The Journal of Family Practice

EVIDENCE SUMMARY

A systematic review of the effect of combined OCPs on women with a family history of breast cancer found no additional increase in risk.¹ Investigators identified 3 retrospective cohort studies (N=66,500, with 8500 cases) and 7 case-control studies (total 10,500 cases) from the past 40 years, most including women from the United States and Canada, but one including women from 5 continents.

In most trials, women of reproductive age using combined OCPs had 1 or more first-degree female relatives with breast cancer, although a few trials also included second-degree relatives. Women ranged in age from 20 to 79 years at diagnosis, and most trials controlled for age, parity, menstrual and menopausal history, duration of OCP exposure, and age at first use. Follow-up intervals for the retrospective cohort studies ranged from 5 to 16 years. Investigators were unable to combine results because of heterogenous populations.

Three of the cohort studies found no significant difference in breast cancer risk between OCP users and nonusers, regardless of age or duration of use. One cohort study found an increased risk in women taking older, higher-dose OCPs from before 1975 (relative risk [RR]=3.3; 95% confidence interval [CI], 1.5-7.2). All of the case-control studies found no significant difference in breast cancer risk for any age of starting, duration of OCP use, or degree of relative with breast cancer.

A meta-analysis of 54 case-control studies (6757 cases), comprising approximately 90% of the epidemiologic information on this topic, also found no significant difference in breast cancer risk related to OCP use among women with one or more first-degree relatives with breast cancer.² Investigators found that neither recent OCP use (<10 years, RR=0.77; 95% CI, 0.54-1.11) nor past OCP use (>10 years, RR=1.01; 95% CI, 0.80-1.28) affected risk of developing breast cancer.

Three additional case-control studies involving women with a family history of breast cancer also found no significant association for breast cancer incidence among OCP users compared with nonusers.^3-5

 

 

Modern combined OCPs don’t raise risk in women with BRCA1/2 mutations


A meta-analysis of 5 studies (one retrospective cohort, 4 case-control, with a total of 2855 breast cancer cases and 2944 controls) evaluated whether combined OCPs increased the risk of breast cancer in women, all of whom were carrying BRCA1/2 mutations.⁶

Using modern combined OCPs didn’t raise the risk of breast cancer in BRCA1/2 carriers overall (RR=1.13; 95% CI, 0.88-1.45) or separately in BRCA1 carriers (5 studies, RR=1.09; 95% CI, 0.77-1.54) or BRCA2 carriers (3 studies, RR=1.15; 95% CI, 0.88-1.45).

However, pre-1975 (higher dose) combined OCPs produced significantly increased risk (RR=1.47; 95% CI, 1.06-2.04). Similarly, women who had used combined OCPs >10 years before the study (older women, likely to have been using pre-1975 OCPs) also had significantly increased risk (RR=1.46; 95% CI, 1.07-2.07).

A bit of good news:
 Combined OCPs reduce ovarian cancer risk

The analysis also determined that combined OCPs significantly reduced the risk of ovarian cancer in women carrying BRCA1/2 mutations (RR=0.50; 95% CI, 0.33-0.75), with an additional linear decrease in risk for each 10 years of OCP use (RR=0.64; 95% CI, 0.53-0.78).

RECOMMENDATIONS

Combined oral contraceptive pills significantly reduced the risk of ovarian cancer in women carrying BRCA1/2 mutations. The World Health Organization guidelines outlining criteria for contraceptive use state that OCPs don’t alter the risk of breast cancer among women with either a family history of breast cancer or breast cancer susceptibility genes.⁷

The American College of Obstetricians and Gynecologists (ACOG) says that a positive family history of breast cancer shouldn’t be regarded as a contraindication to OCP use.⁸ ACOG also says that women with the BRCA1 mutation have an increased risk of breast cancer if they used OCPs for longer than 5 years before age 30, but this risk may be more than balanced by the benefit of a greatly reduced risk of ovarian cancer.

EVIDENCE SUMMARY

A systematic review of the effect of combined OCPs on women with a family history of breast cancer found no additional increase in risk.¹ Investigators identified 3 retrospective cohort studies (N=66,500, with 8500 cases) and 7 case-control studies (total 10,500 cases) from the past 40 years, most including women from the United States and Canada, but one including women from 5 continents.

In most trials, women of reproductive age using combined OCPs had 1 or more first-degree female relatives with breast cancer, although a few trials also included second-degree relatives. Women ranged in age from 20 to 79 years at diagnosis, and most trials controlled for age, parity, menstrual and menopausal history, duration of OCP exposure, and age at first use. Follow-up intervals for the retrospective cohort studies ranged from 5 to 16 years. Investigators were unable to combine results because of heterogenous populations.

Three of the cohort studies found no significant difference in breast cancer risk between OCP users and nonusers, regardless of age or duration of use. One cohort study found an increased risk in women taking older, higher-dose OCPs from before 1975 (relative risk [RR]=3.3; 95% confidence interval [CI], 1.5-7.2). All of the case-control studies found no significant difference in breast cancer risk for any age of starting, duration of OCP use, or degree of relative with breast cancer.

A meta-analysis of 54 case-control studies (6757 cases), comprising approximately 90% of the epidemiologic information on this topic, also found no significant difference in breast cancer risk related to OCP use among women with one or more first-degree relatives with breast cancer.² Investigators found that neither recent OCP use (<10 years, RR=0.77; 95% CI, 0.54-1.11) nor past OCP use (>10 years, RR=1.01; 95% CI, 0.80-1.28) affected risk of developing breast cancer.

Three additional case-control studies involving women with a family history of breast cancer also found no significant association for breast cancer incidence among OCP users compared with nonusers.^3-5

 

 

Modern combined OCPs don’t raise risk in women with BRCA1/2 mutations


A meta-analysis of 5 studies (one retrospective cohort, 4 case-control, with a total of 2855 breast cancer cases and 2944 controls) evaluated whether combined OCPs increased the risk of breast cancer in women, all of whom were carrying BRCA1/2 mutations.⁶

Using modern combined OCPs didn’t raise the risk of breast cancer in BRCA1/2 carriers overall (RR=1.13; 95% CI, 0.88-1.45) or separately in BRCA1 carriers (5 studies, RR=1.09; 95% CI, 0.77-1.54) or BRCA2 carriers (3 studies, RR=1.15; 95% CI, 0.88-1.45).

However, pre-1975 (higher dose) combined OCPs produced significantly increased risk (RR=1.47; 95% CI, 1.06-2.04). Similarly, women who had used combined OCPs >10 years before the study (older women, likely to have been using pre-1975 OCPs) also had significantly increased risk (RR=1.46; 95% CI, 1.07-2.07).

A bit of good news:
 Combined OCPs reduce ovarian cancer risk

The analysis also determined that combined OCPs significantly reduced the risk of ovarian cancer in women carrying BRCA1/2 mutations (RR=0.50; 95% CI, 0.33-0.75), with an additional linear decrease in risk for each 10 years of OCP use (RR=0.64; 95% CI, 0.53-0.78).

RECOMMENDATIONS

Combined oral contraceptive pills significantly reduced the risk of ovarian cancer in women carrying BRCA1/2 mutations. The World Health Organization guidelines outlining criteria for contraceptive use state that OCPs don’t alter the risk of breast cancer among women with either a family history of breast cancer or breast cancer susceptibility genes.⁷

The American College of Obstetricians and Gynecologists (ACOG) says that a positive family history of breast cancer shouldn’t be regarded as a contraindication to OCP use.⁸ ACOG also says that women with the BRCA1 mutation have an increased risk of breast cancer if they used OCPs for longer than 5 years before age 30, but this risk may be more than balanced by the benefit of a greatly reduced risk of ovarian cancer.

EVIDENCE SUMMARY

A systematic review of the effect of combined OCPs on women with a family history of breast cancer found no additional increase in risk.¹ Investigators identified 3 retrospective cohort studies (N=66,500, with 8500 cases) and 7 case-control studies (total 10,500 cases) from the past 40 years, most including women from the United States and Canada, but one including women from 5 continents.

In most trials, women of reproductive age using combined OCPs had 1 or more first-degree female relatives with breast cancer, although a few trials also included second-degree relatives. Women ranged in age from 20 to 79 years at diagnosis, and most trials controlled for age, parity, menstrual and menopausal history, duration of OCP exposure, and age at first use. Follow-up intervals for the retrospective cohort studies ranged from 5 to 16 years. Investigators were unable to combine results because of heterogenous populations.

Three of the cohort studies found no significant difference in breast cancer risk between OCP users and nonusers, regardless of age or duration of use. One cohort study found an increased risk in women taking older, higher-dose OCPs from before 1975 (relative risk [RR]=3.3; 95% confidence interval [CI], 1.5-7.2). All of the case-control studies found no significant difference in breast cancer risk for any age of starting, duration of OCP use, or degree of relative with breast cancer.

A meta-analysis of 54 case-control studies (6757 cases), comprising approximately 90% of the epidemiologic information on this topic, also found no significant difference in breast cancer risk related to OCP use among women with one or more first-degree relatives with breast cancer.² Investigators found that neither recent OCP use (<10 years, RR=0.77; 95% CI, 0.54-1.11) nor past OCP use (>10 years, RR=1.01; 95% CI, 0.80-1.28) affected risk of developing breast cancer.

Three additional case-control studies involving women with a family history of breast cancer also found no significant association for breast cancer incidence among OCP users compared with nonusers.^3-5

 

 

Modern combined OCPs don’t raise risk in women with BRCA1/2 mutations


A meta-analysis of 5 studies (one retrospective cohort, 4 case-control, with a total of 2855 breast cancer cases and 2944 controls) evaluated whether combined OCPs increased the risk of breast cancer in women, all of whom were carrying BRCA1/2 mutations.⁶

Using modern combined OCPs didn’t raise the risk of breast cancer in BRCA1/2 carriers overall (RR=1.13; 95% CI, 0.88-1.45) or separately in BRCA1 carriers (5 studies, RR=1.09; 95% CI, 0.77-1.54) or BRCA2 carriers (3 studies, RR=1.15; 95% CI, 0.88-1.45).

However, pre-1975 (higher dose) combined OCPs produced significantly increased risk (RR=1.47; 95% CI, 1.06-2.04). Similarly, women who had used combined OCPs >10 years before the study (older women, likely to have been using pre-1975 OCPs) also had significantly increased risk (RR=1.46; 95% CI, 1.07-2.07).

A bit of good news:
 Combined OCPs reduce ovarian cancer risk

The analysis also determined that combined OCPs significantly reduced the risk of ovarian cancer in women carrying BRCA1/2 mutations (RR=0.50; 95% CI, 0.33-0.75), with an additional linear decrease in risk for each 10 years of OCP use (RR=0.64; 95% CI, 0.53-0.78).

RECOMMENDATIONS

Combined oral contraceptive pills significantly reduced the risk of ovarian cancer in women carrying BRCA1/2 mutations. The World Health Organization guidelines outlining criteria for contraceptive use state that OCPs don’t alter the risk of breast cancer among women with either a family history of breast cancer or breast cancer susceptibility genes.⁷

The American College of Obstetricians and Gynecologists (ACOG) says that a positive family history of breast cancer shouldn’t be regarded as a contraindication to OCP use.⁸ ACOG also says that women with the BRCA1 mutation have an increased risk of breast cancer if they used OCPs for longer than 5 years before age 30, but this risk may be more than balanced by the benefit of a greatly reduced risk of ovarian cancer.

Illustrative case

A 40-year-old man comes to your office for follow-up of medial left knee pain he’s had for 3 months that hasn’t responded to conservative treatment. The pain developed gradually, without a history of trauma. The patient has no signs of degenerative joint disease on x-ray but magnetic resonance imaging (MRI) reveals a tear of the medial meniscus. Should you refer him for meniscectomy?

Patients and doctors alike tend to look for a treatment that will “fix” the problem, which may be why we have continued to use arthroscopic partial meniscectomy to attempt to relieve symptoms of meniscal tears despite a lack of evidence to support the practice.

Guidelines from the American Academy of Orthopaedic Surgeons state that the evidence for medial meniscectomy in patients with a torn meniscus and osteoarthritis (OA) is inconclusive; the organization offers no guidelines for patients with a torn meniscus who don’t have OA.² The American College of Occupational and Environmental Medicine states that there is insufficient evidence to support arthroscopic partial meniscectomy for symptomatic, torn medial menisci for select patients and “the vast majority of patients [with medial meniscal tears] do not require surgery.”³ Previous studies have concluded that arthroscopic surgery for OA of the knee provides no additional benefit to optimized physical and medical therapy.⁴ Furthermore, research by Katz et al⁵ shows that meniscectomy provides no benefit over conservative treatment in functional status at 6 months in patients with OA and a medial meniscal tear.

That said, arthroscopic partial meniscectomy is still the most common orthopedic procedure in the United States.¹ Although its use has decreased over the last 15 years, it is performed nearly 700,000 times annually at a cost of approximately $4 billion.^1,6,7 Like any surgical procedure, meniscectomy carries a risk of complications. In the double-blind, randomized trial reported on here, Sihvonen et al¹ compared meniscectomy to a sham procedure for patients with knee pain, but not OA.

STUDY SUMMARY: Meniscectomy and sham surgery 
are equally effective


Sihvonen et al¹ conducted a randomized, double-blind, sham-controlled trial at 5 orthopedic clinics in Finland. Patients ages 35 to 65 years were enrolled if they had clinical findings of a medial meniscus tear and knee pain for >3 months that wasn’t relieved by conservative treatment. The trial excluded patients who had an obvious traumatic onset of symptoms; clinical or radiological evidence of knee OA; a locked knee that could not be straightened; knee instability or decreased range of motion; previous surgery on the affected knee; fracture within the past 12 months on the affected limb; or other notable pathology on MRI or during arthroscopy.

Before randomization, 160 patients underwent diagnostic arthroscopy. Fourteen patients were excluded: 6 because they did not actually have a medial meniscal tear, one because he also had a lateral meniscus tear, 3 due to a major chondral flap, 2 who had already undergone meniscal repair, and 2 due to an osteochondral microfracture.

At the end of the diagnostic arthroscopy, each patient was blindly randomized to arthroscopic partial meniscectomy or sham surgery. To simulate the meniscectomy procedure, the surgeon similarly manipulated the knee, made comparable noise and vibration using tools and suction, and ensured that the patient was kept in the operating room (OR) for a comparable time. Only the orthopedic surgeon and OR staff were aware of which surgery the patient underwent, and these staff members were not included in further treatment or follow-up. After the procedure, all patients received the same walking aids and instructions for a graduated exercise program.

The 70 patients in the meniscectomy group and the 76 in the sham surgery group were similar in age (mean: 52 years), sex, body mass index, and duration of pain (mean: 10 months). Patients in both groups also had similar tears noted on arthroscopy.

Three primary outcomes were measured before surgery and at 12 months: knee pain, knee symptoms and function, and quality of life. Knee pain after exercise was evaluated on a 0 to 10 scale, with 0 indicating no pain. The validated Lysholm knee score was used to assess knee symptoms and function and the Western Ontario Meniscal Evaluation Tool (WOMET) was utilized to evaluate quality of life; both are 100-point scales in which lower scores indicate more severe symptoms.

Both groups had marked improvement in pain and function from baseline to 12 months, and there was no significant difference between the 2 groups. Knee pain scores improved by 3.1 in the meniscectomy group and 3.3 in the sham surgery group.


Lysholm symptom and function scores improved 21.7 points in the meniscectomy group and 23.3 points in the sham surgery group (a change of 11.5 points would have been considered clinically significant). The mean between-group difference was -1.6 points (95% confidence interval [CI], -7.2 to 4.0).

Both meniscectomy and sham surgery led
 to marked improvement at 12 months, with no significant differences in outcomes. WOMET quality of life scores improved 24.6 points in the meniscectomy group and 27.1 points in the sham surgery (a change of 15.5 points would have been considered clinically significant). The mean between-group difference was -2.5 points (95% CI, -9.2 to 4.1).

There were no significant between-group differences in serious adverse events or number of patients who required subsequent knee surgery. Similar proportions in each group thought they had sham surgery, which confirmed the effectiveness of the blinding. Ninety-six percent of patients in the sham procedure group and 93% in the meniscectomy group reported they would be willing to repeat the procedure.

WHAT'S NEW: Recommend physical therapy,
 exercise instead of surgery


Previous studies of arthroscopic partial meniscectomy to treat degenerative meniscal tears in patients with knee OA found no benefit.^6,8 This study specifically examined patients without OA and found arthroscopic partial meniscectomy offered no benefit over sham surgery.

In addition to fewer referrals for meniscectomy, these findings could lead to another change in practice: Physicians may be less likely to order an MRI to confirm the diagnosis of a medial meniscal tear, since doing so will not change their therapeutic approach. This approach centers on recommending that patients with a degenerative meniscal tear start and stick with physical therapy and their designated exercise regimen.

CAVEATS: Surgery might be effective for more active patients

This study, as well as previous research, did not look at surgery for an acute medial meniscus tear following a traumatic incident, such as a fall or direct blow. Additionally, these results are based on improved outcomes in activities of daily living, and may not extend to patients who engage in high-level functioning, such as sports or strenuous work. The sham surgery group received lavage, which could be considered an active treatment, although a previous trial found lavage had no benefit over conservative treatment in patients with knee OA.⁴

CHALLENGES TO IMPLEMENTATION: It might be hard to convince patients they don’t need surgery

Some patients expect immediate intervention with surgery. It may be difficult to convince such patients that active participation in physical therapy can lead to the same outcomes as surgery. Spending time with your patient to explain the injury, what happens during surgery, and the evidence that shows a lack of difference in outcomes can lead to fewer surgeries. Most patients and physicians will want to do an MRI after 3 months of persistent pain to determine the diagnosis, although some may be comfortable with continuing conservative treatment.

Acknowledgement
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Click here to view PURL METHODOLOGY

Illustrative case

A 40-year-old man comes to your office for follow-up of medial left knee pain he’s had for 3 months that hasn’t responded to conservative treatment. The pain developed gradually, without a history of trauma. The patient has no signs of degenerative joint disease on x-ray but magnetic resonance imaging (MRI) reveals a tear of the medial meniscus. Should you refer him for meniscectomy?

Patients and doctors alike tend to look for a treatment that will “fix” the problem, which may be why we have continued to use arthroscopic partial meniscectomy to attempt to relieve symptoms of meniscal tears despite a lack of evidence to support the practice.

Guidelines from the American Academy of Orthopaedic Surgeons state that the evidence for medial meniscectomy in patients with a torn meniscus and osteoarthritis (OA) is inconclusive; the organization offers no guidelines for patients with a torn meniscus who don’t have OA.² The American College of Occupational and Environmental Medicine states that there is insufficient evidence to support arthroscopic partial meniscectomy for symptomatic, torn medial menisci for select patients and “the vast majority of patients [with medial meniscal tears] do not require surgery.”³ Previous studies have concluded that arthroscopic surgery for OA of the knee provides no additional benefit to optimized physical and medical therapy.⁴ Furthermore, research by Katz et al⁵ shows that meniscectomy provides no benefit over conservative treatment in functional status at 6 months in patients with OA and a medial meniscal tear.

That said, arthroscopic partial meniscectomy is still the most common orthopedic procedure in the United States.¹ Although its use has decreased over the last 15 years, it is performed nearly 700,000 times annually at a cost of approximately $4 billion.^1,6,7 Like any surgical procedure, meniscectomy carries a risk of complications. In the double-blind, randomized trial reported on here, Sihvonen et al¹ compared meniscectomy to a sham procedure for patients with knee pain, but not OA.

STUDY SUMMARY: Meniscectomy and sham surgery 
are equally effective


Sihvonen et al¹ conducted a randomized, double-blind, sham-controlled trial at 5 orthopedic clinics in Finland. Patients ages 35 to 65 years were enrolled if they had clinical findings of a medial meniscus tear and knee pain for >3 months that wasn’t relieved by conservative treatment. The trial excluded patients who had an obvious traumatic onset of symptoms; clinical or radiological evidence of knee OA; a locked knee that could not be straightened; knee instability or decreased range of motion; previous surgery on the affected knee; fracture within the past 12 months on the affected limb; or other notable pathology on MRI or during arthroscopy.

Before randomization, 160 patients underwent diagnostic arthroscopy. Fourteen patients were excluded: 6 because they did not actually have a medial meniscal tear, one because he also had a lateral meniscus tear, 3 due to a major chondral flap, 2 who had already undergone meniscal repair, and 2 due to an osteochondral microfracture.

At the end of the diagnostic arthroscopy, each patient was blindly randomized to arthroscopic partial meniscectomy or sham surgery. To simulate the meniscectomy procedure, the surgeon similarly manipulated the knee, made comparable noise and vibration using tools and suction, and ensured that the patient was kept in the operating room (OR) for a comparable time. Only the orthopedic surgeon and OR staff were aware of which surgery the patient underwent, and these staff members were not included in further treatment or follow-up. After the procedure, all patients received the same walking aids and instructions for a graduated exercise program.

The 70 patients in the meniscectomy group and the 76 in the sham surgery group were similar in age (mean: 52 years), sex, body mass index, and duration of pain (mean: 10 months). Patients in both groups also had similar tears noted on arthroscopy.

Three primary outcomes were measured before surgery and at 12 months: knee pain, knee symptoms and function, and quality of life. Knee pain after exercise was evaluated on a 0 to 10 scale, with 0 indicating no pain. The validated Lysholm knee score was used to assess knee symptoms and function and the Western Ontario Meniscal Evaluation Tool (WOMET) was utilized to evaluate quality of life; both are 100-point scales in which lower scores indicate more severe symptoms.

Both groups had marked improvement in pain and function from baseline to 12 months, and there was no significant difference between the 2 groups. Knee pain scores improved by 3.1 in the meniscectomy group and 3.3 in the sham surgery group.


Lysholm symptom and function scores improved 21.7 points in the meniscectomy group and 23.3 points in the sham surgery group (a change of 11.5 points would have been considered clinically significant). The mean between-group difference was -1.6 points (95% confidence interval [CI], -7.2 to 4.0).

Both meniscectomy and sham surgery led
 to marked improvement at 12 months, with no significant differences in outcomes. WOMET quality of life scores improved 24.6 points in the meniscectomy group and 27.1 points in the sham surgery (a change of 15.5 points would have been considered clinically significant). The mean between-group difference was -2.5 points (95% CI, -9.2 to 4.1).

There were no significant between-group differences in serious adverse events or number of patients who required subsequent knee surgery. Similar proportions in each group thought they had sham surgery, which confirmed the effectiveness of the blinding. Ninety-six percent of patients in the sham procedure group and 93% in the meniscectomy group reported they would be willing to repeat the procedure.

WHAT'S NEW: Recommend physical therapy,
 exercise instead of surgery


Previous studies of arthroscopic partial meniscectomy to treat degenerative meniscal tears in patients with knee OA found no benefit.^6,8 This study specifically examined patients without OA and found arthroscopic partial meniscectomy offered no benefit over sham surgery.

In addition to fewer referrals for meniscectomy, these findings could lead to another change in practice: Physicians may be less likely to order an MRI to confirm the diagnosis of a medial meniscal tear, since doing so will not change their therapeutic approach. This approach centers on recommending that patients with a degenerative meniscal tear start and stick with physical therapy and their designated exercise regimen.

CAVEATS: Surgery might be effective for more active patients

This study, as well as previous research, did not look at surgery for an acute medial meniscus tear following a traumatic incident, such as a fall or direct blow. Additionally, these results are based on improved outcomes in activities of daily living, and may not extend to patients who engage in high-level functioning, such as sports or strenuous work. The sham surgery group received lavage, which could be considered an active treatment, although a previous trial found lavage had no benefit over conservative treatment in patients with knee OA.⁴

CHALLENGES TO IMPLEMENTATION: It might be hard to convince patients they don’t need surgery

Some patients expect immediate intervention with surgery. It may be difficult to convince such patients that active participation in physical therapy can lead to the same outcomes as surgery. Spending time with your patient to explain the injury, what happens during surgery, and the evidence that shows a lack of difference in outcomes can lead to fewer surgeries. Most patients and physicians will want to do an MRI after 3 months of persistent pain to determine the diagnosis, although some may be comfortable with continuing conservative treatment.

Acknowledgement
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Click here to view PURL METHODOLOGY

Illustrative case

A 40-year-old man comes to your office for follow-up of medial left knee pain he’s had for 3 months that hasn’t responded to conservative treatment. The pain developed gradually, without a history of trauma. The patient has no signs of degenerative joint disease on x-ray but magnetic resonance imaging (MRI) reveals a tear of the medial meniscus. Should you refer him for meniscectomy?

Patients and doctors alike tend to look for a treatment that will “fix” the problem, which may be why we have continued to use arthroscopic partial meniscectomy to attempt to relieve symptoms of meniscal tears despite a lack of evidence to support the practice.

Guidelines from the American Academy of Orthopaedic Surgeons state that the evidence for medial meniscectomy in patients with a torn meniscus and osteoarthritis (OA) is inconclusive; the organization offers no guidelines for patients with a torn meniscus who don’t have OA.² The American College of Occupational and Environmental Medicine states that there is insufficient evidence to support arthroscopic partial meniscectomy for symptomatic, torn medial menisci for select patients and “the vast majority of patients [with medial meniscal tears] do not require surgery.”³ Previous studies have concluded that arthroscopic surgery for OA of the knee provides no additional benefit to optimized physical and medical therapy.⁴ Furthermore, research by Katz et al⁵ shows that meniscectomy provides no benefit over conservative treatment in functional status at 6 months in patients with OA and a medial meniscal tear.

That said, arthroscopic partial meniscectomy is still the most common orthopedic procedure in the United States.¹ Although its use has decreased over the last 15 years, it is performed nearly 700,000 times annually at a cost of approximately $4 billion.^1,6,7 Like any surgical procedure, meniscectomy carries a risk of complications. In the double-blind, randomized trial reported on here, Sihvonen et al¹ compared meniscectomy to a sham procedure for patients with knee pain, but not OA.

STUDY SUMMARY: Meniscectomy and sham surgery 
are equally effective


Sihvonen et al¹ conducted a randomized, double-blind, sham-controlled trial at 5 orthopedic clinics in Finland. Patients ages 35 to 65 years were enrolled if they had clinical findings of a medial meniscus tear and knee pain for >3 months that wasn’t relieved by conservative treatment. The trial excluded patients who had an obvious traumatic onset of symptoms; clinical or radiological evidence of knee OA; a locked knee that could not be straightened; knee instability or decreased range of motion; previous surgery on the affected knee; fracture within the past 12 months on the affected limb; or other notable pathology on MRI or during arthroscopy.

Before randomization, 160 patients underwent diagnostic arthroscopy. Fourteen patients were excluded: 6 because they did not actually have a medial meniscal tear, one because he also had a lateral meniscus tear, 3 due to a major chondral flap, 2 who had already undergone meniscal repair, and 2 due to an osteochondral microfracture.

At the end of the diagnostic arthroscopy, each patient was blindly randomized to arthroscopic partial meniscectomy or sham surgery. To simulate the meniscectomy procedure, the surgeon similarly manipulated the knee, made comparable noise and vibration using tools and suction, and ensured that the patient was kept in the operating room (OR) for a comparable time. Only the orthopedic surgeon and OR staff were aware of which surgery the patient underwent, and these staff members were not included in further treatment or follow-up. After the procedure, all patients received the same walking aids and instructions for a graduated exercise program.

The 70 patients in the meniscectomy group and the 76 in the sham surgery group were similar in age (mean: 52 years), sex, body mass index, and duration of pain (mean: 10 months). Patients in both groups also had similar tears noted on arthroscopy.

Three primary outcomes were measured before surgery and at 12 months: knee pain, knee symptoms and function, and quality of life. Knee pain after exercise was evaluated on a 0 to 10 scale, with 0 indicating no pain. The validated Lysholm knee score was used to assess knee symptoms and function and the Western Ontario Meniscal Evaluation Tool (WOMET) was utilized to evaluate quality of life; both are 100-point scales in which lower scores indicate more severe symptoms.

Both groups had marked improvement in pain and function from baseline to 12 months, and there was no significant difference between the 2 groups. Knee pain scores improved by 3.1 in the meniscectomy group and 3.3 in the sham surgery group.


Lysholm symptom and function scores improved 21.7 points in the meniscectomy group and 23.3 points in the sham surgery group (a change of 11.5 points would have been considered clinically significant). The mean between-group difference was -1.6 points (95% confidence interval [CI], -7.2 to 4.0).

Both meniscectomy and sham surgery led
 to marked improvement at 12 months, with no significant differences in outcomes. WOMET quality of life scores improved 24.6 points in the meniscectomy group and 27.1 points in the sham surgery (a change of 15.5 points would have been considered clinically significant). The mean between-group difference was -2.5 points (95% CI, -9.2 to 4.1).

There were no significant between-group differences in serious adverse events or number of patients who required subsequent knee surgery. Similar proportions in each group thought they had sham surgery, which confirmed the effectiveness of the blinding. Ninety-six percent of patients in the sham procedure group and 93% in the meniscectomy group reported they would be willing to repeat the procedure.

WHAT'S NEW: Recommend physical therapy,
 exercise instead of surgery


Previous studies of arthroscopic partial meniscectomy to treat degenerative meniscal tears in patients with knee OA found no benefit.^6,8 This study specifically examined patients without OA and found arthroscopic partial meniscectomy offered no benefit over sham surgery.

In addition to fewer referrals for meniscectomy, these findings could lead to another change in practice: Physicians may be less likely to order an MRI to confirm the diagnosis of a medial meniscal tear, since doing so will not change their therapeutic approach. This approach centers on recommending that patients with a degenerative meniscal tear start and stick with physical therapy and their designated exercise regimen.

CAVEATS: Surgery might be effective for more active patients

This study, as well as previous research, did not look at surgery for an acute medial meniscus tear following a traumatic incident, such as a fall or direct blow. Additionally, these results are based on improved outcomes in activities of daily living, and may not extend to patients who engage in high-level functioning, such as sports or strenuous work. The sham surgery group received lavage, which could be considered an active treatment, although a previous trial found lavage had no benefit over conservative treatment in patients with knee OA.⁴

CHALLENGES TO IMPLEMENTATION: It might be hard to convince patients they don’t need surgery

Some patients expect immediate intervention with surgery. It may be difficult to convince such patients that active participation in physical therapy can lead to the same outcomes as surgery. Spending time with your patient to explain the injury, what happens during surgery, and the evidence that shows a lack of difference in outcomes can lead to fewer surgeries. Most patients and physicians will want to do an MRI after 3 months of persistent pain to determine the diagnosis, although some may be comfortable with continuing conservative treatment.

Acknowledgement
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Click here to view PURL METHODOLOGY

As physicians and the Centers for Disease Control and Prevention (CDC) prepare for the upcoming influenza season, many of the recommendations remain unchanged from last season. Vaccination continues to be recommended for everyone 6 months of age and older. However, for the first time, a specific vaccine is preferred for children ages 2 through 8 years. Here’s what you need to know about this change, as well as how to handle vaccination in patients who are, or might be, allergic to eggs.

Use LAIV for kids ages 
2 through 8 (if available)


For the first time, the CDC’s Advisory Committee on Immunization Practices (ACIP) has stated a preference for a specific influenza vaccine for a specific age group. It recommends using the live attenuated influenza vaccine (LAIV), which is a nasal spray, for children ages 2 through 8 years.¹

A systematic review found evidence of increased efficacy of LAIV compared to inactivated influenza vaccine (IIV) in this age group; both types of vaccine have similar rates of adverse reactions.² This increased effectiveness results in 46 fewer cases of confirmed influenza per 1000 children vaccinated (number needed to treat=24). Although the evidence of LAIV’s increased effectiveness was found for children ages 2 to 6 years, ACIP extended this recommendation through age 8 because this is the age through which physicians need to consider 2 doses of vaccine for a child previously unvaccinated with the influenza vaccine. Children younger than age 2 should receive IIV3 or IIV4.³

ACIP realizes that due to programmatic constraints it would be difficult to vaccinate all children with LAIV this year and is emphasizing that it should be implemented when feasible this year but no later than the 2015 to 2016 influenza season. IIV is effective in children and should be given if LAIV is not available or is contraindicated. Vaccine should not be delayed in the hopes of receiving LAIV if IIV is available.¹

LAIV should not be used in children <2 years or adults >49. This vaccine is contraindicated in children and adolescents who are taking chronic aspirin therapy, pregnant women, those who are immunosuppressed, those with a history of egg allergy, or those who have taken influenza antiviral medications in the past 48 hours.¹ LAIV also is not recommended for children ages 2 through 4 years who have asthma or had a wheezing episode in the past 12 months.¹

There are precautions for the use of LAIV in patients with chronic medical conditions that can place them at high risk for complications from influenza, such as chronic lung, heart, renal, neurologic, liver, blood, or metabolic disorders, including asthma and diabetes.¹

Which vaccine for patients
 who are allergic to eggs?


Two influenza vaccines are now available that are not prepared in embryonated eggs: recombinant influenza vaccine (RIV3) and cell culture-based inactivated influenza vaccine (ccIIV3). Both are trivalent products that contain antigens from 2 influenza A viruses and one influenza B virus and were introduced in time for the 2013 to 2014 flu season. The RIV3 is considered egg-free but ccIIV3 is not, although the amount of egg protein in it is miniscule, estimated at 5 × 10^-8 mcg/0.5 mL dose.¹ Neither product is licensed for children younger than 18 years and RIV3 is licensed only for those ages 18 through 49 years.

Patients who experience only hives after egg exposure can receive any of the flu vaccines except LAIV, and only because of a lack of data on this product, not because it has been shown to be less safe than the other vaccines. Patients who are unsure if they have an egg allergy or only get hives when they eat eggs should be observed for at least 30 minutes¹ following injection as a precaution. Those ages 18 through 49 who have a history of severe reactions to eggs should receive RIV3. Patients younger than 18 years of age and older than 49 years of age can receive IIV vaccines approved for their specific age group. Any patient who is severely allergic and who cannot receive an egg-free vaccine should be vaccinated by a physician with experience managing severe allergic conditions.

Although severe, anaphylactic reactions to influenza vaccine are very rare, physicians should be equipped and prepared to respond to a severe allergic reaction after providing influenza vaccine to anyone with a history of an egg allergy.

Additional tips and resources

In addition to the LAIV, RIV3, and ccIIV3 vaccines described here, 10 other vaccines are available, including 5 egg-based IIV3 products in standard-dose form, 1 IIV3 vaccine for intradermal use, 1 high-dose IIV3 product for patients ages 65 or older, and 3 standard-dose IIV4 products. More details on each of these vaccines are available at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6207a1.htm?_%20cid=rr6207a1_w#Tab1.

Regardless of which type of flu vaccine they receive, children 6 months through 8 years should receive 2 doses, at least 4 weeks apart, unless they received:

• 1 dose in 2013 to 2014, or

• 2 or more doses of seasonal influenza vaccine since July 2010, or
• 2 or more doses of seasonal influenza vaccine before July 2010 and ≥1 dose of monovalent H1N1 vaccine, or

• at least 1 dose of seasonal influenza vaccine prior to July 2010 and ≥1 after.

Patients between the ages of 18 and 49 with severe egg allergies should receive RIV3. Vaccine effectiveness. The CDC estimated that vaccine effectiveness during the 2013 to 2014 flu season was 66%.³ While this degree of effectiveness is important for minimizing the morbidity and mortality from influenza each year, it’s important to appreciate the limitations of the vaccine and not rely on it as the only prevention intervention.

Other forms of prevention. We need to advise and practice good respiratory hygiene, frequent hand washing, self-isolation when sick, effective infection control practices at health care facilities, targeted early treatment with antivirals, and targeted pre- and post-exposure antiviral chemoprevention. Details on each of these interventions, including recommendations on the use of antiviral medications, can be found on the CDC Web site at http://www.cdc.gov/flu.

As physicians and the Centers for Disease Control and Prevention (CDC) prepare for the upcoming influenza season, many of the recommendations remain unchanged from last season. Vaccination continues to be recommended for everyone 6 months of age and older. However, for the first time, a specific vaccine is preferred for children ages 2 through 8 years. Here’s what you need to know about this change, as well as how to handle vaccination in patients who are, or might be, allergic to eggs.

Use LAIV for kids ages 
2 through 8 (if available)


For the first time, the CDC’s Advisory Committee on Immunization Practices (ACIP) has stated a preference for a specific influenza vaccine for a specific age group. It recommends using the live attenuated influenza vaccine (LAIV), which is a nasal spray, for children ages 2 through 8 years.¹

A systematic review found evidence of increased efficacy of LAIV compared to inactivated influenza vaccine (IIV) in this age group; both types of vaccine have similar rates of adverse reactions.² This increased effectiveness results in 46 fewer cases of confirmed influenza per 1000 children vaccinated (number needed to treat=24). Although the evidence of LAIV’s increased effectiveness was found for children ages 2 to 6 years, ACIP extended this recommendation through age 8 because this is the age through which physicians need to consider 2 doses of vaccine for a child previously unvaccinated with the influenza vaccine. Children younger than age 2 should receive IIV3 or IIV4.³

ACIP realizes that due to programmatic constraints it would be difficult to vaccinate all children with LAIV this year and is emphasizing that it should be implemented when feasible this year but no later than the 2015 to 2016 influenza season. IIV is effective in children and should be given if LAIV is not available or is contraindicated. Vaccine should not be delayed in the hopes of receiving LAIV if IIV is available.¹

LAIV should not be used in children <2 years or adults >49. This vaccine is contraindicated in children and adolescents who are taking chronic aspirin therapy, pregnant women, those who are immunosuppressed, those with a history of egg allergy, or those who have taken influenza antiviral medications in the past 48 hours.¹ LAIV also is not recommended for children ages 2 through 4 years who have asthma or had a wheezing episode in the past 12 months.¹

There are precautions for the use of LAIV in patients with chronic medical conditions that can place them at high risk for complications from influenza, such as chronic lung, heart, renal, neurologic, liver, blood, or metabolic disorders, including asthma and diabetes.¹

Which vaccine for patients
 who are allergic to eggs?


Two influenza vaccines are now available that are not prepared in embryonated eggs: recombinant influenza vaccine (RIV3) and cell culture-based inactivated influenza vaccine (ccIIV3). Both are trivalent products that contain antigens from 2 influenza A viruses and one influenza B virus and were introduced in time for the 2013 to 2014 flu season. The RIV3 is considered egg-free but ccIIV3 is not, although the amount of egg protein in it is miniscule, estimated at 5 × 10^-8 mcg/0.5 mL dose.¹ Neither product is licensed for children younger than 18 years and RIV3 is licensed only for those ages 18 through 49 years.

Patients who experience only hives after egg exposure can receive any of the flu vaccines except LAIV, and only because of a lack of data on this product, not because it has been shown to be less safe than the other vaccines. Patients who are unsure if they have an egg allergy or only get hives when they eat eggs should be observed for at least 30 minutes¹ following injection as a precaution. Those ages 18 through 49 who have a history of severe reactions to eggs should receive RIV3. Patients younger than 18 years of age and older than 49 years of age can receive IIV vaccines approved for their specific age group. Any patient who is severely allergic and who cannot receive an egg-free vaccine should be vaccinated by a physician with experience managing severe allergic conditions.

Although severe, anaphylactic reactions to influenza vaccine are very rare, physicians should be equipped and prepared to respond to a severe allergic reaction after providing influenza vaccine to anyone with a history of an egg allergy.

Additional tips and resources

In addition to the LAIV, RIV3, and ccIIV3 vaccines described here, 10 other vaccines are available, including 5 egg-based IIV3 products in standard-dose form, 1 IIV3 vaccine for intradermal use, 1 high-dose IIV3 product for patients ages 65 or older, and 3 standard-dose IIV4 products. More details on each of these vaccines are available at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6207a1.htm?_%20cid=rr6207a1_w#Tab1.

Regardless of which type of flu vaccine they receive, children 6 months through 8 years should receive 2 doses, at least 4 weeks apart, unless they received:

• 1 dose in 2013 to 2014, or

• 2 or more doses of seasonal influenza vaccine since July 2010, or
• 2 or more doses of seasonal influenza vaccine before July 2010 and ≥1 dose of monovalent H1N1 vaccine, or

• at least 1 dose of seasonal influenza vaccine prior to July 2010 and ≥1 after.

Patients between the ages of 18 and 49 with severe egg allergies should receive RIV3. Vaccine effectiveness. The CDC estimated that vaccine effectiveness during the 2013 to 2014 flu season was 66%.³ While this degree of effectiveness is important for minimizing the morbidity and mortality from influenza each year, it’s important to appreciate the limitations of the vaccine and not rely on it as the only prevention intervention.

Other forms of prevention. We need to advise and practice good respiratory hygiene, frequent hand washing, self-isolation when sick, effective infection control practices at health care facilities, targeted early treatment with antivirals, and targeted pre- and post-exposure antiviral chemoprevention. Details on each of these interventions, including recommendations on the use of antiviral medications, can be found on the CDC Web site at http://www.cdc.gov/flu.

As physicians and the Centers for Disease Control and Prevention (CDC) prepare for the upcoming influenza season, many of the recommendations remain unchanged from last season. Vaccination continues to be recommended for everyone 6 months of age and older. However, for the first time, a specific vaccine is preferred for children ages 2 through 8 years. Here’s what you need to know about this change, as well as how to handle vaccination in patients who are, or might be, allergic to eggs.

Use LAIV for kids ages 
2 through 8 (if available)


For the first time, the CDC’s Advisory Committee on Immunization Practices (ACIP) has stated a preference for a specific influenza vaccine for a specific age group. It recommends using the live attenuated influenza vaccine (LAIV), which is a nasal spray, for children ages 2 through 8 years.¹

A systematic review found evidence of increased efficacy of LAIV compared to inactivated influenza vaccine (IIV) in this age group; both types of vaccine have similar rates of adverse reactions.² This increased effectiveness results in 46 fewer cases of confirmed influenza per 1000 children vaccinated (number needed to treat=24). Although the evidence of LAIV’s increased effectiveness was found for children ages 2 to 6 years, ACIP extended this recommendation through age 8 because this is the age through which physicians need to consider 2 doses of vaccine for a child previously unvaccinated with the influenza vaccine. Children younger than age 2 should receive IIV3 or IIV4.³

ACIP realizes that due to programmatic constraints it would be difficult to vaccinate all children with LAIV this year and is emphasizing that it should be implemented when feasible this year but no later than the 2015 to 2016 influenza season. IIV is effective in children and should be given if LAIV is not available or is contraindicated. Vaccine should not be delayed in the hopes of receiving LAIV if IIV is available.¹

LAIV should not be used in children <2 years or adults >49. This vaccine is contraindicated in children and adolescents who are taking chronic aspirin therapy, pregnant women, those who are immunosuppressed, those with a history of egg allergy, or those who have taken influenza antiviral medications in the past 48 hours.¹ LAIV also is not recommended for children ages 2 through 4 years who have asthma or had a wheezing episode in the past 12 months.¹

There are precautions for the use of LAIV in patients with chronic medical conditions that can place them at high risk for complications from influenza, such as chronic lung, heart, renal, neurologic, liver, blood, or metabolic disorders, including asthma and diabetes.¹

Which vaccine for patients
 who are allergic to eggs?


Two influenza vaccines are now available that are not prepared in embryonated eggs: recombinant influenza vaccine (RIV3) and cell culture-based inactivated influenza vaccine (ccIIV3). Both are trivalent products that contain antigens from 2 influenza A viruses and one influenza B virus and were introduced in time for the 2013 to 2014 flu season. The RIV3 is considered egg-free but ccIIV3 is not, although the amount of egg protein in it is miniscule, estimated at 5 × 10^-8 mcg/0.5 mL dose.¹ Neither product is licensed for children younger than 18 years and RIV3 is licensed only for those ages 18 through 49 years.

Patients who experience only hives after egg exposure can receive any of the flu vaccines except LAIV, and only because of a lack of data on this product, not because it has been shown to be less safe than the other vaccines. Patients who are unsure if they have an egg allergy or only get hives when they eat eggs should be observed for at least 30 minutes¹ following injection as a precaution. Those ages 18 through 49 who have a history of severe reactions to eggs should receive RIV3. Patients younger than 18 years of age and older than 49 years of age can receive IIV vaccines approved for their specific age group. Any patient who is severely allergic and who cannot receive an egg-free vaccine should be vaccinated by a physician with experience managing severe allergic conditions.

Although severe, anaphylactic reactions to influenza vaccine are very rare, physicians should be equipped and prepared to respond to a severe allergic reaction after providing influenza vaccine to anyone with a history of an egg allergy.

Additional tips and resources

In addition to the LAIV, RIV3, and ccIIV3 vaccines described here, 10 other vaccines are available, including 5 egg-based IIV3 products in standard-dose form, 1 IIV3 vaccine for intradermal use, 1 high-dose IIV3 product for patients ages 65 or older, and 3 standard-dose IIV4 products. More details on each of these vaccines are available at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6207a1.htm?_%20cid=rr6207a1_w#Tab1.

Regardless of which type of flu vaccine they receive, children 6 months through 8 years should receive 2 doses, at least 4 weeks apart, unless they received:

• 1 dose in 2013 to 2014, or

• 2 or more doses of seasonal influenza vaccine since July 2010, or
• 2 or more doses of seasonal influenza vaccine before July 2010 and ≥1 dose of monovalent H1N1 vaccine, or

• at least 1 dose of seasonal influenza vaccine prior to July 2010 and ≥1 after.

Patients between the ages of 18 and 49 with severe egg allergies should receive RIV3. Vaccine effectiveness. The CDC estimated that vaccine effectiveness during the 2013 to 2014 flu season was 66%.³ While this degree of effectiveness is important for minimizing the morbidity and mortality from influenza each year, it’s important to appreciate the limitations of the vaccine and not rely on it as the only prevention intervention.

Other forms of prevention. We need to advise and practice good respiratory hygiene, frequent hand washing, self-isolation when sick, effective infection control practices at health care facilities, targeted early treatment with antivirals, and targeted pre- and post-exposure antiviral chemoprevention. Details on each of these interventions, including recommendations on the use of antiviral medications, can be found on the CDC Web site at http://www.cdc.gov/flu.

An 18-year-old Caucasian male sought care for an ill-defined reticulated patch on his right plantar arch (FIGURE 1). The patient said that the lesion had gradually appeared 2 years earlier, had grown slowly, and was occasionally itchy. Physical exam revealed a lacy violaceous, hyperpigmented, reticulated patch that was blanchable and nontender to palpation.

Our patient denied having a history of trauma to the area or a coagulation or connective tissue disorder. The lesion didn’t vary with temperature or season, and there were no known triggers. The patient’s left plantar arch was unchanged.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis:
 Erythema ab igne


Upon further questioning, the patient acknowledged that he occasionally rested his bare feet around a portable heater under his desk while using his computer for a few hours each day (FIGURE 2). He often kept his right foot on the heater while he let his left foot rest on the ground. A punch biopsy was performed; the findings, when combined with the patient’s report of having exposed his foot to heat, supported the diagnosis of erythema ab igne (EAI).

Erythema 
ab igne with atypical distributions have been linked to the use of laptop computers, car seat heaters, and cell phones. EAI commonly presents as an asymptomatic reticulated erythematous to violaceous patch in an area of the body that has been in contact with heat.¹ It originally was described on the bilateral anterior lower extremities after prolonged exposure to burning stoves or open fires.¹ With the advent of central heating, these presentations have decreased, but there has been a resurgence of EAI with atypical distributions as a result of evolving technology and new heating sources. Reported causes of EAI include heating pads,^1,2 laptop computers³ (FIGURE 3), car seat heaters,⁴ hot water bottles, popcorn bags, cell phones,⁵ and space heaters that have resulted in patches on the breast, thighs, arms, and, in our patient, foot.^1-5

Blood work, biopsy
 can help narrow the differential

The differential for EAI includes livedo reticularis, livedo racemosa, cutis marmorata, and cutis marmorata telangiectasia. Livedo reticularis can be associated with autoimmune conditions and coagulopathies. Livedo racemosa is a typical sign of Sneddon’s syndrome and can be seen in up to 70% of patients with antiphospholipid-antibody syndrome and systemic lupus erythematosus. Diagnosis of these conditions is confirmed by elevated coagulation factors, presence of autoimmune antibodies, or history of cerebrovascular accident.⁶ These tests would be normal in EAI.

Histopathologic changes observed in EAI include an atrophic epidermis with an interface dermatitis, vasodilation, and dermal pigmentation. Necrotic keratinocytes and focal hyperkeratosis can be noted, along with squamous atypia. Although these changes are nonspecific, they can be used to confirm an EAI diagnosis in patients for whom the affected area has been exposed to a heat source.

Histologically, EAI is similar to actinic keratosis, with epidermal changes showing squamous atypia.² Due to the similarities, these lesions are sometimes referred to as “thermal keratosis.” Some researchers have suggested that the thermal heat may induce epithelial changes in the same way that ultraviolet light produces epithelial changes.⁷

Rarely, EAI can turn into cancer. There have been a few reported cases of EAI transforming into squamous cell carcinoma or Merkel cell carcinoma; squamous cell carcinoma is more common, and tends to occur after a long latent period (up to 30 years).^7-9 EAI lesions often begin as a chronic ulcer and tend not to heal. If the lesion continues to evolve (ie, ulcerate), a biopsy may be warranted to rule out a malignant transformation.

Eliminate heat exposure,
 consider a topical treatment

Treatment of acute EAI involves eliminating the offending heat source. The hyperpigmentation will slowly resolve over months to years.⁴ Persistent exposure to heat sources can lead to chronic EAI, which is more difficult to eliminate.

Because hyperpigmentation can be visually unappealing and emotionally distressing, some patients prefer active treatment. EAI has been effectively treated with 4% hydroquinone topical cream twice a day and tretinoin topical cream at night.^2,10,11 Lesions that have epithelial atypia have improved with 5-fluorouracil topical cream.⁷

EAI also has been successfully treated with laser therapy with the 1064-nm Q-switched Nd:YAG laser with low fluence at 2-week intervals.⁹

Our patient declined topical therapy. He improved after a few months of avoiding the heater under his desk.

CORRESPONDENCE
Megan Morrison, DO, 5333 McAuley Drive Suite R-5003, Ypsilanti, MI 48197; memorrison10@gmail.com

An 18-year-old Caucasian male sought care for an ill-defined reticulated patch on his right plantar arch (FIGURE 1). The patient said that the lesion had gradually appeared 2 years earlier, had grown slowly, and was occasionally itchy. Physical exam revealed a lacy violaceous, hyperpigmented, reticulated patch that was blanchable and nontender to palpation.

Our patient denied having a history of trauma to the area or a coagulation or connective tissue disorder. The lesion didn’t vary with temperature or season, and there were no known triggers. The patient’s left plantar arch was unchanged.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis:
 Erythema ab igne


Upon further questioning, the patient acknowledged that he occasionally rested his bare feet around a portable heater under his desk while using his computer for a few hours each day (FIGURE 2). He often kept his right foot on the heater while he let his left foot rest on the ground. A punch biopsy was performed; the findings, when combined with the patient’s report of having exposed his foot to heat, supported the diagnosis of erythema ab igne (EAI).

Erythema 
ab igne with atypical distributions have been linked to the use of laptop computers, car seat heaters, and cell phones. EAI commonly presents as an asymptomatic reticulated erythematous to violaceous patch in an area of the body that has been in contact with heat.¹ It originally was described on the bilateral anterior lower extremities after prolonged exposure to burning stoves or open fires.¹ With the advent of central heating, these presentations have decreased, but there has been a resurgence of EAI with atypical distributions as a result of evolving technology and new heating sources. Reported causes of EAI include heating pads,^1,2 laptop computers³ (FIGURE 3), car seat heaters,⁴ hot water bottles, popcorn bags, cell phones,⁵ and space heaters that have resulted in patches on the breast, thighs, arms, and, in our patient, foot.^1-5

Blood work, biopsy
 can help narrow the differential

The differential for EAI includes livedo reticularis, livedo racemosa, cutis marmorata, and cutis marmorata telangiectasia. Livedo reticularis can be associated with autoimmune conditions and coagulopathies. Livedo racemosa is a typical sign of Sneddon’s syndrome and can be seen in up to 70% of patients with antiphospholipid-antibody syndrome and systemic lupus erythematosus. Diagnosis of these conditions is confirmed by elevated coagulation factors, presence of autoimmune antibodies, or history of cerebrovascular accident.⁶ These tests would be normal in EAI.

Histopathologic changes observed in EAI include an atrophic epidermis with an interface dermatitis, vasodilation, and dermal pigmentation. Necrotic keratinocytes and focal hyperkeratosis can be noted, along with squamous atypia. Although these changes are nonspecific, they can be used to confirm an EAI diagnosis in patients for whom the affected area has been exposed to a heat source.

Histologically, EAI is similar to actinic keratosis, with epidermal changes showing squamous atypia.² Due to the similarities, these lesions are sometimes referred to as “thermal keratosis.” Some researchers have suggested that the thermal heat may induce epithelial changes in the same way that ultraviolet light produces epithelial changes.⁷

Rarely, EAI can turn into cancer. There have been a few reported cases of EAI transforming into squamous cell carcinoma or Merkel cell carcinoma; squamous cell carcinoma is more common, and tends to occur after a long latent period (up to 30 years).^7-9 EAI lesions often begin as a chronic ulcer and tend not to heal. If the lesion continues to evolve (ie, ulcerate), a biopsy may be warranted to rule out a malignant transformation.

Eliminate heat exposure,
 consider a topical treatment

Treatment of acute EAI involves eliminating the offending heat source. The hyperpigmentation will slowly resolve over months to years.⁴ Persistent exposure to heat sources can lead to chronic EAI, which is more difficult to eliminate.

Because hyperpigmentation can be visually unappealing and emotionally distressing, some patients prefer active treatment. EAI has been effectively treated with 4% hydroquinone topical cream twice a day and tretinoin topical cream at night.^2,10,11 Lesions that have epithelial atypia have improved with 5-fluorouracil topical cream.⁷

EAI also has been successfully treated with laser therapy with the 1064-nm Q-switched Nd:YAG laser with low fluence at 2-week intervals.⁹

Our patient declined topical therapy. He improved after a few months of avoiding the heater under his desk.

CORRESPONDENCE
Megan Morrison, DO, 5333 McAuley Drive Suite R-5003, Ypsilanti, MI 48197; memorrison10@gmail.com

An 18-year-old Caucasian male sought care for an ill-defined reticulated patch on his right plantar arch (FIGURE 1). The patient said that the lesion had gradually appeared 2 years earlier, had grown slowly, and was occasionally itchy. Physical exam revealed a lacy violaceous, hyperpigmented, reticulated patch that was blanchable and nontender to palpation.

Our patient denied having a history of trauma to the area or a coagulation or connective tissue disorder. The lesion didn’t vary with temperature or season, and there were no known triggers. The patient’s left plantar arch was unchanged.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis:
 Erythema ab igne


Upon further questioning, the patient acknowledged that he occasionally rested his bare feet around a portable heater under his desk while using his computer for a few hours each day (FIGURE 2). He often kept his right foot on the heater while he let his left foot rest on the ground. A punch biopsy was performed; the findings, when combined with the patient’s report of having exposed his foot to heat, supported the diagnosis of erythema ab igne (EAI).

Erythema 
ab igne with atypical distributions have been linked to the use of laptop computers, car seat heaters, and cell phones. EAI commonly presents as an asymptomatic reticulated erythematous to violaceous patch in an area of the body that has been in contact with heat.¹ It originally was described on the bilateral anterior lower extremities after prolonged exposure to burning stoves or open fires.¹ With the advent of central heating, these presentations have decreased, but there has been a resurgence of EAI with atypical distributions as a result of evolving technology and new heating sources. Reported causes of EAI include heating pads,^1,2 laptop computers³ (FIGURE 3), car seat heaters,⁴ hot water bottles, popcorn bags, cell phones,⁵ and space heaters that have resulted in patches on the breast, thighs, arms, and, in our patient, foot.^1-5

Blood work, biopsy
 can help narrow the differential

The differential for EAI includes livedo reticularis, livedo racemosa, cutis marmorata, and cutis marmorata telangiectasia. Livedo reticularis can be associated with autoimmune conditions and coagulopathies. Livedo racemosa is a typical sign of Sneddon’s syndrome and can be seen in up to 70% of patients with antiphospholipid-antibody syndrome and systemic lupus erythematosus. Diagnosis of these conditions is confirmed by elevated coagulation factors, presence of autoimmune antibodies, or history of cerebrovascular accident.⁶ These tests would be normal in EAI.

Histopathologic changes observed in EAI include an atrophic epidermis with an interface dermatitis, vasodilation, and dermal pigmentation. Necrotic keratinocytes and focal hyperkeratosis can be noted, along with squamous atypia. Although these changes are nonspecific, they can be used to confirm an EAI diagnosis in patients for whom the affected area has been exposed to a heat source.

Histologically, EAI is similar to actinic keratosis, with epidermal changes showing squamous atypia.² Due to the similarities, these lesions are sometimes referred to as “thermal keratosis.” Some researchers have suggested that the thermal heat may induce epithelial changes in the same way that ultraviolet light produces epithelial changes.⁷

Rarely, EAI can turn into cancer. There have been a few reported cases of EAI transforming into squamous cell carcinoma or Merkel cell carcinoma; squamous cell carcinoma is more common, and tends to occur after a long latent period (up to 30 years).^7-9 EAI lesions often begin as a chronic ulcer and tend not to heal. If the lesion continues to evolve (ie, ulcerate), a biopsy may be warranted to rule out a malignant transformation.

Eliminate heat exposure,
 consider a topical treatment

Treatment of acute EAI involves eliminating the offending heat source. The hyperpigmentation will slowly resolve over months to years.⁴ Persistent exposure to heat sources can lead to chronic EAI, which is more difficult to eliminate.

Because hyperpigmentation can be visually unappealing and emotionally distressing, some patients prefer active treatment. EAI has been effectively treated with 4% hydroquinone topical cream twice a day and tretinoin topical cream at night.^2,10,11 Lesions that have epithelial atypia have improved with 5-fluorouracil topical cream.⁷

EAI also has been successfully treated with laser therapy with the 1064-nm Q-switched Nd:YAG laser with low fluence at 2-week intervals.⁹

Our patient declined topical therapy. He improved after a few months of avoiding the heater under his desk.

CORRESPONDENCE
Megan Morrison, DO, 5333 McAuley Drive Suite R-5003, Ypsilanti, MI 48197; memorrison10@gmail.com

THE CASE

An 8-month-old Afghan-American girl was brought to the emergency department (ED) for evaluation of a fever and cough. She had been a full-term newborn and was otherwise healthy and up-to-date on routine immunizations. The patient was alert and crying, but consolable. The patient’s pulse was 140 beats/min, axillary temperature was 100.3°F, and respiratory rate was 25 breaths/min. She had rhinorrhea and scattered rhonchi on lung examination; no abnormal skin findings were reported. A chest x-ray showed nonspecific perihilar streaking without consolidation, which the ED physician interpreted as likely reflecting a viral or reactive airway disease. The patient was diagnosed with possible atypical pneumonia and prescribed a course of oral azithromycin (5 mg/kg/d for 7 days).

Two days later, the baby’s parents brought her to our outpatient office because she still had a fever and had developed a rash that had moved from her face to her trunk to her upper arms. The girl also had a wet cough, rhinorrhea, pharyngitis, emesis, nonbloody diarrhea, and poor fluid intake with low urine output. She was fussy and unable to produce tears while crying.

She had an axillary temperature of 100.5°F and a respiratory rate of 60 breaths/min. She also had mild facial edema, copious nasal discharge, erythematous ear canals with opaque, bulging tympanic membranes, right eye discharge, tachycardia, and tachypnea. The patient had pink to violaceous blanching papules and plaques of varied size and shape on her face, chest, abdomen, back, genitals, and upper arms. The plaques were surrounded by halos. She had no lesions on her oral mucosa, palms, or soles.

The parents indicated that the baby’s fever and accompanying symptoms had started 5 days after she and her mother had returned from a 6-week trip to Kabul, Afghanistan to visit family. They stayed in air-conditioned housing, didn’t travel rurally, and had no known exposure to illness. The patient had taken malaria prophylaxis as prescribed.

Due to the appearance of the patient’s rash and the fact that it had appeared soon after she started an antibiotic, we suspected she had a drug allergy that was complicating an upper respiratory viral syndrome with moderate (7%-10% loss of body weight) dehydration. However, given the history of travel along with the presence of cough, rhinorrhea, diarrhea, and a descending rash beginning on the face, we also considered measles.

We instructed the parents to immediately take their daughter to the regional children’s medical center for intravenous fluids and further evaluation. However, possibly due to miscommunication or cultural barriers, they did not go to the children’s hospital ED.

THE DIAGNOSIS

The next day, the Centers for Disease Control and Prevention (CDC) notified us that there had been a case of measles in a child who had been on the same return flight from Afghanistan as our patient. The CDC also confirmed a recent measles outbreak in Kabul.

The local public health department immediately reached out to the patient’s parents, tested the infant, and quarantined the family. Subsequent serologic and polymerase chain reaction (PCR) testing confirmed measles.

DISCUSSION

The appearance of the patient’s rash soon after she started an antibiotic led us to initially suspect a drug allergy.Measles (English measles/rubeola) is a highly contagious morbillivirus in the paramyxovirus family that spreads quickly through respiratory droplets and remains suspended in nonventilated waiting rooms after an infected patient has left.¹

Measles is a leading cause of vaccine-preventable childhood mortality in the world, accounting for an estimated 46% of 1.7 million deaths in 2000.² Measles disproportionately affects poorer communities, where vaccines may not be available. If just 10% of the population is not immunized, outbreaks can occur.³

Fortunately, thanks to increased immunization, the number of deaths due to measles worldwide has been on the decline, from approximately 733,000 in 2001 to 164,000 in 2008.^3,4 Measles is no longer endemic in the United States and is near elimination in the Western Hemisphere if vaccination coverage remains high.

Vaccination. If not traveling internationally, children should receive measles-mumps-rubella (MMR) vaccination between 12 and 15 months and the second dose should be given before they reach age 4.⁵ However, the CDC reported that in 2014, the number of measles cases in the United States had reached a 20-year high, with 593 cases reported as of August 8.⁶ Many of these cases involved Americans who were not vaccinated before traveling to countries where the disease was prevalent.⁴

Before traveling internationally, infants ages 6 to 11 months should receive one MMR vaccination and children >12 months should receive 2 doses before leaving the United States.⁵

Look for fever, rash, and “the 3 Cs”

During its incubation period, the measles virus replicates in the epithelial cells and spreads first to the local lymphatics and then hematogenously to multiple organs.⁴ A fever typically develops 10 days after exposure; the rash develops about 4 days later.⁴

The measles rash is maculopapular and starts on the face, progresses to the trunk and then limbs, and coalesces (FIGURE). The rash typically lasts 3 to 5 days and clears in the same distribution that it appeared.³ The rash is part of a classic clinical presentation that also includes the “3 Cs” (cough, coryza [rhinorrhea], and conjunctivitis). In addition, patients may develop diarrhea and/or Koplik spots, an enanthem of small blue-white haloed lesions on the buccal mucosa (not palate) that are an early manifestation of illness.

Complications occur in around 40% of patients.⁷ Pneumonia is most common; other complications include croup and otitis media. Stomatitis may hinder children from eating. Rare but serious complications include late central nervous system manifestations such as encephalomyelitis, which affects 1/1000 people with measles.⁷ Measles inclusion body encephalitis and subacute sclerosing panencephalitis may emerge months to years after the acute infection and can cause progressive cognitive deterioration and death.⁷

Timing of fever 
helps narrow the diagnosis

The differential diagnosis for fever and rash in a returning traveler is broad (TABLE 1)^8-10 and can be narrowed by a thorough history and exam (TABLE 2).^10,11 Reportable public health conditions must be considered in all returning travelers who present with fever, particularly malaria, due to the possibility of acute deterioration.^12,13 The timing of fever in relation to travel helps narrow the differential diagnosis. If the incubation period is <21 days, many viral infections (including measles, dengue fever, and chikungunya), malaria (especially falciparum), typhoid fever, leptospirosis, and rickettsial diseases should receive top consideration. If the period is >21 days, other causes are more likely.¹⁴

TABLE 2
Taking a returning traveler's history: What to ask^10,11

The diagnosis of measles can be confirmed by serologic testing for measles-specific immunoglobulin M (IgM) antibodies (which may not be detected until 4 or more days after the onset of rash) or a 4-fold rise in immunoglobulin G. Detection of measles ribonucleic acid by PCR assay also can provide confirmation.³

Vitamin A can lower risk
 of mortality, blindness

Treatment of measles consists of supportive care and administration of vitamin A—regardless of the patient’s nutritional status. Vitamin A reduces mortality, decreases the risk of corneal damage, and promotes more rapid recovery and shortened hospital stays.^1,15 World Health Organization guidelines recommend administering specific dosages of vitamin A on 2 consecutive days based on the patient’s age (TABLE 3).¹⁶ For patients with an underlying vitamin A deficiency, a third dose 2 to 4 weeks later is recommended.¹⁷

Our patient

We prescribed vitamin A for our patient but did not administer it. The patient did not follow up and we were not able to confirm the outcome.

THE TAKEAWAY

Vitamin A can lower mortality, decrease the risk of corneal damage, and promote rapid recovery in patients with measles.Before patients travel, counsel them on the need for appropriate immunizations. The MMR vaccine should be given to any child older than age 6 months who will be traveling to a high-risk setting. Health-related information for people who plan to travel is available from the CDC at http://wwwnc.cdc.gov/travel and the US Department of State at http://travel.state.gov/content/passports/english/country.html.

To evaluate fever and rash in an individual returning from travel, take a thorough personal and travel history. Suspect measles in patients who present with cough, rhinorrhea, conjunctivitis, diarrhea, and a descending rash that began on the face. The diagnosis can be confirmed with serologic or PCR testing. Treatment should include supportive measures and vitamin A, regardless of the patient’s nutritional status.

THE CASE

An 8-month-old Afghan-American girl was brought to the emergency department (ED) for evaluation of a fever and cough. She had been a full-term newborn and was otherwise healthy and up-to-date on routine immunizations. The patient was alert and crying, but consolable. The patient’s pulse was 140 beats/min, axillary temperature was 100.3°F, and respiratory rate was 25 breaths/min. She had rhinorrhea and scattered rhonchi on lung examination; no abnormal skin findings were reported. A chest x-ray showed nonspecific perihilar streaking without consolidation, which the ED physician interpreted as likely reflecting a viral or reactive airway disease. The patient was diagnosed with possible atypical pneumonia and prescribed a course of oral azithromycin (5 mg/kg/d for 7 days).

Two days later, the baby’s parents brought her to our outpatient office because she still had a fever and had developed a rash that had moved from her face to her trunk to her upper arms. The girl also had a wet cough, rhinorrhea, pharyngitis, emesis, nonbloody diarrhea, and poor fluid intake with low urine output. She was fussy and unable to produce tears while crying.

She had an axillary temperature of 100.5°F and a respiratory rate of 60 breaths/min. She also had mild facial edema, copious nasal discharge, erythematous ear canals with opaque, bulging tympanic membranes, right eye discharge, tachycardia, and tachypnea. The patient had pink to violaceous blanching papules and plaques of varied size and shape on her face, chest, abdomen, back, genitals, and upper arms. The plaques were surrounded by halos. She had no lesions on her oral mucosa, palms, or soles.

The parents indicated that the baby’s fever and accompanying symptoms had started 5 days after she and her mother had returned from a 6-week trip to Kabul, Afghanistan to visit family. They stayed in air-conditioned housing, didn’t travel rurally, and had no known exposure to illness. The patient had taken malaria prophylaxis as prescribed.

Due to the appearance of the patient’s rash and the fact that it had appeared soon after she started an antibiotic, we suspected she had a drug allergy that was complicating an upper respiratory viral syndrome with moderate (7%-10% loss of body weight) dehydration. However, given the history of travel along with the presence of cough, rhinorrhea, diarrhea, and a descending rash beginning on the face, we also considered measles.

We instructed the parents to immediately take their daughter to the regional children’s medical center for intravenous fluids and further evaluation. However, possibly due to miscommunication or cultural barriers, they did not go to the children’s hospital ED.

THE DIAGNOSIS

The next day, the Centers for Disease Control and Prevention (CDC) notified us that there had been a case of measles in a child who had been on the same return flight from Afghanistan as our patient. The CDC also confirmed a recent measles outbreak in Kabul.

The local public health department immediately reached out to the patient’s parents, tested the infant, and quarantined the family. Subsequent serologic and polymerase chain reaction (PCR) testing confirmed measles.

DISCUSSION

The appearance of the patient’s rash soon after she started an antibiotic led us to initially suspect a drug allergy.Measles (English measles/rubeola) is a highly contagious morbillivirus in the paramyxovirus family that spreads quickly through respiratory droplets and remains suspended in nonventilated waiting rooms after an infected patient has left.¹

Measles is a leading cause of vaccine-preventable childhood mortality in the world, accounting for an estimated 46% of 1.7 million deaths in 2000.² Measles disproportionately affects poorer communities, where vaccines may not be available. If just 10% of the population is not immunized, outbreaks can occur.³

Fortunately, thanks to increased immunization, the number of deaths due to measles worldwide has been on the decline, from approximately 733,000 in 2001 to 164,000 in 2008.^3,4 Measles is no longer endemic in the United States and is near elimination in the Western Hemisphere if vaccination coverage remains high.

Vaccination. If not traveling internationally, children should receive measles-mumps-rubella (MMR) vaccination between 12 and 15 months and the second dose should be given before they reach age 4.⁵ However, the CDC reported that in 2014, the number of measles cases in the United States had reached a 20-year high, with 593 cases reported as of August 8.⁶ Many of these cases involved Americans who were not vaccinated before traveling to countries where the disease was prevalent.⁴

Before traveling internationally, infants ages 6 to 11 months should receive one MMR vaccination and children >12 months should receive 2 doses before leaving the United States.⁵

Look for fever, rash, and “the 3 Cs”

During its incubation period, the measles virus replicates in the epithelial cells and spreads first to the local lymphatics and then hematogenously to multiple organs.⁴ A fever typically develops 10 days after exposure; the rash develops about 4 days later.⁴

The measles rash is maculopapular and starts on the face, progresses to the trunk and then limbs, and coalesces (FIGURE). The rash typically lasts 3 to 5 days and clears in the same distribution that it appeared.³ The rash is part of a classic clinical presentation that also includes the “3 Cs” (cough, coryza [rhinorrhea], and conjunctivitis). In addition, patients may develop diarrhea and/or Koplik spots, an enanthem of small blue-white haloed lesions on the buccal mucosa (not palate) that are an early manifestation of illness.

Complications occur in around 40% of patients.⁷ Pneumonia is most common; other complications include croup and otitis media. Stomatitis may hinder children from eating. Rare but serious complications include late central nervous system manifestations such as encephalomyelitis, which affects 1/1000 people with measles.⁷ Measles inclusion body encephalitis and subacute sclerosing panencephalitis may emerge months to years after the acute infection and can cause progressive cognitive deterioration and death.⁷

Timing of fever 
helps narrow the diagnosis

The differential diagnosis for fever and rash in a returning traveler is broad (TABLE 1)^8-10 and can be narrowed by a thorough history and exam (TABLE 2).^10,11 Reportable public health conditions must be considered in all returning travelers who present with fever, particularly malaria, due to the possibility of acute deterioration.^12,13 The timing of fever in relation to travel helps narrow the differential diagnosis. If the incubation period is <21 days, many viral infections (including measles, dengue fever, and chikungunya), malaria (especially falciparum), typhoid fever, leptospirosis, and rickettsial diseases should receive top consideration. If the period is >21 days, other causes are more likely.¹⁴

TABLE 2
Taking a returning traveler's history: What to ask^10,11

The diagnosis of measles can be confirmed by serologic testing for measles-specific immunoglobulin M (IgM) antibodies (which may not be detected until 4 or more days after the onset of rash) or a 4-fold rise in immunoglobulin G. Detection of measles ribonucleic acid by PCR assay also can provide confirmation.³

Vitamin A can lower risk
 of mortality, blindness

Treatment of measles consists of supportive care and administration of vitamin A—regardless of the patient’s nutritional status. Vitamin A reduces mortality, decreases the risk of corneal damage, and promotes more rapid recovery and shortened hospital stays.^1,15 World Health Organization guidelines recommend administering specific dosages of vitamin A on 2 consecutive days based on the patient’s age (TABLE 3).¹⁶ For patients with an underlying vitamin A deficiency, a third dose 2 to 4 weeks later is recommended.¹⁷

Our patient

We prescribed vitamin A for our patient but did not administer it. The patient did not follow up and we were not able to confirm the outcome.

THE TAKEAWAY

Vitamin A can lower mortality, decrease the risk of corneal damage, and promote rapid recovery in patients with measles.Before patients travel, counsel them on the need for appropriate immunizations. The MMR vaccine should be given to any child older than age 6 months who will be traveling to a high-risk setting. Health-related information for people who plan to travel is available from the CDC at http://wwwnc.cdc.gov/travel and the US Department of State at http://travel.state.gov/content/passports/english/country.html.

To evaluate fever and rash in an individual returning from travel, take a thorough personal and travel history. Suspect measles in patients who present with cough, rhinorrhea, conjunctivitis, diarrhea, and a descending rash that began on the face. The diagnosis can be confirmed with serologic or PCR testing. Treatment should include supportive measures and vitamin A, regardless of the patient’s nutritional status.

THE CASE

An 8-month-old Afghan-American girl was brought to the emergency department (ED) for evaluation of a fever and cough. She had been a full-term newborn and was otherwise healthy and up-to-date on routine immunizations. The patient was alert and crying, but consolable. The patient’s pulse was 140 beats/min, axillary temperature was 100.3°F, and respiratory rate was 25 breaths/min. She had rhinorrhea and scattered rhonchi on lung examination; no abnormal skin findings were reported. A chest x-ray showed nonspecific perihilar streaking without consolidation, which the ED physician interpreted as likely reflecting a viral or reactive airway disease. The patient was diagnosed with possible atypical pneumonia and prescribed a course of oral azithromycin (5 mg/kg/d for 7 days).

Two days later, the baby’s parents brought her to our outpatient office because she still had a fever and had developed a rash that had moved from her face to her trunk to her upper arms. The girl also had a wet cough, rhinorrhea, pharyngitis, emesis, nonbloody diarrhea, and poor fluid intake with low urine output. She was fussy and unable to produce tears while crying.

She had an axillary temperature of 100.5°F and a respiratory rate of 60 breaths/min. She also had mild facial edema, copious nasal discharge, erythematous ear canals with opaque, bulging tympanic membranes, right eye discharge, tachycardia, and tachypnea. The patient had pink to violaceous blanching papules and plaques of varied size and shape on her face, chest, abdomen, back, genitals, and upper arms. The plaques were surrounded by halos. She had no lesions on her oral mucosa, palms, or soles.

The parents indicated that the baby’s fever and accompanying symptoms had started 5 days after she and her mother had returned from a 6-week trip to Kabul, Afghanistan to visit family. They stayed in air-conditioned housing, didn’t travel rurally, and had no known exposure to illness. The patient had taken malaria prophylaxis as prescribed.

Due to the appearance of the patient’s rash and the fact that it had appeared soon after she started an antibiotic, we suspected she had a drug allergy that was complicating an upper respiratory viral syndrome with moderate (7%-10% loss of body weight) dehydration. However, given the history of travel along with the presence of cough, rhinorrhea, diarrhea, and a descending rash beginning on the face, we also considered measles.

We instructed the parents to immediately take their daughter to the regional children’s medical center for intravenous fluids and further evaluation. However, possibly due to miscommunication or cultural barriers, they did not go to the children’s hospital ED.

THE DIAGNOSIS

The next day, the Centers for Disease Control and Prevention (CDC) notified us that there had been a case of measles in a child who had been on the same return flight from Afghanistan as our patient. The CDC also confirmed a recent measles outbreak in Kabul.

The local public health department immediately reached out to the patient’s parents, tested the infant, and quarantined the family. Subsequent serologic and polymerase chain reaction (PCR) testing confirmed measles.

DISCUSSION

The appearance of the patient’s rash soon after she started an antibiotic led us to initially suspect a drug allergy.Measles (English measles/rubeola) is a highly contagious morbillivirus in the paramyxovirus family that spreads quickly through respiratory droplets and remains suspended in nonventilated waiting rooms after an infected patient has left.¹

Measles is a leading cause of vaccine-preventable childhood mortality in the world, accounting for an estimated 46% of 1.7 million deaths in 2000.² Measles disproportionately affects poorer communities, where vaccines may not be available. If just 10% of the population is not immunized, outbreaks can occur.³

Fortunately, thanks to increased immunization, the number of deaths due to measles worldwide has been on the decline, from approximately 733,000 in 2001 to 164,000 in 2008.^3,4 Measles is no longer endemic in the United States and is near elimination in the Western Hemisphere if vaccination coverage remains high.

Vaccination. If not traveling internationally, children should receive measles-mumps-rubella (MMR) vaccination between 12 and 15 months and the second dose should be given before they reach age 4.⁵ However, the CDC reported that in 2014, the number of measles cases in the United States had reached a 20-year high, with 593 cases reported as of August 8.⁶ Many of these cases involved Americans who were not vaccinated before traveling to countries where the disease was prevalent.⁴

Before traveling internationally, infants ages 6 to 11 months should receive one MMR vaccination and children >12 months should receive 2 doses before leaving the United States.⁵

Look for fever, rash, and “the 3 Cs”

During its incubation period, the measles virus replicates in the epithelial cells and spreads first to the local lymphatics and then hematogenously to multiple organs.⁴ A fever typically develops 10 days after exposure; the rash develops about 4 days later.⁴

The measles rash is maculopapular and starts on the face, progresses to the trunk and then limbs, and coalesces (FIGURE). The rash typically lasts 3 to 5 days and clears in the same distribution that it appeared.³ The rash is part of a classic clinical presentation that also includes the “3 Cs” (cough, coryza [rhinorrhea], and conjunctivitis). In addition, patients may develop diarrhea and/or Koplik spots, an enanthem of small blue-white haloed lesions on the buccal mucosa (not palate) that are an early manifestation of illness.

Complications occur in around 40% of patients.⁷ Pneumonia is most common; other complications include croup and otitis media. Stomatitis may hinder children from eating. Rare but serious complications include late central nervous system manifestations such as encephalomyelitis, which affects 1/1000 people with measles.⁷ Measles inclusion body encephalitis and subacute sclerosing panencephalitis may emerge months to years after the acute infection and can cause progressive cognitive deterioration and death.⁷

Timing of fever 
helps narrow the diagnosis

The differential diagnosis for fever and rash in a returning traveler is broad (TABLE 1)^8-10 and can be narrowed by a thorough history and exam (TABLE 2).^10,11 Reportable public health conditions must be considered in all returning travelers who present with fever, particularly malaria, due to the possibility of acute deterioration.^12,13 The timing of fever in relation to travel helps narrow the differential diagnosis. If the incubation period is <21 days, many viral infections (including measles, dengue fever, and chikungunya), malaria (especially falciparum), typhoid fever, leptospirosis, and rickettsial diseases should receive top consideration. If the period is >21 days, other causes are more likely.¹⁴

TABLE 2
Taking a returning traveler's history: What to ask^10,11

The diagnosis of measles can be confirmed by serologic testing for measles-specific immunoglobulin M (IgM) antibodies (which may not be detected until 4 or more days after the onset of rash) or a 4-fold rise in immunoglobulin G. Detection of measles ribonucleic acid by PCR assay also can provide confirmation.³

Vitamin A can lower risk
 of mortality, blindness

Treatment of measles consists of supportive care and administration of vitamin A—regardless of the patient’s nutritional status. Vitamin A reduces mortality, decreases the risk of corneal damage, and promotes more rapid recovery and shortened hospital stays.^1,15 World Health Organization guidelines recommend administering specific dosages of vitamin A on 2 consecutive days based on the patient’s age (TABLE 3).¹⁶ For patients with an underlying vitamin A deficiency, a third dose 2 to 4 weeks later is recommended.¹⁷

Our patient

We prescribed vitamin A for our patient but did not administer it. The patient did not follow up and we were not able to confirm the outcome.

THE TAKEAWAY

Vitamin A can lower mortality, decrease the risk of corneal damage, and promote rapid recovery in patients with measles.Before patients travel, counsel them on the need for appropriate immunizations. The MMR vaccine should be given to any child older than age 6 months who will be traveling to a high-risk setting. Health-related information for people who plan to travel is available from the CDC at http://wwwnc.cdc.gov/travel and the US Department of State at http://travel.state.gov/content/passports/english/country.html.

To evaluate fever and rash in an individual returning from travel, take a thorough personal and travel history. Suspect measles in patients who present with cough, rhinorrhea, conjunctivitis, diarrhea, and a descending rash that began on the face. The diagnosis can be confirmed with serologic or PCR testing. Treatment should include supportive measures and vitamin A, regardless of the patient’s nutritional status.