New York University (NYU): Pediatric Rheumatology

NEW YORK – Kidney function may be the single best determinant of outcome in Henoch-Schönlein purpura, according to Dr. Philip Kahn.

Although only 1%-3% of patients develop end-stage renal disease, Henoch-Schönlein purpura (HSP) accounts for up to 20% of children on dialysis, Dr. Kahn said at a meeting sponsored by New York University.

The most common form of vasculitis in children, HSP is generally self-limiting. "Most renal manifestations of HSP will resolve spontaneously. A minority of patients with HSP will develop nephrotic-range proteinuria and elevated creatinine, with or without hypertension," according to Dr. Kahn, a pediatric rheumatologist affiliated with the New York University Langone Medical Center. "This increases the risk of progressive disease, and necessitates dialysis for a small minority of these patients."

About 40% of patients with HSP may be hospitalized at some point during their illness, and severe renal insufficiency is cited as one of the primary reasons for hospitalization.

HSP may account for about one-half of all vasculitis cases in the United States. A full 90% of HSP cases present during childhood, with a mean age of onset of 4-7 years. The characteristic clinical features of HSP are nephritis, purpura, arthritis/arthralgia, and abdominal pain. Symptoms typically last for about 4 weeks.

Between 20% and 54% of HSP patients have glomerulonephritis, said Dr. Kahn. Many patients will have asymptomatic hematuria, with mild or no proteinuria. "We see a gamut of urinalysis abnormalities: 14% have isolated hematuria, 9% have isolated proteinuria, 56% have both hematuria and proteinuria, 20% have nephrotic syndrome, and 1% have nephrotic-nephritic syndrome," said Dr. Kahn. For 85% of patients, nephritis develops within the first 4 weeks.

Patients with transient hematuria and proteinuria generally have an excellent prognosis, he said, and renal symptoms usually resolve spontaneously. However, counterintuitively up to 20% of patients who develop mild proteinuria may still have a poor outcome with advanced renal disease on biopsy, emphasizing that the biopsy may not mirror the clinical symptoms. Of those with nephrotic-range proteinuria and elevated creatinine levels, with or without hypertension, 1%-3% develop progressive disease. "Studies have shown that long-term persistent renal abnormalities are more likely to present with nephrotic syndrome, yet symptoms do resolve for half of these patients, no matter what the treatment," said Dr. Kahn.

A recent report indicated that 8 years after HSP, those with nephritis at the onset of HSP had more than a threefold increased risk of hypertension and/or urine abnormalities, as well as an increased risk of pregnancy-related proteinuria.

Typically, patients with overt renal disease are managed by nephrologists. About 40% of patients with HSP may be hospitalized at some point during their illness, and severe renal insufficiency is cited as one of the primary reasons for hospitalization.

To monitor renal involvement in HSP patients, Dr. Kahn recommended doing urinalysis dipstick and blood pressure monitoring weekly for the first 1-2 months after diagnosis, then monthly for the next 6 months, followed by every other month until the completion of 1 year. Neither biopsy nor symptoms reliably predict outcome, said Dr. Kahn. Pathologic findings of HSP appear identical to those of IgA nephropathy, with histologic findings including mesangial proliferation, focal and segmental proliferation, and severe crescentic glomerulonephritis. Electron dense deposits can be seen in mesangial areas under electron microscopy. Immunofluorescence can reveal large, globular mesangial IgA deposits, which occasionally also include IgG and IgM. The presence of crescents may not necessarily foretell poor prognosis, although generally patients with greater than 50% crescents do not recover fully.

There is no well-accepted treatment for HSP-related nephritis. Most evidence comes from small retrospective cohort studies, with marked differences in the definitions of renal involvement, dosing regimens, and glucocorticoid modes of delivery. Variable results have been reported for cyclophosphamide, cyclosporine, mycophenolate mofetil, azathioprine, antiplatelet therapy, and plasmapheresis.

Whether glucocorticoids can be used to treat or prevent HSP-related nephritis is controversial. A meta-analysis of patients treated between 1956 and 2007 comparing outcomes of prednisone treatment versus supportive care suggested that the use of corticosteroids early in the disease reduced the risk of developing persistent renal disease (Pediatrics 2007;120:1079-87). On the other hand, a Cochrane review of 10 randomized, controlled trials that included 1,230 patients failed to demonstrate any benefit of prednisone in preventing serious long-term kidney disease in HSP (Arch. Dis. Child. 2009;94:132-7).

HSP may recur in about one-third of patients within 4 months, with the second bout being milder and briefer than the first. There is some evidence that the risk of recurrence increases in those with more severe disease, including patients who have had nephritis, an elevated erythrocyte sedimentation rate, or steroid treatment.

Renal impairment in HSP patients may also resurface during pregnancy. In a 24-year follow-up of patients who had severe HSP and glomerulonephritis at onset, 16 of 23 pregnancies (70%) were complicated by hypertension, proteinuria, or both, and 56% of the 9 women with complicated pregnancies had a poor renal outcome (Lancet 2002;360:666-70). For this reason, all women with HSP renal symptoms, however mild, should be carefully monitored during and after pregnancy.

Dr. Kahn said he had no relevant financial disclosures.

NEW YORK – Kidney function may be the single best determinant of outcome in Henoch-Schönlein purpura, according to Dr. Philip Kahn.

Although only 1%-3% of patients develop end-stage renal disease, Henoch-Schönlein purpura (HSP) accounts for up to 20% of children on dialysis, Dr. Kahn said at a meeting sponsored by New York University.

The most common form of vasculitis in children, HSP is generally self-limiting. "Most renal manifestations of HSP will resolve spontaneously. A minority of patients with HSP will develop nephrotic-range proteinuria and elevated creatinine, with or without hypertension," according to Dr. Kahn, a pediatric rheumatologist affiliated with the New York University Langone Medical Center. "This increases the risk of progressive disease, and necessitates dialysis for a small minority of these patients."

About 40% of patients with HSP may be hospitalized at some point during their illness, and severe renal insufficiency is cited as one of the primary reasons for hospitalization.

HSP may account for about one-half of all vasculitis cases in the United States. A full 90% of HSP cases present during childhood, with a mean age of onset of 4-7 years. The characteristic clinical features of HSP are nephritis, purpura, arthritis/arthralgia, and abdominal pain. Symptoms typically last for about 4 weeks.

Between 20% and 54% of HSP patients have glomerulonephritis, said Dr. Kahn. Many patients will have asymptomatic hematuria, with mild or no proteinuria. "We see a gamut of urinalysis abnormalities: 14% have isolated hematuria, 9% have isolated proteinuria, 56% have both hematuria and proteinuria, 20% have nephrotic syndrome, and 1% have nephrotic-nephritic syndrome," said Dr. Kahn. For 85% of patients, nephritis develops within the first 4 weeks.

Patients with transient hematuria and proteinuria generally have an excellent prognosis, he said, and renal symptoms usually resolve spontaneously. However, counterintuitively up to 20% of patients who develop mild proteinuria may still have a poor outcome with advanced renal disease on biopsy, emphasizing that the biopsy may not mirror the clinical symptoms. Of those with nephrotic-range proteinuria and elevated creatinine levels, with or without hypertension, 1%-3% develop progressive disease. "Studies have shown that long-term persistent renal abnormalities are more likely to present with nephrotic syndrome, yet symptoms do resolve for half of these patients, no matter what the treatment," said Dr. Kahn.

A recent report indicated that 8 years after HSP, those with nephritis at the onset of HSP had more than a threefold increased risk of hypertension and/or urine abnormalities, as well as an increased risk of pregnancy-related proteinuria.

Typically, patients with overt renal disease are managed by nephrologists. About 40% of patients with HSP may be hospitalized at some point during their illness, and severe renal insufficiency is cited as one of the primary reasons for hospitalization.

To monitor renal involvement in HSP patients, Dr. Kahn recommended doing urinalysis dipstick and blood pressure monitoring weekly for the first 1-2 months after diagnosis, then monthly for the next 6 months, followed by every other month until the completion of 1 year. Neither biopsy nor symptoms reliably predict outcome, said Dr. Kahn. Pathologic findings of HSP appear identical to those of IgA nephropathy, with histologic findings including mesangial proliferation, focal and segmental proliferation, and severe crescentic glomerulonephritis. Electron dense deposits can be seen in mesangial areas under electron microscopy. Immunofluorescence can reveal large, globular mesangial IgA deposits, which occasionally also include IgG and IgM. The presence of crescents may not necessarily foretell poor prognosis, although generally patients with greater than 50% crescents do not recover fully.

There is no well-accepted treatment for HSP-related nephritis. Most evidence comes from small retrospective cohort studies, with marked differences in the definitions of renal involvement, dosing regimens, and glucocorticoid modes of delivery. Variable results have been reported for cyclophosphamide, cyclosporine, mycophenolate mofetil, azathioprine, antiplatelet therapy, and plasmapheresis.

Whether glucocorticoids can be used to treat or prevent HSP-related nephritis is controversial. A meta-analysis of patients treated between 1956 and 2007 comparing outcomes of prednisone treatment versus supportive care suggested that the use of corticosteroids early in the disease reduced the risk of developing persistent renal disease (Pediatrics 2007;120:1079-87). On the other hand, a Cochrane review of 10 randomized, controlled trials that included 1,230 patients failed to demonstrate any benefit of prednisone in preventing serious long-term kidney disease in HSP (Arch. Dis. Child. 2009;94:132-7).

HSP may recur in about one-third of patients within 4 months, with the second bout being milder and briefer than the first. There is some evidence that the risk of recurrence increases in those with more severe disease, including patients who have had nephritis, an elevated erythrocyte sedimentation rate, or steroid treatment.

Renal impairment in HSP patients may also resurface during pregnancy. In a 24-year follow-up of patients who had severe HSP and glomerulonephritis at onset, 16 of 23 pregnancies (70%) were complicated by hypertension, proteinuria, or both, and 56% of the 9 women with complicated pregnancies had a poor renal outcome (Lancet 2002;360:666-70). For this reason, all women with HSP renal symptoms, however mild, should be carefully monitored during and after pregnancy.

Dr. Kahn said he had no relevant financial disclosures.

NEW YORK – Kidney function may be the single best determinant of outcome in Henoch-Schönlein purpura, according to Dr. Philip Kahn.

Although only 1%-3% of patients develop end-stage renal disease, Henoch-Schönlein purpura (HSP) accounts for up to 20% of children on dialysis, Dr. Kahn said at a meeting sponsored by New York University.

The most common form of vasculitis in children, HSP is generally self-limiting. "Most renal manifestations of HSP will resolve spontaneously. A minority of patients with HSP will develop nephrotic-range proteinuria and elevated creatinine, with or without hypertension," according to Dr. Kahn, a pediatric rheumatologist affiliated with the New York University Langone Medical Center. "This increases the risk of progressive disease, and necessitates dialysis for a small minority of these patients."

About 40% of patients with HSP may be hospitalized at some point during their illness, and severe renal insufficiency is cited as one of the primary reasons for hospitalization.

HSP may account for about one-half of all vasculitis cases in the United States. A full 90% of HSP cases present during childhood, with a mean age of onset of 4-7 years. The characteristic clinical features of HSP are nephritis, purpura, arthritis/arthralgia, and abdominal pain. Symptoms typically last for about 4 weeks.

Between 20% and 54% of HSP patients have glomerulonephritis, said Dr. Kahn. Many patients will have asymptomatic hematuria, with mild or no proteinuria. "We see a gamut of urinalysis abnormalities: 14% have isolated hematuria, 9% have isolated proteinuria, 56% have both hematuria and proteinuria, 20% have nephrotic syndrome, and 1% have nephrotic-nephritic syndrome," said Dr. Kahn. For 85% of patients, nephritis develops within the first 4 weeks.

Patients with transient hematuria and proteinuria generally have an excellent prognosis, he said, and renal symptoms usually resolve spontaneously. However, counterintuitively up to 20% of patients who develop mild proteinuria may still have a poor outcome with advanced renal disease on biopsy, emphasizing that the biopsy may not mirror the clinical symptoms. Of those with nephrotic-range proteinuria and elevated creatinine levels, with or without hypertension, 1%-3% develop progressive disease. "Studies have shown that long-term persistent renal abnormalities are more likely to present with nephrotic syndrome, yet symptoms do resolve for half of these patients, no matter what the treatment," said Dr. Kahn.

A recent report indicated that 8 years after HSP, those with nephritis at the onset of HSP had more than a threefold increased risk of hypertension and/or urine abnormalities, as well as an increased risk of pregnancy-related proteinuria.

Typically, patients with overt renal disease are managed by nephrologists. About 40% of patients with HSP may be hospitalized at some point during their illness, and severe renal insufficiency is cited as one of the primary reasons for hospitalization.

To monitor renal involvement in HSP patients, Dr. Kahn recommended doing urinalysis dipstick and blood pressure monitoring weekly for the first 1-2 months after diagnosis, then monthly for the next 6 months, followed by every other month until the completion of 1 year. Neither biopsy nor symptoms reliably predict outcome, said Dr. Kahn. Pathologic findings of HSP appear identical to those of IgA nephropathy, with histologic findings including mesangial proliferation, focal and segmental proliferation, and severe crescentic glomerulonephritis. Electron dense deposits can be seen in mesangial areas under electron microscopy. Immunofluorescence can reveal large, globular mesangial IgA deposits, which occasionally also include IgG and IgM. The presence of crescents may not necessarily foretell poor prognosis, although generally patients with greater than 50% crescents do not recover fully.

There is no well-accepted treatment for HSP-related nephritis. Most evidence comes from small retrospective cohort studies, with marked differences in the definitions of renal involvement, dosing regimens, and glucocorticoid modes of delivery. Variable results have been reported for cyclophosphamide, cyclosporine, mycophenolate mofetil, azathioprine, antiplatelet therapy, and plasmapheresis.

Whether glucocorticoids can be used to treat or prevent HSP-related nephritis is controversial. A meta-analysis of patients treated between 1956 and 2007 comparing outcomes of prednisone treatment versus supportive care suggested that the use of corticosteroids early in the disease reduced the risk of developing persistent renal disease (Pediatrics 2007;120:1079-87). On the other hand, a Cochrane review of 10 randomized, controlled trials that included 1,230 patients failed to demonstrate any benefit of prednisone in preventing serious long-term kidney disease in HSP (Arch. Dis. Child. 2009;94:132-7).

HSP may recur in about one-third of patients within 4 months, with the second bout being milder and briefer than the first. There is some evidence that the risk of recurrence increases in those with more severe disease, including patients who have had nephritis, an elevated erythrocyte sedimentation rate, or steroid treatment.

Renal impairment in HSP patients may also resurface during pregnancy. In a 24-year follow-up of patients who had severe HSP and glomerulonephritis at onset, 16 of 23 pregnancies (70%) were complicated by hypertension, proteinuria, or both, and 56% of the 9 women with complicated pregnancies had a poor renal outcome (Lancet 2002;360:666-70). For this reason, all women with HSP renal symptoms, however mild, should be carefully monitored during and after pregnancy.

Dr. Kahn said he had no relevant financial disclosures.

NEW YORK – Poststreptococcal reactive arthritis in a child means fewer cardiac sequelae and less need for prophylactic antibiotics, making it worth looking for when the obvious diagnosis seems to be acute rheumatic fever, according to Dr. Stanford T. Shulman, who spoke at a meeting sponsored by New York University.

"There are several reasons why it is important to differentiate poststreptococcal reactive arthritis from [acute rheumatic fever (ARF)]," explained Dr. Shulman, chief of infectious diseases at the Children’s Memorial Hospital in Chicago and the Virginia H. Rogers Professor of Pediatric Infectious Diseases at Northwestern University, Chicago. "Rheumatic fever frequently recurs and requires long-term antibiotics to prevent recurrence."

Not fulfilling the Jones criteria is one of the first clues of PSRA. The updated 1992 Jones criteria specifies that the diagnosis of ARF relies on the presence of two of the major criteria (that is, carditis, polyarthritis of large joints, chorea, erythema marginatum, and subcutaneous nodules) or one major and two minor (arthralgia, fever, elevation of the acute phase reactants C-reactive protein and erythrocyte sedimentation rate, prolonged PR interval on an echocardiogram) criteria, plus evidence of a recent group A streptococcal infection.

Heart involvement is controversial in PSRA and if it occurs, it is quite rare, said Dr. Shulman. But carditis is the common in acute rheumatic fever and accounts for its importance. Patients with ARF who have carditis characteristically have valvulitis with mitral regurgitation most commonly, followed by mitral and aortic regurgitation. Aortic regurgitation alone is rare in ARF. Patients with only pericarditis and/or myocarditis without valvulitis do not have rheumatic heart disease. After reviewing eight clinical reports representing 120 clinical cases of PSRA, Dr. Shulman concluded that it was questionable whether carditis can occur in children with PSRA, but that carditis was completely absent in several series of adults with PSRA.

There are other ways to differentiate PSRA from ARF. Symptoms of PSRA have an acute onset, usually less than 2 weeks from the time of streptococcal infection, compared with 2-3 weeks for ARF. Arthritic symptoms are brief with ARF (about 6 days). But, in PSRA, they can last for 8 weeks or longer and may be recurrent. In PSRA, the arthritis can affect any joint, large or small, and symptoms may be symmetric or asymmetric with axial involvement. In contrast, ARF arthritis is not symmetric and does not usually affect small joints or the axis. With ARF, arthritic symptoms typically migrate but are non-migratory with PSRA. Patients in either group may complain of morning stiffness.

Response to treatment is another way to distinguish the two. If a patient with poststreptococcal arthritis responds poorly or not at all to NSAIDs, then the diagnosis is much more likely to be PSRA; ARF patients respond very promptly to such treatment, says Dr. Shulman.

Both the American Heart Association and the American Academy of Pediatrics recommend that patients with acute rheumatic fever receive antistreptococcus prophylaxis until they are 21 years old. The 2009 American Heart Association Scientific Statement recommends that patients with PSRA should be observed carefully for several months for clinical evidence of carditis and should receive up to 1 year of secondary prophylaxis after the onset of symptoms and discontinue if no findings of carditis are apparent. Dr. Shulman said he gives either IM penicillin every 4 weeks or twice daily oral penicillin for 1-2 years, which should be discontinued if no evidence of valvular disease appears. If valvular disease is found, the patient is then considered to have ARF and should continue to receive long-term secondary prophylaxis.

The good news is that there has been a dramatic decrease in the number of rheumatogenic strains of group A streptococcus in circulation, says Dr. Shulman. By comparing the prevalence of rheumatogenic and nonrheumatogenic strains of group A strep in samples from 468 children with pharyngitis taken in 1961-1968 with samples from 450 children with pharyngitis taken in 2000-2004, Dr. Shulman found that in the 1960s, two-thirds of group A strep strains in circulation were rheumatogenic, while in the later sample only one-quarter were. He and his colleagues recently completed a large 13-center U.S. and Canadian study analyzing the subtypes of group A streptococcal infection more recently in circulation through the use of M protein typing.

Dr. Shulman is a member of Merck’s speakers bureau and has research support from Quidel.

NEW YORK – Poststreptococcal reactive arthritis in a child means fewer cardiac sequelae and less need for prophylactic antibiotics, making it worth looking for when the obvious diagnosis seems to be acute rheumatic fever, according to Dr. Stanford T. Shulman, who spoke at a meeting sponsored by New York University.

"There are several reasons why it is important to differentiate poststreptococcal reactive arthritis from [acute rheumatic fever (ARF)]," explained Dr. Shulman, chief of infectious diseases at the Children’s Memorial Hospital in Chicago and the Virginia H. Rogers Professor of Pediatric Infectious Diseases at Northwestern University, Chicago. "Rheumatic fever frequently recurs and requires long-term antibiotics to prevent recurrence."

Not fulfilling the Jones criteria is one of the first clues of PSRA. The updated 1992 Jones criteria specifies that the diagnosis of ARF relies on the presence of two of the major criteria (that is, carditis, polyarthritis of large joints, chorea, erythema marginatum, and subcutaneous nodules) or one major and two minor (arthralgia, fever, elevation of the acute phase reactants C-reactive protein and erythrocyte sedimentation rate, prolonged PR interval on an echocardiogram) criteria, plus evidence of a recent group A streptococcal infection.

Heart involvement is controversial in PSRA and if it occurs, it is quite rare, said Dr. Shulman. But carditis is the common in acute rheumatic fever and accounts for its importance. Patients with ARF who have carditis characteristically have valvulitis with mitral regurgitation most commonly, followed by mitral and aortic regurgitation. Aortic regurgitation alone is rare in ARF. Patients with only pericarditis and/or myocarditis without valvulitis do not have rheumatic heart disease. After reviewing eight clinical reports representing 120 clinical cases of PSRA, Dr. Shulman concluded that it was questionable whether carditis can occur in children with PSRA, but that carditis was completely absent in several series of adults with PSRA.

There are other ways to differentiate PSRA from ARF. Symptoms of PSRA have an acute onset, usually less than 2 weeks from the time of streptococcal infection, compared with 2-3 weeks for ARF. Arthritic symptoms are brief with ARF (about 6 days). But, in PSRA, they can last for 8 weeks or longer and may be recurrent. In PSRA, the arthritis can affect any joint, large or small, and symptoms may be symmetric or asymmetric with axial involvement. In contrast, ARF arthritis is not symmetric and does not usually affect small joints or the axis. With ARF, arthritic symptoms typically migrate but are non-migratory with PSRA. Patients in either group may complain of morning stiffness.

Response to treatment is another way to distinguish the two. If a patient with poststreptococcal arthritis responds poorly or not at all to NSAIDs, then the diagnosis is much more likely to be PSRA; ARF patients respond very promptly to such treatment, says Dr. Shulman.

Both the American Heart Association and the American Academy of Pediatrics recommend that patients with acute rheumatic fever receive antistreptococcus prophylaxis until they are 21 years old. The 2009 American Heart Association Scientific Statement recommends that patients with PSRA should be observed carefully for several months for clinical evidence of carditis and should receive up to 1 year of secondary prophylaxis after the onset of symptoms and discontinue if no findings of carditis are apparent. Dr. Shulman said he gives either IM penicillin every 4 weeks or twice daily oral penicillin for 1-2 years, which should be discontinued if no evidence of valvular disease appears. If valvular disease is found, the patient is then considered to have ARF and should continue to receive long-term secondary prophylaxis.

The good news is that there has been a dramatic decrease in the number of rheumatogenic strains of group A streptococcus in circulation, says Dr. Shulman. By comparing the prevalence of rheumatogenic and nonrheumatogenic strains of group A strep in samples from 468 children with pharyngitis taken in 1961-1968 with samples from 450 children with pharyngitis taken in 2000-2004, Dr. Shulman found that in the 1960s, two-thirds of group A strep strains in circulation were rheumatogenic, while in the later sample only one-quarter were. He and his colleagues recently completed a large 13-center U.S. and Canadian study analyzing the subtypes of group A streptococcal infection more recently in circulation through the use of M protein typing.

Dr. Shulman is a member of Merck’s speakers bureau and has research support from Quidel.

NEW YORK – Poststreptococcal reactive arthritis in a child means fewer cardiac sequelae and less need for prophylactic antibiotics, making it worth looking for when the obvious diagnosis seems to be acute rheumatic fever, according to Dr. Stanford T. Shulman, who spoke at a meeting sponsored by New York University.

"There are several reasons why it is important to differentiate poststreptococcal reactive arthritis from [acute rheumatic fever (ARF)]," explained Dr. Shulman, chief of infectious diseases at the Children’s Memorial Hospital in Chicago and the Virginia H. Rogers Professor of Pediatric Infectious Diseases at Northwestern University, Chicago. "Rheumatic fever frequently recurs and requires long-term antibiotics to prevent recurrence."

Not fulfilling the Jones criteria is one of the first clues of PSRA. The updated 1992 Jones criteria specifies that the diagnosis of ARF relies on the presence of two of the major criteria (that is, carditis, polyarthritis of large joints, chorea, erythema marginatum, and subcutaneous nodules) or one major and two minor (arthralgia, fever, elevation of the acute phase reactants C-reactive protein and erythrocyte sedimentation rate, prolonged PR interval on an echocardiogram) criteria, plus evidence of a recent group A streptococcal infection.

Heart involvement is controversial in PSRA and if it occurs, it is quite rare, said Dr. Shulman. But carditis is the common in acute rheumatic fever and accounts for its importance. Patients with ARF who have carditis characteristically have valvulitis with mitral regurgitation most commonly, followed by mitral and aortic regurgitation. Aortic regurgitation alone is rare in ARF. Patients with only pericarditis and/or myocarditis without valvulitis do not have rheumatic heart disease. After reviewing eight clinical reports representing 120 clinical cases of PSRA, Dr. Shulman concluded that it was questionable whether carditis can occur in children with PSRA, but that carditis was completely absent in several series of adults with PSRA.

There are other ways to differentiate PSRA from ARF. Symptoms of PSRA have an acute onset, usually less than 2 weeks from the time of streptococcal infection, compared with 2-3 weeks for ARF. Arthritic symptoms are brief with ARF (about 6 days). But, in PSRA, they can last for 8 weeks or longer and may be recurrent. In PSRA, the arthritis can affect any joint, large or small, and symptoms may be symmetric or asymmetric with axial involvement. In contrast, ARF arthritis is not symmetric and does not usually affect small joints or the axis. With ARF, arthritic symptoms typically migrate but are non-migratory with PSRA. Patients in either group may complain of morning stiffness.

Response to treatment is another way to distinguish the two. If a patient with poststreptococcal arthritis responds poorly or not at all to NSAIDs, then the diagnosis is much more likely to be PSRA; ARF patients respond very promptly to such treatment, says Dr. Shulman.

Both the American Heart Association and the American Academy of Pediatrics recommend that patients with acute rheumatic fever receive antistreptococcus prophylaxis until they are 21 years old. The 2009 American Heart Association Scientific Statement recommends that patients with PSRA should be observed carefully for several months for clinical evidence of carditis and should receive up to 1 year of secondary prophylaxis after the onset of symptoms and discontinue if no findings of carditis are apparent. Dr. Shulman said he gives either IM penicillin every 4 weeks or twice daily oral penicillin for 1-2 years, which should be discontinued if no evidence of valvular disease appears. If valvular disease is found, the patient is then considered to have ARF and should continue to receive long-term secondary prophylaxis.

The good news is that there has been a dramatic decrease in the number of rheumatogenic strains of group A streptococcus in circulation, says Dr. Shulman. By comparing the prevalence of rheumatogenic and nonrheumatogenic strains of group A strep in samples from 468 children with pharyngitis taken in 1961-1968 with samples from 450 children with pharyngitis taken in 2000-2004, Dr. Shulman found that in the 1960s, two-thirds of group A strep strains in circulation were rheumatogenic, while in the later sample only one-quarter were. He and his colleagues recently completed a large 13-center U.S. and Canadian study analyzing the subtypes of group A streptococcal infection more recently in circulation through the use of M protein typing.

Dr. Shulman is a member of Merck’s speakers bureau and has research support from Quidel.

NEW YORK – An intensive program that includes physical, occupational, and psychological therapy can help most children suffering from pain amplification syndrome to become fully functional within the first 1-2 weeks of treatment and pain free within the first month, according to Dr. David D. Sherry, who spoke at a meeting sponsored by the New York University. The improvements tend to be durable and relapses resolve quickly, often through self care.

A very painful medical condition, amplified musculoskeletal pain or reflex neurovascular dystrophy (RND) usually affects a limb but can cause pain anywhere on the body. Some children have pain all over and a few have intermittent attacks of pain. "The pain these children experience, however, is much more intense than one would normally expect because the pain signal is amplified," according to Dr. Sherry, chief of the rheumatology section at the Children’s Hospital of Philadelphia.

Dr. Sherry described several of the 1,900 cases he has seen in his practice, among them a 12-year-old girl who had banged her foot during basketball. Her foot was cold and blue 3 days later, she could not wear a sock, and she was on crutches. Another 12-year-old patient had fallen at school; in the 2 years since, she had been unable to sit because of pain in her buttocks. A third case was a 14-year-old girl with widespread pain of unknown origin, many positive findings in a review of systems, and multiple painful points, who has not attended school for 2 years. "Remember, all of these children are suffering," noted Dr. Sherry.

Dr. Sherry’s typical RND patient is female, about 12 years old, and has had symptoms for about a year. These girls tend to have pain in their lower extremities and most say the pain is constant and in multiple sites. The pain often begins after minor trauma, is worse with rest, and increases over time. Patients often have allodynia, but the area of allodynia characteristically has variable borders. Some patients have autonomic signs, such as limbs that are cold, clammy, and cyanotic and dystrophic skin. Lab tests are normal although MRI may show edema.

"Some of these kids tend to have multiple diagnoses of stress fractures," says Dr. Sherry. They have overt signs of autonomic dysfunction so the patients and families do not accept that it is "all in the patient’s head."

Nevertheless psychological stress seems to play a role in at least 80% of children with RND. The most common stresses seen in children with RND involve family and school issues. Dr. Sherry reported there being some common personality features in affected children. For instance, the typical patient is "pseudomature," excels in school and sports, and strives to please people and be a perfectionist. Often the patient and her mother seem overly enmeshed with each other, as manifested by "finishing each other’s sentences" or dressing alike. The fathers are often detached. An odd characteristic is an incongruent affect: "amplified pain tends to make the patient smile," says Dr. Sherry.

To break the cycle of pain, the first thing Dr. Sherry recommends is to halt all medical testing and discontinue medications. Depending on the severity of the problem, he then advocates a specialized strenuous program of exercise. During a typical day, the child may participate in pool activities, physical therapy (animal walks, 90-foot runs, step-ups, mini-trampoline jumping, ball exercises), and occupational therapy (stepping in and out of a bathtub, getting up and down from the floor, window painting, writing). Music therapy provides methods of coping, including music-assisted relaxation techniques; and songwriting allows self-expression. Patients also meet with psychologists for counseling sessions. Art therapy is also used to try to help the children connect to their feelings.

While some patients are able to do this at home, most children need daily outpatient therapy lasting 5 to 6 hours a day. "A few children require hospitalization, especially those who are severely incapacitated, those who have marked pain behaviors such as night time screaming and those who need a behavior-modification program." During this time, most children begin to regain function although pain may initially increase because of all the exercise.

The average child requires 2-4 weeks of this exercise program. Physical therapists also use towel and lotion rubs and massage to desensitize areas that are particularly painful to touch. Patients are expected to exercise at home on weekends. During this time, participants do not attend school. Parents are not allowed in the gyms; they are encouraged to participate in parent counseling groups and maintain their normal routines.

Upon completion of the exercise program, the children return home to restart their normal activities, including return to school. For children who have been absent from school, Dr. Sherry’s staff works with school staff members to reintegrate the child gradually, sometimes beginning by just having the child spend time in the parking lot or school library. Patients are expected to exercise at home for about 45 minutes a day, and counseling is usually recommended. During this time, pain starts to recede. In the last part of the program, children can stop formal home exercise and hopefully function without pain.

Within the first 1-2 weeks, 80% of patients become fully functional and 95% are fully functional within the first month. After 1 month, 75% are free of pain, according to Dr. Sherry.

Preliminary results are available from an ongoing study in which patients were evaluated for pain and function before the start and after completion of the exercise program, as well as at 1-year follow-up. Preliminary data on 20 subjects showed the mean pain score on a visual analog scale (VAS) before the program was 62.7 out of 100; after the program ended the VAS significantly decreased to 33.9 (P less than .01) and after 1 year, the mean VAS was significantly decreased further to 17.3 (P = .02). Similar trends were seen for fine-motor control, manual coordination, and a total motor composite score. Significant improvements were also seen by the end of the exercise program in body coordination and strength and agility (both P less than .01) but scores remained stable once the program was completed.

Do patients relapse? In an earlier study of 49 patients with an amplified pain syndrome who were followed for 5 years, nearly one-third relapsed (Clin. J. Pain 1999;15:218-23). The median time to relapse was 2 months and 79% relapsed within the first 6 months. "The important thing was that most relapses resolved quickly with 50% of patients able to control their relapse at home by themselves," says Dr. Sherry.

"Within a few weeks, we can get most kids fully functional without drugs or invasive procedures. Kids who won’t put a shoe on, kids who can’t walk, kids on crutches, kids who have been in a wheelchair for 2 years. Within a couple of weeks, we get them to be at least weight bearing."

Dr. Sherry reported having no relevant financial disclosures.

NEW YORK – An intensive program that includes physical, occupational, and psychological therapy can help most children suffering from pain amplification syndrome to become fully functional within the first 1-2 weeks of treatment and pain free within the first month, according to Dr. David D. Sherry, who spoke at a meeting sponsored by the New York University. The improvements tend to be durable and relapses resolve quickly, often through self care.

A very painful medical condition, amplified musculoskeletal pain or reflex neurovascular dystrophy (RND) usually affects a limb but can cause pain anywhere on the body. Some children have pain all over and a few have intermittent attacks of pain. "The pain these children experience, however, is much more intense than one would normally expect because the pain signal is amplified," according to Dr. Sherry, chief of the rheumatology section at the Children’s Hospital of Philadelphia.

Dr. Sherry described several of the 1,900 cases he has seen in his practice, among them a 12-year-old girl who had banged her foot during basketball. Her foot was cold and blue 3 days later, she could not wear a sock, and she was on crutches. Another 12-year-old patient had fallen at school; in the 2 years since, she had been unable to sit because of pain in her buttocks. A third case was a 14-year-old girl with widespread pain of unknown origin, many positive findings in a review of systems, and multiple painful points, who has not attended school for 2 years. "Remember, all of these children are suffering," noted Dr. Sherry.

Dr. Sherry’s typical RND patient is female, about 12 years old, and has had symptoms for about a year. These girls tend to have pain in their lower extremities and most say the pain is constant and in multiple sites. The pain often begins after minor trauma, is worse with rest, and increases over time. Patients often have allodynia, but the area of allodynia characteristically has variable borders. Some patients have autonomic signs, such as limbs that are cold, clammy, and cyanotic and dystrophic skin. Lab tests are normal although MRI may show edema.

"Some of these kids tend to have multiple diagnoses of stress fractures," says Dr. Sherry. They have overt signs of autonomic dysfunction so the patients and families do not accept that it is "all in the patient’s head."

Nevertheless psychological stress seems to play a role in at least 80% of children with RND. The most common stresses seen in children with RND involve family and school issues. Dr. Sherry reported there being some common personality features in affected children. For instance, the typical patient is "pseudomature," excels in school and sports, and strives to please people and be a perfectionist. Often the patient and her mother seem overly enmeshed with each other, as manifested by "finishing each other’s sentences" or dressing alike. The fathers are often detached. An odd characteristic is an incongruent affect: "amplified pain tends to make the patient smile," says Dr. Sherry.

To break the cycle of pain, the first thing Dr. Sherry recommends is to halt all medical testing and discontinue medications. Depending on the severity of the problem, he then advocates a specialized strenuous program of exercise. During a typical day, the child may participate in pool activities, physical therapy (animal walks, 90-foot runs, step-ups, mini-trampoline jumping, ball exercises), and occupational therapy (stepping in and out of a bathtub, getting up and down from the floor, window painting, writing). Music therapy provides methods of coping, including music-assisted relaxation techniques; and songwriting allows self-expression. Patients also meet with psychologists for counseling sessions. Art therapy is also used to try to help the children connect to their feelings.

While some patients are able to do this at home, most children need daily outpatient therapy lasting 5 to 6 hours a day. "A few children require hospitalization, especially those who are severely incapacitated, those who have marked pain behaviors such as night time screaming and those who need a behavior-modification program." During this time, most children begin to regain function although pain may initially increase because of all the exercise.

The average child requires 2-4 weeks of this exercise program. Physical therapists also use towel and lotion rubs and massage to desensitize areas that are particularly painful to touch. Patients are expected to exercise at home on weekends. During this time, participants do not attend school. Parents are not allowed in the gyms; they are encouraged to participate in parent counseling groups and maintain their normal routines.

Upon completion of the exercise program, the children return home to restart their normal activities, including return to school. For children who have been absent from school, Dr. Sherry’s staff works with school staff members to reintegrate the child gradually, sometimes beginning by just having the child spend time in the parking lot or school library. Patients are expected to exercise at home for about 45 minutes a day, and counseling is usually recommended. During this time, pain starts to recede. In the last part of the program, children can stop formal home exercise and hopefully function without pain.

Within the first 1-2 weeks, 80% of patients become fully functional and 95% are fully functional within the first month. After 1 month, 75% are free of pain, according to Dr. Sherry.

Preliminary results are available from an ongoing study in which patients were evaluated for pain and function before the start and after completion of the exercise program, as well as at 1-year follow-up. Preliminary data on 20 subjects showed the mean pain score on a visual analog scale (VAS) before the program was 62.7 out of 100; after the program ended the VAS significantly decreased to 33.9 (P less than .01) and after 1 year, the mean VAS was significantly decreased further to 17.3 (P = .02). Similar trends were seen for fine-motor control, manual coordination, and a total motor composite score. Significant improvements were also seen by the end of the exercise program in body coordination and strength and agility (both P less than .01) but scores remained stable once the program was completed.

Do patients relapse? In an earlier study of 49 patients with an amplified pain syndrome who were followed for 5 years, nearly one-third relapsed (Clin. J. Pain 1999;15:218-23). The median time to relapse was 2 months and 79% relapsed within the first 6 months. "The important thing was that most relapses resolved quickly with 50% of patients able to control their relapse at home by themselves," says Dr. Sherry.

"Within a few weeks, we can get most kids fully functional without drugs or invasive procedures. Kids who won’t put a shoe on, kids who can’t walk, kids on crutches, kids who have been in a wheelchair for 2 years. Within a couple of weeks, we get them to be at least weight bearing."

Dr. Sherry reported having no relevant financial disclosures.

NEW YORK – An intensive program that includes physical, occupational, and psychological therapy can help most children suffering from pain amplification syndrome to become fully functional within the first 1-2 weeks of treatment and pain free within the first month, according to Dr. David D. Sherry, who spoke at a meeting sponsored by the New York University. The improvements tend to be durable and relapses resolve quickly, often through self care.

A very painful medical condition, amplified musculoskeletal pain or reflex neurovascular dystrophy (RND) usually affects a limb but can cause pain anywhere on the body. Some children have pain all over and a few have intermittent attacks of pain. "The pain these children experience, however, is much more intense than one would normally expect because the pain signal is amplified," according to Dr. Sherry, chief of the rheumatology section at the Children’s Hospital of Philadelphia.

Dr. Sherry described several of the 1,900 cases he has seen in his practice, among them a 12-year-old girl who had banged her foot during basketball. Her foot was cold and blue 3 days later, she could not wear a sock, and she was on crutches. Another 12-year-old patient had fallen at school; in the 2 years since, she had been unable to sit because of pain in her buttocks. A third case was a 14-year-old girl with widespread pain of unknown origin, many positive findings in a review of systems, and multiple painful points, who has not attended school for 2 years. "Remember, all of these children are suffering," noted Dr. Sherry.

Dr. Sherry’s typical RND patient is female, about 12 years old, and has had symptoms for about a year. These girls tend to have pain in their lower extremities and most say the pain is constant and in multiple sites. The pain often begins after minor trauma, is worse with rest, and increases over time. Patients often have allodynia, but the area of allodynia characteristically has variable borders. Some patients have autonomic signs, such as limbs that are cold, clammy, and cyanotic and dystrophic skin. Lab tests are normal although MRI may show edema.

"Some of these kids tend to have multiple diagnoses of stress fractures," says Dr. Sherry. They have overt signs of autonomic dysfunction so the patients and families do not accept that it is "all in the patient’s head."

Nevertheless psychological stress seems to play a role in at least 80% of children with RND. The most common stresses seen in children with RND involve family and school issues. Dr. Sherry reported there being some common personality features in affected children. For instance, the typical patient is "pseudomature," excels in school and sports, and strives to please people and be a perfectionist. Often the patient and her mother seem overly enmeshed with each other, as manifested by "finishing each other’s sentences" or dressing alike. The fathers are often detached. An odd characteristic is an incongruent affect: "amplified pain tends to make the patient smile," says Dr. Sherry.

To break the cycle of pain, the first thing Dr. Sherry recommends is to halt all medical testing and discontinue medications. Depending on the severity of the problem, he then advocates a specialized strenuous program of exercise. During a typical day, the child may participate in pool activities, physical therapy (animal walks, 90-foot runs, step-ups, mini-trampoline jumping, ball exercises), and occupational therapy (stepping in and out of a bathtub, getting up and down from the floor, window painting, writing). Music therapy provides methods of coping, including music-assisted relaxation techniques; and songwriting allows self-expression. Patients also meet with psychologists for counseling sessions. Art therapy is also used to try to help the children connect to their feelings.

While some patients are able to do this at home, most children need daily outpatient therapy lasting 5 to 6 hours a day. "A few children require hospitalization, especially those who are severely incapacitated, those who have marked pain behaviors such as night time screaming and those who need a behavior-modification program." During this time, most children begin to regain function although pain may initially increase because of all the exercise.

The average child requires 2-4 weeks of this exercise program. Physical therapists also use towel and lotion rubs and massage to desensitize areas that are particularly painful to touch. Patients are expected to exercise at home on weekends. During this time, participants do not attend school. Parents are not allowed in the gyms; they are encouraged to participate in parent counseling groups and maintain their normal routines.

Upon completion of the exercise program, the children return home to restart their normal activities, including return to school. For children who have been absent from school, Dr. Sherry’s staff works with school staff members to reintegrate the child gradually, sometimes beginning by just having the child spend time in the parking lot or school library. Patients are expected to exercise at home for about 45 minutes a day, and counseling is usually recommended. During this time, pain starts to recede. In the last part of the program, children can stop formal home exercise and hopefully function without pain.

Within the first 1-2 weeks, 80% of patients become fully functional and 95% are fully functional within the first month. After 1 month, 75% are free of pain, according to Dr. Sherry.

Preliminary results are available from an ongoing study in which patients were evaluated for pain and function before the start and after completion of the exercise program, as well as at 1-year follow-up. Preliminary data on 20 subjects showed the mean pain score on a visual analog scale (VAS) before the program was 62.7 out of 100; after the program ended the VAS significantly decreased to 33.9 (P less than .01) and after 1 year, the mean VAS was significantly decreased further to 17.3 (P = .02). Similar trends were seen for fine-motor control, manual coordination, and a total motor composite score. Significant improvements were also seen by the end of the exercise program in body coordination and strength and agility (both P less than .01) but scores remained stable once the program was completed.

Do patients relapse? In an earlier study of 49 patients with an amplified pain syndrome who were followed for 5 years, nearly one-third relapsed (Clin. J. Pain 1999;15:218-23). The median time to relapse was 2 months and 79% relapsed within the first 6 months. "The important thing was that most relapses resolved quickly with 50% of patients able to control their relapse at home by themselves," says Dr. Sherry.

"Within a few weeks, we can get most kids fully functional without drugs or invasive procedures. Kids who won’t put a shoe on, kids who can’t walk, kids on crutches, kids who have been in a wheelchair for 2 years. Within a couple of weeks, we get them to be at least weight bearing."

Dr. Sherry reported having no relevant financial disclosures.