The SVS is debuting a new “Ask the Expert” series at the Vascular Annual Meeting this year, and we need members’ help to build it. “Expert” will consist of four, one-hour sessions, one daily Wednesday through Friday, with cases submitted by members. Please submit a case study you wish to be considered for discussion with one of our experts -- and we hope you attend if your case is selected. The deadline will be in mid-May. Topics are Coding, Aortic Care for Occlusive Disease, Hemodialysis and PAD. Submit your cases here. Email education@vascularsociety with questions

The SVS is debuting a new “Ask the Expert” series at the Vascular Annual Meeting this year, and we need members’ help to build it. “Expert” will consist of four, one-hour sessions, one daily Wednesday through Friday, with cases submitted by members. Please submit a case study you wish to be considered for discussion with one of our experts -- and we hope you attend if your case is selected. The deadline will be in mid-May. Topics are Coding, Aortic Care for Occlusive Disease, Hemodialysis and PAD. Submit your cases here. Email education@vascularsociety with questions

The SVS is debuting a new “Ask the Expert” series at the Vascular Annual Meeting this year, and we need members’ help to build it. “Expert” will consist of four, one-hour sessions, one daily Wednesday through Friday, with cases submitted by members. Please submit a case study you wish to be considered for discussion with one of our experts -- and we hope you attend if your case is selected. The deadline will be in mid-May. Topics are Coding, Aortic Care for Occlusive Disease, Hemodialysis and PAD. Submit your cases here. Email education@vascularsociety with questions

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.

Physicians voice deep concern over potential changes to Title X. Advice on when to treat acute hepatitis C virus infection. Both obesity and weight loss are linked to rheumatoid arthritis disability, And tai chi confers long-term benefit in COPD.

Listen to the MDedge Daily News podcast for all the details on today’s top news.




 

Physicians voice deep concern over potential changes to Title X. Advice on when to treat acute hepatitis C virus infection. Both obesity and weight loss are linked to rheumatoid arthritis disability, And tai chi confers long-term benefit in COPD.

Listen to the MDedge Daily News podcast for all the details on today’s top news.




 

Physicians voice deep concern over potential changes to Title X. Advice on when to treat acute hepatitis C virus infection. Both obesity and weight loss are linked to rheumatoid arthritis disability, And tai chi confers long-term benefit in COPD.

Listen to the MDedge Daily News podcast for all the details on today’s top news.




 

About 30% to 50% of patients taking interferon-α (IFN-α), a common treatment for hepatitis C virus (HCV) infection, develop anxiety, depression, or other neuropsychiatric symptoms.

Some research has suggested that IFN-α might induce changes in tryptophan metabolism (lowering brain serotonin) or in glutamine and glutamate levels in the anterior cingulate cortex. But little work has touched on the neuropsychological mechanisms involved in the mood-lowering effects, say researchers from University of Oxford and Warneford Hospital Oxford, in the UK. Interferon-α is known to potently activate the pro-inflammatory cytokine network to produce its antiviral effects. The findings offer “intriguing evidence” indicating that exposure to inflammation by immune system activation may alter affective information processing, leading to depression in some patients.

The researchers conducted a study in 17 patients with HCV infection, measuring changes in emotional processing. They assessed participants’ mood state at baseline and 6 to 8 weeks later after a battery of tests for depression, anxiety, and fatigue. Psychological tasks included facial expression recognition and emotional categorization.

The researchers found significant correlations between pre- and post-IFN-α depressed mood scores. Notably, after IFN-α treatment, patients were more accurate at detecting facial expressions of disgust and paid less attention to the happy faces.

The negative biases in emotional processing were not simply a consequence of depression, the researchers say. It is possible that increased recognition of disgust represents a neuropsychological marker of depressive disorders related to inflammation. It seems conceivable, the researchers note, that effects on disgust recognition represent a complex interplay between inflammatory pathways and neurocircuits, which may in part be modulated by serotonin function.

The connection between disgust recognition and mood disorders has been seen before. Some researchers say it relates to feelings of social rejection, shame, and guilt. These study findings may highlight an effect more specific to inflammatory pathways. If depressive behaviors are regulated by the immune system, the researchers suggest finding out how inflammation plays a part can help define new treatment for infection.

Source:
Cooper CM, Godlewska B, Sharpley AL, Barnes E, Cowen PJ, Harmer CJ. Psychol Med. 2018;48(6):998-1007.
doi: 10.1017/S0033291717002379.

About 30% to 50% of patients taking interferon-α (IFN-α), a common treatment for hepatitis C virus (HCV) infection, develop anxiety, depression, or other neuropsychiatric symptoms.

Some research has suggested that IFN-α might induce changes in tryptophan metabolism (lowering brain serotonin) or in glutamine and glutamate levels in the anterior cingulate cortex. But little work has touched on the neuropsychological mechanisms involved in the mood-lowering effects, say researchers from University of Oxford and Warneford Hospital Oxford, in the UK. Interferon-α is known to potently activate the pro-inflammatory cytokine network to produce its antiviral effects. The findings offer “intriguing evidence” indicating that exposure to inflammation by immune system activation may alter affective information processing, leading to depression in some patients.

The researchers conducted a study in 17 patients with HCV infection, measuring changes in emotional processing. They assessed participants’ mood state at baseline and 6 to 8 weeks later after a battery of tests for depression, anxiety, and fatigue. Psychological tasks included facial expression recognition and emotional categorization.

The researchers found significant correlations between pre- and post-IFN-α depressed mood scores. Notably, after IFN-α treatment, patients were more accurate at detecting facial expressions of disgust and paid less attention to the happy faces.

The negative biases in emotional processing were not simply a consequence of depression, the researchers say. It is possible that increased recognition of disgust represents a neuropsychological marker of depressive disorders related to inflammation. It seems conceivable, the researchers note, that effects on disgust recognition represent a complex interplay between inflammatory pathways and neurocircuits, which may in part be modulated by serotonin function.

The connection between disgust recognition and mood disorders has been seen before. Some researchers say it relates to feelings of social rejection, shame, and guilt. These study findings may highlight an effect more specific to inflammatory pathways. If depressive behaviors are regulated by the immune system, the researchers suggest finding out how inflammation plays a part can help define new treatment for infection.

Source:
Cooper CM, Godlewska B, Sharpley AL, Barnes E, Cowen PJ, Harmer CJ. Psychol Med. 2018;48(6):998-1007.
doi: 10.1017/S0033291717002379.

About 30% to 50% of patients taking interferon-α (IFN-α), a common treatment for hepatitis C virus (HCV) infection, develop anxiety, depression, or other neuropsychiatric symptoms.

Some research has suggested that IFN-α might induce changes in tryptophan metabolism (lowering brain serotonin) or in glutamine and glutamate levels in the anterior cingulate cortex. But little work has touched on the neuropsychological mechanisms involved in the mood-lowering effects, say researchers from University of Oxford and Warneford Hospital Oxford, in the UK. Interferon-α is known to potently activate the pro-inflammatory cytokine network to produce its antiviral effects. The findings offer “intriguing evidence” indicating that exposure to inflammation by immune system activation may alter affective information processing, leading to depression in some patients.

The researchers conducted a study in 17 patients with HCV infection, measuring changes in emotional processing. They assessed participants’ mood state at baseline and 6 to 8 weeks later after a battery of tests for depression, anxiety, and fatigue. Psychological tasks included facial expression recognition and emotional categorization.

The researchers found significant correlations between pre- and post-IFN-α depressed mood scores. Notably, after IFN-α treatment, patients were more accurate at detecting facial expressions of disgust and paid less attention to the happy faces.

The negative biases in emotional processing were not simply a consequence of depression, the researchers say. It is possible that increased recognition of disgust represents a neuropsychological marker of depressive disorders related to inflammation. It seems conceivable, the researchers note, that effects on disgust recognition represent a complex interplay between inflammatory pathways and neurocircuits, which may in part be modulated by serotonin function.

The connection between disgust recognition and mood disorders has been seen before. Some researchers say it relates to feelings of social rejection, shame, and guilt. These study findings may highlight an effect more specific to inflammatory pathways. If depressive behaviors are regulated by the immune system, the researchers suggest finding out how inflammation plays a part can help define new treatment for infection.

Source:
Cooper CM, Godlewska B, Sharpley AL, Barnes E, Cowen PJ, Harmer CJ. Psychol Med. 2018;48(6):998-1007.
doi: 10.1017/S0033291717002379.

Portola Pharmaceuticals

The US Food and Drug Administration (FDA) has granted accelerated approval for andexanet alfa (Andexxa®), the first antidote for the reversal of factor Xa inhibitors.

Andexanet alfa is approved for use in patients treated with rivaroxaban or apixaban when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

Andexanet alfa was granted accelerated approval for this indication based on the drug’s anti-factor Xa activity in healthy volunteers.

Continued FDA approval of andexanet alfa may be contingent upon post-marketing study results to demonstrate an improvement in hemostasis in patients taking rivaroxaban or apixaban who require reversal of anticoagulation.

The post-marketing requirement is a trial in which patients will be randomized to receive either andexanet alfa or usual care. This study is scheduled to start in 2019, with results expected to be available in 2023.

Portola Pharmaceuticals, Inc., said it expects to launch andexanet alfa in early June. This drug will be produced using the generation 1 manufacturing process.

A broader commercial launch of andexanet alfa is anticipated in early 2019, dependent upon FDA approval of the generation 2 manufacturing process.

Supporting trials

The FDA’s approval of andexanet alfa is supported by data from a pair of phase 3 studies—ANNEXA-R and ANNEXA-A.

These trials were designed to evaluate the safety and efficacy of andexanet alfa in reversing the anticoagulant activity of rivaroxaban and apixaban in healthy volunteers.

Results from both studies were published in NEJM in 2015.

The FDA also assessed interim data from the ongoing ANNEXA-4 study as part of the review and approval of andexanet alfa.

In ANNEXA-4, researchers are evaluating andexanet alfa in patients experiencing major bleeding while taking factor Xa inhibitors.

Interim results from this trial were presented at the American College of Cardiology’s 67th Annual Scientific Session & Expo in March.

About andexanet alfa

Andexanet alfa is a modified human factor Xa molecule that acts as a decoy to target and sequester both oral and injectable factor Xa inhibitors in the blood. Once bound, the factor Xa inhibitors are unable to bind to and inhibit native factor Xa, thus potentially allowing for the restoration of normal hemostatic processes.

Portola Pharmaceuticals first submitted the biologics license application (BLA) for andexanet alfa in December 2015. The FDA had already granted andexanet alfa orphan drug designation earlier in 2015 and breakthrough therapy designation in 2013.

With its first BLA submission, Portola was seeking approval for andexanet alfa as a reversal agent for patients anticoagulated with an oral or injectable factor Xa inhibitor—apixaban, rivaroxaban, edoxaban, or enoxaparin—who experience serious uncontrolled or life-threatening bleeding or who require urgent or emergency surgery.

In August 2016, the FDA issued a complete response letter explaining why the agency could not approve andexanet alfa for this indication.

The FDA requested additional information related to manufacturing of the drug and asked Portola for additional data to support the inclusion of edoxaban and enoxaparin on andexanet alfa’s label. This was because the ANNEXA-A and ANNEXA-R trials only included subjects who received apixaban or rivaroxaban.

In August 2017, Portola resubmitted the BLA for andexanet alfa. This time, the company sought approval of the drug only for patients on apixaban or rivaroxaban who are experiencing uncontrolled or life-threatening bleeding.

For additional information on andexanet alfa, visit https://www.andexxa.com/.

Portola Pharmaceuticals

The US Food and Drug Administration (FDA) has granted accelerated approval for andexanet alfa (Andexxa®), the first antidote for the reversal of factor Xa inhibitors.

Andexanet alfa is approved for use in patients treated with rivaroxaban or apixaban when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

Andexanet alfa was granted accelerated approval for this indication based on the drug’s anti-factor Xa activity in healthy volunteers.

Continued FDA approval of andexanet alfa may be contingent upon post-marketing study results to demonstrate an improvement in hemostasis in patients taking rivaroxaban or apixaban who require reversal of anticoagulation.

The post-marketing requirement is a trial in which patients will be randomized to receive either andexanet alfa or usual care. This study is scheduled to start in 2019, with results expected to be available in 2023.

Portola Pharmaceuticals, Inc., said it expects to launch andexanet alfa in early June. This drug will be produced using the generation 1 manufacturing process.

A broader commercial launch of andexanet alfa is anticipated in early 2019, dependent upon FDA approval of the generation 2 manufacturing process.

Supporting trials

The FDA’s approval of andexanet alfa is supported by data from a pair of phase 3 studies—ANNEXA-R and ANNEXA-A.

These trials were designed to evaluate the safety and efficacy of andexanet alfa in reversing the anticoagulant activity of rivaroxaban and apixaban in healthy volunteers.

Results from both studies were published in NEJM in 2015.

The FDA also assessed interim data from the ongoing ANNEXA-4 study as part of the review and approval of andexanet alfa.

In ANNEXA-4, researchers are evaluating andexanet alfa in patients experiencing major bleeding while taking factor Xa inhibitors.

Interim results from this trial were presented at the American College of Cardiology’s 67th Annual Scientific Session & Expo in March.

About andexanet alfa

Andexanet alfa is a modified human factor Xa molecule that acts as a decoy to target and sequester both oral and injectable factor Xa inhibitors in the blood. Once bound, the factor Xa inhibitors are unable to bind to and inhibit native factor Xa, thus potentially allowing for the restoration of normal hemostatic processes.

Portola Pharmaceuticals first submitted the biologics license application (BLA) for andexanet alfa in December 2015. The FDA had already granted andexanet alfa orphan drug designation earlier in 2015 and breakthrough therapy designation in 2013.

With its first BLA submission, Portola was seeking approval for andexanet alfa as a reversal agent for patients anticoagulated with an oral or injectable factor Xa inhibitor—apixaban, rivaroxaban, edoxaban, or enoxaparin—who experience serious uncontrolled or life-threatening bleeding or who require urgent or emergency surgery.

In August 2016, the FDA issued a complete response letter explaining why the agency could not approve andexanet alfa for this indication.

The FDA requested additional information related to manufacturing of the drug and asked Portola for additional data to support the inclusion of edoxaban and enoxaparin on andexanet alfa’s label. This was because the ANNEXA-A and ANNEXA-R trials only included subjects who received apixaban or rivaroxaban.

In August 2017, Portola resubmitted the BLA for andexanet alfa. This time, the company sought approval of the drug only for patients on apixaban or rivaroxaban who are experiencing uncontrolled or life-threatening bleeding.

For additional information on andexanet alfa, visit https://www.andexxa.com/.

Portola Pharmaceuticals

The US Food and Drug Administration (FDA) has granted accelerated approval for andexanet alfa (Andexxa®), the first antidote for the reversal of factor Xa inhibitors.

Andexanet alfa is approved for use in patients treated with rivaroxaban or apixaban when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.

Andexanet alfa was granted accelerated approval for this indication based on the drug’s anti-factor Xa activity in healthy volunteers.

Continued FDA approval of andexanet alfa may be contingent upon post-marketing study results to demonstrate an improvement in hemostasis in patients taking rivaroxaban or apixaban who require reversal of anticoagulation.

The post-marketing requirement is a trial in which patients will be randomized to receive either andexanet alfa or usual care. This study is scheduled to start in 2019, with results expected to be available in 2023.

Portola Pharmaceuticals, Inc., said it expects to launch andexanet alfa in early June. This drug will be produced using the generation 1 manufacturing process.

A broader commercial launch of andexanet alfa is anticipated in early 2019, dependent upon FDA approval of the generation 2 manufacturing process.

Supporting trials

The FDA’s approval of andexanet alfa is supported by data from a pair of phase 3 studies—ANNEXA-R and ANNEXA-A.

These trials were designed to evaluate the safety and efficacy of andexanet alfa in reversing the anticoagulant activity of rivaroxaban and apixaban in healthy volunteers.

Results from both studies were published in NEJM in 2015.

The FDA also assessed interim data from the ongoing ANNEXA-4 study as part of the review and approval of andexanet alfa.

In ANNEXA-4, researchers are evaluating andexanet alfa in patients experiencing major bleeding while taking factor Xa inhibitors.

Interim results from this trial were presented at the American College of Cardiology’s 67th Annual Scientific Session & Expo in March.

About andexanet alfa

Andexanet alfa is a modified human factor Xa molecule that acts as a decoy to target and sequester both oral and injectable factor Xa inhibitors in the blood. Once bound, the factor Xa inhibitors are unable to bind to and inhibit native factor Xa, thus potentially allowing for the restoration of normal hemostatic processes.

Portola Pharmaceuticals first submitted the biologics license application (BLA) for andexanet alfa in December 2015. The FDA had already granted andexanet alfa orphan drug designation earlier in 2015 and breakthrough therapy designation in 2013.

With its first BLA submission, Portola was seeking approval for andexanet alfa as a reversal agent for patients anticoagulated with an oral or injectable factor Xa inhibitor—apixaban, rivaroxaban, edoxaban, or enoxaparin—who experience serious uncontrolled or life-threatening bleeding or who require urgent or emergency surgery.

In August 2016, the FDA issued a complete response letter explaining why the agency could not approve andexanet alfa for this indication.

The FDA requested additional information related to manufacturing of the drug and asked Portola for additional data to support the inclusion of edoxaban and enoxaparin on andexanet alfa’s label. This was because the ANNEXA-A and ANNEXA-R trials only included subjects who received apixaban or rivaroxaban.

In August 2017, Portola resubmitted the BLA for andexanet alfa. This time, the company sought approval of the drug only for patients on apixaban or rivaroxaban who are experiencing uncontrolled or life-threatening bleeding.

For additional information on andexanet alfa, visit https://www.andexxa.com/.

The wide array of comorbidities and treatment variables can make diabetes a difficult disease to manage—and to live with. Providers must be equipped to address the complexities and complications that affect patients with diabetes. In December 2016, the American Diabetes Association published a position statement recognizing the psychosocial factors (environmental, social, behavioral, and emotional) that affect medical outcomes and psychological well-being in persons with diabetes. These include self-management, diabetes distress, psychological comorbidities, and life-course considerations.¹

SELF-MANAGEMENT

A patient’s perception of his or her ability to self-manage diabetes is an important psychosocial factor in treatment and management outcomes. Training patients with diabetes in self-care skills and the use of technologies­—at the time of diagnosis, annually, and/or when complications or transitions in care occur—can empower patients to assume an active role in their daily management. These interventions can be tailored to address specific, individualized problems that contribute to suboptimal glycemic outcomes, such as issues in numeracy or coping, food insecurity, or lack of support. Employing a nonjudgmental approach that normalizes periodic lapses in self-management may help encourage patients and minimize their resistance to self-management.

DIABETES DISTRESS

The frustration, worry, anger, guilt, and burnout imposed by diabetes and its management (via glucose monitoring, medication dosing, and insulin titration) is known as diabetes distress. With a reported prevalence of 18% to 45%, this disease burden is quite common.² Because high levels of diabetes distress are associated with low self-efficacy, poor glycemic outcomes, and suboptimal exercise/dietary habits, referral for counseling should be considered if a patient expresses feelings of distress.

Use of validated screening tools, such as Problem Areas in Diabetes (PAID)^3,4 or the Diabetes Distress Scale (DDS)⁵, can aid in routine monitoring for diabetes distress. (See the Table for more information.) If distress is identified in specific self-care areas, further patient education on self-management is appropriate.

PSYCHOLOGICAL COMORBIDITIES

Depression, anxiety, disordered eating, and serious mental illness (eg, schizophrenia) are known psychological comorbidities of diabetes. Screening for symptoms using patient-appropriate, standardized/validated tools should occur at initial visit, at periodic intervals, and when there is a change in disease, treatment, or life circumstance.

Depression

Patients with diabetes should be screened for depression when medical status worsens or when complications occur; it is recommended to include caregivers and family members in this assessment. Patients who screen positive for depression should be referred to mental health providers who have experience with cognitive behavioral therapy, interpersonal therapy, or other evidence-based treatment approaches, and who can provide collaborative care alongside the diabetes treatment team. Once diagnosed with depression, patients should be screened annually.

Anxiety

Expression of fear, dread, or irrational thoughts, avoidant and/or repetitious behaviors, and social withdrawal are signs of anxiety that should prompt screening. Consider screening for anxiety in patients who express worry about diabetes complications, insulin injections or infusion, taking medications, and/or hypoglycemia that interferes with self-management behaviors.

Continue to: Patients with hypoglycemia unawareness...

Patients with hypoglycemia unawareness, which can co-occur with fear of hypoglycemia, can increase self-monitoring of glucose with a glucometer or continuous glucose monitor. Blood Glucose Awareness Training (or other similar evidence-based intervention) can be used to help reestablish awareness of hypoglycemia and reduce fear of hypoglycemia.^6-8 Providers can deliver hypoglycemia awareness education in the clinic.

Disordered Eating

When hyperglycemia and weight loss are unexplained by self-reported medication dosing, diet, and exercise, consider screening for disordered or disrupted eating (see Table for screening tools). In addition, reviewing the medical regimen is recommended to identify potential treatment-related effects on hunger/caloric intake.

Cognitive Impairment

Since research has shown significantly increased rates of diabetes among persons with serious mental illness (eg, schizophrenia), annual screening for prediabetes and diabetes is recommended for those taking atypical antipsychotic medications. Furthermore, some of the effects of serious mental illness—such as disordered thinking and impaired judgment—make it difficult for a patient to engage in risk-reducing behaviors or (if diagnosed) to manage diabetes. Therefore, monitoring of diabetes self-care activities should be incorporated into treatment goals for persons with these comorbid conditions.

Continue to: CONCLUSION

As providers, we should be familiar with the evidence-based, validated tools available to identify the psychosocial comorbidities of diabetes. Screening and assessing patients for psychosocial/behavioral challenges should be performed at an initial visit, at periodic intervals, and whenever there is a change in disease, treatment, or life circumstances.

Health care alliances with behavioral/mental health providers who are knowledgeable about diabetes treatment and the psychosocial aspects of diabetes are key. Patient-centered care is essential to promote optimal medical outcomes and psychological well-being. As members of the health care team, we must be respectful and responsive to patient preferences, needs, and values; clinical decisions should be guided by patient values. If A1C is not at goal despite maximized medication therapy and lifestyle modification, consider identifying and addressing any psychosocial factors that may be involved.

The wide array of comorbidities and treatment variables can make diabetes a difficult disease to manage—and to live with. Providers must be equipped to address the complexities and complications that affect patients with diabetes. In December 2016, the American Diabetes Association published a position statement recognizing the psychosocial factors (environmental, social, behavioral, and emotional) that affect medical outcomes and psychological well-being in persons with diabetes. These include self-management, diabetes distress, psychological comorbidities, and life-course considerations.¹

SELF-MANAGEMENT

A patient’s perception of his or her ability to self-manage diabetes is an important psychosocial factor in treatment and management outcomes. Training patients with diabetes in self-care skills and the use of technologies­—at the time of diagnosis, annually, and/or when complications or transitions in care occur—can empower patients to assume an active role in their daily management. These interventions can be tailored to address specific, individualized problems that contribute to suboptimal glycemic outcomes, such as issues in numeracy or coping, food insecurity, or lack of support. Employing a nonjudgmental approach that normalizes periodic lapses in self-management may help encourage patients and minimize their resistance to self-management.

DIABETES DISTRESS

The frustration, worry, anger, guilt, and burnout imposed by diabetes and its management (via glucose monitoring, medication dosing, and insulin titration) is known as diabetes distress. With a reported prevalence of 18% to 45%, this disease burden is quite common.² Because high levels of diabetes distress are associated with low self-efficacy, poor glycemic outcomes, and suboptimal exercise/dietary habits, referral for counseling should be considered if a patient expresses feelings of distress.

Use of validated screening tools, such as Problem Areas in Diabetes (PAID)^3,4 or the Diabetes Distress Scale (DDS)⁵, can aid in routine monitoring for diabetes distress. (See the Table for more information.) If distress is identified in specific self-care areas, further patient education on self-management is appropriate.

PSYCHOLOGICAL COMORBIDITIES

Depression, anxiety, disordered eating, and serious mental illness (eg, schizophrenia) are known psychological comorbidities of diabetes. Screening for symptoms using patient-appropriate, standardized/validated tools should occur at initial visit, at periodic intervals, and when there is a change in disease, treatment, or life circumstance.

Depression

Patients with diabetes should be screened for depression when medical status worsens or when complications occur; it is recommended to include caregivers and family members in this assessment. Patients who screen positive for depression should be referred to mental health providers who have experience with cognitive behavioral therapy, interpersonal therapy, or other evidence-based treatment approaches, and who can provide collaborative care alongside the diabetes treatment team. Once diagnosed with depression, patients should be screened annually.

Anxiety

Expression of fear, dread, or irrational thoughts, avoidant and/or repetitious behaviors, and social withdrawal are signs of anxiety that should prompt screening. Consider screening for anxiety in patients who express worry about diabetes complications, insulin injections or infusion, taking medications, and/or hypoglycemia that interferes with self-management behaviors.

Continue to: Patients with hypoglycemia unawareness...

Patients with hypoglycemia unawareness, which can co-occur with fear of hypoglycemia, can increase self-monitoring of glucose with a glucometer or continuous glucose monitor. Blood Glucose Awareness Training (or other similar evidence-based intervention) can be used to help reestablish awareness of hypoglycemia and reduce fear of hypoglycemia.^6-8 Providers can deliver hypoglycemia awareness education in the clinic.

Disordered Eating

When hyperglycemia and weight loss are unexplained by self-reported medication dosing, diet, and exercise, consider screening for disordered or disrupted eating (see Table for screening tools). In addition, reviewing the medical regimen is recommended to identify potential treatment-related effects on hunger/caloric intake.

Cognitive Impairment

Since research has shown significantly increased rates of diabetes among persons with serious mental illness (eg, schizophrenia), annual screening for prediabetes and diabetes is recommended for those taking atypical antipsychotic medications. Furthermore, some of the effects of serious mental illness—such as disordered thinking and impaired judgment—make it difficult for a patient to engage in risk-reducing behaviors or (if diagnosed) to manage diabetes. Therefore, monitoring of diabetes self-care activities should be incorporated into treatment goals for persons with these comorbid conditions.

Continue to: CONCLUSION

As providers, we should be familiar with the evidence-based, validated tools available to identify the psychosocial comorbidities of diabetes. Screening and assessing patients for psychosocial/behavioral challenges should be performed at an initial visit, at periodic intervals, and whenever there is a change in disease, treatment, or life circumstances.

Health care alliances with behavioral/mental health providers who are knowledgeable about diabetes treatment and the psychosocial aspects of diabetes are key. Patient-centered care is essential to promote optimal medical outcomes and psychological well-being. As members of the health care team, we must be respectful and responsive to patient preferences, needs, and values; clinical decisions should be guided by patient values. If A1C is not at goal despite maximized medication therapy and lifestyle modification, consider identifying and addressing any psychosocial factors that may be involved.

The wide array of comorbidities and treatment variables can make diabetes a difficult disease to manage—and to live with. Providers must be equipped to address the complexities and complications that affect patients with diabetes. In December 2016, the American Diabetes Association published a position statement recognizing the psychosocial factors (environmental, social, behavioral, and emotional) that affect medical outcomes and psychological well-being in persons with diabetes. These include self-management, diabetes distress, psychological comorbidities, and life-course considerations.¹

SELF-MANAGEMENT

A patient’s perception of his or her ability to self-manage diabetes is an important psychosocial factor in treatment and management outcomes. Training patients with diabetes in self-care skills and the use of technologies­—at the time of diagnosis, annually, and/or when complications or transitions in care occur—can empower patients to assume an active role in their daily management. These interventions can be tailored to address specific, individualized problems that contribute to suboptimal glycemic outcomes, such as issues in numeracy or coping, food insecurity, or lack of support. Employing a nonjudgmental approach that normalizes periodic lapses in self-management may help encourage patients and minimize their resistance to self-management.

DIABETES DISTRESS

The frustration, worry, anger, guilt, and burnout imposed by diabetes and its management (via glucose monitoring, medication dosing, and insulin titration) is known as diabetes distress. With a reported prevalence of 18% to 45%, this disease burden is quite common.² Because high levels of diabetes distress are associated with low self-efficacy, poor glycemic outcomes, and suboptimal exercise/dietary habits, referral for counseling should be considered if a patient expresses feelings of distress.

Use of validated screening tools, such as Problem Areas in Diabetes (PAID)^3,4 or the Diabetes Distress Scale (DDS)⁵, can aid in routine monitoring for diabetes distress. (See the Table for more information.) If distress is identified in specific self-care areas, further patient education on self-management is appropriate.

PSYCHOLOGICAL COMORBIDITIES

Depression, anxiety, disordered eating, and serious mental illness (eg, schizophrenia) are known psychological comorbidities of diabetes. Screening for symptoms using patient-appropriate, standardized/validated tools should occur at initial visit, at periodic intervals, and when there is a change in disease, treatment, or life circumstance.

Depression

Patients with diabetes should be screened for depression when medical status worsens or when complications occur; it is recommended to include caregivers and family members in this assessment. Patients who screen positive for depression should be referred to mental health providers who have experience with cognitive behavioral therapy, interpersonal therapy, or other evidence-based treatment approaches, and who can provide collaborative care alongside the diabetes treatment team. Once diagnosed with depression, patients should be screened annually.

Anxiety

Expression of fear, dread, or irrational thoughts, avoidant and/or repetitious behaviors, and social withdrawal are signs of anxiety that should prompt screening. Consider screening for anxiety in patients who express worry about diabetes complications, insulin injections or infusion, taking medications, and/or hypoglycemia that interferes with self-management behaviors.

Continue to: Patients with hypoglycemia unawareness...

Patients with hypoglycemia unawareness, which can co-occur with fear of hypoglycemia, can increase self-monitoring of glucose with a glucometer or continuous glucose monitor. Blood Glucose Awareness Training (or other similar evidence-based intervention) can be used to help reestablish awareness of hypoglycemia and reduce fear of hypoglycemia.^6-8 Providers can deliver hypoglycemia awareness education in the clinic.

Disordered Eating

When hyperglycemia and weight loss are unexplained by self-reported medication dosing, diet, and exercise, consider screening for disordered or disrupted eating (see Table for screening tools). In addition, reviewing the medical regimen is recommended to identify potential treatment-related effects on hunger/caloric intake.

Cognitive Impairment

Since research has shown significantly increased rates of diabetes among persons with serious mental illness (eg, schizophrenia), annual screening for prediabetes and diabetes is recommended for those taking atypical antipsychotic medications. Furthermore, some of the effects of serious mental illness—such as disordered thinking and impaired judgment—make it difficult for a patient to engage in risk-reducing behaviors or (if diagnosed) to manage diabetes. Therefore, monitoring of diabetes self-care activities should be incorporated into treatment goals for persons with these comorbid conditions.

Continue to: CONCLUSION

As providers, we should be familiar with the evidence-based, validated tools available to identify the psychosocial comorbidities of diabetes. Screening and assessing patients for psychosocial/behavioral challenges should be performed at an initial visit, at periodic intervals, and whenever there is a change in disease, treatment, or life circumstances.

Health care alliances with behavioral/mental health providers who are knowledgeable about diabetes treatment and the psychosocial aspects of diabetes are key. Patient-centered care is essential to promote optimal medical outcomes and psychological well-being. As members of the health care team, we must be respectful and responsive to patient preferences, needs, and values; clinical decisions should be guided by patient values. If A1C is not at goal despite maximized medication therapy and lifestyle modification, consider identifying and addressing any psychosocial factors that may be involved.

MAUI, HAWAII – The addition of the two latest treatment regimens to receive approval for hepatitis C essentially closes the circle on treatment of this disease, Steven L. Flamm, MD, declared at the Gastroenterology Updates, IBD, Liver Disease meeting.

“We now have good options available for all the hepatitis C scenarios you will ever see in your practice,” said Dr. Flamm, professor of medicine and chief of the hepatology program at Northwestern University, Chicago.

Bruce Jancin/MDedge News

[email protected]

MAUI, HAWAII – The addition of the two latest treatment regimens to receive approval for hepatitis C essentially closes the circle on treatment of this disease, Steven L. Flamm, MD, declared at the Gastroenterology Updates, IBD, Liver Disease meeting.

“We now have good options available for all the hepatitis C scenarios you will ever see in your practice,” said Dr. Flamm, professor of medicine and chief of the hepatology program at Northwestern University, Chicago.

Bruce Jancin/MDedge News

[email protected]

MAUI, HAWAII – The addition of the two latest treatment regimens to receive approval for hepatitis C essentially closes the circle on treatment of this disease, Steven L. Flamm, MD, declared at the Gastroenterology Updates, IBD, Liver Disease meeting.

“We now have good options available for all the hepatitis C scenarios you will ever see in your practice,” said Dr. Flamm, professor of medicine and chief of the hepatology program at Northwestern University, Chicago.

Bruce Jancin/MDedge News

[email protected]

MADRID – An attempt to balance effective treatment with good antibiotic stewardship fell short when patients with cellulitis who got 6 days of flucloxacillin relapsed significantly sooner and more frequently than did those who received the standard 12 days of treatment.

While cellulitis cure rates at 14 and 28 days were similar between the two groups, 90-day relapse rates were significantly higher for those who took the 6-day course (23.5% vs. 6%), Duncan R. Cranendonk, MD, said at the European Congress of Clinical Microbiology and Infectious Diseases annual conference. The cohort demographics perhaps played into this finding: Most of the group was elderly, hospitalized, and had comorbid conditions.

Michele G. Sullivan/MDedge News

“However, this is the population clinicians are most likely to see,” said Dr Cranendonk of the University of Amsterdam. “It appears that therapy cannot be safely shortened in this population.”

In light of recent antibiotic trials showing that shorter courses can be as effective as prolonged treatment, Dr. Cranendonk and his colleagues conducted the DANCE (Duration of Antibiotic Therapy for Cellulitis) trial. The study investigated the efficacy of an abbreviated course of intravenous flucloxacillin among 248 patients with cellulitis admitted to 11 Dutch hospitals. At treatment day 6, those who had clinically improved after their initial treatment were randomized to 6 additional days of IV flucloxacillin or to placebo. The primary outcome was cure by day 14 without relapse by day 28.

A 2004 study successfully paved the way for DANCE, Dr. Cranendonk noted. That trial examined 5 versus 10 days of levofloxacin 500 mg for uncomplicated cellulitis in 87 patients. The outcome was positive: There was no significant difference in clinical outcome between the two arms, with a 98% cure rate in both groups.

[email protected]

SOURCE: Cranendonk et al. ECCMID 2018, Abstract O1122

MADRID – An attempt to balance effective treatment with good antibiotic stewardship fell short when patients with cellulitis who got 6 days of flucloxacillin relapsed significantly sooner and more frequently than did those who received the standard 12 days of treatment.

While cellulitis cure rates at 14 and 28 days were similar between the two groups, 90-day relapse rates were significantly higher for those who took the 6-day course (23.5% vs. 6%), Duncan R. Cranendonk, MD, said at the European Congress of Clinical Microbiology and Infectious Diseases annual conference. The cohort demographics perhaps played into this finding: Most of the group was elderly, hospitalized, and had comorbid conditions.

Michele G. Sullivan/MDedge News

“However, this is the population clinicians are most likely to see,” said Dr Cranendonk of the University of Amsterdam. “It appears that therapy cannot be safely shortened in this population.”

In light of recent antibiotic trials showing that shorter courses can be as effective as prolonged treatment, Dr. Cranendonk and his colleagues conducted the DANCE (Duration of Antibiotic Therapy for Cellulitis) trial. The study investigated the efficacy of an abbreviated course of intravenous flucloxacillin among 248 patients with cellulitis admitted to 11 Dutch hospitals. At treatment day 6, those who had clinically improved after their initial treatment were randomized to 6 additional days of IV flucloxacillin or to placebo. The primary outcome was cure by day 14 without relapse by day 28.

A 2004 study successfully paved the way for DANCE, Dr. Cranendonk noted. That trial examined 5 versus 10 days of levofloxacin 500 mg for uncomplicated cellulitis in 87 patients. The outcome was positive: There was no significant difference in clinical outcome between the two arms, with a 98% cure rate in both groups.

[email protected]

SOURCE: Cranendonk et al. ECCMID 2018, Abstract O1122

MADRID – An attempt to balance effective treatment with good antibiotic stewardship fell short when patients with cellulitis who got 6 days of flucloxacillin relapsed significantly sooner and more frequently than did those who received the standard 12 days of treatment.

While cellulitis cure rates at 14 and 28 days were similar between the two groups, 90-day relapse rates were significantly higher for those who took the 6-day course (23.5% vs. 6%), Duncan R. Cranendonk, MD, said at the European Congress of Clinical Microbiology and Infectious Diseases annual conference. The cohort demographics perhaps played into this finding: Most of the group was elderly, hospitalized, and had comorbid conditions.

Michele G. Sullivan/MDedge News

“However, this is the population clinicians are most likely to see,” said Dr Cranendonk of the University of Amsterdam. “It appears that therapy cannot be safely shortened in this population.”

In light of recent antibiotic trials showing that shorter courses can be as effective as prolonged treatment, Dr. Cranendonk and his colleagues conducted the DANCE (Duration of Antibiotic Therapy for Cellulitis) trial. The study investigated the efficacy of an abbreviated course of intravenous flucloxacillin among 248 patients with cellulitis admitted to 11 Dutch hospitals. At treatment day 6, those who had clinically improved after their initial treatment were randomized to 6 additional days of IV flucloxacillin or to placebo. The primary outcome was cure by day 14 without relapse by day 28.

A 2004 study successfully paved the way for DANCE, Dr. Cranendonk noted. That trial examined 5 versus 10 days of levofloxacin 500 mg for uncomplicated cellulitis in 87 patients. The outcome was positive: There was no significant difference in clinical outcome between the two arms, with a 98% cure rate in both groups.

[email protected]

SOURCE: Cranendonk et al. ECCMID 2018, Abstract O1122

Inappropriate treatment of gonorrhea persists despite growing antibiotic resistance, investigators reported in the Morbidity and Mortality Weekly Report.

In 2016, about 19% of gonorrhea cases diagnosed in the United States were not treated according to recommendations from the Centers for Disease Control and Prevention, wrote Emily J. Weston, MPH, and her associates. They recommended additional training and education on the need for providers to follow treatment recommendations.

SOURCE: Weston EJ et al. MMWR. 2018 Apr 27. doi: 10.15585/mmwr.mm6716a4

Inappropriate treatment of gonorrhea persists despite growing antibiotic resistance, investigators reported in the Morbidity and Mortality Weekly Report.

In 2016, about 19% of gonorrhea cases diagnosed in the United States were not treated according to recommendations from the Centers for Disease Control and Prevention, wrote Emily J. Weston, MPH, and her associates. They recommended additional training and education on the need for providers to follow treatment recommendations.

SOURCE: Weston EJ et al. MMWR. 2018 Apr 27. doi: 10.15585/mmwr.mm6716a4

Inappropriate treatment of gonorrhea persists despite growing antibiotic resistance, investigators reported in the Morbidity and Mortality Weekly Report.

In 2016, about 19% of gonorrhea cases diagnosed in the United States were not treated according to recommendations from the Centers for Disease Control and Prevention, wrote Emily J. Weston, MPH, and her associates. They recommended additional training and education on the need for providers to follow treatment recommendations.

SOURCE: Weston EJ et al. MMWR. 2018 Apr 27. doi: 10.15585/mmwr.mm6716a4

WASHINGTON – An all-comer observational study associated endovascular treatment of lower limb peripheral artery disease (PAD) with low event rates and substantial improvements in quality of life at 18 months, even in Rutherford stage 6 patients.

Although the proportion of patients with Rutherford stage 6 PAD was relatively small, the study results showed that peripheral vascular intervention “can be successful in this patient population as evidenced by a high freedom from major amputation,” reported William Gray, MD, system chief of the division of cardiovascular disease at the Lankenau Heart Group, Wynnewood, Pa., at CRT 2018, sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

Ted Bosworth/MDedge News

WASHINGTON – An all-comer observational study associated endovascular treatment of lower limb peripheral artery disease (PAD) with low event rates and substantial improvements in quality of life at 18 months, even in Rutherford stage 6 patients.

Although the proportion of patients with Rutherford stage 6 PAD was relatively small, the study results showed that peripheral vascular intervention “can be successful in this patient population as evidenced by a high freedom from major amputation,” reported William Gray, MD, system chief of the division of cardiovascular disease at the Lankenau Heart Group, Wynnewood, Pa., at CRT 2018, sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

Ted Bosworth/MDedge News

WASHINGTON – An all-comer observational study associated endovascular treatment of lower limb peripheral artery disease (PAD) with low event rates and substantial improvements in quality of life at 18 months, even in Rutherford stage 6 patients.

Although the proportion of patients with Rutherford stage 6 PAD was relatively small, the study results showed that peripheral vascular intervention “can be successful in this patient population as evidenced by a high freedom from major amputation,” reported William Gray, MD, system chief of the division of cardiovascular disease at the Lankenau Heart Group, Wynnewood, Pa., at CRT 2018, sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

Ted Bosworth/MDedge News