BOSTON – Neoadjuvant chemotherapy and radiation appear to offer long-term benefits in patients with high-risk soft tissue sarcomas of the extremities.

The key word is “appear,” however, because the idea is drawn more from inference than from evidence, and not all sarcoma specialists are convinced that neoadjuvant chemotherapy and radiation add anything more than toxicity.

In studies presented at the annual meeting of the American Society of Radiation Oncology, including a retrospective case series and a national database review, investigators found evidence supporting the use of combined modality therapy with radiation and chemotherapy in patients with soft tissue sarcomas of the extremities.

“Large high-grade extremity soft-tissue sarcomas are at high risk of failure and death compared to our typical high-risk patients who present with one [risk] factor,” said Omar Mahmoud, MD, PhD, from the Rutgers Cancer Institute of New Jersey, New Brunswick.

He and his colleagues combed through the National Cancer Database to identify 3,840 otherwise healthy patients with grade 3 or 4 soft-tissue sarcomas (STS) of the extremities of various histologies larger than 8 cm, who underwent surgical resections during 2004-2013.

They looked at overall survival in patients who received no neoadjuvant or adjuvant therapy and those who received either neoadjuvant or adjuvant chemotherapy and/or radiation therapy. They used propensity score matching to adjust for imbalances of covariates across treatment subgroups.

They found that chemotherapy was associated with significantly better 5-year overall survival, at 57%, compared with 45% with no chemotherapy (P less than .001)

In multivariate analysis, age older than 50 years, positive tumor margins, larger tumors, and tumors located in the trunk or pelvis were associated with worse prognosis, whereas receipt of chemotherapy and radiotherapy were associated independently with better prognosis.

Out to 100 months (8.3 years) of follow-up, overall survival was significantly higher for patients who received combined modality adjunctive therapies, compared with either single modality therapy (chemotherapy or radiotherapy alone) or no therapy (P less than .001).

Using propensity score matching to compare patients who received combined vs. single-modality therapy, the investigators found that combined therapies were associated with significantly better overall survival, with a hazard ratio of 0.72 (95% confidence interval, 0.62-0.84).

There was no difference in survival according to the timing of therapy, whether preoperative, postoperative, or concurrent), however.

Finally, looking at survival among all subgroups, they saw that combined therapies remained significantly better than single-modality therapies (P less than .001).

Drop the ‘D’ in MAID?

In a separate study, Neilayan Sen, MD, and colleagues from Rush University Medical Center in Chicago reported that a modified protocol involving neoadjuvant chemotherapy interdigitated with radiation followed by surgery and adjuvant chemotherapy was associated with good disease control and survival and lower toxicity in patients with large STS of the extremities or abdominal wall.

The original protocol, dubbed MAID (mesna, doxorubicin, ifosfamide, dacarbazine), was shown in the RTOG 9514 trial to be associated with higher rates of disease-free, distant disease-free, and overall survival than older regimens, but at the price of high short-term toxicities. Among 64 evaluable patients, 97% had grade 3 or higher toxicities, including three deaths, two of which were from myelodysplasia.

To see whether they could match the efficacy of MAID while reducing toxicity, the Rush team modified the MAID protocol by dropping the dacarbazine. For the radiation component, they used either 3-D conformal radiation therapy or intensity-modulated radiation therapy, set the maximum dose penetration (Dmax) at 112% or less, and used reduced volumes while maintaining the dose and fractions (44 Gy delivered in 22 fractions, 11 each between chemotherapy cycles 1-2 and 2-3). Patients then underwent surgery, followed by three additional cycles of chemotherapy.

In a retrospective analysis of 26 patients treated with the modified protocol, there were no toxicity-related amputations, and no amputations were required for tumor management. Two patients had in-field fractures.

At a median follow-up of 39 months, 25 of the 26 patients were still alive and there were no cases of treatment-related malignancies or myelodysplasia.

The 3-year actuarial results with MAI also compared favorably with those of RTOG 9514, with locoregional recurrence-free survival rates of 87.2% with the modified protocol vs. 82.4% for the original MAID protocol, distant metastasis-free survival of 67.9% vs. 64.%, respectively, disease-free survival of 67.9% vs. 56.6%, and overall survival of 93.3% vs. 75.1%.

“The omission of dacarbazine does not compromise any disease-control endpoints. With the integration of 3-D techniques as well as intensity modulation and smaller fields than were used in [RTOG] 9514, there’s a significantly reduced grade 4 and 5 toxicity rate. We think that the integration of image guidance with reduced target volume parameters further,” Dr. Sen said.
 

Better Agents Needed

Elizabeth H Baldini, MD, MPH, from the Dana-Farber/Brigham & Women’s Cancer Center, Boston, the invited discussant, agreed that there is a need for better systemic therapy to reduce the risk of distant recurrence in patients with high-risk localized sarcomas.

“But the bottom line is that the benefit of chemotherapy with the agents we have today is uncertain,” she said.

Assessment of systemic chemotherapy in sarcoma is hampered by the rarity of the tumors, with more than 50 different histologic subtypes, and wide tumor heterogeneity, and although the studies reported here appear to show benefit for chemotherapy, they appear to overlap with those for surgery and radiation alone, she said.

Session comoderator Yen-Lin Evelyn Chen, MD, a radiation oncologist at Massachusetts General Hospital Cancer Center, Boston, said in an interview that studies presented during the session show that, “chemotherapy in experienced hands can be delivered safely.”

Dr. Chen added, however, that the local control rates reported by Dr. Sen and colleagues were a little lower than she would have expected in the modern era, suggesting that either the radiation modification or elimination of dacarbazine may have played a role.

BOSTON – Neoadjuvant chemotherapy and radiation appear to offer long-term benefits in patients with high-risk soft tissue sarcomas of the extremities.

The key word is “appear,” however, because the idea is drawn more from inference than from evidence, and not all sarcoma specialists are convinced that neoadjuvant chemotherapy and radiation add anything more than toxicity.

In studies presented at the annual meeting of the American Society of Radiation Oncology, including a retrospective case series and a national database review, investigators found evidence supporting the use of combined modality therapy with radiation and chemotherapy in patients with soft tissue sarcomas of the extremities.

“Large high-grade extremity soft-tissue sarcomas are at high risk of failure and death compared to our typical high-risk patients who present with one [risk] factor,” said Omar Mahmoud, MD, PhD, from the Rutgers Cancer Institute of New Jersey, New Brunswick.

He and his colleagues combed through the National Cancer Database to identify 3,840 otherwise healthy patients with grade 3 or 4 soft-tissue sarcomas (STS) of the extremities of various histologies larger than 8 cm, who underwent surgical resections during 2004-2013.

They looked at overall survival in patients who received no neoadjuvant or adjuvant therapy and those who received either neoadjuvant or adjuvant chemotherapy and/or radiation therapy. They used propensity score matching to adjust for imbalances of covariates across treatment subgroups.

They found that chemotherapy was associated with significantly better 5-year overall survival, at 57%, compared with 45% with no chemotherapy (P less than .001)

In multivariate analysis, age older than 50 years, positive tumor margins, larger tumors, and tumors located in the trunk or pelvis were associated with worse prognosis, whereas receipt of chemotherapy and radiotherapy were associated independently with better prognosis.

Out to 100 months (8.3 years) of follow-up, overall survival was significantly higher for patients who received combined modality adjunctive therapies, compared with either single modality therapy (chemotherapy or radiotherapy alone) or no therapy (P less than .001).

Using propensity score matching to compare patients who received combined vs. single-modality therapy, the investigators found that combined therapies were associated with significantly better overall survival, with a hazard ratio of 0.72 (95% confidence interval, 0.62-0.84).

There was no difference in survival according to the timing of therapy, whether preoperative, postoperative, or concurrent), however.

Finally, looking at survival among all subgroups, they saw that combined therapies remained significantly better than single-modality therapies (P less than .001).

Drop the ‘D’ in MAID?

In a separate study, Neilayan Sen, MD, and colleagues from Rush University Medical Center in Chicago reported that a modified protocol involving neoadjuvant chemotherapy interdigitated with radiation followed by surgery and adjuvant chemotherapy was associated with good disease control and survival and lower toxicity in patients with large STS of the extremities or abdominal wall.

The original protocol, dubbed MAID (mesna, doxorubicin, ifosfamide, dacarbazine), was shown in the RTOG 9514 trial to be associated with higher rates of disease-free, distant disease-free, and overall survival than older regimens, but at the price of high short-term toxicities. Among 64 evaluable patients, 97% had grade 3 or higher toxicities, including three deaths, two of which were from myelodysplasia.

To see whether they could match the efficacy of MAID while reducing toxicity, the Rush team modified the MAID protocol by dropping the dacarbazine. For the radiation component, they used either 3-D conformal radiation therapy or intensity-modulated radiation therapy, set the maximum dose penetration (Dmax) at 112% or less, and used reduced volumes while maintaining the dose and fractions (44 Gy delivered in 22 fractions, 11 each between chemotherapy cycles 1-2 and 2-3). Patients then underwent surgery, followed by three additional cycles of chemotherapy.

In a retrospective analysis of 26 patients treated with the modified protocol, there were no toxicity-related amputations, and no amputations were required for tumor management. Two patients had in-field fractures.

At a median follow-up of 39 months, 25 of the 26 patients were still alive and there were no cases of treatment-related malignancies or myelodysplasia.

The 3-year actuarial results with MAI also compared favorably with those of RTOG 9514, with locoregional recurrence-free survival rates of 87.2% with the modified protocol vs. 82.4% for the original MAID protocol, distant metastasis-free survival of 67.9% vs. 64.%, respectively, disease-free survival of 67.9% vs. 56.6%, and overall survival of 93.3% vs. 75.1%.

“The omission of dacarbazine does not compromise any disease-control endpoints. With the integration of 3-D techniques as well as intensity modulation and smaller fields than were used in [RTOG] 9514, there’s a significantly reduced grade 4 and 5 toxicity rate. We think that the integration of image guidance with reduced target volume parameters further,” Dr. Sen said.
 

Better Agents Needed

Elizabeth H Baldini, MD, MPH, from the Dana-Farber/Brigham & Women’s Cancer Center, Boston, the invited discussant, agreed that there is a need for better systemic therapy to reduce the risk of distant recurrence in patients with high-risk localized sarcomas.

“But the bottom line is that the benefit of chemotherapy with the agents we have today is uncertain,” she said.

Assessment of systemic chemotherapy in sarcoma is hampered by the rarity of the tumors, with more than 50 different histologic subtypes, and wide tumor heterogeneity, and although the studies reported here appear to show benefit for chemotherapy, they appear to overlap with those for surgery and radiation alone, she said.

Session comoderator Yen-Lin Evelyn Chen, MD, a radiation oncologist at Massachusetts General Hospital Cancer Center, Boston, said in an interview that studies presented during the session show that, “chemotherapy in experienced hands can be delivered safely.”

Dr. Chen added, however, that the local control rates reported by Dr. Sen and colleagues were a little lower than she would have expected in the modern era, suggesting that either the radiation modification or elimination of dacarbazine may have played a role.

BOSTON – Neoadjuvant chemotherapy and radiation appear to offer long-term benefits in patients with high-risk soft tissue sarcomas of the extremities.

The key word is “appear,” however, because the idea is drawn more from inference than from evidence, and not all sarcoma specialists are convinced that neoadjuvant chemotherapy and radiation add anything more than toxicity.

In studies presented at the annual meeting of the American Society of Radiation Oncology, including a retrospective case series and a national database review, investigators found evidence supporting the use of combined modality therapy with radiation and chemotherapy in patients with soft tissue sarcomas of the extremities.

“Large high-grade extremity soft-tissue sarcomas are at high risk of failure and death compared to our typical high-risk patients who present with one [risk] factor,” said Omar Mahmoud, MD, PhD, from the Rutgers Cancer Institute of New Jersey, New Brunswick.

He and his colleagues combed through the National Cancer Database to identify 3,840 otherwise healthy patients with grade 3 or 4 soft-tissue sarcomas (STS) of the extremities of various histologies larger than 8 cm, who underwent surgical resections during 2004-2013.

They looked at overall survival in patients who received no neoadjuvant or adjuvant therapy and those who received either neoadjuvant or adjuvant chemotherapy and/or radiation therapy. They used propensity score matching to adjust for imbalances of covariates across treatment subgroups.

They found that chemotherapy was associated with significantly better 5-year overall survival, at 57%, compared with 45% with no chemotherapy (P less than .001)

In multivariate analysis, age older than 50 years, positive tumor margins, larger tumors, and tumors located in the trunk or pelvis were associated with worse prognosis, whereas receipt of chemotherapy and radiotherapy were associated independently with better prognosis.

Out to 100 months (8.3 years) of follow-up, overall survival was significantly higher for patients who received combined modality adjunctive therapies, compared with either single modality therapy (chemotherapy or radiotherapy alone) or no therapy (P less than .001).

Using propensity score matching to compare patients who received combined vs. single-modality therapy, the investigators found that combined therapies were associated with significantly better overall survival, with a hazard ratio of 0.72 (95% confidence interval, 0.62-0.84).

There was no difference in survival according to the timing of therapy, whether preoperative, postoperative, or concurrent), however.

Finally, looking at survival among all subgroups, they saw that combined therapies remained significantly better than single-modality therapies (P less than .001).

Drop the ‘D’ in MAID?

In a separate study, Neilayan Sen, MD, and colleagues from Rush University Medical Center in Chicago reported that a modified protocol involving neoadjuvant chemotherapy interdigitated with radiation followed by surgery and adjuvant chemotherapy was associated with good disease control and survival and lower toxicity in patients with large STS of the extremities or abdominal wall.

The original protocol, dubbed MAID (mesna, doxorubicin, ifosfamide, dacarbazine), was shown in the RTOG 9514 trial to be associated with higher rates of disease-free, distant disease-free, and overall survival than older regimens, but at the price of high short-term toxicities. Among 64 evaluable patients, 97% had grade 3 or higher toxicities, including three deaths, two of which were from myelodysplasia.

To see whether they could match the efficacy of MAID while reducing toxicity, the Rush team modified the MAID protocol by dropping the dacarbazine. For the radiation component, they used either 3-D conformal radiation therapy or intensity-modulated radiation therapy, set the maximum dose penetration (Dmax) at 112% or less, and used reduced volumes while maintaining the dose and fractions (44 Gy delivered in 22 fractions, 11 each between chemotherapy cycles 1-2 and 2-3). Patients then underwent surgery, followed by three additional cycles of chemotherapy.

In a retrospective analysis of 26 patients treated with the modified protocol, there were no toxicity-related amputations, and no amputations were required for tumor management. Two patients had in-field fractures.

At a median follow-up of 39 months, 25 of the 26 patients were still alive and there were no cases of treatment-related malignancies or myelodysplasia.

The 3-year actuarial results with MAI also compared favorably with those of RTOG 9514, with locoregional recurrence-free survival rates of 87.2% with the modified protocol vs. 82.4% for the original MAID protocol, distant metastasis-free survival of 67.9% vs. 64.%, respectively, disease-free survival of 67.9% vs. 56.6%, and overall survival of 93.3% vs. 75.1%.

“The omission of dacarbazine does not compromise any disease-control endpoints. With the integration of 3-D techniques as well as intensity modulation and smaller fields than were used in [RTOG] 9514, there’s a significantly reduced grade 4 and 5 toxicity rate. We think that the integration of image guidance with reduced target volume parameters further,” Dr. Sen said.
 

Better Agents Needed

Elizabeth H Baldini, MD, MPH, from the Dana-Farber/Brigham & Women’s Cancer Center, Boston, the invited discussant, agreed that there is a need for better systemic therapy to reduce the risk of distant recurrence in patients with high-risk localized sarcomas.

“But the bottom line is that the benefit of chemotherapy with the agents we have today is uncertain,” she said.

Assessment of systemic chemotherapy in sarcoma is hampered by the rarity of the tumors, with more than 50 different histologic subtypes, and wide tumor heterogeneity, and although the studies reported here appear to show benefit for chemotherapy, they appear to overlap with those for surgery and radiation alone, she said.

Session comoderator Yen-Lin Evelyn Chen, MD, a radiation oncologist at Massachusetts General Hospital Cancer Center, Boston, said in an interview that studies presented during the session show that, “chemotherapy in experienced hands can be delivered safely.”

Dr. Chen added, however, that the local control rates reported by Dr. Sen and colleagues were a little lower than she would have expected in the modern era, suggesting that either the radiation modification or elimination of dacarbazine may have played a role.

Sudden and fulminant reactivation of hepatitis B virus (HBV) infections are occurring among some patients who received direct-acting antiviral (DAA) medicines for concomitant chronic hepatitis C virus, the U.S. Food and Drug Administration has said.

HBV reactivation has been reported in 24 patients since 2013, the agency said in an Oct. 4 statement. One patient died, and one required a liver transplant, likely because of treatment delay, as HBV reactivation wasn’t a primary diagnostic candidate.

[email protected]

Sudden and fulminant reactivation of hepatitis B virus (HBV) infections are occurring among some patients who received direct-acting antiviral (DAA) medicines for concomitant chronic hepatitis C virus, the U.S. Food and Drug Administration has said.

HBV reactivation has been reported in 24 patients since 2013, the agency said in an Oct. 4 statement. One patient died, and one required a liver transplant, likely because of treatment delay, as HBV reactivation wasn’t a primary diagnostic candidate.

[email protected]

Sudden and fulminant reactivation of hepatitis B virus (HBV) infections are occurring among some patients who received direct-acting antiviral (DAA) medicines for concomitant chronic hepatitis C virus, the U.S. Food and Drug Administration has said.

HBV reactivation has been reported in 24 patients since 2013, the agency said in an Oct. 4 statement. One patient died, and one required a liver transplant, likely because of treatment delay, as HBV reactivation wasn’t a primary diagnostic candidate.

[email protected]

To improve patient care and outcomes, leading dermatologists offered their recommendations on acne scar treatments. Consideration must be given to:

• Effaclar BB Blur
  La Roche-Posay Laboratoire Dermatologique
  “Unfortunately, acne scars are permanent, but by applying cosmetics over the skin, you can minimize their appearance. Combining ingredients that give cosmetic coverage, minimize pores, and absorb oil, this product gives the skin a brighter, more even complexion.”
  — Joshua Zeichner, MD, New York, New York

• Fraxel
  Valeant Pharmaceuticals International, Inc
  Recommended by Gary Goldenberg, MD, New York, New York

• Glytone Rejuvenating Mini Peel Gel
  Pierre Fabre Dermo Cosmetique USA
  “This gel product contains a low concentration of glycolic acid. It can be applied at home, left on the skin for 10 minutes, and neutralized with water.”
  —Cherise M. Levi, DO, New York, New York

• SkinMedica Retinol Complex 0.25
  Allergan
  “Retinol will help to minimize acne scarring.”
  — Shari Lipner, MD, PhD, New York, New York

Cutis invites readers to send us their recommendations. Cleansing devices and self-tanners will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

To improve patient care and outcomes, leading dermatologists offered their recommendations on acne scar treatments. Consideration must be given to:

• Effaclar BB Blur
  La Roche-Posay Laboratoire Dermatologique
  “Unfortunately, acne scars are permanent, but by applying cosmetics over the skin, you can minimize their appearance. Combining ingredients that give cosmetic coverage, minimize pores, and absorb oil, this product gives the skin a brighter, more even complexion.”
  — Joshua Zeichner, MD, New York, New York

• Fraxel
  Valeant Pharmaceuticals International, Inc
  Recommended by Gary Goldenberg, MD, New York, New York

• Glytone Rejuvenating Mini Peel Gel
  Pierre Fabre Dermo Cosmetique USA
  “This gel product contains a low concentration of glycolic acid. It can be applied at home, left on the skin for 10 minutes, and neutralized with water.”
  —Cherise M. Levi, DO, New York, New York

• SkinMedica Retinol Complex 0.25
  Allergan
  “Retinol will help to minimize acne scarring.”
  — Shari Lipner, MD, PhD, New York, New York

Cutis invites readers to send us their recommendations. Cleansing devices and self-tanners will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

To improve patient care and outcomes, leading dermatologists offered their recommendations on acne scar treatments. Consideration must be given to:

• Effaclar BB Blur
  La Roche-Posay Laboratoire Dermatologique
  “Unfortunately, acne scars are permanent, but by applying cosmetics over the skin, you can minimize their appearance. Combining ingredients that give cosmetic coverage, minimize pores, and absorb oil, this product gives the skin a brighter, more even complexion.”
  — Joshua Zeichner, MD, New York, New York

• Fraxel
  Valeant Pharmaceuticals International, Inc
  Recommended by Gary Goldenberg, MD, New York, New York

• Glytone Rejuvenating Mini Peel Gel
  Pierre Fabre Dermo Cosmetique USA
  “This gel product contains a low concentration of glycolic acid. It can be applied at home, left on the skin for 10 minutes, and neutralized with water.”
  —Cherise M. Levi, DO, New York, New York

• SkinMedica Retinol Complex 0.25
  Allergan
  “Retinol will help to minimize acne scarring.”
  — Shari Lipner, MD, PhD, New York, New York

Cutis invites readers to send us their recommendations. Cleansing devices and self-tanners will be featured in upcoming editions of Cosmetic Corner. Please e-mail your recommendation(s) to the Editorial Office.

Disclaimer: Opinions expressed herein do not necessarily reflect those of Cutis or Frontline Medical Communications Inc. and shall not be used for product endorsement purposes. Any reference made to a specific commercial product does not indicate or imply that Cutis or Frontline Medical Communications Inc. endorses, recommends, or favors the product mentioned. No guarantee is given to the effects of recommended products.

Those of us who care for patients with migraine dread seeing patients who come to the office wearing dark sunglasses, even in a dimly lit examination room. In neuro-ophthalmology, the "sunglasses sign" is a predictor of non-organic visual loss and is often associated with a lawsuit, disability, workers' compensation claim, or a highly positive review of systems. While not specifically studied in a headache medicine practice, the sunglasses sign often goes hand in hand with chronic migraine, severe light intolerance to the point of social isolation, comorbid depression, and anxiety. It indicates that the provider is about to tackle a difficult case. Exposure to bright light may trigger a migraine, and heightened light sensitivity may herald a migraine attack. Photophobia is a major source of discomfort and disability for migraine patients during attacks and, in some cases, between attacks. It is often either overlooked or trivialized. The discovery of the melanopsin system clarifies that photophobia has a neurologic basis involving retinothalamic pathways and may be considered similarly to the central sensitization of migraine pain.  

As Dr. Digre points out, dry eyes are a frequent cause of photophobia that is underdiagnosed, even by eye care providers. Patients with dry eyes often experience ocular itching, burning, foreign body sensation, a sense of dryness, reflex tearing, and conjunctival injection. Ocular inflammation, while uncommon, is another potential source of eye pain and photophobia. However, many migraine patients have photophobia that seems to be purely related to having migraine, and they sometimes take extreme measures to live in darkness. Patients with severe light aversion need our support and guidance to help them "come back into the light" gradually by treating any underlying ocular condition and slowly transitioning them to lighter lenses (including FL-41 and other tints). Awareness of the causes and treatments of photophobia, both ocular and central, is an important aspect of headache care that has the potential to vastly improve the quality of life of our patients.  

—Deborah I. Friedman, MD, MPH
Professor of Neurology & Neurotherapeutics and Ophthalmology
University of Texas Southwestern Medical Center
Dallas

Suggested Reading

Bengtzen R, Woodward M, Lynn MJ, et al. The "sunglasses sign" predicts nonorganic visual loss in neuro-ophthalmologic practice. Neurology. 2008;70(3):218-221.

Those of us who care for patients with migraine dread seeing patients who come to the office wearing dark sunglasses, even in a dimly lit examination room. In neuro-ophthalmology, the "sunglasses sign" is a predictor of non-organic visual loss and is often associated with a lawsuit, disability, workers' compensation claim, or a highly positive review of systems. While not specifically studied in a headache medicine practice, the sunglasses sign often goes hand in hand with chronic migraine, severe light intolerance to the point of social isolation, comorbid depression, and anxiety. It indicates that the provider is about to tackle a difficult case. Exposure to bright light may trigger a migraine, and heightened light sensitivity may herald a migraine attack. Photophobia is a major source of discomfort and disability for migraine patients during attacks and, in some cases, between attacks. It is often either overlooked or trivialized. The discovery of the melanopsin system clarifies that photophobia has a neurologic basis involving retinothalamic pathways and may be considered similarly to the central sensitization of migraine pain.  

As Dr. Digre points out, dry eyes are a frequent cause of photophobia that is underdiagnosed, even by eye care providers. Patients with dry eyes often experience ocular itching, burning, foreign body sensation, a sense of dryness, reflex tearing, and conjunctival injection. Ocular inflammation, while uncommon, is another potential source of eye pain and photophobia. However, many migraine patients have photophobia that seems to be purely related to having migraine, and they sometimes take extreme measures to live in darkness. Patients with severe light aversion need our support and guidance to help them "come back into the light" gradually by treating any underlying ocular condition and slowly transitioning them to lighter lenses (including FL-41 and other tints). Awareness of the causes and treatments of photophobia, both ocular and central, is an important aspect of headache care that has the potential to vastly improve the quality of life of our patients.  

—Deborah I. Friedman, MD, MPH
Professor of Neurology & Neurotherapeutics and Ophthalmology
University of Texas Southwestern Medical Center
Dallas

Suggested Reading

Bengtzen R, Woodward M, Lynn MJ, et al. The "sunglasses sign" predicts nonorganic visual loss in neuro-ophthalmologic practice. Neurology. 2008;70(3):218-221.

Those of us who care for patients with migraine dread seeing patients who come to the office wearing dark sunglasses, even in a dimly lit examination room. In neuro-ophthalmology, the "sunglasses sign" is a predictor of non-organic visual loss and is often associated with a lawsuit, disability, workers' compensation claim, or a highly positive review of systems. While not specifically studied in a headache medicine practice, the sunglasses sign often goes hand in hand with chronic migraine, severe light intolerance to the point of social isolation, comorbid depression, and anxiety. It indicates that the provider is about to tackle a difficult case. Exposure to bright light may trigger a migraine, and heightened light sensitivity may herald a migraine attack. Photophobia is a major source of discomfort and disability for migraine patients during attacks and, in some cases, between attacks. It is often either overlooked or trivialized. The discovery of the melanopsin system clarifies that photophobia has a neurologic basis involving retinothalamic pathways and may be considered similarly to the central sensitization of migraine pain.  

As Dr. Digre points out, dry eyes are a frequent cause of photophobia that is underdiagnosed, even by eye care providers. Patients with dry eyes often experience ocular itching, burning, foreign body sensation, a sense of dryness, reflex tearing, and conjunctival injection. Ocular inflammation, while uncommon, is another potential source of eye pain and photophobia. However, many migraine patients have photophobia that seems to be purely related to having migraine, and they sometimes take extreme measures to live in darkness. Patients with severe light aversion need our support and guidance to help them "come back into the light" gradually by treating any underlying ocular condition and slowly transitioning them to lighter lenses (including FL-41 and other tints). Awareness of the causes and treatments of photophobia, both ocular and central, is an important aspect of headache care that has the potential to vastly improve the quality of life of our patients.  

—Deborah I. Friedman, MD, MPH
Professor of Neurology & Neurotherapeutics and Ophthalmology
University of Texas Southwestern Medical Center
Dallas

Suggested Reading

Bengtzen R, Woodward M, Lynn MJ, et al. The "sunglasses sign" predicts nonorganic visual loss in neuro-ophthalmologic practice. Neurology. 2008;70(3):218-221.

SAN DIEGO—Among patients with migraine, eye-related symptoms such as dry eyes and photophobia are common and treatable, said Kathleen B. Digre, MD, Professor of Neurology and Ophthalmology at the University of Utah in Salt Lake City. Neurologists should treat eye-related conditions “in hopes that we can improve our patients’ migraine,” Dr. Digre said at the 58th Annual Scientific Meeting of the American Headache Society.

Dry Eyes

About 20% to 30% of people over age 45 have dry eyes. Dry eyes are more common in women than in men. Reading, computer use, and watching television may worsen dry eye symptoms due to reduced blinking during those activities. Dry climate, hormones, and certain medications used for migraine, such as amitriptyline and antihistamines, can cause or worsen dry eye symptoms. About 45% of people with Sjögren’s syndrome, a condition that causes dry eyes, have migraine. Furthermore, dry eyes are associated with photophobia, Dr. Digre said.

Koktekir et al in 2012 examined tear film function in patients with episodic migraine versus controls and found that migraineurs had significantly more tear film dysfunction, as measured by Schirmer’s test, tear film breakup time, lissamine green stain, and the Ocular Surface Disease Index.

In a case–control study published in Headache in 2015, Krista I. Kinard, MD, Adjunct Assistant Professor of Ophthalmology at the University of Utah, Dr. Digre, and colleagues examined 19 patients with chronic migraine and 30 controls. Tear film breakup time, basal tear cell secretion, and corneal sensitivity did not differ between the groups. Using corneal microscopy, however, the researchers found that controls had denser nerve fibers than patients with chronic migraine. On the Dry Eye Questionnaire, all patients with chronic migraine scored above 6, a result consistent with dry eye syndrome, whereas controls scored less than 3, as expected. Future research should evaluate whether dry eye symptoms result from the migraine process or whether dry eye symptoms may lead to chronic migraine by continuous stimulation, Dr. Digre said.

Therapeutic Options

Over-the-counter artificial tears, gels, and ointments may be safe and effective treatments for dry eyes. A review published in 2016 found that in two trials, polyacrylic acid-based artificial tears more effectively treated dry eye symptoms than polyvinyl alcohol-based artificial tears. Dr. Digre avoids preservatives in artificial tears because some people are sensitive to them. Oral flaxseed oil or fish oil also may help patients. If symptoms do not improve, an ophthalmologist may consider more aggressive dry eye therapy, such as punctal plugs, she said.

Photophobia

Photophobia is one of the major diagnostic criteria of migraine, and migraine is the most common cause of photophobia, Dr. Digre said. Ninety percent of people with migraine have photophobia during a migraine attack. Ocular inflammation, including dry eye, retinal disease, and cone dystrophy, is associated with photophobia. Certain brain disorders, including meningitis, pituitary tumors, and progressive supranuclear palsy, can cause photophobia. In addition, some psychiatric conditions, such as depression, and certain medications, including stimulants, have been associated with photophobia.

Photophobia has an anatomic basis, and patients without vision may still be light sensitive, Dr. Digre said. The discovery of the melanopsin pathway, a pathway of intrinsically photoactive retinal ganglion cells that function when exposed to light and inform circadian rhythm, was a breakthrough in understanding photophobia, she said.

Delwig et al in 2012 reported that when newborn mice with melanopsin-expressing intrinsically photoactive retinal ganglion cells were exposed to light, the mice vocalized in a way that is similar to when mice are distressed by having to leave the litter. Mice without melanopsin do not exhibit this same aversive behavior, Dr. Digre said. Jones et al in 2013 described a melanopsin antagonist that reverses light aversion in mice.

Light sensitivity may be associated with depression and anxiety. To assess the prevalence of anxiety and depression symptoms in migraineurs with and without interictal photophobia, Llop et al studied 16 patients with episodic migraine who had interictal photophobia, 16 patients with episodic migraine who had photophobia only during migraine attacks, and 16 controls. Migraineurs with interictal photophobia had higher scores on the Beck Depression Inventory and Beck Anxiety Inventory, compared with subjects without interictal photophobia.

Treating Light Sensitivity

Tinted lenses may help patients with migraine and photophobia. Good et al in 1991 published a study that included 20 children with migraine. Patients wore glasses with FL-41–tinted lenses (ie, a rose-colored tint) or blue-tinted lenses. Patients with FL-41–tinted lenses had reduced headache frequency at four months, whereas patients with blue-tinted lenses did not experience a sustained reduction in headache frequency.

Patients with photophobia should not keep themselves in the dark. “Every single person who comes in with three layers of sunglasses, you have to tell them that the more you stay in the dark, the worse this is going to get,” Dr. Digre said. “We have to … slowly peel off the sunglasses, lift up the shades, and start getting used to more light.”

Botulinum toxin, sympathetic nerve blocks, gabapentin, and melatonin have been used in people with photophobia. Importantly, physicians should treat any underlying psychiatric or neurologic condition, including migraine, that may be driving patients’ light sensitivity, Dr. Digre said.

—Jake Remaly

Suggested Reading

Delwig A, Logan AM, Copenhagen DR, Ahn AH. Light evokes melanopsin-dependent vocalization and neural activation associated with aversive experience in neonatal mice. PLoS One. 2012;7(9):e43787.

Good PA, Taylor RH, Mortimer MJ. The use of tinted glasses in childhood migraine. Headache. 1991;31(8):533-536.

Jones KA, Hatori M, Mure LS, et al. Small-molecule antagonists of melanopsin-mediated phototransduction. Nat Chem Biol. 2013;9(10):630-635.

Kinard KI, Smith AG, Singleton JR, et al. Chronic migraine is associated with reduced corneal nerve fiber density and symptoms of dry eye. Headache. 2015;55(4):543-549.

Koktekir BE, Celik G, Karalezli A, Kal A. Dry eyes and migraines: is there really a correlation? Cornea. 2012;31(12):1414-1416.

Llop SM, Frandsen JE, Digre KB, et al. Increased prevalence of depression and anxiety in patients with migraine and interictal photophobia. J Headache Pain. 2016;17:34.

Noseda R, Kainz V, Jakubowski M, et al. A neural mechanism for exacerbation of headache by light. Nat Neurosci. 2010;13(2):239-245.

Pucker AD, Ng SM, Nichols JJ. Over the counter (OTC) artificial tear drops for dry eye syndrome. Cochrane Database Syst Rev. 2016 Feb 23;2:CD009729.

SAN DIEGO—Among patients with migraine, eye-related symptoms such as dry eyes and photophobia are common and treatable, said Kathleen B. Digre, MD, Professor of Neurology and Ophthalmology at the University of Utah in Salt Lake City. Neurologists should treat eye-related conditions “in hopes that we can improve our patients’ migraine,” Dr. Digre said at the 58th Annual Scientific Meeting of the American Headache Society.

Dry Eyes

About 20% to 30% of people over age 45 have dry eyes. Dry eyes are more common in women than in men. Reading, computer use, and watching television may worsen dry eye symptoms due to reduced blinking during those activities. Dry climate, hormones, and certain medications used for migraine, such as amitriptyline and antihistamines, can cause or worsen dry eye symptoms. About 45% of people with Sjögren’s syndrome, a condition that causes dry eyes, have migraine. Furthermore, dry eyes are associated with photophobia, Dr. Digre said.

Koktekir et al in 2012 examined tear film function in patients with episodic migraine versus controls and found that migraineurs had significantly more tear film dysfunction, as measured by Schirmer’s test, tear film breakup time, lissamine green stain, and the Ocular Surface Disease Index.

In a case–control study published in Headache in 2015, Krista I. Kinard, MD, Adjunct Assistant Professor of Ophthalmology at the University of Utah, Dr. Digre, and colleagues examined 19 patients with chronic migraine and 30 controls. Tear film breakup time, basal tear cell secretion, and corneal sensitivity did not differ between the groups. Using corneal microscopy, however, the researchers found that controls had denser nerve fibers than patients with chronic migraine. On the Dry Eye Questionnaire, all patients with chronic migraine scored above 6, a result consistent with dry eye syndrome, whereas controls scored less than 3, as expected. Future research should evaluate whether dry eye symptoms result from the migraine process or whether dry eye symptoms may lead to chronic migraine by continuous stimulation, Dr. Digre said.

Therapeutic Options

Over-the-counter artificial tears, gels, and ointments may be safe and effective treatments for dry eyes. A review published in 2016 found that in two trials, polyacrylic acid-based artificial tears more effectively treated dry eye symptoms than polyvinyl alcohol-based artificial tears. Dr. Digre avoids preservatives in artificial tears because some people are sensitive to them. Oral flaxseed oil or fish oil also may help patients. If symptoms do not improve, an ophthalmologist may consider more aggressive dry eye therapy, such as punctal plugs, she said.

Photophobia

Photophobia is one of the major diagnostic criteria of migraine, and migraine is the most common cause of photophobia, Dr. Digre said. Ninety percent of people with migraine have photophobia during a migraine attack. Ocular inflammation, including dry eye, retinal disease, and cone dystrophy, is associated with photophobia. Certain brain disorders, including meningitis, pituitary tumors, and progressive supranuclear palsy, can cause photophobia. In addition, some psychiatric conditions, such as depression, and certain medications, including stimulants, have been associated with photophobia.

Photophobia has an anatomic basis, and patients without vision may still be light sensitive, Dr. Digre said. The discovery of the melanopsin pathway, a pathway of intrinsically photoactive retinal ganglion cells that function when exposed to light and inform circadian rhythm, was a breakthrough in understanding photophobia, she said.

Delwig et al in 2012 reported that when newborn mice with melanopsin-expressing intrinsically photoactive retinal ganglion cells were exposed to light, the mice vocalized in a way that is similar to when mice are distressed by having to leave the litter. Mice without melanopsin do not exhibit this same aversive behavior, Dr. Digre said. Jones et al in 2013 described a melanopsin antagonist that reverses light aversion in mice.

Light sensitivity may be associated with depression and anxiety. To assess the prevalence of anxiety and depression symptoms in migraineurs with and without interictal photophobia, Llop et al studied 16 patients with episodic migraine who had interictal photophobia, 16 patients with episodic migraine who had photophobia only during migraine attacks, and 16 controls. Migraineurs with interictal photophobia had higher scores on the Beck Depression Inventory and Beck Anxiety Inventory, compared with subjects without interictal photophobia.

Treating Light Sensitivity

Tinted lenses may help patients with migraine and photophobia. Good et al in 1991 published a study that included 20 children with migraine. Patients wore glasses with FL-41–tinted lenses (ie, a rose-colored tint) or blue-tinted lenses. Patients with FL-41–tinted lenses had reduced headache frequency at four months, whereas patients with blue-tinted lenses did not experience a sustained reduction in headache frequency.

Patients with photophobia should not keep themselves in the dark. “Every single person who comes in with three layers of sunglasses, you have to tell them that the more you stay in the dark, the worse this is going to get,” Dr. Digre said. “We have to … slowly peel off the sunglasses, lift up the shades, and start getting used to more light.”

Botulinum toxin, sympathetic nerve blocks, gabapentin, and melatonin have been used in people with photophobia. Importantly, physicians should treat any underlying psychiatric or neurologic condition, including migraine, that may be driving patients’ light sensitivity, Dr. Digre said.

—Jake Remaly

Suggested Reading

Delwig A, Logan AM, Copenhagen DR, Ahn AH. Light evokes melanopsin-dependent vocalization and neural activation associated with aversive experience in neonatal mice. PLoS One. 2012;7(9):e43787.

Good PA, Taylor RH, Mortimer MJ. The use of tinted glasses in childhood migraine. Headache. 1991;31(8):533-536.

Jones KA, Hatori M, Mure LS, et al. Small-molecule antagonists of melanopsin-mediated phototransduction. Nat Chem Biol. 2013;9(10):630-635.

Kinard KI, Smith AG, Singleton JR, et al. Chronic migraine is associated with reduced corneal nerve fiber density and symptoms of dry eye. Headache. 2015;55(4):543-549.

Koktekir BE, Celik G, Karalezli A, Kal A. Dry eyes and migraines: is there really a correlation? Cornea. 2012;31(12):1414-1416.

Llop SM, Frandsen JE, Digre KB, et al. Increased prevalence of depression and anxiety in patients with migraine and interictal photophobia. J Headache Pain. 2016;17:34.

Noseda R, Kainz V, Jakubowski M, et al. A neural mechanism for exacerbation of headache by light. Nat Neurosci. 2010;13(2):239-245.

Pucker AD, Ng SM, Nichols JJ. Over the counter (OTC) artificial tear drops for dry eye syndrome. Cochrane Database Syst Rev. 2016 Feb 23;2:CD009729.

SAN DIEGO—Among patients with migraine, eye-related symptoms such as dry eyes and photophobia are common and treatable, said Kathleen B. Digre, MD, Professor of Neurology and Ophthalmology at the University of Utah in Salt Lake City. Neurologists should treat eye-related conditions “in hopes that we can improve our patients’ migraine,” Dr. Digre said at the 58th Annual Scientific Meeting of the American Headache Society.

Dry Eyes

About 20% to 30% of people over age 45 have dry eyes. Dry eyes are more common in women than in men. Reading, computer use, and watching television may worsen dry eye symptoms due to reduced blinking during those activities. Dry climate, hormones, and certain medications used for migraine, such as amitriptyline and antihistamines, can cause or worsen dry eye symptoms. About 45% of people with Sjögren’s syndrome, a condition that causes dry eyes, have migraine. Furthermore, dry eyes are associated with photophobia, Dr. Digre said.

Koktekir et al in 2012 examined tear film function in patients with episodic migraine versus controls and found that migraineurs had significantly more tear film dysfunction, as measured by Schirmer’s test, tear film breakup time, lissamine green stain, and the Ocular Surface Disease Index.

In a case–control study published in Headache in 2015, Krista I. Kinard, MD, Adjunct Assistant Professor of Ophthalmology at the University of Utah, Dr. Digre, and colleagues examined 19 patients with chronic migraine and 30 controls. Tear film breakup time, basal tear cell secretion, and corneal sensitivity did not differ between the groups. Using corneal microscopy, however, the researchers found that controls had denser nerve fibers than patients with chronic migraine. On the Dry Eye Questionnaire, all patients with chronic migraine scored above 6, a result consistent with dry eye syndrome, whereas controls scored less than 3, as expected. Future research should evaluate whether dry eye symptoms result from the migraine process or whether dry eye symptoms may lead to chronic migraine by continuous stimulation, Dr. Digre said.

Therapeutic Options

Over-the-counter artificial tears, gels, and ointments may be safe and effective treatments for dry eyes. A review published in 2016 found that in two trials, polyacrylic acid-based artificial tears more effectively treated dry eye symptoms than polyvinyl alcohol-based artificial tears. Dr. Digre avoids preservatives in artificial tears because some people are sensitive to them. Oral flaxseed oil or fish oil also may help patients. If symptoms do not improve, an ophthalmologist may consider more aggressive dry eye therapy, such as punctal plugs, she said.

Photophobia

Photophobia is one of the major diagnostic criteria of migraine, and migraine is the most common cause of photophobia, Dr. Digre said. Ninety percent of people with migraine have photophobia during a migraine attack. Ocular inflammation, including dry eye, retinal disease, and cone dystrophy, is associated with photophobia. Certain brain disorders, including meningitis, pituitary tumors, and progressive supranuclear palsy, can cause photophobia. In addition, some psychiatric conditions, such as depression, and certain medications, including stimulants, have been associated with photophobia.

Photophobia has an anatomic basis, and patients without vision may still be light sensitive, Dr. Digre said. The discovery of the melanopsin pathway, a pathway of intrinsically photoactive retinal ganglion cells that function when exposed to light and inform circadian rhythm, was a breakthrough in understanding photophobia, she said.

Delwig et al in 2012 reported that when newborn mice with melanopsin-expressing intrinsically photoactive retinal ganglion cells were exposed to light, the mice vocalized in a way that is similar to when mice are distressed by having to leave the litter. Mice without melanopsin do not exhibit this same aversive behavior, Dr. Digre said. Jones et al in 2013 described a melanopsin antagonist that reverses light aversion in mice.

Light sensitivity may be associated with depression and anxiety. To assess the prevalence of anxiety and depression symptoms in migraineurs with and without interictal photophobia, Llop et al studied 16 patients with episodic migraine who had interictal photophobia, 16 patients with episodic migraine who had photophobia only during migraine attacks, and 16 controls. Migraineurs with interictal photophobia had higher scores on the Beck Depression Inventory and Beck Anxiety Inventory, compared with subjects without interictal photophobia.

Treating Light Sensitivity

Tinted lenses may help patients with migraine and photophobia. Good et al in 1991 published a study that included 20 children with migraine. Patients wore glasses with FL-41–tinted lenses (ie, a rose-colored tint) or blue-tinted lenses. Patients with FL-41–tinted lenses had reduced headache frequency at four months, whereas patients with blue-tinted lenses did not experience a sustained reduction in headache frequency.

Patients with photophobia should not keep themselves in the dark. “Every single person who comes in with three layers of sunglasses, you have to tell them that the more you stay in the dark, the worse this is going to get,” Dr. Digre said. “We have to … slowly peel off the sunglasses, lift up the shades, and start getting used to more light.”

Botulinum toxin, sympathetic nerve blocks, gabapentin, and melatonin have been used in people with photophobia. Importantly, physicians should treat any underlying psychiatric or neurologic condition, including migraine, that may be driving patients’ light sensitivity, Dr. Digre said.

—Jake Remaly

Suggested Reading

Delwig A, Logan AM, Copenhagen DR, Ahn AH. Light evokes melanopsin-dependent vocalization and neural activation associated with aversive experience in neonatal mice. PLoS One. 2012;7(9):e43787.

Good PA, Taylor RH, Mortimer MJ. The use of tinted glasses in childhood migraine. Headache. 1991;31(8):533-536.

Jones KA, Hatori M, Mure LS, et al. Small-molecule antagonists of melanopsin-mediated phototransduction. Nat Chem Biol. 2013;9(10):630-635.

Kinard KI, Smith AG, Singleton JR, et al. Chronic migraine is associated with reduced corneal nerve fiber density and symptoms of dry eye. Headache. 2015;55(4):543-549.

Koktekir BE, Celik G, Karalezli A, Kal A. Dry eyes and migraines: is there really a correlation? Cornea. 2012;31(12):1414-1416.

Llop SM, Frandsen JE, Digre KB, et al. Increased prevalence of depression and anxiety in patients with migraine and interictal photophobia. J Headache Pain. 2016;17:34.

Noseda R, Kainz V, Jakubowski M, et al. A neural mechanism for exacerbation of headache by light. Nat Neurosci. 2010;13(2):239-245.

Pucker AD, Ng SM, Nichols JJ. Over the counter (OTC) artificial tear drops for dry eye syndrome. Cochrane Database Syst Rev. 2016 Feb 23;2:CD009729.

Patients with HIV facial lipoatrophy (FLA) had improved quality of life scores after treatment with hyaluronic acid (HA) filler, report Derek Ho of the Sacramento VA Medical Center, and coauthors.

A prospective, open-label, phase I and II study assessed 20 patients with an HIV FLA Carruthers Lipoatrophy Severity Scale (CLSS) grade of 2 or higher, who had not received treatment for HIV FLA in the past year. Volumizing of the cheeks and temples was performed using a 20 mg/mL HA filler, with an optional touch-up at 2 weeks follow-up. Patients were given a vision exam before treatment, immediately after treatment, and 15 minutes after treatment.

Quality of life was assessed before treatment and at 12 months follow-up using the Dermatology Life Quality Index (DLQI). Satisfaction was evaluated using a subject satisfaction questionnaire at 12 months follow-up, Mr. Ho and his colleagues reported.

DLQI scores were 1.6±3.0 (range = 0-11) and 0.5±1.2 (range = 0-5) at baseline and follow-up, respectively, the authors said. Additionally, 100% of patients reported high satisfaction as indicated by answers on the subject satisfaction questionnaire, they added.

The investigators warned, however, that they would not recommend the DLQI in the future as a measure of quality of life, as this scale focuses on disability, and fails to account for mental health issues.

Still, the findings highlight “the importance of educating and offering aesthetic and corrective treatment to all patients with HIV FLA,” the authors concluded.

Read the full article in the Journal of Drugs in Dermatology.

Patients with HIV facial lipoatrophy (FLA) had improved quality of life scores after treatment with hyaluronic acid (HA) filler, report Derek Ho of the Sacramento VA Medical Center, and coauthors.

A prospective, open-label, phase I and II study assessed 20 patients with an HIV FLA Carruthers Lipoatrophy Severity Scale (CLSS) grade of 2 or higher, who had not received treatment for HIV FLA in the past year. Volumizing of the cheeks and temples was performed using a 20 mg/mL HA filler, with an optional touch-up at 2 weeks follow-up. Patients were given a vision exam before treatment, immediately after treatment, and 15 minutes after treatment.

Quality of life was assessed before treatment and at 12 months follow-up using the Dermatology Life Quality Index (DLQI). Satisfaction was evaluated using a subject satisfaction questionnaire at 12 months follow-up, Mr. Ho and his colleagues reported.

DLQI scores were 1.6±3.0 (range = 0-11) and 0.5±1.2 (range = 0-5) at baseline and follow-up, respectively, the authors said. Additionally, 100% of patients reported high satisfaction as indicated by answers on the subject satisfaction questionnaire, they added.

The investigators warned, however, that they would not recommend the DLQI in the future as a measure of quality of life, as this scale focuses on disability, and fails to account for mental health issues.

Still, the findings highlight “the importance of educating and offering aesthetic and corrective treatment to all patients with HIV FLA,” the authors concluded.

Read the full article in the Journal of Drugs in Dermatology.

Patients with HIV facial lipoatrophy (FLA) had improved quality of life scores after treatment with hyaluronic acid (HA) filler, report Derek Ho of the Sacramento VA Medical Center, and coauthors.

A prospective, open-label, phase I and II study assessed 20 patients with an HIV FLA Carruthers Lipoatrophy Severity Scale (CLSS) grade of 2 or higher, who had not received treatment for HIV FLA in the past year. Volumizing of the cheeks and temples was performed using a 20 mg/mL HA filler, with an optional touch-up at 2 weeks follow-up. Patients were given a vision exam before treatment, immediately after treatment, and 15 minutes after treatment.

Quality of life was assessed before treatment and at 12 months follow-up using the Dermatology Life Quality Index (DLQI). Satisfaction was evaluated using a subject satisfaction questionnaire at 12 months follow-up, Mr. Ho and his colleagues reported.

DLQI scores were 1.6±3.0 (range = 0-11) and 0.5±1.2 (range = 0-5) at baseline and follow-up, respectively, the authors said. Additionally, 100% of patients reported high satisfaction as indicated by answers on the subject satisfaction questionnaire, they added.

The investigators warned, however, that they would not recommend the DLQI in the future as a measure of quality of life, as this scale focuses on disability, and fails to account for mental health issues.

Still, the findings highlight “the importance of educating and offering aesthetic and corrective treatment to all patients with HIV FLA,” the authors concluded.

Read the full article in the Journal of Drugs in Dermatology.

Long-acting bronchodilators, including tiotropium, do not appear to increase the risk of cardiovascular events in the first year of use, according to a study in patients with chronic obstructive pulmonary disease.

Long-acting bronchodilators are recommended as first-line maintenance therapy for chronic obstructive pulmonary disease (COPD), but they can cause cardiac complications, wrote Samy Suissa, PhD, and his colleagues at the Centre for Clinical Epidemiology, Lady Davis Institute, Montreal.

“Indeed, long-acting anticholinergics are believed to suppress parasympathetic control, while LABAs [long-acting beta2-agonists] stimulate sympathetic tone, possibly leading to tachyarrhythmia and coronary insufficiency,” the authors wrote (Chest. 2016 Aug 20. doi: 10.1016/j.chest.2016.08.001). “Furthermore, these pharmacologic effects would be expected to occur immediately at initiation of therapy.”

However, the observational studies and randomized trials comparing the safety of LABAs and the long-acting anticholinergic tiotropium have shown inconclusive results, possibly because of insufficient numbers, short follow-ups or “treatment-experienced” patients.

Dr. Suissa and his colleagues analyzed data from 26,442 new tiotropium users and 26,442 LABA initiators from a U.K. primary care database. Participants in each arm were matched on high-dimensional propensity scores and prior inhaled corticosteroid use, and followed for 1 year for occurrence of acute myocardial infarction, stroke, heart failure, arrhythmia, and pneumonia.

The researchers saw no significant difference between tiotropium and LABA users in the risk of acute myocardial infarction (hazard ratio, 1.10; 95% CI, 0.88-1.38), stroke (HR, 1.02; 95% CI, 0.78-1.34), arrhythmia (HR, 0.81; 95% CI, 0.60-1.09), or heart failure (HR, 0.90; 95% CI, 0.79-1.02). This was the case even when the current exposure time window was varied from 60-day periods to 30- or 90-day periods.

There was a significantly lower incidence of pneumonia in individuals treated with tiotropium (HR, 0.81; 95% CI, 0.72-0.92), which the authors suggested was likely due to the presence of inhaled corticosteroids in many LABAs.

“In our study, 78% of the LABA users were receiving a combined inhaler that included an inhaled corticosteroid, two-thirds of which were for fluticasone, which has been associated with an up to twofold increase in the risk of pneumonia,” they reported.

The authors acknowledged that the presence of an inhaled corticosteroid in combination with many of the LABAs could attract criticism that the study was therefore not a strict comparison between tiotropium and a LABA. However, they noted that the study aimed to represent the real-world experience of clinical practice.

“In this real-world–setting study of the treatment of COPD, the initiation of maintenance treatment with tiotropium compared with a LABA does not increase cardiovascular risk, but reduces significantly the risk of pneumonia, albeit a likely adverse effect of the inhaled corticosteroid component present in many LABA inhalers,” the authors wrote.

“This differential risk that appears to confer a safety advantage to tiotropium as the initial long-acting bronchodilator in COPD should be considered against the comparative effectiveness of these two treatments at initiation,” they noted.

The Canadian Institutes of Health Research, the Canadian Foundation for Innovation, and Boehringer Ingelheim supported the study. One author disclosed ties with Boehringer Ingelheim, AstraZeneca, Novartis, and Pfizer. No other conflicts of interest were declared.

Long-acting bronchodilators, including tiotropium, do not appear to increase the risk of cardiovascular events in the first year of use, according to a study in patients with chronic obstructive pulmonary disease.

Long-acting bronchodilators are recommended as first-line maintenance therapy for chronic obstructive pulmonary disease (COPD), but they can cause cardiac complications, wrote Samy Suissa, PhD, and his colleagues at the Centre for Clinical Epidemiology, Lady Davis Institute, Montreal.

“Indeed, long-acting anticholinergics are believed to suppress parasympathetic control, while LABAs [long-acting beta2-agonists] stimulate sympathetic tone, possibly leading to tachyarrhythmia and coronary insufficiency,” the authors wrote (Chest. 2016 Aug 20. doi: 10.1016/j.chest.2016.08.001). “Furthermore, these pharmacologic effects would be expected to occur immediately at initiation of therapy.”

However, the observational studies and randomized trials comparing the safety of LABAs and the long-acting anticholinergic tiotropium have shown inconclusive results, possibly because of insufficient numbers, short follow-ups or “treatment-experienced” patients.

Dr. Suissa and his colleagues analyzed data from 26,442 new tiotropium users and 26,442 LABA initiators from a U.K. primary care database. Participants in each arm were matched on high-dimensional propensity scores and prior inhaled corticosteroid use, and followed for 1 year for occurrence of acute myocardial infarction, stroke, heart failure, arrhythmia, and pneumonia.

The researchers saw no significant difference between tiotropium and LABA users in the risk of acute myocardial infarction (hazard ratio, 1.10; 95% CI, 0.88-1.38), stroke (HR, 1.02; 95% CI, 0.78-1.34), arrhythmia (HR, 0.81; 95% CI, 0.60-1.09), or heart failure (HR, 0.90; 95% CI, 0.79-1.02). This was the case even when the current exposure time window was varied from 60-day periods to 30- or 90-day periods.

There was a significantly lower incidence of pneumonia in individuals treated with tiotropium (HR, 0.81; 95% CI, 0.72-0.92), which the authors suggested was likely due to the presence of inhaled corticosteroids in many LABAs.

“In our study, 78% of the LABA users were receiving a combined inhaler that included an inhaled corticosteroid, two-thirds of which were for fluticasone, which has been associated with an up to twofold increase in the risk of pneumonia,” they reported.

The authors acknowledged that the presence of an inhaled corticosteroid in combination with many of the LABAs could attract criticism that the study was therefore not a strict comparison between tiotropium and a LABA. However, they noted that the study aimed to represent the real-world experience of clinical practice.

“In this real-world–setting study of the treatment of COPD, the initiation of maintenance treatment with tiotropium compared with a LABA does not increase cardiovascular risk, but reduces significantly the risk of pneumonia, albeit a likely adverse effect of the inhaled corticosteroid component present in many LABA inhalers,” the authors wrote.

“This differential risk that appears to confer a safety advantage to tiotropium as the initial long-acting bronchodilator in COPD should be considered against the comparative effectiveness of these two treatments at initiation,” they noted.

The Canadian Institutes of Health Research, the Canadian Foundation for Innovation, and Boehringer Ingelheim supported the study. One author disclosed ties with Boehringer Ingelheim, AstraZeneca, Novartis, and Pfizer. No other conflicts of interest were declared.

Long-acting bronchodilators, including tiotropium, do not appear to increase the risk of cardiovascular events in the first year of use, according to a study in patients with chronic obstructive pulmonary disease.

Long-acting bronchodilators are recommended as first-line maintenance therapy for chronic obstructive pulmonary disease (COPD), but they can cause cardiac complications, wrote Samy Suissa, PhD, and his colleagues at the Centre for Clinical Epidemiology, Lady Davis Institute, Montreal.

“Indeed, long-acting anticholinergics are believed to suppress parasympathetic control, while LABAs [long-acting beta2-agonists] stimulate sympathetic tone, possibly leading to tachyarrhythmia and coronary insufficiency,” the authors wrote (Chest. 2016 Aug 20. doi: 10.1016/j.chest.2016.08.001). “Furthermore, these pharmacologic effects would be expected to occur immediately at initiation of therapy.”

However, the observational studies and randomized trials comparing the safety of LABAs and the long-acting anticholinergic tiotropium have shown inconclusive results, possibly because of insufficient numbers, short follow-ups or “treatment-experienced” patients.

Dr. Suissa and his colleagues analyzed data from 26,442 new tiotropium users and 26,442 LABA initiators from a U.K. primary care database. Participants in each arm were matched on high-dimensional propensity scores and prior inhaled corticosteroid use, and followed for 1 year for occurrence of acute myocardial infarction, stroke, heart failure, arrhythmia, and pneumonia.

The researchers saw no significant difference between tiotropium and LABA users in the risk of acute myocardial infarction (hazard ratio, 1.10; 95% CI, 0.88-1.38), stroke (HR, 1.02; 95% CI, 0.78-1.34), arrhythmia (HR, 0.81; 95% CI, 0.60-1.09), or heart failure (HR, 0.90; 95% CI, 0.79-1.02). This was the case even when the current exposure time window was varied from 60-day periods to 30- or 90-day periods.

There was a significantly lower incidence of pneumonia in individuals treated with tiotropium (HR, 0.81; 95% CI, 0.72-0.92), which the authors suggested was likely due to the presence of inhaled corticosteroids in many LABAs.

“In our study, 78% of the LABA users were receiving a combined inhaler that included an inhaled corticosteroid, two-thirds of which were for fluticasone, which has been associated with an up to twofold increase in the risk of pneumonia,” they reported.

The authors acknowledged that the presence of an inhaled corticosteroid in combination with many of the LABAs could attract criticism that the study was therefore not a strict comparison between tiotropium and a LABA. However, they noted that the study aimed to represent the real-world experience of clinical practice.

“In this real-world–setting study of the treatment of COPD, the initiation of maintenance treatment with tiotropium compared with a LABA does not increase cardiovascular risk, but reduces significantly the risk of pneumonia, albeit a likely adverse effect of the inhaled corticosteroid component present in many LABA inhalers,” the authors wrote.

“This differential risk that appears to confer a safety advantage to tiotropium as the initial long-acting bronchodilator in COPD should be considered against the comparative effectiveness of these two treatments at initiation,” they noted.

The Canadian Institutes of Health Research, the Canadian Foundation for Innovation, and Boehringer Ingelheim supported the study. One author disclosed ties with Boehringer Ingelheim, AstraZeneca, Novartis, and Pfizer. No other conflicts of interest were declared.

Naturally occurring variations on or near the NPC1L1 gene, which is linked to lower LDL-cholesterol levels, were associated with a higher risk of type 2 diabetes in a meta-analysis reported online Oct. 4 in JAMA.

©Christian Jasiuk/Thinkstock

Some cholesterol-lowering medications, notably ezetimibe, work by inhibiting the action of the NPC1L1 gene. The findings of this meta-analysis suggest that by doing so, these cholesterol-lowering agents may raise the risk of type 2 diabetes, said Luca A. Lotta, MD, PhD, of the Medical Research Council Epidemiology Unit, University of Cambridge (U.K.), and his associates. The investigators examined gene-association analyses in several studies and databases covering 50,775 adults with type 2 diabetes and 270,269 control subjects in Europe and the United States during 1991-2016. They found that alleles at the NPC1L1 locus that are known to be associated with lower LDL-cholesterol levels also were strongly associated with higher rates of diabetes. For every genetically predicted reduction in LDL-C of 1 mmol/L, the risk for type 2 diabetes increased (odds ratio, 2.42).

The estimated absolute risk difference was 5.3 incident cases/1,000 person-years for every genetically predicted 1-mmol/L reduction in LDL-C, Dr. Lotta and his associates said (JAMA. 2016 Oct. 4. doi: 10.1001/jama.2016.14568).

These findings are consistent with reports that link cholesterol-lowering medications with weight gain and a higher incidence of new-onset type 2 diabetes, as well as with the clinical observation that patients with familial hypercholesterolemia carry a lower risk for diabetes. “These results warrant the continued monitoring of the glycemic effects of ezetimibe in clinical trials and in clinical practice,” the researchers noted.

Naturally occurring variations on or near the NPC1L1 gene, which is linked to lower LDL-cholesterol levels, were associated with a higher risk of type 2 diabetes in a meta-analysis reported online Oct. 4 in JAMA.

©Christian Jasiuk/Thinkstock

Some cholesterol-lowering medications, notably ezetimibe, work by inhibiting the action of the NPC1L1 gene. The findings of this meta-analysis suggest that by doing so, these cholesterol-lowering agents may raise the risk of type 2 diabetes, said Luca A. Lotta, MD, PhD, of the Medical Research Council Epidemiology Unit, University of Cambridge (U.K.), and his associates. The investigators examined gene-association analyses in several studies and databases covering 50,775 adults with type 2 diabetes and 270,269 control subjects in Europe and the United States during 1991-2016. They found that alleles at the NPC1L1 locus that are known to be associated with lower LDL-cholesterol levels also were strongly associated with higher rates of diabetes. For every genetically predicted reduction in LDL-C of 1 mmol/L, the risk for type 2 diabetes increased (odds ratio, 2.42).

The estimated absolute risk difference was 5.3 incident cases/1,000 person-years for every genetically predicted 1-mmol/L reduction in LDL-C, Dr. Lotta and his associates said (JAMA. 2016 Oct. 4. doi: 10.1001/jama.2016.14568).

These findings are consistent with reports that link cholesterol-lowering medications with weight gain and a higher incidence of new-onset type 2 diabetes, as well as with the clinical observation that patients with familial hypercholesterolemia carry a lower risk for diabetes. “These results warrant the continued monitoring of the glycemic effects of ezetimibe in clinical trials and in clinical practice,” the researchers noted.

Naturally occurring variations on or near the NPC1L1 gene, which is linked to lower LDL-cholesterol levels, were associated with a higher risk of type 2 diabetes in a meta-analysis reported online Oct. 4 in JAMA.

©Christian Jasiuk/Thinkstock

Some cholesterol-lowering medications, notably ezetimibe, work by inhibiting the action of the NPC1L1 gene. The findings of this meta-analysis suggest that by doing so, these cholesterol-lowering agents may raise the risk of type 2 diabetes, said Luca A. Lotta, MD, PhD, of the Medical Research Council Epidemiology Unit, University of Cambridge (U.K.), and his associates. The investigators examined gene-association analyses in several studies and databases covering 50,775 adults with type 2 diabetes and 270,269 control subjects in Europe and the United States during 1991-2016. They found that alleles at the NPC1L1 locus that are known to be associated with lower LDL-cholesterol levels also were strongly associated with higher rates of diabetes. For every genetically predicted reduction in LDL-C of 1 mmol/L, the risk for type 2 diabetes increased (odds ratio, 2.42).

The estimated absolute risk difference was 5.3 incident cases/1,000 person-years for every genetically predicted 1-mmol/L reduction in LDL-C, Dr. Lotta and his associates said (JAMA. 2016 Oct. 4. doi: 10.1001/jama.2016.14568).

These findings are consistent with reports that link cholesterol-lowering medications with weight gain and a higher incidence of new-onset type 2 diabetes, as well as with the clinical observation that patients with familial hypercholesterolemia carry a lower risk for diabetes. “These results warrant the continued monitoring of the glycemic effects of ezetimibe in clinical trials and in clinical practice,” the researchers noted.

WAIKOLOA, HAWAII – Trauma training for general surgery residents has significantly declined in recent years, results from an analysis of the Accreditation Council for Graduate Medical Education data registry on surgical education showed.

Aaron Strumwasser, MD, an attending trauma surgeon and surgical intensivist at the Los Angeles County/University of Southern California Medical Center, characterized the decline in trauma training as “sobering.” In an effort to test their hypothesis that trauma training for general surgery residents is on the decline since the inception of the 80-hour workweek, Dr. Strumwasser and his associates set out to compare the operative caseloads before and after the inception of the 80-hour workweek; to note trends in specific operative domains and determine if deficiencies exist and to determine whether subspecialty training (specifically, vascular fellowship and integrated vascular surgery residency) has altered general surgery resident operative volume. They extracted data from the ACGME database on resident trauma volume for trauma cases by category and by resident training year for the years 1999-2015. Only those cases logged as primary surgery were included. The researchers subdivided trauma cases into five domains: head and neck, thoracic, abdomen, solid organ, and extremity. Resident trauma experience (operative caseload) was compared, based on before the inception of the 80-hour workweek (1999-2002) and after (2003-present).

Spotmatik/Thinkstock

[email protected]

WAIKOLOA, HAWAII – Trauma training for general surgery residents has significantly declined in recent years, results from an analysis of the Accreditation Council for Graduate Medical Education data registry on surgical education showed.

Aaron Strumwasser, MD, an attending trauma surgeon and surgical intensivist at the Los Angeles County/University of Southern California Medical Center, characterized the decline in trauma training as “sobering.” In an effort to test their hypothesis that trauma training for general surgery residents is on the decline since the inception of the 80-hour workweek, Dr. Strumwasser and his associates set out to compare the operative caseloads before and after the inception of the 80-hour workweek; to note trends in specific operative domains and determine if deficiencies exist and to determine whether subspecialty training (specifically, vascular fellowship and integrated vascular surgery residency) has altered general surgery resident operative volume. They extracted data from the ACGME database on resident trauma volume for trauma cases by category and by resident training year for the years 1999-2015. Only those cases logged as primary surgery were included. The researchers subdivided trauma cases into five domains: head and neck, thoracic, abdomen, solid organ, and extremity. Resident trauma experience (operative caseload) was compared, based on before the inception of the 80-hour workweek (1999-2002) and after (2003-present).

Spotmatik/Thinkstock

[email protected]

WAIKOLOA, HAWAII – Trauma training for general surgery residents has significantly declined in recent years, results from an analysis of the Accreditation Council for Graduate Medical Education data registry on surgical education showed.

Aaron Strumwasser, MD, an attending trauma surgeon and surgical intensivist at the Los Angeles County/University of Southern California Medical Center, characterized the decline in trauma training as “sobering.” In an effort to test their hypothesis that trauma training for general surgery residents is on the decline since the inception of the 80-hour workweek, Dr. Strumwasser and his associates set out to compare the operative caseloads before and after the inception of the 80-hour workweek; to note trends in specific operative domains and determine if deficiencies exist and to determine whether subspecialty training (specifically, vascular fellowship and integrated vascular surgery residency) has altered general surgery resident operative volume. They extracted data from the ACGME database on resident trauma volume for trauma cases by category and by resident training year for the years 1999-2015. Only those cases logged as primary surgery were included. The researchers subdivided trauma cases into five domains: head and neck, thoracic, abdomen, solid organ, and extremity. Resident trauma experience (operative caseload) was compared, based on before the inception of the 80-hour workweek (1999-2002) and after (2003-present).

Spotmatik/Thinkstock

[email protected]

LAS VEGAS – Patients with rheumatoid arthritis who have pulmonary symptoms and a restrictive pulmonary function test pattern have a high likelihood for a diagnosis of interstitial lung disease, making it necessary to put it high on the differential and to begin working collaboratively with pulmonologists, according to Jon T. Giles, MD.

Overall, 8%-15% of RA patients will develop clinically significant interstitial lung disease (ILD), although radiographic evidence of ILD can be seen in up to half of RA patients, and in one study about one in four patients had evidence of ILD on CT scanning within 2 years of RA diagnosis. The overall risk for RA patients to develop ILD has been shown to be nine times higher than for matched controls (Arthritis Rheum. 2010 Jun;62[6]:1583-91), Dr. Giles said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

An “alphabet soup” of ILD subtypes

Though there’s an “alphabet soup” of subtypes of ILD in RA, 90% of RA patients with ILD will have one of two conditions: usual interstitial pneumonitis (RA-UIP) or nonspecific interstitial pneumonitis (RA-NSIP). It’s not entirely clear whether one type of RA-ILD has a survival advantage over the other, Dr. Giles said.

Care for RA patients should include screening for ILD, said Dr. Giles. Physicians should ask about dry cough, dyspnea, and decreased exercise tolerance. Signs of ILD can include diminished oxygen saturation, a cardiac exam consistent with right heart disease, and rales. It’s not clear, he said, whether periodic chest radiographs or pulmonary function testing in asymptomatic RA patients is warranted.

Positive findings should prompt pulmonary function testing to include DLCO (diffusing capacity of lung for carbon monoxide), which may or may not be reduced in patients with clinically significant ILD. However, testing will show a restrictive pattern. A high-resolution chest CT should also be obtained.

Further evaluation should be done collaboratively with pulmonologists, and preferably with an ILD center, said Dr. Giles. A bronchoalveolar lavage and/or a lung biopsy may be considered.

Radiographic features of RA-UIP can include reticulation and honeycombing, predominantly seen in a subpleural and basilar distribution. Traction bronchiectasis may or may not be present. If a biopsy is performed, the histologic presentation of RA-UIP includes subpleural patches of dense fibrosis and honeycombing adjacent to healthy lung tissue; fibroblastic foci may be seen in the fibrotic regions.

In differentiating RA-UIP from interstitial pulmonary fibrosis (IPF), Dr. Giles said that lymphoid hyperplasia with germinal centers and peribronchial lesions are both more common in RA-UIP than in IPF. By contrast, fibroblastic foci are less common in RA-UIP than in IPF.

Sorting out the relationship between the use of disease-modifying antirheumatic drugs and ILD in RA is complicated by “complexities of attribution,” said Dr. Giles, since “RA patients with the most severe or refractory disease are more likely to both be exposed to a great number of RA therapies and higher doses and more combinations, and to have more risk factors for ILD.” Additionally, hypersensitivity pneumonitis can share some features with some subtypes of RA-ILD.

Treatment goals

Beyond maximizing smoking-cessation intervention, which should be done for all currently smoking ILD patients, treatment goals for RA-ILD are “a balancing act,” Dr. Giles said. Immunizations should be up to date for all RA-ILD patients, and any concomitant pulmonary conditions, such as asthma or chronic obstructive pulmonary disorder, should also be optimally treated. An early evaluation for lung transplant is warranted for RA-ILD as well, he said.

If patients are symptomatic, then the goal is symptom reduction, with the extent of radiographically or histologically documented involvement and the rate of decline to be factored into treatment decisions.

Immunosuppressive treatments for RA-ILD, Dr. Giles said, “are not supported by any randomized clinical trials.” However, corticosteroids are often effective for RA-NSIP; “UIP is often not steroid responsive,” he said. Other agents can include azathioprine, which can give a “double whammy” effect by addressing joint and lung disease. However, azathioprine should not be used concurrently with corticosteroids, he said.

Mycophenolate mofetil (CellCept) has known antifibrotic effects, and there have been case reports of improvement in RA-ILD. Cyclophosphamide is also occasionally used. A host of other treatments have been attempted, including the antifibrotics pirfenidone (Esbriet) and nintedanib (Ofev), although these have been studied only in interstitial pulmonary fibrosis, said Dr. Giles. “Treating symptomatic RA-ILD is always a challenge,” he said.

Dr. Giles has been a consultant to Roche/Genentech and Proximagen and has received grant funding from Pfizer.

Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – Patients with rheumatoid arthritis who have pulmonary symptoms and a restrictive pulmonary function test pattern have a high likelihood for a diagnosis of interstitial lung disease, making it necessary to put it high on the differential and to begin working collaboratively with pulmonologists, according to Jon T. Giles, MD.

Overall, 8%-15% of RA patients will develop clinically significant interstitial lung disease (ILD), although radiographic evidence of ILD can be seen in up to half of RA patients, and in one study about one in four patients had evidence of ILD on CT scanning within 2 years of RA diagnosis. The overall risk for RA patients to develop ILD has been shown to be nine times higher than for matched controls (Arthritis Rheum. 2010 Jun;62[6]:1583-91), Dr. Giles said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

An “alphabet soup” of ILD subtypes

Though there’s an “alphabet soup” of subtypes of ILD in RA, 90% of RA patients with ILD will have one of two conditions: usual interstitial pneumonitis (RA-UIP) or nonspecific interstitial pneumonitis (RA-NSIP). It’s not entirely clear whether one type of RA-ILD has a survival advantage over the other, Dr. Giles said.

Care for RA patients should include screening for ILD, said Dr. Giles. Physicians should ask about dry cough, dyspnea, and decreased exercise tolerance. Signs of ILD can include diminished oxygen saturation, a cardiac exam consistent with right heart disease, and rales. It’s not clear, he said, whether periodic chest radiographs or pulmonary function testing in asymptomatic RA patients is warranted.

Positive findings should prompt pulmonary function testing to include DLCO (diffusing capacity of lung for carbon monoxide), which may or may not be reduced in patients with clinically significant ILD. However, testing will show a restrictive pattern. A high-resolution chest CT should also be obtained.

Further evaluation should be done collaboratively with pulmonologists, and preferably with an ILD center, said Dr. Giles. A bronchoalveolar lavage and/or a lung biopsy may be considered.

Radiographic features of RA-UIP can include reticulation and honeycombing, predominantly seen in a subpleural and basilar distribution. Traction bronchiectasis may or may not be present. If a biopsy is performed, the histologic presentation of RA-UIP includes subpleural patches of dense fibrosis and honeycombing adjacent to healthy lung tissue; fibroblastic foci may be seen in the fibrotic regions.

In differentiating RA-UIP from interstitial pulmonary fibrosis (IPF), Dr. Giles said that lymphoid hyperplasia with germinal centers and peribronchial lesions are both more common in RA-UIP than in IPF. By contrast, fibroblastic foci are less common in RA-UIP than in IPF.

Sorting out the relationship between the use of disease-modifying antirheumatic drugs and ILD in RA is complicated by “complexities of attribution,” said Dr. Giles, since “RA patients with the most severe or refractory disease are more likely to both be exposed to a great number of RA therapies and higher doses and more combinations, and to have more risk factors for ILD.” Additionally, hypersensitivity pneumonitis can share some features with some subtypes of RA-ILD.

Treatment goals

Beyond maximizing smoking-cessation intervention, which should be done for all currently smoking ILD patients, treatment goals for RA-ILD are “a balancing act,” Dr. Giles said. Immunizations should be up to date for all RA-ILD patients, and any concomitant pulmonary conditions, such as asthma or chronic obstructive pulmonary disorder, should also be optimally treated. An early evaluation for lung transplant is warranted for RA-ILD as well, he said.

If patients are symptomatic, then the goal is symptom reduction, with the extent of radiographically or histologically documented involvement and the rate of decline to be factored into treatment decisions.

Immunosuppressive treatments for RA-ILD, Dr. Giles said, “are not supported by any randomized clinical trials.” However, corticosteroids are often effective for RA-NSIP; “UIP is often not steroid responsive,” he said. Other agents can include azathioprine, which can give a “double whammy” effect by addressing joint and lung disease. However, azathioprine should not be used concurrently with corticosteroids, he said.

Mycophenolate mofetil (CellCept) has known antifibrotic effects, and there have been case reports of improvement in RA-ILD. Cyclophosphamide is also occasionally used. A host of other treatments have been attempted, including the antifibrotics pirfenidone (Esbriet) and nintedanib (Ofev), although these have been studied only in interstitial pulmonary fibrosis, said Dr. Giles. “Treating symptomatic RA-ILD is always a challenge,” he said.

Dr. Giles has been a consultant to Roche/Genentech and Proximagen and has received grant funding from Pfizer.

Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes

LAS VEGAS – Patients with rheumatoid arthritis who have pulmonary symptoms and a restrictive pulmonary function test pattern have a high likelihood for a diagnosis of interstitial lung disease, making it necessary to put it high on the differential and to begin working collaboratively with pulmonologists, according to Jon T. Giles, MD.

Overall, 8%-15% of RA patients will develop clinically significant interstitial lung disease (ILD), although radiographic evidence of ILD can be seen in up to half of RA patients, and in one study about one in four patients had evidence of ILD on CT scanning within 2 years of RA diagnosis. The overall risk for RA patients to develop ILD has been shown to be nine times higher than for matched controls (Arthritis Rheum. 2010 Jun;62[6]:1583-91), Dr. Giles said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

An “alphabet soup” of ILD subtypes

Though there’s an “alphabet soup” of subtypes of ILD in RA, 90% of RA patients with ILD will have one of two conditions: usual interstitial pneumonitis (RA-UIP) or nonspecific interstitial pneumonitis (RA-NSIP). It’s not entirely clear whether one type of RA-ILD has a survival advantage over the other, Dr. Giles said.

Care for RA patients should include screening for ILD, said Dr. Giles. Physicians should ask about dry cough, dyspnea, and decreased exercise tolerance. Signs of ILD can include diminished oxygen saturation, a cardiac exam consistent with right heart disease, and rales. It’s not clear, he said, whether periodic chest radiographs or pulmonary function testing in asymptomatic RA patients is warranted.

Positive findings should prompt pulmonary function testing to include DLCO (diffusing capacity of lung for carbon monoxide), which may or may not be reduced in patients with clinically significant ILD. However, testing will show a restrictive pattern. A high-resolution chest CT should also be obtained.

Further evaluation should be done collaboratively with pulmonologists, and preferably with an ILD center, said Dr. Giles. A bronchoalveolar lavage and/or a lung biopsy may be considered.

Radiographic features of RA-UIP can include reticulation and honeycombing, predominantly seen in a subpleural and basilar distribution. Traction bronchiectasis may or may not be present. If a biopsy is performed, the histologic presentation of RA-UIP includes subpleural patches of dense fibrosis and honeycombing adjacent to healthy lung tissue; fibroblastic foci may be seen in the fibrotic regions.

In differentiating RA-UIP from interstitial pulmonary fibrosis (IPF), Dr. Giles said that lymphoid hyperplasia with germinal centers and peribronchial lesions are both more common in RA-UIP than in IPF. By contrast, fibroblastic foci are less common in RA-UIP than in IPF.

Sorting out the relationship between the use of disease-modifying antirheumatic drugs and ILD in RA is complicated by “complexities of attribution,” said Dr. Giles, since “RA patients with the most severe or refractory disease are more likely to both be exposed to a great number of RA therapies and higher doses and more combinations, and to have more risk factors for ILD.” Additionally, hypersensitivity pneumonitis can share some features with some subtypes of RA-ILD.

Treatment goals

Beyond maximizing smoking-cessation intervention, which should be done for all currently smoking ILD patients, treatment goals for RA-ILD are “a balancing act,” Dr. Giles said. Immunizations should be up to date for all RA-ILD patients, and any concomitant pulmonary conditions, such as asthma or chronic obstructive pulmonary disorder, should also be optimally treated. An early evaluation for lung transplant is warranted for RA-ILD as well, he said.

If patients are symptomatic, then the goal is symptom reduction, with the extent of radiographically or histologically documented involvement and the rate of decline to be factored into treatment decisions.

Immunosuppressive treatments for RA-ILD, Dr. Giles said, “are not supported by any randomized clinical trials.” However, corticosteroids are often effective for RA-NSIP; “UIP is often not steroid responsive,” he said. Other agents can include azathioprine, which can give a “double whammy” effect by addressing joint and lung disease. However, azathioprine should not be used concurrently with corticosteroids, he said.

Mycophenolate mofetil (CellCept) has known antifibrotic effects, and there have been case reports of improvement in RA-ILD. Cyclophosphamide is also occasionally used. A host of other treatments have been attempted, including the antifibrotics pirfenidone (Esbriet) and nintedanib (Ofev), although these have been studied only in interstitial pulmonary fibrosis, said Dr. Giles. “Treating symptomatic RA-ILD is always a challenge,” he said.

Dr. Giles has been a consultant to Roche/Genentech and Proximagen and has received grant funding from Pfizer.

Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

On Twitter @karioakes