CCR 12

DESTIN, FLA. – Myopathy that occurs following initiation of statin therapy certainly may result from the drug, but don’t be too quick to rule out other causes.

In one case described by Dr. Robert Wortmann at the Congress of Clinical Rheumatology, the problem was actually profound hypothyroidism.

The 58-year-old patient, a physician who presented with muscle weakness of 6 months’ duration, had started taking a statin 1 month prior as treatment for hyperlipidemia. The patient’s creatine phosphokinase (CPK) values ranged from 1,100 to 1,500 U/L, and both the muscle weakness and CPK elevations persisted at 3 months after discontinuation of the statin.

Statins, as well as fibric acid derivatives and niacin, are important considerations in patients with myopathic symptoms. They can be associated with asymptomatic "hyper-CPK-emia"; transient myalgia and cramps with increased or normal CPK levels; persistent myalgia and cramps or weakness with increased or normal CPK levels; and rhabdomyolysis with myoglobinuria, renal failure, and, when these are unrecognized and untreated, death, said Dr. Wortmann, professor of medicine at Dartmouth Medical School, Lebanon, N.H.

Statin myopathies can occur due to various triggers.

"We know that when you take a statin and interfere with cholesterol synthesis, you can interfere with membrane formation, and this can lead to specific membrane effects and damage and myopathy," he explained, adding that certain genetic polymorphisms – particularly those associated with statin metabolism – also seem to put some people at greater risk for statin myopathies, as does the unmasking of underlying metabolic disorders by statins in some patients.

A particularly interesting statin myopathy is immune-mediated necrotizing myopathy, Dr. Wortmann said.

This potentially painful and debilitating myopathy appears to be associated with anti-HMG CoA reductase antibodies, and it is believed to be immune mediated because it responds to immunosuppressive therapy, he noted.

Patients with this necrotizing myopathy typically require multiple drugs given simultaneously to control the disease.

In the case presented by Dr. Wortmann, however, the problem was much simpler.

"I share this with you because I walked right by this. This was my mistake," he said, explaining that he had arranged for the physician to undergo an electromyogram and muscle biopsy.

"Fortunately, he went and saw his primary care physician again before we could get those done, [who] checked his [thyroid stimulating hormone] and it was way up there. He treated the hypothyroidism, his CPK went back to normal, his muscle symptoms went away, and he was continued on his statin," Dr. Wortmann said.

The most common musculoskeletal manifestation of hypothyroidism is carpal tunnel syndrome, but it can also be associated with sensory or sensorimotor polyneuropathy, asymptomatic hyper-CPK-emia, and myopathy. Myopathy is usually proximal, and may involve myalgias and cramps, with normal or high CPK levels, he noted, adding that although one older case report involved a patient with levels as high as 21,000 U/L, most are in the 700- to 1,200-U/L range.

"So hypothyroidism is a good thing to screen for if you see someone with muscle weakness, because if you pick it up, it’s easy [to manage]," he said. "The take-home message is that just because you see a patient who’s taking a drug [then] experience a side effect that may be found from that drug, it doesn’t mean that’s where it’s coming from."

Dr. Wortmann reported that he had no financial conflicts of interest that were relevant to his presentation.

DESTIN, FLA. – Myopathy that occurs following initiation of statin therapy certainly may result from the drug, but don’t be too quick to rule out other causes.

In one case described by Dr. Robert Wortmann at the Congress of Clinical Rheumatology, the problem was actually profound hypothyroidism.

The 58-year-old patient, a physician who presented with muscle weakness of 6 months’ duration, had started taking a statin 1 month prior as treatment for hyperlipidemia. The patient’s creatine phosphokinase (CPK) values ranged from 1,100 to 1,500 U/L, and both the muscle weakness and CPK elevations persisted at 3 months after discontinuation of the statin.

Statins, as well as fibric acid derivatives and niacin, are important considerations in patients with myopathic symptoms. They can be associated with asymptomatic "hyper-CPK-emia"; transient myalgia and cramps with increased or normal CPK levels; persistent myalgia and cramps or weakness with increased or normal CPK levels; and rhabdomyolysis with myoglobinuria, renal failure, and, when these are unrecognized and untreated, death, said Dr. Wortmann, professor of medicine at Dartmouth Medical School, Lebanon, N.H.

Statin myopathies can occur due to various triggers.

"We know that when you take a statin and interfere with cholesterol synthesis, you can interfere with membrane formation, and this can lead to specific membrane effects and damage and myopathy," he explained, adding that certain genetic polymorphisms – particularly those associated with statin metabolism – also seem to put some people at greater risk for statin myopathies, as does the unmasking of underlying metabolic disorders by statins in some patients.

A particularly interesting statin myopathy is immune-mediated necrotizing myopathy, Dr. Wortmann said.

This potentially painful and debilitating myopathy appears to be associated with anti-HMG CoA reductase antibodies, and it is believed to be immune mediated because it responds to immunosuppressive therapy, he noted.

Patients with this necrotizing myopathy typically require multiple drugs given simultaneously to control the disease.

In the case presented by Dr. Wortmann, however, the problem was much simpler.

"I share this with you because I walked right by this. This was my mistake," he said, explaining that he had arranged for the physician to undergo an electromyogram and muscle biopsy.

"Fortunately, he went and saw his primary care physician again before we could get those done, [who] checked his [thyroid stimulating hormone] and it was way up there. He treated the hypothyroidism, his CPK went back to normal, his muscle symptoms went away, and he was continued on his statin," Dr. Wortmann said.

The most common musculoskeletal manifestation of hypothyroidism is carpal tunnel syndrome, but it can also be associated with sensory or sensorimotor polyneuropathy, asymptomatic hyper-CPK-emia, and myopathy. Myopathy is usually proximal, and may involve myalgias and cramps, with normal or high CPK levels, he noted, adding that although one older case report involved a patient with levels as high as 21,000 U/L, most are in the 700- to 1,200-U/L range.

"So hypothyroidism is a good thing to screen for if you see someone with muscle weakness, because if you pick it up, it’s easy [to manage]," he said. "The take-home message is that just because you see a patient who’s taking a drug [then] experience a side effect that may be found from that drug, it doesn’t mean that’s where it’s coming from."

Dr. Wortmann reported that he had no financial conflicts of interest that were relevant to his presentation.

DESTIN, FLA. – Myopathy that occurs following initiation of statin therapy certainly may result from the drug, but don’t be too quick to rule out other causes.

In one case described by Dr. Robert Wortmann at the Congress of Clinical Rheumatology, the problem was actually profound hypothyroidism.

The 58-year-old patient, a physician who presented with muscle weakness of 6 months’ duration, had started taking a statin 1 month prior as treatment for hyperlipidemia. The patient’s creatine phosphokinase (CPK) values ranged from 1,100 to 1,500 U/L, and both the muscle weakness and CPK elevations persisted at 3 months after discontinuation of the statin.

Statins, as well as fibric acid derivatives and niacin, are important considerations in patients with myopathic symptoms. They can be associated with asymptomatic "hyper-CPK-emia"; transient myalgia and cramps with increased or normal CPK levels; persistent myalgia and cramps or weakness with increased or normal CPK levels; and rhabdomyolysis with myoglobinuria, renal failure, and, when these are unrecognized and untreated, death, said Dr. Wortmann, professor of medicine at Dartmouth Medical School, Lebanon, N.H.

Statin myopathies can occur due to various triggers.

"We know that when you take a statin and interfere with cholesterol synthesis, you can interfere with membrane formation, and this can lead to specific membrane effects and damage and myopathy," he explained, adding that certain genetic polymorphisms – particularly those associated with statin metabolism – also seem to put some people at greater risk for statin myopathies, as does the unmasking of underlying metabolic disorders by statins in some patients.

A particularly interesting statin myopathy is immune-mediated necrotizing myopathy, Dr. Wortmann said.

This potentially painful and debilitating myopathy appears to be associated with anti-HMG CoA reductase antibodies, and it is believed to be immune mediated because it responds to immunosuppressive therapy, he noted.

Patients with this necrotizing myopathy typically require multiple drugs given simultaneously to control the disease.

In the case presented by Dr. Wortmann, however, the problem was much simpler.

"I share this with you because I walked right by this. This was my mistake," he said, explaining that he had arranged for the physician to undergo an electromyogram and muscle biopsy.

"Fortunately, he went and saw his primary care physician again before we could get those done, [who] checked his [thyroid stimulating hormone] and it was way up there. He treated the hypothyroidism, his CPK went back to normal, his muscle symptoms went away, and he was continued on his statin," Dr. Wortmann said.

The most common musculoskeletal manifestation of hypothyroidism is carpal tunnel syndrome, but it can also be associated with sensory or sensorimotor polyneuropathy, asymptomatic hyper-CPK-emia, and myopathy. Myopathy is usually proximal, and may involve myalgias and cramps, with normal or high CPK levels, he noted, adding that although one older case report involved a patient with levels as high as 21,000 U/L, most are in the 700- to 1,200-U/L range.

"So hypothyroidism is a good thing to screen for if you see someone with muscle weakness, because if you pick it up, it’s easy [to manage]," he said. "The take-home message is that just because you see a patient who’s taking a drug [then] experience a side effect that may be found from that drug, it doesn’t mean that’s where it’s coming from."

Dr. Wortmann reported that he had no financial conflicts of interest that were relevant to his presentation.

DESTIN, FLA. – An increasing number of patients are presenting with muscular dystrophy in adulthood.

"We’re now finding more and more patients who are presenting with muscular dystrophy [and] becoming symptomatic in adulthood, not just at age 20, but even at age 30, 40, or 50 years old," Dr. Robert Wortmann said at the Congress of Clinical Rheumatology.

In one case, a patient was diagnosed with a limb-girdle muscular dystrophy at 82 years of age, said Dr. Wortmann, professor of medicine at Dartmouth Medical School, Lebanon, N.H.

"So these are more common, more prevalent, and we’re learning a lot more about this disease," he added.

As an example, Dr. Wortmann presented one case involving a 20-year-old Brazilian exchange student with a 6-month history of progressive proximal muscle weakness. She had creatine phosphokinase (CPK) values that ranged between 20 and 60 times the upper limit of normal; a muscle biopsy showed lymphocytic inflammation. Corticosteroid and methotrexate treatment did not improve her condition.

She was found to have an autosomal recessive limb-girdle muscular dystrophy associated with dysferlin deficiency (limb-girdle muscular dystrophy type 2B, or LGMD2B). Dysferlin is one of the most common proteins to be deficient in this type of muscular dystrophy, Dr. Wortmann said.

Characteristics of LGMD2B include symmetric proximal myopathy, onset at 11-48 years of age (which has been expanded from an earlier identified range of late teens to early 20s), and very high CPK levels.

Caused by genetic defects in muscle cell proteins, muscular dystrophies are typically characterized by proximal muscle weakness, and later by muscle wasting. Early on in dystrophy, histology will look very similar to that of polymyositis.

"It may not be as profound a lymphocytic infiltrate, but it’s the same cells and the same distribution within the tissue," he said.

In fact, about 30% of cases in one series were first diagnosed with polymyositis, he said, noting that patients may even have some response to steroids.

Over time, however, this inflammation tends to decrease, and the muscle wastes and is replaced by fibrous tissue and fat," he said.

The muscle wasting represents an important distinction between polymyositis and muscular dystrophies, noted Dr. Wortmann.

The roles of various proteins in the associated genetic abnormalities continue to be defined, and limb-girdle muscular dystrophy is now considered to have 7 different autosomal dominant forms with different gene mutations, and 11 autosomal recessive forms that affect different structured proteins in the muscle and result in the identical presentation to polymyositis – including the LGMD2B disease identified in the case patient.

Not all patients with limb-girdle muscular dystrophy present with proximal myopathy, however.

In some cases, Miyoshi myopathy occurs, which is distal, late-onset myopathy. In other cases, there is mixed proximal and distal myopathy, he said.

"One thing I don’t understand – and I hope we learn some day why – is that some genetic disease that affects muscle will cause one phenotypic expression in one patient, and the same genetic defect in another patient will cause a different presentation," Dr. Wortmann said, adding that those that first appear to be polymyositis are generally the cases referred to rheumatologists and those with distal myopathy are generally those referred to neurologists.

Dr. Wortmann disclosed a financial relationship with Questcor.

DESTIN, FLA. – An increasing number of patients are presenting with muscular dystrophy in adulthood.

"We’re now finding more and more patients who are presenting with muscular dystrophy [and] becoming symptomatic in adulthood, not just at age 20, but even at age 30, 40, or 50 years old," Dr. Robert Wortmann said at the Congress of Clinical Rheumatology.

In one case, a patient was diagnosed with a limb-girdle muscular dystrophy at 82 years of age, said Dr. Wortmann, professor of medicine at Dartmouth Medical School, Lebanon, N.H.

"So these are more common, more prevalent, and we’re learning a lot more about this disease," he added.

As an example, Dr. Wortmann presented one case involving a 20-year-old Brazilian exchange student with a 6-month history of progressive proximal muscle weakness. She had creatine phosphokinase (CPK) values that ranged between 20 and 60 times the upper limit of normal; a muscle biopsy showed lymphocytic inflammation. Corticosteroid and methotrexate treatment did not improve her condition.

She was found to have an autosomal recessive limb-girdle muscular dystrophy associated with dysferlin deficiency (limb-girdle muscular dystrophy type 2B, or LGMD2B). Dysferlin is one of the most common proteins to be deficient in this type of muscular dystrophy, Dr. Wortmann said.

Characteristics of LGMD2B include symmetric proximal myopathy, onset at 11-48 years of age (which has been expanded from an earlier identified range of late teens to early 20s), and very high CPK levels.

Caused by genetic defects in muscle cell proteins, muscular dystrophies are typically characterized by proximal muscle weakness, and later by muscle wasting. Early on in dystrophy, histology will look very similar to that of polymyositis.

"It may not be as profound a lymphocytic infiltrate, but it’s the same cells and the same distribution within the tissue," he said.

In fact, about 30% of cases in one series were first diagnosed with polymyositis, he said, noting that patients may even have some response to steroids.

Over time, however, this inflammation tends to decrease, and the muscle wastes and is replaced by fibrous tissue and fat," he said.

The muscle wasting represents an important distinction between polymyositis and muscular dystrophies, noted Dr. Wortmann.

The roles of various proteins in the associated genetic abnormalities continue to be defined, and limb-girdle muscular dystrophy is now considered to have 7 different autosomal dominant forms with different gene mutations, and 11 autosomal recessive forms that affect different structured proteins in the muscle and result in the identical presentation to polymyositis – including the LGMD2B disease identified in the case patient.

Not all patients with limb-girdle muscular dystrophy present with proximal myopathy, however.

In some cases, Miyoshi myopathy occurs, which is distal, late-onset myopathy. In other cases, there is mixed proximal and distal myopathy, he said.

"One thing I don’t understand – and I hope we learn some day why – is that some genetic disease that affects muscle will cause one phenotypic expression in one patient, and the same genetic defect in another patient will cause a different presentation," Dr. Wortmann said, adding that those that first appear to be polymyositis are generally the cases referred to rheumatologists and those with distal myopathy are generally those referred to neurologists.

Dr. Wortmann disclosed a financial relationship with Questcor.

DESTIN, FLA. – An increasing number of patients are presenting with muscular dystrophy in adulthood.

"We’re now finding more and more patients who are presenting with muscular dystrophy [and] becoming symptomatic in adulthood, not just at age 20, but even at age 30, 40, or 50 years old," Dr. Robert Wortmann said at the Congress of Clinical Rheumatology.

In one case, a patient was diagnosed with a limb-girdle muscular dystrophy at 82 years of age, said Dr. Wortmann, professor of medicine at Dartmouth Medical School, Lebanon, N.H.

"So these are more common, more prevalent, and we’re learning a lot more about this disease," he added.

As an example, Dr. Wortmann presented one case involving a 20-year-old Brazilian exchange student with a 6-month history of progressive proximal muscle weakness. She had creatine phosphokinase (CPK) values that ranged between 20 and 60 times the upper limit of normal; a muscle biopsy showed lymphocytic inflammation. Corticosteroid and methotrexate treatment did not improve her condition.

She was found to have an autosomal recessive limb-girdle muscular dystrophy associated with dysferlin deficiency (limb-girdle muscular dystrophy type 2B, or LGMD2B). Dysferlin is one of the most common proteins to be deficient in this type of muscular dystrophy, Dr. Wortmann said.

Characteristics of LGMD2B include symmetric proximal myopathy, onset at 11-48 years of age (which has been expanded from an earlier identified range of late teens to early 20s), and very high CPK levels.

Caused by genetic defects in muscle cell proteins, muscular dystrophies are typically characterized by proximal muscle weakness, and later by muscle wasting. Early on in dystrophy, histology will look very similar to that of polymyositis.

"It may not be as profound a lymphocytic infiltrate, but it’s the same cells and the same distribution within the tissue," he said.

In fact, about 30% of cases in one series were first diagnosed with polymyositis, he said, noting that patients may even have some response to steroids.

Over time, however, this inflammation tends to decrease, and the muscle wastes and is replaced by fibrous tissue and fat," he said.

The muscle wasting represents an important distinction between polymyositis and muscular dystrophies, noted Dr. Wortmann.

The roles of various proteins in the associated genetic abnormalities continue to be defined, and limb-girdle muscular dystrophy is now considered to have 7 different autosomal dominant forms with different gene mutations, and 11 autosomal recessive forms that affect different structured proteins in the muscle and result in the identical presentation to polymyositis – including the LGMD2B disease identified in the case patient.

Not all patients with limb-girdle muscular dystrophy present with proximal myopathy, however.

In some cases, Miyoshi myopathy occurs, which is distal, late-onset myopathy. In other cases, there is mixed proximal and distal myopathy, he said.

"One thing I don’t understand – and I hope we learn some day why – is that some genetic disease that affects muscle will cause one phenotypic expression in one patient, and the same genetic defect in another patient will cause a different presentation," Dr. Wortmann said, adding that those that first appear to be polymyositis are generally the cases referred to rheumatologists and those with distal myopathy are generally those referred to neurologists.

Dr. Wortmann disclosed a financial relationship with Questcor.

SAN DESTIN, FLA. – Many patients with mixed connective tissue disease may represent a subset of systemic scleroderma, rather than a disease involving overlapping connective tissue disorders as is commonly believed, or a subset of lupus as some have suggested over the years, Dr. Virginia Steen said at the Congress of Clinical Rheumatology.

Several factors associated with clinical presentation support this argument, said Dr. Steen, professor of medicine at Georgetown University in Washington.

Nail Fold Capillaries/Digital Ulcers

For example, data from a study of nail fold capillary abnormalities in mixed connective tissue disease (MCTD) showed that the abnormalities took a sclerodermatous pattern in 64% of 22 patients, compared with a systemic lupus erythematosus (SLE) pattern in 23%, and a nonspecific pattern in 14%, she said.

Compared with typical findings in SLE, there was significantly greater capillary loss, and more of the bushy capillary formations seen in scleroderma.

"So it did tend to be more scleroderma-like, and this is particularly important, because we do see a lot of MCTD patients who have digital ulcers," she said. In most cases, the ulcers are ischemic and are caused by vascular changes similar to scleroderma, rather than due to a lupus vasculitis, she added.

Arthritis/Joint Involvement

Arthritis in MCTD also has different characteristics than arthritis seen in lupus, and more similarities to scleroderma. The arthritis in MCTD tends to be erosive, unlike arthritis seen in SLE, and it tends to be small, marginal, and asymmetric, occurring in the wrists and fingers. Other musculoskeletal features similar to those in scleroderma include calcinosis, distal tuft resorption, and acro-osteolysis.

Although MCTD patients do tend to get Jaccoud’s subluxation, much as SLE patients do, this occurs to a lesser extent than in lupus, and the frequency of cyclic citrullinated peptides is low as well (9% in one study).

"Hand arthritis is often quite mixed," Dr. Steen said.

Muscle Involvement

Muscle involvement is rarely the presenting feature in MCTD, but it is usually present in early disease, and although the perivascular and endomysial inflammation is more typical of dermatomyositis, there tends to not be a lot of skin involvement associated with this.

Furthermore, there is an increase in the thickness of vessel walls, which is fairly unique, and the immunochemical profile in these cases differs from what is typically seen with myositis in that creatine phosphokinase levels are lower, Dr. Steen said.

Also, the effects on muscle tend to be milder in MCTD, with some patients experiencing no symptoms, and it may not progress.

Skin Involvement

Skin involvement patterns also indicate that MCTD is actually a scleroderma subset. Skin involvement is much less common in MCTD than in SLE.

"It’s a lupuslike skin disease similar to subacute cutaneous lupus, but it also has vascular ectasia, hypovascularity, or luminal occlusion of the vessels, so it’s a little bit atypical," Dr. Steen said.

Also, lupus band test positivity is uncommon, and the most common skin manifestations are more scleroderma-like, with puffy fingers and sclerodactyly, she added. Patients with skin involvement usually have limited scleroderma, but about 20% go on to develop diffuse cutaneous scleroderma.

Gastrointestinal Involvement

Providing more evidence is the fact that esophageal involvement and the very severe small bowel dysmotility commonly seen in MCTD are identical to those seen in scleroderma, Dr. Steen said.

"There doesn’t seem to be any difference in the pattern, and as in scleroderma, it doesn’t respond to steroids or immunosuppressants. You really just have to treat it symptomatically," she noted.

Interstitial Lung Disease

Interstitial lung disease is a more challenging area, according to Dr. Steen. It is common in patients diagnosed with MCTD, but there is a lack of prospective study data. In a 2010 study, 66% of 144 patients with very early nonspecific interstitial pneumonitis (NSIP) were treated with steroids; 50% responded, and 50% went on to develop more severe and progressive fibrosis requiring immunosuppressive therapy.

"So there wasn’t a clear pattern where you would think this was a unique type of inflammatory interstitial pneumonitis that is clearly steroid responsive like some of the NSIPs that aren’t associated with connective tissues disease are. There is more fibrosis, and it does seem to be more typically scleroderma related than an independent type of lung disease," she said.

Pulmonary Hypertension

Pulmonary hypertension is one of the biggest challenges in MCTD, Dr. Steen said. Several studies have shown a significant association with pulmonary hypertension and mortality in these patients.

A small study of MCTD patients showed a large decrease in the DLCO (diffusing capacity of the lung for carbon monoxide), she said. Some of these patients had increased pulmonary artery pressure, and there were seven patients who actually had pulmonary arterial hypertension. The available autopsies revealed that the patients tended to have pretty typical pulmonary arteriolopathy, similar to what we see in scleroderma, with a striking intimal proliferation of the vasculature, she said.

Also, as in scleroderma, the pulmonary vessels – even in patients who didn’t have pulmonary hypertension – had similar but less extensive disease, she added.

Based on these various findings, which together show a great deal of similarity to scleroderma while highlighting numerous differences from other connective tissue diseases, Dr. Steen said she is increasingly convinced that MCTD is not a unique entity, mixed disease, or subset of lupus, but is actually a subset of systemic scleroderma.

Dr. Steen reported having no disclosures relevant to her presentation.

SAN DESTIN, FLA. – Many patients with mixed connective tissue disease may represent a subset of systemic scleroderma, rather than a disease involving overlapping connective tissue disorders as is commonly believed, or a subset of lupus as some have suggested over the years, Dr. Virginia Steen said at the Congress of Clinical Rheumatology.

Several factors associated with clinical presentation support this argument, said Dr. Steen, professor of medicine at Georgetown University in Washington.

Nail Fold Capillaries/Digital Ulcers

For example, data from a study of nail fold capillary abnormalities in mixed connective tissue disease (MCTD) showed that the abnormalities took a sclerodermatous pattern in 64% of 22 patients, compared with a systemic lupus erythematosus (SLE) pattern in 23%, and a nonspecific pattern in 14%, she said.

Compared with typical findings in SLE, there was significantly greater capillary loss, and more of the bushy capillary formations seen in scleroderma.

"So it did tend to be more scleroderma-like, and this is particularly important, because we do see a lot of MCTD patients who have digital ulcers," she said. In most cases, the ulcers are ischemic and are caused by vascular changes similar to scleroderma, rather than due to a lupus vasculitis, she added.

Arthritis/Joint Involvement

Arthritis in MCTD also has different characteristics than arthritis seen in lupus, and more similarities to scleroderma. The arthritis in MCTD tends to be erosive, unlike arthritis seen in SLE, and it tends to be small, marginal, and asymmetric, occurring in the wrists and fingers. Other musculoskeletal features similar to those in scleroderma include calcinosis, distal tuft resorption, and acro-osteolysis.

Although MCTD patients do tend to get Jaccoud’s subluxation, much as SLE patients do, this occurs to a lesser extent than in lupus, and the frequency of cyclic citrullinated peptides is low as well (9% in one study).

"Hand arthritis is often quite mixed," Dr. Steen said.

Muscle Involvement

Muscle involvement is rarely the presenting feature in MCTD, but it is usually present in early disease, and although the perivascular and endomysial inflammation is more typical of dermatomyositis, there tends to not be a lot of skin involvement associated with this.

Furthermore, there is an increase in the thickness of vessel walls, which is fairly unique, and the immunochemical profile in these cases differs from what is typically seen with myositis in that creatine phosphokinase levels are lower, Dr. Steen said.

Also, the effects on muscle tend to be milder in MCTD, with some patients experiencing no symptoms, and it may not progress.

Skin Involvement

Skin involvement patterns also indicate that MCTD is actually a scleroderma subset. Skin involvement is much less common in MCTD than in SLE.

"It’s a lupuslike skin disease similar to subacute cutaneous lupus, but it also has vascular ectasia, hypovascularity, or luminal occlusion of the vessels, so it’s a little bit atypical," Dr. Steen said.

Also, lupus band test positivity is uncommon, and the most common skin manifestations are more scleroderma-like, with puffy fingers and sclerodactyly, she added. Patients with skin involvement usually have limited scleroderma, but about 20% go on to develop diffuse cutaneous scleroderma.

Gastrointestinal Involvement

Providing more evidence is the fact that esophageal involvement and the very severe small bowel dysmotility commonly seen in MCTD are identical to those seen in scleroderma, Dr. Steen said.

"There doesn’t seem to be any difference in the pattern, and as in scleroderma, it doesn’t respond to steroids or immunosuppressants. You really just have to treat it symptomatically," she noted.

Interstitial Lung Disease

Interstitial lung disease is a more challenging area, according to Dr. Steen. It is common in patients diagnosed with MCTD, but there is a lack of prospective study data. In a 2010 study, 66% of 144 patients with very early nonspecific interstitial pneumonitis (NSIP) were treated with steroids; 50% responded, and 50% went on to develop more severe and progressive fibrosis requiring immunosuppressive therapy.

"So there wasn’t a clear pattern where you would think this was a unique type of inflammatory interstitial pneumonitis that is clearly steroid responsive like some of the NSIPs that aren’t associated with connective tissues disease are. There is more fibrosis, and it does seem to be more typically scleroderma related than an independent type of lung disease," she said.

Pulmonary Hypertension

Pulmonary hypertension is one of the biggest challenges in MCTD, Dr. Steen said. Several studies have shown a significant association with pulmonary hypertension and mortality in these patients.

A small study of MCTD patients showed a large decrease in the DLCO (diffusing capacity of the lung for carbon monoxide), she said. Some of these patients had increased pulmonary artery pressure, and there were seven patients who actually had pulmonary arterial hypertension. The available autopsies revealed that the patients tended to have pretty typical pulmonary arteriolopathy, similar to what we see in scleroderma, with a striking intimal proliferation of the vasculature, she said.

Also, as in scleroderma, the pulmonary vessels – even in patients who didn’t have pulmonary hypertension – had similar but less extensive disease, she added.

Based on these various findings, which together show a great deal of similarity to scleroderma while highlighting numerous differences from other connective tissue diseases, Dr. Steen said she is increasingly convinced that MCTD is not a unique entity, mixed disease, or subset of lupus, but is actually a subset of systemic scleroderma.

Dr. Steen reported having no disclosures relevant to her presentation.

SAN DESTIN, FLA. – Many patients with mixed connective tissue disease may represent a subset of systemic scleroderma, rather than a disease involving overlapping connective tissue disorders as is commonly believed, or a subset of lupus as some have suggested over the years, Dr. Virginia Steen said at the Congress of Clinical Rheumatology.

Several factors associated with clinical presentation support this argument, said Dr. Steen, professor of medicine at Georgetown University in Washington.

Nail Fold Capillaries/Digital Ulcers

For example, data from a study of nail fold capillary abnormalities in mixed connective tissue disease (MCTD) showed that the abnormalities took a sclerodermatous pattern in 64% of 22 patients, compared with a systemic lupus erythematosus (SLE) pattern in 23%, and a nonspecific pattern in 14%, she said.

Compared with typical findings in SLE, there was significantly greater capillary loss, and more of the bushy capillary formations seen in scleroderma.

"So it did tend to be more scleroderma-like, and this is particularly important, because we do see a lot of MCTD patients who have digital ulcers," she said. In most cases, the ulcers are ischemic and are caused by vascular changes similar to scleroderma, rather than due to a lupus vasculitis, she added.

Arthritis/Joint Involvement

Arthritis in MCTD also has different characteristics than arthritis seen in lupus, and more similarities to scleroderma. The arthritis in MCTD tends to be erosive, unlike arthritis seen in SLE, and it tends to be small, marginal, and asymmetric, occurring in the wrists and fingers. Other musculoskeletal features similar to those in scleroderma include calcinosis, distal tuft resorption, and acro-osteolysis.

Although MCTD patients do tend to get Jaccoud’s subluxation, much as SLE patients do, this occurs to a lesser extent than in lupus, and the frequency of cyclic citrullinated peptides is low as well (9% in one study).

"Hand arthritis is often quite mixed," Dr. Steen said.

Muscle Involvement

Muscle involvement is rarely the presenting feature in MCTD, but it is usually present in early disease, and although the perivascular and endomysial inflammation is more typical of dermatomyositis, there tends to not be a lot of skin involvement associated with this.

Furthermore, there is an increase in the thickness of vessel walls, which is fairly unique, and the immunochemical profile in these cases differs from what is typically seen with myositis in that creatine phosphokinase levels are lower, Dr. Steen said.

Also, the effects on muscle tend to be milder in MCTD, with some patients experiencing no symptoms, and it may not progress.

Skin Involvement

Skin involvement patterns also indicate that MCTD is actually a scleroderma subset. Skin involvement is much less common in MCTD than in SLE.

"It’s a lupuslike skin disease similar to subacute cutaneous lupus, but it also has vascular ectasia, hypovascularity, or luminal occlusion of the vessels, so it’s a little bit atypical," Dr. Steen said.

Also, lupus band test positivity is uncommon, and the most common skin manifestations are more scleroderma-like, with puffy fingers and sclerodactyly, she added. Patients with skin involvement usually have limited scleroderma, but about 20% go on to develop diffuse cutaneous scleroderma.

Gastrointestinal Involvement

Providing more evidence is the fact that esophageal involvement and the very severe small bowel dysmotility commonly seen in MCTD are identical to those seen in scleroderma, Dr. Steen said.

"There doesn’t seem to be any difference in the pattern, and as in scleroderma, it doesn’t respond to steroids or immunosuppressants. You really just have to treat it symptomatically," she noted.

Interstitial Lung Disease

Interstitial lung disease is a more challenging area, according to Dr. Steen. It is common in patients diagnosed with MCTD, but there is a lack of prospective study data. In a 2010 study, 66% of 144 patients with very early nonspecific interstitial pneumonitis (NSIP) were treated with steroids; 50% responded, and 50% went on to develop more severe and progressive fibrosis requiring immunosuppressive therapy.

"So there wasn’t a clear pattern where you would think this was a unique type of inflammatory interstitial pneumonitis that is clearly steroid responsive like some of the NSIPs that aren’t associated with connective tissues disease are. There is more fibrosis, and it does seem to be more typically scleroderma related than an independent type of lung disease," she said.

Pulmonary Hypertension

Pulmonary hypertension is one of the biggest challenges in MCTD, Dr. Steen said. Several studies have shown a significant association with pulmonary hypertension and mortality in these patients.

A small study of MCTD patients showed a large decrease in the DLCO (diffusing capacity of the lung for carbon monoxide), she said. Some of these patients had increased pulmonary artery pressure, and there were seven patients who actually had pulmonary arterial hypertension. The available autopsies revealed that the patients tended to have pretty typical pulmonary arteriolopathy, similar to what we see in scleroderma, with a striking intimal proliferation of the vasculature, she said.

Also, as in scleroderma, the pulmonary vessels – even in patients who didn’t have pulmonary hypertension – had similar but less extensive disease, she added.

Based on these various findings, which together show a great deal of similarity to scleroderma while highlighting numerous differences from other connective tissue diseases, Dr. Steen said she is increasingly convinced that MCTD is not a unique entity, mixed disease, or subset of lupus, but is actually a subset of systemic scleroderma.

Dr. Steen reported having no disclosures relevant to her presentation.

DESTIN, FLA. – A 2010 study by Dr. Anna-Luise A. Katzenstein and her colleagues was the first to show that interstitial fibrosis is remarkably common and often severe in cigarette smokers, including those with no clinical evidence of interstitial lung disease.

Pathologic specimens showed that interstitial fibrosis occurred in 12 of 20 smokers (60%) but in none of 3 nonsmokers; three of the smokers with fibrosis had well-defined smoking-related disorders such as respiratory bronchiolitis–interstitial lung disease (RB-ILD), but 9 had pathology showing more than 10% fibrosis on their lung biopsies (Hum. Pathol. 2010;41:316-25). They were considered to have smoking-related interstitial lung disease, Dr. David Moller said at the Congress of Clinical Rheumatology.

"More recently this has been described as [combined pulmonary fibrosis and emphysema, or CPFE syndrome], and it’s largely with the advent of high resolution computed tomography scanning that it has been appreciated how common fibrosis is in association with emphysema," said Dr. Moller, professor of medicine and director of the sarcoidosis clinic at Johns Hopkins University, Baltimore.

Typically, patients with CPFE syndrome have upper-lobe emphysema and lower-lobe fibrosis, he said.

"Because of that, you can get relatively normalized lung volumes and spirometry, but what characterizes these patients is a severe reduction in diffusing capacity. This is often associated with a pulmonary hypertension, which can be a major determinant of survival," he added.

CPFE syndrome is more common in males than females, and is found in 19%-51% of smokers with emphysema on chest CT who have no defined underlying interstitial lung disease. On biopsy, a number of pathological patterns may be seen, including usual interstitial pneumonitis (UIP), nonspecific interstitial pneumonia, and RB-ILD, Dr. Moller said.

Mortality is increased in patients with this syndrome, compared with those who smoke and have chronic obstructive pulmonary disease, and survival ranges from 35% to 80% at 5 years, he added, noting that the mortality rate is unclear in patients who may have underlying idiopathic pulmonary fibrosis.

The syndrome is strongly associated with smoking but is also associated with lung cancer, asbestos and mineral dust exposures, and pulmonary hypertension. A 2011 study demonstrated that CPFE is also associated with connective tissue disease.

In that retrospective study of 34 patients with both connective tissue disease and CPFE syndrome who were followed for about 8 years, 18 had rheumatoid arthritis, 10 had systemic sclerosis, 2 had mixed connective tissues disease, 2 had overlapping connective tissue disease, 1 had Sjögren’s syndrome, and 1 had polymyositis.

High resolution CT showed emphysema of the upper lobes of the lungs and pulmonary fibrosis of the lower lobes in all patients, and all experienced dyspnea during exercise. Pulmonary hypertension was present in five of the systemic sclerosis patients, and four of these patients died during follow-up (Arthritis Rheum. 2011;63:295-304).

The patients in this study were significantly younger than a historical control group of patients with idiopathic CPFE syndrome, and were more frequently female than male, Dr. Moller noted.

Compared with patients with connective tissue disease and lung fibrosis without emphysema, however, the study patients with connective tissue disease and CPFE had higher lung volumes, lower diffusion capacity, higher pulmonary pressures and were more frequently male than female.

There was also some suggestion that those with connective tissue disease and CPFE syndrome may have less severe outcomes than did those with idiopathic CPFE syndrome, but again, pulmonary hypertension is the key to the clinical course, Dr. Moller said.

The authors of this study concluded that CPFE syndrome should be included as a novel, distinct pulmonary manifestation within the spectrum of connective tissue disease–associated lung diseases in smokers and former smokers – particularly those with rheumatoid arthritis or systemic sclerosis.

Treatment for CPFE syndrome includes smoking cessation and treating the underlying cause when it is apparent, Dr. Moller said.

Dr. Moller reported having no financial disclosures.

DESTIN, FLA. – A 2010 study by Dr. Anna-Luise A. Katzenstein and her colleagues was the first to show that interstitial fibrosis is remarkably common and often severe in cigarette smokers, including those with no clinical evidence of interstitial lung disease.

Pathologic specimens showed that interstitial fibrosis occurred in 12 of 20 smokers (60%) but in none of 3 nonsmokers; three of the smokers with fibrosis had well-defined smoking-related disorders such as respiratory bronchiolitis–interstitial lung disease (RB-ILD), but 9 had pathology showing more than 10% fibrosis on their lung biopsies (Hum. Pathol. 2010;41:316-25). They were considered to have smoking-related interstitial lung disease, Dr. David Moller said at the Congress of Clinical Rheumatology.

"More recently this has been described as [combined pulmonary fibrosis and emphysema, or CPFE syndrome], and it’s largely with the advent of high resolution computed tomography scanning that it has been appreciated how common fibrosis is in association with emphysema," said Dr. Moller, professor of medicine and director of the sarcoidosis clinic at Johns Hopkins University, Baltimore.

Typically, patients with CPFE syndrome have upper-lobe emphysema and lower-lobe fibrosis, he said.

"Because of that, you can get relatively normalized lung volumes and spirometry, but what characterizes these patients is a severe reduction in diffusing capacity. This is often associated with a pulmonary hypertension, which can be a major determinant of survival," he added.

CPFE syndrome is more common in males than females, and is found in 19%-51% of smokers with emphysema on chest CT who have no defined underlying interstitial lung disease. On biopsy, a number of pathological patterns may be seen, including usual interstitial pneumonitis (UIP), nonspecific interstitial pneumonia, and RB-ILD, Dr. Moller said.

Mortality is increased in patients with this syndrome, compared with those who smoke and have chronic obstructive pulmonary disease, and survival ranges from 35% to 80% at 5 years, he added, noting that the mortality rate is unclear in patients who may have underlying idiopathic pulmonary fibrosis.

The syndrome is strongly associated with smoking but is also associated with lung cancer, asbestos and mineral dust exposures, and pulmonary hypertension. A 2011 study demonstrated that CPFE is also associated with connective tissue disease.

In that retrospective study of 34 patients with both connective tissue disease and CPFE syndrome who were followed for about 8 years, 18 had rheumatoid arthritis, 10 had systemic sclerosis, 2 had mixed connective tissues disease, 2 had overlapping connective tissue disease, 1 had Sjögren’s syndrome, and 1 had polymyositis.

High resolution CT showed emphysema of the upper lobes of the lungs and pulmonary fibrosis of the lower lobes in all patients, and all experienced dyspnea during exercise. Pulmonary hypertension was present in five of the systemic sclerosis patients, and four of these patients died during follow-up (Arthritis Rheum. 2011;63:295-304).

The patients in this study were significantly younger than a historical control group of patients with idiopathic CPFE syndrome, and were more frequently female than male, Dr. Moller noted.

Compared with patients with connective tissue disease and lung fibrosis without emphysema, however, the study patients with connective tissue disease and CPFE had higher lung volumes, lower diffusion capacity, higher pulmonary pressures and were more frequently male than female.

There was also some suggestion that those with connective tissue disease and CPFE syndrome may have less severe outcomes than did those with idiopathic CPFE syndrome, but again, pulmonary hypertension is the key to the clinical course, Dr. Moller said.

The authors of this study concluded that CPFE syndrome should be included as a novel, distinct pulmonary manifestation within the spectrum of connective tissue disease–associated lung diseases in smokers and former smokers – particularly those with rheumatoid arthritis or systemic sclerosis.

Treatment for CPFE syndrome includes smoking cessation and treating the underlying cause when it is apparent, Dr. Moller said.

Dr. Moller reported having no financial disclosures.

DESTIN, FLA. – A 2010 study by Dr. Anna-Luise A. Katzenstein and her colleagues was the first to show that interstitial fibrosis is remarkably common and often severe in cigarette smokers, including those with no clinical evidence of interstitial lung disease.

Pathologic specimens showed that interstitial fibrosis occurred in 12 of 20 smokers (60%) but in none of 3 nonsmokers; three of the smokers with fibrosis had well-defined smoking-related disorders such as respiratory bronchiolitis–interstitial lung disease (RB-ILD), but 9 had pathology showing more than 10% fibrosis on their lung biopsies (Hum. Pathol. 2010;41:316-25). They were considered to have smoking-related interstitial lung disease, Dr. David Moller said at the Congress of Clinical Rheumatology.

"More recently this has been described as [combined pulmonary fibrosis and emphysema, or CPFE syndrome], and it’s largely with the advent of high resolution computed tomography scanning that it has been appreciated how common fibrosis is in association with emphysema," said Dr. Moller, professor of medicine and director of the sarcoidosis clinic at Johns Hopkins University, Baltimore.

Typically, patients with CPFE syndrome have upper-lobe emphysema and lower-lobe fibrosis, he said.

"Because of that, you can get relatively normalized lung volumes and spirometry, but what characterizes these patients is a severe reduction in diffusing capacity. This is often associated with a pulmonary hypertension, which can be a major determinant of survival," he added.

CPFE syndrome is more common in males than females, and is found in 19%-51% of smokers with emphysema on chest CT who have no defined underlying interstitial lung disease. On biopsy, a number of pathological patterns may be seen, including usual interstitial pneumonitis (UIP), nonspecific interstitial pneumonia, and RB-ILD, Dr. Moller said.

Mortality is increased in patients with this syndrome, compared with those who smoke and have chronic obstructive pulmonary disease, and survival ranges from 35% to 80% at 5 years, he added, noting that the mortality rate is unclear in patients who may have underlying idiopathic pulmonary fibrosis.

The syndrome is strongly associated with smoking but is also associated with lung cancer, asbestos and mineral dust exposures, and pulmonary hypertension. A 2011 study demonstrated that CPFE is also associated with connective tissue disease.

In that retrospective study of 34 patients with both connective tissue disease and CPFE syndrome who were followed for about 8 years, 18 had rheumatoid arthritis, 10 had systemic sclerosis, 2 had mixed connective tissues disease, 2 had overlapping connective tissue disease, 1 had Sjögren’s syndrome, and 1 had polymyositis.

High resolution CT showed emphysema of the upper lobes of the lungs and pulmonary fibrosis of the lower lobes in all patients, and all experienced dyspnea during exercise. Pulmonary hypertension was present in five of the systemic sclerosis patients, and four of these patients died during follow-up (Arthritis Rheum. 2011;63:295-304).

The patients in this study were significantly younger than a historical control group of patients with idiopathic CPFE syndrome, and were more frequently female than male, Dr. Moller noted.

Compared with patients with connective tissue disease and lung fibrosis without emphysema, however, the study patients with connective tissue disease and CPFE had higher lung volumes, lower diffusion capacity, higher pulmonary pressures and were more frequently male than female.

There was also some suggestion that those with connective tissue disease and CPFE syndrome may have less severe outcomes than did those with idiopathic CPFE syndrome, but again, pulmonary hypertension is the key to the clinical course, Dr. Moller said.

The authors of this study concluded that CPFE syndrome should be included as a novel, distinct pulmonary manifestation within the spectrum of connective tissue disease–associated lung diseases in smokers and former smokers – particularly those with rheumatoid arthritis or systemic sclerosis.

Treatment for CPFE syndrome includes smoking cessation and treating the underlying cause when it is apparent, Dr. Moller said.

Dr. Moller reported having no financial disclosures.

SANDESTIN, FLA. – The successful management of severe diffuse skin thickening in scleroderma patients requires early aggressive treatment, including physical therapy, according to Dr. Virginia Steen.

"We don’t have any clear-cut treatment for severe skin disease, but one of the most important things we have to do is aggressive physical therapy – and make sure that they keep moving," Dr. Steen, professor of medicine at Georgetown University, Washington, D.C., said at the Congress of Clinical Rheumatology.

Keeping these patients moving requires that they be provided with adequate analgesia, she added.

A treatment option for those with a great deal of tendon, joint, and muscle involvement (in addition to skin involvement) is methotrexate at 15-25 mg/week, she said, noting that methotrexate is known to be helpful with these aspects of scleroderma, and some additional studies have shown it may be helpful for the skin as well. One randomized, controlled study of 71 patients, for example, showed a slight advantage for methotrexate over placebo for early diffuse scleroderma (Arthritis Rheum. 2001;44:1351-8).

Similarly, mycophenolate (CellCept), which has been shown in multiple open-label studies to be useful for scleroderma patients with lung involvement, also appears to have some beneficial effects on the skin, so consider its use in patients with both lung and skin involvement, Dr. Steen advised.

Cyclophosphamide (Cytoxan) is another drug that may be helpful in those with both lung and skin involvement.

"Cytoxan isn’t very dramatic in the skin, but you certainly may want to use it if you have any lung involvement," she said, noting that the Scleroderma Lung Study demonstrated that it is better than placebo in scleroderma lung disease (Ann. Rheum. Dis. 2007;66:1641-7). "I also still use d-penicillamine," she noted, explaining she prescribes this to patients with just skin involvement who don’t need treatment that is "too aggressive otherwise."

Although the lack of straightforward answers about how to target diffuse skin thickening in scleroderma is frustrating, there is encouraging news on the horizon.

"There are a lot of things at least in the works in terms of antifibrotic processes," Dr. Steen said, explaining that alteration of myocytes and myofibroblasts in animal models has been shown to reverse fibrosis, and work is ongoing.

Protein kinase inhibitors, for example, are of interest, and although the effects are not dramatic, they may have some benefit, except that there was significant toxicity, which led to discontinuation of one study. Other potential therapies involve transforming growth factor–beta antagonists, connective tissue growth factor antagonists, peroxisome proliferator–activated receptor gamma ligands, and interleuken-6 antagonists.

Ongoing work with the anti–IL-6 tocilizumab (Actemra), for example, is showing some intriguing results that could have implications for the treatment of the subset of patients with very high IL-6 leading to a fibrotic signature, Dr. Steen said.

Some preliminary animal model studies of tocilizumab showed that it improves the skin in mice with increased IL-6 and scleroderma and there is now a controlled trial of tocilizumab in early diffuse scleroderma.

"Although, there have only been a few case reports of Actemra in scleroderma, we are excited about its potential as an effective antifibrotic agent in scleroderma," Dr. Steen said in an interview.

Dr. Steen disclosed that she has received grant funding, consulting fees, and/or speaking fees from Actelion, Genentec/Roche , Gilead Pharmaceuticals, Pfizer, and United Therapeutics.

SANDESTIN, FLA. – The successful management of severe diffuse skin thickening in scleroderma patients requires early aggressive treatment, including physical therapy, according to Dr. Virginia Steen.

"We don’t have any clear-cut treatment for severe skin disease, but one of the most important things we have to do is aggressive physical therapy – and make sure that they keep moving," Dr. Steen, professor of medicine at Georgetown University, Washington, D.C., said at the Congress of Clinical Rheumatology.

Keeping these patients moving requires that they be provided with adequate analgesia, she added.

A treatment option for those with a great deal of tendon, joint, and muscle involvement (in addition to skin involvement) is methotrexate at 15-25 mg/week, she said, noting that methotrexate is known to be helpful with these aspects of scleroderma, and some additional studies have shown it may be helpful for the skin as well. One randomized, controlled study of 71 patients, for example, showed a slight advantage for methotrexate over placebo for early diffuse scleroderma (Arthritis Rheum. 2001;44:1351-8).

Similarly, mycophenolate (CellCept), which has been shown in multiple open-label studies to be useful for scleroderma patients with lung involvement, also appears to have some beneficial effects on the skin, so consider its use in patients with both lung and skin involvement, Dr. Steen advised.

Cyclophosphamide (Cytoxan) is another drug that may be helpful in those with both lung and skin involvement.

"Cytoxan isn’t very dramatic in the skin, but you certainly may want to use it if you have any lung involvement," she said, noting that the Scleroderma Lung Study demonstrated that it is better than placebo in scleroderma lung disease (Ann. Rheum. Dis. 2007;66:1641-7). "I also still use d-penicillamine," she noted, explaining she prescribes this to patients with just skin involvement who don’t need treatment that is "too aggressive otherwise."

Although the lack of straightforward answers about how to target diffuse skin thickening in scleroderma is frustrating, there is encouraging news on the horizon.

"There are a lot of things at least in the works in terms of antifibrotic processes," Dr. Steen said, explaining that alteration of myocytes and myofibroblasts in animal models has been shown to reverse fibrosis, and work is ongoing.

Protein kinase inhibitors, for example, are of interest, and although the effects are not dramatic, they may have some benefit, except that there was significant toxicity, which led to discontinuation of one study. Other potential therapies involve transforming growth factor–beta antagonists, connective tissue growth factor antagonists, peroxisome proliferator–activated receptor gamma ligands, and interleuken-6 antagonists.

Ongoing work with the anti–IL-6 tocilizumab (Actemra), for example, is showing some intriguing results that could have implications for the treatment of the subset of patients with very high IL-6 leading to a fibrotic signature, Dr. Steen said.

Some preliminary animal model studies of tocilizumab showed that it improves the skin in mice with increased IL-6 and scleroderma and there is now a controlled trial of tocilizumab in early diffuse scleroderma.

"Although, there have only been a few case reports of Actemra in scleroderma, we are excited about its potential as an effective antifibrotic agent in scleroderma," Dr. Steen said in an interview.

Dr. Steen disclosed that she has received grant funding, consulting fees, and/or speaking fees from Actelion, Genentec/Roche , Gilead Pharmaceuticals, Pfizer, and United Therapeutics.

SANDESTIN, FLA. – The successful management of severe diffuse skin thickening in scleroderma patients requires early aggressive treatment, including physical therapy, according to Dr. Virginia Steen.

"We don’t have any clear-cut treatment for severe skin disease, but one of the most important things we have to do is aggressive physical therapy – and make sure that they keep moving," Dr. Steen, professor of medicine at Georgetown University, Washington, D.C., said at the Congress of Clinical Rheumatology.

Keeping these patients moving requires that they be provided with adequate analgesia, she added.

A treatment option for those with a great deal of tendon, joint, and muscle involvement (in addition to skin involvement) is methotrexate at 15-25 mg/week, she said, noting that methotrexate is known to be helpful with these aspects of scleroderma, and some additional studies have shown it may be helpful for the skin as well. One randomized, controlled study of 71 patients, for example, showed a slight advantage for methotrexate over placebo for early diffuse scleroderma (Arthritis Rheum. 2001;44:1351-8).

Similarly, mycophenolate (CellCept), which has been shown in multiple open-label studies to be useful for scleroderma patients with lung involvement, also appears to have some beneficial effects on the skin, so consider its use in patients with both lung and skin involvement, Dr. Steen advised.

Cyclophosphamide (Cytoxan) is another drug that may be helpful in those with both lung and skin involvement.

"Cytoxan isn’t very dramatic in the skin, but you certainly may want to use it if you have any lung involvement," she said, noting that the Scleroderma Lung Study demonstrated that it is better than placebo in scleroderma lung disease (Ann. Rheum. Dis. 2007;66:1641-7). "I also still use d-penicillamine," she noted, explaining she prescribes this to patients with just skin involvement who don’t need treatment that is "too aggressive otherwise."

Although the lack of straightforward answers about how to target diffuse skin thickening in scleroderma is frustrating, there is encouraging news on the horizon.

"There are a lot of things at least in the works in terms of antifibrotic processes," Dr. Steen said, explaining that alteration of myocytes and myofibroblasts in animal models has been shown to reverse fibrosis, and work is ongoing.

Protein kinase inhibitors, for example, are of interest, and although the effects are not dramatic, they may have some benefit, except that there was significant toxicity, which led to discontinuation of one study. Other potential therapies involve transforming growth factor–beta antagonists, connective tissue growth factor antagonists, peroxisome proliferator–activated receptor gamma ligands, and interleuken-6 antagonists.

Ongoing work with the anti–IL-6 tocilizumab (Actemra), for example, is showing some intriguing results that could have implications for the treatment of the subset of patients with very high IL-6 leading to a fibrotic signature, Dr. Steen said.

Some preliminary animal model studies of tocilizumab showed that it improves the skin in mice with increased IL-6 and scleroderma and there is now a controlled trial of tocilizumab in early diffuse scleroderma.

"Although, there have only been a few case reports of Actemra in scleroderma, we are excited about its potential as an effective antifibrotic agent in scleroderma," Dr. Steen said in an interview.

Dr. Steen disclosed that she has received grant funding, consulting fees, and/or speaking fees from Actelion, Genentec/Roche , Gilead Pharmaceuticals, Pfizer, and United Therapeutics.

DESTIN, FLA. – Management of lupus nephritis during pregnancy gets close attention in ACR’s new nephritis guidelines.

No treatment is necessary in pregnant women with prior lupus nephritis who have no current evidence of systemic or renal disease activity, while those with mild systemic activity may be treated with hydroxychloroquine, according to the guidelines, which are published in the June issue of Arthritis Care & Research.

"There are good data suggesting hydroxychloroquine controls lupus in women who are pregnant, resulting in fewer flares" Dr. Bevra H. Hahn said at the Congress of Clinical Rheumatology. Dr. Hahn, professor of medicine and chief of the division of rheumatology at the University of California, Los Angeles, led the ACR core working group that helped with development of the guidelines.

In patients with clinically active nephritis or with substantial extrarenal disease activity, glucocorticoids may be prescribed at doses necessary to control disease activity (Arthritis Care Res. 2012;64:797-08).

"I start at 0.5 mg/kg per day," Dr. Hahn said of glucocorticoids under these circumstances. She noted that only steroids that are metabolized by placental enzymes should be used so that the drug does not reach the fetus.

She and her coauthors cautioned, however, that high-dose glucocorticoid therapy is associated with a high risk of maternal complications – including hypertension and diabetes mellitus – in patients with systemic lupus erythematosus (SLE). They also stress that mycophenolate mofetil, cyclophosphamide, and methotrexate should be avoided in pregnancy, because they are established human teratogens.

Azathioprine, though listed as pregnancy category D indicating teratogenic risk, has been shown in cross-sectional studies to be associated with very low risk of fetal abnormalities and can be added if necessary, according to the task force panel charged with developing the guidelines.

The azathioprine dose, however, should not exceed 2 mg/kg per day in pregnant women, Dr. Hahn said.

The task force has recommended that pregnant patients with a persistently active nephritis and documented or suspected class III or IV disease with crescents may be candidates for delivery after 28 weeks if the fetus is viable. The recommendations with respect to pregnancy were based on level C evidence, indicating they were based on consensus, expert opinion, and case series.

For women with SLE and nephritis who are not pregnant, but who have concerns about fertility preservation, the task force panel recommended that mycophenolate mofetil was preferable to cyclophosphamide for induction therapy, because cyclophosphamide has been shown to cause permanent infertility in both women and men.

For example, one study showed that 6 months of high-dose intravenous cyclophosphamide with a cumulative dose of 4.4 g-10 g was associated with sustained amenorrhea in about 10% of young women, and the risk increased with age.

However, the physician should be certain the patient is not pregnant before prescribing mycophenolate mofetil or mycophenolic acid, and treatment should be stopped for at least 6 weeks before pregnancy is attempted.

The guidelines were sponsored by the American College of Rheumatology via a competitive grant mechanism. Dr. Hahn has received consultant fees, speaking fees, and/or honoraria from UCB and Abbott and has served on the data and safety monitoring board for Anthera. The complete list of disclosures for the guideline authors is available with the full text of the article.

DESTIN, FLA. – Management of lupus nephritis during pregnancy gets close attention in ACR’s new nephritis guidelines.

No treatment is necessary in pregnant women with prior lupus nephritis who have no current evidence of systemic or renal disease activity, while those with mild systemic activity may be treated with hydroxychloroquine, according to the guidelines, which are published in the June issue of Arthritis Care & Research.

"There are good data suggesting hydroxychloroquine controls lupus in women who are pregnant, resulting in fewer flares" Dr. Bevra H. Hahn said at the Congress of Clinical Rheumatology. Dr. Hahn, professor of medicine and chief of the division of rheumatology at the University of California, Los Angeles, led the ACR core working group that helped with development of the guidelines.

In patients with clinically active nephritis or with substantial extrarenal disease activity, glucocorticoids may be prescribed at doses necessary to control disease activity (Arthritis Care Res. 2012;64:797-08).

"I start at 0.5 mg/kg per day," Dr. Hahn said of glucocorticoids under these circumstances. She noted that only steroids that are metabolized by placental enzymes should be used so that the drug does not reach the fetus.

She and her coauthors cautioned, however, that high-dose glucocorticoid therapy is associated with a high risk of maternal complications – including hypertension and diabetes mellitus – in patients with systemic lupus erythematosus (SLE). They also stress that mycophenolate mofetil, cyclophosphamide, and methotrexate should be avoided in pregnancy, because they are established human teratogens.

Azathioprine, though listed as pregnancy category D indicating teratogenic risk, has been shown in cross-sectional studies to be associated with very low risk of fetal abnormalities and can be added if necessary, according to the task force panel charged with developing the guidelines.

The azathioprine dose, however, should not exceed 2 mg/kg per day in pregnant women, Dr. Hahn said.

The task force has recommended that pregnant patients with a persistently active nephritis and documented or suspected class III or IV disease with crescents may be candidates for delivery after 28 weeks if the fetus is viable. The recommendations with respect to pregnancy were based on level C evidence, indicating they were based on consensus, expert opinion, and case series.

For women with SLE and nephritis who are not pregnant, but who have concerns about fertility preservation, the task force panel recommended that mycophenolate mofetil was preferable to cyclophosphamide for induction therapy, because cyclophosphamide has been shown to cause permanent infertility in both women and men.

For example, one study showed that 6 months of high-dose intravenous cyclophosphamide with a cumulative dose of 4.4 g-10 g was associated with sustained amenorrhea in about 10% of young women, and the risk increased with age.

However, the physician should be certain the patient is not pregnant before prescribing mycophenolate mofetil or mycophenolic acid, and treatment should be stopped for at least 6 weeks before pregnancy is attempted.

The guidelines were sponsored by the American College of Rheumatology via a competitive grant mechanism. Dr. Hahn has received consultant fees, speaking fees, and/or honoraria from UCB and Abbott and has served on the data and safety monitoring board for Anthera. The complete list of disclosures for the guideline authors is available with the full text of the article.

DESTIN, FLA. – Management of lupus nephritis during pregnancy gets close attention in ACR’s new nephritis guidelines.

No treatment is necessary in pregnant women with prior lupus nephritis who have no current evidence of systemic or renal disease activity, while those with mild systemic activity may be treated with hydroxychloroquine, according to the guidelines, which are published in the June issue of Arthritis Care & Research.

"There are good data suggesting hydroxychloroquine controls lupus in women who are pregnant, resulting in fewer flares" Dr. Bevra H. Hahn said at the Congress of Clinical Rheumatology. Dr. Hahn, professor of medicine and chief of the division of rheumatology at the University of California, Los Angeles, led the ACR core working group that helped with development of the guidelines.

In patients with clinically active nephritis or with substantial extrarenal disease activity, glucocorticoids may be prescribed at doses necessary to control disease activity (Arthritis Care Res. 2012;64:797-08).

"I start at 0.5 mg/kg per day," Dr. Hahn said of glucocorticoids under these circumstances. She noted that only steroids that are metabolized by placental enzymes should be used so that the drug does not reach the fetus.

She and her coauthors cautioned, however, that high-dose glucocorticoid therapy is associated with a high risk of maternal complications – including hypertension and diabetes mellitus – in patients with systemic lupus erythematosus (SLE). They also stress that mycophenolate mofetil, cyclophosphamide, and methotrexate should be avoided in pregnancy, because they are established human teratogens.

Azathioprine, though listed as pregnancy category D indicating teratogenic risk, has been shown in cross-sectional studies to be associated with very low risk of fetal abnormalities and can be added if necessary, according to the task force panel charged with developing the guidelines.

The azathioprine dose, however, should not exceed 2 mg/kg per day in pregnant women, Dr. Hahn said.

The task force has recommended that pregnant patients with a persistently active nephritis and documented or suspected class III or IV disease with crescents may be candidates for delivery after 28 weeks if the fetus is viable. The recommendations with respect to pregnancy were based on level C evidence, indicating they were based on consensus, expert opinion, and case series.

For women with SLE and nephritis who are not pregnant, but who have concerns about fertility preservation, the task force panel recommended that mycophenolate mofetil was preferable to cyclophosphamide for induction therapy, because cyclophosphamide has been shown to cause permanent infertility in both women and men.

For example, one study showed that 6 months of high-dose intravenous cyclophosphamide with a cumulative dose of 4.4 g-10 g was associated with sustained amenorrhea in about 10% of young women, and the risk increased with age.

However, the physician should be certain the patient is not pregnant before prescribing mycophenolate mofetil or mycophenolic acid, and treatment should be stopped for at least 6 weeks before pregnancy is attempted.

The guidelines were sponsored by the American College of Rheumatology via a competitive grant mechanism. Dr. Hahn has received consultant fees, speaking fees, and/or honoraria from UCB and Abbott and has served on the data and safety monitoring board for Anthera. The complete list of disclosures for the guideline authors is available with the full text of the article.

DESTIN, Fla. – Renal biopsy, unless strongly contraindicated, should be performed in every patient with clinical evidence of active lupus nephritis that has not been previously treated so that glomerular disease can be classified by current International Society of Nephrology/Renal Pathology Society classification, according to updated lupus nephritis treatment guidelines from the American College of Rheumatology.

Biopsy also will allow evaluation of disease for activity and chronicity and for tubular and vascular changes, as well as for the identification of additional or alternative causes of renal disease, according to the guidelines, which are published in the June issue of Arthritis Care and Research (Arthritis Care Res. 2012;54:797-808).

In fact, the recommended therapeutic strategies in the updated guidelines require knowledge of the classification of nephritis based on renal biopsy, according to Dr. Bevra H. Hahn, speaking at a meeting that happened to coincide with the online release of the guidelines on May 4.

For example, histologic class I and class II disease generally do not require immunosuppressive treatment; class III and class IV disease – and class V disease when combined with class III and IV disease – require aggressive therapy with glucocorticoids and immunosuppressive agents; and patients with class V disease alone (pure membranous lupus nephritis) with nephritic range proteinuria should be started on prednisone at 0.5mg/kg per day plus mycophenolate mofetil at 2-3 g total daily. Class VI disease generally requires preparation for renal replacement therapy.

The guidelines update those published in 1999, which represented a more general approach to systemic lupus erythematosus (SLE). These new guidelines more directly address nephritis, including case identification, treatment, and monitoring, and they include data on newer therapeutic modalities, including mycophenolate mofetil, mycophenolic acid, and rituximab, which were not available at the time the previous guidelines were developed, said Dr. Hahn, who led the core working group that helped develop the new guidelines.

They also address special situations such as pregnancy.

The core working group, along with a core executive group and a task force panel of experts used the validated modified RAND/University of California at Los Angeles Appropriateness Method, which involves a systematic literature view and expert opinion (based on voting by the task force panel) to develop the new guidelines.

The biopsy recommendation and the related therapeutic recommendations are based on level C evidence, indicating they were derived by consensus, expert opinion, and case series. Indications for renal biopsy, according to the task force panel include increasing serum creatinine without compelling alternative causes, confirmed proteinuria of 1 g or more/24 hours, and combinations of proteinuria of 0.5 g or more/24 hours plus hematuria (defined as 5 or more red blood cells per high power field) and proteinuria of 0.5 g or more/24 hours plus cellular casts – as long at these findings are confirmed in at least two tests conducted within a short time period and in the absence of alternative causes.

The task force panel also addressed adjunctive treatments, specifically recommending that:

• All patients with SLE be treated with a background of hydroxychloroquine unless contraindicated. This level C recommendation is based on recent cross-sectional and prospective controlled trial data indicating it is of benefit for reducing flare rates, is associated with significantly lower damage accrual (including renal damage), and may be associated with reduced risk of clotting events.

• Careful attention be paid to control of hypertension, with a target of no more than 130/80 mm Hg. This recommendation is based on level A evidence for nondiabetic chronic renal disease, indicating it is derived from multiple randomized controlled trials or a meta-analysis.

• Women of child-bearing potential who have active or prior lupus nephritis be counseled about the pregnancy risks conferred by the disease and its treatments. This recommendation is based on level C evidence.

Other task force panel recommendations specifically address induction of improvement in patients with International Society of Nephrology class III/IV lupus glomerulonephritis, induction of improvement in those with class IV or IV/V disease with cellular crescents, maintaining improvement in those who respond to induction therapy, and changing therapies in those who do not. Additional recommendations address the identification of vascular disease in patients with SLE and renal abnormalities, treatment of lupus nephritis patients who are pregnant, and monitoring the activity of lupus nephritis, Dr. Hahn said.

The new recommendations are "heavily based on induction with mycophenolate mofetil or cyclophosphamide, and on maintenance with mycophenolate mofetil or azathioprine," she noted.

"Nephritis remains one of the most devastating complications of lupus," she and her coauthors wrote, noting that the incidence increased during the 1980s and 1990s, with no decline seen as of 2004, despite the availability of new therapeutic regimens.

Standardized incidence rates for end-stage renal disease in the United States have risen in a number of populations, including younger patients, African Americans, and those living in the South.

"We hope that institution of these recommendations might lead to reductions in these trends. Furthermore, they may allow us to evaluate whether those who receive the recommended therapies are less likely to develop end-stage renal disease," they continued, concluding that while much progress has been made since lupus nephritis was associated with a near-terminal prognosis, these recommendations represent an effort to further improve outcomes and decrease morbidity and mortality in SLE.

The guidelines were sponsored by the American College of Rheumatology via a competitive grant mechanism. Dr. Hahn has received consultant fees, speaking fees, and/or honoraria from UCB and Abbott and has served on the data and safety monitoring board for Anthera. The complete list of disclosures for the guideline authors is available with the full text of the article.

DESTIN, Fla. – Renal biopsy, unless strongly contraindicated, should be performed in every patient with clinical evidence of active lupus nephritis that has not been previously treated so that glomerular disease can be classified by current International Society of Nephrology/Renal Pathology Society classification, according to updated lupus nephritis treatment guidelines from the American College of Rheumatology.

Biopsy also will allow evaluation of disease for activity and chronicity and for tubular and vascular changes, as well as for the identification of additional or alternative causes of renal disease, according to the guidelines, which are published in the June issue of Arthritis Care and Research (Arthritis Care Res. 2012;54:797-808).

In fact, the recommended therapeutic strategies in the updated guidelines require knowledge of the classification of nephritis based on renal biopsy, according to Dr. Bevra H. Hahn, speaking at a meeting that happened to coincide with the online release of the guidelines on May 4.

For example, histologic class I and class II disease generally do not require immunosuppressive treatment; class III and class IV disease – and class V disease when combined with class III and IV disease – require aggressive therapy with glucocorticoids and immunosuppressive agents; and patients with class V disease alone (pure membranous lupus nephritis) with nephritic range proteinuria should be started on prednisone at 0.5mg/kg per day plus mycophenolate mofetil at 2-3 g total daily. Class VI disease generally requires preparation for renal replacement therapy.

The guidelines update those published in 1999, which represented a more general approach to systemic lupus erythematosus (SLE). These new guidelines more directly address nephritis, including case identification, treatment, and monitoring, and they include data on newer therapeutic modalities, including mycophenolate mofetil, mycophenolic acid, and rituximab, which were not available at the time the previous guidelines were developed, said Dr. Hahn, who led the core working group that helped develop the new guidelines.

They also address special situations such as pregnancy.

The core working group, along with a core executive group and a task force panel of experts used the validated modified RAND/University of California at Los Angeles Appropriateness Method, which involves a systematic literature view and expert opinion (based on voting by the task force panel) to develop the new guidelines.

The biopsy recommendation and the related therapeutic recommendations are based on level C evidence, indicating they were derived by consensus, expert opinion, and case series. Indications for renal biopsy, according to the task force panel include increasing serum creatinine without compelling alternative causes, confirmed proteinuria of 1 g or more/24 hours, and combinations of proteinuria of 0.5 g or more/24 hours plus hematuria (defined as 5 or more red blood cells per high power field) and proteinuria of 0.5 g or more/24 hours plus cellular casts – as long at these findings are confirmed in at least two tests conducted within a short time period and in the absence of alternative causes.

The task force panel also addressed adjunctive treatments, specifically recommending that:

• All patients with SLE be treated with a background of hydroxychloroquine unless contraindicated. This level C recommendation is based on recent cross-sectional and prospective controlled trial data indicating it is of benefit for reducing flare rates, is associated with significantly lower damage accrual (including renal damage), and may be associated with reduced risk of clotting events.

• Careful attention be paid to control of hypertension, with a target of no more than 130/80 mm Hg. This recommendation is based on level A evidence for nondiabetic chronic renal disease, indicating it is derived from multiple randomized controlled trials or a meta-analysis.

• Women of child-bearing potential who have active or prior lupus nephritis be counseled about the pregnancy risks conferred by the disease and its treatments. This recommendation is based on level C evidence.

Other task force panel recommendations specifically address induction of improvement in patients with International Society of Nephrology class III/IV lupus glomerulonephritis, induction of improvement in those with class IV or IV/V disease with cellular crescents, maintaining improvement in those who respond to induction therapy, and changing therapies in those who do not. Additional recommendations address the identification of vascular disease in patients with SLE and renal abnormalities, treatment of lupus nephritis patients who are pregnant, and monitoring the activity of lupus nephritis, Dr. Hahn said.

The new recommendations are "heavily based on induction with mycophenolate mofetil or cyclophosphamide, and on maintenance with mycophenolate mofetil or azathioprine," she noted.

"Nephritis remains one of the most devastating complications of lupus," she and her coauthors wrote, noting that the incidence increased during the 1980s and 1990s, with no decline seen as of 2004, despite the availability of new therapeutic regimens.

Standardized incidence rates for end-stage renal disease in the United States have risen in a number of populations, including younger patients, African Americans, and those living in the South.

"We hope that institution of these recommendations might lead to reductions in these trends. Furthermore, they may allow us to evaluate whether those who receive the recommended therapies are less likely to develop end-stage renal disease," they continued, concluding that while much progress has been made since lupus nephritis was associated with a near-terminal prognosis, these recommendations represent an effort to further improve outcomes and decrease morbidity and mortality in SLE.

The guidelines were sponsored by the American College of Rheumatology via a competitive grant mechanism. Dr. Hahn has received consultant fees, speaking fees, and/or honoraria from UCB and Abbott and has served on the data and safety monitoring board for Anthera. The complete list of disclosures for the guideline authors is available with the full text of the article.

DESTIN, Fla. – Renal biopsy, unless strongly contraindicated, should be performed in every patient with clinical evidence of active lupus nephritis that has not been previously treated so that glomerular disease can be classified by current International Society of Nephrology/Renal Pathology Society classification, according to updated lupus nephritis treatment guidelines from the American College of Rheumatology.

Biopsy also will allow evaluation of disease for activity and chronicity and for tubular and vascular changes, as well as for the identification of additional or alternative causes of renal disease, according to the guidelines, which are published in the June issue of Arthritis Care and Research (Arthritis Care Res. 2012;54:797-808).

In fact, the recommended therapeutic strategies in the updated guidelines require knowledge of the classification of nephritis based on renal biopsy, according to Dr. Bevra H. Hahn, speaking at a meeting that happened to coincide with the online release of the guidelines on May 4.

For example, histologic class I and class II disease generally do not require immunosuppressive treatment; class III and class IV disease – and class V disease when combined with class III and IV disease – require aggressive therapy with glucocorticoids and immunosuppressive agents; and patients with class V disease alone (pure membranous lupus nephritis) with nephritic range proteinuria should be started on prednisone at 0.5mg/kg per day plus mycophenolate mofetil at 2-3 g total daily. Class VI disease generally requires preparation for renal replacement therapy.

The guidelines update those published in 1999, which represented a more general approach to systemic lupus erythematosus (SLE). These new guidelines more directly address nephritis, including case identification, treatment, and monitoring, and they include data on newer therapeutic modalities, including mycophenolate mofetil, mycophenolic acid, and rituximab, which were not available at the time the previous guidelines were developed, said Dr. Hahn, who led the core working group that helped develop the new guidelines.

They also address special situations such as pregnancy.

The core working group, along with a core executive group and a task force panel of experts used the validated modified RAND/University of California at Los Angeles Appropriateness Method, which involves a systematic literature view and expert opinion (based on voting by the task force panel) to develop the new guidelines.

The biopsy recommendation and the related therapeutic recommendations are based on level C evidence, indicating they were derived by consensus, expert opinion, and case series. Indications for renal biopsy, according to the task force panel include increasing serum creatinine without compelling alternative causes, confirmed proteinuria of 1 g or more/24 hours, and combinations of proteinuria of 0.5 g or more/24 hours plus hematuria (defined as 5 or more red blood cells per high power field) and proteinuria of 0.5 g or more/24 hours plus cellular casts – as long at these findings are confirmed in at least two tests conducted within a short time period and in the absence of alternative causes.

The task force panel also addressed adjunctive treatments, specifically recommending that:

• All patients with SLE be treated with a background of hydroxychloroquine unless contraindicated. This level C recommendation is based on recent cross-sectional and prospective controlled trial data indicating it is of benefit for reducing flare rates, is associated with significantly lower damage accrual (including renal damage), and may be associated with reduced risk of clotting events.

• Careful attention be paid to control of hypertension, with a target of no more than 130/80 mm Hg. This recommendation is based on level A evidence for nondiabetic chronic renal disease, indicating it is derived from multiple randomized controlled trials or a meta-analysis.

• Women of child-bearing potential who have active or prior lupus nephritis be counseled about the pregnancy risks conferred by the disease and its treatments. This recommendation is based on level C evidence.

Other task force panel recommendations specifically address induction of improvement in patients with International Society of Nephrology class III/IV lupus glomerulonephritis, induction of improvement in those with class IV or IV/V disease with cellular crescents, maintaining improvement in those who respond to induction therapy, and changing therapies in those who do not. Additional recommendations address the identification of vascular disease in patients with SLE and renal abnormalities, treatment of lupus nephritis patients who are pregnant, and monitoring the activity of lupus nephritis, Dr. Hahn said.

The new recommendations are "heavily based on induction with mycophenolate mofetil or cyclophosphamide, and on maintenance with mycophenolate mofetil or azathioprine," she noted.

"Nephritis remains one of the most devastating complications of lupus," she and her coauthors wrote, noting that the incidence increased during the 1980s and 1990s, with no decline seen as of 2004, despite the availability of new therapeutic regimens.

Standardized incidence rates for end-stage renal disease in the United States have risen in a number of populations, including younger patients, African Americans, and those living in the South.

"We hope that institution of these recommendations might lead to reductions in these trends. Furthermore, they may allow us to evaluate whether those who receive the recommended therapies are less likely to develop end-stage renal disease," they continued, concluding that while much progress has been made since lupus nephritis was associated with a near-terminal prognosis, these recommendations represent an effort to further improve outcomes and decrease morbidity and mortality in SLE.

The guidelines were sponsored by the American College of Rheumatology via a competitive grant mechanism. Dr. Hahn has received consultant fees, speaking fees, and/or honoraria from UCB and Abbott and has served on the data and safety monitoring board for Anthera. The complete list of disclosures for the guideline authors is available with the full text of the article.