A novel type of talk therapy that pays as much attention to building positive mood as it does to reducing depressed mood may work as well, if not better, than cognitive-behavioral therapy (CBT) for anhedonic depression, results of a pilot trial suggest.
 

While the trial was not adequately powered to test if augmented depression therapy (ADepT) is superior to CBT, “results nevertheless were encouraging,” lead author Barnaby Dunn, PhD, professor of clinical psychology, University of Exeter (England), said in an interview.

The trial showed that ADepT is feasible, acceptable, and “not worse than CBT,” also showing the “potential to be better than CBT in clinical outcomes,” Dr. Dunn said.

“By building positive mood, ADepT may help individuals stay well for longer in the future,” he noted.

The early results were published online in eClinicalMedicine. 
 

Dual approach

“There are two sides to the depression coin – heightened negative mood and reduced positive mood. Classic CBT focuses mainly on repairing negative mood and pays less attention to building positive mood,” Dr. Dunn explained.

He said when he speaks to clients about what is key to recovery from depression, they often mention the importance of reconnecting to the positive.

“ADepT pays equal attention to building the positives as it does reducing the negatives, giving clients new skills to ‘act opposite’ to old ways of thinking and feeling that can stop them making the most of opportunities and being able to experience well-being,” Dr. Dunn said.

ADepT is an individual therapy delivered over 15 acute and 5 booster sessions, which is similar in “dose” to classic CBT, Dr. Dunn said.

The primary focus of ADepT is building well-being (capacity to experience pleasure, meaning, and social connection in life) and functional recovery, with depression conceptualized as patterns of thinking, feeling, and behaving that serve as barriers to achieving this goal.

Patients work with trained therapists to overcome barriers to being resilient (managing challenges to reduce negative affect) and thriving (taking opportunities to maximize positive affect).

A total of 82 adults with a moderate to severe current major depressive episode with features of anhedonia took part in the pilot trial. They were randomly allocated 1:1 to either 20 individual sessions of ADepT or CBT, delivered in the University of Exeter Accessing Evidence Based Psychological Therapies outpatient clinic.

Researcher-blinded assessments were completed at intake and after 6, 12, and 18 months. Coprimary outcomes were depression, measured via the Patient Health Questionnaire and well-being, gauged with the Warwick Edinburgh Mental Wellbeing Scale at 6 months.

Within-group analyses showed that both ADepT and CBT led to clinically meaningful improvements in depression, well-being, and all other secondary outcomes, including measures of anhedonia, Dr. Dunn said.

Between-group effects favored ADepT over CBT for depression and well-being. “For example, about 80% of clients no longer met diagnostic criteria for depression after ADepT, compared to around 56% of clients in CBT,” Dr. Dunn said.

“There were also numerically bigger gains in well-being and reductions in anhedonia in ADepT relative to CBT. A greater number of clients who recovered at the end of therapy stayed well over the longer term in ADepT relative to CBT,” he noted.

ADepT costs the same amount to deliver as CBT “but resulted in greater gains in quality of life, meaning it showed a high probability of being cost effective,” Dr. Dunn said.

ADepT has also been designed so that trained CBT therapists will be able to deliver it with minimal additional training.

“The next step,” said Dr. Dunn, “is a bigger definitive trial, which will formally test if ADepT is clinically superior to and better value for money than CBT when delivering ADepT in more routine care settings [U.K. NHS clinics rather than specialist university mood disorder center].”

The trial was funded by a Career Development Fellowship awarded to Dr. Dunn by the National Institute for Health and Care Research. Dr. Dunn has a book contract with Guilford Press to write the ADepT treatment manual and receives occasional payment or honoraria (including support for attending meetings) for delivering workshops and talks on ADepT.

A version of this article first appeared on Medscape.com.

A novel type of talk therapy that pays as much attention to building positive mood as it does to reducing depressed mood may work as well, if not better, than cognitive-behavioral therapy (CBT) for anhedonic depression, results of a pilot trial suggest.
 

While the trial was not adequately powered to test if augmented depression therapy (ADepT) is superior to CBT, “results nevertheless were encouraging,” lead author Barnaby Dunn, PhD, professor of clinical psychology, University of Exeter (England), said in an interview.

The trial showed that ADepT is feasible, acceptable, and “not worse than CBT,” also showing the “potential to be better than CBT in clinical outcomes,” Dr. Dunn said.

“By building positive mood, ADepT may help individuals stay well for longer in the future,” he noted.

The early results were published online in eClinicalMedicine. 
 

Dual approach

“There are two sides to the depression coin – heightened negative mood and reduced positive mood. Classic CBT focuses mainly on repairing negative mood and pays less attention to building positive mood,” Dr. Dunn explained.

He said when he speaks to clients about what is key to recovery from depression, they often mention the importance of reconnecting to the positive.

“ADepT pays equal attention to building the positives as it does reducing the negatives, giving clients new skills to ‘act opposite’ to old ways of thinking and feeling that can stop them making the most of opportunities and being able to experience well-being,” Dr. Dunn said.

ADepT is an individual therapy delivered over 15 acute and 5 booster sessions, which is similar in “dose” to classic CBT, Dr. Dunn said.

The primary focus of ADepT is building well-being (capacity to experience pleasure, meaning, and social connection in life) and functional recovery, with depression conceptualized as patterns of thinking, feeling, and behaving that serve as barriers to achieving this goal.

Patients work with trained therapists to overcome barriers to being resilient (managing challenges to reduce negative affect) and thriving (taking opportunities to maximize positive affect).

A total of 82 adults with a moderate to severe current major depressive episode with features of anhedonia took part in the pilot trial. They were randomly allocated 1:1 to either 20 individual sessions of ADepT or CBT, delivered in the University of Exeter Accessing Evidence Based Psychological Therapies outpatient clinic.

Researcher-blinded assessments were completed at intake and after 6, 12, and 18 months. Coprimary outcomes were depression, measured via the Patient Health Questionnaire and well-being, gauged with the Warwick Edinburgh Mental Wellbeing Scale at 6 months.

Within-group analyses showed that both ADepT and CBT led to clinically meaningful improvements in depression, well-being, and all other secondary outcomes, including measures of anhedonia, Dr. Dunn said.

Between-group effects favored ADepT over CBT for depression and well-being. “For example, about 80% of clients no longer met diagnostic criteria for depression after ADepT, compared to around 56% of clients in CBT,” Dr. Dunn said.

“There were also numerically bigger gains in well-being and reductions in anhedonia in ADepT relative to CBT. A greater number of clients who recovered at the end of therapy stayed well over the longer term in ADepT relative to CBT,” he noted.

ADepT costs the same amount to deliver as CBT “but resulted in greater gains in quality of life, meaning it showed a high probability of being cost effective,” Dr. Dunn said.

ADepT has also been designed so that trained CBT therapists will be able to deliver it with minimal additional training.

“The next step,” said Dr. Dunn, “is a bigger definitive trial, which will formally test if ADepT is clinically superior to and better value for money than CBT when delivering ADepT in more routine care settings [U.K. NHS clinics rather than specialist university mood disorder center].”

The trial was funded by a Career Development Fellowship awarded to Dr. Dunn by the National Institute for Health and Care Research. Dr. Dunn has a book contract with Guilford Press to write the ADepT treatment manual and receives occasional payment or honoraria (including support for attending meetings) for delivering workshops and talks on ADepT.

A version of this article first appeared on Medscape.com.

A novel type of talk therapy that pays as much attention to building positive mood as it does to reducing depressed mood may work as well, if not better, than cognitive-behavioral therapy (CBT) for anhedonic depression, results of a pilot trial suggest.
 

While the trial was not adequately powered to test if augmented depression therapy (ADepT) is superior to CBT, “results nevertheless were encouraging,” lead author Barnaby Dunn, PhD, professor of clinical psychology, University of Exeter (England), said in an interview.

The trial showed that ADepT is feasible, acceptable, and “not worse than CBT,” also showing the “potential to be better than CBT in clinical outcomes,” Dr. Dunn said.

“By building positive mood, ADepT may help individuals stay well for longer in the future,” he noted.

The early results were published online in eClinicalMedicine. 
 

Dual approach

“There are two sides to the depression coin – heightened negative mood and reduced positive mood. Classic CBT focuses mainly on repairing negative mood and pays less attention to building positive mood,” Dr. Dunn explained.

He said when he speaks to clients about what is key to recovery from depression, they often mention the importance of reconnecting to the positive.

“ADepT pays equal attention to building the positives as it does reducing the negatives, giving clients new skills to ‘act opposite’ to old ways of thinking and feeling that can stop them making the most of opportunities and being able to experience well-being,” Dr. Dunn said.

ADepT is an individual therapy delivered over 15 acute and 5 booster sessions, which is similar in “dose” to classic CBT, Dr. Dunn said.

The primary focus of ADepT is building well-being (capacity to experience pleasure, meaning, and social connection in life) and functional recovery, with depression conceptualized as patterns of thinking, feeling, and behaving that serve as barriers to achieving this goal.

Patients work with trained therapists to overcome barriers to being resilient (managing challenges to reduce negative affect) and thriving (taking opportunities to maximize positive affect).

A total of 82 adults with a moderate to severe current major depressive episode with features of anhedonia took part in the pilot trial. They were randomly allocated 1:1 to either 20 individual sessions of ADepT or CBT, delivered in the University of Exeter Accessing Evidence Based Psychological Therapies outpatient clinic.

Researcher-blinded assessments were completed at intake and after 6, 12, and 18 months. Coprimary outcomes were depression, measured via the Patient Health Questionnaire and well-being, gauged with the Warwick Edinburgh Mental Wellbeing Scale at 6 months.

Within-group analyses showed that both ADepT and CBT led to clinically meaningful improvements in depression, well-being, and all other secondary outcomes, including measures of anhedonia, Dr. Dunn said.

Between-group effects favored ADepT over CBT for depression and well-being. “For example, about 80% of clients no longer met diagnostic criteria for depression after ADepT, compared to around 56% of clients in CBT,” Dr. Dunn said.

“There were also numerically bigger gains in well-being and reductions in anhedonia in ADepT relative to CBT. A greater number of clients who recovered at the end of therapy stayed well over the longer term in ADepT relative to CBT,” he noted.

ADepT costs the same amount to deliver as CBT “but resulted in greater gains in quality of life, meaning it showed a high probability of being cost effective,” Dr. Dunn said.

ADepT has also been designed so that trained CBT therapists will be able to deliver it with minimal additional training.

“The next step,” said Dr. Dunn, “is a bigger definitive trial, which will formally test if ADepT is clinically superior to and better value for money than CBT when delivering ADepT in more routine care settings [U.K. NHS clinics rather than specialist university mood disorder center].”

The trial was funded by a Career Development Fellowship awarded to Dr. Dunn by the National Institute for Health and Care Research. Dr. Dunn has a book contract with Guilford Press to write the ADepT treatment manual and receives occasional payment or honoraria (including support for attending meetings) for delivering workshops and talks on ADepT.

A version of this article first appeared on Medscape.com.

Except for a drop in the number of sexually transmitted infections (STIs) early in the COVID-19 pandemic (March and April 2020), the incidence of STIs has been rising throughout this century.¹ In 2018, 1 in 5 people in the United States had an STI; 26 million new cases were reported that year, resulting in direct costs of $16 billion—85% of which was for the care of HIV infection.² Also that year, infection with Chlamydia trachomatis (chlamydia), Trichomonas vaginalis (trichomoniasis), herpesvirus type 2 (genital herpes), and/or human papillomavirus (condylomata acuminata) constituted 97.6% of all prevalent and 93.1% of all incident STIs.³ Almost half (45.5%) of new cases of STIs occur in people between the ages of 15 and 24 years.³

Three factors—changing social patterns, including the increase of social networking; the ability of antiviral therapy to decrease the spread of HIV, leading to a reduction in condom use; and increasing antibiotic resistance—have converged to force changes in screening and treatment recommendations. In this article, we summarize updated guidance for primary care clinicians from several sources—including the Centers for Disease Control and Prevention (CDC), the US Preventive Services Task Force (USPSTF), and the American Society for Colposcopy and Cervical Pathology (ASCCP)—on diagnosing STIs (TABLE 1^4-13) and providing guideline-based treatment ­(Table 2¹⁴). Because of the breadth and complexity of HIV disease, it is not addressed here.

Chlamydia

Infection with Chlamydia trachomatis—the most commonly reported bacterial STI in the United States—primarily causes cervicitis in women and proctitis in men, and can cause urethritis and pharyngitis in men and women. Prevalence is highest in sexually active people younger than 24 years.¹⁵

Because most infected people are asymptomatic and show no signs of illness on physical exam, screening is recommended for all sexually active women younger than 25 years and all men who have sex with men (MSM).⁴ No studies have established proper screening intervals; a reasonable approach, therefore, is to repeat screening for patients who have a sexual history that confers a new or persistent risk for infection since their last negative result.

Depending on the location of the infection, symptoms of chlamydia can include vaginal or penile irritation or discharge, dysuria, pelvic or rectal pain, and sore throat. Breakthrough bleeding in a patient who is taking an oral contraceptive should raise suspicion for chlamydia.

Untreated chlamydia can lead to pelvic inflammatory disease (PID), tubo-ovarian abscess, tubal factor infertility, ectopic pregnancy, and chronic pelvic pain. Infection can be transmitted vertically (mother to baby) antenatally, which can cause ophthalmia neonatorum and pneumonia in these newborns.

Diagnosis. The diagnosis of chlamydia is made using nucleic acid amplification testing (NAAT). Specimens can be collected by the clinician or the patient (self collected) using a vaginal, rectal, or oropharyngeal swab, or a combination of these, and can be obtained from urine or liquid-based cytology material.¹⁶

Continue to: Treatment

Treatment. Recommendations for treating chlamydia were updated by the CDC in its 2021 treatment guidelines (Table 2¹⁴). Doxycycline 100 mg bid for 7 days is the preferred regimen; alternative regiments are (1) azithromycin 1 g in a single dose and (2) levofloxacin 500 mg daily for 7 days.⁴ A meta-analysis¹⁷ and a Cochrane review¹⁸ showed that the rate of treatment failure was higher among men when they were treated with azithromycin instead of doxycycline; furthermore, a randomized controlled trial demonstrated that doxycycline is more effective than azithromycin (cure rate, 100%, compared to 74%) at treating rectal chlamydia in MSM.¹⁹

Azithromycin is efficacious for urogenital infection in women; however, there is concern that the 33% to 83% of women who have concomitant rectal infection (despite reporting no receptive anorectal sexual activity) would be insufficiently treated. Outside pregnancy, the CDC does not recommend a test of cure but does recommend follow-up testing for reinfection in 3 months. Patients should abstain from sexual activity until 7 days after all sexual partners have been treated.

Expedited partner therapy (EPT) is the practice of treating sexual partners of patients with known chlamydia (and patients with gonococcal infection). Unless prohibited by law in your state, offer EPT to patients with chlamydia if they cannot ensure that their sexual partners from the past 60 days will seek timely treatment.^a

Breakthrough bleeding in a patient who is taking an oral contraceptive should raise suspicion for chlamydia.

Evidence to support EPT comes from 3 US clinical trials, whose subjects comprised heterosexual men and women with chlamydia or gonorrhea.^21-23 The role of EPT for MSM is unclear; data are limited. Shared ­decision-making is recommended to determine whether EPT should be provided, to ensure that co-infection with other bacterial STIs (eg, syphilis) or HIV is not missed.^24-26

^a Visit www.cdc.gov/std/ept to read updated information about laws and regulations regarding EPT in your state.²⁰

Gonorrhea

Gonorrhea is the second most-reported bacterial communicable disease.⁵ Infection with Neisseria gonorrhoeae causes urethral discharge in men, leading them to seek treatment; infected women, however, are often asymptomatic. Infected men and women might not recognize symptoms until they have transmitted the disease. Women have a slower natural clearance of gonococcal infection, which might explain their higher prevalence.²⁷ Delayed recognition of symptoms can result in complications, including PID.⁵

Diagnosis. Specimens for NAAT can be obtained from urine, endocervical, vaginal, rectal, pharyngeal, and male urethral specimens. Reported sexual behaviors and exposures of women and transgender or gender-diverse people should be taken into consideration to determine whether rectal or pharyngeal testing, or both, should be performed.²⁸ MSM should be screened annually at sites of contact, including the urethra, rectum, and pharynx.²⁸ All patients with urogenital or rectal gonorrhea should be asked about oral sexual exposure; if reported, pharyngeal testing should be performed.⁵

NAAT of urine is at least as sensitive as testing of an endocervical specimen; the same specimen can be used to test for chlamydia and gonorrhea. Patient-collected specimens are a reasonable alternative to clinician-collected swab specimens.²⁹

Continue to: Treatment

Treatment is complicated by the ability of gonorrhea to develop resistance. Intramuscular ceftriaxone 500 mg in a single dose cures 98% to 99% of infections in the United States; however, monitoring local resistance patterns in the community is an important component of treatment.²⁸ (See Table 2¹⁴ for an alternative regimen for cephalosporin-allergic patients and for treating gonococcal conjunctivitis and disseminated infection.)

Unless prohibited by law in your state, offer expedited partner therapy to patients with chlamydia if they cannot ensure that their sexual partners from the past 60 days will seek timely treatment.

In 2007, the CDC identified widespread quinolone-resistant gonococcal strains; therefore, fluoroquinolones no longer are recommended for treating gonorrhea.³⁰ Cefixime has demonstrated only limited success in treating pharyngeal gonorrhea and does not attain a bactericidal level as high as ceftriaxone does; cefixime therefore is recommended only if ceftriaxone is unavailable.²⁸ The national Gonococcal Isolate Surveillance Project is finding emerging evidence of the reduced susceptibility of N gonorrhoeae to azithromycin—making dual therapy for gonococcal infection no longer a recommendation.²⁸

Patients should abstain from sex until 7 days after all sex partners have been treated for gonorrhea. As with chlamydia, the CDC does not recommend a test of cure for uncomplicated urogenital or rectal gonorrhea unless the patient is pregnant, but does recommend testing for reinfection 3 months after treatment.¹⁴ For patients with pharyngeal gonorrhea, a test of cure is recommended 7 to 14 days after initial treatment, due to challenges in treatment and because this site of infection is a potential source of antibiotic resistance.²⁸

Trichomoniasis

T vaginalis, the most common nonviral STI worldwide,³¹ can manifest as a yellow-green vaginal discharge with or without vaginal discomfort, dysuria, epididymitis, and prostatitis; most cases, however, are asymptomatic. On examination, the cervix might be erythematous with punctate lesions (known as strawberry cervix).

Unlike most STIs, trichomoniasis is as common in women older than 24 years as it is in younger women. Infection is associated with a lower educational level, lower socioeconomic status, and having ≥ 2 sexual partners in the past year.³² Prevalence is approximately 10 times as high in Black women as it is in White women.

T vaginalis infection is associated with an increase in the risk for preterm birth, premature rupture of membranes, cervical cancer, and HIV infection. With a lack of high-quality clinical trials on the efficacy of screening, women with HIV are the only group for whom routine screening is recommended.⁶

Diagnosis. NAAT for trichomoniasis is now available in conjunction with gonorrhea and chlamydia testing of specimens on vaginal or urethral swabs and of urine specimens and liquid Pap smears.

Continue to: Treatment

Treatment. Because of greater efficacy, the treatment recommendation for women has changed from a single 2-g dose of oral metronidazole to 500 mg twice daily for 7 days. The 2-g single oral dose is still recommended for men⁷ (Table 2¹⁴ lists alternative regimens).

Mycoplasma genitalium

Infection with M genitalium is common and often asymptomatic. The disease causes approximately 20% of all cases of nongonococcal and nonchlamydial urethritis in men and about 40% of persistent or recurrent infections. M genitalium is present in approximately 20% of women with cervicitis and has been associated with PID, preterm delivery, spontaneous abortion, and infertility.

There are limited and conflicting data regarding outcomes in infected patients other than those with persistent or recurrent infection; furthermore, resistance to azithromycin is increasing rapidly, resulting in an increase in treatment failures. Screening therefore is not recommended, and testing is recommended only in men with nongonococcal urethritis.^33,34

Diagnosis. NAAT can be performed on urine or on a urethral, penile meatal, endocervical, or vaginal swab; men with recurrent urethritis or women with recurrent cervicitis should be tested. NAAT also can be considered in women with PID. Testing the specimen for the microorganism’s resistance to macrolide antibiotics is recommended (if such testing is available).

Treatment is initiated with doxycycline 100 mg twice daily for 7 days. If the organism is macrolide sensitive, follow with azithromycin 1 g orally on Day 1, then 500 mg/d for 3 more days. If the organism is macrolide resistant or testing is unavailable, follow doxycycline with oral moxifloxacin 400 mg/d for 7 days.³³

Genital herpes (mostly herpesvirus type 2)

Genital herpes, characterized by painful, recurrent outbreaks of genital and anal lesions,³⁵ is a lifelong infection that increases in prevalence with age.⁸ Because many infected people have disease that is undiagnosed or mild or have unrecognizable symptoms during viral shedding, most genital herpes infections are transmitted by people who are unaware that they are contagious.³⁶ Herpesvirus type 2 (HSV-2) causes most cases of genital herpes, although an increasing percentage of cases are attributed to HSV type 1 (HSV-1) through receptive oral sex from a person who has an oral HSV-1 lesion.

Intramuscular ceftriaxone 500 mg in a single dose cures 98% to 99% of gonococcal infections in the United States; monitoring local resistance patterns in the community is important.

Importantly, HSV-2–infected people are 2 to 3 times more likely to become infected with HIV than people who are not HSV-2 infected.³⁷ This is becauseCD4+ T cells concentrate at the site of HSV lesions and express a higher level of cell-surface receptors that HIV uses to enter cells. HIV replicates 3 to 5 times more quickly in HSV-infected tissue.³⁸

Continue to: HSV can become disseminated...

HSV can become disseminated, particularly in immunosuppressed people, and can manifest as encephalitis, hepatitis, and pneumonitis. Beyond its significant burden on health, HSV carries significant psychosocial consequences.⁹

Diagnosis. Clinical diagnosis can be challenging if classic lesions are absent at evaluation. If genital lesions are present, HSV can be identified by NAAT or culture of a specimen of those lesions. False-negative antibody results might be more frequent in early stages of infection; repeating antibody testing 12 weeks after presumed time of acquisition might therefore be indicated, based on clinical judgment. HSV-2 antibody positivity implies anogenital infection because almost all HSV-2 infections are sexually acquired.

HSV-1 antibody positivity alone is more difficult to interpret because this finding does not distinguish between oral and genital lesions, and most HSV-1 seropositivity is acquired during childhood.³⁶ HSV polymerase chain reaction (PCR) testing of blood should not be performed to diagnose genital herpes infection, except in settings in which there is concern about disseminated infection.

Treatment. Management should address the acute episode and the chronic nature of genital herpes. Antivirals will not eradicate latent virus; rather, the goals of treatment are to:

• attenuate current infection
• prevent recurrence
• improve quality of life
• suppress the virus to prevent transmission to sexual partners.

All patients experiencing an initial episode of genital herpes should be treated, regardless of symptoms, due to the potential for prolonged or severe symptoms during recurrent episodes.⁹ Three drugs—acyclovir, valacyclovir, and famciclovir—are approved by the US Food and Drug Administration (FDA) to treat genital herpes and appear equally effective (TABLE 2¹⁴).

Antiviral therapy for recurrent genital HSV infection can be administered either as suppressive therapy to reduce the frequency of recurrences or episodically to shorten the duration of lesions:

• Suppressive therapy reduces the frequency of recurrence by 70% to 80% among patients with frequent outbreaks. Long-term safety and efficacy are well established.
• Episodic therapy is most effective if started within 1 day after onset of lesions or during the prodrome.³⁶

There is no specific recommendation for when to choose suppressive over episodic therapy; most patients prefer suppressive therapy because it improves quality of life. Use shared clinical decision-making to determine the best option for an individual patient.

Continue to: Human papillomavirus

Condylomata acuminata (genital warts) are caused by human papillomavirus (HPV), most commonly types 6 and 11, which manifest as soft papules or plaques on the external genitalia, perineum, perianal skin, and groin. The warts are usually asymptomatic but can be painful or pruritic, depending on size and location.

Diagnosis is made by visual inspection and can be confirmed by biopsy if lesions are atypical. Lesions can resolve spontaneously, remain unchanged, or grow in size or number.

Treatment. The aim of treatment is relief of symptoms and removal of warts. Treatment does not eradicate HPV infection. Multiple treatments are available that can be applied by the patient as a cream, gel, or ointment or administered by the provider, including cryotherapy, surgical removal, and solutions. The decision on how to treat should be based on the number, size, and location of lesions; patient preference; cost; convenience; and the modality’s adverse effects (TABLE 2¹⁴).

HPV-associated cancers and precancers. This is a broad (and separate) topic. HPV types 16 and 18 cause most cases of cervical, penile, vulvar, vaginal, anal, and oropharyngeal cancer and precancer.³⁹ The USPSTF, the American Cancer Society, and the American College of Obstetricians and Gynecologists all have recommendations for cervical cancer screening in the United States.⁴⁰ Refer to guidelines of the ASCCP for recommendations on abnormal screening tests.⁴¹

Prevention of genital warts. The 9-­valent HPV vaccine available in the United States is safe and effective and helps protect against viral types 6, 11, 16, 18, 31, 33, 45, 52, and 58. Types 6 and 11 are the principal causes of genital warts. Types 16 and 18 cause 66% of cervical cancer. The vaccination series can be started at age 9 years and is recommended for everyone through age 26 years. Only 2 doses are needed if the first dose is given prior to age 15 years; given after that age, a 3-dose series is utilized. Refer to CDC vaccine guidelines⁴² for details on the exact timing of vaccination.

Trichomoniasis can manifest as a yellowgreen vaginal discharge with or without vaginal discomfort, dysuria, epididymitis, and prostatitis; most cases, however, are asymptomatic.

Vaccination for women ages 27 to 45 years is not universally recommended because most people have been exposed to HPV by that age. However, the vaccine can still be administered, depending on clinical circumstances and the risk for new infection.⁴²

Syphilis

Caused by the spirochete Treponema pallidum, syphilis manifests across a spectrum—from congenital to tertiary. The inability of medical science to develop a method for culturing the spirochete has confounded diagnosis and treatment.

Continue to: Since reaching a historic...

Since reaching a historic nadir of incidence in 2000 (5979 cases in the United States), there has been an increasingly rapid rise in that number: to 130,000 in 2020. More than 50% of cases are in MSM; however, the number of cases in heterosexual women is rapidly increasing.⁴³

Routine screening for syphilis should be performed in any person who is at risk: all pregnant women in the first trimester (and in the third trimester and at delivery if they are at risk or live in a community where prevalence is high) and annually in sexually active MSM or anyone with HIV infection.¹⁰

Diagnosis. Examination by dark-field microscopy, testing by PCR, and direct fluorescent antibody assay for T pallidum from lesion tissue or exudate provide definitive diagnosis for early and congenital syphilis, but are often unavailable.

Presumptive diagnosis requires 2 serologic tests:

• Nontreponemal tests (the VDRL and rapid plasma reagin tests) identify anticardiolipin antibodies released during syphilis infection, although results also can be elevated in autoimmune disease or after certain immunizations, including the COVID-19 vaccine.
• Treponemal tests (the fluorescent treponemal antibody absorbed assay, T pallidum particulate agglutination assay, enzyme immunoassay, and chemiluminescence immunoassay) are specific antibody tests.

Historically, reactive nontreponemal tests, which are less expensive and easier to perform, were followed by a treponemal test to confirm the presumptive diagnosis. This method continues to be reasonable when screening patients in a low-prevalence population.¹¹ The reverse sequence screening algorithm (ie, begin with a treponemal test) is now frequently used. With this method, a positive treponemal test must be confirmed with a nontreponemal test. If the treponemal test is positive and the nontreponemal test is negative, another treponemal test must be positive to confirm the diagnosis. This algorithm is useful in high-risk populations because it provides earlier detection of recently acquired syphilis and enhanced detection of late latent syphilis.^12,13,44 The CDC has not stated a diagnostic preference.

Once the diagnosis is made, a complete history (including a sexual history and a history of syphilis testing and treatment) and a physical exam are necessary to confirm stage of disease.⁴⁵

Special circumstances. Neurosyphilis, ocular syphilis, and otosyphilis refer to the site of infection and can occur at any stage of disease. The nervous system usually is infected within hours of initial infection, but symptoms might take weeks or years to ­develop—or might never manifest. Any time a patient develops neurologic, ophthalmologic, or audiologic symptoms, careful neurologic and ophthalmologic evaluation should be performed and the patient should be tested for HIV.

Continue to: Lumbar puncture is warranted...

Lumbar puncture is warranted for evaluation of cerebrospinal fluid if neurologic symptoms are present but is not necessary for isolated ocular syphilis or otosyphilis without neurologic findings. Treatment should not be delayed for test results if ocular syphilis is suspected because permanent blindness can develop. Any patient at high risk for an STI who presents with neurologic or ophthalmologic symptoms should be tested for syphilis and HIV.⁴⁵

Pregnant women who have a diagnosis of syphilis should be treated with penicillin immediately because treatment ≥ 30 days prior to delivery is likely to prevent most ­cases of congenital syphilis. However, a course of penicillin might not prevent stillbirth or congenital syphilis in a gravely infected fetus, evidenced by fetal syphilis on a sonogram at the time of treatment. Additional doses of penicillin in pregnant women with early syphilis might be indicated if there is evidence of ­fetal syphilis on ultrasonography. All women who deliver a stillborn infant (≥ 20 weeks’ ­gestation) should be tested for syphilis at ­delivery.⁴⁶

All patients in whom primary or secondary syphilis has been diagnosed should be tested for HIV at the time of diagnosis and treatment; if the result is negative, they should be offered preexposure prophylaxis (PrEP; discussed shortly). If the incidence of HIV in your community is high, repeat testing for HIV in 3 months. Clinical and serologic evaluation should be performed 6 and 12 months after treatment.⁴⁷

Treatment. Penicillin remains the standard treatment for syphilis. Primary, secondary, and early tertiary stages (including in pregnancy) are treated with benzathine penicillin G 2.4 million units intramuscular (IM) in a single dose. For pregnant patients, repeating that dose in 1 week generally is recommended. Patients in the late latent (> 1 year) or tertiary stage receive the same dose of penicillin, which is then repeated weekly, for a total of 3 doses. Doxycycline and ceftriaxone are alternatives, except in ­pregnancy.

Antivirals will not eradicate latent herpesvirus; rather, the goals of treatment are to attenuate current infection, prevent recurrence, and improve quality of life.

Warn patients of the Jarisch-Herxheimer reaction: fever, headache, and myalgias associated with initiation of treatment in the presence of the high bacterial load seen in early syphilis. Treatment is symptomatic, but the Jarisch-Herxheimer reaction can cause fetal distress in pregnancy.

Otosyphilis, ocular syphilis, and neurosyphilis require intravenous (IV) aqueous crystalline penicillin G 3 to 4 million U every 4 hours for 10 to 14 days.⁴⁵ Alternatively, procaine penicillin G 2.4 million U/d IM can be given daily with oral probenecid 500 mg qid, both for 10 to 14 days (TABLE 2¹⁴).

Screening andprevention of STIs

Screening recommendations

Follow USPSTF screening guidelines for STIs.^10,48-54 Screen annually for:

• gonorrhea and chlamydia in women ages 15 to 24 years and in women older than 25 years if they are at increased risk
• gonorrhea, chlamydia, syphilis, and HIV in MSM, and hepatitis C if they are HIV positive
• trichomoniasis in women who are HIV positive.

Continue to: Consider the community in which...

Vaccination against human papillomavirus is not universally recommended for women ages 27 to 45 years because most people have been exposed to HPV by that age.

Consider the community in which you practice when determining risk; you might want to consult local public health authorities for information about local epidemiology and guidance on determining which of your patients are at increased risk.

Preexposure prophylaxis

According to the CDC, all sexually active adults and adolescents should be informed about the availability of PrEP to prevent HIV infection. PrEP should be (1) available to anyone who requests it and (2) recommended for anyone who is sexually active and who practices sexual behaviors that place them at substantial risk for exposure to or acquisition of HIV, or both.

The recommended treatment protocol for men and women who have either an HIV-positive partner or inconsistent condom use or who have had a bacterial STI in the previous 6 months is oral emtricitabine 200 mg plus tenofovir disoproxil fumarate 300 mg/d (sold as Truvada-F/TDF). Men and transgender women (ie, assigned male at birth) with at-risk behaviors also can use emtricitabine plus tenofovir alafenamide 25 mg/d (sold as Descovy-F/TAF).

In addition, cabotegravir plus rilpirivine (sold as Cabenuva), IM every 2 months, was approved by the FDA for PrEP in 2021.

Pregnant women who have syphilis should be treated with penicillin immediately: Treatment ≥ 30 days prior to delivery is likely to prevent most cases of congenital syphilis.

Creatinine clearance should be assessed at baseline and yearly (every 6 months for those older than 50 years) in patients taking PrEP. All patients must be tested for HIV at initiation of treatment and every 3 months thereafter (every 4 months for cabotegravir plus rilpirivine). Patients should be screened for bacterial STIs every 6 months (every 3 months for MSM and transgender women); screening for chlamydia should be done yearly. For patients being treated with emtricitabine plus tenofovir alafenamide, weight and a lipid profile (cholesterol and triglycerides) should be assessed annually.⁵⁵

Postexposure prophylaxis

The sharp rise in the incidence of STIs in the past few years has brought renewed interest in postexposure prophylaxis (PEP) for STIs. Although PEP should be standard in cases of sexual assault, this protocol also can be considered in other instances of high-risk exposure.

CDC recommendations for PEP in cases of assault are⁵⁶:

• ceftriaxone 500 mg IM in a single dose (1 g if weight is ≥ 150 kg) plus
• doxycycline 100 mg bid for 7 days plus
• metronidazole 2 g bid for 7 days (for vaginal exposure)
• pregnancy evaluation and emergency contraception
• hepatitis B risk evaluation and vaccination, with or without hepatitis B immune globulin
• HIV risk evaluation, based on CDC guidelines, and possible HIV prophylaxis (PrEP)
• HPV vaccination for patients ages 9 to 26 years if they are not already fully vaccinated.

CORRESPONDENCE
Belinda Vail, MD, 3901 Rainbow Boulevard, Mail Stop 4010, Kansas City, KS 66160; [email protected]

Except for a drop in the number of sexually transmitted infections (STIs) early in the COVID-19 pandemic (March and April 2020), the incidence of STIs has been rising throughout this century.¹ In 2018, 1 in 5 people in the United States had an STI; 26 million new cases were reported that year, resulting in direct costs of $16 billion—85% of which was for the care of HIV infection.² Also that year, infection with Chlamydia trachomatis (chlamydia), Trichomonas vaginalis (trichomoniasis), herpesvirus type 2 (genital herpes), and/or human papillomavirus (condylomata acuminata) constituted 97.6% of all prevalent and 93.1% of all incident STIs.³ Almost half (45.5%) of new cases of STIs occur in people between the ages of 15 and 24 years.³

Three factors—changing social patterns, including the increase of social networking; the ability of antiviral therapy to decrease the spread of HIV, leading to a reduction in condom use; and increasing antibiotic resistance—have converged to force changes in screening and treatment recommendations. In this article, we summarize updated guidance for primary care clinicians from several sources—including the Centers for Disease Control and Prevention (CDC), the US Preventive Services Task Force (USPSTF), and the American Society for Colposcopy and Cervical Pathology (ASCCP)—on diagnosing STIs (TABLE 1^4-13) and providing guideline-based treatment ­(Table 2¹⁴). Because of the breadth and complexity of HIV disease, it is not addressed here.

Chlamydia

Infection with Chlamydia trachomatis—the most commonly reported bacterial STI in the United States—primarily causes cervicitis in women and proctitis in men, and can cause urethritis and pharyngitis in men and women. Prevalence is highest in sexually active people younger than 24 years.¹⁵

Because most infected people are asymptomatic and show no signs of illness on physical exam, screening is recommended for all sexually active women younger than 25 years and all men who have sex with men (MSM).⁴ No studies have established proper screening intervals; a reasonable approach, therefore, is to repeat screening for patients who have a sexual history that confers a new or persistent risk for infection since their last negative result.

Depending on the location of the infection, symptoms of chlamydia can include vaginal or penile irritation or discharge, dysuria, pelvic or rectal pain, and sore throat. Breakthrough bleeding in a patient who is taking an oral contraceptive should raise suspicion for chlamydia.

Untreated chlamydia can lead to pelvic inflammatory disease (PID), tubo-ovarian abscess, tubal factor infertility, ectopic pregnancy, and chronic pelvic pain. Infection can be transmitted vertically (mother to baby) antenatally, which can cause ophthalmia neonatorum and pneumonia in these newborns.

Diagnosis. The diagnosis of chlamydia is made using nucleic acid amplification testing (NAAT). Specimens can be collected by the clinician or the patient (self collected) using a vaginal, rectal, or oropharyngeal swab, or a combination of these, and can be obtained from urine or liquid-based cytology material.¹⁶

Continue to: Treatment

Treatment. Recommendations for treating chlamydia were updated by the CDC in its 2021 treatment guidelines (Table 2¹⁴). Doxycycline 100 mg bid for 7 days is the preferred regimen; alternative regiments are (1) azithromycin 1 g in a single dose and (2) levofloxacin 500 mg daily for 7 days.⁴ A meta-analysis¹⁷ and a Cochrane review¹⁸ showed that the rate of treatment failure was higher among men when they were treated with azithromycin instead of doxycycline; furthermore, a randomized controlled trial demonstrated that doxycycline is more effective than azithromycin (cure rate, 100%, compared to 74%) at treating rectal chlamydia in MSM.¹⁹

Azithromycin is efficacious for urogenital infection in women; however, there is concern that the 33% to 83% of women who have concomitant rectal infection (despite reporting no receptive anorectal sexual activity) would be insufficiently treated. Outside pregnancy, the CDC does not recommend a test of cure but does recommend follow-up testing for reinfection in 3 months. Patients should abstain from sexual activity until 7 days after all sexual partners have been treated.

Expedited partner therapy (EPT) is the practice of treating sexual partners of patients with known chlamydia (and patients with gonococcal infection). Unless prohibited by law in your state, offer EPT to patients with chlamydia if they cannot ensure that their sexual partners from the past 60 days will seek timely treatment.^a

Breakthrough bleeding in a patient who is taking an oral contraceptive should raise suspicion for chlamydia.

Evidence to support EPT comes from 3 US clinical trials, whose subjects comprised heterosexual men and women with chlamydia or gonorrhea.^21-23 The role of EPT for MSM is unclear; data are limited. Shared ­decision-making is recommended to determine whether EPT should be provided, to ensure that co-infection with other bacterial STIs (eg, syphilis) or HIV is not missed.^24-26

^a Visit www.cdc.gov/std/ept to read updated information about laws and regulations regarding EPT in your state.²⁰

Gonorrhea

Gonorrhea is the second most-reported bacterial communicable disease.⁵ Infection with Neisseria gonorrhoeae causes urethral discharge in men, leading them to seek treatment; infected women, however, are often asymptomatic. Infected men and women might not recognize symptoms until they have transmitted the disease. Women have a slower natural clearance of gonococcal infection, which might explain their higher prevalence.²⁷ Delayed recognition of symptoms can result in complications, including PID.⁵

Diagnosis. Specimens for NAAT can be obtained from urine, endocervical, vaginal, rectal, pharyngeal, and male urethral specimens. Reported sexual behaviors and exposures of women and transgender or gender-diverse people should be taken into consideration to determine whether rectal or pharyngeal testing, or both, should be performed.²⁸ MSM should be screened annually at sites of contact, including the urethra, rectum, and pharynx.²⁸ All patients with urogenital or rectal gonorrhea should be asked about oral sexual exposure; if reported, pharyngeal testing should be performed.⁵

NAAT of urine is at least as sensitive as testing of an endocervical specimen; the same specimen can be used to test for chlamydia and gonorrhea. Patient-collected specimens are a reasonable alternative to clinician-collected swab specimens.²⁹

Continue to: Treatment

Treatment is complicated by the ability of gonorrhea to develop resistance. Intramuscular ceftriaxone 500 mg in a single dose cures 98% to 99% of infections in the United States; however, monitoring local resistance patterns in the community is an important component of treatment.²⁸ (See Table 2¹⁴ for an alternative regimen for cephalosporin-allergic patients and for treating gonococcal conjunctivitis and disseminated infection.)

Unless prohibited by law in your state, offer expedited partner therapy to patients with chlamydia if they cannot ensure that their sexual partners from the past 60 days will seek timely treatment.

In 2007, the CDC identified widespread quinolone-resistant gonococcal strains; therefore, fluoroquinolones no longer are recommended for treating gonorrhea.³⁰ Cefixime has demonstrated only limited success in treating pharyngeal gonorrhea and does not attain a bactericidal level as high as ceftriaxone does; cefixime therefore is recommended only if ceftriaxone is unavailable.²⁸ The national Gonococcal Isolate Surveillance Project is finding emerging evidence of the reduced susceptibility of N gonorrhoeae to azithromycin—making dual therapy for gonococcal infection no longer a recommendation.²⁸

Patients should abstain from sex until 7 days after all sex partners have been treated for gonorrhea. As with chlamydia, the CDC does not recommend a test of cure for uncomplicated urogenital or rectal gonorrhea unless the patient is pregnant, but does recommend testing for reinfection 3 months after treatment.¹⁴ For patients with pharyngeal gonorrhea, a test of cure is recommended 7 to 14 days after initial treatment, due to challenges in treatment and because this site of infection is a potential source of antibiotic resistance.²⁸

Trichomoniasis

T vaginalis, the most common nonviral STI worldwide,³¹ can manifest as a yellow-green vaginal discharge with or without vaginal discomfort, dysuria, epididymitis, and prostatitis; most cases, however, are asymptomatic. On examination, the cervix might be erythematous with punctate lesions (known as strawberry cervix).

Unlike most STIs, trichomoniasis is as common in women older than 24 years as it is in younger women. Infection is associated with a lower educational level, lower socioeconomic status, and having ≥ 2 sexual partners in the past year.³² Prevalence is approximately 10 times as high in Black women as it is in White women.

T vaginalis infection is associated with an increase in the risk for preterm birth, premature rupture of membranes, cervical cancer, and HIV infection. With a lack of high-quality clinical trials on the efficacy of screening, women with HIV are the only group for whom routine screening is recommended.⁶

Diagnosis. NAAT for trichomoniasis is now available in conjunction with gonorrhea and chlamydia testing of specimens on vaginal or urethral swabs and of urine specimens and liquid Pap smears.

Continue to: Treatment

Treatment. Because of greater efficacy, the treatment recommendation for women has changed from a single 2-g dose of oral metronidazole to 500 mg twice daily for 7 days. The 2-g single oral dose is still recommended for men⁷ (Table 2¹⁴ lists alternative regimens).

Mycoplasma genitalium

Infection with M genitalium is common and often asymptomatic. The disease causes approximately 20% of all cases of nongonococcal and nonchlamydial urethritis in men and about 40% of persistent or recurrent infections. M genitalium is present in approximately 20% of women with cervicitis and has been associated with PID, preterm delivery, spontaneous abortion, and infertility.

There are limited and conflicting data regarding outcomes in infected patients other than those with persistent or recurrent infection; furthermore, resistance to azithromycin is increasing rapidly, resulting in an increase in treatment failures. Screening therefore is not recommended, and testing is recommended only in men with nongonococcal urethritis.^33,34

Diagnosis. NAAT can be performed on urine or on a urethral, penile meatal, endocervical, or vaginal swab; men with recurrent urethritis or women with recurrent cervicitis should be tested. NAAT also can be considered in women with PID. Testing the specimen for the microorganism’s resistance to macrolide antibiotics is recommended (if such testing is available).

Treatment is initiated with doxycycline 100 mg twice daily for 7 days. If the organism is macrolide sensitive, follow with azithromycin 1 g orally on Day 1, then 500 mg/d for 3 more days. If the organism is macrolide resistant or testing is unavailable, follow doxycycline with oral moxifloxacin 400 mg/d for 7 days.³³

Genital herpes (mostly herpesvirus type 2)

Genital herpes, characterized by painful, recurrent outbreaks of genital and anal lesions,³⁵ is a lifelong infection that increases in prevalence with age.⁸ Because many infected people have disease that is undiagnosed or mild or have unrecognizable symptoms during viral shedding, most genital herpes infections are transmitted by people who are unaware that they are contagious.³⁶ Herpesvirus type 2 (HSV-2) causes most cases of genital herpes, although an increasing percentage of cases are attributed to HSV type 1 (HSV-1) through receptive oral sex from a person who has an oral HSV-1 lesion.

Intramuscular ceftriaxone 500 mg in a single dose cures 98% to 99% of gonococcal infections in the United States; monitoring local resistance patterns in the community is important.

Importantly, HSV-2–infected people are 2 to 3 times more likely to become infected with HIV than people who are not HSV-2 infected.³⁷ This is becauseCD4+ T cells concentrate at the site of HSV lesions and express a higher level of cell-surface receptors that HIV uses to enter cells. HIV replicates 3 to 5 times more quickly in HSV-infected tissue.³⁸

Continue to: HSV can become disseminated...

HSV can become disseminated, particularly in immunosuppressed people, and can manifest as encephalitis, hepatitis, and pneumonitis. Beyond its significant burden on health, HSV carries significant psychosocial consequences.⁹

Diagnosis. Clinical diagnosis can be challenging if classic lesions are absent at evaluation. If genital lesions are present, HSV can be identified by NAAT or culture of a specimen of those lesions. False-negative antibody results might be more frequent in early stages of infection; repeating antibody testing 12 weeks after presumed time of acquisition might therefore be indicated, based on clinical judgment. HSV-2 antibody positivity implies anogenital infection because almost all HSV-2 infections are sexually acquired.

HSV-1 antibody positivity alone is more difficult to interpret because this finding does not distinguish between oral and genital lesions, and most HSV-1 seropositivity is acquired during childhood.³⁶ HSV polymerase chain reaction (PCR) testing of blood should not be performed to diagnose genital herpes infection, except in settings in which there is concern about disseminated infection.

Treatment. Management should address the acute episode and the chronic nature of genital herpes. Antivirals will not eradicate latent virus; rather, the goals of treatment are to:

• attenuate current infection
• prevent recurrence
• improve quality of life
• suppress the virus to prevent transmission to sexual partners.

All patients experiencing an initial episode of genital herpes should be treated, regardless of symptoms, due to the potential for prolonged or severe symptoms during recurrent episodes.⁹ Three drugs—acyclovir, valacyclovir, and famciclovir—are approved by the US Food and Drug Administration (FDA) to treat genital herpes and appear equally effective (TABLE 2¹⁴).

Antiviral therapy for recurrent genital HSV infection can be administered either as suppressive therapy to reduce the frequency of recurrences or episodically to shorten the duration of lesions:

• Suppressive therapy reduces the frequency of recurrence by 70% to 80% among patients with frequent outbreaks. Long-term safety and efficacy are well established.
• Episodic therapy is most effective if started within 1 day after onset of lesions or during the prodrome.³⁶

There is no specific recommendation for when to choose suppressive over episodic therapy; most patients prefer suppressive therapy because it improves quality of life. Use shared clinical decision-making to determine the best option for an individual patient.

Continue to: Human papillomavirus

Condylomata acuminata (genital warts) are caused by human papillomavirus (HPV), most commonly types 6 and 11, which manifest as soft papules or plaques on the external genitalia, perineum, perianal skin, and groin. The warts are usually asymptomatic but can be painful or pruritic, depending on size and location.

Diagnosis is made by visual inspection and can be confirmed by biopsy if lesions are atypical. Lesions can resolve spontaneously, remain unchanged, or grow in size or number.

Treatment. The aim of treatment is relief of symptoms and removal of warts. Treatment does not eradicate HPV infection. Multiple treatments are available that can be applied by the patient as a cream, gel, or ointment or administered by the provider, including cryotherapy, surgical removal, and solutions. The decision on how to treat should be based on the number, size, and location of lesions; patient preference; cost; convenience; and the modality’s adverse effects (TABLE 2¹⁴).

HPV-associated cancers and precancers. This is a broad (and separate) topic. HPV types 16 and 18 cause most cases of cervical, penile, vulvar, vaginal, anal, and oropharyngeal cancer and precancer.³⁹ The USPSTF, the American Cancer Society, and the American College of Obstetricians and Gynecologists all have recommendations for cervical cancer screening in the United States.⁴⁰ Refer to guidelines of the ASCCP for recommendations on abnormal screening tests.⁴¹

Prevention of genital warts. The 9-­valent HPV vaccine available in the United States is safe and effective and helps protect against viral types 6, 11, 16, 18, 31, 33, 45, 52, and 58. Types 6 and 11 are the principal causes of genital warts. Types 16 and 18 cause 66% of cervical cancer. The vaccination series can be started at age 9 years and is recommended for everyone through age 26 years. Only 2 doses are needed if the first dose is given prior to age 15 years; given after that age, a 3-dose series is utilized. Refer to CDC vaccine guidelines⁴² for details on the exact timing of vaccination.

Trichomoniasis can manifest as a yellowgreen vaginal discharge with or without vaginal discomfort, dysuria, epididymitis, and prostatitis; most cases, however, are asymptomatic.

Vaccination for women ages 27 to 45 years is not universally recommended because most people have been exposed to HPV by that age. However, the vaccine can still be administered, depending on clinical circumstances and the risk for new infection.⁴²

Syphilis

Caused by the spirochete Treponema pallidum, syphilis manifests across a spectrum—from congenital to tertiary. The inability of medical science to develop a method for culturing the spirochete has confounded diagnosis and treatment.

Continue to: Since reaching a historic...

Since reaching a historic nadir of incidence in 2000 (5979 cases in the United States), there has been an increasingly rapid rise in that number: to 130,000 in 2020. More than 50% of cases are in MSM; however, the number of cases in heterosexual women is rapidly increasing.⁴³

Routine screening for syphilis should be performed in any person who is at risk: all pregnant women in the first trimester (and in the third trimester and at delivery if they are at risk or live in a community where prevalence is high) and annually in sexually active MSM or anyone with HIV infection.¹⁰

Diagnosis. Examination by dark-field microscopy, testing by PCR, and direct fluorescent antibody assay for T pallidum from lesion tissue or exudate provide definitive diagnosis for early and congenital syphilis, but are often unavailable.

Presumptive diagnosis requires 2 serologic tests:

• Nontreponemal tests (the VDRL and rapid plasma reagin tests) identify anticardiolipin antibodies released during syphilis infection, although results also can be elevated in autoimmune disease or after certain immunizations, including the COVID-19 vaccine.
• Treponemal tests (the fluorescent treponemal antibody absorbed assay, T pallidum particulate agglutination assay, enzyme immunoassay, and chemiluminescence immunoassay) are specific antibody tests.

Historically, reactive nontreponemal tests, which are less expensive and easier to perform, were followed by a treponemal test to confirm the presumptive diagnosis. This method continues to be reasonable when screening patients in a low-prevalence population.¹¹ The reverse sequence screening algorithm (ie, begin with a treponemal test) is now frequently used. With this method, a positive treponemal test must be confirmed with a nontreponemal test. If the treponemal test is positive and the nontreponemal test is negative, another treponemal test must be positive to confirm the diagnosis. This algorithm is useful in high-risk populations because it provides earlier detection of recently acquired syphilis and enhanced detection of late latent syphilis.^12,13,44 The CDC has not stated a diagnostic preference.

Once the diagnosis is made, a complete history (including a sexual history and a history of syphilis testing and treatment) and a physical exam are necessary to confirm stage of disease.⁴⁵

Special circumstances. Neurosyphilis, ocular syphilis, and otosyphilis refer to the site of infection and can occur at any stage of disease. The nervous system usually is infected within hours of initial infection, but symptoms might take weeks or years to ­develop—or might never manifest. Any time a patient develops neurologic, ophthalmologic, or audiologic symptoms, careful neurologic and ophthalmologic evaluation should be performed and the patient should be tested for HIV.

Continue to: Lumbar puncture is warranted...

Lumbar puncture is warranted for evaluation of cerebrospinal fluid if neurologic symptoms are present but is not necessary for isolated ocular syphilis or otosyphilis without neurologic findings. Treatment should not be delayed for test results if ocular syphilis is suspected because permanent blindness can develop. Any patient at high risk for an STI who presents with neurologic or ophthalmologic symptoms should be tested for syphilis and HIV.⁴⁵

Pregnant women who have a diagnosis of syphilis should be treated with penicillin immediately because treatment ≥ 30 days prior to delivery is likely to prevent most ­cases of congenital syphilis. However, a course of penicillin might not prevent stillbirth or congenital syphilis in a gravely infected fetus, evidenced by fetal syphilis on a sonogram at the time of treatment. Additional doses of penicillin in pregnant women with early syphilis might be indicated if there is evidence of ­fetal syphilis on ultrasonography. All women who deliver a stillborn infant (≥ 20 weeks’ ­gestation) should be tested for syphilis at ­delivery.⁴⁶

All patients in whom primary or secondary syphilis has been diagnosed should be tested for HIV at the time of diagnosis and treatment; if the result is negative, they should be offered preexposure prophylaxis (PrEP; discussed shortly). If the incidence of HIV in your community is high, repeat testing for HIV in 3 months. Clinical and serologic evaluation should be performed 6 and 12 months after treatment.⁴⁷

Treatment. Penicillin remains the standard treatment for syphilis. Primary, secondary, and early tertiary stages (including in pregnancy) are treated with benzathine penicillin G 2.4 million units intramuscular (IM) in a single dose. For pregnant patients, repeating that dose in 1 week generally is recommended. Patients in the late latent (> 1 year) or tertiary stage receive the same dose of penicillin, which is then repeated weekly, for a total of 3 doses. Doxycycline and ceftriaxone are alternatives, except in ­pregnancy.

Antivirals will not eradicate latent herpesvirus; rather, the goals of treatment are to attenuate current infection, prevent recurrence, and improve quality of life.

Warn patients of the Jarisch-Herxheimer reaction: fever, headache, and myalgias associated with initiation of treatment in the presence of the high bacterial load seen in early syphilis. Treatment is symptomatic, but the Jarisch-Herxheimer reaction can cause fetal distress in pregnancy.

Otosyphilis, ocular syphilis, and neurosyphilis require intravenous (IV) aqueous crystalline penicillin G 3 to 4 million U every 4 hours for 10 to 14 days.⁴⁵ Alternatively, procaine penicillin G 2.4 million U/d IM can be given daily with oral probenecid 500 mg qid, both for 10 to 14 days (TABLE 2¹⁴).

Screening andprevention of STIs

Screening recommendations

Follow USPSTF screening guidelines for STIs.^10,48-54 Screen annually for:

• gonorrhea and chlamydia in women ages 15 to 24 years and in women older than 25 years if they are at increased risk
• gonorrhea, chlamydia, syphilis, and HIV in MSM, and hepatitis C if they are HIV positive
• trichomoniasis in women who are HIV positive.

Continue to: Consider the community in which...

Vaccination against human papillomavirus is not universally recommended for women ages 27 to 45 years because most people have been exposed to HPV by that age.

Consider the community in which you practice when determining risk; you might want to consult local public health authorities for information about local epidemiology and guidance on determining which of your patients are at increased risk.

Preexposure prophylaxis

According to the CDC, all sexually active adults and adolescents should be informed about the availability of PrEP to prevent HIV infection. PrEP should be (1) available to anyone who requests it and (2) recommended for anyone who is sexually active and who practices sexual behaviors that place them at substantial risk for exposure to or acquisition of HIV, or both.

The recommended treatment protocol for men and women who have either an HIV-positive partner or inconsistent condom use or who have had a bacterial STI in the previous 6 months is oral emtricitabine 200 mg plus tenofovir disoproxil fumarate 300 mg/d (sold as Truvada-F/TDF). Men and transgender women (ie, assigned male at birth) with at-risk behaviors also can use emtricitabine plus tenofovir alafenamide 25 mg/d (sold as Descovy-F/TAF).

In addition, cabotegravir plus rilpirivine (sold as Cabenuva), IM every 2 months, was approved by the FDA for PrEP in 2021.

Pregnant women who have syphilis should be treated with penicillin immediately: Treatment ≥ 30 days prior to delivery is likely to prevent most cases of congenital syphilis.

Creatinine clearance should be assessed at baseline and yearly (every 6 months for those older than 50 years) in patients taking PrEP. All patients must be tested for HIV at initiation of treatment and every 3 months thereafter (every 4 months for cabotegravir plus rilpirivine). Patients should be screened for bacterial STIs every 6 months (every 3 months for MSM and transgender women); screening for chlamydia should be done yearly. For patients being treated with emtricitabine plus tenofovir alafenamide, weight and a lipid profile (cholesterol and triglycerides) should be assessed annually.⁵⁵

Postexposure prophylaxis

The sharp rise in the incidence of STIs in the past few years has brought renewed interest in postexposure prophylaxis (PEP) for STIs. Although PEP should be standard in cases of sexual assault, this protocol also can be considered in other instances of high-risk exposure.

CDC recommendations for PEP in cases of assault are⁵⁶:

• ceftriaxone 500 mg IM in a single dose (1 g if weight is ≥ 150 kg) plus
• doxycycline 100 mg bid for 7 days plus
• metronidazole 2 g bid for 7 days (for vaginal exposure)
• pregnancy evaluation and emergency contraception
• hepatitis B risk evaluation and vaccination, with or without hepatitis B immune globulin
• HIV risk evaluation, based on CDC guidelines, and possible HIV prophylaxis (PrEP)
• HPV vaccination for patients ages 9 to 26 years if they are not already fully vaccinated.

CORRESPONDENCE
Belinda Vail, MD, 3901 Rainbow Boulevard, Mail Stop 4010, Kansas City, KS 66160; [email protected]

Except for a drop in the number of sexually transmitted infections (STIs) early in the COVID-19 pandemic (March and April 2020), the incidence of STIs has been rising throughout this century.¹ In 2018, 1 in 5 people in the United States had an STI; 26 million new cases were reported that year, resulting in direct costs of $16 billion—85% of which was for the care of HIV infection.² Also that year, infection with Chlamydia trachomatis (chlamydia), Trichomonas vaginalis (trichomoniasis), herpesvirus type 2 (genital herpes), and/or human papillomavirus (condylomata acuminata) constituted 97.6% of all prevalent and 93.1% of all incident STIs.³ Almost half (45.5%) of new cases of STIs occur in people between the ages of 15 and 24 years.³

Three factors—changing social patterns, including the increase of social networking; the ability of antiviral therapy to decrease the spread of HIV, leading to a reduction in condom use; and increasing antibiotic resistance—have converged to force changes in screening and treatment recommendations. In this article, we summarize updated guidance for primary care clinicians from several sources—including the Centers for Disease Control and Prevention (CDC), the US Preventive Services Task Force (USPSTF), and the American Society for Colposcopy and Cervical Pathology (ASCCP)—on diagnosing STIs (TABLE 1^4-13) and providing guideline-based treatment ­(Table 2¹⁴). Because of the breadth and complexity of HIV disease, it is not addressed here.

Chlamydia

Infection with Chlamydia trachomatis—the most commonly reported bacterial STI in the United States—primarily causes cervicitis in women and proctitis in men, and can cause urethritis and pharyngitis in men and women. Prevalence is highest in sexually active people younger than 24 years.¹⁵

Because most infected people are asymptomatic and show no signs of illness on physical exam, screening is recommended for all sexually active women younger than 25 years and all men who have sex with men (MSM).⁴ No studies have established proper screening intervals; a reasonable approach, therefore, is to repeat screening for patients who have a sexual history that confers a new or persistent risk for infection since their last negative result.

Depending on the location of the infection, symptoms of chlamydia can include vaginal or penile irritation or discharge, dysuria, pelvic or rectal pain, and sore throat. Breakthrough bleeding in a patient who is taking an oral contraceptive should raise suspicion for chlamydia.

Untreated chlamydia can lead to pelvic inflammatory disease (PID), tubo-ovarian abscess, tubal factor infertility, ectopic pregnancy, and chronic pelvic pain. Infection can be transmitted vertically (mother to baby) antenatally, which can cause ophthalmia neonatorum and pneumonia in these newborns.

Diagnosis. The diagnosis of chlamydia is made using nucleic acid amplification testing (NAAT). Specimens can be collected by the clinician or the patient (self collected) using a vaginal, rectal, or oropharyngeal swab, or a combination of these, and can be obtained from urine or liquid-based cytology material.¹⁶

Continue to: Treatment

Treatment. Recommendations for treating chlamydia were updated by the CDC in its 2021 treatment guidelines (Table 2¹⁴). Doxycycline 100 mg bid for 7 days is the preferred regimen; alternative regiments are (1) azithromycin 1 g in a single dose and (2) levofloxacin 500 mg daily for 7 days.⁴ A meta-analysis¹⁷ and a Cochrane review¹⁸ showed that the rate of treatment failure was higher among men when they were treated with azithromycin instead of doxycycline; furthermore, a randomized controlled trial demonstrated that doxycycline is more effective than azithromycin (cure rate, 100%, compared to 74%) at treating rectal chlamydia in MSM.¹⁹

Azithromycin is efficacious for urogenital infection in women; however, there is concern that the 33% to 83% of women who have concomitant rectal infection (despite reporting no receptive anorectal sexual activity) would be insufficiently treated. Outside pregnancy, the CDC does not recommend a test of cure but does recommend follow-up testing for reinfection in 3 months. Patients should abstain from sexual activity until 7 days after all sexual partners have been treated.

Expedited partner therapy (EPT) is the practice of treating sexual partners of patients with known chlamydia (and patients with gonococcal infection). Unless prohibited by law in your state, offer EPT to patients with chlamydia if they cannot ensure that their sexual partners from the past 60 days will seek timely treatment.^a

Breakthrough bleeding in a patient who is taking an oral contraceptive should raise suspicion for chlamydia.

Evidence to support EPT comes from 3 US clinical trials, whose subjects comprised heterosexual men and women with chlamydia or gonorrhea.^21-23 The role of EPT for MSM is unclear; data are limited. Shared ­decision-making is recommended to determine whether EPT should be provided, to ensure that co-infection with other bacterial STIs (eg, syphilis) or HIV is not missed.^24-26

^a Visit www.cdc.gov/std/ept to read updated information about laws and regulations regarding EPT in your state.²⁰

Gonorrhea

Gonorrhea is the second most-reported bacterial communicable disease.⁵ Infection with Neisseria gonorrhoeae causes urethral discharge in men, leading them to seek treatment; infected women, however, are often asymptomatic. Infected men and women might not recognize symptoms until they have transmitted the disease. Women have a slower natural clearance of gonococcal infection, which might explain their higher prevalence.²⁷ Delayed recognition of symptoms can result in complications, including PID.⁵

Diagnosis. Specimens for NAAT can be obtained from urine, endocervical, vaginal, rectal, pharyngeal, and male urethral specimens. Reported sexual behaviors and exposures of women and transgender or gender-diverse people should be taken into consideration to determine whether rectal or pharyngeal testing, or both, should be performed.²⁸ MSM should be screened annually at sites of contact, including the urethra, rectum, and pharynx.²⁸ All patients with urogenital or rectal gonorrhea should be asked about oral sexual exposure; if reported, pharyngeal testing should be performed.⁵

NAAT of urine is at least as sensitive as testing of an endocervical specimen; the same specimen can be used to test for chlamydia and gonorrhea. Patient-collected specimens are a reasonable alternative to clinician-collected swab specimens.²⁹

Continue to: Treatment

Treatment is complicated by the ability of gonorrhea to develop resistance. Intramuscular ceftriaxone 500 mg in a single dose cures 98% to 99% of infections in the United States; however, monitoring local resistance patterns in the community is an important component of treatment.²⁸ (See Table 2¹⁴ for an alternative regimen for cephalosporin-allergic patients and for treating gonococcal conjunctivitis and disseminated infection.)

Unless prohibited by law in your state, offer expedited partner therapy to patients with chlamydia if they cannot ensure that their sexual partners from the past 60 days will seek timely treatment.

In 2007, the CDC identified widespread quinolone-resistant gonococcal strains; therefore, fluoroquinolones no longer are recommended for treating gonorrhea.³⁰ Cefixime has demonstrated only limited success in treating pharyngeal gonorrhea and does not attain a bactericidal level as high as ceftriaxone does; cefixime therefore is recommended only if ceftriaxone is unavailable.²⁸ The national Gonococcal Isolate Surveillance Project is finding emerging evidence of the reduced susceptibility of N gonorrhoeae to azithromycin—making dual therapy for gonococcal infection no longer a recommendation.²⁸

Patients should abstain from sex until 7 days after all sex partners have been treated for gonorrhea. As with chlamydia, the CDC does not recommend a test of cure for uncomplicated urogenital or rectal gonorrhea unless the patient is pregnant, but does recommend testing for reinfection 3 months after treatment.¹⁴ For patients with pharyngeal gonorrhea, a test of cure is recommended 7 to 14 days after initial treatment, due to challenges in treatment and because this site of infection is a potential source of antibiotic resistance.²⁸

Trichomoniasis

T vaginalis, the most common nonviral STI worldwide,³¹ can manifest as a yellow-green vaginal discharge with or without vaginal discomfort, dysuria, epididymitis, and prostatitis; most cases, however, are asymptomatic. On examination, the cervix might be erythematous with punctate lesions (known as strawberry cervix).

Unlike most STIs, trichomoniasis is as common in women older than 24 years as it is in younger women. Infection is associated with a lower educational level, lower socioeconomic status, and having ≥ 2 sexual partners in the past year.³² Prevalence is approximately 10 times as high in Black women as it is in White women.

T vaginalis infection is associated with an increase in the risk for preterm birth, premature rupture of membranes, cervical cancer, and HIV infection. With a lack of high-quality clinical trials on the efficacy of screening, women with HIV are the only group for whom routine screening is recommended.⁶

Diagnosis. NAAT for trichomoniasis is now available in conjunction with gonorrhea and chlamydia testing of specimens on vaginal or urethral swabs and of urine specimens and liquid Pap smears.

Continue to: Treatment

Treatment. Because of greater efficacy, the treatment recommendation for women has changed from a single 2-g dose of oral metronidazole to 500 mg twice daily for 7 days. The 2-g single oral dose is still recommended for men⁷ (Table 2¹⁴ lists alternative regimens).

Mycoplasma genitalium

Infection with M genitalium is common and often asymptomatic. The disease causes approximately 20% of all cases of nongonococcal and nonchlamydial urethritis in men and about 40% of persistent or recurrent infections. M genitalium is present in approximately 20% of women with cervicitis and has been associated with PID, preterm delivery, spontaneous abortion, and infertility.

There are limited and conflicting data regarding outcomes in infected patients other than those with persistent or recurrent infection; furthermore, resistance to azithromycin is increasing rapidly, resulting in an increase in treatment failures. Screening therefore is not recommended, and testing is recommended only in men with nongonococcal urethritis.^33,34

Diagnosis. NAAT can be performed on urine or on a urethral, penile meatal, endocervical, or vaginal swab; men with recurrent urethritis or women with recurrent cervicitis should be tested. NAAT also can be considered in women with PID. Testing the specimen for the microorganism’s resistance to macrolide antibiotics is recommended (if such testing is available).

Treatment is initiated with doxycycline 100 mg twice daily for 7 days. If the organism is macrolide sensitive, follow with azithromycin 1 g orally on Day 1, then 500 mg/d for 3 more days. If the organism is macrolide resistant or testing is unavailable, follow doxycycline with oral moxifloxacin 400 mg/d for 7 days.³³

Genital herpes (mostly herpesvirus type 2)

Genital herpes, characterized by painful, recurrent outbreaks of genital and anal lesions,³⁵ is a lifelong infection that increases in prevalence with age.⁸ Because many infected people have disease that is undiagnosed or mild or have unrecognizable symptoms during viral shedding, most genital herpes infections are transmitted by people who are unaware that they are contagious.³⁶ Herpesvirus type 2 (HSV-2) causes most cases of genital herpes, although an increasing percentage of cases are attributed to HSV type 1 (HSV-1) through receptive oral sex from a person who has an oral HSV-1 lesion.

Intramuscular ceftriaxone 500 mg in a single dose cures 98% to 99% of gonococcal infections in the United States; monitoring local resistance patterns in the community is important.

Importantly, HSV-2–infected people are 2 to 3 times more likely to become infected with HIV than people who are not HSV-2 infected.³⁷ This is becauseCD4+ T cells concentrate at the site of HSV lesions and express a higher level of cell-surface receptors that HIV uses to enter cells. HIV replicates 3 to 5 times more quickly in HSV-infected tissue.³⁸

Continue to: HSV can become disseminated...

HSV can become disseminated, particularly in immunosuppressed people, and can manifest as encephalitis, hepatitis, and pneumonitis. Beyond its significant burden on health, HSV carries significant psychosocial consequences.⁹

Diagnosis. Clinical diagnosis can be challenging if classic lesions are absent at evaluation. If genital lesions are present, HSV can be identified by NAAT or culture of a specimen of those lesions. False-negative antibody results might be more frequent in early stages of infection; repeating antibody testing 12 weeks after presumed time of acquisition might therefore be indicated, based on clinical judgment. HSV-2 antibody positivity implies anogenital infection because almost all HSV-2 infections are sexually acquired.

HSV-1 antibody positivity alone is more difficult to interpret because this finding does not distinguish between oral and genital lesions, and most HSV-1 seropositivity is acquired during childhood.³⁶ HSV polymerase chain reaction (PCR) testing of blood should not be performed to diagnose genital herpes infection, except in settings in which there is concern about disseminated infection.

Treatment. Management should address the acute episode and the chronic nature of genital herpes. Antivirals will not eradicate latent virus; rather, the goals of treatment are to:

• attenuate current infection
• prevent recurrence
• improve quality of life
• suppress the virus to prevent transmission to sexual partners.

All patients experiencing an initial episode of genital herpes should be treated, regardless of symptoms, due to the potential for prolonged or severe symptoms during recurrent episodes.⁹ Three drugs—acyclovir, valacyclovir, and famciclovir—are approved by the US Food and Drug Administration (FDA) to treat genital herpes and appear equally effective (TABLE 2¹⁴).

Antiviral therapy for recurrent genital HSV infection can be administered either as suppressive therapy to reduce the frequency of recurrences or episodically to shorten the duration of lesions:

• Suppressive therapy reduces the frequency of recurrence by 70% to 80% among patients with frequent outbreaks. Long-term safety and efficacy are well established.
• Episodic therapy is most effective if started within 1 day after onset of lesions or during the prodrome.³⁶

There is no specific recommendation for when to choose suppressive over episodic therapy; most patients prefer suppressive therapy because it improves quality of life. Use shared clinical decision-making to determine the best option for an individual patient.

Continue to: Human papillomavirus

Condylomata acuminata (genital warts) are caused by human papillomavirus (HPV), most commonly types 6 and 11, which manifest as soft papules or plaques on the external genitalia, perineum, perianal skin, and groin. The warts are usually asymptomatic but can be painful or pruritic, depending on size and location.

Diagnosis is made by visual inspection and can be confirmed by biopsy if lesions are atypical. Lesions can resolve spontaneously, remain unchanged, or grow in size or number.

Treatment. The aim of treatment is relief of symptoms and removal of warts. Treatment does not eradicate HPV infection. Multiple treatments are available that can be applied by the patient as a cream, gel, or ointment or administered by the provider, including cryotherapy, surgical removal, and solutions. The decision on how to treat should be based on the number, size, and location of lesions; patient preference; cost; convenience; and the modality’s adverse effects (TABLE 2¹⁴).

HPV-associated cancers and precancers. This is a broad (and separate) topic. HPV types 16 and 18 cause most cases of cervical, penile, vulvar, vaginal, anal, and oropharyngeal cancer and precancer.³⁹ The USPSTF, the American Cancer Society, and the American College of Obstetricians and Gynecologists all have recommendations for cervical cancer screening in the United States.⁴⁰ Refer to guidelines of the ASCCP for recommendations on abnormal screening tests.⁴¹

Prevention of genital warts. The 9-­valent HPV vaccine available in the United States is safe and effective and helps protect against viral types 6, 11, 16, 18, 31, 33, 45, 52, and 58. Types 6 and 11 are the principal causes of genital warts. Types 16 and 18 cause 66% of cervical cancer. The vaccination series can be started at age 9 years and is recommended for everyone through age 26 years. Only 2 doses are needed if the first dose is given prior to age 15 years; given after that age, a 3-dose series is utilized. Refer to CDC vaccine guidelines⁴² for details on the exact timing of vaccination.

Trichomoniasis can manifest as a yellowgreen vaginal discharge with or without vaginal discomfort, dysuria, epididymitis, and prostatitis; most cases, however, are asymptomatic.

Vaccination for women ages 27 to 45 years is not universally recommended because most people have been exposed to HPV by that age. However, the vaccine can still be administered, depending on clinical circumstances and the risk for new infection.⁴²

Syphilis

Caused by the spirochete Treponema pallidum, syphilis manifests across a spectrum—from congenital to tertiary. The inability of medical science to develop a method for culturing the spirochete has confounded diagnosis and treatment.

Continue to: Since reaching a historic...

Since reaching a historic nadir of incidence in 2000 (5979 cases in the United States), there has been an increasingly rapid rise in that number: to 130,000 in 2020. More than 50% of cases are in MSM; however, the number of cases in heterosexual women is rapidly increasing.⁴³

Routine screening for syphilis should be performed in any person who is at risk: all pregnant women in the first trimester (and in the third trimester and at delivery if they are at risk or live in a community where prevalence is high) and annually in sexually active MSM or anyone with HIV infection.¹⁰

Diagnosis. Examination by dark-field microscopy, testing by PCR, and direct fluorescent antibody assay for T pallidum from lesion tissue or exudate provide definitive diagnosis for early and congenital syphilis, but are often unavailable.

Presumptive diagnosis requires 2 serologic tests:

• Nontreponemal tests (the VDRL and rapid plasma reagin tests) identify anticardiolipin antibodies released during syphilis infection, although results also can be elevated in autoimmune disease or after certain immunizations, including the COVID-19 vaccine.
• Treponemal tests (the fluorescent treponemal antibody absorbed assay, T pallidum particulate agglutination assay, enzyme immunoassay, and chemiluminescence immunoassay) are specific antibody tests.

Historically, reactive nontreponemal tests, which are less expensive and easier to perform, were followed by a treponemal test to confirm the presumptive diagnosis. This method continues to be reasonable when screening patients in a low-prevalence population.¹¹ The reverse sequence screening algorithm (ie, begin with a treponemal test) is now frequently used. With this method, a positive treponemal test must be confirmed with a nontreponemal test. If the treponemal test is positive and the nontreponemal test is negative, another treponemal test must be positive to confirm the diagnosis. This algorithm is useful in high-risk populations because it provides earlier detection of recently acquired syphilis and enhanced detection of late latent syphilis.^12,13,44 The CDC has not stated a diagnostic preference.

Once the diagnosis is made, a complete history (including a sexual history and a history of syphilis testing and treatment) and a physical exam are necessary to confirm stage of disease.⁴⁵

Special circumstances. Neurosyphilis, ocular syphilis, and otosyphilis refer to the site of infection and can occur at any stage of disease. The nervous system usually is infected within hours of initial infection, but symptoms might take weeks or years to ­develop—or might never manifest. Any time a patient develops neurologic, ophthalmologic, or audiologic symptoms, careful neurologic and ophthalmologic evaluation should be performed and the patient should be tested for HIV.

Continue to: Lumbar puncture is warranted...

Lumbar puncture is warranted for evaluation of cerebrospinal fluid if neurologic symptoms are present but is not necessary for isolated ocular syphilis or otosyphilis without neurologic findings. Treatment should not be delayed for test results if ocular syphilis is suspected because permanent blindness can develop. Any patient at high risk for an STI who presents with neurologic or ophthalmologic symptoms should be tested for syphilis and HIV.⁴⁵

Pregnant women who have a diagnosis of syphilis should be treated with penicillin immediately because treatment ≥ 30 days prior to delivery is likely to prevent most ­cases of congenital syphilis. However, a course of penicillin might not prevent stillbirth or congenital syphilis in a gravely infected fetus, evidenced by fetal syphilis on a sonogram at the time of treatment. Additional doses of penicillin in pregnant women with early syphilis might be indicated if there is evidence of ­fetal syphilis on ultrasonography. All women who deliver a stillborn infant (≥ 20 weeks’ ­gestation) should be tested for syphilis at ­delivery.⁴⁶

All patients in whom primary or secondary syphilis has been diagnosed should be tested for HIV at the time of diagnosis and treatment; if the result is negative, they should be offered preexposure prophylaxis (PrEP; discussed shortly). If the incidence of HIV in your community is high, repeat testing for HIV in 3 months. Clinical and serologic evaluation should be performed 6 and 12 months after treatment.⁴⁷

Treatment. Penicillin remains the standard treatment for syphilis. Primary, secondary, and early tertiary stages (including in pregnancy) are treated with benzathine penicillin G 2.4 million units intramuscular (IM) in a single dose. For pregnant patients, repeating that dose in 1 week generally is recommended. Patients in the late latent (> 1 year) or tertiary stage receive the same dose of penicillin, which is then repeated weekly, for a total of 3 doses. Doxycycline and ceftriaxone are alternatives, except in ­pregnancy.

Antivirals will not eradicate latent herpesvirus; rather, the goals of treatment are to attenuate current infection, prevent recurrence, and improve quality of life.

Warn patients of the Jarisch-Herxheimer reaction: fever, headache, and myalgias associated with initiation of treatment in the presence of the high bacterial load seen in early syphilis. Treatment is symptomatic, but the Jarisch-Herxheimer reaction can cause fetal distress in pregnancy.

Otosyphilis, ocular syphilis, and neurosyphilis require intravenous (IV) aqueous crystalline penicillin G 3 to 4 million U every 4 hours for 10 to 14 days.⁴⁵ Alternatively, procaine penicillin G 2.4 million U/d IM can be given daily with oral probenecid 500 mg qid, both for 10 to 14 days (TABLE 2¹⁴).

Screening andprevention of STIs

Screening recommendations

Follow USPSTF screening guidelines for STIs.^10,48-54 Screen annually for:

• gonorrhea and chlamydia in women ages 15 to 24 years and in women older than 25 years if they are at increased risk
• gonorrhea, chlamydia, syphilis, and HIV in MSM, and hepatitis C if they are HIV positive
• trichomoniasis in women who are HIV positive.

Continue to: Consider the community in which...

Vaccination against human papillomavirus is not universally recommended for women ages 27 to 45 years because most people have been exposed to HPV by that age.

Consider the community in which you practice when determining risk; you might want to consult local public health authorities for information about local epidemiology and guidance on determining which of your patients are at increased risk.

Preexposure prophylaxis

According to the CDC, all sexually active adults and adolescents should be informed about the availability of PrEP to prevent HIV infection. PrEP should be (1) available to anyone who requests it and (2) recommended for anyone who is sexually active and who practices sexual behaviors that place them at substantial risk for exposure to or acquisition of HIV, or both.

The recommended treatment protocol for men and women who have either an HIV-positive partner or inconsistent condom use or who have had a bacterial STI in the previous 6 months is oral emtricitabine 200 mg plus tenofovir disoproxil fumarate 300 mg/d (sold as Truvada-F/TDF). Men and transgender women (ie, assigned male at birth) with at-risk behaviors also can use emtricitabine plus tenofovir alafenamide 25 mg/d (sold as Descovy-F/TAF).

In addition, cabotegravir plus rilpirivine (sold as Cabenuva), IM every 2 months, was approved by the FDA for PrEP in 2021.

Pregnant women who have syphilis should be treated with penicillin immediately: Treatment ≥ 30 days prior to delivery is likely to prevent most cases of congenital syphilis.

Creatinine clearance should be assessed at baseline and yearly (every 6 months for those older than 50 years) in patients taking PrEP. All patients must be tested for HIV at initiation of treatment and every 3 months thereafter (every 4 months for cabotegravir plus rilpirivine). Patients should be screened for bacterial STIs every 6 months (every 3 months for MSM and transgender women); screening for chlamydia should be done yearly. For patients being treated with emtricitabine plus tenofovir alafenamide, weight and a lipid profile (cholesterol and triglycerides) should be assessed annually.⁵⁵

Postexposure prophylaxis

The sharp rise in the incidence of STIs in the past few years has brought renewed interest in postexposure prophylaxis (PEP) for STIs. Although PEP should be standard in cases of sexual assault, this protocol also can be considered in other instances of high-risk exposure.

CDC recommendations for PEP in cases of assault are⁵⁶:

• ceftriaxone 500 mg IM in a single dose (1 g if weight is ≥ 150 kg) plus
• doxycycline 100 mg bid for 7 days plus
• metronidazole 2 g bid for 7 days (for vaginal exposure)
• pregnancy evaluation and emergency contraception
• hepatitis B risk evaluation and vaccination, with or without hepatitis B immune globulin
• HIV risk evaluation, based on CDC guidelines, and possible HIV prophylaxis (PrEP)
• HPV vaccination for patients ages 9 to 26 years if they are not already fully vaccinated.

CORRESPONDENCE
Belinda Vail, MD, 3901 Rainbow Boulevard, Mail Stop 4010, Kansas City, KS 66160; [email protected]

Evidence summary

Continuous glucose monitoring: Nonsignificant reductions in event rates

A 2021 multicenter RCT (N = 175) evaluated CGM effectiveness in patients with basal ­insulin–treated T2D.¹ Patients (mean age, 57 years; mean A1C, 9.1%) wore a blinded CGM device for baseline glucose measurement (minimum of 168 hours) before being randomly assigned to either CGM (n = 116) or traditional blood glucose monitoring (BGM; n = 59). At 8-month follow-up, patients in the BGM group again had blinded sensors placed. A significant reduction in hypoglycemia duration was observed for the CGM group vs the BGM group at 8 months for glucose values < 70 mg/mL (adjusted mean difference [aMD] = –0.24%; 95% CI, –0.42 to –0.05) and < 54 mg/dL (aMD = –0.10%; 95% CI, –0.15 to –0.04). A nonsignificant decrease in severe hypoglycemic events requiring resuscitative assistance occurred for BGM (2%) vs CGM (1%) patients. Study limitations included virtual visits due to COVID-19 and a short follow-­up period.

A 2022 multicenter prospective study (N = 174) examined CGM effects on hypoglycemia frequency and severity in adults with T2D.² Patients with insulin-requiring T2D (mean age, 61 years; mean A1C, 8.0%) participated in a 12-month study with 6 months of self-monitored blood glucose (SMBG) followed by 6 months of CGM use. The primary outcome was the rate of severe hypoglycemic events. A nonsignificant decrease was observed in the CGM group compared to the SMBG group for hypoglycemic event rate, per participant per 6-month period (relative risk [RR] = 0.43; 95% CI, 0.07-2.64). Four moderate hypoglycemic adverse events occurred in the SMBG phase vs 2 in the CGM phase. Financial support by the study sponsor decreases the study’s validity.

A 2021 prospective study (N = 90) evaluated the use of CGM to improve glycemic control.³ Patients younger than 66 years with insulin-treated T2D and an A1C > 7.5% participated in a 7-day blinded CGM cycle every 4 months for 1 year. A nonsignificant decrease in hypoglycemia duration was observed for glucose values < 70 mg/dL and < 54 mg/dL at 12 months. No change in hypoglycemic event rate was seen with the use of CGM. Funding by the device manufacturer was a limitation of this study.

Flash glucose monitoring: Mixed results on hypoglycemia events

A 2019 open-label RCT (N = 82) assessed the effectiveness of FGM on diabetes control.⁴ Patients with insulin-treated T2D were randomly assigned to the intervention or standard­-care groups. The intervention group (n = 46; mean age, 66 years; mean A1C, 8.3%) used the FGM system for 10 weeks, while the standard-care group (n = 36; mean age, 70 years; mean A1C, 8.9%) maintained use of their glucometers. Both groups received similar types and duration of counseling. Treatment satisfaction was the primary outcome; total hypoglycemic events was a secondary outcome. No significant difference in the number of hypoglycemic episodes was observed between the intervention and control groups at 55 to 70 mg/dL (RR = 0.79; 95% CI, 0.44-1.4) or < 54 mg/dL (RR = 1.27; 95% CI, 0.38-4.2). No adverse events of severe hypoglycemia occurred during the study. Funding by the device manufacturer was a limitation of this study.

Continuous glucose monitoring and flash glucose monitoring do not decrease symptomatic hypoglycemia episodes but do lower time in hypoglycemia.

A 2017 open-label, multicenter RCT (N = 224) assessed FGM efficacy.⁵ Adults (mean age, 59 years; mean A1C, 8.8%) with T2D on intensive insulin therapy were randomized to FGM (n = 149) or SMBG (n = 75) after a 14-day masked baseline period. The 6-month treatment phase was unblinded. The duration of hypoglycemic events (glucose values < 70 mg/dL and < 55 mg/dL) was obtained from the sensors. Compared to the SMBG group, the FGM group spent 43% less time at < 70 mg/dL (aMD = –0.47 ± 0.13 h/d; P = .0006) and 53% less time at < 55 mg/dL (aMD = –0.22 ± 0.068 h/d; P = .0014). Hypoglycemic event rates significantly decreased by 28% (aMD = –0.16 ± 0.065; P = 0.016) and 44% (aMD = –0.12 ± 0.037; P = .0017) for glucose levels < 70 mg/dL and < 55 mg/dL, respectively. A nonsignificant difference occurred in severe hypoglycemic events requiring third-party assistance for the FGM (2%) vs control (1%) groups. Involvement of the device manufacturer and unblinded group allocations are study limitations.

A 2021 single-arm, multicenter prospective study looked at the impact of FGM on glycemic control in adults with insulin-treated T2D (N = 90; mean age, 64 years; mean A1C, 7.5%).⁶ After a 14-day baseline period consisting of masked sensor readings paired with self-monitored fingerstick tests, participants were followed for 11 weeks using the sensor to monitor glucose levels. The primary outcome was amount of time spent in hypoglycemia (< 70 mg/dL), with secondary outcomes including time and events in hypoglycemia (< 70, < 55, or < 45 mg/dL). No significant decrease in hypoglycemia duration or hypoglycemic event rates at < 70, < 55, or < 45 mg/­dL was observed for FGM compared to baseline. Adverse events were observed in 64% of participants; 94% of the events were hypoglycemia related. Serious adverse events were reported for 5.3% of participants. The single-arm study format, lack of generalizability due to the single-race study population, and sponsor support were study limitations.

Editor’s takeaway

This reasonably good evidence shows a decrease in measured or monitored hypoglycemia, a disease-oriented outcome, but it did not reach statistical significance for symptomatic hypoglycemia (1% vs 2%), a patient-oriented outcome. Nevertheless, in patients reporting symptomatic hypoglycemia, a continuous or flash glucose monitor may allow for more aggressive glucose control.

Evidence summary

Continuous glucose monitoring: Nonsignificant reductions in event rates

A 2021 multicenter RCT (N = 175) evaluated CGM effectiveness in patients with basal ­insulin–treated T2D.¹ Patients (mean age, 57 years; mean A1C, 9.1%) wore a blinded CGM device for baseline glucose measurement (minimum of 168 hours) before being randomly assigned to either CGM (n = 116) or traditional blood glucose monitoring (BGM; n = 59). At 8-month follow-up, patients in the BGM group again had blinded sensors placed. A significant reduction in hypoglycemia duration was observed for the CGM group vs the BGM group at 8 months for glucose values < 70 mg/mL (adjusted mean difference [aMD] = –0.24%; 95% CI, –0.42 to –0.05) and < 54 mg/dL (aMD = –0.10%; 95% CI, –0.15 to –0.04). A nonsignificant decrease in severe hypoglycemic events requiring resuscitative assistance occurred for BGM (2%) vs CGM (1%) patients. Study limitations included virtual visits due to COVID-19 and a short follow-­up period.

A 2022 multicenter prospective study (N = 174) examined CGM effects on hypoglycemia frequency and severity in adults with T2D.² Patients with insulin-requiring T2D (mean age, 61 years; mean A1C, 8.0%) participated in a 12-month study with 6 months of self-monitored blood glucose (SMBG) followed by 6 months of CGM use. The primary outcome was the rate of severe hypoglycemic events. A nonsignificant decrease was observed in the CGM group compared to the SMBG group for hypoglycemic event rate, per participant per 6-month period (relative risk [RR] = 0.43; 95% CI, 0.07-2.64). Four moderate hypoglycemic adverse events occurred in the SMBG phase vs 2 in the CGM phase. Financial support by the study sponsor decreases the study’s validity.

A 2021 prospective study (N = 90) evaluated the use of CGM to improve glycemic control.³ Patients younger than 66 years with insulin-treated T2D and an A1C > 7.5% participated in a 7-day blinded CGM cycle every 4 months for 1 year. A nonsignificant decrease in hypoglycemia duration was observed for glucose values < 70 mg/dL and < 54 mg/dL at 12 months. No change in hypoglycemic event rate was seen with the use of CGM. Funding by the device manufacturer was a limitation of this study.

Flash glucose monitoring: Mixed results on hypoglycemia events

A 2019 open-label RCT (N = 82) assessed the effectiveness of FGM on diabetes control.⁴ Patients with insulin-treated T2D were randomly assigned to the intervention or standard­-care groups. The intervention group (n = 46; mean age, 66 years; mean A1C, 8.3%) used the FGM system for 10 weeks, while the standard-care group (n = 36; mean age, 70 years; mean A1C, 8.9%) maintained use of their glucometers. Both groups received similar types and duration of counseling. Treatment satisfaction was the primary outcome; total hypoglycemic events was a secondary outcome. No significant difference in the number of hypoglycemic episodes was observed between the intervention and control groups at 55 to 70 mg/dL (RR = 0.79; 95% CI, 0.44-1.4) or < 54 mg/dL (RR = 1.27; 95% CI, 0.38-4.2). No adverse events of severe hypoglycemia occurred during the study. Funding by the device manufacturer was a limitation of this study.

Continuous glucose monitoring and flash glucose monitoring do not decrease symptomatic hypoglycemia episodes but do lower time in hypoglycemia.

A 2017 open-label, multicenter RCT (N = 224) assessed FGM efficacy.⁵ Adults (mean age, 59 years; mean A1C, 8.8%) with T2D on intensive insulin therapy were randomized to FGM (n = 149) or SMBG (n = 75) after a 14-day masked baseline period. The 6-month treatment phase was unblinded. The duration of hypoglycemic events (glucose values < 70 mg/dL and < 55 mg/dL) was obtained from the sensors. Compared to the SMBG group, the FGM group spent 43% less time at < 70 mg/dL (aMD = –0.47 ± 0.13 h/d; P = .0006) and 53% less time at < 55 mg/dL (aMD = –0.22 ± 0.068 h/d; P = .0014). Hypoglycemic event rates significantly decreased by 28% (aMD = –0.16 ± 0.065; P = 0.016) and 44% (aMD = –0.12 ± 0.037; P = .0017) for glucose levels < 70 mg/dL and < 55 mg/dL, respectively. A nonsignificant difference occurred in severe hypoglycemic events requiring third-party assistance for the FGM (2%) vs control (1%) groups. Involvement of the device manufacturer and unblinded group allocations are study limitations.

A 2021 single-arm, multicenter prospective study looked at the impact of FGM on glycemic control in adults with insulin-treated T2D (N = 90; mean age, 64 years; mean A1C, 7.5%).⁶ After a 14-day baseline period consisting of masked sensor readings paired with self-monitored fingerstick tests, participants were followed for 11 weeks using the sensor to monitor glucose levels. The primary outcome was amount of time spent in hypoglycemia (< 70 mg/dL), with secondary outcomes including time and events in hypoglycemia (< 70, < 55, or < 45 mg/dL). No significant decrease in hypoglycemia duration or hypoglycemic event rates at < 70, < 55, or < 45 mg/­dL was observed for FGM compared to baseline. Adverse events were observed in 64% of participants; 94% of the events were hypoglycemia related. Serious adverse events were reported for 5.3% of participants. The single-arm study format, lack of generalizability due to the single-race study population, and sponsor support were study limitations.

Editor’s takeaway

This reasonably good evidence shows a decrease in measured or monitored hypoglycemia, a disease-oriented outcome, but it did not reach statistical significance for symptomatic hypoglycemia (1% vs 2%), a patient-oriented outcome. Nevertheless, in patients reporting symptomatic hypoglycemia, a continuous or flash glucose monitor may allow for more aggressive glucose control.

Evidence summary

Continuous glucose monitoring: Nonsignificant reductions in event rates

A 2021 multicenter RCT (N = 175) evaluated CGM effectiveness in patients with basal ­insulin–treated T2D.¹ Patients (mean age, 57 years; mean A1C, 9.1%) wore a blinded CGM device for baseline glucose measurement (minimum of 168 hours) before being randomly assigned to either CGM (n = 116) or traditional blood glucose monitoring (BGM; n = 59). At 8-month follow-up, patients in the BGM group again had blinded sensors placed. A significant reduction in hypoglycemia duration was observed for the CGM group vs the BGM group at 8 months for glucose values < 70 mg/mL (adjusted mean difference [aMD] = –0.24%; 95% CI, –0.42 to –0.05) and < 54 mg/dL (aMD = –0.10%; 95% CI, –0.15 to –0.04). A nonsignificant decrease in severe hypoglycemic events requiring resuscitative assistance occurred for BGM (2%) vs CGM (1%) patients. Study limitations included virtual visits due to COVID-19 and a short follow-­up period.

A 2022 multicenter prospective study (N = 174) examined CGM effects on hypoglycemia frequency and severity in adults with T2D.² Patients with insulin-requiring T2D (mean age, 61 years; mean A1C, 8.0%) participated in a 12-month study with 6 months of self-monitored blood glucose (SMBG) followed by 6 months of CGM use. The primary outcome was the rate of severe hypoglycemic events. A nonsignificant decrease was observed in the CGM group compared to the SMBG group for hypoglycemic event rate, per participant per 6-month period (relative risk [RR] = 0.43; 95% CI, 0.07-2.64). Four moderate hypoglycemic adverse events occurred in the SMBG phase vs 2 in the CGM phase. Financial support by the study sponsor decreases the study’s validity.

A 2021 prospective study (N = 90) evaluated the use of CGM to improve glycemic control.³ Patients younger than 66 years with insulin-treated T2D and an A1C > 7.5% participated in a 7-day blinded CGM cycle every 4 months for 1 year. A nonsignificant decrease in hypoglycemia duration was observed for glucose values < 70 mg/dL and < 54 mg/dL at 12 months. No change in hypoglycemic event rate was seen with the use of CGM. Funding by the device manufacturer was a limitation of this study.

Flash glucose monitoring: Mixed results on hypoglycemia events

A 2019 open-label RCT (N = 82) assessed the effectiveness of FGM on diabetes control.⁴ Patients with insulin-treated T2D were randomly assigned to the intervention or standard­-care groups. The intervention group (n = 46; mean age, 66 years; mean A1C, 8.3%) used the FGM system for 10 weeks, while the standard-care group (n = 36; mean age, 70 years; mean A1C, 8.9%) maintained use of their glucometers. Both groups received similar types and duration of counseling. Treatment satisfaction was the primary outcome; total hypoglycemic events was a secondary outcome. No significant difference in the number of hypoglycemic episodes was observed between the intervention and control groups at 55 to 70 mg/dL (RR = 0.79; 95% CI, 0.44-1.4) or < 54 mg/dL (RR = 1.27; 95% CI, 0.38-4.2). No adverse events of severe hypoglycemia occurred during the study. Funding by the device manufacturer was a limitation of this study.

Continuous glucose monitoring and flash glucose monitoring do not decrease symptomatic hypoglycemia episodes but do lower time in hypoglycemia.

A 2017 open-label, multicenter RCT (N = 224) assessed FGM efficacy.⁵ Adults (mean age, 59 years; mean A1C, 8.8%) with T2D on intensive insulin therapy were randomized to FGM (n = 149) or SMBG (n = 75) after a 14-day masked baseline period. The 6-month treatment phase was unblinded. The duration of hypoglycemic events (glucose values < 70 mg/dL and < 55 mg/dL) was obtained from the sensors. Compared to the SMBG group, the FGM group spent 43% less time at < 70 mg/dL (aMD = –0.47 ± 0.13 h/d; P = .0006) and 53% less time at < 55 mg/dL (aMD = –0.22 ± 0.068 h/d; P = .0014). Hypoglycemic event rates significantly decreased by 28% (aMD = –0.16 ± 0.065; P = 0.016) and 44% (aMD = –0.12 ± 0.037; P = .0017) for glucose levels < 70 mg/dL and < 55 mg/dL, respectively. A nonsignificant difference occurred in severe hypoglycemic events requiring third-party assistance for the FGM (2%) vs control (1%) groups. Involvement of the device manufacturer and unblinded group allocations are study limitations.

A 2021 single-arm, multicenter prospective study looked at the impact of FGM on glycemic control in adults with insulin-treated T2D (N = 90; mean age, 64 years; mean A1C, 7.5%).⁶ After a 14-day baseline period consisting of masked sensor readings paired with self-monitored fingerstick tests, participants were followed for 11 weeks using the sensor to monitor glucose levels. The primary outcome was amount of time spent in hypoglycemia (< 70 mg/dL), with secondary outcomes including time and events in hypoglycemia (< 70, < 55, or < 45 mg/dL). No significant decrease in hypoglycemia duration or hypoglycemic event rates at < 70, < 55, or < 45 mg/­dL was observed for FGM compared to baseline. Adverse events were observed in 64% of participants; 94% of the events were hypoglycemia related. Serious adverse events were reported for 5.3% of participants. The single-arm study format, lack of generalizability due to the single-race study population, and sponsor support were study limitations.

Editor’s takeaway

This reasonably good evidence shows a decrease in measured or monitored hypoglycemia, a disease-oriented outcome, but it did not reach statistical significance for symptomatic hypoglycemia (1% vs 2%), a patient-oriented outcome. Nevertheless, in patients reporting symptomatic hypoglycemia, a continuous or flash glucose monitor may allow for more aggressive glucose control.

Whenever someone asks me what I do, I happily reply, “I’m just a simple country doctor.” That is, in part, why I am honored to be granted the opportunity to serve as editor-in-chief of The Journal of Family Practice (JFP). As our late colleague Dr. John Hickner noted in his first JFP editorial, he and the 2 editors-in-chief before him (Drs. Jeff Susman and Mark Ebell) were also of the small-town family doc tradition.¹

My goal as this journal’s editorin-chief will be to continue its high academic standing while maintaining its utility for busy clinicians.

My small-town roots trace back to rural South Carolina. I am a first-generation college student and attended medical school on a Navy Health Professions Scholarship. After completing my residency training, I had the privilege of serving for 5 years in the Navy (2 of those years were overseas), where I practiced and taught full-scope family medicine. I saw patients of all ages, attended deliveries, and provided inpatient hospital care, as well as performed a full range of procedures and tests, including colposcopies, skin procedures, vasectomies, flexible sigmoidoscopies, and exercise treadmill testing.

Following military service and completion of a 2-year fellowship and Master of Public Health degree (while working nights at a rural emergency department), I began work at the University of North Carolina at Chapel Hill. I had the good fortune of spending the next 11 years as a faculty member there, where I advanced my research and teaching career. In 2017, I was named the Chair of Family Medicine and Community Health at Duke University School of Medicine, where I continue to have an active outpatient practice.

My experiences have shaped my belief that it is critical that family medicine maintain its presence (and advance its prominence) both in our communities and at our large academic medicine centers, championing service to rural areas, promoting health equity, and advocating for the importance of high-quality primary care delivery and training. No matter where we are, our work is valuable, and we make a difference. Like my predecessors, I have a love of evidence-based medicine. I also have a love of writing, which I can trace back to my days as an intern. I am excited to be able to apply what I have learned over the years to help maintain the rigor, practicality, and relevance of JFP while simultaneously helping to nurture new authors and peer reviewers.

My goal as this journal’s editor-in-chief will be to continue its high academic standing while maintaining its utility for busy clinicians. The provision of evidence-based clinical review articles that are succinct and practical, along with departments (eg, Photo Rounds, Behavioral Health Consult, Practice Alert, PURLs), will remain the journal’s major focus. Within this framework, I also want to share the best evidence and ideas on other aspects of practicing medicine, such as quality improvement, population health, and health equity. I’ll be looking to increase recruitment and mentorship of authors from diverse backgrounds, including those historically ­underrepresented in medicine.

I look forward to working with the editorial board, associate and assistant editors, and staff of JFP to serve the diverse interests and needs of our readers. To that end, we’ll be looking for your guidance. How else can JFP help you in your day-to-day practice? Please let us know your ideas. Drop us a line at [email protected].

Finally, please join me in thanking Drs. Henry Barry and Kate Rowland for all of their work this past year in keeping JFP going strong!

Whenever someone asks me what I do, I happily reply, “I’m just a simple country doctor.” That is, in part, why I am honored to be granted the opportunity to serve as editor-in-chief of The Journal of Family Practice (JFP). As our late colleague Dr. John Hickner noted in his first JFP editorial, he and the 2 editors-in-chief before him (Drs. Jeff Susman and Mark Ebell) were also of the small-town family doc tradition.¹

My goal as this journal’s editorin-chief will be to continue its high academic standing while maintaining its utility for busy clinicians.

My small-town roots trace back to rural South Carolina. I am a first-generation college student and attended medical school on a Navy Health Professions Scholarship. After completing my residency training, I had the privilege of serving for 5 years in the Navy (2 of those years were overseas), where I practiced and taught full-scope family medicine. I saw patients of all ages, attended deliveries, and provided inpatient hospital care, as well as performed a full range of procedures and tests, including colposcopies, skin procedures, vasectomies, flexible sigmoidoscopies, and exercise treadmill testing.

Following military service and completion of a 2-year fellowship and Master of Public Health degree (while working nights at a rural emergency department), I began work at the University of North Carolina at Chapel Hill. I had the good fortune of spending the next 11 years as a faculty member there, where I advanced my research and teaching career. In 2017, I was named the Chair of Family Medicine and Community Health at Duke University School of Medicine, where I continue to have an active outpatient practice.

My experiences have shaped my belief that it is critical that family medicine maintain its presence (and advance its prominence) both in our communities and at our large academic medicine centers, championing service to rural areas, promoting health equity, and advocating for the importance of high-quality primary care delivery and training. No matter where we are, our work is valuable, and we make a difference. Like my predecessors, I have a love of evidence-based medicine. I also have a love of writing, which I can trace back to my days as an intern. I am excited to be able to apply what I have learned over the years to help maintain the rigor, practicality, and relevance of JFP while simultaneously helping to nurture new authors and peer reviewers.

My goal as this journal’s editor-in-chief will be to continue its high academic standing while maintaining its utility for busy clinicians. The provision of evidence-based clinical review articles that are succinct and practical, along with departments (eg, Photo Rounds, Behavioral Health Consult, Practice Alert, PURLs), will remain the journal’s major focus. Within this framework, I also want to share the best evidence and ideas on other aspects of practicing medicine, such as quality improvement, population health, and health equity. I’ll be looking to increase recruitment and mentorship of authors from diverse backgrounds, including those historically ­underrepresented in medicine.

I look forward to working with the editorial board, associate and assistant editors, and staff of JFP to serve the diverse interests and needs of our readers. To that end, we’ll be looking for your guidance. How else can JFP help you in your day-to-day practice? Please let us know your ideas. Drop us a line at [email protected].

Finally, please join me in thanking Drs. Henry Barry and Kate Rowland for all of their work this past year in keeping JFP going strong!

Whenever someone asks me what I do, I happily reply, “I’m just a simple country doctor.” That is, in part, why I am honored to be granted the opportunity to serve as editor-in-chief of The Journal of Family Practice (JFP). As our late colleague Dr. John Hickner noted in his first JFP editorial, he and the 2 editors-in-chief before him (Drs. Jeff Susman and Mark Ebell) were also of the small-town family doc tradition.¹

My goal as this journal’s editorin-chief will be to continue its high academic standing while maintaining its utility for busy clinicians.

My small-town roots trace back to rural South Carolina. I am a first-generation college student and attended medical school on a Navy Health Professions Scholarship. After completing my residency training, I had the privilege of serving for 5 years in the Navy (2 of those years were overseas), where I practiced and taught full-scope family medicine. I saw patients of all ages, attended deliveries, and provided inpatient hospital care, as well as performed a full range of procedures and tests, including colposcopies, skin procedures, vasectomies, flexible sigmoidoscopies, and exercise treadmill testing.

Following military service and completion of a 2-year fellowship and Master of Public Health degree (while working nights at a rural emergency department), I began work at the University of North Carolina at Chapel Hill. I had the good fortune of spending the next 11 years as a faculty member there, where I advanced my research and teaching career. In 2017, I was named the Chair of Family Medicine and Community Health at Duke University School of Medicine, where I continue to have an active outpatient practice.

My experiences have shaped my belief that it is critical that family medicine maintain its presence (and advance its prominence) both in our communities and at our large academic medicine centers, championing service to rural areas, promoting health equity, and advocating for the importance of high-quality primary care delivery and training. No matter where we are, our work is valuable, and we make a difference. Like my predecessors, I have a love of evidence-based medicine. I also have a love of writing, which I can trace back to my days as an intern. I am excited to be able to apply what I have learned over the years to help maintain the rigor, practicality, and relevance of JFP while simultaneously helping to nurture new authors and peer reviewers.

My goal as this journal’s editor-in-chief will be to continue its high academic standing while maintaining its utility for busy clinicians. The provision of evidence-based clinical review articles that are succinct and practical, along with departments (eg, Photo Rounds, Behavioral Health Consult, Practice Alert, PURLs), will remain the journal’s major focus. Within this framework, I also want to share the best evidence and ideas on other aspects of practicing medicine, such as quality improvement, population health, and health equity. I’ll be looking to increase recruitment and mentorship of authors from diverse backgrounds, including those historically ­underrepresented in medicine.

I look forward to working with the editorial board, associate and assistant editors, and staff of JFP to serve the diverse interests and needs of our readers. To that end, we’ll be looking for your guidance. How else can JFP help you in your day-to-day practice? Please let us know your ideas. Drop us a line at [email protected].

Finally, please join me in thanking Drs. Henry Barry and Kate Rowland for all of their work this past year in keeping JFP going strong!

A 29-YEAR-OLD MAN was referred to the emergency department for fever and rash. Two months prior, he had noticed painful spots on his toes (FIGURE 1). Soon after, a rash of different morphology appeared on his chest and upper extremities. Associated symptoms included hair loss, generalized arthralgias, chills, trouble with balance, and photophobia. The patient denied genital lesions but reported 3 recent cold sores.

On exam, the patient was febrile (102 °F). Skin exam revealed a generalized maculopapular rash on the trunk, arms, and legs with scattered lesions on the palms ­(FIGURE 2). There were tender purpuric macules on the tips of his toes with areas of blanching. His hands had pink plaques on the dorsal fingers (FIGURE 3). Additionally, there was an erythematous papular rash with scale on his cheeks and nasal bridge, patchy areas of hair loss, and a single oral ulcer.

A neurologic exam was notable for mildly unstable gait, an abnormal Babinski reflex on the left side, and a positive Romberg sign. Musculoskeletal exam revealed joint tenderness in his shoulders, elbows, and wrists. Lymphadenopathy was present bilaterally in the axilla.

Lab work was ordered, including a VDRL test and a treponemal antibodies test. Skin biopsies also were taken from lesions on his arm and chest.

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

Our patient’s fever and rash were highly suggestive of either systemic lupus erythematosus (SLE) or secondary syphilis (the “great masquerader”).

Dermatologic findings occur in more than 70% of patients with systemic lupus erythematosus.

In addition to the joint tenderness revealed during the musculoskeletal exam, our patient had several nonspecific lupus findings on skin exam: malar rash, discoid rash on hands, subacute vasculitis (generalized rash), alopecia, and an oral ulcer; he also had the specific finding of chilblains vasculitis of the toes. Lab work and pathology results made the diagnosis clear. Lab work revealed leukopenia, an antinuclear antibody (ANA) result of 1:2560 with speckled appearance, and positive anti-SM antibodies. A dipstick was negative for protein; VDRL and treponemal antibodies tests were also negative. Histopathology showed perivascular lymph histiocytic vacuolar dermatitis with a differential of connective tissue disease, including lupus.

Our patient met the criteria

SLE is a systemic autoimmune disease resulting in chronic inflammation in multiple organ systems; it commonly manifests with vague symptoms of fatigue, fever, and weight loss. The prevalence of SLE in the United States has been reported as high as 241 per 100,000 people. ¹ Women are more likely to be affected, and the incidence is highest among Black people and lowest among Caucasians.^1,2 Risk factors include cigarette smoking and exposure to silica particulate air pollution.

The 2019 European League Against Rheumatism/­American College of Rheumatology criteria for a diagnosis of SLE require that a patient have a positive ANA and some, but not all, additive lab, clinical, and organ-specific findings.³ Findings that clinicians should look for include^3,4

• elevated ANA (≥ 1:80)
• constitutional symptoms (fever)
• hematologic findings (leukopenia, thrombocytopenia, autoimmune hemolysis)
• neuropsychiatric findings (delirium, psychosis, seizure)
• mucocutaneous findings (alopecia, oral ulcers, others)
• serosal findings (effusion, acute pericarditis)
• musculoskeletal findings (joint involvement)
• renal findings (proteinuria)
• antiphospholipid antibodies
• decreased complement proteins
• SLE-specific antibodies.

Dermatologic findings occur in more than 70% of patients with SLE.⁵ They can be nonspecific—eg, classic discoid rash, malar rash, alopecia, maculopapular rash (most commonly on sun-exposed areas, mimicking polymorphous light eruption)—or specific (eg, chilblains).⁵

Continue to: The differential for rash and fever is broad

Syphilis also can manifest with rash and fever. The rash of syphilis is nonpainful and affects the torso and face, with concentration on the palms and soles.^6,7It manifests during syphilis’s secondary stage, 6 to 8 weeks after an untreated infection. Fatigue, malaise, lymphadenopathy, mucosal lesions, ocular symptoms, and nephritis can occur.^8,9 The diagnosis is made through treponemal-specific antibody confirmation of a positive rapid plasma reagin test.⁹ Neurosyphilis is diagnosed via lumbar puncture.⁹

Dermatomyositis is a rare disorder of inflammation in both the skin and muscles. Symptoms include rash, muscle aches, and weakness. Lab abnormalities include elevated creatine kinase levels and ANA. Muscle biopsy confirms the diagnosis.

Erythema multiforme is an ­immunologic-mediated rash consisting of firm targetoid erythematous papules distributed symmetrically on the extremities, including palms/soles. It typically appears after a viral infection, immunization, or new medications (eg, antibiotics, nonsteroidal anti-­inflammatory drugs, or phenothiazines) initiated 1 to 3 weeks prior to the appearance of the rash. History and appearance inform the diagnosis.

Polymorphic light eruption is a rash of variable appearance on sun-exposed areas that results from a sensitivity to sunlight after lack of exposure for a period of time. Symptoms include burning and itching.

Treatment and outcome

Treat patients with SLE with hydroxychloroquine (200-400 mg/d) to suppress inflammation and with low-dose oral steroids such as prednisone (7.5 mg/d) for intermittent exacerbations. Higher steroid doses are sometimes needed for signs of organ inflammation. Patients with increased disease activity will require immunosuppressive therapy with ­disease-modifying antirheumatic drugs, such as methotrexate (7.5-25 mg/wk), mycophenolate (2-3 g/d), azathioprine (1.5-2.5 mg/kg/d), and biologic infusions.⁴ Additionally, in 2021, the US Food and Drug Administration approved anifrolumab (Saphnelo) and voclosporin (Lupkynis) for the treatment of SLE.⁴

Our patient was admitted for further evaluation. A lumbar puncture was performed because of his balance issues; it showed an elevated protein level, but further work-up did not find an infectious or malignant source. Balance improved with hydration. The patient remained hospitalized for 9 days, during which his fever subsided. His pain improved after initiation of hydroxychloroquine 400 mg/d. Follow-up with Rheumatology was arranged for further care.

A 29-YEAR-OLD MAN was referred to the emergency department for fever and rash. Two months prior, he had noticed painful spots on his toes (FIGURE 1). Soon after, a rash of different morphology appeared on his chest and upper extremities. Associated symptoms included hair loss, generalized arthralgias, chills, trouble with balance, and photophobia. The patient denied genital lesions but reported 3 recent cold sores.

On exam, the patient was febrile (102 °F). Skin exam revealed a generalized maculopapular rash on the trunk, arms, and legs with scattered lesions on the palms ­(FIGURE 2). There were tender purpuric macules on the tips of his toes with areas of blanching. His hands had pink plaques on the dorsal fingers (FIGURE 3). Additionally, there was an erythematous papular rash with scale on his cheeks and nasal bridge, patchy areas of hair loss, and a single oral ulcer.

A neurologic exam was notable for mildly unstable gait, an abnormal Babinski reflex on the left side, and a positive Romberg sign. Musculoskeletal exam revealed joint tenderness in his shoulders, elbows, and wrists. Lymphadenopathy was present bilaterally in the axilla.

Lab work was ordered, including a VDRL test and a treponemal antibodies test. Skin biopsies also were taken from lesions on his arm and chest.

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

Our patient’s fever and rash were highly suggestive of either systemic lupus erythematosus (SLE) or secondary syphilis (the “great masquerader”).

Dermatologic findings occur in more than 70% of patients with systemic lupus erythematosus.

In addition to the joint tenderness revealed during the musculoskeletal exam, our patient had several nonspecific lupus findings on skin exam: malar rash, discoid rash on hands, subacute vasculitis (generalized rash), alopecia, and an oral ulcer; he also had the specific finding of chilblains vasculitis of the toes. Lab work and pathology results made the diagnosis clear. Lab work revealed leukopenia, an antinuclear antibody (ANA) result of 1:2560 with speckled appearance, and positive anti-SM antibodies. A dipstick was negative for protein; VDRL and treponemal antibodies tests were also negative. Histopathology showed perivascular lymph histiocytic vacuolar dermatitis with a differential of connective tissue disease, including lupus.

Our patient met the criteria

SLE is a systemic autoimmune disease resulting in chronic inflammation in multiple organ systems; it commonly manifests with vague symptoms of fatigue, fever, and weight loss. The prevalence of SLE in the United States has been reported as high as 241 per 100,000 people. ¹ Women are more likely to be affected, and the incidence is highest among Black people and lowest among Caucasians.^1,2 Risk factors include cigarette smoking and exposure to silica particulate air pollution.

The 2019 European League Against Rheumatism/­American College of Rheumatology criteria for a diagnosis of SLE require that a patient have a positive ANA and some, but not all, additive lab, clinical, and organ-specific findings.³ Findings that clinicians should look for include^3,4

• elevated ANA (≥ 1:80)
• constitutional symptoms (fever)
• hematologic findings (leukopenia, thrombocytopenia, autoimmune hemolysis)
• neuropsychiatric findings (delirium, psychosis, seizure)
• mucocutaneous findings (alopecia, oral ulcers, others)
• serosal findings (effusion, acute pericarditis)
• musculoskeletal findings (joint involvement)
• renal findings (proteinuria)
• antiphospholipid antibodies
• decreased complement proteins
• SLE-specific antibodies.

Dermatologic findings occur in more than 70% of patients with SLE.⁵ They can be nonspecific—eg, classic discoid rash, malar rash, alopecia, maculopapular rash (most commonly on sun-exposed areas, mimicking polymorphous light eruption)—or specific (eg, chilblains).⁵

Continue to: The differential for rash and fever is broad

Syphilis also can manifest with rash and fever. The rash of syphilis is nonpainful and affects the torso and face, with concentration on the palms and soles.^6,7It manifests during syphilis’s secondary stage, 6 to 8 weeks after an untreated infection. Fatigue, malaise, lymphadenopathy, mucosal lesions, ocular symptoms, and nephritis can occur.^8,9 The diagnosis is made through treponemal-specific antibody confirmation of a positive rapid plasma reagin test.⁹ Neurosyphilis is diagnosed via lumbar puncture.⁹

Dermatomyositis is a rare disorder of inflammation in both the skin and muscles. Symptoms include rash, muscle aches, and weakness. Lab abnormalities include elevated creatine kinase levels and ANA. Muscle biopsy confirms the diagnosis.

Erythema multiforme is an ­immunologic-mediated rash consisting of firm targetoid erythematous papules distributed symmetrically on the extremities, including palms/soles. It typically appears after a viral infection, immunization, or new medications (eg, antibiotics, nonsteroidal anti-­inflammatory drugs, or phenothiazines) initiated 1 to 3 weeks prior to the appearance of the rash. History and appearance inform the diagnosis.

Polymorphic light eruption is a rash of variable appearance on sun-exposed areas that results from a sensitivity to sunlight after lack of exposure for a period of time. Symptoms include burning and itching.

Treatment and outcome

Treat patients with SLE with hydroxychloroquine (200-400 mg/d) to suppress inflammation and with low-dose oral steroids such as prednisone (7.5 mg/d) for intermittent exacerbations. Higher steroid doses are sometimes needed for signs of organ inflammation. Patients with increased disease activity will require immunosuppressive therapy with ­disease-modifying antirheumatic drugs, such as methotrexate (7.5-25 mg/wk), mycophenolate (2-3 g/d), azathioprine (1.5-2.5 mg/kg/d), and biologic infusions.⁴ Additionally, in 2021, the US Food and Drug Administration approved anifrolumab (Saphnelo) and voclosporin (Lupkynis) for the treatment of SLE.⁴

Our patient was admitted for further evaluation. A lumbar puncture was performed because of his balance issues; it showed an elevated protein level, but further work-up did not find an infectious or malignant source. Balance improved with hydration. The patient remained hospitalized for 9 days, during which his fever subsided. His pain improved after initiation of hydroxychloroquine 400 mg/d. Follow-up with Rheumatology was arranged for further care.

A 29-YEAR-OLD MAN was referred to the emergency department for fever and rash. Two months prior, he had noticed painful spots on his toes (FIGURE 1). Soon after, a rash of different morphology appeared on his chest and upper extremities. Associated symptoms included hair loss, generalized arthralgias, chills, trouble with balance, and photophobia. The patient denied genital lesions but reported 3 recent cold sores.

On exam, the patient was febrile (102 °F). Skin exam revealed a generalized maculopapular rash on the trunk, arms, and legs with scattered lesions on the palms ­(FIGURE 2). There were tender purpuric macules on the tips of his toes with areas of blanching. His hands had pink plaques on the dorsal fingers (FIGURE 3). Additionally, there was an erythematous papular rash with scale on his cheeks and nasal bridge, patchy areas of hair loss, and a single oral ulcer.

A neurologic exam was notable for mildly unstable gait, an abnormal Babinski reflex on the left side, and a positive Romberg sign. Musculoskeletal exam revealed joint tenderness in his shoulders, elbows, and wrists. Lymphadenopathy was present bilaterally in the axilla.

Lab work was ordered, including a VDRL test and a treponemal antibodies test. Skin biopsies also were taken from lesions on his arm and chest.

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

Our patient’s fever and rash were highly suggestive of either systemic lupus erythematosus (SLE) or secondary syphilis (the “great masquerader”).

Dermatologic findings occur in more than 70% of patients with systemic lupus erythematosus.

In addition to the joint tenderness revealed during the musculoskeletal exam, our patient had several nonspecific lupus findings on skin exam: malar rash, discoid rash on hands, subacute vasculitis (generalized rash), alopecia, and an oral ulcer; he also had the specific finding of chilblains vasculitis of the toes. Lab work and pathology results made the diagnosis clear. Lab work revealed leukopenia, an antinuclear antibody (ANA) result of 1:2560 with speckled appearance, and positive anti-SM antibodies. A dipstick was negative for protein; VDRL and treponemal antibodies tests were also negative. Histopathology showed perivascular lymph histiocytic vacuolar dermatitis with a differential of connective tissue disease, including lupus.

Our patient met the criteria

SLE is a systemic autoimmune disease resulting in chronic inflammation in multiple organ systems; it commonly manifests with vague symptoms of fatigue, fever, and weight loss. The prevalence of SLE in the United States has been reported as high as 241 per 100,000 people. ¹ Women are more likely to be affected, and the incidence is highest among Black people and lowest among Caucasians.^1,2 Risk factors include cigarette smoking and exposure to silica particulate air pollution.

The 2019 European League Against Rheumatism/­American College of Rheumatology criteria for a diagnosis of SLE require that a patient have a positive ANA and some, but not all, additive lab, clinical, and organ-specific findings.³ Findings that clinicians should look for include^3,4

• elevated ANA (≥ 1:80)
• constitutional symptoms (fever)
• hematologic findings (leukopenia, thrombocytopenia, autoimmune hemolysis)
• neuropsychiatric findings (delirium, psychosis, seizure)
• mucocutaneous findings (alopecia, oral ulcers, others)
• serosal findings (effusion, acute pericarditis)
• musculoskeletal findings (joint involvement)
• renal findings (proteinuria)
• antiphospholipid antibodies
• decreased complement proteins
• SLE-specific antibodies.

Dermatologic findings occur in more than 70% of patients with SLE.⁵ They can be nonspecific—eg, classic discoid rash, malar rash, alopecia, maculopapular rash (most commonly on sun-exposed areas, mimicking polymorphous light eruption)—or specific (eg, chilblains).⁵

Continue to: The differential for rash and fever is broad

Syphilis also can manifest with rash and fever. The rash of syphilis is nonpainful and affects the torso and face, with concentration on the palms and soles.^6,7It manifests during syphilis’s secondary stage, 6 to 8 weeks after an untreated infection. Fatigue, malaise, lymphadenopathy, mucosal lesions, ocular symptoms, and nephritis can occur.^8,9 The diagnosis is made through treponemal-specific antibody confirmation of a positive rapid plasma reagin test.⁹ Neurosyphilis is diagnosed via lumbar puncture.⁹

Dermatomyositis is a rare disorder of inflammation in both the skin and muscles. Symptoms include rash, muscle aches, and weakness. Lab abnormalities include elevated creatine kinase levels and ANA. Muscle biopsy confirms the diagnosis.

Erythema multiforme is an ­immunologic-mediated rash consisting of firm targetoid erythematous papules distributed symmetrically on the extremities, including palms/soles. It typically appears after a viral infection, immunization, or new medications (eg, antibiotics, nonsteroidal anti-­inflammatory drugs, or phenothiazines) initiated 1 to 3 weeks prior to the appearance of the rash. History and appearance inform the diagnosis.

Polymorphic light eruption is a rash of variable appearance on sun-exposed areas that results from a sensitivity to sunlight after lack of exposure for a period of time. Symptoms include burning and itching.

Treatment and outcome

Treat patients with SLE with hydroxychloroquine (200-400 mg/d) to suppress inflammation and with low-dose oral steroids such as prednisone (7.5 mg/d) for intermittent exacerbations. Higher steroid doses are sometimes needed for signs of organ inflammation. Patients with increased disease activity will require immunosuppressive therapy with ­disease-modifying antirheumatic drugs, such as methotrexate (7.5-25 mg/wk), mycophenolate (2-3 g/d), azathioprine (1.5-2.5 mg/kg/d), and biologic infusions.⁴ Additionally, in 2021, the US Food and Drug Administration approved anifrolumab (Saphnelo) and voclosporin (Lupkynis) for the treatment of SLE.⁴

Our patient was admitted for further evaluation. A lumbar puncture was performed because of his balance issues; it showed an elevated protein level, but further work-up did not find an infectious or malignant source. Balance improved with hydration. The patient remained hospitalized for 9 days, during which his fever subsided. His pain improved after initiation of hydroxychloroquine 400 mg/d. Follow-up with Rheumatology was arranged for further care.

A 55-YEAR-OLD WOMAN developed a small red papule on her left hand that, over the course of a week, progressed rapidly into an ulcerated nodule with accompanying swelling and pain. She reported concomitant fatigue, unintentional weight loss, and swollen axillary lymph nodes. Past medical history included rheumatoid arthritis.

A physical examination of her left hand revealed a tender, erythematous to violaceous nodule with ulceration and crust and surrounding diffuse erythema and edema ­(FIGURE). She also had several enlarged, nontender right axillary lymph nodes. Initial lab evaluation was significant for leukocytosis (13.8 K/uL) with increased neutrophils, lymphocytes, and eosinophils. Two punch biopsies were performed and the samples submitted for hematoxylin and eosin (H&E) staining and tissue culture.

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

The results of H&E were consistent with neutrophilic dermatosis of the dorsal hands (NDDH). Tissue culture was negative for fungus, bacteria, and atypical mycobacteria, confirming the diagnosis.

NDDH often is mistaken for an infectious abscess and unsuccessfully treated with antimicrobial agents.

NDDH is a neutrophilic dermatosis and considered a localized variant of Sweet syndrome, manifesting on the dorsal hands as suppurative, erythematous to violaceous papules, plaques, or nodules that often undergo necrosis, blistering, and ulceration. The diagnosis can be made clinically, although a biopsy is usually performed for confirmation. It is characterized histologically by a dense dermal neutrophilic infiltrate along with dermal ­edema.¹

The pathogenesis of NDDH is not fully known.² It is often preceded by trauma and may be associated with recent infection (respiratory, gastrointestinal), inflammatory bowel disease, autoimmune disease (eg, rheumatoid arthritis), or malignancy.¹ The most common associated malignancies are hematologic, such as myelodysplastic syndrome, leukemia, or lymphoma, although solid tumors also can be seen.^1,3 Therefore, patients who receive a diagnosis of NDDH typically require further work-up to rule out these associated conditions. NDDH is a rare enough entity that incidence/prevalence data aren’t available or likely to be accurate.

The differential includes infection and neoplastic processes

NDDH often is mistaken for an infectious abscess and unsuccessfully treated with antimicrobial agents, such as those commonly used for staphylococcus and streptococcus skin and soft-tissue infections. Thus, wound or tissue culture may be considered to exclude infection from the differential diagnosis. In addition to infectious processes such as sporotrichosis or an atypical mycobacterial infection, the differential includes other neutrophilic dermatoses and neoplastic processes such as lymphoma or leukemia cutis.

Sporotrichosis is caused by Sporothrix schenckii and usually spreads proximally after entering through a wound or cut. Special stains on histology and culture are needed to make the diagnosis.

Continue to: Atypical mycobacterial infections

Atypical mycobacterial infections usually enter through an area of trauma and spread proximally after inoculation. Atypical mycobacterial infections can be diagnosed via biopsy with special stains, culture, and polymerase chain reaction of the tissue.

Neutrophilic dermatoses are a broad category of dermatoses that include NDDH, pyoderma gangrenosum, and Sweet syndrome. This category of dermatoses is differentiated by morphology and distribution of lesions.

Lymphoma can be primary cutaneous or secondary to a systemic lymphoma. A biopsy will show a collection of atypical lymphocytes.

Treatment begins with steroids

Treatment with topical (eg, 0.05% clobetasol ointment bid), intralesional (10 to 40 mg/mL triamcinolone acetonide), or systemic (eg, prednisone 0.5 to 1 mg/kg tapered over the course of 1-2 months) steroids is considered first-line therapy and often results in rapid clinical improvement. Agents such as dapsone (25 to 150 mg/d) and/or colchicine (0.6 mg bid to tid) may be used in recalcitrant cases or in patients for whom steroids are contra­indicated.²

Our patient’s NDDH was treated with prednisone (~1.0 mg/kg daily tapered over the course of 6 weeks). She was referred to Hematology/­Oncology for further work-up of her constitutional symptoms, lymphadenopathy,­ and leukocytosis. Ultimately, she received a diagnosis of concomitant chronic lymphocytic leukemia/small lymphocytic lymphoma. The patient required no immediate treatment for her indolent lymphoma and was advised that she would need to get blood work done on a regular basis and have annual check-ups.

A 55-YEAR-OLD WOMAN developed a small red papule on her left hand that, over the course of a week, progressed rapidly into an ulcerated nodule with accompanying swelling and pain. She reported concomitant fatigue, unintentional weight loss, and swollen axillary lymph nodes. Past medical history included rheumatoid arthritis.

A physical examination of her left hand revealed a tender, erythematous to violaceous nodule with ulceration and crust and surrounding diffuse erythema and edema ­(FIGURE). She also had several enlarged, nontender right axillary lymph nodes. Initial lab evaluation was significant for leukocytosis (13.8 K/uL) with increased neutrophils, lymphocytes, and eosinophils. Two punch biopsies were performed and the samples submitted for hematoxylin and eosin (H&E) staining and tissue culture.

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

The results of H&E were consistent with neutrophilic dermatosis of the dorsal hands (NDDH). Tissue culture was negative for fungus, bacteria, and atypical mycobacteria, confirming the diagnosis.

NDDH often is mistaken for an infectious abscess and unsuccessfully treated with antimicrobial agents.

NDDH is a neutrophilic dermatosis and considered a localized variant of Sweet syndrome, manifesting on the dorsal hands as suppurative, erythematous to violaceous papules, plaques, or nodules that often undergo necrosis, blistering, and ulceration. The diagnosis can be made clinically, although a biopsy is usually performed for confirmation. It is characterized histologically by a dense dermal neutrophilic infiltrate along with dermal ­edema.¹

The pathogenesis of NDDH is not fully known.² It is often preceded by trauma and may be associated with recent infection (respiratory, gastrointestinal), inflammatory bowel disease, autoimmune disease (eg, rheumatoid arthritis), or malignancy.¹ The most common associated malignancies are hematologic, such as myelodysplastic syndrome, leukemia, or lymphoma, although solid tumors also can be seen.^1,3 Therefore, patients who receive a diagnosis of NDDH typically require further work-up to rule out these associated conditions. NDDH is a rare enough entity that incidence/prevalence data aren’t available or likely to be accurate.

The differential includes infection and neoplastic processes

NDDH often is mistaken for an infectious abscess and unsuccessfully treated with antimicrobial agents, such as those commonly used for staphylococcus and streptococcus skin and soft-tissue infections. Thus, wound or tissue culture may be considered to exclude infection from the differential diagnosis. In addition to infectious processes such as sporotrichosis or an atypical mycobacterial infection, the differential includes other neutrophilic dermatoses and neoplastic processes such as lymphoma or leukemia cutis.

Sporotrichosis is caused by Sporothrix schenckii and usually spreads proximally after entering through a wound or cut. Special stains on histology and culture are needed to make the diagnosis.

Continue to: Atypical mycobacterial infections

Atypical mycobacterial infections usually enter through an area of trauma and spread proximally after inoculation. Atypical mycobacterial infections can be diagnosed via biopsy with special stains, culture, and polymerase chain reaction of the tissue.

Neutrophilic dermatoses are a broad category of dermatoses that include NDDH, pyoderma gangrenosum, and Sweet syndrome. This category of dermatoses is differentiated by morphology and distribution of lesions.

Lymphoma can be primary cutaneous or secondary to a systemic lymphoma. A biopsy will show a collection of atypical lymphocytes.

Treatment begins with steroids

Treatment with topical (eg, 0.05% clobetasol ointment bid), intralesional (10 to 40 mg/mL triamcinolone acetonide), or systemic (eg, prednisone 0.5 to 1 mg/kg tapered over the course of 1-2 months) steroids is considered first-line therapy and often results in rapid clinical improvement. Agents such as dapsone (25 to 150 mg/d) and/or colchicine (0.6 mg bid to tid) may be used in recalcitrant cases or in patients for whom steroids are contra­indicated.²

Our patient’s NDDH was treated with prednisone (~1.0 mg/kg daily tapered over the course of 6 weeks). She was referred to Hematology/­Oncology for further work-up of her constitutional symptoms, lymphadenopathy,­ and leukocytosis. Ultimately, she received a diagnosis of concomitant chronic lymphocytic leukemia/small lymphocytic lymphoma. The patient required no immediate treatment for her indolent lymphoma and was advised that she would need to get blood work done on a regular basis and have annual check-ups.

A 55-YEAR-OLD WOMAN developed a small red papule on her left hand that, over the course of a week, progressed rapidly into an ulcerated nodule with accompanying swelling and pain. She reported concomitant fatigue, unintentional weight loss, and swollen axillary lymph nodes. Past medical history included rheumatoid arthritis.

A physical examination of her left hand revealed a tender, erythematous to violaceous nodule with ulceration and crust and surrounding diffuse erythema and edema ­(FIGURE). She also had several enlarged, nontender right axillary lymph nodes. Initial lab evaluation was significant for leukocytosis (13.8 K/uL) with increased neutrophils, lymphocytes, and eosinophils. Two punch biopsies were performed and the samples submitted for hematoxylin and eosin (H&E) staining and tissue culture.

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

The results of H&E were consistent with neutrophilic dermatosis of the dorsal hands (NDDH). Tissue culture was negative for fungus, bacteria, and atypical mycobacteria, confirming the diagnosis.

NDDH often is mistaken for an infectious abscess and unsuccessfully treated with antimicrobial agents.

NDDH is a neutrophilic dermatosis and considered a localized variant of Sweet syndrome, manifesting on the dorsal hands as suppurative, erythematous to violaceous papules, plaques, or nodules that often undergo necrosis, blistering, and ulceration. The diagnosis can be made clinically, although a biopsy is usually performed for confirmation. It is characterized histologically by a dense dermal neutrophilic infiltrate along with dermal ­edema.¹

The pathogenesis of NDDH is not fully known.² It is often preceded by trauma and may be associated with recent infection (respiratory, gastrointestinal), inflammatory bowel disease, autoimmune disease (eg, rheumatoid arthritis), or malignancy.¹ The most common associated malignancies are hematologic, such as myelodysplastic syndrome, leukemia, or lymphoma, although solid tumors also can be seen.^1,3 Therefore, patients who receive a diagnosis of NDDH typically require further work-up to rule out these associated conditions. NDDH is a rare enough entity that incidence/prevalence data aren’t available or likely to be accurate.

The differential includes infection and neoplastic processes

NDDH often is mistaken for an infectious abscess and unsuccessfully treated with antimicrobial agents, such as those commonly used for staphylococcus and streptococcus skin and soft-tissue infections. Thus, wound or tissue culture may be considered to exclude infection from the differential diagnosis. In addition to infectious processes such as sporotrichosis or an atypical mycobacterial infection, the differential includes other neutrophilic dermatoses and neoplastic processes such as lymphoma or leukemia cutis.

Sporotrichosis is caused by Sporothrix schenckii and usually spreads proximally after entering through a wound or cut. Special stains on histology and culture are needed to make the diagnosis.

Continue to: Atypical mycobacterial infections

Atypical mycobacterial infections usually enter through an area of trauma and spread proximally after inoculation. Atypical mycobacterial infections can be diagnosed via biopsy with special stains, culture, and polymerase chain reaction of the tissue.

Neutrophilic dermatoses are a broad category of dermatoses that include NDDH, pyoderma gangrenosum, and Sweet syndrome. This category of dermatoses is differentiated by morphology and distribution of lesions.

Lymphoma can be primary cutaneous or secondary to a systemic lymphoma. A biopsy will show a collection of atypical lymphocytes.

Treatment begins with steroids

Treatment with topical (eg, 0.05% clobetasol ointment bid), intralesional (10 to 40 mg/mL triamcinolone acetonide), or systemic (eg, prednisone 0.5 to 1 mg/kg tapered over the course of 1-2 months) steroids is considered first-line therapy and often results in rapid clinical improvement. Agents such as dapsone (25 to 150 mg/d) and/or colchicine (0.6 mg bid to tid) may be used in recalcitrant cases or in patients for whom steroids are contra­indicated.²

Our patient’s NDDH was treated with prednisone (~1.0 mg/kg daily tapered over the course of 6 weeks). She was referred to Hematology/­Oncology for further work-up of her constitutional symptoms, lymphadenopathy,­ and leukocytosis. Ultimately, she received a diagnosis of concomitant chronic lymphocytic leukemia/small lymphocytic lymphoma. The patient required no immediate treatment for her indolent lymphoma and was advised that she would need to get blood work done on a regular basis and have annual check-ups.

THE CASE

A 30-year-old woman sought care at her rural family physician’s office for progressive dyspnea and peripheral edema, which she had been experiencing for several weeks. She was G1P0 and in her 35th week of gestation.

Her medical history was remarkable for mild preeclampsia, which was being managed observantly by her obstetrician in consultation with a maternal-fetal medicine specialist. She had been evaluated by her local hospital’s labor and delivery department and her maternal-fetal medicine specialist earlier in the week and seen the previous day by her obstetrician for these signs and symptoms. They all reassured her and told her these symptoms were normal during pregnancy. No diagnostic studies were performed. However, she remained concerned and decided to see her family physician for another opinion.

Upon presentation to her family physician, the patient was afebrile. Her blood pressure was 135/98 mm Hg; heart rate, 96 beats/min; and respiration, 20 breaths/min and slightly labored. Edema of 2 to 3+ was noted in her lower extremities, hands, and face. Bibasilar breath sounds were diminished, and her abdomen was nontender.

The family physician suspected left ventricular systolic dysfunction. He worked in a small office that lacked access to a laboratory or radiographic studies. However, he did have an ultrasound machine available, and although he was not skilled in echocardiography to assess cardiac function, he was able to obtain a bedside lung ultrasound.

THE DIAGNOSIS

While no B-lines were seen on the lung ultrasound, bilateral plural effusions were noted (FIGURE). This finding, paired with the patient’s signs and symptoms, prompted the family physician to suspect a diagnosis of acute ­decompensated heart failure with presumptive peripartum cardiomyopathy. The patient was immediately driven to the hospital by her family physician for emergency admission with stat obstetric and cardiology ­consultations.

An in-hospital echocardiogram revealed severe global hypokinesia with a left ventricular ejection fraction of 25% to 30%, which confirmed the family physician’s ­suspicions. Laboratory studies were significant for elevated N-terminal pro-brain natriuretic peptide (43,449 pg/mL; normal, < 125 pg/mL), troponin (1.12 ng/mL; normal range, 0-0.10 ng/mL), and white blood cell count (27.6 x 10³/µL). She also had evidence of acute renal injury, with blood urea nitrogen of 46 ­mg/dL (normal range, 7-18 mg/dL), creatinine of 2.0 mg/dL (normal range, 0.5-1.0 mg/dL), and potassium of 7.6 mmol/L (normal range, 3.5-5.1 mmol/L). Emergency delivery was induced by amniotomy, resulting in the birth of a baby girl weighing 5 lb 4 oz (Apgar scores 6, 8, and 9).

This case illustrates the successful use of lung ultrasound to identify a potentially fatal, elusive condition.

Following delivery, the patient was placed on a milrinone infusion and required dialysis. She was emergently transferred to a tertiary care hospital, where she was admitted to the cardiac intensive care unit by the cardiology/heart transplant service with nephrology and obstetric consultations. Hematology and infectious disease specialists were consulted to rule out HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome and sepsis, respectively. Her course of care remained complicated with further testing, including cardiac catheterization and biopsy, which was negative for additional pathology.

Continue to: One week after admission...

One week after admission, she was ­discharged home with a 24-hour wearable external cardiac defibrillator and a confirmed diagnosis of peripartum cardiomyopathy. Her medication regimen included digoxin (125 µg 3 times/wk), spironolactone (25 mg/d), carvedilol (3.125 mg twice daily), sacubitril/valsartan (24 mg/26 mg twice daily), furosemide (20 mg/d as needed for weight gain > 3-4 lb or leg swelling), magnesium oxide (400 mg twice daily), and ferrous sulfate (325 mg/d).

DISCUSSION

Peripartum cardiomyopathy is a rare, life-threatening, idiopathic cardiomyopathy that is responsible for one-half to two-thirds of cardiovascular disease–related maternal deaths in the United States.^1,2 It manifests in late pregnancy or early in the postpartum period and is characterized by left ven­tricular systolic dysfunction with resultant heart failure and an ejection fraction of less than 45%.^1,2

Recognized as early as the 1800s by ­Virchow,^2,3 the incidence of peripartum cardiomyopathy in the United States ranges from 1 in 1000 to 4000 live births and is increasing worldwide.^1,2 While the cause of peripartum cardiomyopathy remains unknown, risk factors include advanced maternal age, African descent, hypertension, preeclampsia, and multiple gestation ­pregnancy.^1,2

Early diagnosis of peripartum cardiomyopathy is imperative for survival of both mother and baby.⁴ This may be difficult because the signs and symptoms of heart failure—such as dyspnea, edema, orthopnea, cough, and chest and abdominal pain—overlap with those of a typical pregnancy, resulting in it ­often being missed on evaluation.^1,2

Dx with echocardiography; in a pinch, consider lung ultrasound

Usually a diagnosis of peripartum cardiomyopathy is established with echocardiography.^1,2 Thus, this case is of significant importance because it illustrates the successful use of lung ultrasound—a simple and easy test—by a rural family doctor to identify this potentially fatal, elusive condition with no additional studies.

Continue to: Use of lung ultrasound...

Use of lung ultrasound in the detection of acute decompensated heart failure is accepted in the medical literature.^5-7 Given clinical correlation, a positive scan is defined by the presence of at least 3 B-lines on a longitudinal plane between 2 ribs or, as seen in our case, by the presence of pleural effusion.^5-8 Lung ultrasound is readily available worldwide, is completely safe in pregnancy, and is considered one of the easiest studies to perform.^7-10

At the patient’s 9-month follow-up visit, she had made a full clinical recovery. Her ejection fraction was 59.8%, and she had stopped all medications. The patient and her child did not experience any continued complications.

THE TAKEAWAY

Family physicians should be aware of peripartum cardiomyopathy—one of the most elusive and life-threatening diseases of pregnancy. When managing a pregnant patient, it is imperative to follow up on complaints such as dyspnea, peripheral edema, and chest and/or abdominal pain. While these symptoms are not unusual during pregnancy, they should always prompt a more thorough evaluation. If peripartum cardiomyopathy is suspected, lung ultrasound is a valuable diagnostic tool for family physicians. Further research is needed before the findings of this case report can be universally applied in the routine prenatal care of women at risk for peripartum cardiomyopathy.

Acknowledgement
The authors thank their daughter, Nickel Cielo Abarbanell, for her help in the preparation of this manuscript.

CORRESPONDENCE
Neal Robert Abarbanell, MD, First Choice Healthcare, 1867 20th Avenue, Vero Beach, FL 32960; neal.abarbanell@ gmail.com

THE CASE

A 30-year-old woman sought care at her rural family physician’s office for progressive dyspnea and peripheral edema, which she had been experiencing for several weeks. She was G1P0 and in her 35th week of gestation.

Her medical history was remarkable for mild preeclampsia, which was being managed observantly by her obstetrician in consultation with a maternal-fetal medicine specialist. She had been evaluated by her local hospital’s labor and delivery department and her maternal-fetal medicine specialist earlier in the week and seen the previous day by her obstetrician for these signs and symptoms. They all reassured her and told her these symptoms were normal during pregnancy. No diagnostic studies were performed. However, she remained concerned and decided to see her family physician for another opinion.

Upon presentation to her family physician, the patient was afebrile. Her blood pressure was 135/98 mm Hg; heart rate, 96 beats/min; and respiration, 20 breaths/min and slightly labored. Edema of 2 to 3+ was noted in her lower extremities, hands, and face. Bibasilar breath sounds were diminished, and her abdomen was nontender.

The family physician suspected left ventricular systolic dysfunction. He worked in a small office that lacked access to a laboratory or radiographic studies. However, he did have an ultrasound machine available, and although he was not skilled in echocardiography to assess cardiac function, he was able to obtain a bedside lung ultrasound.

THE DIAGNOSIS

While no B-lines were seen on the lung ultrasound, bilateral plural effusions were noted (FIGURE). This finding, paired with the patient’s signs and symptoms, prompted the family physician to suspect a diagnosis of acute ­decompensated heart failure with presumptive peripartum cardiomyopathy. The patient was immediately driven to the hospital by her family physician for emergency admission with stat obstetric and cardiology ­consultations.

An in-hospital echocardiogram revealed severe global hypokinesia with a left ventricular ejection fraction of 25% to 30%, which confirmed the family physician’s ­suspicions. Laboratory studies were significant for elevated N-terminal pro-brain natriuretic peptide (43,449 pg/mL; normal, < 125 pg/mL), troponin (1.12 ng/mL; normal range, 0-0.10 ng/mL), and white blood cell count (27.6 x 10³/µL). She also had evidence of acute renal injury, with blood urea nitrogen of 46 ­mg/dL (normal range, 7-18 mg/dL), creatinine of 2.0 mg/dL (normal range, 0.5-1.0 mg/dL), and potassium of 7.6 mmol/L (normal range, 3.5-5.1 mmol/L). Emergency delivery was induced by amniotomy, resulting in the birth of a baby girl weighing 5 lb 4 oz (Apgar scores 6, 8, and 9).

This case illustrates the successful use of lung ultrasound to identify a potentially fatal, elusive condition.

Following delivery, the patient was placed on a milrinone infusion and required dialysis. She was emergently transferred to a tertiary care hospital, where she was admitted to the cardiac intensive care unit by the cardiology/heart transplant service with nephrology and obstetric consultations. Hematology and infectious disease specialists were consulted to rule out HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome and sepsis, respectively. Her course of care remained complicated with further testing, including cardiac catheterization and biopsy, which was negative for additional pathology.

Continue to: One week after admission...

One week after admission, she was ­discharged home with a 24-hour wearable external cardiac defibrillator and a confirmed diagnosis of peripartum cardiomyopathy. Her medication regimen included digoxin (125 µg 3 times/wk), spironolactone (25 mg/d), carvedilol (3.125 mg twice daily), sacubitril/valsartan (24 mg/26 mg twice daily), furosemide (20 mg/d as needed for weight gain > 3-4 lb or leg swelling), magnesium oxide (400 mg twice daily), and ferrous sulfate (325 mg/d).

DISCUSSION

Peripartum cardiomyopathy is a rare, life-threatening, idiopathic cardiomyopathy that is responsible for one-half to two-thirds of cardiovascular disease–related maternal deaths in the United States.^1,2 It manifests in late pregnancy or early in the postpartum period and is characterized by left ven­tricular systolic dysfunction with resultant heart failure and an ejection fraction of less than 45%.^1,2

Recognized as early as the 1800s by ­Virchow,^2,3 the incidence of peripartum cardiomyopathy in the United States ranges from 1 in 1000 to 4000 live births and is increasing worldwide.^1,2 While the cause of peripartum cardiomyopathy remains unknown, risk factors include advanced maternal age, African descent, hypertension, preeclampsia, and multiple gestation ­pregnancy.^1,2

Early diagnosis of peripartum cardiomyopathy is imperative for survival of both mother and baby.⁴ This may be difficult because the signs and symptoms of heart failure—such as dyspnea, edema, orthopnea, cough, and chest and abdominal pain—overlap with those of a typical pregnancy, resulting in it ­often being missed on evaluation.^1,2

Dx with echocardiography; in a pinch, consider lung ultrasound

Usually a diagnosis of peripartum cardiomyopathy is established with echocardiography.^1,2 Thus, this case is of significant importance because it illustrates the successful use of lung ultrasound—a simple and easy test—by a rural family doctor to identify this potentially fatal, elusive condition with no additional studies.

Continue to: Use of lung ultrasound...

Use of lung ultrasound in the detection of acute decompensated heart failure is accepted in the medical literature.^5-7 Given clinical correlation, a positive scan is defined by the presence of at least 3 B-lines on a longitudinal plane between 2 ribs or, as seen in our case, by the presence of pleural effusion.^5-8 Lung ultrasound is readily available worldwide, is completely safe in pregnancy, and is considered one of the easiest studies to perform.^7-10

At the patient’s 9-month follow-up visit, she had made a full clinical recovery. Her ejection fraction was 59.8%, and she had stopped all medications. The patient and her child did not experience any continued complications.

THE TAKEAWAY

Family physicians should be aware of peripartum cardiomyopathy—one of the most elusive and life-threatening diseases of pregnancy. When managing a pregnant patient, it is imperative to follow up on complaints such as dyspnea, peripheral edema, and chest and/or abdominal pain. While these symptoms are not unusual during pregnancy, they should always prompt a more thorough evaluation. If peripartum cardiomyopathy is suspected, lung ultrasound is a valuable diagnostic tool for family physicians. Further research is needed before the findings of this case report can be universally applied in the routine prenatal care of women at risk for peripartum cardiomyopathy.

Acknowledgement
The authors thank their daughter, Nickel Cielo Abarbanell, for her help in the preparation of this manuscript.

CORRESPONDENCE
Neal Robert Abarbanell, MD, First Choice Healthcare, 1867 20th Avenue, Vero Beach, FL 32960; neal.abarbanell@ gmail.com

THE CASE

A 30-year-old woman sought care at her rural family physician’s office for progressive dyspnea and peripheral edema, which she had been experiencing for several weeks. She was G1P0 and in her 35th week of gestation.

Her medical history was remarkable for mild preeclampsia, which was being managed observantly by her obstetrician in consultation with a maternal-fetal medicine specialist. She had been evaluated by her local hospital’s labor and delivery department and her maternal-fetal medicine specialist earlier in the week and seen the previous day by her obstetrician for these signs and symptoms. They all reassured her and told her these symptoms were normal during pregnancy. No diagnostic studies were performed. However, she remained concerned and decided to see her family physician for another opinion.

Upon presentation to her family physician, the patient was afebrile. Her blood pressure was 135/98 mm Hg; heart rate, 96 beats/min; and respiration, 20 breaths/min and slightly labored. Edema of 2 to 3+ was noted in her lower extremities, hands, and face. Bibasilar breath sounds were diminished, and her abdomen was nontender.

The family physician suspected left ventricular systolic dysfunction. He worked in a small office that lacked access to a laboratory or radiographic studies. However, he did have an ultrasound machine available, and although he was not skilled in echocardiography to assess cardiac function, he was able to obtain a bedside lung ultrasound.

THE DIAGNOSIS

While no B-lines were seen on the lung ultrasound, bilateral plural effusions were noted (FIGURE). This finding, paired with the patient’s signs and symptoms, prompted the family physician to suspect a diagnosis of acute ­decompensated heart failure with presumptive peripartum cardiomyopathy. The patient was immediately driven to the hospital by her family physician for emergency admission with stat obstetric and cardiology ­consultations.

An in-hospital echocardiogram revealed severe global hypokinesia with a left ventricular ejection fraction of 25% to 30%, which confirmed the family physician’s ­suspicions. Laboratory studies were significant for elevated N-terminal pro-brain natriuretic peptide (43,449 pg/mL; normal, < 125 pg/mL), troponin (1.12 ng/mL; normal range, 0-0.10 ng/mL), and white blood cell count (27.6 x 10³/µL). She also had evidence of acute renal injury, with blood urea nitrogen of 46 ­mg/dL (normal range, 7-18 mg/dL), creatinine of 2.0 mg/dL (normal range, 0.5-1.0 mg/dL), and potassium of 7.6 mmol/L (normal range, 3.5-5.1 mmol/L). Emergency delivery was induced by amniotomy, resulting in the birth of a baby girl weighing 5 lb 4 oz (Apgar scores 6, 8, and 9).

This case illustrates the successful use of lung ultrasound to identify a potentially fatal, elusive condition.

Following delivery, the patient was placed on a milrinone infusion and required dialysis. She was emergently transferred to a tertiary care hospital, where she was admitted to the cardiac intensive care unit by the cardiology/heart transplant service with nephrology and obstetric consultations. Hematology and infectious disease specialists were consulted to rule out HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome and sepsis, respectively. Her course of care remained complicated with further testing, including cardiac catheterization and biopsy, which was negative for additional pathology.

Continue to: One week after admission...

One week after admission, she was ­discharged home with a 24-hour wearable external cardiac defibrillator and a confirmed diagnosis of peripartum cardiomyopathy. Her medication regimen included digoxin (125 µg 3 times/wk), spironolactone (25 mg/d), carvedilol (3.125 mg twice daily), sacubitril/valsartan (24 mg/26 mg twice daily), furosemide (20 mg/d as needed for weight gain > 3-4 lb or leg swelling), magnesium oxide (400 mg twice daily), and ferrous sulfate (325 mg/d).

DISCUSSION

Peripartum cardiomyopathy is a rare, life-threatening, idiopathic cardiomyopathy that is responsible for one-half to two-thirds of cardiovascular disease–related maternal deaths in the United States.^1,2 It manifests in late pregnancy or early in the postpartum period and is characterized by left ven­tricular systolic dysfunction with resultant heart failure and an ejection fraction of less than 45%.^1,2

Recognized as early as the 1800s by ­Virchow,^2,3 the incidence of peripartum cardiomyopathy in the United States ranges from 1 in 1000 to 4000 live births and is increasing worldwide.^1,2 While the cause of peripartum cardiomyopathy remains unknown, risk factors include advanced maternal age, African descent, hypertension, preeclampsia, and multiple gestation ­pregnancy.^1,2

Early diagnosis of peripartum cardiomyopathy is imperative for survival of both mother and baby.⁴ This may be difficult because the signs and symptoms of heart failure—such as dyspnea, edema, orthopnea, cough, and chest and abdominal pain—overlap with those of a typical pregnancy, resulting in it ­often being missed on evaluation.^1,2

Dx with echocardiography; in a pinch, consider lung ultrasound

Usually a diagnosis of peripartum cardiomyopathy is established with echocardiography.^1,2 Thus, this case is of significant importance because it illustrates the successful use of lung ultrasound—a simple and easy test—by a rural family doctor to identify this potentially fatal, elusive condition with no additional studies.

Continue to: Use of lung ultrasound...

Use of lung ultrasound in the detection of acute decompensated heart failure is accepted in the medical literature.^5-7 Given clinical correlation, a positive scan is defined by the presence of at least 3 B-lines on a longitudinal plane between 2 ribs or, as seen in our case, by the presence of pleural effusion.^5-8 Lung ultrasound is readily available worldwide, is completely safe in pregnancy, and is considered one of the easiest studies to perform.^7-10

At the patient’s 9-month follow-up visit, she had made a full clinical recovery. Her ejection fraction was 59.8%, and she had stopped all medications. The patient and her child did not experience any continued complications.

THE TAKEAWAY

Family physicians should be aware of peripartum cardiomyopathy—one of the most elusive and life-threatening diseases of pregnancy. When managing a pregnant patient, it is imperative to follow up on complaints such as dyspnea, peripheral edema, and chest and/or abdominal pain. While these symptoms are not unusual during pregnancy, they should always prompt a more thorough evaluation. If peripartum cardiomyopathy is suspected, lung ultrasound is a valuable diagnostic tool for family physicians. Further research is needed before the findings of this case report can be universally applied in the routine prenatal care of women at risk for peripartum cardiomyopathy.

Acknowledgement
The authors thank their daughter, Nickel Cielo Abarbanell, for her help in the preparation of this manuscript.

CORRESPONDENCE
Neal Robert Abarbanell, MD, First Choice Healthcare, 1867 20th Avenue, Vero Beach, FL 32960; neal.abarbanell@ gmail.com

ILLUSTRATIVE CASE

A 24-year-old cisgender man with no significant past medical history comes to your office requesting PrEP after starting a new sexual relationship. His partner is a 26-year-old cisgender man with known HIV. The patient reports that balancing graduate school and work has made him very forgetful, and he worries that he won’t remember to take a daily pill. Are there any other PrEP methods you can offer?

The efficacy of PrEP to reduce HIV acquisition has been established across varying populations at high risk for transmission.¹ PrEP has been found to reduce the risk for sexual acquisition of HIV by nearly 99%.²

Although the use of PrEP in the United States has increased steadily since 2012, adherence to an oral formulation remains a significant issue. One study of > 13,000 people found that daily oral PrEP was discontinued by 52% of participants, only 60% of whom reinitiated the therapy after discontinuation.² Although the federal government has required Medicaid and other insurance providers to cover PrEP in an effort to increase access to the medication, this does not necessarily increase adherence to a daily medication in an often otherwise healthy population.

Long-acting injectable forms of PrEP, which have a reduced dosing frequency that may support adherence, have been studied to potentially replace daily oral pills. This latest study compared cabotegravir (CAB-LA), a long-acting IM injection given every 8 weeks, to daily oral PrEP with tenofovir disoproxil fumarate–emtricitabine (TDF-FTC).¹

STUDY SUMMARY

Decreased seroconversion without daily pills

This randomized, double-blind, double-dummy, noninferiority trial compared long-acting injectable vs daily oral PrEP formulations for the prevention of HIV across an international population. Patients were randomized to receive either CAB-LA 600 mg IM every 8 weeks or TDF-FTC 300/200 mg orally daily. The double-dummy methodology meant that those patients receiving active CAB-LA also received a daily oral placebo, while those patients receiving active TDF-FTC also received a placebo injection every 8 weeks.

Study participants were cisgender MSM or transgender women who have sex with men; ages 18 years and older; and in good health but considered to be at high risk for HIV infection. To be included, participants had to have a negative HIV serologic test at enrollment, undetectable blood HIV RNA viral load within 14 days of enrollment, and creatinine clearance ≥ 60 mL/min. Exclusion criteria included intravenous (IV) drug use within 90 days of enrollment, coagulopathy, buttock implants or fillers, a seizure disorder, or a QTc interval > 500 ms.¹

HIV seroconversion occurred in 0.57% of patients receiving long-acting injectable PrEP vs 1.7% of patients receiving daily oral PrEP.

The intention-to-treat population included 4566 patients: 2282 in the CAB-LA group and 2284 in the TDF-FTC group. Demographic characteristics—including age, race, geographic region, and cohort (MSM vs transgender women)—were not significantly different between groups at baseline. The study lasted 153 weeks, and > 86% of patients were retained at 1 year (median follow-up, 1.4 years; interquartile range, 0.8-1.9).

Continue to: The primary efficacy and safety...

The primary efficacy and safety outcomes of interest were HIV infection and occurrence of a grade ≥ 2 adverse drug reaction, respectively. HIV seroconversion occurred in 13 of 2282 (0.57%) patients in the CAB-LA group and 39 of 2284 (1.7%) patients in the TDF-FTC group (hazard ratio = 0.34; 95% CI, 0.18-0.62). The rate of severe adverse drug reactions was similar between groups. The study was stopped early due to the superiority of CAB-LA.

WHAT’S NEW

Demonstrated superiority of injectable vs oral PrEP

The results of this study could have a monumental impact on the spread of HIV. Since adherence is a known limitation of daily oral PrEP, a long-acting injectable is an intriguing option. The 8-week period between injections offers convenience, allowing primary care physicians (PCPs) to schedule their patients in advance. And because every injection is administered in the office, this option would help PCPs track adherence. Witnessed adherence to the medication, and its demonstrated superiority, could have a significant effect on HIV prevention.

The limited serious adverse effects reported by both groups may ease some PCPs’ hesitation to prescribe CAB-LA.

CAVEATS

More injection-site reactions (but little impact on adherence)

Notably, 81.4% of patients in the CAB-LA group had injection-site reactions vs 31.3% in the TDF-FTC group. However, only 2.4% of patients in the CAB-LA group opted to stop receiving the injections because of these reactions.

Standard PrEP reduces the risk for HIV acquisition from IV drug use by 74%.² However, because IV drug use was an exclusion criterion in this study, future research will need to assess CAB-LA’s effectiveness in that population.

CHALLENGES TO IMPLEMENTATION

Price and storage requirementsof CAB-LA may create issues

CAB-LA is expensive, costing more than $25,000 per year—significantly outpricing TDF-FTC, which costs approximately $8300 per year.³ Insurance coverage for PrEP, including CAB-LA, varies widely. Given the superiority reflected in this study, more efforts should be made to lower the cost of the medication.

Another hurdle for CAB-LA is that it requires refrigeration for storage. Although likely not an issue in most of the United States, it will make adoption of this method difficult in other parts of the world.

ILLUSTRATIVE CASE

A 24-year-old cisgender man with no significant past medical history comes to your office requesting PrEP after starting a new sexual relationship. His partner is a 26-year-old cisgender man with known HIV. The patient reports that balancing graduate school and work has made him very forgetful, and he worries that he won’t remember to take a daily pill. Are there any other PrEP methods you can offer?

The efficacy of PrEP to reduce HIV acquisition has been established across varying populations at high risk for transmission.¹ PrEP has been found to reduce the risk for sexual acquisition of HIV by nearly 99%.²

Although the use of PrEP in the United States has increased steadily since 2012, adherence to an oral formulation remains a significant issue. One study of > 13,000 people found that daily oral PrEP was discontinued by 52% of participants, only 60% of whom reinitiated the therapy after discontinuation.² Although the federal government has required Medicaid and other insurance providers to cover PrEP in an effort to increase access to the medication, this does not necessarily increase adherence to a daily medication in an often otherwise healthy population.

Long-acting injectable forms of PrEP, which have a reduced dosing frequency that may support adherence, have been studied to potentially replace daily oral pills. This latest study compared cabotegravir (CAB-LA), a long-acting IM injection given every 8 weeks, to daily oral PrEP with tenofovir disoproxil fumarate–emtricitabine (TDF-FTC).¹

STUDY SUMMARY

Decreased seroconversion without daily pills

This randomized, double-blind, double-dummy, noninferiority trial compared long-acting injectable vs daily oral PrEP formulations for the prevention of HIV across an international population. Patients were randomized to receive either CAB-LA 600 mg IM every 8 weeks or TDF-FTC 300/200 mg orally daily. The double-dummy methodology meant that those patients receiving active CAB-LA also received a daily oral placebo, while those patients receiving active TDF-FTC also received a placebo injection every 8 weeks.

Study participants were cisgender MSM or transgender women who have sex with men; ages 18 years and older; and in good health but considered to be at high risk for HIV infection. To be included, participants had to have a negative HIV serologic test at enrollment, undetectable blood HIV RNA viral load within 14 days of enrollment, and creatinine clearance ≥ 60 mL/min. Exclusion criteria included intravenous (IV) drug use within 90 days of enrollment, coagulopathy, buttock implants or fillers, a seizure disorder, or a QTc interval > 500 ms.¹

HIV seroconversion occurred in 0.57% of patients receiving long-acting injectable PrEP vs 1.7% of patients receiving daily oral PrEP.

The intention-to-treat population included 4566 patients: 2282 in the CAB-LA group and 2284 in the TDF-FTC group. Demographic characteristics—including age, race, geographic region, and cohort (MSM vs transgender women)—were not significantly different between groups at baseline. The study lasted 153 weeks, and > 86% of patients were retained at 1 year (median follow-up, 1.4 years; interquartile range, 0.8-1.9).

Continue to: The primary efficacy and safety...

The primary efficacy and safety outcomes of interest were HIV infection and occurrence of a grade ≥ 2 adverse drug reaction, respectively. HIV seroconversion occurred in 13 of 2282 (0.57%) patients in the CAB-LA group and 39 of 2284 (1.7%) patients in the TDF-FTC group (hazard ratio = 0.34; 95% CI, 0.18-0.62). The rate of severe adverse drug reactions was similar between groups. The study was stopped early due to the superiority of CAB-LA.

WHAT’S NEW

Demonstrated superiority of injectable vs oral PrEP

The results of this study could have a monumental impact on the spread of HIV. Since adherence is a known limitation of daily oral PrEP, a long-acting injectable is an intriguing option. The 8-week period between injections offers convenience, allowing primary care physicians (PCPs) to schedule their patients in advance. And because every injection is administered in the office, this option would help PCPs track adherence. Witnessed adherence to the medication, and its demonstrated superiority, could have a significant effect on HIV prevention.

The limited serious adverse effects reported by both groups may ease some PCPs’ hesitation to prescribe CAB-LA.

CAVEATS

More injection-site reactions (but little impact on adherence)

Notably, 81.4% of patients in the CAB-LA group had injection-site reactions vs 31.3% in the TDF-FTC group. However, only 2.4% of patients in the CAB-LA group opted to stop receiving the injections because of these reactions.

Standard PrEP reduces the risk for HIV acquisition from IV drug use by 74%.² However, because IV drug use was an exclusion criterion in this study, future research will need to assess CAB-LA’s effectiveness in that population.

CHALLENGES TO IMPLEMENTATION

Price and storage requirementsof CAB-LA may create issues

CAB-LA is expensive, costing more than $25,000 per year—significantly outpricing TDF-FTC, which costs approximately $8300 per year.³ Insurance coverage for PrEP, including CAB-LA, varies widely. Given the superiority reflected in this study, more efforts should be made to lower the cost of the medication.

Another hurdle for CAB-LA is that it requires refrigeration for storage. Although likely not an issue in most of the United States, it will make adoption of this method difficult in other parts of the world.

ILLUSTRATIVE CASE

A 24-year-old cisgender man with no significant past medical history comes to your office requesting PrEP after starting a new sexual relationship. His partner is a 26-year-old cisgender man with known HIV. The patient reports that balancing graduate school and work has made him very forgetful, and he worries that he won’t remember to take a daily pill. Are there any other PrEP methods you can offer?

The efficacy of PrEP to reduce HIV acquisition has been established across varying populations at high risk for transmission.¹ PrEP has been found to reduce the risk for sexual acquisition of HIV by nearly 99%.²

Although the use of PrEP in the United States has increased steadily since 2012, adherence to an oral formulation remains a significant issue. One study of > 13,000 people found that daily oral PrEP was discontinued by 52% of participants, only 60% of whom reinitiated the therapy after discontinuation.² Although the federal government has required Medicaid and other insurance providers to cover PrEP in an effort to increase access to the medication, this does not necessarily increase adherence to a daily medication in an often otherwise healthy population.

Long-acting injectable forms of PrEP, which have a reduced dosing frequency that may support adherence, have been studied to potentially replace daily oral pills. This latest study compared cabotegravir (CAB-LA), a long-acting IM injection given every 8 weeks, to daily oral PrEP with tenofovir disoproxil fumarate–emtricitabine (TDF-FTC).¹

STUDY SUMMARY

Decreased seroconversion without daily pills

This randomized, double-blind, double-dummy, noninferiority trial compared long-acting injectable vs daily oral PrEP formulations for the prevention of HIV across an international population. Patients were randomized to receive either CAB-LA 600 mg IM every 8 weeks or TDF-FTC 300/200 mg orally daily. The double-dummy methodology meant that those patients receiving active CAB-LA also received a daily oral placebo, while those patients receiving active TDF-FTC also received a placebo injection every 8 weeks.

Study participants were cisgender MSM or transgender women who have sex with men; ages 18 years and older; and in good health but considered to be at high risk for HIV infection. To be included, participants had to have a negative HIV serologic test at enrollment, undetectable blood HIV RNA viral load within 14 days of enrollment, and creatinine clearance ≥ 60 mL/min. Exclusion criteria included intravenous (IV) drug use within 90 days of enrollment, coagulopathy, buttock implants or fillers, a seizure disorder, or a QTc interval > 500 ms.¹

HIV seroconversion occurred in 0.57% of patients receiving long-acting injectable PrEP vs 1.7% of patients receiving daily oral PrEP.

The intention-to-treat population included 4566 patients: 2282 in the CAB-LA group and 2284 in the TDF-FTC group. Demographic characteristics—including age, race, geographic region, and cohort (MSM vs transgender women)—were not significantly different between groups at baseline. The study lasted 153 weeks, and > 86% of patients were retained at 1 year (median follow-up, 1.4 years; interquartile range, 0.8-1.9).

Continue to: The primary efficacy and safety...

The primary efficacy and safety outcomes of interest were HIV infection and occurrence of a grade ≥ 2 adverse drug reaction, respectively. HIV seroconversion occurred in 13 of 2282 (0.57%) patients in the CAB-LA group and 39 of 2284 (1.7%) patients in the TDF-FTC group (hazard ratio = 0.34; 95% CI, 0.18-0.62). The rate of severe adverse drug reactions was similar between groups. The study was stopped early due to the superiority of CAB-LA.

WHAT’S NEW

Demonstrated superiority of injectable vs oral PrEP

The results of this study could have a monumental impact on the spread of HIV. Since adherence is a known limitation of daily oral PrEP, a long-acting injectable is an intriguing option. The 8-week period between injections offers convenience, allowing primary care physicians (PCPs) to schedule their patients in advance. And because every injection is administered in the office, this option would help PCPs track adherence. Witnessed adherence to the medication, and its demonstrated superiority, could have a significant effect on HIV prevention.

The limited serious adverse effects reported by both groups may ease some PCPs’ hesitation to prescribe CAB-LA.

CAVEATS

More injection-site reactions (but little impact on adherence)

Notably, 81.4% of patients in the CAB-LA group had injection-site reactions vs 31.3% in the TDF-FTC group. However, only 2.4% of patients in the CAB-LA group opted to stop receiving the injections because of these reactions.

Standard PrEP reduces the risk for HIV acquisition from IV drug use by 74%.² However, because IV drug use was an exclusion criterion in this study, future research will need to assess CAB-LA’s effectiveness in that population.

CHALLENGES TO IMPLEMENTATION

Price and storage requirementsof CAB-LA may create issues

CAB-LA is expensive, costing more than $25,000 per year—significantly outpricing TDF-FTC, which costs approximately $8300 per year.³ Insurance coverage for PrEP, including CAB-LA, varies widely. Given the superiority reflected in this study, more efforts should be made to lower the cost of the medication.

Another hurdle for CAB-LA is that it requires refrigeration for storage. Although likely not an issue in most of the United States, it will make adoption of this method difficult in other parts of the world.

The Centers for Disease Control and Prevention (CDC) recently published new recommendations on screening for hepatitis B infection.¹ They recommend screening all adults (ages 18 years and older) at least once.

These recommendations differ in a few ways from those of the US Preventive Services­ Task Force (USPSTF).² This Practice Alert will highlight these differences but also point out areas of agreement between the 2 sets of ­recommendations—and discuss why 2 separate agencies in the US Department of Health and Human Services reached different conclusions on some issues.

First, some background on hepatitis B

An estimated 580,000 to 2.4 million people in the United States have chronic hepatitis B (CHB) infection—and as many as two-thirds are unaware of it.³ In 2020, the Department of Health and Human Services published the Viral Hepatitis National Strategic Plan for the United States with a stated goal of increasing awareness of infection status among those with hepatitis B virus (HBV) from 32% to 90% by 2030.⁴ People living in the United States but born outside the country are at highest risk for CHB; they account for 69% of those with the infection.⁵

The incidence of acute HBV infection has declined markedly since the HBV vaccine was recommended for high-risk adults in 1982 and universally for infants in 1991.^6,7 Overall rates of HBV infection declined fairly steadily starting around 1987—but in 2014, rates began to increase, especially in those ages 40 to 59 years.^8,9 In 2019, 3192 cases were reported; but when one factors in underreporting, the CDC estimates that the number is likely closer to 20,700.¹⁰ This uptick is one reason the Advisory Committee on Immunization Practices changed its HBV vaccination recommendation for adults from a risk-based to a universal recommendation for all unvaccinated adults through age 60 years.¹⁰

Chronic hepatitis B infection has serious consequences

The proportion of those infected with HBV who develop CHB differs by age at infection: 80% to 90% if infected during infancy, 30% if infected before age 6 years, and 1% to 12% if infected as an older child or adult.⁸

CHB infection can lead to chronic liver disease, including cirrhosis of the liver, liver cancer, and liver failure. About 25% of those who develop CHB infection during childhood and 15% of those who develop chronic infection after childhood will die prematurely from cirrhosis or liver cancer.⁸

The American Association for the Study of Liver Diseases (AASLD) classifies CHB into 4 phases that reflect the rate of viral replication and the patient’s immune response.¹¹ These phases are:

• immune-tolerant (minimal inflammation and fibrosis)
• hepatitis B e-antigen (HBeAg)-positive immune-active (moderate-to-severe inflammation or fibrosis)
• inactive CHB (minimal necroinflammation but variable fibrosis), and
• HBeAg-negative immune reactivation (moderate-to-severe inflammation or fibrosis).¹¹

Continue to: The progression from one phase...

The progression from one phase to the next varies by patient, and not all patients will progress through each phase. The AASLD recommends periodically monitoring the HBV DNA and alanine aminotransferase (ALT) levels in those with CHB to track the progression from one phase to the next and to guide treatment decisions.

Treatment can be beneficial for those who meet criteria

The evidence report prepared for USPSTF found that antiviral treatment of those with CHB infection resulted in improved intermediate outcomes (histologic improvement, loss of hepatitis B surface antigen [HBsAg], loss of HBeAg, HBeAg seroconversion, virologic suppression, and normalization of ALT levels). The magnitude of benefit varied by location and study design.¹²

In addition, the evidence review found that antiviral therapy was associated with a decreased risk for overall mortality (relative risk [RR] = 0.15; 95% CI, 0.03-0.69), cirrhosis (RR = 0.72; 95% CI, 0.29-1.77), and hepatocellular carcinoma (RR = 0.60; 95% CI, 0.16-2.33). However, these results came from studies that were “limited due to small numbers of trials, few events, and insufficient duration of follow-up.”¹²

The USPSTF and the CDC both judged that the intermediate outcome results, as well as findings that improved intermediate outcomes lead to decreases in chronic liver disease, are strong enough evidence for their recommendations.

However, not all patients with CHB infection require treatment; estimates of patients with HBV infection meeting AASLD criteria for treatment range from 24% to 48%.¹ The AASLD guideline on the treatment of CHB infection is an excellent resource that makes recommendations on the initial evaluation, ongoing monitoring, and treatment decisions for those with CHB.¹¹

Continue to: How CDC and USPSTF guidance on HBV screeinng differs

The CDC and USPSTF recommendations for HBV screening differ in 3 aspects: whom to screen, whom to classify as at high risk for HBV infection, and what tests to use for screening.

Who should be screened?

The USPSTF recommends screening adults and adolescents who are at high risk for HBV. The CDC recommends screening all adults at least once. Both entities agree that those who are at increased risk should be screened periodically, although the optimal frequency has not been established. The USPSTF does not recommend against screening for the general population, so universal screening (as advocated by the CDC) is not in direct conflict with the USPSTF’s recommendations.

Who is at increased risk for HBV infection?

The CDC and the USPSTF differ slightly on the factors they consider to constitute increased risk for HBV infection. These are listed in ­TABLE 1.^1,2

The CDC lists 6 categories that the ­USPSTF does not mention. However, 4 of these categories are mentioned indirectly in the USPSTF evidence report that accompanies the recommendations, via statements that certain settings have high proportions of people at risk for HBV infection: sexually transmitted infection clinics; HIV testing and treatment centers; health care settings that target services toward people who inject drugs and men who have sex with men; correctional facilities; hemodialysis facilities; and institutions and nonresidential daycare centers for developmentally disabled persons. People who are served at most of these facilities are also at risk for hepatitis C virus infection.

Three categories are listed by the CDC and not by the USPSTF, in either the recommendation or evidence report. These include a history of multiple sex partners; elevated ALT or aspartate aminotransferase levels of unknown origin; and patient request for testing (because they may not want to reveal risk factors).

Continue to: What test(s) should be ordered?

What test(s) should be ordered? 

The USPSTF recommends screening using HBsAg. The CDC recommends using triple-panel screening: HBsAg, anti-hepatitis B surface antigen (anti-HBs), and total antibody to hepatitis B core antigen (anti-HBc).

HBsAg indicates HBV infection, either acute or chronic, or a recent dose of HBV vaccine. Anti-HBs indicate recovery from HBV infection, response to HBV vaccine, or recent receipt of hepatitis B immune globulin. Total anti-HBc develops in all HBV infections, resolved or current, and usually persists for life. Vaccine-induced immunity does not cause anti-HBc to develop.

The USPSTF’s rationale is that testing for HBsAg is more than 98% sensitive and specific for detecting HBV infections.² The CDC recommends triple testing because it can detect those with asymptomatic active HBV infections (this would be a rare occurrence); those who have resolved infection and might be susceptible to reactivation (eg, those who are immunosuppressed); and those who are susceptible and need vaccination.

Interpretation of HBV test results and suggested actions are described in TABLE 2.^1,8,13

Why do the CDC and USPSTF differ?

While it would be optimal if the CDC and the USPSTF coordinated and harmonized recommendations, this is difficult to achieve given their different missions. The USPSTF is charged to make evidence-based recommendations about preventive services such as screenings, behavioral counseling, and preventive medications, which are provided by clinicians to individual patients. The Task Force uses a very strict evidence-based process and will not make recommendations unless there is adequate evidence of efficacy and safety. Members of the Task Force are primary care professionals, and their collaborating professional organizations are primary care focused.

Based on practice-specific characteristics, family physicians should decide if they want to screen all adults or only those at increased risk, and whether to use singleor triple-test screening.

The CDC takes a community-wide, public health perspective. The professionals that work there are not always clinicians. They strive to prevent as much illness as possible, using public health measures and making recommendations to clinicians. They collaborate with professional organizations; on topics such as hepatitis and other infectious diseases, they collaborate with specialty-oriented societies. Given the imperative to act with the best evidence available, their evidence assessment process is not as strict.

The result, at times, is slight differences in recommendations. However, the HBV screening recommendations from the CDC and the USPSTF agree more than they do not. Based on practice-specific characteristics, family physicians should decide if they want to screen all adults or only those at increased risk, and whether to use single- or triple-test screening.

The Centers for Disease Control and Prevention (CDC) recently published new recommendations on screening for hepatitis B infection.¹ They recommend screening all adults (ages 18 years and older) at least once.

These recommendations differ in a few ways from those of the US Preventive Services­ Task Force (USPSTF).² This Practice Alert will highlight these differences but also point out areas of agreement between the 2 sets of ­recommendations—and discuss why 2 separate agencies in the US Department of Health and Human Services reached different conclusions on some issues.

First, some background on hepatitis B

An estimated 580,000 to 2.4 million people in the United States have chronic hepatitis B (CHB) infection—and as many as two-thirds are unaware of it.³ In 2020, the Department of Health and Human Services published the Viral Hepatitis National Strategic Plan for the United States with a stated goal of increasing awareness of infection status among those with hepatitis B virus (HBV) from 32% to 90% by 2030.⁴ People living in the United States but born outside the country are at highest risk for CHB; they account for 69% of those with the infection.⁵

The incidence of acute HBV infection has declined markedly since the HBV vaccine was recommended for high-risk adults in 1982 and universally for infants in 1991.^6,7 Overall rates of HBV infection declined fairly steadily starting around 1987—but in 2014, rates began to increase, especially in those ages 40 to 59 years.^8,9 In 2019, 3192 cases were reported; but when one factors in underreporting, the CDC estimates that the number is likely closer to 20,700.¹⁰ This uptick is one reason the Advisory Committee on Immunization Practices changed its HBV vaccination recommendation for adults from a risk-based to a universal recommendation for all unvaccinated adults through age 60 years.¹⁰

Chronic hepatitis B infection has serious consequences

The proportion of those infected with HBV who develop CHB differs by age at infection: 80% to 90% if infected during infancy, 30% if infected before age 6 years, and 1% to 12% if infected as an older child or adult.⁸

CHB infection can lead to chronic liver disease, including cirrhosis of the liver, liver cancer, and liver failure. About 25% of those who develop CHB infection during childhood and 15% of those who develop chronic infection after childhood will die prematurely from cirrhosis or liver cancer.⁸

The American Association for the Study of Liver Diseases (AASLD) classifies CHB into 4 phases that reflect the rate of viral replication and the patient’s immune response.¹¹ These phases are:

• immune-tolerant (minimal inflammation and fibrosis)
• hepatitis B e-antigen (HBeAg)-positive immune-active (moderate-to-severe inflammation or fibrosis)
• inactive CHB (minimal necroinflammation but variable fibrosis), and
• HBeAg-negative immune reactivation (moderate-to-severe inflammation or fibrosis).¹¹

Continue to: The progression from one phase...

The progression from one phase to the next varies by patient, and not all patients will progress through each phase. The AASLD recommends periodically monitoring the HBV DNA and alanine aminotransferase (ALT) levels in those with CHB to track the progression from one phase to the next and to guide treatment decisions.

Treatment can be beneficial for those who meet criteria

The evidence report prepared for USPSTF found that antiviral treatment of those with CHB infection resulted in improved intermediate outcomes (histologic improvement, loss of hepatitis B surface antigen [HBsAg], loss of HBeAg, HBeAg seroconversion, virologic suppression, and normalization of ALT levels). The magnitude of benefit varied by location and study design.¹²

In addition, the evidence review found that antiviral therapy was associated with a decreased risk for overall mortality (relative risk [RR] = 0.15; 95% CI, 0.03-0.69), cirrhosis (RR = 0.72; 95% CI, 0.29-1.77), and hepatocellular carcinoma (RR = 0.60; 95% CI, 0.16-2.33). However, these results came from studies that were “limited due to small numbers of trials, few events, and insufficient duration of follow-up.”¹²

The USPSTF and the CDC both judged that the intermediate outcome results, as well as findings that improved intermediate outcomes lead to decreases in chronic liver disease, are strong enough evidence for their recommendations.

However, not all patients with CHB infection require treatment; estimates of patients with HBV infection meeting AASLD criteria for treatment range from 24% to 48%.¹ The AASLD guideline on the treatment of CHB infection is an excellent resource that makes recommendations on the initial evaluation, ongoing monitoring, and treatment decisions for those with CHB.¹¹

Continue to: How CDC and USPSTF guidance on HBV screeinng differs

The CDC and USPSTF recommendations for HBV screening differ in 3 aspects: whom to screen, whom to classify as at high risk for HBV infection, and what tests to use for screening.

Who should be screened?

The USPSTF recommends screening adults and adolescents who are at high risk for HBV. The CDC recommends screening all adults at least once. Both entities agree that those who are at increased risk should be screened periodically, although the optimal frequency has not been established. The USPSTF does not recommend against screening for the general population, so universal screening (as advocated by the CDC) is not in direct conflict with the USPSTF’s recommendations.

Who is at increased risk for HBV infection?

The CDC and the USPSTF differ slightly on the factors they consider to constitute increased risk for HBV infection. These are listed in ­TABLE 1.^1,2

The CDC lists 6 categories that the ­USPSTF does not mention. However, 4 of these categories are mentioned indirectly in the USPSTF evidence report that accompanies the recommendations, via statements that certain settings have high proportions of people at risk for HBV infection: sexually transmitted infection clinics; HIV testing and treatment centers; health care settings that target services toward people who inject drugs and men who have sex with men; correctional facilities; hemodialysis facilities; and institutions and nonresidential daycare centers for developmentally disabled persons. People who are served at most of these facilities are also at risk for hepatitis C virus infection.

Three categories are listed by the CDC and not by the USPSTF, in either the recommendation or evidence report. These include a history of multiple sex partners; elevated ALT or aspartate aminotransferase levels of unknown origin; and patient request for testing (because they may not want to reveal risk factors).

Continue to: What test(s) should be ordered?

What test(s) should be ordered? 

The USPSTF recommends screening using HBsAg. The CDC recommends using triple-panel screening: HBsAg, anti-hepatitis B surface antigen (anti-HBs), and total antibody to hepatitis B core antigen (anti-HBc).

HBsAg indicates HBV infection, either acute or chronic, or a recent dose of HBV vaccine. Anti-HBs indicate recovery from HBV infection, response to HBV vaccine, or recent receipt of hepatitis B immune globulin. Total anti-HBc develops in all HBV infections, resolved or current, and usually persists for life. Vaccine-induced immunity does not cause anti-HBc to develop.

The USPSTF’s rationale is that testing for HBsAg is more than 98% sensitive and specific for detecting HBV infections.² The CDC recommends triple testing because it can detect those with asymptomatic active HBV infections (this would be a rare occurrence); those who have resolved infection and might be susceptible to reactivation (eg, those who are immunosuppressed); and those who are susceptible and need vaccination.

Interpretation of HBV test results and suggested actions are described in TABLE 2.^1,8,13

Why do the CDC and USPSTF differ?

While it would be optimal if the CDC and the USPSTF coordinated and harmonized recommendations, this is difficult to achieve given their different missions. The USPSTF is charged to make evidence-based recommendations about preventive services such as screenings, behavioral counseling, and preventive medications, which are provided by clinicians to individual patients. The Task Force uses a very strict evidence-based process and will not make recommendations unless there is adequate evidence of efficacy and safety. Members of the Task Force are primary care professionals, and their collaborating professional organizations are primary care focused.

Based on practice-specific characteristics, family physicians should decide if they want to screen all adults or only those at increased risk, and whether to use singleor triple-test screening.

The CDC takes a community-wide, public health perspective. The professionals that work there are not always clinicians. They strive to prevent as much illness as possible, using public health measures and making recommendations to clinicians. They collaborate with professional organizations; on topics such as hepatitis and other infectious diseases, they collaborate with specialty-oriented societies. Given the imperative to act with the best evidence available, their evidence assessment process is not as strict.

The result, at times, is slight differences in recommendations. However, the HBV screening recommendations from the CDC and the USPSTF agree more than they do not. Based on practice-specific characteristics, family physicians should decide if they want to screen all adults or only those at increased risk, and whether to use single- or triple-test screening.

The Centers for Disease Control and Prevention (CDC) recently published new recommendations on screening for hepatitis B infection.¹ They recommend screening all adults (ages 18 years and older) at least once.

These recommendations differ in a few ways from those of the US Preventive Services­ Task Force (USPSTF).² This Practice Alert will highlight these differences but also point out areas of agreement between the 2 sets of ­recommendations—and discuss why 2 separate agencies in the US Department of Health and Human Services reached different conclusions on some issues.

First, some background on hepatitis B

An estimated 580,000 to 2.4 million people in the United States have chronic hepatitis B (CHB) infection—and as many as two-thirds are unaware of it.³ In 2020, the Department of Health and Human Services published the Viral Hepatitis National Strategic Plan for the United States with a stated goal of increasing awareness of infection status among those with hepatitis B virus (HBV) from 32% to 90% by 2030.⁴ People living in the United States but born outside the country are at highest risk for CHB; they account for 69% of those with the infection.⁵

The incidence of acute HBV infection has declined markedly since the HBV vaccine was recommended for high-risk adults in 1982 and universally for infants in 1991.^6,7 Overall rates of HBV infection declined fairly steadily starting around 1987—but in 2014, rates began to increase, especially in those ages 40 to 59 years.^8,9 In 2019, 3192 cases were reported; but when one factors in underreporting, the CDC estimates that the number is likely closer to 20,700.¹⁰ This uptick is one reason the Advisory Committee on Immunization Practices changed its HBV vaccination recommendation for adults from a risk-based to a universal recommendation for all unvaccinated adults through age 60 years.¹⁰

Chronic hepatitis B infection has serious consequences

The proportion of those infected with HBV who develop CHB differs by age at infection: 80% to 90% if infected during infancy, 30% if infected before age 6 years, and 1% to 12% if infected as an older child or adult.⁸

CHB infection can lead to chronic liver disease, including cirrhosis of the liver, liver cancer, and liver failure. About 25% of those who develop CHB infection during childhood and 15% of those who develop chronic infection after childhood will die prematurely from cirrhosis or liver cancer.⁸

The American Association for the Study of Liver Diseases (AASLD) classifies CHB into 4 phases that reflect the rate of viral replication and the patient’s immune response.¹¹ These phases are:

• immune-tolerant (minimal inflammation and fibrosis)
• hepatitis B e-antigen (HBeAg)-positive immune-active (moderate-to-severe inflammation or fibrosis)
• inactive CHB (minimal necroinflammation but variable fibrosis), and
• HBeAg-negative immune reactivation (moderate-to-severe inflammation or fibrosis).¹¹

Continue to: The progression from one phase...

The progression from one phase to the next varies by patient, and not all patients will progress through each phase. The AASLD recommends periodically monitoring the HBV DNA and alanine aminotransferase (ALT) levels in those with CHB to track the progression from one phase to the next and to guide treatment decisions.

Treatment can be beneficial for those who meet criteria

The evidence report prepared for USPSTF found that antiviral treatment of those with CHB infection resulted in improved intermediate outcomes (histologic improvement, loss of hepatitis B surface antigen [HBsAg], loss of HBeAg, HBeAg seroconversion, virologic suppression, and normalization of ALT levels). The magnitude of benefit varied by location and study design.¹²

In addition, the evidence review found that antiviral therapy was associated with a decreased risk for overall mortality (relative risk [RR] = 0.15; 95% CI, 0.03-0.69), cirrhosis (RR = 0.72; 95% CI, 0.29-1.77), and hepatocellular carcinoma (RR = 0.60; 95% CI, 0.16-2.33). However, these results came from studies that were “limited due to small numbers of trials, few events, and insufficient duration of follow-up.”¹²

The USPSTF and the CDC both judged that the intermediate outcome results, as well as findings that improved intermediate outcomes lead to decreases in chronic liver disease, are strong enough evidence for their recommendations.

However, not all patients with CHB infection require treatment; estimates of patients with HBV infection meeting AASLD criteria for treatment range from 24% to 48%.¹ The AASLD guideline on the treatment of CHB infection is an excellent resource that makes recommendations on the initial evaluation, ongoing monitoring, and treatment decisions for those with CHB.¹¹

Continue to: How CDC and USPSTF guidance on HBV screeinng differs

The CDC and USPSTF recommendations for HBV screening differ in 3 aspects: whom to screen, whom to classify as at high risk for HBV infection, and what tests to use for screening.

Who should be screened?

The USPSTF recommends screening adults and adolescents who are at high risk for HBV. The CDC recommends screening all adults at least once. Both entities agree that those who are at increased risk should be screened periodically, although the optimal frequency has not been established. The USPSTF does not recommend against screening for the general population, so universal screening (as advocated by the CDC) is not in direct conflict with the USPSTF’s recommendations.

Who is at increased risk for HBV infection?

The CDC and the USPSTF differ slightly on the factors they consider to constitute increased risk for HBV infection. These are listed in ­TABLE 1.^1,2

The CDC lists 6 categories that the ­USPSTF does not mention. However, 4 of these categories are mentioned indirectly in the USPSTF evidence report that accompanies the recommendations, via statements that certain settings have high proportions of people at risk for HBV infection: sexually transmitted infection clinics; HIV testing and treatment centers; health care settings that target services toward people who inject drugs and men who have sex with men; correctional facilities; hemodialysis facilities; and institutions and nonresidential daycare centers for developmentally disabled persons. People who are served at most of these facilities are also at risk for hepatitis C virus infection.

Three categories are listed by the CDC and not by the USPSTF, in either the recommendation or evidence report. These include a history of multiple sex partners; elevated ALT or aspartate aminotransferase levels of unknown origin; and patient request for testing (because they may not want to reveal risk factors).

Continue to: What test(s) should be ordered?

What test(s) should be ordered? 

The USPSTF recommends screening using HBsAg. The CDC recommends using triple-panel screening: HBsAg, anti-hepatitis B surface antigen (anti-HBs), and total antibody to hepatitis B core antigen (anti-HBc).

HBsAg indicates HBV infection, either acute or chronic, or a recent dose of HBV vaccine. Anti-HBs indicate recovery from HBV infection, response to HBV vaccine, or recent receipt of hepatitis B immune globulin. Total anti-HBc develops in all HBV infections, resolved or current, and usually persists for life. Vaccine-induced immunity does not cause anti-HBc to develop.

The USPSTF’s rationale is that testing for HBsAg is more than 98% sensitive and specific for detecting HBV infections.² The CDC recommends triple testing because it can detect those with asymptomatic active HBV infections (this would be a rare occurrence); those who have resolved infection and might be susceptible to reactivation (eg, those who are immunosuppressed); and those who are susceptible and need vaccination.

Interpretation of HBV test results and suggested actions are described in TABLE 2.^1,8,13

Why do the CDC and USPSTF differ?

While it would be optimal if the CDC and the USPSTF coordinated and harmonized recommendations, this is difficult to achieve given their different missions. The USPSTF is charged to make evidence-based recommendations about preventive services such as screenings, behavioral counseling, and preventive medications, which are provided by clinicians to individual patients. The Task Force uses a very strict evidence-based process and will not make recommendations unless there is adequate evidence of efficacy and safety. Members of the Task Force are primary care professionals, and their collaborating professional organizations are primary care focused.

Based on practice-specific characteristics, family physicians should decide if they want to screen all adults or only those at increased risk, and whether to use singleor triple-test screening.

The CDC takes a community-wide, public health perspective. The professionals that work there are not always clinicians. They strive to prevent as much illness as possible, using public health measures and making recommendations to clinicians. They collaborate with professional organizations; on topics such as hepatitis and other infectious diseases, they collaborate with specialty-oriented societies. Given the imperative to act with the best evidence available, their evidence assessment process is not as strict.

The result, at times, is slight differences in recommendations. However, the HBV screening recommendations from the CDC and the USPSTF agree more than they do not. Based on practice-specific characteristics, family physicians should decide if they want to screen all adults or only those at increased risk, and whether to use single- or triple-test screening.

Evidence supports what family physicians know to be true: Knee pain is an exceedingly common presenting problem in the primary care office. Estimates of lifetime incidence reach as high as 54%,¹ and the prevalence of knee pain in the general population is increasing.² Knee disability can result from acute or traumatic injuries as well as chronic, degenerative conditions such as osteoarthritis (OA). The decision to pursue orthopedic consultation for a particular injury or painful knee condition can be challenging. To address this, we highlight specific knee diagnoses known to cause pain, with the aim of describing which conditions likely will necessitate surgical consultation—and which won’t.

Acute or nondegenerative knee injuries and pain

Acute knee injuries range in severity from simple contusions and sprains to high-energy, traumatic injuries with resulting joint instability and potential neurovascular compromise. While conservative treatment often is successful for many simple injuries, surgical management—sometimes urgently or emergently—is needed in other cases, as will be detailed shortly.

Neurovascular injury associated with knee dislocations

Acute neurovascular injuries often require emergent surgical intervention. Although rare, tibiofemoral (knee) dislocations pose a significant challenge to the clinician in both diagnosis and management. The reported frequency of popliteal artery injury or rupture following a dislocation varies widely, with rates ranging from 5% to 64%, according to older studies; more recent data, however, suggest the rate is actually as low as 3.3%.³ Vascular injury can lead to irreversible tissue damage and even limb loss if not promptly identified. Identifying a knee dislocation can prove challenging, as spontaneous joint reduction occurs in as many as 50% of cases, potentially shrouding the severity of the injury on initial evaluation.⁴

Immediate immobilization and emergency department transport for monitoring, orthopedics consultation, and vascular ­studies or vascular surgery consultation is recommended in the case of a suspected knee dislocation. In one cross-sectional cohort study, the surgical management of knee ­dislocations yielded favorable outcomes in > 75% of cases.⁵

Tibial plateau fracture

This fracture often occurs as a result of high-energy trauma, such as contact sports or motor vehicle accidents, and is characterized by a proximal tibial fracture line with extension to the articular surface. X-rays often are sufficient for initial diagnosis. Computed tomo­graphy can help rule out a fracture line when clinical suspicion is high and x-rays are nondiagnostic. As noted earlier, any suggestion of neurovascular compromise on physical exam requires an emergent orthopedic surgeon consultation for a possible displaced and unstable (or more complex) injury (FIGURE 1).^6-8

Nondisplaced tibial plateau fractures without supraphysiologic ligamentous laxity on valgus or varus stress testing can be managed safely with protection and early mobilization, gradual progression of weight-bearing, and serial x-rays to ensure fracture healing and stability. Surgical management and fixation are required emergently for open fractures or gross joint instability with vascular or neurologic compromise. Suspicion of these complications is raised by distal neuropathic symptoms of paresthesia or skin anesthesia, progressively worsening pain distal to the knee, or vascular signs of pallor, delayed or lost capillary refill, or decreased or absent distal pulses.

Gross joint instability identified by positive valgus or varus stress testing, positive anterior or posterior drawer testing, or patient inability to tolerate these maneuvers due to pain similarly should raise suspicion for a more significant fracture at risk for concurrent neurovascular injury. Acute compartment syndrome also is a known complication of tibial plateau fractures and similarly requires emergent operative management. Urgent surgical consultation is recommended for fractures with displaced fracture fragments, tibial articular surface step-off or depression, fractures with concurrent joint laxity, or medial plateau fractures.^6-8

Continue to: Patella fractures

Patella fractures

These fractures occur as a direct blow to the front of the knee, such as falling forward onto a hard surface, or indirectly due to a sudden extreme eccentric contraction of the quadriceps muscle. Nondisplaced fractures with an intact knee extension mechanism, which is examined via a supine straight-leg raise or seated knee extension, are managed with weight-bearing as tolerated in strict immobilization in full extension for 4 to 6 weeks, with active range-of-motion and isometric quadriceps exercises beginning in 1 to 2 weeks. Serial x-rays also are obtained to ensure fracture displacement does not occur during the rehabilitation process.⁹

High-quality evidence guiding follow-up care and comparing outcomes of surgical and nonsurgical management of patella fractures is lacking, and studies comparing different surgical techniques are of lower methodological quality.¹⁰ Nevertheless, displaced or comminuted patellar fractures are referred urgently to orthopedic surgical care for fixation, as are those with concurrent loose bodies, chondral surface injuries or articular step-off, or osteochondral fractures.⁹ Inability to perform a straight-leg raise (ie, clinical loss of the knee extension mechanism) suggests a fracture under tension that likely also requires surgical fixation for successful recovery. Neurovascular injuries are unlikely in most patellar fractures but would require emergent surgical consultation.⁹

Ligamentous injury

Tibiofemoral joint laxity occurs as a result of ligamentous injury, with or without tibial plateau fracture. The anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), medial collateral ligament (MCL), and lateral collateral ligament (LCL) comprise the 4 main ligaments of the knee. The ACL resists anterior tibial translation and rotational forces, while the PCL resists posterior tibial translation. The MCL and LCL resist valgus and varus stress, respectively.

Ligament injuries are classified as Grades 1 to 3¹¹:

• Grade 1 sprains. The ligament is stretched, but there is no macroscopic tearing; joint stability is maintained.
• Grade 2 sprains. There are partial macroscopic ligament tears. There is joint laxity due to the partial loss of the ligament’s structural integrity.
• Grade 3 sprains. The ligament is fully avulsed or ruptured with resultant gross joint instability.

Vascular injury can lead to irreversible tissue damage and even limb loss if not promptly identified.

The decision to pursue surgical repair of a knee sprain depends heavily on the likelihood of keeping or regaining and maintaining functional joint stability during the injury recovery and postinjury time periods. Injuries that do not result in joint instability or injuries with a high likelihood of returning to a stable state with conservative measures often do not require surgical intervention.

Continue to: ACL tears

ACL tears occur most commonly via a noncontact event, as when an individual plants their foot and suddenly changes direction during sport or other physical activity. Treatment hinges on patient activity levels and participation in sports. Patients who do not plan to engage in athletic movements (that require changes in direction or planting and twisting) and who otherwise maintain satisfactory joint stability during activities of daily living may elect to defer or even altogether avoid surgical reconstruction of isolated ACL tears. One pair of studies demonstrated equivalent outcomes in surgical and nonsurgical management in 121 young, nonelite athletes at 2- and 5-year follow-up, although the crossover from the nonsurgical to surgical groups was high.^12,13 Athletes who regain satisfactory function and stability nonoperatively can defer surgical intervention. However, the majority of active patients and athletes will require surgical ACL reconstruction to return to pre-injury functional levels.¹⁴

PCL sprains occur as a result of sudden posteriorly directed force on the tibia, such as when the knee is hyperextended or a patient falls directly onto a flexed knee. Patients with Grade 1 and 2 isolated sprains generally will recover with conservative care, as will patients with some Grade 3 complete tears that do not fully compromise joint stability. However, high-grade PCL injuries often are comorbid with posterolateral corner or other injuries, leading to a higher likelihood of joint instability and thus the need for surgical intervention for the best chance at an optimal outcome.¹⁵

MCL sprain. Surgical management is not required in an isolated Grade 1 or 2 MCL sprain, as the hallmarks of recovery—return of joint stability, knee strength and range of motion, and pain ­reduction—can be achieved successfully with conservative management. Isolated Grade 3 MCL sprains are also successfully managed nonoperatively¹⁶ except in specific cases, such as a concurrent large avulsion fracture.¹⁷

LCL sprain. Similarly, isolated Grade 1 and 2 LCL sprains generally do not require surgical intervention. However, Grade 3 LCL injuries usually do, as persistent joint instability and poor functional outcomes are more common with nonsurgical management.^18-20 Additionally, high-grade LCL injuries frequently manifest with comorbid meniscus injuries or sprains of the posterolateral corner of the knee, a complex anatomic structure that provides both static and dynamic tibiofemoral joint stability. Surgical repair or reconstruction of the posterolateral corner frequently is necessary for optimal functional outcomes.²¹

Multiligamentous sprains frequently lead to gross joint instability and necessitate orthopedic surgeon consultation to determine the best treatment plan; this should be done emergently if neurovascular compromise is suspected. A common injury combination is simultaneous ACL and MCL sprains with or without meniscus injury. In these cases, some surgeons will choose to defer ACL reconstruction until after MCL healing is achieved. This allows the patient to regain valgus stability of the joint prior to performing ACL reconstruction to regain rotational and anterior stability.²⁰

Continue to: Patellar dislocations

Patellar dislocations represent a relatively common knee injury in young active patients, often occurring in a noncontact fashion when a valgus force is applied to an externally rotated and planted lower leg. A chief risk factor for a patellar dislocation is a history of prior dislocation. If rehabilitation following a dislocation is insufficient to regain patellofemoral joint stability, or if certain risk factors for recurrent dislocation are present, surgical intervention, such as medial patellofemoral ligament (MPFL) reconstruction or tibial tubercle transfer, is considered.²² A systematic review concluded that MPFL reconstruction following a first-time dislocation yielded lower redislocation rates of 7% compared to 30% with nonoperative treatment.²³

Major tendon rupture

Patellar tendon ruptures occur when a sudden eccentric force is applied to the knee, such as when landing from a jump with the knee flexed. Patellar tendon ruptures frequently are clinically apparent, with patients demonstrating a high-riding patella and loss of active knee extension. Quadriceps tendon ruptures often result from a similar injury mechanism in older patients, with a similar loss of active knee extension and a palpable gap superior to the patella.²⁴

Partial tears in patients who can maintain full extension of the knee against gravity are treated nonoperatively, but early surgical repair is indicated for complete quadriceps or patellar tendon ruptures to achieve optimal outcomes. Prompt diagnosis and treatment are critical, as repair delayed beyond 1 to 2 weeks postinjury is associated with worse outcomes.^25-28

Surgical management and fixation are required emergently for open fractures or gross joint instability with vascular or neurologic compromise.

Even with prompt treatment, return to sport is not guaranteed. According to a recent systematic review, athletes returned to play 88.9% and 89.8% of the time following patellar and quadriceps tendon repairs, respectively. However, returning to the same level of play was less common and achieved 80.8% (patellar tendon repair) and 70% (quadriceps tendon repair) of the time. Return-to-work rates were higher, at 96% for both surgical treatments.²⁹

Locked knee and acute meniscus tears in younger patients

In some acute knee injuries, meniscus tears, loose cartilage bodies or osteochondral defects, or other internal structures can become interposed between the femoral and tibial surfaces, preventing both active and passive knee extension. Such injuries are often severely painful and functionally debilitating. While manipulation under anesthesia can acutely restore joint function,³⁰ diagnostic and therapeutic arthroscopy often is pursued for definitive treatment.³¹ Compared to the gold standard of diagnostic arthroscopy, preoperative magnetic resonance imaging (MRI) carries positive and negative predictive values of 85% and 77%, respectively, in identifying or ruling out the anatomic structure responsible for a locked knee. ³² As such, MRI has been proposed as a method to avoid performing arthroscopy on a patient with a “pseudo-locked” knee, or loss of range of motion due to pain but without a true mechanical block.³²

Continue to: Depending on the location...

Depending on the location, size, and shape of an acute meniscus tear in younger patients, surgical repair may be an option to preserve long-term joint function. In one case series of patients younger than 20 years, 62% of meniscus repairs yielded good outcomes after a mean follow-up period of 16.8 years.³³

Osteochondritis dissecans

Osteochondritis dissecans is characterized by subchondral bone osteonecrosis that most often occurs in pediatric patients, potentially causing the separation of a fragment of articular cartilage and subchondral bone into the joint space (FIGURE 2). In early stages, nonoperative treatment consisting of prolonged rest followed by physical therapy to gradually return to activity is recommended to prevent small, low-grade lesions from progressing to unstable or separated fragments. Arthroscopy, which consists of microfracture or other surgical resurfacing techniques to restore joint integrity, is pursued in more advanced cases of unstable or separated fragments.

High-quality data guiding the management of osteochondritis dissecans are lacking, and these recommendations are based on consensus guidelines.³⁴

Septic arthritis

Septic arthritis is a medical emergency caused by the hematogenous spread of microorganisms, most often staphylococci and streptococci species. Less commonly, it arises from direct inoculation through an open wound or, rarely, iatrogenically following a joint injection procedure. Clinical signs of septic arthritis include joint pain, joint swelling, and fever. Passive range of motion of the joint is often severely painful. Synovial fluid studies consistent with septic arthritis include an elevated white blood cell count greater than 25,000/mcL with polymorphonuclear cell predominance.³⁵ The knee accounts for more than 50% of septic arthritis cases, and surgical drainage usually is required to achieve infection source control and decrease morbidity and mortality due to destruction of articular cartilage when treatment is delayed.³⁶

Chronic knee injuries and pain

Surgical intervention for chronic knee injuries and pain generally is considered when patients demonstrate significant functional impairment and persistent symptoms despite pursuing numerous nonsurgical treatment options. A significant portion of chronic knee pain is due to degenerative processes such as OA or meniscus injuries, or tears without a history of trauma that do not cause locking of the knee. Treatments for degenerative knee pain include supervised exercise, physical therapy, bracing, offloading with a cane or other equipment, topical or oral ­anti-inflammatories or analgesics, and injectable therapies such as intra-articular ­corticosteroids.³⁷

Continue to: Other common causes...

Other common causes of chronic knee pain include chronic tendinopathy or biomechanical syndromes such as patellofemoral pain syndrome or iliotibial band syndrome. Surgical treatment of these conditions is pursued in select cases and only after exhausting nonoperative treatment programs, as recommended by international consensus statements,³⁸ societal guidelines,³⁹ and expert opinion.⁴⁰ High-quality data on the effectiveness, or ineffectiveness, of surgical intervention for these conditions are lacking.

A chief risk factor for a patellar dislocation is a history of prior dislocation.

Despite being one of the most commonly performed surgical procedures in the United States,⁴¹ arthroscopic partial meniscectomy treatment of degenerative meniscus tears does not lead to improved outcomes compared to nonsurgical management, according to multiple recent studies.^42-45 Evidence does not support routine arthroscopic intervention for degenerative meniscus tears or OA,⁴² and recent guidelines recommend against it⁴⁶ or to pursue it only after nonsurgical treatments have failed.³⁷

Surgical management of degenerative knee conditions generally consists of partial or total arthroplasty and is similarly considered after failure of conservative measures. Appropriate use criteria that account for multiple clinical and patient factors are used to enhance patient selection for the procedure.⁴⁷

Takeaways

Primary care clinicians will treat patients sustaining knee injuries and see many patients with knee pain in the outpatient setting. Treatment options vary considerably depending on the underlying diagnosis and resulting functional losses. Several categories of clinical presentation, including neurovascular injury, unstable or displaced fractures, joint instability, major tendon rupture, significant mechanical symptoms such as a locked knee, certain osteochondral injuries, and septic arthritis, likely or almost always warrant surgical consultation ­(TABLE^3-10,12-36). Occasionally, as in the case of neurovascular injury or septic arthritis, such consultation should be emergent.

CORRESPONDENCE
David M. Siebert, MD, Sports Medicine Center at Husky Stadium, 3800 Montlake Boulevard NE, Seattle, WA 98195; [email protected]

Evidence supports what family physicians know to be true: Knee pain is an exceedingly common presenting problem in the primary care office. Estimates of lifetime incidence reach as high as 54%,¹ and the prevalence of knee pain in the general population is increasing.² Knee disability can result from acute or traumatic injuries as well as chronic, degenerative conditions such as osteoarthritis (OA). The decision to pursue orthopedic consultation for a particular injury or painful knee condition can be challenging. To address this, we highlight specific knee diagnoses known to cause pain, with the aim of describing which conditions likely will necessitate surgical consultation—and which won’t.

Acute or nondegenerative knee injuries and pain

Acute knee injuries range in severity from simple contusions and sprains to high-energy, traumatic injuries with resulting joint instability and potential neurovascular compromise. While conservative treatment often is successful for many simple injuries, surgical management—sometimes urgently or emergently—is needed in other cases, as will be detailed shortly.

Neurovascular injury associated with knee dislocations

Acute neurovascular injuries often require emergent surgical intervention. Although rare, tibiofemoral (knee) dislocations pose a significant challenge to the clinician in both diagnosis and management. The reported frequency of popliteal artery injury or rupture following a dislocation varies widely, with rates ranging from 5% to 64%, according to older studies; more recent data, however, suggest the rate is actually as low as 3.3%.³ Vascular injury can lead to irreversible tissue damage and even limb loss if not promptly identified. Identifying a knee dislocation can prove challenging, as spontaneous joint reduction occurs in as many as 50% of cases, potentially shrouding the severity of the injury on initial evaluation.⁴

Immediate immobilization and emergency department transport for monitoring, orthopedics consultation, and vascular ­studies or vascular surgery consultation is recommended in the case of a suspected knee dislocation. In one cross-sectional cohort study, the surgical management of knee ­dislocations yielded favorable outcomes in > 75% of cases.⁵

Tibial plateau fracture

This fracture often occurs as a result of high-energy trauma, such as contact sports or motor vehicle accidents, and is characterized by a proximal tibial fracture line with extension to the articular surface. X-rays often are sufficient for initial diagnosis. Computed tomo­graphy can help rule out a fracture line when clinical suspicion is high and x-rays are nondiagnostic. As noted earlier, any suggestion of neurovascular compromise on physical exam requires an emergent orthopedic surgeon consultation for a possible displaced and unstable (or more complex) injury (FIGURE 1).^6-8

Nondisplaced tibial plateau fractures without supraphysiologic ligamentous laxity on valgus or varus stress testing can be managed safely with protection and early mobilization, gradual progression of weight-bearing, and serial x-rays to ensure fracture healing and stability. Surgical management and fixation are required emergently for open fractures or gross joint instability with vascular or neurologic compromise. Suspicion of these complications is raised by distal neuropathic symptoms of paresthesia or skin anesthesia, progressively worsening pain distal to the knee, or vascular signs of pallor, delayed or lost capillary refill, or decreased or absent distal pulses.

Gross joint instability identified by positive valgus or varus stress testing, positive anterior or posterior drawer testing, or patient inability to tolerate these maneuvers due to pain similarly should raise suspicion for a more significant fracture at risk for concurrent neurovascular injury. Acute compartment syndrome also is a known complication of tibial plateau fractures and similarly requires emergent operative management. Urgent surgical consultation is recommended for fractures with displaced fracture fragments, tibial articular surface step-off or depression, fractures with concurrent joint laxity, or medial plateau fractures.^6-8

Continue to: Patella fractures

Patella fractures

These fractures occur as a direct blow to the front of the knee, such as falling forward onto a hard surface, or indirectly due to a sudden extreme eccentric contraction of the quadriceps muscle. Nondisplaced fractures with an intact knee extension mechanism, which is examined via a supine straight-leg raise or seated knee extension, are managed with weight-bearing as tolerated in strict immobilization in full extension for 4 to 6 weeks, with active range-of-motion and isometric quadriceps exercises beginning in 1 to 2 weeks. Serial x-rays also are obtained to ensure fracture displacement does not occur during the rehabilitation process.⁹

High-quality evidence guiding follow-up care and comparing outcomes of surgical and nonsurgical management of patella fractures is lacking, and studies comparing different surgical techniques are of lower methodological quality.¹⁰ Nevertheless, displaced or comminuted patellar fractures are referred urgently to orthopedic surgical care for fixation, as are those with concurrent loose bodies, chondral surface injuries or articular step-off, or osteochondral fractures.⁹ Inability to perform a straight-leg raise (ie, clinical loss of the knee extension mechanism) suggests a fracture under tension that likely also requires surgical fixation for successful recovery. Neurovascular injuries are unlikely in most patellar fractures but would require emergent surgical consultation.⁹

Ligamentous injury

Tibiofemoral joint laxity occurs as a result of ligamentous injury, with or without tibial plateau fracture. The anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), medial collateral ligament (MCL), and lateral collateral ligament (LCL) comprise the 4 main ligaments of the knee. The ACL resists anterior tibial translation and rotational forces, while the PCL resists posterior tibial translation. The MCL and LCL resist valgus and varus stress, respectively.

Ligament injuries are classified as Grades 1 to 3¹¹:

• Grade 1 sprains. The ligament is stretched, but there is no macroscopic tearing; joint stability is maintained.
• Grade 2 sprains. There are partial macroscopic ligament tears. There is joint laxity due to the partial loss of the ligament’s structural integrity.
• Grade 3 sprains. The ligament is fully avulsed or ruptured with resultant gross joint instability.

Vascular injury can lead to irreversible tissue damage and even limb loss if not promptly identified.

The decision to pursue surgical repair of a knee sprain depends heavily on the likelihood of keeping or regaining and maintaining functional joint stability during the injury recovery and postinjury time periods. Injuries that do not result in joint instability or injuries with a high likelihood of returning to a stable state with conservative measures often do not require surgical intervention.

Continue to: ACL tears

ACL tears occur most commonly via a noncontact event, as when an individual plants their foot and suddenly changes direction during sport or other physical activity. Treatment hinges on patient activity levels and participation in sports. Patients who do not plan to engage in athletic movements (that require changes in direction or planting and twisting) and who otherwise maintain satisfactory joint stability during activities of daily living may elect to defer or even altogether avoid surgical reconstruction of isolated ACL tears. One pair of studies demonstrated equivalent outcomes in surgical and nonsurgical management in 121 young, nonelite athletes at 2- and 5-year follow-up, although the crossover from the nonsurgical to surgical groups was high.^12,13 Athletes who regain satisfactory function and stability nonoperatively can defer surgical intervention. However, the majority of active patients and athletes will require surgical ACL reconstruction to return to pre-injury functional levels.¹⁴

PCL sprains occur as a result of sudden posteriorly directed force on the tibia, such as when the knee is hyperextended or a patient falls directly onto a flexed knee. Patients with Grade 1 and 2 isolated sprains generally will recover with conservative care, as will patients with some Grade 3 complete tears that do not fully compromise joint stability. However, high-grade PCL injuries often are comorbid with posterolateral corner or other injuries, leading to a higher likelihood of joint instability and thus the need for surgical intervention for the best chance at an optimal outcome.¹⁵

MCL sprain. Surgical management is not required in an isolated Grade 1 or 2 MCL sprain, as the hallmarks of recovery—return of joint stability, knee strength and range of motion, and pain ­reduction—can be achieved successfully with conservative management. Isolated Grade 3 MCL sprains are also successfully managed nonoperatively¹⁶ except in specific cases, such as a concurrent large avulsion fracture.¹⁷

LCL sprain. Similarly, isolated Grade 1 and 2 LCL sprains generally do not require surgical intervention. However, Grade 3 LCL injuries usually do, as persistent joint instability and poor functional outcomes are more common with nonsurgical management.^18-20 Additionally, high-grade LCL injuries frequently manifest with comorbid meniscus injuries or sprains of the posterolateral corner of the knee, a complex anatomic structure that provides both static and dynamic tibiofemoral joint stability. Surgical repair or reconstruction of the posterolateral corner frequently is necessary for optimal functional outcomes.²¹

Multiligamentous sprains frequently lead to gross joint instability and necessitate orthopedic surgeon consultation to determine the best treatment plan; this should be done emergently if neurovascular compromise is suspected. A common injury combination is simultaneous ACL and MCL sprains with or without meniscus injury. In these cases, some surgeons will choose to defer ACL reconstruction until after MCL healing is achieved. This allows the patient to regain valgus stability of the joint prior to performing ACL reconstruction to regain rotational and anterior stability.²⁰

Continue to: Patellar dislocations

Patellar dislocations represent a relatively common knee injury in young active patients, often occurring in a noncontact fashion when a valgus force is applied to an externally rotated and planted lower leg. A chief risk factor for a patellar dislocation is a history of prior dislocation. If rehabilitation following a dislocation is insufficient to regain patellofemoral joint stability, or if certain risk factors for recurrent dislocation are present, surgical intervention, such as medial patellofemoral ligament (MPFL) reconstruction or tibial tubercle transfer, is considered.²² A systematic review concluded that MPFL reconstruction following a first-time dislocation yielded lower redislocation rates of 7% compared to 30% with nonoperative treatment.²³

Major tendon rupture

Patellar tendon ruptures occur when a sudden eccentric force is applied to the knee, such as when landing from a jump with the knee flexed. Patellar tendon ruptures frequently are clinically apparent, with patients demonstrating a high-riding patella and loss of active knee extension. Quadriceps tendon ruptures often result from a similar injury mechanism in older patients, with a similar loss of active knee extension and a palpable gap superior to the patella.²⁴

Partial tears in patients who can maintain full extension of the knee against gravity are treated nonoperatively, but early surgical repair is indicated for complete quadriceps or patellar tendon ruptures to achieve optimal outcomes. Prompt diagnosis and treatment are critical, as repair delayed beyond 1 to 2 weeks postinjury is associated with worse outcomes.^25-28

Surgical management and fixation are required emergently for open fractures or gross joint instability with vascular or neurologic compromise.

Even with prompt treatment, return to sport is not guaranteed. According to a recent systematic review, athletes returned to play 88.9% and 89.8% of the time following patellar and quadriceps tendon repairs, respectively. However, returning to the same level of play was less common and achieved 80.8% (patellar tendon repair) and 70% (quadriceps tendon repair) of the time. Return-to-work rates were higher, at 96% for both surgical treatments.²⁹

Locked knee and acute meniscus tears in younger patients

In some acute knee injuries, meniscus tears, loose cartilage bodies or osteochondral defects, or other internal structures can become interposed between the femoral and tibial surfaces, preventing both active and passive knee extension. Such injuries are often severely painful and functionally debilitating. While manipulation under anesthesia can acutely restore joint function,³⁰ diagnostic and therapeutic arthroscopy often is pursued for definitive treatment.³¹ Compared to the gold standard of diagnostic arthroscopy, preoperative magnetic resonance imaging (MRI) carries positive and negative predictive values of 85% and 77%, respectively, in identifying or ruling out the anatomic structure responsible for a locked knee. ³² As such, MRI has been proposed as a method to avoid performing arthroscopy on a patient with a “pseudo-locked” knee, or loss of range of motion due to pain but without a true mechanical block.³²

Continue to: Depending on the location...

Depending on the location, size, and shape of an acute meniscus tear in younger patients, surgical repair may be an option to preserve long-term joint function. In one case series of patients younger than 20 years, 62% of meniscus repairs yielded good outcomes after a mean follow-up period of 16.8 years.³³

Osteochondritis dissecans

Osteochondritis dissecans is characterized by subchondral bone osteonecrosis that most often occurs in pediatric patients, potentially causing the separation of a fragment of articular cartilage and subchondral bone into the joint space (FIGURE 2). In early stages, nonoperative treatment consisting of prolonged rest followed by physical therapy to gradually return to activity is recommended to prevent small, low-grade lesions from progressing to unstable or separated fragments. Arthroscopy, which consists of microfracture or other surgical resurfacing techniques to restore joint integrity, is pursued in more advanced cases of unstable or separated fragments.

High-quality data guiding the management of osteochondritis dissecans are lacking, and these recommendations are based on consensus guidelines.³⁴

Septic arthritis

Septic arthritis is a medical emergency caused by the hematogenous spread of microorganisms, most often staphylococci and streptococci species. Less commonly, it arises from direct inoculation through an open wound or, rarely, iatrogenically following a joint injection procedure. Clinical signs of septic arthritis include joint pain, joint swelling, and fever. Passive range of motion of the joint is often severely painful. Synovial fluid studies consistent with septic arthritis include an elevated white blood cell count greater than 25,000/mcL with polymorphonuclear cell predominance.³⁵ The knee accounts for more than 50% of septic arthritis cases, and surgical drainage usually is required to achieve infection source control and decrease morbidity and mortality due to destruction of articular cartilage when treatment is delayed.³⁶

Chronic knee injuries and pain

Surgical intervention for chronic knee injuries and pain generally is considered when patients demonstrate significant functional impairment and persistent symptoms despite pursuing numerous nonsurgical treatment options. A significant portion of chronic knee pain is due to degenerative processes such as OA or meniscus injuries, or tears without a history of trauma that do not cause locking of the knee. Treatments for degenerative knee pain include supervised exercise, physical therapy, bracing, offloading with a cane or other equipment, topical or oral ­anti-inflammatories or analgesics, and injectable therapies such as intra-articular ­corticosteroids.³⁷

Continue to: Other common causes...

Other common causes of chronic knee pain include chronic tendinopathy or biomechanical syndromes such as patellofemoral pain syndrome or iliotibial band syndrome. Surgical treatment of these conditions is pursued in select cases and only after exhausting nonoperative treatment programs, as recommended by international consensus statements,³⁸ societal guidelines,³⁹ and expert opinion.⁴⁰ High-quality data on the effectiveness, or ineffectiveness, of surgical intervention for these conditions are lacking.

A chief risk factor for a patellar dislocation is a history of prior dislocation.

Despite being one of the most commonly performed surgical procedures in the United States,⁴¹ arthroscopic partial meniscectomy treatment of degenerative meniscus tears does not lead to improved outcomes compared to nonsurgical management, according to multiple recent studies.^42-45 Evidence does not support routine arthroscopic intervention for degenerative meniscus tears or OA,⁴² and recent guidelines recommend against it⁴⁶ or to pursue it only after nonsurgical treatments have failed.³⁷

Surgical management of degenerative knee conditions generally consists of partial or total arthroplasty and is similarly considered after failure of conservative measures. Appropriate use criteria that account for multiple clinical and patient factors are used to enhance patient selection for the procedure.⁴⁷

Takeaways

Primary care clinicians will treat patients sustaining knee injuries and see many patients with knee pain in the outpatient setting. Treatment options vary considerably depending on the underlying diagnosis and resulting functional losses. Several categories of clinical presentation, including neurovascular injury, unstable or displaced fractures, joint instability, major tendon rupture, significant mechanical symptoms such as a locked knee, certain osteochondral injuries, and septic arthritis, likely or almost always warrant surgical consultation ­(TABLE^3-10,12-36). Occasionally, as in the case of neurovascular injury or septic arthritis, such consultation should be emergent.

CORRESPONDENCE
David M. Siebert, MD, Sports Medicine Center at Husky Stadium, 3800 Montlake Boulevard NE, Seattle, WA 98195; [email protected]

Evidence supports what family physicians know to be true: Knee pain is an exceedingly common presenting problem in the primary care office. Estimates of lifetime incidence reach as high as 54%,¹ and the prevalence of knee pain in the general population is increasing.² Knee disability can result from acute or traumatic injuries as well as chronic, degenerative conditions such as osteoarthritis (OA). The decision to pursue orthopedic consultation for a particular injury or painful knee condition can be challenging. To address this, we highlight specific knee diagnoses known to cause pain, with the aim of describing which conditions likely will necessitate surgical consultation—and which won’t.

Acute or nondegenerative knee injuries and pain

Acute knee injuries range in severity from simple contusions and sprains to high-energy, traumatic injuries with resulting joint instability and potential neurovascular compromise. While conservative treatment often is successful for many simple injuries, surgical management—sometimes urgently or emergently—is needed in other cases, as will be detailed shortly.

Neurovascular injury associated with knee dislocations

Acute neurovascular injuries often require emergent surgical intervention. Although rare, tibiofemoral (knee) dislocations pose a significant challenge to the clinician in both diagnosis and management. The reported frequency of popliteal artery injury or rupture following a dislocation varies widely, with rates ranging from 5% to 64%, according to older studies; more recent data, however, suggest the rate is actually as low as 3.3%.³ Vascular injury can lead to irreversible tissue damage and even limb loss if not promptly identified. Identifying a knee dislocation can prove challenging, as spontaneous joint reduction occurs in as many as 50% of cases, potentially shrouding the severity of the injury on initial evaluation.⁴

Immediate immobilization and emergency department transport for monitoring, orthopedics consultation, and vascular ­studies or vascular surgery consultation is recommended in the case of a suspected knee dislocation. In one cross-sectional cohort study, the surgical management of knee ­dislocations yielded favorable outcomes in > 75% of cases.⁵

Tibial plateau fracture

This fracture often occurs as a result of high-energy trauma, such as contact sports or motor vehicle accidents, and is characterized by a proximal tibial fracture line with extension to the articular surface. X-rays often are sufficient for initial diagnosis. Computed tomo­graphy can help rule out a fracture line when clinical suspicion is high and x-rays are nondiagnostic. As noted earlier, any suggestion of neurovascular compromise on physical exam requires an emergent orthopedic surgeon consultation for a possible displaced and unstable (or more complex) injury (FIGURE 1).^6-8

Nondisplaced tibial plateau fractures without supraphysiologic ligamentous laxity on valgus or varus stress testing can be managed safely with protection and early mobilization, gradual progression of weight-bearing, and serial x-rays to ensure fracture healing and stability. Surgical management and fixation are required emergently for open fractures or gross joint instability with vascular or neurologic compromise. Suspicion of these complications is raised by distal neuropathic symptoms of paresthesia or skin anesthesia, progressively worsening pain distal to the knee, or vascular signs of pallor, delayed or lost capillary refill, or decreased or absent distal pulses.

Gross joint instability identified by positive valgus or varus stress testing, positive anterior or posterior drawer testing, or patient inability to tolerate these maneuvers due to pain similarly should raise suspicion for a more significant fracture at risk for concurrent neurovascular injury. Acute compartment syndrome also is a known complication of tibial plateau fractures and similarly requires emergent operative management. Urgent surgical consultation is recommended for fractures with displaced fracture fragments, tibial articular surface step-off or depression, fractures with concurrent joint laxity, or medial plateau fractures.^6-8

Continue to: Patella fractures

Patella fractures

These fractures occur as a direct blow to the front of the knee, such as falling forward onto a hard surface, or indirectly due to a sudden extreme eccentric contraction of the quadriceps muscle. Nondisplaced fractures with an intact knee extension mechanism, which is examined via a supine straight-leg raise or seated knee extension, are managed with weight-bearing as tolerated in strict immobilization in full extension for 4 to 6 weeks, with active range-of-motion and isometric quadriceps exercises beginning in 1 to 2 weeks. Serial x-rays also are obtained to ensure fracture displacement does not occur during the rehabilitation process.⁹

High-quality evidence guiding follow-up care and comparing outcomes of surgical and nonsurgical management of patella fractures is lacking, and studies comparing different surgical techniques are of lower methodological quality.¹⁰ Nevertheless, displaced or comminuted patellar fractures are referred urgently to orthopedic surgical care for fixation, as are those with concurrent loose bodies, chondral surface injuries or articular step-off, or osteochondral fractures.⁹ Inability to perform a straight-leg raise (ie, clinical loss of the knee extension mechanism) suggests a fracture under tension that likely also requires surgical fixation for successful recovery. Neurovascular injuries are unlikely in most patellar fractures but would require emergent surgical consultation.⁹

Ligamentous injury

Tibiofemoral joint laxity occurs as a result of ligamentous injury, with or without tibial plateau fracture. The anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), medial collateral ligament (MCL), and lateral collateral ligament (LCL) comprise the 4 main ligaments of the knee. The ACL resists anterior tibial translation and rotational forces, while the PCL resists posterior tibial translation. The MCL and LCL resist valgus and varus stress, respectively.

Ligament injuries are classified as Grades 1 to 3¹¹:

• Grade 1 sprains. The ligament is stretched, but there is no macroscopic tearing; joint stability is maintained.
• Grade 2 sprains. There are partial macroscopic ligament tears. There is joint laxity due to the partial loss of the ligament’s structural integrity.
• Grade 3 sprains. The ligament is fully avulsed or ruptured with resultant gross joint instability.

Vascular injury can lead to irreversible tissue damage and even limb loss if not promptly identified.

The decision to pursue surgical repair of a knee sprain depends heavily on the likelihood of keeping or regaining and maintaining functional joint stability during the injury recovery and postinjury time periods. Injuries that do not result in joint instability or injuries with a high likelihood of returning to a stable state with conservative measures often do not require surgical intervention.

Continue to: ACL tears

ACL tears occur most commonly via a noncontact event, as when an individual plants their foot and suddenly changes direction during sport or other physical activity. Treatment hinges on patient activity levels and participation in sports. Patients who do not plan to engage in athletic movements (that require changes in direction or planting and twisting) and who otherwise maintain satisfactory joint stability during activities of daily living may elect to defer or even altogether avoid surgical reconstruction of isolated ACL tears. One pair of studies demonstrated equivalent outcomes in surgical and nonsurgical management in 121 young, nonelite athletes at 2- and 5-year follow-up, although the crossover from the nonsurgical to surgical groups was high.^12,13 Athletes who regain satisfactory function and stability nonoperatively can defer surgical intervention. However, the majority of active patients and athletes will require surgical ACL reconstruction to return to pre-injury functional levels.¹⁴

PCL sprains occur as a result of sudden posteriorly directed force on the tibia, such as when the knee is hyperextended or a patient falls directly onto a flexed knee. Patients with Grade 1 and 2 isolated sprains generally will recover with conservative care, as will patients with some Grade 3 complete tears that do not fully compromise joint stability. However, high-grade PCL injuries often are comorbid with posterolateral corner or other injuries, leading to a higher likelihood of joint instability and thus the need for surgical intervention for the best chance at an optimal outcome.¹⁵

MCL sprain. Surgical management is not required in an isolated Grade 1 or 2 MCL sprain, as the hallmarks of recovery—return of joint stability, knee strength and range of motion, and pain ­reduction—can be achieved successfully with conservative management. Isolated Grade 3 MCL sprains are also successfully managed nonoperatively¹⁶ except in specific cases, such as a concurrent large avulsion fracture.¹⁷

LCL sprain. Similarly, isolated Grade 1 and 2 LCL sprains generally do not require surgical intervention. However, Grade 3 LCL injuries usually do, as persistent joint instability and poor functional outcomes are more common with nonsurgical management.^18-20 Additionally, high-grade LCL injuries frequently manifest with comorbid meniscus injuries or sprains of the posterolateral corner of the knee, a complex anatomic structure that provides both static and dynamic tibiofemoral joint stability. Surgical repair or reconstruction of the posterolateral corner frequently is necessary for optimal functional outcomes.²¹

Multiligamentous sprains frequently lead to gross joint instability and necessitate orthopedic surgeon consultation to determine the best treatment plan; this should be done emergently if neurovascular compromise is suspected. A common injury combination is simultaneous ACL and MCL sprains with or without meniscus injury. In these cases, some surgeons will choose to defer ACL reconstruction until after MCL healing is achieved. This allows the patient to regain valgus stability of the joint prior to performing ACL reconstruction to regain rotational and anterior stability.²⁰

Continue to: Patellar dislocations

Patellar dislocations represent a relatively common knee injury in young active patients, often occurring in a noncontact fashion when a valgus force is applied to an externally rotated and planted lower leg. A chief risk factor for a patellar dislocation is a history of prior dislocation. If rehabilitation following a dislocation is insufficient to regain patellofemoral joint stability, or if certain risk factors for recurrent dislocation are present, surgical intervention, such as medial patellofemoral ligament (MPFL) reconstruction or tibial tubercle transfer, is considered.²² A systematic review concluded that MPFL reconstruction following a first-time dislocation yielded lower redislocation rates of 7% compared to 30% with nonoperative treatment.²³

Major tendon rupture

Patellar tendon ruptures occur when a sudden eccentric force is applied to the knee, such as when landing from a jump with the knee flexed. Patellar tendon ruptures frequently are clinically apparent, with patients demonstrating a high-riding patella and loss of active knee extension. Quadriceps tendon ruptures often result from a similar injury mechanism in older patients, with a similar loss of active knee extension and a palpable gap superior to the patella.²⁴

Partial tears in patients who can maintain full extension of the knee against gravity are treated nonoperatively, but early surgical repair is indicated for complete quadriceps or patellar tendon ruptures to achieve optimal outcomes. Prompt diagnosis and treatment are critical, as repair delayed beyond 1 to 2 weeks postinjury is associated with worse outcomes.^25-28

Surgical management and fixation are required emergently for open fractures or gross joint instability with vascular or neurologic compromise.

Even with prompt treatment, return to sport is not guaranteed. According to a recent systematic review, athletes returned to play 88.9% and 89.8% of the time following patellar and quadriceps tendon repairs, respectively. However, returning to the same level of play was less common and achieved 80.8% (patellar tendon repair) and 70% (quadriceps tendon repair) of the time. Return-to-work rates were higher, at 96% for both surgical treatments.²⁹

Locked knee and acute meniscus tears in younger patients

In some acute knee injuries, meniscus tears, loose cartilage bodies or osteochondral defects, or other internal structures can become interposed between the femoral and tibial surfaces, preventing both active and passive knee extension. Such injuries are often severely painful and functionally debilitating. While manipulation under anesthesia can acutely restore joint function,³⁰ diagnostic and therapeutic arthroscopy often is pursued for definitive treatment.³¹ Compared to the gold standard of diagnostic arthroscopy, preoperative magnetic resonance imaging (MRI) carries positive and negative predictive values of 85% and 77%, respectively, in identifying or ruling out the anatomic structure responsible for a locked knee. ³² As such, MRI has been proposed as a method to avoid performing arthroscopy on a patient with a “pseudo-locked” knee, or loss of range of motion due to pain but without a true mechanical block.³²

Continue to: Depending on the location...

Depending on the location, size, and shape of an acute meniscus tear in younger patients, surgical repair may be an option to preserve long-term joint function. In one case series of patients younger than 20 years, 62% of meniscus repairs yielded good outcomes after a mean follow-up period of 16.8 years.³³

Osteochondritis dissecans

Osteochondritis dissecans is characterized by subchondral bone osteonecrosis that most often occurs in pediatric patients, potentially causing the separation of a fragment of articular cartilage and subchondral bone into the joint space (FIGURE 2). In early stages, nonoperative treatment consisting of prolonged rest followed by physical therapy to gradually return to activity is recommended to prevent small, low-grade lesions from progressing to unstable or separated fragments. Arthroscopy, which consists of microfracture or other surgical resurfacing techniques to restore joint integrity, is pursued in more advanced cases of unstable or separated fragments.

High-quality data guiding the management of osteochondritis dissecans are lacking, and these recommendations are based on consensus guidelines.³⁴

Septic arthritis

Septic arthritis is a medical emergency caused by the hematogenous spread of microorganisms, most often staphylococci and streptococci species. Less commonly, it arises from direct inoculation through an open wound or, rarely, iatrogenically following a joint injection procedure. Clinical signs of septic arthritis include joint pain, joint swelling, and fever. Passive range of motion of the joint is often severely painful. Synovial fluid studies consistent with septic arthritis include an elevated white blood cell count greater than 25,000/mcL with polymorphonuclear cell predominance.³⁵ The knee accounts for more than 50% of septic arthritis cases, and surgical drainage usually is required to achieve infection source control and decrease morbidity and mortality due to destruction of articular cartilage when treatment is delayed.³⁶

Chronic knee injuries and pain

Surgical intervention for chronic knee injuries and pain generally is considered when patients demonstrate significant functional impairment and persistent symptoms despite pursuing numerous nonsurgical treatment options. A significant portion of chronic knee pain is due to degenerative processes such as OA or meniscus injuries, or tears without a history of trauma that do not cause locking of the knee. Treatments for degenerative knee pain include supervised exercise, physical therapy, bracing, offloading with a cane or other equipment, topical or oral ­anti-inflammatories or analgesics, and injectable therapies such as intra-articular ­corticosteroids.³⁷

Continue to: Other common causes...

Other common causes of chronic knee pain include chronic tendinopathy or biomechanical syndromes such as patellofemoral pain syndrome or iliotibial band syndrome. Surgical treatment of these conditions is pursued in select cases and only after exhausting nonoperative treatment programs, as recommended by international consensus statements,³⁸ societal guidelines,³⁹ and expert opinion.⁴⁰ High-quality data on the effectiveness, or ineffectiveness, of surgical intervention for these conditions are lacking.

A chief risk factor for a patellar dislocation is a history of prior dislocation.

Despite being one of the most commonly performed surgical procedures in the United States,⁴¹ arthroscopic partial meniscectomy treatment of degenerative meniscus tears does not lead to improved outcomes compared to nonsurgical management, according to multiple recent studies.^42-45 Evidence does not support routine arthroscopic intervention for degenerative meniscus tears or OA,⁴² and recent guidelines recommend against it⁴⁶ or to pursue it only after nonsurgical treatments have failed.³⁷

Surgical management of degenerative knee conditions generally consists of partial or total arthroplasty and is similarly considered after failure of conservative measures. Appropriate use criteria that account for multiple clinical and patient factors are used to enhance patient selection for the procedure.⁴⁷

Takeaways

Primary care clinicians will treat patients sustaining knee injuries and see many patients with knee pain in the outpatient setting. Treatment options vary considerably depending on the underlying diagnosis and resulting functional losses. Several categories of clinical presentation, including neurovascular injury, unstable or displaced fractures, joint instability, major tendon rupture, significant mechanical symptoms such as a locked knee, certain osteochondral injuries, and septic arthritis, likely or almost always warrant surgical consultation ­(TABLE^3-10,12-36). Occasionally, as in the case of neurovascular injury or septic arthritis, such consultation should be emergent.

CORRESPONDENCE
David M. Siebert, MD, Sports Medicine Center at Husky Stadium, 3800 Montlake Boulevard NE, Seattle, WA 98195; [email protected]