The Journal of Family Practice

Due to the condition’s persistence and the negative KOH prep, erythrasma was the most likely diagnosis.

Erythrasma is caused by a bacterial infection with Corynebacterium minutissimum. It occurs in intertriginous areas that tend to be moist and irritated by friction. The erythema is usually a dull red, rather than the bright red that one would see with yeast infections. In addition, there is typically central pallor.

Woods lamp examination can confirm the diagnosis by showing coral pink fluorescence. In this patient, however, there was no fluorescence because the patient had recently washed the area and, thus, removed the porphyrins produced by C minutissimum. Biopsy for pathology is not usually necessary.

Erythrasma is treated with topical clindamycin, fusidic acid, or mupirocin. Oral macrolides and tetracyclines are also effective.¹ Due to the chronicity of the erythrasma and the discomfort it caused, this patient opted for oral doxycycline 100 mg twice daily for 10 days. At follow-up 2 weeks later, the erythrasma had resolved.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque

Due to the condition’s persistence and the negative KOH prep, erythrasma was the most likely diagnosis.

Erythrasma is caused by a bacterial infection with Corynebacterium minutissimum. It occurs in intertriginous areas that tend to be moist and irritated by friction. The erythema is usually a dull red, rather than the bright red that one would see with yeast infections. In addition, there is typically central pallor.

Woods lamp examination can confirm the diagnosis by showing coral pink fluorescence. In this patient, however, there was no fluorescence because the patient had recently washed the area and, thus, removed the porphyrins produced by C minutissimum. Biopsy for pathology is not usually necessary.

Erythrasma is treated with topical clindamycin, fusidic acid, or mupirocin. Oral macrolides and tetracyclines are also effective.¹ Due to the chronicity of the erythrasma and the discomfort it caused, this patient opted for oral doxycycline 100 mg twice daily for 10 days. At follow-up 2 weeks later, the erythrasma had resolved.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque

Due to the condition’s persistence and the negative KOH prep, erythrasma was the most likely diagnosis.

Erythrasma is caused by a bacterial infection with Corynebacterium minutissimum. It occurs in intertriginous areas that tend to be moist and irritated by friction. The erythema is usually a dull red, rather than the bright red that one would see with yeast infections. In addition, there is typically central pallor.

Woods lamp examination can confirm the diagnosis by showing coral pink fluorescence. In this patient, however, there was no fluorescence because the patient had recently washed the area and, thus, removed the porphyrins produced by C minutissimum. Biopsy for pathology is not usually necessary.

Erythrasma is treated with topical clindamycin, fusidic acid, or mupirocin. Oral macrolides and tetracyclines are also effective.¹ Due to the chronicity of the erythrasma and the discomfort it caused, this patient opted for oral doxycycline 100 mg twice daily for 10 days. At follow-up 2 weeks later, the erythrasma had resolved.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque

REFERENCES

1. CDC. COVID Data Tracker. Accessed June 3, 2021. https://covid.cdc.gov/covid-data-tracker/#datatracker-home
2. WHO Coronavirus (COVID-19) Dashboard. Accessed June 3, 2021. https://covid19.who.int/
3. CDC. Demographic trends of people receiving COVID-19 vaccinations in the United States. Accessed June 3, 2021. https://covid.cdc.gov/covid-data-tracker/#vaccination-demographics-trends
4. Shimabukuro T. Update: thrombosis with thrombocytopenia syndrome (TTS) following COVID-19 vaccination. Presentation to the Advisory Committee on Immunization Practices, May 12, 2021. Accessed June 3, 2021. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-05-12/07-COVID-Shimabukuro-508.pdf
5. Fleming-Dutra K. CDC COVID-19 vaccine effectiveness studies. Presentation to the Advisory Committee on Immunization Practices, May 12, 2021. Accessed June 3, 2021. www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-05-12/09-COVID-Fleming-Dutra-508.pdf
6. Scobie H. Update on emerging SARS-CoV-2 variants and vaccine considerations. Presentation to the Advisory Committee on Immunization Practices, May 12, 2021. Accessed June 3, 2021. www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-05-12/10-COVID-Scobie-508.pdf

REFERENCES

1. CDC. COVID Data Tracker. Accessed June 3, 2021. https://covid.cdc.gov/covid-data-tracker/#datatracker-home
2. WHO Coronavirus (COVID-19) Dashboard. Accessed June 3, 2021. https://covid19.who.int/
3. CDC. Demographic trends of people receiving COVID-19 vaccinations in the United States. Accessed June 3, 2021. https://covid.cdc.gov/covid-data-tracker/#vaccination-demographics-trends
4. Shimabukuro T. Update: thrombosis with thrombocytopenia syndrome (TTS) following COVID-19 vaccination. Presentation to the Advisory Committee on Immunization Practices, May 12, 2021. Accessed June 3, 2021. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-05-12/07-COVID-Shimabukuro-508.pdf
5. Fleming-Dutra K. CDC COVID-19 vaccine effectiveness studies. Presentation to the Advisory Committee on Immunization Practices, May 12, 2021. Accessed June 3, 2021. www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-05-12/09-COVID-Fleming-Dutra-508.pdf
6. Scobie H. Update on emerging SARS-CoV-2 variants and vaccine considerations. Presentation to the Advisory Committee on Immunization Practices, May 12, 2021. Accessed June 3, 2021. www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-05-12/10-COVID-Scobie-508.pdf

REFERENCES

1. CDC. COVID Data Tracker. Accessed June 3, 2021. https://covid.cdc.gov/covid-data-tracker/#datatracker-home
2. WHO Coronavirus (COVID-19) Dashboard. Accessed June 3, 2021. https://covid19.who.int/
3. CDC. Demographic trends of people receiving COVID-19 vaccinations in the United States. Accessed June 3, 2021. https://covid.cdc.gov/covid-data-tracker/#vaccination-demographics-trends
4. Shimabukuro T. Update: thrombosis with thrombocytopenia syndrome (TTS) following COVID-19 vaccination. Presentation to the Advisory Committee on Immunization Practices, May 12, 2021. Accessed June 3, 2021. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-05-12/07-COVID-Shimabukuro-508.pdf
5. Fleming-Dutra K. CDC COVID-19 vaccine effectiveness studies. Presentation to the Advisory Committee on Immunization Practices, May 12, 2021. Accessed June 3, 2021. www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-05-12/09-COVID-Fleming-Dutra-508.pdf
6. Scobie H. Update on emerging SARS-CoV-2 variants and vaccine considerations. Presentation to the Advisory Committee on Immunization Practices, May 12, 2021. Accessed June 3, 2021. www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-05-12/10-COVID-Scobie-508.pdf

The intertriginous findings, along with results from a punch biopsy showing resolving lichenoid inflammation with post-inflammatory pigmentary alteration, indicated a diagnosis of lichen planus pigmentosus inversus (LPPI).

Insidious onset of usually asymptomatic, sometimes mildly pruritic, well-defined, hyperpigmented macules and patches with occasional Wickham striae of the intertriginous areas is characteristic of LPPI. It is a variant of lichen planus pigmentosus, which conversely occurs on sun-exposed areas. The etiology is unknown and there is no association with medications or sun exposure. Pathophysiology is thought to be chronic inflammation, mediated by T-lymphocyte cytotoxic activity against basal keratinocytes.¹

At the time of this patient’s clinical presentation, the differential diagnoses for new onset hyperpigmentation included confluent and reticulated papillomatosis, post-inflammatory hyperpigmentation, and erythema dyschromicum perstans. However, further tests were ordered for diagnostic clarification.

The clinical course of LPPI is variable. In some cases, there is complete resolution of lesions without treatment, while in other cases, lesions may last for years despite treatment and the condition may recur. Current management options include topical calcineurin inhibitors (tacrolimus and pimecrolimus) and topical steroids. Response to these topical medications may be variable. The patient in this case was started on topical tacrolimus 0.1% twice daily, with follow-up in 3 months.

‌

Text courtesy of Rachel Rose, BS, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque. Photo courtesy of Daniel Stulberg, MD, FAAFP.

The intertriginous findings, along with results from a punch biopsy showing resolving lichenoid inflammation with post-inflammatory pigmentary alteration, indicated a diagnosis of lichen planus pigmentosus inversus (LPPI).

Insidious onset of usually asymptomatic, sometimes mildly pruritic, well-defined, hyperpigmented macules and patches with occasional Wickham striae of the intertriginous areas is characteristic of LPPI. It is a variant of lichen planus pigmentosus, which conversely occurs on sun-exposed areas. The etiology is unknown and there is no association with medications or sun exposure. Pathophysiology is thought to be chronic inflammation, mediated by T-lymphocyte cytotoxic activity against basal keratinocytes.¹

At the time of this patient’s clinical presentation, the differential diagnoses for new onset hyperpigmentation included confluent and reticulated papillomatosis, post-inflammatory hyperpigmentation, and erythema dyschromicum perstans. However, further tests were ordered for diagnostic clarification.

The clinical course of LPPI is variable. In some cases, there is complete resolution of lesions without treatment, while in other cases, lesions may last for years despite treatment and the condition may recur. Current management options include topical calcineurin inhibitors (tacrolimus and pimecrolimus) and topical steroids. Response to these topical medications may be variable. The patient in this case was started on topical tacrolimus 0.1% twice daily, with follow-up in 3 months.

‌

Text courtesy of Rachel Rose, BS, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque. Photo courtesy of Daniel Stulberg, MD, FAAFP.

The intertriginous findings, along with results from a punch biopsy showing resolving lichenoid inflammation with post-inflammatory pigmentary alteration, indicated a diagnosis of lichen planus pigmentosus inversus (LPPI).

Insidious onset of usually asymptomatic, sometimes mildly pruritic, well-defined, hyperpigmented macules and patches with occasional Wickham striae of the intertriginous areas is characteristic of LPPI. It is a variant of lichen planus pigmentosus, which conversely occurs on sun-exposed areas. The etiology is unknown and there is no association with medications or sun exposure. Pathophysiology is thought to be chronic inflammation, mediated by T-lymphocyte cytotoxic activity against basal keratinocytes.¹

At the time of this patient’s clinical presentation, the differential diagnoses for new onset hyperpigmentation included confluent and reticulated papillomatosis, post-inflammatory hyperpigmentation, and erythema dyschromicum perstans. However, further tests were ordered for diagnostic clarification.

The clinical course of LPPI is variable. In some cases, there is complete resolution of lesions without treatment, while in other cases, lesions may last for years despite treatment and the condition may recur. Current management options include topical calcineurin inhibitors (tacrolimus and pimecrolimus) and topical steroids. Response to these topical medications may be variable. The patient in this case was started on topical tacrolimus 0.1% twice daily, with follow-up in 3 months.

‌

Text courtesy of Rachel Rose, BS, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque. Photo courtesy of Daniel Stulberg, MD, FAAFP.

A potassium hydroxide (KOH) mount of skin scrapings from the patient’s feet and hand confirmed a diagnosis of unilateral tinea manuum and bilateral tinea pedis—the so-called 2-foot, 1-hand syndrome. Additionally, nail clippings from the patient’s right hand confirmed onychomycosis.

Tinea is common and caused by various dermatophytes that are ubiquitous in soil. Often there is a history of atopic dermatitis or xerosis leading to skin barrier dysfunction. Immunosuppression and diabetes mellitus are also predisposing factors. Trichophyton rubrum is a commonly isolated cause.

On the hands, tinea may be challenging to distinguish from irritant dermatitis, atopic dermatitis, and contact dermatitis. A KOH prep test should be considered for any red, scaly rash, especially on the hands and feet. Curiously, the incidence of unilateral tinea manuum and bilateral tinea pedis occurs relatively frequently and can affect either the dominant or nondominant hand. The cause of this asymmetry is speculative.

Topical therapy with various antifungals—terbinafine, clotrimazole, ketoconazole, ciclopirox—can be effective, but challenging to apply to affected areas. For the treatment of nail disease, oral therapy with terbinafine or itraconazole is usually indicated (6 weeks for fingernails and 12 weeks for toenails). Terbinafine is generally tolerated very well for both 6- and 12-week courses. Some clinicians consider lab monitoring unnecessary because the risk of hepatic injury from terbinafine is uncertain; others consider it worthwhile to check liver function test results prior to initiation of terbinafine and after 6 weeks of therapy, with either a 6- or 12-week course.¹

Since the patient in this case had skin and nail disease, oral therapy with terbinafine 250 mg/d for 6 weeks was prescribed. His skin cleared within 3 weeks and his nails cleared after 6 months. It is important to counsel patients with nail disease that treatment will end before they see a clinical improvement. Fingernails typically require 6 months to see clearance and toenails require 18 months.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

A potassium hydroxide (KOH) mount of skin scrapings from the patient’s feet and hand confirmed a diagnosis of unilateral tinea manuum and bilateral tinea pedis—the so-called 2-foot, 1-hand syndrome. Additionally, nail clippings from the patient’s right hand confirmed onychomycosis.

Tinea is common and caused by various dermatophytes that are ubiquitous in soil. Often there is a history of atopic dermatitis or xerosis leading to skin barrier dysfunction. Immunosuppression and diabetes mellitus are also predisposing factors. Trichophyton rubrum is a commonly isolated cause.

On the hands, tinea may be challenging to distinguish from irritant dermatitis, atopic dermatitis, and contact dermatitis. A KOH prep test should be considered for any red, scaly rash, especially on the hands and feet. Curiously, the incidence of unilateral tinea manuum and bilateral tinea pedis occurs relatively frequently and can affect either the dominant or nondominant hand. The cause of this asymmetry is speculative.

Topical therapy with various antifungals—terbinafine, clotrimazole, ketoconazole, ciclopirox—can be effective, but challenging to apply to affected areas. For the treatment of nail disease, oral therapy with terbinafine or itraconazole is usually indicated (6 weeks for fingernails and 12 weeks for toenails). Terbinafine is generally tolerated very well for both 6- and 12-week courses. Some clinicians consider lab monitoring unnecessary because the risk of hepatic injury from terbinafine is uncertain; others consider it worthwhile to check liver function test results prior to initiation of terbinafine and after 6 weeks of therapy, with either a 6- or 12-week course.¹

Since the patient in this case had skin and nail disease, oral therapy with terbinafine 250 mg/d for 6 weeks was prescribed. His skin cleared within 3 weeks and his nails cleared after 6 months. It is important to counsel patients with nail disease that treatment will end before they see a clinical improvement. Fingernails typically require 6 months to see clearance and toenails require 18 months.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

A potassium hydroxide (KOH) mount of skin scrapings from the patient’s feet and hand confirmed a diagnosis of unilateral tinea manuum and bilateral tinea pedis—the so-called 2-foot, 1-hand syndrome. Additionally, nail clippings from the patient’s right hand confirmed onychomycosis.

Tinea is common and caused by various dermatophytes that are ubiquitous in soil. Often there is a history of atopic dermatitis or xerosis leading to skin barrier dysfunction. Immunosuppression and diabetes mellitus are also predisposing factors. Trichophyton rubrum is a commonly isolated cause.

On the hands, tinea may be challenging to distinguish from irritant dermatitis, atopic dermatitis, and contact dermatitis. A KOH prep test should be considered for any red, scaly rash, especially on the hands and feet. Curiously, the incidence of unilateral tinea manuum and bilateral tinea pedis occurs relatively frequently and can affect either the dominant or nondominant hand. The cause of this asymmetry is speculative.

Topical therapy with various antifungals—terbinafine, clotrimazole, ketoconazole, ciclopirox—can be effective, but challenging to apply to affected areas. For the treatment of nail disease, oral therapy with terbinafine or itraconazole is usually indicated (6 weeks for fingernails and 12 weeks for toenails). Terbinafine is generally tolerated very well for both 6- and 12-week courses. Some clinicians consider lab monitoring unnecessary because the risk of hepatic injury from terbinafine is uncertain; others consider it worthwhile to check liver function test results prior to initiation of terbinafine and after 6 weeks of therapy, with either a 6- or 12-week course.¹

Since the patient in this case had skin and nail disease, oral therapy with terbinafine 250 mg/d for 6 weeks was prescribed. His skin cleared within 3 weeks and his nails cleared after 6 months. It is important to counsel patients with nail disease that treatment will end before they see a clinical improvement. Fingernails typically require 6 months to see clearance and toenails require 18 months.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

Paronychia, or an ingrown nail, is caused by the introduction of bacteria into the nail fold, which can cause cellulitis and/or abscess formation. Typically, a single nail is involved, although multiple nails may be affected in rare, chemotherapy-induced cases. Generally, nail grooming behaviors, abnormal or scarred nail matrix architecture, nail biting, and wet work are the causes of acute or chronic disease.¹

Conservative options are a reasonable first choice when there is no abscess. These include soaks 2 to 3 times daily for 15 to 20 minutes in hot water or water treated with an antiseptic, such as chlorhexidine. Topical or oral antibiotics aimed at suspected organisms may be helpful. Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus, is a common isolate. Psuedomonas is characteristic in cases involving trauma to the hand and frequent workplace water exposure, as can happen in foodservice, farming, and marine industries.

When an abscess has formed (as in this case), or when conservative treatments fail, incision and drainage or partial nail avulsion can be curative and successful with, or without, antibiotics. Patients with recurrent paronychia in the same location may benefit from partial nail avulsion with partial matrix removal. This can be done surgically or with phenol.

In this case, the patient underwent lateral partial nail avulsion, which also served as an incision and drainage. She was not given antibiotics and her nail regrew within 6 months; there was no recurrence. She was counseled not to cut the nail plate too aggressively.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

Paronychia, or an ingrown nail, is caused by the introduction of bacteria into the nail fold, which can cause cellulitis and/or abscess formation. Typically, a single nail is involved, although multiple nails may be affected in rare, chemotherapy-induced cases. Generally, nail grooming behaviors, abnormal or scarred nail matrix architecture, nail biting, and wet work are the causes of acute or chronic disease.¹

Conservative options are a reasonable first choice when there is no abscess. These include soaks 2 to 3 times daily for 15 to 20 minutes in hot water or water treated with an antiseptic, such as chlorhexidine. Topical or oral antibiotics aimed at suspected organisms may be helpful. Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus, is a common isolate. Psuedomonas is characteristic in cases involving trauma to the hand and frequent workplace water exposure, as can happen in foodservice, farming, and marine industries.

When an abscess has formed (as in this case), or when conservative treatments fail, incision and drainage or partial nail avulsion can be curative and successful with, or without, antibiotics. Patients with recurrent paronychia in the same location may benefit from partial nail avulsion with partial matrix removal. This can be done surgically or with phenol.

In this case, the patient underwent lateral partial nail avulsion, which also served as an incision and drainage. She was not given antibiotics and her nail regrew within 6 months; there was no recurrence. She was counseled not to cut the nail plate too aggressively.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

Paronychia, or an ingrown nail, is caused by the introduction of bacteria into the nail fold, which can cause cellulitis and/or abscess formation. Typically, a single nail is involved, although multiple nails may be affected in rare, chemotherapy-induced cases. Generally, nail grooming behaviors, abnormal or scarred nail matrix architecture, nail biting, and wet work are the causes of acute or chronic disease.¹

Conservative options are a reasonable first choice when there is no abscess. These include soaks 2 to 3 times daily for 15 to 20 minutes in hot water or water treated with an antiseptic, such as chlorhexidine. Topical or oral antibiotics aimed at suspected organisms may be helpful. Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus, is a common isolate. Psuedomonas is characteristic in cases involving trauma to the hand and frequent workplace water exposure, as can happen in foodservice, farming, and marine industries.

When an abscess has formed (as in this case), or when conservative treatments fail, incision and drainage or partial nail avulsion can be curative and successful with, or without, antibiotics. Patients with recurrent paronychia in the same location may benefit from partial nail avulsion with partial matrix removal. This can be done surgically or with phenol.

In this case, the patient underwent lateral partial nail avulsion, which also served as an incision and drainage. She was not given antibiotics and her nail regrew within 6 months; there was no recurrence. She was counseled not to cut the nail plate too aggressively.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

In February, an article published by the American Medical Association pointed out that income inequality is likely the cause for health disparity among races.¹ The topic of health disparities was also the subject of the editorial published in the January/February issue, “Systemic racism and health disparities: a statement from editors of family medicine journals” (J Fam Pract. 2021;70:3-5).

It would be interesting to compare health outcomes among Blacks, Latinos, and Whites stratified by income/poverty levels. I suspect that much of the racial inequality would fade with that. There are so many questions to ask in relation to these issues rather than chalk everything up to racism. Does education, dietary choices, exercise, substance abuse, or cultural priorities factor into the differences? If everyone suddenly had equal access to care and equal financial resources, would there be any difference, or would behavior patterns remain unchanged?

I would hope we could avoid groupthink and be willing to intelligently and critically evaluate these issues so that the underlying problems can be effectively addressed.

Steven Mull, MD
Rockford, IL

In February, an article published by the American Medical Association pointed out that income inequality is likely the cause for health disparity among races.¹ The topic of health disparities was also the subject of the editorial published in the January/February issue, “Systemic racism and health disparities: a statement from editors of family medicine journals” (J Fam Pract. 2021;70:3-5).

It would be interesting to compare health outcomes among Blacks, Latinos, and Whites stratified by income/poverty levels. I suspect that much of the racial inequality would fade with that. There are so many questions to ask in relation to these issues rather than chalk everything up to racism. Does education, dietary choices, exercise, substance abuse, or cultural priorities factor into the differences? If everyone suddenly had equal access to care and equal financial resources, would there be any difference, or would behavior patterns remain unchanged?

I would hope we could avoid groupthink and be willing to intelligently and critically evaluate these issues so that the underlying problems can be effectively addressed.

Steven Mull, MD
Rockford, IL

In February, an article published by the American Medical Association pointed out that income inequality is likely the cause for health disparity among races.¹ The topic of health disparities was also the subject of the editorial published in the January/February issue, “Systemic racism and health disparities: a statement from editors of family medicine journals” (J Fam Pract. 2021;70:3-5).

It would be interesting to compare health outcomes among Blacks, Latinos, and Whites stratified by income/poverty levels. I suspect that much of the racial inequality would fade with that. There are so many questions to ask in relation to these issues rather than chalk everything up to racism. Does education, dietary choices, exercise, substance abuse, or cultural priorities factor into the differences? If everyone suddenly had equal access to care and equal financial resources, would there be any difference, or would behavior patterns remain unchanged?

I would hope we could avoid groupthink and be willing to intelligently and critically evaluate these issues so that the underlying problems can be effectively addressed.

Steven Mull, MD
Rockford, IL

It was encouraging to see your editorial, “Systemic racism and health disparities: a statement from editors of family medicine journals” (J Fam Pract. 2021;70:3-5), because to solve a problem you must first recognize the problem exists. There was a publication several years ago that went deeply into this subject.¹ I worked with the Medicaid population for 20 years, and I observed things similar to what was described in that paper.

Health disparities should be looked at as if structured around zip codes. People who live in low-income/­poverty areas usually have to deal with at least 3 main problems. The first issue involves lack of healthy food options. In low-income areas, food choice is often limited, forcing many to purchase their meals from fast food restaurants, dollar stores, or a “corner store.” In addition to being a food desert, a low-income area may have a poor public school system, and studies have shown that good health outcomes are linked to higher education. Poor medical intelligence is another problem connected to low-income patients. These patients tend to have a hard time keeping up with what medicine they are taking and cannot offer much insight into their medical condition. Furthermore, it is possible that in a busy practice, patient education is not what it should be, and a patient’s silence during a visit should not be accepted as an understanding of what a doctor has told them.

Hopefully, recognizing these issues will help provide a starting point for each doctor to gain better awareness into this problem.

Robert W. Sessoms, MD
Daytona Beach, FL

It was encouraging to see your editorial, “Systemic racism and health disparities: a statement from editors of family medicine journals” (J Fam Pract. 2021;70:3-5), because to solve a problem you must first recognize the problem exists. There was a publication several years ago that went deeply into this subject.¹ I worked with the Medicaid population for 20 years, and I observed things similar to what was described in that paper.

Health disparities should be looked at as if structured around zip codes. People who live in low-income/­poverty areas usually have to deal with at least 3 main problems. The first issue involves lack of healthy food options. In low-income areas, food choice is often limited, forcing many to purchase their meals from fast food restaurants, dollar stores, or a “corner store.” In addition to being a food desert, a low-income area may have a poor public school system, and studies have shown that good health outcomes are linked to higher education. Poor medical intelligence is another problem connected to low-income patients. These patients tend to have a hard time keeping up with what medicine they are taking and cannot offer much insight into their medical condition. Furthermore, it is possible that in a busy practice, patient education is not what it should be, and a patient’s silence during a visit should not be accepted as an understanding of what a doctor has told them.

Hopefully, recognizing these issues will help provide a starting point for each doctor to gain better awareness into this problem.

Robert W. Sessoms, MD
Daytona Beach, FL

It was encouraging to see your editorial, “Systemic racism and health disparities: a statement from editors of family medicine journals” (J Fam Pract. 2021;70:3-5), because to solve a problem you must first recognize the problem exists. There was a publication several years ago that went deeply into this subject.¹ I worked with the Medicaid population for 20 years, and I observed things similar to what was described in that paper.

Health disparities should be looked at as if structured around zip codes. People who live in low-income/­poverty areas usually have to deal with at least 3 main problems. The first issue involves lack of healthy food options. In low-income areas, food choice is often limited, forcing many to purchase their meals from fast food restaurants, dollar stores, or a “corner store.” In addition to being a food desert, a low-income area may have a poor public school system, and studies have shown that good health outcomes are linked to higher education. Poor medical intelligence is another problem connected to low-income patients. These patients tend to have a hard time keeping up with what medicine they are taking and cannot offer much insight into their medical condition. Furthermore, it is possible that in a busy practice, patient education is not what it should be, and a patient’s silence during a visit should not be accepted as an understanding of what a doctor has told them.

Hopefully, recognizing these issues will help provide a starting point for each doctor to gain better awareness into this problem.

Robert W. Sessoms, MD
Daytona Beach, FL

Evidence summary

No difference in overall hypoglycemia risk between glargine and NPH

A 2015 systematic review and meta-analysis of 28 RCTs compared efficacy and safety outcomes for insulin glargine, NPH insulin, premixed insulin preparations, and insulin detemir in 12,669 adults with type 2 ­diabetes (T2D) who were also taking an oral antidiabetic drug (OAD).¹ In the comparison of glargine to NPH, there was no difference in risk for hypoglycemia (5 trials; N not provided; risk ratio [RR] = 0.92; 0.84-1.001).

Symptomatic hypoglycemia (6 RCTs; RR = 0.89; 0.83-0.96) and nocturnal hypoglycemia (6 RCTs; RR = 0.63; 0.51-0.77) occurred significantly less frequently in those treated with glargine and an OAD compared to NPH and an OAD. The risk for severe hypoglycemia was not different between regimens (5 RCTs; RR = 0.76; 0.47-1.23). Weight gain was also similar (6 RCTs; weighted mean difference [WMD] = 0.36 kg [–0.12 to 0.84]). This review was limited by the fact that many of the trials were of moderate quality, the majority were funded by pharmaceutical companies, fasting glucose goals varied between trials, and some trials had a short duration (6 months).

There may be some advantages of glargine over NPH

A 2008 meta-analysis of 12 RCTs (5 of which were not included in the 2015 review) with 4385 patients with T2D compared fasting plasma glucose (FPG), A1C, hypoglycemia, and body weight for patients treated with NPH vs with glargine.² Researchers found a significant difference in patient-reported hypoglycemia (10 trials; N not provided; 59% vs 53%; P < .001), symptomatic hypoglycemia (6 trials; 51% vs 43%; P < .0001), and nocturnal hypoglycemia (8 trials; 33% vs 19%; P < .001), favoring glargine over NPH. However, there was no difference between these 2 groups in confirmed hypoglycemia (2 trials; 10% vs 6.3%; P = .11) or severe hypoglycemia (7 trials; 2.4% vs 1.4%; P = .07). Of note, there was no difference between groups in FPG or A1C and a smaller weight gain in the NPH group (6 trials; WMD = 0.33 kg; 95% CI, –0.61 to –0.06). This review did not assess potential biases in the included trials.

Other results indicate a significant benefit from glargine

A 2014 RCT (published after the systematic review search date) compared hypoglycemia risk between NPH and glargine in 1017 adults ages 30 to 70 years who’d had T2D for at least 1 year.³ Patients were randomized to receive an OAD paired with either once-daily glargine or twice-daily NPH. Insulin doses were titrated over the first 3 years of the study to achieve standard glycemic control (described as FPG < 120 mg/dL; this goal was changed to < 100 mg/dL after the first year).

Over 5 years, once-daily glargine resulted in a significantly lower risk for all symptomatic hypoglycemia (odds ratio [OR] = 0.71; 95% CI, 0.52-0.98) and for any severe event (OR = 0.62; 95% CI, 0.41-0.95) compared to NPH. Using a logistic regression model, the authors predicted that if 25 patients were treated with NPH instead of glargine, 1 additional patient would experience at least 1 severe hypoglycemic event. This trial was funded by a pharmaceutical company.

Hypoglycemia requiring hospital care was similar for basal insulin and NPH

A 2018 retrospective observational study (N = 25,489) analyzed the association between the initiation of basal insulin analogs vs NPH with hypoglycemia-related ED visits or hospital admissions.⁴ Adults older than 19 years with clinically recognized diabetes were identified using electronic medical records; those included in the analysis had newly initiated basal insulin therapy during the prior 12 months. Data was gathered via chart review.

The difference in ED visits or hospital admissions was not different between groups (mean difference = 3.1 events per 100 person-years; 95% CI, –1.5 to 7.7). Among 4428 patients matched by propensity score, there was again no difference for hypoglycemia-related ED visits or hospital admissions with insulin analog use (adjusted hazard ratio = 1.16; 95% CI, 0.71-1.78).

Editor’s takeaway

Meta-analysis of large RCTs shows the glargine insulin adverse effects profile, specifically nonsevere hypoglycemia, to be inconsistently better than NPH. These small differences, plus once-daily dosing, may encourage prescribing of analog basal insulin, but price and the need for more than once-daily dosing remain worthy considerations.

Evidence summary

No difference in overall hypoglycemia risk between glargine and NPH

A 2015 systematic review and meta-analysis of 28 RCTs compared efficacy and safety outcomes for insulin glargine, NPH insulin, premixed insulin preparations, and insulin detemir in 12,669 adults with type 2 ­diabetes (T2D) who were also taking an oral antidiabetic drug (OAD).¹ In the comparison of glargine to NPH, there was no difference in risk for hypoglycemia (5 trials; N not provided; risk ratio [RR] = 0.92; 0.84-1.001).

Symptomatic hypoglycemia (6 RCTs; RR = 0.89; 0.83-0.96) and nocturnal hypoglycemia (6 RCTs; RR = 0.63; 0.51-0.77) occurred significantly less frequently in those treated with glargine and an OAD compared to NPH and an OAD. The risk for severe hypoglycemia was not different between regimens (5 RCTs; RR = 0.76; 0.47-1.23). Weight gain was also similar (6 RCTs; weighted mean difference [WMD] = 0.36 kg [–0.12 to 0.84]). This review was limited by the fact that many of the trials were of moderate quality, the majority were funded by pharmaceutical companies, fasting glucose goals varied between trials, and some trials had a short duration (6 months).

There may be some advantages of glargine over NPH

A 2008 meta-analysis of 12 RCTs (5 of which were not included in the 2015 review) with 4385 patients with T2D compared fasting plasma glucose (FPG), A1C, hypoglycemia, and body weight for patients treated with NPH vs with glargine.² Researchers found a significant difference in patient-reported hypoglycemia (10 trials; N not provided; 59% vs 53%; P < .001), symptomatic hypoglycemia (6 trials; 51% vs 43%; P < .0001), and nocturnal hypoglycemia (8 trials; 33% vs 19%; P < .001), favoring glargine over NPH. However, there was no difference between these 2 groups in confirmed hypoglycemia (2 trials; 10% vs 6.3%; P = .11) or severe hypoglycemia (7 trials; 2.4% vs 1.4%; P = .07). Of note, there was no difference between groups in FPG or A1C and a smaller weight gain in the NPH group (6 trials; WMD = 0.33 kg; 95% CI, –0.61 to –0.06). This review did not assess potential biases in the included trials.

Other results indicate a significant benefit from glargine

A 2014 RCT (published after the systematic review search date) compared hypoglycemia risk between NPH and glargine in 1017 adults ages 30 to 70 years who’d had T2D for at least 1 year.³ Patients were randomized to receive an OAD paired with either once-daily glargine or twice-daily NPH. Insulin doses were titrated over the first 3 years of the study to achieve standard glycemic control (described as FPG < 120 mg/dL; this goal was changed to < 100 mg/dL after the first year).

Over 5 years, once-daily glargine resulted in a significantly lower risk for all symptomatic hypoglycemia (odds ratio [OR] = 0.71; 95% CI, 0.52-0.98) and for any severe event (OR = 0.62; 95% CI, 0.41-0.95) compared to NPH. Using a logistic regression model, the authors predicted that if 25 patients were treated with NPH instead of glargine, 1 additional patient would experience at least 1 severe hypoglycemic event. This trial was funded by a pharmaceutical company.

Hypoglycemia requiring hospital care was similar for basal insulin and NPH

A 2018 retrospective observational study (N = 25,489) analyzed the association between the initiation of basal insulin analogs vs NPH with hypoglycemia-related ED visits or hospital admissions.⁴ Adults older than 19 years with clinically recognized diabetes were identified using electronic medical records; those included in the analysis had newly initiated basal insulin therapy during the prior 12 months. Data was gathered via chart review.

The difference in ED visits or hospital admissions was not different between groups (mean difference = 3.1 events per 100 person-years; 95% CI, –1.5 to 7.7). Among 4428 patients matched by propensity score, there was again no difference for hypoglycemia-related ED visits or hospital admissions with insulin analog use (adjusted hazard ratio = 1.16; 95% CI, 0.71-1.78).

Editor’s takeaway

Meta-analysis of large RCTs shows the glargine insulin adverse effects profile, specifically nonsevere hypoglycemia, to be inconsistently better than NPH. These small differences, plus once-daily dosing, may encourage prescribing of analog basal insulin, but price and the need for more than once-daily dosing remain worthy considerations.

Evidence summary

No difference in overall hypoglycemia risk between glargine and NPH

A 2015 systematic review and meta-analysis of 28 RCTs compared efficacy and safety outcomes for insulin glargine, NPH insulin, premixed insulin preparations, and insulin detemir in 12,669 adults with type 2 ­diabetes (T2D) who were also taking an oral antidiabetic drug (OAD).¹ In the comparison of glargine to NPH, there was no difference in risk for hypoglycemia (5 trials; N not provided; risk ratio [RR] = 0.92; 0.84-1.001).

Symptomatic hypoglycemia (6 RCTs; RR = 0.89; 0.83-0.96) and nocturnal hypoglycemia (6 RCTs; RR = 0.63; 0.51-0.77) occurred significantly less frequently in those treated with glargine and an OAD compared to NPH and an OAD. The risk for severe hypoglycemia was not different between regimens (5 RCTs; RR = 0.76; 0.47-1.23). Weight gain was also similar (6 RCTs; weighted mean difference [WMD] = 0.36 kg [–0.12 to 0.84]). This review was limited by the fact that many of the trials were of moderate quality, the majority were funded by pharmaceutical companies, fasting glucose goals varied between trials, and some trials had a short duration (6 months).

There may be some advantages of glargine over NPH

A 2008 meta-analysis of 12 RCTs (5 of which were not included in the 2015 review) with 4385 patients with T2D compared fasting plasma glucose (FPG), A1C, hypoglycemia, and body weight for patients treated with NPH vs with glargine.² Researchers found a significant difference in patient-reported hypoglycemia (10 trials; N not provided; 59% vs 53%; P < .001), symptomatic hypoglycemia (6 trials; 51% vs 43%; P < .0001), and nocturnal hypoglycemia (8 trials; 33% vs 19%; P < .001), favoring glargine over NPH. However, there was no difference between these 2 groups in confirmed hypoglycemia (2 trials; 10% vs 6.3%; P = .11) or severe hypoglycemia (7 trials; 2.4% vs 1.4%; P = .07). Of note, there was no difference between groups in FPG or A1C and a smaller weight gain in the NPH group (6 trials; WMD = 0.33 kg; 95% CI, –0.61 to –0.06). This review did not assess potential biases in the included trials.

Other results indicate a significant benefit from glargine

A 2014 RCT (published after the systematic review search date) compared hypoglycemia risk between NPH and glargine in 1017 adults ages 30 to 70 years who’d had T2D for at least 1 year.³ Patients were randomized to receive an OAD paired with either once-daily glargine or twice-daily NPH. Insulin doses were titrated over the first 3 years of the study to achieve standard glycemic control (described as FPG < 120 mg/dL; this goal was changed to < 100 mg/dL after the first year).

Over 5 years, once-daily glargine resulted in a significantly lower risk for all symptomatic hypoglycemia (odds ratio [OR] = 0.71; 95% CI, 0.52-0.98) and for any severe event (OR = 0.62; 95% CI, 0.41-0.95) compared to NPH. Using a logistic regression model, the authors predicted that if 25 patients were treated with NPH instead of glargine, 1 additional patient would experience at least 1 severe hypoglycemic event. This trial was funded by a pharmaceutical company.

Hypoglycemia requiring hospital care was similar for basal insulin and NPH

A 2018 retrospective observational study (N = 25,489) analyzed the association between the initiation of basal insulin analogs vs NPH with hypoglycemia-related ED visits or hospital admissions.⁴ Adults older than 19 years with clinically recognized diabetes were identified using electronic medical records; those included in the analysis had newly initiated basal insulin therapy during the prior 12 months. Data was gathered via chart review.

The difference in ED visits or hospital admissions was not different between groups (mean difference = 3.1 events per 100 person-years; 95% CI, –1.5 to 7.7). Among 4428 patients matched by propensity score, there was again no difference for hypoglycemia-related ED visits or hospital admissions with insulin analog use (adjusted hazard ratio = 1.16; 95% CI, 0.71-1.78).

Editor’s takeaway

Meta-analysis of large RCTs shows the glargine insulin adverse effects profile, specifically nonsevere hypoglycemia, to be inconsistently better than NPH. These small differences, plus once-daily dosing, may encourage prescribing of analog basal insulin, but price and the need for more than once-daily dosing remain worthy considerations.

A 45-year-old woman visited the clinic 6 weeks after having a stroke while on her motorcycle, which resulted in a crash. She had not been wearing a helmet and was uncertain if she had sustained a head injury. She said that during the hospital stay following the accident, she was diagnosed as hypertensive; she denied any other significant prior medical history.

Following the crash, she said she’d been experiencing weakness in her right arm and leg and had been unable to open her right eye. When her right eye was opened manually, she said she had double vision and sensitivity to light.

On exam, the patient had exotropia with hypotropia of her right eye. Additionally, she had anisocoria with an enlarged, nonreactive right pupil (FIGURE 1A). She was unable to adduct, supraduct, or infraduct her right eye (FIGURE 1B). Her cranial nerves were ­otherwise intact. On manual strength testing, she had 4/5 strength of both her right upper and lower extremities.

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

This patient had a complete third nerve palsy (TNP). This is defined as palsy involving all of the muscles innervated by the oculomotor nerve, with pupillary involvement.¹ The oculomotor nerve supplies motor innervation to the levator palpebrae superioris, superior rectus, medial rectus, inferior rectus, and inferior oblique muscles and parasympathetic innervation to the pupillary constrictor and ciliary muscles.² As a result, patients present with exotropia and hypotropia on exam with anisocoria. Diplopia, ptosis, and an enlarged pupil are classic symptoms of TNP.²

Computed tomography (CT) of the brain performed immediately after this patient’s accident demonstrated a 15-mm hemorrhage within the left basal ganglia with mild associated edema, and a small focus of hyperattenuation within the right aspect of the suprasellar cistern. There was no evidence of skull fracture. CT angiography (CTA) of the brain showed no evidence of aneurysm.

Diplopia, ptosis, and an enlarged pupil are classic symptoms of TNP.

Several days later, magnetic resonance imaging (MRI) of the brain confirmed prior CT findings and revealed hemorrhagic contusions along the anterior and medial left temporal lobe. Additionally, the MRI showed subtle subdural hemorrhages along the midline falx and right parietal region, as well as diffuse subarachnoid hemorrhage around both hemispheres, the interpeduncular cistern, and the suprasellar cistern (FIGURE 2). The basal ganglia hemorrhage was believed to have been a result of uncontrolled hypertension. The hemorrhage was responsible for her right-sided weakness and was the presumed cause of the accident. The other findings were due to head trauma. Her TNP was most likely caused by both compression and irritation of the right oculomotor nerve.

An uncommon occurrence

A population-based study identified the annual incidence of TNP to be 4 per 100,000.¹ The mean age of onset was 42 years. The incidence in patients older than 60 years was greater than the incidence in those younger than 60.² Isolated TNP occurred in approximately 40% of cases.²

Complete TNP is typically indicative of compression of the ipsilateral third nerve.² The most common region for third nerve injury is the subarachnoid space, where the oculomotor nerve is vulnerable to compression, often by an aneurysm arising from the junction of the internal carotid and posterior communicating arteries.³

Continue to: Incomplete TNP

Incomplete TNP is often microvascular in origin and requires evaluation for diabetes and hypertension. Microvascular TNP is ­frequently painful but usually self-resolves after 2 to 4 months.² Giant cell arteritis may also cause an isolated, painful TNP.²

A varied differential diagnosis and a TNP link to COVID-19

The differential diagnosis for TNP includes the following:

Orbital apex injury is usually seen after high-energy craniofacial trauma.⁴ Orbital apex fractures present with different signs and symptoms, depending on the degree of injury to neural and vascular structures. Various syndromes come into play, the most common being superior orbital fissure syndrome, which is characterized by dysfunction of cranial nerves III, IV, V, and VI.⁴ Features include ophthalmoplegia, upper eyelid ptosis, a nonreactive dilated pupil, anesthesia over the ipsilateral forehead, loss of corneal reflex, orbital pain, and proptosis.⁴ 

In patients with suspected orbital apex fractures, it’s important to assess for the presence of an optic neuropathy, an evolving orbital compartment syndrome, or a ruptured globe, because these 3 things may demand acute intervention.⁴ 

Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial disorder characterized by a slow, progressive paralysis of the extraocular muscles.⁵ Patients usually experience bilateral, symmetrical, progressive ptosis, followed by ophthalmoparesis months to years later. Ciliary and iris muscles are not involved. CPEO often occurs with other systemic features of mitochondrial dysfunction that can cause significant morbidity and mortality.⁵ 

Continue to: Graves ophthalmopathy

Graves ophthalmopathy arises from soft-tissue enlargement in the orbit, leading to increased pressure within the bony cavity.⁶ Approximately 40% of patients with Graves ophthalmopathy present with restrictive extraocular myopathy; however > 90% have eyelid retraction, as opposed to ptosis.⁷ 

Guillain-Barré syndrome (GBS) is an acute, demyelinating immune-mediated polyneuropathy involving the spinal roots, peripheral nerves, and often the cranial nerves.⁸ The Miller Fisher variant of GBS is characterized by bilateral ophthalmoparesis, areflexia, and ataxia.⁸ At the early stage of illness, the presentation may be similar to TNP.⁸ Brain imaging is normal in patients with GBS; the diagnosis is established via characteristic electromyography and cerebrospinal fluid findings.⁸ 

Myasthenia gravis often manifests with variable ptosis associated with diplopia.⁹ Symptoms may be unilateral or bilateral. The ice-pack test has been identified as a simple, preliminary test for ocular myasthenia. The test involves the application of an ice-pack over the lids for 5 minutes. A 50% reduction in at least 1 component of ocular deviation is considered a positive response.¹⁰ Its specificity reportedly reaches 100%, with a sensitivity of 80%.¹⁰

COVID-19 infection may also include neurologic manifestations. There are an increasing number of case reports of central nervous system abnormalities including TNP.^11,12 

Trauma, tumors, or an aneurysm could be at work in TNP

TNP associated with trauma usually develops secondary to compression from an expanding hematoma, although it may also be a result of irritation of the nerve from blood in the subarachnoid space.¹³ Estimates of the incidence of TNP due to trauma range from 12% to 26% of cases.^1,14 Vehicle-related injury is the most frequent cause of trauma-related TNP.¹⁴

Continue to: Pituitary tumors

Pituitary tumors most commonly involve the oculomotor nerve; 14% to 30% of pituitary tumors lead to TNP.¹³ Pituitary apoplexy secondary to infarction or hemorrhage is often associated with visual field defects and TNP.¹³

An underlying aneurysm manifests in a minority (10% to 15%) of patients presenting with TNP.³

Imaging is key to getting at the cause of TNP

The evaluation of patients presenting with acute TNP should be focused first on detecting an aneurysmal compressive lesion.³ CTA is the imaging modality of choice. 

Once an aneurysm has been ruled out, the work-up should include a lumbar puncture and an erythrocyte sedimentation rate. Older patients should be assessed for conditions such as hypertension or diabetes that put them at risk for microvascular disease.³ If microvascular TNP is unlikely, MRI with MR angiography is recommended to exclude other potential etiologies of TNP.³ If the patient is younger than 50 years of age, consider potential infectious and inflammatory etiologies (eg, giant cell arteritis).³

Treatment options are varied

The treatment of patients with TNP is specific to the disease state. For those patients with vascular risk factors and a presumptive diagnosis of microvascular TNP, it is reasonable to observe the patient for 2 to 3 months.³ Antiplatelet therapy is usually initiated. Patching 1 eye is useful in alleviating diplopia, particularly in the short term. In most cases, deficits related to TNP resolve over weeks to months. Deficits that persist beyond 6 months may require surgical intervention.

Continue to: "The tip of the iceberg"

TNP may signal a neurologic emergency, such as an aneurysm, or other conditions such as pituitary disease or giant cell arteritis. Any patient presenting with acute onset of TNP should undergo a noninvasive neuroimaging study.³

Our patient was treated for hypertension; however, she was lost to follow-up.

A 45-year-old woman visited the clinic 6 weeks after having a stroke while on her motorcycle, which resulted in a crash. She had not been wearing a helmet and was uncertain if she had sustained a head injury. She said that during the hospital stay following the accident, she was diagnosed as hypertensive; she denied any other significant prior medical history.

Following the crash, she said she’d been experiencing weakness in her right arm and leg and had been unable to open her right eye. When her right eye was opened manually, she said she had double vision and sensitivity to light.

On exam, the patient had exotropia with hypotropia of her right eye. Additionally, she had anisocoria with an enlarged, nonreactive right pupil (FIGURE 1A). She was unable to adduct, supraduct, or infraduct her right eye (FIGURE 1B). Her cranial nerves were ­otherwise intact. On manual strength testing, she had 4/5 strength of both her right upper and lower extremities.

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

This patient had a complete third nerve palsy (TNP). This is defined as palsy involving all of the muscles innervated by the oculomotor nerve, with pupillary involvement.¹ The oculomotor nerve supplies motor innervation to the levator palpebrae superioris, superior rectus, medial rectus, inferior rectus, and inferior oblique muscles and parasympathetic innervation to the pupillary constrictor and ciliary muscles.² As a result, patients present with exotropia and hypotropia on exam with anisocoria. Diplopia, ptosis, and an enlarged pupil are classic symptoms of TNP.²

Computed tomography (CT) of the brain performed immediately after this patient’s accident demonstrated a 15-mm hemorrhage within the left basal ganglia with mild associated edema, and a small focus of hyperattenuation within the right aspect of the suprasellar cistern. There was no evidence of skull fracture. CT angiography (CTA) of the brain showed no evidence of aneurysm.

Diplopia, ptosis, and an enlarged pupil are classic symptoms of TNP.

Several days later, magnetic resonance imaging (MRI) of the brain confirmed prior CT findings and revealed hemorrhagic contusions along the anterior and medial left temporal lobe. Additionally, the MRI showed subtle subdural hemorrhages along the midline falx and right parietal region, as well as diffuse subarachnoid hemorrhage around both hemispheres, the interpeduncular cistern, and the suprasellar cistern (FIGURE 2). The basal ganglia hemorrhage was believed to have been a result of uncontrolled hypertension. The hemorrhage was responsible for her right-sided weakness and was the presumed cause of the accident. The other findings were due to head trauma. Her TNP was most likely caused by both compression and irritation of the right oculomotor nerve.

An uncommon occurrence

A population-based study identified the annual incidence of TNP to be 4 per 100,000.¹ The mean age of onset was 42 years. The incidence in patients older than 60 years was greater than the incidence in those younger than 60.² Isolated TNP occurred in approximately 40% of cases.²

Complete TNP is typically indicative of compression of the ipsilateral third nerve.² The most common region for third nerve injury is the subarachnoid space, where the oculomotor nerve is vulnerable to compression, often by an aneurysm arising from the junction of the internal carotid and posterior communicating arteries.³

Continue to: Incomplete TNP

Incomplete TNP is often microvascular in origin and requires evaluation for diabetes and hypertension. Microvascular TNP is ­frequently painful but usually self-resolves after 2 to 4 months.² Giant cell arteritis may also cause an isolated, painful TNP.²

A varied differential diagnosis and a TNP link to COVID-19

The differential diagnosis for TNP includes the following:

Orbital apex injury is usually seen after high-energy craniofacial trauma.⁴ Orbital apex fractures present with different signs and symptoms, depending on the degree of injury to neural and vascular structures. Various syndromes come into play, the most common being superior orbital fissure syndrome, which is characterized by dysfunction of cranial nerves III, IV, V, and VI.⁴ Features include ophthalmoplegia, upper eyelid ptosis, a nonreactive dilated pupil, anesthesia over the ipsilateral forehead, loss of corneal reflex, orbital pain, and proptosis.⁴ 

In patients with suspected orbital apex fractures, it’s important to assess for the presence of an optic neuropathy, an evolving orbital compartment syndrome, or a ruptured globe, because these 3 things may demand acute intervention.⁴ 

Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial disorder characterized by a slow, progressive paralysis of the extraocular muscles.⁵ Patients usually experience bilateral, symmetrical, progressive ptosis, followed by ophthalmoparesis months to years later. Ciliary and iris muscles are not involved. CPEO often occurs with other systemic features of mitochondrial dysfunction that can cause significant morbidity and mortality.⁵ 

Continue to: Graves ophthalmopathy

Graves ophthalmopathy arises from soft-tissue enlargement in the orbit, leading to increased pressure within the bony cavity.⁶ Approximately 40% of patients with Graves ophthalmopathy present with restrictive extraocular myopathy; however > 90% have eyelid retraction, as opposed to ptosis.⁷ 

Guillain-Barré syndrome (GBS) is an acute, demyelinating immune-mediated polyneuropathy involving the spinal roots, peripheral nerves, and often the cranial nerves.⁸ The Miller Fisher variant of GBS is characterized by bilateral ophthalmoparesis, areflexia, and ataxia.⁸ At the early stage of illness, the presentation may be similar to TNP.⁸ Brain imaging is normal in patients with GBS; the diagnosis is established via characteristic electromyography and cerebrospinal fluid findings.⁸ 

Myasthenia gravis often manifests with variable ptosis associated with diplopia.⁹ Symptoms may be unilateral or bilateral. The ice-pack test has been identified as a simple, preliminary test for ocular myasthenia. The test involves the application of an ice-pack over the lids for 5 minutes. A 50% reduction in at least 1 component of ocular deviation is considered a positive response.¹⁰ Its specificity reportedly reaches 100%, with a sensitivity of 80%.¹⁰

COVID-19 infection may also include neurologic manifestations. There are an increasing number of case reports of central nervous system abnormalities including TNP.^11,12 

Trauma, tumors, or an aneurysm could be at work in TNP

TNP associated with trauma usually develops secondary to compression from an expanding hematoma, although it may also be a result of irritation of the nerve from blood in the subarachnoid space.¹³ Estimates of the incidence of TNP due to trauma range from 12% to 26% of cases.^1,14 Vehicle-related injury is the most frequent cause of trauma-related TNP.¹⁴

Continue to: Pituitary tumors

Pituitary tumors most commonly involve the oculomotor nerve; 14% to 30% of pituitary tumors lead to TNP.¹³ Pituitary apoplexy secondary to infarction or hemorrhage is often associated with visual field defects and TNP.¹³

An underlying aneurysm manifests in a minority (10% to 15%) of patients presenting with TNP.³

Imaging is key to getting at the cause of TNP

The evaluation of patients presenting with acute TNP should be focused first on detecting an aneurysmal compressive lesion.³ CTA is the imaging modality of choice. 

Once an aneurysm has been ruled out, the work-up should include a lumbar puncture and an erythrocyte sedimentation rate. Older patients should be assessed for conditions such as hypertension or diabetes that put them at risk for microvascular disease.³ If microvascular TNP is unlikely, MRI with MR angiography is recommended to exclude other potential etiologies of TNP.³ If the patient is younger than 50 years of age, consider potential infectious and inflammatory etiologies (eg, giant cell arteritis).³

Treatment options are varied

The treatment of patients with TNP is specific to the disease state. For those patients with vascular risk factors and a presumptive diagnosis of microvascular TNP, it is reasonable to observe the patient for 2 to 3 months.³ Antiplatelet therapy is usually initiated. Patching 1 eye is useful in alleviating diplopia, particularly in the short term. In most cases, deficits related to TNP resolve over weeks to months. Deficits that persist beyond 6 months may require surgical intervention.

Continue to: "The tip of the iceberg"

TNP may signal a neurologic emergency, such as an aneurysm, or other conditions such as pituitary disease or giant cell arteritis. Any patient presenting with acute onset of TNP should undergo a noninvasive neuroimaging study.³

Our patient was treated for hypertension; however, she was lost to follow-up.

A 45-year-old woman visited the clinic 6 weeks after having a stroke while on her motorcycle, which resulted in a crash. She had not been wearing a helmet and was uncertain if she had sustained a head injury. She said that during the hospital stay following the accident, she was diagnosed as hypertensive; she denied any other significant prior medical history.

Following the crash, she said she’d been experiencing weakness in her right arm and leg and had been unable to open her right eye. When her right eye was opened manually, she said she had double vision and sensitivity to light.

On exam, the patient had exotropia with hypotropia of her right eye. Additionally, she had anisocoria with an enlarged, nonreactive right pupil (FIGURE 1A). She was unable to adduct, supraduct, or infraduct her right eye (FIGURE 1B). Her cranial nerves were ­otherwise intact. On manual strength testing, she had 4/5 strength of both her right upper and lower extremities.

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

This patient had a complete third nerve palsy (TNP). This is defined as palsy involving all of the muscles innervated by the oculomotor nerve, with pupillary involvement.¹ The oculomotor nerve supplies motor innervation to the levator palpebrae superioris, superior rectus, medial rectus, inferior rectus, and inferior oblique muscles and parasympathetic innervation to the pupillary constrictor and ciliary muscles.² As a result, patients present with exotropia and hypotropia on exam with anisocoria. Diplopia, ptosis, and an enlarged pupil are classic symptoms of TNP.²

Computed tomography (CT) of the brain performed immediately after this patient’s accident demonstrated a 15-mm hemorrhage within the left basal ganglia with mild associated edema, and a small focus of hyperattenuation within the right aspect of the suprasellar cistern. There was no evidence of skull fracture. CT angiography (CTA) of the brain showed no evidence of aneurysm.

Diplopia, ptosis, and an enlarged pupil are classic symptoms of TNP.

Several days later, magnetic resonance imaging (MRI) of the brain confirmed prior CT findings and revealed hemorrhagic contusions along the anterior and medial left temporal lobe. Additionally, the MRI showed subtle subdural hemorrhages along the midline falx and right parietal region, as well as diffuse subarachnoid hemorrhage around both hemispheres, the interpeduncular cistern, and the suprasellar cistern (FIGURE 2). The basal ganglia hemorrhage was believed to have been a result of uncontrolled hypertension. The hemorrhage was responsible for her right-sided weakness and was the presumed cause of the accident. The other findings were due to head trauma. Her TNP was most likely caused by both compression and irritation of the right oculomotor nerve.

An uncommon occurrence

A population-based study identified the annual incidence of TNP to be 4 per 100,000.¹ The mean age of onset was 42 years. The incidence in patients older than 60 years was greater than the incidence in those younger than 60.² Isolated TNP occurred in approximately 40% of cases.²

Complete TNP is typically indicative of compression of the ipsilateral third nerve.² The most common region for third nerve injury is the subarachnoid space, where the oculomotor nerve is vulnerable to compression, often by an aneurysm arising from the junction of the internal carotid and posterior communicating arteries.³

Continue to: Incomplete TNP

Incomplete TNP is often microvascular in origin and requires evaluation for diabetes and hypertension. Microvascular TNP is ­frequently painful but usually self-resolves after 2 to 4 months.² Giant cell arteritis may also cause an isolated, painful TNP.²

A varied differential diagnosis and a TNP link to COVID-19

The differential diagnosis for TNP includes the following:

Orbital apex injury is usually seen after high-energy craniofacial trauma.⁴ Orbital apex fractures present with different signs and symptoms, depending on the degree of injury to neural and vascular structures. Various syndromes come into play, the most common being superior orbital fissure syndrome, which is characterized by dysfunction of cranial nerves III, IV, V, and VI.⁴ Features include ophthalmoplegia, upper eyelid ptosis, a nonreactive dilated pupil, anesthesia over the ipsilateral forehead, loss of corneal reflex, orbital pain, and proptosis.⁴ 

In patients with suspected orbital apex fractures, it’s important to assess for the presence of an optic neuropathy, an evolving orbital compartment syndrome, or a ruptured globe, because these 3 things may demand acute intervention.⁴ 

Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial disorder characterized by a slow, progressive paralysis of the extraocular muscles.⁵ Patients usually experience bilateral, symmetrical, progressive ptosis, followed by ophthalmoparesis months to years later. Ciliary and iris muscles are not involved. CPEO often occurs with other systemic features of mitochondrial dysfunction that can cause significant morbidity and mortality.⁵ 

Continue to: Graves ophthalmopathy

Graves ophthalmopathy arises from soft-tissue enlargement in the orbit, leading to increased pressure within the bony cavity.⁶ Approximately 40% of patients with Graves ophthalmopathy present with restrictive extraocular myopathy; however > 90% have eyelid retraction, as opposed to ptosis.⁷ 

Guillain-Barré syndrome (GBS) is an acute, demyelinating immune-mediated polyneuropathy involving the spinal roots, peripheral nerves, and often the cranial nerves.⁸ The Miller Fisher variant of GBS is characterized by bilateral ophthalmoparesis, areflexia, and ataxia.⁸ At the early stage of illness, the presentation may be similar to TNP.⁸ Brain imaging is normal in patients with GBS; the diagnosis is established via characteristic electromyography and cerebrospinal fluid findings.⁸ 

Myasthenia gravis often manifests with variable ptosis associated with diplopia.⁹ Symptoms may be unilateral or bilateral. The ice-pack test has been identified as a simple, preliminary test for ocular myasthenia. The test involves the application of an ice-pack over the lids for 5 minutes. A 50% reduction in at least 1 component of ocular deviation is considered a positive response.¹⁰ Its specificity reportedly reaches 100%, with a sensitivity of 80%.¹⁰

COVID-19 infection may also include neurologic manifestations. There are an increasing number of case reports of central nervous system abnormalities including TNP.^11,12 

Trauma, tumors, or an aneurysm could be at work in TNP

TNP associated with trauma usually develops secondary to compression from an expanding hematoma, although it may also be a result of irritation of the nerve from blood in the subarachnoid space.¹³ Estimates of the incidence of TNP due to trauma range from 12% to 26% of cases.^1,14 Vehicle-related injury is the most frequent cause of trauma-related TNP.¹⁴

Continue to: Pituitary tumors

Pituitary tumors most commonly involve the oculomotor nerve; 14% to 30% of pituitary tumors lead to TNP.¹³ Pituitary apoplexy secondary to infarction or hemorrhage is often associated with visual field defects and TNP.¹³

An underlying aneurysm manifests in a minority (10% to 15%) of patients presenting with TNP.³

Imaging is key to getting at the cause of TNP

The evaluation of patients presenting with acute TNP should be focused first on detecting an aneurysmal compressive lesion.³ CTA is the imaging modality of choice. 

Once an aneurysm has been ruled out, the work-up should include a lumbar puncture and an erythrocyte sedimentation rate. Older patients should be assessed for conditions such as hypertension or diabetes that put them at risk for microvascular disease.³ If microvascular TNP is unlikely, MRI with MR angiography is recommended to exclude other potential etiologies of TNP.³ If the patient is younger than 50 years of age, consider potential infectious and inflammatory etiologies (eg, giant cell arteritis).³

Treatment options are varied

The treatment of patients with TNP is specific to the disease state. For those patients with vascular risk factors and a presumptive diagnosis of microvascular TNP, it is reasonable to observe the patient for 2 to 3 months.³ Antiplatelet therapy is usually initiated. Patching 1 eye is useful in alleviating diplopia, particularly in the short term. In most cases, deficits related to TNP resolve over weeks to months. Deficits that persist beyond 6 months may require surgical intervention.

Continue to: "The tip of the iceberg"

TNP may signal a neurologic emergency, such as an aneurysm, or other conditions such as pituitary disease or giant cell arteritis. Any patient presenting with acute onset of TNP should undergo a noninvasive neuroimaging study.³

Our patient was treated for hypertension; however, she was lost to follow-up.

Liver cirrhosis is implicated in 75% to 85% of ascites cases in the Western world, with heart failure or malignancy accounting for fewer cases.¹ Among patients who have decompensated cirrhosis with ascites, annual mortality is 20%.² Another study showed a 3-year survival rate after onset of ascites of only 56%.³ It is vital for primary care physicians (PCPs) to be alert for ascites not only in patients who have risk factors for chronic liver disease and cirrhosis—eg, a history of alcohol use disorder, chronic viral infections (hepatitis B and C), or metabolic syndrome—but also in patients with abnormal liver function tests and thrombocytopenia. In this review, we discuss the initial assessment of ascites and its long-term management, concentrating on the role of the PCP.

Pathophysiology: Vasodilation leads to a cascade

Splanchnic vasodilation is the main underlying event triggering a pathologic cascade that leads to the development of ascites.⁴ Initially portal hypertension in the setting of liver inflammation and fibrosis causes the release of inflammatory cytokines such as nitric oxide and carbon monoxide. This, in turn, causes the pathologic dilation of splanchnic circulation that decreases effective circulating volume. Activation of the sympathetic nervous system, vasopressin, and renin-­angiotensin-aldosterone system (RAAS) then causes the proximal and distal tubules to increase renal absorption of sodium and water.⁵ The resulting volume overload further decreases the heart’s ability to maintain circulating volume, leading to increased activation of compensating symptoms. This vicious cycle eventually manifests as ascites.⁶

A complex interplay of cirrhosis-associated immune dysfunction (CAID), gut dysbiosis, and increased translocation of microorganisms into ascitic fluid is also an important aspect of the pathogenesis.⁷ CAID (FIGURE 1)^7,8 is an immunodeficient state due to cirrhosis with reduced phagocytic activity by neutrophils and macrophages, T- and B-cell hypoproliferation, and reduced cytotoxicity of natural killer cells. In parallel, there is increased production of inflammatory cytokines due to the effects of damage-associated molecular patterns (DAMPs) from hepatocytes and ­pathogen-associated molecular patterns (PAMPs) from the gut microbiota on the immune system, which leads to many of the manifestations of decompensated cirrhosis including ascites.⁸

Key in on these elementsof the history and exam

Each step of the basic work-up for ascites provides opportunities to refine or redirect the diagnostic inquiry (TABLE).