A 9-Month-Old Girl with Fevers

Posted by Carla Rothaus • August 21st, 2015

A Girl with Recurrent FeversIn a new Case Record of the Massachusetts General Hospital, a 9-month-old girl presented with a 2-month history of recurrent fevers. Examination revealed fever and tachycardia and was otherwise normal; chest and abdominal imaging studies showed no evidence of infection. Additional diagnostic tests were performed.

Septic arthritis is a pediatric orthopedic emergency.

Clinical Pearls

• What is the definition of fever of unknown origin in children, and how often is infection the cause?

While the terms recurrent fever and fever of unknown origin are often used interchangeably, and the differential diagnosis is similar for both, there are specific definitions for fever of unknown origin. In 1961, fever of unknown origin was defined as a temperature of greater than 38.3 degrees C (101 degrees F) “on several occasions,” a duration of illness of greater than 3 weeks, and no cause of fever despite 1 week of inpatient investigation. Over subsequent decades, there have been amendments to the definition and proposals for different categories. Although there is no single generally accepted definition, a working definition would include a temperature of greater than 38.3 degrees C (101 degrees F), a duration of illness of at least 1 week, and a negative initial outpatient or inpatient evaluation, which includes history taking, physical examination, and routine laboratory testing. The differential diagnosis of fever of unknown origin is broad. A systematic review of 18 studies performed between 1950 and 2010 involving children who were evaluated for fever of unknown origin showed that half had infections, fewer than 10% had collagen vascular disease or malignant tumors, and almost one quarter had no diagnosis.

Table 2. Differential Diagnosis of Pediatric Fever of Unknown Origin.

What clinical features can help to distinguish septic arthritis from toxic synovitis?

Features that can help in distinguishing septic arthritis from toxic synovitis in children are an inability to bear weight, fever, and elevations of the erythrocyte sedimentation rate (>40 mm per hour) and white-cell count (>12,000 per cubic millimeter).

Morning Report Questions

Q: What are some of the microorganisms identified in septic arthritis affecting young children?

A: The microbiologic features of septic arthritis can vary depending on age, immunization history, possible exposures, and the presence of chronic conditions. Methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) are the most common causes in all age groups. Of the types of streptococci, group B streptococcus is most common in infants younger than 3 months of age, group A streptococcus is most common in infants older than 3 months of age, and Streptococcus pneumoniae is most common in infants older than 3 months of age who are not immunized. The gram-negative bacillus Kingella kingae is increasingly identified in patients with septic arthritis who are between 3 months and 3 years of age.

Q: What long term sequelae may result from septic arthritis in children?

A: Septic arthritis is a pediatric orthopedic emergency. Early diagnosis and expedited treatment are critical for a satisfactory outcome. Although bone has the ability to repair itself, articular and epiphyseal cartilage does not. In addition to the effect of the infection on the child’s general health, there is a risk of considerable damage to the joint. Potent proteolytic enzymes are released in the joint directly from the bacteria and host tissue (i.e., synovial cells and chondrocytes) in response to the infection; these enzymes destroy the hyaline cartilage. Some studies have shown that cartilage destruction begins within 6 to 8 hours after bacterial colonization. Capsular distention, which occurs as a result of the effusion, coupled with muscle spasm, which occurs as a result of pain, can lead to a pathological dislocation of the joint and necessitate the application of a brace. Increased intraarticular pressure, which occurs as a result of the pus accumulation, can lead to avascular necrosis of the femoral head. All these features can lead to limb-length discrepancy, proximal femoral deformity, acetabular dysplasia, and joint stiffness and may lead to degenerative arthritis in the long term.

Figure 3. Imaging Studies of the Pelvis and Hips.

Unprovoked Venous Thromboembolism

Posted by Carla Rothaus • August 21st, 2015

Insight post 8-19-15In this Original Article, a trial showed that the addition of abdominopelvic CT to routine measures in patients with unprovoked venous thrombosis did not detect additional occult cancers. The incidence of cancer in first unprovoked venous thrombosis was 4%, not 10% as had been previously reported.

Carrier et al. conducted a multicenter, open-label, randomized, controlled trial in which patients who had a first unprovoked venous thromboembolism were randomly assigned to undergo limited occult-cancer screening (basic blood testing, chest radiography, and screening for breast, cervical, and prostate cancer) or limited occult-cancer screening in combination with comprehensive computed tomography (CT) of the abdomen and pelvis. CT included a virtual colonoscopy and gastroscopy, biphasic enhanced CT of the liver, parenchymal pancreatography, and uniphasic enhanced CT of the distended bladder. The primary outcome measure was confirmed cancer that was missed by the screening strategy and detected by the end of the 1-year follow-up period.

Clinical Pearls

• What is the association between unprovoked venous thromboembolism and occult malignancy?

Venous thromboembolism is classified as provoked when it is associated with a transient risk factor (e.g., trauma, surgery, prolonged immobility, or pregnancy or the puerperium) and as unprovoked when it is associated with neither a strong transient risk factor nor overt cancer. Unprovoked venous thromboembolism may be the earliest sign of cancer; up to 10% of patients with unprovoked venous thromboembolism receive a diagnosis of cancer in the year after their diagnosis of venous thromboembolism. More than 60% of occult cancers are diagnosed shortly after the diagnosis of unprovoked venous thromboembolism. Thereafter, the incidence rate of cancer diagnosis gradually declines and returns to the rate in the general population after 1 year.

• Is there a consensus about how to evaluate a patient with a first unprovoked venous thromboembolism?

Clinicians, patients, and policymakers struggle with how aggressive to be in screening for occult cancers in patients who present with unprovoked venous thromboembolism. The rationale for screening is to allow early detection and intervention and ultimately reduce cancer-related mortality. However, owing to the paucity of data in this context, there is great variation in practice. Whereas some studies have suggested that a limited screening strategy for occult cancer — including history taking, physical examination, routine blood testing, and chest radiography — is adequate to detect most occult cancers, other studies have suggested that a more extensive screening strategy (e.g., incorporating ultrasonography or CT of the abdomen and pelvis, measurement of tumor markers, or a combination of these) can substantially increase the rate of detection of occult cancer.

Morning Report Questions

Q: Does adding a CT of the abdomen and pelvis to a limited screening strategy for occult cancer lead to fewer missed cancers?

A: In the study by Carrier et al., a screening strategy for occult cancer that included comprehensive CT of the abdomen and pelvis did not lead to fewer missed cancers than the number missed with a limited screening strategy. In the primary outcome analysis, 4 of 14 occult cancers (29%; 95% CI, 8 to 58) were missed by the limited screening strategy (i.e., cancer was diagnosed after the screening strategy had deemed the patient as being free from cancer and before the end of the 1-year follow-up period), whereas 5 of 19 occult cancers (26%; 95% CI, 9 to 51) were missed by the strategy of limited screening plus CT (P=1.0).

Q: Does screening with the addition of CT detect significantly more cancers or reduce cancer-related mortality?

A: In the Carrier et al. study, the screening strategy that included CT did not appear to detect significantly more occult cancers (including early cancers), shorten the time to cancer diagnosis, or reduce cancer-related mortality. A total of 14 patients (3.2%; 95% CI, 1.9 to 5.4) in the limited-screening group and 19 patients (4.5%; 95% CI, 2.9 to 6.9) in the limited-screening-plus-CT group received a diagnosis of occult cancer (P=0.28). In the secondary outcome analyses, there was no significant between-group difference in the mean time to cancer diagnosis (4.2 months in the limited-screening group and 4.0 months in the limited-screening-plus-CT group, P=0.88), the rate of recurrent venous thromboembolism (3.3% and 3.4%, P=1.0), overall mortality (1.4% and 1.2%, P=1.0), or cancer-related mortality (1.4% and 0.9%, P=0.75). The rate of detection of early cancers was 0.23% among those in the limited-screening group and 0.71% in the limited-screening-plus-CT group (P=0.37).

Blood Clots and Buried Cancers

Posted by Rena Xu • August 19th, 2015

Insight post 8-19-15An unprovoked blood clot presents a dilemma. Deep vein thrombosis or pulmonary embolism may be the presenting sign of occult cancer, which makes it tempting to search high and low for a source. Early detection could enable prompt treatment and perhaps a better prognosis, in addition to changing the type of anticoagulation a patient receives. On the other hand, exhaustive screening is expensive and, when imaging is involved, exposes patients to radiation that can actually induce cancer. What’s more, there hasn’t been strong evidence historically to suggest that more comprehensive screening translates to fewer missed malignancies.

The NEJM recently reported the results of a large multicenter study that makes a case against more aggressive screening. The Screening for Occult Malignancy in Patients with Idiopathic Venous Thromboembolism (SOME) trial randomized over 850 patients with an unprovoked clotting event to undergo either limited cancer screening – basic labs, a chest x-ray, mammography and Pap smears for women, PSA testing for men – or those tests plus a comprehensive CT scan of the abdomen and pelvis. This scan included virtual colonoscopy and gastroscopy, as well as multi-phased imaging of the liver and pancreas. The primary study endpoint was the number of missed cancers after one year (most occult malignancies get diagnosed within that time frame after a clotting event).

In the two study arms, similar percentages of patients were diagnosed with cancer in the first year (3.2% in the limited screening arm, versus 4.5% in the limited-screening-plus-CT arm). In the limited screening arm, 4 out of 14 cancers, or 29%, were missed by the initial screening. In the limited-screening-plus-CT arm, a similar proportion of diagnoses were missed – 5 out of 19 cancers, or 26%. There was also no difference between the two groups in the average time to diagnosis, which for both groups was around four months.

“In our trial, a screening strategy for occult cancer that included comprehensive CT of the abdomen and pelvis did not lead to fewer missed cancers than the number missed with a limited screening strategy,” the authors write. For patients with a negative result at the time of limited screening, the incidence of a cancer diagnosis later in the first year was less than 1% — similar to the reported incidence among patients without clot.

Previous studies have suggested that in the year after an unprovoked clot, up to 10% of patients are diagnosed with cancer. In this study, across the two groups, the proportion of patients diagnosed was just under 4%. In an accompanying editorial, Dr. Alok Khorana of the Cleveland Clinic suggests that a relatively younger study patient population could have contributed to this discrepancy. The average age of participants in the SOME trial was 54 years; in contrast, in a prior study of over 500,000 patients, the average patient was more than a decade older. The authors, in turn, suggest that the actual prevalence of occult cancer could be decreasing due to better cancer screening.

“Routine screening with CT of the abdomen and pelvis did not provide a clinically significant benefit,” the authors conclude. It’s possible that adding other forms of imaging would have changed these findings, although a third of study participants also got a CT chest as part of their workup for pulmonary embolism. And among the occult cancers most frequently missed were gynecologic tumors and colorectal tumors; if a comprehensive CT scan of the abdomen and pelvis was unable to make the diagnosis in these patients, it seems unlikely that routine imaging of other regions of the body would have helped.

How do you screen patients for malignancy after an unprovoked clot? When would you perform a CT scan as part of your work-up? What other studies, if any, would you consider?

A Girl with a Chest-Wall Mass

Posted by Carla Rothaus • August 14th, 2015

8-Year-Old Girl with a Chest-Wall Mass 8-14-15In a new Case Record of the Massachusetts General Hospital, an 8-year-old girl with placement of a long-term tracheostomy tube presented with a chest-wall mass. Imaging studies revealed a soft-tissue mass, a pleural effusion, and pulmonary consolidation. A diagnostic procedure was performed.

Bacterial tracheobronchitis and pneumonia are common in children who have undergone tracheostomy, with an annual incidence of up to 88%.

Clinical Pearls

Describe some of the features of pulmonary actinomycosis.

Pulmonary actinomycosis is often polymicrobial, with gram-positive bacteria or anaerobes as common coisolates, and its parenchymal component may cavitate. Small-to-medium-sized pleural effusions may occur, and chest-wall invasion may result in early rib erosion.

What is empyema necessitatis?

Empyema necessitatis is a process characterized by extension of pleural empyema into the chest wall. This condition was first described by Gullan de Baillon in 1640. Empyema necessitatis typically develops over a period of 4 to 8 weeks and is associated with pain, swelling, and lymphadenopathy of the anterolateral chest, often without fever. It can also result in a pleurocutaneous or bronchopleurocutaneous fistula. The publication of only a few relevant case reports since the 19th century indicates that this condition remains extremely rare in children.

Morning Report Questions

Q: What pathogens are associated with empyema necessitatis?

A: Empyema necessitatis was more common in the era before antibiotics. At that time, it was associated with an overall mortality of approximately 66%; the most common pathogens were Mycobacterium tuberculosis (mortality, 87%) and Streptococcus pneumoniae (mortality, 28%). Since antibiotics have been in use, cases of empyema necessitatis are rarely fatal, and actinomyces species are a more common cause than is Streptococcus pneumoniae. Less common pathogens include Staphylococcus aureus, Streptococcus milleri, Fusobacterium nucleatum, Mycobacterium avium, Mycobacterium intracellulare, Burkholderia cepacia, blastomyces species, and Nocardia asteroides.

Q: What are some of the tumors included in the differential diagnosis of a chest-wall mass in a child?

A: Benign tumors that occur in children, such as lymphangioma (cystic hygroma) or hemangioma, arise in the soft tissue of the chest wall and are generally confined to it. Patients with an inflammatory myofibroblastic tumor can present with a soft-tissue mass of the chest wall. It arises from lung parenchyma and can extend into the chest wall, with localized mass effect. Chest-wall invasion is inconsistent and generally occurs no sooner than 12 to 18 months after the onset of symptoms, pleural effusions are uncommon, and lymphadenopathy is rare. In children, rhabdomyosarcoma is the most common malignant tumor arising in the soft tissue of the chest wall. Other soft-tissue sarcomas are relatively rare in children. Pleuropulmonary blastoma arises from the pleura or lung and can invade the chest wall, and usually occurs in children 5 years of age or younger. Malignant fibrous histiocytoma is usually confined to the chest wall and is more common in elderly persons than in children. Lymphomas in the thorax typically arise in the mediastinum and can extend into the anterior chest wall.

Table 2. Differential Diagnosis of Acquired Chest-Wall Deformity or Mass in a Child.

Ischemic Limb Gangrene

Posted by Carla Rothaus • August 14th, 2015

Ischemic Limb Gangrene with Pulses for fb-blogA new review article covers ischemic limb gangrene. A variety of systemic illnesses can be associated with limb gangrene with preservation of arterial pulses. Many such disorders involve venous thrombosis caused by a procoagulant–anticoagulant imbalance often related to low levels of protein C.

There are two distinct syndromes of microthrombosis-associated ischemic limb injury. Venous limb gangrene can complicate thrombocytopenic disorders that are strongly associated with deep-vein thrombosis (e.g., cancer-associated disseminated intravascular coagulation and heparin-induced thrombocytopenia). Usually, only one limb is affected. The potentially reversible, prodromal state of limb-threatening ischemia is phlegmasia cerulean dolens. In contrast, two and sometimes all four limbs are affected in symmetric peripheral gangrene, also featuring acral limb ischemic necrosis but usually without deep-vein thrombosis. The two syndromes have common pathophysiological features of microthrombosis associated with a disturbed procoagulant-anticoagulant balance.

Table 1. Two Syndromes of Ischemic Limb Gangrene with Pulses.  

Clinical Pearls

In patients with cancer, disseminated intravascular coagulation, and evidence of a deep venous thrombosis, how does the administration of warfarin lead to venous limb gangrene?

Laboratory studies support a model of profoundly disturbed procoagulant-anticoagulant balance in patients with cancer in whom venous gangrene develops during warfarin anticoagulation. Uncontrolled thrombin generation is shown by greatly elevated thrombin-antithrombin complexes (a marker of in vivo thrombin generation) together with greatly reduced levels of protein C activity — in other words, the ratio of thrombin-antithrombin complex to protein C is elevated as compared with that in controls. In essence, warfarin does not inhibit cancer-associated hypercoagulability while at the same time it predisposes the patient to microthrombosis by depleting protein C activity (often to <10% of normal levels). The characteristic laboratory picture includes thrombocytopenia and an international normalized ratio (INR) that typically exceeds 4.0; a supratherapeutic INR is a proxy for a severely reduced protein C level.

Is warfarin therapy also implicated in venous limb gangrene associated with heparin-induced thrombocytopenia?

Warfarin therapy is implicated in the majority of patients with heparin-induced thrombocytopenia in whom venous limb gangrene develops. Again, a characteristic feature is a supratherapeutic INR. In such patients, a markedly elevated ratio of thrombin-antithrombin complex to protein C supports a model of profoundly disturbed procoagulant-anticoagulant balance. In the minority of patients with heparin-induced thrombocytopenia in whom venous gangrene develops in the absence of warfarin administration, unusually severe thrombocytopenia (platelet count, <20,000 per cubic millimeter) and laboratory evidence of decompensated disseminated intravascular coagulation (e.g., elevated INR, hypofibrinogenemia, and circulating nucleated red cells) is found.

Figure 1. Clinical Profile of Venous Limb Gangrene and Symmetric Peripheral Gangrene.

Figure 2. Changes in Platelet Count and INR in Three Clinical Scenarios Associated with Ischemic Limb Gangrene with Pulses.

Morning Report Questions

Q: What are some of the clinical features of symmetric peripheral gangrene, and what microorganisms are associated with purpura fulminans?

A: Symmetric peripheral gangrene indicates predominantly acral necrosis, which affects the distal limbs (with more frequent and extensive involvement of the feet than the fingers or hands) but sometimes also the nose, lips, ears, scalp, and genitalia. The term purpura fulminans is used when there is extensive, multicentric, nonacral skin necrosis, although patients usually have acral limb necrosis as well. Septicemia and cardiac failure are the most common underlying disorders, and patients usually have metabolic (lactic) acidosis. Concomitant multiple organ failure (e.g., respiratory, renal, and hepatic) is common. Patients with septicemia-associated disseminated intravascular coagulation that is complicated by dermal manifestations usually present with fever, hypotension, and a petechial rash that evolves to more extensive confluent nonacral and acral purpuric areas of evolving ischemic necrosis. Limb ischemic necrosis typically involves lower limbs before upper limbs; approximately one quarter of patients require four-limb amputations. Mortality exceeds 50%. Purpura fulminans in young children and adolescents is usually associated with meningococcemia (caused by Neisseria meningitidis), whereas in adults Streptococcus pneumoniae (pneumococcus) is most often implicated.

Figure 3. Symmetric Peripheral Gangrene.

Q: How are these syndromes treated?

A: Venous limb gangrene and symmetric peripheral gangrene are observed in a small minority (<1%) of patients with disseminated intravascular coagulation, so treatment considerations are based primarily on theoretical considerations and case-based observations, rather than on results of clinical trials. In a patient who is recognized to have phlegmasia or venous limb gangrene, treatment is based on two principles. The first — for a patient with a prolonged INR that is caused by treatment with a vitamin K antagonist — is the administration of vitamin K (at least 10 mg by slow intravenous infusion, with 5 to 10 mg repeated 12 to 24 hours later if the prolongation in the INR persists or recurs). The second is therapeutic-dose anticoagulation. These measures can be limb-saving in a patient with phlegmasia. Treatment of symmetric peripheral gangrene (with or without purpura fulminans) theoretically involves heparin-based anticoagulation and the substitution of natural anticoagulants. In choosing an anticoagulant, many practitioners favor heparin, since its anticoagulant effect can be monitored directly (by measuring anti-factor Xa levels). However, heparin requires its cofactor, antithrombin, and antithrombin levels can be reduced in patients with consumptive coagulopathies, particularly with concomitant liver dysfunction.

New Interactive Medical Case: “A Man with Bizarre Behavior”

Posted by Jennifer Zeis • August 13th, 2015

IMC813A 24-year-old man was brought to the emergency department by ambulance after exhibiting abnormal and agitated behavior. On presentation, he was wearing only underwear and yelling “I am God!” repeatedly. He was alert, awake, and talkative but was not responsive to direct questioning. Although his speech was fluent, its content was illogical and was not directed toward caregivers.

Test your diagnostic and therapeutic skills with this free Interactive Medical Case, and earn CME credit or MOC points.

Interactive Medical Cases are online simulations based on a real patient’s experience of illness. You follow interactive steps through an evolving patient’s history, diagnosis, and management, from presentation to outcome. During the presentation of the case, you access videos, lab results and brief commentary that explain concepts important for diagnosis and treatment.

You can also browse the list of 38 previous Interactive Medical Cases.

Troponin and Cardiac Events in Stable Ischemic Heart Disease and Diabetes

Posted by James Yeh, M.D. M.P.H. • August 12th, 2015

insight post 8-11-15Ischemic heart disease is one of the leading causes of death world-wide. The ability to risk stratify those at increased risk for cardiovascular events would be beneficial. A number of previous studies have shown that routine troponin elevation may serve as a marker of poor prognosis independent of the traditional cardiovascular risk factors (e.g., hypertension, smoking, hyperlipidemia, diabetes, etc.).

In this week’s issue of NEJM, Everett et al. asked the question whether individuals with diabetes and stable coronary artery disease can be risk stratified using troponin levels and whether those at high risk for cardiovascular events may benefit from prompt coronary revascularization.

In this retrospective cohort study design, 2285 individuals with stable coronary artery disease and type 2 diabetes who were candidates for coronary revascularization were randomized to receive either prompt revascularization plus intense medical therapy or to medical therapy alone. The primary outcome was the composite events of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The median follow-up time was 5 years. Abnormal troponin level was considered to be > 14 ng/dL, corresponding to the upper reference limit (99th percentile) in a healthy population.

At the end of 5 years, those with abnormal baseline troponin level had a higher rate of the primary outcome when compared to those with normal troponin levels (27.1% versus 12.9%). Even after adjusting for traditional cardiovascular risk factors, history of prior myocardial infarction and heart failure, severity of diabetes, the primary outcome remained significantly different in the two groups based on troponin level (1.85, 95% CI 1.48-2.32, P < 0.001). Prompt revascularization was not associated with a reduction in cardiovascular death/myocardial infarction/stroke when compared to medical therapy alone (HR 0.98, 95% CI 0.80-1.19, P=0.83). Prompt revascularization also did not reduce the composite events among those with either baseline normal or abnormal troponin levels.

What did we learn from this study? We learned that elevated baseline troponin levels may be used as prognostic factor in addition to the traditional risks. However, the accompanying editorial by Melloni and Roe from Duke University Medical Center noted the concern that patients with elevated troponin levels were older and had more frequent history of heart failure, myocardial infarction, and chronic kidney disease making such conclusion complicated. We also learned that prompt revascularization did not add additional benefit over medical therapy in the study population which is consistent with previous findings on individuals with stable ischemic heart disease (NEJM. 2009 Jun 11;360(24):2503-15).

How do you risk stratify and manage those with stable ischemic heart disease and coronary artery disease?

What is the utility of biomarkers in guiding your clinical management of such patients?

Coming Home: Medicine from the Frontlines of Indian Country

Posted by Ken Bernard • August 10th, 2015

Editor’s note: This is the first in a series of posts by Dr. Ken Bernard on his experience with the Indian Health Service. 

481px-Indian_Health_Service_Logo.svgBoozhoo, or, “Hello.” I start in the language of my ancestors, the Anishinaabe, which means “Original People.” This summer I will be starting my career as an emergency physician and returning to the “rez” (reservation) after a thirteen year hiatus in the Northeast completing college, medical school, and an emergency medicine residency. What is bringing me back? To answer that, I must start at the beginning.

My life, like many here in the U.S., began with a series of numbers: APGARS of 9 and 9, weight 8 lbs. 3 oz., length 24 inches. There is also a curious ⅜. This last fraction is unique to the roughly five million American Indians and Alaskan Natives (AIAN) from over 566 federally recognized tribes that currently live in the U.S. This amount is recorded on my Certificate of Degree of Indian or Alaskan Native Blood. It is conferred by the Bureau of Indian Affairs and grants my enrollment in the Turtle Mountain Band of Chippewa Indians. Essentially, it is recognition by the federal government of my lineage and the degree of my “Indianness,” so to speak.

However, this little fraction has huge political, socioeconomic, historical, and cultural implications for Native populations. We are the only race whose membership is defined, regulated, and granted by the federal government. Personally, this number has been somewhat confusing. Nationally I am American, culturally I am Native, and ethnically I am a hodgepodge of Turtle Mountain Chippewa and European ancestry. Many consider me to look ethnically ambiguous — my patients often ask if I am Latino, Italian, or Greek. Furthermore, this number, which ties me to my home and heritage, took me farther away from both than I could have ever imagined to gain the knowledge and skills needed to fulfill my dream of becoming a physician. But I want to move away from the discussion of blood quantum for a moment to discuss a few other unsettling numbers that have been looming in my mind over the past few years.

As a researcher of health disparities and quality care, I have run into figures such as: 200%, 300% and 50%, which are the likelihoods that AIAN people are to be impoverished, unemployed, or obtain a college degree, respectively, when compared with the rest of the U.S. population. Forty-three percent represents the annual budget shortfall, and $3,348 is the per capita health expenditure, of the Indian Health Service (IHS), which is less than any other federally funded program including the federal prison system.

Or how about 20%? This is the annual physician vacancy rate within the IHS, which persists despite generous scholarship and loan repayment programs like the one I was grateful to earn. Inequities in social determinants of health and health care access, in addition to generational trauma, cultural erosion, and racial discrimination, have contributed to other disturbing facts. AIAN adults can expect to die five years earlier than their fellow U.S. citizens and have a 50% higher age-adjusted mortality rate from all causes. And AIAN neonatal mortality and death of young AIAN adults from intentional and unintentional injuries is 200% higher than their U.S. counterparts.

So now back to my “3/8thness” and my calling to serve Native people through the IHS. What do I do with the other 5/8ths or the leftovers? Why doesn’t anyone feel the need to define the 5/8ths of me that have been deemed “not Indian”? Well, that is easy. One dinner with my family and me would demonstrate to anyone observing that I am all in, 100% Indian, with no proportion of me that has ever wanted to be anything but a physician who serves Native people.

Our dinner ritual has been practiced for generations. The adolescents and healthy adults prepare and serve the food, first to elders, then the ill or frail followed by expectant mothers or moms with infants, and honored guests.

Next, the food is laid out on the table and a line naturally forms with the youngest first. The prep and service team eats last, once all others are comfortable and full. This small, quiet ritual is an important expression of our dedication to one another. It is a sign of respect and gratitude to those elders who have worked so hard in making sure we have had a chance to thrive. It is recognition that we are only as strong as our weakest members who deserve our compassion, love, and care.

So really, my call to service had nothing to do with fractions or percentages, but with values that lead most of us to medicine such as: service, compassion, justice, altruism, community, dedication, and love. As a researcher and physician I have come to appreciate that we need to look past numbers to understand the context and experience of individual patients. As a person and proud member of the Turtle Mountain Band of Chippewa I have never paid much attention to this notion of 3/8ths, but instead look to the foundation of cultural values and beliefs taught to me by elders and my community, which have brought me back to serve the Navajo and Hopi Nations at the Tuba City Regional Health Center in Northern Arizona.

I am excited to be able to share my experiences during this journey. I hope to not only raise awareness about the challenges on the front lines of medicine in Indian Country, but also encourage others to follow their passion and calling.

Chronic Cough

Posted by Carla Rothaus • August 7th, 2015

Cause of Chronic Cough 8-6-15In a new Clinical Problem-Solving article, a 63-year-old nonsmoking man presented with a 2-year history of dry cough. Videos showing transthoracic echocardiograms obtained before and during the course of the patient’s treatment are available.

Whipple’s disease may be difficult to recognize; its rarity and nonspecific clinical features (overlapping with those of many chronic inflammatory diseases) often result in delayed diagnosis (up to 2 to 6 years after the onset of symptoms, according to some case series).

Clinical Pearls

What causes Whipple’s disease?

Whipple’s disease is a chronic infectious disease that affects multiple organ systems; it is a rare disease, with a reported annual incidence of less than 1 case per 1,000,000 people. It is caused by Tropheryma whipplei, a ubiquitous environmental organism. T. whipplei is thought to be acquired by fecal-oral transmission and is found in sewage-plant effluxes.

What is the most common profile of a patient diagnosed with Whipple’s disease?

The disease appears to occur more frequently in persons of European ancestry than in persons of other ancestries and more frequently in men than in women (male:female ratio, 4:1). It most often manifests in middle age, although cases occur across the age spectrum.

Morning Report Questions

Q: What are some of the typical manifestations of Whipple’s disease?

A: Whipple’s disease has a broad spectrum of symptoms and signs; typical manifestations (and their frequency in case series) include weight loss (in 92% of patients), diarrhea (in 76%), arthralgia (in 67%), abdominal pain (in 55%), fever (in 38%), supranuclear ophthalmoplegia (in 32%), headache (in 10%), anemia (in 85%), lymphadenopathy (in 60%), endocarditis (in 30%, and usually culture-negative), and pulmonary involvement (in 30 to 40%, approximately half of whom have cough). The typical presentation is a prodrome of arthritis, followed by persistent diarrhea and weight loss; arthritis can precede the gastrointestinal symptoms by many years. Although Whipple’s disease is uncommon, chronic infection with T. whipplei should be considered in any patient with persistent unexplained arthralgias or gastrointestinal or systemic symptoms.

Q: What is the diagnostic test of choice for Whipple’s disease and how is it treated?

A: The diagnostic test of choice is upper gastrointestinal endoscopy with biopsies (although other tissue sites may be sampled). Identification of the 16S ribosomal RNA gene with the use of a polymerase-chain-reaction assay (e.g., from feces or saliva) has high sensitivity and specificity for the organism but should not be used in isolation for diagnosis. Culture is not useful in diagnosis, because it may take months for the organism to grow and requires special techniques; serologic testing is nonspecific. In the absence of randomized trials, treatment recommendations are guided largely by case series. First-line treatment typically involves 2 weeks of ceftriaxone, followed by at least 1 year of trimethoprim-sulfamethoxazole. For patients who have a sulfa allergy or desire only oral therapy, doxycycline plus hydroxychloroquine may be substituted for either or both ceftriaxone and trimethoprim sulfamethoxazole (with response rates in case series similar to those reported with standard therapy).

Figure 2. Pathological Findings.

Pregnancy Complicated by Venous Thrombosis

Posted by Carla Rothaus • August 7th, 2015

Pregnancy Complicated by Venous Thrombosis 8-6-15A new Clinical Practice article provides an overview of venous thrombosis in pregnancy. Low-molecular-weight heparins are generally preferred for the treatment of venous thromboembolism in pregnant women. Coumarins are contraindicated in pregnancy but can be used after delivery.

Although the absolute incidence of venous thromboembolism in pregnancy is low (1 or 2 cases per 1000 pregnancies), this risk is approximately five times as high as the risk among women who are not pregnant. These risks reflect the venous stasis and procoagulant changes in coagulation and fibrinolysis, which are considered to be part of physiologic preparation for the hemostatic challenge of delivery.

Clinical Pearls

Are there any distinguishing clinical features of deep-venous thrombosis associated with pregnancy, and when does venous thromboembolism associated with pregnancy most often occur?

The clinical diagnosis of venous thrombosis is unreliable in pregnancy. Suggestive symptoms and signs, such as leg swelling and dyspnea, may be difficult to differentiate from the physiologic changes of pregnancy. As compared with deep-vein thrombosis in nonpregnant persons, deep-vein thrombosis in pregnant women occurs more frequently in the left leg (85%, vs. 55% in the left leg among nonpregnant persons) and is more often proximal (72% in the iliofemoral veins, vs. 9% in the iliofemoral veins among nonpregnant persons), with a greater risk of embolic complications and the post-thrombotic syndrome. Thrombotic events occur throughout pregnancy, with more than half occurring before 20 weeks of gestation. The risk increases further in the puerperium (the 6-week period after delivery), probably owing to endothelial damage to the pelvic vessels that occurs during delivery. Recent data indicate that an increased relative risk (but low absolute risk) persists until 12 weeks after delivery. However, approximately 80% of postpartum thromboembolic events occur in the first 3 weeks after delivery.

What is the recommended evaluation for suspected venous thromboembolism occurring during pregnancy?

Suspected deep-vein thrombosis is best assessed by means of compression duplex ultrasonographic examination, including examination of the iliofemoral region. In women with a negative result on ultrasonography in whom clinical suspicion of deep-vein thrombosis is high, it may be prudent to repeat the test after 3 to 7 days. In cases in which iliocaval venous thrombosis is suspected but ultrasonography cannot detect a thrombus, magnetic resonance or conventional x-ray venography may be considered. Chest radiographic findings are normal in the majority of cases of pulmonary embolism, but they can show pulmonary features that point to an alternative diagnosis or nonspecific features of pulmonary embolism such as atelectasis or regional oligemia. Since deep-vein thrombosis is often present in patients with pulmonary embolism, ultrasonographic venography is useful in patients who have possible symptoms or signs of deep-vein thrombosis. If deep-vein thrombosis is detected, further radiologic studies do not have to be performed to confirm a pulmonary embolism. In women with normal findings on chest radiography, ventilation-perfusion lung scanning is often recommended, since it has a high negative predictive value, owing to the low prevalence of coexisting pulmonary problems that can result in indeterminate or false positive results. Moreover, the ventilation component can often be omitted, thereby minimizing the dose of radiation to the fetus. Whereas computed tomographic (CT) pulmonary angiography (CTPA), with its high sensitivity and specificity, is usually the first-line test to detect pulmonary embolism in nonpregnant patients, it is used less often in pregnant women.

Morning Report Questions

Q: What is the recommended treatment for venous thromboembolism associated with pregnancy?

A: Anticoagulation in pregnancy typically involves unfractionated heparin or low-molecular-weight heparin, which do not cross the placenta or enter breast milk. In contrast, vitamin K antagonists such as warfarin are contraindicated in pregnancy, since they cross the placenta and their use is associated with embryopathy, central nervous system abnormalities, pregnancy loss, and fetal anticoagulation with possible bleeding. Low-molecular-weight heparins have largely replaced unfractionated heparin for the management of venous thromboembolism in pregnancy. Typical agents include dalteparin (at a dose of 200 IU per kilogram of body weight daily or 100 IU per kilogram twice daily), enoxaparin (1.5 mg per kilogram daily or 1 mg per kilogram twice daily), and tinzaparin (175 units per kilogram daily). Data are limited regarding the use of fondaparinux in pregnancy. Oral direct thrombin inhibitors such as dabigatran and anti-factor Xa inhibitors such as rivaroxaban should generally be avoided during pregnancy. These agents may cross the placenta with possible adverse fetal effects. Thrombolysis in pregnancy is reserved for massive life-threatening pulmonary embolism with hemodynamic compromise or for proximal deep-vein thrombosis that is threatening leg viability. Caval filters are sometimes used in women who have recurrent pulmonary embolisms despite adequate anticoagulation or in whom anticoagulation is contraindicated, or in women in whom acute deep-vein thrombosis has developed close to the time of delivery.

Q: What adjustments are made to heparin therapy with the approach of labor and delivery?

A: Women should be advised to discontinue injections of heparin if labor starts or is suspected. Neuraxial anesthesia is usually deferred until at least 24 hours after the last dose, given a small risk of epidural hematoma associated with administration of neuraxial anesthesia before that time. After delivery, low-molecular-weight heparin should not be administered for at least 4 hours after spinal anesthesia or removal of an epidural catheter. After delivery, anticoagulant treatment is continued for at least 6 weeks, with a minimum total duration of 3 months.

Table 1. Summary of Recommendations for Which There is Consensus and Uncertainties and Variations in Guidelines for the Management of Venous Thromboembolism in Pregnancy.