Dermatology

SANDESTIN, FLA. – Even when you know a patient’s serology and hear their symptoms and think you have a bead on their rheumatic disease, you might not. It’s vital to check the skin in patients with rheumatic disease to be sure the right disease is being treated and that they don’t actually have a more severe condition that might progress suddenly if left unchecked, said Alisa Femia, MD, assistant professor of dermatology at the annual Congress of Clinical Rheumatology.

In a session filled with pearls for rheumatologists on what to look for on their patients’ skin to help guide diagnosis and treatment, she told the story of a woman whom a rheumatologist colleague had correctly diagnosed with dermatomyositis. She was started on prednisone and mycophenolate mofetil, but her skin disease did not clear.

After examining her skin, Dr. Femia became immediately concerned.

“Despite prednisone, despite mycophenolate, here not only does she have Gottron’s papules, but she has erosions within her Gottron’s papules,” Dr. Femia said. The woman also had erosions within papules on her palms.

These were telltale signs of MDA5-associated dermatomyositis, which studies have found to be linked with interstitial lung disease (J Am Acad Dermatol. 2011 Jul;65[1]:25-34). Under her care, these patients ideally undergo lung monitoring every 3 months, Dr. Femia said.

“That is a form of dermatomyositis that you cannot miss,” she said.

The effects of discoid lupus are another reason to take special care in skin examination. Once the disease, which involves a scaling of the skin, is obvious, there can be permanent aesthetic effects that could have been avoided with earlier detection and treatment, Dr. Femia said.

Clinicians should also be on the lookout for volume loss, or contour change, in discoid lupus patients, because that’s a sign of lupus panniculitis, which involves deeper lesions mainly to fatty areas such as the cheeks or thighs. The disease can progress fast, with sudden, massive loss of body volume, so therapy should be escalated quickly, she said.

“We want to treat these patients aggressively in order to avoid this.”

SOURCE: Femia A. CCR 2018.

SANDESTIN, FLA. – Even when you know a patient’s serology and hear their symptoms and think you have a bead on their rheumatic disease, you might not. It’s vital to check the skin in patients with rheumatic disease to be sure the right disease is being treated and that they don’t actually have a more severe condition that might progress suddenly if left unchecked, said Alisa Femia, MD, assistant professor of dermatology at the annual Congress of Clinical Rheumatology.

In a session filled with pearls for rheumatologists on what to look for on their patients’ skin to help guide diagnosis and treatment, she told the story of a woman whom a rheumatologist colleague had correctly diagnosed with dermatomyositis. She was started on prednisone and mycophenolate mofetil, but her skin disease did not clear.

After examining her skin, Dr. Femia became immediately concerned.

“Despite prednisone, despite mycophenolate, here not only does she have Gottron’s papules, but she has erosions within her Gottron’s papules,” Dr. Femia said. The woman also had erosions within papules on her palms.

These were telltale signs of MDA5-associated dermatomyositis, which studies have found to be linked with interstitial lung disease (J Am Acad Dermatol. 2011 Jul;65[1]:25-34). Under her care, these patients ideally undergo lung monitoring every 3 months, Dr. Femia said.

“That is a form of dermatomyositis that you cannot miss,” she said.

The effects of discoid lupus are another reason to take special care in skin examination. Once the disease, which involves a scaling of the skin, is obvious, there can be permanent aesthetic effects that could have been avoided with earlier detection and treatment, Dr. Femia said.

Clinicians should also be on the lookout for volume loss, or contour change, in discoid lupus patients, because that’s a sign of lupus panniculitis, which involves deeper lesions mainly to fatty areas such as the cheeks or thighs. The disease can progress fast, with sudden, massive loss of body volume, so therapy should be escalated quickly, she said.

“We want to treat these patients aggressively in order to avoid this.”

SOURCE: Femia A. CCR 2018.

SANDESTIN, FLA. – Even when you know a patient’s serology and hear their symptoms and think you have a bead on their rheumatic disease, you might not. It’s vital to check the skin in patients with rheumatic disease to be sure the right disease is being treated and that they don’t actually have a more severe condition that might progress suddenly if left unchecked, said Alisa Femia, MD, assistant professor of dermatology at the annual Congress of Clinical Rheumatology.

In a session filled with pearls for rheumatologists on what to look for on their patients’ skin to help guide diagnosis and treatment, she told the story of a woman whom a rheumatologist colleague had correctly diagnosed with dermatomyositis. She was started on prednisone and mycophenolate mofetil, but her skin disease did not clear.

After examining her skin, Dr. Femia became immediately concerned.

“Despite prednisone, despite mycophenolate, here not only does she have Gottron’s papules, but she has erosions within her Gottron’s papules,” Dr. Femia said. The woman also had erosions within papules on her palms.

These were telltale signs of MDA5-associated dermatomyositis, which studies have found to be linked with interstitial lung disease (J Am Acad Dermatol. 2011 Jul;65[1]:25-34). Under her care, these patients ideally undergo lung monitoring every 3 months, Dr. Femia said.

“That is a form of dermatomyositis that you cannot miss,” she said.

The effects of discoid lupus are another reason to take special care in skin examination. Once the disease, which involves a scaling of the skin, is obvious, there can be permanent aesthetic effects that could have been avoided with earlier detection and treatment, Dr. Femia said.

Clinicians should also be on the lookout for volume loss, or contour change, in discoid lupus patients, because that’s a sign of lupus panniculitis, which involves deeper lesions mainly to fatty areas such as the cheeks or thighs. The disease can progress fast, with sudden, massive loss of body volume, so therapy should be escalated quickly, she said.

“We want to treat these patients aggressively in order to avoid this.”

SOURCE: Femia A. CCR 2018.

A guidelines-based educational program on treating acne in teenagers has led to significant improvements in pediatricians’ management of the condition and decreased referrals to dermatologists, new research suggests.

A research letter published online May in the Journal of the American Academy of Dermatology described the results of a study involving 116 pediatricians, who participated in an educational program, including brief live sessions, on how to manage acne in teenagers.

Rawpixel/Thinkstock

Ms. Borok and her coauthors wrote that their educational program and prescribing tool aimed to address this practice gap without increasing the workload for pediatricians or dermatologists. “Adherence to guidelines by pediatricians has the potential to improve treatment provided in the primary care setting, better patient satisfaction, and allow greater access to dermatologists and pediatric dermatologists for patients with more severe acne and other conditions.”

Acknowledging that the study took place over a relatively short period of time, the authors said future research would examine the impact of the educational program and ordering tool on patient acne outcomes.

No funding or conflicts of interest were declared.

SOURCE: Borok J et al. J Am Acad Dermatol. 2018 May 9. doi: 10.1016/j.jaad.2018.04.055.
 

A guidelines-based educational program on treating acne in teenagers has led to significant improvements in pediatricians’ management of the condition and decreased referrals to dermatologists, new research suggests.

A research letter published online May in the Journal of the American Academy of Dermatology described the results of a study involving 116 pediatricians, who participated in an educational program, including brief live sessions, on how to manage acne in teenagers.

Rawpixel/Thinkstock

Ms. Borok and her coauthors wrote that their educational program and prescribing tool aimed to address this practice gap without increasing the workload for pediatricians or dermatologists. “Adherence to guidelines by pediatricians has the potential to improve treatment provided in the primary care setting, better patient satisfaction, and allow greater access to dermatologists and pediatric dermatologists for patients with more severe acne and other conditions.”

Acknowledging that the study took place over a relatively short period of time, the authors said future research would examine the impact of the educational program and ordering tool on patient acne outcomes.

No funding or conflicts of interest were declared.

SOURCE: Borok J et al. J Am Acad Dermatol. 2018 May 9. doi: 10.1016/j.jaad.2018.04.055.
 

A guidelines-based educational program on treating acne in teenagers has led to significant improvements in pediatricians’ management of the condition and decreased referrals to dermatologists, new research suggests.

A research letter published online May in the Journal of the American Academy of Dermatology described the results of a study involving 116 pediatricians, who participated in an educational program, including brief live sessions, on how to manage acne in teenagers.

Rawpixel/Thinkstock

Ms. Borok and her coauthors wrote that their educational program and prescribing tool aimed to address this practice gap without increasing the workload for pediatricians or dermatologists. “Adherence to guidelines by pediatricians has the potential to improve treatment provided in the primary care setting, better patient satisfaction, and allow greater access to dermatologists and pediatric dermatologists for patients with more severe acne and other conditions.”

Acknowledging that the study took place over a relatively short period of time, the authors said future research would examine the impact of the educational program and ordering tool on patient acne outcomes.

No funding or conflicts of interest were declared.

SOURCE: Borok J et al. J Am Acad Dermatol. 2018 May 9. doi: 10.1016/j.jaad.2018.04.055.
 

The FP suspected that this was a melanoma.

He thought through the ABCDEs of melanoma and saw that it was Asymmetric, had an irregular Border, had varied Colors, the Diameter was larger than 6 mm, and it was Evolving. The FP also noted that one area was elevated and another area (the center) seemed to be regressing. Using his dermatoscope, he noted strong evidence of regression in the center and an “atypical network.” He told the patient that this was very suspicious for melanoma and recommended a skin biopsy without delay. The patient agreed and after local anesthesia with lidocaine with epinephrine, a saucerization biopsy was performed using a DermaBlade. (See the Watch & Learn video on “Shave biopsy.”) The FP easily removed all of the visible tumor with the saucerization (deep shave). The bleeding was stopped with topical aluminum chloride, and the specimen was sent in formalin to the pathologist. The pathology report came back as a melanoma of 2.1 mm depth arising in a pre-existing nevus.

The patient was referred to a surgical oncologist for sentinel lymph node biopsy and excision with wide margins.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Congenital nevi. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine, 2nd ed. New York, NY: McGraw-Hill; 2013:953-957.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP suspected that this was a melanoma.

He thought through the ABCDEs of melanoma and saw that it was Asymmetric, had an irregular Border, had varied Colors, the Diameter was larger than 6 mm, and it was Evolving. The FP also noted that one area was elevated and another area (the center) seemed to be regressing. Using his dermatoscope, he noted strong evidence of regression in the center and an “atypical network.” He told the patient that this was very suspicious for melanoma and recommended a skin biopsy without delay. The patient agreed and after local anesthesia with lidocaine with epinephrine, a saucerization biopsy was performed using a DermaBlade. (See the Watch & Learn video on “Shave biopsy.”) The FP easily removed all of the visible tumor with the saucerization (deep shave). The bleeding was stopped with topical aluminum chloride, and the specimen was sent in formalin to the pathologist. The pathology report came back as a melanoma of 2.1 mm depth arising in a pre-existing nevus.

The patient was referred to a surgical oncologist for sentinel lymph node biopsy and excision with wide margins.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Congenital nevi. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine, 2nd ed. New York, NY: McGraw-Hill; 2013:953-957.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP suspected that this was a melanoma.

He thought through the ABCDEs of melanoma and saw that it was Asymmetric, had an irregular Border, had varied Colors, the Diameter was larger than 6 mm, and it was Evolving. The FP also noted that one area was elevated and another area (the center) seemed to be regressing. Using his dermatoscope, he noted strong evidence of regression in the center and an “atypical network.” He told the patient that this was very suspicious for melanoma and recommended a skin biopsy without delay. The patient agreed and after local anesthesia with lidocaine with epinephrine, a saucerization biopsy was performed using a DermaBlade. (See the Watch & Learn video on “Shave biopsy.”) The FP easily removed all of the visible tumor with the saucerization (deep shave). The bleeding was stopped with topical aluminum chloride, and the specimen was sent in formalin to the pathologist. The pathology report came back as a melanoma of 2.1 mm depth arising in a pre-existing nevus.

The patient was referred to a surgical oncologist for sentinel lymph node biopsy and excision with wide margins.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Congenital nevi. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine, 2nd ed. New York, NY: McGraw-Hill; 2013:953-957.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

Vitamin B12 deficiency can cause skin hyperpigmentation and partial paralysis, but these issues can be easily treated early on with vitamin B12 shots, said Ashish Agarwal, MD, and his colleagues at the Postgraduate Institute of Medical Education and Research in Chandigarh, India.

A 6-year-old boy, who had been previously healthy, presented with darkening of his hands and feet over a 4-month period. It also was noted that the skin on his palms and soles was thin and shiny. His walking gait had become abnormal in the previous 2 weeks; his legs were stiff when he walked, which caused him to fall and led to difficulty climbing stairs. The boy had no personal or family history of muscle issues or neurological issues. The boy’s personal history revealed that he ate a vegetarian diet.

A clinical diagnosis was made of megaloblastic anemia with subacute degeneration of the cord caused by vitamin B12 deficiency, a diagnosis not uncommon among vegetarians. The boy was started on daily intramuscular injections of B12 for 2 weeks, followed by weekly injections for a month. Monthly injections then were administered for the next 2 months. In the first few weeks, the hyperpigmentation began improving. At his 4-month follow-up, the boy was asymptomatic with reversal of the hyperpigmentation.

Dr. Agarwal and his associates concluded that skin darkening is an important clue toward underlying hematologic and neurologic manifestations of B12 deficiency.

ilacy@mdedge.com

SOURCE: Agarwal A et al. J Pediatr. 2018. doi: 10.1016/j.jpeds.2018.03.073.

Vitamin B12 deficiency can cause skin hyperpigmentation and partial paralysis, but these issues can be easily treated early on with vitamin B12 shots, said Ashish Agarwal, MD, and his colleagues at the Postgraduate Institute of Medical Education and Research in Chandigarh, India.

A 6-year-old boy, who had been previously healthy, presented with darkening of his hands and feet over a 4-month period. It also was noted that the skin on his palms and soles was thin and shiny. His walking gait had become abnormal in the previous 2 weeks; his legs were stiff when he walked, which caused him to fall and led to difficulty climbing stairs. The boy had no personal or family history of muscle issues or neurological issues. The boy’s personal history revealed that he ate a vegetarian diet.

A clinical diagnosis was made of megaloblastic anemia with subacute degeneration of the cord caused by vitamin B12 deficiency, a diagnosis not uncommon among vegetarians. The boy was started on daily intramuscular injections of B12 for 2 weeks, followed by weekly injections for a month. Monthly injections then were administered for the next 2 months. In the first few weeks, the hyperpigmentation began improving. At his 4-month follow-up, the boy was asymptomatic with reversal of the hyperpigmentation.

Dr. Agarwal and his associates concluded that skin darkening is an important clue toward underlying hematologic and neurologic manifestations of B12 deficiency.

ilacy@mdedge.com

SOURCE: Agarwal A et al. J Pediatr. 2018. doi: 10.1016/j.jpeds.2018.03.073.

Vitamin B12 deficiency can cause skin hyperpigmentation and partial paralysis, but these issues can be easily treated early on with vitamin B12 shots, said Ashish Agarwal, MD, and his colleagues at the Postgraduate Institute of Medical Education and Research in Chandigarh, India.

A 6-year-old boy, who had been previously healthy, presented with darkening of his hands and feet over a 4-month period. It also was noted that the skin on his palms and soles was thin and shiny. His walking gait had become abnormal in the previous 2 weeks; his legs were stiff when he walked, which caused him to fall and led to difficulty climbing stairs. The boy had no personal or family history of muscle issues or neurological issues. The boy’s personal history revealed that he ate a vegetarian diet.

A clinical diagnosis was made of megaloblastic anemia with subacute degeneration of the cord caused by vitamin B12 deficiency, a diagnosis not uncommon among vegetarians. The boy was started on daily intramuscular injections of B12 for 2 weeks, followed by weekly injections for a month. Monthly injections then were administered for the next 2 months. In the first few weeks, the hyperpigmentation began improving. At his 4-month follow-up, the boy was asymptomatic with reversal of the hyperpigmentation.

Dr. Agarwal and his associates concluded that skin darkening is an important clue toward underlying hematologic and neurologic manifestations of B12 deficiency.

ilacy@mdedge.com

SOURCE: Agarwal A et al. J Pediatr. 2018. doi: 10.1016/j.jpeds.2018.03.073.

Although skin biopsy and the “presence of deep dermal mixed infiltrate with abundant neutrophils surrounding eccrine sweat glands” is considered the preferred method for diagnosing palmoplantar eccrine hidradenitis (PEH), Paola Piccini, MD, and her colleagues at the University of Florence (Italy) caution that biopsy frequently is not needed.

In the days prior to the appearance of erythematous and painful nodules on the soles of his feet, a healthy 8-year-old boy sustained “thermal and mechanical trauma playing football and cycling,” that made walking difficult. The week prior to the injury, he had complained of diarrhea in the absence of fever.

Ika84/iStock/Getty Images

No disclosures were noted.

SOURCE: Piccini, P et al. J. Pediatr. 2018. doi: 10.1016/j.peds.2018.03.017.

Although skin biopsy and the “presence of deep dermal mixed infiltrate with abundant neutrophils surrounding eccrine sweat glands” is considered the preferred method for diagnosing palmoplantar eccrine hidradenitis (PEH), Paola Piccini, MD, and her colleagues at the University of Florence (Italy) caution that biopsy frequently is not needed.

In the days prior to the appearance of erythematous and painful nodules on the soles of his feet, a healthy 8-year-old boy sustained “thermal and mechanical trauma playing football and cycling,” that made walking difficult. The week prior to the injury, he had complained of diarrhea in the absence of fever.

Ika84/iStock/Getty Images

No disclosures were noted.

SOURCE: Piccini, P et al. J. Pediatr. 2018. doi: 10.1016/j.peds.2018.03.017.

Although skin biopsy and the “presence of deep dermal mixed infiltrate with abundant neutrophils surrounding eccrine sweat glands” is considered the preferred method for diagnosing palmoplantar eccrine hidradenitis (PEH), Paola Piccini, MD, and her colleagues at the University of Florence (Italy) caution that biopsy frequently is not needed.

In the days prior to the appearance of erythematous and painful nodules on the soles of his feet, a healthy 8-year-old boy sustained “thermal and mechanical trauma playing football and cycling,” that made walking difficult. The week prior to the injury, he had complained of diarrhea in the absence of fever.

Ika84/iStock/Getty Images

No disclosures were noted.

SOURCE: Piccini, P et al. J. Pediatr. 2018. doi: 10.1016/j.peds.2018.03.017.

Pretreatment ECG screening is unnecessary for most infants with infantile hemangioma who are prescribed propranolol therapy, reported Emily B. Lund, MD, of the University of Chicago, and her associates.

This finding supports previously published studies that pretreatment ECG is not necessary, despite consensus guidelines published in 2013 that recommend ECG screening of high-risk infants presenting with below-normal heart rate, arrhythmia, or family history of either arrhythmia or congenital heart disease.

Courtesy RegionalDerm.com

SOURCE: Lund EB et al. Ped Dermatol. 2018. doi: 10.1111/pde.13508.

Pretreatment ECG screening is unnecessary for most infants with infantile hemangioma who are prescribed propranolol therapy, reported Emily B. Lund, MD, of the University of Chicago, and her associates.

This finding supports previously published studies that pretreatment ECG is not necessary, despite consensus guidelines published in 2013 that recommend ECG screening of high-risk infants presenting with below-normal heart rate, arrhythmia, or family history of either arrhythmia or congenital heart disease.

Courtesy RegionalDerm.com

SOURCE: Lund EB et al. Ped Dermatol. 2018. doi: 10.1111/pde.13508.

Pretreatment ECG screening is unnecessary for most infants with infantile hemangioma who are prescribed propranolol therapy, reported Emily B. Lund, MD, of the University of Chicago, and her associates.

This finding supports previously published studies that pretreatment ECG is not necessary, despite consensus guidelines published in 2013 that recommend ECG screening of high-risk infants presenting with below-normal heart rate, arrhythmia, or family history of either arrhythmia or congenital heart disease.

Courtesy RegionalDerm.com

SOURCE: Lund EB et al. Ped Dermatol. 2018. doi: 10.1111/pde.13508.

A 38-year-old Latino man self-refers to dermatology for evaluation of a mass on his back that first appeared three years ago. Since then, it has grown steadily. There is no pain or discomfort associated with the lesion, and the patient claims to be quite healthy otherwise. There is no antecedent history for the affected area.

EXAMINATION
There is a subcutaneous, rubbery mass in the left infrascapular area. It measures 11 x 6 cm. Palpation reveals the lesion to be uniformly smooth and readily mobile. The overlying skin is free of abnormalities and increased warmth.

What is the diagnosis?

Lipomas are actual tumors, composed completely of adipose tissue contained in a thin, fragile, membranous capsule. Their tendency to develop can be hereditary, though most are spontaneous. They can manifest internally as well.

Superficial lipomas, which often manifest as multiple lesions on the arms and trunk, are usually easy to remove surgically. Lesions that are deeper and older or that appear on the face, however, often require considerable dissection to be freed from surrounding tissue. When excision is attempted, it is essential to remove the entire lesion to prevent recurrence. And, as always, the specimen must be sent for pathologic examination.

Patients often decide against surgery once they understand the issues. This is acceptable, but any deviation from the norm—such as pain, irregular surface texture, change in overlying skin, lack of mobility, or rapid growth—would constitute reasonable grounds for excision.

This man’s lesion likely extended down to the muscle fascia if not into the muscle itself. As a result, surgery would require general anesthesia and placement of a drain in the inferior portion of the wound, since such a large defect would likely invite a collection of blood and serum. For these reasons, he was referred to a general surgeon.

The differential for lipoma includes liposarcoma and angiolipoma. The latter are common and benign but become painful and are often more firm than normal. Histologically, they’re often indistinguishable from ordinary lipomas. Liposarcomas, when superficial, can imitate ordinary lipomas, but their surfaces tend to be more irregular and firm and the lesions themselves less mobile.

TAKE-HOME LEARNING POINTS

• Lipomas are the most common soft-tissue tumor encountered in outpatient practices.
• While the vast majority are benign and easy to remove surgically, most lipomas can be safely left alone.
• When excision is attempted, the entire lesion must be removed lest it regrow.
• Patients with larger, deeper lesions, or those in busy anatomical areas, should be referred to a general surgeon.

A 38-year-old Latino man self-refers to dermatology for evaluation of a mass on his back that first appeared three years ago. Since then, it has grown steadily. There is no pain or discomfort associated with the lesion, and the patient claims to be quite healthy otherwise. There is no antecedent history for the affected area.

EXAMINATION
There is a subcutaneous, rubbery mass in the left infrascapular area. It measures 11 x 6 cm. Palpation reveals the lesion to be uniformly smooth and readily mobile. The overlying skin is free of abnormalities and increased warmth.

What is the diagnosis?

Lipomas are actual tumors, composed completely of adipose tissue contained in a thin, fragile, membranous capsule. Their tendency to develop can be hereditary, though most are spontaneous. They can manifest internally as well.

Superficial lipomas, which often manifest as multiple lesions on the arms and trunk, are usually easy to remove surgically. Lesions that are deeper and older or that appear on the face, however, often require considerable dissection to be freed from surrounding tissue. When excision is attempted, it is essential to remove the entire lesion to prevent recurrence. And, as always, the specimen must be sent for pathologic examination.

Patients often decide against surgery once they understand the issues. This is acceptable, but any deviation from the norm—such as pain, irregular surface texture, change in overlying skin, lack of mobility, or rapid growth—would constitute reasonable grounds for excision.

This man’s lesion likely extended down to the muscle fascia if not into the muscle itself. As a result, surgery would require general anesthesia and placement of a drain in the inferior portion of the wound, since such a large defect would likely invite a collection of blood and serum. For these reasons, he was referred to a general surgeon.

The differential for lipoma includes liposarcoma and angiolipoma. The latter are common and benign but become painful and are often more firm than normal. Histologically, they’re often indistinguishable from ordinary lipomas. Liposarcomas, when superficial, can imitate ordinary lipomas, but their surfaces tend to be more irregular and firm and the lesions themselves less mobile.

TAKE-HOME LEARNING POINTS

• Lipomas are the most common soft-tissue tumor encountered in outpatient practices.
• While the vast majority are benign and easy to remove surgically, most lipomas can be safely left alone.
• When excision is attempted, the entire lesion must be removed lest it regrow.
• Patients with larger, deeper lesions, or those in busy anatomical areas, should be referred to a general surgeon.

A 38-year-old Latino man self-refers to dermatology for evaluation of a mass on his back that first appeared three years ago. Since then, it has grown steadily. There is no pain or discomfort associated with the lesion, and the patient claims to be quite healthy otherwise. There is no antecedent history for the affected area.

EXAMINATION
There is a subcutaneous, rubbery mass in the left infrascapular area. It measures 11 x 6 cm. Palpation reveals the lesion to be uniformly smooth and readily mobile. The overlying skin is free of abnormalities and increased warmth.

What is the diagnosis?

Lipomas are actual tumors, composed completely of adipose tissue contained in a thin, fragile, membranous capsule. Their tendency to develop can be hereditary, though most are spontaneous. They can manifest internally as well.

Superficial lipomas, which often manifest as multiple lesions on the arms and trunk, are usually easy to remove surgically. Lesions that are deeper and older or that appear on the face, however, often require considerable dissection to be freed from surrounding tissue. When excision is attempted, it is essential to remove the entire lesion to prevent recurrence. And, as always, the specimen must be sent for pathologic examination.

Patients often decide against surgery once they understand the issues. This is acceptable, but any deviation from the norm—such as pain, irregular surface texture, change in overlying skin, lack of mobility, or rapid growth—would constitute reasonable grounds for excision.

This man’s lesion likely extended down to the muscle fascia if not into the muscle itself. As a result, surgery would require general anesthesia and placement of a drain in the inferior portion of the wound, since such a large defect would likely invite a collection of blood and serum. For these reasons, he was referred to a general surgeon.

The differential for lipoma includes liposarcoma and angiolipoma. The latter are common and benign but become painful and are often more firm than normal. Histologically, they’re often indistinguishable from ordinary lipomas. Liposarcomas, when superficial, can imitate ordinary lipomas, but their surfaces tend to be more irregular and firm and the lesions themselves less mobile.

TAKE-HOME LEARNING POINTS

• Lipomas are the most common soft-tissue tumor encountered in outpatient practices.
• While the vast majority are benign and easy to remove surgically, most lipomas can be safely left alone.
• When excision is attempted, the entire lesion must be removed lest it regrow.
• Patients with larger, deeper lesions, or those in busy anatomical areas, should be referred to a general surgeon.

The FP recognized this lesion as a congenital nevus.

He was aware that nevi might become more raised during early adulthood, though this was not necessarily a sign of malignant degeneration. He looked at the nevus carefully and saw that it was relatively symmetrical with one predominant color and a light brown coloration on the left edge. (The patient stated it had always been this way.) The surface texture, which could be described as mamillated, was not unusual for congenital nevi. The FP examined the nevus using a dermatoscope and did not see any melanoma-specific structures.

The FP encouraged the patient to monitor the nevus and return for further evaluation if there were any changes or symptoms. He also offered her the option of a biopsy, but stated that it was not medically required. The patient noted that the changes of increased height of the congenital nevus had been very slow over the past 2 years, and she was willing to keep an eye on it. The patient returned in 6 months, and there were no visible changes to the congenital nevus.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Congenital nevi. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:953-957.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP recognized this lesion as a congenital nevus.

He was aware that nevi might become more raised during early adulthood, though this was not necessarily a sign of malignant degeneration. He looked at the nevus carefully and saw that it was relatively symmetrical with one predominant color and a light brown coloration on the left edge. (The patient stated it had always been this way.) The surface texture, which could be described as mamillated, was not unusual for congenital nevi. The FP examined the nevus using a dermatoscope and did not see any melanoma-specific structures.

The FP encouraged the patient to monitor the nevus and return for further evaluation if there were any changes or symptoms. He also offered her the option of a biopsy, but stated that it was not medically required. The patient noted that the changes of increased height of the congenital nevus had been very slow over the past 2 years, and she was willing to keep an eye on it. The patient returned in 6 months, and there were no visible changes to the congenital nevus.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Congenital nevi. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:953-957.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

The FP recognized this lesion as a congenital nevus.

He was aware that nevi might become more raised during early adulthood, though this was not necessarily a sign of malignant degeneration. He looked at the nevus carefully and saw that it was relatively symmetrical with one predominant color and a light brown coloration on the left edge. (The patient stated it had always been this way.) The surface texture, which could be described as mamillated, was not unusual for congenital nevi. The FP examined the nevus using a dermatoscope and did not see any melanoma-specific structures.

The FP encouraged the patient to monitor the nevus and return for further evaluation if there were any changes or symptoms. He also offered her the option of a biopsy, but stated that it was not medically required. The patient noted that the changes of increased height of the congenital nevus had been very slow over the past 2 years, and she was willing to keep an eye on it. The patient returned in 6 months, and there were no visible changes to the congenital nevus.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Smith M. Congenital nevi. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:953-957.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

Two young girls who were patch tested for aluminum contact allergy because of persistent pruritic postvaccinal nodules had atypical results. Instead of the usual eczematous reaction confined to the test area, they exhibited erythema and papules distant from the test area.

In one girl, the reaction consisted of erythematous itchy papules across much of her back on day 2, and by day 4, there were even papules on her chest. In the other girl, erythema, infiltration, and occasional papules covered the whole patch area, and erythematous papules also were seen at some distance from the test area, Nadia Raison-Peyron, MD, of Saint-Eloi Hospital, Montpellier, France, and her colleagues, reported in Pediatric Dermatology.

luiscar/Thinkstock

cpalmer@mdedge.com

SOURCE: Raison-Peyron N et al. Pediatr Dermatol. 2018. doi: 10.1111/pde.13481.

Two young girls who were patch tested for aluminum contact allergy because of persistent pruritic postvaccinal nodules had atypical results. Instead of the usual eczematous reaction confined to the test area, they exhibited erythema and papules distant from the test area.

In one girl, the reaction consisted of erythematous itchy papules across much of her back on day 2, and by day 4, there were even papules on her chest. In the other girl, erythema, infiltration, and occasional papules covered the whole patch area, and erythematous papules also were seen at some distance from the test area, Nadia Raison-Peyron, MD, of Saint-Eloi Hospital, Montpellier, France, and her colleagues, reported in Pediatric Dermatology.

luiscar/Thinkstock

cpalmer@mdedge.com

SOURCE: Raison-Peyron N et al. Pediatr Dermatol. 2018. doi: 10.1111/pde.13481.

Two young girls who were patch tested for aluminum contact allergy because of persistent pruritic postvaccinal nodules had atypical results. Instead of the usual eczematous reaction confined to the test area, they exhibited erythema and papules distant from the test area.

In one girl, the reaction consisted of erythematous itchy papules across much of her back on day 2, and by day 4, there were even papules on her chest. In the other girl, erythema, infiltration, and occasional papules covered the whole patch area, and erythematous papules also were seen at some distance from the test area, Nadia Raison-Peyron, MD, of Saint-Eloi Hospital, Montpellier, France, and her colleagues, reported in Pediatric Dermatology.

luiscar/Thinkstock

cpalmer@mdedge.com

SOURCE: Raison-Peyron N et al. Pediatr Dermatol. 2018. doi: 10.1111/pde.13481.

Systemic sclerosis (SSc), also called scleroderma, is a rare but serious autoimmune connective tissue disease that has multiple fluctuating pathologic manifestations throughout its temporal course. Estimates have shown that the incidence is 10 to 20 cases per 1 million, and the prevalence is 4 to 253 cases per 1 million.^1,2 Given the rarity of this incurable condition, it is vital that primary care providers (PCPs) are able to recognize its unique features early to limit and prevent acute and chronic complications. This case report discusses a patient’s journey with late-diagnosed scleroderma in order to convey these broad manifestations and what providers can do to manage it with their patients.

Case Presentation

Mr. P is a 60-year-old African American male with a history of hypertension, recurrent digital ulcers, pulmonary hypertension (PH), interstitial lung disease (ILD), kidney involvement, congestive heart failure (CHF), and gastroesophageal reflux disease (GERD). Mr. P’s workup began in his late 40s with resistant hypertension, resistant GERD, and multiple hospitalizations for hypertensive urgency. It was not until he was 54 years old that he was diagnosed with mixed connective tissue disorder with sclerodermatous predominance.

Review of systems throughout his medical examinations in his 50s were notable for skin tightening over his hands and shoulders, skin hypopigmentation over his scalp and face, and hair loss. Mr. P was found to have Raynaud phenomenon beginning with his original presentation and digital ulceration without complications of gangrene or autoamputation. Aggregate physical examinations were notable for digital ulceration, skin tightening/sclerodactyly, and telangiectasia. Serologic markers were notable for the following:

• Positive ANA (antinuclear antibody) with titer of 1:1,280/homogenous pattern;
• Positive anti-RNP (antiribonucleoprotein) with titer of 171.2;
• Positive anti-Scl-70 (antitopoisomerase I) with titer of 108.1;
• Positive anti-SM (anti-Smith antibody) with titer of 30.2;
• Positive anti-Ro (SSA) with titer of 107.6;
• Negative anti-La (SSB) with titer of 1.3;
• Negative anti-dsDNA (anti-double stranded DNA) with titer of 9; and
• Negative ACA (anticentromere antibody).

Early transthoracic echocardiograms revealed an ejection fraction (EF) initially at 55% with evidence of left ventricular hypertrophy. Following treatment with phosphodiesterase-5 inhibitors (PDE-5 inhibitors) and endothelin-1 antagonists for pulmonary hypertension, serial transthoracic echocardiograms showed improvement in his EF. 

A chest X-ray did not show signs of ILD, but a subsequent high-resolution computed tomography (HRCT) scan was consistent with chronic ILD with a main pulmonary artery diameter of 3 cm (Figure 1). 

In subsequent years, Mr. P was hospitalized several times, secondary to digit pain, ulcerations, and osteomyelitis. His first episode was 1 year after his scleroderma diagnosis, when he was hospitalized for 6 days for complications of SSc and finger pain. The following year, he had a 3-day hospitalization for hypertensive urgency and right third-digit osteomyelitis, treated initially with IV fluids, levofloxacin, and vancomycin, and then ceftaroline for 1 month. Throughout the next 6 years, Mr. P presented multiple times with fingertip ulcerations and was followed in the Infectious Disease clinic for recurrent osteomyelitis. He found some relief with systemic antibiotics, including augmentin, minocycline, moxifloxacin, and doxycycline.

At age 59, he was hospitalized for scleroderma renal crisis (SRC). Early in his disease, his kidney function was normal, but the SRC was discovered after an abrupt rise in his blood pressure (BP) and an increase in serum creatinine (SCr) from 1.2 mg/dL at baseline to 3.06 mg/dL. The presence of brown granular cast in his urine prompted a renal biopsy that showed thrombotic microangiopathy with schistocytes. Mr. P was started on captopril and remained stable with outpatient follow-up for this renal complication.

Discussion

Initial presentation of SSc can occur along a spectrum of its pathophysiology. A more severe presentation, like the one seen in Mr. P, seems to occur more frequently in African American patients relative to white patients.³ Differentiating between the 2 types—diffuse vs limited SSc—is vital to managing patients and disease progression. Limited-type SSc is more common (60%) and less severe with slower progression than is diffuse SSc. 

Diffuse-type SSc (35%) includes features such as skin thickening and tightening, ILD, SRC, tendon friction rubs (palpable crepitus over tendons), and skin pigment changes.⁴ The specific involvement of the renal and cardiopulmonary systems accounts for the higher mortality rates in the diffuse-type.⁵

Many patients with SSc require periodic hospitalizations throughout their life for the acute complications of the disease. Hospitalized patients often range from age 45 to 64 years and are more often female. However, of hospitalized patients with SSc, in-hospital death rates are higher among men.^3,6 Although these rates have decreased as the pathogenesis of SSc has become better understood, it is important to note that in-hospital mortality in 1995 for all patients with SSc was 7.1% and mean length of stay was 7.5 days, and in 2002 to 2003, 6.3% and 6.6 days, respectively.³ Though the burden of this disease has decreased, mortality and hospitalizations continue to persist at high rates. Understanding the pathogenesis, progression, and treatments of SSc are essential to aiding patients with this diagnosis.

Skin Involvement

A common finding and presentation for patients with SSc is related to skin involvement. Common patient complaints and exam findings include calcinosis along extensor tendons and digits, Raynaud phenomenon (seen in more than 95% of patients), sclerodactyly, telangiectasias, hyper/hypopigmentation, and pruritus.⁴ These findings are useful in diagnosing and monitoring patients for disease progression.

Many of the listed skin manifestations affect patients’ quality of life (QOL) but are not directly associated with mortality. However, a common and feared complication includes skin ulcers and osteomyelitis, seen in 48% and 7.7% of patients, respectively.⁷ Digit ulcers, areas with loss of dermis and epidermis distal to the proximal interphalangeal joints (Figures 2A and 2B), are significant because they parallel a more rapid progression of internal organ involvement.⁸ 

Mr. P required multiple hospitalizations and antibiotic regimens for painful digit ulcers complicated by osteomyelitis (Figure 3). 

Treatment usually is aimed at infections that complicate these skin ulcers and are based on site-specific cultures. Preventive measures are aimed at the risk factors associated with digit ulcers, including decreased whole-body warmth, direct trauma to digits, smoking, and vasoconstrictors (eg, cocaine, sympathomimetics).⁸ Some patients may prevent ulcers by using D-penicillamine, mycophenolate mofetil, and cyclophosphamide, although definitive treatment has not been found.⁴ Calcium channel blockers, PDE-5 inhibitors, endothelin receptor antagonists, and prostacyclin analogues also have been used to reduce the severity of Raynaud phenomenon attacks and to decrease the number of digital ulcers (in addition to their beneficial effects on pulmonary involvement).⁸ Additional pharmacologic agents that have been linked to an improvement in Raynaud phenomenon and digital ulcers include statins, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, intravenous N-acetylcysteine, vitamin E gel, and surgical options (eg, revascularization and sympathectomy).⁸

Pulmonary Involvement

Systemic sclerosis can lead to 2 complications in the lungs, both present in Mr. P: PAH (mean pulmonary arterial pressure > 25 mm Hg) and ILD, which together make lung involvement the leading cause of death for these patients. Limited-type SSc usually is restricted to PAH, whereas diffuse-type SSc usually leads to ILD.⁴

On diagnosis of SSc, an HRCT is indicated to assess the degree of lung involvement. Mr. P’s HRCT showed a 3-cm main pulmonary artery, suggestive of PAH, in addition to evidence of ILD seen on the chest X-ray (Figure 4). 

Pulmonary arterial hypertension is a common finding in patients with SSc and carries a severe prognosis. Risk factors for the development of PAH, when not present on initial diagnosis, include limited-type SSc; late age of onset; Raynaud phenomenon; decreased DLCO, FVC/DLCO < 1.6; increased N-terminal pro-B-type natriuretic peptide (NT-proBNP) serum levels; and the presence of antibodies.⁹ Patients with both SSc and PAH have a 50% to 87% 1-year survival, whereas patients with idiopathic PAH without connective tissue disease have an 88% 1-year survival.⁹

Many patients with lung involvement are asymptomatic, but some have findings of crackles and interstitial thickening on chest X-ray that can progress to cyanosis and right heart failure (cor pulmonale).¹⁰ On discovery of lung involvement (Figure 5), it is important to follow up with a PFT, primarily because the outcomes and prognosis for patients with SSc are correlated with the presenting severity of ILD and the subsequent progression of their DLCO.^4,10 

Treatment is directed at PAH and ILD separately. For PAH, a PDE-5 inhibitor, such as tadalafil or sildenafil, and an endothelin-1 receptor antagonist, such as ambrisentan or bosentan, are indicated. Other PAH treatments include diuretics and prostacyclin analogues (eg, epoprostenol, treprostinil, or iloprost) in addition to warfarin if patients have a history of thrombotic events.⁴ Mr. P’s pulmonologists deferred treatment with prostacyclin analogues given the potential for adverse effects with endothelin-1 receptor inhibitors, PDE-5 inhibitors, and calcium-channel blockers, although combination studies with bosentan and inhaled iloprost have shown promise.¹¹

Like the skin manifestations of SSc, ILD lacks definitive treatment to prevent disease progression. However, some patients benefit from cyclophosphamide, followed by mycophenolate mofetil—which is usually better tolerated—azathioprine, haematopoietic stem cell transplant as rescue therapy, and lung transplant for life-saving treatment.¹⁰

Renal Involvement

Renal involvement in patients with SSc can have profound effects on QOL. Even without clinical renal involvement, glomerular filtration rate (GFR) usually decreases with the progression of vascular damage correlated with age and disease duration.¹² Patients with a history of digital ulcers, like Mr. P, usually have a lower GFR than that of patients without digital ulcers.¹² Monitoring renal function is vital in caring for these patients, because SRC occurs in 2% to 15% of all patients with SSc.^13,14

Scleroderma renal crisis is generally defined as an abruptly elevated BP (> 140/90 mm Hgor > 30 mm Hg rise from baseline) with acute renal failure (elevated SCr) and decreased urine output.¹⁴ Given the rarity of SSc in the population, diagnosis of SRC requires high clinical suspicion. In the case of Mr. P, a workup involving serum analysis, urinalysis, and renal biopsy allowed for a definitive diagnosis. A renal biopsy can show microangiopathic hemolytic anemia and confirm SRC, although it may not be necessary in patients with known SSc presenting with new hypertension, rising creatinine, and unremarkable urine sediment on microscopy.^14,15

Although an acute SRC can be difficult to predict, monitoring renal function and attention to key factors can assist in discovering this SSc complication. Scleroderma renal crisis usually occurs within the first 4 years of SSc diagnosis, often paralleling rapid progression of skin thickening and tightening with higher rates in both African Americans and males.^13,14 Additional predictive factors include diffuse skin involvement, rapid progression of skin involvement, positive anti-RNA polymerase III antibodies, new anemia, new cardiac events (eg, pericardial effusion, pericarditis, left ventricular insufficiency), CHF, tendon friction rubs, arthritis, and recent (within 3 months) high-dose glucocorticoid use.^4,13-15

The presentation of SRC can be nonspecific, often resembling findings related to acute kidney injury. Patients may report malaise, fatigue, fever, headache, seizure, blurred vision, or dyspnea.¹³ Clinical parametersto examine include systolic BP > 140 mm Hgand/or diastolic BP > 90 mm Hg (or an abrupt rise of > 30 or > 20, respectively), SCr increase by 50%+ or > 120% of the upper normal limit, proteinuria at 2+, high protein:creatinine ratio, hematuria > 2+ or > 10 red blood cells (RBCs), platelets < 100,000/mm³, and hypertensive encephalopathy.¹³ Mr. P presented with fatigue, dyspnea, an abrupt rise in BP (156/96 mm Hg), foamy urine, bilateral lower extremity edema (3.9 g/dL albumin), 2+ RBCs, and a SCr of 2.46 mg/dL on admission (a 205% increase from his last baseline of 1.2 mg/dL).

Treatments have had a large impact on the mortality rates of SRC. Following the introduction of ACE inhibitors, mortality from SRC has decreased from 76% to < 10% over recent decades.¹³ In addition to improving survival, these medications also have improved hospitalization outcomes for these patients.³ Captopril is often the medication of choice given its rapid onset and short duration of action relative to other medications in the same class, such as benazepril, enalapril, fosinopril, lisinopril, quinapril, and ramipril.^4,13 Current clinical trials are assessing the specific renal benefits of endothelin-1 receptor antagonists, which often are used for pulmonary and skin involvement.¹⁴ For patients presenting with acute SRC and uremia, dialysis may be necessary (typically predicted by elevated NT-proBNP serum levels), while the decision for transplantation may be indicated at least 2 years after SRC onset and resolution.^4,13-15

Once the acute crisis resolves, it is important to discuss prognosis with patients. The 1-, 2-, 3-, 5-, and 10-year survival rates are 82%, 74%, 71%, 59%, and 47%, respectively; however, when looking at only male patients at 10 years, the survival rate is 17%.¹³ Prevention of SRC can be addressed with daily BP checks and advising patients to seek medical care if they notice a consecutive 2-day abrupt rise.¹³

Cardiac Involvement

Systemic sclerosis has significant effects on patients’ heart function. The introduction of ACE inhibitors has shifted mortality in SSc patients from predominantly SRC to cardiac causes.⁶ Cardiac involvement can occur through a range of processes, including abnormal cardiac conduction, CHF, diastolic dysfunction, mitral valve nodular thickening, and pericardial effusion.³ Even though patients often present with skin findings, an initial cardiac workup is crucial to understanding disease progression and patient prognosis. The severity of the cutaneous manifestations often predicts the degree of diastolic dysfunction.¹⁶

Clinical evidence of cardiac involvement is seen in 20% to 25% of patients with SSc and is associated with a 70% mortality at 5 years when symptoms are evident.¹⁶ Additionally, right ventricular dysfunction at presentation is the strongest marker for all-mortality prognosis, representing the degree of pulmonary involvement, and includes findings such as progressive shortness of breath and systemic edema.⁹

Given the increasing survival of patients with SSc, cardiac involvement is becoming more evident and prominent. Direct treatments for cardiac manifestations are based on the causative feature, namely, focusing on pulmonary and renal involvement, which can be assessed with periodic echocardiograms evaluating left ventricular EF.

Gastrointestinal Involvement

Along with skin manifestations, the gastrointestinal (GI) involvement of SSc can have a significant impact on patients’ QOL without direct contribution to mortality. One of Mr. P’s earliest symptoms that led to a diagnosis of SSc was GERD, which caused a chronic cough, dental erosions, esophageal erosions, duodenal ulcers, dysphagia, abdominal pain, halitosis, pharyngitis, and weight loss. Esophageal involvement occurs in up to 96% of patients with SSc and can include motility abnormalities (eg, strictures and/or muscle dysfunction), lower esophageal sphincter abnormalities, and Barrett esophagus.¹⁷

Additional symptoms of the GI system linked with SSc can occur anywhere along the GI tract and include gastric antral vascular ectasia, causing GI bleeds and pernicious anemia, gastroparesis, bacterial overgrowth, intestinal malabsorption, pseudo-obstruction due to hypomotility, fecal incontinence due to anorectal involvement, and rarely, primary biliary cirrhosis.^4,17 Decreased mobility of the oral aperture secondary to skin thickening and tightening also can contribute to malnutrition by decreasing oral intake.

Treatments are supportive and target symptom relief. Chronic treatment of GERD is often necessary and includes antacids, histamine-2 receptor blockers, and proton pump inhibitors.⁴ Other medications that can help with symptom relief include motility agents (such as metoclopramide, domperidone, prucalopride, tegaserod, and macrolides), osmotic laxatives, and ursodeoxycholic acid for primary biliary cirrhosis.¹⁷ Surgical intervention should be considered depending on the severity and progression of involvement within the GI tract. Behavioral changes that can improve patient symptoms include facial grimacing and other mouth-stretching exercises, frequent smaller meals followed by maintaining a vertical posture, and high fiber diets.¹⁷

Conclusion

Systemic sclerosis is an autoimmune and connective tissue disease with a pathophysiology that can manifest throughout the body. The organ systems that impact patient outcomes include skin, pulmonary, renal, cardiac, and GI. Primary care providers caring for patients diagnosed with SSc should monitor acute management and disease progression in all these systems. Important acute events that can impact morbidity, mortality, and/or QOL include Raynaud phenomenon, SRC, and pericardial effusion. Chronic manifestations that may be present on diagnosis of SSc or may develop while a patient is under a provider’s care include sclerodactyly, tendon calcinosis, PAH, ILD, chronic kidney injury, chronic cardiac damage, GERD, and esophageal dysmotility. While this discussion serves as a pertinent overview of patients with SSc, it is summative, and providers are encouraged to seek a stronger understanding of both the common and rarer manifestations within each of their patients.

Systemic sclerosis (SSc), also called scleroderma, is a rare but serious autoimmune connective tissue disease that has multiple fluctuating pathologic manifestations throughout its temporal course. Estimates have shown that the incidence is 10 to 20 cases per 1 million, and the prevalence is 4 to 253 cases per 1 million.^1,2 Given the rarity of this incurable condition, it is vital that primary care providers (PCPs) are able to recognize its unique features early to limit and prevent acute and chronic complications. This case report discusses a patient’s journey with late-diagnosed scleroderma in order to convey these broad manifestations and what providers can do to manage it with their patients.

Case Presentation

Mr. P is a 60-year-old African American male with a history of hypertension, recurrent digital ulcers, pulmonary hypertension (PH), interstitial lung disease (ILD), kidney involvement, congestive heart failure (CHF), and gastroesophageal reflux disease (GERD). Mr. P’s workup began in his late 40s with resistant hypertension, resistant GERD, and multiple hospitalizations for hypertensive urgency. It was not until he was 54 years old that he was diagnosed with mixed connective tissue disorder with sclerodermatous predominance.

Review of systems throughout his medical examinations in his 50s were notable for skin tightening over his hands and shoulders, skin hypopigmentation over his scalp and face, and hair loss. Mr. P was found to have Raynaud phenomenon beginning with his original presentation and digital ulceration without complications of gangrene or autoamputation. Aggregate physical examinations were notable for digital ulceration, skin tightening/sclerodactyly, and telangiectasia. Serologic markers were notable for the following:

• Positive ANA (antinuclear antibody) with titer of 1:1,280/homogenous pattern;
• Positive anti-RNP (antiribonucleoprotein) with titer of 171.2;
• Positive anti-Scl-70 (antitopoisomerase I) with titer of 108.1;
• Positive anti-SM (anti-Smith antibody) with titer of 30.2;
• Positive anti-Ro (SSA) with titer of 107.6;
• Negative anti-La (SSB) with titer of 1.3;
• Negative anti-dsDNA (anti-double stranded DNA) with titer of 9; and
• Negative ACA (anticentromere antibody).

Early transthoracic echocardiograms revealed an ejection fraction (EF) initially at 55% with evidence of left ventricular hypertrophy. Following treatment with phosphodiesterase-5 inhibitors (PDE-5 inhibitors) and endothelin-1 antagonists for pulmonary hypertension, serial transthoracic echocardiograms showed improvement in his EF. 

A chest X-ray did not show signs of ILD, but a subsequent high-resolution computed tomography (HRCT) scan was consistent with chronic ILD with a main pulmonary artery diameter of 3 cm (Figure 1). 

In subsequent years, Mr. P was hospitalized several times, secondary to digit pain, ulcerations, and osteomyelitis. His first episode was 1 year after his scleroderma diagnosis, when he was hospitalized for 6 days for complications of SSc and finger pain. The following year, he had a 3-day hospitalization for hypertensive urgency and right third-digit osteomyelitis, treated initially with IV fluids, levofloxacin, and vancomycin, and then ceftaroline for 1 month. Throughout the next 6 years, Mr. P presented multiple times with fingertip ulcerations and was followed in the Infectious Disease clinic for recurrent osteomyelitis. He found some relief with systemic antibiotics, including augmentin, minocycline, moxifloxacin, and doxycycline.

At age 59, he was hospitalized for scleroderma renal crisis (SRC). Early in his disease, his kidney function was normal, but the SRC was discovered after an abrupt rise in his blood pressure (BP) and an increase in serum creatinine (SCr) from 1.2 mg/dL at baseline to 3.06 mg/dL. The presence of brown granular cast in his urine prompted a renal biopsy that showed thrombotic microangiopathy with schistocytes. Mr. P was started on captopril and remained stable with outpatient follow-up for this renal complication.

Discussion

Initial presentation of SSc can occur along a spectrum of its pathophysiology. A more severe presentation, like the one seen in Mr. P, seems to occur more frequently in African American patients relative to white patients.³ Differentiating between the 2 types—diffuse vs limited SSc—is vital to managing patients and disease progression. Limited-type SSc is more common (60%) and less severe with slower progression than is diffuse SSc. 

Diffuse-type SSc (35%) includes features such as skin thickening and tightening, ILD, SRC, tendon friction rubs (palpable crepitus over tendons), and skin pigment changes.⁴ The specific involvement of the renal and cardiopulmonary systems accounts for the higher mortality rates in the diffuse-type.⁵

Many patients with SSc require periodic hospitalizations throughout their life for the acute complications of the disease. Hospitalized patients often range from age 45 to 64 years and are more often female. However, of hospitalized patients with SSc, in-hospital death rates are higher among men.^3,6 Although these rates have decreased as the pathogenesis of SSc has become better understood, it is important to note that in-hospital mortality in 1995 for all patients with SSc was 7.1% and mean length of stay was 7.5 days, and in 2002 to 2003, 6.3% and 6.6 days, respectively.³ Though the burden of this disease has decreased, mortality and hospitalizations continue to persist at high rates. Understanding the pathogenesis, progression, and treatments of SSc are essential to aiding patients with this diagnosis.

Skin Involvement

A common finding and presentation for patients with SSc is related to skin involvement. Common patient complaints and exam findings include calcinosis along extensor tendons and digits, Raynaud phenomenon (seen in more than 95% of patients), sclerodactyly, telangiectasias, hyper/hypopigmentation, and pruritus.⁴ These findings are useful in diagnosing and monitoring patients for disease progression.

Many of the listed skin manifestations affect patients’ quality of life (QOL) but are not directly associated with mortality. However, a common and feared complication includes skin ulcers and osteomyelitis, seen in 48% and 7.7% of patients, respectively.⁷ Digit ulcers, areas with loss of dermis and epidermis distal to the proximal interphalangeal joints (Figures 2A and 2B), are significant because they parallel a more rapid progression of internal organ involvement.⁸ 

Mr. P required multiple hospitalizations and antibiotic regimens for painful digit ulcers complicated by osteomyelitis (Figure 3). 

Treatment usually is aimed at infections that complicate these skin ulcers and are based on site-specific cultures. Preventive measures are aimed at the risk factors associated with digit ulcers, including decreased whole-body warmth, direct trauma to digits, smoking, and vasoconstrictors (eg, cocaine, sympathomimetics).⁸ Some patients may prevent ulcers by using D-penicillamine, mycophenolate mofetil, and cyclophosphamide, although definitive treatment has not been found.⁴ Calcium channel blockers, PDE-5 inhibitors, endothelin receptor antagonists, and prostacyclin analogues also have been used to reduce the severity of Raynaud phenomenon attacks and to decrease the number of digital ulcers (in addition to their beneficial effects on pulmonary involvement).⁸ Additional pharmacologic agents that have been linked to an improvement in Raynaud phenomenon and digital ulcers include statins, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, intravenous N-acetylcysteine, vitamin E gel, and surgical options (eg, revascularization and sympathectomy).⁸

Pulmonary Involvement

Systemic sclerosis can lead to 2 complications in the lungs, both present in Mr. P: PAH (mean pulmonary arterial pressure > 25 mm Hg) and ILD, which together make lung involvement the leading cause of death for these patients. Limited-type SSc usually is restricted to PAH, whereas diffuse-type SSc usually leads to ILD.⁴

On diagnosis of SSc, an HRCT is indicated to assess the degree of lung involvement. Mr. P’s HRCT showed a 3-cm main pulmonary artery, suggestive of PAH, in addition to evidence of ILD seen on the chest X-ray (Figure 4). 

Pulmonary arterial hypertension is a common finding in patients with SSc and carries a severe prognosis. Risk factors for the development of PAH, when not present on initial diagnosis, include limited-type SSc; late age of onset; Raynaud phenomenon; decreased DLCO, FVC/DLCO < 1.6; increased N-terminal pro-B-type natriuretic peptide (NT-proBNP) serum levels; and the presence of antibodies.⁹ Patients with both SSc and PAH have a 50% to 87% 1-year survival, whereas patients with idiopathic PAH without connective tissue disease have an 88% 1-year survival.⁹

Many patients with lung involvement are asymptomatic, but some have findings of crackles and interstitial thickening on chest X-ray that can progress to cyanosis and right heart failure (cor pulmonale).¹⁰ On discovery of lung involvement (Figure 5), it is important to follow up with a PFT, primarily because the outcomes and prognosis for patients with SSc are correlated with the presenting severity of ILD and the subsequent progression of their DLCO.^4,10 

Treatment is directed at PAH and ILD separately. For PAH, a PDE-5 inhibitor, such as tadalafil or sildenafil, and an endothelin-1 receptor antagonist, such as ambrisentan or bosentan, are indicated. Other PAH treatments include diuretics and prostacyclin analogues (eg, epoprostenol, treprostinil, or iloprost) in addition to warfarin if patients have a history of thrombotic events.⁴ Mr. P’s pulmonologists deferred treatment with prostacyclin analogues given the potential for adverse effects with endothelin-1 receptor inhibitors, PDE-5 inhibitors, and calcium-channel blockers, although combination studies with bosentan and inhaled iloprost have shown promise.¹¹

Like the skin manifestations of SSc, ILD lacks definitive treatment to prevent disease progression. However, some patients benefit from cyclophosphamide, followed by mycophenolate mofetil—which is usually better tolerated—azathioprine, haematopoietic stem cell transplant as rescue therapy, and lung transplant for life-saving treatment.¹⁰

Renal Involvement

Renal involvement in patients with SSc can have profound effects on QOL. Even without clinical renal involvement, glomerular filtration rate (GFR) usually decreases with the progression of vascular damage correlated with age and disease duration.¹² Patients with a history of digital ulcers, like Mr. P, usually have a lower GFR than that of patients without digital ulcers.¹² Monitoring renal function is vital in caring for these patients, because SRC occurs in 2% to 15% of all patients with SSc.^13,14

Scleroderma renal crisis is generally defined as an abruptly elevated BP (> 140/90 mm Hgor > 30 mm Hg rise from baseline) with acute renal failure (elevated SCr) and decreased urine output.¹⁴ Given the rarity of SSc in the population, diagnosis of SRC requires high clinical suspicion. In the case of Mr. P, a workup involving serum analysis, urinalysis, and renal biopsy allowed for a definitive diagnosis. A renal biopsy can show microangiopathic hemolytic anemia and confirm SRC, although it may not be necessary in patients with known SSc presenting with new hypertension, rising creatinine, and unremarkable urine sediment on microscopy.^14,15

Although an acute SRC can be difficult to predict, monitoring renal function and attention to key factors can assist in discovering this SSc complication. Scleroderma renal crisis usually occurs within the first 4 years of SSc diagnosis, often paralleling rapid progression of skin thickening and tightening with higher rates in both African Americans and males.^13,14 Additional predictive factors include diffuse skin involvement, rapid progression of skin involvement, positive anti-RNA polymerase III antibodies, new anemia, new cardiac events (eg, pericardial effusion, pericarditis, left ventricular insufficiency), CHF, tendon friction rubs, arthritis, and recent (within 3 months) high-dose glucocorticoid use.^4,13-15

The presentation of SRC can be nonspecific, often resembling findings related to acute kidney injury. Patients may report malaise, fatigue, fever, headache, seizure, blurred vision, or dyspnea.¹³ Clinical parametersto examine include systolic BP > 140 mm Hgand/or diastolic BP > 90 mm Hg (or an abrupt rise of > 30 or > 20, respectively), SCr increase by 50%+ or > 120% of the upper normal limit, proteinuria at 2+, high protein:creatinine ratio, hematuria > 2+ or > 10 red blood cells (RBCs), platelets < 100,000/mm³, and hypertensive encephalopathy.¹³ Mr. P presented with fatigue, dyspnea, an abrupt rise in BP (156/96 mm Hg), foamy urine, bilateral lower extremity edema (3.9 g/dL albumin), 2+ RBCs, and a SCr of 2.46 mg/dL on admission (a 205% increase from his last baseline of 1.2 mg/dL).

Treatments have had a large impact on the mortality rates of SRC. Following the introduction of ACE inhibitors, mortality from SRC has decreased from 76% to < 10% over recent decades.¹³ In addition to improving survival, these medications also have improved hospitalization outcomes for these patients.³ Captopril is often the medication of choice given its rapid onset and short duration of action relative to other medications in the same class, such as benazepril, enalapril, fosinopril, lisinopril, quinapril, and ramipril.^4,13 Current clinical trials are assessing the specific renal benefits of endothelin-1 receptor antagonists, which often are used for pulmonary and skin involvement.¹⁴ For patients presenting with acute SRC and uremia, dialysis may be necessary (typically predicted by elevated NT-proBNP serum levels), while the decision for transplantation may be indicated at least 2 years after SRC onset and resolution.^4,13-15

Once the acute crisis resolves, it is important to discuss prognosis with patients. The 1-, 2-, 3-, 5-, and 10-year survival rates are 82%, 74%, 71%, 59%, and 47%, respectively; however, when looking at only male patients at 10 years, the survival rate is 17%.¹³ Prevention of SRC can be addressed with daily BP checks and advising patients to seek medical care if they notice a consecutive 2-day abrupt rise.¹³

Cardiac Involvement

Systemic sclerosis has significant effects on patients’ heart function. The introduction of ACE inhibitors has shifted mortality in SSc patients from predominantly SRC to cardiac causes.⁶ Cardiac involvement can occur through a range of processes, including abnormal cardiac conduction, CHF, diastolic dysfunction, mitral valve nodular thickening, and pericardial effusion.³ Even though patients often present with skin findings, an initial cardiac workup is crucial to understanding disease progression and patient prognosis. The severity of the cutaneous manifestations often predicts the degree of diastolic dysfunction.¹⁶

Clinical evidence of cardiac involvement is seen in 20% to 25% of patients with SSc and is associated with a 70% mortality at 5 years when symptoms are evident.¹⁶ Additionally, right ventricular dysfunction at presentation is the strongest marker for all-mortality prognosis, representing the degree of pulmonary involvement, and includes findings such as progressive shortness of breath and systemic edema.⁹

Given the increasing survival of patients with SSc, cardiac involvement is becoming more evident and prominent. Direct treatments for cardiac manifestations are based on the causative feature, namely, focusing on pulmonary and renal involvement, which can be assessed with periodic echocardiograms evaluating left ventricular EF.

Gastrointestinal Involvement

Along with skin manifestations, the gastrointestinal (GI) involvement of SSc can have a significant impact on patients’ QOL without direct contribution to mortality. One of Mr. P’s earliest symptoms that led to a diagnosis of SSc was GERD, which caused a chronic cough, dental erosions, esophageal erosions, duodenal ulcers, dysphagia, abdominal pain, halitosis, pharyngitis, and weight loss. Esophageal involvement occurs in up to 96% of patients with SSc and can include motility abnormalities (eg, strictures and/or muscle dysfunction), lower esophageal sphincter abnormalities, and Barrett esophagus.¹⁷

Additional symptoms of the GI system linked with SSc can occur anywhere along the GI tract and include gastric antral vascular ectasia, causing GI bleeds and pernicious anemia, gastroparesis, bacterial overgrowth, intestinal malabsorption, pseudo-obstruction due to hypomotility, fecal incontinence due to anorectal involvement, and rarely, primary biliary cirrhosis.^4,17 Decreased mobility of the oral aperture secondary to skin thickening and tightening also can contribute to malnutrition by decreasing oral intake.

Treatments are supportive and target symptom relief. Chronic treatment of GERD is often necessary and includes antacids, histamine-2 receptor blockers, and proton pump inhibitors.⁴ Other medications that can help with symptom relief include motility agents (such as metoclopramide, domperidone, prucalopride, tegaserod, and macrolides), osmotic laxatives, and ursodeoxycholic acid for primary biliary cirrhosis.¹⁷ Surgical intervention should be considered depending on the severity and progression of involvement within the GI tract. Behavioral changes that can improve patient symptoms include facial grimacing and other mouth-stretching exercises, frequent smaller meals followed by maintaining a vertical posture, and high fiber diets.¹⁷

Conclusion

Systemic sclerosis is an autoimmune and connective tissue disease with a pathophysiology that can manifest throughout the body. The organ systems that impact patient outcomes include skin, pulmonary, renal, cardiac, and GI. Primary care providers caring for patients diagnosed with SSc should monitor acute management and disease progression in all these systems. Important acute events that can impact morbidity, mortality, and/or QOL include Raynaud phenomenon, SRC, and pericardial effusion. Chronic manifestations that may be present on diagnosis of SSc or may develop while a patient is under a provider’s care include sclerodactyly, tendon calcinosis, PAH, ILD, chronic kidney injury, chronic cardiac damage, GERD, and esophageal dysmotility. While this discussion serves as a pertinent overview of patients with SSc, it is summative, and providers are encouraged to seek a stronger understanding of both the common and rarer manifestations within each of their patients.

Systemic sclerosis (SSc), also called scleroderma, is a rare but serious autoimmune connective tissue disease that has multiple fluctuating pathologic manifestations throughout its temporal course. Estimates have shown that the incidence is 10 to 20 cases per 1 million, and the prevalence is 4 to 253 cases per 1 million.^1,2 Given the rarity of this incurable condition, it is vital that primary care providers (PCPs) are able to recognize its unique features early to limit and prevent acute and chronic complications. This case report discusses a patient’s journey with late-diagnosed scleroderma in order to convey these broad manifestations and what providers can do to manage it with their patients.

Case Presentation

Mr. P is a 60-year-old African American male with a history of hypertension, recurrent digital ulcers, pulmonary hypertension (PH), interstitial lung disease (ILD), kidney involvement, congestive heart failure (CHF), and gastroesophageal reflux disease (GERD). Mr. P’s workup began in his late 40s with resistant hypertension, resistant GERD, and multiple hospitalizations for hypertensive urgency. It was not until he was 54 years old that he was diagnosed with mixed connective tissue disorder with sclerodermatous predominance.

Review of systems throughout his medical examinations in his 50s were notable for skin tightening over his hands and shoulders, skin hypopigmentation over his scalp and face, and hair loss. Mr. P was found to have Raynaud phenomenon beginning with his original presentation and digital ulceration without complications of gangrene or autoamputation. Aggregate physical examinations were notable for digital ulceration, skin tightening/sclerodactyly, and telangiectasia. Serologic markers were notable for the following:

• Positive ANA (antinuclear antibody) with titer of 1:1,280/homogenous pattern;
• Positive anti-RNP (antiribonucleoprotein) with titer of 171.2;
• Positive anti-Scl-70 (antitopoisomerase I) with titer of 108.1;
• Positive anti-SM (anti-Smith antibody) with titer of 30.2;
• Positive anti-Ro (SSA) with titer of 107.6;
• Negative anti-La (SSB) with titer of 1.3;
• Negative anti-dsDNA (anti-double stranded DNA) with titer of 9; and
• Negative ACA (anticentromere antibody).

Early transthoracic echocardiograms revealed an ejection fraction (EF) initially at 55% with evidence of left ventricular hypertrophy. Following treatment with phosphodiesterase-5 inhibitors (PDE-5 inhibitors) and endothelin-1 antagonists for pulmonary hypertension, serial transthoracic echocardiograms showed improvement in his EF. 

A chest X-ray did not show signs of ILD, but a subsequent high-resolution computed tomography (HRCT) scan was consistent with chronic ILD with a main pulmonary artery diameter of 3 cm (Figure 1). 

In subsequent years, Mr. P was hospitalized several times, secondary to digit pain, ulcerations, and osteomyelitis. His first episode was 1 year after his scleroderma diagnosis, when he was hospitalized for 6 days for complications of SSc and finger pain. The following year, he had a 3-day hospitalization for hypertensive urgency and right third-digit osteomyelitis, treated initially with IV fluids, levofloxacin, and vancomycin, and then ceftaroline for 1 month. Throughout the next 6 years, Mr. P presented multiple times with fingertip ulcerations and was followed in the Infectious Disease clinic for recurrent osteomyelitis. He found some relief with systemic antibiotics, including augmentin, minocycline, moxifloxacin, and doxycycline.

At age 59, he was hospitalized for scleroderma renal crisis (SRC). Early in his disease, his kidney function was normal, but the SRC was discovered after an abrupt rise in his blood pressure (BP) and an increase in serum creatinine (SCr) from 1.2 mg/dL at baseline to 3.06 mg/dL. The presence of brown granular cast in his urine prompted a renal biopsy that showed thrombotic microangiopathy with schistocytes. Mr. P was started on captopril and remained stable with outpatient follow-up for this renal complication.

Discussion

Initial presentation of SSc can occur along a spectrum of its pathophysiology. A more severe presentation, like the one seen in Mr. P, seems to occur more frequently in African American patients relative to white patients.³ Differentiating between the 2 types—diffuse vs limited SSc—is vital to managing patients and disease progression. Limited-type SSc is more common (60%) and less severe with slower progression than is diffuse SSc. 

Diffuse-type SSc (35%) includes features such as skin thickening and tightening, ILD, SRC, tendon friction rubs (palpable crepitus over tendons), and skin pigment changes.⁴ The specific involvement of the renal and cardiopulmonary systems accounts for the higher mortality rates in the diffuse-type.⁵

Many patients with SSc require periodic hospitalizations throughout their life for the acute complications of the disease. Hospitalized patients often range from age 45 to 64 years and are more often female. However, of hospitalized patients with SSc, in-hospital death rates are higher among men.^3,6 Although these rates have decreased as the pathogenesis of SSc has become better understood, it is important to note that in-hospital mortality in 1995 for all patients with SSc was 7.1% and mean length of stay was 7.5 days, and in 2002 to 2003, 6.3% and 6.6 days, respectively.³ Though the burden of this disease has decreased, mortality and hospitalizations continue to persist at high rates. Understanding the pathogenesis, progression, and treatments of SSc are essential to aiding patients with this diagnosis.

Skin Involvement

A common finding and presentation for patients with SSc is related to skin involvement. Common patient complaints and exam findings include calcinosis along extensor tendons and digits, Raynaud phenomenon (seen in more than 95% of patients), sclerodactyly, telangiectasias, hyper/hypopigmentation, and pruritus.⁴ These findings are useful in diagnosing and monitoring patients for disease progression.

Many of the listed skin manifestations affect patients’ quality of life (QOL) but are not directly associated with mortality. However, a common and feared complication includes skin ulcers and osteomyelitis, seen in 48% and 7.7% of patients, respectively.⁷ Digit ulcers, areas with loss of dermis and epidermis distal to the proximal interphalangeal joints (Figures 2A and 2B), are significant because they parallel a more rapid progression of internal organ involvement.⁸ 

Mr. P required multiple hospitalizations and antibiotic regimens for painful digit ulcers complicated by osteomyelitis (Figure 3). 

Treatment usually is aimed at infections that complicate these skin ulcers and are based on site-specific cultures. Preventive measures are aimed at the risk factors associated with digit ulcers, including decreased whole-body warmth, direct trauma to digits, smoking, and vasoconstrictors (eg, cocaine, sympathomimetics).⁸ Some patients may prevent ulcers by using D-penicillamine, mycophenolate mofetil, and cyclophosphamide, although definitive treatment has not been found.⁴ Calcium channel blockers, PDE-5 inhibitors, endothelin receptor antagonists, and prostacyclin analogues also have been used to reduce the severity of Raynaud phenomenon attacks and to decrease the number of digital ulcers (in addition to their beneficial effects on pulmonary involvement).⁸ Additional pharmacologic agents that have been linked to an improvement in Raynaud phenomenon and digital ulcers include statins, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, intravenous N-acetylcysteine, vitamin E gel, and surgical options (eg, revascularization and sympathectomy).⁸

Pulmonary Involvement

Systemic sclerosis can lead to 2 complications in the lungs, both present in Mr. P: PAH (mean pulmonary arterial pressure > 25 mm Hg) and ILD, which together make lung involvement the leading cause of death for these patients. Limited-type SSc usually is restricted to PAH, whereas diffuse-type SSc usually leads to ILD.⁴

On diagnosis of SSc, an HRCT is indicated to assess the degree of lung involvement. Mr. P’s HRCT showed a 3-cm main pulmonary artery, suggestive of PAH, in addition to evidence of ILD seen on the chest X-ray (Figure 4). 

Pulmonary arterial hypertension is a common finding in patients with SSc and carries a severe prognosis. Risk factors for the development of PAH, when not present on initial diagnosis, include limited-type SSc; late age of onset; Raynaud phenomenon; decreased DLCO, FVC/DLCO < 1.6; increased N-terminal pro-B-type natriuretic peptide (NT-proBNP) serum levels; and the presence of antibodies.⁹ Patients with both SSc and PAH have a 50% to 87% 1-year survival, whereas patients with idiopathic PAH without connective tissue disease have an 88% 1-year survival.⁹

Many patients with lung involvement are asymptomatic, but some have findings of crackles and interstitial thickening on chest X-ray that can progress to cyanosis and right heart failure (cor pulmonale).¹⁰ On discovery of lung involvement (Figure 5), it is important to follow up with a PFT, primarily because the outcomes and prognosis for patients with SSc are correlated with the presenting severity of ILD and the subsequent progression of their DLCO.^4,10 

Treatment is directed at PAH and ILD separately. For PAH, a PDE-5 inhibitor, such as tadalafil or sildenafil, and an endothelin-1 receptor antagonist, such as ambrisentan or bosentan, are indicated. Other PAH treatments include diuretics and prostacyclin analogues (eg, epoprostenol, treprostinil, or iloprost) in addition to warfarin if patients have a history of thrombotic events.⁴ Mr. P’s pulmonologists deferred treatment with prostacyclin analogues given the potential for adverse effects with endothelin-1 receptor inhibitors, PDE-5 inhibitors, and calcium-channel blockers, although combination studies with bosentan and inhaled iloprost have shown promise.¹¹

Like the skin manifestations of SSc, ILD lacks definitive treatment to prevent disease progression. However, some patients benefit from cyclophosphamide, followed by mycophenolate mofetil—which is usually better tolerated—azathioprine, haematopoietic stem cell transplant as rescue therapy, and lung transplant for life-saving treatment.¹⁰

Renal Involvement

Renal involvement in patients with SSc can have profound effects on QOL. Even without clinical renal involvement, glomerular filtration rate (GFR) usually decreases with the progression of vascular damage correlated with age and disease duration.¹² Patients with a history of digital ulcers, like Mr. P, usually have a lower GFR than that of patients without digital ulcers.¹² Monitoring renal function is vital in caring for these patients, because SRC occurs in 2% to 15% of all patients with SSc.^13,14

Scleroderma renal crisis is generally defined as an abruptly elevated BP (> 140/90 mm Hgor > 30 mm Hg rise from baseline) with acute renal failure (elevated SCr) and decreased urine output.¹⁴ Given the rarity of SSc in the population, diagnosis of SRC requires high clinical suspicion. In the case of Mr. P, a workup involving serum analysis, urinalysis, and renal biopsy allowed for a definitive diagnosis. A renal biopsy can show microangiopathic hemolytic anemia and confirm SRC, although it may not be necessary in patients with known SSc presenting with new hypertension, rising creatinine, and unremarkable urine sediment on microscopy.^14,15

Although an acute SRC can be difficult to predict, monitoring renal function and attention to key factors can assist in discovering this SSc complication. Scleroderma renal crisis usually occurs within the first 4 years of SSc diagnosis, often paralleling rapid progression of skin thickening and tightening with higher rates in both African Americans and males.^13,14 Additional predictive factors include diffuse skin involvement, rapid progression of skin involvement, positive anti-RNA polymerase III antibodies, new anemia, new cardiac events (eg, pericardial effusion, pericarditis, left ventricular insufficiency), CHF, tendon friction rubs, arthritis, and recent (within 3 months) high-dose glucocorticoid use.^4,13-15

The presentation of SRC can be nonspecific, often resembling findings related to acute kidney injury. Patients may report malaise, fatigue, fever, headache, seizure, blurred vision, or dyspnea.¹³ Clinical parametersto examine include systolic BP > 140 mm Hgand/or diastolic BP > 90 mm Hg (or an abrupt rise of > 30 or > 20, respectively), SCr increase by 50%+ or > 120% of the upper normal limit, proteinuria at 2+, high protein:creatinine ratio, hematuria > 2+ or > 10 red blood cells (RBCs), platelets < 100,000/mm³, and hypertensive encephalopathy.¹³ Mr. P presented with fatigue, dyspnea, an abrupt rise in BP (156/96 mm Hg), foamy urine, bilateral lower extremity edema (3.9 g/dL albumin), 2+ RBCs, and a SCr of 2.46 mg/dL on admission (a 205% increase from his last baseline of 1.2 mg/dL).

Treatments have had a large impact on the mortality rates of SRC. Following the introduction of ACE inhibitors, mortality from SRC has decreased from 76% to < 10% over recent decades.¹³ In addition to improving survival, these medications also have improved hospitalization outcomes for these patients.³ Captopril is often the medication of choice given its rapid onset and short duration of action relative to other medications in the same class, such as benazepril, enalapril, fosinopril, lisinopril, quinapril, and ramipril.^4,13 Current clinical trials are assessing the specific renal benefits of endothelin-1 receptor antagonists, which often are used for pulmonary and skin involvement.¹⁴ For patients presenting with acute SRC and uremia, dialysis may be necessary (typically predicted by elevated NT-proBNP serum levels), while the decision for transplantation may be indicated at least 2 years after SRC onset and resolution.^4,13-15

Once the acute crisis resolves, it is important to discuss prognosis with patients. The 1-, 2-, 3-, 5-, and 10-year survival rates are 82%, 74%, 71%, 59%, and 47%, respectively; however, when looking at only male patients at 10 years, the survival rate is 17%.¹³ Prevention of SRC can be addressed with daily BP checks and advising patients to seek medical care if they notice a consecutive 2-day abrupt rise.¹³

Cardiac Involvement

Systemic sclerosis has significant effects on patients’ heart function. The introduction of ACE inhibitors has shifted mortality in SSc patients from predominantly SRC to cardiac causes.⁶ Cardiac involvement can occur through a range of processes, including abnormal cardiac conduction, CHF, diastolic dysfunction, mitral valve nodular thickening, and pericardial effusion.³ Even though patients often present with skin findings, an initial cardiac workup is crucial to understanding disease progression and patient prognosis. The severity of the cutaneous manifestations often predicts the degree of diastolic dysfunction.¹⁶

Clinical evidence of cardiac involvement is seen in 20% to 25% of patients with SSc and is associated with a 70% mortality at 5 years when symptoms are evident.¹⁶ Additionally, right ventricular dysfunction at presentation is the strongest marker for all-mortality prognosis, representing the degree of pulmonary involvement, and includes findings such as progressive shortness of breath and systemic edema.⁹

Given the increasing survival of patients with SSc, cardiac involvement is becoming more evident and prominent. Direct treatments for cardiac manifestations are based on the causative feature, namely, focusing on pulmonary and renal involvement, which can be assessed with periodic echocardiograms evaluating left ventricular EF.

Gastrointestinal Involvement

Along with skin manifestations, the gastrointestinal (GI) involvement of SSc can have a significant impact on patients’ QOL without direct contribution to mortality. One of Mr. P’s earliest symptoms that led to a diagnosis of SSc was GERD, which caused a chronic cough, dental erosions, esophageal erosions, duodenal ulcers, dysphagia, abdominal pain, halitosis, pharyngitis, and weight loss. Esophageal involvement occurs in up to 96% of patients with SSc and can include motility abnormalities (eg, strictures and/or muscle dysfunction), lower esophageal sphincter abnormalities, and Barrett esophagus.¹⁷

Additional symptoms of the GI system linked with SSc can occur anywhere along the GI tract and include gastric antral vascular ectasia, causing GI bleeds and pernicious anemia, gastroparesis, bacterial overgrowth, intestinal malabsorption, pseudo-obstruction due to hypomotility, fecal incontinence due to anorectal involvement, and rarely, primary biliary cirrhosis.^4,17 Decreased mobility of the oral aperture secondary to skin thickening and tightening also can contribute to malnutrition by decreasing oral intake.

Treatments are supportive and target symptom relief. Chronic treatment of GERD is often necessary and includes antacids, histamine-2 receptor blockers, and proton pump inhibitors.⁴ Other medications that can help with symptom relief include motility agents (such as metoclopramide, domperidone, prucalopride, tegaserod, and macrolides), osmotic laxatives, and ursodeoxycholic acid for primary biliary cirrhosis.¹⁷ Surgical intervention should be considered depending on the severity and progression of involvement within the GI tract. Behavioral changes that can improve patient symptoms include facial grimacing and other mouth-stretching exercises, frequent smaller meals followed by maintaining a vertical posture, and high fiber diets.¹⁷

Conclusion

Systemic sclerosis is an autoimmune and connective tissue disease with a pathophysiology that can manifest throughout the body. The organ systems that impact patient outcomes include skin, pulmonary, renal, cardiac, and GI. Primary care providers caring for patients diagnosed with SSc should monitor acute management and disease progression in all these systems. Important acute events that can impact morbidity, mortality, and/or QOL include Raynaud phenomenon, SRC, and pericardial effusion. Chronic manifestations that may be present on diagnosis of SSc or may develop while a patient is under a provider’s care include sclerodactyly, tendon calcinosis, PAH, ILD, chronic kidney injury, chronic cardiac damage, GERD, and esophageal dysmotility. While this discussion serves as a pertinent overview of patients with SSc, it is summative, and providers are encouraged to seek a stronger understanding of both the common and rarer manifestations within each of their patients.