Clinical Advisor May/June 2023

LEGAL ADVISOR

DNP Sued for Use of Doctor in Office

FEATURE

Pneumothorax: Improving Diagnosis and Management in Premenopausal Patients

Nonalcoholic and alcoholic liver disease are suspects in bone disease.

FEATURE

A Case of Severe Monthly Headaches in Teacher: Workup and Treatment

DERMATOLOGIC LOOK-ALIKES

Raised Itchy Nodules

A FASTER* COUNTDOWN TO ONSET OF RELIEF WITH FLEXIBLE PRN DOSING

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• Introducing the first10 and only11 OTC nasal antihistamine spray9

• Astepro® Allergy is different than intranasal steroid (INS) sprays: Relief starts in 30 minutes,* while INS sprays take hours to start to provide relief and can take between 3 and 14 days to reach maximum efficacy levels1-8,†

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• Powerful,steroid-free nasal symptom relief for up to 24 hours8,9

RECOMMEND ASTEPRO

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References:

1. Data on file. Bayer. Study 20877. Onset of action. 2. Flonase® website. Accessed July 23, 2021. https://www.flonase.com/faqs/

3. Flonase® Prescribing Information. GlaxoSmithKline; 2019. 4. GSK health partner website. Accessed September 17, 2021. https://www.gskhealthpartner.com/ en-us/respiratory-health/brands/flonase-products/flonase/dosing-administration-flonase-allergy-relief/

5. Nasacort® website. Accessed September 17, 2021. https://www.nasacort.com/allergy-nasal-spray-nasacort-faqs/

6. Nasacort® AQ. Prescribing information. Sanofi-aventis U.S. LLC; 2008. 7. Rhinocort website. Accessed November 11, 2021. https://www.rhinocort.com/allergy-nasal-spray/adult-otc-spray

8. Shah S, Berger W, Lumry W, La Force C, Wheeler W, Sacks H. Efficacy and safety of azelastine 0.15% nasal spray and azelastine 0.10% nasal spray in patients with seasonal allergic rhinitis. Allergy Asthma Proc. 2009;30(6):628-633. doi:10.2500/aap.2009.30.3296

9. NDA 213872. 10. FDA approves a nasal antihistamine for nonprescription use. Approval is a first-in-class and was enabled by the prescription to nonprescription switch process. News release. FDA; June 17, 2021. Accessed October 7, 2021. https://www.fda.gov/news-events/press-announcements/fda-approvesnasal-antihistamine-nonprescription-use

11. Data on file. Bayer. IRI data. Only OTC AH. 12. Ortiz G, Knudtson M. Counseling patients on the use of intransal steroids in allergic rhinitis management. Consultant. 2017;57(6):328-334. 13. Data on file. Bayer. Habits and practices. Bayer and the Bayer Cross are registered trademarks of Bayer. ASTEPRO is a Viatris Company trademark. Used under license. All third party trademarks used herein are registered trademarks of their respective owners.

*On day 1, compared with steroid allergy sprays. †INS onset based on various product information; time to maximum efficacy depends on the INS brand. ‡In a survey of allergy patients that included nasal spray users (n=732), 42% of patients said they administer their INS “some days and not others.”

FROM THE DIRECTOR

Director

Nikki Kean

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Are Hospitals Safe Workplaces?

Recent reports of violence against health care workers in hospitals are raising the question: are hospitals safe workplaces? Health care workers are 5 times more likely to experience violence at the workplace than other professions. Close to 40 states now have laws that either establish or increase penalties for assaults on health care workers, according to the American Nurses Association.

The Joint Commission defines workplace violence as “an act or threat occurring at the workplace that can include: verbal, nonverbal, written, or physical aggression; threatening, intimidating, harassing, or humiliating words or actions; bullying; sabotage; sexual harassment; or physical assaults.”

Despite the increased attention to the problem, the incidence of violence has increased, including during the COVID-19 pandemic. And the data may not represent the whole picture as workplace violence is often under-reported. Some of the reasons given by health care workers for not reporting violence include:

• Patients who are not in their “right mind” cannot be held accountable for their actions.

• Reporting can be time-consuming and difficult for health care employees working under high-stress conditions.

• Fear of retaliation from management and/or colleagues who are concerned that reports of violence reflect poorly on a health care team/workplace.

• No injury occurred or time was lost because of the incident, or the violence wasn’t physical.

• The widespread belief that violence is simply “part of the job.”

The American Association of Nurse Practitioners (AANP) has condemned workplace violence. “We urge all health care facilities to implement comprehensive violence prevention programs and freedom from retaliation for reporting workplace incidents,” said AANP.

The expectation of violence should never be “part of the job.” Yes, health care workers face unique challenges and a potentially dangerous patient population but hospitals need to provide support and security to provide safe spaces for workers.

Nikki Kean, Director The Clinical Adviso r

■

FEATURES

DEPARTMENTS

Early Intervention for Symptomatic Kidney Stones Is Beneficial

Patients with renal colic benefit from early intervention (shockwave lithotripsy, ureteroscopy, or percutaneous nephrolithotomy) compared with delayed intervention.

IV Drug Use-Associated HIV, HCV Risk Is Higher in Women and Adolescents

British researchers evaluated global data on HIV and primary hepatic C virus infection incidence among individuals who use injectable drugs.

Early Mammography Called for Higher-Risk Persons

Women with higher-than-average breast cancer risk, especially Black and Ashkenazi Jewish women, should start screening at 25 to 40 years, according to the American College of Radiology.

Early Biologic Initiation for Crohn Disease Reduces Costs

Patients with CD who started biologic therapy early (≤12 months after diagnosis) had fewer outpatient follow-up visits and decreased total health care costs compared with patients who initiated biologic use later.

Higher Dietary Choline, Betaine Intake Benefits Individuals With Obesity

Higher dietary choline and betaine intake is associated with lower blood pressure and low-density lipoprotein cholesterol levels among individuals with obesity.

Brady Pregerson, MD Clinical Challenge: Altered Mental Status

A 72-year-old man with a history of bradycardia and transient ischemic attack presents for evaluation of altered mental status. He is alert but cannot give any medical history. His medical records show that he was prescribed sulfamethoxazole and trimethoprim for treatment of a urinary tract infection. See the full case at: clinicaladvisor.com/ case_may_jun23

MY PRACTICE

ClinicalAdvisor.com/MyPractice

The Growing Role of PAs in Dermatology Practice

The mean number of dermatology PAs increased by 11.6% annually from 2013 to 2018. With the number of PAs increasing, Cynthia F. Griffith, MPAS, PA-C, and Peter A. Young, MPAS, PA-C, discuss the challenges faced by PAs in this specialty.

THE WAITING ROOM

Official Blog of The Clinical Advisor

ClinicalAdvisor.com/WaitingRoom

Jim Anderson, MPAS, PA-C, DFAAPA Maternity Deserts Pose Increasing Disparities in Prenatal Care

Jim Anderson examines the growth in maternity deserts in rural America, as well as in low-income areas and communities of color.

Advisor Dx

Interact with your peers by viewing the images and offering your diagnosis and comments. To post your answer, obtain more clues, or view similar cases, visit ClinicalAdvisor.com/AdvisorDx . Learn more about diagnosing and treating these conditions, and see how you compare with your fellow colleagues.

DERM DX

Focal Area of Hair Loss

A 49-year-old woman presents with hair loss on the scalp that began 8 months ago. She states the area of hair loss is itchy and painful. She denies any recent use of chemical or thermal hair relaxers. Her medical history is positive for asthma. Examination reveals a 6-cm scaly erythematous alopecic plaque on the left side of her scalp.

CAN YOU DIAGNOSE THIS CASE?

• Lichen planopilaris

• Tinea capitis

• Discoid lupus erythematosus

• Psoriasis

● See the full case at clinicaladvisor.com/dermdx_may_june23

Check out some of our latest cases below! ORTHO DX

Osteochondroma

In partnership with Online CME for Physician Assistants CME4PAC

A 19-year-old man presents with left thigh pain. On examination, a palpable mass is felt near the left side of the distal thigh about 2 inches above the superior pole of the patella. As he bends and straightens his knee, popping sounds are heard. Imaging of the knee shows a mass on the lateral distal femur.

WHAT IS THE NEXT STEP IN TREATMENT?

• Observation

• Bone biopsy

• Percutaneous ablation

• Surgical resection

● See the full case at clinicaladvisor.com/orthodx_may_june23

Interview With Karli Burridge, PA-C, FOMA

Providing a Roadmap for Individualized Obesity Management Programs

Karli Burridge, PA-C, FOMA, is the president of PAs in Obesity Medicine and serves on the board of the Illinois Obesity Society. She is the founder and owner of Gaining Health and works at the Ascension Medical Weight Management program in Westmont, Illinois.

How long have you been in practice?

PA Burridge: I have been in practice for almost 14 years. When I graduated from PA school at Midwestern University, I was not aware that the specialty of obesity medicine existed. The field has grown and expanded immensely in the last 10 years and is currently the fastest-growing medical specialty. Clinicians are eager to learn about evidence-based obesity management.

Q: What experience(s) got you interested in obesity medicine?

PA Burridge: I have always been a believer in holistic care and by that I mean treating the whole person — mind and body. I graduated from university with degrees in psychology and physiology and went on to graduate school for clinical exercise physiology because of the health benefits of physical activity. However, I discovered that to work directly with patients with obesity it was best to have a clinical license, which is why I decided to go to PA school.

Upon graduation, my plan was to work in primary care and focus on disease prevention and health promotion, wanting to help patients with lifestyle factors and weight management. However, outside of the concepts of energy balance and recommending that people eat less and move more, none of my training included additional strategies and tools to assist patients with weight management. In 2009, obesity was not officially recognized as a disease by the American Medical

Association (this did not occur until 2013), and we didn’t learn much about obesity or how to manage it in my medical training. I found that it was surprisingly challenging to help patients lose weight and keep it off long-term, which frustrated both myself and my patients.

It wasn’t until a few years later when I landed a job in bariatric surgery that I learned about the complexities of obesity and the numerous hormones and neuroendocrine systems that can make it exceedingly difficult for people with obesity to lose weight and maintain weight reduction. Once I discovered this science and had a better understanding of how I could help my patients, I wanted to learn everything I could about surgical and medical obesity treatments. Now, I combine my passion for healthy lifestyle changes with evidence-based tools like metabolic and bariatric surgery and/or pharmacotherapy, as well as a thorough assessment of other factors that may be contributing to the development of obesity. I individualize treatment for my patients which makes a significant difference in their health and well-being.

Q: What are the biggest health challenges facing patients with obesity?

PA Burridge: One of the biggest challenges is access to care. Few patients have access to clinicians who have been trained in obesity medicine and, often, even those who have found an obesity specialist don’t have coverage for evidencebased treatments like antiobesity medications.

I have always been a big believer in holistic care … treating the whole person.

Another challenge is access to healthful foods. Unfortunately, ultra-processed foods tend to be more cost-effective than healthful, whole foods, which contributes to the health disparities that we see with medical conditions such as obesity.

Q: Tell us about why you started Gaining Health?

PA Burridge: Today, 42% of the US adult population and 20% of the pediatric population have obesity; this number is projected to reach 58% of adults by 2035, according to the World Obesity Federation’s 2023 report.We need more clinicians who are trained in evidence-based, compassionate obesity care. However, training and education are just the beginning.Taking that education and then developing a comprehensive obesity treatment program can take a lot of time and effort; many busy clinicians just don’t have the time and bandwidth to develop a program from scratch.

I started Gaining Health so that clinicians wouldn’t have to recreate the wheel every time someone wanted to start an obesity program. With Gaining Health, we provide a roadmap and resources that clinicians use to develop their programs. They can get their programs up and running faster, more efficiently, and at a much lower cost. It has been very fulfilling to see so many clinicians start their obesity programs. As a bonus, the clinicians are also finding a renewed love for their profession because they are getting to do what they have always wanted to do: help their patients get healthier and feel better.

Q:Who were your mentors in the PA field?

PA Burridge: I have had several incredible mentors who have helped me throughout my career. Two that really stand out are Sandra Christensen, MSN, ARNP, FNP-BS, FOMA, who was my mentor when I first joined the Obesity Medicine Association (OMA) and has been like family ever since. The other is Amy Ingersoll, PA-C, a trailblazer and leader in the field of obesity medicine and with whom I cofounded PAs in Obesity Medicine in 2017. Many others have guided and supported me throughout my journey in this field.

Q: What aspects of your profession are most rewarding/challenging?

PA Burridge: Most rewarding is when a patient recognizes that their weight is not all their fault and that there is hope that they can be a healthier, happier version of themselves. Most challenging is when patients do not have access to these lifechanging and lifesaving treatments.

Q: Have you found a way to overcome these challenges?

PA Burridge: I advocate for the Treat and Reduce Obesity Act. I try to enhance awareness of obesity as a disease and that evidence-based treatments should be covered, just like they are for other chronic diseases. I also talk about this on the Gaining Health podcast, including episode 11 which is all about advocacy and where we stand as a country in terms of coverage.

Q: How do you avoid burnout? What do you do for fun?

PA Burridge: I try to be holistic about my self-care. I try to exercise, walk outside, meditate, eat well, and get 8 hours of sleep on most days. Some days are better than others but like I tell my patients, it’s about consistency, not perfection! For fun, I recently started taking ballroom dancing classes — my favorites are the rhythm dances like salsa, cha-cha, and rumba!

Q: Is there anything else you would like to tell our readers?

PA Burridge: I encourage clinicians to become educated in obesity medicine! PAs are perfectly positioned to be the leaders in this field and we need PAs in all kinds of specialties to be able to help patients with obesity. Obesity causes or contributes to the development of over 236 other medical conditions.When we treat obesity, everything else gets better, too. You can learn about obesity through the AAPA Obesity Toolkit and you can join PAs in Obesity Medicine. The OMA is another great place to receive education on obesity. Lastly, if you want to start an obesity program, check out www.Gaininghealth.com, and listen to our weekly podcast. ■

Few patients have access to clinicians who have been trained in obesity medicine.

Half of US Parents Believe Social Media Is Harming Their Children’s Mental Health

HALF OF US parents think social media is detrimental to their children’s mental health, according to findings from a recent Harris Poll.

The finding highlights growing concerns about how these platforms affect children’s and adolescents’ wellbeing, according to the On Our Sleeves Movement for Children’s Mental Health, which commissioned the survey. In the past year, some platforms have introduced safety measures and lawmakers have discussed bills that would limit user access to social media.

“This is a positive step, but parents can’t trust that this is enough,” said Ariana Hoet, PhD, a pediatric psychologist and clinical director of On Our Sleeves.

“Social media has the ability to increase anxiety and depression in children when used inappropriately, as well as potentially open them up to inappropriate sharing, hurtful language, bullying, and more.”

“Taking an active role in their social media engagement, instead of simply limiting their exposure, can help them feel comfortable to ask questions, report concerns, and seek help when they need it,” Dr. Hoet said.

More than 2000 US adults, including 711 parents of children younger than 18 years of age, were surveyed in late March and early April 2023.The number of adults who said social media has a positive impact on children’s mental health

decreased from 43% in 2022 to just over one-third during the survey period.

Despite the results, fewer parents now said they were comfortable talking with their children about mental health — 86% compared with 91% in 2022.

On Our Sleeves offers free guides with tools to start conversations about social media and how to set boundaries to keep kids safe.

Workplace Discrimination Linked to Hypertension Among US Workers

Discrimination in the workplace is associated with an elevated risk for hypertension among US workers, according to study findings published online in the Journal of the American Heart Association.

Jian Li, MD, PhD, from the Fielding School of Public Health at the University of California in Los Angeles, and colleagues examined the prospective association of workplace discrimination with onset of hypertension using data from the Midlife in the United States cohort study. A total of 1246 participants were included in the main analysis.

The researchers found that 319 workers reported onset of hypertension during a follow-up of 9923.17 person-years. Participants with low, intermediate, and high levels of workplace

discrimination had incidence rates of hypertension of 25.90, 30.84, and 39.33 per 1000 person-years, respectively. Compared with workers with low exposure, those with high exposure to workplace discrimination had a higher risk for hypertension (adjusted hazard ratio, 1.54; 95% CI, 1.11–2.13). Slightly stronger associations were seen in a sensitivity analysis. An exposureresponse association was seen in a trend analysis.

“There are several implications from these findings,” Dr Li said in a statement. “First, we should increase public awareness that work is an important social determinant of health. Second, in addition to traditional risk factors, stressful experiences at work due to discrimination are an emerging risk factor for high blood pressure.” ■

Children’s use of social media is linked to increased anxiety and depression.

Pneumothorax: Improving Diagnosis and Management in Premenopausal Patients

Approximately 35% of premenopausal women diagnosed with primary spontaneous pneumothorax meet criteria for catamenial pneumothorax.

Differentiating between spontaneous pneumothorax and catamenial pneumothorax in premenopausal patients can be difficult given the overlapping presentation and symptoms of these conditions. Many patients with catamenial pneumothorax are initially diagnosed with spontaneous pneumothorax until information linking the lung collapse to menstrual cycle history is obtained. Understanding the workup and treatment for both conditions is essential to providing timely care to patients who present with sudden chest pain, difficulty breathing, shortness of breath, and cough.

Primary spontaneous pneumothorax (PSP) presents without a precipitating external event and in the absence of lung disease.1 Although PSP is not associated with lung disease, 90% of patients have unrecognized lung abnormalities such as subpleural blebs and/or bullae that likely predispose patients to pneumothorax.2-4 Catamenial pneumothorax is a type of secondary spontaneous pneumothorax that is characterized by the recurrent accumulation of air in the plural cavity the day before and within 72 hours after the onset of menstruation in premenopausal patients.5 Experts believe catamenial pneumothorax is associated with thoracic endometriosis but the etiology is still not well understood. Approximately 3% to 6% of PSP occurring in premenopausal patients meets the criteria for catamenial pneumothorax; however, recent studies indicate that the rate may be as high as 35%.5

The thoracic cavity is the most common extrapelvic location of endometriosis.

The incidence of PSP in the US has not been updated in decades and the National Institutes of Health is currently working on this data. Findings from a recent Danish study reported a PCP incidence of 12.3 cases/100,000 for males and 2.2 cases/100,000 for females.6 Risk factors for developing PSP include cigarette smoking, male sex, above-average height in men, and activities such as scuba diving, being at high altitudes, and flying.1

Etiology

Primary Spontaneous Pneumothorax

Although the etiology is not well understood and has many different components, most researchers believe that spontaneous rupture of a subpleural bleb or bulla typically causes PSP. However, it is unclear how often these lesions are actually the site of air leakage.

Many times only a minority of the blebs are ruptured at the time of thoracoscopy evaluation or surgery.1 Another abnormality that is often present is pleural porosity, which is described as areas of disrupted mesothelial cells at the visceral pleura replaced by an inflammatory elastofibrotic layer allowing air leakage into the pleural space. These lesions may explain the high rate of recurrent pneumothorax after bullectomy (20%) without pleurodesis.7 The development of blebs, bullae, and areas of pleural porosity may be linked to a variety of factors. These include distal airway inflammation, hereditary predisposition, anatomic abnormalities of the bronchial tree, ectomorphic physiognomy with more negative intrapleural pressures and apical ischemia at the apices, low body mass index and caloric restriction, and abnormal connective tissue.1

Catamenial Pneumothorax

Three main theories behind the development of catamenial pneumothorax have been proposed. The first suggests that the increase in prostaglandin levels during ovulation causes contraction of blood vessels and bronchioles and, at the same time, sensitizes pre-existing pulmonary blebs making them more prone to rupture, which leads to rupture of alveoli and the flow of air into the pleural space.5 The second theory is that “liquefaction of cervical mucus plugs during menses allows retrograde airflow through the uterus and the fallopian tubes into the peritoneal cavity…. Through diaphragmatic defects resulting from the sloughing of endometrial implants, the air passes through into the pleural cavity causing a pneumothorax.”5 The third theory involves cyclical swelling and

sloughing of thoracic endometrial implants inside terminal bronchioles causing “localized hyperinflation by a checkvalve mechanism, which in turn causes a pneumothorax.”5

Clinical Presentation of Pneumothorax

Almost all patients with PSP report sudden ipsilateral chest pain, which may resolve spontaneously within 24 hours. Patients may present with dyspnea that is often mild. Although patients with PSP have no history of underlying pulmonary disease, decreased breath sounds and decreased tactile fremitus are usually present in larger pneumothoraxes and percussion is hyper-resonant.

Catamenial pneumothorax presents with ipsilateral chest pain (typically on the right side), dyspnea, and/or shoulder pain. Patients will present with symptoms that began 1 day before and within 72 hours after onset of menstruation.3 Thoracic endometriosis is defined as the presence of ectopic endometrial tissue in the thoracic cavity, which is the most frequent extrapelvic location of endometriosis.8 Endometriosis is associated with spontaneous pneumothorax; in fact, the most common manifestation of thoracic endometriosis syndrome is catamenial pneumothorax. The presence of pelvic endometriosis was reported in 55% of patients with catamenial pneumothorax, according to Gil et al.9 Endometriosis should be considered in premenopausal patients presenting with symptoms of chest pain and shortness of breath. Taking a thorough history including gynecologic history and diseases is crucial in premenopausal patients presenting with catamenial pneumothorax.

Diagnosis of Pneumothorax

Along with physical examination, diagnosis can be confirmed by an upright posteroanterior chest radiograph, which also can be used to estimate the size of the pneumothorax. In patients with a small PSP, however, computed tomography (CT) may be necessary to diagnose the presence of pleural air.1 Because of cost and access, a CT scan should only be used in unclear cases, especially in patients aged 10 to 40 years with minor pneumothorax or complex cases with additional soft tissue edema, pulmonary disease, or unsuccessful tube thoracostomy.2 Blebs and bullae seen on CT can help influence treatment choice and may indicate a more invasive, surgical approach to treatment to prevent recurrence.

The diagnosis of catamenial pneumothorax is often made clinically based on patient history of shortness of breath

Patients with catamenial pneumothorax presents with ipsilateral chest pain (typically on the right side), labored breathing, and/or shoulder pain.

and recurrent chest pain that is temporally related to the menstrual cycle. In these cases, CT and magnetic resonance imaging (MRI) are typically used to confirm the diagnosis of catamenial pneumothoraxes. A CT scan with contrast is usually performed first and can identify endometrial tissue/ lesions on the diaphragm.9 MRI is better for diagnosing pleural nodules and diaphragmatic or hemorrhagic lesions because its sensitivity for soft tissues is superior to that of CT imaging.9 Chest radiography can diagnose pneumothorax but plays a minimal role in the diagnosis of pleural and diaphragmatic lesions, which are typically associated with catamenial pneumothoraxes. In the Gil study, diaphragmatic lesions were found in approximately 89% of cases as visualized by laparoscopy.9

Treatment of Pneumothorax

The main treatment goals of PSP are to remove air from the pleural cavity and prevent recurrence. When determining the type of intervention to perform, clinicians must consider the chance of recurrence and any associated factors leading to pneumothorax (blebs and/or bullae, catamenial pneumothorax, thoracic endometriosis).Treatment methods include conservative treatment or surgical intervention, with the most common approach to surgery being video-assisted thoracoscopic surgery (VATS,Table).9,10

If the patient is stable and the distance between the lung and chest wall is less than or equal to 2 to 3 cm, 100% oxygen, and observation are the treatment of choice.11 However, if the patient is unstable and/or the distance between the lung and the chest wall is greater than 3 cm, thoracentesis or chest tube placement is recommended.11

A study by Olesen et al compared the treatment of first episodes of PSP by simple chest tube insertion vs chest

tube insertion and VATS pleurodesis. In this study, blebs were measured as less than 1 cm and greater than 1 cm. The 1-year recurrence rate was significantly lower in the intervention group compared with those who received chest tube drainage (29% vs 49%, respectively). When stratified by bullae size, VATS proved significantly better for larger bullae (≥1 cm; P =.014). The study authors observed a sizeresponse relationship with larger bullae associated with an increased risk of recurrence.12

Recent studies have challenged the need to remove air from the pleural cavity of stable PCP patients, “introducing conservative management as a valuable therapeutic option,” noted Plojoux et al.13 Other less invasive options discussed by the authors were needle aspiration and graded talc poudrage pleurodesis to prevent recurrence.13 In patients less than age 18 years, conservative treatment was associated with a greater risk of recurrence compared with patients who underwent surgery.14 Multiple studies have also shown that surgery reduces ipsilateral recurrence in children.14

VATS pleurodesis or chemical pleurodesis to prevent a future recurrence is recommended in all patients with a recurrent PSP, with an initial spontaneous pneumothorax that required VATS or tube thoracostomy/blebectomy, and who have an occupation or hobby where the risk of recurrence is increased (eg, a pilot or scuba diver).11

For patients diagnosed with catamenial pneumothorax and/or thoracic endometriosis who have a high probability of recurrent pneumothorax, surgical intervention should be considered as a first-line therapy to lessen the chance of recurrence compared with medical treatment only.8 In the patient population with thoracic endometriosis associated with catamenial pneumothorax, surgical treatment combined with hormone therapy is associated with better results than surgery alone.5

Conservative treatment Rest, oxygen therapy, thoracocentesis, or chest tube placement

Surgical treatment Stapling or removal of blebs and bullae (blebectomy), wedge resection (apical wedge pleurectomy), and pleurodesis (abrasion-mechanical or talc-chemical)

Postoperative treatment of catamenial pneumothorax with gonadotropin-releasing hormone (GnRH) agonists or oral contraceptives similar to that for pelvic endometriosis can be administered for symptom relief and reduce recurrences as well as suppress concomitant pelvic endometriosis.9 In premenopausal patients who don’t wish to conceive and are diagnosed with catamenial pneumothorax that is endometriosis related or nonendometriosis related, hormonal therapy/ovulatory suppressants as preventive therapy for future recurrence should be considered.

In women with catamenial pneumothorax, a CT scan with contrast is usually performed first and can identify endometrial tissue/lesions on the diaphragm.

TABLE. Treatment Options for Pneumothorax9,10

Prognosis

The prognosis is very good in patients who receive timely treatment, which prevents progression to potentially lifethreatening tension pneumothorax and obstructive shock. To ensure pneumothoraxes are not missed, clinicians should have a low threshold to evaluate for SPS in a patient who presents with dyspnea and chest pain.10 In the case of a premenopausal woman who presents with dyspnea and chest pain, the clinician should suspect catamenial pneumothorax and capture their menstrual history.

Recurrence rates range from 14% to 55% over 1 to 5 years but the highest risk is within the first 30 days.9,11 It is important to identify risk factors for reoccurrence early, so proper treatment can be performed to prevent reoccurrence. Identification of blebs and bullae, catamenial pneumothorax, and endometriosis-related pneumothorax all increase the risk of reoccurrence and, therefore, require more invasive/surgical treatment. Missed or improper diagnosis of these specific conditions can lead to what could have been a preventable reoccurrence, further procedures, and hospital stays. ■

Carlie Overley, PA-C, works with the Advanced Neurosurgery Associates team at Northside Hospital in metropolitan Atlanta, GA. She recently graduated from Augusta University’s Physician Assistant program as a member of the Alpha Eta National Honor Society.

References

1. Noppen M. Spontaneous pneumothorax: epidemiology, pathophysiology and cause. Eur Respir Rev. 2010;19(117):217-219.

2. Schnell J, Korvllos A, Lopez-Pastorini A, Lefering RR, Stoelben E. Spontaneous pneumothorax. Dtsch Arztebl Int. 2017:114(44):739-744.

3. Lesur O, Delorme N, Fromaget JM, Bernadac P, Polu JM. Computed tomography in the etiologic assessment of idiopathic spontaneous pneumothorax. Chest. 1990;98:341-347.

4. Donahue DM, Wright CD,Viale G, Mathisen DJ. Resection of pulmonary blebs and pleurodesis for spontaneous pneumothorax. Chest. 1993;104: 1767-1769.

5. Shrestha B, Shrestha S, Peters P, Ura M, Windsor M, Naidoo R. Catamenial pneumothorax, a commonly misdiagnosed thoracic condition: multicentre experience and audit of a small case series with review of the literature. Heart Lung Circ. 2019; 28(6):850-857.

6. Olesen WH, Titlestad IL, Anderen PE, Lindahl-Jacobsen R, Lich PT. Incidence of primary spontaneous pneumothorax: a validated, registerbased nationwide study. ERJ Open Res. 2019;5(2):00022-2019.

7. Horio H, Nomori H, Kobayashi R, et al. Impact of additional pleurodesis in video-assisted thoracoscopic bullectomy for primary spontaneous pneumothorax. Surg Endosc. 2002;16(4):630-634.

8. Visouli AN, Zarogoulidis K, Kougioumtzi I, et al. Catamenial pneumothorax. J Thorac Dis. 2014;6(Suppl 4):S448-460.

9. Gil Y, Tulandi T. Diagnosis and treatment of catamenial pneumothorax: a systematic review. J Minim Invasive Gynecol. 2020;27(1):48-53.

10. Vuong NL, Elshafay A, Thao LP, et al. Efficacy of treatments in primary spontaneous pneumothorax: a systematic review and network meta-analysis of randomized clinical trials. Respir Med. 2018;137: 152-166.

11. Segraves JM, Dulohery MM. Primary spontaneous pneumothorax due to high bleb burden. Respir Med Case Rep. 2016;19:109-111.

12. Olesen WH, Katballe N, Sindby JE, et al. Surgical treatment versus conventional chest tube drainage in primary spontaneous pneumothorax: a randomized controlled trial. Eur J Cardiothorac Surg. 2018;54(1):113-121.

13. Plojoux J, Froudarakis M, Janssens JP, Soccal PM, Tschopp JM. New insights and improved strategies for the management of primary spontaneous pneumothorax. Clin Respir J. 2019;13(4):195-201.

14. Ng GYH, Nah SA, Teoh OH, Ong LY. Primary spontaneous pneumothorax in children: factors predicting recurrence and contralateral occurrence. Pediatr Surg Int. 2020;36(3):383-389. Check

The prognosis is very good in patients who receive timely treatment, which prevents progression to potentially life-threatening pneumothorax.

Men’s Bones Break Too: Role of Liver Disease in Cause of Osteoporosis

Although less common in men than women, osteoporosis affects approximately 16% of men aged 50 years and older, and 1 in 4 men older than 50 years will break a bone because of osteoporosis.1,2 Outcomes of fragility fractures are worse in men than in women; 1 in 3 men who experience a hip fracture at age 75 to 84 years will die within the first year.3-5 However, few men consider themselves at risk for osteoporosis despite having risk factors for this condition including obesity, diabetes, sedentary lifestyle, smoking, alcohol use disorder, kidney disease, and liver disease.6 Men are also less frequently screened for bone mineral density (BMD) loss at midlife compared with women.6

This review will focus on liver disease as a risk factor for osteoporosis in men as both of these conditions typically progress asymptomatically until fracture, abnormal liver enzymes, or steatosis on imaging are detected. Screening and treatment recommendations for osteoporosis in all men will be outlined.

Osteoporosis in Patients With NAFLD

Nonalcoholic fatty liver disease (NAFLD) affects approximately 30% of the US population, with the subtype of nonalcoholic steatohepatitis affecting 5%.7,8 The condition affects up to 75% of those who are overweight and one-third to two-thirds of people with type 2 diabetes.8-10 The number of people in the US with NAFLD is expected

In men, nonalcoholic fatty liver disease and alcoholic liver disease are underrecognized causes of osteoporosis, which affects 16% of older men.

Few men consider themselves at risk for osteoporosis.

to reach 100 million by 2030 owing to the projected increase in obesity and type 2 diabetes rates.8

The prevalence and severity of NAFLD are higher in men than in premenopausal women; however, postmenopausal women have higher rates than men.11 The disease is most commonly found among Hispanic individuals followed by non-Hispanic White individuals and Asian Americans.9 Non-Hispanic Black patients have a significantly lower risk of NAFLD compared with non-Hispanic White patients.9,12

Multiple pathogenic pathways exist in NAFLD that contribute to a proinflammatory state, placing the individual at higher risk for osteoporosis. Individuals with NAFLD often can be described as those with an expanded and inflamed visceral adipose tissue and accompanying metabolic syndrome, including obesity. This dysfunctional inflamed tissue plays a role in targeting the liver, which can be a source of proinflammatory, procoagulant, and profibrogenic factors.7 These inflammatory processes can affect both the bone and the metabolic/hormonal processes that often affect those with NAFLD.The release of proinflammatory cytokines and hormones from this inflamed adipose tissue is also involved in developing systemic insulin resistance, which can adversely affect bone structure and quality.7

Chronic inflammation is interesting when considering the pathogenesis of osteopenia/osteoporosis.Tumor necrosis factor (TNF)-alpha stimulates osteoclastogenesis while also inhibiting

POLL POSITION

osteoblastic activity.7 Tumor necrosis factor-alpha also inhibits osteoclast apoptosis, inhibits osteoblast differentiation, and increases apoptosis for these cells.13 An inverse association exists between TNF-alpha and vitamin D levels, which also could inversely affect skeletal metabolism.14

Osteopontin enhances bone resorption and reduces bone deposition. In NAFLD, osteopontin is overexpressed. Osteoprotegerin is a glycoprotein impacting bone turnover in part because of its role as a decoy receptor for the receptor activator of nuclear factor kappa-B ligand (RANK-L), which inhibits osteoclast differentiation and activation.15 Osteoprotegerin also promotes cell survival by inhibiting TNFrelated apoptosis-inducing ligand (TRAIL)-induced apoptosis.15

It is not surprising that decreased osteoprotegerin levels are linked to abdominal obesity, insulin resistance, and NAFLD.16

Osteocalcin, which is a noncollagen protein within the bone matrix, is primarily expressed by osteoblasts. Decreased osteocalcin levels are linked in a graded relationship with the presence and severity of NAFLD.7 The hormone leptin plays a role in the bone microarchitectural process and has a possible antisteatotic but also a proinflammatory and profibrogenic action, which exerts regulatory effects on BMD in individuals with NAFLD.7

Vitamin D3 has a wide variety of effects on the body including bone mineralization. Noncirrhotic NAFLD individuals with low levels of serum 25-hydroxyvitamin D3 have greater severity of NAFLD fibrosis/steatosis, independent of other risk factors.7 In addition to the cellular changes associated with NAFLD linked to osteoporosis, the population of individuals with NAFLD is typically more sedentary than healthy control groups, which reduces mechanical stress loading that aids bone strengthening.7

Osteoporosis in Alcoholic Liver Disease

Alcoholic liver disease (ALD) is also linked to an increased risk for osteoporosis and is more common in men than women. The term ALD is used to describe a spectrum of diseases ranging from alcoholic fatty liver disease (AFLD) to advanced ALD (including alcoholic hepatitis, cirrhosis, and cirrhosis complications). The overall prevalence of ALD in the US is estimated at 8.1% in the general population and 9.0% among men.17 The prevalence of alcoholic-fatty liver disease in the US is 4.3% (60.6% men).18

For more polls, visit ClinicalAdvisor.com/Polls.

The incidence of osteoporosis among patients with ALD ranges from 11% to 22% in those without liver cirrhosis to 20% to 50% among those with liver cirrhosis.7

Multiple pathogenic pathways exist in NAFLD that contribute to a proinflammatory state, placing the individual at higher risk for osteoporosis.

Nonalcoholic fatty liver disease is most commonly found among this racial/ethnic group:

Changes in bone architecture in individuals with ALD and pancreatitis are similar to those with NAFLD, but heavy alcohol consumption could directly harm and reduce osteoblasts.19 Altered vitamin D, testosterone, and parathyroid hormone levels are also sequelae of chronic alcohol consumption, which leads to decreased bone formation.19 In addition to the proinflammatory cytokines that are increased in NAFLD, sclerostin (which regulates part of the bone formation pathway) is increased in end-stage ALD patients.19 In both cirrhotic and noncirrhotic liver disease, bone deterioration is part of the disease process. Cirrhotic patients develop metabolic bone disease and alcoholic or viral cirrhosis patients frequently have osteodystrophy.7 Young patients with cirrhosis (particularly related to alcoholism) have an excess risk of bone fractures.7

Caution should be used in overgeneralizing findings to those patients with non-alcoholic steatohepatitis (NASH)-cirrhosis, but it is worth studying to see if these patients have similar risks for bone fractures and decreased BMD.

Osteoporosis Screening in Men

Osteoporosis screening tools appear to have equal predictive value in both men and women.20 However, insufficient evidence is available to inform guidelines on when men should first receive a dual-energy x-ray absorptiometry (DEXA) or BMD testing.4 Indications for BMD testing are listed in Table 1, however, chronic liver disease is not usually mentioned as a risk factor.20,21

The United States Preventative Services Task Force (USPSTF) changed their recommendation for screening of men to only include those with the following risk factors for osteoporosis20:

• Low body mass

• Chronic corticosteroid use

• Heavy alcohol consumption

• Current smoking

• Previous fractures

• Recent falls

The National Osteoporosis Foundation (NOF), rebranded as the Bone Health and Osteoporosis Foundation (BHOF) in October 2021, recommends screening for men aged 50 to 59 years with risk factors or aged 50 years and older with a history of adult-aged fracture.21

In a cohort of men who had sustained a fragility fracture, 92.8% had not previously received an osteoporosis diagnosis and only 6% had undergone a DEXA screening 2 years prior to their fracture.4 Even among men with additional

high-risk characteristics, including use of β-blocker medications, mobility impairment, or opioid use, screening rates were low.4 Less well-known risk factors for osteoporosis now include hypogonadism, NAFLD, hemochromatosis, and biliary disease.7,22

Osteoporosis Treatment in Men

Studies assessing the efficacy of osteoporosis medications in men are lacking and the USPSTF noted that assumptions cannot be derived from studies in postmenopausal women as the underlying biology of bones may differ based on differences in sex hormone.20 In the American College of Physicians (ACP) 2023 updated guideline on the pharmacologic treatment of primary osteoporosis, the group now recommends that clinicians preferentially use bisphosphonates as first-line therapy in both women and men with osteoporosis (Table 2, page 18).23 The ACP also suggested that the RANK ligand inhibitor (denosumab) can be used as a second-line pharmacologic treatment to reduce the risk of fractures in males diagnosed with primary osteoporosis who have contraindications to or experience adverse effects from bisphosphonates. Both of these recommendations were considered conditional and are based on low-certainty evidence.

TABLE 1. Indications for Bone Mineral Density Testing20,21

Women ≥65 y and men ≥70 y regardless of risk factors

Younger postmenopausal women, women in the menopausal transition, and men 50-69 y with clinical risk factors for fracture

Adults with conditions (rheumatoid arthritis, autoimmune disease, or diseases affecting bone health) or medications (eg, glucocorticoids) associated with low bone mass

Heavy alcohol consumption

Smoking history

Recent falls

Adults aged ≥50 y with a history of adult-age fracture

Source: US Preventive Services Task Force et al20 and Leboff et al.21

Men with noncirrhotic NAFLD and low levels of serum 25-hydroxyvitamin D 3 have greater severity of NAFLD fibrosis/steatosis.

TABLE 2. American College of Physicians Guideline on Pharmacologic Treatment of Osteoporosis23

Recommendation GRADE

Use bisphosphonates (alendronate, ibandronate, risedronate, zoledronate) as initial treatment to reduce the risk of fractures in postmenopausal females and males diagnosed with primary osteoporosis

Use bisphosphonates as initial treatment to reduce the risk of fractures in males diagnosed with primary osteoporosis

Use the RANK ligand inhibitor denosumab as a second-line pharmacologic treatment to reduce the risk of fractures in postmenopausal females and males diagnosed with primary osteoporosis who have contraindications to or experience adverse effects of bisphosphonates

Use the sclerostin inhibitor romosozumab or the recombinant PTH teriparatide followed by a bisphosphonate to reduce the risk of fractures only in females with primary osteoporosis at very high risk of fracture

Use an individualized approach to decisions regarding use of bisphosphonates in females older than 65 y with osteopenia to reduce the risk of fractures

Strong recommendation; high-certainty evidence

Conditional recommendation; low-certainty evidence

Conditional recommendation; low-certainty evidence

Romosozumab; moderate-certainty evidence Teriparatide; low-certainty evidence

Conditional recommendation; low-certainty evidence

ACP, American College of Physicians; GRADE, Grading of Recommendations Assessment, Development, and Evaluation; PTH, parathyroid hormone

Source: Qaseem et al.23

The ACP’s recommendations on osteoporosis treatment in males are based on a systematic review of 6 randomizedcontrolled studies and 4 observational studies that included only males with osteoporosis or in which patient outcomes were stratified by sex.23 The group found no evidence of differences in treatment benefits or harms by sex. Data on bisphosphonates suggested a reduction in radiographic vertebral fractures in men (absolute risk difference, 140 fewer events per 1000 patients) compared with placebo in trials assessing outcomes at least 36 months from treatment initiation. None of the trials were designed to evaluate the effects of treatment on hip fractures in men and the ACP concluded that bisphosphonates probably did not reduce other nonvertebral fracture outcomes.

The parathyroid hormone-related peptide analog abaloparatide is the most recently approved agent for use in men with osteoporosis at high risk for fracture; the drug was first approved for use in postmenopausal women. Approval in men was based on results of a phase 3 trial in which abaloparatide significantly increased BMD at the lumbar spine (primary outcome) at 6 and 12 months and also significantly increased BMD at the hip and femoral neck at 12 months.24 At the time of publication of the ACP guideline, the group concluded that data on the benefits and harms of abaloparatide was inconclusive.23

The ACP’s review showed no difference in the risk for serious adverse events among males based on high-certainty evidence.23 Additionally, no difference in withdrawals due to adverse events or atrial fibrillation was found among males; this information was based on moderate- and low-certainty evidence, respectively.

Longer treatment with bisphosphonates in males was linked to a higher risk for atypical femoral fractures and osteonecrosis of the jaw, and zoledronate was linked to an increased likelihood of pyrexia, myalgia, and arthralgia in older males, according to the ACP.23

Conclusion

Osteoporosis is a highly underscreened and undertreated disease in men. Risk factors for osteoporosis are different in men vs women, and practitioners need to be aware of whom to screen and effective screening tools. More research is needed to determine if other newer classes of medications, such as injectable anabolic agents, would benefit men with osteoporosis who have comorbid liver diseases such as NAFLD, cirrhosis, and NASH. ■

Karen D. French, DNP, FNP-C, RN, is a practicing FNP in a large hepatology/GI practice in Southern California. She is director of the FNP program and an associate professor at Azusa Pacific University in Azusa, California.

References

1. National Osteoporosis Foundation. Healthcare Professionals Toolkit. 2019. Accessed March 30, 2023. https://www.bonesource.org/ healthcare-professionals-toolkit

2. Osteoporosis by the numbers. Bone Health and Osteoporosis Foundation. Updated April 1, 2029. Accessed March 30, 2023. https://www.bonehealthandosteoporosis.org/wp-content/uploads/BHOF_infographic_1pager_ updated-4.1.19-2.pdf

3. Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A. Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res. 2007;22(3):465-475.

4. Williams S, Daigle S, Weiss R, Wang Y, Arora T, Curtis J. Characterization of older male patients with a fragility fracture [abstract]. Arthritis Rheumatol. 2020;72(suppl 10). https://acrabstracts.org/abstract/ characterization-of-older-male-patients-with-a-fragility-fracture/

5. von Friesendorff M, McGuigan FE, Besjakov J, Akesson K. Hip fracture in men—survival and subsequent fractures: a cohort study with 22-year followup. J Am Geriatr Soc. 2011;59(5):806-813.

6. Osteoporosis in men. National Institutes of Health. Updated October 2018. Accessed April 5, 2022. https://www.bones.nih.gov/health-info/bone/ osteoporosis/men

7.Targher G, Lonardo A, Rossini M. Nonalcoholic fatty liver disease and decreased bone mineral density: is there a link? J Endocrinol Invest. 2015;38(8):817-825.

8. Cotter TG, Rinella M. Nonalcoholic fatty liver disease 2020: the state of the disease. Gastroenterology. 2020;158(7):1851-1864.

9. Nonalcoholic fatty liver disease (NAFLD). American Liver Foundation. Updated August 5, 2022. Accessed April 4, 2023. https://liverfoundation.org/ about-your-liver/facts-about-liver-disease/fatty-liver-disease/

10. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease — meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73-84.

11. Lonardo A, Nascimbeni F, Ballestri S, Fairweather D, Win S, Than TA, Abdelmalek MF, Suzuki A. Sex differences in nonalcoholic fatty liver disease: state of the art and identification of research gaps. Hepatology. 2019;70(4):1457-1469.

12. Schneider AL, Lazo M, Selvin E, Clark JM. Racial differences in nonalcoholic fatty liver disease in the U.S. population. Obesity (Silver Spring). 2014;22(1):292-299.

13. Nanes MS. Tumor necrosis factor-alpha: molecular and cellular mechanisms in skeletal pathology. Gene. 2003;321:1-15.

14. Peterson CA, Heffernan ME. Serum tumor necrosis factor-alpha concentrations are negatively correlated with serum 25(OH)D concentrations in healthy women. J Inflamm (Lond). 2008;5:10.

15. Reid P, Holen I. Pathophysiological roles of osteoprotegerin (OPG). Eur J Cell Biol. 2009;88(1):1-17.

16. Blázquez-Medela AM, López-Novoa JM, Martínez-Salgado C. Osteoprotegerin and diabetes-associated pathologies. Curr Mol Med. 2011;11(5):401-416.

17. Dang K, Hirode G, Singal AK, Sundaram V, Wong RJ. Alcoholic liver disease epidemiology in the United States: a retrospective analysis of 3 US databases. Am J Gastroenterol. 2020;115(1):96-104.

18. Wong T, Dang K, Ladhani S, Singal AK, Wong RJ. Prevalence of alcoholic fatty liver disease among adults in the United States, 2001-2016. JAMA 2019;321(17):1723-1725.

19. Jadzic J, Milovanovic P, Cvetkovic D, et al. Mechano-structural alteration in proximal femora of individuals with alcoholic liver disease: Implications for increased bone fragility. Bone. 2021;150:116020.

20. US Preventive Services Task Force; Curry SJ, Krist AH, Owens DK, et al. Screening for osteoporosis to prevent fractures: US Preventive Services Task Force recommendation statement. JAMA. 2018;319(24):2521-2531.

21. LeBoff MS, Greenspan SL, Insogna KL, Lewiecki EM, Saag KG, Singer AJ, Siris ES. The clinician’s guide to prevention and treatment of osteoporosis. Osteoporos Int. 2022;33(10):2049-2102.

22. Siqueira MMLG, Casulari LA, Freitas WM, Carneiro MV, Mendes LSC. Risk factors associated with fracture of the lumbosacral spine and its compromise in the quality of life of cirrhotics. Arq Gastroenterol. 2022;59(1):9-15.

23. Qaseem A, Hicks LA, Etxeandia-Ikobaltzeta I, Shamliyan T, Cooney TG; Clinical Guidelines Committee of the American College of Physicians. Pharmacologic treatment of primary osteoporosis or low bone mass to prevent fractures in adults: a living clinical guideline from the American College of Physicians. Ann Intern Med. 2023;176(2):224-238.

24. Czerwinski E, Cardona J, Plebanski R, et al. The efficacy and safety of abaloparatide-SC in men with osteoporosis: a randomized clinical trial. J Bone Miner Res. 2022;37(12):2435-2442.

A Case of Severe Monthly Headaches in Teacher: Workup and Treatment

A35-year-old Black woman presents to the emergency department (ED) with a severe headache around her right temple and eye, which is accompanied by nausea, light sensitivity, and mental fog. She is a high school teacher and her headache began suddenly about 3 hours earlier while she was giving a presentation to her colleagues. She describes the pain as throbbing, severe, constant, and disabling. She denies having fever, motor weakness, or problems with gait and balance.

The patient has experienced this type of headache since the age of 12 years. Her mother suffered from similar headaches when she was younger.The patient was diagnosed with menstrual migraines at the age of 25 years and was told to take ibuprofen as needed. Her headaches have significantly increased in frequency in the last year while she was completing graduate school studies. She thinks the headaches are an “occupational hazard” as most teachers she works with experience headaches.

The headaches usually start suddenly, 2 days before her menstrual cycle, and last from several hours to 2 to 3 days if not treated.The headaches are associated with nausea and light sensitivity 80% of the time. The patient notes that she has 2 to 4 headache days a month that are not associated with her menstrual cycle.

She has been to the ED on 3 occasions for migraines in the last year. Medication history includes ibuprofen, which she notes works only 30% to 50% of the time, and topiramate, which she stopped after a week because of significant cognitive side effects

Migraine affects approximately 15% of the US population.

The patient’s severe headaches have increased in frequency in the last year, often accompanying her menstrual cycle but also occurring randomly.

FEATURE: VERA GIBB, DNP, APRN, FNP-C, AQH, CCTP; SAFA’A AL-ARABI, PHD, RN, MPH, MSN, CNL

and inability to focus at work. Her primary care physician (PCP) told her she cannot take propranolol because of her history of asthma but said that the headaches will subside when she goes through menopause. She has not tried any other preventive agents. Diagnostic workup prior to this visit included a computed tomography (CT) scan and magnetic resonance imaging (MRI), both of which were negative for other secondary causes of headache (eg, tumors, bleeding, infections).

Discussion

Migraine is a chronic neuroinflammatory disorder that occurs across a patient’s lifespan. Patients can experience episodic exacerbations and age-dependent changes in clinical presentation and prevalence. Migraine affects approximately 15%

of the US population1,2 and is more common than type 1 diabetes, asthma, and epilepsy combined.3,4 According to the American Migraine Foundation, 1 in 4 American households have a person with migraines. Women have a 3-fold higher prevalence of migraine compared with men, with 30% of women experiencing migraines in their lifetime.3

Racial disparities in migraine diagnosis and management are also found. The American Migraine Foundation noted that only 47% of Black patients and 50% of Hispanic patients with headaches have an official headache diagnosis compared with 70% of White patients.5 Black patients with migraine also report higher pain intensity than White patients but are less likely to receive acute pain medication. Only 14% of Black patients receive prescriptions for acute migraine medications compared

TABLE 1. Pharmacotherapy for Migraine and Headache Treatment13

Generic Brand Dose

Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonist

Rimegepant Nurtec ODT

Ubrogepant Ubrelvy

Zavegepant Zavzpret

Ergot Alkaloid

Dihydroergotamine

mesylate

Migranal

Trudhesa

Adults: 75 mg once as needed (max daily dose). The safety of using more than 18 doses in a 30-day period has not been established. Children: not established.

Adults: Initially 50 mg or 100 mg tablet; may give a second dose ≥2 hrs after initial dose (max 200 mg/d). The safety of treating more than 8 migraines in a 30-day period has not been established. Children: not established.

Adults: Maximum dose 10 mg (1 spray) in 24-hour period. The safety of treating more than 8 migraines in a 30-day period has not been established. Children: Not established

Adults: 1 mL IV at 1 hr intervals; max 2 doses/day. Or, 1 mL IM or SC at 1 hr intervals; max 3 doses/day. For all: max 6 doses/wk. Not for chronic use. Children: not established.

Adults: 1 nasal spray in each nostril, repeat 15 mins later; max 6 sprays/24 hrs and 8 sprays/wk. Children: not established.

Adults: 1 nasal spray in each nostril, may repeat at least 1 hr later if needed; max 2 doses (4 sprays) within 24 hrs or 3 doses (6 sprays) within 7 days. Children: not established.

Ergotamine tartrate

Caffeine

Ergotamine tartrate

Caffeine

Adults: 2 tablets at onset of attack, then 1 tab every ½ hr if needed; max 6 tabs/attack, 10 tabs/wk. Children: not recommended.

Adults: 1 rectal suppository at onset of attack, then 1 supp after 1 hr if needed; max 2 supps/attack, 5 supps/wk. Children: not recommended.

Non-Steroidal Anti-inflammatory (NSAID)

Celecoxib Elyxyb

Adults: 120 mg (4.8 mL) oral solution. Max: 120 mg/d. Use for the fewest number of days per month, as needed. Moderate hepatic impairment, CYP2C9 poor metabolizers: max 60 mg (2.4 mL). Children: not established.

Diclofenac potassium Cambia ≥18 yrs: Mix 1 packet (50 mg) with 30–60 mL of water only and drink immediately. Packet contains phenylalanine. Not interchangeable with other forms of diclofenac. <18 yrs: not recommended.

Ibuprofen Advil Migraine ≥18 yrs: Usually 400 mg once daily. Max 2 caps/24 hrs. <18 yrs: consult physician.

Selective 5-HT1B/1D Receptor Agonist

Almotriptan (as malate)

≥12 yrs: 6.25–12.5 mg single dose tablets; may repeat once after 2 hrs; max 25 mg/24 hrs. Hepatic impairment, CrCl 10–30 mL/min, or concomitant potent CYP3A4 inhibitors: initially 6.25 mg once; max 12.5 mg/24 hrs. The safety of treating an average of more than 4 migraines over 30 days is not established. <12yrs: not established.

Eletriptan HBr Relpax ≥18 yrs: one 20 mg or 40 mg tablet; max single dose: 40 mg. May repeat once after 2 hrs; max 80 mg/day. The safety of treating an average of more than 3 headaches in a 30-day period has not been established. <18 yrs: not established.

Frovatriptan (as succinate)

Frova ≥18 yrs: 2.5 mg tablet with fluids; may repeat once after 2 hrs; max 7.5 mg/24 hrs. The safety of treating an average of more than 4 headaches in a 30-day period has not been established. <18 yrs: not recommended.

Naratriptan HCl Amerge ≥18 yrs: 1 mg or 2.5 mg tablet with fluids; may repeat once after 4 hrs; max 5 mg/24 hrs. The safety of treating, on average, more than 4 headaches in a 30-day period has not been established. Mild-to-moderate renal/hepatic impairment: initially 1 mg; max 2.5 mg/24 hrs. <18 yrs: not recommended.

Rizatriptan (as benzoate)

Maxalt ≥18 yrs: Initially 5 mg or 10 mg tablet or ODT; may repeat after 2 hrs; max 30 mg/24 hrs. Concomitant propranolol: 5 mg; max 15 mg/24 hrs.The safety of treating, on average, more than 4 headaches in a 30-day period has not been established. <6 yrs: not established. 6–17yrs (<40 kg): 5 mg; (≥40 kg): 10 mg. Concomitant propranolol (≥40 kg only): max 5 mg/24 hrs. The efficacy and safety of treating with ≥1 dose/24 hrs have not been established. ODT contains phenylalanine.

Maxalt-MLT

with 37% of White patients.5 Migraines impose a substantial direct and indirect financial burden.The combined cost of direct medical expenses and lost productivity from migraines is $20 million in the US alone.3 On average, a person with migraine misses 9 workdays annually because of their condition.6

Migraine is one of the most common and debilitating diseases encountered by primary care providers (PCPs).4 Primary care is the predominant site for migraine consultation and management for 70.3% of patients, and migraine accounts for 5 to 9 million PCP office visits annually in the US.1,7 Most patients (73.5%) who present with migraine symptoms to a PCP are not referred to a neurologist and remain in primary care.8

Disease Course and Treatment

Migraines are often undiagnosed and undertreated.The understanding of migraines shifted in the late 1990s.9-11 Modern understanding of migraine pathophysiology radically changed

the migraine treatment paradigm, ushering in a new era of migraine-specific therapies such as 5-hydroxytryptamine 1F (5-HT1F) receptor agonists and calcitonin gene-related peptide (CGRP) receptor antagonists (Table 1).12,13 Neuromodulatory devices approved by the Food and Drug Administration (FDA), including Cefaly, Nerivio, and Relivion, are guideline-recommended for acute treatment of migraines and gammaCore is approved to treat and prevent migraines in people older than age 12 years.14 As with any chronic disease, migraine prevention is the cornerstone of migraine management.15 Episodic migraine (EM) is 0 to 14 headache days per month and chronic migraine (CM) is 15 or more headache days per month.16

The American Headache Society (AHS) recommends migraine preventive management for patients with 6 or more migraine headache days per month.14 The AHS guidance outlines strategies for optimal drug selection of preventive treatment and agents with established efficacy in migraine

TABLE 1. Pharmacotherapy for Migraine and Headache Treatment13

Generic Brand Dose

Selective 5-HT1B/1D Receptor Agonist (continued)

Sumatriptan Imitrex Injection ≥18 yrs: 6 mg SC (may start at lower dose if 6 mg not tolerated). May repeat after 1 hr; max two 6 mg doses in 24 hrs. <18 yrs: not recommended.

Imitrex Nasal Spray ≥18 yrs: One 5 mg, 10 mg, or 20 mg nasal spray. May repeat dose once after 2 hrs; max 40 mg/day. The safety of treating an average of more than 4 headaches in a 30-day period has not been established. <18 yrs: not recommended.

Imitrex Tablets ≥18 yrs: 25–100 mg once, swallow tablet whole with fluids as soon as possible after migraine onset; may repeat dose at intervals of at least 2 hrs, max 200 mg/day; or single-dose tablets up to 100 mg/day if injection has been used. The safety of treating an average of more than 4 headaches in a 30-day period has not been established. <18 yrs: not recommended.

Onzetra Xsail ≥ 18 yrs: One nosepiece (11mg) in each nostril (22 mg total), using Xsail delivery device. May repeat once after ≥ 2 hrs; max 44 mg (4 nosepieces)/day or one dose of Onzetra Xsail and one dose of another sumatriptan product separated by ≥ 2 hrs. The safety of treating an average of more than 4 headaches in a 30-day period has not been established. <18 yrs: not established.

Tosymra ≥18 yrs: 10 mg as single nasal spray in one nostril. Reevaluate if no response. Max cumulative dose: 30 mg in 24 hrs with each dose separated by ≥1 hr. May also be given ≥1 hr after another sumatriptan product. <18 yrs: not recommended.

Zembrace Symtouch ≥18 yrs: 3 mg SC. May repeat after ≥1 hr; max 12 mg in 24 hrs. May also be given ≥1 hr after another sumatriptan product. <18 yrs: not recommended.

Zomig-ZMT

Zolmitriptan Zomig ≥18 yrs: Initially 1.25–2.5 mg tablets or ODT; max recommended single dose: 5 mg. If headache returns, may repeat after 2 hrs; max 10 mg/day. The safety of treating an average of more than 3 headaches in a 30-day period has not been established. Hepatic impairment (moderate to severe): 1.25 mg; (severe): max 5 mg/day. Concomitant cimetidine: max single dose: 2.5 mg, not to exceed 5 mg in 24 hrs. <18 yrs: Not recommended. ODT contains phenylalanine

Zomig Nasal Spray ≥12 yrs: Initially 2.5 mg nasal spray used once; max single dose: 5 mg. If headache returns, may repeat once after 2 hrs; max 10 mg/day. The safety of treating an average of more than 4 headaches in a 30-day period has not been established. Moderate to severe hepatic impairment: not recommended; use other forms. Concomitant cimetidine: max single dose: 2.5 mg, not to exceed 5 mg in 24 hrs. <12 yrs: Not established.

Selective 5-HT1B/1D Receptor Agonist + Non-Steroidal Anti-Inflammatory (NSAID)

Sumatriptan

succinate/naproxen

sodium

Treximet ≥12 yrs: 1 tablet (85/500 mg) once; may repeat once after 2 hrs; max 2 tablets/day. Mild-to-moderate hepatic impairment: 1 tab (10/60 mg)/day. The safety of treating an average of more than 5 migraines in a 30-day period has not been established. <12 yrs: Not established. 12–17 yrs: 1 tablet (10/60 mg) once; max 1 tablet (85/500 mg) a day. The safety of treating an average of more than 2 migraines in a 30-day period has not been established.

Selective 5-HT1F Receptor Agonist

Lasmiditan Reyvow Adults: 50–200 mg tablets once as needed; max 1 dose/24 hrs. The safety of treating an average of >4 migraines in a 30-day period has not been established. Children: Not established.

NOTES

IM, intramuscular; IV, intravenous; ODT, orally disintegrating tablets; SC, subcutaneous injection; soln, solution; supp, suppositories aTable is not an inclusive list of medications, official indications, and/or dosages. Please see drug monographs at eMPR.com, contact companies for full drug labeling and/or consult your health care provider. Reprinted with permission from eMPR.com.

prevention.14 The AHS also recommends considering use of neuromodulatory devices as an adjunct to the existing treatment plan for all patients requiring preventive treatment.14

Clinicians Need More Migraine Training

Despite the relatively high prevalence and morbidity associated with migraine, more than one-quarter of PCPs (28%) lack familiarity with the AHS recommendations and 53% fail to prescribe migraine preventive medications.17 The average gap between diagnosis and initiation of preventive medications is 4 years and the majority of patients with episodic migraines who meet criteria for preventive therapy are not prescribed treatments. Suboptimal migraine preventive management results in frequent office visits, increased disability, barbiturate and opioid overuse, absenteeism, and increased rates of urgent care and ED visits. The inadequate use of preventive management strategies is concerning given the high rates of

TABLE 2. Pharmacotherapy for Migraine Prevention13

Generic Brand Dose

PROPHYLAXIS

Antiepileptic Drugs

Divalproex sodium Depakote

Depakote ER

Topiramate Topamax Capsules

Topamax

Eprontia

migraine-related disability and high percentage of ED visits with migraine as the chief complaint (25%).18

No standardized approach exists for teaching headache medicine in medical school, PA, or nurse practitioner (NP) programs. Education in headache medicine varies from institution to institution. On average, less than 2 hours are dedicated to headache disorders in medical schools despite the very high prevalence of headache disorders in the general population. Most graduates do not receive the training needed to recognize and treat headache disorders during residency.17

The American Migraine Prevalence and Prevention (AMPP) study showed that PCPs are hesitant to prescribe migraine preventive medications because of the lack of understanding of AHS treatment guidelines and novel therapies.8

Another barrier is the lag time between publication and uptake in clinical practice. On average, it takes 17 years from the publication of research findings to implementation in clinical

Adults: Initially 250 mg delayed-release tablet twice daily; usual max 1 g/day. Elderly: reduce initial dose and titrate slowly; monitor. Concomitant rufinamide: initiate at a low dose and titrate. Children: Not recommended.

Adults: 500 mg extended-release tablet once daily for 1 week, then 1 g once daily. Elderly: reduce initial dose and titrate slowly; monitor. Concomitant rufinamide: initiate at a low dose and titrate. Children: Use other forms.

≥12 yrs: Titrate at 1-week intervals to target dose of 100 mg/day. Initially 25 mg once daily in the PM, then 25 mg twice daily, then 25 mg in the AM and 50 mg in the PM, then 50 mg twice daily. <12 yrs: Not established.

Adults: Initially 25 mg once daily in the PM, then 25 mg twice daily, then 25 mg in the AM and 50 mg in the PM, then to target dose 50 mg twice daily. Titrate at 1 wk intervals. Children: Not established.

Beta-Blockers

Propranolol

Timolol

Inderal LA

Adults: Initially 80 mg scored tablet daily in divided doses. Usual range: 160–240 mg/day. Discontinue if poor result after 4–6 wks. Children: Not recommended.

Adults: Initially 10 mg tablet twice daily. Increase weekly if needed; max 30 mg daily in 2 divided doses. Evaluate at 6–8 wks. Children: Not recommended.

Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonist

Atogepant Qulipta

Eptinezumab-jjmr Vyepti

Erenumab-aooe Aimovig

Fremanezumab-vfrm Ajovy

Galcanezumab-gnlm Emgality

Adults: Episodic migraine: 10 mg, 30 mg, or 60 mg tablets once daily. Chronic migraine: 60 mg tablet once daily. Children: Not established.

Adults: IV infusion over 30 mins. 100 mg every 3 mos; some patients may benefit from 300 mg every 3 mos.

Children: Not established.

Adults: 70 mg SC once monthly; some patients may benefit from 140 mg monthly. Children: Not established.

Adults: 225 mg SC once monthly or 675 mg (three 225 mg injections) every 3 mos. Children: Not established.

Adults: Initially 240 mg SC loading dose (two 120 mg injections), followed by 120 mg monthly.

Children: Not established.

Rimegepant Nurtec ODT Adults: Episodic migraine: 75 mg ODT every other day. The safety of using more than 18 doses in a 30-day period has not been established. Children: Not established.

NOTES

IM, intramuscular; IV, intravenous; ODT, orally disintegrating tablets; SC, subcutaneous injection; soln, solution; supp, suppositories aTable is not an inclusive list of medications, official indications, and/or dosages. Please see drug monographs at eMPR.com, contact companies for full drug labeling and/or consult your health care provider. Reprinted with permission from eMPR.com.

practice. According to Haines and Jones’s Translation Model, these long delays result in suboptimal patient care outcomes. To build an overall culture change, multiple dissemination approaches to aid PCPs with complex migraine preventive management should be utilized.19

Preventive migraine therapies include pharmacologic (Table 2) and biobehavioral therapies, as well as neuromodulation devices for migraine patients with 6 or more migraine headache days per month.The AHS launched the First Contact — Headache in Primary Care website16 to provide access to current information from headache specialists and to provide educational resources for PCPs.

Case Resolution

The patient was diagnosed with episodic menstrually-related migraines. She was prescribed frovatriptan 2.5 mg to be started 2 days prior to the onset of menses for menstrual migraine prophylaxis (2.5 mg twice daily for 6 days). She was also prescribed rimegepant as needed for acute headache (75 mg for a total of 8 doses a month). Rimegepant is an orally disintegrating tablet that has a fast onset of action. She wanted a fast-acting medication that did not need to be taken with water because it is difficult for her to leave the classroom when her headache starts. She is very pleased with her treatment outcome: since starting frovatriptan, she has experienced only 1 or 2 moderate headaches a month, for which she takes rimegepant, which works within 15 to 20 minutes.

Conclusion

When possible, migraine should be managed by a primary care provider. However, many primary care providers do not utilize the full spectrum of migraine preventive management options and prescribe preventive medications mostly for patients with chronic migraines.The lack of familiarity with the current AHS recommendations could be the single most important factor contributing to the failure to treat migraines preventively. Adherence to the latest AHS migraine preventive management recommendations helps to improve inadequate preventive treatment, minimize barbiturate and opioid overuse, and decrease the average 4-year gap between diagnosis and initiation of preventive medications. Providers can also download the free Android or Apple app Primary Care Migraine© developed by The National Headache Foundation (www.pcmigraine.com). ■

Vera Gibb, DNP,APRN, FNP-C,AQH, CCTP, is an assistant professor in the Graduate Studies Department of The University of Texas Medical Branch at Galveston School of Nursing, Galveston,Texas. She practices at Village Medical, Friendswood,Texas. Safa’a Al-Arabi, PhD, RN, MPH, MSN, is an associate professor and the Clinical Nurse Leader (CNL) Track Administrator in the Graduate Studies Department of The University of Texas Medical Branch at Galveston School of Nursing.

References

1. Lipton RB, Nicholson RA, Reed ML, Diagnosis, consultation, treatment, and impact of migraine in the US: results of the OVERCOME (US) study. Headache. 2022;62(2):122-140.

2. Burch R, Rizzoli P, Loder E. The prevalence and impact of migraine and severe headache in the United States: figures and trends from government health studies. Headache. 2018;58(4):496-505.

3. American Migraine Foundation. Migraine Facts. Accessed May 3, 2023. https://americanmigrainefoundation.org/resource-library/migraine-facts/

4. Biglione B, Gitin A, Gorelick PB, Hennekens C. Aspirin in the treatment and prevention of migraine headaches: possible additional clinical options for primary healthcare providers. Am J Med. 2020;133(4):412-416.

5. American Migraine Foundation. Racial disparities in migraine and headache care. Accessed May 4, 2023. https://americanmigrainefoundation.org/ resource-library/racial-disparities-in-migraine-care/

6. Bonafede M, Sapra S, Shah N, Tepper S, Cappell K, Desai P. Direct and indirect healthcare resource utilization and costs among migraine patients in the United States. Headache. 2018;58(5):700-714.

7. Minen M, Shome A, Halpern A, et al. A migraine management training program for primary care providers: an overview of a survey and pilot study findings, lessons learned, and considerations for further research. Headache 2016;56(4):725-740.

8. Takaki H, Onozuka D, Hagihara A. Migraine-preventive prescription patterns by physician specialty in ambulatory care settings in the United States. Prev Med Rep. 2017;9:62-67.

9. Aguirrezabal I, Pérez de San Román MS, Cobos-Campos R, et al. Effectiveness of a primary care-based group educational intervention in the management of patients with migraine: a randomized controlled trial. Prim Health Care Res Dev. 2019;20:e155.

10. Gifford LS, Butler DS. The integration of pain sciences into clinical practice. J Hand Ther. 1997;10(2):86-95.

11. Trachsel LA, Munakomi S, Cascella M. Pain theory. StatPearls [Internet]. StatPearls Publishing; April 20, 2022. Accessed May 3, 2023.

12. Bohm PE, Stancampiano FF, Rozen TD. Migraine headache: updates and future developments. Mayo Clin Proc. 2018;93(11):1648-1653.

13. Migraine and Headache Treatments. MPR. Updated March 10, 2023. Accessed May 3, 2023. https://www.empr.com/charts/migraine-and-headache-treatments/

14. Ailani J, Burch RC, Robbins MS; Board of Directors of the American Headache Society.The American Headache Society consensus statement: update on integrating new migraine treatments into clinical practice. Headache. 2021;61(7):1021-1039.

15. Robbins MS. Diagnosis and management of headache: a review. JAMA 2021;325(18):1874-1885.

16. Katsarava Z, Buse DC, Manack AN, Lipton RB. Defining the differences between episodic migraine and chronic migraine. Curr Pain Headache Rep. 2012;16(1):86-92.

17. American Headache Society. First contact — headache in primary care Accessed May 4, 2023. https://americanheadachesociety.org/primarycare

18. Robbins MS, Victorio MCC, Bailey M, et al. Quality improvement in neurology: headache quality measurement set. Headache. 2021;61(1):219-226.

19. White KM, Dudley-Brown S, Terhaar MF. Translation of Evidence Into Nursing and Healthcare. 3rd ed. Springer Publishing Company; 2019.

Dermatologic Look-Alikes

Raised Itchy Nodules

RISHABH LOHRAY;TALIA NOORILY, MD

A 62-year-old Black man with a history of atopic dermatitis presents to the clinic with persistent itchy bumps on his arms, legs, and back. The patient reports that the bumps have been present for several years.The bumps are firm and he reports scratching them often. The patient has tried treating the itching with topical corticosteroids with minimal benefit. On physical examination, hyperpigmented hyperkeratotic papules and nodules are found on bilateral extensor forearms, shins, and upper back. Other than the skin condition, the patient is healthy, has no other chronic medical conditions, and takes no medication. No further testing, including biopsy, is performed.

A 45-year-old Black woman presents to the clinic with a 1-year history of bumps on her forearms and elbows. She describes the raised bumps as intensely itchy.The patient reports no other skin condition or similar lesions elsewhere on the body. She has been treating the spots with topical corticosteroid ointment (clobetasol propionate) with minimal benefit.The bumps are not painful. On physical examination, hyperpigmented and violaceous firm papules are scattered on the extensor surfaces of both forearms. A 4-mm punch biopsy is performed. Other than the itchy bumps, the patient does not have any chronic conditions and takes no medications.

CASE #2

CASE #1

Dermatologic Look-Alikes

Nodularis

Prurigo nodularis (PN) is a condition characterized by firm pruritic lesions caused by repeated scratching of intensely itchy skin. It often occurs secondary to other causes of itch including primary dermatologic conditions and systemic conditions.

Data on the prevalence of PN is variable. One study in individuals aged 18 to 64 years found the prevalence of PN to be 72 per 100,000 people.1 Another study reported the prevalence to range from 36.7 to 148.3 per 100,000 people based on the specific diagnostic code used.2 Mean age of presentation is in the sixth and seventh decades of life.1 The condition is slightly more predominant in females and in patients with skin of color, especially Black patients (3.4-fold increased odds compared with White people).1 The disease is significantly associated with anxiety, depression, and other mental health disorders as well as HIV and hematologic malignancies (lymphomas), diabetes, liver and thyroid disorders, and end-stage renal disease.1 Prurigo nodularis is also associated with other dermatologic disorders including atopic dermatitis, psoriasis, and neurotic excoriation.1

The pathophysiology of PN is largely attributed to immune and neural dysregulation.3 The lesions contain dense dermal infiltrates of mast cells, eosinophils, and T-cells, which release mediators and cause a powerful inflammatory response,

include any conditions that might result in intense itching including primary skin conditions such as atopic dermatitis and systemic conditions such as HIV, lymphoma, diabetes, liver disease, thyroid disorders, and end-stage renal disease.

The diagnosis of PN is made clinically when patients describe severe pruritus that is constant, paroxysmal, or intermittent for 6 or more weeks.3 Patients can have associated burning or stinging sensation.3 Physical examination often reveals clustered hyperkeratotic symmetric nodules, usually on extensor surfaces. Patients should be screened for comorbidities including mental health disorders, thyroid disorders, diabetes, HIV, and malignancy.3 Patients should be encouraged to stay up to date with their age-appropriate cancer screenings.The basic laboratory tests recommended for evaluation are a complete blood cell count (CBC) and complete metabolic panel (CMP).3 Additional screens including hemoglobin A1c, thyroid function tests, HIV testing, and hepatitis serologies should also be considered in the presence of additional risk factors as discussed previously.3

A skin biopsy is not usually necessary but may be useful for diagnosis in cases with atypical presentations. Biopsy is characterized by orthohyperkeratosis, irregular epidermal hyperplasia, hypergranulosis, increased dermal fibroblasts and capillaries, and sometimes increased nerve fiber density.3 The differential diagnosis for PN includes hypertrophic lichen planus, pemphigoid nodularis, nodular scabies, multiple keratoacanthomas, cutaneous T-cell lymphoma, dermatofibromas, mastocytosis, and pilomatrixomas.4,5

resulting in intense pruritus.3 Eosinophils are key players and release specific granules such as eosinophil cationic protein, eosinophil protein X, and major basic protein, which are known to be neurotoxic.3 T-cells play a role in the severe itching and inflammation by the action of cytokines interleukin (IL)-31 and IL-4, both of which have increased activity in PN lesions.3 The dermis of PN lesions exhibits neural hyperplasia with an increase in multiple neuropeptides including calcitonin generelated peptide (CGRP) and substance P.3 The former causes neurogenic inflammation by enhancing mast cell and eosinophil activity, which in turn can perpetuate pruritus.3 Risk factors

Hypertrophic lichen planus (LP) is often misdiagnosed as PN. Hypertrophic LP may clinically appear identical to PN, though the former condition commonly presents on the lower legs and may present as thick plaques rather than nodules. On biopsy, the 2 conditions may appear similar with both showing acanthosis of the epidermis, hypergranulosis, hyperkeratosis, and increased fibroblasts and capillaries. However, in hypertrophic lichen planus, basal cell degeneration is found in the tips of the rete ridges.4 Another differential to consider is pemphigoid nodularis, an uncommon form of bullous pemphigoid, which is distinguished by its blistering lesions and biopsy with positive immunofluorescence for basement membrane immunoglobulin G (IgG) and C3 autoantibodies in the basement membrane.4

Treatment for PN is targeted at reducing itch that in turn allows the nodules to heal.3 High-potency topical corticosteroids, which target the immunologic aspect of the disease, are first-line agents.3,5 Flurandrenolide or betamethasone valerate medicated tape or intralesional triamcinolone are other potential options.3 The neurologic pathophysiology can be targeted with anesthetic agents (1% pramoxine solution, lidocaine spray), which have shown some efficacy in chronic PN.3,5 In the nonsteroidal category, 1% pimecrolimus

Physical examination often reveals clustered hyperkeratotic symmetric nodules, usually on extensor surfaces.

Prurigo

cream is effective in reducing itch.3 Another alternative is phototherapy, especially in patients with limited treatment options; narrowband UV-B therapy is a first-line option but PUVA has also shown efficacy.3

Although topical agents and phototherapy work for some patients with PN, most are refractory to these treatments and need adjunctive systemic therapies.3 Systemic immunosuppressants such as cyclosporine and methotrexate target the immunologic aspect of PN and reduce inflammation and itch.3 Similarly gabapentin and pregabalin are systemic therapies for modulating neurologic dysregulation in PN.3 In addition, antidepressants, neurokinin-1 receptor (NK-1) antagonists, and opioid receptor modulators have shown promise.3 In 2022, the FDA approved dupilumab, which inhibits IL-4 and IL-13, for the treatment of PN. Currently, it is the only drug that is FDA approved for PN.

The patient in this case was diagnosed clinically with prurigo nodularis in the setting of atopic dermatitis and was started on therapy with dupilumab injections.

CASE #2 Hypertrophic Lichen Planus

Hypertrophic lichen planus (LP) is a variant of lichen planus. It presents as intensely pruritic, hyperkeratotic nodules and plaques most commonly located on the shins, ankles, and interphalangeal joints in a symmetric distribution, sometimes with fine scaling.6,7 Because of the pruritic nature of the lesions, chronic scratching leads to the formation of firmer, red and/or violet plaques and nodules with follicular accentuation. 6 One author describes the appearance of hypertrophic LP as similar to “rapidly cooled variants of igneous rocks”3 marked by “fine-grained or aphanitic texture” with “occasional vascular vesicular [pocked] surface and variable colors from dark pink to gray-black.”8

Data on the epidemiology of hypertrophic LP is scarce. Most estimates are based on variable data on LP as a whole, with the worldwide incidence estimated to be 1%.9 The condition occurs slightly more frequently in females with age of onset in the fifth and sixth decades of life.9 While many studies suggest that LP does not have a predilection for any particular race or ethnicity,4 some studies have identified a higher prevalence of hypertrophic LP in patients with skin of color.6

The pathophysiology of hypertrophic LP is unknown. Researchers have proposed that CD8+ T cells are activated against basal keratinocytes. Additionally, intracellular adhesion molecule-1 (ICAM-1) and Th1 cytokines such as interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, IL-1, IL-6, and IL-8 are involved in perpetuating the inflammatory response.10 Chronic inflammation, chronic venous insufficiency, Koebner phenomenon, and eosinophils are also significant drivers in the disease pathogenesis.7,11 Variable data also suggest an association between LP and hepatitis C; however, this link remains unproven.10,11 Finally, chronic

hypertrophic LP and the chronic inflammation associated with intense itch-scratch cycles may also lead to the development of squamous cell carcinoma.10,11

Hypertrophic LP may be diagnosed clinically. Biopsy can confirm the diagnosis if necessary.10 Providers should question patients on medication history (to assess for the possibility of drug-induced LP), oral or genital lesions (to assess for mucosal involvement), and dysphagia (to assess for esophageal involvement).10 The patient should have a full body skin examination, including the anogenital region and mucosal surfaces in order to identify all the possible sites of disease.10 While hypertrophic LP most commonly occurs on the shins and ankles, it can also be found on the trunk, upper extremities, mucosal sites, nails, or in a generalized distribution. 11 As mentioned earlier, patients should be assessed for risk factors for hepatitis C as it has been associated with LP, and hepatitis C viral serologies can be checked in those patients.10

Histopathology reveals epidermal hyperplasia, hypergranulosis, and lamellated hyperkeratosis centered on follicular infundibula and acrosyringia.7 Basal cell damage is usually restricted to the tips of the rete ridges and band-like infiltration may be absent in the dermis of hypertrophic LP lesions.7 Finally collagen bundles are oriented vertically in the papillary dermis along with an increased amount of eosinophils.7

The differential diagnosis of hypertrophic LP includes prurigo nodularis (PN), lichen simplex chronicus, squamous cell carcinoma, psoriasis, and nodular scabies.7,11 Because of the clinical similarities between PN and hypertrophic LP, studies have focused on the role of dermoscopy in identifying the

The patient should have a full body skin examination, including the anogenital region and mucosal surfaces.

Dermatologic Look-Alikes

Clinical presentation

Characteristic locations

Associations

• Firm pruritic nodular lesions, possibly with burning or stinging sensation

• Symmetric distribution usually on extensor surfaces

• Mental health disorders

• HIV

• Hematologic malignancies

• Diabetes

• Liver disease

• Thyroid disorders

• End-stage renal disease

• Atopic dermatitis

• Psoriasis

• Neurotic excoriation

Etiology

• Immune and neural dysregulation

• Any cause of itch including primary dermatologic conditions and systemic conditions

• Intensely pruritic hyperkeratotic plaques and nodules

• Shins, ankles, and interphalangeal joints in a symmetric distribution

• Hepatitis C

• Chronic inflammation

• Chronic venous insufficiency

Histology

• Orthohyperkeratosis

• Irregular epidermal hyperplasia

• Hypergranulosis

• Increased dermal fibroblasts and capillaries

• Sometimes increased nerve fiber density

• T-cell activation against basal keratinocytes

Diagnosis

Treatment

• History and physical examination

• First-line treatment: topical corticosteroids

• Systemic immunosuppressants for refractory cases

• Dupilumab is FDA approved for prurigo nodularis

FDA, Food and Drug Administration

differentiating features between the conditions. Although hypertrophic LP and PN both show pearly, white areas on dermoscopy, the areas are more prominent and might possess a starburst appearance in PN.7 Comedo-like openings filled with yellow keratinous plugs are a sign of transepithelial elimination and are only seen in hypertrophic LP and not in PN.7 However, comedo-like openings are not specific for hypertrophic LP and are commonly seen in other skin lesions including seborrheic keratoses.7 Another dermoscopic feature seen in hypertrophic LP and not in PN are gray-blue globules, which are a sign of melanin incontinence that

• Epidermal hyperplasia

• Hypergranulosis

• Lamellated hyperkeratosis centered on follicular infundibula and acrosyringia

• Lichenoid lymphocytic infiltrate

• History and physical examination

• Punch biopsy is often helpful

• First-line treatment: topical corticosteroids

• Systemic immunosuppressants for refractory cases

• Cryotherapy

results from vacuolar degeneration.7 Hypertrophic LP can also resemble squamous cell carcinoma or keratoacanthomas, but shin involvement and absence of lesions in sun-exposed areas can help make the diagnosis of hypertrophic LP.7 Close follow-up and biopsy for lesions that show rapid growth, ulceration, and bleeding are recommended.12

Treatment of hypertrophic LP is similar to the treatment of other variants of LP. Topical corticosteroids include first-line therapy.11 However, systemic steroids, mycophenolate mofetil, acitretin, hydroxychloroquine, cyclosporine, methotrexate, intralesional steroids, and cryotherapy, alone or in combination,

TABLE. Purigo Nodularis vs Hypertrophic Lichen Planus

Prurigo Nodularis1-5

Hypertrophic Lichen Planus6-12

have also shown success.11,12 Findings from recent studies suggest that enoxaparin is an effective alternative because it has anti-inflammatory properties, however, more work is needed to ascertain its efficacy.11 Without proper treatment, hypertrophic LP can persist for many years.6

The biopsy in this case revealed hyperkeratosis, hypergranulosis, epidermal hyperplasia, and lichenoid lymphocytic infiltrate. This patient was diagnosed with hypertrophic LP and was started on therapy with oral prednisone. ■

Rishabh Lohray is a medical student at Baylor College of Medicine in Houston,Texas, and an MBA student at Rice University.Talia Noorily, MD, is a dermatology resident at Baylor College of Medicine.

References

1. Huang AH, Williams KA, Kwatra SG. Prurigo nodularis. J Am Acad Dermatol. 2020;83(6):1559-1565.

2. Ständer S, Augustin M, Berger T, et al. Prevalence of prurigo nodularis in the United States of America: a retrospective database analysis. JAAD Int. 2021;2:28-30.

3. Williams KA, Huang AH, Belzberg M, Kwatra SG. Prurigo nodularis: pathogenesis and management. J Am Acad Dermatol. 2020;83(6):1567-1575.

4. Kwon CD, Khanna R, Williams KA, Kwatra MM, Kwatra SG. Diagnostic workup and evaluation of patients with prurigo nodularis. Medicines (Basel). 2019;6(4):97.

5. Vaidya DC, Schwartz RA. Prurigo nodularis: a benign dermatosis derived from a persistent pruritus. Acta dermatovenerol Croat. 2008;16(1):38-44.

6. Gorouhi F, Davari P, Fazel N. Cutaneous and mucosal lichen planus: a comprehensive review of clinical subtypes, risk factors, diagnosis, and prognosis. ScientificWorldJournal. 2014;2014:742826.

7. Ankad B, Beergouder S. Hypertrophic lichen planus versus prurigo nodularis: a dermoscopic perspective. Dermatol Pract Concept. 2016;6(2):9-15.

8. Welsh JP, Skvarka CB, Allen HB. A novel visual clue for the diagnosis of hypertrophic lichen planus. Arch Dermatol. 2006;142(7):954.

9. Schwager Z, Stern M, Cohen J, Femia A. Clinical epidemiology and treatment of lichen planus: a retrospective review of 2 tertiary care centers. J Am Acad Dermatol. 2019;81(6):1397-1399.

10. Goldstein B, Goldstein A, Mastow E. Lichen planus. UpToDate. Wolters Kluver; 2019.

11. Weston G, Payette M. Update on lichen planus and its clinical variants. Int J Womens Dermatol. 2015;1(3):140-149.

12. Guillen-Climent S, Porcar Saura S, Monteagudo C, Ramón Quiles MD. Hypertrophic lichen planus: importance of follow-up and clinicopathologic correlation. Actas Dermosifiliogr (Engl Ed). 2021;112(2):184-185.

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DNP Sued for Use of Dr in Office

In California, Use of “Dr” Is Restricted to Medical Doctors

BY ANN W. LATNER, JD

Ms E is a nurse practitioner practicing in California. She started her career as a registered nurse in Kentucky before receiving her Doctor of Nursing Practice (DNP) in 2014. In 2020, she completed a PhD in Mind-Body Medicine and Integrative Mental Health through a California university. Ms E’s clinical focus is women’s health, functional medicine, and autoimmune and chronic diseases.

Prior to 2018, Ms E worked for a practice with a supervising physician.When Ms E received her DNP, the physician told her that she needed to “own” her degree, and had his staff refer to her as “Dr Sarah” (her first name) in the office with patients. The name stuck and patients began referring to Ms E as Dr Sarah.

In 2018, Ms E opened a women’s health clinic and launched a website and online digital presence. Ms E’s supervising and collaborating physician was Dr M, an obstetrician-gynecologist. Dr M was located out of state and would travel every 2 or 3 months to review Ms E’s patient files and prescriptions.

In 2022, an investigator from California’s Department of Consumer Affairs (DCA) visited

By referring to herself as Dr Sarah, the complaint said she unfairly elevated her position among health care providers who identify themselves as NPs.

Ms E’s office. The DCA is the governing agency over many professional groups in California, including medical and nursing boards.The investigator told Ms E that the agency had received a phone call from someone reporting that she had been presenting herself as a physician by using the term “Dr Sarah.” According to the California Medical Association, only medical doctors can use the title Doctor. Ms E told the investigator that she had always referred to herself as a nurse practitioner and never claimed to be a medical doctor.

After several months of investigation, the case was referred to the District Attorney in the county who charged Ms E with fraud.

Charges Against the DNP

Ms E was charged with violating California’s Business & Professions Code because of unfair business practices and false advertising. The

Cases presented are based on actual occurrences. Names of participants and details have been changed. Cases are informational only; no specific legal advice is intended. Persons pictured are not the actual individuals mentioned in the article.

THE CHOICE IS YOURS!

The same high-quality CME/CE you are accustomed to reviewing in our issues is available online, with more to choose from!

The Role of Maintenance Therapy and the Patient

complaint alleged that she described herself as Dr Sarah with third-party digital health care platforms such as Healthgrades and Sharecare. By referring to herself as Dr Sarah on these sites, the complaint charged that she “unfairly elevated her position among other registered nurse practitioners within these digital platforms who had correctly identified themselves as NPs.” The complaint also noted that search engines like Google can populate search results to capture her title as Dr Sarah, which may mislead the public into believing that Ms E is a physician.

“Defendant, as a nursing medical professional with a doctorate in [nursing practice], owes a duty to accurately promote her credentials while performing and advertising her professional medical services to the public,” read the complaint. “Both the Medical Board of California and the Registered Nursing Board’s

The Fallout Continues

Ms E gave an update on her GoFundMe page. She reported that she had received a citation from the California Medical Board demanding that she pay a separate fine for using the title doctor. In addition, the Board of Nursing has filed a complaint, which Ms E will have to fight or else give up her license in California.

Protecting Yourself

“There are literally hundreds of people in our county who use the term Doctor who are not physicians.They hold a doctoral degree....” wrote Ms E on her GoFundMe page. She is not wrong. Many people who have a doctorate refer to themselves as “doctor,” including our current First Lady. But perhaps the difference is that they don’t do it in a medical setting.

paramount priority is to protect the public. Elevating her doctorate by encouraging patients to call her Dr Sarah improperly shifts the burden of understanding the scope of services a registered nurse can perform. Even more so with the statement,‘I’m Doctor Sarah, a nurse practitioner,’ when California law prescribes who is permitted to say ‘I’m a doctor’ to a patient or the public.”

The Settlement

Ms E retained an attorney and continued to maintain that she had only ever called herself a nurse practitioner and had never held herself out to be a physician, regardless of the Dr Sarah moniker.When the District Attorney sent a settlement letter advising Ms E to pay an almost $20,000 fine to settle the fraud case, her attorney advised her that fighting the case would cost $50,000 and she should consider settling.

Ms E started a GoFundMe page to raise money for the settlement fee and her attorney fees. In November 2022, she settled the case. In addition to the fine, the settlement included being permanently enjoined from referring to herself as a doctor or using the prefix Dr or any other term implying she is a physician in the context of advertising or providing medical treatment to the public. For the first year, she will be required to search online each month to see if anyone is listing her as doctor and have these references removed. For the next 4 years, she will have to perform these searches twice a year. Ms E is also required to promptly correct any patient, staff, or physician who refers to her as doctor in any medical setting.

This case has caused a great deal of consternation among NPs (and probably other nonphysician medical professionals).The District Attorney in the case faulted Ms E for failing to “advise the public that she was not a medical doctor” and failing to “identify her supervising physician,” which is not normally required without a reason. According to Ms E, a legal nonprofit has reached out with the desire to assist her, so it is likely that we have not seen the end of this case.

If you are a nurse practitioner in California, be very aware of how you advertise and market yourself and your services. Make sure that it is completely clear what your degree is and what is the scope of your practice. Do not use the term doctor with regard to yourself in the context of your medical practice. Be extremely careful about using the term doctor with regard to yourself in any written or online materials. To play it safe in California, stick to the permitted titles – certified nurse practitioner or advanced practice registered nurse. ■

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Ann W. Latner, JD, a former criminal defense attorney, is a freelance medical writer in Port Washington, New York.

“The defendant owes a duty to accurately promote her credentials while performing and advertising her professional services.”