Psoriasis Collection

CHICAGO – The prognosis for adults diagnosed with calcinosis remains grim, despite some excellent treatment responses reported in children for this often disabling and disfiguring condition, according to Dr. Lisa Christopher-Stine.

"I have not had a lot of success treating calcinosis in adults," she said at a symposium sponsored by the American College of Rheumatology.

Patrice Wendling/IMNG Medical Media

Calcinosis is a deposition of insoluble calcium salts in the skin. It can often look like scleroderma, and is divided into four categories based on pathogenesis: dystrophic, metastatic, idiopathic, and iatrogenic.

Although rare in adults, it is relatively common in children, affecting up to 40% of patients with juvenile dermatomyositis. Calcinosis is variable in its severity and thought to correlate with poor underlying disease control and a delay in starting therapy, explained Dr. Christopher-Stine, codirector of the Johns Hopkins Myositis Center in Baltimore.

"It’s probably true that if we mitigate the disease early, we can actually prevent calcinosis from developing, but even in patients with well-controlled disease, it seems to have a life of its own," she said.

The hallmarks of calcinosis are firm dermal or subcutaneous papules or nodules, frequently found on sites of microtrauma such as the buttocks, elbows, knees, and hands. Large subcutaneous tumoral deposition can occur on the trunk. Calcification of the muscles is generally asymptomatic and only found incidentally on radiographs.

Although the true etiology of calcinosis remains unknown, it is now thought to be an imbalance of calcium and phosphate metabolism. Causal theories for dystrophic calcinosis focus on soft tissue inflammation or injury that leads to tissue necrosis and alkaline phosphatase release by damaged lysozymes. The alkaline phosphatase acts to inhibit organic phosphates, which are crystal formation inhibitors, thereby allowing calcium to precipitate in the tissues, explained Dr. Christopher-Stine.

"Once calcinosis starts, it often progresses," she said. "It is unstoppable and really quite frustrating."

The complications of calcinosis include pain, cosmetic disfigurement, persistent ulceration, infection, and mechanical compromise, particularly contractures in the fingers and elbows.

There are no controlled studies in the treatment of calcinosis, only anecdotal reports. Dr. Christopher-Stine said she recommends starting with the calcium-channel blocker diltiazem (Cardizem) at an average dosage of 360 mg/day (range, 120-480 mg/day), followed by colchicine (Colcrys) 0.6 mg/day, working up to 1.8 mg/day.

Other potential therapies include warfarin 1 mg/day, intravenous immunoglobulin 2 g/kg divided monthly, bisphosphonates 10 mg/day, sodium thiosulfate 10 g three times a week to start plus topical administration of abatacept (Orencia) and extracorporeal shock wave lithotripsy (J. Am. Acad. Dermatol. 2011;65:15-22; Semin. Arthritis Rheum. 2005;34:805-12). Pamidronate (Aredia), combination thiosulfate/abatacept, and diltiazem have produced excellent responses in children, but clinicians must be realistic about the response rates in adults, she added.

A recent case study reported dramatic improvements with etidronate (Didronel) 800 mg/day for 3 months every 6 months, including softening of the calcinosis, reduced pain, and markedly increased joint mobility in a 26-year-old woman with severe calcinosis associated with dermatomyositis (J. Bone Miner. Metab. 2012;30:114-8).

Daily use of the broad-spectrum tetracycline antibiotic minocycline (Minocin) 50 mg or 100 mg decreased the frequency of ulceration and inflammation associated with calcinosis deposits, but only modestly reduced calcinosis deposits in nine patients with limited cutaneous systemic sclerosis (Ann. Rheum. Dis. 2003;62:267-9).

Dr. Christopher-Stine said that all therapies are worth a trial, but that surgical removal should probably be considered as a last resort, as the trauma from surgery can induce more calcification, poor wound healing, and infections. That said, it may be helpful when functional decline is severe, although a small test site may be best, she suggested.

The Mayo Clinic just reported that excision of symptomatic lesions resulted in 22 complete responses, 5 partial responses, and no response in 1 patient among 28 patients undergoing surgery for calcinosis cutis associated with autoimmune connective tissue disease (Arch. Dermatol. 2012;148:455-62).

Dr. Christopher-Stine reported having no relevant financial relationships.

CHICAGO – The prognosis for adults diagnosed with calcinosis remains grim, despite some excellent treatment responses reported in children for this often disabling and disfiguring condition, according to Dr. Lisa Christopher-Stine.

"I have not had a lot of success treating calcinosis in adults," she said at a symposium sponsored by the American College of Rheumatology.

Patrice Wendling/IMNG Medical Media

Calcinosis is a deposition of insoluble calcium salts in the skin. It can often look like scleroderma, and is divided into four categories based on pathogenesis: dystrophic, metastatic, idiopathic, and iatrogenic.

Although rare in adults, it is relatively common in children, affecting up to 40% of patients with juvenile dermatomyositis. Calcinosis is variable in its severity and thought to correlate with poor underlying disease control and a delay in starting therapy, explained Dr. Christopher-Stine, codirector of the Johns Hopkins Myositis Center in Baltimore.

"It’s probably true that if we mitigate the disease early, we can actually prevent calcinosis from developing, but even in patients with well-controlled disease, it seems to have a life of its own," she said.

The hallmarks of calcinosis are firm dermal or subcutaneous papules or nodules, frequently found on sites of microtrauma such as the buttocks, elbows, knees, and hands. Large subcutaneous tumoral deposition can occur on the trunk. Calcification of the muscles is generally asymptomatic and only found incidentally on radiographs.

Although the true etiology of calcinosis remains unknown, it is now thought to be an imbalance of calcium and phosphate metabolism. Causal theories for dystrophic calcinosis focus on soft tissue inflammation or injury that leads to tissue necrosis and alkaline phosphatase release by damaged lysozymes. The alkaline phosphatase acts to inhibit organic phosphates, which are crystal formation inhibitors, thereby allowing calcium to precipitate in the tissues, explained Dr. Christopher-Stine.

"Once calcinosis starts, it often progresses," she said. "It is unstoppable and really quite frustrating."

The complications of calcinosis include pain, cosmetic disfigurement, persistent ulceration, infection, and mechanical compromise, particularly contractures in the fingers and elbows.

There are no controlled studies in the treatment of calcinosis, only anecdotal reports. Dr. Christopher-Stine said she recommends starting with the calcium-channel blocker diltiazem (Cardizem) at an average dosage of 360 mg/day (range, 120-480 mg/day), followed by colchicine (Colcrys) 0.6 mg/day, working up to 1.8 mg/day.

Other potential therapies include warfarin 1 mg/day, intravenous immunoglobulin 2 g/kg divided monthly, bisphosphonates 10 mg/day, sodium thiosulfate 10 g three times a week to start plus topical administration of abatacept (Orencia) and extracorporeal shock wave lithotripsy (J. Am. Acad. Dermatol. 2011;65:15-22; Semin. Arthritis Rheum. 2005;34:805-12). Pamidronate (Aredia), combination thiosulfate/abatacept, and diltiazem have produced excellent responses in children, but clinicians must be realistic about the response rates in adults, she added.

A recent case study reported dramatic improvements with etidronate (Didronel) 800 mg/day for 3 months every 6 months, including softening of the calcinosis, reduced pain, and markedly increased joint mobility in a 26-year-old woman with severe calcinosis associated with dermatomyositis (J. Bone Miner. Metab. 2012;30:114-8).

Daily use of the broad-spectrum tetracycline antibiotic minocycline (Minocin) 50 mg or 100 mg decreased the frequency of ulceration and inflammation associated with calcinosis deposits, but only modestly reduced calcinosis deposits in nine patients with limited cutaneous systemic sclerosis (Ann. Rheum. Dis. 2003;62:267-9).

Dr. Christopher-Stine said that all therapies are worth a trial, but that surgical removal should probably be considered as a last resort, as the trauma from surgery can induce more calcification, poor wound healing, and infections. That said, it may be helpful when functional decline is severe, although a small test site may be best, she suggested.

The Mayo Clinic just reported that excision of symptomatic lesions resulted in 22 complete responses, 5 partial responses, and no response in 1 patient among 28 patients undergoing surgery for calcinosis cutis associated with autoimmune connective tissue disease (Arch. Dermatol. 2012;148:455-62).

Dr. Christopher-Stine reported having no relevant financial relationships.

CHICAGO – The prognosis for adults diagnosed with calcinosis remains grim, despite some excellent treatment responses reported in children for this often disabling and disfiguring condition, according to Dr. Lisa Christopher-Stine.

"I have not had a lot of success treating calcinosis in adults," she said at a symposium sponsored by the American College of Rheumatology.

Patrice Wendling/IMNG Medical Media

Calcinosis is a deposition of insoluble calcium salts in the skin. It can often look like scleroderma, and is divided into four categories based on pathogenesis: dystrophic, metastatic, idiopathic, and iatrogenic.

Although rare in adults, it is relatively common in children, affecting up to 40% of patients with juvenile dermatomyositis. Calcinosis is variable in its severity and thought to correlate with poor underlying disease control and a delay in starting therapy, explained Dr. Christopher-Stine, codirector of the Johns Hopkins Myositis Center in Baltimore.

"It’s probably true that if we mitigate the disease early, we can actually prevent calcinosis from developing, but even in patients with well-controlled disease, it seems to have a life of its own," she said.

The hallmarks of calcinosis are firm dermal or subcutaneous papules or nodules, frequently found on sites of microtrauma such as the buttocks, elbows, knees, and hands. Large subcutaneous tumoral deposition can occur on the trunk. Calcification of the muscles is generally asymptomatic and only found incidentally on radiographs.

Although the true etiology of calcinosis remains unknown, it is now thought to be an imbalance of calcium and phosphate metabolism. Causal theories for dystrophic calcinosis focus on soft tissue inflammation or injury that leads to tissue necrosis and alkaline phosphatase release by damaged lysozymes. The alkaline phosphatase acts to inhibit organic phosphates, which are crystal formation inhibitors, thereby allowing calcium to precipitate in the tissues, explained Dr. Christopher-Stine.

"Once calcinosis starts, it often progresses," she said. "It is unstoppable and really quite frustrating."

The complications of calcinosis include pain, cosmetic disfigurement, persistent ulceration, infection, and mechanical compromise, particularly contractures in the fingers and elbows.

There are no controlled studies in the treatment of calcinosis, only anecdotal reports. Dr. Christopher-Stine said she recommends starting with the calcium-channel blocker diltiazem (Cardizem) at an average dosage of 360 mg/day (range, 120-480 mg/day), followed by colchicine (Colcrys) 0.6 mg/day, working up to 1.8 mg/day.

Other potential therapies include warfarin 1 mg/day, intravenous immunoglobulin 2 g/kg divided monthly, bisphosphonates 10 mg/day, sodium thiosulfate 10 g three times a week to start plus topical administration of abatacept (Orencia) and extracorporeal shock wave lithotripsy (J. Am. Acad. Dermatol. 2011;65:15-22; Semin. Arthritis Rheum. 2005;34:805-12). Pamidronate (Aredia), combination thiosulfate/abatacept, and diltiazem have produced excellent responses in children, but clinicians must be realistic about the response rates in adults, she added.

A recent case study reported dramatic improvements with etidronate (Didronel) 800 mg/day for 3 months every 6 months, including softening of the calcinosis, reduced pain, and markedly increased joint mobility in a 26-year-old woman with severe calcinosis associated with dermatomyositis (J. Bone Miner. Metab. 2012;30:114-8).

Daily use of the broad-spectrum tetracycline antibiotic minocycline (Minocin) 50 mg or 100 mg decreased the frequency of ulceration and inflammation associated with calcinosis deposits, but only modestly reduced calcinosis deposits in nine patients with limited cutaneous systemic sclerosis (Ann. Rheum. Dis. 2003;62:267-9).

Dr. Christopher-Stine said that all therapies are worth a trial, but that surgical removal should probably be considered as a last resort, as the trauma from surgery can induce more calcification, poor wound healing, and infections. That said, it may be helpful when functional decline is severe, although a small test site may be best, she suggested.

The Mayo Clinic just reported that excision of symptomatic lesions resulted in 22 complete responses, 5 partial responses, and no response in 1 patient among 28 patients undergoing surgery for calcinosis cutis associated with autoimmune connective tissue disease (Arch. Dermatol. 2012;148:455-62).

Dr. Christopher-Stine reported having no relevant financial relationships.

In this month's program, Dr. Craig Leonardi opines on how two investigational monoclonal antibody therapies may stack up against the competition for treating psoriasis.

Then, Dr. Cheryl Gustafson discusses what drugs are most often to blame for cutaneous reactions that lead to ambulatory visits.

Cosmetic counter host Dr. Lily Talakoub offers tips on how to choose the right EHR for your practice.

And finally, Dr. Alan Rockoff tells the tale of how he helped a patient win a bikini contest.

In this month's program, Dr. Craig Leonardi opines on how two investigational monoclonal antibody therapies may stack up against the competition for treating psoriasis.

Then, Dr. Cheryl Gustafson discusses what drugs are most often to blame for cutaneous reactions that lead to ambulatory visits.

Cosmetic counter host Dr. Lily Talakoub offers tips on how to choose the right EHR for your practice.

And finally, Dr. Alan Rockoff tells the tale of how he helped a patient win a bikini contest.

In this month's program, Dr. Craig Leonardi opines on how two investigational monoclonal antibody therapies may stack up against the competition for treating psoriasis.

Then, Dr. Cheryl Gustafson discusses what drugs are most often to blame for cutaneous reactions that lead to ambulatory visits.

Cosmetic counter host Dr. Lily Talakoub offers tips on how to choose the right EHR for your practice.

And finally, Dr. Alan Rockoff tells the tale of how he helped a patient win a bikini contest.

SAN DIEGO – When psoriasis patients present to Dr. Abrar A. Qureshi with concomitant pain or stiffness, he routinely asks, "What is your worst time of day?"

"If patients say they experience an hour or more of profound morning stiffness, think inflammatory arthritis," Dr. Qureshi said at the annual meeting of the American Academy of Dermatology. "Some patients will be stiff in the morning for 5-15 minutes. That’s more suggestive of osteoarthritis, though there is no hard and fast rule."

Dr. Qureshi of the department of dermatology at Brigham and Women’s Hospital, Boston, also asks patients about joint swelling and if they have trouble getting into a car. His recommended physical exam consists of vitals, weight, height, nail changes, inverse psoriasis, swollen joints, warm joints, "sausage" digits, and the Schober test. "We do see patients with fatigue and malaise, occasionally low grade fever, and we always ask about TB exposure," he said.

He emphasized that dermatologists "are on the front line in the care of these patients. It behooves us to think about psoriatic arthritis, because the numbers suggest that 20%-25% of patients with psoriasis may develop psoriatic arthritis. If the diagnosis is missed, this can lead to debilitating pain, permanent joint damage, and disability."

If a psoriasis patient presents with pain or stiffness, consider inflammatory arthritis, including dactylitis and spondyloarthropathy, Dr. Qureshi said. Other differential diagnoses to consider include noninflammatory arthritis (osteoarthritis) or soft tissue problems such as enthesitis. "Osteoarthritis is probably the biggest red herring for dermatologists," he said.

In a study of patients referred by rheumatologists to the department of dermatology at Brigham and Women’s Hospital, the three most common diagnoses made by the rheumatologists prior to referral were psoriatic arthritis (41%), osteoarthritis (27%), and psoriatic arthritis plus osteoarthritis (15%).

Dr. Qureshi said that he had no relevant financial conflicts to disclose.

SAN DIEGO – When psoriasis patients present to Dr. Abrar A. Qureshi with concomitant pain or stiffness, he routinely asks, "What is your worst time of day?"

"If patients say they experience an hour or more of profound morning stiffness, think inflammatory arthritis," Dr. Qureshi said at the annual meeting of the American Academy of Dermatology. "Some patients will be stiff in the morning for 5-15 minutes. That’s more suggestive of osteoarthritis, though there is no hard and fast rule."

Dr. Qureshi of the department of dermatology at Brigham and Women’s Hospital, Boston, also asks patients about joint swelling and if they have trouble getting into a car. His recommended physical exam consists of vitals, weight, height, nail changes, inverse psoriasis, swollen joints, warm joints, "sausage" digits, and the Schober test. "We do see patients with fatigue and malaise, occasionally low grade fever, and we always ask about TB exposure," he said.

He emphasized that dermatologists "are on the front line in the care of these patients. It behooves us to think about psoriatic arthritis, because the numbers suggest that 20%-25% of patients with psoriasis may develop psoriatic arthritis. If the diagnosis is missed, this can lead to debilitating pain, permanent joint damage, and disability."

If a psoriasis patient presents with pain or stiffness, consider inflammatory arthritis, including dactylitis and spondyloarthropathy, Dr. Qureshi said. Other differential diagnoses to consider include noninflammatory arthritis (osteoarthritis) or soft tissue problems such as enthesitis. "Osteoarthritis is probably the biggest red herring for dermatologists," he said.

In a study of patients referred by rheumatologists to the department of dermatology at Brigham and Women’s Hospital, the three most common diagnoses made by the rheumatologists prior to referral were psoriatic arthritis (41%), osteoarthritis (27%), and psoriatic arthritis plus osteoarthritis (15%).

Dr. Qureshi said that he had no relevant financial conflicts to disclose.

SAN DIEGO – When psoriasis patients present to Dr. Abrar A. Qureshi with concomitant pain or stiffness, he routinely asks, "What is your worst time of day?"

"If patients say they experience an hour or more of profound morning stiffness, think inflammatory arthritis," Dr. Qureshi said at the annual meeting of the American Academy of Dermatology. "Some patients will be stiff in the morning for 5-15 minutes. That’s more suggestive of osteoarthritis, though there is no hard and fast rule."

Dr. Qureshi of the department of dermatology at Brigham and Women’s Hospital, Boston, also asks patients about joint swelling and if they have trouble getting into a car. His recommended physical exam consists of vitals, weight, height, nail changes, inverse psoriasis, swollen joints, warm joints, "sausage" digits, and the Schober test. "We do see patients with fatigue and malaise, occasionally low grade fever, and we always ask about TB exposure," he said.

He emphasized that dermatologists "are on the front line in the care of these patients. It behooves us to think about psoriatic arthritis, because the numbers suggest that 20%-25% of patients with psoriasis may develop psoriatic arthritis. If the diagnosis is missed, this can lead to debilitating pain, permanent joint damage, and disability."

If a psoriasis patient presents with pain or stiffness, consider inflammatory arthritis, including dactylitis and spondyloarthropathy, Dr. Qureshi said. Other differential diagnoses to consider include noninflammatory arthritis (osteoarthritis) or soft tissue problems such as enthesitis. "Osteoarthritis is probably the biggest red herring for dermatologists," he said.

In a study of patients referred by rheumatologists to the department of dermatology at Brigham and Women’s Hospital, the three most common diagnoses made by the rheumatologists prior to referral were psoriatic arthritis (41%), osteoarthritis (27%), and psoriatic arthritis plus osteoarthritis (15%).

Dr. Qureshi said that he had no relevant financial conflicts to disclose.

NEW YORK – Management of systemic sclerosis is likely to improve as soon as an ongoing convergence of mechanistic insights, improved understanding of clinical trial design, and interest by industry results in new treatments, according to Dr. Robert F. Spiera.

Of particular note are recent trials, with both positive and negative results, of tyrosine kinase inhibitors (TKIs) and autologous stem cell transplantation, he said at a rheumatology meeting sponsored by New York University.

Even while awaiting a big breakthrough in treatment, "we can now do a lot for our patients with scleroderma," said Dr. Spiera, director of the Scleroderma and Vasculitis Center at the Hospital for Special Surgery in New York.

Therapy for systemic sclerosis (SSc) falls into two categories: treatment of organ-specific complications and disease modification. Major advances have been made in treating organ-specific complications affecting the gastrointestinal system, kidneys, heart and lungs, and musculoskeletal organs, according to Dr. Spiera. Many agents are available to manage symptoms of Raynaud’s phenomenon.

While there are no proven disease-modifying therapies as yet, the search for such therapies in scleroderma has intensified. Immunosuppressive therapy is one approach, and limited success has been achieved with cyclophosphamide. There have been several recent reports investigating immunoablative therapy combined with bone marrow transplantation.

In the ASSIST (American Scleroderma Stem Cell vs. Immune Suppression) Trial, an open-label, randomized, controlled phase II trial, 10 patients received hemopoietic stem-cell transplantation (HSCT) plus 200 mg/kg of intravenous cyclophosphamide and 6.5 mg/kg of IV rabbit antithymocyte globulin. The 9 control patients received 1.0 g/m² of IV cyclophosphamide once a month for 6 months. The authors reported that all 10 HSCT patients improved at or before follow-up at 12 months, compared with none of the 9 treated only with cyclophosphamide (odds ratio, 110; P = .00001) (Lancet 2011;378:498-506). Of the 9 controls, 8 had disease progression, compared with none of those treated by HSCT (P = .0001), and 7 controls eventually underwent HSCT. The outcomes were considered to be an improvement, defined as a decrease in the modified Rodnan skin scores (mRSS) of more than 25% or an increase in forced vital capacity (FVC) of more than 10%.

"These results surprised a lot of people in the scleroderma community," commented Dr. Spiera. He noted that some of the inclusion criteria could be subject to challenge, as they potentially allowed for enrollment of patients with relatively mild disease. He also noted that it was a single-center study, which limits the generalizability of the results, as the morbidity of the intervention is likely center- and experience-dependent.

Another single-center study from Germany reported the outcomes of autologous stem cell transplantation in 26 patients with SSc. Patients received cyclophosphamide and granulocyte colony-stimulating factor for mobilization and cyclophosphamide plus antithymocyte globulin for conditioning before retransfusion of CD34-selected stem cells. Six months after transplantation, 91% of patients improved, as measured by a reduction in the mRSS of 25% or more (Rheumatol. 2012;39:269-75). However, 3 patients died between the mobilization and conditioning treatment, 2 due to severe disease progression and 1 whose death was thought to be treatment related. Seven patients relapsed during 4.4 years of follow-up. Progression-free survival was 74%. During follow-up, 4 patients died, mostly due to pulmonary or cardiac complications of SSc.

More definitive evidence regarding scleroderma may be forthcoming from the ongoing National Institutes of Health SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial. The study will compare the potential benefits of autologous stem cell transplant with those of cyclophosphamide (12 IV treatments at monthly intervals). A composite end point will include mortality, organ failure, change in FVC of more than 10%, change in mRSS of more than 25%, and the Scleroderma Health Assessment Questionnaire (SHAQ). Enrollment in SCOT was completed in May 2011, and randomization continued until Oct. 1, 2011.

Another avenue of active research is the search for antifibrotic therapy. The TKI imatinib is one agent undergoing active scrutiny. According to Dr. Spiera, there are good preclinical data available for imatinib, including reports that imatinib treatment in a mouse model of SSc reduced dermal thickening and prevented the differentiation of resting fibroblasts into myofibroblasts, perhaps by blocking noncanonical transforming growth factor-beta (TGF-beta) pathways and platelet-derived growth factor receptor (PDGFR) signaling (Arthritis Rheum. 2009;60:219-24; Oncogene 2009;28:1285-97).

Clinical findings for the treatment of SSc with imatinib have been mixed. In the largest and longest-observed cohort, Dr. Spiera conducted a prospective, phase IIa, open-label, single-arm clinical trial of 30 patients with diffuse cutaneous SSc of less than 4 years’ duration treated with imatinib 400 mg daily. Patients with both early and late disease were included, and about three-quarters had previously received other treatments, including corticosteroids (46.7%), methotrexate (30.0%), mycophenolate mofetil (20.0%), and autologous stem cell transplantation (3.3%). Twenty-four patients completed 12 months of therapy (Ann. Rheum. Dis. 2011;70:1003-9). Improvements in skin thickening and FVC were observed. The mRSS decreased by 22.4% at 12 months (P = .001), and changes were noted 6 months after initiation of therapy. Patients with early disease (less than 18 months) improved the most. FVC improved by 6.4% predicted (P = .008), and diffusion capacity remained stable. Dr. Spiera questioned the clinical significance of the change in FVC, since not all the patients had interstitial lung disease at baseline.

Treatment with imatinib was tolerated by most patients. Adverse events – including edema, nausea, and myalgias – were common (n = 171), although most (98%) were mild to moderate. There were 24 serious adverse events, and 2 were attributed to imatinib.

Steps were taken to improve tolerability. In 83% of patients, the imatinib dose was adjusted due to myalgia; edema and effusions; gastrointestinal complaints; or other illness. About 60% of patients who developed edema were given furosemide, which proved helpful.

These results stand in contrast to those of another group of investigators who set out to do a 6-month, randomized, double-blind, placebo-controlled proof-of-concept pilot study of imatinib in patients with active diffuse cutaneous SSc (Arthritis Rheum. 2011;63:3547-51). A 4:1 randomization strategy was used, stratifying patients according to current use of methotrexate. Imatinib 200 mg was given twice daily. The goal of the study was to enroll 20 patients. However, the study was discontinued after 10 patients were enrolled (9 who received imatinib and 1 placebo) due to poor tolerability and high rates of adverse events. These events were similar to those reported by Dr. Spiera: edema, fluid retention, fatigue, nausea, cramps/myalgias, and diarrhea, but also alopecia and anemia. According to the authors, the side effects occurred even when the imatinib dose was reduced to 200 mg daily. Two patients were hospitalized because of medication side effects.

No differences were found in any measures of efficacy (that is, changes in mRSS, physician’s global assessment, patient’s global assessment, or HAQ scores), but this was attributed to the small number of patients who actually completed the study.

"I think we are going to see more about [TKIs] for systemic sclerosis," said Dr. Spiera. He noted that clinical trials were underway for other TKIs, such as dasatinib and nilotinib. The TKI BIBF 1120 was shown in a phase II, randomized, placebo-controlled trial to slow down the rate of decline of FVC in patients with idiopathic pulmonary fibrosis (N. Engl. J. Med. 2011;365:1079-87).

While Dr. Spiera called for more randomized controlled trials, he also highlighted some of the challenges faced by those conducting clinical trials in scleroderma. These include the difficulty of recruiting patients with such an uncommon disease, the variety in disease phenotypes, the variable natural history, uncertainty as to what are the most relevant and valid outcome measures, and the ethical ramifications of randomizing patients to placebo.

Dr. Spiera listed research support from BMS, Boehringer Ingelheim, Novartis, Roche/Genentech, and United Therapeutics.

NEW YORK – Management of systemic sclerosis is likely to improve as soon as an ongoing convergence of mechanistic insights, improved understanding of clinical trial design, and interest by industry results in new treatments, according to Dr. Robert F. Spiera.

Of particular note are recent trials, with both positive and negative results, of tyrosine kinase inhibitors (TKIs) and autologous stem cell transplantation, he said at a rheumatology meeting sponsored by New York University.

Even while awaiting a big breakthrough in treatment, "we can now do a lot for our patients with scleroderma," said Dr. Spiera, director of the Scleroderma and Vasculitis Center at the Hospital for Special Surgery in New York.

Therapy for systemic sclerosis (SSc) falls into two categories: treatment of organ-specific complications and disease modification. Major advances have been made in treating organ-specific complications affecting the gastrointestinal system, kidneys, heart and lungs, and musculoskeletal organs, according to Dr. Spiera. Many agents are available to manage symptoms of Raynaud’s phenomenon.

While there are no proven disease-modifying therapies as yet, the search for such therapies in scleroderma has intensified. Immunosuppressive therapy is one approach, and limited success has been achieved with cyclophosphamide. There have been several recent reports investigating immunoablative therapy combined with bone marrow transplantation.

In the ASSIST (American Scleroderma Stem Cell vs. Immune Suppression) Trial, an open-label, randomized, controlled phase II trial, 10 patients received hemopoietic stem-cell transplantation (HSCT) plus 200 mg/kg of intravenous cyclophosphamide and 6.5 mg/kg of IV rabbit antithymocyte globulin. The 9 control patients received 1.0 g/m² of IV cyclophosphamide once a month for 6 months. The authors reported that all 10 HSCT patients improved at or before follow-up at 12 months, compared with none of the 9 treated only with cyclophosphamide (odds ratio, 110; P = .00001) (Lancet 2011;378:498-506). Of the 9 controls, 8 had disease progression, compared with none of those treated by HSCT (P = .0001), and 7 controls eventually underwent HSCT. The outcomes were considered to be an improvement, defined as a decrease in the modified Rodnan skin scores (mRSS) of more than 25% or an increase in forced vital capacity (FVC) of more than 10%.

"These results surprised a lot of people in the scleroderma community," commented Dr. Spiera. He noted that some of the inclusion criteria could be subject to challenge, as they potentially allowed for enrollment of patients with relatively mild disease. He also noted that it was a single-center study, which limits the generalizability of the results, as the morbidity of the intervention is likely center- and experience-dependent.

Another single-center study from Germany reported the outcomes of autologous stem cell transplantation in 26 patients with SSc. Patients received cyclophosphamide and granulocyte colony-stimulating factor for mobilization and cyclophosphamide plus antithymocyte globulin for conditioning before retransfusion of CD34-selected stem cells. Six months after transplantation, 91% of patients improved, as measured by a reduction in the mRSS of 25% or more (Rheumatol. 2012;39:269-75). However, 3 patients died between the mobilization and conditioning treatment, 2 due to severe disease progression and 1 whose death was thought to be treatment related. Seven patients relapsed during 4.4 years of follow-up. Progression-free survival was 74%. During follow-up, 4 patients died, mostly due to pulmonary or cardiac complications of SSc.

More definitive evidence regarding scleroderma may be forthcoming from the ongoing National Institutes of Health SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial. The study will compare the potential benefits of autologous stem cell transplant with those of cyclophosphamide (12 IV treatments at monthly intervals). A composite end point will include mortality, organ failure, change in FVC of more than 10%, change in mRSS of more than 25%, and the Scleroderma Health Assessment Questionnaire (SHAQ). Enrollment in SCOT was completed in May 2011, and randomization continued until Oct. 1, 2011.

Another avenue of active research is the search for antifibrotic therapy. The TKI imatinib is one agent undergoing active scrutiny. According to Dr. Spiera, there are good preclinical data available for imatinib, including reports that imatinib treatment in a mouse model of SSc reduced dermal thickening and prevented the differentiation of resting fibroblasts into myofibroblasts, perhaps by blocking noncanonical transforming growth factor-beta (TGF-beta) pathways and platelet-derived growth factor receptor (PDGFR) signaling (Arthritis Rheum. 2009;60:219-24; Oncogene 2009;28:1285-97).

Clinical findings for the treatment of SSc with imatinib have been mixed. In the largest and longest-observed cohort, Dr. Spiera conducted a prospective, phase IIa, open-label, single-arm clinical trial of 30 patients with diffuse cutaneous SSc of less than 4 years’ duration treated with imatinib 400 mg daily. Patients with both early and late disease were included, and about three-quarters had previously received other treatments, including corticosteroids (46.7%), methotrexate (30.0%), mycophenolate mofetil (20.0%), and autologous stem cell transplantation (3.3%). Twenty-four patients completed 12 months of therapy (Ann. Rheum. Dis. 2011;70:1003-9). Improvements in skin thickening and FVC were observed. The mRSS decreased by 22.4% at 12 months (P = .001), and changes were noted 6 months after initiation of therapy. Patients with early disease (less than 18 months) improved the most. FVC improved by 6.4% predicted (P = .008), and diffusion capacity remained stable. Dr. Spiera questioned the clinical significance of the change in FVC, since not all the patients had interstitial lung disease at baseline.

Treatment with imatinib was tolerated by most patients. Adverse events – including edema, nausea, and myalgias – were common (n = 171), although most (98%) were mild to moderate. There were 24 serious adverse events, and 2 were attributed to imatinib.

Steps were taken to improve tolerability. In 83% of patients, the imatinib dose was adjusted due to myalgia; edema and effusions; gastrointestinal complaints; or other illness. About 60% of patients who developed edema were given furosemide, which proved helpful.

These results stand in contrast to those of another group of investigators who set out to do a 6-month, randomized, double-blind, placebo-controlled proof-of-concept pilot study of imatinib in patients with active diffuse cutaneous SSc (Arthritis Rheum. 2011;63:3547-51). A 4:1 randomization strategy was used, stratifying patients according to current use of methotrexate. Imatinib 200 mg was given twice daily. The goal of the study was to enroll 20 patients. However, the study was discontinued after 10 patients were enrolled (9 who received imatinib and 1 placebo) due to poor tolerability and high rates of adverse events. These events were similar to those reported by Dr. Spiera: edema, fluid retention, fatigue, nausea, cramps/myalgias, and diarrhea, but also alopecia and anemia. According to the authors, the side effects occurred even when the imatinib dose was reduced to 200 mg daily. Two patients were hospitalized because of medication side effects.

No differences were found in any measures of efficacy (that is, changes in mRSS, physician’s global assessment, patient’s global assessment, or HAQ scores), but this was attributed to the small number of patients who actually completed the study.

"I think we are going to see more about [TKIs] for systemic sclerosis," said Dr. Spiera. He noted that clinical trials were underway for other TKIs, such as dasatinib and nilotinib. The TKI BIBF 1120 was shown in a phase II, randomized, placebo-controlled trial to slow down the rate of decline of FVC in patients with idiopathic pulmonary fibrosis (N. Engl. J. Med. 2011;365:1079-87).

While Dr. Spiera called for more randomized controlled trials, he also highlighted some of the challenges faced by those conducting clinical trials in scleroderma. These include the difficulty of recruiting patients with such an uncommon disease, the variety in disease phenotypes, the variable natural history, uncertainty as to what are the most relevant and valid outcome measures, and the ethical ramifications of randomizing patients to placebo.

Dr. Spiera listed research support from BMS, Boehringer Ingelheim, Novartis, Roche/Genentech, and United Therapeutics.

NEW YORK – Management of systemic sclerosis is likely to improve as soon as an ongoing convergence of mechanistic insights, improved understanding of clinical trial design, and interest by industry results in new treatments, according to Dr. Robert F. Spiera.

Of particular note are recent trials, with both positive and negative results, of tyrosine kinase inhibitors (TKIs) and autologous stem cell transplantation, he said at a rheumatology meeting sponsored by New York University.

Even while awaiting a big breakthrough in treatment, "we can now do a lot for our patients with scleroderma," said Dr. Spiera, director of the Scleroderma and Vasculitis Center at the Hospital for Special Surgery in New York.

Therapy for systemic sclerosis (SSc) falls into two categories: treatment of organ-specific complications and disease modification. Major advances have been made in treating organ-specific complications affecting the gastrointestinal system, kidneys, heart and lungs, and musculoskeletal organs, according to Dr. Spiera. Many agents are available to manage symptoms of Raynaud’s phenomenon.

While there are no proven disease-modifying therapies as yet, the search for such therapies in scleroderma has intensified. Immunosuppressive therapy is one approach, and limited success has been achieved with cyclophosphamide. There have been several recent reports investigating immunoablative therapy combined with bone marrow transplantation.

In the ASSIST (American Scleroderma Stem Cell vs. Immune Suppression) Trial, an open-label, randomized, controlled phase II trial, 10 patients received hemopoietic stem-cell transplantation (HSCT) plus 200 mg/kg of intravenous cyclophosphamide and 6.5 mg/kg of IV rabbit antithymocyte globulin. The 9 control patients received 1.0 g/m² of IV cyclophosphamide once a month for 6 months. The authors reported that all 10 HSCT patients improved at or before follow-up at 12 months, compared with none of the 9 treated only with cyclophosphamide (odds ratio, 110; P = .00001) (Lancet 2011;378:498-506). Of the 9 controls, 8 had disease progression, compared with none of those treated by HSCT (P = .0001), and 7 controls eventually underwent HSCT. The outcomes were considered to be an improvement, defined as a decrease in the modified Rodnan skin scores (mRSS) of more than 25% or an increase in forced vital capacity (FVC) of more than 10%.

"These results surprised a lot of people in the scleroderma community," commented Dr. Spiera. He noted that some of the inclusion criteria could be subject to challenge, as they potentially allowed for enrollment of patients with relatively mild disease. He also noted that it was a single-center study, which limits the generalizability of the results, as the morbidity of the intervention is likely center- and experience-dependent.

Another single-center study from Germany reported the outcomes of autologous stem cell transplantation in 26 patients with SSc. Patients received cyclophosphamide and granulocyte colony-stimulating factor for mobilization and cyclophosphamide plus antithymocyte globulin for conditioning before retransfusion of CD34-selected stem cells. Six months after transplantation, 91% of patients improved, as measured by a reduction in the mRSS of 25% or more (Rheumatol. 2012;39:269-75). However, 3 patients died between the mobilization and conditioning treatment, 2 due to severe disease progression and 1 whose death was thought to be treatment related. Seven patients relapsed during 4.4 years of follow-up. Progression-free survival was 74%. During follow-up, 4 patients died, mostly due to pulmonary or cardiac complications of SSc.

More definitive evidence regarding scleroderma may be forthcoming from the ongoing National Institutes of Health SCOT (Scleroderma: Cyclophosphamide or Transplantation) trial. The study will compare the potential benefits of autologous stem cell transplant with those of cyclophosphamide (12 IV treatments at monthly intervals). A composite end point will include mortality, organ failure, change in FVC of more than 10%, change in mRSS of more than 25%, and the Scleroderma Health Assessment Questionnaire (SHAQ). Enrollment in SCOT was completed in May 2011, and randomization continued until Oct. 1, 2011.

Another avenue of active research is the search for antifibrotic therapy. The TKI imatinib is one agent undergoing active scrutiny. According to Dr. Spiera, there are good preclinical data available for imatinib, including reports that imatinib treatment in a mouse model of SSc reduced dermal thickening and prevented the differentiation of resting fibroblasts into myofibroblasts, perhaps by blocking noncanonical transforming growth factor-beta (TGF-beta) pathways and platelet-derived growth factor receptor (PDGFR) signaling (Arthritis Rheum. 2009;60:219-24; Oncogene 2009;28:1285-97).

Clinical findings for the treatment of SSc with imatinib have been mixed. In the largest and longest-observed cohort, Dr. Spiera conducted a prospective, phase IIa, open-label, single-arm clinical trial of 30 patients with diffuse cutaneous SSc of less than 4 years’ duration treated with imatinib 400 mg daily. Patients with both early and late disease were included, and about three-quarters had previously received other treatments, including corticosteroids (46.7%), methotrexate (30.0%), mycophenolate mofetil (20.0%), and autologous stem cell transplantation (3.3%). Twenty-four patients completed 12 months of therapy (Ann. Rheum. Dis. 2011;70:1003-9). Improvements in skin thickening and FVC were observed. The mRSS decreased by 22.4% at 12 months (P = .001), and changes were noted 6 months after initiation of therapy. Patients with early disease (less than 18 months) improved the most. FVC improved by 6.4% predicted (P = .008), and diffusion capacity remained stable. Dr. Spiera questioned the clinical significance of the change in FVC, since not all the patients had interstitial lung disease at baseline.

Treatment with imatinib was tolerated by most patients. Adverse events – including edema, nausea, and myalgias – were common (n = 171), although most (98%) were mild to moderate. There were 24 serious adverse events, and 2 were attributed to imatinib.

Steps were taken to improve tolerability. In 83% of patients, the imatinib dose was adjusted due to myalgia; edema and effusions; gastrointestinal complaints; or other illness. About 60% of patients who developed edema were given furosemide, which proved helpful.

These results stand in contrast to those of another group of investigators who set out to do a 6-month, randomized, double-blind, placebo-controlled proof-of-concept pilot study of imatinib in patients with active diffuse cutaneous SSc (Arthritis Rheum. 2011;63:3547-51). A 4:1 randomization strategy was used, stratifying patients according to current use of methotrexate. Imatinib 200 mg was given twice daily. The goal of the study was to enroll 20 patients. However, the study was discontinued after 10 patients were enrolled (9 who received imatinib and 1 placebo) due to poor tolerability and high rates of adverse events. These events were similar to those reported by Dr. Spiera: edema, fluid retention, fatigue, nausea, cramps/myalgias, and diarrhea, but also alopecia and anemia. According to the authors, the side effects occurred even when the imatinib dose was reduced to 200 mg daily. Two patients were hospitalized because of medication side effects.

No differences were found in any measures of efficacy (that is, changes in mRSS, physician’s global assessment, patient’s global assessment, or HAQ scores), but this was attributed to the small number of patients who actually completed the study.

"I think we are going to see more about [TKIs] for systemic sclerosis," said Dr. Spiera. He noted that clinical trials were underway for other TKIs, such as dasatinib and nilotinib. The TKI BIBF 1120 was shown in a phase II, randomized, placebo-controlled trial to slow down the rate of decline of FVC in patients with idiopathic pulmonary fibrosis (N. Engl. J. Med. 2011;365:1079-87).

While Dr. Spiera called for more randomized controlled trials, he also highlighted some of the challenges faced by those conducting clinical trials in scleroderma. These include the difficulty of recruiting patients with such an uncommon disease, the variety in disease phenotypes, the variable natural history, uncertainty as to what are the most relevant and valid outcome measures, and the ethical ramifications of randomizing patients to placebo.

Dr. Spiera listed research support from BMS, Boehringer Ingelheim, Novartis, Roche/Genentech, and United Therapeutics.

Patients with rheumatic disease who take anti-tumor necrosis factor drugs are four times more likely to develop mycobacterial diseases than patients not taking the drugs, and up to 14 times more likely to die from those diseases.

Anti-TNF drugs were associated with significantly increased risks for tuberculosis and nontuberculous mycobacterial disease, Dr. Kevin Winthrop and colleagues reported in the April 20 online edition of the Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2012 April 20 [doi:10.1136/annrheumdis-2011-200690]). Because most of the deaths in their retrospective study occurred in patients with nontubercular mycobacterial (NTM) disease, physicians should consider anti-TNF agents carefully in such patients, they said.

"It is currently unclear if patients with active NTM disease can safely receive anti-TNF therapy," wrote Dr. Winthrop of the Oregon Health and Science University, Portland, and his coauthors. "These cases [in this study] and the reports of others, suggest patients with NTM disease should discontinue anti-TNF therapy."

The investigators extracted their data from a large health care database, identifying 8,418 patients who took anti-TNF medications from 2000-2008. Most of these subjects had a diagnosis of rheumatoid arthritis (61%); 64% were female and 61% white.

There were 16 cases of tuberculosis and 18 cases of NTM that developed after the initiation of therapy. Among the TB cases, 69% (11) were pulmonary and 25% (4) extrapulmonary. Disease location was unknown in one patient. Rheumatoid arthritis was the most common diagnosis in this group (75%; 12 patients); one patient had Crohn’s disease, one had ulcerative colitis, and three had psoriasis. Their median age was 57 years.

Tuberculosis developed a median of 670 days after beginning the drug, but the time of onset varied widely (1-3,181 days). At the time of diagnosis, nine (44%) were taking prednisone and four (25%) were taking methotrexate; most (63%) were taking anti-TNF drugs.

Three patients (19%) died during the study period, with a median time of 74 days between disease onset and death.

Of the NTM cases, 67% (12) were pulmonary and four (22%) extrapulmonary; disease location was unknown in two patients. All of the patents had rheumatoid arthritis. Three (15%) also had psoriasis and two (11%) ankylosing spondylitis. Their median age was 68 years.

The median onset of disease was 1,027 days after beginning therapy (range 77-2,832). At the time of diagnosis nine (50%) were taking prednisone and two (11%) were taking methotrexate; most (83%) were also taking anti-TNF drugs.

Seven of this group (39%) died during the study period, with a median time of 569 days (range 21-2,127 days) between disease onset and death.

Both tuberculosis and NTM were more common in anti-TNF exposed patients than in the general population. In exposed patients, the investigators calculated a rate of 105 NTM cases and 56 tuberculosis cases per 100,000 persons per year, compared to 3 and 4 per 100,000 respectively in the general population. Incidence of both diseases was highest among those taking monoclonal antibodies (123 tuberculosis and 168 NTM cases per 100,000). Etanercept was associated with the lowest incidence – 17 tuberculosis and 35 NTM cases per 100,000.

Compared to non-infected anti-TNF users, those with tuberculosis were less likely to be white and significantly more likely to have diabetes or chronic renal disease. Those with NTM were significantly older, and more likely to be white, have gastroesophageal reflux disease, or chronic lung disease.

All of those with NTM had a diagnosis of rheumatoid arthritis, compared to 60% of uninfected anti-TNF users. NTM patients were four times more likely to have used infliximab than the uninfected group (67% vs. 33%; odds ratio, 4.0).

The investigators also stratified findings by age. In an analysis of patients 50 years and older, they found a significant association between NTM and a rheumatoid arthritis diagnosis. "All seven of the observed NTM case deaths were in this group," they noted. "NTM disease rates were substantially higher in this ... subset."

The finding of more NTM than tuberculosis cases is "not surprising," the authors wrote, "Given the low prevalence of tuberculosis in the U.S. and given that tuberculosis screening guidelines have been well-publicized in the last 5 years, making it likely that tuberculosis cases were averted in our study population."

Nevertheless, the study highlights the importance of identifying risk factors for both diseases in patients taking anti-TNF medications.

"These include chronic renal disease and diabetes mellitus for tuberculosis and chronic lung disease for NTM. These associations are important for physicians to recognize when considering anti-TNF therapy use."

The study was funded by a grant from UCB Pharmaceuticals. Dr. Winthrop has received grant money from the company as advisory board remuneration from Amgen, Genentech, and Oxford Immunotec. Coauthors also reported a number of disclosures, including links to UCB.

Patients with rheumatic disease who take anti-tumor necrosis factor drugs are four times more likely to develop mycobacterial diseases than patients not taking the drugs, and up to 14 times more likely to die from those diseases.

Anti-TNF drugs were associated with significantly increased risks for tuberculosis and nontuberculous mycobacterial disease, Dr. Kevin Winthrop and colleagues reported in the April 20 online edition of the Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2012 April 20 [doi:10.1136/annrheumdis-2011-200690]). Because most of the deaths in their retrospective study occurred in patients with nontubercular mycobacterial (NTM) disease, physicians should consider anti-TNF agents carefully in such patients, they said.

"It is currently unclear if patients with active NTM disease can safely receive anti-TNF therapy," wrote Dr. Winthrop of the Oregon Health and Science University, Portland, and his coauthors. "These cases [in this study] and the reports of others, suggest patients with NTM disease should discontinue anti-TNF therapy."

The investigators extracted their data from a large health care database, identifying 8,418 patients who took anti-TNF medications from 2000-2008. Most of these subjects had a diagnosis of rheumatoid arthritis (61%); 64% were female and 61% white.

There were 16 cases of tuberculosis and 18 cases of NTM that developed after the initiation of therapy. Among the TB cases, 69% (11) were pulmonary and 25% (4) extrapulmonary. Disease location was unknown in one patient. Rheumatoid arthritis was the most common diagnosis in this group (75%; 12 patients); one patient had Crohn’s disease, one had ulcerative colitis, and three had psoriasis. Their median age was 57 years.

Tuberculosis developed a median of 670 days after beginning the drug, but the time of onset varied widely (1-3,181 days). At the time of diagnosis, nine (44%) were taking prednisone and four (25%) were taking methotrexate; most (63%) were taking anti-TNF drugs.

Three patients (19%) died during the study period, with a median time of 74 days between disease onset and death.

Of the NTM cases, 67% (12) were pulmonary and four (22%) extrapulmonary; disease location was unknown in two patients. All of the patents had rheumatoid arthritis. Three (15%) also had psoriasis and two (11%) ankylosing spondylitis. Their median age was 68 years.

The median onset of disease was 1,027 days after beginning therapy (range 77-2,832). At the time of diagnosis nine (50%) were taking prednisone and two (11%) were taking methotrexate; most (83%) were also taking anti-TNF drugs.

Seven of this group (39%) died during the study period, with a median time of 569 days (range 21-2,127 days) between disease onset and death.

Both tuberculosis and NTM were more common in anti-TNF exposed patients than in the general population. In exposed patients, the investigators calculated a rate of 105 NTM cases and 56 tuberculosis cases per 100,000 persons per year, compared to 3 and 4 per 100,000 respectively in the general population. Incidence of both diseases was highest among those taking monoclonal antibodies (123 tuberculosis and 168 NTM cases per 100,000). Etanercept was associated with the lowest incidence – 17 tuberculosis and 35 NTM cases per 100,000.

Compared to non-infected anti-TNF users, those with tuberculosis were less likely to be white and significantly more likely to have diabetes or chronic renal disease. Those with NTM were significantly older, and more likely to be white, have gastroesophageal reflux disease, or chronic lung disease.

All of those with NTM had a diagnosis of rheumatoid arthritis, compared to 60% of uninfected anti-TNF users. NTM patients were four times more likely to have used infliximab than the uninfected group (67% vs. 33%; odds ratio, 4.0).

The investigators also stratified findings by age. In an analysis of patients 50 years and older, they found a significant association between NTM and a rheumatoid arthritis diagnosis. "All seven of the observed NTM case deaths were in this group," they noted. "NTM disease rates were substantially higher in this ... subset."

The finding of more NTM than tuberculosis cases is "not surprising," the authors wrote, "Given the low prevalence of tuberculosis in the U.S. and given that tuberculosis screening guidelines have been well-publicized in the last 5 years, making it likely that tuberculosis cases were averted in our study population."

Nevertheless, the study highlights the importance of identifying risk factors for both diseases in patients taking anti-TNF medications.

"These include chronic renal disease and diabetes mellitus for tuberculosis and chronic lung disease for NTM. These associations are important for physicians to recognize when considering anti-TNF therapy use."

The study was funded by a grant from UCB Pharmaceuticals. Dr. Winthrop has received grant money from the company as advisory board remuneration from Amgen, Genentech, and Oxford Immunotec. Coauthors also reported a number of disclosures, including links to UCB.

Patients with rheumatic disease who take anti-tumor necrosis factor drugs are four times more likely to develop mycobacterial diseases than patients not taking the drugs, and up to 14 times more likely to die from those diseases.

Anti-TNF drugs were associated with significantly increased risks for tuberculosis and nontuberculous mycobacterial disease, Dr. Kevin Winthrop and colleagues reported in the April 20 online edition of the Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2012 April 20 [doi:10.1136/annrheumdis-2011-200690]). Because most of the deaths in their retrospective study occurred in patients with nontubercular mycobacterial (NTM) disease, physicians should consider anti-TNF agents carefully in such patients, they said.

"It is currently unclear if patients with active NTM disease can safely receive anti-TNF therapy," wrote Dr. Winthrop of the Oregon Health and Science University, Portland, and his coauthors. "These cases [in this study] and the reports of others, suggest patients with NTM disease should discontinue anti-TNF therapy."

The investigators extracted their data from a large health care database, identifying 8,418 patients who took anti-TNF medications from 2000-2008. Most of these subjects had a diagnosis of rheumatoid arthritis (61%); 64% were female and 61% white.

There were 16 cases of tuberculosis and 18 cases of NTM that developed after the initiation of therapy. Among the TB cases, 69% (11) were pulmonary and 25% (4) extrapulmonary. Disease location was unknown in one patient. Rheumatoid arthritis was the most common diagnosis in this group (75%; 12 patients); one patient had Crohn’s disease, one had ulcerative colitis, and three had psoriasis. Their median age was 57 years.

Tuberculosis developed a median of 670 days after beginning the drug, but the time of onset varied widely (1-3,181 days). At the time of diagnosis, nine (44%) were taking prednisone and four (25%) were taking methotrexate; most (63%) were taking anti-TNF drugs.

Three patients (19%) died during the study period, with a median time of 74 days between disease onset and death.

Of the NTM cases, 67% (12) were pulmonary and four (22%) extrapulmonary; disease location was unknown in two patients. All of the patents had rheumatoid arthritis. Three (15%) also had psoriasis and two (11%) ankylosing spondylitis. Their median age was 68 years.

The median onset of disease was 1,027 days after beginning therapy (range 77-2,832). At the time of diagnosis nine (50%) were taking prednisone and two (11%) were taking methotrexate; most (83%) were also taking anti-TNF drugs.

Seven of this group (39%) died during the study period, with a median time of 569 days (range 21-2,127 days) between disease onset and death.

Both tuberculosis and NTM were more common in anti-TNF exposed patients than in the general population. In exposed patients, the investigators calculated a rate of 105 NTM cases and 56 tuberculosis cases per 100,000 persons per year, compared to 3 and 4 per 100,000 respectively in the general population. Incidence of both diseases was highest among those taking monoclonal antibodies (123 tuberculosis and 168 NTM cases per 100,000). Etanercept was associated with the lowest incidence – 17 tuberculosis and 35 NTM cases per 100,000.

Compared to non-infected anti-TNF users, those with tuberculosis were less likely to be white and significantly more likely to have diabetes or chronic renal disease. Those with NTM were significantly older, and more likely to be white, have gastroesophageal reflux disease, or chronic lung disease.

All of those with NTM had a diagnosis of rheumatoid arthritis, compared to 60% of uninfected anti-TNF users. NTM patients were four times more likely to have used infliximab than the uninfected group (67% vs. 33%; odds ratio, 4.0).

The investigators also stratified findings by age. In an analysis of patients 50 years and older, they found a significant association between NTM and a rheumatoid arthritis diagnosis. "All seven of the observed NTM case deaths were in this group," they noted. "NTM disease rates were substantially higher in this ... subset."

The finding of more NTM than tuberculosis cases is "not surprising," the authors wrote, "Given the low prevalence of tuberculosis in the U.S. and given that tuberculosis screening guidelines have been well-publicized in the last 5 years, making it likely that tuberculosis cases were averted in our study population."

Nevertheless, the study highlights the importance of identifying risk factors for both diseases in patients taking anti-TNF medications.

"These include chronic renal disease and diabetes mellitus for tuberculosis and chronic lung disease for NTM. These associations are important for physicians to recognize when considering anti-TNF therapy use."

The study was funded by a grant from UCB Pharmaceuticals. Dr. Winthrop has received grant money from the company as advisory board remuneration from Amgen, Genentech, and Oxford Immunotec. Coauthors also reported a number of disclosures, including links to UCB.

VICTORIA, B.C. – Some patients with systemic lupus erythematosus may be more likely than others to experience a prolonged remission, new data suggest.

In a study of more than 1,500 patients who had SLE, about 2% achieved a remission lasting at least 5 years on either no medication or only antimalarial drugs, Anjali Papneja reported at the annual meeting of the Canadian Rheumatology Association.

The prolonged remissions lasted on average almost 12 years. Nearly a third of the patients had had a monophasic clinical disease course, characterized by only a single flare, before their remission.

Patients achieving a prolonged remission were more likely to be white, had milder disease, and were less likely to have involvement of certain organ systems and to have received steroids or other immunosuppressive agents prior to remission onset.

"Prolonged remission is an infrequent outcome among SLE patients, but it generally lasts for over a decade, and it is preceded by an atypically monophasic clinical course in a significant minority," Ms. Papneja commented.

"We want to know what makes these patients different, how they can be treated most effectively, and how we can harness this unique and desirable outcome more generally," she added.

An attendee asked what the remission rate was if patients who achieved remission on stable immunosuppressive regimens and/or low-dose prednisone were also included.

The reason for including only those patients who had remitted off all steroids and immunosuppressive agents was to distinguish those whose SLE was in true remission (i.e., those in the cohort), from those whose disease was merely suppressed by the ongoing use of these medications, replied Ms. Papneja, a medical student at the University of Toronto. "But they do remain on antimalarials because in recent decades, it has been found that these patients have cardiovascular protective benefits from antimalarials."

The investigators studied all patients with SLE followed at the university’s Lupus Clinic from July 1970 through May 2011.

Patients were defined as having a prolonged remission if they did not have any clinical disease activity for at least 5 years, had regular clinic visits, and received no immunosuppressive medications or at most antimalarial drugs during the remission.

With a mean duration of follow-up of nearly 22 years, 2.4% of the 1,613 patients studied achieved a prolonged remission, after a mean disease duration of about 9 years. These sustained remissions lasted an average of nearly 12 years.

By type, 44% of the remissions were serologically and clinically quiescent, 28% were serologically active but clinically quiescent, and 28% fluctuated between these types.

In the years leading up to the remission, the majority of patients (71%) had a relapsing-remitting clinical course, but a sizable proportion (29%) had a monophasic course. "It’s worthwhile to study these patients further to determine at what point we can safely define a disease course as being monophasic," Ms. Papneja commented. None of the patients achieving prolonged remission had a chronic active course.

In a case-control comparison, in which each patient who achieved prolonged remission was matched with three who did not, the former were more likely to be white (82% vs. 72%), had a lower SLE Disease Activity Index (SLEDAI-2K) score at their first clinic visit (8 vs. 10.6), and had a lower adjusted mean SLEDAI-2K score in the 3 years leading up to remission (3 vs. 5.9).

The group achieving prolonged remission was also significantly less likely to have skin, pulmonary, and central nervous system involvement, but "we noted that there was no difference in renal involvement between cases and controls," she pointed out. Additionally, they were less likely to have received steroids (58% vs. 80%) and other immunosuppressive agents (24% vs. 47%) prior to remission onset, also seeming to point to milder disease.

A study limitation, Ms. Papneja acknowledged, was that only patients continuing care at the clinic were included, and the clinic’s attrition rate was about 10%. Thus, some patients achieving remission and dropping out of care, or having a flare and seeking treatment elsewhere, may have been lost to follow-up.

Ms. Papneja disclosed that she had no relevant conflicts of interest.

VICTORIA, B.C. – Some patients with systemic lupus erythematosus may be more likely than others to experience a prolonged remission, new data suggest.

In a study of more than 1,500 patients who had SLE, about 2% achieved a remission lasting at least 5 years on either no medication or only antimalarial drugs, Anjali Papneja reported at the annual meeting of the Canadian Rheumatology Association.

The prolonged remissions lasted on average almost 12 years. Nearly a third of the patients had had a monophasic clinical disease course, characterized by only a single flare, before their remission.

Patients achieving a prolonged remission were more likely to be white, had milder disease, and were less likely to have involvement of certain organ systems and to have received steroids or other immunosuppressive agents prior to remission onset.

"Prolonged remission is an infrequent outcome among SLE patients, but it generally lasts for over a decade, and it is preceded by an atypically monophasic clinical course in a significant minority," Ms. Papneja commented.

"We want to know what makes these patients different, how they can be treated most effectively, and how we can harness this unique and desirable outcome more generally," she added.

An attendee asked what the remission rate was if patients who achieved remission on stable immunosuppressive regimens and/or low-dose prednisone were also included.

The reason for including only those patients who had remitted off all steroids and immunosuppressive agents was to distinguish those whose SLE was in true remission (i.e., those in the cohort), from those whose disease was merely suppressed by the ongoing use of these medications, replied Ms. Papneja, a medical student at the University of Toronto. "But they do remain on antimalarials because in recent decades, it has been found that these patients have cardiovascular protective benefits from antimalarials."

The investigators studied all patients with SLE followed at the university’s Lupus Clinic from July 1970 through May 2011.

Patients were defined as having a prolonged remission if they did not have any clinical disease activity for at least 5 years, had regular clinic visits, and received no immunosuppressive medications or at most antimalarial drugs during the remission.

With a mean duration of follow-up of nearly 22 years, 2.4% of the 1,613 patients studied achieved a prolonged remission, after a mean disease duration of about 9 years. These sustained remissions lasted an average of nearly 12 years.

By type, 44% of the remissions were serologically and clinically quiescent, 28% were serologically active but clinically quiescent, and 28% fluctuated between these types.

In the years leading up to the remission, the majority of patients (71%) had a relapsing-remitting clinical course, but a sizable proportion (29%) had a monophasic course. "It’s worthwhile to study these patients further to determine at what point we can safely define a disease course as being monophasic," Ms. Papneja commented. None of the patients achieving prolonged remission had a chronic active course.

In a case-control comparison, in which each patient who achieved prolonged remission was matched with three who did not, the former were more likely to be white (82% vs. 72%), had a lower SLE Disease Activity Index (SLEDAI-2K) score at their first clinic visit (8 vs. 10.6), and had a lower adjusted mean SLEDAI-2K score in the 3 years leading up to remission (3 vs. 5.9).

The group achieving prolonged remission was also significantly less likely to have skin, pulmonary, and central nervous system involvement, but "we noted that there was no difference in renal involvement between cases and controls," she pointed out. Additionally, they were less likely to have received steroids (58% vs. 80%) and other immunosuppressive agents (24% vs. 47%) prior to remission onset, also seeming to point to milder disease.

A study limitation, Ms. Papneja acknowledged, was that only patients continuing care at the clinic were included, and the clinic’s attrition rate was about 10%. Thus, some patients achieving remission and dropping out of care, or having a flare and seeking treatment elsewhere, may have been lost to follow-up.

Ms. Papneja disclosed that she had no relevant conflicts of interest.

VICTORIA, B.C. – Some patients with systemic lupus erythematosus may be more likely than others to experience a prolonged remission, new data suggest.

In a study of more than 1,500 patients who had SLE, about 2% achieved a remission lasting at least 5 years on either no medication or only antimalarial drugs, Anjali Papneja reported at the annual meeting of the Canadian Rheumatology Association.

The prolonged remissions lasted on average almost 12 years. Nearly a third of the patients had had a monophasic clinical disease course, characterized by only a single flare, before their remission.

Patients achieving a prolonged remission were more likely to be white, had milder disease, and were less likely to have involvement of certain organ systems and to have received steroids or other immunosuppressive agents prior to remission onset.

"Prolonged remission is an infrequent outcome among SLE patients, but it generally lasts for over a decade, and it is preceded by an atypically monophasic clinical course in a significant minority," Ms. Papneja commented.

"We want to know what makes these patients different, how they can be treated most effectively, and how we can harness this unique and desirable outcome more generally," she added.

An attendee asked what the remission rate was if patients who achieved remission on stable immunosuppressive regimens and/or low-dose prednisone were also included.

The reason for including only those patients who had remitted off all steroids and immunosuppressive agents was to distinguish those whose SLE was in true remission (i.e., those in the cohort), from those whose disease was merely suppressed by the ongoing use of these medications, replied Ms. Papneja, a medical student at the University of Toronto. "But they do remain on antimalarials because in recent decades, it has been found that these patients have cardiovascular protective benefits from antimalarials."

The investigators studied all patients with SLE followed at the university’s Lupus Clinic from July 1970 through May 2011.

Patients were defined as having a prolonged remission if they did not have any clinical disease activity for at least 5 years, had regular clinic visits, and received no immunosuppressive medications or at most antimalarial drugs during the remission.

With a mean duration of follow-up of nearly 22 years, 2.4% of the 1,613 patients studied achieved a prolonged remission, after a mean disease duration of about 9 years. These sustained remissions lasted an average of nearly 12 years.

By type, 44% of the remissions were serologically and clinically quiescent, 28% were serologically active but clinically quiescent, and 28% fluctuated between these types.

In the years leading up to the remission, the majority of patients (71%) had a relapsing-remitting clinical course, but a sizable proportion (29%) had a monophasic course. "It’s worthwhile to study these patients further to determine at what point we can safely define a disease course as being monophasic," Ms. Papneja commented. None of the patients achieving prolonged remission had a chronic active course.

In a case-control comparison, in which each patient who achieved prolonged remission was matched with three who did not, the former were more likely to be white (82% vs. 72%), had a lower SLE Disease Activity Index (SLEDAI-2K) score at their first clinic visit (8 vs. 10.6), and had a lower adjusted mean SLEDAI-2K score in the 3 years leading up to remission (3 vs. 5.9).

The group achieving prolonged remission was also significantly less likely to have skin, pulmonary, and central nervous system involvement, but "we noted that there was no difference in renal involvement between cases and controls," she pointed out. Additionally, they were less likely to have received steroids (58% vs. 80%) and other immunosuppressive agents (24% vs. 47%) prior to remission onset, also seeming to point to milder disease.

A study limitation, Ms. Papneja acknowledged, was that only patients continuing care at the clinic were included, and the clinic’s attrition rate was about 10%. Thus, some patients achieving remission and dropping out of care, or having a flare and seeking treatment elsewhere, may have been lost to follow-up.

Ms. Papneja disclosed that she had no relevant conflicts of interest.

NEW YORK – Do not rush to biopsy every patient with Sjögren’s syndrome who presents with salivary gland enlargement, Dr. Steven E. Carsons said at a rheumatology meeting sponsored by New York University.

"My approach to lymphoma surveillance in Sjögren’s syndrome is to depend on clinical judgment, relying on the bedside exam coupled with basic laboratory measures," said Dr. Carsons, professor of medicine at the State University of New York at Stony Brook.

It’s important to remain cognizant of the fact that patients with Sjögren’s syndrome (SS) have a 16- to 40-fold increased relative risk of malignant non-Hodgkin’s lymphoma, commonly of the mucosa-associated lymphoid tissue (MALT) in the salivary glands. Given that half of patients with primary SS present with salivary gland enlargement at some point during their illness, it is impractical to biopsy them all.

Chronic inflammation of salivary and lachrymal glands is characteristic of SS. Salivary dysfunctions, such as dry mouth, salivary gland swelling, and abnormal scintigraphy or sialography, are key elements of the American-European Consensus Criteria for SS. In primary SS, enlargement of the salivary gland may be due to benign causes such as inflammation or blockage. Conditions other than SS to consider when evaluating swollen salivary glands are sialadenitis due to infection with hepatitis C or HIV, the presence of IgG4-related systemic disease, sarcoidosis, and amyloidosis or isolated salivary gland lymphoma or other neoplasms.

The risk of lymphoma is increased in SS patients. Cohort studies report that about 5%-10% of patients with primary SS develop malignant B cell non-Hodgkin’s lymphoma (Sjögren’s Syndrome, in "Kelley’s Textbook of Rheumatology," 8th ed., Saunders, 2009, pp. 1149-68). The cumulative risk has recently been estimated as ranging from 3.4% in the first 5 years to 9.8% at 15 years (Semin. Arthritis Rheum. 2011;41:415-23).

Because it is impractical to biopsy every patient who presents with enlarged salivary glands, Dr. Carsons said that his clinical suspicions are raised when a patient develops enlargement of the salivary gland over time or when a firm nodule emerges, especially when the patient also develops lymphadenopathy, splenomegaly, weight loss, fever, or pulmonary infiltration. Loss of specific autoreactivities, such as antinuclear antibodies and anti-Sjögren’s syndrome A and B antibodies, may also indicate malignant transformation.

If any of these clinical findings are present, a biopsy is warranted, according to Dr. Carsons. The biopsy can be excisional, either by core needle or by excision of the node. Appropriate tissue analyses include immunoglobulin light-chain typing, hematoxylin and eosin staining, immunohistochemistry, and gene rearrangement studies. "I find pathology studies are not always conclusive," said Dr. Carsons. "Even the most prevalent rearrangements seen in [MALT] lymphomas are only present in 18% of cases." Intense glandular inflammation can produce histologic changes that may be difficult for pathologists to distinguish from lymphoma.

At this point, imaging studies may be considered, but Dr. Carsons noted that these results do not yield specific diagnoses. Even findings from PET imaging may show intermediate avidity in the presence of active inflammation. "Sometimes, there is still no conclusion at the end of the workup. Then we move back, reset the algorithm, and follow the patient clinically."

When the diagnosis of non-Hodgkin’s lymphoma is made, management strategies should take into account both the stage of the malignancy and the activity of extraglandular primary SS ("Sjögren’s Syndrome," Springer, 2011, pp. 345-55). According to Dr. Carsons, most MALT lymphomas are usually indolent, with a 5-year survival of 86%-95% regardless of whether the lymphoma is localized. Incidentally discovered non-Hodgkin’s lymphoma in patients with primary SS may not progress, even when untreated. For those reasons, if the lymphoma is asymptomatic and the primary SS disease activity is low, it is acceptable to follow a course of watchful waiting, and treatments should focus on the SS symptoms using medications, such as hydroxychloroquinolone or NSAIDs.

When the lymphoma is symptomatic but localized, and the SS activity is low, watchful waiting may still be appropriate or it may be time to begin treatment with low-dose radiation therapy for the lymphoma. Medications for SS should be continued.

If the lymphoma becomes symptomatic and/or disseminated and SS activity is high, rituximab should be initiated, with or without cyclophosphamide or a chemotherapy regimen consisting of cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine, and prednisone.

Rituximab may show promise for patients with primary Sjögren’s even in the absence of lymphoma. In a randomized, single-center trial of 30 patients with SS, a regimen of rituximab 1,000 mg twice a month stimulated salivary flow and significantly improved oral and ocular dryness as well as other Sjögren’s symptoms (Arthritis Rheum. 2010;62:960-8).

Dr. Carsons reported no relevant financial relationships.

NEW YORK – Do not rush to biopsy every patient with Sjögren’s syndrome who presents with salivary gland enlargement, Dr. Steven E. Carsons said at a rheumatology meeting sponsored by New York University.

"My approach to lymphoma surveillance in Sjögren’s syndrome is to depend on clinical judgment, relying on the bedside exam coupled with basic laboratory measures," said Dr. Carsons, professor of medicine at the State University of New York at Stony Brook.

It’s important to remain cognizant of the fact that patients with Sjögren’s syndrome (SS) have a 16- to 40-fold increased relative risk of malignant non-Hodgkin’s lymphoma, commonly of the mucosa-associated lymphoid tissue (MALT) in the salivary glands. Given that half of patients with primary SS present with salivary gland enlargement at some point during their illness, it is impractical to biopsy them all.

Chronic inflammation of salivary and lachrymal glands is characteristic of SS. Salivary dysfunctions, such as dry mouth, salivary gland swelling, and abnormal scintigraphy or sialography, are key elements of the American-European Consensus Criteria for SS. In primary SS, enlargement of the salivary gland may be due to benign causes such as inflammation or blockage. Conditions other than SS to consider when evaluating swollen salivary glands are sialadenitis due to infection with hepatitis C or HIV, the presence of IgG4-related systemic disease, sarcoidosis, and amyloidosis or isolated salivary gland lymphoma or other neoplasms.

The risk of lymphoma is increased in SS patients. Cohort studies report that about 5%-10% of patients with primary SS develop malignant B cell non-Hodgkin’s lymphoma (Sjögren’s Syndrome, in "Kelley’s Textbook of Rheumatology," 8th ed., Saunders, 2009, pp. 1149-68). The cumulative risk has recently been estimated as ranging from 3.4% in the first 5 years to 9.8% at 15 years (Semin. Arthritis Rheum. 2011;41:415-23).

Because it is impractical to biopsy every patient who presents with enlarged salivary glands, Dr. Carsons said that his clinical suspicions are raised when a patient develops enlargement of the salivary gland over time or when a firm nodule emerges, especially when the patient also develops lymphadenopathy, splenomegaly, weight loss, fever, or pulmonary infiltration. Loss of specific autoreactivities, such as antinuclear antibodies and anti-Sjögren’s syndrome A and B antibodies, may also indicate malignant transformation.

If any of these clinical findings are present, a biopsy is warranted, according to Dr. Carsons. The biopsy can be excisional, either by core needle or by excision of the node. Appropriate tissue analyses include immunoglobulin light-chain typing, hematoxylin and eosin staining, immunohistochemistry, and gene rearrangement studies. "I find pathology studies are not always conclusive," said Dr. Carsons. "Even the most prevalent rearrangements seen in [MALT] lymphomas are only present in 18% of cases." Intense glandular inflammation can produce histologic changes that may be difficult for pathologists to distinguish from lymphoma.

At this point, imaging studies may be considered, but Dr. Carsons noted that these results do not yield specific diagnoses. Even findings from PET imaging may show intermediate avidity in the presence of active inflammation. "Sometimes, there is still no conclusion at the end of the workup. Then we move back, reset the algorithm, and follow the patient clinically."

When the diagnosis of non-Hodgkin’s lymphoma is made, management strategies should take into account both the stage of the malignancy and the activity of extraglandular primary SS ("Sjögren’s Syndrome," Springer, 2011, pp. 345-55). According to Dr. Carsons, most MALT lymphomas are usually indolent, with a 5-year survival of 86%-95% regardless of whether the lymphoma is localized. Incidentally discovered non-Hodgkin’s lymphoma in patients with primary SS may not progress, even when untreated. For those reasons, if the lymphoma is asymptomatic and the primary SS disease activity is low, it is acceptable to follow a course of watchful waiting, and treatments should focus on the SS symptoms using medications, such as hydroxychloroquinolone or NSAIDs.

When the lymphoma is symptomatic but localized, and the SS activity is low, watchful waiting may still be appropriate or it may be time to begin treatment with low-dose radiation therapy for the lymphoma. Medications for SS should be continued.

If the lymphoma becomes symptomatic and/or disseminated and SS activity is high, rituximab should be initiated, with or without cyclophosphamide or a chemotherapy regimen consisting of cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine, and prednisone.

Rituximab may show promise for patients with primary Sjögren’s even in the absence of lymphoma. In a randomized, single-center trial of 30 patients with SS, a regimen of rituximab 1,000 mg twice a month stimulated salivary flow and significantly improved oral and ocular dryness as well as other Sjögren’s symptoms (Arthritis Rheum. 2010;62:960-8).

Dr. Carsons reported no relevant financial relationships.

NEW YORK – Do not rush to biopsy every patient with Sjögren’s syndrome who presents with salivary gland enlargement, Dr. Steven E. Carsons said at a rheumatology meeting sponsored by New York University.

"My approach to lymphoma surveillance in Sjögren’s syndrome is to depend on clinical judgment, relying on the bedside exam coupled with basic laboratory measures," said Dr. Carsons, professor of medicine at the State University of New York at Stony Brook.

It’s important to remain cognizant of the fact that patients with Sjögren’s syndrome (SS) have a 16- to 40-fold increased relative risk of malignant non-Hodgkin’s lymphoma, commonly of the mucosa-associated lymphoid tissue (MALT) in the salivary glands. Given that half of patients with primary SS present with salivary gland enlargement at some point during their illness, it is impractical to biopsy them all.

Chronic inflammation of salivary and lachrymal glands is characteristic of SS. Salivary dysfunctions, such as dry mouth, salivary gland swelling, and abnormal scintigraphy or sialography, are key elements of the American-European Consensus Criteria for SS. In primary SS, enlargement of the salivary gland may be due to benign causes such as inflammation or blockage. Conditions other than SS to consider when evaluating swollen salivary glands are sialadenitis due to infection with hepatitis C or HIV, the presence of IgG4-related systemic disease, sarcoidosis, and amyloidosis or isolated salivary gland lymphoma or other neoplasms.

The risk of lymphoma is increased in SS patients. Cohort studies report that about 5%-10% of patients with primary SS develop malignant B cell non-Hodgkin’s lymphoma (Sjögren’s Syndrome, in "Kelley’s Textbook of Rheumatology," 8th ed., Saunders, 2009, pp. 1149-68). The cumulative risk has recently been estimated as ranging from 3.4% in the first 5 years to 9.8% at 15 years (Semin. Arthritis Rheum. 2011;41:415-23).

Because it is impractical to biopsy every patient who presents with enlarged salivary glands, Dr. Carsons said that his clinical suspicions are raised when a patient develops enlargement of the salivary gland over time or when a firm nodule emerges, especially when the patient also develops lymphadenopathy, splenomegaly, weight loss, fever, or pulmonary infiltration. Loss of specific autoreactivities, such as antinuclear antibodies and anti-Sjögren’s syndrome A and B antibodies, may also indicate malignant transformation.

If any of these clinical findings are present, a biopsy is warranted, according to Dr. Carsons. The biopsy can be excisional, either by core needle or by excision of the node. Appropriate tissue analyses include immunoglobulin light-chain typing, hematoxylin and eosin staining, immunohistochemistry, and gene rearrangement studies. "I find pathology studies are not always conclusive," said Dr. Carsons. "Even the most prevalent rearrangements seen in [MALT] lymphomas are only present in 18% of cases." Intense glandular inflammation can produce histologic changes that may be difficult for pathologists to distinguish from lymphoma.

At this point, imaging studies may be considered, but Dr. Carsons noted that these results do not yield specific diagnoses. Even findings from PET imaging may show intermediate avidity in the presence of active inflammation. "Sometimes, there is still no conclusion at the end of the workup. Then we move back, reset the algorithm, and follow the patient clinically."

When the diagnosis of non-Hodgkin’s lymphoma is made, management strategies should take into account both the stage of the malignancy and the activity of extraglandular primary SS ("Sjögren’s Syndrome," Springer, 2011, pp. 345-55). According to Dr. Carsons, most MALT lymphomas are usually indolent, with a 5-year survival of 86%-95% regardless of whether the lymphoma is localized. Incidentally discovered non-Hodgkin’s lymphoma in patients with primary SS may not progress, even when untreated. For those reasons, if the lymphoma is asymptomatic and the primary SS disease activity is low, it is acceptable to follow a course of watchful waiting, and treatments should focus on the SS symptoms using medications, such as hydroxychloroquinolone or NSAIDs.

When the lymphoma is symptomatic but localized, and the SS activity is low, watchful waiting may still be appropriate or it may be time to begin treatment with low-dose radiation therapy for the lymphoma. Medications for SS should be continued.

If the lymphoma becomes symptomatic and/or disseminated and SS activity is high, rituximab should be initiated, with or without cyclophosphamide or a chemotherapy regimen consisting of cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride), vincristine, and prednisone.

Rituximab may show promise for patients with primary Sjögren’s even in the absence of lymphoma. In a randomized, single-center trial of 30 patients with SS, a regimen of rituximab 1,000 mg twice a month stimulated salivary flow and significantly improved oral and ocular dryness as well as other Sjögren’s symptoms (Arthritis Rheum. 2010;62:960-8).

Dr. Carsons reported no relevant financial relationships.

Biologic agents that block the action of tumor necrosis factor have dramatically improved patient outcomes. But they sometimes have little effect or lose effectiveness over time, necessitating a change in therapy. Emerging evidence, recently incorporated into a treatment algorithm, is helping to guide selection of the next biologic for such patients in a rational, personalized way (Rheumatology 2012;51:600-9).

Primary vs. Secondary Nonresponse

The first key consideration in selecting the next therapy is whether the patient has primary or secondary nonresponse to the anti-TNF agent, as this influences the odds of response to another agent in this class. The distinction is not clear-cut, but generally, primary nonresponse manifests 12-16 weeks after starting the agent, whereas secondary nonresponse emerges after 6-12 months.

In the context of anti-TNF therapy, compared with their counterparts having a response, primary nonresponders appear to have disease that is less dependent on TNF and to have a lower proinflammatory gene profile in the synovium.

In contrast, the reason for secondary nonresponse is usually unrelated to the disease process, and instead often is due to the development of antibodies against the TNF blocker – either human antichimeric antibodies (HACAs), as in the case of infliximab (Remicade), or human antihuman antibodies (HAHAs), as in the case of adalimumab (Humira).

Thus, primary nonresponders to TNF blockers are less likely to respond to other agents in this class, whereas secondary nonresponders seem to respond almost as well as patients who have never been given one of these agents before (EULAR 2008, abstract FRI0125).

Presence vs. Absence of Autoantibodies

The second key consideration after failure of a TNF blocker is whether the patient has autoantibodies, specifically, rheumatoid factor and/or anti–citrullinated protein antibodies (ACPAs), as their presence influences the odds of response to the B cell–depleting agent rituximab (Rituxan).

Autoantibody-positive patients have a better response than their autoantibody-negative counterparts to rituximab (EULAR 2009, abstract FRI0256). Occasionally, patients who appear to be autoantibody negative still benefit, likely because they have autoantibodies that we cannot yet detect.

Taken together, current data suggest that among primary anti-TNF nonresponders, patients who are autoantibody positive are most likely to benefit from three agents having other mechanisms of action: rituximab; abatacept (Orencia), a T-cell costimulation modulator; and tocilizumab (Actemra), an antibody to the interleukin-6 receptor. Those who are antibody negative are more likely to benefit only from abatacept or tocilizumab.

Among secondary nonresponders, patients who are autoantibody positive appear to have the most options – another anti-TNF agent, rituximab, abatacept, and tocilizumab – whereas those who are autoantibody negative are likely to benefit from any of these agents except rituximab.

Future Directions

We may be able to refine this personalized approach in the future. For example, the type 1 interferon signature may protect against rituximab-induced B cell depletion, as a higher signature in peripheral blood is associated with a lack of clinical response to this agent (Arthritis Rheum. 2010;62:3607-14). There may well be other predictive markers too, so we may one day be able to apply a multimarker panel in the clinic.

Also, additional treatment factors being identified may help guide the selection among multiple agents. For instance, a patient’s ability to take methotrexate, often given in combination with biologics, may play a role, as evidence suggests that tocilizumab given as monotherapy is just as effective as combinations of TNF blockers with methotrexate.

Identification of predictive biomarkers, while challenging and expensive, will help to optimize treatment. There is a very clear need to come up with a much more sophisticated approach as opposed to the current one based on clinical measures. There has been progress in this area, but we need to continue to invest in biomarker research because this is really a more rational approach and the way forward.

Dr. Tak is professor of medicine at the AMC/University of Amsterdam and Senior Vice President/Head, Therapy Area Immunoinflammation at GlaxoSmithKline. He disclosed that he has been a consultant to Abbott, Amgen, Merck, Pfizer, and Roche/Genentech.

Biologic agents that block the action of tumor necrosis factor have dramatically improved patient outcomes. But they sometimes have little effect or lose effectiveness over time, necessitating a change in therapy. Emerging evidence, recently incorporated into a treatment algorithm, is helping to guide selection of the next biologic for such patients in a rational, personalized way (Rheumatology 2012;51:600-9).

Primary vs. Secondary Nonresponse

The first key consideration in selecting the next therapy is whether the patient has primary or secondary nonresponse to the anti-TNF agent, as this influences the odds of response to another agent in this class. The distinction is not clear-cut, but generally, primary nonresponse manifests 12-16 weeks after starting the agent, whereas secondary nonresponse emerges after 6-12 months.

In the context of anti-TNF therapy, compared with their counterparts having a response, primary nonresponders appear to have disease that is less dependent on TNF and to have a lower proinflammatory gene profile in the synovium.

In contrast, the reason for secondary nonresponse is usually unrelated to the disease process, and instead often is due to the development of antibodies against the TNF blocker – either human antichimeric antibodies (HACAs), as in the case of infliximab (Remicade), or human antihuman antibodies (HAHAs), as in the case of adalimumab (Humira).

Thus, primary nonresponders to TNF blockers are less likely to respond to other agents in this class, whereas secondary nonresponders seem to respond almost as well as patients who have never been given one of these agents before (EULAR 2008, abstract FRI0125).

Presence vs. Absence of Autoantibodies

The second key consideration after failure of a TNF blocker is whether the patient has autoantibodies, specifically, rheumatoid factor and/or anti–citrullinated protein antibodies (ACPAs), as their presence influences the odds of response to the B cell–depleting agent rituximab (Rituxan).

Autoantibody-positive patients have a better response than their autoantibody-negative counterparts to rituximab (EULAR 2009, abstract FRI0256). Occasionally, patients who appear to be autoantibody negative still benefit, likely because they have autoantibodies that we cannot yet detect.

Taken together, current data suggest that among primary anti-TNF nonresponders, patients who are autoantibody positive are most likely to benefit from three agents having other mechanisms of action: rituximab; abatacept (Orencia), a T-cell costimulation modulator; and tocilizumab (Actemra), an antibody to the interleukin-6 receptor. Those who are antibody negative are more likely to benefit only from abatacept or tocilizumab.

Among secondary nonresponders, patients who are autoantibody positive appear to have the most options – another anti-TNF agent, rituximab, abatacept, and tocilizumab – whereas those who are autoantibody negative are likely to benefit from any of these agents except rituximab.

Future Directions

We may be able to refine this personalized approach in the future. For example, the type 1 interferon signature may protect against rituximab-induced B cell depletion, as a higher signature in peripheral blood is associated with a lack of clinical response to this agent (Arthritis Rheum. 2010;62:3607-14). There may well be other predictive markers too, so we may one day be able to apply a multimarker panel in the clinic.

Also, additional treatment factors being identified may help guide the selection among multiple agents. For instance, a patient’s ability to take methotrexate, often given in combination with biologics, may play a role, as evidence suggests that tocilizumab given as monotherapy is just as effective as combinations of TNF blockers with methotrexate.

Identification of predictive biomarkers, while challenging and expensive, will help to optimize treatment. There is a very clear need to come up with a much more sophisticated approach as opposed to the current one based on clinical measures. There has been progress in this area, but we need to continue to invest in biomarker research because this is really a more rational approach and the way forward.

Dr. Tak is professor of medicine at the AMC/University of Amsterdam and Senior Vice President/Head, Therapy Area Immunoinflammation at GlaxoSmithKline. He disclosed that he has been a consultant to Abbott, Amgen, Merck, Pfizer, and Roche/Genentech.

Biologic agents that block the action of tumor necrosis factor have dramatically improved patient outcomes. But they sometimes have little effect or lose effectiveness over time, necessitating a change in therapy. Emerging evidence, recently incorporated into a treatment algorithm, is helping to guide selection of the next biologic for such patients in a rational, personalized way (Rheumatology 2012;51:600-9).

Primary vs. Secondary Nonresponse

The first key consideration in selecting the next therapy is whether the patient has primary or secondary nonresponse to the anti-TNF agent, as this influences the odds of response to another agent in this class. The distinction is not clear-cut, but generally, primary nonresponse manifests 12-16 weeks after starting the agent, whereas secondary nonresponse emerges after 6-12 months.

In the context of anti-TNF therapy, compared with their counterparts having a response, primary nonresponders appear to have disease that is less dependent on TNF and to have a lower proinflammatory gene profile in the synovium.

In contrast, the reason for secondary nonresponse is usually unrelated to the disease process, and instead often is due to the development of antibodies against the TNF blocker – either human antichimeric antibodies (HACAs), as in the case of infliximab (Remicade), or human antihuman antibodies (HAHAs), as in the case of adalimumab (Humira).

Thus, primary nonresponders to TNF blockers are less likely to respond to other agents in this class, whereas secondary nonresponders seem to respond almost as well as patients who have never been given one of these agents before (EULAR 2008, abstract FRI0125).

Presence vs. Absence of Autoantibodies

The second key consideration after failure of a TNF blocker is whether the patient has autoantibodies, specifically, rheumatoid factor and/or anti–citrullinated protein antibodies (ACPAs), as their presence influences the odds of response to the B cell–depleting agent rituximab (Rituxan).

Autoantibody-positive patients have a better response than their autoantibody-negative counterparts to rituximab (EULAR 2009, abstract FRI0256). Occasionally, patients who appear to be autoantibody negative still benefit, likely because they have autoantibodies that we cannot yet detect.

Taken together, current data suggest that among primary anti-TNF nonresponders, patients who are autoantibody positive are most likely to benefit from three agents having other mechanisms of action: rituximab; abatacept (Orencia), a T-cell costimulation modulator; and tocilizumab (Actemra), an antibody to the interleukin-6 receptor. Those who are antibody negative are more likely to benefit only from abatacept or tocilizumab.

Among secondary nonresponders, patients who are autoantibody positive appear to have the most options – another anti-TNF agent, rituximab, abatacept, and tocilizumab – whereas those who are autoantibody negative are likely to benefit from any of these agents except rituximab.

Future Directions

We may be able to refine this personalized approach in the future. For example, the type 1 interferon signature may protect against rituximab-induced B cell depletion, as a higher signature in peripheral blood is associated with a lack of clinical response to this agent (Arthritis Rheum. 2010;62:3607-14). There may well be other predictive markers too, so we may one day be able to apply a multimarker panel in the clinic.

Also, additional treatment factors being identified may help guide the selection among multiple agents. For instance, a patient’s ability to take methotrexate, often given in combination with biologics, may play a role, as evidence suggests that tocilizumab given as monotherapy is just as effective as combinations of TNF blockers with methotrexate.

Identification of predictive biomarkers, while challenging and expensive, will help to optimize treatment. There is a very clear need to come up with a much more sophisticated approach as opposed to the current one based on clinical measures. There has been progress in this area, but we need to continue to invest in biomarker research because this is really a more rational approach and the way forward.

Dr. Tak is professor of medicine at the AMC/University of Amsterdam and Senior Vice President/Head, Therapy Area Immunoinflammation at GlaxoSmithKline. He disclosed that he has been a consultant to Abbott, Amgen, Merck, Pfizer, and Roche/Genentech.

MIAMI BEACH – A diagnosis of pediatric psoriasis is a major event for a child and their family – especially given the long-term medical and psychosocial implications – so proceed cautiously, said Dr. Ronald C. Hansen.

"I am never in a big hurry to make the diagnosis of psoriasis if I am not sure. When you make the diagnosis, you are pretty much saying: ‘You are going to have some degree of psoriasis the rest of your life," Dr. Hansen said at the South Beach Symposium.

And, "I never ever underestimate the impact of psoriasis on the child’s life," he said. "I’ve had 5-year-olds already psychologically stricken."

Affected children – particularly those with more severe disease – will be self-conscious and avoid undressing before gym class or joining others to swim at a pool, said Dr. Hansen, chief of pediatric dermatology at Phoenix Children’s Hospital. "These kids end up loathing their bodies." Psoriasis often has long-term impacts on relationships and intimacy as well.

"The psychosocial impacts ... are immense," agreed session moderator Dr. Lawrence A. Schachner. Because of this, consider whether your patient needs psychosocial counseling when you diagnose psoriasis, added Dr. Schachner, who is director of pediatric dermatology at the University of Miami.

Pediatric psoriasis impacts the whole family. Counsel parents that psoriasis will require a long-term commitment to provide care for their child.

The onset of childhood psoriasis can occur at any age, even at birth. "It is genetically loaded," Dr. Hansen said.

For example, a child born to unaffected parents has about a 4% chance of developing psoriasis, he said. In contrast, a child born to one parent with psoriasis has a 28% likelihood of also developing psoriasis, and if both parents are affected, it jumps to 65%. The chances are even greater if the child has a sibling with psoriasis.

A clinical tip is to ask parents about a history of diaper dermatitis. In his experience, when Dr. Hansen suspects childhood psoriasis, he asks families about whether the child has had difficult diaper rashes. "The parents roll their eyes and say, ‘Yes, diaper rashes from hell.’ This is one of the things I hear routinely when I make the diagnosis in a 4-year-old."

Umbilical and scalp involvement often suggest psoriasis. Severe seborrheic dermatitis, for example, is another diagnostic clue. "We all know about the flaky, persistent scalp dermatitis, sometimes misdiagnosed as seborrheic dermatitis, but again it’s the seborrheic dermatitis from hell. It doesn’t respond to usual treatments," he said.

Even with a rash that looks like psoriasis, most children will have something else: seborrheic dermatitis, atopic dermatitis, or a candidal infection. "If it’s the first time I see this rash, I don’t make the diagnosis of psoriasis. ... Maybe about 20% of them will end up with psoriasis," Dr. Hansen said.

In contrast to adults with psoriasis, pediatric patients can present with prominent, full facial involvement. Flexural involvement is common in all ages, and the lesions can be thick and white or erythematous.

Be particularly thorough with your differential diagnosis of annular psoriasis. "The annular form can fool us. There are a lot of things that cause rings," Dr. Hansen said. A misdiagnosis of extensive tinea can occur, for example.

Some children with psoriasis can have extensive nail involvement. But "nail pits typify psoriasis. ... You can only use nail pits as a diagnostic [criterion] for psoriasis if the cuticle and proximal nail fold are intact," he said.

Pustular psoriasis is rare but important to diagnose in children, Dr. Hansen said. "These patients can be physically quite ill, and treatment has to be instituted right away."

Acute generalized pustular psoriasis is a severe form. Patients can present with fevers, polyarthritis, alopecia, cholestatic jaundice, acute respiratory distress syndrome, eye complications, conjunctivitis, and other adverse signs and comorbidities. "These kids tend to be medical emergencies," Dr. Hansen said. "Consider hospitalization if they have fever."

Many potential factors can elicit this condition. Acute generalized pustular psoriasis can be triggered by an upper respiratory infection or urinary tract infection. "Infections can open the door to anyone already predisposed to get psoriasis," Dr. Hansen said. Withdrawal from systemic or topical steroids and sunburn are other triggers. "Interestingly enough, the [tumor necrosis factor] antagonists which we use to treat psoriasis can also precipitate generalized pustular psoriasis. This confuses most people," he said.

Dr. Hansen disclosed that is a researcher for Novartis. Dr. Schachner disclosed that he is a consultant for Beiersdorf and a researcher/investigator for Astellas, Ferndale, Novartis, Organogenesis, and Stiefel. Both receive royalties from Elsevier, which also owns this news organization.

MIAMI BEACH – A diagnosis of pediatric psoriasis is a major event for a child and their family – especially given the long-term medical and psychosocial implications – so proceed cautiously, said Dr. Ronald C. Hansen.

"I am never in a big hurry to make the diagnosis of psoriasis if I am not sure. When you make the diagnosis, you are pretty much saying: ‘You are going to have some degree of psoriasis the rest of your life," Dr. Hansen said at the South Beach Symposium.

And, "I never ever underestimate the impact of psoriasis on the child’s life," he said. "I’ve had 5-year-olds already psychologically stricken."

Affected children – particularly those with more severe disease – will be self-conscious and avoid undressing before gym class or joining others to swim at a pool, said Dr. Hansen, chief of pediatric dermatology at Phoenix Children’s Hospital. "These kids end up loathing their bodies." Psoriasis often has long-term impacts on relationships and intimacy as well.

"The psychosocial impacts ... are immense," agreed session moderator Dr. Lawrence A. Schachner. Because of this, consider whether your patient needs psychosocial counseling when you diagnose psoriasis, added Dr. Schachner, who is director of pediatric dermatology at the University of Miami.

Pediatric psoriasis impacts the whole family. Counsel parents that psoriasis will require a long-term commitment to provide care for their child.

The onset of childhood psoriasis can occur at any age, even at birth. "It is genetically loaded," Dr. Hansen said.

For example, a child born to unaffected parents has about a 4% chance of developing psoriasis, he said. In contrast, a child born to one parent with psoriasis has a 28% likelihood of also developing psoriasis, and if both parents are affected, it jumps to 65%. The chances are even greater if the child has a sibling with psoriasis.

A clinical tip is to ask parents about a history of diaper dermatitis. In his experience, when Dr. Hansen suspects childhood psoriasis, he asks families about whether the child has had difficult diaper rashes. "The parents roll their eyes and say, ‘Yes, diaper rashes from hell.’ This is one of the things I hear routinely when I make the diagnosis in a 4-year-old."

Umbilical and scalp involvement often suggest psoriasis. Severe seborrheic dermatitis, for example, is another diagnostic clue. "We all know about the flaky, persistent scalp dermatitis, sometimes misdiagnosed as seborrheic dermatitis, but again it’s the seborrheic dermatitis from hell. It doesn’t respond to usual treatments," he said.

Even with a rash that looks like psoriasis, most children will have something else: seborrheic dermatitis, atopic dermatitis, or a candidal infection. "If it’s the first time I see this rash, I don’t make the diagnosis of psoriasis. ... Maybe about 20% of them will end up with psoriasis," Dr. Hansen said.

In contrast to adults with psoriasis, pediatric patients can present with prominent, full facial involvement. Flexural involvement is common in all ages, and the lesions can be thick and white or erythematous.

Be particularly thorough with your differential diagnosis of annular psoriasis. "The annular form can fool us. There are a lot of things that cause rings," Dr. Hansen said. A misdiagnosis of extensive tinea can occur, for example.

Some children with psoriasis can have extensive nail involvement. But "nail pits typify psoriasis. ... You can only use nail pits as a diagnostic [criterion] for psoriasis if the cuticle and proximal nail fold are intact," he said.

Pustular psoriasis is rare but important to diagnose in children, Dr. Hansen said. "These patients can be physically quite ill, and treatment has to be instituted right away."

Acute generalized pustular psoriasis is a severe form. Patients can present with fevers, polyarthritis, alopecia, cholestatic jaundice, acute respiratory distress syndrome, eye complications, conjunctivitis, and other adverse signs and comorbidities. "These kids tend to be medical emergencies," Dr. Hansen said. "Consider hospitalization if they have fever."

Many potential factors can elicit this condition. Acute generalized pustular psoriasis can be triggered by an upper respiratory infection or urinary tract infection. "Infections can open the door to anyone already predisposed to get psoriasis," Dr. Hansen said. Withdrawal from systemic or topical steroids and sunburn are other triggers. "Interestingly enough, the [tumor necrosis factor] antagonists which we use to treat psoriasis can also precipitate generalized pustular psoriasis. This confuses most people," he said.

Dr. Hansen disclosed that is a researcher for Novartis. Dr. Schachner disclosed that he is a consultant for Beiersdorf and a researcher/investigator for Astellas, Ferndale, Novartis, Organogenesis, and Stiefel. Both receive royalties from Elsevier, which also owns this news organization.

MIAMI BEACH – A diagnosis of pediatric psoriasis is a major event for a child and their family – especially given the long-term medical and psychosocial implications – so proceed cautiously, said Dr. Ronald C. Hansen.

"I am never in a big hurry to make the diagnosis of psoriasis if I am not sure. When you make the diagnosis, you are pretty much saying: ‘You are going to have some degree of psoriasis the rest of your life," Dr. Hansen said at the South Beach Symposium.

And, "I never ever underestimate the impact of psoriasis on the child’s life," he said. "I’ve had 5-year-olds already psychologically stricken."

Affected children – particularly those with more severe disease – will be self-conscious and avoid undressing before gym class or joining others to swim at a pool, said Dr. Hansen, chief of pediatric dermatology at Phoenix Children’s Hospital. "These kids end up loathing their bodies." Psoriasis often has long-term impacts on relationships and intimacy as well.

"The psychosocial impacts ... are immense," agreed session moderator Dr. Lawrence A. Schachner. Because of this, consider whether your patient needs psychosocial counseling when you diagnose psoriasis, added Dr. Schachner, who is director of pediatric dermatology at the University of Miami.

Pediatric psoriasis impacts the whole family. Counsel parents that psoriasis will require a long-term commitment to provide care for their child.

The onset of childhood psoriasis can occur at any age, even at birth. "It is genetically loaded," Dr. Hansen said.

For example, a child born to unaffected parents has about a 4% chance of developing psoriasis, he said. In contrast, a child born to one parent with psoriasis has a 28% likelihood of also developing psoriasis, and if both parents are affected, it jumps to 65%. The chances are even greater if the child has a sibling with psoriasis.

A clinical tip is to ask parents about a history of diaper dermatitis. In his experience, when Dr. Hansen suspects childhood psoriasis, he asks families about whether the child has had difficult diaper rashes. "The parents roll their eyes and say, ‘Yes, diaper rashes from hell.’ This is one of the things I hear routinely when I make the diagnosis in a 4-year-old."

Umbilical and scalp involvement often suggest psoriasis. Severe seborrheic dermatitis, for example, is another diagnostic clue. "We all know about the flaky, persistent scalp dermatitis, sometimes misdiagnosed as seborrheic dermatitis, but again it’s the seborrheic dermatitis from hell. It doesn’t respond to usual treatments," he said.

Even with a rash that looks like psoriasis, most children will have something else: seborrheic dermatitis, atopic dermatitis, or a candidal infection. "If it’s the first time I see this rash, I don’t make the diagnosis of psoriasis. ... Maybe about 20% of them will end up with psoriasis," Dr. Hansen said.

In contrast to adults with psoriasis, pediatric patients can present with prominent, full facial involvement. Flexural involvement is common in all ages, and the lesions can be thick and white or erythematous.

Be particularly thorough with your differential diagnosis of annular psoriasis. "The annular form can fool us. There are a lot of things that cause rings," Dr. Hansen said. A misdiagnosis of extensive tinea can occur, for example.

Some children with psoriasis can have extensive nail involvement. But "nail pits typify psoriasis. ... You can only use nail pits as a diagnostic [criterion] for psoriasis if the cuticle and proximal nail fold are intact," he said.

Pustular psoriasis is rare but important to diagnose in children, Dr. Hansen said. "These patients can be physically quite ill, and treatment has to be instituted right away."

Acute generalized pustular psoriasis is a severe form. Patients can present with fevers, polyarthritis, alopecia, cholestatic jaundice, acute respiratory distress syndrome, eye complications, conjunctivitis, and other adverse signs and comorbidities. "These kids tend to be medical emergencies," Dr. Hansen said. "Consider hospitalization if they have fever."

Many potential factors can elicit this condition. Acute generalized pustular psoriasis can be triggered by an upper respiratory infection or urinary tract infection. "Infections can open the door to anyone already predisposed to get psoriasis," Dr. Hansen said. Withdrawal from systemic or topical steroids and sunburn are other triggers. "Interestingly enough, the [tumor necrosis factor] antagonists which we use to treat psoriasis can also precipitate generalized pustular psoriasis. This confuses most people," he said.

Dr. Hansen disclosed that is a researcher for Novartis. Dr. Schachner disclosed that he is a consultant for Beiersdorf and a researcher/investigator for Astellas, Ferndale, Novartis, Organogenesis, and Stiefel. Both receive royalties from Elsevier, which also owns this news organization.

SAN DIEGO – A large study has determined that psoriasis is not an independent risk factor for ischemic heart disease, based on Framingham Risk Scores.

While previous studies have demonstrated that cardiac mortality is increased in patients with psoriasis, it is also known that people with the skin condition have a higher prevalence of smoking, alcohol consumption, obesity, diabetes, and dyslipidemia, researchers reported in a poster session at the annual meeting of the American Academy of Dermatology.

"Is this increase in ischemic heart disease due to traditional risk factors, or is psoriasis an additional independent risk factor?" wrote the investigators, who were led by Dr. Marian T. McEvoy, in the abstract.

They performed a population-based analysis of 1,338 adults with psoriasis who resided in Olmstead County, Minn., between 1998 and 2008 to evaluate the validity of the Framingham Risk Score (FRS) in predicting the incidence of ischemic heart disease in the study cohort. The FRS is a validated measure of standard ischemic heart disease risk factors.

Dr. McEvoy, a dermatologist at the Mayo Clinic in Rochester, Minn., and her associates compared the risk of cardiac death and myocardial infarction based on the FRS with the actual incidence of myocardial infarction and cardiac death in the study population, which was limited to patients older than age 30 but younger than age 80. They used Poisson regression models and standardized incidence ratios for statistical analysis.

The researchers reported that full Framingham risk factors were available for 974 of the 1,338 patients (73%). They predicted that the median 10-year risk of cardiac events based on the FRS was 3.8%, while the observed 10-year risk of cardiac events was 5.5%. However, there were 44 observed cardiac events compared with 47.7 FRS-predicted cardiac events, which translated into a standardized incidence ratio between the two groups of 0.9. Standardized incidence ratios also showed no statistically significant differences between the two groups when analyzed by gender, by age greater than 65 years, by age less than 65 years, and by whether patients were receiving systemic treatment or not.

"If psoriasis was an independent risk factor for ischemic heart disease, the observed incidence of cardiac events would have been in excess of predicted," the researchers wrote in their poster. "Since there was no statistical difference between actual and predicted events, psoriasis is not an independent risk factor for ischemic heart disease."

In a later interview, Dr. McEvoy acknowledged certain limitations of the study, including the fact that the small number of observed cardiac events (44) limited the statistical power of the study. "Since this is a retrospective study, we did not have a good tool to assess severity of psoriasis," she said. "We used surrogates based on therapy to identify those with ‘more severe disease.’ The Framingham Risk Score was valid for this group also."

The study was partially funded by a grant from Pfizer, and was made possible by a grant from Amgen/Wyeth and by the Rochester Epidemiology Project.

SAN DIEGO – A large study has determined that psoriasis is not an independent risk factor for ischemic heart disease, based on Framingham Risk Scores.

While previous studies have demonstrated that cardiac mortality is increased in patients with psoriasis, it is also known that people with the skin condition have a higher prevalence of smoking, alcohol consumption, obesity, diabetes, and dyslipidemia, researchers reported in a poster session at the annual meeting of the American Academy of Dermatology.

"Is this increase in ischemic heart disease due to traditional risk factors, or is psoriasis an additional independent risk factor?" wrote the investigators, who were led by Dr. Marian T. McEvoy, in the abstract.

They performed a population-based analysis of 1,338 adults with psoriasis who resided in Olmstead County, Minn., between 1998 and 2008 to evaluate the validity of the Framingham Risk Score (FRS) in predicting the incidence of ischemic heart disease in the study cohort. The FRS is a validated measure of standard ischemic heart disease risk factors.

Dr. McEvoy, a dermatologist at the Mayo Clinic in Rochester, Minn., and her associates compared the risk of cardiac death and myocardial infarction based on the FRS with the actual incidence of myocardial infarction and cardiac death in the study population, which was limited to patients older than age 30 but younger than age 80. They used Poisson regression models and standardized incidence ratios for statistical analysis.

The researchers reported that full Framingham risk factors were available for 974 of the 1,338 patients (73%). They predicted that the median 10-year risk of cardiac events based on the FRS was 3.8%, while the observed 10-year risk of cardiac events was 5.5%. However, there were 44 observed cardiac events compared with 47.7 FRS-predicted cardiac events, which translated into a standardized incidence ratio between the two groups of 0.9. Standardized incidence ratios also showed no statistically significant differences between the two groups when analyzed by gender, by age greater than 65 years, by age less than 65 years, and by whether patients were receiving systemic treatment or not.

"If psoriasis was an independent risk factor for ischemic heart disease, the observed incidence of cardiac events would have been in excess of predicted," the researchers wrote in their poster. "Since there was no statistical difference between actual and predicted events, psoriasis is not an independent risk factor for ischemic heart disease."

In a later interview, Dr. McEvoy acknowledged certain limitations of the study, including the fact that the small number of observed cardiac events (44) limited the statistical power of the study. "Since this is a retrospective study, we did not have a good tool to assess severity of psoriasis," she said. "We used surrogates based on therapy to identify those with ‘more severe disease.’ The Framingham Risk Score was valid for this group also."

The study was partially funded by a grant from Pfizer, and was made possible by a grant from Amgen/Wyeth and by the Rochester Epidemiology Project.

SAN DIEGO – A large study has determined that psoriasis is not an independent risk factor for ischemic heart disease, based on Framingham Risk Scores.

While previous studies have demonstrated that cardiac mortality is increased in patients with psoriasis, it is also known that people with the skin condition have a higher prevalence of smoking, alcohol consumption, obesity, diabetes, and dyslipidemia, researchers reported in a poster session at the annual meeting of the American Academy of Dermatology.

"Is this increase in ischemic heart disease due to traditional risk factors, or is psoriasis an additional independent risk factor?" wrote the investigators, who were led by Dr. Marian T. McEvoy, in the abstract.

They performed a population-based analysis of 1,338 adults with psoriasis who resided in Olmstead County, Minn., between 1998 and 2008 to evaluate the validity of the Framingham Risk Score (FRS) in predicting the incidence of ischemic heart disease in the study cohort. The FRS is a validated measure of standard ischemic heart disease risk factors.

Dr. McEvoy, a dermatologist at the Mayo Clinic in Rochester, Minn., and her associates compared the risk of cardiac death and myocardial infarction based on the FRS with the actual incidence of myocardial infarction and cardiac death in the study population, which was limited to patients older than age 30 but younger than age 80. They used Poisson regression models and standardized incidence ratios for statistical analysis.

The researchers reported that full Framingham risk factors were available for 974 of the 1,338 patients (73%). They predicted that the median 10-year risk of cardiac events based on the FRS was 3.8%, while the observed 10-year risk of cardiac events was 5.5%. However, there were 44 observed cardiac events compared with 47.7 FRS-predicted cardiac events, which translated into a standardized incidence ratio between the two groups of 0.9. Standardized incidence ratios also showed no statistically significant differences between the two groups when analyzed by gender, by age greater than 65 years, by age less than 65 years, and by whether patients were receiving systemic treatment or not.

"If psoriasis was an independent risk factor for ischemic heart disease, the observed incidence of cardiac events would have been in excess of predicted," the researchers wrote in their poster. "Since there was no statistical difference between actual and predicted events, psoriasis is not an independent risk factor for ischemic heart disease."

In a later interview, Dr. McEvoy acknowledged certain limitations of the study, including the fact that the small number of observed cardiac events (44) limited the statistical power of the study. "Since this is a retrospective study, we did not have a good tool to assess severity of psoriasis," she said. "We used surrogates based on therapy to identify those with ‘more severe disease.’ The Framingham Risk Score was valid for this group also."

The study was partially funded by a grant from Pfizer, and was made possible by a grant from Amgen/Wyeth and by the Rochester Epidemiology Project.