Lymphocytic Interstitial Pneumonia

Introduction

Background

Lymphocytic interstitial pneumonia (LIP) is a syndrome of fever, cough, and dyspnea, with bibasilar pulmonary infiltrates consisting of dense interstitial accumulations of lymphocytes and plasma cells.

LIP may be associated with autoimmune and lymphoproliferative disorders, including rheumatoid arthritis, Hashimoto thyroiditis, myasthenia gravis, pernicious anemia, autoerythrocyte sensitization syndrome, chronic active hepatitis, common variable immunodeficiency, Sjögren syndrome, allogeneic bone marrow transplantation, lupus, and lymphoma. Pseudolymphoma represents a localized masslike variant of LIP.

LIP is also associated with infection via human immunodeficiency virus (HIV) type 1, Epstein-Barr virus, and human T-cell leukemia virus (HTLV) type 1.

Pathophysiology

Patients may have symptoms related to the above disorders.

HIV-related LIP may be part of a continuum of lymphocytic infiltrative disorders, such as pulmonary lymphoid hyperplasia in children and radiographically clear lymphocytic alveolitis in adults. Patients positive for HLA-DR5 and HLA-DR6 alleles are predisposed to developing a diffuse visceral lymphocytosis syndrome with LIP.

LIP has been reported to occur as part of immune reconstitution syndrome.

Frequency

United States

LIP is an uncommon disease. However, LIP is found in 22-75% of pediatric patients with HIV who have pulmonary disease. In contrast, among adult patients with HIV, LIP accounts for only 3% of HIV-related pulmonary pathology.

International

Small series have been reported in Europe, southwestern Japan, Africa, and the Caribbean basin.

Mortality/Morbidity

Mortality and morbidity data are inexact because of the lack of reported follow-up and the rarity of the disease.

• In the population who does not have HIV infection, half the patients improve with treatment but relapse is common. End-stage fibrosis may follow despite treatment. In the past, high mortality was reported in older patients.
• Patients with HIV-associated LIP display slower decline in CD4⁺ T-cell counts and longer survival than individuals who have HIV infection but do not have LIP.
• Patients with HIV infection but not LIP generally respond to treatment.

Race

• LIP has been found in every race and HIV risk group. Whether racial or geographic predispositions are crucial remains unclear.
• Many reports describe HIV and HTLV type 1–associated LIP among individuals of African ancestry.³
• LIP appears to cluster in southwestern Japan, where HTLV type 1 is endemic.

Sex

• LIP is more common in women when not associated with HIV infection.
• HIV-associated sicca syndrome occurs most often in males.⁴

Age

• Most cases not associated with HIV occur in the fourth and seventh decades of life, at an average age of 56 years.
• LIP is common only in children with HIV. In children with HIV infection, LIP has been designated an AIDS-defining illness by the US Centers for Disease Control and Prevention.

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Folic Acid Supplements May Fight Allergy Symptoms

With spring sneaking up on us, pollen is in the air and allergy sufferers everywhere are breathing a congested sigh of disdain. Even though outdoor barbeques, marathons, work-related outings, picnics, markets and festivals are planned throughout the summer, people who sneeze, cough, and generally feel miserable when the wind blows are not welcoming this change. Emerging research shows that B9—also known as folic acid—the component that keeps red blood cells healthy and has been shown to reduce birth defects associated with the spine may also help curb such miserable hot-weather symptoms. According to the Centers for Disease Control (CDC) about 25 million Americans are living with allergies due to their environment and asthma is the biggest portion of a chronic condition that children are afflicted by affecting 7 percent of all age groups throughout the United States.

The study was conducted at the Johns Hopkins Children’s Center, hoping to keep allergy symptoms (including asthma) at bay. By looking through the records of over 8,000 patients between the ages of 2 and 85, researchers tracked the folic acid levels against people with lung issues and allergy symptoms to find a pattern. Patients with higher blood levels of folic acid had less antibodies that trigger immunity response throughout the body.

The results were recently printed in The Journal of Allergy and Clinical Immunology and in a press release done by Johns Hopkins which lead researcher and pediatric allergist Dr. Elizabeth Matsui says that this is a breakthrough in allergy response, “Our findings are a clear indication that folic acid may indeed help regulate immune response to allergens, and may reduce allergy and asthma symptoms,” she adds that folic acid on its own won’t be a cure and more studies will eventually be done, “But we still need to figure out the exact mechanism behind it, and to do so, we need studies that follow people receiving treatment with folic acid before we even consider supplementation with folic acid to treat or prevent allergies and asthma.”

Even if popping B9 supplements may not help prevent this year’s allergy season, it is good to know that there is hope for the future. Usually found in leafy, green vegetables (also rich in vitamin K), nuts, beans, grains, and cereal products, healthy men and women are supposed to ingest 400 micrograms per day.

Believed to be the first study of its kind linking folic acid to allergy symptoms, these findings are new and exciting. More specifics of the findings include records like patients with lower folic acid levels in their blood (also known as folate levels) incur a 40 percent higher risk of wheezing than people with higher levels. Other risks involved with low folate levels are a 30 percent higher risk of developing allergies, 31 percent higher risk of allergy symptoms, and 16 percent higher risk of asthma.

Funded by the National Institutes of Health (NIH), the next step to the study is to use a controlled experiment using a placebo group alongside patients with both allergies and asthma.

Scientists decree that folic acid is not a cure-all and will not be ready for use as an allergy preventative for at least a few years. Although a lot of allergies are based on the type of landscape you live around, but if you are prone to allergen sensitivity, you will most likely find something to trigger the effects. Asthma is more tricky but because this is a rising condition among children, it merits research and this discovery seems to be shedding light that may eventually help. If folic acid is not already consciously part of your on your shopping list, it may be helpful to stock up on foods already rich in the nutrient…just in case.

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Everything Is Coming Up Rose Hips

Growing up I did not have any allergies, but a check-up with my pediatrician at age 12 confirmed an allergy when I told my doctor that cantaloupe melon makes the roof of my mouth itch uncontrollably. After I was told to stop eating cantaloupe (and the rest of the ripe, sweet melon family including avocado), I reluctantly went home with a food allergy. With a huge focus the past few years on the dangers of peanut allergies, from taking the tiny dangerous bags off of airplanes to banning peanuts and peanut butter-related items from school cafeterias across the globe, a food allergy awareness week is just the thing to kick start more campaigns to keep meals at their safest.

Starting today, Saturday May 10, to the following Saturday May 16th, Food Allergy Awareness Week takes place ensuring consumers safer ways to avoid the high or low profile foods that spark your family’s allergic needs. The Food Allergy and Anaphylaxis Network (FAAN) created the Food Allergy Awareness Week in May of 1997 in order to use the media coverage to educate.

This year’s theme is “Take Action, Prevent Reactions.” Schools, communities, and outreach organizations will be taking part in trying to spread the word about this growing hidden danger. You can download posters, fliers, statistics and other promotional and informational materials from the FAAN website to help with your local efforts.

FAAN’s goal for 2009 is to get proclamations from all 50 states that legislation will declare Food Allergy Awareness Week to promote it on a larger scale. With 4 percent of the population suffering from food allergies and around 50,000 emergency visits per year, this is becoming a widespread problem. So far communities across the country have been helping to get states on board and the FAAN has already convinced Connecticut, Georgia, Maine, Nebraska, Illinois, Nevada, Wisconsin, and Texas to sign on to proclamations. To make and send a proclamation, find a template on the FAAN website and send it to your governor for approval.

In terms of education, there are educational DVDs and children’s books aimed at making sure school-aged children are aware of the dangers of bringing banned foods to school and making sure to keep their lunches to themselves if they happen to have an allergy. There are also cookbooks for the healthy and safe at-home chef in order to keep those food allergies at bay.

By reminding consumers with allergies to “CAP It,” the FAAN tries to get people to remember three simple steps to keeping healthy: Carry your medicine; Avoid your allergen; and Plan ahead to prevent reaction. The CEO of FAAN, Julia Bradsher, says that although food allergies are a pain, they need to be managed, “Food allergies can be challenging to manage, but we know that reactions can be prevented by taking a few simple steps….Adults and children with food allergies and their families can empower themselves every day by taking steps to safeguard against reactions. By sharing their knowledge with others during Food Allergy Awareness Week and throughout the year, we hope to reduce the number of reactions and save lives.”

With over 30,000 members worldwide, FAAN is developing quite a fan base and they hope to become better known in your state when new proclamations are announced. Affecting around one of every 25 Americans and countless friends and families, food allergies are lurking inside millions of people from the playground to the boardroom, so take action now and stay safe.

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Researchers Say U.S. Obesity Epidemic Due to Overeating

The debate about whether the chicken or the egg came first has had some steep competition in recent years—what’s to blame for the obesity epidemic in America? Some experts say it’s genetics, some say environmental chemicals are to blame, others say it’s our slothful lifestyle filled with hours of television and video games. But Australian researchers say the rise in obesity is due almost entirely to overeating, and they have the numbers to prove it.

For their study, Professor Boyd Swinburn of Deakin University in Victoria, Australia and colleagues calculated how much adults need to eat in order to maintain a stable weight and how much children must eat to maintain a normal growth curve under normal living conditions. Then, using national food supply data from the 1970s and the early 2000s, they figured out how much Americans were actually eating. From this information, the researchers could predict how much weight Americans would be expected to gain over the 30-year period had food intake been the only influence. Next they used NHANES data on population weight during that time period to determine how much weight was actually gained.

According to the researchers, the predicted and actual weight increase in children matched exactly, indicating that the increase in caloric intake alone could explain the additional pounds. Adults gained less than the data predicted—18.9 pounds versus 23.8 pounds—which “suggests that excess food intake still explains the weight gain, but there may have been increases in physical activity over the 30 years that have blunted what would otherwise have been a higher weight gain,” Swinburn noted.

“There have been a lot of assumptions that both reduced physical activity and increased energy intake have been major drivers of the obesity epidemic. Until now, nobody has proposed how to quantify their relative contributions to the rise in obesity since the 1970s,” said Swinburn. “This study demonstrates that the weight gain in the American population seems to be virtually all explained by eating more calories. It appears that changes in physical activity played a minimal role.” He added that the findings would “probably be similar” for other developed countries as well.

Swinburn said that for the U.S. population to revert to the leaner 1970s levels, children would have to cut their daily caloric intake by about 350 calories—the equivalent of a can of fizzy drink and a small portion of French fries, and adults by about 500 calories—about the same as a Big Mac burger. Alternatively children would have to walk an extra two-and-a-half hours a day, and adults for nearly two hours. “Getting everybody to walk an extra two hours a day is not really a feasible option for countering the epidemic,” Swinburn said. “We need to limit our expectations of what an increase in physical activity can achieve.” In short, Americans must eat less, he said.

However, Swinburn emphasized that the findings in no way seek to negate the value of physical activity. “We absolutely need to continue to promote increased physical activity and a healthy diet because they are both obviously beneficial factors in terms of obesity,” he said. “But when it comes to placing priorities, I think it needs to be on reducing energy intake. It’s particularly important for policymakers to focus on the energy intake side of the equation.”

Other experts agree with the study’s conclusions. “We have long suspected that the decrease in physical activity seen during the past 30 years is playing a minor role in the change in body weight,” said Dr. Robert Lustig, an obesity researcher at the University of California San Francisco. “This was inferred by the fact that virtually all studies of increased exercise in obesity did not translate into weight loss.” He added that exercise plays an essential role in the obesity epidemic, not because it reduces excess weight, but because it improves health. For example, twenty minutes of jogging burns the equivalent of a chocolate chip cookie, he said. Therefore, Americans “need a complete overhaul of our diet if we are to solve the obesity epidemic,” Dr. Lustig said.

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Child Hunger a Growing Issue in the U.S.

Based on the 2005-2007 data from the U.S. Census Bureau and the Agriculture Department, at least 17 percent of children across America have the potential to go hungry. Children who lack proper nourishment during their developmental stages of life risk long-term affects, such as developmental, behavioral, and academic problems. Children are a key component to our future, and nourishment is significant to children prospering, both mentally and physically.

Thousands of children go hungry across the United States daily. The government has developed ways to ensure school-aged children are provided nutritious meals each school day. However, it may be hard for the government to extend this assistance to children aged five and under, which are not in school. A new study recently conducted by a non-profit anti-hunger group called Feeding America, concentrated primarily on hunger in children below the age of five. The group found that approximately 17 percent of children in this age group are at risk of going hungry. They found that 11 states actually had more than 20 percent of children under five who were at risk of going hungry. They included the top state of Mississippi, then North Carolina, Ohio, Kentucky, Texas, New Mexico, Kansas, South Carolina, Tennessee, Idaho and Arkansas. Feeding America operates centers to feed the hungry around the U.S

According to Dr. John Cook, an associate professor of pediatrics at Boston Medical Center and lead researcher of the report, hunger is based on two main factors across each state, the states level of employment and poverty rates, as well as the offerings of food and income assistance programs. Hunger seems to be a major problem across the U.S that continues to need attention. The newly released study was not based on data gathered during this new downturn in the economic market, which probably mean the numbers are currently even worse than expected. Vicki Escarra, president and chief executive of Feeding America said, "These children without the availability of nutrition don't have the chance to spring back." She noted that her organization is currently lobbying for additional federal funding for food bank programs to target young children.

This new data should help us be more aware of our hunger situation here in the United States. Children are not just going hungry in other countries, but there are over 12 million children at risk of going hungry here in the U.S. each day. It is very important for communities to support their local food banks and charities that target these groups and look to our government for more financial support and food for our hungry children. Without food and nutrition in their developmental stages in life, children may be left with impairments and the lifelong affects of childhood hunger.

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Esophageal Stricture

Introduction

Background

Disease processes that can produce esophageal strictures can be grouped into 3 general categories: (1) intrinsic diseases that narrow the esophageal lumen through inflammation, fibrosis, or neoplasia; (2) extrinsic diseases that compromise the esophageal lumen by direct invasion or lymph node enlargement; and (3) diseases that disrupt esophageal peristalsis and/or lower esophageal sphincter (LES) function by their effects on esophageal smooth muscle and its innervation.

Many diseases can cause esophageal stricture formation. These include acid peptic, autoimmune, infectious, caustic, congenital, iatrogenic, medication-induced, radiation-induced, malignant, and idiopathic disease processes.

The etiology of esophageal stricture can usually be identified using radiologic and endoscopic modalities and can be confirmed by endoscopic visualization and tissue biopsy. Use of manometry can be diagnostic when dysmotility is suspected as the primary process. CT scan and endoscopic ultrasound are valuable aids in the staging of malignant stricture. Fortunately, most benign esophageal strictures are amenable to pharmacological, endoscopic, and/or surgical interventions.

Because peptic strictures account for 70-80% of all cases of esophageal stricture, peptic stricture is the focus of this article. A detailed discussion of possible benign and malignant processes associated with esophageal stricture and its management is beyond the scope of this article.

Pathophysiology

Peptic strictures are sequelae of gastroesophageal reflux–induced esophagitis, and they usually originate from the squamocolumnar junction and average 1-4 cm in length.

• Two major factors involved in the development of a peptic stricture are as follows:
  • Dysfunctional lower esophageal sphincter: Mean LES pressures are lower in patients with peptic strictures compared with healthy controls or patients with milder degrees of reflux disease. A study by Ahtaridis et al (1979) showed that patients with peptic strictures had a mean LES pressure of 4.9 mm Hg versus 20 mm Hg in control patients. LES pressure of less than 8 mm Hg appeared to correlate significantly with the presence of peptic esophageal stricture without any overlap in controls.
  • Disordered motility resulting in poor esophageal clearance: In the same study, Ahtaridis et al (1979) demonstrated that 64% of patients with strictures had motility disorders compared with 32% of patients without strictures.
• Other possible associated factors include the following:
  • Presence of a hiatal hernia: Hiatal hernias are found in 10-15% of the general population, 42% of patients with reflux symptoms and no esophagitis, 63% of patients with esophagitis, and 85% of patients with peptic strictures. This suggests that hiatal hernias may play a significant role.
  • Acid and pepsin secretion: This does not appear to be a major factor. Patients with peptic strictures have been demonstrated to have the same acid and pepsin secretion rates as gender-matched and age-matched controls with esophagitis but no stricture formation. In fact, some authors believe that alkaline reflux may play an important role.
  • Gastric emptying: No good evidence suggests that delayed emptying plays a role.

Frequency

United States

Gastroesophageal reflux affects approximately 40% of adults. Strictures are estimated to occur in 7-23% of untreated patients with reflux disease.

Gastroesophageal reflux disease accounts for approximately 70-80% of all cases of esophageal stricture. Postoperative strictures account for about 10%, and corrosive strictures account for less than 5%.

The overall frequency of initial and subsequent dilations for peptic stricture appears to have decreased gradually since the introduction of proton pump inhibitors (PPIs) in the market in 1989. This has been borne out by data at the author's institution and in 2 large community hospitals in Wisconsin. It is also in keeping with the general experience of gastroenterologists in the United States.

Mortality/Morbidity

The mortality rate is not increased unless a procedure-related perforation occurs or the stricture is malignant. However, the morbidity for peptic strictures is significant.

• Most patients undergo a chronic relapsing course with an increased risk of food impaction and pulmonary aspiration.
• Frequently, coexistent Barrett esophagus and its attendant complications occur.
• The need for repeated dilatation potentially increases the risk of perforation.

Race

Peptic strictures are 10-fold more common in whites than African Americans or Asians.

Sex

Peptic strictures are 2- to 3-fold more common in men than in women.

Age

Patients tend to be older, with a longer duration of reflux symptoms.

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Esophageal Spasm

Introduction

Background

Broadly, esophageal spasm can be subdivided into 2 distinct entities: (1) diffuse esophageal spasm (DES), in which contractions are uncoordinated, and (2) nutcracker esophagus, in which contractions proceed in a coordinated manner, but the amplitude is excessive.

Symptoms can include dysphagia, regurgitation, and noncardiac chest pain. Because of the vague symptoms and difficulty in diagnosis, esophageal spasm often is not diagnosed and is undertreated. Many patients with manometric and radiologic aberrations may not have any appreciable symptoms.

Currently, manometry is the best diagnostic modality. Treatment includes calcium channel blockers, botulinum toxin, nitrates, tricyclic antidepressants, dilatation, myotomy, and esophagectomy. Research is ongoing to unlock the underlying causes to improve our diagnostic capabilities and therapeutic regimens in the future.

Pathophysiology

The esophagus is comprised of 2 layers of muscle, the inner circular and the outer longitudinal layers. Arbitrarily, the esophagus can be divided into 3 zones, each with separate yet integrated anatomy and physiology.

Esophageal zones

Upper zone: Comprised entirely of striated muscle, this zone initiates the contractions that propel the food bolus down the esophagus. The upper esophageal sphincter (UES), named the cricopharyngeus muscle, is located in the upper zone.

Middle zone: Comprised of striated and smooth muscles, the inner circular muscle layer and the outer longitudinal muscle layer work in conjunction to propel the food bolus.

Lower zone: The lower segment is the lower esophageal sphincter (LES). This sphincter is a thickening of the smooth muscle that is contracted tonically to prevent reflux. At rest, the pressure in the LES is usually 15-25 mm Hg. For food to pass into the stomach, the LES relaxes.

Upper esophageal sphincter

When functioning properly, the esophagus can detect the presence of a food bolus at the UES and then coordinate progression of the food down the esophagus to the stomach. When this does not occur in a coordinated fashion, the patient can develop symptoms of esophageal spasm.

The UES is contracted tonically. Manometric evaluation of the UES reveals constant spiking activity. As food is sensed at the UES, the laryngeal muscles contract to move the cricoid cartilage anteriorly. The tonic contraction of the UES is inhibited, opening the UES to allow passage of food. The inner circular muscles and longitudinal muscles of the remainder of the upper zone then propel the food. To propel the food, the longitudinal muscles must contract, followed immediately by contraction of the circular muscles. At the end of the upper zone, the initial wave dies out as another wave starts, propelling the food down to the middle zone. The nucleus solitarius in the brainstem controls swallowing in the upper zone.

Esophageal middle zone

The middle zone propels the food bolus from the upper zone to the lower zone. This segment consists of 2 muscle layers, an inner circular and outerlongitudinal layer.

In the middle zone, the striated muscle transitions to smooth, or involuntary, muscle. The wave propagates down the esophagus by coordinated contractions. Again, the longitudinal muscles must contract before the circular muscle contracts. Furthermore, contraction of the muscles must proceed caudally in an organized manner. If the muscle contraction is not orderly, the food bolus cannot progress.

Two forces propel the food from cephalad to caudad. First, gravity pulls the food caudally. The organized contractions of the muscles propel the food caudally. If a myotomy is performed, the contractions will be ineffective. Only gravity forces the food caudally. Thus, patients who have had a myotomy are more likely to have dysphagia.

Lower esophageal sphincter

The lower zone is comprised of the LES. This is a condensation of the smooth muscles. Tonically, this muscle is contracted and must relax to allow food to pass. Failure of the LES to relax to allow a food bolus to pass is termed achalasia (see Achalasia).

Diffuse esophageal spasms

Simplistically, DESs occur when the propagative waves do not progress correctly. Usually, several segments of the esophagus contract simultaneously, preventing the propagation of the food bolus. The usual presentation is intermittent dysphagia with occasional chest pain. Myotomy, which is performed only in extreme cases, can relieve the uncoordinated contractions.

Nutcracker esophagus

Nutcracker esophagus occurs when the amplitude of the contractions exceeds 2 standard deviations from normal. The contractions proceed in an organized manner, propelling food down the esophagus. These patients often present with chest pain, but they present with dysphagia less often than patients with DES.

Because the progression of the contractions occurs normally, patients often do not benefit from a myotomy. Even though the increased amplitude of the contractions can be demonstrated using manometry, the symptoms often do not correlate with the manometrically documented contractions.

The symptoms of DES and nutcracker esophagus may overlap and can be distinguished only by motility study.

Frequency

United States

The true incidence of esophageal spasm cannot be determined. The symptoms range from mild to severe. Patients with mild symptoms often do not seek medical attention. Because of the similarity of symptoms of reflux disease and esophageal spasm, many patients may be misdiagnosed with reflux. Furthermore, reflux and spasm can occur concomitantly.

International

Because the symptoms are mild (or even absent) in many patients, true incidence is not known.

Mortality/Morbidity

• Mortality is very rare, but morbidity can be significant.
• 
  
• Morbidity arises from an inability to eat, secondary to the pain, and the subsequent decline in nutritional status. The pain can be incapacitating, preventing normal activity and leading to considerable psychological challenges and impairment in the patient's quality of life.
• 
  
• The chest pain can mimic cardiac, pulmonary, or rheumatological chest pain, instigating appropriate workup.

Race

• This condition seemingly is more common in whites.

Sex

• This condition may be more common in women than in men.

Age

• This condition is rare in children, and incidence increases with age.

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Esophageal Motility Disorders

Introduction

Background

The esophagus functions solely to deliver food from the mouth to the stomach where the process of digestion can begin. Efficient transport by the esophagus requires a coordinated, sequential motility pattern that propels food from above and clears acid and bile reflux from below. Disruption of this highly integrated muscular motion limits delivery of food and fluid, as well as causes a bothersome sense of dysphagia and chest pain. Disorders of esophageal motility are referred to as primary or secondary esophageal motility disorders and categorized according to their abnormal manometric patterns.

Anatomy

The tubular esophagus is a muscular organ, approximately 25 cm in length, and has specialized sphincters at proximal and distal ends. The upper esophageal sphincter (UES) is comprised of several striated muscles, creating a tonically closed valve and preventing air from entering into the gastrointestinal tract. The lower esophageal sphincter (LES) is composed entirely of smooth muscle and maintains a steady baseline tone to prevent gastric reflux into the esophagus.

The body of the esophagus is similarly composed of 2 muscle types. The proximal esophagus is predominantly striated muscle, while the distal esophagus and the remainder of the GI tract contain smooth muscle. The mid esophagus contains a graded transition of striated and smooth muscle types. The muscle is oriented in 2 perpendicular opposing layers: an inner circular layer and an outer longitudinal layer, known collectively as the muscularis propria. The longitudinal muscle is responsible for shortening the esophagus, while the circular muscle forms lumen-occluding ring contractions.

Esophageal peristalsis

The coordination of these simultaneously contracting muscle layers produces the motility pattern known as peristalsis. Peristalsis is a sequential, coordinated contraction wave that travels the entire length of the esophagus, propelling intraluminal contents distally to the stomach. The LES relaxes during swallows and stays opened until the peristaltic wave travels through the LES, then contracts and redevelops resting basal tone. Low peristaltic amplitudes normally occur at the transition zone between the striated and smooth muscle portions; however, the peristalsis is uninterrupted.

Primary peristalsis is the peristaltic wave triggered by the swallowing center. The peristaltic contraction wave travels at a speed of 2 cm/s and correlates with manometry-recorded contractions. The relationship of contraction and food bolus is more complex because of intrabolus pressures from above (contraction from above) and the resistance from below (outflow resistance).

The secondary peristaltic wave is induced by esophageal distension from the retained bolus, refluxed material, or swallowed air. The primary role is to clear the esophagus of retained food or any gastroesophageal refluxate.

Tertiary contractions are simultaneous, isolated, dysfunctional contractions. These contractions are nonperistaltic, have no known physiologic role, and are observed with increased frequency in elderly people. Radiographic description of this phenomenon has been called presbyesophagus.

Esophageal motility disorders

Esophageal motility disorders are not uncommon in gastroenterology. The spectrum of these disorders ranges from the well-defined primary esophageal motility disorders (PEMDs) to very nonspecific disorders that may play a more indirect role in reflux disease and otherwise be asymptomatic. Esophageal motility disorders may occur as manifestations of systemic diseases, referred to as secondary motility disorders.

Esophageal motility disorders are less common than mechanical and inflammatory diseases affecting the esophagus, such as reflux esophagitis, peptic strictures, and mucosal rings. The clinical presentation of a motility disorder is varied, but, classically, dysphagia and chest pain are reported. In 80% of patients, the cause of a patient's dysphagia can be suggested from the history, including dysmotility of the esophagus. Before entertaining a diagnosis of a motility disorder, first and foremost, the physician must evaluate for a mechanical obstructing lesion.

Esophageal motility disorders discussed in this article include the following:

• Achalasia
• Spastic esophageal motility disorders, including diffuse esophageal spasm (DES), nutcracker esophagus, and hypertensive LES
• Nonspecific esophageal motility disorder (inefficient esophageal motility disorder)
• Secondary esophageal motility disorders related to scleroderma, diabetes mellitus, alcohol consumption, psychiatric disorders, and presbyesophagus

Pathophysiology

The pathophysiology of the primary esophageal motility disorders is poorly defined, with the exception of achalasia. The underlying cause of all the primary motility disorders remains elusive. The secondary motility disorders, such as scleroderma esophagus or esophageal motility disorder of diabetes, are better understood from the standpoint of the preexisting underlying disorders.

Achalasia

Achalasia is the best defined primary motility disorder and the only one with an established pathology. The predominant neuropathologic process of achalasia involves the loss of ganglion cells from the wall of the esophagus, starting at the LES and developing proximally. The degree of ganglion cell loss parallels the disease duration such that, at 10 years, ganglion cells are likely completely absent. At the LES, the loss of inhibitory nerves is demonstrated by loss of nitric oxide synthase and vasoactive intestinal peptide (VIP) immunohistochemistry staining. Variable amounts of inflammatory cells have been described within the myenteric plexus along with the disappearing nerves. In the peristaltic esophageal body, achalasia is characterized by a loss of intrinsic acetylcholine-containing nerves. Extrinsic nerves may also be affected, characterized by Wallerian degeneration of the axoplasm and myelin sheaths within the vagus nerve and dorsal motor nucleus. Anatomically, the circular muscle layer at the

LES is thickened, but, microscopically, individual muscle cells are grossly normal.

The physiologic process of achalasia is correlated most directly to the loss of the inhibitory nerves at the sphincter, resulting in failure of the LES to completely relax and causing relative obstruction. Manometry may reveal elevated LES pressure greater than 40 mm Hg in more than 60% of patients; however, hypertensive LES is not universal or required for the manometric diagnosis. The loss of nerves along the esophageal body causes aperistalsis, leading to stasis of ingested food and subsequent dilation of the esophagus. Nonperistaltic isolated contractions or low-amplitude simultaneous contractions of the esophageal body may be observed. If high-amplitude (>60 mm Hg) simultaneous contractions occur, the entity is categorized as vigorous achalasia, which may represent an early stage of classic achalasia. Physiologic characteristics of achalasia are additionally useful in assisting with establishing the diagnosis through chemical challenge testing.

With the partial ganglion cell loss in patients with achalasia, edrophonium (acetylcholine esterase inhibitor) increases LES pressure while atropine (muscarinic antagonist) decreases LES pressure. This characteristic likely explains why the botulinum toxin (acetylcholine release inhibitor) may have therapeutic benefit in patients with achalasia.

Spastic motility disorders of the esophageal body

No documented abnormalities exist regarding the distribution of myenteric neurons in patients diagnosed with spastic motility disorders of the esophageal body, but diffuse fragmentation of vagal filaments, increased endoneural collagen, and mitochondrial fragmentation are described. There appears to be a functional imbalance between excitatory and inhibitory postganglionic pathways, disrupting the coordinated components of peristalsis. In DES, muscular hypertrophy or hyperplasia has been described in the distal two thirds of the esophagus. Muscle wall thickening has been described in patients who are asymptomatic and, conversely, has been absent in some patients with typical symptoms and manometric findings. This controversial finding causes difficulty in attributing symptoms or manometric abnormalities to muscle structure changes. In addition, anxiety states may also play a role in some patients.

Scleroderma esophagus

In scleroderma, the primary defect in this systemic process is related to smooth muscle atrophy and fibrosis. Esophageal dysmotility develops as the smooth muscle of the esophagus is replaced by scar tissue, gradually leading to progressive loss of peristalsis and a weakening of LES. Motility is preserved at the proximal striated muscle portion of the esophagus.

Frequency

United States

Esophageal motility disorders, excluding achalasia, lack population-based studies. The 2 best-characterized motility disorders, achalasia and DES, represent only a small percentage of diagnosed motility disorders. The incidence of achalasia is 1-3 case per 100,000 population per year. As with any other chronic illness, prevalence exceeds incidence significantly. Familial clustering is observed, but a genetic relationship is not established. Nutcracker esophagus is the most common motility disorder (>40% of all motility disorders diagnosed), but it is the most controversial in significance.

International

In Europe, the incidence of achalasia is similar to that of the United States.

Mortality/Morbidity

• Achalasia is associated with significant and progressive symptomatic discomfort. When advanced, this condition can lead to such severe dysphagia that malnutrition, weight loss, and dehydration can develop. Increased incidence of both esophageal squamous cell and adenocarcinoma is observed in patients with long-standing achalasia. Therapeutic procedures and operations are associated with a small but significant risk of mortality and morbidity.
• Spastic esophageal motility disorders are associated with symptomatic discomfort but do not lead to the severity of dysphagia observed in patients with achalasia. Chest pain is, in fact, a more common complaint that may precipitate emergency room visits and cardiologic evaluations.
• Scleroderma esophagus is associated with severe and progressive acid reflux symptoms and complications. Associated complications, including strictures, Barrett esophagus, and adenocarcinoma of the esophagus, are the concern.

Race

Racial and environmental differences in the incidence of achalasia and other esophageal motility disorders might be present; however, because of the low incidence of disease and underdiagnosis in developing countries, these differences have not been demonstrated. Racial differences in the incidence of achalasia and other esophageal motility disorders have not been established.

Sex

Achalasia affects both sexes in equal numbers. No reliable information for other motility disorders exists.

Age

Achalasia commonly presents in the fifth decade but rarely may develop in children as well as in elderly persons.

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Esophageal Lymphoma

Introduction

Background

Primary esophageal lymphoma is a rare occurrence, with fewer than 25 cases reported in the past 25 years. In a series of 1467 cases of GI lymphoma, primary esophageal lymphoma accounted for only 3 cases. In general, involvement of the esophagus is most commonly a result of contiguous spread from the proximal stomach, adjacent mediastinal lymph nodes, or cervical lymph nodes. Persons with the disorder have varying presentations and relatively poor prognoses. Since the advent of HIV infection/AIDS, esophageal lymphoma has become an important, though still rare, part of the differential diagnosis in immunosuppressed patients presenting with symptoms referable to the esophagus.

Pathophysiology

The diagnosis of esophageal lymphoma is divided into 2 categories based upon site of origin. Most lymphomas involving the esophagus are thought to represent secondary involvement by an adjacent site. In most cases, esophageal lymphomas involving the distal esophagus represent extension from the proximal stomach. Lymphomas arising in the middle third of the esophagus may be secondary to mediastinal lymph node enlargement with involvement of the esophagus. A third site of involvement is the proximal esophagus, which may represent extension from adjacent cervical lymph nodes.

The etiology of primary esophageal lymphoma is unknown; however, HIV infection is a risk factor for its development. The initial site of lymphomatous involvement in primary esophageal lymphoma is submucosal lymphoid patches, which then extend to involve the mucosa. Additionally, prior exposure to Epstein-Barr virus (EBV) may play some role in the development of esophageal lymphoma.

Dawson et al developed the following 5 criteria needed to identify a primary GI lymphoma¹ :

1. No palpable superficial lymph nodes
2. Normal chest radiograph findings with no evidence of lymphadenopathy
3. Normal WBC count
4. Predominant lesion within the GI tract with lymph node involvement confined to the lymph node chain involved in drainage of that specific GI segment
5. No involvement of the liver or spleen

Frequency

United States

GI tract lymphoma is fairly common, comprising approximately 10% of all lymphomas. In non-Hodgkin lymphoma, the most common extranodal site is the GI tract, which is involved in 5-20% of patients during life and up to 50% of patients at autopsy. The most common GI sites for lymphoma are the stomach (48-50%), small bowel (30-37%), and ileocecal region (12-13%). The esophagus is the least common site of involvement, with less than 1% of patients with GI lymphoma presenting with esophageal involvement.

Mortality/Morbidity

The data regarding prognosis of GI lymphoma indicate a variable mortality rate. Prognosis depends on the stage of disease at diagnosis and the feasibility of surgery or chemotherapy. Mortality also depends on the underlying health of the patient, as demonstrated by the overall poor prognoses of patients who are infected with HIV. The presence of AIDS, a CD4 count of less than 100/µL, and a low Karnofsky score are associated with a poor prognosis. Better outcomes are associated with a good performance status, an absence of opportunistic infections, and a CD4 count of greater than 100/µL. Additionally, patients with T-cell lymphoma have higher rates of esophageal perforation and poorer overall survival rates as compared with those patients demonstrating a B-cell phenotype.

Sex

Because of the extreme rarity of esophageal lymphoma and the small number of reported cases, a trend cannot be established regarding which sex is most commonly affected. In one series, 12 of 17 patients were men. In another report of patients with HIV-associated esophageal lymphoma, the patients were typically 40-year-old men who were profoundly immunosuppressed. A final series of 6 cases of primary esophageal lymphoma included 5 men and 1 woman.

Age

The age at presentation of esophageal lymphoma is highly variable, with cases reported in patients as young as 17 years and as old as 86 years. One case series that evaluated 763 patients infected with HIV, 22 of whom presented with non-Hodgkin lymphoma, revealed a mean age of 38.8 years ± 7.8 (SD). Half of these patients had GI involvement, and 2 had esophageal involvement. In one series, patients with primary esophageal lymphoma not associated with HIV infection/AIDS tended to be older (mean age, 61 y) than those in the HIV infection/AIDS associated group (mean age, 40 y).

Clinical

History

Symptoms can include dysphagia (most common), odynophagia, weight loss, chest pain, fever, fatigue, abdominal pain, and hoarseness. Patients may present with a history consistent with secondary achalasia. Patients do not typically present with fever or night sweats (B symptoms).

• Invasion of the esophagus may result in hemorrhage, obstruction, or perforation with a tracheoesophageal fistula.
• 
  
• Esophagotracheal fistulae most often result in death secondary to aspiration pneumonia. Even when surgically repaired, such fistulae are likely to recur.
• 
  
• Patients with HIV/AIDS
  
  
  • In patients with HIV, consider underlying esophageal lymphoma in a clinical presentation consistent with infectious esophagitis not responsive to adequate therapy. This is especially true when esophageal ulcerations are present.
  • 
    
  • In patients with HIV, consider underlying esophageal lymphoma in a clinical setting consistent with idiopathic esophageal ulceration not responsive to oral steroid therapy.
  • 
    
  • Most patients who are known to have AIDS prior to diagnosis of esophageal lymphoma have a history of opportunistic infections, such as those caused by Pneumocystis carinii (eg, P carinii pneumonia), Candida species, cytomegalovirus, and herpes simplex virus.

Physical

• Physical examination is generally not helpful in diagnosing esophageal lymphoma.
• 
  
• Ten cases of esophageal lymphoma in patients without HIV have been reviewed.
• • Nine of these 10 patients appeared to have primary esophageal lymphoma.
  • 
    
  • One of these 9 patients was found to have mild anemia; otherwise, all physical examination findings were reported as normal.
  • 
    
  • Cervical lymphadenopathy was a prominent finding of the physical examination of the sole patient who appeared to have esophageal involvement of a previously diagnosed non-Hodgkin lymphoma.
  • 
    
• Physical examination appears to be most useful in excluding generalized peripheral lymphadenopathy, which, by definition, should not be present in primary esophageal lymphoma.
• 
  

Causes

The etiology of primary GI lymphoma is unknown.

• HIV infection/AIDS: HIV infection has been recognized as a risk factor for the development of primary GI lymphoma; the relative risk of developing non-Hodgkin lymphoma for persons infected with HIV is 104 times that of people who are not infected with the virus.
• 
  
• Epstein-Barr virus
• • Most of the GI tract lymphomas are of the B-cell type; however, the significance of the EBV as an etiologic factor is controversial.
  • 
    
  • Although EBV is strongly related to B-cell proliferation in Burkitt lymphoma, its exact role in GI lymphoma is unknown.
  • 
    
• Oncogenes: DNA probes have found the proto-oncogene C-myc transcription in 75% of AIDS-associated lymphomas, which suggests a role for the C-myc oncogene.

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Esophageal Leiomyoma

Introduction

Background

Benign tumors of the esophagus are rare lesions that constitute less than 1% of esophageal neoplasms. Nearly two thirds of benign esophageal tumors are leiomyomas; the others mostly are polyps and cysts. Thus, leiomyomas are the most common benign tumors of the esophagus.

Pathophysiology

Leiomyomas represent a hyperproliferation of interlacing bundles of smooth muscle cells that are well-demarcated by adjacent tissue or by a smooth connective tissue capsule. They usually arise as intramural growths, most commonly along the distal two thirds of the esophagus. They are multiple in approximately 5% of patients.

The majority of leiomyomas have been discovered incidentally during evaluation for dysphagia or during autopsy. Bleeding rarely occurs in cases of benign disease but typically is observed with leiomyosarcoma, the malignant counterpart of this tumor. The potential for malignant degeneration of leiomyomas is extremely small. In the distal esophagus, leiomyomas may reach large proportions and may encroach on the cardia of the stomach.

Frequency

International

Esophageal leiomyomas comprise less than 0.6% of all esophageal neoplasms, both in the United States and worldwide.

Race

No known differences

Sex

No known differences

Age

Typically occur in individuals aged 20-50 years

Clinical

History

• Esophageal leiomyomas rarely cause symptoms when they are smaller than 5 cm in diameter.
• Large tumors can cause dysphagia, vague retrosternal discomfort, chest pain, esophageal obstruction, and regurgitation.
• Rarely, they can cause gastrointestinal bleeding, with erosion through the mucosa.

Physical

• Other than the nonspecific symptoms associated with esophageal leiomyomas, very few physical findings are ever noted.
• In extremely rare cases where severe esophageal obstruction is caused by a leiomyoma, weight loss and muscle wasting may be observed.

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Esophageal Hematoma

Introduction

Background

Esophageal hematoma is a rare condition that can be spontaneous or secondary to trauma, toxic ingestion, or medical intervention.

Marks and Keet reported a case of a spontaneous intramural hematoma of the esophagus in 1968. This uncommon condition has now been well documented in the literature.

Pathophysiology

Vomiting can lead to increased intraesophageal pressure that may result in mucosal tears (Mallory-Weiss syndrome), transmural perforation (Boerhaave syndrome), or intramural hematoma of the esophagus. The hemorrhage occurs within submucosal tissues.

Intrinsic esophageal disease, such as achalasia, is rare in patients with esophageal hematoma.

Esophageal hematoma may occur at various sites of the esophagus. The mechanism producing the hematoma may determine the site. For example, a hematoma from vomiting would be in the region of the esophagogastric junction, and a hematoma from a caustic substance might be at points of narrowing.

Mortality/Morbidity

• If the hematoma is associated with a perforation of the esophagus, septic complications (eg, mediastinitis, abscess formation) are likely to occur.
• The mortality rate associated with esophageal perforations is about 10-20%.

Sex

Approximately 80% of intramural hematomas occur in women.

Age

Primarily middle-aged women are affected. In a literature review of 31 patients, the mean age was 67 years.

Clinical

History

• Spontaneous intramural hematoma of the esophagus usually presents initially with severe retrosternal or epigastric pain with or without radiation. The pain is described as abrupt in onset and is aggravated by swallowing.
• In one meta-analysis, 32% of patients presented with the triad of chest pain, hematemesis, and dysphagia; 99% of patients had at least one of these symptoms.

Physical

A complete and thorough physical examination should be performed.

• Asking a patient to take a sip of water as part of the general examination may help to unmask symptoms of dysphagia. This may help toward distinguishing between cardiac chest pain and an esophageal disorder causing chest pain.
• Palpation looking for the presence of crepitus (suggesting the presence of air under the skin) along the neck, back, and chest can help to rule in or out the presence of an esophageal perforation.

Causes

Esophageal hematomas typically occur in the setting of vomiting or retching, although spontaneous hematomas (more commonly in patients with bleeding disorders) may also occur.

• Precipitating or predisposing factors to esophageal hematoma include the following:
  • Coagulopathies, such as hemophilia, or treatment with anticoagulants or aspirin
  • Instrumentation, such as with endoscopy or variceal sclerotherapy
  • Foreign body ingestion
  • Chest trauma
  • Food-induced injury, as a result of abrasive trauma by foodstuffs
  • Cardioversion and subsequent anticoagulation
  • Toxin ingestion

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Esophageal Diverticula

Background

A diverticulum is a sac or pouch arising from a tubular organ, such as the esophagus. This article focuses on diverticula of the esophagus. As is common practice, Zenker diverticulum, a type of diverticulum that arises from the posterior hypopharynx, is also discussed in this article.

Pathophysiology

Besides anatomical location, several other ways to classify diverticula of the esophagus and hypopharynx exist. Congenital diverticula are diverticula that are present at birth, while acquired diverticula develop later in life. Diverticula of the esophageal body can sometimes be difficult to classify as congenital or acquired.

Diverticula also may be classified on the basis of histopathology. True diverticula contain all layers of the intestinal tract wall. False diverticula, also known as pseudodiverticula, occur when herniation of mucosa and submucosa through a defect in the muscular wall occurs (eg, Zenker diverticulum). A special type of pseudodiverticula, believed to represent dilated excretory ducts of esophageal submucosal glands, is observed in the condition esophageal intramural pseudodiverticulosis.

Finally, acquired diverticula of the esophagus and hypopharynx also may be classified according to their pathogenesis as pulsion diverticula or traction diverticula. Pulsion diverticula form as a result of high intraluminal pressures against weaknesses in the GI tract wall. Zenker diverticulum occurs due to increased pressure in the oropharynx during swallowing against a closed upper esophageal sphincter. An epiphrenic diverticulum occurs from increased pressure during esophageal propulsive contractions against a closed lower esophageal sphincter. In contrast, traction diverticula occur as a consequence of pulling forces on the outside of the esophagus from an adjacent inflammatory process (eg, involvement of inflamed mediastinal lymph nodes in tuberculosis or histoplasmosis).

Age

Most esophageal diverticula occur in middle-aged adults and elderly people. Presentation in infants and children is rarely seen.

Zenker diverticula typically present in people older than 50 years and especially present during the seventh and eighth decades of life.

Clinical

History

• Zenker diverticula (see Media files 1-2) are formed by the herniation of mucosa through an area of weakness in the posterior wall of the hypopharynx (the Killian triangle).
  • Sometimes Zenker diverticula are called pharyngoesophageal diverticula because of their close proximity to the cervical esophagus; however, this is somewhat of a misnomer because the diverticula actually arise from the hypopharynx rather than from the esophagus.
  • Of the diverticula discussed in this article, Zenker diverticula are the most common type to cause symptoms.
  • Zenker diverticula are an acquired pulsion-type of diverticula that probably develop because of the aging process. They form in the posterior hypopharynx at a point where a defect in the muscular wall, between the inferior pharyngeal constrictor muscle and the cricopharyngeal sphincter (Killian triangle), usually exists.
  • Zenker diverticula are believed to occur because of an outflow obstruction caused when loss of coordination of the buccal squirt (ie, swallowing movement of the tongue posteriorly with contraction of the oropharyngeal muscles) and opening of the cricopharyngeus (ie, the upper esophageal sphincter) occurs. The noncompliant cricopharyngeus muscle becomes fibrotic over time.
  • Oropharyngeal dysphagia, usually to solids and to liquids, is the most common symptom. Retention of food material and secretions in the diverticulum, particularly when diverticula are large, can result in regurgitation of undigested food, halitosis, cough, and even aspiration pneumonia. The patient may note food on the pillow upon awakening in the morning. With very large diverticula, a mass in the neck occasionally can be detected. Cancer rarely has been reported in association with Zenker diverticula.
• Diverticula of the esophageal body are relatively rare. They primarily occur in the middle and distal esophagus (see Media file 3).
  • Diverticula that occur in the distal esophagus, in the lower 6-10 cm, are termed epiphrenic diverticula (see Media file 4).
  • Diverticula of the mid and distal esophagus may have various etiologies. For instance, some diverticula in the mid esophagus are congenital in origin; others are of the traction variety. With the latter, diverticula develop by traction from contiguous mediastinal inflammation and adenopathy, eg, pulmonary tuberculosis and histoplasmosis. The diverticula that develop by traction and adenopathy usually are asymptomatic.
  • Retention of undigested food in large diverticula occasionally results in regurgitation, nocturnal cough, and aspiration pneumonia.
  • Occasional epiphrenic diverticula occur in the setting of long-standing peptic esophagitis and strictures, and they rarely are symptomatic. Other rare causes of diverticula of the mid and distal esophagus include iatrogenic surgical injury to the esophagus and Ehlers-Danlos syndrome (weakness of collagen). Perhaps the most common causes of mid esophageal and epiphrenic diverticula are motility disorders of the esophageal body, including achalasia, diffuse esophageal spasm, and hypertensive lower esophageal sphincter.
  • Dysphagia is the most common symptom associated with mid esophageal and epiphrenic diverticula, although it usually is related more to the underlying motility disturbance than to the diverticulum per se. However, on occasion, the diverticulum may be responsible for the dysphagia, particularly if it is very large and filled with food or a bezoar. Regurgitation and aspiration may be related to large mid esophageal and epiphrenic diverticula; however, in patients with achalasia, regurgitation and aspiration are more likely to be related to poor esophageal emptying from the underlying motility disturbance (eg, hypertensive lower esophageal sphincter that fails to relax, absence of esophageal body peristalsis).
• Esophageal intramural pseudodiverticulosis is a very rare condition in which numerous 1- to 4-mm, saccular, flask-shaped outpouchings form in the wall of the esophagus (see Media files 5-6). Pseudodiverticula can number from a few to a hundred or more. This condition can be segmental or diffuse. About 200 cases have been reported in the literature.
  • Pseudodiverticula are formed by dilatation of the esophageal submucosal glands that communicate with the esophageal lumen.
  • Esophageal intraluminal pseudodiverticulosis generally is believed to be an acquired condition. While the precise pathogenesis is uncertain, inflammation and stasis appear to be factors. One hypothesis states that blockage of intramural ducts by inflammatory debris results in dilation of the submucosal glands.
  • Most patients with esophageal intraluminal pseudodiverticulosis have underlying esophageal strictures or dysmotility of the esophageal body. Esophageal intraluminal pseudodiverticulosis also has been reported as a consequence of corrosive injury to the esophagus, although most patients have associated strictures.
  • Dysphagia is the most common symptom associated with esophageal intramural pseudodiverticulosis. In most cases, esophageal intraluminal pseudodiverticulosis is related to the associated esophageal stricture or dysmotility.
  • An isolated case report cited significant bleeding from a distal esophageal diverticulum. The authors speculated that the bleeding resulted from food stasis, bacterial overgrowth, or chronic inflammation.
• See related CME at Diagnostic Evaluation of Dysphagia.
• See related CME at Treatment Options for Esophageal Strictures.

Physical

• Findings on physical examination often are normal in patients with symptomatic esophageal diverticula. However, many patients relate a history of dysphagia, chest pain, or regurgitation.
• Although the physical examination findings are often normal, a large Zenker diverticulum may present as a neck mass on physical examination. Halitosis also may be present and is secondary to accumulated food debris or medicines within the diverticulum.
• Signs and symptoms of aspiration pneumonia may accompany the presence of large symptomatic diverticula.

Causes

• Most diverticula are caused by an underlying motility disorder of the esophagus.
• Structural lesions, including a noncompliant cricopharyngeus muscle (ie, Zenker diverticulum), incomplete or uncoordinated relaxation of the lower esophageal sphincter, or strictures, may play a role as well.
• An underlying inflammatory process within the mediastinum has been associated with mid esophageal diverticula.

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Choledocholithiasis

Background

Symptomatic cholelithiasis is a common medical problem, which makes cholecystectomy one of the most frequently performed surgical procedures in the world. Choledocholithiasis complicates the workup and management of cholelithiasis, necessitates additional diagnostic and therapeutic procedures, and adds to the morbidity and mortality of gallstone disease. Management of choledocholithiasis has been the subject of much debate over the past several years, especially with the advent of new laparoscopic techniques and greater experience with endoscopic procedures.

Pathophysiology

Choledocholithiasis occurs as a result of either the primary formation of stones in the common bile duct (CBD) or the passage of gallstones from the gallbladder through the cystic duct into the CBD. Bile stasis, bactibilia, chemical imbalances, pH imbalances, increased bilirubin excretion, and the formation of sludge are among the principal factors thought to lead to the formation of these stones.

Gallstones are differentiated by their chemical composition. Cholesterol stones are composed mainly of cholesterol, black pigment stones are mainly pigment, and brown pigment stones are made up of a mix of pigment and bile lipids. Obstruction of the CBD by gallstones leads to symptoms and complications that include pain, jaundice, cholangitis, pancreatitis, and sepsis.

Frequency

United States

The incidence rate for gallstones is 10-20%. Approximately 600,000 cholecystectomies are performed in the United States every year, and choledocholithiasis complicates 10-15% of these cases.

International

The international incidence rate is higher, mainly because of the additional problem of primary CBD stones caused by parasitic infestation with Ascaris lumbricoides and Clonorchis sinensis.

Race

Differences in etiology and incidence are observed in persons of different races. In the Asian population, infestation with A lumbricoides and C sinensis is thought to promote bile stasis and, hence, formation of primary CBD stones.

Sex

Cholelithiasis occurs more frequently in females than in males.

Age

In the United States, the incidence rate for gallstones is approximately 40% in individuals older than 60 years. In individuals undergoing cholecystectomy for symptomatic cholelithiasis, 8-15% of patients younger than 60 years have CBD stones, compared to 15-60% of patients older than 60 years.

Clinical

History

Patients with choledocholithiasis may be completely asymptomatic; in approximately 7% of cases, the stones are found incidentally during cholecystectomy. Stones are seen in 1% of autopsies performed on individuals older than 60 years who died of unrelated causes. Approximately 25-50% of asymptomatic CBD stones eventually cause symptoms and require treatment. Symptoms occur when the stones obstruct the CBD. The clinical presentation varies depending on the degree and level of obstruction and on the presence or absence of biliary infection.

• A history of cholelithiasis is not essential for the diagnosis of choledocholithiasis because gallbladder stones can be asymptomatic.
• Pain is the most frequent presenting symptom. The pain is colicky in nature, moderate in severity, and located in the right upper quadrant of the abdomen. The pain is intermittent, transient, and recurrent and may be associated with nausea and vomiting. If the pain is severe, consider a coexisting condition as the primary cause of the pain.
• Jaundice occurs when the CBD becomes obstructed and conjugated bilirubin enters the bloodstream. A history of clay-colored stools and tea-colored urine is obtained from such patients in approximately 50% of cases. The jaundice can be episodic.
• Fever is an indication of cholangitis, and the classic Charcot triad of fever, jaundice, and right upper quadrant pain strongly favors the diagnosis. A recent study on patients with cholangitis showed fever in 92% of patients, jaundice in 65%, pain in 42%, and all 3 in 19%. Cholangitis has a varied presentation, from a mild self-limiting illness to septic shock, observed in 5% of patients.
• Gallstones are responsible for 50% of all cases of pancreatitis. Conversely, 4-8% of patients with gallstones develop pancreatitis. Pancreatitis can be precipitated if CBD obstruction occurs at the level of the ampulla of Vater. Pancreatic pain is different from biliary pain. The pain is located in the epigastric and midabdominal areas and is sharp, severe, continuous, and radiates to the back. Nausea and vomiting are frequently present, and a similar previous episode is reported by approximately 15% patients.
• A history of benign CBD strictures, sclerosing cholangitis, sphincter of Oddi dysfunction, and cystic dilatation of the CBD are important in the diagnosis of secondary biliary stones.
• The presence of parasitic infestation with A lumbricoides or C sinensis may result in the development of primary CBD stones, observed in appropriate populations with the so-called Oriental cholangiohepatitis.

Physical

Specific findings upon physical examination are few and are principally abdominal tenderness and jaundice.

• Tenderness is found in the right upper quadrant of the abdomen. It is moderate in severity, and guarding (voluntary or involuntary) or rebound is absent. Severe tenderness, including the Murphy sign, should suggest the presence of acute cholecystitis, either concomitantly or alone.
• The extent of icterus depends on the severity and duration of CBD obstruction.
• Systemic signs such as fever, hypotension, and flushing may be present and are often indicative of infection, sepsis, or both.

Causes

CBD stones are either primary or secondary. Primary stones arise within the biliary duct system, while secondary stones develop in the gallbladder and migrate to the CBD. In the United States, up to 85% of all CBD stones are secondary in origin.

• Primary CBD stones are caused by conditions leading to bile stasis and chronic bactibilia. Up to 90% of patients with brown pigment CBD stones have bile culture results positive for bacteria. Primary duct stones are usually brown pigment stones. Brown stones differ from black pigment stones by having a higher content of cholesterol. Brown stones are soft and earthy in consistency and take the shape of the duct.
  • In Western populations, biliary stasis is secondary to factors such as sphincter of Oddi dysfunction, benign biliary strictures, sclerosing cholangitis, and cystic dilatation of the bile ducts. Bile stasis promotes growth of bacteria, which produce phospholipase A1, thus releasing fatty acids from biliary phospholipids. The duct epithelium and/or bacteria (eg, Escherichia coli) produce beta-glucuronidase in amounts sufficient to deconjugate bilirubin diglucuronide. The presence of free fatty acids, deconjugated bilirubin, and bile acids leads to the formation of insoluble calcium bilirubinate particles. With the loss of bile acids, cholesterol becomes insoluble, resulting in the formation of biliary sludge. The sludge also contains mucin and bacterial cytoskeletons, which further aid in stone formation.
  • In Asian populations, infestation with A lumbricoides and C sinensis may promote stasis by either blocking the biliary ducts or by damaging the duct walls, resulting in stricture formation. Bactibilia is also common in these instances, probably secondary to episodic portal bacteremia. Some authors have suggested that the stones are formed because of the bactibilia alone and that the parasites' presence is just a coincidence.
• Secondary CBD stones arise from the gallbladder, migrate to the CBD, and have a typical spectrum of cholesterol stones and black pigment stones. Bacteria can be cultured from the surface of cholesterol and pigment stones but not from the core, suggesting that bacteria do not play a role in their formation.
  • The prerequisites for the formation of cholesterol stones are cholesterol supersaturation, stasis, and accelerated nucleation. The sex of the patient, parity, obesity, weight loss, and genetics are risk factors for the development of cholesterol stones.
  • Black pigment stones typically occur in conditions in which bilirubin excretion is increased, as in hemolytic disorders and in situations associated with profound gallbladder stasis such as prolonged fasting and long-term parenteral nutrition. Pigment stones are more common in patients with cirrhosis and ileal disease, although the exact mechanism of stone formation under these conditions is not understood.

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What is Leigh's Disease?

Leigh's disease is a rare inherited neurometabolic disorder that affects the central nervous system. This progressive disorder begins in infants between the ages of three months and two years. Rarely, it occurs in teenagers and adults. Leigh's disease can be caused by mutations in mitochondrial DNA or by deficiencies of an enzyme called pyruvate dehydrogenase. Symptoms of Leigh's disease usually progress rapidly. The earliest signs may be poor sucking ability,and the loss of head control and motor skills.These symptoms may be accompanied by loss of appetite, vomiting, irritability, continuous crying, and seizures. As the disorder progresses, symptoms may also include generalized weakness, lack of muscle tone, and episodes of lactic acidosis, which can lead to impairment of respiratory and kidney function.

In Leigh’s disease, genetic mutations in mitochondrial DNA interfere with the energy sources that run cells in an area of the brain that plays a role in motor movements. The primary function of mitochondria is to convert the energy in glucose and fatty acids into a substance called adenosine triphosphate ( ATP). The energy in ATP drives virtually all of a cell's metabolic functions. Genetic mutations in mitochondrial DNA, therefore, result in a chronic lack of energy in these cells, which in turn affects the central nervous system and causes progressive degeneration of motor functions.

There is also a form of Leigh’s disease (called X-linked Leigh's disease) which is the result of mutations in a gene that produces another group of substances that are important for cell metabolism. This gene is only found on the X chromosome.

Is there any treatment?

The most common treatment for Leigh disease is thiamine or Vitamin B1. Oral sodium bicarbonate or sodium citrate may also be prescribed to manage lactic acidosis. Researchers are currently testing dichloroacetate to establish its effectiveness in treating lactic acidosis. In individuals who have the X-linked form of Leigh’s disease, a high-fat, low-carbohydrate diet may be recommended.

What is the prognosis?

The prognosis for individuals with Leigh's disease is poor. Individuals who lack mitochondrial complex IV activity and those with pyruvate dehydrogenase deficiency tend to have the worst prognosis and die within a few years. Those with partial deficiencies have a better prognosis, and may live to be 6 or 7 years of age. Some have survived to their mid-teenage years.

What research is being done?

The NINDS supports and encourages a broad range of basic and clinical research on neurogenetic disorders such as Leigh's disease. The goal of this research is to understand what causes these disorders and then to apply these findings to new ways to diagnose, treat, and prevent them.

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Reiter Syndrome

Reiter syndrome, also known as reactive arthritis with conjunctivitis/urethritis/diarrhea, is a rare disease with psoriasis-like symptoms which often occurs after a bacterial infection. The syndrome often follows an infectious urethritis (infection of the tube that carries urine from the bladder to the genital area) or infectious diarrhea. It is more common in patients who have the genetic marker called HLA-B27 (as is psoriasis). Symptoms include inflammation of the eyes, arthritis and a thick scaly foot rash which mimics psoriasis called keratoderma blenorrhagicum. Initial treatments include conservative measures such as range-of-motion exercises and joint injections of anti-inflammatory steroid medications. Fore more severe cases, methotrexate, infliximab, acetretin and cyclosporine may be used.

The disease is named after Hans Reiter, who unfortunately was also a Nazi war criminal involved in involuntary sterilization and concentration camp experiments involving typhus. For this reason the much more cumbersome reactive arthritis with conjunctivitis/urethritis/diarrhea moniker is sometimes preferred.

Take-Home Message

If your stubborn foot psoriasis is accompanied by eye inflammation and arthritis and was preceded by a bacterial infection, you may wish to ask your doctor about the possibility of Reiter syndrome.

_Source:

_{James W, Berger T, Elston D. Andrew's Diseases of the Skin. Saunders (Elsevier) Canada. 2006 pages 202-203}

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Corneal diseases

Cornea - a front part of an external fibrous envelope of an eyeball; nonvascular, high-sensitivity, transparent, an optically homogeneous envelope with smooth, a smooth surface. Except for protective and basic function the cornea is the main refracting surface of optical system of an eye.

Diseases of a cornea makes about 25 % of the general number of diseases of eyes, and quite often are the reasons of blindness and lowering of vision.

Diseases of a cornea are rather various. Most often there are inflammatory diseases of a cornea (keratitis), differing greater variety of forms and being one of principal causes of decrease in sight and blindness, and also keratikonus. The Most frequent reasons of keratitis and keratoconjunctivitis are virus and bacterial infections.

Keratikonus - a condition of an eye at which the normal spherical form of a cornea is broken, the cornea is bent. On a surface of an eye the camber similar to a cone that leads to strong easing of sight develops.

Dystrophies and degenerations of a cornea happen primary and secondary. In a basis primary local and general infringements of a metabolism with adjournment in a cornea of products of a pathological exchange lay. Secondary dystrophies develop after transferred keratitis, traumas, burns of eyes.

For the prevention of heavy complications of diseases of a cornea are required: proper diagnostics, duly and active treatment. Various medicinal substances are applied to local treatment in the form of drops, injections. Methods of electrophoresis, phonophoresis, treatment by laser radiation are used also.

For carrying out of purposeful treatment bacterial keratitis definition of sensitivity of microflora to antibiotics by crop of defeat separated from the center is necessary.

Instruction to the patient after change of a cornea

To you the microsurgery of change of a cornea is lead. The thin seam keeping a donor fabric, can long-standing time (about one year) to remain in a cornea. It allows you to start to work with the moderate physical activity earlier. At the same time, it is necessary to remember the periodic medical control over a condition of a seam.
Durable healing of a wound after change of a cornea comes only in 6-10 months after operation. Therefore after an extract from a hospital it is necessary for you to continue the recommended treatment in house conditions. Instilling drops or loading ointments can be made the purest hands before a mirror or in a prone position, as well as by means of relatives, using those receptions with which you have got acquainted in a hospital.

During the first month to sleep it is necessary on a back or on the party opposite to the operated eye. The food can be usual, it is necessary to exclude alcoholic drinks. Surplus of sweets is not desirable. Easy gymnastic exercises without jumps, run and inclinations are useful. During rest and walks during the first year after operation it is necessary to avoid stay on the bright sun. It is impossible to sunbathe. It is possible to use the blacked out glasses. The replaced cornea during several months, and sometimes several years, has the lowered sensitivity. Therefore it is impossible to rub sharply an eye a scarf or a hand, it is necessary to be cautious at washing, to cover the operated eye during a strong wind and to avoid walks in frosty days even on the second or the next years after operation. It will help to save a cornea from damages and freezing injury.

You can watch TV, go to museums, cinema and theatre if it is not connected with difficult and close moving to transport. It is possible to start the usual or limited work in 2-4 months depending on a condition of the operated eye and working conditions. Expansion of the general mode should be carried out one step at a time, however during the first year work with a slope of a head downwards, outdoor games, run, heavy physical work is absolutely counter-indicative. After an output for work do not forget to show to the oculist each 2-3 months within the first year after operation, especially if it is not removed an encircling stitch.

In case of occurrence of reddening and an ache in an eye, and blear-eyedness to you it is necessary for photophobia to see a doctor promptly. Only early the begun treatment can prevent deterioration of vision.

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Factors and the conditions causing irritation of a dental pulp

The irritation of a pulp of a tooth can arise owing to caries of a teeth, as a result of preparation of a tooth and carious cavities, under influence a filler material, owing to penetration of microorganisms at not tight seal, at an exposure dentin.

Caries of a tooth serves as a principal cause of changes in a pulp and its inflammations. Already at initial damage dentin fibrilloblasts react adjournment secondary and formation of a layer scleroid dentin (adjournment of salts of calcium on walls of dentinal canaliculus) down to full occlusion of dentinal canaliculus. These processes should be considered as display of protective mechanisms of a pulp on action of a cue.

At processing of a caries and destruction of enamel of a bacterium get in dentin, however the inflammation of a pulp does not arise. It is established, that first signs of an inflammation come, when carious the cavity is separated from a pulp by a layer of 1,1 mm [Reeves R., Stanley H. R., 1996], i.e. the pulp practically is not infected up to an instant of penetration of microorganisms in secondary dentin [Massler, Pawlak J., 1977].

Preparation of a cavity without use of a water spray leads to its damage. Thus probability of damage of the in direct proportion area of preparation and depth of damage. Thus, preparation of a tooth under vinirs or artificial crownwork without due cooling serves a serious risk factor for a pulp.

Filler materials. There are the numerous data specifying irritating influence various of filler materials. From cements the most expressed adverse action renders silicate though specify, that it is shown at formation of a clearance between edge of enamel and dentin as microorganisms nestle close in dentin [Brannstrom, 1979].

Composites also are considered as irritating materials. First of all, toxicity of composites of the first generation was marked. Materials let out now as specify numerous supervision, render insignificant influence on a pulp.

During many years use of bondings was studied at sealing. It is proved, that improvement of a compounding bondings has allowed to achieve favorable reaction of a pulp to used composites.

Regional permeability as considers a number of researchers, is a principal cause of irritation of a pulp after sealing. The leading part thus belongs to microorganisms. With the purpose of the prevention of the specified changes in a pulp it is recommended to spend padding fabrics of a tooth and use bonding systems.

The exposure of dentin can occur after loss of a seal, as a result of deleting fabrics, at erosion, etc., that is accompanied by sensitivity action of irritating factors. Sensitivity can arise also at an exposure cervical dentin because canaliculus of dentin become opened.

The sheeting (direct) provides:

1) clarification of a surface of a pulp;

2) drying of a cavity;

3) imposing on the naked pulp of medical paste;

4) a seal from zinc oxide eugenic acid cement;

5) imposing of a constant seal.

Most widely used materials for protection of a pulp contain all calcium hydroxide. As a result of it above a site of an exposure it is postponed secondary dentin, forming the dentin bridge. Consider, that formation of a barrier occurs not due to the calcium containing in a material, closing a pulp.

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