The Journal of Family Practice

EVIDENCE SUMMARY

An international prospective cohort study analyzed data from 14,687 patients, 4802 of whom were on an ACEI or ARB, to study the effect on 30-day morbidity and mortality of withholding the medications 24 hours before a noncardiac surgery.¹ Of the ACEI or ARB users, 26% (1245) withheld their medication and 3557 continued it 24 hours before surgery.

Large study shows benefit in withholding meds

Patients who withheld the ACEI or ARB were less likely to experience the primary composite outcome of all-cause death, stroke, or myocardial injury (150/1245 [12%] vs 459/3557 [12.9%]; adjusted relative risk [RR] = 0.82; 95% confidence interval [CI], 0.70-0.96; P = .01; number needed to treat [NNT] = 116) and intraoperative hypotension (adjusted RR = 0.80; 95% CI, 0.72-0.93; P < .001; NNT = 18). For the NNT calculation, which the investigators didn’t perform, the treatment is the number needed to withhold an ACEI or ARB to show benefit.

Smaller, weaker studies yield different results

A retrospective cohort analysis of propensity-matched ACEI users with ACEI nonusers (9028 in each group) undergoing noncardiac surgery compared intra- and postoperative respiratory complications or mortality.² The study found no association with either 30-day mortality (odds ratio [OR] = 0.93; 95% CI, 0.73-1.19) or the composite of in-hospital morbidity and mortality (OR = 1.06; 95% CI, 0.97-1.15). Limitations included comparison of users with nonusers as opposed to an intention-to-withhold study, the retrospective nature of the study, and the fact that outcomes were gathered from ICD-9 billing codes rather than obtained prospectively.

A Cochrane review assessed the benefits and harms of perioperative ACEIs or ARBs on mortality and morbidity in adults undergoing any type of surgery.³ Seven RCTs with a total of 571 participants were included in the review. Overall, the review didn’t find evidence to support prevention of mortality, morbidity, and complications by perioperative ACEIs or ARBs because the included studies were of low and very low methodological quality, had a high risk for bias, and lacked power. Moreover, the review didn’t assess the effect of withholding ACEIs or ARBs before surgery.

A random-effects meta-analysis of 5 studies (3 randomized trials and 2 observational studies) totaling 434 patients suggested that patients receiving ACEIs or ARBs immediately before surgery were more likely to develop hypotension requiring vasopressors (RR = 1.50; 95% CI, 1.15-1.96).⁴ Sufficient data weren’t available to assess other outcomes, and the included studies were relatively small and generally not powered to observe clinically significant consequences nor designed to measure the incidence of patient-important outcomes.

Continue to: RECOMMENDATIONS

RECOMMENDATIONS

The 2014 American College of Cardiology/American Heart Association Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery states that continuing ACEIs or ARBs perioperatively is reasonable (class IIa recommendation [moderate benefit of treatment relative to risk]; level of evidence [LOE], B [data from limited populations and single randomized or nonrandomized trials]). ⁵

The guideline also recommends that if ACEIs or ARBs are held before surgery, it is reasonable to restart them as soon as clinically feasible postoperatively (class IIa recommendation; LOE, C [data from very limited populations and consensus opinion or case studies]).

Editor’s Takeaway

The results of the large prospective cohort contradict those of previous smaller, methodologically weaker studies, and the new findings should be taken seriously.¹ Nevertheless, selection bias (why did investigators stop the ACEI?) remains. Until we have a large RCT, the preop question to ask may be why not stop the ACEI?

EVIDENCE SUMMARY

An international prospective cohort study analyzed data from 14,687 patients, 4802 of whom were on an ACEI or ARB, to study the effect on 30-day morbidity and mortality of withholding the medications 24 hours before a noncardiac surgery.¹ Of the ACEI or ARB users, 26% (1245) withheld their medication and 3557 continued it 24 hours before surgery.

Large study shows benefit in withholding meds

Patients who withheld the ACEI or ARB were less likely to experience the primary composite outcome of all-cause death, stroke, or myocardial injury (150/1245 [12%] vs 459/3557 [12.9%]; adjusted relative risk [RR] = 0.82; 95% confidence interval [CI], 0.70-0.96; P = .01; number needed to treat [NNT] = 116) and intraoperative hypotension (adjusted RR = 0.80; 95% CI, 0.72-0.93; P < .001; NNT = 18). For the NNT calculation, which the investigators didn’t perform, the treatment is the number needed to withhold an ACEI or ARB to show benefit.

Smaller, weaker studies yield different results

A retrospective cohort analysis of propensity-matched ACEI users with ACEI nonusers (9028 in each group) undergoing noncardiac surgery compared intra- and postoperative respiratory complications or mortality.² The study found no association with either 30-day mortality (odds ratio [OR] = 0.93; 95% CI, 0.73-1.19) or the composite of in-hospital morbidity and mortality (OR = 1.06; 95% CI, 0.97-1.15). Limitations included comparison of users with nonusers as opposed to an intention-to-withhold study, the retrospective nature of the study, and the fact that outcomes were gathered from ICD-9 billing codes rather than obtained prospectively.

A Cochrane review assessed the benefits and harms of perioperative ACEIs or ARBs on mortality and morbidity in adults undergoing any type of surgery.³ Seven RCTs with a total of 571 participants were included in the review. Overall, the review didn’t find evidence to support prevention of mortality, morbidity, and complications by perioperative ACEIs or ARBs because the included studies were of low and very low methodological quality, had a high risk for bias, and lacked power. Moreover, the review didn’t assess the effect of withholding ACEIs or ARBs before surgery.

A random-effects meta-analysis of 5 studies (3 randomized trials and 2 observational studies) totaling 434 patients suggested that patients receiving ACEIs or ARBs immediately before surgery were more likely to develop hypotension requiring vasopressors (RR = 1.50; 95% CI, 1.15-1.96).⁴ Sufficient data weren’t available to assess other outcomes, and the included studies were relatively small and generally not powered to observe clinically significant consequences nor designed to measure the incidence of patient-important outcomes.

Continue to: RECOMMENDATIONS

RECOMMENDATIONS

The 2014 American College of Cardiology/American Heart Association Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery states that continuing ACEIs or ARBs perioperatively is reasonable (class IIa recommendation [moderate benefit of treatment relative to risk]; level of evidence [LOE], B [data from limited populations and single randomized or nonrandomized trials]). ⁵

The guideline also recommends that if ACEIs or ARBs are held before surgery, it is reasonable to restart them as soon as clinically feasible postoperatively (class IIa recommendation; LOE, C [data from very limited populations and consensus opinion or case studies]).

Editor’s Takeaway

The results of the large prospective cohort contradict those of previous smaller, methodologically weaker studies, and the new findings should be taken seriously.¹ Nevertheless, selection bias (why did investigators stop the ACEI?) remains. Until we have a large RCT, the preop question to ask may be why not stop the ACEI?

EVIDENCE SUMMARY

An international prospective cohort study analyzed data from 14,687 patients, 4802 of whom were on an ACEI or ARB, to study the effect on 30-day morbidity and mortality of withholding the medications 24 hours before a noncardiac surgery.¹ Of the ACEI or ARB users, 26% (1245) withheld their medication and 3557 continued it 24 hours before surgery.

Large study shows benefit in withholding meds

Patients who withheld the ACEI or ARB were less likely to experience the primary composite outcome of all-cause death, stroke, or myocardial injury (150/1245 [12%] vs 459/3557 [12.9%]; adjusted relative risk [RR] = 0.82; 95% confidence interval [CI], 0.70-0.96; P = .01; number needed to treat [NNT] = 116) and intraoperative hypotension (adjusted RR = 0.80; 95% CI, 0.72-0.93; P < .001; NNT = 18). For the NNT calculation, which the investigators didn’t perform, the treatment is the number needed to withhold an ACEI or ARB to show benefit.

Smaller, weaker studies yield different results

A retrospective cohort analysis of propensity-matched ACEI users with ACEI nonusers (9028 in each group) undergoing noncardiac surgery compared intra- and postoperative respiratory complications or mortality.² The study found no association with either 30-day mortality (odds ratio [OR] = 0.93; 95% CI, 0.73-1.19) or the composite of in-hospital morbidity and mortality (OR = 1.06; 95% CI, 0.97-1.15). Limitations included comparison of users with nonusers as opposed to an intention-to-withhold study, the retrospective nature of the study, and the fact that outcomes were gathered from ICD-9 billing codes rather than obtained prospectively.

A Cochrane review assessed the benefits and harms of perioperative ACEIs or ARBs on mortality and morbidity in adults undergoing any type of surgery.³ Seven RCTs with a total of 571 participants were included in the review. Overall, the review didn’t find evidence to support prevention of mortality, morbidity, and complications by perioperative ACEIs or ARBs because the included studies were of low and very low methodological quality, had a high risk for bias, and lacked power. Moreover, the review didn’t assess the effect of withholding ACEIs or ARBs before surgery.

A random-effects meta-analysis of 5 studies (3 randomized trials and 2 observational studies) totaling 434 patients suggested that patients receiving ACEIs or ARBs immediately before surgery were more likely to develop hypotension requiring vasopressors (RR = 1.50; 95% CI, 1.15-1.96).⁴ Sufficient data weren’t available to assess other outcomes, and the included studies were relatively small and generally not powered to observe clinically significant consequences nor designed to measure the incidence of patient-important outcomes.

Continue to: RECOMMENDATIONS

RECOMMENDATIONS

The 2014 American College of Cardiology/American Heart Association Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery states that continuing ACEIs or ARBs perioperatively is reasonable (class IIa recommendation [moderate benefit of treatment relative to risk]; level of evidence [LOE], B [data from limited populations and single randomized or nonrandomized trials]). ⁵

The guideline also recommends that if ACEIs or ARBs are held before surgery, it is reasonable to restart them as soon as clinically feasible postoperatively (class IIa recommendation; LOE, C [data from very limited populations and consensus opinion or case studies]).

Editor’s Takeaway

The results of the large prospective cohort contradict those of previous smaller, methodologically weaker studies, and the new findings should be taken seriously.¹ Nevertheless, selection bias (why did investigators stop the ACEI?) remains. Until we have a large RCT, the preop question to ask may be why not stop the ACEI?

Just like the 2018 hypertension treatment guidelines, the 2018 Guidelines on the Management of Blood Cholesterol developed by the American College of Cardiology and the American Heart Association (ACC/AHA) have made treatment decisions much more complicated. In this issue of JFP, Wójcik and Shapiro summarize the 70-page document to help family physicians and other primary health care professionals use these complex guidelines in everyday practice.

The good news is that not much has changed from the 2013 ACC/AHA cholesterol guidelines regarding the treatment of patients with established cardiovascular disease and diabetes mellitus, and those with familial hyperlipidemia—the groups at highest risk for major cardiovascular events. Most of these patients should be treated aggressively, and a target low-density lipoprotein of 70 mg/dL is recommended.

I find the recommendations for adults ages 75 and older and for children and teens to be problematic.

The new guidelines recommend using ezetimibe or a PCSK9 inhibitor if the goal of 70 mg/dL cannot be achieved with a statin alone. There is randomized trial evidence to support the benefit of this aggressive approach. Generic ezetimibe costs about $20 per month,¹ but the PCSK9 inhibitors are about $500 per month,^2,3 so cost may be a treatment barrier for the 2 monoclonal antibodies approved for cardiovascular prevention: evolocumab and alirocumab.

For primary prevention, the new guidelines are much more complicated. They divide cardiovascular risk into 4 tiers depending on the 10-year risk for atherosclerotic cardiovascular disease calculated using the “pooled cohort equation.” Treatment recommendations are more aggressive for those at higher risk. Although it intuitively makes sense to treat those at higher risk more aggressively, there is no clinical trial evidence to support this approach’s superiority over the simpler approach recommended in the 2013 guidelines.

I find the recommendations for screening and primary prevention in adults ages 75 and older and for children and teens to be problematic. A meta-analysis of 28 studies found no statin treatment benefit for primary prevention in those older than 70.⁴ And there are no randomized trials showing benefit of screening and treating children and teens for hyperlipidemia.

On a positive note, most patients do not need to fast prior to having their lipids measured.

Read the 2018 cholesterol treatment guideline summary in this issue of JFP. But as you do so, remember that guidelines are guidelines; they are not mandates for treatment. You may need to customize these guidelines for your practice and your patients. In my opinion, the simpler 2013 cholesterol guidelines remain good guidelines.

Just like the 2018 hypertension treatment guidelines, the 2018 Guidelines on the Management of Blood Cholesterol developed by the American College of Cardiology and the American Heart Association (ACC/AHA) have made treatment decisions much more complicated. In this issue of JFP, Wójcik and Shapiro summarize the 70-page document to help family physicians and other primary health care professionals use these complex guidelines in everyday practice.

The good news is that not much has changed from the 2013 ACC/AHA cholesterol guidelines regarding the treatment of patients with established cardiovascular disease and diabetes mellitus, and those with familial hyperlipidemia—the groups at highest risk for major cardiovascular events. Most of these patients should be treated aggressively, and a target low-density lipoprotein of 70 mg/dL is recommended.

I find the recommendations for adults ages 75 and older and for children and teens to be problematic.

The new guidelines recommend using ezetimibe or a PCSK9 inhibitor if the goal of 70 mg/dL cannot be achieved with a statin alone. There is randomized trial evidence to support the benefit of this aggressive approach. Generic ezetimibe costs about $20 per month,¹ but the PCSK9 inhibitors are about $500 per month,^2,3 so cost may be a treatment barrier for the 2 monoclonal antibodies approved for cardiovascular prevention: evolocumab and alirocumab.

For primary prevention, the new guidelines are much more complicated. They divide cardiovascular risk into 4 tiers depending on the 10-year risk for atherosclerotic cardiovascular disease calculated using the “pooled cohort equation.” Treatment recommendations are more aggressive for those at higher risk. Although it intuitively makes sense to treat those at higher risk more aggressively, there is no clinical trial evidence to support this approach’s superiority over the simpler approach recommended in the 2013 guidelines.

I find the recommendations for screening and primary prevention in adults ages 75 and older and for children and teens to be problematic. A meta-analysis of 28 studies found no statin treatment benefit for primary prevention in those older than 70.⁴ And there are no randomized trials showing benefit of screening and treating children and teens for hyperlipidemia.

On a positive note, most patients do not need to fast prior to having their lipids measured.

Read the 2018 cholesterol treatment guideline summary in this issue of JFP. But as you do so, remember that guidelines are guidelines; they are not mandates for treatment. You may need to customize these guidelines for your practice and your patients. In my opinion, the simpler 2013 cholesterol guidelines remain good guidelines.

Just like the 2018 hypertension treatment guidelines, the 2018 Guidelines on the Management of Blood Cholesterol developed by the American College of Cardiology and the American Heart Association (ACC/AHA) have made treatment decisions much more complicated. In this issue of JFP, Wójcik and Shapiro summarize the 70-page document to help family physicians and other primary health care professionals use these complex guidelines in everyday practice.

The good news is that not much has changed from the 2013 ACC/AHA cholesterol guidelines regarding the treatment of patients with established cardiovascular disease and diabetes mellitus, and those with familial hyperlipidemia—the groups at highest risk for major cardiovascular events. Most of these patients should be treated aggressively, and a target low-density lipoprotein of 70 mg/dL is recommended.

I find the recommendations for adults ages 75 and older and for children and teens to be problematic.

The new guidelines recommend using ezetimibe or a PCSK9 inhibitor if the goal of 70 mg/dL cannot be achieved with a statin alone. There is randomized trial evidence to support the benefit of this aggressive approach. Generic ezetimibe costs about $20 per month,¹ but the PCSK9 inhibitors are about $500 per month,^2,3 so cost may be a treatment barrier for the 2 monoclonal antibodies approved for cardiovascular prevention: evolocumab and alirocumab.

For primary prevention, the new guidelines are much more complicated. They divide cardiovascular risk into 4 tiers depending on the 10-year risk for atherosclerotic cardiovascular disease calculated using the “pooled cohort equation.” Treatment recommendations are more aggressive for those at higher risk. Although it intuitively makes sense to treat those at higher risk more aggressively, there is no clinical trial evidence to support this approach’s superiority over the simpler approach recommended in the 2013 guidelines.

I find the recommendations for screening and primary prevention in adults ages 75 and older and for children and teens to be problematic. A meta-analysis of 28 studies found no statin treatment benefit for primary prevention in those older than 70.⁴ And there are no randomized trials showing benefit of screening and treating children and teens for hyperlipidemia.

On a positive note, most patients do not need to fast prior to having their lipids measured.

Read the 2018 cholesterol treatment guideline summary in this issue of JFP. But as you do so, remember that guidelines are guidelines; they are not mandates for treatment. You may need to customize these guidelines for your practice and your patients. In my opinion, the simpler 2013 cholesterol guidelines remain good guidelines.

THE CASE

A 29-year-old G7P2315 woman gave birth to a girl at 37 weeks via spontaneous vaginal delivery. APGAR scores were 9 and 9. Birth weight was 2760 g. Cardiovascular and pulmonary examinations were normal (heart rate, 154 beats/min; respiratory rate, 52 breaths/min). Following delivery, the neonate appeared healthy, had a lusty cry, and had no visible craniofacial or cutaneous abnormalities; however, the bilateral knees were hyperextended to 90° to 110° (FIGURE 1A).

The mother had started prenatal care at 7 weeks with 10 total visits to her family physician (JD) throughout the pregnancy. Routine laboratory screening and prenatal ultrasounds (including an anatomy scan) were normal. She had a history of 3 preterm deliveries at 35 weeks, 36 weeks, and 36 weeks, respectively, and had been on progesterone shots once weekly starting at 18 weeks during the current pregnancy. She had no history of infections or recent travel. Her family history was remarkable for a sister who gave birth to a child with thrombocytopenia absent radius syndrome.

THE DIAGNOSIS

The neonate tolerated passive flexion of the knees to a neutral position. Hip examination demonstrated appropriate range of movement with negative Ortolani and Barlow tests. The infant’s feet aligned correctly, with toes in the front and heels in the back, and an x-ray of the bilateral knees showed no fractures or dislocation.

Based on the clinical examination and x-ray findings, we made a diagnosis of congenital genu recurvatum. A pediatric orthopedics consultation was obtained, and the knees were placed in short leg splints in comfortable flexion to neutral on Day 1 of life. She was discharged the next day.

DISCUSSION

Congenital genu recurvatum, also known as congenital dislocation of the knee, is a rare condition involving abnormal hyperextension of the unilateral or bilateral knees with limited flexion.¹ Reports in the literature are limited, but there seems to be a female predominance among known cases of congenital genu recurvatum.² The clinical presentation varies. Finding may be isolated to the knee(s) but also can present in association with other congenital abnormalities, such as developmental dysplasia of the hip, clubfoot, and hindfoot and forefoot deformities.^3,4

Diagnosis is made clinically with radiographic imaging

Diagnosis of congenital genu recurvatum is made clinically and can be confirmed via radiographic imaging of the knees.5 Clinical diagnosis requires assessment of the degree of hyperextension and palpation of the femoral condyles, which become more prominent as the severity of the hyperextension increases.⁶ X-rays help assess if a true dislocation or subluxation of the tibia on the femur has occurred. Based on the clinical and radiographic findings, congenital genu recurvatum typically is classified according to 3 levels of severity: grade 1 classification only involves hyperextension of the knees without dislocation or subluxation, grade 2 involves the same characteristic hyperextension along with  anterior subluxation of the tibia on the femur, and grade 3 includes hyperextension with true dislocation of the tibia on the femur.¹ Grades 1 and 2 on this spectrum technically are diagnosed as congenital genu recurvatum while grade 3 is diagnosed as a congenital dislocation of the knee,⁷ although the 2 terms are used interchangeably in the literature. We classified our case as a grade 1 congenital genu recurvatum based on the clinical and radiographic findings.

Congenital knee hyperextension has intrinsic and extrinsic causes

Hyperextension of the knees at birth may be caused by various intrinsic or extrinsic factors. Intrinsic causes may include breech position, lack of intrauterine space, trauma to the mother, quadriceps contracture or fibrosis, absence of the suprapatellar pouch, deficient or hypoplastic anterior cruciate ligament, pathological tissues, arthrogryposis, or genetic disorders such as Larsen syndrome or achondroplasia.⁶

Continue to: Extrinsic causes...

Extrinsic causes may include traumatic dislocation during the birthing process³ or intrauterine pressure leading to malposition of the joints. When intrauterine pressure is combined with reduced intrauterine space, this phenomenon is known as packaging disorder.⁶ Entanglement of the umbilical cord around the legs of the fetus during development may be another potential factor.¹Of note: Cases involving both extrinsic or intrinsic etiologies can present with associated abnormalities that include congenital dislocation of the hip, congenital hip dysplasia, spina bifida, and/or cleft palate—in addition to knee hyperextension.

The exact etiology in our patient was unknown, but we determined the cause was extrinsic based on the lack of other genetic abnormalities. We initially considered a possible connection between our patient’s diagnosis and her family history of thrombocytopenia absent radius syndrome, but it was later determined that both were isolated cases and the limb abnormalities were coincidental.

Treatment options and outcomes for extrinsic and intrinsic etiologies depend on the severity of the hyperextension and any associated abnormalities, as well as the time in which therapy is initiated.¹ Reduction of the hyperextension within 24 hours of birth has been associated with excellent outcomes.⁸ Regardless of the cause, all cases of congenital genu recurvatum should first be treated conservatively. Evidence has suggested that conservative therapy involving early gentle manipulation of the knee combined with serial splinting and casting should be the first line of treatment.⁶ If initial treatment attempts fail or in cases occurring later in life, surgical interventions (eg, quadriceps release procedures such as percutaneous quadriceps recession or V-Y quadricepsplasty, proximal tibial closing-wedge, anterior displacement osteotomy) likely is warranted.^6,9

Our patient. At 1 week of life, our patient’s short leg splints were replaced with long leg splints with a maximal flexion of 20° to 30° (FIGURE 1B). Weekly follow-ups with serial casting were initiated in the pediatric orthopedics clinic. At 3 weeks of life, the patient’s knee flexion had improved and the splints were removed (FIGURE 1C). Upon clinical examination, the bilateral knees were extended to a neutral position, and both could be actively and passively flexed to 90°. The patient was referred to Physical Therapy to perform range of movement exercises on the knees.

IMAGE COURTESY OF: METROHEALTH MEDICAL CENTER, CASE WESTERN RESERVE UNIVERSITY, CLEVELAND, OHIO

At 8 weeks of life, the bilateral legs were in full extension, and knee flexion was up to 130°. Physical therapy for knee range of movement exercise was continued on a weekly basis until 6 months of life, then twice monthly until the patient was 1 year old. Ultimately, the hyperextension was corrected, and the patient started walking at around 16 months of age. Her prognosis is good, and she will be able to participate in low-impact sports, after consulting with her orthopedist.

IMAGE COURTESY OF: METROHEALTH MEDICAL CENTER, CASE WESTERN RESERVE UNIVERSITY, CLEVELAND, OHIO

Continue to: THE TAKEAWAY

THE TAKEAWAY

Congenital genu recurvatum is a rare condition that presents with abnormal hyperextension of the knee(s) with limited flexion. Early diagnosis and assessment of the severity of the hyperextension is crucial in determining the type of intervention to pursue. Conservative management entails serial casting and splinting to increase knee flexion. If conservative management fails or if the diagnosis is made later in life, surgical options often are pursued.

CORRESPONDENCE
Jaividhya Dasarathy, MD, FAAFP, 2500 MetroHealth Medical Drive, Cleveland, OH 44109; jxd114@case.edu

THE CASE

A 29-year-old G7P2315 woman gave birth to a girl at 37 weeks via spontaneous vaginal delivery. APGAR scores were 9 and 9. Birth weight was 2760 g. Cardiovascular and pulmonary examinations were normal (heart rate, 154 beats/min; respiratory rate, 52 breaths/min). Following delivery, the neonate appeared healthy, had a lusty cry, and had no visible craniofacial or cutaneous abnormalities; however, the bilateral knees were hyperextended to 90° to 110° (FIGURE 1A).

The mother had started prenatal care at 7 weeks with 10 total visits to her family physician (JD) throughout the pregnancy. Routine laboratory screening and prenatal ultrasounds (including an anatomy scan) were normal. She had a history of 3 preterm deliveries at 35 weeks, 36 weeks, and 36 weeks, respectively, and had been on progesterone shots once weekly starting at 18 weeks during the current pregnancy. She had no history of infections or recent travel. Her family history was remarkable for a sister who gave birth to a child with thrombocytopenia absent radius syndrome.

THE DIAGNOSIS

The neonate tolerated passive flexion of the knees to a neutral position. Hip examination demonstrated appropriate range of movement with negative Ortolani and Barlow tests. The infant’s feet aligned correctly, with toes in the front and heels in the back, and an x-ray of the bilateral knees showed no fractures or dislocation.

Based on the clinical examination and x-ray findings, we made a diagnosis of congenital genu recurvatum. A pediatric orthopedics consultation was obtained, and the knees were placed in short leg splints in comfortable flexion to neutral on Day 1 of life. She was discharged the next day.

DISCUSSION

Congenital genu recurvatum, also known as congenital dislocation of the knee, is a rare condition involving abnormal hyperextension of the unilateral or bilateral knees with limited flexion.¹ Reports in the literature are limited, but there seems to be a female predominance among known cases of congenital genu recurvatum.² The clinical presentation varies. Finding may be isolated to the knee(s) but also can present in association with other congenital abnormalities, such as developmental dysplasia of the hip, clubfoot, and hindfoot and forefoot deformities.^3,4

Diagnosis is made clinically with radiographic imaging

Diagnosis of congenital genu recurvatum is made clinically and can be confirmed via radiographic imaging of the knees.5 Clinical diagnosis requires assessment of the degree of hyperextension and palpation of the femoral condyles, which become more prominent as the severity of the hyperextension increases.⁶ X-rays help assess if a true dislocation or subluxation of the tibia on the femur has occurred. Based on the clinical and radiographic findings, congenital genu recurvatum typically is classified according to 3 levels of severity: grade 1 classification only involves hyperextension of the knees without dislocation or subluxation, grade 2 involves the same characteristic hyperextension along with  anterior subluxation of the tibia on the femur, and grade 3 includes hyperextension with true dislocation of the tibia on the femur.¹ Grades 1 and 2 on this spectrum technically are diagnosed as congenital genu recurvatum while grade 3 is diagnosed as a congenital dislocation of the knee,⁷ although the 2 terms are used interchangeably in the literature. We classified our case as a grade 1 congenital genu recurvatum based on the clinical and radiographic findings.

Congenital knee hyperextension has intrinsic and extrinsic causes

Hyperextension of the knees at birth may be caused by various intrinsic or extrinsic factors. Intrinsic causes may include breech position, lack of intrauterine space, trauma to the mother, quadriceps contracture or fibrosis, absence of the suprapatellar pouch, deficient or hypoplastic anterior cruciate ligament, pathological tissues, arthrogryposis, or genetic disorders such as Larsen syndrome or achondroplasia.⁶

Continue to: Extrinsic causes...

Extrinsic causes may include traumatic dislocation during the birthing process³ or intrauterine pressure leading to malposition of the joints. When intrauterine pressure is combined with reduced intrauterine space, this phenomenon is known as packaging disorder.⁶ Entanglement of the umbilical cord around the legs of the fetus during development may be another potential factor.¹Of note: Cases involving both extrinsic or intrinsic etiologies can present with associated abnormalities that include congenital dislocation of the hip, congenital hip dysplasia, spina bifida, and/or cleft palate—in addition to knee hyperextension.

The exact etiology in our patient was unknown, but we determined the cause was extrinsic based on the lack of other genetic abnormalities. We initially considered a possible connection between our patient’s diagnosis and her family history of thrombocytopenia absent radius syndrome, but it was later determined that both were isolated cases and the limb abnormalities were coincidental.

Treatment options and outcomes for extrinsic and intrinsic etiologies depend on the severity of the hyperextension and any associated abnormalities, as well as the time in which therapy is initiated.¹ Reduction of the hyperextension within 24 hours of birth has been associated with excellent outcomes.⁸ Regardless of the cause, all cases of congenital genu recurvatum should first be treated conservatively. Evidence has suggested that conservative therapy involving early gentle manipulation of the knee combined with serial splinting and casting should be the first line of treatment.⁶ If initial treatment attempts fail or in cases occurring later in life, surgical interventions (eg, quadriceps release procedures such as percutaneous quadriceps recession or V-Y quadricepsplasty, proximal tibial closing-wedge, anterior displacement osteotomy) likely is warranted.^6,9

Our patient. At 1 week of life, our patient’s short leg splints were replaced with long leg splints with a maximal flexion of 20° to 30° (FIGURE 1B). Weekly follow-ups with serial casting were initiated in the pediatric orthopedics clinic. At 3 weeks of life, the patient’s knee flexion had improved and the splints were removed (FIGURE 1C). Upon clinical examination, the bilateral knees were extended to a neutral position, and both could be actively and passively flexed to 90°. The patient was referred to Physical Therapy to perform range of movement exercises on the knees.

IMAGE COURTESY OF: METROHEALTH MEDICAL CENTER, CASE WESTERN RESERVE UNIVERSITY, CLEVELAND, OHIO

At 8 weeks of life, the bilateral legs were in full extension, and knee flexion was up to 130°. Physical therapy for knee range of movement exercise was continued on a weekly basis until 6 months of life, then twice monthly until the patient was 1 year old. Ultimately, the hyperextension was corrected, and the patient started walking at around 16 months of age. Her prognosis is good, and she will be able to participate in low-impact sports, after consulting with her orthopedist.

IMAGE COURTESY OF: METROHEALTH MEDICAL CENTER, CASE WESTERN RESERVE UNIVERSITY, CLEVELAND, OHIO

Continue to: THE TAKEAWAY

THE TAKEAWAY

Congenital genu recurvatum is a rare condition that presents with abnormal hyperextension of the knee(s) with limited flexion. Early diagnosis and assessment of the severity of the hyperextension is crucial in determining the type of intervention to pursue. Conservative management entails serial casting and splinting to increase knee flexion. If conservative management fails or if the diagnosis is made later in life, surgical options often are pursued.

CORRESPONDENCE
Jaividhya Dasarathy, MD, FAAFP, 2500 MetroHealth Medical Drive, Cleveland, OH 44109; jxd114@case.edu

THE CASE

A 29-year-old G7P2315 woman gave birth to a girl at 37 weeks via spontaneous vaginal delivery. APGAR scores were 9 and 9. Birth weight was 2760 g. Cardiovascular and pulmonary examinations were normal (heart rate, 154 beats/min; respiratory rate, 52 breaths/min). Following delivery, the neonate appeared healthy, had a lusty cry, and had no visible craniofacial or cutaneous abnormalities; however, the bilateral knees were hyperextended to 90° to 110° (FIGURE 1A).

The mother had started prenatal care at 7 weeks with 10 total visits to her family physician (JD) throughout the pregnancy. Routine laboratory screening and prenatal ultrasounds (including an anatomy scan) were normal. She had a history of 3 preterm deliveries at 35 weeks, 36 weeks, and 36 weeks, respectively, and had been on progesterone shots once weekly starting at 18 weeks during the current pregnancy. She had no history of infections or recent travel. Her family history was remarkable for a sister who gave birth to a child with thrombocytopenia absent radius syndrome.

THE DIAGNOSIS

The neonate tolerated passive flexion of the knees to a neutral position. Hip examination demonstrated appropriate range of movement with negative Ortolani and Barlow tests. The infant’s feet aligned correctly, with toes in the front and heels in the back, and an x-ray of the bilateral knees showed no fractures or dislocation.

Based on the clinical examination and x-ray findings, we made a diagnosis of congenital genu recurvatum. A pediatric orthopedics consultation was obtained, and the knees were placed in short leg splints in comfortable flexion to neutral on Day 1 of life. She was discharged the next day.

DISCUSSION

Congenital genu recurvatum, also known as congenital dislocation of the knee, is a rare condition involving abnormal hyperextension of the unilateral or bilateral knees with limited flexion.¹ Reports in the literature are limited, but there seems to be a female predominance among known cases of congenital genu recurvatum.² The clinical presentation varies. Finding may be isolated to the knee(s) but also can present in association with other congenital abnormalities, such as developmental dysplasia of the hip, clubfoot, and hindfoot and forefoot deformities.^3,4

Diagnosis is made clinically with radiographic imaging

Diagnosis of congenital genu recurvatum is made clinically and can be confirmed via radiographic imaging of the knees.5 Clinical diagnosis requires assessment of the degree of hyperextension and palpation of the femoral condyles, which become more prominent as the severity of the hyperextension increases.⁶ X-rays help assess if a true dislocation or subluxation of the tibia on the femur has occurred. Based on the clinical and radiographic findings, congenital genu recurvatum typically is classified according to 3 levels of severity: grade 1 classification only involves hyperextension of the knees without dislocation or subluxation, grade 2 involves the same characteristic hyperextension along with  anterior subluxation of the tibia on the femur, and grade 3 includes hyperextension with true dislocation of the tibia on the femur.¹ Grades 1 and 2 on this spectrum technically are diagnosed as congenital genu recurvatum while grade 3 is diagnosed as a congenital dislocation of the knee,⁷ although the 2 terms are used interchangeably in the literature. We classified our case as a grade 1 congenital genu recurvatum based on the clinical and radiographic findings.

Congenital knee hyperextension has intrinsic and extrinsic causes

Hyperextension of the knees at birth may be caused by various intrinsic or extrinsic factors. Intrinsic causes may include breech position, lack of intrauterine space, trauma to the mother, quadriceps contracture or fibrosis, absence of the suprapatellar pouch, deficient or hypoplastic anterior cruciate ligament, pathological tissues, arthrogryposis, or genetic disorders such as Larsen syndrome or achondroplasia.⁶

Continue to: Extrinsic causes...

Extrinsic causes may include traumatic dislocation during the birthing process³ or intrauterine pressure leading to malposition of the joints. When intrauterine pressure is combined with reduced intrauterine space, this phenomenon is known as packaging disorder.⁶ Entanglement of the umbilical cord around the legs of the fetus during development may be another potential factor.¹Of note: Cases involving both extrinsic or intrinsic etiologies can present with associated abnormalities that include congenital dislocation of the hip, congenital hip dysplasia, spina bifida, and/or cleft palate—in addition to knee hyperextension.

The exact etiology in our patient was unknown, but we determined the cause was extrinsic based on the lack of other genetic abnormalities. We initially considered a possible connection between our patient’s diagnosis and her family history of thrombocytopenia absent radius syndrome, but it was later determined that both were isolated cases and the limb abnormalities were coincidental.

Treatment options and outcomes for extrinsic and intrinsic etiologies depend on the severity of the hyperextension and any associated abnormalities, as well as the time in which therapy is initiated.¹ Reduction of the hyperextension within 24 hours of birth has been associated with excellent outcomes.⁸ Regardless of the cause, all cases of congenital genu recurvatum should first be treated conservatively. Evidence has suggested that conservative therapy involving early gentle manipulation of the knee combined with serial splinting and casting should be the first line of treatment.⁶ If initial treatment attempts fail or in cases occurring later in life, surgical interventions (eg, quadriceps release procedures such as percutaneous quadriceps recession or V-Y quadricepsplasty, proximal tibial closing-wedge, anterior displacement osteotomy) likely is warranted.^6,9

Our patient. At 1 week of life, our patient’s short leg splints were replaced with long leg splints with a maximal flexion of 20° to 30° (FIGURE 1B). Weekly follow-ups with serial casting were initiated in the pediatric orthopedics clinic. At 3 weeks of life, the patient’s knee flexion had improved and the splints were removed (FIGURE 1C). Upon clinical examination, the bilateral knees were extended to a neutral position, and both could be actively and passively flexed to 90°. The patient was referred to Physical Therapy to perform range of movement exercises on the knees.

IMAGE COURTESY OF: METROHEALTH MEDICAL CENTER, CASE WESTERN RESERVE UNIVERSITY, CLEVELAND, OHIO

At 8 weeks of life, the bilateral legs were in full extension, and knee flexion was up to 130°. Physical therapy for knee range of movement exercise was continued on a weekly basis until 6 months of life, then twice monthly until the patient was 1 year old. Ultimately, the hyperextension was corrected, and the patient started walking at around 16 months of age. Her prognosis is good, and she will be able to participate in low-impact sports, after consulting with her orthopedist.

IMAGE COURTESY OF: METROHEALTH MEDICAL CENTER, CASE WESTERN RESERVE UNIVERSITY, CLEVELAND, OHIO

Continue to: THE TAKEAWAY

THE TAKEAWAY

Congenital genu recurvatum is a rare condition that presents with abnormal hyperextension of the knee(s) with limited flexion. Early diagnosis and assessment of the severity of the hyperextension is crucial in determining the type of intervention to pursue. Conservative management entails serial casting and splinting to increase knee flexion. If conservative management fails or if the diagnosis is made later in life, surgical options often are pursued.

CORRESPONDENCE
Jaividhya Dasarathy, MD, FAAFP, 2500 MetroHealth Medical Drive, Cleveland, OH 44109; jxd114@case.edu

A 25-year-old woman presented with an exceedingly tender right ear. She’d had the helix of her ear pierced 3 days prior to presentation and 2 days after that, the ear had become tender. The tenderness was progressively worsening and associated with throbbing pain. The patient, who’d had her ears pierced before, was otherwise in good health and denied fever, chills, or travel outside of the country. She had been going to the gym regularly and took frequent showers. Physical examination revealed an erythematous swollen ear that was tender to the touch (FIGURE). The entire auricle was swollen except for the earlobe. The patient also reported purulent material draining from the helical piercing site.

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

Auricular perichondritis is an inflammation of the connective tissue surrounding the cartilage of the ear. Infectious and autoimmune factors may play a role. The underlying cartilage also may become involved. A useful clinical clue to the diagnosis of auricular perichondritis is sparing of the earlobe, which does not contain cartilage. Autoimmune causes typically have bilateral involvement. Infectious causes are usually associated with trauma and purulent drainage at the wound site. Ear piercings are an increasingly common cause, but perichondritis due to minor trauma, as a surgical complication, or in the absence of an obvious inciting trigger can occur. A careful history usually will reveal the cause.

In this case, the patient indicated that an open piercing gun at a shopping mall kiosk had been used to pierce her ear. Piercing with a sterile straight needle would have been preferable and less likely to be associated with secondary infection, as the shearing trauma to the perichondrium experienced with a piercing gun is thought to predispose to infection.¹ Exposure to fresh water from the shower could have been a source for Pseudomonas infection.¹

Differential: Pinpointing the diagnosis early is vital

A red and tender ear can raise a differential diagnosis that includes erysipelas, relapsing polychondritis, and auricular perichondritis. Erysipelas is a bacterial infection that spreads through the lymphatic system and is associated with intense and well-demarcated erythema. Erysipelas typically involves the face or lower legs. Infection after piercing or traumatic injury should raise suspicion of pseudomonal infection.^2-5 Untreated infection can spread quickly and lead to permanent ear deformity. Although the same pattern of inflammation can be seen in relapsing polychondritis, relapsing polychondritis typically involves both ears as well as the eyes and joints.

Prompt treatment is necessary to avoid cosmetic disfigurement

The timing of the reaction in our patient made infection obvious because Pseudomonas aeruginosa seems to have a particular affinity for damaged cartilage.²

Prompt treatment is necessary as infection can spread quickly and lead to cosmetic disfigurement.

Ciprofloxacin 500 mg twice daily is the treatment of choice. Although many skin infections can be empirically treated with oral cephalosporin, penicillin, or erythromycin, it is important to recognize that infected piercing sites and auricular perichondritis due to pseudomonal infection will not respond to these agents. That’s because these agents do not provide as good coverage for Pseudomonas as they do for Staphylococci or other bacteria more often associated with skin infection. Treatment with an agent such as amoxicillin and clavulanic acid or oral cephalexin can mean the loss of valuable time and subsequent cosmetic disfigurement.⁶

Continue to: When fluctuance is present...

When fluctuance is present, incision and drainage, or even debridement, may be necessary. When extensive infection leads to cartilage necrosis and liquefaction, treatment is difficult and may result in lasting disfigurement. Prompt empiric treatment currently is considered the best option.⁶

Our patient was prescribed a course of ciprofloxacin 500 mg every 12 hours for 10 days. She noted improvement within 2 days, and the infection resolved without complication.

CORRESPONDENCE
Matthew F. Helm, MD, Penn State Health Hershey Medical Center, 500 University Dr, HU14, Hershey, PA 17033; mhelm2@pennstatehealth.psu.edu

A 25-year-old woman presented with an exceedingly tender right ear. She’d had the helix of her ear pierced 3 days prior to presentation and 2 days after that, the ear had become tender. The tenderness was progressively worsening and associated with throbbing pain. The patient, who’d had her ears pierced before, was otherwise in good health and denied fever, chills, or travel outside of the country. She had been going to the gym regularly and took frequent showers. Physical examination revealed an erythematous swollen ear that was tender to the touch (FIGURE). The entire auricle was swollen except for the earlobe. The patient also reported purulent material draining from the helical piercing site.

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

Auricular perichondritis is an inflammation of the connective tissue surrounding the cartilage of the ear. Infectious and autoimmune factors may play a role. The underlying cartilage also may become involved. A useful clinical clue to the diagnosis of auricular perichondritis is sparing of the earlobe, which does not contain cartilage. Autoimmune causes typically have bilateral involvement. Infectious causes are usually associated with trauma and purulent drainage at the wound site. Ear piercings are an increasingly common cause, but perichondritis due to minor trauma, as a surgical complication, or in the absence of an obvious inciting trigger can occur. A careful history usually will reveal the cause.

In this case, the patient indicated that an open piercing gun at a shopping mall kiosk had been used to pierce her ear. Piercing with a sterile straight needle would have been preferable and less likely to be associated with secondary infection, as the shearing trauma to the perichondrium experienced with a piercing gun is thought to predispose to infection.¹ Exposure to fresh water from the shower could have been a source for Pseudomonas infection.¹

Differential: Pinpointing the diagnosis early is vital

A red and tender ear can raise a differential diagnosis that includes erysipelas, relapsing polychondritis, and auricular perichondritis. Erysipelas is a bacterial infection that spreads through the lymphatic system and is associated with intense and well-demarcated erythema. Erysipelas typically involves the face or lower legs. Infection after piercing or traumatic injury should raise suspicion of pseudomonal infection.^2-5 Untreated infection can spread quickly and lead to permanent ear deformity. Although the same pattern of inflammation can be seen in relapsing polychondritis, relapsing polychondritis typically involves both ears as well as the eyes and joints.

Prompt treatment is necessary to avoid cosmetic disfigurement

The timing of the reaction in our patient made infection obvious because Pseudomonas aeruginosa seems to have a particular affinity for damaged cartilage.²

Prompt treatment is necessary as infection can spread quickly and lead to cosmetic disfigurement.

Ciprofloxacin 500 mg twice daily is the treatment of choice. Although many skin infections can be empirically treated with oral cephalosporin, penicillin, or erythromycin, it is important to recognize that infected piercing sites and auricular perichondritis due to pseudomonal infection will not respond to these agents. That’s because these agents do not provide as good coverage for Pseudomonas as they do for Staphylococci or other bacteria more often associated with skin infection. Treatment with an agent such as amoxicillin and clavulanic acid or oral cephalexin can mean the loss of valuable time and subsequent cosmetic disfigurement.⁶

Continue to: When fluctuance is present...

When fluctuance is present, incision and drainage, or even debridement, may be necessary. When extensive infection leads to cartilage necrosis and liquefaction, treatment is difficult and may result in lasting disfigurement. Prompt empiric treatment currently is considered the best option.⁶

Our patient was prescribed a course of ciprofloxacin 500 mg every 12 hours for 10 days. She noted improvement within 2 days, and the infection resolved without complication.

CORRESPONDENCE
Matthew F. Helm, MD, Penn State Health Hershey Medical Center, 500 University Dr, HU14, Hershey, PA 17033; mhelm2@pennstatehealth.psu.edu

A 25-year-old woman presented with an exceedingly tender right ear. She’d had the helix of her ear pierced 3 days prior to presentation and 2 days after that, the ear had become tender. The tenderness was progressively worsening and associated with throbbing pain. The patient, who’d had her ears pierced before, was otherwise in good health and denied fever, chills, or travel outside of the country. She had been going to the gym regularly and took frequent showers. Physical examination revealed an erythematous swollen ear that was tender to the touch (FIGURE). The entire auricle was swollen except for the earlobe. The patient also reported purulent material draining from the helical piercing site.

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

Auricular perichondritis is an inflammation of the connective tissue surrounding the cartilage of the ear. Infectious and autoimmune factors may play a role. The underlying cartilage also may become involved. A useful clinical clue to the diagnosis of auricular perichondritis is sparing of the earlobe, which does not contain cartilage. Autoimmune causes typically have bilateral involvement. Infectious causes are usually associated with trauma and purulent drainage at the wound site. Ear piercings are an increasingly common cause, but perichondritis due to minor trauma, as a surgical complication, or in the absence of an obvious inciting trigger can occur. A careful history usually will reveal the cause.

In this case, the patient indicated that an open piercing gun at a shopping mall kiosk had been used to pierce her ear. Piercing with a sterile straight needle would have been preferable and less likely to be associated with secondary infection, as the shearing trauma to the perichondrium experienced with a piercing gun is thought to predispose to infection.¹ Exposure to fresh water from the shower could have been a source for Pseudomonas infection.¹

Differential: Pinpointing the diagnosis early is vital

A red and tender ear can raise a differential diagnosis that includes erysipelas, relapsing polychondritis, and auricular perichondritis. Erysipelas is a bacterial infection that spreads through the lymphatic system and is associated with intense and well-demarcated erythema. Erysipelas typically involves the face or lower legs. Infection after piercing or traumatic injury should raise suspicion of pseudomonal infection.^2-5 Untreated infection can spread quickly and lead to permanent ear deformity. Although the same pattern of inflammation can be seen in relapsing polychondritis, relapsing polychondritis typically involves both ears as well as the eyes and joints.

Prompt treatment is necessary to avoid cosmetic disfigurement

The timing of the reaction in our patient made infection obvious because Pseudomonas aeruginosa seems to have a particular affinity for damaged cartilage.²

Prompt treatment is necessary as infection can spread quickly and lead to cosmetic disfigurement.

Ciprofloxacin 500 mg twice daily is the treatment of choice. Although many skin infections can be empirically treated with oral cephalosporin, penicillin, or erythromycin, it is important to recognize that infected piercing sites and auricular perichondritis due to pseudomonal infection will not respond to these agents. That’s because these agents do not provide as good coverage for Pseudomonas as they do for Staphylococci or other bacteria more often associated with skin infection. Treatment with an agent such as amoxicillin and clavulanic acid or oral cephalexin can mean the loss of valuable time and subsequent cosmetic disfigurement.⁶

Continue to: When fluctuance is present...

When fluctuance is present, incision and drainage, or even debridement, may be necessary. When extensive infection leads to cartilage necrosis and liquefaction, treatment is difficult and may result in lasting disfigurement. Prompt empiric treatment currently is considered the best option.⁶

Our patient was prescribed a course of ciprofloxacin 500 mg every 12 hours for 10 days. She noted improvement within 2 days, and the infection resolved without complication.

CORRESPONDENCE
Matthew F. Helm, MD, Penn State Health Hershey Medical Center, 500 University Dr, HU14, Hershey, PA 17033; mhelm2@pennstatehealth.psu.edu

THE CASE

A primiparous mother gave birth to a girl at 38 and 4/7 weeks via uncomplicated vaginal delivery. Prenatal labs were normal. Neonatal physical examination was normal and the child’s birth weight was in the 33rd percentile. APGAR scores were 8 and 9. The neonate was afebrile during hospitalization, with a heart rate of 120 to 150 beats/min and a respiratory rate of 30 to 48 breaths/min. Her preductal and postductal oxygen saturations were 100% and 98%, respectively. She was discharged on Day 2 of life, having lost only 3% of her birth weight.

The patient was seen in clinic on Day 6 of life for a well-child exam and was in the 17th percentile for weight. At another visit for a well-child exam on Day 14 of life, she had not fully regained her birth weight. At both visits, the mother reported no issues with breastfeeding and said she was supplementing with formula. The patient was seen again for follow-up on Days 16 and 21 of life and demonstrated no weight gain despite close follow-up with the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), which determined the newborn had some breastfeeding issues but seemed to be consuming adequate calories. However, WIC assessments revealed that during feeding, the child was expending too many calories and had nasal congestion. The patient was admitted to the hospital on Day 21 of life with a diagnosis of failure to thrive (FTT), at which point she was in the 12th percentile for weight.

THE DIAGNOSIS

Shortly after the infant was admitted, she showed signs of respiratory distress. On physical examination, the on-call resident noted intermittent retractions with inspiratory stridor, and the patient demonstrated intermittent severe oxygen desaturations into the 70s. She also was sucking her pacifier furiously, which appeared to provide some relief from the respiratory distress. The child’s parents noted that she had demonstrated intermittent periods of respiratory distress since shortly after birth that seemed to be increasing in frequency.

Upon careful examination, the on-call resident identified a cystic lesion at the base of the child’s tongue. The otolaryngologist on call was brought in for an urgent consultation but was unable to visualize the lesion on physical examination and did not recommend further intervention at that time. The patient continued to demonstrate respiratory distress with hypoxia and was transferred to the pediatric intensive care unit for close monitoring.

The next morning a second otolaryngology consultation was requested. A computed tomography scan of the neck demonstrated a 1.5-cm cystic-appearing mass at the base of the tongue that was obstructing the patient’s airway. Direct flexible bronchoscopy confirmed the radiographic findings. The patient underwent immediate surgical resection of the lesion using a laser. A clear and milky gray cystic fluid exuded from the cyst when the lesion was pierced. The otolaryngologist visualized a widely patent airway following excision of the lesion (FIGURE).

Pathology results revealed no evidence of malignancy. The final diagnosis was a simple base-of-tongue cyst.

DISCUSSION

Failure to thrive is common in neonates and occurs most often due to inadequate caloric intake; however, it also can be caused by systemic disease associated with inadequate gastrointestinal absorption or increased caloric expenditure, such as congenital heart disease, renal disease (eg, renal tubular acidosis), chronic pulmonary disease (eg, cystic fibrosis), laryngomalacia, malignancy, immunodeficiency, or thyroid disease.¹

Continue to: Respiratory distress

Respiratory distress in neonates also is common but tends to occur shortly after birth.² Conditions associated with respiratory distress in neonates include transient tachypnea of the newborn, respiratory distress syndrome, pneumothorax, persistent pulmonary hypertension of the newborn, pneumonia, and meconium aspiration syndrome.² Interestingly, there are additional reports in the literature of FTT and respiratory distress in neonates caused by obstructive pharyngeal lesions.^3-5

Mechanical obstruction should be considered in neonates with failure to thrive and respiratory distress.

Base-of-tongue cysts are rare in infants. Fewer than 50 cases were reported prior to 2011, with many being described as asymptomatic nonpainful lesions.⁶ Given the anatomic location of base-of-tongue cysts, the differential diagnosis should also include mucoceles, thyroglossal duct cysts, dermoid cysts, epidermoid cysts, vallecular cysts, hemangiomas, cystic hygromas, lymphangiomas, thyroid remnant cysts, teratomas, and hamartomas.^4,7,8 When tongue cysts are initially discovered, inspiratory stridor, FTT, swallowing deficits, oxygen desaturation, respiratory failure, and/or acute life-threatening events have been reported.^6,9,10

One important clinical observation made in our case was the use of an external apparatus to relieve the neonate’s respiratory distress. During physical examination, the on-call resident noted the patient was furiously sucking her pacifier, which seemed to reduce the respiratory difficulty and desaturations. It is known that non-nutritive sucking (NNS) can provide provisions for stress relief, improve oxygenation, and provide proprioceptive positioning of key anatomical structures within the oral cavity.¹¹ Without the use of an external apparatus like a pacifier during restful states, neonates may develop vacuum-glossoptosis syndrome, in which the dorsum of the tongue and the soft palate adhere to the posterior pharyngeal wall and obstruct the airway.¹² Our patient may have used the pacifier as an NNS task to move the tongue forward and break the glossoptosis-pharyngeal seal by sucking hard and fast during periods of respiratory distress, which reduced the potential for a vacuum-glossoptosis phenomenon that was likely created by the cyst during restful states.

Our patient was seen in clinic for follow-up after surgery on Day 35 of life. She was thriving and her weight was in the 24th percentile. She was seen again on Day 67 of life for a well-child exam and was in the 43rd percentile for weight.

THE TAKEAWAY

Non-nutritive sucking with a pacifier may relieve airway obstruction caused by base-of-tongue cysts.

There is a sizeable list of possible diagnoses to consider when a neonate presents with FTT and respiratory distress. It is important to consider mechanical obstruction as a possible diagnosis and one which, if identified early, may be lifesaving. Our case demonstrates a proposed mechanism by which a mechanical obstruction such as a base-of-tongue cyst can cause the vacuum-glossoptosis syndrome; it also highlights NNS as a potential means of overcoming this phenomenon.

CORRESPONDENCE
Benjamin P. Hansen, MD, Renown Medical Group, 4796 Caughlin Pkwy, Ste 108, Reno, NV 89519; Bhansen7000@gmail.com

THE CASE

A primiparous mother gave birth to a girl at 38 and 4/7 weeks via uncomplicated vaginal delivery. Prenatal labs were normal. Neonatal physical examination was normal and the child’s birth weight was in the 33rd percentile. APGAR scores were 8 and 9. The neonate was afebrile during hospitalization, with a heart rate of 120 to 150 beats/min and a respiratory rate of 30 to 48 breaths/min. Her preductal and postductal oxygen saturations were 100% and 98%, respectively. She was discharged on Day 2 of life, having lost only 3% of her birth weight.

The patient was seen in clinic on Day 6 of life for a well-child exam and was in the 17th percentile for weight. At another visit for a well-child exam on Day 14 of life, she had not fully regained her birth weight. At both visits, the mother reported no issues with breastfeeding and said she was supplementing with formula. The patient was seen again for follow-up on Days 16 and 21 of life and demonstrated no weight gain despite close follow-up with the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), which determined the newborn had some breastfeeding issues but seemed to be consuming adequate calories. However, WIC assessments revealed that during feeding, the child was expending too many calories and had nasal congestion. The patient was admitted to the hospital on Day 21 of life with a diagnosis of failure to thrive (FTT), at which point she was in the 12th percentile for weight.

THE DIAGNOSIS

Shortly after the infant was admitted, she showed signs of respiratory distress. On physical examination, the on-call resident noted intermittent retractions with inspiratory stridor, and the patient demonstrated intermittent severe oxygen desaturations into the 70s. She also was sucking her pacifier furiously, which appeared to provide some relief from the respiratory distress. The child’s parents noted that she had demonstrated intermittent periods of respiratory distress since shortly after birth that seemed to be increasing in frequency.

Upon careful examination, the on-call resident identified a cystic lesion at the base of the child’s tongue. The otolaryngologist on call was brought in for an urgent consultation but was unable to visualize the lesion on physical examination and did not recommend further intervention at that time. The patient continued to demonstrate respiratory distress with hypoxia and was transferred to the pediatric intensive care unit for close monitoring.

The next morning a second otolaryngology consultation was requested. A computed tomography scan of the neck demonstrated a 1.5-cm cystic-appearing mass at the base of the tongue that was obstructing the patient’s airway. Direct flexible bronchoscopy confirmed the radiographic findings. The patient underwent immediate surgical resection of the lesion using a laser. A clear and milky gray cystic fluid exuded from the cyst when the lesion was pierced. The otolaryngologist visualized a widely patent airway following excision of the lesion (FIGURE).

Pathology results revealed no evidence of malignancy. The final diagnosis was a simple base-of-tongue cyst.

DISCUSSION

Failure to thrive is common in neonates and occurs most often due to inadequate caloric intake; however, it also can be caused by systemic disease associated with inadequate gastrointestinal absorption or increased caloric expenditure, such as congenital heart disease, renal disease (eg, renal tubular acidosis), chronic pulmonary disease (eg, cystic fibrosis), laryngomalacia, malignancy, immunodeficiency, or thyroid disease.¹

Continue to: Respiratory distress

Respiratory distress in neonates also is common but tends to occur shortly after birth.² Conditions associated with respiratory distress in neonates include transient tachypnea of the newborn, respiratory distress syndrome, pneumothorax, persistent pulmonary hypertension of the newborn, pneumonia, and meconium aspiration syndrome.² Interestingly, there are additional reports in the literature of FTT and respiratory distress in neonates caused by obstructive pharyngeal lesions.^3-5

Mechanical obstruction should be considered in neonates with failure to thrive and respiratory distress.

Base-of-tongue cysts are rare in infants. Fewer than 50 cases were reported prior to 2011, with many being described as asymptomatic nonpainful lesions.⁶ Given the anatomic location of base-of-tongue cysts, the differential diagnosis should also include mucoceles, thyroglossal duct cysts, dermoid cysts, epidermoid cysts, vallecular cysts, hemangiomas, cystic hygromas, lymphangiomas, thyroid remnant cysts, teratomas, and hamartomas.^4,7,8 When tongue cysts are initially discovered, inspiratory stridor, FTT, swallowing deficits, oxygen desaturation, respiratory failure, and/or acute life-threatening events have been reported.^6,9,10

One important clinical observation made in our case was the use of an external apparatus to relieve the neonate’s respiratory distress. During physical examination, the on-call resident noted the patient was furiously sucking her pacifier, which seemed to reduce the respiratory difficulty and desaturations. It is known that non-nutritive sucking (NNS) can provide provisions for stress relief, improve oxygenation, and provide proprioceptive positioning of key anatomical structures within the oral cavity.¹¹ Without the use of an external apparatus like a pacifier during restful states, neonates may develop vacuum-glossoptosis syndrome, in which the dorsum of the tongue and the soft palate adhere to the posterior pharyngeal wall and obstruct the airway.¹² Our patient may have used the pacifier as an NNS task to move the tongue forward and break the glossoptosis-pharyngeal seal by sucking hard and fast during periods of respiratory distress, which reduced the potential for a vacuum-glossoptosis phenomenon that was likely created by the cyst during restful states.

Our patient was seen in clinic for follow-up after surgery on Day 35 of life. She was thriving and her weight was in the 24th percentile. She was seen again on Day 67 of life for a well-child exam and was in the 43rd percentile for weight.

THE TAKEAWAY

Non-nutritive sucking with a pacifier may relieve airway obstruction caused by base-of-tongue cysts.

There is a sizeable list of possible diagnoses to consider when a neonate presents with FTT and respiratory distress. It is important to consider mechanical obstruction as a possible diagnosis and one which, if identified early, may be lifesaving. Our case demonstrates a proposed mechanism by which a mechanical obstruction such as a base-of-tongue cyst can cause the vacuum-glossoptosis syndrome; it also highlights NNS as a potential means of overcoming this phenomenon.

CORRESPONDENCE
Benjamin P. Hansen, MD, Renown Medical Group, 4796 Caughlin Pkwy, Ste 108, Reno, NV 89519; Bhansen7000@gmail.com

THE CASE

A primiparous mother gave birth to a girl at 38 and 4/7 weeks via uncomplicated vaginal delivery. Prenatal labs were normal. Neonatal physical examination was normal and the child’s birth weight was in the 33rd percentile. APGAR scores were 8 and 9. The neonate was afebrile during hospitalization, with a heart rate of 120 to 150 beats/min and a respiratory rate of 30 to 48 breaths/min. Her preductal and postductal oxygen saturations were 100% and 98%, respectively. She was discharged on Day 2 of life, having lost only 3% of her birth weight.

The patient was seen in clinic on Day 6 of life for a well-child exam and was in the 17th percentile for weight. At another visit for a well-child exam on Day 14 of life, she had not fully regained her birth weight. At both visits, the mother reported no issues with breastfeeding and said she was supplementing with formula. The patient was seen again for follow-up on Days 16 and 21 of life and demonstrated no weight gain despite close follow-up with the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), which determined the newborn had some breastfeeding issues but seemed to be consuming adequate calories. However, WIC assessments revealed that during feeding, the child was expending too many calories and had nasal congestion. The patient was admitted to the hospital on Day 21 of life with a diagnosis of failure to thrive (FTT), at which point she was in the 12th percentile for weight.

THE DIAGNOSIS

Shortly after the infant was admitted, she showed signs of respiratory distress. On physical examination, the on-call resident noted intermittent retractions with inspiratory stridor, and the patient demonstrated intermittent severe oxygen desaturations into the 70s. She also was sucking her pacifier furiously, which appeared to provide some relief from the respiratory distress. The child’s parents noted that she had demonstrated intermittent periods of respiratory distress since shortly after birth that seemed to be increasing in frequency.

Upon careful examination, the on-call resident identified a cystic lesion at the base of the child’s tongue. The otolaryngologist on call was brought in for an urgent consultation but was unable to visualize the lesion on physical examination and did not recommend further intervention at that time. The patient continued to demonstrate respiratory distress with hypoxia and was transferred to the pediatric intensive care unit for close monitoring.

The next morning a second otolaryngology consultation was requested. A computed tomography scan of the neck demonstrated a 1.5-cm cystic-appearing mass at the base of the tongue that was obstructing the patient’s airway. Direct flexible bronchoscopy confirmed the radiographic findings. The patient underwent immediate surgical resection of the lesion using a laser. A clear and milky gray cystic fluid exuded from the cyst when the lesion was pierced. The otolaryngologist visualized a widely patent airway following excision of the lesion (FIGURE).

Pathology results revealed no evidence of malignancy. The final diagnosis was a simple base-of-tongue cyst.

DISCUSSION

Failure to thrive is common in neonates and occurs most often due to inadequate caloric intake; however, it also can be caused by systemic disease associated with inadequate gastrointestinal absorption or increased caloric expenditure, such as congenital heart disease, renal disease (eg, renal tubular acidosis), chronic pulmonary disease (eg, cystic fibrosis), laryngomalacia, malignancy, immunodeficiency, or thyroid disease.¹

Continue to: Respiratory distress

Respiratory distress in neonates also is common but tends to occur shortly after birth.² Conditions associated with respiratory distress in neonates include transient tachypnea of the newborn, respiratory distress syndrome, pneumothorax, persistent pulmonary hypertension of the newborn, pneumonia, and meconium aspiration syndrome.² Interestingly, there are additional reports in the literature of FTT and respiratory distress in neonates caused by obstructive pharyngeal lesions.^3-5

Mechanical obstruction should be considered in neonates with failure to thrive and respiratory distress.

Base-of-tongue cysts are rare in infants. Fewer than 50 cases were reported prior to 2011, with many being described as asymptomatic nonpainful lesions.⁶ Given the anatomic location of base-of-tongue cysts, the differential diagnosis should also include mucoceles, thyroglossal duct cysts, dermoid cysts, epidermoid cysts, vallecular cysts, hemangiomas, cystic hygromas, lymphangiomas, thyroid remnant cysts, teratomas, and hamartomas.^4,7,8 When tongue cysts are initially discovered, inspiratory stridor, FTT, swallowing deficits, oxygen desaturation, respiratory failure, and/or acute life-threatening events have been reported.^6,9,10

One important clinical observation made in our case was the use of an external apparatus to relieve the neonate’s respiratory distress. During physical examination, the on-call resident noted the patient was furiously sucking her pacifier, which seemed to reduce the respiratory difficulty and desaturations. It is known that non-nutritive sucking (NNS) can provide provisions for stress relief, improve oxygenation, and provide proprioceptive positioning of key anatomical structures within the oral cavity.¹¹ Without the use of an external apparatus like a pacifier during restful states, neonates may develop vacuum-glossoptosis syndrome, in which the dorsum of the tongue and the soft palate adhere to the posterior pharyngeal wall and obstruct the airway.¹² Our patient may have used the pacifier as an NNS task to move the tongue forward and break the glossoptosis-pharyngeal seal by sucking hard and fast during periods of respiratory distress, which reduced the potential for a vacuum-glossoptosis phenomenon that was likely created by the cyst during restful states.

Our patient was seen in clinic for follow-up after surgery on Day 35 of life. She was thriving and her weight was in the 24th percentile. She was seen again on Day 67 of life for a well-child exam and was in the 43rd percentile for weight.

THE TAKEAWAY

Non-nutritive sucking with a pacifier may relieve airway obstruction caused by base-of-tongue cysts.

There is a sizeable list of possible diagnoses to consider when a neonate presents with FTT and respiratory distress. It is important to consider mechanical obstruction as a possible diagnosis and one which, if identified early, may be lifesaving. Our case demonstrates a proposed mechanism by which a mechanical obstruction such as a base-of-tongue cyst can cause the vacuum-glossoptosis syndrome; it also highlights NNS as a potential means of overcoming this phenomenon.

CORRESPONDENCE
Benjamin P. Hansen, MD, Renown Medical Group, 4796 Caughlin Pkwy, Ste 108, Reno, NV 89519; Bhansen7000@gmail.com

ILLUSTRATIVE CASE

Ms. M is a 55-year-old woman who is generally healthy, but who was diagnosed recently with severe vitamin D deficiency (serum 25-hydroxyvitamin D level of 8 ng/mL). She is being seen for her second episode of acute viral bronchitis in the past 6 months. She has no significant smoking or exposure history, no history of asthma, and takes no respiratory medications. Standard treatment for her level of vitamin D deficiency is 50,000 IU/week in bolus dosing, but is that your best option in this case?

Acute respiratory tract infections (ARTIs) include nonspecific upper respiratory illnesses, otitis media, sinusitis (~70% viral), pharyngitis, acute bronchitis (also ~70% viral), influenza, respiratory syncytial virus, and pneumonia.^1,2 In the United States, ARTIs strain the health care system and are the most common cause of ambulatory care visits, accounting for almost 120 million, or about 10% of all visits, per year.³ In addition, ARTIs account for almost 50% of antibiotic prescriptions for adults and almost 75% of antibiotic prescriptions for children—many of which are unnecessary.^2,4

While patient and parent education, antibiotic stewardship programs, and demand management may reduce inappropriate antibiotic use and the overall burden of ARTIs on the health care system, prevention of infections is a powerful tool within the overall approach to managing ARTIs.

STUDY SUMMARY

Vitamin D protects against ARTIs, but only in smaller doses

This 2017 systematic review and meta-analysis of 25 trials (N=10,933) evaluated vitamin D supplementation for the prevention of ARTIs in the primary care setting. Individual participant data were reevaluated to reduce risk of bias. The Cochrane risk of bias tool was used to address threats to validity.

The review and meta-analysis included institutional review board–approved, randomized, double-blind, placebo-controlled trials of vitamin D₃ or vitamin D₂ supplementation of any duration and in any language. The incidence of ARTI was a prespecified efficacy outcome. Duration of the included randomized controlled trials (RCTs) ranged from 7 weeks to 1.5 years.

Outcomes. The primary outcome was an incidence of at least 1 ARTI. Secondary outcomes included incidence of upper and lower ARTIs; incidence of adverse reactions to vitamin D; incidence of emergency department visits or hospital admission or both for ARTI; use of antimicrobials for ARTI; absence from work or school due to ARTI, and mortality (ARTI-related and all-cause).

Findings. Daily or weekly vitamin D supplementation (in doses ranging from < 20 to ≥ 50 µg/d) reduced the risk for ARTI (adjusted odds ratio [AOR] = 0.88; 95% confidence interval [CI], 0.81-0.96; number needed to treat [NNT] = 33). In subgroup analysis, daily or weekly vitamin D was protective (AOR = 0.81; 95% CI, 0.72-0.91), but bolus dosing (≥ 30,000 IU) was not (AOR = 0.97; 95% CI, 0.86-1.10).

Continue to: In 2-step analysis...

This study found that low-dose daily or weekly vitamin D supplementation was protective against acute respiratory tract infections, but bolus dosing was not.

In 2-step analysis, patients benefited who: had baseline circulating 25-hydroxyvitamin D concentrations < 10 ng/mL (AOR = 0.30; 95% CI, 0.17-0.53; NNT = 4); had baseline circulating 25-hydroxyvitamin D levels of 10 to 28 ng/mL (AOR = 0.75; 95% CI, 0.60-0.95; NNT = 15); were ages 1.1 to 15.9 years (AOR = 0.59; 95% CI, 0.45-0.79); were ages 16 to 65 years (AOR = 0.79; 95% CI, 0.63-0.99); or had a body mass index < 25 (AOR = 0.82; 95% CI, 0.71-0.95).

Higher D levels are a different story. Vitamin D supplementation in people with circulating levels of 25-hydroxyvitamin D ≥ 30 ng/mL did not appear to provide benefit (AOR = 0.96; 95% CI, 0.78-1.18). Supplementation in this population did not influence any of the secondary outcomes, including risk for all-cause serious adverse events (AOR = 0.98; 95% CI, 0.80-1.20).

WHAT’S NEW

A more accurate snapshot

Previous studies of vitamin D and respiratory tract infections were mostly observational in nature. Those that were RCTs used variable doses of vitamin D, had variable baseline 25-hydroxyvitamin D levels, and employed various methods to monitor ARTI symptoms/incidence.^5-8 This is the first systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials with supplementation using vitamin D₃ or vitamin D₂ that used individual participant-level data, which gives a more accurate estimate of outcomes when compared with traditional meta-analyses.

CAVEATS

Only the most deficient benefit?

Vitamin D supplementation was safe and protected against ARTIs overall, but the greatest effect of vitamin D supplementation on the prevention of ARTIs was noted in those who were most severely vitamin D deficient (those with circulating 25-hydroxyvitamin levels < 10 ng/mL, NNT = 4; 10-28 ng/mL, NNT = 15). There was no demonstrable effect once circulating 25-hydroxyvitamin D levels reached 30 ng/mL.

CHALLENGES TO IMPLEMENTATION

Breaking tradition

The study found that both daily and weekly doses of vitamin D were effective in reducing the incidence of ARTIs, but the doses used were much lower than the commonly used 10,000 to 50,000 IU bolus doses, which were ineffective in reducing ARTIs in the current meta-analysis. Since bolus dosing is an ingrained practice for many providers, changing this may prove challenging.

Continue to: In addition...

In addition, the authors of the study suggest that one of the ways to provide this level of vitamin D is through food fortification, but food fortification is often complicated by emotional and/or political issues that could thwart implementation.

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.

ILLUSTRATIVE CASE

Ms. M is a 55-year-old woman who is generally healthy, but who was diagnosed recently with severe vitamin D deficiency (serum 25-hydroxyvitamin D level of 8 ng/mL). She is being seen for her second episode of acute viral bronchitis in the past 6 months. She has no significant smoking or exposure history, no history of asthma, and takes no respiratory medications. Standard treatment for her level of vitamin D deficiency is 50,000 IU/week in bolus dosing, but is that your best option in this case?

Acute respiratory tract infections (ARTIs) include nonspecific upper respiratory illnesses, otitis media, sinusitis (~70% viral), pharyngitis, acute bronchitis (also ~70% viral), influenza, respiratory syncytial virus, and pneumonia.^1,2 In the United States, ARTIs strain the health care system and are the most common cause of ambulatory care visits, accounting for almost 120 million, or about 10% of all visits, per year.³ In addition, ARTIs account for almost 50% of antibiotic prescriptions for adults and almost 75% of antibiotic prescriptions for children—many of which are unnecessary.^2,4

While patient and parent education, antibiotic stewardship programs, and demand management may reduce inappropriate antibiotic use and the overall burden of ARTIs on the health care system, prevention of infections is a powerful tool within the overall approach to managing ARTIs.

STUDY SUMMARY

Vitamin D protects against ARTIs, but only in smaller doses

This 2017 systematic review and meta-analysis of 25 trials (N=10,933) evaluated vitamin D supplementation for the prevention of ARTIs in the primary care setting. Individual participant data were reevaluated to reduce risk of bias. The Cochrane risk of bias tool was used to address threats to validity.

The review and meta-analysis included institutional review board–approved, randomized, double-blind, placebo-controlled trials of vitamin D₃ or vitamin D₂ supplementation of any duration and in any language. The incidence of ARTI was a prespecified efficacy outcome. Duration of the included randomized controlled trials (RCTs) ranged from 7 weeks to 1.5 years.

Outcomes. The primary outcome was an incidence of at least 1 ARTI. Secondary outcomes included incidence of upper and lower ARTIs; incidence of adverse reactions to vitamin D; incidence of emergency department visits or hospital admission or both for ARTI; use of antimicrobials for ARTI; absence from work or school due to ARTI, and mortality (ARTI-related and all-cause).

Findings. Daily or weekly vitamin D supplementation (in doses ranging from < 20 to ≥ 50 µg/d) reduced the risk for ARTI (adjusted odds ratio [AOR] = 0.88; 95% confidence interval [CI], 0.81-0.96; number needed to treat [NNT] = 33). In subgroup analysis, daily or weekly vitamin D was protective (AOR = 0.81; 95% CI, 0.72-0.91), but bolus dosing (≥ 30,000 IU) was not (AOR = 0.97; 95% CI, 0.86-1.10).

Continue to: In 2-step analysis...

This study found that low-dose daily or weekly vitamin D supplementation was protective against acute respiratory tract infections, but bolus dosing was not.

In 2-step analysis, patients benefited who: had baseline circulating 25-hydroxyvitamin D concentrations < 10 ng/mL (AOR = 0.30; 95% CI, 0.17-0.53; NNT = 4); had baseline circulating 25-hydroxyvitamin D levels of 10 to 28 ng/mL (AOR = 0.75; 95% CI, 0.60-0.95; NNT = 15); were ages 1.1 to 15.9 years (AOR = 0.59; 95% CI, 0.45-0.79); were ages 16 to 65 years (AOR = 0.79; 95% CI, 0.63-0.99); or had a body mass index < 25 (AOR = 0.82; 95% CI, 0.71-0.95).

Higher D levels are a different story. Vitamin D supplementation in people with circulating levels of 25-hydroxyvitamin D ≥ 30 ng/mL did not appear to provide benefit (AOR = 0.96; 95% CI, 0.78-1.18). Supplementation in this population did not influence any of the secondary outcomes, including risk for all-cause serious adverse events (AOR = 0.98; 95% CI, 0.80-1.20).

WHAT’S NEW

A more accurate snapshot

Previous studies of vitamin D and respiratory tract infections were mostly observational in nature. Those that were RCTs used variable doses of vitamin D, had variable baseline 25-hydroxyvitamin D levels, and employed various methods to monitor ARTI symptoms/incidence.^5-8 This is the first systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials with supplementation using vitamin D₃ or vitamin D₂ that used individual participant-level data, which gives a more accurate estimate of outcomes when compared with traditional meta-analyses.

CAVEATS

Only the most deficient benefit?

Vitamin D supplementation was safe and protected against ARTIs overall, but the greatest effect of vitamin D supplementation on the prevention of ARTIs was noted in those who were most severely vitamin D deficient (those with circulating 25-hydroxyvitamin levels < 10 ng/mL, NNT = 4; 10-28 ng/mL, NNT = 15). There was no demonstrable effect once circulating 25-hydroxyvitamin D levels reached 30 ng/mL.

CHALLENGES TO IMPLEMENTATION

Breaking tradition

The study found that both daily and weekly doses of vitamin D were effective in reducing the incidence of ARTIs, but the doses used were much lower than the commonly used 10,000 to 50,000 IU bolus doses, which were ineffective in reducing ARTIs in the current meta-analysis. Since bolus dosing is an ingrained practice for many providers, changing this may prove challenging.

Continue to: In addition...

In addition, the authors of the study suggest that one of the ways to provide this level of vitamin D is through food fortification, but food fortification is often complicated by emotional and/or political issues that could thwart implementation.

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.

ILLUSTRATIVE CASE

Ms. M is a 55-year-old woman who is generally healthy, but who was diagnosed recently with severe vitamin D deficiency (serum 25-hydroxyvitamin D level of 8 ng/mL). She is being seen for her second episode of acute viral bronchitis in the past 6 months. She has no significant smoking or exposure history, no history of asthma, and takes no respiratory medications. Standard treatment for her level of vitamin D deficiency is 50,000 IU/week in bolus dosing, but is that your best option in this case?

Acute respiratory tract infections (ARTIs) include nonspecific upper respiratory illnesses, otitis media, sinusitis (~70% viral), pharyngitis, acute bronchitis (also ~70% viral), influenza, respiratory syncytial virus, and pneumonia.^1,2 In the United States, ARTIs strain the health care system and are the most common cause of ambulatory care visits, accounting for almost 120 million, or about 10% of all visits, per year.³ In addition, ARTIs account for almost 50% of antibiotic prescriptions for adults and almost 75% of antibiotic prescriptions for children—many of which are unnecessary.^2,4

While patient and parent education, antibiotic stewardship programs, and demand management may reduce inappropriate antibiotic use and the overall burden of ARTIs on the health care system, prevention of infections is a powerful tool within the overall approach to managing ARTIs.

STUDY SUMMARY

Vitamin D protects against ARTIs, but only in smaller doses

This 2017 systematic review and meta-analysis of 25 trials (N=10,933) evaluated vitamin D supplementation for the prevention of ARTIs in the primary care setting. Individual participant data were reevaluated to reduce risk of bias. The Cochrane risk of bias tool was used to address threats to validity.

The review and meta-analysis included institutional review board–approved, randomized, double-blind, placebo-controlled trials of vitamin D₃ or vitamin D₂ supplementation of any duration and in any language. The incidence of ARTI was a prespecified efficacy outcome. Duration of the included randomized controlled trials (RCTs) ranged from 7 weeks to 1.5 years.

Outcomes. The primary outcome was an incidence of at least 1 ARTI. Secondary outcomes included incidence of upper and lower ARTIs; incidence of adverse reactions to vitamin D; incidence of emergency department visits or hospital admission or both for ARTI; use of antimicrobials for ARTI; absence from work or school due to ARTI, and mortality (ARTI-related and all-cause).

Findings. Daily or weekly vitamin D supplementation (in doses ranging from < 20 to ≥ 50 µg/d) reduced the risk for ARTI (adjusted odds ratio [AOR] = 0.88; 95% confidence interval [CI], 0.81-0.96; number needed to treat [NNT] = 33). In subgroup analysis, daily or weekly vitamin D was protective (AOR = 0.81; 95% CI, 0.72-0.91), but bolus dosing (≥ 30,000 IU) was not (AOR = 0.97; 95% CI, 0.86-1.10).

Continue to: In 2-step analysis...

This study found that low-dose daily or weekly vitamin D supplementation was protective against acute respiratory tract infections, but bolus dosing was not.

In 2-step analysis, patients benefited who: had baseline circulating 25-hydroxyvitamin D concentrations < 10 ng/mL (AOR = 0.30; 95% CI, 0.17-0.53; NNT = 4); had baseline circulating 25-hydroxyvitamin D levels of 10 to 28 ng/mL (AOR = 0.75; 95% CI, 0.60-0.95; NNT = 15); were ages 1.1 to 15.9 years (AOR = 0.59; 95% CI, 0.45-0.79); were ages 16 to 65 years (AOR = 0.79; 95% CI, 0.63-0.99); or had a body mass index < 25 (AOR = 0.82; 95% CI, 0.71-0.95).

Higher D levels are a different story. Vitamin D supplementation in people with circulating levels of 25-hydroxyvitamin D ≥ 30 ng/mL did not appear to provide benefit (AOR = 0.96; 95% CI, 0.78-1.18). Supplementation in this population did not influence any of the secondary outcomes, including risk for all-cause serious adverse events (AOR = 0.98; 95% CI, 0.80-1.20).

WHAT’S NEW

A more accurate snapshot

Previous studies of vitamin D and respiratory tract infections were mostly observational in nature. Those that were RCTs used variable doses of vitamin D, had variable baseline 25-hydroxyvitamin D levels, and employed various methods to monitor ARTI symptoms/incidence.^5-8 This is the first systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials with supplementation using vitamin D₃ or vitamin D₂ that used individual participant-level data, which gives a more accurate estimate of outcomes when compared with traditional meta-analyses.

CAVEATS

Only the most deficient benefit?

Vitamin D supplementation was safe and protected against ARTIs overall, but the greatest effect of vitamin D supplementation on the prevention of ARTIs was noted in those who were most severely vitamin D deficient (those with circulating 25-hydroxyvitamin levels < 10 ng/mL, NNT = 4; 10-28 ng/mL, NNT = 15). There was no demonstrable effect once circulating 25-hydroxyvitamin D levels reached 30 ng/mL.

CHALLENGES TO IMPLEMENTATION

Breaking tradition

The study found that both daily and weekly doses of vitamin D were effective in reducing the incidence of ARTIs, but the doses used were much lower than the commonly used 10,000 to 50,000 IU bolus doses, which were ineffective in reducing ARTIs in the current meta-analysis. Since bolus dosing is an ingrained practice for many providers, changing this may prove challenging.

Continue to: In addition...

In addition, the authors of the study suggest that one of the ways to provide this level of vitamin D is through food fortification, but food fortification is often complicated by emotional and/or political issues that could thwart implementation.

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.

CASE

A 38-year-old man presents to your primary care clinic with chronic low back stiffness and pain. You have evaluated and treated this patient for this complaint for more than a year. His symptoms are worse in the morning upon wakening and improve with activity and anti-inflammatory medications. He denies any trauma or change in his activity level. His medical history includes chronic insertional Achilles pain and plantar fasciopathy, both for approximately 2 years. The patient reports no systemic or constitutional symptoms, and no pertinent family history.

How would you proceed with his work-up?

Ankylosing spondylitis (AS) is a form of arthritis that primarily affects the spine and sacroiliac joints. It is the most common spondyloarthropathy (SpA)—a family of disorders that also includes psoriatic arthritis; arthritis associated with inflammatory bowel disease; reactive arthritis; and juvenile SpA.¹ AS is most prevalent in Caucasians and may affect 0.1% to 1.4% of the population.²

Historically, a diagnosis of AS required radiographic evidence of inflammation of the axial spine or sacrum that manifested as chronic stiffness and back pain. However, the disease can also be mild or take time for radiographic evidence to appear. So an umbrella term emerged—axial spondyloarthritis (axSpA)—that includes both AS and the less severe form, called nonradiographic axSpA (nr-axSpA). While patients with AS exhibit radiographic abnormalities consistent with sacroiliitis, patients with early, or nr-axSpA, do not have radiographic abnormalities of the sacroiliac (SI) joint or axial spine.

In clinical practice, the distinction between AS and nr-axSpA has limited impact on the management of individual patients. However, early recognition, intervention, and treatment in patients who do not meet radiographic criteria for AS can improve patient-oriented outcomes.

The family physician (FP)’s role. It is not necessary that FPs be able to make a definitive diagnosis, but FPs should:

• be able to recognize the symptoms of inflammatory back pain (IBP);
• know which radiographic and laboratory studies to obtain and when;
• know the Assessment of SpondyloArthritis international Society (ASAS) criteria³ that assist in identifying patients at risk for axSpA; and
• know when to refer moderate- to high-risk patients to rheumatologists for assistance with the diagnosis.

FPs should have a high index of suspicion in any patient who has chronic back pain (> 3 months) with other features of SpA, and should pay special attention to young adult patients (< 45 years) who have IBP features.

Continue to: Definitive data to show...

Definitive data to show what percentage of patients with nr-axSpA progress to AS are lacking. However, early identification of AS is important, as those who go undiagnosed have increased back pain, stiffness, progressive loss of mobility, and decreased quality of life. In addition, patients diagnosed after significant sacroiliitis is visible are less responsive to treatment.⁴

It takes an average of 5 to 7 years for patients with radiographic evidence of ankylosing spondylitis to receive the proper diagnosis.

What follows is a review of what you’ll see and the tools that will help with diagnosis and referral.

The diagnosis dilemma

In the past, the modified New York criteria have been used to define AS, but they require the presence of both clinical symptoms and radiographic findings indicative of sacroiliitis for an AS designation.^5,6 Because radiographic sacroiliitis can be a late finding in axSpA and nonexistent in nr-asSpA, these criteria are of limited clinical utility.

To assist in early identification, the ASAS published criteria to classify patients with early axSpA prior to radiographic manifestations.³ While not strictly diagnostic, these criteria combine patient history that includes evidence of IBP, human leukocyte antigen (HLA)-B27 positivity, and radiography to assist health care providers in identifying patients who may have axSpA and need prompt referral to a rheumatologist.

Easy to miss, even with evidence. It takes an average of 5 to 7 years for patients with radiographic evidence of AS to receive the proper diagnosis.⁷ There are several reasons for this. First, the axSpA spectrum encompasses a small percentage of patients who present to health care providers with back pain. In addition, many providers overlook the signs and symptoms of IBP, which are a hallmark of the condition. And finally, as stated earlier, true criteria for the diagnosis of axSpA do not exist.

Continue to: In addition...

In addition, AS predominantly affects people in the third and fourth decades of life, but as many as 5% of patients of all ages with chronic back pain (> 3 months) can be classified as having AS.⁸ In patients who have IBP features, 14% can be classified as having axSpA.⁹ Therefore, it is important to recognize the features of IBP (TABLE 1¹⁰). The presence of 4 of the 5 of IBP features has a sensitivity of 77% and a specificity of 91.7% for IBP.¹⁰

A different kind of back pain. The vast majority of patients presenting with low back pain will have features of mechanical back pain, which include improvement with rest, mild and short-lived morning stiffness and/or pain upon waking, and the absence of inflammatory markers. Those with axSpA, on the other hand, are more likely to report improvement of pain with exercise, no improvement with rest, and pain at night with improvement upon rising. While the presence of IBP features alone isn’t diagnostic for nr-axSpA or AS, such features should increase your suspicion, especially when such features are present in younger patients.

Physical exam findings

Physical exam findings are neither sensitive nor specific for the diagnosis of an axSpA disorder, but can help build a case for one. The physical exam can also assist in identifying comorbid conditions including uveitis, psoriasis, dactylitis, and enthesitis. Experts do not recommend using serial measurements of axial range of motion because they are time-consuming, and normative values are highly variable.

On examination of the peripheral joints and feet, note any swollen, tender, or deformed joints, as well as any dactylitis. Although any enthesis can be affected in axSpA, the insertional points of the Achilles and the plantar fascia are the most typical,¹ so pay particular attention to these areas. On skin exam, note any evidence of psoriatic manifestations. Refer all patients with suspected uveitis to an ophthalmologist for confirmation of the diagnosis.

Lab studies: Not definitive, but helpful

No laboratory studies confirm a diagnosis of nr-axSpA or AS; however, 2 studies—C-reactive protein (CRP) and HLA-B27—are important, as levels are listed as part of ASAS’s axSpA features (TABLE 2³) and are factors that should be considered when deciding whether a referral is needed (TABLE 3¹¹). As such, HLA-B27 and CRP testing should be performed in all patients suspected of having an axSpA spectrum disorder.

Continue to: HLA-B27 is...

HLA-B27 is positive in 70% to 95% of patients with axSpA and can help build a case for the disorder.^6,12 CRP is useful too, as an elevated CRP has important treatment implications (more on that in a bit).⁶

Other diagnoses in the differential include: degenerative disc disease, lumbar spondylosis, congenital vertebral anomalies, and osteoarthritis of the SI joint, bone metastasis, or primary bone tumors.¹

Start with plain x-rays. The American College of Radiology (ACR) published appropriateness criteria for obtaining x-rays in patients suspected of having axSpA.¹³ Plain x-rays of the spine and SI joint are recommended for the initial evaluation. Magnetic resonance imaging (MRI) of the SI joint and/or spine should be obtained if the initial x-rays are negative or equivocal. Patient symptomology and/or exam findings determine whether to include the SI joint and/or spine. If the patient has subjective and objective findings concerning for pathology of both, then an MRI of the spine and SI joint is warranted.

HLA-B27 is positive in 70%-95% of patients with axSpA.

Alternatively, computed tomography (CT) can be substituted if MRI is unavailable. In patients with known axSpA, surveillance radiography should not occur more often than every 2 years.⁶

Timely referral is essential

Timely referral to a rheumatologist is an essential part of early diagnosis and treatment. Advances in treatment options for axSpA have become available in recent years and offer new hope for patients.

Continue to: As the presence of IBP...

As the presence of IBP features portends a 3-fold increase in the risk for axSpA,⁸ we propose an approach to the referral of patients with IBP features that deviates slightly from the ASAS algorithm. We believe it is within the scope of FPs to recognize IBP features, order appropriate ancillary studies, start a trial of nonsteroidal anti-inflammatory drugs (NSAIDs), and follow-up with patients in 2 to 4 weeks to review results and evaluate treatment response. As such, all patients < 45 years old with IBP symptoms (TABLE 1¹⁰) for 3 months or longer should be sent for laboratory workup (HLA-B27, CRP) and plain radiographs of the sacroiliac joints and lumbar spine.

The only modifiable predictor of progression to axSpA is smoking.

Older patients, patients with IBP features for < 3 months, or patients < 45 years with IBP that have negative lab testing and negative radiographs should start an exercise program, be treated with an NSAID, and be assessed for ASAS spondyloarthritis features (TABLE 2³).

Any patient with positive lab testing, positive radiographs, or ≥ 1 ASAS axSpA features should be referred to Rheumatology (TABLE 3¹¹). Patients with a negative radiograph should be evaluated with an MRI of the SI joints or spine (driven by pain location) and referred to Rheumatology if positive.

Keep in mind that not all patients fit neatly into an algorithm or a classification system. Therefore, we recommend that any patient with IBP features who fails to improve after 3 months of an exercise program, for whom you have a high index of suspicion for possible axSpA spectrum disease, receive appropriate ancillary studies and referral for expert consultation.

Exercise and NSAIDs form the basis of treatment

The purpose of treating patients with a suspected axSpA spectrum disorder is to decrease pain and stiffness, improve function and quality of life, and, ideally, halt or slow progression of disease. The only modifiable predictor of progression to axSpA is smoking; as such, encourage tobacco cessation if appropriate.¹⁴

Continue to: Nonpharmacologic treatment...

Nonpharmacologic treatment, such as regular aerobic exercise and strength training, should be prescribed for all patients with axSpA.⁶ Regular exercise is helpful in improving lower back pain, function, and spinal mobility. Combination endurance and strength-training programs are associated with the greatest benefits, and aquatic therapy is better than land-based therapy for pain.¹⁵ That said, recommend land-based exercises over no exercise when pool-based therapy is unavailable.

NSAIDs (eg, ibuprofen 200-800 mg at variable frequency, up to a maximum dose of 2400 mg/d; naproxen 250-500 mg bid) are the core treatment for patients with axSpA, as they improve pain, function, and quality of life.⁶ Both traditional NSAIDs and cyclooxygenase II (COX-II) inhibitors are effective; no differences in efficacy exist between the classes.^6,15,16

Prompt diagnosis of patients with ankylosing spondylitis is important because those diagnosed after significant sacroiliitis is visible are less responsive to treatment.

NSAIDs have been shown to be as safe as placebo for up to 12 weeks of continuous use in patients without gastritis or renal disease.¹⁶ In patients with a gastrointestinal comorbidity, use NSAIDs cautiously.¹⁷

If adequate pain relief is not obtained after 2 to 4 weeks of NSAID use, try a different NSAID prior to escalating treatment.⁶ More research is needed to evaluate the effect of NSAIDs on spinal radiographic progression of disease because of conflicting results of existing studies.¹⁶

Unlike with other rheumatologic disorders, oral glucocorticoids and traditional disease-modifying anti-rheumatic drugs (DMARDs) are not effective in axSpA and should not be prescribed.¹⁸

Continue to: Other agents

Other agents. In patients who continue to have symptoms, or cannot tolerate 12 weeks of NSAIDs, newer biologic DMARDs may be considered. Tumor necrosis factor inhibitors (TNFi) and interleukin-17 inhibitors (IL-17i) have shown the best efficacy.^18,19 In patients with AS, these medications improve pain and function, increase the chance of achieving partial remission of symptoms, and reduce CRP levels and MRI-detectable inflammation of the SI joint and/or spine.^1,19 At this time, these medications are reserved for use in patients with clinical symptoms consistent with, and radiographic evidence of, axSpA, or in patients with nr-axSpA who have elevated CRP levels.¹⁸

For patients diagnosed with axSpA, an elevated CRP, short symptom duration (or young age), and inflammation noted on MRI seem to be the best predictors of a good response to TNFi.²⁰ All patients in whom biologic DMARDS are considered should be referred to a rheumatologist because of cost, potential adverse effects, and stringent indications for use.

Surveil disease progression to prevent complications

We don’t yet know if progression of axSpA is linear or if the process can be slowed or halted with timely treatment. We do know that the natural history of structural progression is low in patients with early nr-axSpA.

Examples of validated online tools that can assist in measuring patient response to treatment and/or progression of disease follow.²¹ They can be used alone or in combination to help monitor treatment and progression of disease.

• The Ankylosing Spondylitis Disease Activity Score (ASDAS) (https://www.asas-group.org/clinical-instruments/asdas-calculator/). This measure of disease activity uses a 5-item patient assessment and CRP level measurement.
• The Bath Ankylosing Spondylitis Functional Index (BASFI) (http://basdai.com/BASFI.php). The BASFI consists of 8 items pertaining to everyday function and 2 items assessing the ability of patients to cope with everyday life.
• The Ankylosing Spondylitis Quality of Life Scale (ASQoL; http://oml.eular.org/sysModules/obxOml/docs/ID_32/ASQoL%20Questionnaire%20English.pdf).The ASQoL is an 18-item questionnaire related to the impact of disease on sleep, mood, motivation, and activities of daily living, among others.

Comorbidities. Patients with axSpA have an increased lifetime risk for cardiovascular disease, osteoporosis, fracture, inflammatory bowel disease, and iritis.⁶ Acute back pain in a patient with axSpA should be evaluated for a fracture and not automatically deemed an axSpA flare.¹³ Obtain a CT scan of the spine for all patients with known spine ankyloses who are suspected of having a fracture (because of the low sensitivity of plain radiography).¹³

Continue to: Prognosis

Prognosis. AS is a progressive long-term medical condition. Patients may experience progressive spinal deformity, hip joint or sacroiliac arthroses, or neurologic compromise after trauma. Reserve surgical referral for patients with spinal deformity that significantly affects quality of life and is severe or progressing despite nonpharmacologic and pharmacologic measures. Refer patients with an unstable spinal fracture for surgical intervention.⁶

Order HLA-B27 and C-reactive protein testing in all patients suspected of having an axial spondyloarthritis spectrum disorder.

Advise patients of available local, national, and international support groups. The National Ankylosis Spondylitis Society (NASS) based in the United Kingdom and the Spondylitis Association of America (SAA) are patient-friendly, nonprofit organizations that provide resources and information to people to help them learn about and cope with their condition.

CASE

You diagnose IBP in this patient and proceed with a work-up. You order x-rays of the back and SI joint, a CRP level, and an HLA-B27 test. X-rays and laboratory studies are negative. The patient is encouraged by your recommendation to start an aerobic and strength training home exercise program. In addition, you prescribe naproxen 500 mg bid and ask the patient to return in 1 month.

On follow-up he states that the naproxen is working well to control his pain. Upon further chart review and questioning, the patient confirms a history of chronic plantar fasciosis and psoriasis that he has controlled with intermittent topical steroids. He denies visual disturbances or gastrointestinal complaints. You refer him to a rheumatologist, where biologic agents are discussed but not prescribed at this time.

CORRESPONDENCE
Carlton J Covey, MD, FAAFP, Nellis Family Medicine Residency Program, 4700 Las Vegas Blvd. North, Nellis AFB, NV 89191; carlton.j.covey.mil@mail.mil