Results of the phase 3 ENDEAVOR trial suggest combination carfilzomib and dexamethasone prolongs progression-free survival (PFS) in patients with relapsed or refractory multiple myeloma (MM), when compared to bortezomib plus dexamethasone.

The median PFS was 18.7 months in the carfilzomib arm and 9.4 months in the bortezomib arm.

It is not clear whether this translates to an improvement in overall survival, as those data are not yet mature.

Treatment discontinuation due to adverse events (AEs) and on-study deaths were comparable between the treatment arms, although there were several AEs that occurred more frequently in the carfilzomib arm than the bortezomib arm.

These results were published in The Lancet Oncology. The trial was funded by Onyx Pharmaceuticals, Inc., a subsidiary of Amgen.

Patient treatment and characteristics

The ENDEAVOR trial included 929 patients with relapsed/refractory MM who had received 1 to 3 prior therapeutic regimens. They were randomized to receive carfilzomib in combination with low-dose dexamethasone (n=464) or bortezomib with low-dose dexamethasone (n=465) until progression.

Patients received carfilzomib as a 30-minute infusion on days 1, 2, 8, 9, 15, and 16 of 28-day treatment cycles, along with 20 mg of dexamethasone. For cycle 1 only, carfilzomib was administered at 20 mg/m² on days 1 and 2, followed by escalation to 56 mg/m² from day 8. Patients who tolerated 56 mg/m² in cycle 1 were kept at this dose for subsequent cycles.

Patients who received bortezomib (1.3 mg/m²) with low-dose dexamethasone (20 mg) were given bortezomib subcutaneously or intravenously at the discretion of the investigator. More than 75% of the patients received bortezomib subcutaneously.

Baseline characteristics were generally balanced between the treatment arms. Both arms had a median age of 65 (overall range, 30-89), and about half were male. Three-quarters of patients in both arms were white, a little over 10% were Asian, 2% were black, and about 10% did not report race/ethnicity.

A majority of patients in both arms (more than 90%) had an ECOG score of 0 or 1. Most patients (more than 60%) had standard-risk cytogenetics.

The median number of prior treatment regimens was 2 in both arms. Patients in both arms had received prior lenalidomide (38% in both arms), thalidomide (45% in the carfilzomib arm and 53% in the bortezomib arm), bortezomib (54% in both arms), and carfilzomib (<1% in both arms).

Results

The median PFS in the carfilzomib arm was roughly double that of the bortezomib arm—18.7 months and 9.4 months, respectively. The hazard ratio was 0.53 (P<0.0001).

Overall survival data are not mature and are still being monitored.

The overall response rate was 77% in the carfilzomib arm and 63% in the bortezomib arm (P<0.0001). The duration of response was 21.3 months and 10.4 months, respectively.

The proportion of patients achieving a very good partial response or better was 54.3% in the carfilzomib arm and 29% in the bortezomib arm (P<0.0001). The complete response rates were 13% and 6%, respectively (P<0.001).

Treatment discontinuation due to AEs and on-study deaths were comparable between the arms. There were 75 deaths in the carfilzomib arm and 88 deaths in the bortezomib arm.

Of the 263 patients in the carfilzomib arm who discontinued treatment, 65 did so because of AEs. Of the 351 patients in the bortezomib arm who discontinued treatment, 73 did so because of AEs.

A number of known AEs were reported at a higher rate in the carfilzomib arm than the bortezomib arm, including any-grade dyspnea (28% vs 13%), hypertension (25% vs 3%), pyrexia (27% vs 14%), cough (25% vs 15%), cardiac failure (8% vs 3%), and acute renal failure (8% vs 5%).

 

Rates of grade 3 or higher AEs were 73% in the carfilzomib arm and 67% in the bortezomib arm. Grade 3 or higher AEs of interest in the carfilzomib and bortezomib arms, respectively, were hypertension (9% vs 3%), dyspnea (5% vs 2%), cardiac failure (5% vs 2%), acute renal failure (4% vs 3%), ischemic heart disease (2% vs 2%), and pulmonary hypertension (0.6% vs 0.2%).

Results of the phase 3 ENDEAVOR trial suggest combination carfilzomib and dexamethasone prolongs progression-free survival (PFS) in patients with relapsed or refractory multiple myeloma (MM), when compared to bortezomib plus dexamethasone.

The median PFS was 18.7 months in the carfilzomib arm and 9.4 months in the bortezomib arm.

It is not clear whether this translates to an improvement in overall survival, as those data are not yet mature.

Treatment discontinuation due to adverse events (AEs) and on-study deaths were comparable between the treatment arms, although there were several AEs that occurred more frequently in the carfilzomib arm than the bortezomib arm.

These results were published in The Lancet Oncology. The trial was funded by Onyx Pharmaceuticals, Inc., a subsidiary of Amgen.

Patient treatment and characteristics

The ENDEAVOR trial included 929 patients with relapsed/refractory MM who had received 1 to 3 prior therapeutic regimens. They were randomized to receive carfilzomib in combination with low-dose dexamethasone (n=464) or bortezomib with low-dose dexamethasone (n=465) until progression.

Patients received carfilzomib as a 30-minute infusion on days 1, 2, 8, 9, 15, and 16 of 28-day treatment cycles, along with 20 mg of dexamethasone. For cycle 1 only, carfilzomib was administered at 20 mg/m² on days 1 and 2, followed by escalation to 56 mg/m² from day 8. Patients who tolerated 56 mg/m² in cycle 1 were kept at this dose for subsequent cycles.

Patients who received bortezomib (1.3 mg/m²) with low-dose dexamethasone (20 mg) were given bortezomib subcutaneously or intravenously at the discretion of the investigator. More than 75% of the patients received bortezomib subcutaneously.

Baseline characteristics were generally balanced between the treatment arms. Both arms had a median age of 65 (overall range, 30-89), and about half were male. Three-quarters of patients in both arms were white, a little over 10% were Asian, 2% were black, and about 10% did not report race/ethnicity.

A majority of patients in both arms (more than 90%) had an ECOG score of 0 or 1. Most patients (more than 60%) had standard-risk cytogenetics.

The median number of prior treatment regimens was 2 in both arms. Patients in both arms had received prior lenalidomide (38% in both arms), thalidomide (45% in the carfilzomib arm and 53% in the bortezomib arm), bortezomib (54% in both arms), and carfilzomib (<1% in both arms).

Results

The median PFS in the carfilzomib arm was roughly double that of the bortezomib arm—18.7 months and 9.4 months, respectively. The hazard ratio was 0.53 (P<0.0001).

Overall survival data are not mature and are still being monitored.

The overall response rate was 77% in the carfilzomib arm and 63% in the bortezomib arm (P<0.0001). The duration of response was 21.3 months and 10.4 months, respectively.

The proportion of patients achieving a very good partial response or better was 54.3% in the carfilzomib arm and 29% in the bortezomib arm (P<0.0001). The complete response rates were 13% and 6%, respectively (P<0.001).

Treatment discontinuation due to AEs and on-study deaths were comparable between the arms. There were 75 deaths in the carfilzomib arm and 88 deaths in the bortezomib arm.

Of the 263 patients in the carfilzomib arm who discontinued treatment, 65 did so because of AEs. Of the 351 patients in the bortezomib arm who discontinued treatment, 73 did so because of AEs.

A number of known AEs were reported at a higher rate in the carfilzomib arm than the bortezomib arm, including any-grade dyspnea (28% vs 13%), hypertension (25% vs 3%), pyrexia (27% vs 14%), cough (25% vs 15%), cardiac failure (8% vs 3%), and acute renal failure (8% vs 5%).

 

Rates of grade 3 or higher AEs were 73% in the carfilzomib arm and 67% in the bortezomib arm. Grade 3 or higher AEs of interest in the carfilzomib and bortezomib arms, respectively, were hypertension (9% vs 3%), dyspnea (5% vs 2%), cardiac failure (5% vs 2%), acute renal failure (4% vs 3%), ischemic heart disease (2% vs 2%), and pulmonary hypertension (0.6% vs 0.2%).

Results of the phase 3 ENDEAVOR trial suggest combination carfilzomib and dexamethasone prolongs progression-free survival (PFS) in patients with relapsed or refractory multiple myeloma (MM), when compared to bortezomib plus dexamethasone.

The median PFS was 18.7 months in the carfilzomib arm and 9.4 months in the bortezomib arm.

It is not clear whether this translates to an improvement in overall survival, as those data are not yet mature.

Treatment discontinuation due to adverse events (AEs) and on-study deaths were comparable between the treatment arms, although there were several AEs that occurred more frequently in the carfilzomib arm than the bortezomib arm.

These results were published in The Lancet Oncology. The trial was funded by Onyx Pharmaceuticals, Inc., a subsidiary of Amgen.

Patient treatment and characteristics

The ENDEAVOR trial included 929 patients with relapsed/refractory MM who had received 1 to 3 prior therapeutic regimens. They were randomized to receive carfilzomib in combination with low-dose dexamethasone (n=464) or bortezomib with low-dose dexamethasone (n=465) until progression.

Patients received carfilzomib as a 30-minute infusion on days 1, 2, 8, 9, 15, and 16 of 28-day treatment cycles, along with 20 mg of dexamethasone. For cycle 1 only, carfilzomib was administered at 20 mg/m² on days 1 and 2, followed by escalation to 56 mg/m² from day 8. Patients who tolerated 56 mg/m² in cycle 1 were kept at this dose for subsequent cycles.

Patients who received bortezomib (1.3 mg/m²) with low-dose dexamethasone (20 mg) were given bortezomib subcutaneously or intravenously at the discretion of the investigator. More than 75% of the patients received bortezomib subcutaneously.

Baseline characteristics were generally balanced between the treatment arms. Both arms had a median age of 65 (overall range, 30-89), and about half were male. Three-quarters of patients in both arms were white, a little over 10% were Asian, 2% were black, and about 10% did not report race/ethnicity.

A majority of patients in both arms (more than 90%) had an ECOG score of 0 or 1. Most patients (more than 60%) had standard-risk cytogenetics.

The median number of prior treatment regimens was 2 in both arms. Patients in both arms had received prior lenalidomide (38% in both arms), thalidomide (45% in the carfilzomib arm and 53% in the bortezomib arm), bortezomib (54% in both arms), and carfilzomib (<1% in both arms).

Results

The median PFS in the carfilzomib arm was roughly double that of the bortezomib arm—18.7 months and 9.4 months, respectively. The hazard ratio was 0.53 (P<0.0001).

Overall survival data are not mature and are still being monitored.

The overall response rate was 77% in the carfilzomib arm and 63% in the bortezomib arm (P<0.0001). The duration of response was 21.3 months and 10.4 months, respectively.

The proportion of patients achieving a very good partial response or better was 54.3% in the carfilzomib arm and 29% in the bortezomib arm (P<0.0001). The complete response rates were 13% and 6%, respectively (P<0.001).

Treatment discontinuation due to AEs and on-study deaths were comparable between the arms. There were 75 deaths in the carfilzomib arm and 88 deaths in the bortezomib arm.

Of the 263 patients in the carfilzomib arm who discontinued treatment, 65 did so because of AEs. Of the 351 patients in the bortezomib arm who discontinued treatment, 73 did so because of AEs.

A number of known AEs were reported at a higher rate in the carfilzomib arm than the bortezomib arm, including any-grade dyspnea (28% vs 13%), hypertension (25% vs 3%), pyrexia (27% vs 14%), cough (25% vs 15%), cardiac failure (8% vs 3%), and acute renal failure (8% vs 5%).

 

Rates of grade 3 or higher AEs were 73% in the carfilzomib arm and 67% in the bortezomib arm. Grade 3 or higher AEs of interest in the carfilzomib and bortezomib arms, respectively, were hypertension (9% vs 3%), dyspnea (5% vs 2%), cardiac failure (5% vs 2%), acute renal failure (4% vs 3%), ischemic heart disease (2% vs 2%), and pulmonary hypertension (0.6% vs 0.2%).

In high-risk patients, blood pressure lowering is associated with significant reductions in vascular events for a range of comorbidities and baseline blood pressures, said the authors of a meta-analysis of 123 randomized controlled trials published in the last 50 years.

Each 10–mm Hg reduction in systolic blood pressure was associated with a 20% reduction in major cardiovascular disease events (95% confidence interval, 0.77-0.83), a 17% reduction in coronary heart disease (95% CI, 0.78-0.88), a 27% reduction in stroke (95% CI, 0.68-0.77), and a 28% reduction in heart failure (95% CI, 0.67-0.78), based on the meta-analysis published Dec. 23 by the Lancet.

©crossstudio/ThinkStock

The exception was a lack of overall benefit of blood pressure lowering for renal failure events, a finding consistent with a previous meta-analysis of moderate versus intensive blood pressure reduction.

“Lowering of blood pressure into what has been regarded the normotensive range should therefore be routinely considered for the prevention of cardiovascular disease among those deemed to be of sufficient absolute risk,” wrote Dena Ettehad of the George Institute for Global Health, Oxford, and coauthors.

“Revision is urgently needed to recent blood pressure lowering guidelines that have relaxed the blood pressure lowering thresholds,” they added.

The researchers conducted a meta-analysis of blood pressure lowering treatment, involving a total of 613,815 participants and a minimum of 1,000 patient-years of follow-up in each study arm.

The analysis indicated that a 10–mm Hg reduction in systolic blood pressure achieved an overall 13% reduction in all-cause mortality (95% CI, 0.84-0.91) but had no significant impact on the risk of renal failure events.

These effects remained similar even when the effects were compared between strata of mean baseline systolic blood pressure, baseline coronary heart disease, or baseline cardiovascular disease (Lancet 2015 Dec 23. doi: 10.1016/S0140-6736(15)01225-8).

“In stratified analyses, we saw no strong evidence that proportional effects were diminished in trials that included people with lower baseline systolic blood pressure (less than 130 mm Hg), and major cardiovascular events were clearly reduced in high-risk patients with various baseline comorbidities,” the investigators wrote.

“Both of these major findings – the efficacy of blood pressure lowering below 130 mm Hg and the similar proportional effects in high-risk populations – are consistent with and extend the findings of the SPRINT trial,” they said.

The authors did note greater proportional reductions in the risk of stroke in populations without a history of cerebrovascular disease, compared with those with a history.

Populations without diabetes had significantly greater proportional reductions in risk, compared with those with diabetes, while populations without chronic kidney disease had greater proportional reductions in the risk of major cardiovascular disease events, compared with those with chronic kidney disease.

The five classes of antihypertensives were generally as effective as each other in reducing the risk of major outcomes.

The authors noted that, while there were small but significant differences between drug classes for outcomes, these effects may have been the result of differences in control regimens or the concurrent use of multiple drug classes in many trials.

Two authors were supported by the National Institute of Health Research, one by the Clarendon Fund, and one by the Rhodes Trust. The George Institute is supported by the Oxford Martin School. Two authors declared grants from Servier, and one also declared investments for the development of a polypill. No other conflicts of interest were declared.

In high-risk patients, blood pressure lowering is associated with significant reductions in vascular events for a range of comorbidities and baseline blood pressures, said the authors of a meta-analysis of 123 randomized controlled trials published in the last 50 years.

Each 10–mm Hg reduction in systolic blood pressure was associated with a 20% reduction in major cardiovascular disease events (95% confidence interval, 0.77-0.83), a 17% reduction in coronary heart disease (95% CI, 0.78-0.88), a 27% reduction in stroke (95% CI, 0.68-0.77), and a 28% reduction in heart failure (95% CI, 0.67-0.78), based on the meta-analysis published Dec. 23 by the Lancet.

©crossstudio/ThinkStock

The exception was a lack of overall benefit of blood pressure lowering for renal failure events, a finding consistent with a previous meta-analysis of moderate versus intensive blood pressure reduction.

“Lowering of blood pressure into what has been regarded the normotensive range should therefore be routinely considered for the prevention of cardiovascular disease among those deemed to be of sufficient absolute risk,” wrote Dena Ettehad of the George Institute for Global Health, Oxford, and coauthors.

“Revision is urgently needed to recent blood pressure lowering guidelines that have relaxed the blood pressure lowering thresholds,” they added.

The researchers conducted a meta-analysis of blood pressure lowering treatment, involving a total of 613,815 participants and a minimum of 1,000 patient-years of follow-up in each study arm.

The analysis indicated that a 10–mm Hg reduction in systolic blood pressure achieved an overall 13% reduction in all-cause mortality (95% CI, 0.84-0.91) but had no significant impact on the risk of renal failure events.

These effects remained similar even when the effects were compared between strata of mean baseline systolic blood pressure, baseline coronary heart disease, or baseline cardiovascular disease (Lancet 2015 Dec 23. doi: 10.1016/S0140-6736(15)01225-8).

“In stratified analyses, we saw no strong evidence that proportional effects were diminished in trials that included people with lower baseline systolic blood pressure (less than 130 mm Hg), and major cardiovascular events were clearly reduced in high-risk patients with various baseline comorbidities,” the investigators wrote.

“Both of these major findings – the efficacy of blood pressure lowering below 130 mm Hg and the similar proportional effects in high-risk populations – are consistent with and extend the findings of the SPRINT trial,” they said.

The authors did note greater proportional reductions in the risk of stroke in populations without a history of cerebrovascular disease, compared with those with a history.

Populations without diabetes had significantly greater proportional reductions in risk, compared with those with diabetes, while populations without chronic kidney disease had greater proportional reductions in the risk of major cardiovascular disease events, compared with those with chronic kidney disease.

The five classes of antihypertensives were generally as effective as each other in reducing the risk of major outcomes.

The authors noted that, while there were small but significant differences between drug classes for outcomes, these effects may have been the result of differences in control regimens or the concurrent use of multiple drug classes in many trials.

Two authors were supported by the National Institute of Health Research, one by the Clarendon Fund, and one by the Rhodes Trust. The George Institute is supported by the Oxford Martin School. Two authors declared grants from Servier, and one also declared investments for the development of a polypill. No other conflicts of interest were declared.

In high-risk patients, blood pressure lowering is associated with significant reductions in vascular events for a range of comorbidities and baseline blood pressures, said the authors of a meta-analysis of 123 randomized controlled trials published in the last 50 years.

Each 10–mm Hg reduction in systolic blood pressure was associated with a 20% reduction in major cardiovascular disease events (95% confidence interval, 0.77-0.83), a 17% reduction in coronary heart disease (95% CI, 0.78-0.88), a 27% reduction in stroke (95% CI, 0.68-0.77), and a 28% reduction in heart failure (95% CI, 0.67-0.78), based on the meta-analysis published Dec. 23 by the Lancet.

©crossstudio/ThinkStock

The exception was a lack of overall benefit of blood pressure lowering for renal failure events, a finding consistent with a previous meta-analysis of moderate versus intensive blood pressure reduction.

“Lowering of blood pressure into what has been regarded the normotensive range should therefore be routinely considered for the prevention of cardiovascular disease among those deemed to be of sufficient absolute risk,” wrote Dena Ettehad of the George Institute for Global Health, Oxford, and coauthors.

“Revision is urgently needed to recent blood pressure lowering guidelines that have relaxed the blood pressure lowering thresholds,” they added.

The researchers conducted a meta-analysis of blood pressure lowering treatment, involving a total of 613,815 participants and a minimum of 1,000 patient-years of follow-up in each study arm.

The analysis indicated that a 10–mm Hg reduction in systolic blood pressure achieved an overall 13% reduction in all-cause mortality (95% CI, 0.84-0.91) but had no significant impact on the risk of renal failure events.

These effects remained similar even when the effects were compared between strata of mean baseline systolic blood pressure, baseline coronary heart disease, or baseline cardiovascular disease (Lancet 2015 Dec 23. doi: 10.1016/S0140-6736(15)01225-8).

“In stratified analyses, we saw no strong evidence that proportional effects were diminished in trials that included people with lower baseline systolic blood pressure (less than 130 mm Hg), and major cardiovascular events were clearly reduced in high-risk patients with various baseline comorbidities,” the investigators wrote.

“Both of these major findings – the efficacy of blood pressure lowering below 130 mm Hg and the similar proportional effects in high-risk populations – are consistent with and extend the findings of the SPRINT trial,” they said.

The authors did note greater proportional reductions in the risk of stroke in populations without a history of cerebrovascular disease, compared with those with a history.

Populations without diabetes had significantly greater proportional reductions in risk, compared with those with diabetes, while populations without chronic kidney disease had greater proportional reductions in the risk of major cardiovascular disease events, compared with those with chronic kidney disease.

The five classes of antihypertensives were generally as effective as each other in reducing the risk of major outcomes.

The authors noted that, while there were small but significant differences between drug classes for outcomes, these effects may have been the result of differences in control regimens or the concurrent use of multiple drug classes in many trials.

Two authors were supported by the National Institute of Health Research, one by the Clarendon Fund, and one by the Rhodes Trust. The George Institute is supported by the Oxford Martin School. Two authors declared grants from Servier, and one also declared investments for the development of a polypill. No other conflicts of interest were declared.

Secukinumab, an interleukin 17-A inhibitor approved for the treatment of moderate to severe psoriasis, significantly reduced the signs and symptoms of ankylosing spondylitis in two phase III trials, researchers reported Dec. 23 in the New England Journal of Medicine.

The results of the double-blind MEASURE 1 and MEASURE 2 trials extend the positive results of the phase II study, according to Dr. Dominique Baeten of the Academic Medical Center at the University of Amsterdam and his colleagues (N Engl J Med. 2015 Dec 23. doi: 10.1056/NEJMoa1505066).

“Although head-to-head trials would be required to fully assess the efficacy and safety of secukinumab versus TNF-inhibitors, the [20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response criteria] response rates achieved with secukinumab at week 16 in our studies were similar to those reported in phase III studies of anti-TNF agents in which most of the patients had not received previous anti-TNF therapy (response rates of 58% to 64% at weeks 12 to 24), even though 30% to 40% of the patients in our studies had had no response to previous anti-TNF treatment,” the authors wrote.

“Thus, secukinumab not only is effective in patients who have not received TNF agents previously but also may be effective in patients in whom previous anti-TNF treatment failed,” they added.

In MEASURE 1, 371 patients received intravenous secukinumab (10 mg/kg of body weight) or matched placebo at weeks 0, 2, and 4, followed by subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks starting at week 8.

The study’s primary endpoint of ASAS20 response rates at week 16 were 61%, 60%, and 29% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively, (P less than .001 for both comparisons with placebo).

In MEASURE 2, 219 patients received subcutaneous secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3; and every 4 weeks starting at week 4.

At week 16, patients in the placebo group were randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg.

In this trial, ASAS20 rates were 61%, 41%, and 28% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P less than .001 for the 150-mg dose and P = .10 for the 75-mg dose).

The researchers noted that the ineffectiveness of the 75-mg dose in MEASURE 2 suggests that the efficacy of secukinumab at the 75-mg dose in MEASURE 1 may have been due to the greater exposure at week 16 as a result of the intravenous loading regimen, not to the 75-mg subcutaneous maintenance dose.

The safety profile of secukinumab in the present studies was consistent with previous studies of secukinumab for ankylosing spondylitis and moderate-to-severe plaque psoriasis, Dr. Baeten and his associates said.

During the entire treatment period, pooled exposure-adjusted incidence rates of grade 3 or 4 neutropenia, candida infections, and Crohn’s disease were 0.7, 0.9, and 0.7 cases per 100 patient-years, respectively, in secukinumab-treated patients.

Overall, the results suggest that interleukin-17A plays a role in the pathogenesis of ankylosing spondylitis, and they validate inhibition of this cytokine as a potential therapeutic approach, the study authors concluded.

The study was sponsored by Novartis Pharma. Dr. Baeten has received a grant from Novartis to study the impact of IL-17A blockade in experimental models of spondyloarthritis. He also has been a consultant for Novartis for the design and conduct of the secukinumab program in ankylosing spondylitis and psoriatic arthritis.

Secukinumab, an interleukin 17-A inhibitor approved for the treatment of moderate to severe psoriasis, significantly reduced the signs and symptoms of ankylosing spondylitis in two phase III trials, researchers reported Dec. 23 in the New England Journal of Medicine.

The results of the double-blind MEASURE 1 and MEASURE 2 trials extend the positive results of the phase II study, according to Dr. Dominique Baeten of the Academic Medical Center at the University of Amsterdam and his colleagues (N Engl J Med. 2015 Dec 23. doi: 10.1056/NEJMoa1505066).

“Although head-to-head trials would be required to fully assess the efficacy and safety of secukinumab versus TNF-inhibitors, the [20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response criteria] response rates achieved with secukinumab at week 16 in our studies were similar to those reported in phase III studies of anti-TNF agents in which most of the patients had not received previous anti-TNF therapy (response rates of 58% to 64% at weeks 12 to 24), even though 30% to 40% of the patients in our studies had had no response to previous anti-TNF treatment,” the authors wrote.

“Thus, secukinumab not only is effective in patients who have not received TNF agents previously but also may be effective in patients in whom previous anti-TNF treatment failed,” they added.

In MEASURE 1, 371 patients received intravenous secukinumab (10 mg/kg of body weight) or matched placebo at weeks 0, 2, and 4, followed by subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks starting at week 8.

The study’s primary endpoint of ASAS20 response rates at week 16 were 61%, 60%, and 29% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively, (P less than .001 for both comparisons with placebo).

In MEASURE 2, 219 patients received subcutaneous secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3; and every 4 weeks starting at week 4.

At week 16, patients in the placebo group were randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg.

In this trial, ASAS20 rates were 61%, 41%, and 28% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P less than .001 for the 150-mg dose and P = .10 for the 75-mg dose).

The researchers noted that the ineffectiveness of the 75-mg dose in MEASURE 2 suggests that the efficacy of secukinumab at the 75-mg dose in MEASURE 1 may have been due to the greater exposure at week 16 as a result of the intravenous loading regimen, not to the 75-mg subcutaneous maintenance dose.

The safety profile of secukinumab in the present studies was consistent with previous studies of secukinumab for ankylosing spondylitis and moderate-to-severe plaque psoriasis, Dr. Baeten and his associates said.

During the entire treatment period, pooled exposure-adjusted incidence rates of grade 3 or 4 neutropenia, candida infections, and Crohn’s disease were 0.7, 0.9, and 0.7 cases per 100 patient-years, respectively, in secukinumab-treated patients.

Overall, the results suggest that interleukin-17A plays a role in the pathogenesis of ankylosing spondylitis, and they validate inhibition of this cytokine as a potential therapeutic approach, the study authors concluded.

The study was sponsored by Novartis Pharma. Dr. Baeten has received a grant from Novartis to study the impact of IL-17A blockade in experimental models of spondyloarthritis. He also has been a consultant for Novartis for the design and conduct of the secukinumab program in ankylosing spondylitis and psoriatic arthritis.

Secukinumab, an interleukin 17-A inhibitor approved for the treatment of moderate to severe psoriasis, significantly reduced the signs and symptoms of ankylosing spondylitis in two phase III trials, researchers reported Dec. 23 in the New England Journal of Medicine.

The results of the double-blind MEASURE 1 and MEASURE 2 trials extend the positive results of the phase II study, according to Dr. Dominique Baeten of the Academic Medical Center at the University of Amsterdam and his colleagues (N Engl J Med. 2015 Dec 23. doi: 10.1056/NEJMoa1505066).

“Although head-to-head trials would be required to fully assess the efficacy and safety of secukinumab versus TNF-inhibitors, the [20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response criteria] response rates achieved with secukinumab at week 16 in our studies were similar to those reported in phase III studies of anti-TNF agents in which most of the patients had not received previous anti-TNF therapy (response rates of 58% to 64% at weeks 12 to 24), even though 30% to 40% of the patients in our studies had had no response to previous anti-TNF treatment,” the authors wrote.

“Thus, secukinumab not only is effective in patients who have not received TNF agents previously but also may be effective in patients in whom previous anti-TNF treatment failed,” they added.

In MEASURE 1, 371 patients received intravenous secukinumab (10 mg/kg of body weight) or matched placebo at weeks 0, 2, and 4, followed by subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks starting at week 8.

The study’s primary endpoint of ASAS20 response rates at week 16 were 61%, 60%, and 29% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively, (P less than .001 for both comparisons with placebo).

In MEASURE 2, 219 patients received subcutaneous secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3; and every 4 weeks starting at week 4.

At week 16, patients in the placebo group were randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg.

In this trial, ASAS20 rates were 61%, 41%, and 28% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P less than .001 for the 150-mg dose and P = .10 for the 75-mg dose).

The researchers noted that the ineffectiveness of the 75-mg dose in MEASURE 2 suggests that the efficacy of secukinumab at the 75-mg dose in MEASURE 1 may have been due to the greater exposure at week 16 as a result of the intravenous loading regimen, not to the 75-mg subcutaneous maintenance dose.

The safety profile of secukinumab in the present studies was consistent with previous studies of secukinumab for ankylosing spondylitis and moderate-to-severe plaque psoriasis, Dr. Baeten and his associates said.

During the entire treatment period, pooled exposure-adjusted incidence rates of grade 3 or 4 neutropenia, candida infections, and Crohn’s disease were 0.7, 0.9, and 0.7 cases per 100 patient-years, respectively, in secukinumab-treated patients.

Overall, the results suggest that interleukin-17A plays a role in the pathogenesis of ankylosing spondylitis, and they validate inhibition of this cytokine as a potential therapeutic approach, the study authors concluded.

The study was sponsored by Novartis Pharma. Dr. Baeten has received a grant from Novartis to study the impact of IL-17A blockade in experimental models of spondyloarthritis. He also has been a consultant for Novartis for the design and conduct of the secukinumab program in ankylosing spondylitis and psoriatic arthritis.

European respiratory disease and infectious disease specialists have banded together to issue new clinical guidelines on the diagnosis and management of an uncommon but serious problem: chronic pulmonary aspergillosis (CPA).

Pulmonary infections with Aspergillus species, although uncommon, are a complicating factor in several lung diseases, especially tuberculosis, and aspergillosis is a serious, often fatal opportunistic infection in transplant recipients who are on chronic immunosuppression or patients who are immunocompromised from disease or cytotoxic chemotherapy.

Approximately 240,000 people in Europe and 3 million people worldwide have chronic pulmonary aspergillosis (CPA). The Centers for Disease Control and Prevention notes that because aspergillosis is not classified as a reportable disease, data on the actual incidence of infections in the United States are hard to come by.

“You don’t see this every day, whether you’re an infectious disease specialist or pulmonologist, so you really can’t rely on your experience to guide you in managing these cases, which is why guidelines such as this can be very helpful,” commented Dr. Norman Edelman, a pulmonologist and senior consultant for scientific affairs for the American Lung Association.

The guidelines, issued by the European Society for Clinical Microbiology and Infectious Diseases in cooperation with the European Confederation of Medical Mycology and the European Respiratory Society, are an attempt to provide clinicians with the best possible evidence-based guidance on managing patients with aspergillosis, primarily those with CPA (Eur Respir J. 2015. doi: 10.1183/13993003.00583-2015).

Dr. Edelman noted that the most frequent presentation he sees – and that very infrequently – is allergic bronchopulmonary aspergillosis in patients with asthma.

The most recent U.S. guidelines, issued under the aegis of the Infectious Diseases Society of America (IDSA) in 2000 and revised in 2008 (CID 2008;46:327-360), differ from the European recommendations in their level of detail, explained Prof. David W. Denning, professor of infectious diseases in global health at the University of Manchester (England) and lead author of the European guidelines.

“The IDSA guidelines assume that you know how to make the diagnosis, but actually for chronic pulmonary aspergillosis that’s not so easy with some patients,” he said in an interview.

“The European ones go into in great detail the diagnosis, the radiology, whether this test is better than that test, how they all add up, and all that sort of stuff,” he said,

The European guidelines also make recommendations for duration of therapy and comment on the use of steroids and immunotherapy with interferon-gamma, Dr. Denning noted.

Diagnostic criteria

The European guidelines categorize Aspergillus infections according to differences in clinical management:

• Simple aspergilloma. A single pulmonary cavity containing a fungal ball, supported by serologic or microbiologic evidence of infections with Aspergillus species in patients who are not immunocompromised and are asymptomatic or have only minor symptoms and no radiographic evidence of progression for at least 3 months.

• Chronic cavitary pulmonary aspergillosis (CCPA). The presence of one or more pulmonary cavities that may contain one or more aspergillomas or irregular intraluminal material, evidence of Aspergillus species, significant pulmonary/systemic symptoms, and overt progression on radiography over 3 or more months of observations.

• Chronic fibrosing pulmonary aspergillosis (CFPA). Severe, fibrotic destruction of at least two lung lobes as a complication of CCPA, causing a major loss of lung function. The guidelines note that destruction of a single lobe is designated as CCPA of that lobe.

• Aspergillus nodules. This unusual presentation is marked by the presence of one or more nodules that may or may not cavitate. The nodules may resemble tuberculoma, carcinoma of the lung, or coccidioidomycosis; histology is required to make an accurate diagnosis.

• Subacute invasive aspergillosis (SAIA). This can occur over the course of 1-3 months in patients who are mildly immunocompromised. Radiologic features can vary, and may include cavitation, the presence of nodules, and progressive consolidation with the appearance of abscess formation. Fungal hyphae (filaments) can be seen in biopsied lung tissues, and there may be evidence of Aspergillus galactomannan antigen in respiratory fluids or blood.

Treatment

The guidelines note that most of the evidence for managing CPA are based on cohort studies and case reports rather than randomized clinical trials, and that there have been no head-to-head trials comparing oral triazole agents.

For treatment of CPA, the European guidelines recommend:

• Itraconazole 200 mg twice daily, with therapeutic drug monitoring and dose adjustment as necessary (Grade A [strong] recommendation).

• Voriconazole 150-200 mg twice daily, with monitoring and dose adjustment. The guidelines recommend lower doses for patients older than 70 years, those with low body weight, significant liver disease, and/or those of Northeast Asian descent, who may be genetically inclined to slow drug metabolism (Grade A).

 

• Posaconazole liquid 400 mg twice daily, or tablets 300 mg once daily (Grade B [moderate] recommendation].

In general, the recommended duration of therapy for control of infection in patients with CPA or curative intent for patients with SAIA or chronic necrotizing pulmonary aspergillosis is 6 months or more, depending on patient status and drug tolerance.

For patients with CPA with progressive disease, those whom therapy has failed, or those who are intolerant of or have disease resistant to triazoles, intravenous therapy with micafungin, 150 mg day (Grade B); amphotericin B deoxycholate, 0.7-1.0 mg/kg per day (Grade C [marginal] recommendation); liposomal amphotericin B, 3 mg/kg per day (Grade B); or caspofungin, 50-70 mg/day (Grade C) are recommended.

The guidelines also recommend surgical excision of simple aspergilloma, preferably by a video-assisted thoracic surgery technique, if technically feasible.

“In my own experience, we resort to surgery very infrequently,” Dr. Edelman said.

He noted that it would be helpful if the guidelines had also allergic bronchopulmonary aspergillosis as a separate entity.

Ideal not always achievable

Prof. Denning points out that the optimum therapies and practices described in the guidelines can’t always be implemented. Worldwide, he said, antifungal therapy is not widely available, with the exception of fluconazole, which has no activity against Aspergillus, and is inferior to itraconazole and other extended azoles for other fungal diseases such as histoplasmosis, blastomycosis, and paracoccidioidomycosis.

The price of antifungal therapies can also be a barrier to effective treatment in many parts of the world.

“If you’re having to pay for your medicines and you’re living on $5 or $10 a day in Kenya, say, you can’t afford to buy them. So even if the drugs are physically there, it may not be really affordable for a course of therapy for these patients, and there’s some advocacy to be done around that for the whole world,” he said.

The guidelines were funded primarily by grants from ESCMID and ERS with additional support from ECMM. Authors’ travel expenses were funded jointly by ESCMID and ERS. Dr. Denning has received grant support and founder shares in F2G, and has received grants from the Fungal Research Trust, Wellcome Trust, Moulton Trust, Medical Research Council, Chronic Granulomatous Disease Research Trust, National Institute of Allergy and Infectious Diseases, National Institute of Health Research and the European Union, and AstraZeneca. Dr. Edelman reported no relevant disclosures.

[email protected]

European respiratory disease and infectious disease specialists have banded together to issue new clinical guidelines on the diagnosis and management of an uncommon but serious problem: chronic pulmonary aspergillosis (CPA).

Pulmonary infections with Aspergillus species, although uncommon, are a complicating factor in several lung diseases, especially tuberculosis, and aspergillosis is a serious, often fatal opportunistic infection in transplant recipients who are on chronic immunosuppression or patients who are immunocompromised from disease or cytotoxic chemotherapy.

Approximately 240,000 people in Europe and 3 million people worldwide have chronic pulmonary aspergillosis (CPA). The Centers for Disease Control and Prevention notes that because aspergillosis is not classified as a reportable disease, data on the actual incidence of infections in the United States are hard to come by.

“You don’t see this every day, whether you’re an infectious disease specialist or pulmonologist, so you really can’t rely on your experience to guide you in managing these cases, which is why guidelines such as this can be very helpful,” commented Dr. Norman Edelman, a pulmonologist and senior consultant for scientific affairs for the American Lung Association.

The guidelines, issued by the European Society for Clinical Microbiology and Infectious Diseases in cooperation with the European Confederation of Medical Mycology and the European Respiratory Society, are an attempt to provide clinicians with the best possible evidence-based guidance on managing patients with aspergillosis, primarily those with CPA (Eur Respir J. 2015. doi: 10.1183/13993003.00583-2015).

Dr. Edelman noted that the most frequent presentation he sees – and that very infrequently – is allergic bronchopulmonary aspergillosis in patients with asthma.

The most recent U.S. guidelines, issued under the aegis of the Infectious Diseases Society of America (IDSA) in 2000 and revised in 2008 (CID 2008;46:327-360), differ from the European recommendations in their level of detail, explained Prof. David W. Denning, professor of infectious diseases in global health at the University of Manchester (England) and lead author of the European guidelines.

“The IDSA guidelines assume that you know how to make the diagnosis, but actually for chronic pulmonary aspergillosis that’s not so easy with some patients,” he said in an interview.

“The European ones go into in great detail the diagnosis, the radiology, whether this test is better than that test, how they all add up, and all that sort of stuff,” he said,

The European guidelines also make recommendations for duration of therapy and comment on the use of steroids and immunotherapy with interferon-gamma, Dr. Denning noted.

Diagnostic criteria

The European guidelines categorize Aspergillus infections according to differences in clinical management:

• Simple aspergilloma. A single pulmonary cavity containing a fungal ball, supported by serologic or microbiologic evidence of infections with Aspergillus species in patients who are not immunocompromised and are asymptomatic or have only minor symptoms and no radiographic evidence of progression for at least 3 months.

• Chronic cavitary pulmonary aspergillosis (CCPA). The presence of one or more pulmonary cavities that may contain one or more aspergillomas or irregular intraluminal material, evidence of Aspergillus species, significant pulmonary/systemic symptoms, and overt progression on radiography over 3 or more months of observations.

• Chronic fibrosing pulmonary aspergillosis (CFPA). Severe, fibrotic destruction of at least two lung lobes as a complication of CCPA, causing a major loss of lung function. The guidelines note that destruction of a single lobe is designated as CCPA of that lobe.

• Aspergillus nodules. This unusual presentation is marked by the presence of one or more nodules that may or may not cavitate. The nodules may resemble tuberculoma, carcinoma of the lung, or coccidioidomycosis; histology is required to make an accurate diagnosis.

• Subacute invasive aspergillosis (SAIA). This can occur over the course of 1-3 months in patients who are mildly immunocompromised. Radiologic features can vary, and may include cavitation, the presence of nodules, and progressive consolidation with the appearance of abscess formation. Fungal hyphae (filaments) can be seen in biopsied lung tissues, and there may be evidence of Aspergillus galactomannan antigen in respiratory fluids or blood.

Treatment

The guidelines note that most of the evidence for managing CPA are based on cohort studies and case reports rather than randomized clinical trials, and that there have been no head-to-head trials comparing oral triazole agents.

For treatment of CPA, the European guidelines recommend:

• Itraconazole 200 mg twice daily, with therapeutic drug monitoring and dose adjustment as necessary (Grade A [strong] recommendation).

• Voriconazole 150-200 mg twice daily, with monitoring and dose adjustment. The guidelines recommend lower doses for patients older than 70 years, those with low body weight, significant liver disease, and/or those of Northeast Asian descent, who may be genetically inclined to slow drug metabolism (Grade A).

 

• Posaconazole liquid 400 mg twice daily, or tablets 300 mg once daily (Grade B [moderate] recommendation].

In general, the recommended duration of therapy for control of infection in patients with CPA or curative intent for patients with SAIA or chronic necrotizing pulmonary aspergillosis is 6 months or more, depending on patient status and drug tolerance.

For patients with CPA with progressive disease, those whom therapy has failed, or those who are intolerant of or have disease resistant to triazoles, intravenous therapy with micafungin, 150 mg day (Grade B); amphotericin B deoxycholate, 0.7-1.0 mg/kg per day (Grade C [marginal] recommendation); liposomal amphotericin B, 3 mg/kg per day (Grade B); or caspofungin, 50-70 mg/day (Grade C) are recommended.

The guidelines also recommend surgical excision of simple aspergilloma, preferably by a video-assisted thoracic surgery technique, if technically feasible.

“In my own experience, we resort to surgery very infrequently,” Dr. Edelman said.

He noted that it would be helpful if the guidelines had also allergic bronchopulmonary aspergillosis as a separate entity.

Ideal not always achievable

Prof. Denning points out that the optimum therapies and practices described in the guidelines can’t always be implemented. Worldwide, he said, antifungal therapy is not widely available, with the exception of fluconazole, which has no activity against Aspergillus, and is inferior to itraconazole and other extended azoles for other fungal diseases such as histoplasmosis, blastomycosis, and paracoccidioidomycosis.

The price of antifungal therapies can also be a barrier to effective treatment in many parts of the world.

“If you’re having to pay for your medicines and you’re living on $5 or $10 a day in Kenya, say, you can’t afford to buy them. So even if the drugs are physically there, it may not be really affordable for a course of therapy for these patients, and there’s some advocacy to be done around that for the whole world,” he said.

The guidelines were funded primarily by grants from ESCMID and ERS with additional support from ECMM. Authors’ travel expenses were funded jointly by ESCMID and ERS. Dr. Denning has received grant support and founder shares in F2G, and has received grants from the Fungal Research Trust, Wellcome Trust, Moulton Trust, Medical Research Council, Chronic Granulomatous Disease Research Trust, National Institute of Allergy and Infectious Diseases, National Institute of Health Research and the European Union, and AstraZeneca. Dr. Edelman reported no relevant disclosures.

[email protected]

European respiratory disease and infectious disease specialists have banded together to issue new clinical guidelines on the diagnosis and management of an uncommon but serious problem: chronic pulmonary aspergillosis (CPA).

Pulmonary infections with Aspergillus species, although uncommon, are a complicating factor in several lung diseases, especially tuberculosis, and aspergillosis is a serious, often fatal opportunistic infection in transplant recipients who are on chronic immunosuppression or patients who are immunocompromised from disease or cytotoxic chemotherapy.

Approximately 240,000 people in Europe and 3 million people worldwide have chronic pulmonary aspergillosis (CPA). The Centers for Disease Control and Prevention notes that because aspergillosis is not classified as a reportable disease, data on the actual incidence of infections in the United States are hard to come by.

“You don’t see this every day, whether you’re an infectious disease specialist or pulmonologist, so you really can’t rely on your experience to guide you in managing these cases, which is why guidelines such as this can be very helpful,” commented Dr. Norman Edelman, a pulmonologist and senior consultant for scientific affairs for the American Lung Association.

The guidelines, issued by the European Society for Clinical Microbiology and Infectious Diseases in cooperation with the European Confederation of Medical Mycology and the European Respiratory Society, are an attempt to provide clinicians with the best possible evidence-based guidance on managing patients with aspergillosis, primarily those with CPA (Eur Respir J. 2015. doi: 10.1183/13993003.00583-2015).

Dr. Edelman noted that the most frequent presentation he sees – and that very infrequently – is allergic bronchopulmonary aspergillosis in patients with asthma.

The most recent U.S. guidelines, issued under the aegis of the Infectious Diseases Society of America (IDSA) in 2000 and revised in 2008 (CID 2008;46:327-360), differ from the European recommendations in their level of detail, explained Prof. David W. Denning, professor of infectious diseases in global health at the University of Manchester (England) and lead author of the European guidelines.

“The IDSA guidelines assume that you know how to make the diagnosis, but actually for chronic pulmonary aspergillosis that’s not so easy with some patients,” he said in an interview.

“The European ones go into in great detail the diagnosis, the radiology, whether this test is better than that test, how they all add up, and all that sort of stuff,” he said,

The European guidelines also make recommendations for duration of therapy and comment on the use of steroids and immunotherapy with interferon-gamma, Dr. Denning noted.

Diagnostic criteria

The European guidelines categorize Aspergillus infections according to differences in clinical management:

• Simple aspergilloma. A single pulmonary cavity containing a fungal ball, supported by serologic or microbiologic evidence of infections with Aspergillus species in patients who are not immunocompromised and are asymptomatic or have only minor symptoms and no radiographic evidence of progression for at least 3 months.

• Chronic cavitary pulmonary aspergillosis (CCPA). The presence of one or more pulmonary cavities that may contain one or more aspergillomas or irregular intraluminal material, evidence of Aspergillus species, significant pulmonary/systemic symptoms, and overt progression on radiography over 3 or more months of observations.

• Chronic fibrosing pulmonary aspergillosis (CFPA). Severe, fibrotic destruction of at least two lung lobes as a complication of CCPA, causing a major loss of lung function. The guidelines note that destruction of a single lobe is designated as CCPA of that lobe.

• Aspergillus nodules. This unusual presentation is marked by the presence of one or more nodules that may or may not cavitate. The nodules may resemble tuberculoma, carcinoma of the lung, or coccidioidomycosis; histology is required to make an accurate diagnosis.

• Subacute invasive aspergillosis (SAIA). This can occur over the course of 1-3 months in patients who are mildly immunocompromised. Radiologic features can vary, and may include cavitation, the presence of nodules, and progressive consolidation with the appearance of abscess formation. Fungal hyphae (filaments) can be seen in biopsied lung tissues, and there may be evidence of Aspergillus galactomannan antigen in respiratory fluids or blood.

Treatment

The guidelines note that most of the evidence for managing CPA are based on cohort studies and case reports rather than randomized clinical trials, and that there have been no head-to-head trials comparing oral triazole agents.

For treatment of CPA, the European guidelines recommend:

• Itraconazole 200 mg twice daily, with therapeutic drug monitoring and dose adjustment as necessary (Grade A [strong] recommendation).

• Voriconazole 150-200 mg twice daily, with monitoring and dose adjustment. The guidelines recommend lower doses for patients older than 70 years, those with low body weight, significant liver disease, and/or those of Northeast Asian descent, who may be genetically inclined to slow drug metabolism (Grade A).

 

• Posaconazole liquid 400 mg twice daily, or tablets 300 mg once daily (Grade B [moderate] recommendation].

In general, the recommended duration of therapy for control of infection in patients with CPA or curative intent for patients with SAIA or chronic necrotizing pulmonary aspergillosis is 6 months or more, depending on patient status and drug tolerance.

For patients with CPA with progressive disease, those whom therapy has failed, or those who are intolerant of or have disease resistant to triazoles, intravenous therapy with micafungin, 150 mg day (Grade B); amphotericin B deoxycholate, 0.7-1.0 mg/kg per day (Grade C [marginal] recommendation); liposomal amphotericin B, 3 mg/kg per day (Grade B); or caspofungin, 50-70 mg/day (Grade C) are recommended.

The guidelines also recommend surgical excision of simple aspergilloma, preferably by a video-assisted thoracic surgery technique, if technically feasible.

“In my own experience, we resort to surgery very infrequently,” Dr. Edelman said.

He noted that it would be helpful if the guidelines had also allergic bronchopulmonary aspergillosis as a separate entity.

Ideal not always achievable

Prof. Denning points out that the optimum therapies and practices described in the guidelines can’t always be implemented. Worldwide, he said, antifungal therapy is not widely available, with the exception of fluconazole, which has no activity against Aspergillus, and is inferior to itraconazole and other extended azoles for other fungal diseases such as histoplasmosis, blastomycosis, and paracoccidioidomycosis.

The price of antifungal therapies can also be a barrier to effective treatment in many parts of the world.

“If you’re having to pay for your medicines and you’re living on $5 or $10 a day in Kenya, say, you can’t afford to buy them. So even if the drugs are physically there, it may not be really affordable for a course of therapy for these patients, and there’s some advocacy to be done around that for the whole world,” he said.

The guidelines were funded primarily by grants from ESCMID and ERS with additional support from ECMM. Authors’ travel expenses were funded jointly by ESCMID and ERS. Dr. Denning has received grant support and founder shares in F2G, and has received grants from the Fungal Research Trust, Wellcome Trust, Moulton Trust, Medical Research Council, Chronic Granulomatous Disease Research Trust, National Institute of Allergy and Infectious Diseases, National Institute of Health Research and the European Union, and AstraZeneca. Dr. Edelman reported no relevant disclosures.

[email protected]

Chutzpah is a Yiddish word that entered American English, joining bagel and nosh. The usual translations of chutzpah – “nerve” or “effrontery” – are correct enough, but leave out the zest implied by chutzpah’s classic case: a man who kills his parents and throws himself on the mercy of the court because he is an orphan.

We all meet patients with chutzpah, which can be amusing, impressive – even breathtaking.

Take for instance the woman who paged me one evening last month. “I visit your nurse for cosmetic stuff,” she said when I called her back. “Your prices for laser hair removal were high, though, so I went to a spa where I could use a Groupon.”

How nice, I thought.

“Anyhow,” she continued, “I went for a treatment at the spa today, and now I have little red bumps all over my thighs. I thought it might be a reaction, and since you are my dermatologist I called to ask what to do.”

Good to be needed.

Then the next week I got another call, this time from a man I hadn’t seen in a long time. “I really like you as a dermatologist,” he began.

“Thank you,” I murmured.

“I saw this spot on my leg that worried me,” he said. “I was going to show it to you, but your office is in an old building, and old buildings don’t agree with me.”

As I scratched my head, he went on. “So I went to another dermatologist who works in a newer building. He did a biopsy and told me I have skin cancer. He said I should have surgery to take it off. I consider you my dermatologist, though, so I called to ask whether you think surgery is a good idea.”

I said I thought it was. I did not add that he should look for an old surgeon in a new building.

These patients are fresh in my mind, but it doesn’t take much effort to come up with others.

“Mr. Skillman wants a refill on his steroid cream,” says my secretary.

“Sure,” I tell her. “E-scribe it over.”

“No,” she says. “He wants a hard copy mailed to him.”

“Does he have one of those mail order pharmacies that requires a written script?”

“No.”

“But it’s so much simpler to call it in or do it by computer. Why does he have to have a hard copy?”

“I don’t know. But he insists on having one.”

I could go on and on. So could you, I’m sure.

When confronted with chutzpah, you have two options: challenge the person showing it and refuse to go along with his demands, or just sigh, comply, and move on. In general, I go with option #2.

First of all, anyone pushy enough to act this way will not react well to being pushed back. (“What’s your problem? Are you too busy to write a prescription? Too stingy to mail it?”)

Second, and perhaps more to the point, many people who display chutzpah don’t know that’s what they are doing. The woman who went for laser at the Groupon spa really has no idea I’d think it odd for her to call me about a complication instead of the spa personnel who lasered her legs. On some level, she figures that they probably don’t know (look how cheap they are), and thinks I should be flattered to be asked. After all, I’m her dermatologist.

Some people with chutzpah are aggressive and difficult and don’t care if they’re being offensive. A lot more are just clueless. The fellow who bores the daylights out of everyone at dinner parties with long, pointless stories doesn’t know he’s being tedious. He just doesn’t pick up social cues.

Most patients, like most people, are polite and deferential. The rest, though, are more memorable.

My building is indeed old. One hundred years ago it was the swankiest apartment house around. Every flat had rooms for a butler, a maid, and a chauffeur for their Packard motorcar. Then the builder went belly-up during the Depression, and the new owner converted it to medical offices. Downward mobility works for me.

Faced with chutzpah, I shrug, smile, and get on with it. Enough people can still tolerate old buildings, and old dermatologists.

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. Write to him at [email protected].

Chutzpah is a Yiddish word that entered American English, joining bagel and nosh. The usual translations of chutzpah – “nerve” or “effrontery” – are correct enough, but leave out the zest implied by chutzpah’s classic case: a man who kills his parents and throws himself on the mercy of the court because he is an orphan.

We all meet patients with chutzpah, which can be amusing, impressive – even breathtaking.

Take for instance the woman who paged me one evening last month. “I visit your nurse for cosmetic stuff,” she said when I called her back. “Your prices for laser hair removal were high, though, so I went to a spa where I could use a Groupon.”

How nice, I thought.

“Anyhow,” she continued, “I went for a treatment at the spa today, and now I have little red bumps all over my thighs. I thought it might be a reaction, and since you are my dermatologist I called to ask what to do.”

Good to be needed.

Then the next week I got another call, this time from a man I hadn’t seen in a long time. “I really like you as a dermatologist,” he began.

“Thank you,” I murmured.

“I saw this spot on my leg that worried me,” he said. “I was going to show it to you, but your office is in an old building, and old buildings don’t agree with me.”

As I scratched my head, he went on. “So I went to another dermatologist who works in a newer building. He did a biopsy and told me I have skin cancer. He said I should have surgery to take it off. I consider you my dermatologist, though, so I called to ask whether you think surgery is a good idea.”

I said I thought it was. I did not add that he should look for an old surgeon in a new building.

These patients are fresh in my mind, but it doesn’t take much effort to come up with others.

“Mr. Skillman wants a refill on his steroid cream,” says my secretary.

“Sure,” I tell her. “E-scribe it over.”

“No,” she says. “He wants a hard copy mailed to him.”

“Does he have one of those mail order pharmacies that requires a written script?”

“No.”

“But it’s so much simpler to call it in or do it by computer. Why does he have to have a hard copy?”

“I don’t know. But he insists on having one.”

I could go on and on. So could you, I’m sure.

When confronted with chutzpah, you have two options: challenge the person showing it and refuse to go along with his demands, or just sigh, comply, and move on. In general, I go with option #2.

First of all, anyone pushy enough to act this way will not react well to being pushed back. (“What’s your problem? Are you too busy to write a prescription? Too stingy to mail it?”)

Second, and perhaps more to the point, many people who display chutzpah don’t know that’s what they are doing. The woman who went for laser at the Groupon spa really has no idea I’d think it odd for her to call me about a complication instead of the spa personnel who lasered her legs. On some level, she figures that they probably don’t know (look how cheap they are), and thinks I should be flattered to be asked. After all, I’m her dermatologist.

Some people with chutzpah are aggressive and difficult and don’t care if they’re being offensive. A lot more are just clueless. The fellow who bores the daylights out of everyone at dinner parties with long, pointless stories doesn’t know he’s being tedious. He just doesn’t pick up social cues.

Most patients, like most people, are polite and deferential. The rest, though, are more memorable.

My building is indeed old. One hundred years ago it was the swankiest apartment house around. Every flat had rooms for a butler, a maid, and a chauffeur for their Packard motorcar. Then the builder went belly-up during the Depression, and the new owner converted it to medical offices. Downward mobility works for me.

Faced with chutzpah, I shrug, smile, and get on with it. Enough people can still tolerate old buildings, and old dermatologists.

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. Write to him at [email protected].

Chutzpah is a Yiddish word that entered American English, joining bagel and nosh. The usual translations of chutzpah – “nerve” or “effrontery” – are correct enough, but leave out the zest implied by chutzpah’s classic case: a man who kills his parents and throws himself on the mercy of the court because he is an orphan.

We all meet patients with chutzpah, which can be amusing, impressive – even breathtaking.

Take for instance the woman who paged me one evening last month. “I visit your nurse for cosmetic stuff,” she said when I called her back. “Your prices for laser hair removal were high, though, so I went to a spa where I could use a Groupon.”

How nice, I thought.

“Anyhow,” she continued, “I went for a treatment at the spa today, and now I have little red bumps all over my thighs. I thought it might be a reaction, and since you are my dermatologist I called to ask what to do.”

Good to be needed.

Then the next week I got another call, this time from a man I hadn’t seen in a long time. “I really like you as a dermatologist,” he began.

“Thank you,” I murmured.

“I saw this spot on my leg that worried me,” he said. “I was going to show it to you, but your office is in an old building, and old buildings don’t agree with me.”

As I scratched my head, he went on. “So I went to another dermatologist who works in a newer building. He did a biopsy and told me I have skin cancer. He said I should have surgery to take it off. I consider you my dermatologist, though, so I called to ask whether you think surgery is a good idea.”

I said I thought it was. I did not add that he should look for an old surgeon in a new building.

These patients are fresh in my mind, but it doesn’t take much effort to come up with others.

“Mr. Skillman wants a refill on his steroid cream,” says my secretary.

“Sure,” I tell her. “E-scribe it over.”

“No,” she says. “He wants a hard copy mailed to him.”

“Does he have one of those mail order pharmacies that requires a written script?”

“No.”

“But it’s so much simpler to call it in or do it by computer. Why does he have to have a hard copy?”

“I don’t know. But he insists on having one.”

I could go on and on. So could you, I’m sure.

When confronted with chutzpah, you have two options: challenge the person showing it and refuse to go along with his demands, or just sigh, comply, and move on. In general, I go with option #2.

First of all, anyone pushy enough to act this way will not react well to being pushed back. (“What’s your problem? Are you too busy to write a prescription? Too stingy to mail it?”)

Second, and perhaps more to the point, many people who display chutzpah don’t know that’s what they are doing. The woman who went for laser at the Groupon spa really has no idea I’d think it odd for her to call me about a complication instead of the spa personnel who lasered her legs. On some level, she figures that they probably don’t know (look how cheap they are), and thinks I should be flattered to be asked. After all, I’m her dermatologist.

Some people with chutzpah are aggressive and difficult and don’t care if they’re being offensive. A lot more are just clueless. The fellow who bores the daylights out of everyone at dinner parties with long, pointless stories doesn’t know he’s being tedious. He just doesn’t pick up social cues.

Most patients, like most people, are polite and deferential. The rest, though, are more memorable.

My building is indeed old. One hundred years ago it was the swankiest apartment house around. Every flat had rooms for a butler, a maid, and a chauffeur for their Packard motorcar. Then the builder went belly-up during the Depression, and the new owner converted it to medical offices. Downward mobility works for me.

Faced with chutzpah, I shrug, smile, and get on with it. Enough people can still tolerate old buildings, and old dermatologists.

Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. Write to him at [email protected].

Since Title IX passed in 1972, women have become exponentially more involved in competitive sports, from high school to professional levels. With more women engaging in serious athletics, the specific challenges they face have come to the forefront of sports medicine. These problems include the female athlete triad, concussions, exercise safety in pregnancy, anterior cruciate ligament (ACL) injuries, and continued sex discrimination and social injustice. Orthopedists treating female athletes should be aware of these problems, each of which is discussed in this review.

1. Female athlete triad

In 1992, the term female athlete triad was coined to describe 3 problems that often coexist in high-intensity female athletes.¹ Since then, the definition has evolved, but the problem has remained essentially the same. The modern definition incorporates menstrual abnormalities, low energy availability with or without disordered eating, and decreased bone mineral density (BMD).²

With intense exercise and weight loss comes a variety of menstrual disturbances.³ In affected athletes, the hypothalamus is underactivated, and changes in gonadotropin-releasing hormone and luteinizing hormone lead to decreased estrogen production. Research suggests abnormal menses result from having inadequate energy and insufficient caloric intake to support extensive exercise.¹ This phenomenon can occur in athletes in any sport but is most prevalent in lean-body sports, such as swimming, gymnastics, and ballet. The incidence of abnormal menses is as high as 79% in ballet dancers but only 5% in the general population.³ Menstrual abnormalities indicate hormonal abnormalities that can interfere with growth and maturation in young athletes.

Although full-blown eating disorders are uncommon among female athletes, disordered eating patterns are often found among women in competitive sports. Disordered eating can involve a spectrum of inadequate caloric intake and purging behavior, such as vomiting or laxative abuse, and has been reported in up to 25% of collegiate female athletes.⁴ Physicians must recognize these conditions and initiate counseling and treatment when appropriate. Women with disordered eating are at risk for developing electrolyte imbalances, malnutrition syndromes, and osteopenia.

Although careful evaluation and counseling are important, physicians must note that, in most cases, athletics participation may also protect against disordered eating and body image difficulties. A study of 146 college-age women found better body satisfaction among athletes than among nonathletes.⁵ Lean-sport athletes (eg, swimmers, gymnasts) were at higher risk for disordered eating and body image problems than other athletes were. Similarly, other studies have found that a majority of athletes have healthy eating habits.⁴

For poorly nourished and hormonally imbalanced female athletes, decreased BMD poses substantial risk. One study found a significant difference in BMD between athletes with amenorrhea and athletes with normal menses.⁶ In a cohort of female Navy recruits, those with amenorrhea were at 91% higher risk for stress fractures; calcium and vitamin D supplementation reduced risk by 20%.⁷ Osteopenia may be a special problem for prepubescent athletes. Girls who engage in intense exercise and have delayed menarche may have a low estrogen state, predisposing them to low BMD.³ Osteopenia and osteoporosis are difficult to reverse and can put these athletes at risk for stress fractures the rest of their lives. If unrecognized, stress fractures can end an athlete’s career.

Recommendations for dual-energy X-ray absorptiometry (DXA) include testing female athletes who have a diagnosed eating disorder, body mass index under 17.5, history of delayed menarche, oligomenorrhea, 2 prior stress fractures, or prior abnormal DXA scan. Complete testing recommendations appear in the 2014 consensus statement on the female athlete triad and return to sport.^2,8

Orthopedists performing physical examinations for sports participation can screen for the female athlete triad through thoughtful questioning about menstrual history, nutrition habits, and stress fracture symptoms. Best treatment for a diagnosed case of the triad is multidisciplinary care with strong social support. When abnormal menses are an issue, referral to a gynecologist or endocrinologist and consideration of estrogen replacement should be discussed. Some cases require a psychiatrist’s assistance in treating disordered eating. Athletic trainers, coaches, and parents should be involved over the treatment course.¹ Orthopedists must counsel women with osteopenia and osteoporosis about decreasing exercise to a safe level, improving nutritional intake, and supplementing with calcium (1200-1500 mg/d) and vitamin D (600-800 IU/d).^3,7

2. Concussions

Increasing awareness of males’ sport-related concussions, particularly of concussions that occur during National Football League practice and games, has made physicians and researchers more aware of the rate of concussion in female athletes. That rate has increased, and, according to some reports, the risk for sport-related injury is higher for female athletes.⁹ A study of high school athletes found that the rate of concussion in girl’s soccer was second only to that in football.¹⁰

 

Concussions are categorized as mild traumatic brain injuries, and manifestations of the diagnosis are divided into physical, emotional, cognitive, and observed symptoms. The spectrum of symptoms is wide, ranging from difficulty concentrating and thinking clearly to headaches and dizziness.¹¹ Compared with male athletes who sustain a concussion, female athletes report more of these concussive symptoms and have worse visual memory scores.¹²

Efforts to change sports at the player level have been resisted. Helmets have been proposed for field hockey and lacrosse but have not passed stringent concussion testing. In soccer, which has a high rate of concussion, a reform to eliminate heading the ball has been considered. Resistance to these suggestions stems from the thought that changes could alter the traditions of the games. Some individuals have indicated that helmets may give players a false sense of security and thereby cause them to play more aggressively.

Orthopedic surgeons must be aware of concussion symptoms. Multiple concussions may have a cumulative effect on functional ability and emotional well-being and may lead to chronic traumatic encephalopathy.¹³ Concern about the long-term effects of concussion has led to the implementation of universal “return to play” laws. These laws vary by state but have 3 steps in common: Educate coaches, players, and athletes; remove athletes from play; and obtain health care professionals’ permission to return to play.¹⁴ These guidelines set up an action plan for treating an athlete who has sustained a concussion.

Encouraging results of educating coaches have been noted. Coaches who were given Centers for Disease Control and Prevention–sponsored material on preventing, recognizing, and responding to concussions were able to effectively address concussions; 6 months later, 63% were better able to appreciate the severity of concussions.¹⁵ Continued education of athletic communities should help bring this injury to the attention of those treating female athletes.

3. Exercise safety in pregnancy

Women in sports can continue their athletic regimens during pregnancy. It is important to address challenges to the pregnant woman and to the fetus when assessing the risks of exercise.

The physiologic changes that occur during pregnancy may affect how a pregnant athlete responds to stress. Plasma volume, red blood cell volume, and cardiac function and output all increase during normal pregnancy.^3,16 Abnormal heart rate during pregnancy can adversely affect the fetus. During and after exercise, fetal bradycardia can occur. Therefore, recommendations should include not exceeding pre-pregnancy activity levels.³ Careful monitoring of exercise intensity is recommended by the American College of Obstetrics and Gynecology; the guideline is to maintain less than 70% of maximal heart rate.^17,18

The negative effects of exercise on the pregnant athlete are limited, but it is important to educate patients and to consider preventive strategies. One physiologic change that occurs during pregnancy is ligamentous laxity, which is caused by the hormone relaxin.¹⁶ Ligamentous laxity has the potential to put pregnant athletes at risk for soft-tissue and bony injury during impact sports. However, the positive effects of exercise during pregnancy include improved appetite, sleep, and emotional health.¹⁹ Aerobic exercise during pregnancy may reverse insulin resistance as demonstrated in animal studies; though this outcome has not been demonstrated in human studies,²⁰ women should be reassured that moderate exercise has overall beneficial effects.

Some research suggests that exercise may expose the fetus to hyperthermia, blood sugar changes, physical injury, and premature labor.¹⁶ Typically, fetal heat is dissipated from the mother. After intense exercise, maternal body temperature rises and leads to some degree of fetal hyperthermia.¹⁶ Animal model studies have suggested that hyperthermia may result in a slightly higher rate of congenital abnormalities. Pregnant women should keep their exercise routines to less than 60 minutes, should exercise in a thermally regulated environment, and should keep themselves hydrated to avoid fetal hyperthermia.¹⁸

Reduced blood flow, accompanied by a deficit of oxygen to the uterus and the developing fetus, is another concern for pregnant athletes. During exercise, when more blood is flowing to the muscles, less is flowing to the uterus.¹⁶ Furthermore, during the third trimester, women should avoid supine exercise, as venous outflow is poor with the body in that position.²¹

Elite athletes who continue training during pregnancy should be carefully counseled about adjusting their training regimens. Because of increased cardiac output and blood volume, the heart rate will be lower than usual, demanding an adjustment in interpretation. Blood cell counts do not increase as much as plasma volume does—often leading to relative anemia. For elite athletes, this means iron supplementation is crucial.²² Thermal regulation may be more difficult, as training regimens may demand prolonged exercise. Physicians should recommend adequate hydration for these athletes.¹⁸

 

Although continued exercise is generally safe for a pregnant athlete and her fetus, caution is required when there is increased risk for premature delivery, or other special conditions exist. Multiple gestation, placenta previa, history of early labor or premature births, and incompetent cervix all contraindicate aerobic exercise during pregnancy.¹⁸ With these exceptions in mind, physicians can safely counsel pregnant women to do moderate exercise 30 minutes every day.^17,18 Other recommendations are listed at the American College of Obstetricians and Gynecologists website.²³

4. Anterior cruciate ligament injuries

ACL injuries affect a staggering number of athletes. In the United States, approximately 100,000 people sustain these injuries annually.²⁴ As they occur up to 8 times more often in women than in men, ACL injuries are a top concern for physicians treating female athletes.

This disproportionate injury rate is influenced by differences between male and female anatomy. The width and shape of the femoral intercondylar notch have been studied as potential variables influencing the risk for ACL injury. Analysis of notch-view radiographs revealed a significant inverse relationship between notch width and ACL injury.²⁵ A-shaped notches, notches with a significantly larger base and a narrowed roof, were more prevalent in women but did not correlate with increased risk for ACL injury. Studies have shown that female athletes with a noncontact ACL injury have a higher lateral tibial plateau posterior slope; this slope is associated with increased peak anteromedial ACL strain, which may contribute to injury.²⁶ An analysis of magnetic resonance imaging scans in patients with and without ACL injury revealed that, for female patients, decreased femoral intercondylar notch width at the anterior outlet combined with increased lateral compartment posterior slope correlated best with risk for ACL injury.²⁷

Although static anatomical factors contribute to ACL injuries in female athletes, dynamic neuromuscular influences are potential opportunities for intervention. Female athletes with high relative quadriceps strength and weak hamstring strength may be at increased risk for ACL injury.²⁸ This “quadriceps dominance” becomes important in sports involving high-risk activities, such as running, cutting, pivoting, and jumping. In addition, compared with male athletes, female athletes demonstrate increased lateral trunk motion and knee valgus torque while landing during noncontact ACL tears, making core stability a factor in ACL injury.²⁹

The collaborative efforts of physicians, physical therapists, athletic trainers, and coaches have yielded multifactorial neuromuscular training programs for the prevention of noncontact ACL injuries. Ideal ACL prevention protocols involve sessions that last for at least 10 minutes and take place 3 times a week. At these sessions, exercises are focused on strengthening, balance, and proprioceptive training.³⁰ The programs last about 8 weeks, but sustained benefits require maintenance after the program has been completed and during the off-season. Program adherence must be encouraged and can be facilitated by varying workouts and raising risk awareness. The most effective programs have reduced the relative risk of noncontact ACL injuries by 75% to 100%.³¹ These promising results have led to increased focus on program implementation in an effort to prevent ACL injury.

5. Continued sex discrimination and social injustice

In 1972, Title IX was passed as part of the Education Amendments Act. Title IX states, “No person in the United States shall, on the basis of sex, be excluded from participation in, be denied the benefits of, or be subjected to discrimination under any educational program or activity receiving Federal financial assistance.” Passage of this law, which has implications outside of athletic participation, marked an important turning point in women’s ability to participate equally in college sports.^32,33 The Civil Rights Restoration Act, passed in 1988, strengthened Title IX and made it applicable to all institutions receiving federal funding.³⁴ Before the 1970s, women typically were restricted to club sports, and funding and participation opportunities were weighted heavily toward men. Over the past 40 years, women’s participation in high school, college, and professional sports has taken a huge leap forward.³² For example, the number of women participating in high school sports increased from 294,000 (7.4% of all athletes) in 1972 to 3.4 million (>41% of all athletes) in 2014.

Despite advances in women’s civil rights, examples of inequality in US schools remain, particularly in the distribution of funding, which still strongly favors men’s football.³² Men’s sports receive 90% of media coverage.³³ In 2002, women represented 55% of college students but only 42% of varsity athletes.³⁴ The schools that have complied the least with Title IX are schools in the Midwest and the South and those with football teams.³⁴ Women are underrepresented as coaches, and funding continues to be disproportionately spent on men’s sports.

 

For women, the benefits of participating in sports are far-reaching and significant. These benefits include improvements in academic success, mental health, and responsible behavior.³³ Women’s gaining acceptance and respect throughout the athletic world seems to have carried over elsewhere. Although many institutions remain noncompliant with Title IX, efforts continue to have a strongly positive effect on gender equality in the United States.

Since Title IX passed in 1972, women have become exponentially more involved in competitive sports, from high school to professional levels. With more women engaging in serious athletics, the specific challenges they face have come to the forefront of sports medicine. These problems include the female athlete triad, concussions, exercise safety in pregnancy, anterior cruciate ligament (ACL) injuries, and continued sex discrimination and social injustice. Orthopedists treating female athletes should be aware of these problems, each of which is discussed in this review.

1. Female athlete triad

In 1992, the term female athlete triad was coined to describe 3 problems that often coexist in high-intensity female athletes.¹ Since then, the definition has evolved, but the problem has remained essentially the same. The modern definition incorporates menstrual abnormalities, low energy availability with or without disordered eating, and decreased bone mineral density (BMD).²

With intense exercise and weight loss comes a variety of menstrual disturbances.³ In affected athletes, the hypothalamus is underactivated, and changes in gonadotropin-releasing hormone and luteinizing hormone lead to decreased estrogen production. Research suggests abnormal menses result from having inadequate energy and insufficient caloric intake to support extensive exercise.¹ This phenomenon can occur in athletes in any sport but is most prevalent in lean-body sports, such as swimming, gymnastics, and ballet. The incidence of abnormal menses is as high as 79% in ballet dancers but only 5% in the general population.³ Menstrual abnormalities indicate hormonal abnormalities that can interfere with growth and maturation in young athletes.

Although full-blown eating disorders are uncommon among female athletes, disordered eating patterns are often found among women in competitive sports. Disordered eating can involve a spectrum of inadequate caloric intake and purging behavior, such as vomiting or laxative abuse, and has been reported in up to 25% of collegiate female athletes.⁴ Physicians must recognize these conditions and initiate counseling and treatment when appropriate. Women with disordered eating are at risk for developing electrolyte imbalances, malnutrition syndromes, and osteopenia.

Although careful evaluation and counseling are important, physicians must note that, in most cases, athletics participation may also protect against disordered eating and body image difficulties. A study of 146 college-age women found better body satisfaction among athletes than among nonathletes.⁵ Lean-sport athletes (eg, swimmers, gymnasts) were at higher risk for disordered eating and body image problems than other athletes were. Similarly, other studies have found that a majority of athletes have healthy eating habits.⁴

For poorly nourished and hormonally imbalanced female athletes, decreased BMD poses substantial risk. One study found a significant difference in BMD between athletes with amenorrhea and athletes with normal menses.⁶ In a cohort of female Navy recruits, those with amenorrhea were at 91% higher risk for stress fractures; calcium and vitamin D supplementation reduced risk by 20%.⁷ Osteopenia may be a special problem for prepubescent athletes. Girls who engage in intense exercise and have delayed menarche may have a low estrogen state, predisposing them to low BMD.³ Osteopenia and osteoporosis are difficult to reverse and can put these athletes at risk for stress fractures the rest of their lives. If unrecognized, stress fractures can end an athlete’s career.

Recommendations for dual-energy X-ray absorptiometry (DXA) include testing female athletes who have a diagnosed eating disorder, body mass index under 17.5, history of delayed menarche, oligomenorrhea, 2 prior stress fractures, or prior abnormal DXA scan. Complete testing recommendations appear in the 2014 consensus statement on the female athlete triad and return to sport.^2,8

Orthopedists performing physical examinations for sports participation can screen for the female athlete triad through thoughtful questioning about menstrual history, nutrition habits, and stress fracture symptoms. Best treatment for a diagnosed case of the triad is multidisciplinary care with strong social support. When abnormal menses are an issue, referral to a gynecologist or endocrinologist and consideration of estrogen replacement should be discussed. Some cases require a psychiatrist’s assistance in treating disordered eating. Athletic trainers, coaches, and parents should be involved over the treatment course.¹ Orthopedists must counsel women with osteopenia and osteoporosis about decreasing exercise to a safe level, improving nutritional intake, and supplementing with calcium (1200-1500 mg/d) and vitamin D (600-800 IU/d).^3,7

2. Concussions

Increasing awareness of males’ sport-related concussions, particularly of concussions that occur during National Football League practice and games, has made physicians and researchers more aware of the rate of concussion in female athletes. That rate has increased, and, according to some reports, the risk for sport-related injury is higher for female athletes.⁹ A study of high school athletes found that the rate of concussion in girl’s soccer was second only to that in football.¹⁰

 

Concussions are categorized as mild traumatic brain injuries, and manifestations of the diagnosis are divided into physical, emotional, cognitive, and observed symptoms. The spectrum of symptoms is wide, ranging from difficulty concentrating and thinking clearly to headaches and dizziness.¹¹ Compared with male athletes who sustain a concussion, female athletes report more of these concussive symptoms and have worse visual memory scores.¹²

Efforts to change sports at the player level have been resisted. Helmets have been proposed for field hockey and lacrosse but have not passed stringent concussion testing. In soccer, which has a high rate of concussion, a reform to eliminate heading the ball has been considered. Resistance to these suggestions stems from the thought that changes could alter the traditions of the games. Some individuals have indicated that helmets may give players a false sense of security and thereby cause them to play more aggressively.

Orthopedic surgeons must be aware of concussion symptoms. Multiple concussions may have a cumulative effect on functional ability and emotional well-being and may lead to chronic traumatic encephalopathy.¹³ Concern about the long-term effects of concussion has led to the implementation of universal “return to play” laws. These laws vary by state but have 3 steps in common: Educate coaches, players, and athletes; remove athletes from play; and obtain health care professionals’ permission to return to play.¹⁴ These guidelines set up an action plan for treating an athlete who has sustained a concussion.

Encouraging results of educating coaches have been noted. Coaches who were given Centers for Disease Control and Prevention–sponsored material on preventing, recognizing, and responding to concussions were able to effectively address concussions; 6 months later, 63% were better able to appreciate the severity of concussions.¹⁵ Continued education of athletic communities should help bring this injury to the attention of those treating female athletes.

3. Exercise safety in pregnancy

Women in sports can continue their athletic regimens during pregnancy. It is important to address challenges to the pregnant woman and to the fetus when assessing the risks of exercise.

The physiologic changes that occur during pregnancy may affect how a pregnant athlete responds to stress. Plasma volume, red blood cell volume, and cardiac function and output all increase during normal pregnancy.^3,16 Abnormal heart rate during pregnancy can adversely affect the fetus. During and after exercise, fetal bradycardia can occur. Therefore, recommendations should include not exceeding pre-pregnancy activity levels.³ Careful monitoring of exercise intensity is recommended by the American College of Obstetrics and Gynecology; the guideline is to maintain less than 70% of maximal heart rate.^17,18

The negative effects of exercise on the pregnant athlete are limited, but it is important to educate patients and to consider preventive strategies. One physiologic change that occurs during pregnancy is ligamentous laxity, which is caused by the hormone relaxin.¹⁶ Ligamentous laxity has the potential to put pregnant athletes at risk for soft-tissue and bony injury during impact sports. However, the positive effects of exercise during pregnancy include improved appetite, sleep, and emotional health.¹⁹ Aerobic exercise during pregnancy may reverse insulin resistance as demonstrated in animal studies; though this outcome has not been demonstrated in human studies,²⁰ women should be reassured that moderate exercise has overall beneficial effects.

Some research suggests that exercise may expose the fetus to hyperthermia, blood sugar changes, physical injury, and premature labor.¹⁶ Typically, fetal heat is dissipated from the mother. After intense exercise, maternal body temperature rises and leads to some degree of fetal hyperthermia.¹⁶ Animal model studies have suggested that hyperthermia may result in a slightly higher rate of congenital abnormalities. Pregnant women should keep their exercise routines to less than 60 minutes, should exercise in a thermally regulated environment, and should keep themselves hydrated to avoid fetal hyperthermia.¹⁸

Reduced blood flow, accompanied by a deficit of oxygen to the uterus and the developing fetus, is another concern for pregnant athletes. During exercise, when more blood is flowing to the muscles, less is flowing to the uterus.¹⁶ Furthermore, during the third trimester, women should avoid supine exercise, as venous outflow is poor with the body in that position.²¹

Elite athletes who continue training during pregnancy should be carefully counseled about adjusting their training regimens. Because of increased cardiac output and blood volume, the heart rate will be lower than usual, demanding an adjustment in interpretation. Blood cell counts do not increase as much as plasma volume does—often leading to relative anemia. For elite athletes, this means iron supplementation is crucial.²² Thermal regulation may be more difficult, as training regimens may demand prolonged exercise. Physicians should recommend adequate hydration for these athletes.¹⁸

 

Although continued exercise is generally safe for a pregnant athlete and her fetus, caution is required when there is increased risk for premature delivery, or other special conditions exist. Multiple gestation, placenta previa, history of early labor or premature births, and incompetent cervix all contraindicate aerobic exercise during pregnancy.¹⁸ With these exceptions in mind, physicians can safely counsel pregnant women to do moderate exercise 30 minutes every day.^17,18 Other recommendations are listed at the American College of Obstetricians and Gynecologists website.²³

4. Anterior cruciate ligament injuries

ACL injuries affect a staggering number of athletes. In the United States, approximately 100,000 people sustain these injuries annually.²⁴ As they occur up to 8 times more often in women than in men, ACL injuries are a top concern for physicians treating female athletes.

This disproportionate injury rate is influenced by differences between male and female anatomy. The width and shape of the femoral intercondylar notch have been studied as potential variables influencing the risk for ACL injury. Analysis of notch-view radiographs revealed a significant inverse relationship between notch width and ACL injury.²⁵ A-shaped notches, notches with a significantly larger base and a narrowed roof, were more prevalent in women but did not correlate with increased risk for ACL injury. Studies have shown that female athletes with a noncontact ACL injury have a higher lateral tibial plateau posterior slope; this slope is associated with increased peak anteromedial ACL strain, which may contribute to injury.²⁶ An analysis of magnetic resonance imaging scans in patients with and without ACL injury revealed that, for female patients, decreased femoral intercondylar notch width at the anterior outlet combined with increased lateral compartment posterior slope correlated best with risk for ACL injury.²⁷

Although static anatomical factors contribute to ACL injuries in female athletes, dynamic neuromuscular influences are potential opportunities for intervention. Female athletes with high relative quadriceps strength and weak hamstring strength may be at increased risk for ACL injury.²⁸ This “quadriceps dominance” becomes important in sports involving high-risk activities, such as running, cutting, pivoting, and jumping. In addition, compared with male athletes, female athletes demonstrate increased lateral trunk motion and knee valgus torque while landing during noncontact ACL tears, making core stability a factor in ACL injury.²⁹

The collaborative efforts of physicians, physical therapists, athletic trainers, and coaches have yielded multifactorial neuromuscular training programs for the prevention of noncontact ACL injuries. Ideal ACL prevention protocols involve sessions that last for at least 10 minutes and take place 3 times a week. At these sessions, exercises are focused on strengthening, balance, and proprioceptive training.³⁰ The programs last about 8 weeks, but sustained benefits require maintenance after the program has been completed and during the off-season. Program adherence must be encouraged and can be facilitated by varying workouts and raising risk awareness. The most effective programs have reduced the relative risk of noncontact ACL injuries by 75% to 100%.³¹ These promising results have led to increased focus on program implementation in an effort to prevent ACL injury.

5. Continued sex discrimination and social injustice

In 1972, Title IX was passed as part of the Education Amendments Act. Title IX states, “No person in the United States shall, on the basis of sex, be excluded from participation in, be denied the benefits of, or be subjected to discrimination under any educational program or activity receiving Federal financial assistance.” Passage of this law, which has implications outside of athletic participation, marked an important turning point in women’s ability to participate equally in college sports.^32,33 The Civil Rights Restoration Act, passed in 1988, strengthened Title IX and made it applicable to all institutions receiving federal funding.³⁴ Before the 1970s, women typically were restricted to club sports, and funding and participation opportunities were weighted heavily toward men. Over the past 40 years, women’s participation in high school, college, and professional sports has taken a huge leap forward.³² For example, the number of women participating in high school sports increased from 294,000 (7.4% of all athletes) in 1972 to 3.4 million (>41% of all athletes) in 2014.

Despite advances in women’s civil rights, examples of inequality in US schools remain, particularly in the distribution of funding, which still strongly favors men’s football.³² Men’s sports receive 90% of media coverage.³³ In 2002, women represented 55% of college students but only 42% of varsity athletes.³⁴ The schools that have complied the least with Title IX are schools in the Midwest and the South and those with football teams.³⁴ Women are underrepresented as coaches, and funding continues to be disproportionately spent on men’s sports.

 

For women, the benefits of participating in sports are far-reaching and significant. These benefits include improvements in academic success, mental health, and responsible behavior.³³ Women’s gaining acceptance and respect throughout the athletic world seems to have carried over elsewhere. Although many institutions remain noncompliant with Title IX, efforts continue to have a strongly positive effect on gender equality in the United States.

Since Title IX passed in 1972, women have become exponentially more involved in competitive sports, from high school to professional levels. With more women engaging in serious athletics, the specific challenges they face have come to the forefront of sports medicine. These problems include the female athlete triad, concussions, exercise safety in pregnancy, anterior cruciate ligament (ACL) injuries, and continued sex discrimination and social injustice. Orthopedists treating female athletes should be aware of these problems, each of which is discussed in this review.

1. Female athlete triad

In 1992, the term female athlete triad was coined to describe 3 problems that often coexist in high-intensity female athletes.¹ Since then, the definition has evolved, but the problem has remained essentially the same. The modern definition incorporates menstrual abnormalities, low energy availability with or without disordered eating, and decreased bone mineral density (BMD).²

With intense exercise and weight loss comes a variety of menstrual disturbances.³ In affected athletes, the hypothalamus is underactivated, and changes in gonadotropin-releasing hormone and luteinizing hormone lead to decreased estrogen production. Research suggests abnormal menses result from having inadequate energy and insufficient caloric intake to support extensive exercise.¹ This phenomenon can occur in athletes in any sport but is most prevalent in lean-body sports, such as swimming, gymnastics, and ballet. The incidence of abnormal menses is as high as 79% in ballet dancers but only 5% in the general population.³ Menstrual abnormalities indicate hormonal abnormalities that can interfere with growth and maturation in young athletes.

Although full-blown eating disorders are uncommon among female athletes, disordered eating patterns are often found among women in competitive sports. Disordered eating can involve a spectrum of inadequate caloric intake and purging behavior, such as vomiting or laxative abuse, and has been reported in up to 25% of collegiate female athletes.⁴ Physicians must recognize these conditions and initiate counseling and treatment when appropriate. Women with disordered eating are at risk for developing electrolyte imbalances, malnutrition syndromes, and osteopenia.

Although careful evaluation and counseling are important, physicians must note that, in most cases, athletics participation may also protect against disordered eating and body image difficulties. A study of 146 college-age women found better body satisfaction among athletes than among nonathletes.⁵ Lean-sport athletes (eg, swimmers, gymnasts) were at higher risk for disordered eating and body image problems than other athletes were. Similarly, other studies have found that a majority of athletes have healthy eating habits.⁴

For poorly nourished and hormonally imbalanced female athletes, decreased BMD poses substantial risk. One study found a significant difference in BMD between athletes with amenorrhea and athletes with normal menses.⁶ In a cohort of female Navy recruits, those with amenorrhea were at 91% higher risk for stress fractures; calcium and vitamin D supplementation reduced risk by 20%.⁷ Osteopenia may be a special problem for prepubescent athletes. Girls who engage in intense exercise and have delayed menarche may have a low estrogen state, predisposing them to low BMD.³ Osteopenia and osteoporosis are difficult to reverse and can put these athletes at risk for stress fractures the rest of their lives. If unrecognized, stress fractures can end an athlete’s career.

Recommendations for dual-energy X-ray absorptiometry (DXA) include testing female athletes who have a diagnosed eating disorder, body mass index under 17.5, history of delayed menarche, oligomenorrhea, 2 prior stress fractures, or prior abnormal DXA scan. Complete testing recommendations appear in the 2014 consensus statement on the female athlete triad and return to sport.^2,8

Orthopedists performing physical examinations for sports participation can screen for the female athlete triad through thoughtful questioning about menstrual history, nutrition habits, and stress fracture symptoms. Best treatment for a diagnosed case of the triad is multidisciplinary care with strong social support. When abnormal menses are an issue, referral to a gynecologist or endocrinologist and consideration of estrogen replacement should be discussed. Some cases require a psychiatrist’s assistance in treating disordered eating. Athletic trainers, coaches, and parents should be involved over the treatment course.¹ Orthopedists must counsel women with osteopenia and osteoporosis about decreasing exercise to a safe level, improving nutritional intake, and supplementing with calcium (1200-1500 mg/d) and vitamin D (600-800 IU/d).^3,7

2. Concussions

Increasing awareness of males’ sport-related concussions, particularly of concussions that occur during National Football League practice and games, has made physicians and researchers more aware of the rate of concussion in female athletes. That rate has increased, and, according to some reports, the risk for sport-related injury is higher for female athletes.⁹ A study of high school athletes found that the rate of concussion in girl’s soccer was second only to that in football.¹⁰

 

Concussions are categorized as mild traumatic brain injuries, and manifestations of the diagnosis are divided into physical, emotional, cognitive, and observed symptoms. The spectrum of symptoms is wide, ranging from difficulty concentrating and thinking clearly to headaches and dizziness.¹¹ Compared with male athletes who sustain a concussion, female athletes report more of these concussive symptoms and have worse visual memory scores.¹²

Efforts to change sports at the player level have been resisted. Helmets have been proposed for field hockey and lacrosse but have not passed stringent concussion testing. In soccer, which has a high rate of concussion, a reform to eliminate heading the ball has been considered. Resistance to these suggestions stems from the thought that changes could alter the traditions of the games. Some individuals have indicated that helmets may give players a false sense of security and thereby cause them to play more aggressively.

Orthopedic surgeons must be aware of concussion symptoms. Multiple concussions may have a cumulative effect on functional ability and emotional well-being and may lead to chronic traumatic encephalopathy.¹³ Concern about the long-term effects of concussion has led to the implementation of universal “return to play” laws. These laws vary by state but have 3 steps in common: Educate coaches, players, and athletes; remove athletes from play; and obtain health care professionals’ permission to return to play.¹⁴ These guidelines set up an action plan for treating an athlete who has sustained a concussion.

Encouraging results of educating coaches have been noted. Coaches who were given Centers for Disease Control and Prevention–sponsored material on preventing, recognizing, and responding to concussions were able to effectively address concussions; 6 months later, 63% were better able to appreciate the severity of concussions.¹⁵ Continued education of athletic communities should help bring this injury to the attention of those treating female athletes.

3. Exercise safety in pregnancy

Women in sports can continue their athletic regimens during pregnancy. It is important to address challenges to the pregnant woman and to the fetus when assessing the risks of exercise.

The physiologic changes that occur during pregnancy may affect how a pregnant athlete responds to stress. Plasma volume, red blood cell volume, and cardiac function and output all increase during normal pregnancy.^3,16 Abnormal heart rate during pregnancy can adversely affect the fetus. During and after exercise, fetal bradycardia can occur. Therefore, recommendations should include not exceeding pre-pregnancy activity levels.³ Careful monitoring of exercise intensity is recommended by the American College of Obstetrics and Gynecology; the guideline is to maintain less than 70% of maximal heart rate.^17,18

The negative effects of exercise on the pregnant athlete are limited, but it is important to educate patients and to consider preventive strategies. One physiologic change that occurs during pregnancy is ligamentous laxity, which is caused by the hormone relaxin.¹⁶ Ligamentous laxity has the potential to put pregnant athletes at risk for soft-tissue and bony injury during impact sports. However, the positive effects of exercise during pregnancy include improved appetite, sleep, and emotional health.¹⁹ Aerobic exercise during pregnancy may reverse insulin resistance as demonstrated in animal studies; though this outcome has not been demonstrated in human studies,²⁰ women should be reassured that moderate exercise has overall beneficial effects.

Some research suggests that exercise may expose the fetus to hyperthermia, blood sugar changes, physical injury, and premature labor.¹⁶ Typically, fetal heat is dissipated from the mother. After intense exercise, maternal body temperature rises and leads to some degree of fetal hyperthermia.¹⁶ Animal model studies have suggested that hyperthermia may result in a slightly higher rate of congenital abnormalities. Pregnant women should keep their exercise routines to less than 60 minutes, should exercise in a thermally regulated environment, and should keep themselves hydrated to avoid fetal hyperthermia.¹⁸

Reduced blood flow, accompanied by a deficit of oxygen to the uterus and the developing fetus, is another concern for pregnant athletes. During exercise, when more blood is flowing to the muscles, less is flowing to the uterus.¹⁶ Furthermore, during the third trimester, women should avoid supine exercise, as venous outflow is poor with the body in that position.²¹

Elite athletes who continue training during pregnancy should be carefully counseled about adjusting their training regimens. Because of increased cardiac output and blood volume, the heart rate will be lower than usual, demanding an adjustment in interpretation. Blood cell counts do not increase as much as plasma volume does—often leading to relative anemia. For elite athletes, this means iron supplementation is crucial.²² Thermal regulation may be more difficult, as training regimens may demand prolonged exercise. Physicians should recommend adequate hydration for these athletes.¹⁸

 

Although continued exercise is generally safe for a pregnant athlete and her fetus, caution is required when there is increased risk for premature delivery, or other special conditions exist. Multiple gestation, placenta previa, history of early labor or premature births, and incompetent cervix all contraindicate aerobic exercise during pregnancy.¹⁸ With these exceptions in mind, physicians can safely counsel pregnant women to do moderate exercise 30 minutes every day.^17,18 Other recommendations are listed at the American College of Obstetricians and Gynecologists website.²³

4. Anterior cruciate ligament injuries

ACL injuries affect a staggering number of athletes. In the United States, approximately 100,000 people sustain these injuries annually.²⁴ As they occur up to 8 times more often in women than in men, ACL injuries are a top concern for physicians treating female athletes.

This disproportionate injury rate is influenced by differences between male and female anatomy. The width and shape of the femoral intercondylar notch have been studied as potential variables influencing the risk for ACL injury. Analysis of notch-view radiographs revealed a significant inverse relationship between notch width and ACL injury.²⁵ A-shaped notches, notches with a significantly larger base and a narrowed roof, were more prevalent in women but did not correlate with increased risk for ACL injury. Studies have shown that female athletes with a noncontact ACL injury have a higher lateral tibial plateau posterior slope; this slope is associated with increased peak anteromedial ACL strain, which may contribute to injury.²⁶ An analysis of magnetic resonance imaging scans in patients with and without ACL injury revealed that, for female patients, decreased femoral intercondylar notch width at the anterior outlet combined with increased lateral compartment posterior slope correlated best with risk for ACL injury.²⁷

Although static anatomical factors contribute to ACL injuries in female athletes, dynamic neuromuscular influences are potential opportunities for intervention. Female athletes with high relative quadriceps strength and weak hamstring strength may be at increased risk for ACL injury.²⁸ This “quadriceps dominance” becomes important in sports involving high-risk activities, such as running, cutting, pivoting, and jumping. In addition, compared with male athletes, female athletes demonstrate increased lateral trunk motion and knee valgus torque while landing during noncontact ACL tears, making core stability a factor in ACL injury.²⁹

The collaborative efforts of physicians, physical therapists, athletic trainers, and coaches have yielded multifactorial neuromuscular training programs for the prevention of noncontact ACL injuries. Ideal ACL prevention protocols involve sessions that last for at least 10 minutes and take place 3 times a week. At these sessions, exercises are focused on strengthening, balance, and proprioceptive training.³⁰ The programs last about 8 weeks, but sustained benefits require maintenance after the program has been completed and during the off-season. Program adherence must be encouraged and can be facilitated by varying workouts and raising risk awareness. The most effective programs have reduced the relative risk of noncontact ACL injuries by 75% to 100%.³¹ These promising results have led to increased focus on program implementation in an effort to prevent ACL injury.

5. Continued sex discrimination and social injustice

In 1972, Title IX was passed as part of the Education Amendments Act. Title IX states, “No person in the United States shall, on the basis of sex, be excluded from participation in, be denied the benefits of, or be subjected to discrimination under any educational program or activity receiving Federal financial assistance.” Passage of this law, which has implications outside of athletic participation, marked an important turning point in women’s ability to participate equally in college sports.^32,33 The Civil Rights Restoration Act, passed in 1988, strengthened Title IX and made it applicable to all institutions receiving federal funding.³⁴ Before the 1970s, women typically were restricted to club sports, and funding and participation opportunities were weighted heavily toward men. Over the past 40 years, women’s participation in high school, college, and professional sports has taken a huge leap forward.³² For example, the number of women participating in high school sports increased from 294,000 (7.4% of all athletes) in 1972 to 3.4 million (>41% of all athletes) in 2014.

Despite advances in women’s civil rights, examples of inequality in US schools remain, particularly in the distribution of funding, which still strongly favors men’s football.³² Men’s sports receive 90% of media coverage.³³ In 2002, women represented 55% of college students but only 42% of varsity athletes.³⁴ The schools that have complied the least with Title IX are schools in the Midwest and the South and those with football teams.³⁴ Women are underrepresented as coaches, and funding continues to be disproportionately spent on men’s sports.

 

For women, the benefits of participating in sports are far-reaching and significant. These benefits include improvements in academic success, mental health, and responsible behavior.³³ Women’s gaining acceptance and respect throughout the athletic world seems to have carried over elsewhere. Although many institutions remain noncompliant with Title IX, efforts continue to have a strongly positive effect on gender equality in the United States.

A new and novel technique for obtaining the patient-directed valgus stress radiograph of the knee.

To read the authors' full article click here.

A new and novel technique for obtaining the patient-directed valgus stress radiograph of the knee.

To read the authors' full article click here.

A new and novel technique for obtaining the patient-directed valgus stress radiograph of the knee.

To read the authors' full article click here.

Medial-compartment partial knee arthroplasty (unicompartmental replacement) is an accepted surgical intervention for anteromedial osteoarthritis of the knee.1 The radiographic investigations required in the workup of these patients should include weight-bearing standing anteroposterior (AP), lateral, and sunrise (Merchant) views, as well as a valgus stress AP radiograph to assess the functionality of the lateral compartment. The method of properly obtaining the valgus stress film has been well described by the Oxford Group.2 Its recommended radiographic technique requires that a surgeon or a radiologic technologist perform the valgus stress maneuver, manually, while another technologist shoots the film. The 2 consequences of this technique are that it requires 2 individuals to obtain the film, and it subjects the individual who is applying the stress to some level of radiation exposure, which is undesirable. Because of this and the time inconvenience, many surgeons omit the valgus stress radiograph, which can lead to the adverse outcome of missing a lateral compartment that is functionally incompetent, resulting in the potential for early lateral compartment progression of osteoarthritis and the need for revision surgery, usually to a total knee arthroplasty.

In an attempt to mitigate these barriers to obtaining the necessary valgus stress radiograph, Dr. Mauerhan’s team developed a technique that could be done with the assistance of the patient and would require only 1 technologist to perform. Additionally, this project was a quality improvement initiative, because it lowered radiation exposure to all personnel involved in obtaining the correct films.

Materials and Methods

We initiated the project using weight-bearing strategies to impart the valgus stress view of the knee. After trying several different wedges and blocks, and varying patient instructions, we realized a different approach to this problem would be required to find an acceptable solution. We redirected our efforts to effectively performing the stress view with the patient in a supine position on the radiograph table. Ultimately, we decided that a much stiffer wedge and a denser object to squeeze would facilitate obtaining a proper film. Considering all available options, a youth size 4 soccer ball (diameter, 11 in) was introduced along with a slightly larger positioning wedge. The soccer ball was wrapped with 4-in Coban wrap (3M) to create a nonslip surface. This change in patient positioning, along with a standardized 7º to 10º cephalic radiographic tube angulation, helped to correct issues with tibial plateau visualization. Once these changes were enacted, we obtained fairly consistent positive results, and we instituted this patient-directed valgus stress view of the knee, along with a manual valgus stress view for comparison.

The protocol for obtaining the patient-directed valgus stress view of the knee is as follows: The patient lays supine with a dense 45º spine-positioning wedge (Burlington Medical Supplies) placed under both knees and the patient’s heels on the examining table. The radiographic tube is angled cephalad 7º to 10º centered on the inferior pole of the patella, using a 40-in source to image-receptor distance, collimated to part; the image receptor is placed under the affected knee, below the positioning wedge. The affected knee is rotated to the “true” AP position (the patella will be centered between the femoral condyles on the AP exposure), and the ball is placed between the patient’s legs just above the ankle joint. The technologist demonstrates to the patient how to squeeze the ball while maintaining contact of heels with the table. The technologist can exit the room and obtain the exposure, which is taken while the patient is squeezing the ball, as shown in Figures 1A and 1B. Examples of the standing AP, manual stress, and patient-directed valgus radiographs are shown in Figures 2A-2C. The entire technique is demonstrated in the Video.

 

 

Medial-compartment partial knee arthroplasty (unicompartmental replacement) is an accepted surgical intervention for anteromedial osteoarthritis of the knee.1 The radiographic investigations required in the workup of these patients should include weight-bearing standing anteroposterior (AP), lateral, and sunrise (Merchant) views, as well as a valgus stress AP radiograph to assess the functionality of the lateral compartment. The method of properly obtaining the valgus stress film has been well described by the Oxford Group.2 Its recommended radiographic technique requires that a surgeon or a radiologic technologist perform the valgus stress maneuver, manually, while another technologist shoots the film. The 2 consequences of this technique are that it requires 2 individuals to obtain the film, and it subjects the individual who is applying the stress to some level of radiation exposure, which is undesirable. Because of this and the time inconvenience, many surgeons omit the valgus stress radiograph, which can lead to the adverse outcome of missing a lateral compartment that is functionally incompetent, resulting in the potential for early lateral compartment progression of osteoarthritis and the need for revision surgery, usually to a total knee arthroplasty.

In an attempt to mitigate these barriers to obtaining the necessary valgus stress radiograph, Dr. Mauerhan’s team developed a technique that could be done with the assistance of the patient and would require only 1 technologist to perform. Additionally, this project was a quality improvement initiative, because it lowered radiation exposure to all personnel involved in obtaining the correct films.

Materials and Methods

We initiated the project using weight-bearing strategies to impart the valgus stress view of the knee. After trying several different wedges and blocks, and varying patient instructions, we realized a different approach to this problem would be required to find an acceptable solution. We redirected our efforts to effectively performing the stress view with the patient in a supine position on the radiograph table. Ultimately, we decided that a much stiffer wedge and a denser object to squeeze would facilitate obtaining a proper film. Considering all available options, a youth size 4 soccer ball (diameter, 11 in) was introduced along with a slightly larger positioning wedge. The soccer ball was wrapped with 4-in Coban wrap (3M) to create a nonslip surface. This change in patient positioning, along with a standardized 7º to 10º cephalic radiographic tube angulation, helped to correct issues with tibial plateau visualization. Once these changes were enacted, we obtained fairly consistent positive results, and we instituted this patient-directed valgus stress view of the knee, along with a manual valgus stress view for comparison.

The protocol for obtaining the patient-directed valgus stress view of the knee is as follows: The patient lays supine with a dense 45º spine-positioning wedge (Burlington Medical Supplies) placed under both knees and the patient’s heels on the examining table. The radiographic tube is angled cephalad 7º to 10º centered on the inferior pole of the patella, using a 40-in source to image-receptor distance, collimated to part; the image receptor is placed under the affected knee, below the positioning wedge. The affected knee is rotated to the “true” AP position (the patella will be centered between the femoral condyles on the AP exposure), and the ball is placed between the patient’s legs just above the ankle joint. The technologist demonstrates to the patient how to squeeze the ball while maintaining contact of heels with the table. The technologist can exit the room and obtain the exposure, which is taken while the patient is squeezing the ball, as shown in Figures 1A and 1B. Examples of the standing AP, manual stress, and patient-directed valgus radiographs are shown in Figures 2A-2C. The entire technique is demonstrated in the Video.

 

 

Medial-compartment partial knee arthroplasty (unicompartmental replacement) is an accepted surgical intervention for anteromedial osteoarthritis of the knee.1 The radiographic investigations required in the workup of these patients should include weight-bearing standing anteroposterior (AP), lateral, and sunrise (Merchant) views, as well as a valgus stress AP radiograph to assess the functionality of the lateral compartment. The method of properly obtaining the valgus stress film has been well described by the Oxford Group.2 Its recommended radiographic technique requires that a surgeon or a radiologic technologist perform the valgus stress maneuver, manually, while another technologist shoots the film. The 2 consequences of this technique are that it requires 2 individuals to obtain the film, and it subjects the individual who is applying the stress to some level of radiation exposure, which is undesirable. Because of this and the time inconvenience, many surgeons omit the valgus stress radiograph, which can lead to the adverse outcome of missing a lateral compartment that is functionally incompetent, resulting in the potential for early lateral compartment progression of osteoarthritis and the need for revision surgery, usually to a total knee arthroplasty.

In an attempt to mitigate these barriers to obtaining the necessary valgus stress radiograph, Dr. Mauerhan’s team developed a technique that could be done with the assistance of the patient and would require only 1 technologist to perform. Additionally, this project was a quality improvement initiative, because it lowered radiation exposure to all personnel involved in obtaining the correct films.

Materials and Methods

We initiated the project using weight-bearing strategies to impart the valgus stress view of the knee. After trying several different wedges and blocks, and varying patient instructions, we realized a different approach to this problem would be required to find an acceptable solution. We redirected our efforts to effectively performing the stress view with the patient in a supine position on the radiograph table. Ultimately, we decided that a much stiffer wedge and a denser object to squeeze would facilitate obtaining a proper film. Considering all available options, a youth size 4 soccer ball (diameter, 11 in) was introduced along with a slightly larger positioning wedge. The soccer ball was wrapped with 4-in Coban wrap (3M) to create a nonslip surface. This change in patient positioning, along with a standardized 7º to 10º cephalic radiographic tube angulation, helped to correct issues with tibial plateau visualization. Once these changes were enacted, we obtained fairly consistent positive results, and we instituted this patient-directed valgus stress view of the knee, along with a manual valgus stress view for comparison.

The protocol for obtaining the patient-directed valgus stress view of the knee is as follows: The patient lays supine with a dense 45º spine-positioning wedge (Burlington Medical Supplies) placed under both knees and the patient’s heels on the examining table. The radiographic tube is angled cephalad 7º to 10º centered on the inferior pole of the patella, using a 40-in source to image-receptor distance, collimated to part; the image receptor is placed under the affected knee, below the positioning wedge. The affected knee is rotated to the “true” AP position (the patella will be centered between the femoral condyles on the AP exposure), and the ball is placed between the patient’s legs just above the ankle joint. The technologist demonstrates to the patient how to squeeze the ball while maintaining contact of heels with the table. The technologist can exit the room and obtain the exposure, which is taken while the patient is squeezing the ball, as shown in Figures 1A and 1B. Examples of the standing AP, manual stress, and patient-directed valgus radiographs are shown in Figures 2A-2C. The entire technique is demonstrated in the Video.

 

 

Just as psychiatrists are adapting to DSM-5, they have to cope with implementation of the 10th edition of the International Statistical Classification of Diseases and Related Health Problems (ICD-10). This challenge raises questions: What is the importance of understanding ICD-10? How will it affect the practice of psychiatry?

Furthermore, how does ICD-10 relate to DSM-5 and Current Procedural Terminology (CPT)? How does it differ from ICD-9? What are the ICD-10-Clinical Modification (CM) and ICD-10-Procedures (PCS)?Learning the essence of the changes, and understanding what impact they have on your clinical work, are necessary to ensure that your practice keeps pace with professional and legal standards of care. The effort involved is not onerous, however, and can improve the quality and efficiency of your care and how you document it.

In this article, we provide you with an overview of ICD-10; highlight major changes of the new classification; explain its relevance to clinical practice; and offer guidelines for implementing it effectively. We also emphasize that a good understanding of DSM-5 facilitates appreciation of ICD-10 and makes its implementation fairly easy and straightforward.

To begin, we provide a glossary of ICD-related terms and a review of additional definitions, distinctions, and dates (Box).^1-6

Major changes from ICD-9
No question: ICD-10 is going to significantly influence your practice and your reimbursement. Furthermore, a number of revisions in ICD-10 have the potential to meaningfully improve clinical documentation and communication and to enhance your ability to precisely describe the complexity of your patients—with implications for billing.

ICD-10 differs from ICD-9 in organization, structure, code composition, and level of detail. In addition, ICD-10 makes some changes in terminology and definitions, with the goal of improving precision.

ICD-10 also is much larger than ICD-9.The total number of medical diagnostic codes has increased more than 5-fold—from approximately 13,000 to 69,000. This expansion allows for greater specificity in diagnosis and enables differentiation of an initial clinical encounter from a subsequent encounter.

To accommodate the expansion in the number of codes, the 5-digit numeric codes used in ICD-9 have been replaced in ICD-10 by 7-digit alphanumeric codes:

• the first digit always is a letter
• the second and third digits are numbers followed by a decimal point
• the fourth though seventh digits can be letters or numbers
• the first 3 digits denote the diagnostic category
• the fourth through sixth digits provide diagnostic detail
• the seventh digit provides information about the nature of the encounter (eg, initial, subsequent, or sequel, denoted respectively by “A,” “D,” and “S” in the seventh digit).

The number of 3-digit categories for psychiatric disorders has increased from 30 in ICD-9 (290-319) to 100 in ICD-10 (F00-F99). Only the first 5 digits are used for the section on mental disorders in ICD-10, with the first digit always “F” and the second digit a number denoting the broad type of disorders. The second and third digits in conjunction define the major category of the disorder; the fourth and fifth digits provide additional descriptive detail about the disorder (Table).

ICD-9 ‘V’ codes are out
What were called “V” codes in ICD-9—factors that influence health status and contact with health services—have been replaced by “Z” codes in ICD-10. These “Z” codes provide greater detail and precision than “V” codes provided.

Examples of “Z” codes relevant to psychiatry are:

Z00 General psychiatric examination (eg, of a person who does not have a complaint or diagnosis)

Z03 Examination for suspected mental and behavioral disorder

Z04 Examination for medicolegal or other purposes; Z04.8 is relevant laboratory testing, such as drug testing of urine or blood

Z50 Care involving rehabilitation (substance use disorder, etc.)

Z60 Problem related to social environment

Z61 Problem related to negative life events in childhood

Z63 Problem related to primary support group, including family circumstances

Z64-Z65 Problem related to other psychosocial circumstances

Z70-Z71 Condition requiring counseling, not elsewhere classified

Z73 Problem related to difficulty with life management (burnout, stress, role conflict, etc.)

Z75 Problem related to medical facilities and other aspects of health care (eg, awaiting admission)

Z81 Family history of mental or behavioral disorders

Z85-Z91 Personal history of various disorders (must be absent or in full remission at the moment); Z86.51, for example, refers to a history of combat and operational stress reaction.

Greater precision is now possible when coding for treatment-related adverse effects. A particular adverse effect now is coded under the relevant system, along with its attribution to the specific substance. Obesity attributable to antipsychotic treatment,^7,8 for example, is coded as E66.1.

Integrating DSM-5 and ICD-10
Because DSM-5 lists corresponding ICD-10-CM codes for all disorders, you will find it much easier than other physicians to implement ICD-10. DSM-5 includes ICD-9-CM and ICD-10-CM codes for each DSM-5 disorder (for example, the ICD-9-CM code for schizophrenia is 295.x; the ICD-10-CM code is F20.9).⁹

 

Furthermore, a number of changes from ICD-9-CM to ICD-10-CM enable documentation of greater diagnostic specificity; for example, DSM-5 schizoaffective disorder, bipolar type, and schizoaffective disorder, depressive type, are distinctly coded as F25.0 and F25.1, respectively, in ICD-10-CM, whereas both were coded as 295.7 in ICD-9-CM.¹⁰

You will continue to use DSM-5 criteria to guide your diagnostic process, translating the DSM-5 diagnosis (diagnoses) into corresponding ICD-10-CM codes. Experience with DSM-5 substantially simplifies the transition to ICD-10.

Key differences between DSM-5 and ICD-10
There are notable differences in organization and content between DSM-5 and ICD-10.

The 20 chapters in DSM-5 begin with neuro­developmental disorders; neurocognitive disorders are toward the end (ie, childhood to late life). In contrast, neurocognitive disorders (ie, “dementia”) appear at the beginning of ICD-10; neurodevelopmental disorders are at the end.

Elimination of schizophrenia subtypes in DSM-5 necessitates coding of all schizophrenia as F20.9 in ICD-10-CM because F20.0-F20.8 are specific subtypes. DSM-5 schizophreniform disorder is coded F20.81.

Substance abuse and substance dependence continue to be separate in ICD-10-CM, but they are combined in a single category of substance use disorders in DSM-5. The correct ICD-10-CM code (ie, abuse vs dependence) is determined by the severity of the substance use disorder: “Mild” coding as abuse (F1x.1) and “moderate” and “severe” coding as dependence (F2x.2), with x denoting the substance abused.

There can be multiple applicable diagnoses associated with a clinical encounter, as there was with ICD-9-CM. Give precedence to the diagnosis that best represents the nature of the presenting problem; list other diagnoses in the order of their relevance. DSM-5 and ICD-10-CM are similar in this regard.

ICD-10-CM uses only subtypes, in contrast to the use of subtypes and specifiers in DSM-5 to describe variability in disorders across patients. It is possible, however, to code certain DSM-5 specifiers in ICD-10-CM. (This is discussed in the “Recording Procedures” section of the DSM-5 text and summarized at the beginning of the manual, and appears in the “Appendix.”) To code the catatonia specifier in the context of schizoaffective disorder, depressive type, for example, use ICD-10-CM code F25.1 for the disorder and add code F06.1 for the catatonia specifier.¹¹

How will ICD-10 affect your practice?
As of October 1, 2015, all health care facilities were to have become ICD-10 compliant. Furthermore, any Health Insurance Portability and Accountability Act-covered entity must use ICD-10-CM codes if it expects to be reimbursed for health care services.

Mental health practitioners might think that the transition from ICD-9-CM to ICD-10-CM involves only billers and coders, not them. They are wrong. All clinicians are responsible for documenting their diagnostic and treatment services properly. Medical records must contain adequate information to support any diagnostic (ICD-10-CM) and treatment (CPT) codes that are applied to a given clinical encounter.

The greater detail and specificity that are provided by ICD-10-CM allow more accurate recording of clinical complexity, which, in turn, influences reimbursement. However, good documentation is necessary for proper coding. Because clinicians are ultimately responsible for proper diagnostic coding, good understanding of ICD-10-CM is essential to be able to code properly.

Similar to the expansion of ICD-10-CM (from volumes 1 and 2 of ICD-9-CM), ICD-10-PCS has undergone similar expansion (from volume 3 of ICD-9-CM), with a corresponding increase in specificity. For example, there are now 5 distinct codes for electroconvulsive therapy (GZB0ZZZ-GZB4ZZZ) that distinguish unilateral from bilateral electrode placement and single from multiple stimulations.

DSM-5 will continue to be the frameworkfor psychiatric assessment and diagnosis. ICD-10-CM will be the coding system to accurately denote DSM-5 diagnoses. The Centers for Medicare and Medicaid Services (CMS) and the National Center for Health Statistics recognize DSM-5 as the means to identify proper ICD-10-CM codes for mental disorders. CMS also has announced that, although ICD-10-CM codes are necessary for reimbursement, use of an incorrect code will not be the basis for denying a Medicare claim for 1 year.

Making ICD-10 part of practice
Here are several keys to implementing ICD-10 with minimum pain and maximum benefit.

Multiple diagnosis codes should be listed in the order of their relevance to the clinical encounter.

Visit type. The seventh character of the ICD-10-CM code denotes the type of visit (initial, subsequent, or sequela) and must be provided:

• An initial encounter is one in which the patient first receives active treatment.
• A subsequent encounter refers to a follow-up visit in which the patient receives routine care during the healing or recovery phase.
• A sequel encounter is one in which a patient receives treatment for complications or conditions that arise as a direct result of the initial condition.

 

The transition to ICD-10 should be facilitated by adoption of DSM-5. Continue using DSM-5 to determine the correct diagnosis or diagnoses of the mental disorder, then apply the corresponding ICD-10-CM code(s). The better you understand and apply DSM-5, the more precise you can be in utilizing the greater specificity and accuracy afforded by ICD-10-CM coding.

Document well. Good understanding of the structure and organization of ICD-10-CM facilitates efficient, comprehensive documentation. This, in turn, will foster better clinical communication and appropriate reimbursement.

Know your payers—in particular, their policies regarding differential reimbursement for clinical complexity (based on ICD-10-CM/PCS). Medical practices that are part of an accountable care organization, and those that have risk-adjusted contracts must pay special attention to documenting clinical complexity when coding.

Know your electronic health care record, understand what tools it offers to efficiently translate DSM-5 diagnoses into appropriate ICD-10-CM codes, and use those tools efficiently.

Review your medical record documentation for the top 20 conditions in your practice, in the context of their definition in ICD-10-CM.

If you have coders who do ICD-10-CM coding for you, review a few patient charts with them to compare your sense of the patient’s clinical complexity and their coding based on your documentation.

Changes in DSM-5 have encouraged clinicians to improve their assessment of patients and provide measurement-based care. The significant changes in ICD-10-CM should provide the impetus for you to hone your ability to provide documentation. Sufficient flexibility exists within guidelines to permit individualization of the style of documentation.

Because all DSM-5 diagnoses map to appropriate ICD-10-CM codes, effective use of DSM-5 should make the transition to ICD-10 easy.

Bottom Line
Compared with ICD-9, definitions of mental health diagnoses have been improved in ICD-10, and more elaborate code descriptions in ICD-10-CM provide for greater precision when you report a diagnosis. The result? More accurate and efficient documentation of the care you provide and better reimbursement. Understanding what impact the changes in ICD-10 will have on your clinical work will ensure that your practice keeps pace with professional and legal standards of care.

Related Resources
• Blue Cross Blue Shield of Michigan ICD-10 update: mental and behavioral health ICD-10-CM codes. http://www.bcbsm.com/content/dam/public/Providers/Documents/help/faqs/icd10-update-mentalhealth.pdf.
• American Psychiatric Association ICD-10 tutorial. http://www.psychiatry.org/psychiatrists/practice/dsm/icd-10.

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Just as psychiatrists are adapting to DSM-5, they have to cope with implementation of the 10th edition of the International Statistical Classification of Diseases and Related Health Problems (ICD-10). This challenge raises questions: What is the importance of understanding ICD-10? How will it affect the practice of psychiatry?

Furthermore, how does ICD-10 relate to DSM-5 and Current Procedural Terminology (CPT)? How does it differ from ICD-9? What are the ICD-10-Clinical Modification (CM) and ICD-10-Procedures (PCS)?Learning the essence of the changes, and understanding what impact they have on your clinical work, are necessary to ensure that your practice keeps pace with professional and legal standards of care. The effort involved is not onerous, however, and can improve the quality and efficiency of your care and how you document it.

In this article, we provide you with an overview of ICD-10; highlight major changes of the new classification; explain its relevance to clinical practice; and offer guidelines for implementing it effectively. We also emphasize that a good understanding of DSM-5 facilitates appreciation of ICD-10 and makes its implementation fairly easy and straightforward.

To begin, we provide a glossary of ICD-related terms and a review of additional definitions, distinctions, and dates (Box).^1-6

Major changes from ICD-9
No question: ICD-10 is going to significantly influence your practice and your reimbursement. Furthermore, a number of revisions in ICD-10 have the potential to meaningfully improve clinical documentation and communication and to enhance your ability to precisely describe the complexity of your patients—with implications for billing.

ICD-10 differs from ICD-9 in organization, structure, code composition, and level of detail. In addition, ICD-10 makes some changes in terminology and definitions, with the goal of improving precision.

ICD-10 also is much larger than ICD-9.The total number of medical diagnostic codes has increased more than 5-fold—from approximately 13,000 to 69,000. This expansion allows for greater specificity in diagnosis and enables differentiation of an initial clinical encounter from a subsequent encounter.

To accommodate the expansion in the number of codes, the 5-digit numeric codes used in ICD-9 have been replaced in ICD-10 by 7-digit alphanumeric codes:

• the first digit always is a letter
• the second and third digits are numbers followed by a decimal point
• the fourth though seventh digits can be letters or numbers
• the first 3 digits denote the diagnostic category
• the fourth through sixth digits provide diagnostic detail
• the seventh digit provides information about the nature of the encounter (eg, initial, subsequent, or sequel, denoted respectively by “A,” “D,” and “S” in the seventh digit).

The number of 3-digit categories for psychiatric disorders has increased from 30 in ICD-9 (290-319) to 100 in ICD-10 (F00-F99). Only the first 5 digits are used for the section on mental disorders in ICD-10, with the first digit always “F” and the second digit a number denoting the broad type of disorders. The second and third digits in conjunction define the major category of the disorder; the fourth and fifth digits provide additional descriptive detail about the disorder (Table).

ICD-9 ‘V’ codes are out
What were called “V” codes in ICD-9—factors that influence health status and contact with health services—have been replaced by “Z” codes in ICD-10. These “Z” codes provide greater detail and precision than “V” codes provided.

Examples of “Z” codes relevant to psychiatry are:

Z00 General psychiatric examination (eg, of a person who does not have a complaint or diagnosis)

Z03 Examination for suspected mental and behavioral disorder

Z04 Examination for medicolegal or other purposes; Z04.8 is relevant laboratory testing, such as drug testing of urine or blood

Z50 Care involving rehabilitation (substance use disorder, etc.)

Z60 Problem related to social environment

Z61 Problem related to negative life events in childhood

Z63 Problem related to primary support group, including family circumstances

Z64-Z65 Problem related to other psychosocial circumstances

Z70-Z71 Condition requiring counseling, not elsewhere classified

Z73 Problem related to difficulty with life management (burnout, stress, role conflict, etc.)

Z75 Problem related to medical facilities and other aspects of health care (eg, awaiting admission)

Z81 Family history of mental or behavioral disorders

Z85-Z91 Personal history of various disorders (must be absent or in full remission at the moment); Z86.51, for example, refers to a history of combat and operational stress reaction.

Greater precision is now possible when coding for treatment-related adverse effects. A particular adverse effect now is coded under the relevant system, along with its attribution to the specific substance. Obesity attributable to antipsychotic treatment,^7,8 for example, is coded as E66.1.

Integrating DSM-5 and ICD-10
Because DSM-5 lists corresponding ICD-10-CM codes for all disorders, you will find it much easier than other physicians to implement ICD-10. DSM-5 includes ICD-9-CM and ICD-10-CM codes for each DSM-5 disorder (for example, the ICD-9-CM code for schizophrenia is 295.x; the ICD-10-CM code is F20.9).⁹

 

Furthermore, a number of changes from ICD-9-CM to ICD-10-CM enable documentation of greater diagnostic specificity; for example, DSM-5 schizoaffective disorder, bipolar type, and schizoaffective disorder, depressive type, are distinctly coded as F25.0 and F25.1, respectively, in ICD-10-CM, whereas both were coded as 295.7 in ICD-9-CM.¹⁰

You will continue to use DSM-5 criteria to guide your diagnostic process, translating the DSM-5 diagnosis (diagnoses) into corresponding ICD-10-CM codes. Experience with DSM-5 substantially simplifies the transition to ICD-10.

Key differences between DSM-5 and ICD-10
There are notable differences in organization and content between DSM-5 and ICD-10.

The 20 chapters in DSM-5 begin with neuro­developmental disorders; neurocognitive disorders are toward the end (ie, childhood to late life). In contrast, neurocognitive disorders (ie, “dementia”) appear at the beginning of ICD-10; neurodevelopmental disorders are at the end.

Elimination of schizophrenia subtypes in DSM-5 necessitates coding of all schizophrenia as F20.9 in ICD-10-CM because F20.0-F20.8 are specific subtypes. DSM-5 schizophreniform disorder is coded F20.81.

Substance abuse and substance dependence continue to be separate in ICD-10-CM, but they are combined in a single category of substance use disorders in DSM-5. The correct ICD-10-CM code (ie, abuse vs dependence) is determined by the severity of the substance use disorder: “Mild” coding as abuse (F1x.1) and “moderate” and “severe” coding as dependence (F2x.2), with x denoting the substance abused.

There can be multiple applicable diagnoses associated with a clinical encounter, as there was with ICD-9-CM. Give precedence to the diagnosis that best represents the nature of the presenting problem; list other diagnoses in the order of their relevance. DSM-5 and ICD-10-CM are similar in this regard.

ICD-10-CM uses only subtypes, in contrast to the use of subtypes and specifiers in DSM-5 to describe variability in disorders across patients. It is possible, however, to code certain DSM-5 specifiers in ICD-10-CM. (This is discussed in the “Recording Procedures” section of the DSM-5 text and summarized at the beginning of the manual, and appears in the “Appendix.”) To code the catatonia specifier in the context of schizoaffective disorder, depressive type, for example, use ICD-10-CM code F25.1 for the disorder and add code F06.1 for the catatonia specifier.¹¹

How will ICD-10 affect your practice?
As of October 1, 2015, all health care facilities were to have become ICD-10 compliant. Furthermore, any Health Insurance Portability and Accountability Act-covered entity must use ICD-10-CM codes if it expects to be reimbursed for health care services.

Mental health practitioners might think that the transition from ICD-9-CM to ICD-10-CM involves only billers and coders, not them. They are wrong. All clinicians are responsible for documenting their diagnostic and treatment services properly. Medical records must contain adequate information to support any diagnostic (ICD-10-CM) and treatment (CPT) codes that are applied to a given clinical encounter.

The greater detail and specificity that are provided by ICD-10-CM allow more accurate recording of clinical complexity, which, in turn, influences reimbursement. However, good documentation is necessary for proper coding. Because clinicians are ultimately responsible for proper diagnostic coding, good understanding of ICD-10-CM is essential to be able to code properly.

Similar to the expansion of ICD-10-CM (from volumes 1 and 2 of ICD-9-CM), ICD-10-PCS has undergone similar expansion (from volume 3 of ICD-9-CM), with a corresponding increase in specificity. For example, there are now 5 distinct codes for electroconvulsive therapy (GZB0ZZZ-GZB4ZZZ) that distinguish unilateral from bilateral electrode placement and single from multiple stimulations.

DSM-5 will continue to be the frameworkfor psychiatric assessment and diagnosis. ICD-10-CM will be the coding system to accurately denote DSM-5 diagnoses. The Centers for Medicare and Medicaid Services (CMS) and the National Center for Health Statistics recognize DSM-5 as the means to identify proper ICD-10-CM codes for mental disorders. CMS also has announced that, although ICD-10-CM codes are necessary for reimbursement, use of an incorrect code will not be the basis for denying a Medicare claim for 1 year.

Making ICD-10 part of practice
Here are several keys to implementing ICD-10 with minimum pain and maximum benefit.

Multiple diagnosis codes should be listed in the order of their relevance to the clinical encounter.

Visit type. The seventh character of the ICD-10-CM code denotes the type of visit (initial, subsequent, or sequela) and must be provided:

• An initial encounter is one in which the patient first receives active treatment.
• A subsequent encounter refers to a follow-up visit in which the patient receives routine care during the healing or recovery phase.
• A sequel encounter is one in which a patient receives treatment for complications or conditions that arise as a direct result of the initial condition.

 

The transition to ICD-10 should be facilitated by adoption of DSM-5. Continue using DSM-5 to determine the correct diagnosis or diagnoses of the mental disorder, then apply the corresponding ICD-10-CM code(s). The better you understand and apply DSM-5, the more precise you can be in utilizing the greater specificity and accuracy afforded by ICD-10-CM coding.

Document well. Good understanding of the structure and organization of ICD-10-CM facilitates efficient, comprehensive documentation. This, in turn, will foster better clinical communication and appropriate reimbursement.

Know your payers—in particular, their policies regarding differential reimbursement for clinical complexity (based on ICD-10-CM/PCS). Medical practices that are part of an accountable care organization, and those that have risk-adjusted contracts must pay special attention to documenting clinical complexity when coding.

Know your electronic health care record, understand what tools it offers to efficiently translate DSM-5 diagnoses into appropriate ICD-10-CM codes, and use those tools efficiently.

Review your medical record documentation for the top 20 conditions in your practice, in the context of their definition in ICD-10-CM.

If you have coders who do ICD-10-CM coding for you, review a few patient charts with them to compare your sense of the patient’s clinical complexity and their coding based on your documentation.

Changes in DSM-5 have encouraged clinicians to improve their assessment of patients and provide measurement-based care. The significant changes in ICD-10-CM should provide the impetus for you to hone your ability to provide documentation. Sufficient flexibility exists within guidelines to permit individualization of the style of documentation.

Because all DSM-5 diagnoses map to appropriate ICD-10-CM codes, effective use of DSM-5 should make the transition to ICD-10 easy.

Bottom Line
Compared with ICD-9, definitions of mental health diagnoses have been improved in ICD-10, and more elaborate code descriptions in ICD-10-CM provide for greater precision when you report a diagnosis. The result? More accurate and efficient documentation of the care you provide and better reimbursement. Understanding what impact the changes in ICD-10 will have on your clinical work will ensure that your practice keeps pace with professional and legal standards of care.

Related Resources
• Blue Cross Blue Shield of Michigan ICD-10 update: mental and behavioral health ICD-10-CM codes. http://www.bcbsm.com/content/dam/public/Providers/Documents/help/faqs/icd10-update-mentalhealth.pdf.
• American Psychiatric Association ICD-10 tutorial. http://www.psychiatry.org/psychiatrists/practice/dsm/icd-10.

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Just as psychiatrists are adapting to DSM-5, they have to cope with implementation of the 10th edition of the International Statistical Classification of Diseases and Related Health Problems (ICD-10). This challenge raises questions: What is the importance of understanding ICD-10? How will it affect the practice of psychiatry?

Furthermore, how does ICD-10 relate to DSM-5 and Current Procedural Terminology (CPT)? How does it differ from ICD-9? What are the ICD-10-Clinical Modification (CM) and ICD-10-Procedures (PCS)?Learning the essence of the changes, and understanding what impact they have on your clinical work, are necessary to ensure that your practice keeps pace with professional and legal standards of care. The effort involved is not onerous, however, and can improve the quality and efficiency of your care and how you document it.

In this article, we provide you with an overview of ICD-10; highlight major changes of the new classification; explain its relevance to clinical practice; and offer guidelines for implementing it effectively. We also emphasize that a good understanding of DSM-5 facilitates appreciation of ICD-10 and makes its implementation fairly easy and straightforward.

To begin, we provide a glossary of ICD-related terms and a review of additional definitions, distinctions, and dates (Box).^1-6

Major changes from ICD-9
No question: ICD-10 is going to significantly influence your practice and your reimbursement. Furthermore, a number of revisions in ICD-10 have the potential to meaningfully improve clinical documentation and communication and to enhance your ability to precisely describe the complexity of your patients—with implications for billing.

ICD-10 differs from ICD-9 in organization, structure, code composition, and level of detail. In addition, ICD-10 makes some changes in terminology and definitions, with the goal of improving precision.

ICD-10 also is much larger than ICD-9.The total number of medical diagnostic codes has increased more than 5-fold—from approximately 13,000 to 69,000. This expansion allows for greater specificity in diagnosis and enables differentiation of an initial clinical encounter from a subsequent encounter.

To accommodate the expansion in the number of codes, the 5-digit numeric codes used in ICD-9 have been replaced in ICD-10 by 7-digit alphanumeric codes:

• the first digit always is a letter
• the second and third digits are numbers followed by a decimal point
• the fourth though seventh digits can be letters or numbers
• the first 3 digits denote the diagnostic category
• the fourth through sixth digits provide diagnostic detail
• the seventh digit provides information about the nature of the encounter (eg, initial, subsequent, or sequel, denoted respectively by “A,” “D,” and “S” in the seventh digit).

The number of 3-digit categories for psychiatric disorders has increased from 30 in ICD-9 (290-319) to 100 in ICD-10 (F00-F99). Only the first 5 digits are used for the section on mental disorders in ICD-10, with the first digit always “F” and the second digit a number denoting the broad type of disorders. The second and third digits in conjunction define the major category of the disorder; the fourth and fifth digits provide additional descriptive detail about the disorder (Table).

ICD-9 ‘V’ codes are out
What were called “V” codes in ICD-9—factors that influence health status and contact with health services—have been replaced by “Z” codes in ICD-10. These “Z” codes provide greater detail and precision than “V” codes provided.

Examples of “Z” codes relevant to psychiatry are:

Z00 General psychiatric examination (eg, of a person who does not have a complaint or diagnosis)

Z03 Examination for suspected mental and behavioral disorder

Z04 Examination for medicolegal or other purposes; Z04.8 is relevant laboratory testing, such as drug testing of urine or blood

Z50 Care involving rehabilitation (substance use disorder, etc.)

Z60 Problem related to social environment

Z61 Problem related to negative life events in childhood

Z63 Problem related to primary support group, including family circumstances

Z64-Z65 Problem related to other psychosocial circumstances

Z70-Z71 Condition requiring counseling, not elsewhere classified

Z73 Problem related to difficulty with life management (burnout, stress, role conflict, etc.)

Z75 Problem related to medical facilities and other aspects of health care (eg, awaiting admission)

Z81 Family history of mental or behavioral disorders

Z85-Z91 Personal history of various disorders (must be absent or in full remission at the moment); Z86.51, for example, refers to a history of combat and operational stress reaction.

Greater precision is now possible when coding for treatment-related adverse effects. A particular adverse effect now is coded under the relevant system, along with its attribution to the specific substance. Obesity attributable to antipsychotic treatment,^7,8 for example, is coded as E66.1.

Integrating DSM-5 and ICD-10
Because DSM-5 lists corresponding ICD-10-CM codes for all disorders, you will find it much easier than other physicians to implement ICD-10. DSM-5 includes ICD-9-CM and ICD-10-CM codes for each DSM-5 disorder (for example, the ICD-9-CM code for schizophrenia is 295.x; the ICD-10-CM code is F20.9).⁹

 

Furthermore, a number of changes from ICD-9-CM to ICD-10-CM enable documentation of greater diagnostic specificity; for example, DSM-5 schizoaffective disorder, bipolar type, and schizoaffective disorder, depressive type, are distinctly coded as F25.0 and F25.1, respectively, in ICD-10-CM, whereas both were coded as 295.7 in ICD-9-CM.¹⁰

You will continue to use DSM-5 criteria to guide your diagnostic process, translating the DSM-5 diagnosis (diagnoses) into corresponding ICD-10-CM codes. Experience with DSM-5 substantially simplifies the transition to ICD-10.

Key differences between DSM-5 and ICD-10
There are notable differences in organization and content between DSM-5 and ICD-10.

The 20 chapters in DSM-5 begin with neuro­developmental disorders; neurocognitive disorders are toward the end (ie, childhood to late life). In contrast, neurocognitive disorders (ie, “dementia”) appear at the beginning of ICD-10; neurodevelopmental disorders are at the end.

Elimination of schizophrenia subtypes in DSM-5 necessitates coding of all schizophrenia as F20.9 in ICD-10-CM because F20.0-F20.8 are specific subtypes. DSM-5 schizophreniform disorder is coded F20.81.

Substance abuse and substance dependence continue to be separate in ICD-10-CM, but they are combined in a single category of substance use disorders in DSM-5. The correct ICD-10-CM code (ie, abuse vs dependence) is determined by the severity of the substance use disorder: “Mild” coding as abuse (F1x.1) and “moderate” and “severe” coding as dependence (F2x.2), with x denoting the substance abused.

There can be multiple applicable diagnoses associated with a clinical encounter, as there was with ICD-9-CM. Give precedence to the diagnosis that best represents the nature of the presenting problem; list other diagnoses in the order of their relevance. DSM-5 and ICD-10-CM are similar in this regard.

ICD-10-CM uses only subtypes, in contrast to the use of subtypes and specifiers in DSM-5 to describe variability in disorders across patients. It is possible, however, to code certain DSM-5 specifiers in ICD-10-CM. (This is discussed in the “Recording Procedures” section of the DSM-5 text and summarized at the beginning of the manual, and appears in the “Appendix.”) To code the catatonia specifier in the context of schizoaffective disorder, depressive type, for example, use ICD-10-CM code F25.1 for the disorder and add code F06.1 for the catatonia specifier.¹¹

How will ICD-10 affect your practice?
As of October 1, 2015, all health care facilities were to have become ICD-10 compliant. Furthermore, any Health Insurance Portability and Accountability Act-covered entity must use ICD-10-CM codes if it expects to be reimbursed for health care services.

Mental health practitioners might think that the transition from ICD-9-CM to ICD-10-CM involves only billers and coders, not them. They are wrong. All clinicians are responsible for documenting their diagnostic and treatment services properly. Medical records must contain adequate information to support any diagnostic (ICD-10-CM) and treatment (CPT) codes that are applied to a given clinical encounter.

The greater detail and specificity that are provided by ICD-10-CM allow more accurate recording of clinical complexity, which, in turn, influences reimbursement. However, good documentation is necessary for proper coding. Because clinicians are ultimately responsible for proper diagnostic coding, good understanding of ICD-10-CM is essential to be able to code properly.

Similar to the expansion of ICD-10-CM (from volumes 1 and 2 of ICD-9-CM), ICD-10-PCS has undergone similar expansion (from volume 3 of ICD-9-CM), with a corresponding increase in specificity. For example, there are now 5 distinct codes for electroconvulsive therapy (GZB0ZZZ-GZB4ZZZ) that distinguish unilateral from bilateral electrode placement and single from multiple stimulations.

DSM-5 will continue to be the frameworkfor psychiatric assessment and diagnosis. ICD-10-CM will be the coding system to accurately denote DSM-5 diagnoses. The Centers for Medicare and Medicaid Services (CMS) and the National Center for Health Statistics recognize DSM-5 as the means to identify proper ICD-10-CM codes for mental disorders. CMS also has announced that, although ICD-10-CM codes are necessary for reimbursement, use of an incorrect code will not be the basis for denying a Medicare claim for 1 year.

Making ICD-10 part of practice
Here are several keys to implementing ICD-10 with minimum pain and maximum benefit.

Multiple diagnosis codes should be listed in the order of their relevance to the clinical encounter.

Visit type. The seventh character of the ICD-10-CM code denotes the type of visit (initial, subsequent, or sequela) and must be provided:

• An initial encounter is one in which the patient first receives active treatment.
• A subsequent encounter refers to a follow-up visit in which the patient receives routine care during the healing or recovery phase.
• A sequel encounter is one in which a patient receives treatment for complications or conditions that arise as a direct result of the initial condition.

 

The transition to ICD-10 should be facilitated by adoption of DSM-5. Continue using DSM-5 to determine the correct diagnosis or diagnoses of the mental disorder, then apply the corresponding ICD-10-CM code(s). The better you understand and apply DSM-5, the more precise you can be in utilizing the greater specificity and accuracy afforded by ICD-10-CM coding.

Document well. Good understanding of the structure and organization of ICD-10-CM facilitates efficient, comprehensive documentation. This, in turn, will foster better clinical communication and appropriate reimbursement.

Know your payers—in particular, their policies regarding differential reimbursement for clinical complexity (based on ICD-10-CM/PCS). Medical practices that are part of an accountable care organization, and those that have risk-adjusted contracts must pay special attention to documenting clinical complexity when coding.

Know your electronic health care record, understand what tools it offers to efficiently translate DSM-5 diagnoses into appropriate ICD-10-CM codes, and use those tools efficiently.

Review your medical record documentation for the top 20 conditions in your practice, in the context of their definition in ICD-10-CM.

If you have coders who do ICD-10-CM coding for you, review a few patient charts with them to compare your sense of the patient’s clinical complexity and their coding based on your documentation.

Changes in DSM-5 have encouraged clinicians to improve their assessment of patients and provide measurement-based care. The significant changes in ICD-10-CM should provide the impetus for you to hone your ability to provide documentation. Sufficient flexibility exists within guidelines to permit individualization of the style of documentation.

Because all DSM-5 diagnoses map to appropriate ICD-10-CM codes, effective use of DSM-5 should make the transition to ICD-10 easy.

Bottom Line
Compared with ICD-9, definitions of mental health diagnoses have been improved in ICD-10, and more elaborate code descriptions in ICD-10-CM provide for greater precision when you report a diagnosis. The result? More accurate and efficient documentation of the care you provide and better reimbursement. Understanding what impact the changes in ICD-10 will have on your clinical work will ensure that your practice keeps pace with professional and legal standards of care.

Related Resources
• Blue Cross Blue Shield of Michigan ICD-10 update: mental and behavioral health ICD-10-CM codes. http://www.bcbsm.com/content/dam/public/Providers/Documents/help/faqs/icd10-update-mentalhealth.pdf.
• American Psychiatric Association ICD-10 tutorial. http://www.psychiatry.org/psychiatrists/practice/dsm/icd-10.

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Isolated brachialis muscle atrophy has been rarely reported. Among the few cases in the literature, 1 was attributed to a presumed compartment syndrome,1 1 to a displaced clavicle fracture,2 and 3 to neuralgic amyotrophy.3,4 We present a case of isolated brachialis muscle atrophy of unknown etiology, the presentation of which is consistent with neuralgic amyotrophy, also known as Parsonage-Turner syndrome or brachial plexitis. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 37-year-old right-handed highway worker presented for evaluation of right-arm muscle atrophy. One year earlier, while lifting heavy bags at work, he felt a painful strain in his right arm, although there was no bruising or swelling. Approximately 4 weeks after this incident, he developed right shoulder pain and began to notice a slight decrease in the muscle mass of his right anterior arm. On evaluation at an outside facility, the physician noted some brachialis muscle atrophy. His shoulder pain was attributed to acromioclavicular joint problems. After an initial trial of physical therapy that did not alleviate this joint pain, an acromioclavicular joint resection was performed, and his pain improved. The brachialis muscle atrophy continued to progress, however. Over the course of the next 6 months, the patient noticed a continually decreasing muscle mass in his right arm, as well as arm fatigue with routine recreational activities. On follow-up, again at an outside institution, the treating physicians noted continued atrophy of the distal arm corresponding to the region of the brachialis musculature. Magnetic resonance imaging showed continuity of the brachialis muscle and tendon, with muscle atrophy. The patient was able to return to work, although with a subjective decrease in right elbow flexion strength.

On presentation at our institution, the patient complained of right arm weakness with heavy use but did not have pain or sensory complaints. His medical history was otherwise unremarkable. Physical examination revealed obvious wasting of the right brachialis muscle, most notable on the lateral aspect of the distal arm (Figures 1, 2A, 2B). His biceps muscle was functioning with full strength and had a normal bulk. He had a normal range of active and passive motion, including full extension and flexion of both elbows, as well as complete pronosupination of the forearms. There was no focal tenderness. Manual muscle testing of both upper extremities was completely normal except for 4/5 flexion strength of the right elbow. Neurovascular examination also revealed normal findings, including intact sensation over the radiolateral forearm. A second magnetic resonance image showed that the brachialis muscle had completely atrophied. Because the clinical examination and imaging studies both indicated isolated brachialis atrophy without deficit elsewhere along the musculocutaneous nerve, electromyography was not performed. The patient was fully functional and working at his usual occupation, and no further intervention was recommended.

 

Discussion

Isolated wasting of the brachialis muscle is extremely rare with few reports in the literature. Farmer and colleagues¹ reported a case of brachialis atrophy that was presumed to have resulted from exercise-induced chronic compartment syndrome. In that case, the patient developed a prodrome of arm pain followed by brachialis muscle atrophy. This patient was treated with oral anti-inflammatory agents with improvement in pain but without recovery of the brachialis muscle. While this case was attributed to compartment syndrome, it is likely that it represented neuralgic amyotrophy because there was no evidence of elbow flexion contracture, which would have accompanied true necrosis of the brachialis muscle as seen in compartment syndrome. However, acute compartment syndrome of the brachialis muscle after minor trauma has been reported.⁵ In that case, full-scale compartment syndrome was treated with rapid fasciotomy, with complete recovery of the brachialis.

Isolated brachialis atrophy has also been described in the setting of a displaced midshaft clavicle fracture in an elite athlete.² Two fracture fragments were thought to have injured the brachial plexus, separately causing brachialis atrophy and altered sensation over the clavicular head of the deltoid muscle. Atrophy remained 1 year after injury.

Although it had been occasionally reported, the first large series of patients with sporadic neuralgic amyotrophy in the upper extremity was reported by Parsonage and Turner⁶ in 1948. They described 136 patients who developed flaccid paralysis and atrophy of various muscles of the shoulder girdle and/or upper extremity. This was generally preceded by acute pain in the shoulder girdle, often associated with antecedent viral infection, stress, illness, or other precipitating factors.

To our knowledge, there have been 3 other reported cases of neuralgic amyotrophy of the brachialis muscle. Watson and colleagues³ presented 2 patients with nonspecific, neurogenic shoulder pain after which an indolent, progressive atrophy of the brachialis muscle ensued.³ Van Tongel and colleagues⁴ described a more traditional case of Parsonage-Turner syndrome, with bilateral wasting of the shoulder girdle that also exhibited unilateral brachialis atrophy without affecting other muscles in the arm.⁴ Our case, with shoulder pain followed by muscle atrophy, fits the pattern of neuralgic amyotrophy.

 

Others have similarly described isolated wasting of 1 muscle with the sparing of other muscles with a common innervation. Isolated atrophy of the extensor or flexor pollicis longus has been reported as variants of either posterior or anterior interosseous neuropathy, respectively.^7,8 Nerve fibers in the brachial plexus destined to innervate muscles supplied by the anterior interosseous nerve may be the cause of the motor deficit in cases of anterior interosseous nerve palsy, which seem to be associated with brachial plexitis.⁹

We present a case of isolated brachialis muscle atrophy after a minor trauma that may have resulted from Parsonage-Turner syndrome or a variant of brachial plexitis. The constellation of shoulder and arm pain, with subsequent muscle atrophy, makes this diagnosis likely.

Isolated brachialis muscle atrophy has been rarely reported. Among the few cases in the literature, 1 was attributed to a presumed compartment syndrome,1 1 to a displaced clavicle fracture,2 and 3 to neuralgic amyotrophy.3,4 We present a case of isolated brachialis muscle atrophy of unknown etiology, the presentation of which is consistent with neuralgic amyotrophy, also known as Parsonage-Turner syndrome or brachial plexitis. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 37-year-old right-handed highway worker presented for evaluation of right-arm muscle atrophy. One year earlier, while lifting heavy bags at work, he felt a painful strain in his right arm, although there was no bruising or swelling. Approximately 4 weeks after this incident, he developed right shoulder pain and began to notice a slight decrease in the muscle mass of his right anterior arm. On evaluation at an outside facility, the physician noted some brachialis muscle atrophy. His shoulder pain was attributed to acromioclavicular joint problems. After an initial trial of physical therapy that did not alleviate this joint pain, an acromioclavicular joint resection was performed, and his pain improved. The brachialis muscle atrophy continued to progress, however. Over the course of the next 6 months, the patient noticed a continually decreasing muscle mass in his right arm, as well as arm fatigue with routine recreational activities. On follow-up, again at an outside institution, the treating physicians noted continued atrophy of the distal arm corresponding to the region of the brachialis musculature. Magnetic resonance imaging showed continuity of the brachialis muscle and tendon, with muscle atrophy. The patient was able to return to work, although with a subjective decrease in right elbow flexion strength.

On presentation at our institution, the patient complained of right arm weakness with heavy use but did not have pain or sensory complaints. His medical history was otherwise unremarkable. Physical examination revealed obvious wasting of the right brachialis muscle, most notable on the lateral aspect of the distal arm (Figures 1, 2A, 2B). His biceps muscle was functioning with full strength and had a normal bulk. He had a normal range of active and passive motion, including full extension and flexion of both elbows, as well as complete pronosupination of the forearms. There was no focal tenderness. Manual muscle testing of both upper extremities was completely normal except for 4/5 flexion strength of the right elbow. Neurovascular examination also revealed normal findings, including intact sensation over the radiolateral forearm. A second magnetic resonance image showed that the brachialis muscle had completely atrophied. Because the clinical examination and imaging studies both indicated isolated brachialis atrophy without deficit elsewhere along the musculocutaneous nerve, electromyography was not performed. The patient was fully functional and working at his usual occupation, and no further intervention was recommended.

 

Discussion

Isolated wasting of the brachialis muscle is extremely rare with few reports in the literature. Farmer and colleagues¹ reported a case of brachialis atrophy that was presumed to have resulted from exercise-induced chronic compartment syndrome. In that case, the patient developed a prodrome of arm pain followed by brachialis muscle atrophy. This patient was treated with oral anti-inflammatory agents with improvement in pain but without recovery of the brachialis muscle. While this case was attributed to compartment syndrome, it is likely that it represented neuralgic amyotrophy because there was no evidence of elbow flexion contracture, which would have accompanied true necrosis of the brachialis muscle as seen in compartment syndrome. However, acute compartment syndrome of the brachialis muscle after minor trauma has been reported.⁵ In that case, full-scale compartment syndrome was treated with rapid fasciotomy, with complete recovery of the brachialis.

Isolated brachialis atrophy has also been described in the setting of a displaced midshaft clavicle fracture in an elite athlete.² Two fracture fragments were thought to have injured the brachial plexus, separately causing brachialis atrophy and altered sensation over the clavicular head of the deltoid muscle. Atrophy remained 1 year after injury.

Although it had been occasionally reported, the first large series of patients with sporadic neuralgic amyotrophy in the upper extremity was reported by Parsonage and Turner⁶ in 1948. They described 136 patients who developed flaccid paralysis and atrophy of various muscles of the shoulder girdle and/or upper extremity. This was generally preceded by acute pain in the shoulder girdle, often associated with antecedent viral infection, stress, illness, or other precipitating factors.

To our knowledge, there have been 3 other reported cases of neuralgic amyotrophy of the brachialis muscle. Watson and colleagues³ presented 2 patients with nonspecific, neurogenic shoulder pain after which an indolent, progressive atrophy of the brachialis muscle ensued.³ Van Tongel and colleagues⁴ described a more traditional case of Parsonage-Turner syndrome, with bilateral wasting of the shoulder girdle that also exhibited unilateral brachialis atrophy without affecting other muscles in the arm.⁴ Our case, with shoulder pain followed by muscle atrophy, fits the pattern of neuralgic amyotrophy.

 

Others have similarly described isolated wasting of 1 muscle with the sparing of other muscles with a common innervation. Isolated atrophy of the extensor or flexor pollicis longus has been reported as variants of either posterior or anterior interosseous neuropathy, respectively.^7,8 Nerve fibers in the brachial plexus destined to innervate muscles supplied by the anterior interosseous nerve may be the cause of the motor deficit in cases of anterior interosseous nerve palsy, which seem to be associated with brachial plexitis.⁹

We present a case of isolated brachialis muscle atrophy after a minor trauma that may have resulted from Parsonage-Turner syndrome or a variant of brachial plexitis. The constellation of shoulder and arm pain, with subsequent muscle atrophy, makes this diagnosis likely.

Isolated brachialis muscle atrophy has been rarely reported. Among the few cases in the literature, 1 was attributed to a presumed compartment syndrome,1 1 to a displaced clavicle fracture,2 and 3 to neuralgic amyotrophy.3,4 We present a case of isolated brachialis muscle atrophy of unknown etiology, the presentation of which is consistent with neuralgic amyotrophy, also known as Parsonage-Turner syndrome or brachial plexitis. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 37-year-old right-handed highway worker presented for evaluation of right-arm muscle atrophy. One year earlier, while lifting heavy bags at work, he felt a painful strain in his right arm, although there was no bruising or swelling. Approximately 4 weeks after this incident, he developed right shoulder pain and began to notice a slight decrease in the muscle mass of his right anterior arm. On evaluation at an outside facility, the physician noted some brachialis muscle atrophy. His shoulder pain was attributed to acromioclavicular joint problems. After an initial trial of physical therapy that did not alleviate this joint pain, an acromioclavicular joint resection was performed, and his pain improved. The brachialis muscle atrophy continued to progress, however. Over the course of the next 6 months, the patient noticed a continually decreasing muscle mass in his right arm, as well as arm fatigue with routine recreational activities. On follow-up, again at an outside institution, the treating physicians noted continued atrophy of the distal arm corresponding to the region of the brachialis musculature. Magnetic resonance imaging showed continuity of the brachialis muscle and tendon, with muscle atrophy. The patient was able to return to work, although with a subjective decrease in right elbow flexion strength.

On presentation at our institution, the patient complained of right arm weakness with heavy use but did not have pain or sensory complaints. His medical history was otherwise unremarkable. Physical examination revealed obvious wasting of the right brachialis muscle, most notable on the lateral aspect of the distal arm (Figures 1, 2A, 2B). His biceps muscle was functioning with full strength and had a normal bulk. He had a normal range of active and passive motion, including full extension and flexion of both elbows, as well as complete pronosupination of the forearms. There was no focal tenderness. Manual muscle testing of both upper extremities was completely normal except for 4/5 flexion strength of the right elbow. Neurovascular examination also revealed normal findings, including intact sensation over the radiolateral forearm. A second magnetic resonance image showed that the brachialis muscle had completely atrophied. Because the clinical examination and imaging studies both indicated isolated brachialis atrophy without deficit elsewhere along the musculocutaneous nerve, electromyography was not performed. The patient was fully functional and working at his usual occupation, and no further intervention was recommended.

 

Discussion

Isolated wasting of the brachialis muscle is extremely rare with few reports in the literature. Farmer and colleagues¹ reported a case of brachialis atrophy that was presumed to have resulted from exercise-induced chronic compartment syndrome. In that case, the patient developed a prodrome of arm pain followed by brachialis muscle atrophy. This patient was treated with oral anti-inflammatory agents with improvement in pain but without recovery of the brachialis muscle. While this case was attributed to compartment syndrome, it is likely that it represented neuralgic amyotrophy because there was no evidence of elbow flexion contracture, which would have accompanied true necrosis of the brachialis muscle as seen in compartment syndrome. However, acute compartment syndrome of the brachialis muscle after minor trauma has been reported.⁵ In that case, full-scale compartment syndrome was treated with rapid fasciotomy, with complete recovery of the brachialis.

Isolated brachialis atrophy has also been described in the setting of a displaced midshaft clavicle fracture in an elite athlete.² Two fracture fragments were thought to have injured the brachial plexus, separately causing brachialis atrophy and altered sensation over the clavicular head of the deltoid muscle. Atrophy remained 1 year after injury.

Although it had been occasionally reported, the first large series of patients with sporadic neuralgic amyotrophy in the upper extremity was reported by Parsonage and Turner⁶ in 1948. They described 136 patients who developed flaccid paralysis and atrophy of various muscles of the shoulder girdle and/or upper extremity. This was generally preceded by acute pain in the shoulder girdle, often associated with antecedent viral infection, stress, illness, or other precipitating factors.

To our knowledge, there have been 3 other reported cases of neuralgic amyotrophy of the brachialis muscle. Watson and colleagues³ presented 2 patients with nonspecific, neurogenic shoulder pain after which an indolent, progressive atrophy of the brachialis muscle ensued.³ Van Tongel and colleagues⁴ described a more traditional case of Parsonage-Turner syndrome, with bilateral wasting of the shoulder girdle that also exhibited unilateral brachialis atrophy without affecting other muscles in the arm.⁴ Our case, with shoulder pain followed by muscle atrophy, fits the pattern of neuralgic amyotrophy.

 

Others have similarly described isolated wasting of 1 muscle with the sparing of other muscles with a common innervation. Isolated atrophy of the extensor or flexor pollicis longus has been reported as variants of either posterior or anterior interosseous neuropathy, respectively.^7,8 Nerve fibers in the brachial plexus destined to innervate muscles supplied by the anterior interosseous nerve may be the cause of the motor deficit in cases of anterior interosseous nerve palsy, which seem to be associated with brachial plexitis.⁹

We present a case of isolated brachialis muscle atrophy after a minor trauma that may have resulted from Parsonage-Turner syndrome or a variant of brachial plexitis. The constellation of shoulder and arm pain, with subsequent muscle atrophy, makes this diagnosis likely.