Infectious Diseases

A 50-year-old man with Crohn disease and psoriatic arthritis treated with infliximab and methotrexate presented to a tertiary care hospital with fever, cough, and chest discomfort. The symptoms had first appeared 2 weeks earlier, and he had gone to an urgent care center, where he was prescribed a 5-day course of azithromycin and a corticosteroid, but this had not relieved his symptoms.

Bronchoscopy revealed edematous mucosa throughout, with minimal secretion. Specimens for bacterial, acid-fast bacillus, and fungal cultures were obtained from bronchoalveolar lavage. Endobronchial lymph node biopsy with ultrasonographic guidance revealed nonnecrotizing granuloma.

Bronchoalveolar lavage cultures showed no growth, but the patient’s serum histoplasma antigen was positive at 5.99 ng/dL (reference range: none detected), leading to the diagnosis of mediastinal granuloma due to histoplasmosis with possible dissemination. His immunosuppressant drugs were stopped, and oral itraconazole was started.

At a follow-up visit 2 months later, his serum antigen level had decreased to 0.68 ng/dL, and he had no symptoms whatsoever. At a visit 1 month after that, infliximab and methotrexate were restarted because of an exacerbation of Crohn disease. His oral itraconazole treatment was to be continued for at least 12 months, given the high suspicion for disseminated histoplasmosis while on immunosuppressant therapy.

DIFFERENTIAL DIAGNOSIS OF GRANULOMATOUS LUNG DISEASE AND LYMPHADENOPATHY

The differential diagnosis of granulomatous lung disease and lymphadenopathy is broad and includes noninfectious and infectious conditions.¹

Noninfectious causes include lymphoma, sarcoidosis, inflammatory bowel disease, hypersensitivity pneumonia, side effects of drugs (eg, methotrexate, etanercept), rheumatoid nodules, vasculitis (eg, Churg-Strauss syndrome, granulomatosis with polyangiitis, primary amyloidosis, pneumoconiosis (eg, beryllium, cobalt), and Castleman disease.

There is concern that tumor necrosis factor antagonists may increase the risk of lymphoma, but a 2017 study found no evidence of this.²

Infectious conditions associated with granulomatous lung disease include tuberculosis, nontuberculous mycobacterial infection, fungal infection (eg, Cryptococcus, Coccidioides, Histoplasma, Blastomyces), brucellosis, tularemia (respiratory type B), parasitic infection (eg, Toxocara, Leishmania, Echinococcus, Schistosoma), and Whipple disease.

HISTOPLASMOSIS

Histoplasmosis, caused by infection with Histoplasma capsulatum, is the most prevalent endemic mycotic disease in the United States.³ The fungus is commonly found in the Ohio and Mississippi River valleys in the United States, and also in Central and South America and Asia.

Risk factors for histoplasmosis include living in or traveling to an endemic area, exposure to aerosolized soil that contains spores, and exposure to bats or birds and their droppings.⁴

Fewer than 5% of exposed individuals develop symptoms, which include fever, chills, headache, myalgia, anorexia, cough, and chest pain.⁵ Patients may experience symptoms shortly after exposure or may remain free of symptoms for years, with intermittent relapses of symptoms.⁶ Hilar or mediastinal lymphadenopathy is common in acute pulmonary histoplasmosis.⁷

The risk of disseminated histoplasmosis is greater in patients with reduced cell-mediated immunity, such as in human immunodeficiency virus infection, acquired immunodeficiency syndrome, solid-organ or bone marrow transplant, hematologic malignancies, immunosuppression (corticosteroids, disease-modifying antirheumatic drugs, and tumor necrosis factor antagonists), and congenital T-cell deficiencies.⁸

In a retrospective study, infliximab was the tumor necrosis factor antagonist most commonly associated with histoplasmosis.⁹ In a study of patients with rheumatoid arthritis, the disease-modifying drug most commonly associated was methotrexate.¹⁰

Isolation of H capsulatum from clinical specimens remains the gold standard for confirmation of histoplasmosis. The sensitivity of culture to detect H capsulatum depends on the clinical manifestations: it is 74% in patients with disseminated histoplasmosis, but only 42% in patients with acute pulmonary histoplasmosis.¹¹ The serum histoplasma antigen test has a sensitivity of 91.8% in disseminated histoplasmosis, 87.5% in chronic pulmonary histoplasmosis, and 83% in acute pulmonary histoplasmosis.¹²

Urine testing for histoplasma antigen has generally proven to be slightly more sensitive than serum testing in all manifestations of histoplasmosis.¹³ Combining urine and serum testing increases the likelihood of antigen detection.

TREATMENT

Asymptomatic patients with mediastinal histoplasmosis do not require treatment. (Note: in some cases, lymphadenopathy is found incidentally, and biopsy is done to rule out malignancy.)

Standard treatment of symptomatic mediastinal histoplasmosis is oral itraconazole 200 mg, 3 times daily for 3 days, followed by 200 mg orally once or twice daily for 6 to 12 weeks.¹⁴

Although stopping immunosuppressant drugs is considered the standard of care in treating histoplasmosis in immunocompromised patients, there are no guidelines on when to resume them. However, a retrospective study of 98 cases of histoplasmosis in patients on tumor necrosis factor antagonists found that resuming immunosuppressants might be safe with close monitoring during the course of antifungal therapy.⁹ The role of long-term suppressive therapy with antifungal agents in patients on chronic immunosuppressive therapy is still unknown and needs further study.

TAKE-HOME MESSAGES

• Histoplasmosis is the most prevalent endemic mycotic disease in the United States, and mediastinal lymphadenopathy is commonly seen in acute pulmonary histoplasmosis.
• Histoplasmosis should be included in the differential diagnosis of granulomatous lung disease in patients from an endemic area or with a history of travel to an endemic area.
• Immunosuppressive agents such as tumor necrosis factor antagonists and disease-modifying antirheumatic drugs can predispose to invasive fungal infection, including histoplasmosis.
• While isolation of H capsulatum from culture remains the gold standard for the diagnosis of histoplasmosis, the histoplasma antigen tests (serum and urine) is more sensitive than culture.

A 50-year-old man with Crohn disease and psoriatic arthritis treated with infliximab and methotrexate presented to a tertiary care hospital with fever, cough, and chest discomfort. The symptoms had first appeared 2 weeks earlier, and he had gone to an urgent care center, where he was prescribed a 5-day course of azithromycin and a corticosteroid, but this had not relieved his symptoms.

Bronchoscopy revealed edematous mucosa throughout, with minimal secretion. Specimens for bacterial, acid-fast bacillus, and fungal cultures were obtained from bronchoalveolar lavage. Endobronchial lymph node biopsy with ultrasonographic guidance revealed nonnecrotizing granuloma.

Bronchoalveolar lavage cultures showed no growth, but the patient’s serum histoplasma antigen was positive at 5.99 ng/dL (reference range: none detected), leading to the diagnosis of mediastinal granuloma due to histoplasmosis with possible dissemination. His immunosuppressant drugs were stopped, and oral itraconazole was started.

At a follow-up visit 2 months later, his serum antigen level had decreased to 0.68 ng/dL, and he had no symptoms whatsoever. At a visit 1 month after that, infliximab and methotrexate were restarted because of an exacerbation of Crohn disease. His oral itraconazole treatment was to be continued for at least 12 months, given the high suspicion for disseminated histoplasmosis while on immunosuppressant therapy.

DIFFERENTIAL DIAGNOSIS OF GRANULOMATOUS LUNG DISEASE AND LYMPHADENOPATHY

The differential diagnosis of granulomatous lung disease and lymphadenopathy is broad and includes noninfectious and infectious conditions.¹

Noninfectious causes include lymphoma, sarcoidosis, inflammatory bowel disease, hypersensitivity pneumonia, side effects of drugs (eg, methotrexate, etanercept), rheumatoid nodules, vasculitis (eg, Churg-Strauss syndrome, granulomatosis with polyangiitis, primary amyloidosis, pneumoconiosis (eg, beryllium, cobalt), and Castleman disease.

There is concern that tumor necrosis factor antagonists may increase the risk of lymphoma, but a 2017 study found no evidence of this.²

Infectious conditions associated with granulomatous lung disease include tuberculosis, nontuberculous mycobacterial infection, fungal infection (eg, Cryptococcus, Coccidioides, Histoplasma, Blastomyces), brucellosis, tularemia (respiratory type B), parasitic infection (eg, Toxocara, Leishmania, Echinococcus, Schistosoma), and Whipple disease.

HISTOPLASMOSIS

Histoplasmosis, caused by infection with Histoplasma capsulatum, is the most prevalent endemic mycotic disease in the United States.³ The fungus is commonly found in the Ohio and Mississippi River valleys in the United States, and also in Central and South America and Asia.

Risk factors for histoplasmosis include living in or traveling to an endemic area, exposure to aerosolized soil that contains spores, and exposure to bats or birds and their droppings.⁴

Fewer than 5% of exposed individuals develop symptoms, which include fever, chills, headache, myalgia, anorexia, cough, and chest pain.⁵ Patients may experience symptoms shortly after exposure or may remain free of symptoms for years, with intermittent relapses of symptoms.⁶ Hilar or mediastinal lymphadenopathy is common in acute pulmonary histoplasmosis.⁷

The risk of disseminated histoplasmosis is greater in patients with reduced cell-mediated immunity, such as in human immunodeficiency virus infection, acquired immunodeficiency syndrome, solid-organ or bone marrow transplant, hematologic malignancies, immunosuppression (corticosteroids, disease-modifying antirheumatic drugs, and tumor necrosis factor antagonists), and congenital T-cell deficiencies.⁸

In a retrospective study, infliximab was the tumor necrosis factor antagonist most commonly associated with histoplasmosis.⁹ In a study of patients with rheumatoid arthritis, the disease-modifying drug most commonly associated was methotrexate.¹⁰

Isolation of H capsulatum from clinical specimens remains the gold standard for confirmation of histoplasmosis. The sensitivity of culture to detect H capsulatum depends on the clinical manifestations: it is 74% in patients with disseminated histoplasmosis, but only 42% in patients with acute pulmonary histoplasmosis.¹¹ The serum histoplasma antigen test has a sensitivity of 91.8% in disseminated histoplasmosis, 87.5% in chronic pulmonary histoplasmosis, and 83% in acute pulmonary histoplasmosis.¹²

Urine testing for histoplasma antigen has generally proven to be slightly more sensitive than serum testing in all manifestations of histoplasmosis.¹³ Combining urine and serum testing increases the likelihood of antigen detection.

TREATMENT

Asymptomatic patients with mediastinal histoplasmosis do not require treatment. (Note: in some cases, lymphadenopathy is found incidentally, and biopsy is done to rule out malignancy.)

Standard treatment of symptomatic mediastinal histoplasmosis is oral itraconazole 200 mg, 3 times daily for 3 days, followed by 200 mg orally once or twice daily for 6 to 12 weeks.¹⁴

Although stopping immunosuppressant drugs is considered the standard of care in treating histoplasmosis in immunocompromised patients, there are no guidelines on when to resume them. However, a retrospective study of 98 cases of histoplasmosis in patients on tumor necrosis factor antagonists found that resuming immunosuppressants might be safe with close monitoring during the course of antifungal therapy.⁹ The role of long-term suppressive therapy with antifungal agents in patients on chronic immunosuppressive therapy is still unknown and needs further study.

TAKE-HOME MESSAGES

• Histoplasmosis is the most prevalent endemic mycotic disease in the United States, and mediastinal lymphadenopathy is commonly seen in acute pulmonary histoplasmosis.
• Histoplasmosis should be included in the differential diagnosis of granulomatous lung disease in patients from an endemic area or with a history of travel to an endemic area.
• Immunosuppressive agents such as tumor necrosis factor antagonists and disease-modifying antirheumatic drugs can predispose to invasive fungal infection, including histoplasmosis.
• While isolation of H capsulatum from culture remains the gold standard for the diagnosis of histoplasmosis, the histoplasma antigen tests (serum and urine) is more sensitive than culture.

A 50-year-old man with Crohn disease and psoriatic arthritis treated with infliximab and methotrexate presented to a tertiary care hospital with fever, cough, and chest discomfort. The symptoms had first appeared 2 weeks earlier, and he had gone to an urgent care center, where he was prescribed a 5-day course of azithromycin and a corticosteroid, but this had not relieved his symptoms.

Bronchoscopy revealed edematous mucosa throughout, with minimal secretion. Specimens for bacterial, acid-fast bacillus, and fungal cultures were obtained from bronchoalveolar lavage. Endobronchial lymph node biopsy with ultrasonographic guidance revealed nonnecrotizing granuloma.

Bronchoalveolar lavage cultures showed no growth, but the patient’s serum histoplasma antigen was positive at 5.99 ng/dL (reference range: none detected), leading to the diagnosis of mediastinal granuloma due to histoplasmosis with possible dissemination. His immunosuppressant drugs were stopped, and oral itraconazole was started.

At a follow-up visit 2 months later, his serum antigen level had decreased to 0.68 ng/dL, and he had no symptoms whatsoever. At a visit 1 month after that, infliximab and methotrexate were restarted because of an exacerbation of Crohn disease. His oral itraconazole treatment was to be continued for at least 12 months, given the high suspicion for disseminated histoplasmosis while on immunosuppressant therapy.

DIFFERENTIAL DIAGNOSIS OF GRANULOMATOUS LUNG DISEASE AND LYMPHADENOPATHY

The differential diagnosis of granulomatous lung disease and lymphadenopathy is broad and includes noninfectious and infectious conditions.¹

Noninfectious causes include lymphoma, sarcoidosis, inflammatory bowel disease, hypersensitivity pneumonia, side effects of drugs (eg, methotrexate, etanercept), rheumatoid nodules, vasculitis (eg, Churg-Strauss syndrome, granulomatosis with polyangiitis, primary amyloidosis, pneumoconiosis (eg, beryllium, cobalt), and Castleman disease.

There is concern that tumor necrosis factor antagonists may increase the risk of lymphoma, but a 2017 study found no evidence of this.²

Infectious conditions associated with granulomatous lung disease include tuberculosis, nontuberculous mycobacterial infection, fungal infection (eg, Cryptococcus, Coccidioides, Histoplasma, Blastomyces), brucellosis, tularemia (respiratory type B), parasitic infection (eg, Toxocara, Leishmania, Echinococcus, Schistosoma), and Whipple disease.

HISTOPLASMOSIS

Histoplasmosis, caused by infection with Histoplasma capsulatum, is the most prevalent endemic mycotic disease in the United States.³ The fungus is commonly found in the Ohio and Mississippi River valleys in the United States, and also in Central and South America and Asia.

Risk factors for histoplasmosis include living in or traveling to an endemic area, exposure to aerosolized soil that contains spores, and exposure to bats or birds and their droppings.⁴

Fewer than 5% of exposed individuals develop symptoms, which include fever, chills, headache, myalgia, anorexia, cough, and chest pain.⁵ Patients may experience symptoms shortly after exposure or may remain free of symptoms for years, with intermittent relapses of symptoms.⁶ Hilar or mediastinal lymphadenopathy is common in acute pulmonary histoplasmosis.⁷

The risk of disseminated histoplasmosis is greater in patients with reduced cell-mediated immunity, such as in human immunodeficiency virus infection, acquired immunodeficiency syndrome, solid-organ or bone marrow transplant, hematologic malignancies, immunosuppression (corticosteroids, disease-modifying antirheumatic drugs, and tumor necrosis factor antagonists), and congenital T-cell deficiencies.⁸

In a retrospective study, infliximab was the tumor necrosis factor antagonist most commonly associated with histoplasmosis.⁹ In a study of patients with rheumatoid arthritis, the disease-modifying drug most commonly associated was methotrexate.¹⁰

Isolation of H capsulatum from clinical specimens remains the gold standard for confirmation of histoplasmosis. The sensitivity of culture to detect H capsulatum depends on the clinical manifestations: it is 74% in patients with disseminated histoplasmosis, but only 42% in patients with acute pulmonary histoplasmosis.¹¹ The serum histoplasma antigen test has a sensitivity of 91.8% in disseminated histoplasmosis, 87.5% in chronic pulmonary histoplasmosis, and 83% in acute pulmonary histoplasmosis.¹²

Urine testing for histoplasma antigen has generally proven to be slightly more sensitive than serum testing in all manifestations of histoplasmosis.¹³ Combining urine and serum testing increases the likelihood of antigen detection.

TREATMENT

Asymptomatic patients with mediastinal histoplasmosis do not require treatment. (Note: in some cases, lymphadenopathy is found incidentally, and biopsy is done to rule out malignancy.)

Standard treatment of symptomatic mediastinal histoplasmosis is oral itraconazole 200 mg, 3 times daily for 3 days, followed by 200 mg orally once or twice daily for 6 to 12 weeks.¹⁴

Although stopping immunosuppressant drugs is considered the standard of care in treating histoplasmosis in immunocompromised patients, there are no guidelines on when to resume them. However, a retrospective study of 98 cases of histoplasmosis in patients on tumor necrosis factor antagonists found that resuming immunosuppressants might be safe with close monitoring during the course of antifungal therapy.⁹ The role of long-term suppressive therapy with antifungal agents in patients on chronic immunosuppressive therapy is still unknown and needs further study.

TAKE-HOME MESSAGES

• Histoplasmosis is the most prevalent endemic mycotic disease in the United States, and mediastinal lymphadenopathy is commonly seen in acute pulmonary histoplasmosis.
• Histoplasmosis should be included in the differential diagnosis of granulomatous lung disease in patients from an endemic area or with a history of travel to an endemic area.
• Immunosuppressive agents such as tumor necrosis factor antagonists and disease-modifying antirheumatic drugs can predispose to invasive fungal infection, including histoplasmosis.
• While isolation of H capsulatum from culture remains the gold standard for the diagnosis of histoplasmosis, the histoplasma antigen tests (serum and urine) is more sensitive than culture.

An 18-year-old man without any significant medical history was transferred from another hospital for higher-level care after presenting with unremitting chest pain. He had been in his usual state of good health until 7 days before presentation, when he developed mild rhinorrhea and a sore throat, but not a cough. He went to an outpatient clinic, where a rapid test for group A streptococci was done; the result was negative, and he was sent home on supportive measures.

On the day of admission, he awoke with severe, pressure-like, midsternal, nonradiating pain, which he rated 10 on a scale of 10. The pain intensified in the supine position and improved with sitting. A complete review of systems was otherwise negative. He denied having had similar symptoms in the past, as well as sick contacts, recent travel, toxin exposure, illicit substance abuse, pets at home, or tick bites. His family history was negative for cardiac arrhythmias, premature coronary artery disease, thoracic aneurysms or dissection, and infiltrative disorders. His surgical and social histories were unremarkable. He said he had no drug allergies.

On examination, his temperature was 38.1°C (100.6°F), heart rate 101 beats per minute, blood pressure 142/78 mm Hg, respiratory rate 16 breaths per minute, and oxygen saturation 98% on room air. He appeared anxious but was in no acute distress. Neck examination showed no elevation in jugular venous pulsation, bruits, thyromegaly, or lymphadenopathy. Cardiac examination revealed tachycardia without murmurs, rubs, or gallops. Lungs were clear to auscultation. Examination of all 4 extremities found 2+ pulses (on a scale of 0 to 4+) throughout and no cyanosis, clubbing, or edema. Abdominal, neurologic, and dermatologic examinations were unremarkable.

Further blood testing revealed the following:

• Troponin I (3 hours after the first level) 15.5 ng/mL
• B-type natriuretic peptide 200 mg/dL (reference range 0–100 mg/dL)
• C-reactive protein 0.9 mg/dL (reference range 0.0–0.8 mg/dL)
• Erythrocyte sedimentation rate 10 mm/h (reference range < 15 mm/h).

Metabolic and hematologic assessments were unremarkable. A toxicology screen for drugs of abuse was negative. Viral serologic testing was not done.

A chest radiograph showed no acute cardiopulmonary processes.

Given his presenting symptoms, persistent tachycardia, rapidly rising troponin I level, and electrocardiogram showing diffuse ST elevation, he was taken for urgent cardiac catheterization. Coronary angiography revealed no evidence of atherosclerotic disease, acute thrombosis, dissection, or aneurysm. Echocardiography 2 hours after the procedure showed a normal ejection fraction and no regional wall-motion abnormalities or valvular heart disease.

1. Which test should be done next to further evaluate this patient’s chest pain?

• Serum viral serologic testing
• Serum free light chain assay
• Nuclear myocardial perfusion study
• Cardiac magnetic resonance imaging (MRI)
• Endomyocardial biopsy

In this patient without ischemic coronary disease or valvular heart disease, the recent upper respiratory tract prodrome, active positional chest pain, and diffuse electrocardiographic changes raise the possibility of myocarditis with pericardial involvement.

Viral serologic tests

Viral serologic tests are often obtained in the workup of myocarditis as a noninvasive means of detecting an infectious cause.

However, this approach has several problems. First, a positive serologic result is a signal of the peripheral immune response to a pathogen but does not necessarily indicate active myocardial inflammation. Additionally, circulating immunoglobulin G against cardiotropic viruses is commonly found, even in the absence of myocarditis.¹ This is often the result of a high prevalence and exposure to these viruses in the general population. Further, trials have shown no correlation between serologic results and organisms identified by endomyocardial biopsy.²

Thus, serologic testing seems to be of limited utility, reserved for testing for infection with Borrelia burgdorferi (Lyme disease) in endemic areas, hepatitis C virus, human immunodeficiency virus in patients at high risk, Rickettsia conorii, and Rickettsia rickettsii.³

Serum free light chain testing for amyloidosis

Serum free light chain testing is replacing serum and urine protein electrophoresis in the workup of cardiac amyloidosis,⁴ as electrophoresis has poor sensitivity.^4,5

Cardiac amyloidosis often affects older persons, although in rare cases it can affect young patients who carry mutations in the transthyretin gene (ATTR amyloidosis).⁶ This diagnosis is unlikely in our patient, as he has no other affected organ systems (amyloidosis often affects the renal and neurologic systems), normal QRS voltages on electrocardiography (which are often but not always low in amyloidosis), and no left ventricular hypertrophy or diastolic dysfunction on echocardiography (which are often seen in amyloidosis).⁴

Nuclear perfusion imaging for sarcoidosis

Nuclear imaging has a limited role in evaluating myocarditis,³ but positron-emission tomography with fluorine-18 fluorodeoxyglucose has a diagnostic role in sarcoidosis, an immune-mediated cause of myocarditis.⁷

Based on the acuity of the patient’s presentation, preceded by upper respiratory tract symptoms, sarcoidosis is less likely. Sarcoidosis is difficult to diagnose, although when it is the cause of myocarditis, some clues exist, as patients usually present with heart failure symptoms, a second- or third-degree atrioventricular block, or a dilated left ventricle on echocardiography.³ All of these were absent in our patient.

Cardiac MRI

Cardiac MRI has undergone many advances, making it an extremely useful noninvasive test. It has excellent utility as a stand-alone test in diagnosing myocarditis and has synergistic value when combined with endomyocardial biopsy.⁸ It is indicated in hemodynamically stable patients with a clinical suspicion of myocarditis, persistent symptoms, absence of heart failure, and when imaging findings will change management. It is particularly useful to help elucidate a cause and guide tailored therapy.⁹ Therefore, it is a reasonable next step in the diagnostic pathway for this patient.¹⁰

Cardiac MRI also allows for concurrent assessment of scar. In myocardial infarction, the late gadolinium enhancement is subendocardial or transmural. In myocarditis, the pattern differs, being found in the subepicardial lateral free wall (in most patients with parvovirus B19) and mid-myocardial septum (in most patients with herpesvirus 6).^9,11 Cardiac MRI also confers prognostic information for patients with suspected myocarditis.¹²

The Lake Louise criteria⁹ for the diagnosis of myocarditis require 2 of the following:

• Evidence of myocardial edema
• Increased ratio of early gadolinium enhancement between myocardium and skeletal muscle (indicates hyperemia)
• At least 1 focal lesion with nonischemic late gadolinium enhancement (indicates cardiac myocyte injury or scarring).

The Lake Louise criteria may be replaced by T1 and T2 mapping, which was found to be considerably better for diagnosing myocarditis when the 2 were compared.^9,13,14

Endomyocardial biopsy

Endomyocardial biopsy should not be delayed while waiting for cardiac MRI in patients who are hemodynamically unstable or present with life-threatening features (ventricular arrhythmia, left ventricular failure, or resuscitation after sudden cardiac death).^3,10

The indications for endomyocardial biopsy have been highly debated. The 2013 guidelines from the European Society of Cardiology (ESC) recommending endomyocardial biopsy  in all clinically suspected cases of myocarditis have only heightened the controversy.³ The American Heart Association (AHA) guidelines reserve biopsy for patients with suspected myocarditis who have acute or subacute heart failure symptoms or who do not respond to standard medical therapy.¹⁵ Other reasonable indications may include the following: myocarditis with life-threatening ventricular arrhythmias, suspicion of giant cell myocarditis, necrotizing eosinophilic myocarditis, or cardiac sarcoidosis.¹⁶

Endomyocardial biopsy is the only way to make a definitive diagnosis of myocarditis.³ However, given the patchy distribution of myocardial involvement, a negative result does not rule out myocarditis. The diagnostic utility can be improved by increasing the number of samples taken (at least 3 but up to 10), obtaining samples from both ventricles, and using cardiac MRI data to determine which sites to biopsy.^3,13,17,18

Noninvasive testing such as cardiac MRI does not distinguish cell type or etiology (viral vs nonviral).³ Further, endomyocardial biopsy must be performed before immunosuppressive therapy can be safely started.^3,16 At experienced centers, the complication rate is 0% to 0.8%.³ The addition of immunohistochemical testing and viral genomic detection by polymerase chain reaction testing have increased the sensitivity of this technique.¹⁹ Finally, endomyocardial biopsy can help rule out some of the other possibilities in the differential diagnosis for myocarditis, including infiltrative and storage diseases, and possibly cardiac tumors.³

Of additional note, the diffuse ST-segment elevation seen on the patient’s electrocardiogram (Figure 1) is indicative of subepicardial inflammation. Since the distribution involves more than one epicardial coronary territory, this helps to differentiate the changes from those that occur with myocardial infarction.²⁰

Causes of myocarditis are numerous (Table 1),^3,21,22 but viral and postinfectious etiologies remain the most common causes of acute myocarditis.²³

• Parvovirus B19
• Coxsackievirus B
• Adenovirus species
• Human herpesvirus 6
• Staphylococcus aureus
• Corynebacterium diphtheria
• Trypanosoma cruzi
• Influenza H1/N1

INFECTIOUS CAUSES OF MYOCARDITIS

Coxsackievirus B was the agent most often linked to this condition from the 1950s through the 1990s. However, in the last 2 decades, adenovirus species and human herpesvirus 6 have been increasingly encountered, and recently, parvovirus B19 has been credited as the most common culprit,^11,23 at least in the Western world. In developing nations, T cruzi and C diphtheria are the most common offenders^.21

S aureus is a common cause of endocarditis, but it rarely plays a role in myocarditis. When it does, the myocarditis is often the sequela of profound bacteremia. This was much more common before antibiotics were invented.^24,25

Influenza H1/N1 is not among the most common causes of viral myocarditis, but it should be considered during flu season, given its ability to result in fulminant myocarditis.^3,26

TREATMENT FOR MYOCARDITIS

3. Which treatment is the most appropriate at this time?

• Intravenous immunoglobulin
• Interferon beta
• Acyclovir
• Prednisone
• Colchicine

Treatment for myocarditis depends on the cause but always includes supportive care to address the constellation of presenting symptoms. Standard therapies for tachy- or bradyarrhythmias, heart failure, and hemodynamic derangement should be started.

Supportive care

In patients with severe left ventricular dysfunction, an implantable cardiac electronic device, left ventricular assist device, or heart transplant may ultimately be needed. However, if possible these should be deferred for several months to determine response to treatment, since the myocardium can possibly recover.¹⁶

Diuretics, beta-blockers, angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors, and aldosterone antagonists should be given as part of guideline-directed medical therapy for patients with heart failure and reduced ejection fraction.^3,27 However, whether and how the patient should be weaned from these agents after disease recovery are unknown.³

Intravenous immunoglobulin

Intravenous immunoglobulin in high doses has had mixed results. Its efficacy is well documented in children,²¹ but limited supportive data are available in adults.³ As such, recent ESC guidelines do not provide recommendations regarding its use in adults.³

Interferon beta

Interferon beta has shown promise in improving New York Heart Association class and left ventricular ejection fraction.³ This is attributed to its effects on eliminating adenoviral species and enteroviruses. Treatment of enteroviral organisms in particular has been associated with improved 10-year prognosis.³ Interferon beta also has in vitro data showing efficacy at diminishing apoptosis from parvovirus B19.²⁸

Nucleoside analogues

Empiric treatment with nucleoside analogues (acyclovir, ganciclovir, and valacyclovir) has been tried for patients in whom human herpesvirus is suspected as the causative organism, although with unconfirmed effects.³ Consultation with an infectious disease specialist is recommended before starting these agents, and biopsy is often needed beforehand.³

Immunosuppressive agents

Immunosuppressive agents such as prednisone, azathioprine, and cyclosporine can be used in cases of biopsy-proven disease with manifestations of severe heart failure, especially if biopsy results reveal sarcoidosis, giant cell myocarditis, or necrotizing eosinophilic myocarditis. Although the results were neutral in the Myocarditis Treatment Trial,²⁹ the cause of myocarditis in this trial was unknown. Therapy with such agents should be initiated after active infection is ruled out, which also would require a biopsy.

Colchicine

Mechanisms of chest pain in myocarditis include associated pericarditis and coronary artery vasospasm.^3,23 Our patient’s chest pain changed when he changed position, possibly indicating associated pericarditis. In myocarditis with accompanying pericarditis symptoms, colchicine (1–2 mg as an initial dose and then 0.6 mg daily for up to 3 months) can be helpful in alleviating symptoms.^21,30 Thus, starting this agent in a patient who presents with myocarditis in absence of heart failure, arrhythmias, or left ventricular dysfunction is prudent.

Colchicine is used mainly to address the pain associated with pericarditis. For patients who present with pericarditis without myocarditis, nonsteroidal anti-inflammatory drugs (NSAIDs) remain the first-line treatment, with the addition of colchicine leading to faster symptom resolution.³⁰ The benefit of colchicine for isolated myocarditis is not well established, with only limited data showing some clinical effects.³¹

The patient was given colchicine 1.2 mg on the first day and then 0.6 mg daily. Within 2 days, his chest pain had resolved. He did not receive any immunosuppressive agents.

DISCHARGE INSTRUCTIONS

4. Before discharge, this patient should be instructed to do which of the following?

• Take over-the-counter NSAIDs to supplement the effects of colchicine
• Avoid competitive sports and athletics for at least 6 months
• Call to schedule repeat cardiac MRI
• No further instruction is needed

NSAIDs are used by themselves or in combination with colchicine in the treatment of pericarditis, but their use may be associated with worse outcomes in myocarditis.^3,21 Thus, their use is not recommended in most cases.³

Excessive physical activity should be avoided for at least 6 months after the clinical syndrome resolves. This recommendation is included in the most recent ESC guidelines but is based mainly on expert opinion and murine models with coxsackievirus B.³ Periodic reassessment is indicated with exercise stress testing before return to strenuous activity.^3,16,32 Testing should look for exercise tolerance, and exercise electrocardiography also helps to evaluate for clinically relevant arrythmias.

Cardiac MRI can help clarify the prognosis in myocarditis, but the role of repeat testing in guiding therapy is limited.³ Indications for repeat cardiac MRI include presence of 0 or 1 of the Lake Louise criteria (recall that 2 are necessary to make the diagnosis) with recurrence of symptoms and a high suspicion for myocardial inflammation.^3,9 Repeat cardiac MRI was not performed for our patient.

CASE CONCLUDED

The patient was evaluated in the cardiology clinic within 1 week of discharge. At that time, he was in sinus tachycardia with a heart rate of 102 bpm, and he was instructed to avoid any exercise until further notice.

At 6-month follow-up, the sinus tachycardia had resolved. However, because persistent tachycardia had been noted at the first postdischarge visit, and in view of the extent of myocardial involvement, he underwent exercise treadmill testing to evaluate for ventricular arrhythmias. The study did show premature ventricular complexes and 1 ventricular couplet at submaximal exercise levels. As this indicated a higher risk of exercise-induced arrhythmias, he was asked to continue normal activity levels but to abstain from exercise until the next evaluation.

During his 1-year follow-up, a repeat treadmill test showed no ventricular ectopy. Holter monitoring was ordered and showed no premature ventricular complexes, supraventricular arrhythmias, or atrioventricular block within the 48-hour period.

At his 2-year evaluation, he had returned to playing basketball and soccer on weekends and reported no recurrence of his initial symptoms.

KEY POINTS

• 

  Cardiac MRI has emerged as an excellent noninvasive imaging modality for the diagnosis of myocarditis.
• Treatment of myocarditis depends on the cause and severity of the patient’s presentation, spanning the spectrum from conservative care to immunosuppressive agents and even heart failure therapy.
• Excessive physical activity should be avoided for the first 6 months after disease diagnosis and treatment.
• If myocarditis is associated with pericardial involvement, colchicine is the agent of choice, and NSAIDs should be avoided.

Our suggested strategy for approaching myocarditis is shown in Figure 3.

An 18-year-old man without any significant medical history was transferred from another hospital for higher-level care after presenting with unremitting chest pain. He had been in his usual state of good health until 7 days before presentation, when he developed mild rhinorrhea and a sore throat, but not a cough. He went to an outpatient clinic, where a rapid test for group A streptococci was done; the result was negative, and he was sent home on supportive measures.

On the day of admission, he awoke with severe, pressure-like, midsternal, nonradiating pain, which he rated 10 on a scale of 10. The pain intensified in the supine position and improved with sitting. A complete review of systems was otherwise negative. He denied having had similar symptoms in the past, as well as sick contacts, recent travel, toxin exposure, illicit substance abuse, pets at home, or tick bites. His family history was negative for cardiac arrhythmias, premature coronary artery disease, thoracic aneurysms or dissection, and infiltrative disorders. His surgical and social histories were unremarkable. He said he had no drug allergies.

On examination, his temperature was 38.1°C (100.6°F), heart rate 101 beats per minute, blood pressure 142/78 mm Hg, respiratory rate 16 breaths per minute, and oxygen saturation 98% on room air. He appeared anxious but was in no acute distress. Neck examination showed no elevation in jugular venous pulsation, bruits, thyromegaly, or lymphadenopathy. Cardiac examination revealed tachycardia without murmurs, rubs, or gallops. Lungs were clear to auscultation. Examination of all 4 extremities found 2+ pulses (on a scale of 0 to 4+) throughout and no cyanosis, clubbing, or edema. Abdominal, neurologic, and dermatologic examinations were unremarkable.

Further blood testing revealed the following:

• Troponin I (3 hours after the first level) 15.5 ng/mL
• B-type natriuretic peptide 200 mg/dL (reference range 0–100 mg/dL)
• C-reactive protein 0.9 mg/dL (reference range 0.0–0.8 mg/dL)
• Erythrocyte sedimentation rate 10 mm/h (reference range < 15 mm/h).

Metabolic and hematologic assessments were unremarkable. A toxicology screen for drugs of abuse was negative. Viral serologic testing was not done.

A chest radiograph showed no acute cardiopulmonary processes.

Given his presenting symptoms, persistent tachycardia, rapidly rising troponin I level, and electrocardiogram showing diffuse ST elevation, he was taken for urgent cardiac catheterization. Coronary angiography revealed no evidence of atherosclerotic disease, acute thrombosis, dissection, or aneurysm. Echocardiography 2 hours after the procedure showed a normal ejection fraction and no regional wall-motion abnormalities or valvular heart disease.

1. Which test should be done next to further evaluate this patient’s chest pain?

• Serum viral serologic testing
• Serum free light chain assay
• Nuclear myocardial perfusion study
• Cardiac magnetic resonance imaging (MRI)
• Endomyocardial biopsy

In this patient without ischemic coronary disease or valvular heart disease, the recent upper respiratory tract prodrome, active positional chest pain, and diffuse electrocardiographic changes raise the possibility of myocarditis with pericardial involvement.

Viral serologic tests

Viral serologic tests are often obtained in the workup of myocarditis as a noninvasive means of detecting an infectious cause.

However, this approach has several problems. First, a positive serologic result is a signal of the peripheral immune response to a pathogen but does not necessarily indicate active myocardial inflammation. Additionally, circulating immunoglobulin G against cardiotropic viruses is commonly found, even in the absence of myocarditis.¹ This is often the result of a high prevalence and exposure to these viruses in the general population. Further, trials have shown no correlation between serologic results and organisms identified by endomyocardial biopsy.²

Thus, serologic testing seems to be of limited utility, reserved for testing for infection with Borrelia burgdorferi (Lyme disease) in endemic areas, hepatitis C virus, human immunodeficiency virus in patients at high risk, Rickettsia conorii, and Rickettsia rickettsii.³

Serum free light chain testing for amyloidosis

Serum free light chain testing is replacing serum and urine protein electrophoresis in the workup of cardiac amyloidosis,⁴ as electrophoresis has poor sensitivity.^4,5

Cardiac amyloidosis often affects older persons, although in rare cases it can affect young patients who carry mutations in the transthyretin gene (ATTR amyloidosis).⁶ This diagnosis is unlikely in our patient, as he has no other affected organ systems (amyloidosis often affects the renal and neurologic systems), normal QRS voltages on electrocardiography (which are often but not always low in amyloidosis), and no left ventricular hypertrophy or diastolic dysfunction on echocardiography (which are often seen in amyloidosis).⁴

Nuclear perfusion imaging for sarcoidosis

Nuclear imaging has a limited role in evaluating myocarditis,³ but positron-emission tomography with fluorine-18 fluorodeoxyglucose has a diagnostic role in sarcoidosis, an immune-mediated cause of myocarditis.⁷

Based on the acuity of the patient’s presentation, preceded by upper respiratory tract symptoms, sarcoidosis is less likely. Sarcoidosis is difficult to diagnose, although when it is the cause of myocarditis, some clues exist, as patients usually present with heart failure symptoms, a second- or third-degree atrioventricular block, or a dilated left ventricle on echocardiography.³ All of these were absent in our patient.

Cardiac MRI

Cardiac MRI has undergone many advances, making it an extremely useful noninvasive test. It has excellent utility as a stand-alone test in diagnosing myocarditis and has synergistic value when combined with endomyocardial biopsy.⁸ It is indicated in hemodynamically stable patients with a clinical suspicion of myocarditis, persistent symptoms, absence of heart failure, and when imaging findings will change management. It is particularly useful to help elucidate a cause and guide tailored therapy.⁹ Therefore, it is a reasonable next step in the diagnostic pathway for this patient.¹⁰

Cardiac MRI also allows for concurrent assessment of scar. In myocardial infarction, the late gadolinium enhancement is subendocardial or transmural. In myocarditis, the pattern differs, being found in the subepicardial lateral free wall (in most patients with parvovirus B19) and mid-myocardial septum (in most patients with herpesvirus 6).^9,11 Cardiac MRI also confers prognostic information for patients with suspected myocarditis.¹²

The Lake Louise criteria⁹ for the diagnosis of myocarditis require 2 of the following:

• Evidence of myocardial edema
• Increased ratio of early gadolinium enhancement between myocardium and skeletal muscle (indicates hyperemia)
• At least 1 focal lesion with nonischemic late gadolinium enhancement (indicates cardiac myocyte injury or scarring).

The Lake Louise criteria may be replaced by T1 and T2 mapping, which was found to be considerably better for diagnosing myocarditis when the 2 were compared.^9,13,14

Endomyocardial biopsy

Endomyocardial biopsy should not be delayed while waiting for cardiac MRI in patients who are hemodynamically unstable or present with life-threatening features (ventricular arrhythmia, left ventricular failure, or resuscitation after sudden cardiac death).^3,10

The indications for endomyocardial biopsy have been highly debated. The 2013 guidelines from the European Society of Cardiology (ESC) recommending endomyocardial biopsy  in all clinically suspected cases of myocarditis have only heightened the controversy.³ The American Heart Association (AHA) guidelines reserve biopsy for patients with suspected myocarditis who have acute or subacute heart failure symptoms or who do not respond to standard medical therapy.¹⁵ Other reasonable indications may include the following: myocarditis with life-threatening ventricular arrhythmias, suspicion of giant cell myocarditis, necrotizing eosinophilic myocarditis, or cardiac sarcoidosis.¹⁶

Endomyocardial biopsy is the only way to make a definitive diagnosis of myocarditis.³ However, given the patchy distribution of myocardial involvement, a negative result does not rule out myocarditis. The diagnostic utility can be improved by increasing the number of samples taken (at least 3 but up to 10), obtaining samples from both ventricles, and using cardiac MRI data to determine which sites to biopsy.^3,13,17,18

Noninvasive testing such as cardiac MRI does not distinguish cell type or etiology (viral vs nonviral).³ Further, endomyocardial biopsy must be performed before immunosuppressive therapy can be safely started.^3,16 At experienced centers, the complication rate is 0% to 0.8%.³ The addition of immunohistochemical testing and viral genomic detection by polymerase chain reaction testing have increased the sensitivity of this technique.¹⁹ Finally, endomyocardial biopsy can help rule out some of the other possibilities in the differential diagnosis for myocarditis, including infiltrative and storage diseases, and possibly cardiac tumors.³

Of additional note, the diffuse ST-segment elevation seen on the patient’s electrocardiogram (Figure 1) is indicative of subepicardial inflammation. Since the distribution involves more than one epicardial coronary territory, this helps to differentiate the changes from those that occur with myocardial infarction.²⁰

Causes of myocarditis are numerous (Table 1),^3,21,22 but viral and postinfectious etiologies remain the most common causes of acute myocarditis.²³

• Parvovirus B19
• Coxsackievirus B
• Adenovirus species
• Human herpesvirus 6
• Staphylococcus aureus
• Corynebacterium diphtheria
• Trypanosoma cruzi
• Influenza H1/N1

INFECTIOUS CAUSES OF MYOCARDITIS

Coxsackievirus B was the agent most often linked to this condition from the 1950s through the 1990s. However, in the last 2 decades, adenovirus species and human herpesvirus 6 have been increasingly encountered, and recently, parvovirus B19 has been credited as the most common culprit,^11,23 at least in the Western world. In developing nations, T cruzi and C diphtheria are the most common offenders^.21

S aureus is a common cause of endocarditis, but it rarely plays a role in myocarditis. When it does, the myocarditis is often the sequela of profound bacteremia. This was much more common before antibiotics were invented.^24,25

Influenza H1/N1 is not among the most common causes of viral myocarditis, but it should be considered during flu season, given its ability to result in fulminant myocarditis.^3,26

TREATMENT FOR MYOCARDITIS

3. Which treatment is the most appropriate at this time?

• Intravenous immunoglobulin
• Interferon beta
• Acyclovir
• Prednisone
• Colchicine

Treatment for myocarditis depends on the cause but always includes supportive care to address the constellation of presenting symptoms. Standard therapies for tachy- or bradyarrhythmias, heart failure, and hemodynamic derangement should be started.

Supportive care

In patients with severe left ventricular dysfunction, an implantable cardiac electronic device, left ventricular assist device, or heart transplant may ultimately be needed. However, if possible these should be deferred for several months to determine response to treatment, since the myocardium can possibly recover.¹⁶

Diuretics, beta-blockers, angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors, and aldosterone antagonists should be given as part of guideline-directed medical therapy for patients with heart failure and reduced ejection fraction.^3,27 However, whether and how the patient should be weaned from these agents after disease recovery are unknown.³

Intravenous immunoglobulin

Intravenous immunoglobulin in high doses has had mixed results. Its efficacy is well documented in children,²¹ but limited supportive data are available in adults.³ As such, recent ESC guidelines do not provide recommendations regarding its use in adults.³

Interferon beta

Interferon beta has shown promise in improving New York Heart Association class and left ventricular ejection fraction.³ This is attributed to its effects on eliminating adenoviral species and enteroviruses. Treatment of enteroviral organisms in particular has been associated with improved 10-year prognosis.³ Interferon beta also has in vitro data showing efficacy at diminishing apoptosis from parvovirus B19.²⁸

Nucleoside analogues

Empiric treatment with nucleoside analogues (acyclovir, ganciclovir, and valacyclovir) has been tried for patients in whom human herpesvirus is suspected as the causative organism, although with unconfirmed effects.³ Consultation with an infectious disease specialist is recommended before starting these agents, and biopsy is often needed beforehand.³

Immunosuppressive agents

Immunosuppressive agents such as prednisone, azathioprine, and cyclosporine can be used in cases of biopsy-proven disease with manifestations of severe heart failure, especially if biopsy results reveal sarcoidosis, giant cell myocarditis, or necrotizing eosinophilic myocarditis. Although the results were neutral in the Myocarditis Treatment Trial,²⁹ the cause of myocarditis in this trial was unknown. Therapy with such agents should be initiated after active infection is ruled out, which also would require a biopsy.

Colchicine

Mechanisms of chest pain in myocarditis include associated pericarditis and coronary artery vasospasm.^3,23 Our patient’s chest pain changed when he changed position, possibly indicating associated pericarditis. In myocarditis with accompanying pericarditis symptoms, colchicine (1–2 mg as an initial dose and then 0.6 mg daily for up to 3 months) can be helpful in alleviating symptoms.^21,30 Thus, starting this agent in a patient who presents with myocarditis in absence of heart failure, arrhythmias, or left ventricular dysfunction is prudent.

Colchicine is used mainly to address the pain associated with pericarditis. For patients who present with pericarditis without myocarditis, nonsteroidal anti-inflammatory drugs (NSAIDs) remain the first-line treatment, with the addition of colchicine leading to faster symptom resolution.³⁰ The benefit of colchicine for isolated myocarditis is not well established, with only limited data showing some clinical effects.³¹

The patient was given colchicine 1.2 mg on the first day and then 0.6 mg daily. Within 2 days, his chest pain had resolved. He did not receive any immunosuppressive agents.

DISCHARGE INSTRUCTIONS

4. Before discharge, this patient should be instructed to do which of the following?

• Take over-the-counter NSAIDs to supplement the effects of colchicine
• Avoid competitive sports and athletics for at least 6 months
• Call to schedule repeat cardiac MRI
• No further instruction is needed

NSAIDs are used by themselves or in combination with colchicine in the treatment of pericarditis, but their use may be associated with worse outcomes in myocarditis.^3,21 Thus, their use is not recommended in most cases.³

Excessive physical activity should be avoided for at least 6 months after the clinical syndrome resolves. This recommendation is included in the most recent ESC guidelines but is based mainly on expert opinion and murine models with coxsackievirus B.³ Periodic reassessment is indicated with exercise stress testing before return to strenuous activity.^3,16,32 Testing should look for exercise tolerance, and exercise electrocardiography also helps to evaluate for clinically relevant arrythmias.

Cardiac MRI can help clarify the prognosis in myocarditis, but the role of repeat testing in guiding therapy is limited.³ Indications for repeat cardiac MRI include presence of 0 or 1 of the Lake Louise criteria (recall that 2 are necessary to make the diagnosis) with recurrence of symptoms and a high suspicion for myocardial inflammation.^3,9 Repeat cardiac MRI was not performed for our patient.

CASE CONCLUDED

The patient was evaluated in the cardiology clinic within 1 week of discharge. At that time, he was in sinus tachycardia with a heart rate of 102 bpm, and he was instructed to avoid any exercise until further notice.

At 6-month follow-up, the sinus tachycardia had resolved. However, because persistent tachycardia had been noted at the first postdischarge visit, and in view of the extent of myocardial involvement, he underwent exercise treadmill testing to evaluate for ventricular arrhythmias. The study did show premature ventricular complexes and 1 ventricular couplet at submaximal exercise levels. As this indicated a higher risk of exercise-induced arrhythmias, he was asked to continue normal activity levels but to abstain from exercise until the next evaluation.

During his 1-year follow-up, a repeat treadmill test showed no ventricular ectopy. Holter monitoring was ordered and showed no premature ventricular complexes, supraventricular arrhythmias, or atrioventricular block within the 48-hour period.

At his 2-year evaluation, he had returned to playing basketball and soccer on weekends and reported no recurrence of his initial symptoms.

KEY POINTS

• 

  Cardiac MRI has emerged as an excellent noninvasive imaging modality for the diagnosis of myocarditis.
• Treatment of myocarditis depends on the cause and severity of the patient’s presentation, spanning the spectrum from conservative care to immunosuppressive agents and even heart failure therapy.
• Excessive physical activity should be avoided for the first 6 months after disease diagnosis and treatment.
• If myocarditis is associated with pericardial involvement, colchicine is the agent of choice, and NSAIDs should be avoided.

Our suggested strategy for approaching myocarditis is shown in Figure 3.

An 18-year-old man without any significant medical history was transferred from another hospital for higher-level care after presenting with unremitting chest pain. He had been in his usual state of good health until 7 days before presentation, when he developed mild rhinorrhea and a sore throat, but not a cough. He went to an outpatient clinic, where a rapid test for group A streptococci was done; the result was negative, and he was sent home on supportive measures.

On the day of admission, he awoke with severe, pressure-like, midsternal, nonradiating pain, which he rated 10 on a scale of 10. The pain intensified in the supine position and improved with sitting. A complete review of systems was otherwise negative. He denied having had similar symptoms in the past, as well as sick contacts, recent travel, toxin exposure, illicit substance abuse, pets at home, or tick bites. His family history was negative for cardiac arrhythmias, premature coronary artery disease, thoracic aneurysms or dissection, and infiltrative disorders. His surgical and social histories were unremarkable. He said he had no drug allergies.

On examination, his temperature was 38.1°C (100.6°F), heart rate 101 beats per minute, blood pressure 142/78 mm Hg, respiratory rate 16 breaths per minute, and oxygen saturation 98% on room air. He appeared anxious but was in no acute distress. Neck examination showed no elevation in jugular venous pulsation, bruits, thyromegaly, or lymphadenopathy. Cardiac examination revealed tachycardia without murmurs, rubs, or gallops. Lungs were clear to auscultation. Examination of all 4 extremities found 2+ pulses (on a scale of 0 to 4+) throughout and no cyanosis, clubbing, or edema. Abdominal, neurologic, and dermatologic examinations were unremarkable.

Further blood testing revealed the following:

• Troponin I (3 hours after the first level) 15.5 ng/mL
• B-type natriuretic peptide 200 mg/dL (reference range 0–100 mg/dL)
• C-reactive protein 0.9 mg/dL (reference range 0.0–0.8 mg/dL)
• Erythrocyte sedimentation rate 10 mm/h (reference range < 15 mm/h).

Metabolic and hematologic assessments were unremarkable. A toxicology screen for drugs of abuse was negative. Viral serologic testing was not done.

A chest radiograph showed no acute cardiopulmonary processes.

Given his presenting symptoms, persistent tachycardia, rapidly rising troponin I level, and electrocardiogram showing diffuse ST elevation, he was taken for urgent cardiac catheterization. Coronary angiography revealed no evidence of atherosclerotic disease, acute thrombosis, dissection, or aneurysm. Echocardiography 2 hours after the procedure showed a normal ejection fraction and no regional wall-motion abnormalities or valvular heart disease.

1. Which test should be done next to further evaluate this patient’s chest pain?

• Serum viral serologic testing
• Serum free light chain assay
• Nuclear myocardial perfusion study
• Cardiac magnetic resonance imaging (MRI)
• Endomyocardial biopsy

In this patient without ischemic coronary disease or valvular heart disease, the recent upper respiratory tract prodrome, active positional chest pain, and diffuse electrocardiographic changes raise the possibility of myocarditis with pericardial involvement.

Viral serologic tests

Viral serologic tests are often obtained in the workup of myocarditis as a noninvasive means of detecting an infectious cause.

However, this approach has several problems. First, a positive serologic result is a signal of the peripheral immune response to a pathogen but does not necessarily indicate active myocardial inflammation. Additionally, circulating immunoglobulin G against cardiotropic viruses is commonly found, even in the absence of myocarditis.¹ This is often the result of a high prevalence and exposure to these viruses in the general population. Further, trials have shown no correlation between serologic results and organisms identified by endomyocardial biopsy.²

Thus, serologic testing seems to be of limited utility, reserved for testing for infection with Borrelia burgdorferi (Lyme disease) in endemic areas, hepatitis C virus, human immunodeficiency virus in patients at high risk, Rickettsia conorii, and Rickettsia rickettsii.³

Serum free light chain testing for amyloidosis

Serum free light chain testing is replacing serum and urine protein electrophoresis in the workup of cardiac amyloidosis,⁴ as electrophoresis has poor sensitivity.^4,5

Cardiac amyloidosis often affects older persons, although in rare cases it can affect young patients who carry mutations in the transthyretin gene (ATTR amyloidosis).⁶ This diagnosis is unlikely in our patient, as he has no other affected organ systems (amyloidosis often affects the renal and neurologic systems), normal QRS voltages on electrocardiography (which are often but not always low in amyloidosis), and no left ventricular hypertrophy or diastolic dysfunction on echocardiography (which are often seen in amyloidosis).⁴

Nuclear perfusion imaging for sarcoidosis

Nuclear imaging has a limited role in evaluating myocarditis,³ but positron-emission tomography with fluorine-18 fluorodeoxyglucose has a diagnostic role in sarcoidosis, an immune-mediated cause of myocarditis.⁷

Based on the acuity of the patient’s presentation, preceded by upper respiratory tract symptoms, sarcoidosis is less likely. Sarcoidosis is difficult to diagnose, although when it is the cause of myocarditis, some clues exist, as patients usually present with heart failure symptoms, a second- or third-degree atrioventricular block, or a dilated left ventricle on echocardiography.³ All of these were absent in our patient.

Cardiac MRI

Cardiac MRI has undergone many advances, making it an extremely useful noninvasive test. It has excellent utility as a stand-alone test in diagnosing myocarditis and has synergistic value when combined with endomyocardial biopsy.⁸ It is indicated in hemodynamically stable patients with a clinical suspicion of myocarditis, persistent symptoms, absence of heart failure, and when imaging findings will change management. It is particularly useful to help elucidate a cause and guide tailored therapy.⁹ Therefore, it is a reasonable next step in the diagnostic pathway for this patient.¹⁰

Cardiac MRI also allows for concurrent assessment of scar. In myocardial infarction, the late gadolinium enhancement is subendocardial or transmural. In myocarditis, the pattern differs, being found in the subepicardial lateral free wall (in most patients with parvovirus B19) and mid-myocardial septum (in most patients with herpesvirus 6).^9,11 Cardiac MRI also confers prognostic information for patients with suspected myocarditis.¹²

The Lake Louise criteria⁹ for the diagnosis of myocarditis require 2 of the following:

• Evidence of myocardial edema
• Increased ratio of early gadolinium enhancement between myocardium and skeletal muscle (indicates hyperemia)
• At least 1 focal lesion with nonischemic late gadolinium enhancement (indicates cardiac myocyte injury or scarring).

The Lake Louise criteria may be replaced by T1 and T2 mapping, which was found to be considerably better for diagnosing myocarditis when the 2 were compared.^9,13,14

Endomyocardial biopsy

Endomyocardial biopsy should not be delayed while waiting for cardiac MRI in patients who are hemodynamically unstable or present with life-threatening features (ventricular arrhythmia, left ventricular failure, or resuscitation after sudden cardiac death).^3,10

The indications for endomyocardial biopsy have been highly debated. The 2013 guidelines from the European Society of Cardiology (ESC) recommending endomyocardial biopsy  in all clinically suspected cases of myocarditis have only heightened the controversy.³ The American Heart Association (AHA) guidelines reserve biopsy for patients with suspected myocarditis who have acute or subacute heart failure symptoms or who do not respond to standard medical therapy.¹⁵ Other reasonable indications may include the following: myocarditis with life-threatening ventricular arrhythmias, suspicion of giant cell myocarditis, necrotizing eosinophilic myocarditis, or cardiac sarcoidosis.¹⁶

Endomyocardial biopsy is the only way to make a definitive diagnosis of myocarditis.³ However, given the patchy distribution of myocardial involvement, a negative result does not rule out myocarditis. The diagnostic utility can be improved by increasing the number of samples taken (at least 3 but up to 10), obtaining samples from both ventricles, and using cardiac MRI data to determine which sites to biopsy.^3,13,17,18

Noninvasive testing such as cardiac MRI does not distinguish cell type or etiology (viral vs nonviral).³ Further, endomyocardial biopsy must be performed before immunosuppressive therapy can be safely started.^3,16 At experienced centers, the complication rate is 0% to 0.8%.³ The addition of immunohistochemical testing and viral genomic detection by polymerase chain reaction testing have increased the sensitivity of this technique.¹⁹ Finally, endomyocardial biopsy can help rule out some of the other possibilities in the differential diagnosis for myocarditis, including infiltrative and storage diseases, and possibly cardiac tumors.³

Of additional note, the diffuse ST-segment elevation seen on the patient’s electrocardiogram (Figure 1) is indicative of subepicardial inflammation. Since the distribution involves more than one epicardial coronary territory, this helps to differentiate the changes from those that occur with myocardial infarction.²⁰

Causes of myocarditis are numerous (Table 1),^3,21,22 but viral and postinfectious etiologies remain the most common causes of acute myocarditis.²³

• Parvovirus B19
• Coxsackievirus B
• Adenovirus species
• Human herpesvirus 6
• Staphylococcus aureus
• Corynebacterium diphtheria
• Trypanosoma cruzi
• Influenza H1/N1

INFECTIOUS CAUSES OF MYOCARDITIS

Coxsackievirus B was the agent most often linked to this condition from the 1950s through the 1990s. However, in the last 2 decades, adenovirus species and human herpesvirus 6 have been increasingly encountered, and recently, parvovirus B19 has been credited as the most common culprit,^11,23 at least in the Western world. In developing nations, T cruzi and C diphtheria are the most common offenders^.21

S aureus is a common cause of endocarditis, but it rarely plays a role in myocarditis. When it does, the myocarditis is often the sequela of profound bacteremia. This was much more common before antibiotics were invented.^24,25

Influenza H1/N1 is not among the most common causes of viral myocarditis, but it should be considered during flu season, given its ability to result in fulminant myocarditis.^3,26

TREATMENT FOR MYOCARDITIS

3. Which treatment is the most appropriate at this time?

• Intravenous immunoglobulin
• Interferon beta
• Acyclovir
• Prednisone
• Colchicine

Treatment for myocarditis depends on the cause but always includes supportive care to address the constellation of presenting symptoms. Standard therapies for tachy- or bradyarrhythmias, heart failure, and hemodynamic derangement should be started.

Supportive care

In patients with severe left ventricular dysfunction, an implantable cardiac electronic device, left ventricular assist device, or heart transplant may ultimately be needed. However, if possible these should be deferred for several months to determine response to treatment, since the myocardium can possibly recover.¹⁶

Diuretics, beta-blockers, angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors, and aldosterone antagonists should be given as part of guideline-directed medical therapy for patients with heart failure and reduced ejection fraction.^3,27 However, whether and how the patient should be weaned from these agents after disease recovery are unknown.³

Intravenous immunoglobulin

Intravenous immunoglobulin in high doses has had mixed results. Its efficacy is well documented in children,²¹ but limited supportive data are available in adults.³ As such, recent ESC guidelines do not provide recommendations regarding its use in adults.³

Interferon beta

Interferon beta has shown promise in improving New York Heart Association class and left ventricular ejection fraction.³ This is attributed to its effects on eliminating adenoviral species and enteroviruses. Treatment of enteroviral organisms in particular has been associated with improved 10-year prognosis.³ Interferon beta also has in vitro data showing efficacy at diminishing apoptosis from parvovirus B19.²⁸

Nucleoside analogues

Empiric treatment with nucleoside analogues (acyclovir, ganciclovir, and valacyclovir) has been tried for patients in whom human herpesvirus is suspected as the causative organism, although with unconfirmed effects.³ Consultation with an infectious disease specialist is recommended before starting these agents, and biopsy is often needed beforehand.³

Immunosuppressive agents

Immunosuppressive agents such as prednisone, azathioprine, and cyclosporine can be used in cases of biopsy-proven disease with manifestations of severe heart failure, especially if biopsy results reveal sarcoidosis, giant cell myocarditis, or necrotizing eosinophilic myocarditis. Although the results were neutral in the Myocarditis Treatment Trial,²⁹ the cause of myocarditis in this trial was unknown. Therapy with such agents should be initiated after active infection is ruled out, which also would require a biopsy.

Colchicine

Mechanisms of chest pain in myocarditis include associated pericarditis and coronary artery vasospasm.^3,23 Our patient’s chest pain changed when he changed position, possibly indicating associated pericarditis. In myocarditis with accompanying pericarditis symptoms, colchicine (1–2 mg as an initial dose and then 0.6 mg daily for up to 3 months) can be helpful in alleviating symptoms.^21,30 Thus, starting this agent in a patient who presents with myocarditis in absence of heart failure, arrhythmias, or left ventricular dysfunction is prudent.

Colchicine is used mainly to address the pain associated with pericarditis. For patients who present with pericarditis without myocarditis, nonsteroidal anti-inflammatory drugs (NSAIDs) remain the first-line treatment, with the addition of colchicine leading to faster symptom resolution.³⁰ The benefit of colchicine for isolated myocarditis is not well established, with only limited data showing some clinical effects.³¹

The patient was given colchicine 1.2 mg on the first day and then 0.6 mg daily. Within 2 days, his chest pain had resolved. He did not receive any immunosuppressive agents.

DISCHARGE INSTRUCTIONS

4. Before discharge, this patient should be instructed to do which of the following?

• Take over-the-counter NSAIDs to supplement the effects of colchicine
• Avoid competitive sports and athletics for at least 6 months
• Call to schedule repeat cardiac MRI
• No further instruction is needed

NSAIDs are used by themselves or in combination with colchicine in the treatment of pericarditis, but their use may be associated with worse outcomes in myocarditis.^3,21 Thus, their use is not recommended in most cases.³

Excessive physical activity should be avoided for at least 6 months after the clinical syndrome resolves. This recommendation is included in the most recent ESC guidelines but is based mainly on expert opinion and murine models with coxsackievirus B.³ Periodic reassessment is indicated with exercise stress testing before return to strenuous activity.^3,16,32 Testing should look for exercise tolerance, and exercise electrocardiography also helps to evaluate for clinically relevant arrythmias.

Cardiac MRI can help clarify the prognosis in myocarditis, but the role of repeat testing in guiding therapy is limited.³ Indications for repeat cardiac MRI include presence of 0 or 1 of the Lake Louise criteria (recall that 2 are necessary to make the diagnosis) with recurrence of symptoms and a high suspicion for myocardial inflammation.^3,9 Repeat cardiac MRI was not performed for our patient.

CASE CONCLUDED

The patient was evaluated in the cardiology clinic within 1 week of discharge. At that time, he was in sinus tachycardia with a heart rate of 102 bpm, and he was instructed to avoid any exercise until further notice.

At 6-month follow-up, the sinus tachycardia had resolved. However, because persistent tachycardia had been noted at the first postdischarge visit, and in view of the extent of myocardial involvement, he underwent exercise treadmill testing to evaluate for ventricular arrhythmias. The study did show premature ventricular complexes and 1 ventricular couplet at submaximal exercise levels. As this indicated a higher risk of exercise-induced arrhythmias, he was asked to continue normal activity levels but to abstain from exercise until the next evaluation.

During his 1-year follow-up, a repeat treadmill test showed no ventricular ectopy. Holter monitoring was ordered and showed no premature ventricular complexes, supraventricular arrhythmias, or atrioventricular block within the 48-hour period.

At his 2-year evaluation, he had returned to playing basketball and soccer on weekends and reported no recurrence of his initial symptoms.

KEY POINTS

• 

  Cardiac MRI has emerged as an excellent noninvasive imaging modality for the diagnosis of myocarditis.
• Treatment of myocarditis depends on the cause and severity of the patient’s presentation, spanning the spectrum from conservative care to immunosuppressive agents and even heart failure therapy.
• Excessive physical activity should be avoided for the first 6 months after disease diagnosis and treatment.
• If myocarditis is associated with pericardial involvement, colchicine is the agent of choice, and NSAIDs should be avoided.

Our suggested strategy for approaching myocarditis is shown in Figure 3.

A new study has reaffirmed that, as methicillin‐sensitive Staphylococcus aureus (MSSA) remains the most common skin infection in pediatric atopic dermatitis (AD) patients, first‐generation cephalosporins remain the appropriate empiric therapy.

“Clindamycin, tetracyclines, or TMP‐SMX can be considered in patients suspected to have, or with a history of, MRSA [methicillin‐resistant S. aureus] infection,” wrote Cristopher C. Briscoe, MD, of the Washington University School of Medicine in St. Louis, Missouri, and his coauthors. The study was published in Pediatric Dermatology.

To determine the optimal empiric antibiotic for pediatric AD patients with skin infections, the researchers analyzed skin cultures from 106 patients seen at Saint Louis Children’s Hospital (SLCH). The results were also compared to cultures from pediatric patients who presented at the SLCH emergency department (ED) with S. aureus skin abscesses.

Of the 170 cultures that grew S. aureus, 130 (77.8%) grew MSSA, and 37 (22.2%) grew MRSA. Three of the cultures grew both. The prevalence of MRSA in the cohort differed from the prevalence in the ED patients (44%). The prevalence of either infection did not differ significantly by age, sex or race, though the average number of cultures in African American patients topped the average for Caucasian patients (1.8 vs. 1.2, P less than .003).

All patients with MSSA – in both the cohort and the ED – proved 100% susceptible to cefazolin. Cohort patients with MSSA saw lower susceptibility to doxycycline compared to the ED patients (89.4% vs. 97%), as did MRSA cohort patients to trimethoprim‐sulfamethoxazole (92% vs. 98%).

“When a patient with AD walks into your office and looks like they have an infection of their eczema, your go-to antibiotic is going to be one that targets MSSA,” said coauthor Carrie Coughlin, MD, of the Washington University School of Medicine in an interview. “You’ll still do a culture to prove or disprove that assumption, but it gives you a guide to help make that patient better in the short term while you work things up.”

“Also, remember that MSSA is not ‘better’ to have than MRSA,” she added. “You can now see some of the virulence factors from MRSA strains in MSSA strains, so treating both of them is important.”

The authors acknowledged their study’s limitations, including the limited generalizability of a single-center design and a lack of information as to the body sites from which the cultures were obtained. They were also unable to reliably determine prior antibiotic exposure, noting that “future work could examine whether prior exposure differed significantly in the MRSA and MSSA groups.”

The study was funded by grants from the Agency for Healthcare Research and Quality. The authors reported no conflicts of interest.


SOURCE: Briscoe CC et al. Pediatr Dermatol. 2019 May 24. doi: 10.1111/pde.13867.

A new study has reaffirmed that, as methicillin‐sensitive Staphylococcus aureus (MSSA) remains the most common skin infection in pediatric atopic dermatitis (AD) patients, first‐generation cephalosporins remain the appropriate empiric therapy.

“Clindamycin, tetracyclines, or TMP‐SMX can be considered in patients suspected to have, or with a history of, MRSA [methicillin‐resistant S. aureus] infection,” wrote Cristopher C. Briscoe, MD, of the Washington University School of Medicine in St. Louis, Missouri, and his coauthors. The study was published in Pediatric Dermatology.

To determine the optimal empiric antibiotic for pediatric AD patients with skin infections, the researchers analyzed skin cultures from 106 patients seen at Saint Louis Children’s Hospital (SLCH). The results were also compared to cultures from pediatric patients who presented at the SLCH emergency department (ED) with S. aureus skin abscesses.

Of the 170 cultures that grew S. aureus, 130 (77.8%) grew MSSA, and 37 (22.2%) grew MRSA. Three of the cultures grew both. The prevalence of MRSA in the cohort differed from the prevalence in the ED patients (44%). The prevalence of either infection did not differ significantly by age, sex or race, though the average number of cultures in African American patients topped the average for Caucasian patients (1.8 vs. 1.2, P less than .003).

All patients with MSSA – in both the cohort and the ED – proved 100% susceptible to cefazolin. Cohort patients with MSSA saw lower susceptibility to doxycycline compared to the ED patients (89.4% vs. 97%), as did MRSA cohort patients to trimethoprim‐sulfamethoxazole (92% vs. 98%).

“When a patient with AD walks into your office and looks like they have an infection of their eczema, your go-to antibiotic is going to be one that targets MSSA,” said coauthor Carrie Coughlin, MD, of the Washington University School of Medicine in an interview. “You’ll still do a culture to prove or disprove that assumption, but it gives you a guide to help make that patient better in the short term while you work things up.”

“Also, remember that MSSA is not ‘better’ to have than MRSA,” she added. “You can now see some of the virulence factors from MRSA strains in MSSA strains, so treating both of them is important.”

The authors acknowledged their study’s limitations, including the limited generalizability of a single-center design and a lack of information as to the body sites from which the cultures were obtained. They were also unable to reliably determine prior antibiotic exposure, noting that “future work could examine whether prior exposure differed significantly in the MRSA and MSSA groups.”

The study was funded by grants from the Agency for Healthcare Research and Quality. The authors reported no conflicts of interest.


SOURCE: Briscoe CC et al. Pediatr Dermatol. 2019 May 24. doi: 10.1111/pde.13867.

A new study has reaffirmed that, as methicillin‐sensitive Staphylococcus aureus (MSSA) remains the most common skin infection in pediatric atopic dermatitis (AD) patients, first‐generation cephalosporins remain the appropriate empiric therapy.

“Clindamycin, tetracyclines, or TMP‐SMX can be considered in patients suspected to have, or with a history of, MRSA [methicillin‐resistant S. aureus] infection,” wrote Cristopher C. Briscoe, MD, of the Washington University School of Medicine in St. Louis, Missouri, and his coauthors. The study was published in Pediatric Dermatology.

To determine the optimal empiric antibiotic for pediatric AD patients with skin infections, the researchers analyzed skin cultures from 106 patients seen at Saint Louis Children’s Hospital (SLCH). The results were also compared to cultures from pediatric patients who presented at the SLCH emergency department (ED) with S. aureus skin abscesses.

Of the 170 cultures that grew S. aureus, 130 (77.8%) grew MSSA, and 37 (22.2%) grew MRSA. Three of the cultures grew both. The prevalence of MRSA in the cohort differed from the prevalence in the ED patients (44%). The prevalence of either infection did not differ significantly by age, sex or race, though the average number of cultures in African American patients topped the average for Caucasian patients (1.8 vs. 1.2, P less than .003).

All patients with MSSA – in both the cohort and the ED – proved 100% susceptible to cefazolin. Cohort patients with MSSA saw lower susceptibility to doxycycline compared to the ED patients (89.4% vs. 97%), as did MRSA cohort patients to trimethoprim‐sulfamethoxazole (92% vs. 98%).

“When a patient with AD walks into your office and looks like they have an infection of their eczema, your go-to antibiotic is going to be one that targets MSSA,” said coauthor Carrie Coughlin, MD, of the Washington University School of Medicine in an interview. “You’ll still do a culture to prove or disprove that assumption, but it gives you a guide to help make that patient better in the short term while you work things up.”

“Also, remember that MSSA is not ‘better’ to have than MRSA,” she added. “You can now see some of the virulence factors from MRSA strains in MSSA strains, so treating both of them is important.”

The authors acknowledged their study’s limitations, including the limited generalizability of a single-center design and a lack of information as to the body sites from which the cultures were obtained. They were also unable to reliably determine prior antibiotic exposure, noting that “future work could examine whether prior exposure differed significantly in the MRSA and MSSA groups.”

The study was funded by grants from the Agency for Healthcare Research and Quality. The authors reported no conflicts of interest.


SOURCE: Briscoe CC et al. Pediatr Dermatol. 2019 May 24. doi: 10.1111/pde.13867.

Parents who accepted, denied, or partially accepted participation in the Dutch National Immunization Program reached their decisions through different methods, according to Kim A.G.J. Romijnders of the National Institute for Public Health and the Environment in Bilthoven, the Netherlands, and associates.

MarianVejcik/Getty Images

For the study published in Vaccine, the investigators conducted a series of 12 focus groups: 3 with accepters (n = 19), 3 with deniers (n =12), and 6 with partial accepters (n =24); in the partial accepters groups, there were three groups with parents delaying vaccination and three with parents refusing some vaccinations. Three-quarters of participants were women, the average age was 39 years, and 96% had at least university education. Parents were asked about their knowledge, attitudes, deliberation, and information needs regarding childhood vaccination.

Vaccine accepters regarded the decision to vaccinate their children as self-evident, but deniers and partial accepters reported conducting extensive deliberation on the pros and cons of vaccination. Deniers and partial accepters, in general, perceived fewer risks of vaccine-preventable diseases, more risks of vaccine side effects, less social support from their environment, less trust in child welfare centers, and provided less information than accepters.

The investigators noted that vaccine deniers tended to rely on anecdotal evidence, while the deliberation that partial accepters undertook was both time consuming and difficult. This process alienated them from their child vaccine provider, with trust being lost when the provider either refused or was unable to answer questions. Partial accepters also reported a lack of social support from friends, family, and providers regarding partial vaccine acceptance.

“The findings can facilitate informed decision making among parents by promoting an open dialogue at the [child welfare center], and improving the type and form of information presented. An open dialogue between parents and [child vaccine providers] may increase deliberation among parents, strengthen positive attitudes, prevent misperceptions, and resolve decisional conflict,” the investigators concluded.

The study was supported by the Dutch National Institute for Public Health and the Environment; the authors reported no conflicts of interest.

[email protected]

SOURCE: Romijnders KAGJ et al. Vaccine. 2019 Aug 2. doi: 10.1016/j.vaccine.2019.07.060.

Parents who accepted, denied, or partially accepted participation in the Dutch National Immunization Program reached their decisions through different methods, according to Kim A.G.J. Romijnders of the National Institute for Public Health and the Environment in Bilthoven, the Netherlands, and associates.

MarianVejcik/Getty Images

For the study published in Vaccine, the investigators conducted a series of 12 focus groups: 3 with accepters (n = 19), 3 with deniers (n =12), and 6 with partial accepters (n =24); in the partial accepters groups, there were three groups with parents delaying vaccination and three with parents refusing some vaccinations. Three-quarters of participants were women, the average age was 39 years, and 96% had at least university education. Parents were asked about their knowledge, attitudes, deliberation, and information needs regarding childhood vaccination.

Vaccine accepters regarded the decision to vaccinate their children as self-evident, but deniers and partial accepters reported conducting extensive deliberation on the pros and cons of vaccination. Deniers and partial accepters, in general, perceived fewer risks of vaccine-preventable diseases, more risks of vaccine side effects, less social support from their environment, less trust in child welfare centers, and provided less information than accepters.

The investigators noted that vaccine deniers tended to rely on anecdotal evidence, while the deliberation that partial accepters undertook was both time consuming and difficult. This process alienated them from their child vaccine provider, with trust being lost when the provider either refused or was unable to answer questions. Partial accepters also reported a lack of social support from friends, family, and providers regarding partial vaccine acceptance.

“The findings can facilitate informed decision making among parents by promoting an open dialogue at the [child welfare center], and improving the type and form of information presented. An open dialogue between parents and [child vaccine providers] may increase deliberation among parents, strengthen positive attitudes, prevent misperceptions, and resolve decisional conflict,” the investigators concluded.

The study was supported by the Dutch National Institute for Public Health and the Environment; the authors reported no conflicts of interest.

[email protected]

SOURCE: Romijnders KAGJ et al. Vaccine. 2019 Aug 2. doi: 10.1016/j.vaccine.2019.07.060.

Parents who accepted, denied, or partially accepted participation in the Dutch National Immunization Program reached their decisions through different methods, according to Kim A.G.J. Romijnders of the National Institute for Public Health and the Environment in Bilthoven, the Netherlands, and associates.

MarianVejcik/Getty Images

For the study published in Vaccine, the investigators conducted a series of 12 focus groups: 3 with accepters (n = 19), 3 with deniers (n =12), and 6 with partial accepters (n =24); in the partial accepters groups, there were three groups with parents delaying vaccination and three with parents refusing some vaccinations. Three-quarters of participants were women, the average age was 39 years, and 96% had at least university education. Parents were asked about their knowledge, attitudes, deliberation, and information needs regarding childhood vaccination.

Vaccine accepters regarded the decision to vaccinate their children as self-evident, but deniers and partial accepters reported conducting extensive deliberation on the pros and cons of vaccination. Deniers and partial accepters, in general, perceived fewer risks of vaccine-preventable diseases, more risks of vaccine side effects, less social support from their environment, less trust in child welfare centers, and provided less information than accepters.

The investigators noted that vaccine deniers tended to rely on anecdotal evidence, while the deliberation that partial accepters undertook was both time consuming and difficult. This process alienated them from their child vaccine provider, with trust being lost when the provider either refused or was unable to answer questions. Partial accepters also reported a lack of social support from friends, family, and providers regarding partial vaccine acceptance.

“The findings can facilitate informed decision making among parents by promoting an open dialogue at the [child welfare center], and improving the type and form of information presented. An open dialogue between parents and [child vaccine providers] may increase deliberation among parents, strengthen positive attitudes, prevent misperceptions, and resolve decisional conflict,” the investigators concluded.

The study was supported by the Dutch National Institute for Public Health and the Environment; the authors reported no conflicts of interest.

[email protected]

SOURCE: Romijnders KAGJ et al. Vaccine. 2019 Aug 2. doi: 10.1016/j.vaccine.2019.07.060.

The Food and Drug Administration has warned that certain hepatitis C virus medications have led to rare instances of worsening liver function or liver failure.

Many of the affected patients had signs or symptoms of moderate to severe liver impairment (Child-Pugh class B or C), and given that these medications – glecaprevir/pibrentasvir (Mavyret), elbasvir/grazoprevir (Zepatier), and sofosbuvir/velpatasvir/voxilaprevir (Vosevi) – are not indicated for such patients, they should not have been prescribed in the first place, the FDA noted in the drug safety communication. Some cases had other preexisting risk factors, such as liver cancer, alcohol abuse, or serious medical illnesses associated with liver problems.

In most cases, impairment or decompensation occurred within the first 4 weeks of starting treatment, and symptoms resolved or new-onset worsening of liver function improved after stopping. These medicines have been widely used and, among patients with no or mild liver impairment, have been shown to be safe and effective.

Health care professionals should continue prescribing these medicines as indicated; they should assess patients at baseline for severity of liver disease and other risk factors and closely monitor these patients after for signs and symptoms of worsening liver function. Patients should be aware that the risk of injury is rare and continue taking prescribed medicines; if they develop fatigue, weakness, loss of appetite, nausea and vomiting, yellow eyes or skin, or light-colored stools, they should talk with their health care professional but should continue taking the medications in question until instructed to do otherwise.

The full communication is available on the FDA website and includes more facts about these drugs and information for patients and health care professionals.

[email protected]

The Food and Drug Administration has warned that certain hepatitis C virus medications have led to rare instances of worsening liver function or liver failure.

Many of the affected patients had signs or symptoms of moderate to severe liver impairment (Child-Pugh class B or C), and given that these medications – glecaprevir/pibrentasvir (Mavyret), elbasvir/grazoprevir (Zepatier), and sofosbuvir/velpatasvir/voxilaprevir (Vosevi) – are not indicated for such patients, they should not have been prescribed in the first place, the FDA noted in the drug safety communication. Some cases had other preexisting risk factors, such as liver cancer, alcohol abuse, or serious medical illnesses associated with liver problems.

In most cases, impairment or decompensation occurred within the first 4 weeks of starting treatment, and symptoms resolved or new-onset worsening of liver function improved after stopping. These medicines have been widely used and, among patients with no or mild liver impairment, have been shown to be safe and effective.

Health care professionals should continue prescribing these medicines as indicated; they should assess patients at baseline for severity of liver disease and other risk factors and closely monitor these patients after for signs and symptoms of worsening liver function. Patients should be aware that the risk of injury is rare and continue taking prescribed medicines; if they develop fatigue, weakness, loss of appetite, nausea and vomiting, yellow eyes or skin, or light-colored stools, they should talk with their health care professional but should continue taking the medications in question until instructed to do otherwise.

The full communication is available on the FDA website and includes more facts about these drugs and information for patients and health care professionals.

[email protected]

The Food and Drug Administration has warned that certain hepatitis C virus medications have led to rare instances of worsening liver function or liver failure.

Many of the affected patients had signs or symptoms of moderate to severe liver impairment (Child-Pugh class B or C), and given that these medications – glecaprevir/pibrentasvir (Mavyret), elbasvir/grazoprevir (Zepatier), and sofosbuvir/velpatasvir/voxilaprevir (Vosevi) – are not indicated for such patients, they should not have been prescribed in the first place, the FDA noted in the drug safety communication. Some cases had other preexisting risk factors, such as liver cancer, alcohol abuse, or serious medical illnesses associated with liver problems.

In most cases, impairment or decompensation occurred within the first 4 weeks of starting treatment, and symptoms resolved or new-onset worsening of liver function improved after stopping. These medicines have been widely used and, among patients with no or mild liver impairment, have been shown to be safe and effective.

Health care professionals should continue prescribing these medicines as indicated; they should assess patients at baseline for severity of liver disease and other risk factors and closely monitor these patients after for signs and symptoms of worsening liver function. Patients should be aware that the risk of injury is rare and continue taking prescribed medicines; if they develop fatigue, weakness, loss of appetite, nausea and vomiting, yellow eyes or skin, or light-colored stools, they should talk with their health care professional but should continue taking the medications in question until instructed to do otherwise.

The full communication is available on the FDA website and includes more facts about these drugs and information for patients and health care professionals.

[email protected]

SEATTLE – If your hospital’s methicillin-resistant Staphylococcus aureus rate is less than 10%, cefazolin is a reasonable empiric choice for pediatric acute hematogenous osteomyelitis (AHO). It covers the usual suspects: methicillin-susceptible Staphylococcus aureus, group A Streptococcus, and Kingella.

Above the 10% mark, coverage should include considerations of MRSA; clindamycin is good option so long as 85% of isolates are susceptible. Above that, it’s time for vancomycin, according to Nivedita Srinivas, MD, a pediatric infectious disease specialist at Stanford (Calif.) University.

There are no practice guidelines in the United States for the diagnosis and management of AHO in children; Dr. Srinivas and colleagues sought to plug the gaps in a talk at Pediatric Hospitalist Medicine.

Pediatric AHO is more common in children under 5 years old and in boys. Lower extremities are the usual targets. Staphylococcus aureus, group B Streptococcus, and gram negatives are the most common causes in newborns; Staphylococcus aureus, group A Streptococcus, and Kingella in older infants and preschoolers; and Staphylococcus aureus and group A Streptococcus in older children.

About half the time, treatment remains empiric because nothing grows out on culture, and there are a few clinical pearls to keep in mind in those cases. A family history of boils or spider bites is suspicious for MRSA, and coverage should include Salmonella in children with abnormal hemoglobins and Streptococcus pneumoniae in children without a spleen or with functional asplenia. Pseudomonas has to be kept in mind with puncture wounds, and Brucella in children who drink unpasteurized milk, Dr. Srinivas said.

A switch from IV to oral therapy is appropriate when C-reactive protein (CRP) drops 50% from its peak or below 3 mg/dL, positive cultures – if any – turn negative, fever has been absent for 24 hours, there’s no sign of metastatic disease, and patients have markedly reduced pain and can bear weight on the infected limb, said copresenter Marie Wang, MD, also a pediatric infectious disease specialist at Stanford.

The oral switch, of course, must have similar coverage as the IV antibiotic: high-dose cephalexin for cefazolin, for instance. Children can be sent home on a PICC line to continue IV treatment, but they won’t do any better than children switched to an oral treatment, and the indwelling catheter can cause problems, she said.

Pleuritic or other sudden pain at a distant site suggests septic emboli. “[Staphylococcus aureus] is notorious for going places you don’t” expect it to go “and forming microabscesses, which become larger abscesses” and need to be drained, said the third presenter, Russell McCulloh, MD, a pediatric infectious disease specialist at the University of Nebraska Medical Center, Omaha.

Four weeks of antibiotics are usually enough, so long as there aren’t complications such as septic thrombophlebitis, endocarditis, sickle cell disease, skull involvement, or immunodeficiencies. Source control and good, postdischarge care – including regular CRP and antibiotic toxicity labs – are critical. Monitoring is recommended for a year.

“X-rays are good at looking for longer-term complications, but bony abnormalities are not going to show up for the first 2 weeks,” Dr. McCulloh said.

The presenters didn’t have any relevant disclosures. The meeting was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

[email protected]

SEATTLE – If your hospital’s methicillin-resistant Staphylococcus aureus rate is less than 10%, cefazolin is a reasonable empiric choice for pediatric acute hematogenous osteomyelitis (AHO). It covers the usual suspects: methicillin-susceptible Staphylococcus aureus, group A Streptococcus, and Kingella.

Above the 10% mark, coverage should include considerations of MRSA; clindamycin is good option so long as 85% of isolates are susceptible. Above that, it’s time for vancomycin, according to Nivedita Srinivas, MD, a pediatric infectious disease specialist at Stanford (Calif.) University.

There are no practice guidelines in the United States for the diagnosis and management of AHO in children; Dr. Srinivas and colleagues sought to plug the gaps in a talk at Pediatric Hospitalist Medicine.

Pediatric AHO is more common in children under 5 years old and in boys. Lower extremities are the usual targets. Staphylococcus aureus, group B Streptococcus, and gram negatives are the most common causes in newborns; Staphylococcus aureus, group A Streptococcus, and Kingella in older infants and preschoolers; and Staphylococcus aureus and group A Streptococcus in older children.

About half the time, treatment remains empiric because nothing grows out on culture, and there are a few clinical pearls to keep in mind in those cases. A family history of boils or spider bites is suspicious for MRSA, and coverage should include Salmonella in children with abnormal hemoglobins and Streptococcus pneumoniae in children without a spleen or with functional asplenia. Pseudomonas has to be kept in mind with puncture wounds, and Brucella in children who drink unpasteurized milk, Dr. Srinivas said.

A switch from IV to oral therapy is appropriate when C-reactive protein (CRP) drops 50% from its peak or below 3 mg/dL, positive cultures – if any – turn negative, fever has been absent for 24 hours, there’s no sign of metastatic disease, and patients have markedly reduced pain and can bear weight on the infected limb, said copresenter Marie Wang, MD, also a pediatric infectious disease specialist at Stanford.

The oral switch, of course, must have similar coverage as the IV antibiotic: high-dose cephalexin for cefazolin, for instance. Children can be sent home on a PICC line to continue IV treatment, but they won’t do any better than children switched to an oral treatment, and the indwelling catheter can cause problems, she said.

Pleuritic or other sudden pain at a distant site suggests septic emboli. “[Staphylococcus aureus] is notorious for going places you don’t” expect it to go “and forming microabscesses, which become larger abscesses” and need to be drained, said the third presenter, Russell McCulloh, MD, a pediatric infectious disease specialist at the University of Nebraska Medical Center, Omaha.

Four weeks of antibiotics are usually enough, so long as there aren’t complications such as septic thrombophlebitis, endocarditis, sickle cell disease, skull involvement, or immunodeficiencies. Source control and good, postdischarge care – including regular CRP and antibiotic toxicity labs – are critical. Monitoring is recommended for a year.

“X-rays are good at looking for longer-term complications, but bony abnormalities are not going to show up for the first 2 weeks,” Dr. McCulloh said.

The presenters didn’t have any relevant disclosures. The meeting was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

[email protected]

SEATTLE – If your hospital’s methicillin-resistant Staphylococcus aureus rate is less than 10%, cefazolin is a reasonable empiric choice for pediatric acute hematogenous osteomyelitis (AHO). It covers the usual suspects: methicillin-susceptible Staphylococcus aureus, group A Streptococcus, and Kingella.

Above the 10% mark, coverage should include considerations of MRSA; clindamycin is good option so long as 85% of isolates are susceptible. Above that, it’s time for vancomycin, according to Nivedita Srinivas, MD, a pediatric infectious disease specialist at Stanford (Calif.) University.

There are no practice guidelines in the United States for the diagnosis and management of AHO in children; Dr. Srinivas and colleagues sought to plug the gaps in a talk at Pediatric Hospitalist Medicine.

Pediatric AHO is more common in children under 5 years old and in boys. Lower extremities are the usual targets. Staphylococcus aureus, group B Streptococcus, and gram negatives are the most common causes in newborns; Staphylococcus aureus, group A Streptococcus, and Kingella in older infants and preschoolers; and Staphylococcus aureus and group A Streptococcus in older children.

About half the time, treatment remains empiric because nothing grows out on culture, and there are a few clinical pearls to keep in mind in those cases. A family history of boils or spider bites is suspicious for MRSA, and coverage should include Salmonella in children with abnormal hemoglobins and Streptococcus pneumoniae in children without a spleen or with functional asplenia. Pseudomonas has to be kept in mind with puncture wounds, and Brucella in children who drink unpasteurized milk, Dr. Srinivas said.

A switch from IV to oral therapy is appropriate when C-reactive protein (CRP) drops 50% from its peak or below 3 mg/dL, positive cultures – if any – turn negative, fever has been absent for 24 hours, there’s no sign of metastatic disease, and patients have markedly reduced pain and can bear weight on the infected limb, said copresenter Marie Wang, MD, also a pediatric infectious disease specialist at Stanford.

The oral switch, of course, must have similar coverage as the IV antibiotic: high-dose cephalexin for cefazolin, for instance. Children can be sent home on a PICC line to continue IV treatment, but they won’t do any better than children switched to an oral treatment, and the indwelling catheter can cause problems, she said.

Pleuritic or other sudden pain at a distant site suggests septic emboli. “[Staphylococcus aureus] is notorious for going places you don’t” expect it to go “and forming microabscesses, which become larger abscesses” and need to be drained, said the third presenter, Russell McCulloh, MD, a pediatric infectious disease specialist at the University of Nebraska Medical Center, Omaha.

Four weeks of antibiotics are usually enough, so long as there aren’t complications such as septic thrombophlebitis, endocarditis, sickle cell disease, skull involvement, or immunodeficiencies. Source control and good, postdischarge care – including regular CRP and antibiotic toxicity labs – are critical. Monitoring is recommended for a year.

“X-rays are good at looking for longer-term complications, but bony abnormalities are not going to show up for the first 2 weeks,” Dr. McCulloh said.

The presenters didn’t have any relevant disclosures. The meeting was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

[email protected]

The U.S. Preventive Services Task Force has issued a draft recommendation statement for screening for hepatitis C virus (HCV) infection in adolescents and adults, and now suggests that all adults aged 18-79 years receive screening.

Wikimedia Commons/BruceBlaus

This proposal represents an update and expansion of its current recommendation for screening for HCV infection. The draft recommendation incorporates new evidence and would replace the recommendation made in 2013, which calls for screening in persons at high risk for infection and one-time screening in adults born between 1945 and 1965 (Grade B).

“Today, more people are infected with hepatitis C than there were a decade ago, but there are now better treatments available. The evidence now shows more people can benefit from screening; therefore, we are recommending to screen all adults ages 18-79 for hepatitis C,” task force chair Douglas K. Owens, MD, MS, said in a bulletin issued by the USPSTF.

To update the previous recommendation, the USPSTF conducted a systematic review that included a total of 97 studies. No direct evidence was found regarding the benefits of HCV screening versus no screening or repeat versus one-time screening, and no new studies analyzed the psychological and social consequences of HCV screening.

Evidence concerning direct-acting antiviral (DAA) treatment was more compelling given that 49 trials found DAA therapy to be associated with pooled sustained virologic response (SVR) rates between 95.5% and 98.9% across genotypes. The rate of serious adverse events caused by DAA treatment was 1.9%, and the discontinuation of treatment because of adverse events was 0.4%. In seven trials involving adolescents, SVR rates after antiviral treatment were similar to those in adults.

Achieving an SVR after DAA treatment was associated with a decreased risk in those treated of all-cause mortality (hazard ratio, 0.40; 95% confidence interval, 0.28-0.56), liver mortality (HR, 0.11; 95% CI, 0.04-0.27), cirrhosis (HR, 0.36; 95% CI, 0.33-0.40), and hepatocellular carcinoma (HR, 0.29; 95% CI, 0.23-0.38), compared with those who did not respond.

Because of the evidence collected, the USPSTF issued a B recommendation for HCV screening in adults and recommended screening for all people aged 18-79 years in the draft recommendation statement. “Clinicians may want to consider screening in adolescents younger than age 18 years and in adults older than age 79 years who are at high risk [for HCV],” the proposal says.

The draft recommendation statement and evidence review is available at www.uspreventiveservicestaskforce.org. The public comment period will last until Sept. 23, 2019.

[email protected]

The U.S. Preventive Services Task Force has issued a draft recommendation statement for screening for hepatitis C virus (HCV) infection in adolescents and adults, and now suggests that all adults aged 18-79 years receive screening.

Wikimedia Commons/BruceBlaus

This proposal represents an update and expansion of its current recommendation for screening for HCV infection. The draft recommendation incorporates new evidence and would replace the recommendation made in 2013, which calls for screening in persons at high risk for infection and one-time screening in adults born between 1945 and 1965 (Grade B).

“Today, more people are infected with hepatitis C than there were a decade ago, but there are now better treatments available. The evidence now shows more people can benefit from screening; therefore, we are recommending to screen all adults ages 18-79 for hepatitis C,” task force chair Douglas K. Owens, MD, MS, said in a bulletin issued by the USPSTF.

To update the previous recommendation, the USPSTF conducted a systematic review that included a total of 97 studies. No direct evidence was found regarding the benefits of HCV screening versus no screening or repeat versus one-time screening, and no new studies analyzed the psychological and social consequences of HCV screening.

Evidence concerning direct-acting antiviral (DAA) treatment was more compelling given that 49 trials found DAA therapy to be associated with pooled sustained virologic response (SVR) rates between 95.5% and 98.9% across genotypes. The rate of serious adverse events caused by DAA treatment was 1.9%, and the discontinuation of treatment because of adverse events was 0.4%. In seven trials involving adolescents, SVR rates after antiviral treatment were similar to those in adults.

Achieving an SVR after DAA treatment was associated with a decreased risk in those treated of all-cause mortality (hazard ratio, 0.40; 95% confidence interval, 0.28-0.56), liver mortality (HR, 0.11; 95% CI, 0.04-0.27), cirrhosis (HR, 0.36; 95% CI, 0.33-0.40), and hepatocellular carcinoma (HR, 0.29; 95% CI, 0.23-0.38), compared with those who did not respond.

Because of the evidence collected, the USPSTF issued a B recommendation for HCV screening in adults and recommended screening for all people aged 18-79 years in the draft recommendation statement. “Clinicians may want to consider screening in adolescents younger than age 18 years and in adults older than age 79 years who are at high risk [for HCV],” the proposal says.

The draft recommendation statement and evidence review is available at www.uspreventiveservicestaskforce.org. The public comment period will last until Sept. 23, 2019.

[email protected]

The U.S. Preventive Services Task Force has issued a draft recommendation statement for screening for hepatitis C virus (HCV) infection in adolescents and adults, and now suggests that all adults aged 18-79 years receive screening.

Wikimedia Commons/BruceBlaus

This proposal represents an update and expansion of its current recommendation for screening for HCV infection. The draft recommendation incorporates new evidence and would replace the recommendation made in 2013, which calls for screening in persons at high risk for infection and one-time screening in adults born between 1945 and 1965 (Grade B).

“Today, more people are infected with hepatitis C than there were a decade ago, but there are now better treatments available. The evidence now shows more people can benefit from screening; therefore, we are recommending to screen all adults ages 18-79 for hepatitis C,” task force chair Douglas K. Owens, MD, MS, said in a bulletin issued by the USPSTF.

To update the previous recommendation, the USPSTF conducted a systematic review that included a total of 97 studies. No direct evidence was found regarding the benefits of HCV screening versus no screening or repeat versus one-time screening, and no new studies analyzed the psychological and social consequences of HCV screening.

Evidence concerning direct-acting antiviral (DAA) treatment was more compelling given that 49 trials found DAA therapy to be associated with pooled sustained virologic response (SVR) rates between 95.5% and 98.9% across genotypes. The rate of serious adverse events caused by DAA treatment was 1.9%, and the discontinuation of treatment because of adverse events was 0.4%. In seven trials involving adolescents, SVR rates after antiviral treatment were similar to those in adults.

Achieving an SVR after DAA treatment was associated with a decreased risk in those treated of all-cause mortality (hazard ratio, 0.40; 95% confidence interval, 0.28-0.56), liver mortality (HR, 0.11; 95% CI, 0.04-0.27), cirrhosis (HR, 0.36; 95% CI, 0.33-0.40), and hepatocellular carcinoma (HR, 0.29; 95% CI, 0.23-0.38), compared with those who did not respond.

Because of the evidence collected, the USPSTF issued a B recommendation for HCV screening in adults and recommended screening for all people aged 18-79 years in the draft recommendation statement. “Clinicians may want to consider screening in adolescents younger than age 18 years and in adults older than age 79 years who are at high risk [for HCV],” the proposal says.

The draft recommendation statement and evidence review is available at www.uspreventiveservicestaskforce.org. The public comment period will last until Sept. 23, 2019.

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SEATTLE – Rady Children’s Hospital in San Diego has been doing continuous positive airway pressure for infants with bronchiolitis on the general pediatrics floors safely and with no problems for nearly 20 years, according to a presentation at Pediatric Hospital Medicine.

It’s newsworthy because “very, very few” hospitals do bronchiolitis continuous positive airway pressure (CPAP) outside of the ICU. “The perception is that there are complications, and you might miss kids that are really sick if you keep them on the floor.” However, “we have been doing it safely for so long that no one thinks twice about it,” said Christiane Lenzen, MD, a pediatric hospitalist at Rady and an assistant clinical professor of pediatrics at the University of California, San Diego.

It doesn’t matter if children have congenital heart disease, chronic lung disease, or other problems, she said, “if they are stable enough for the floor, we will see if it’s okay.”

Rady’s hand was forced on the issue because it has a large catchment area but limited ICU beds, so for practical reasons and within certain limits, CPAP moved to the floors. One of Dr. Lenzen’s colleagues noted that, as long as there’s nurse and respiratory leadership buy in, “it’s actually quite easy to pull off in a very safe manner.”

Rady has a significant advantage over community hospitals and other places considering the approach, because it has onsite pediatric ICU services for when things head south. Over the past 3 or so years, 52% of the children the pediatric hospital medicine service started on CPAP (168/324) had to be transferred to the ICU; 17% were ultimately intubated.

Many of those transfers were caused by comorbidities, not CPAP failure, but other times children needed greater respiratory support; in general, the floor CPAP limit is 6 cm H₂O and a fraction of inspired oxygen of 50%. Also, sometimes children needed to be sedated for CPAP, which isn’t done on the floor.

With the 52% transfer rate, “I would worry about patients who are sick enough to need CPAP staying” in a hospital without quick access to ICU services, Dr. Lenzen said at the meeting sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

Even so, among 324 children who at least initially were treated with CPAP on the floor – out of 2,424 admitted to the pediatric hospital medicine service with bronchiolitis – there hasn’t been a single pneumothorax, aspiration event, or CPAP equipment–related injury, she said.

CPAP on the floor has several benefits. ICU resources are conserved, patient handoffs and the work of transfers into and out of the ICU are avoided, families don’t have to get used to a new treatment team, and infants aren’t subjected to the jarring ICU environment.

For it to work, though, staff “really need to be on top of this,” and “it needs to be very tightly controlled” with order sets and other measures, the presenters said. There’s regular training at Rady for nurses, respiratory therapists, and hospitalists on CPAP equipment, airway management, monitoring, troubleshooting, and other essentials.

Almost all children on the pediatric floors have a trial of high-flow nasal cannula with an upper limit of 8 L/min. If the Respiratory Assessment Score hasn’t improved in an hour, CPAP is considered. If a child is admitted with a score above 10 and they seem to be worsening, they go straight to CPAP.

Children alternate between nasal prongs and nasal masks to prevent pressure necrosis, and are kept nil per os while on CPAP. They are on continual pulse oximetry and cardiorespiratory monitoring. Vital signs and respiratory scores are checked frequently, more so for children who are struggling.

The patient-to-nurse ratio drops from the usual 4:1 to 3:1 when a child goes on CPAP, and to 2:1 if necessary. Traveling nurses aren’t allowed to take CPAP cases.

The presenters didn’t report any disclosures.

This article was updated 8/27/19.

[email protected]

SEATTLE – Rady Children’s Hospital in San Diego has been doing continuous positive airway pressure for infants with bronchiolitis on the general pediatrics floors safely and with no problems for nearly 20 years, according to a presentation at Pediatric Hospital Medicine.

It’s newsworthy because “very, very few” hospitals do bronchiolitis continuous positive airway pressure (CPAP) outside of the ICU. “The perception is that there are complications, and you might miss kids that are really sick if you keep them on the floor.” However, “we have been doing it safely for so long that no one thinks twice about it,” said Christiane Lenzen, MD, a pediatric hospitalist at Rady and an assistant clinical professor of pediatrics at the University of California, San Diego.

It doesn’t matter if children have congenital heart disease, chronic lung disease, or other problems, she said, “if they are stable enough for the floor, we will see if it’s okay.”

Rady’s hand was forced on the issue because it has a large catchment area but limited ICU beds, so for practical reasons and within certain limits, CPAP moved to the floors. One of Dr. Lenzen’s colleagues noted that, as long as there’s nurse and respiratory leadership buy in, “it’s actually quite easy to pull off in a very safe manner.”

Rady has a significant advantage over community hospitals and other places considering the approach, because it has onsite pediatric ICU services for when things head south. Over the past 3 or so years, 52% of the children the pediatric hospital medicine service started on CPAP (168/324) had to be transferred to the ICU; 17% were ultimately intubated.

Many of those transfers were caused by comorbidities, not CPAP failure, but other times children needed greater respiratory support; in general, the floor CPAP limit is 6 cm H₂O and a fraction of inspired oxygen of 50%. Also, sometimes children needed to be sedated for CPAP, which isn’t done on the floor.

With the 52% transfer rate, “I would worry about patients who are sick enough to need CPAP staying” in a hospital without quick access to ICU services, Dr. Lenzen said at the meeting sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

Even so, among 324 children who at least initially were treated with CPAP on the floor – out of 2,424 admitted to the pediatric hospital medicine service with bronchiolitis – there hasn’t been a single pneumothorax, aspiration event, or CPAP equipment–related injury, she said.

CPAP on the floor has several benefits. ICU resources are conserved, patient handoffs and the work of transfers into and out of the ICU are avoided, families don’t have to get used to a new treatment team, and infants aren’t subjected to the jarring ICU environment.

For it to work, though, staff “really need to be on top of this,” and “it needs to be very tightly controlled” with order sets and other measures, the presenters said. There’s regular training at Rady for nurses, respiratory therapists, and hospitalists on CPAP equipment, airway management, monitoring, troubleshooting, and other essentials.

Almost all children on the pediatric floors have a trial of high-flow nasal cannula with an upper limit of 8 L/min. If the Respiratory Assessment Score hasn’t improved in an hour, CPAP is considered. If a child is admitted with a score above 10 and they seem to be worsening, they go straight to CPAP.

Children alternate between nasal prongs and nasal masks to prevent pressure necrosis, and are kept nil per os while on CPAP. They are on continual pulse oximetry and cardiorespiratory monitoring. Vital signs and respiratory scores are checked frequently, more so for children who are struggling.

The patient-to-nurse ratio drops from the usual 4:1 to 3:1 when a child goes on CPAP, and to 2:1 if necessary. Traveling nurses aren’t allowed to take CPAP cases.

The presenters didn’t report any disclosures.

This article was updated 8/27/19.

[email protected]

SEATTLE – Rady Children’s Hospital in San Diego has been doing continuous positive airway pressure for infants with bronchiolitis on the general pediatrics floors safely and with no problems for nearly 20 years, according to a presentation at Pediatric Hospital Medicine.

It’s newsworthy because “very, very few” hospitals do bronchiolitis continuous positive airway pressure (CPAP) outside of the ICU. “The perception is that there are complications, and you might miss kids that are really sick if you keep them on the floor.” However, “we have been doing it safely for so long that no one thinks twice about it,” said Christiane Lenzen, MD, a pediatric hospitalist at Rady and an assistant clinical professor of pediatrics at the University of California, San Diego.

It doesn’t matter if children have congenital heart disease, chronic lung disease, or other problems, she said, “if they are stable enough for the floor, we will see if it’s okay.”

Rady’s hand was forced on the issue because it has a large catchment area but limited ICU beds, so for practical reasons and within certain limits, CPAP moved to the floors. One of Dr. Lenzen’s colleagues noted that, as long as there’s nurse and respiratory leadership buy in, “it’s actually quite easy to pull off in a very safe manner.”

Rady has a significant advantage over community hospitals and other places considering the approach, because it has onsite pediatric ICU services for when things head south. Over the past 3 or so years, 52% of the children the pediatric hospital medicine service started on CPAP (168/324) had to be transferred to the ICU; 17% were ultimately intubated.

Many of those transfers were caused by comorbidities, not CPAP failure, but other times children needed greater respiratory support; in general, the floor CPAP limit is 6 cm H₂O and a fraction of inspired oxygen of 50%. Also, sometimes children needed to be sedated for CPAP, which isn’t done on the floor.

With the 52% transfer rate, “I would worry about patients who are sick enough to need CPAP staying” in a hospital without quick access to ICU services, Dr. Lenzen said at the meeting sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

Even so, among 324 children who at least initially were treated with CPAP on the floor – out of 2,424 admitted to the pediatric hospital medicine service with bronchiolitis – there hasn’t been a single pneumothorax, aspiration event, or CPAP equipment–related injury, she said.

CPAP on the floor has several benefits. ICU resources are conserved, patient handoffs and the work of transfers into and out of the ICU are avoided, families don’t have to get used to a new treatment team, and infants aren’t subjected to the jarring ICU environment.

For it to work, though, staff “really need to be on top of this,” and “it needs to be very tightly controlled” with order sets and other measures, the presenters said. There’s regular training at Rady for nurses, respiratory therapists, and hospitalists on CPAP equipment, airway management, monitoring, troubleshooting, and other essentials.

Almost all children on the pediatric floors have a trial of high-flow nasal cannula with an upper limit of 8 L/min. If the Respiratory Assessment Score hasn’t improved in an hour, CPAP is considered. If a child is admitted with a score above 10 and they seem to be worsening, they go straight to CPAP.

Children alternate between nasal prongs and nasal masks to prevent pressure necrosis, and are kept nil per os while on CPAP. They are on continual pulse oximetry and cardiorespiratory monitoring. Vital signs and respiratory scores are checked frequently, more so for children who are struggling.

The patient-to-nurse ratio drops from the usual 4:1 to 3:1 when a child goes on CPAP, and to 2:1 if necessary. Traveling nurses aren’t allowed to take CPAP cases.

The presenters didn’t report any disclosures.

This article was updated 8/27/19.

[email protected]

Slightly more than half of adolescents in the United States have been fully vaccinated against the human papillomavirus, according to a report published in Morbidity and Mortality Weekly Report.

Joseph Abbott/Thinkstock

Researchers analyzed data from 18,700 adolescents aged 13-17 years – 48% of whom were female – in the 2018 National Immunization Survey–Teen to discover that 51% of adolescents were up to date with the human papillomavirus (HPV) vaccine, and 68% had received at least one dose of the vaccine.

There was an increase in HPV vaccination coverage from 2017 to 2018, but this was attributable to a 4.4 percentage point increase in males who were up to date, compared with a 0.6 percentage point increase in females.

“Although HPV vaccina­tion coverage improved, increases among all adolescents were modest compared with increases in previous years and were observed only among males,” wrote Tanja Y. Walker of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, and coauthors.

The number of adolescents who had at least one dose of the quadrivalent meningococ­cal conjugate (4MenB) vaccine increased by 1.5 percentage points to 86.6%, while among individuals aged 17 years, coverage with two or more doses of 4MenB vaccine increased by 6.5 percentage points to 50.8%. Tdap coverage remained the same at 89% (MMWR 2019;68(33):718-23).

Slightly more than half of adolescents in the United States have been fully vaccinated against the human papillomavirus, according to a report published in Morbidity and Mortality Weekly Report.

Joseph Abbott/Thinkstock

Researchers analyzed data from 18,700 adolescents aged 13-17 years – 48% of whom were female – in the 2018 National Immunization Survey–Teen to discover that 51% of adolescents were up to date with the human papillomavirus (HPV) vaccine, and 68% had received at least one dose of the vaccine.

There was an increase in HPV vaccination coverage from 2017 to 2018, but this was attributable to a 4.4 percentage point increase in males who were up to date, compared with a 0.6 percentage point increase in females.

“Although HPV vaccina­tion coverage improved, increases among all adolescents were modest compared with increases in previous years and were observed only among males,” wrote Tanja Y. Walker of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, and coauthors.

The number of adolescents who had at least one dose of the quadrivalent meningococ­cal conjugate (4MenB) vaccine increased by 1.5 percentage points to 86.6%, while among individuals aged 17 years, coverage with two or more doses of 4MenB vaccine increased by 6.5 percentage points to 50.8%. Tdap coverage remained the same at 89% (MMWR 2019;68(33):718-23).

Slightly more than half of adolescents in the United States have been fully vaccinated against the human papillomavirus, according to a report published in Morbidity and Mortality Weekly Report.

Joseph Abbott/Thinkstock

Researchers analyzed data from 18,700 adolescents aged 13-17 years – 48% of whom were female – in the 2018 National Immunization Survey–Teen to discover that 51% of adolescents were up to date with the human papillomavirus (HPV) vaccine, and 68% had received at least one dose of the vaccine.

There was an increase in HPV vaccination coverage from 2017 to 2018, but this was attributable to a 4.4 percentage point increase in males who were up to date, compared with a 0.6 percentage point increase in females.

“Although HPV vaccina­tion coverage improved, increases among all adolescents were modest compared with increases in previous years and were observed only among males,” wrote Tanja Y. Walker of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, and coauthors.

The number of adolescents who had at least one dose of the quadrivalent meningococ­cal conjugate (4MenB) vaccine increased by 1.5 percentage points to 86.6%, while among individuals aged 17 years, coverage with two or more doses of 4MenB vaccine increased by 6.5 percentage points to 50.8%. Tdap coverage remained the same at 89% (MMWR 2019;68(33):718-23).

Vaccination status should be reviewed annually for patients with autoimmune inflammatory rheumatic diseases, according to updated recommendations from the European League Against Rheumatism.

luiscar/Thinkstock

Patients with autoimmune inflammatory rheumatic diseases (AIIRD) are at increased risk for infections, and vaccination has been shown to reduce risk by “potentially translating into a lower rate of hospital admissions due to infections, emergency room visits, and the rate of invasive infectious diseases,” wrote Victoria Furer, MD, of Tel Aviv Sourasky Medical Center, and members of the task force that updated the recommendations, which were published in Annals of the Rheumatic Diseases.

However, AIIRD patients often go unvaccinated because of a lack of awareness or concerns about vaccine safety and efficacy, they said (Ann Rheum Dis. 2019 Aug 14. doi: 10.1136/annrheumdis-2019-215882).

The task force consisted of 21 experts, including patients, rheumatologists, immunologists, an infectious disease specialist, and health professionals in rheumatology representing eight countries. They evaluated data from four systematic literature reviews and developed nine recommendations based on six key principles.

“For each recommendation, the level of evidence for the incidence/prevalence of vaccine preventable infection in AIIRD, and efficacy/immunogenicity/safety of vaccination were stated, when available, followed by the strength of recommendation and the level of agreement,” the task force wrote.

These overarching principles start with an annual assessment of vaccination status by the AIIRD patient’s rheumatology team. Other principles include explanation of an individualized vaccination program to the patient as a foundation for joint decision-making, vaccinating patients during quiescent disease periods, vaccinating in advance of planned immunosuppression when possible, considering non-live vaccines for AIIRD patients also treated with systemic glucocorticoids and DMARDs, and considering live-attenuated vaccines with caution.

Several of the nine recommendations developed by the task force are modified from the previous recommendations issued in 2011. The task force made its recommendations with an eye toward optimizing individual risk stratification and avoiding “unnecessary” vaccination in AIIRD patients with low risk of infection as part of the update process. A notable change from the 2011 guidelines is the recommendation of both influenza and pneumococcal vaccinations for the majority of patients with AIIRD as opposed to all patients to emphasize the importance of individualized risk assessment, the task force noted.

The recommendations state that influenza vaccination and pneumococcal vaccination should be “strongly considered” for patients with AIIRD, and patients also should receive tetanus toxoid vaccination according to recommendations for the general population. However, clinicians should consider passive immunization for patients treated with B-cell depleting therapy, the task force wrote.

AIIRD patients at risk for hepatitis A and B should receive vaccinations for those diseases, with boosters or passive immunization if indicated, and high-risk patients may consider herpes zoster vaccination, according to the recommendations.

In addition, AIIRD patients – especially patients with systemic lupus erythematosus – should receive human papilloma virus vaccination according to recommendations for the general population, but AIIRD patients should avoid yellow fever vaccination, the task force stated. However, for AIIRD patients traveling to areas of yellow fever risk, “withholding immunosuppressive therapy to allow a safe vaccination or measuring serology in previously exposed patients may be considered.”

Finally, mothers treated with biologics during the second half of pregnancy should avoid live-attenuated vaccines for their newborns, and immunocompetent household members of AIIRD patients should be encouraged to follow national guidelines for routine vaccination with the exception of the oral polio vaccine, the task force concluded.

Vaccination status should be reviewed annually for patients with autoimmune inflammatory rheumatic diseases, according to updated recommendations from the European League Against Rheumatism.

luiscar/Thinkstock

Patients with autoimmune inflammatory rheumatic diseases (AIIRD) are at increased risk for infections, and vaccination has been shown to reduce risk by “potentially translating into a lower rate of hospital admissions due to infections, emergency room visits, and the rate of invasive infectious diseases,” wrote Victoria Furer, MD, of Tel Aviv Sourasky Medical Center, and members of the task force that updated the recommendations, which were published in Annals of the Rheumatic Diseases.

However, AIIRD patients often go unvaccinated because of a lack of awareness or concerns about vaccine safety and efficacy, they said (Ann Rheum Dis. 2019 Aug 14. doi: 10.1136/annrheumdis-2019-215882).

The task force consisted of 21 experts, including patients, rheumatologists, immunologists, an infectious disease specialist, and health professionals in rheumatology representing eight countries. They evaluated data from four systematic literature reviews and developed nine recommendations based on six key principles.

“For each recommendation, the level of evidence for the incidence/prevalence of vaccine preventable infection in AIIRD, and efficacy/immunogenicity/safety of vaccination were stated, when available, followed by the strength of recommendation and the level of agreement,” the task force wrote.

These overarching principles start with an annual assessment of vaccination status by the AIIRD patient’s rheumatology team. Other principles include explanation of an individualized vaccination program to the patient as a foundation for joint decision-making, vaccinating patients during quiescent disease periods, vaccinating in advance of planned immunosuppression when possible, considering non-live vaccines for AIIRD patients also treated with systemic glucocorticoids and DMARDs, and considering live-attenuated vaccines with caution.

Several of the nine recommendations developed by the task force are modified from the previous recommendations issued in 2011. The task force made its recommendations with an eye toward optimizing individual risk stratification and avoiding “unnecessary” vaccination in AIIRD patients with low risk of infection as part of the update process. A notable change from the 2011 guidelines is the recommendation of both influenza and pneumococcal vaccinations for the majority of patients with AIIRD as opposed to all patients to emphasize the importance of individualized risk assessment, the task force noted.

The recommendations state that influenza vaccination and pneumococcal vaccination should be “strongly considered” for patients with AIIRD, and patients also should receive tetanus toxoid vaccination according to recommendations for the general population. However, clinicians should consider passive immunization for patients treated with B-cell depleting therapy, the task force wrote.

AIIRD patients at risk for hepatitis A and B should receive vaccinations for those diseases, with boosters or passive immunization if indicated, and high-risk patients may consider herpes zoster vaccination, according to the recommendations.

In addition, AIIRD patients – especially patients with systemic lupus erythematosus – should receive human papilloma virus vaccination according to recommendations for the general population, but AIIRD patients should avoid yellow fever vaccination, the task force stated. However, for AIIRD patients traveling to areas of yellow fever risk, “withholding immunosuppressive therapy to allow a safe vaccination or measuring serology in previously exposed patients may be considered.”

Finally, mothers treated with biologics during the second half of pregnancy should avoid live-attenuated vaccines for their newborns, and immunocompetent household members of AIIRD patients should be encouraged to follow national guidelines for routine vaccination with the exception of the oral polio vaccine, the task force concluded.

Vaccination status should be reviewed annually for patients with autoimmune inflammatory rheumatic diseases, according to updated recommendations from the European League Against Rheumatism.

luiscar/Thinkstock

Patients with autoimmune inflammatory rheumatic diseases (AIIRD) are at increased risk for infections, and vaccination has been shown to reduce risk by “potentially translating into a lower rate of hospital admissions due to infections, emergency room visits, and the rate of invasive infectious diseases,” wrote Victoria Furer, MD, of Tel Aviv Sourasky Medical Center, and members of the task force that updated the recommendations, which were published in Annals of the Rheumatic Diseases.

However, AIIRD patients often go unvaccinated because of a lack of awareness or concerns about vaccine safety and efficacy, they said (Ann Rheum Dis. 2019 Aug 14. doi: 10.1136/annrheumdis-2019-215882).

The task force consisted of 21 experts, including patients, rheumatologists, immunologists, an infectious disease specialist, and health professionals in rheumatology representing eight countries. They evaluated data from four systematic literature reviews and developed nine recommendations based on six key principles.

“For each recommendation, the level of evidence for the incidence/prevalence of vaccine preventable infection in AIIRD, and efficacy/immunogenicity/safety of vaccination were stated, when available, followed by the strength of recommendation and the level of agreement,” the task force wrote.

These overarching principles start with an annual assessment of vaccination status by the AIIRD patient’s rheumatology team. Other principles include explanation of an individualized vaccination program to the patient as a foundation for joint decision-making, vaccinating patients during quiescent disease periods, vaccinating in advance of planned immunosuppression when possible, considering non-live vaccines for AIIRD patients also treated with systemic glucocorticoids and DMARDs, and considering live-attenuated vaccines with caution.

Several of the nine recommendations developed by the task force are modified from the previous recommendations issued in 2011. The task force made its recommendations with an eye toward optimizing individual risk stratification and avoiding “unnecessary” vaccination in AIIRD patients with low risk of infection as part of the update process. A notable change from the 2011 guidelines is the recommendation of both influenza and pneumococcal vaccinations for the majority of patients with AIIRD as opposed to all patients to emphasize the importance of individualized risk assessment, the task force noted.

The recommendations state that influenza vaccination and pneumococcal vaccination should be “strongly considered” for patients with AIIRD, and patients also should receive tetanus toxoid vaccination according to recommendations for the general population. However, clinicians should consider passive immunization for patients treated with B-cell depleting therapy, the task force wrote.

AIIRD patients at risk for hepatitis A and B should receive vaccinations for those diseases, with boosters or passive immunization if indicated, and high-risk patients may consider herpes zoster vaccination, according to the recommendations.

In addition, AIIRD patients – especially patients with systemic lupus erythematosus – should receive human papilloma virus vaccination according to recommendations for the general population, but AIIRD patients should avoid yellow fever vaccination, the task force stated. However, for AIIRD patients traveling to areas of yellow fever risk, “withholding immunosuppressive therapy to allow a safe vaccination or measuring serology in previously exposed patients may be considered.”

Finally, mothers treated with biologics during the second half of pregnancy should avoid live-attenuated vaccines for their newborns, and immunocompetent household members of AIIRD patients should be encouraged to follow national guidelines for routine vaccination with the exception of the oral polio vaccine, the task force concluded.