their potential side effects.

In the absence of definitive molecular testing, CACP is best differentiated from other conditions by the presence of certain clinical, laboratory, and radiologic features. Particularly important, according to Dr. Offiah, is the lack of clinical signs of inflammation. “[CACP syndrome] is not associated with inflammatory changes in the synovium. Also, erythrocyte sedimentation rate, C-reactive protein, and complete blood count are normal,” she said. In addition, autoantibodies, including antinuclear antibodies and rheumatoid factor, are negative.

Among the distinguishing radiologic features of CACP are nonerosive arthropathies with smooth flattening of the affected joint surfaces, squaring of the metacarpal and phalangeal heads, coxa vara, short femoral neck, osteopenia, and large acetabular cysts that can be seen on pelvic X-ray.

To date, no effective treatment has been developed for CACP. However, recognition of the condition is important in order to prevent the use of inappropriate and potentially dangerous medications, said Dr. Warman, as well as offer insight into optimal treatment strategies for more common joint conditions.

BOSTON — The immediate initiation of depot medroxyprogesterone acetate to adolescent and young adult women seeking the contraceptive injection resulted in higher continuation rates and substantially diminished unintended pregnancy rates at 6 months, compared with the use of alternative, short-term hormonal methods meant to bridge the period between initial request and injection at a later date, Vaughn I. Rickert, Psy.D., said at the annual meeting of the Society for Adolescent Medicine.

In a study of 334 young women ages 14–26 years who asked for depot medroxyprogesterone (DMPA) during a reproductive health visit at an urban family planning clinic, 101 women were randomized to receive their first DMPA (Depo Provera) injection at the conclusion of the visit, and 233 were randomized to an alternative “quick start” bridge condition whereby they were offered their choice of either oral contraceptive pills, the transdermal patch, or the vaginal ring, said Dr. Rickert of the Mailman School of Public Health at Columbia University in New York.

In a previous study, the Columbia investigators determined that patients who immediately initiated oral contraception at the time of their clinic visit (after a negative urine pregnancy test) were significantly more likely to continue taking the oral contraceptive than were a control group of women who were provided with conventional instructions to wait until their menses began before starting oral contraception (Contraception 2002;66:141–5).

Historically, the rationale for waiting to initiate hormonal contraception “was to be sure the patient was not pregnant and to keep from altering the bleeding pattern,” according to Dr. Rickert. “Unfortunately, with the delayed initiation, many women don't take their first pill, and their motivation wanes.” Similarly, asking women to return to the clinic at a later date for a DMPA injection means that some won't come back for it, thus increasing the likelihood for unintended pregnancies.

The immediate contraception protocol was designed to avoid this outcome, according to Dr. Rickert. While the earlier study looked specifically at the efficacy of the approach with respect to oral contraceptives, the current study sought to determine whether immediate access to DMPA would lead to greater method continuation—and thus pregnancy prevention—over a 6-month period, compared with delaying the injection and providing alternative contraceptive options for the interim period.

All the women enrolled in the study had a negative urine pregnancy test at the time of their initial clinic visit, and none were breast-feeding or currently using other forms of hormonal contraception. In addition, none of the women had received a DMPA injection within the previous 14 weeks nor had any medical contraindications to hormonal contraception, said Dr. Rickert.

All the subjects in both conditions underwent a history, physical, pregnancy test, and structured interview at the initial visit. All were instructed to return to the clinic in 21 days for a repeat urine pregnancy test and, for those assigned to the alternative condition, to receive their first DMPA injection, said Dr. Rickert. In addition, the women were followed through two subsequent appointments for DMPA injections and structured interviews.

The DMPA injections were discontinued in women in whom pregnancy was detected at any visit, in those who refused injection at any visit, or in those for whom more than 98 days had passed since their previous injection, said Dr. Rickert.

Of the 233 women randomized to the quick start bridge condition, 95 chose oral contraceptive pills, 100 chose the transdermal patch, and 38 chose the vaginal ring. Emergency contraception was provided to 41% of the entire cohort—31 patients in the Depo group and 83 in the bridge group—at the initial visit. Of women who received immediate injection of DMPA, 7 never returned for a follow-up visit, compared with 11 in the bridge group who never returned for a follow-up visit.

As of February 2006, 278 of the women had completed the study. Of this population, 54 were between the ages of 14 and 17 years, 118 were between the ages of 18 and 21, and 106 were between 22 and 26. The sample was more than 90% Latino and approximately 7% African American. “No significant differences were found in baseline demographic or reproductive characteristics,” Dr. Rickert reported.

Bivariate analysis showed no statistically significant difference in the 21-day return rates among those who began DMPA immediately and those who were randomized to use a bridge method prior to the first injection. In addition, “rates of patient satisfaction [with the respective contraceptive protocols] between the two groups were not different at the second and third injections,” said Dr. Rickert.

However, “continuation rates were statistically higher at 6 months in the Depo group compared to the bridge group, meaning that more women in the Depo group received their third injection,” he said. “Also, the Depo group had significantly fewer pregnancies [2, compared with 23 in the bridge group] across the study period.”

Other factors independently associated with 6-month DMPA continuation rates included partners' awareness of DMPA use, returning for the pregnancy test visit, and history of emergency contraceptive pill use, “suggesting continuation is also affected by behaviors consistent with intentions not to become pregnant,” said Dr. Rickert.

These findings support the idea that immediate administration of DMPA with little adverse effect might have a significant impact on contraceptive continuation as well as on the prevention of unintended pregnancies, Dr. Rickert concluded.

ELSEVIER GLOBAL MEDICAL NEWS

BOSTON — The immediate initiation of depot medroxyprogesterone acetate to adolescent and young adult women seeking the contraceptive injection resulted in higher continuation rates and substantially diminished unintended pregnancy rates at 6 months, compared with the use of alternative, short-term hormonal methods meant to bridge the period between initial request and injection at a later date, Vaughn I. Rickert, Psy.D., said at the annual meeting of the Society for Adolescent Medicine.

In a study of 334 young women ages 14–26 years who asked for depot medroxyprogesterone (DMPA) during a reproductive health visit at an urban family planning clinic, 101 women were randomized to receive their first DMPA (Depo Provera) injection at the conclusion of the visit, and 233 were randomized to an alternative “quick start” bridge condition whereby they were offered their choice of either oral contraceptive pills, the transdermal patch, or the vaginal ring, said Dr. Rickert of the Mailman School of Public Health at Columbia University in New York.

In a previous study, the Columbia investigators determined that patients who immediately initiated oral contraception at the time of their clinic visit (after a negative urine pregnancy test) were significantly more likely to continue taking the oral contraceptive than were a control group of women who were provided with conventional instructions to wait until their menses began before starting oral contraception (Contraception 2002;66:141–5).

Historically, the rationale for waiting to initiate hormonal contraception “was to be sure the patient was not pregnant and to keep from altering the bleeding pattern,” according to Dr. Rickert. “Unfortunately, with the delayed initiation, many women don't take their first pill, and their motivation wanes.” Similarly, asking women to return to the clinic at a later date for a DMPA injection means that some won't come back for it, thus increasing the likelihood for unintended pregnancies.

The immediate contraception protocol was designed to avoid this outcome, according to Dr. Rickert. While the earlier study looked specifically at the efficacy of the approach with respect to oral contraceptives, the current study sought to determine whether immediate access to DMPA would lead to greater method continuation—and thus pregnancy prevention—over a 6-month period, compared with delaying the injection and providing alternative contraceptive options for the interim period.

All the women enrolled in the study had a negative urine pregnancy test at the time of their initial clinic visit, and none were breast-feeding or currently using other forms of hormonal contraception. In addition, none of the women had received a DMPA injection within the previous 14 weeks nor had any medical contraindications to hormonal contraception, said Dr. Rickert.

All the subjects in both conditions underwent a history, physical, pregnancy test, and structured interview at the initial visit. All were instructed to return to the clinic in 21 days for a repeat urine pregnancy test and, for those assigned to the alternative condition, to receive their first DMPA injection, said Dr. Rickert. In addition, the women were followed through two subsequent appointments for DMPA injections and structured interviews.

The DMPA injections were discontinued in women in whom pregnancy was detected at any visit, in those who refused injection at any visit, or in those for whom more than 98 days had passed since their previous injection, said Dr. Rickert.

Of the 233 women randomized to the quick start bridge condition, 95 chose oral contraceptive pills, 100 chose the transdermal patch, and 38 chose the vaginal ring. Emergency contraception was provided to 41% of the entire cohort—31 patients in the Depo group and 83 in the bridge group—at the initial visit. Of women who received immediate injection of DMPA, 7 never returned for a follow-up visit, compared with 11 in the bridge group who never returned for a follow-up visit.

As of February 2006, 278 of the women had completed the study. Of this population, 54 were between the ages of 14 and 17 years, 118 were between the ages of 18 and 21, and 106 were between 22 and 26. The sample was more than 90% Latino and approximately 7% African American. “No significant differences were found in baseline demographic or reproductive characteristics,” Dr. Rickert reported.

Bivariate analysis showed no statistically significant difference in the 21-day return rates among those who began DMPA immediately and those who were randomized to use a bridge method prior to the first injection. In addition, “rates of patient satisfaction [with the respective contraceptive protocols] between the two groups were not different at the second and third injections,” said Dr. Rickert.

However, “continuation rates were statistically higher at 6 months in the Depo group compared to the bridge group, meaning that more women in the Depo group received their third injection,” he said. “Also, the Depo group had significantly fewer pregnancies [2, compared with 23 in the bridge group] across the study period.”

Other factors independently associated with 6-month DMPA continuation rates included partners' awareness of DMPA use, returning for the pregnancy test visit, and history of emergency contraceptive pill use, “suggesting continuation is also affected by behaviors consistent with intentions not to become pregnant,” said Dr. Rickert.

These findings support the idea that immediate administration of DMPA with little adverse effect might have a significant impact on contraceptive continuation as well as on the prevention of unintended pregnancies, Dr. Rickert concluded.

ELSEVIER GLOBAL MEDICAL NEWS

BOSTON — The immediate initiation of depot medroxyprogesterone acetate to adolescent and young adult women seeking the contraceptive injection resulted in higher continuation rates and substantially diminished unintended pregnancy rates at 6 months, compared with the use of alternative, short-term hormonal methods meant to bridge the period between initial request and injection at a later date, Vaughn I. Rickert, Psy.D., said at the annual meeting of the Society for Adolescent Medicine.

In a study of 334 young women ages 14–26 years who asked for depot medroxyprogesterone (DMPA) during a reproductive health visit at an urban family planning clinic, 101 women were randomized to receive their first DMPA (Depo Provera) injection at the conclusion of the visit, and 233 were randomized to an alternative “quick start” bridge condition whereby they were offered their choice of either oral contraceptive pills, the transdermal patch, or the vaginal ring, said Dr. Rickert of the Mailman School of Public Health at Columbia University in New York.

In a previous study, the Columbia investigators determined that patients who immediately initiated oral contraception at the time of their clinic visit (after a negative urine pregnancy test) were significantly more likely to continue taking the oral contraceptive than were a control group of women who were provided with conventional instructions to wait until their menses began before starting oral contraception (Contraception 2002;66:141–5).

Historically, the rationale for waiting to initiate hormonal contraception “was to be sure the patient was not pregnant and to keep from altering the bleeding pattern,” according to Dr. Rickert. “Unfortunately, with the delayed initiation, many women don't take their first pill, and their motivation wanes.” Similarly, asking women to return to the clinic at a later date for a DMPA injection means that some won't come back for it, thus increasing the likelihood for unintended pregnancies.

The immediate contraception protocol was designed to avoid this outcome, according to Dr. Rickert. While the earlier study looked specifically at the efficacy of the approach with respect to oral contraceptives, the current study sought to determine whether immediate access to DMPA would lead to greater method continuation—and thus pregnancy prevention—over a 6-month period, compared with delaying the injection and providing alternative contraceptive options for the interim period.

All the women enrolled in the study had a negative urine pregnancy test at the time of their initial clinic visit, and none were breast-feeding or currently using other forms of hormonal contraception. In addition, none of the women had received a DMPA injection within the previous 14 weeks nor had any medical contraindications to hormonal contraception, said Dr. Rickert.

All the subjects in both conditions underwent a history, physical, pregnancy test, and structured interview at the initial visit. All were instructed to return to the clinic in 21 days for a repeat urine pregnancy test and, for those assigned to the alternative condition, to receive their first DMPA injection, said Dr. Rickert. In addition, the women were followed through two subsequent appointments for DMPA injections and structured interviews.

The DMPA injections were discontinued in women in whom pregnancy was detected at any visit, in those who refused injection at any visit, or in those for whom more than 98 days had passed since their previous injection, said Dr. Rickert.

Of the 233 women randomized to the quick start bridge condition, 95 chose oral contraceptive pills, 100 chose the transdermal patch, and 38 chose the vaginal ring. Emergency contraception was provided to 41% of the entire cohort—31 patients in the Depo group and 83 in the bridge group—at the initial visit. Of women who received immediate injection of DMPA, 7 never returned for a follow-up visit, compared with 11 in the bridge group who never returned for a follow-up visit.

As of February 2006, 278 of the women had completed the study. Of this population, 54 were between the ages of 14 and 17 years, 118 were between the ages of 18 and 21, and 106 were between 22 and 26. The sample was more than 90% Latino and approximately 7% African American. “No significant differences were found in baseline demographic or reproductive characteristics,” Dr. Rickert reported.

Bivariate analysis showed no statistically significant difference in the 21-day return rates among those who began DMPA immediately and those who were randomized to use a bridge method prior to the first injection. In addition, “rates of patient satisfaction [with the respective contraceptive protocols] between the two groups were not different at the second and third injections,” said Dr. Rickert.

However, “continuation rates were statistically higher at 6 months in the Depo group compared to the bridge group, meaning that more women in the Depo group received their third injection,” he said. “Also, the Depo group had significantly fewer pregnancies [2, compared with 23 in the bridge group] across the study period.”

Other factors independently associated with 6-month DMPA continuation rates included partners' awareness of DMPA use, returning for the pregnancy test visit, and history of emergency contraceptive pill use, “suggesting continuation is also affected by behaviors consistent with intentions not to become pregnant,” said Dr. Rickert.

These findings support the idea that immediate administration of DMPA with little adverse effect might have a significant impact on contraceptive continuation as well as on the prevention of unintended pregnancies, Dr. Rickert concluded.

ELSEVIER GLOBAL MEDICAL NEWS

STOWE, VT. — Skin involvement is one of the most frequent manifestations of lupus erythematosus, yet the cutaneous signs of the disease are not always recognized, Dr. Victoria P. Werth said at a dermatology conference sponsored by the University of Vermont.

The diagnostic challenge is recognizing these cutaneous conditions, particularly because they encompass as many as 15 different clinical presentations, said Dr. Werth of the University of Pennsylvania, Philadelphia.

It's important to know what to look for, “not only so we can treat the skin problems, but also so we can identify signs of systemic disease when they occur,” she said.

Although systemic lupus erythematosus (SLE) is estimated to occur in 17–48 per 100,000 individuals, the cutaneous variants are thought to be two to three times more prevalent.

Skin findings in cutaneous lupus are generally categorized into lupus-specific and lupus-nonspecific diseases, based on biopsy findings.

“Lupus-specific lesions show histology that is specific to lupus erythematosus, while nonspecific lesions are not histopathologically distinct for the disease and may be seen as a feature of another disease process,” Dr. Werth explained. Some of the more common nonspecific skin findings include alopecia, vasculitis, and Raynaud's phenomenon.

Although skin disease is the second-most frequent clinical manifestation of SLE, cutaneous lupus does not always meet all the American College of Rheumatology's diagnostic criteria for SLE.

Lupus-specific cutaneous lesions are further subdivided into three categories: acute, subacute, and chronic. “The most recognizable acute presentation is the butterfly rash, which comes on abruptly and heals within hours or days, usually without scarring,” Dr. Werth said. Some variations of this rash include bullous formations or blisters.

Subacute manifestations can include annular and/or psoriasiform rashes that are usually highly photosensitive. Chronic cutaneous lupus is “the wastebasket category” for many of the other lupus-specific skin presentations, she said.

The most common chronic cutaneous form is discoid lupus erythematosus, which begins with well-defined scaly lesions that evolve into scarring plaques and often includes follicular involvement that can lead to hair loss.

“Early, aggressive treatment for these patients is important in order to prevent permanent, disfiguring scarring and permanent hair loss,” said Dr. Werth.

She also discussed several of the following less prevalent manifestations of chronic cutaneous lupus:

▸ Chilblain lupus. Associated with itching, cold, and painful swelling of the extremities and toes.

▸ Hypertrophic lupus. Characterized by wartlike bumps.

▸ Lupus profundus. Causes deep dermal nodules on the upper arms and sometimes on the head, chest, or legs.

▸ Lupus tumidus. Presents as broad, indurated plaques.

Because some of these conditions can mimic other skin conditions, “serologic and histologic examinations are critical for confirming a diagnosis,” Dr. Werth said.

Although management for the various lupus subsets does not differ substantially, the clinical distinctions are important because they relate to the likelihood that an individual patient will develop systemic disease, Dr. Werth pointed out.

Nearly all patients with acute cutaneous lupus, and half of those with subacute disease, will meet American College of Rheumatology criteria for SLE. With respect to chronic cutaneous lupus, those with generalized discoid lesions have a 20% chance of developing SLE, those with lupus profundus are estimated to have a 10% chance, those with localized discoid lesions have a 5% chance, and those with lupus tumidus have virtually no chance.

“Patients whose skin conditions put them at higher risk should be followed more closely for evidence of systemic disease,” she said.

Once a diagnosis of cutaneous lupus has been made, the next step is to evaluate the patient for signs of systemic disease. The initial evaluation should include history, physical examination, CBC, sedimentation rate, antinuclear antibody (ANA) testing, and urinalysis. For ANA-positive patients or ANA-negative patients in whom there is suspicion of SLE, Dr. Werth suggests a panel that includes anti-Sjouml;gren's syndrome A, anti-Sjouml;gren's syndrome B, anti-ribonucleoprotein, anti-double-stranded DNA, and anti-Smith antibodies, as well as complement studies.

Patients with positive findings warrant closer monitoring, “especially those with high titer, anti-double-stranded DNA antibody because of an increased risk for renal problems,” she said.

In terms of management, “the first order of business is advising patients to avoid precipitating factors such as heat, certain medications, and sunlight,” Dr. Werth said. “I tell my patients they should not go outside without a sunscreen that has a UVB of 30 or more, as well as a UVA blocker, like Parsol 1789.”

Patients also should avoid drugs that cause subacute lupus-like eruptions, such as thiazides, griseofulvin, terbinafine, calcium channel blockers, and ACE inhibitors, Dr. Werth noted.

In addition to preventive efforts, standard therapies include topical and sometimes intralesional corticosteroids and antimalarial drugs.

“Most patients will respond well to these conservative therapies, but there are 10%–20% of patients with refractory disease who don't respond,” she said. For such patients, there are a range of other treatment options, including thalidomide, dapsone, retinoids, biologics, and immunosuppressants.

“Some of these more aggressive therapies are associated with significant side effects, and should be used sparingly and only when warranted by disease severity,” Dr. Werth said.

“Unfortunately, there is a paucity of data in the literature to aid the clinician in terms of which therapies to employ. Often, the presumed efficacy of these drugs has often been extrapolated from their use in treating systemic lupus.”

It is hoped that new insights into the genetic pathways associated with cutaneous lupus, as well as continued advances in targeted biologic therapies, will lead to the development of more selective, less toxic therapeutic agents.

Among the drugs currently in development, Dr. Werth said, “are a derivative of thalidomide and a new B-cell-specific monoclonal antibody therapy.”

STOWE, VT. — Skin involvement is one of the most frequent manifestations of lupus erythematosus, yet the cutaneous signs of the disease are not always recognized, Dr. Victoria P. Werth said at a dermatology conference sponsored by the University of Vermont.

The diagnostic challenge is recognizing these cutaneous conditions, particularly because they encompass as many as 15 different clinical presentations, said Dr. Werth of the University of Pennsylvania, Philadelphia.

It's important to know what to look for, “not only so we can treat the skin problems, but also so we can identify signs of systemic disease when they occur,” she said.

Although systemic lupus erythematosus (SLE) is estimated to occur in 17–48 per 100,000 individuals, the cutaneous variants are thought to be two to three times more prevalent.

Skin findings in cutaneous lupus are generally categorized into lupus-specific and lupus-nonspecific diseases, based on biopsy findings.

“Lupus-specific lesions show histology that is specific to lupus erythematosus, while nonspecific lesions are not histopathologically distinct for the disease and may be seen as a feature of another disease process,” Dr. Werth explained. Some of the more common nonspecific skin findings include alopecia, vasculitis, and Raynaud's phenomenon.

Although skin disease is the second-most frequent clinical manifestation of SLE, cutaneous lupus does not always meet all the American College of Rheumatology's diagnostic criteria for SLE.

Lupus-specific cutaneous lesions are further subdivided into three categories: acute, subacute, and chronic. “The most recognizable acute presentation is the butterfly rash, which comes on abruptly and heals within hours or days, usually without scarring,” Dr. Werth said. Some variations of this rash include bullous formations or blisters.

Subacute manifestations can include annular and/or psoriasiform rashes that are usually highly photosensitive. Chronic cutaneous lupus is “the wastebasket category” for many of the other lupus-specific skin presentations, she said.

The most common chronic cutaneous form is discoid lupus erythematosus, which begins with well-defined scaly lesions that evolve into scarring plaques and often includes follicular involvement that can lead to hair loss.

“Early, aggressive treatment for these patients is important in order to prevent permanent, disfiguring scarring and permanent hair loss,” said Dr. Werth.

She also discussed several of the following less prevalent manifestations of chronic cutaneous lupus:

▸ Chilblain lupus. Associated with itching, cold, and painful swelling of the extremities and toes.

▸ Hypertrophic lupus. Characterized by wartlike bumps.

▸ Lupus profundus. Causes deep dermal nodules on the upper arms and sometimes on the head, chest, or legs.

▸ Lupus tumidus. Presents as broad, indurated plaques.

Because some of these conditions can mimic other skin conditions, “serologic and histologic examinations are critical for confirming a diagnosis,” Dr. Werth said.

Although management for the various lupus subsets does not differ substantially, the clinical distinctions are important because they relate to the likelihood that an individual patient will develop systemic disease, Dr. Werth pointed out.

Nearly all patients with acute cutaneous lupus, and half of those with subacute disease, will meet American College of Rheumatology criteria for SLE. With respect to chronic cutaneous lupus, those with generalized discoid lesions have a 20% chance of developing SLE, those with lupus profundus are estimated to have a 10% chance, those with localized discoid lesions have a 5% chance, and those with lupus tumidus have virtually no chance.

“Patients whose skin conditions put them at higher risk should be followed more closely for evidence of systemic disease,” she said.

Once a diagnosis of cutaneous lupus has been made, the next step is to evaluate the patient for signs of systemic disease. The initial evaluation should include history, physical examination, CBC, sedimentation rate, antinuclear antibody (ANA) testing, and urinalysis. For ANA-positive patients or ANA-negative patients in whom there is suspicion of SLE, Dr. Werth suggests a panel that includes anti-Sjouml;gren's syndrome A, anti-Sjouml;gren's syndrome B, anti-ribonucleoprotein, anti-double-stranded DNA, and anti-Smith antibodies, as well as complement studies.

Patients with positive findings warrant closer monitoring, “especially those with high titer, anti-double-stranded DNA antibody because of an increased risk for renal problems,” she said.

In terms of management, “the first order of business is advising patients to avoid precipitating factors such as heat, certain medications, and sunlight,” Dr. Werth said. “I tell my patients they should not go outside without a sunscreen that has a UVB of 30 or more, as well as a UVA blocker, like Parsol 1789.”

Patients also should avoid drugs that cause subacute lupus-like eruptions, such as thiazides, griseofulvin, terbinafine, calcium channel blockers, and ACE inhibitors, Dr. Werth noted.

In addition to preventive efforts, standard therapies include topical and sometimes intralesional corticosteroids and antimalarial drugs.

“Most patients will respond well to these conservative therapies, but there are 10%–20% of patients with refractory disease who don't respond,” she said. For such patients, there are a range of other treatment options, including thalidomide, dapsone, retinoids, biologics, and immunosuppressants.

“Some of these more aggressive therapies are associated with significant side effects, and should be used sparingly and only when warranted by disease severity,” Dr. Werth said.

“Unfortunately, there is a paucity of data in the literature to aid the clinician in terms of which therapies to employ. Often, the presumed efficacy of these drugs has often been extrapolated from their use in treating systemic lupus.”

It is hoped that new insights into the genetic pathways associated with cutaneous lupus, as well as continued advances in targeted biologic therapies, will lead to the development of more selective, less toxic therapeutic agents.

Among the drugs currently in development, Dr. Werth said, “are a derivative of thalidomide and a new B-cell-specific monoclonal antibody therapy.”

STOWE, VT. — Skin involvement is one of the most frequent manifestations of lupus erythematosus, yet the cutaneous signs of the disease are not always recognized, Dr. Victoria P. Werth said at a dermatology conference sponsored by the University of Vermont.

The diagnostic challenge is recognizing these cutaneous conditions, particularly because they encompass as many as 15 different clinical presentations, said Dr. Werth of the University of Pennsylvania, Philadelphia.

It's important to know what to look for, “not only so we can treat the skin problems, but also so we can identify signs of systemic disease when they occur,” she said.

Although systemic lupus erythematosus (SLE) is estimated to occur in 17–48 per 100,000 individuals, the cutaneous variants are thought to be two to three times more prevalent.

Skin findings in cutaneous lupus are generally categorized into lupus-specific and lupus-nonspecific diseases, based on biopsy findings.

“Lupus-specific lesions show histology that is specific to lupus erythematosus, while nonspecific lesions are not histopathologically distinct for the disease and may be seen as a feature of another disease process,” Dr. Werth explained. Some of the more common nonspecific skin findings include alopecia, vasculitis, and Raynaud's phenomenon.

Although skin disease is the second-most frequent clinical manifestation of SLE, cutaneous lupus does not always meet all the American College of Rheumatology's diagnostic criteria for SLE.

Lupus-specific cutaneous lesions are further subdivided into three categories: acute, subacute, and chronic. “The most recognizable acute presentation is the butterfly rash, which comes on abruptly and heals within hours or days, usually without scarring,” Dr. Werth said. Some variations of this rash include bullous formations or blisters.

Subacute manifestations can include annular and/or psoriasiform rashes that are usually highly photosensitive. Chronic cutaneous lupus is “the wastebasket category” for many of the other lupus-specific skin presentations, she said.

The most common chronic cutaneous form is discoid lupus erythematosus, which begins with well-defined scaly lesions that evolve into scarring plaques and often includes follicular involvement that can lead to hair loss.

“Early, aggressive treatment for these patients is important in order to prevent permanent, disfiguring scarring and permanent hair loss,” said Dr. Werth.

She also discussed several of the following less prevalent manifestations of chronic cutaneous lupus:

▸ Chilblain lupus. Associated with itching, cold, and painful swelling of the extremities and toes.

▸ Hypertrophic lupus. Characterized by wartlike bumps.

▸ Lupus profundus. Causes deep dermal nodules on the upper arms and sometimes on the head, chest, or legs.

▸ Lupus tumidus. Presents as broad, indurated plaques.

Because some of these conditions can mimic other skin conditions, “serologic and histologic examinations are critical for confirming a diagnosis,” Dr. Werth said.

Although management for the various lupus subsets does not differ substantially, the clinical distinctions are important because they relate to the likelihood that an individual patient will develop systemic disease, Dr. Werth pointed out.

Nearly all patients with acute cutaneous lupus, and half of those with subacute disease, will meet American College of Rheumatology criteria for SLE. With respect to chronic cutaneous lupus, those with generalized discoid lesions have a 20% chance of developing SLE, those with lupus profundus are estimated to have a 10% chance, those with localized discoid lesions have a 5% chance, and those with lupus tumidus have virtually no chance.

“Patients whose skin conditions put them at higher risk should be followed more closely for evidence of systemic disease,” she said.

Once a diagnosis of cutaneous lupus has been made, the next step is to evaluate the patient for signs of systemic disease. The initial evaluation should include history, physical examination, CBC, sedimentation rate, antinuclear antibody (ANA) testing, and urinalysis. For ANA-positive patients or ANA-negative patients in whom there is suspicion of SLE, Dr. Werth suggests a panel that includes anti-Sjouml;gren's syndrome A, anti-Sjouml;gren's syndrome B, anti-ribonucleoprotein, anti-double-stranded DNA, and anti-Smith antibodies, as well as complement studies.

Patients with positive findings warrant closer monitoring, “especially those with high titer, anti-double-stranded DNA antibody because of an increased risk for renal problems,” she said.

In terms of management, “the first order of business is advising patients to avoid precipitating factors such as heat, certain medications, and sunlight,” Dr. Werth said. “I tell my patients they should not go outside without a sunscreen that has a UVB of 30 or more, as well as a UVA blocker, like Parsol 1789.”

Patients also should avoid drugs that cause subacute lupus-like eruptions, such as thiazides, griseofulvin, terbinafine, calcium channel blockers, and ACE inhibitors, Dr. Werth noted.

In addition to preventive efforts, standard therapies include topical and sometimes intralesional corticosteroids and antimalarial drugs.

“Most patients will respond well to these conservative therapies, but there are 10%–20% of patients with refractory disease who don't respond,” she said. For such patients, there are a range of other treatment options, including thalidomide, dapsone, retinoids, biologics, and immunosuppressants.

“Some of these more aggressive therapies are associated with significant side effects, and should be used sparingly and only when warranted by disease severity,” Dr. Werth said.

“Unfortunately, there is a paucity of data in the literature to aid the clinician in terms of which therapies to employ. Often, the presumed efficacy of these drugs has often been extrapolated from their use in treating systemic lupus.”

It is hoped that new insights into the genetic pathways associated with cutaneous lupus, as well as continued advances in targeted biologic therapies, will lead to the development of more selective, less toxic therapeutic agents.

Among the drugs currently in development, Dr. Werth said, “are a derivative of thalidomide and a new B-cell-specific monoclonal antibody therapy.”

BOSTON — The use of insulin early in the management of adolescent type 2 diabetes mellitus may provide substantially improved glycemic control compared with the use of oral hypoglycemic agents alone, Dr. Aneesh K. Tosh said at the annual meeting of the Society for Adolescent Medicine.

Additionally, inpatient admission for newly diagnosed adolescents may provide a more effective means for facilitating intensive disease education compared with outpatient education programs.

A review of 51 patient charts from an adolescent type 2 diabetes mellitus subspecialty clinic showed, via multivariable regression, that the 11 patients who received insulin only at the time of diagnosis experienced a 30% improvement from baseline in their hemoglobin A_1c (HbA_1c) levels compared with a 5% improvement among the 23 patients who received oral agents only, after controlling for age, race, and body mass index. The 6 patients who did not receive insulin or oral agents experienced a 6% improvement from baseline, whereas the 11 who received both insulin and oral agents experienced a 26% improvement, reported Dr. Tosh of the department of pediatrics at Indiana University in Indianapolis.

Furthermore, the regression analysis showed that hospitalization for diabetes eduction was independently associated with improvements in glucose control. Among patients receiving only oral agents, inpatient education was associated with an 11% HbA_1c improvement, compared with a 3% improvement among those receiving outpatient education, said Dr. Tosh. Among patients receiving insulin therapy alone or in combination with an oral agent, inpatient education was associated with a 29% improvement compared with 18% for those who received outpatient education. The inpatient education protocol consisted of 3 days of intensive education about diabetes management and glucose control, whereas the outpatient program consisted of a half-day of education.

“One reason the inpatient program may have led to greater improvements is the fact that it requires, by design, significant parental involvement, which in turn impacts patient understanding and compliance,” said Dr. Tosh. However, there is also the potential for selection bias. “Presumably, patients who were admitted for inpatient management were sicker at diagnosis, so you would expect more substantial improvement.”

Similarly, with respect to the choice of oral agents vs. insulin at diagnosis, patients with lower hemoglobin A_1c initially might be more likely to receive oral agents, Dr. Tosh noted.

Although the study results are limited by the potential selection bias and small sample size, the findings suggest “that we need to take a closer look at the evolving role of insulin therapy for adolescents with type 2 diabetes,” said Dr. Tosh.

Current practice typically favors lifestyle management and oral hypoglycemic agents as first-line therapy for adolescents newly diagnosed with type 2 diabetes, with insulin being reserved for those diagnosed with severe disease or as second-line therapy. “There are a number of examples in the literature of the benefits of early insulin therapy, but most of the studies look at adults. Our findings are a call for studies of insulin management in the growing number of children and adolescents with type 2 diabetes,” Dr. Tosh said.

BOSTON — The use of insulin early in the management of adolescent type 2 diabetes mellitus may provide substantially improved glycemic control compared with the use of oral hypoglycemic agents alone, Dr. Aneesh K. Tosh said at the annual meeting of the Society for Adolescent Medicine.

Additionally, inpatient admission for newly diagnosed adolescents may provide a more effective means for facilitating intensive disease education compared with outpatient education programs.

A review of 51 patient charts from an adolescent type 2 diabetes mellitus subspecialty clinic showed, via multivariable regression, that the 11 patients who received insulin only at the time of diagnosis experienced a 30% improvement from baseline in their hemoglobin A_1c (HbA_1c) levels compared with a 5% improvement among the 23 patients who received oral agents only, after controlling for age, race, and body mass index. The 6 patients who did not receive insulin or oral agents experienced a 6% improvement from baseline, whereas the 11 who received both insulin and oral agents experienced a 26% improvement, reported Dr. Tosh of the department of pediatrics at Indiana University in Indianapolis.

Furthermore, the regression analysis showed that hospitalization for diabetes eduction was independently associated with improvements in glucose control. Among patients receiving only oral agents, inpatient education was associated with an 11% HbA_1c improvement, compared with a 3% improvement among those receiving outpatient education, said Dr. Tosh. Among patients receiving insulin therapy alone or in combination with an oral agent, inpatient education was associated with a 29% improvement compared with 18% for those who received outpatient education. The inpatient education protocol consisted of 3 days of intensive education about diabetes management and glucose control, whereas the outpatient program consisted of a half-day of education.

“One reason the inpatient program may have led to greater improvements is the fact that it requires, by design, significant parental involvement, which in turn impacts patient understanding and compliance,” said Dr. Tosh. However, there is also the potential for selection bias. “Presumably, patients who were admitted for inpatient management were sicker at diagnosis, so you would expect more substantial improvement.”

Similarly, with respect to the choice of oral agents vs. insulin at diagnosis, patients with lower hemoglobin A_1c initially might be more likely to receive oral agents, Dr. Tosh noted.

Although the study results are limited by the potential selection bias and small sample size, the findings suggest “that we need to take a closer look at the evolving role of insulin therapy for adolescents with type 2 diabetes,” said Dr. Tosh.

Current practice typically favors lifestyle management and oral hypoglycemic agents as first-line therapy for adolescents newly diagnosed with type 2 diabetes, with insulin being reserved for those diagnosed with severe disease or as second-line therapy. “There are a number of examples in the literature of the benefits of early insulin therapy, but most of the studies look at adults. Our findings are a call for studies of insulin management in the growing number of children and adolescents with type 2 diabetes,” Dr. Tosh said.

BOSTON — The use of insulin early in the management of adolescent type 2 diabetes mellitus may provide substantially improved glycemic control compared with the use of oral hypoglycemic agents alone, Dr. Aneesh K. Tosh said at the annual meeting of the Society for Adolescent Medicine.

Additionally, inpatient admission for newly diagnosed adolescents may provide a more effective means for facilitating intensive disease education compared with outpatient education programs.

A review of 51 patient charts from an adolescent type 2 diabetes mellitus subspecialty clinic showed, via multivariable regression, that the 11 patients who received insulin only at the time of diagnosis experienced a 30% improvement from baseline in their hemoglobin A_1c (HbA_1c) levels compared with a 5% improvement among the 23 patients who received oral agents only, after controlling for age, race, and body mass index. The 6 patients who did not receive insulin or oral agents experienced a 6% improvement from baseline, whereas the 11 who received both insulin and oral agents experienced a 26% improvement, reported Dr. Tosh of the department of pediatrics at Indiana University in Indianapolis.

Furthermore, the regression analysis showed that hospitalization for diabetes eduction was independently associated with improvements in glucose control. Among patients receiving only oral agents, inpatient education was associated with an 11% HbA_1c improvement, compared with a 3% improvement among those receiving outpatient education, said Dr. Tosh. Among patients receiving insulin therapy alone or in combination with an oral agent, inpatient education was associated with a 29% improvement compared with 18% for those who received outpatient education. The inpatient education protocol consisted of 3 days of intensive education about diabetes management and glucose control, whereas the outpatient program consisted of a half-day of education.

“One reason the inpatient program may have led to greater improvements is the fact that it requires, by design, significant parental involvement, which in turn impacts patient understanding and compliance,” said Dr. Tosh. However, there is also the potential for selection bias. “Presumably, patients who were admitted for inpatient management were sicker at diagnosis, so you would expect more substantial improvement.”

Similarly, with respect to the choice of oral agents vs. insulin at diagnosis, patients with lower hemoglobin A_1c initially might be more likely to receive oral agents, Dr. Tosh noted.

Although the study results are limited by the potential selection bias and small sample size, the findings suggest “that we need to take a closer look at the evolving role of insulin therapy for adolescents with type 2 diabetes,” said Dr. Tosh.

Current practice typically favors lifestyle management and oral hypoglycemic agents as first-line therapy for adolescents newly diagnosed with type 2 diabetes, with insulin being reserved for those diagnosed with severe disease or as second-line therapy. “There are a number of examples in the literature of the benefits of early insulin therapy, but most of the studies look at adults. Our findings are a call for studies of insulin management in the growing number of children and adolescents with type 2 diabetes,” Dr. Tosh said.

BOSTON — Exercises that simulate the mechanically challenging activities of daily living lessen energy expenditures and compensations associated with knee osteoarthritis, Dr. Anthony M. Reginato said at the 10th World Congress on Osteoarthritis.

As such, functional interventions should be an important component of rehabilitation therapy, he said at the congress, which was sponsored by the Osteoarthritis Research Society International.

In a double-blind, randomized trial, Dr. Reginato and his colleagues at Massachusetts General Hospital in Boston analyzed chair rise and box lifting in patients with knee osteoarthritis to determine if functional training or strengthening exercises led to improvements in mechanical energy expenditures (MEE), mechanical energy compensations (MEC), linear and angular momentum, and/or performance duration.

The study included 26 individuals, aged 43–86 years, who had Kellgren-Lawrence grade 2 or 3 knee osteoarthritis and at least two functional limitations on the SF36 physical functioning subscale. Participants were randomized to receive 8 weeks of physical therapy comprising either strength training or functional training.

“The goal of strength training is to address specific impairments, including range of motion and the ability to generate muscle force,” Dr. Reginato said.

In contrast, functional training simulates activities of daily living, such as gait, rising from a chair, and stair climbing, at different speeds and levels of difficulty, the goal of which is to improve neuromuscular control of the whole body, with specific focus on the individual's abilities and safety limits, he explained.

At baseline and postintervention, each participant completed a chair rise test, which required arising from a backless chair, and a box lift test, which required hoisting a plastic case holding a 5-kg metal disk onto a table. During both tasks, investigators calculated ankle, knee, hip, and back MEE and MEC. They also assessed maximum whole body angular momentum, maximum whole body anterior posterior linear momentum, and maximum whole body vertical linear momentum, as well as the intervals between the start and end of each task.

Using univariate analysis of covariance and multivariate analysis of variance to compare between-group differences in score changes relative to baseline, the investigators determined that, in the chair rise, the functional training group had significantly more improvement in energy expenditures and compensations by increasing ankle energy expenditure and decreasing back compensation, compared with the strength training group. And while there were no significant differences in chair rise interval times between the groups, the functional training group had a greater change from baseline in this measure.

In the box lift test, both groups increased their MEE in the back during the “no transfer” phase of lifting, although the strength training group had significantly higher changes in this measure, Dr. Reginato reported. In the transfer phase, the strengthening group had a significantly greater change in MEE in the back, compared with the functional group, which showed a decrease in this measure, and greater change in maximum whole body angular momentum.

The findings suggest that both functional and impairment-level interventions have important roles in the treatment of knee osteoarthritis, he said.

BOSTON — Exercises that simulate the mechanically challenging activities of daily living lessen energy expenditures and compensations associated with knee osteoarthritis, Dr. Anthony M. Reginato said at the 10th World Congress on Osteoarthritis.

As such, functional interventions should be an important component of rehabilitation therapy, he said at the congress, which was sponsored by the Osteoarthritis Research Society International.

In a double-blind, randomized trial, Dr. Reginato and his colleagues at Massachusetts General Hospital in Boston analyzed chair rise and box lifting in patients with knee osteoarthritis to determine if functional training or strengthening exercises led to improvements in mechanical energy expenditures (MEE), mechanical energy compensations (MEC), linear and angular momentum, and/or performance duration.

The study included 26 individuals, aged 43–86 years, who had Kellgren-Lawrence grade 2 or 3 knee osteoarthritis and at least two functional limitations on the SF36 physical functioning subscale. Participants were randomized to receive 8 weeks of physical therapy comprising either strength training or functional training.

“The goal of strength training is to address specific impairments, including range of motion and the ability to generate muscle force,” Dr. Reginato said.

In contrast, functional training simulates activities of daily living, such as gait, rising from a chair, and stair climbing, at different speeds and levels of difficulty, the goal of which is to improve neuromuscular control of the whole body, with specific focus on the individual's abilities and safety limits, he explained.

At baseline and postintervention, each participant completed a chair rise test, which required arising from a backless chair, and a box lift test, which required hoisting a plastic case holding a 5-kg metal disk onto a table. During both tasks, investigators calculated ankle, knee, hip, and back MEE and MEC. They also assessed maximum whole body angular momentum, maximum whole body anterior posterior linear momentum, and maximum whole body vertical linear momentum, as well as the intervals between the start and end of each task.

Using univariate analysis of covariance and multivariate analysis of variance to compare between-group differences in score changes relative to baseline, the investigators determined that, in the chair rise, the functional training group had significantly more improvement in energy expenditures and compensations by increasing ankle energy expenditure and decreasing back compensation, compared with the strength training group. And while there were no significant differences in chair rise interval times between the groups, the functional training group had a greater change from baseline in this measure.

In the box lift test, both groups increased their MEE in the back during the “no transfer” phase of lifting, although the strength training group had significantly higher changes in this measure, Dr. Reginato reported. In the transfer phase, the strengthening group had a significantly greater change in MEE in the back, compared with the functional group, which showed a decrease in this measure, and greater change in maximum whole body angular momentum.

The findings suggest that both functional and impairment-level interventions have important roles in the treatment of knee osteoarthritis, he said.

BOSTON — Exercises that simulate the mechanically challenging activities of daily living lessen energy expenditures and compensations associated with knee osteoarthritis, Dr. Anthony M. Reginato said at the 10th World Congress on Osteoarthritis.

As such, functional interventions should be an important component of rehabilitation therapy, he said at the congress, which was sponsored by the Osteoarthritis Research Society International.

In a double-blind, randomized trial, Dr. Reginato and his colleagues at Massachusetts General Hospital in Boston analyzed chair rise and box lifting in patients with knee osteoarthritis to determine if functional training or strengthening exercises led to improvements in mechanical energy expenditures (MEE), mechanical energy compensations (MEC), linear and angular momentum, and/or performance duration.

The study included 26 individuals, aged 43–86 years, who had Kellgren-Lawrence grade 2 or 3 knee osteoarthritis and at least two functional limitations on the SF36 physical functioning subscale. Participants were randomized to receive 8 weeks of physical therapy comprising either strength training or functional training.

“The goal of strength training is to address specific impairments, including range of motion and the ability to generate muscle force,” Dr. Reginato said.

In contrast, functional training simulates activities of daily living, such as gait, rising from a chair, and stair climbing, at different speeds and levels of difficulty, the goal of which is to improve neuromuscular control of the whole body, with specific focus on the individual's abilities and safety limits, he explained.

At baseline and postintervention, each participant completed a chair rise test, which required arising from a backless chair, and a box lift test, which required hoisting a plastic case holding a 5-kg metal disk onto a table. During both tasks, investigators calculated ankle, knee, hip, and back MEE and MEC. They also assessed maximum whole body angular momentum, maximum whole body anterior posterior linear momentum, and maximum whole body vertical linear momentum, as well as the intervals between the start and end of each task.

Using univariate analysis of covariance and multivariate analysis of variance to compare between-group differences in score changes relative to baseline, the investigators determined that, in the chair rise, the functional training group had significantly more improvement in energy expenditures and compensations by increasing ankle energy expenditure and decreasing back compensation, compared with the strength training group. And while there were no significant differences in chair rise interval times between the groups, the functional training group had a greater change from baseline in this measure.

In the box lift test, both groups increased their MEE in the back during the “no transfer” phase of lifting, although the strength training group had significantly higher changes in this measure, Dr. Reginato reported. In the transfer phase, the strengthening group had a significantly greater change in MEE in the back, compared with the functional group, which showed a decrease in this measure, and greater change in maximum whole body angular momentum.

The findings suggest that both functional and impairment-level interventions have important roles in the treatment of knee osteoarthritis, he said.

BOSTON — Disease progression in early osteoarthritis is associated with combined increases in biochemical markers for the synthesis and degradation of type II collagen, and these changes can be identified before radiologic evidence of the disease is apparent, a study has shown.

The findings suggest that measuring these biomarkers may help identify patients with early knee osteoarthritis who are at high risk for rapid progression, Dr. Patrick Garnero said at the 10th World Congress on Osteoarthritis.

“Currently, the only validated methodology for assessing progression in osteoarthritis is the measurement of joint space width by radiography, which has limited sensitivity,” said Dr. Garnero of the Institut National de la Santé et de la Recherche Médicale in Lyon, France. “When there is radiologic evidence of osteoarthritis, significant joint damage has already occurred,” he said at the congress, which was sponsored by the Osteoarthritis Research Society International. Previous short-term studies in advanced osteoarthritis have shown that baseline levels of serum concentration of the N-propeptide of collagen type IIA (PIIANP) and the urinary excretion of cross-linked C-telopeptide (CTX-II) are associated with disease progression.

Dr. Garnero and his associates at the University of Bristol in England followed 84 patients with early osteoarthritis in one or both knees for 5 years. All of the patients, mean age 62 years, had experienced persistent pain in one or both knees for more than 3 months, and 39% presented with a Kellgren-Lawrence score of less than 2. Using specific ELISA assays, the investigators measured each patient's PIIANP and CTX-II levels and obtained knee radiographs at baseline and at 2, 3, and 5 years. The radiographs were read by two independent readers. “Of interest,” Dr. Garnero said, independent readings showed that “about 60% of the patients had Kellgren-Lawrence scores lower than 2 and about 42% had scores below 0, suggesting a large proportion of this cohort had very early disease.”

“We defined disease progression as either a reduction in the tibiofemoral joint space by at least 2 mm or total replacement of either knee during the 5-year follow up,” Dr. Garnero said. Based on these criteria, 24 had progressive disease and 60 did not.

In the overall cohort there was a “slight but significant” mean PIIANP increase of 1.6% per year and no increase in urinary CTX-II levels during the 5-year follow up. When patients with and without progressive disease were considered independently, however, there were substantial differences. “Both measures were significantly higher throughout the study in the 24 patients with progressive disease compared with the remaining 60 patients,” Dr. Garnero said. Even so, “we could not differentiate the two groups according to x-ray measurements,” suggesting that detectable biomarker changes precede radiologic progression.

When classified by quartile of mean 5-year levels for both PIIANP and CTX-II measures, patients in the highest quartile of PIIANP and in the two highest quartiles for CTX-II were associated with increased risk for progression. The odds ratio for increased progression risk for the highest quartile PIIANP measures alone and the two highest quartiles for CTX-II measures alone were 3.2 and 3.4, respectively, compared with 11.8 for the combination of both markers.

The sensitivity and specificity of the PIIANP top quartile alone were 42% and 82%, respectively, compared with 71% and 58% for the CTX-II top two quartiles. “Combined, the sensitivity and specificity for both markers was 92% and 52%, respectively,” Dr. Garnero said. Because progression of joint damage likely results primarily from an imbalance between degradation and reparative processes, “combining these two markers is more effective in predicting progression than the measurement of a single marker.”

Predicting progression in osteoarthritis is notoriously difficult “because the outcomes vary substantially from patient to patient even if other considerations are the same,” he said.

The findings need to be validated in a larger study, he noted.

BOSTON — Disease progression in early osteoarthritis is associated with combined increases in biochemical markers for the synthesis and degradation of type II collagen, and these changes can be identified before radiologic evidence of the disease is apparent, a study has shown.

The findings suggest that measuring these biomarkers may help identify patients with early knee osteoarthritis who are at high risk for rapid progression, Dr. Patrick Garnero said at the 10th World Congress on Osteoarthritis.

“Currently, the only validated methodology for assessing progression in osteoarthritis is the measurement of joint space width by radiography, which has limited sensitivity,” said Dr. Garnero of the Institut National de la Santé et de la Recherche Médicale in Lyon, France. “When there is radiologic evidence of osteoarthritis, significant joint damage has already occurred,” he said at the congress, which was sponsored by the Osteoarthritis Research Society International. Previous short-term studies in advanced osteoarthritis have shown that baseline levels of serum concentration of the N-propeptide of collagen type IIA (PIIANP) and the urinary excretion of cross-linked C-telopeptide (CTX-II) are associated with disease progression.

Dr. Garnero and his associates at the University of Bristol in England followed 84 patients with early osteoarthritis in one or both knees for 5 years. All of the patients, mean age 62 years, had experienced persistent pain in one or both knees for more than 3 months, and 39% presented with a Kellgren-Lawrence score of less than 2. Using specific ELISA assays, the investigators measured each patient's PIIANP and CTX-II levels and obtained knee radiographs at baseline and at 2, 3, and 5 years. The radiographs were read by two independent readers. “Of interest,” Dr. Garnero said, independent readings showed that “about 60% of the patients had Kellgren-Lawrence scores lower than 2 and about 42% had scores below 0, suggesting a large proportion of this cohort had very early disease.”

“We defined disease progression as either a reduction in the tibiofemoral joint space by at least 2 mm or total replacement of either knee during the 5-year follow up,” Dr. Garnero said. Based on these criteria, 24 had progressive disease and 60 did not.

In the overall cohort there was a “slight but significant” mean PIIANP increase of 1.6% per year and no increase in urinary CTX-II levels during the 5-year follow up. When patients with and without progressive disease were considered independently, however, there were substantial differences. “Both measures were significantly higher throughout the study in the 24 patients with progressive disease compared with the remaining 60 patients,” Dr. Garnero said. Even so, “we could not differentiate the two groups according to x-ray measurements,” suggesting that detectable biomarker changes precede radiologic progression.

When classified by quartile of mean 5-year levels for both PIIANP and CTX-II measures, patients in the highest quartile of PIIANP and in the two highest quartiles for CTX-II were associated with increased risk for progression. The odds ratio for increased progression risk for the highest quartile PIIANP measures alone and the two highest quartiles for CTX-II measures alone were 3.2 and 3.4, respectively, compared with 11.8 for the combination of both markers.

The sensitivity and specificity of the PIIANP top quartile alone were 42% and 82%, respectively, compared with 71% and 58% for the CTX-II top two quartiles. “Combined, the sensitivity and specificity for both markers was 92% and 52%, respectively,” Dr. Garnero said. Because progression of joint damage likely results primarily from an imbalance between degradation and reparative processes, “combining these two markers is more effective in predicting progression than the measurement of a single marker.”

Predicting progression in osteoarthritis is notoriously difficult “because the outcomes vary substantially from patient to patient even if other considerations are the same,” he said.

The findings need to be validated in a larger study, he noted.

BOSTON — Disease progression in early osteoarthritis is associated with combined increases in biochemical markers for the synthesis and degradation of type II collagen, and these changes can be identified before radiologic evidence of the disease is apparent, a study has shown.

The findings suggest that measuring these biomarkers may help identify patients with early knee osteoarthritis who are at high risk for rapid progression, Dr. Patrick Garnero said at the 10th World Congress on Osteoarthritis.

“Currently, the only validated methodology for assessing progression in osteoarthritis is the measurement of joint space width by radiography, which has limited sensitivity,” said Dr. Garnero of the Institut National de la Santé et de la Recherche Médicale in Lyon, France. “When there is radiologic evidence of osteoarthritis, significant joint damage has already occurred,” he said at the congress, which was sponsored by the Osteoarthritis Research Society International. Previous short-term studies in advanced osteoarthritis have shown that baseline levels of serum concentration of the N-propeptide of collagen type IIA (PIIANP) and the urinary excretion of cross-linked C-telopeptide (CTX-II) are associated with disease progression.

Dr. Garnero and his associates at the University of Bristol in England followed 84 patients with early osteoarthritis in one or both knees for 5 years. All of the patients, mean age 62 years, had experienced persistent pain in one or both knees for more than 3 months, and 39% presented with a Kellgren-Lawrence score of less than 2. Using specific ELISA assays, the investigators measured each patient's PIIANP and CTX-II levels and obtained knee radiographs at baseline and at 2, 3, and 5 years. The radiographs were read by two independent readers. “Of interest,” Dr. Garnero said, independent readings showed that “about 60% of the patients had Kellgren-Lawrence scores lower than 2 and about 42% had scores below 0, suggesting a large proportion of this cohort had very early disease.”

“We defined disease progression as either a reduction in the tibiofemoral joint space by at least 2 mm or total replacement of either knee during the 5-year follow up,” Dr. Garnero said. Based on these criteria, 24 had progressive disease and 60 did not.

In the overall cohort there was a “slight but significant” mean PIIANP increase of 1.6% per year and no increase in urinary CTX-II levels during the 5-year follow up. When patients with and without progressive disease were considered independently, however, there were substantial differences. “Both measures were significantly higher throughout the study in the 24 patients with progressive disease compared with the remaining 60 patients,” Dr. Garnero said. Even so, “we could not differentiate the two groups according to x-ray measurements,” suggesting that detectable biomarker changes precede radiologic progression.

When classified by quartile of mean 5-year levels for both PIIANP and CTX-II measures, patients in the highest quartile of PIIANP and in the two highest quartiles for CTX-II were associated with increased risk for progression. The odds ratio for increased progression risk for the highest quartile PIIANP measures alone and the two highest quartiles for CTX-II measures alone were 3.2 and 3.4, respectively, compared with 11.8 for the combination of both markers.

The sensitivity and specificity of the PIIANP top quartile alone were 42% and 82%, respectively, compared with 71% and 58% for the CTX-II top two quartiles. “Combined, the sensitivity and specificity for both markers was 92% and 52%, respectively,” Dr. Garnero said. Because progression of joint damage likely results primarily from an imbalance between degradation and reparative processes, “combining these two markers is more effective in predicting progression than the measurement of a single marker.”

Predicting progression in osteoarthritis is notoriously difficult “because the outcomes vary substantially from patient to patient even if other considerations are the same,” he said.

The findings need to be validated in a larger study, he noted.

STOWE, VT. — All squamous cell carcinomas require attention, but not all of them require emergency attention, said Dr. Glenn D. Goldman at a dermatology conference sponsored by the University of Vermont.

Thanks to effective public health campaigns in recent years, there has been a dramatic increase in patient and physician awareness of the potential seriousness of squamous cell carcinoma. The flip side of this successful educational program has been its contribution to the notion that all patients with a positive biopsy for the cancer must have a dermatology consult within days of the report.

“I can't tell you how many calls we get from patients and providers requesting immediate consultations because when they go through the [appointment office], they're told we are booking out a couple of months,” said Dr. Goldman of the division of dermatology at the University of Vermont. “As a result, I am constantly squeezing people into my schedule for 'emergency' consults, which drives the nurse manager nuts. And a lot of the time, when the patient comes in, it's clear that it's not really urgent, which drives me nuts.

“The truth is, not all squamous cell carcinomas are created equal. Many are minimally invasive and slowly advancing, whereas others are very invasive and advancing daily,” said Dr. Goldman. And although it's important that all squamous cell carcinomas be thoroughly removed and appropriately treated in a timely manner, some require more immediate attention than others, and it's usually not that difficult to tell the difference, he said.

“There are a handful of clues that will let you know you're dealing with a bad squamous cell carcinoma,” Dr. Goldman said. When any of these are present, “it's a sign that the lesion is aggressive and needs to be treated quickly and with great care.”

The first indicator of a bad lesion is that it is new and has developed rapidly within a short period. “Often, someone will come in with a squame that has been sitting there literally for years without changing much, and it could probably sit there for another year without causing a problem,” said Dr. Goldman. “It's the person who just noticed this thing a few weeks ago, and since then it has grown and changed daily, that you have to worry about.”

Also of concern is the patient who “is experiencing true neuropathic pain—not just the type of pain caused by a squame that feels like a screw if you put pressure on it—but the dull, searing neuropathic pain that doesn't go away,” said Dr. Goldman. Such pain could indicate nerve damage from metastases, he noted.

Immunosuppressed patients, such as transplant patients or those with chronic lymphocytic leukemia, who develop squamous cell carcinomas generally require aggressive treatment because their lesions often multiply and enlarge quickly, said Dr. Goldman.

Finally, “old men with squamous cell carcinoma tend to have bad luck with it, particularly if it is on the temple, which is one of the areas at highest risk for metastases,” Dr. Goldman said. “This is fairly well known in the derm community, but it's not written about much in the national literature.”

There also are several telltale indicators that a squamous cell carcinoma is not going to be difficult to cure and doesn't require immediate action. These include lesions that start as a patch or a plaque and those that are slow growing and nontender, Dr. Goldman said. Often, with such growths, “the biopsy itself is the cure,” he said. “More than 60% of the time, the biopsy will have gotten the whole thing. The clinical exam will reveal no residual squamous cell carcinoma, and the pathology will bear this out.”

Although these less serious squamous cell carcinomas do require treatment, “they can easily wait 1 to 2 months before being treated,” Dr. Goldman said.

STOWE, VT. — All squamous cell carcinomas require attention, but not all of them require emergency attention, said Dr. Glenn D. Goldman at a dermatology conference sponsored by the University of Vermont.

Thanks to effective public health campaigns in recent years, there has been a dramatic increase in patient and physician awareness of the potential seriousness of squamous cell carcinoma. The flip side of this successful educational program has been its contribution to the notion that all patients with a positive biopsy for the cancer must have a dermatology consult within days of the report.

“I can't tell you how many calls we get from patients and providers requesting immediate consultations because when they go through the [appointment office], they're told we are booking out a couple of months,” said Dr. Goldman of the division of dermatology at the University of Vermont. “As a result, I am constantly squeezing people into my schedule for 'emergency' consults, which drives the nurse manager nuts. And a lot of the time, when the patient comes in, it's clear that it's not really urgent, which drives me nuts.

“The truth is, not all squamous cell carcinomas are created equal. Many are minimally invasive and slowly advancing, whereas others are very invasive and advancing daily,” said Dr. Goldman. And although it's important that all squamous cell carcinomas be thoroughly removed and appropriately treated in a timely manner, some require more immediate attention than others, and it's usually not that difficult to tell the difference, he said.

“There are a handful of clues that will let you know you're dealing with a bad squamous cell carcinoma,” Dr. Goldman said. When any of these are present, “it's a sign that the lesion is aggressive and needs to be treated quickly and with great care.”

The first indicator of a bad lesion is that it is new and has developed rapidly within a short period. “Often, someone will come in with a squame that has been sitting there literally for years without changing much, and it could probably sit there for another year without causing a problem,” said Dr. Goldman. “It's the person who just noticed this thing a few weeks ago, and since then it has grown and changed daily, that you have to worry about.”

Also of concern is the patient who “is experiencing true neuropathic pain—not just the type of pain caused by a squame that feels like a screw if you put pressure on it—but the dull, searing neuropathic pain that doesn't go away,” said Dr. Goldman. Such pain could indicate nerve damage from metastases, he noted.

Immunosuppressed patients, such as transplant patients or those with chronic lymphocytic leukemia, who develop squamous cell carcinomas generally require aggressive treatment because their lesions often multiply and enlarge quickly, said Dr. Goldman.

Finally, “old men with squamous cell carcinoma tend to have bad luck with it, particularly if it is on the temple, which is one of the areas at highest risk for metastases,” Dr. Goldman said. “This is fairly well known in the derm community, but it's not written about much in the national literature.”

There also are several telltale indicators that a squamous cell carcinoma is not going to be difficult to cure and doesn't require immediate action. These include lesions that start as a patch or a plaque and those that are slow growing and nontender, Dr. Goldman said. Often, with such growths, “the biopsy itself is the cure,” he said. “More than 60% of the time, the biopsy will have gotten the whole thing. The clinical exam will reveal no residual squamous cell carcinoma, and the pathology will bear this out.”

Although these less serious squamous cell carcinomas do require treatment, “they can easily wait 1 to 2 months before being treated,” Dr. Goldman said.

STOWE, VT. — All squamous cell carcinomas require attention, but not all of them require emergency attention, said Dr. Glenn D. Goldman at a dermatology conference sponsored by the University of Vermont.

Thanks to effective public health campaigns in recent years, there has been a dramatic increase in patient and physician awareness of the potential seriousness of squamous cell carcinoma. The flip side of this successful educational program has been its contribution to the notion that all patients with a positive biopsy for the cancer must have a dermatology consult within days of the report.

“I can't tell you how many calls we get from patients and providers requesting immediate consultations because when they go through the [appointment office], they're told we are booking out a couple of months,” said Dr. Goldman of the division of dermatology at the University of Vermont. “As a result, I am constantly squeezing people into my schedule for 'emergency' consults, which drives the nurse manager nuts. And a lot of the time, when the patient comes in, it's clear that it's not really urgent, which drives me nuts.

“The truth is, not all squamous cell carcinomas are created equal. Many are minimally invasive and slowly advancing, whereas others are very invasive and advancing daily,” said Dr. Goldman. And although it's important that all squamous cell carcinomas be thoroughly removed and appropriately treated in a timely manner, some require more immediate attention than others, and it's usually not that difficult to tell the difference, he said.

“There are a handful of clues that will let you know you're dealing with a bad squamous cell carcinoma,” Dr. Goldman said. When any of these are present, “it's a sign that the lesion is aggressive and needs to be treated quickly and with great care.”

The first indicator of a bad lesion is that it is new and has developed rapidly within a short period. “Often, someone will come in with a squame that has been sitting there literally for years without changing much, and it could probably sit there for another year without causing a problem,” said Dr. Goldman. “It's the person who just noticed this thing a few weeks ago, and since then it has grown and changed daily, that you have to worry about.”

Also of concern is the patient who “is experiencing true neuropathic pain—not just the type of pain caused by a squame that feels like a screw if you put pressure on it—but the dull, searing neuropathic pain that doesn't go away,” said Dr. Goldman. Such pain could indicate nerve damage from metastases, he noted.

Immunosuppressed patients, such as transplant patients or those with chronic lymphocytic leukemia, who develop squamous cell carcinomas generally require aggressive treatment because their lesions often multiply and enlarge quickly, said Dr. Goldman.

Finally, “old men with squamous cell carcinoma tend to have bad luck with it, particularly if it is on the temple, which is one of the areas at highest risk for metastases,” Dr. Goldman said. “This is fairly well known in the derm community, but it's not written about much in the national literature.”

There also are several telltale indicators that a squamous cell carcinoma is not going to be difficult to cure and doesn't require immediate action. These include lesions that start as a patch or a plaque and those that are slow growing and nontender, Dr. Goldman said. Often, with such growths, “the biopsy itself is the cure,” he said. “More than 60% of the time, the biopsy will have gotten the whole thing. The clinical exam will reveal no residual squamous cell carcinoma, and the pathology will bear this out.”

Although these less serious squamous cell carcinomas do require treatment, “they can easily wait 1 to 2 months before being treated,” Dr. Goldman said.