April 1, 2009

Dear Doctor,

Every year our heart fills with joy when the auspicious moment of announcingthe new volume of Medical Newsletter arrives. This is the moment to thankyou for strengthening the bondage of love, reliability and trust between us.Your faith is our inspiration to proceed closer to perfection. Cutaneous woundis something which people have to deal more or less in their every day life.Although some conditions are life threatening, they can be handled quiteperfectly if the remedies are well informed. For this purpose, we havediscussed 'Current Management of Acute Cutaneous Wounds' in this issue. Ourdesire is to update you with the latest management options for cutaneouswounds.

With the advancement of Medical Science, the health professionals have nowmanaged to identify several new forms of diseases and their treatmentstrategies. One such type of disease is eosinophilic esophagitis. This diseasecondition is seldom discussed in our community. Therefore, many may remainin the dark about its diagnosis and management. We have highlighted‘Eosinophilic Esophagitis’ this time. Non-visible hematuria is a disease conditionthat bothers the physicians quite often. Sometimes this may become difficultto diagnose resulting in delay in treatment. In order to enlighten this topic wehave discussed 'Evaluation of Non-Visible Hematuria in Primary Care'. This mayhelp to understand the nature of this condition and its latest availablemanagement options.

In 'Procedure and Practice' we have described the 'Placement of a Femoral VenousCatheter'- their usefulness for certain treatments. We hope that this will provideyou with well equipped information and will help to enhance furthersophistication in your treatment procedures. Tobacco smoking has emerged asthe modern epidemic of human world. Although seen as a harmless practice,this is one of the major causes of several deadly diseases like cancer as well assome like asthma and COPD which may completely hamper the daily life of aperson. It is the duty of every health related authority to create awarenessspecially among the youth to abandon cigarette smoking in order to create ahealthy and active society of tomorrow's world. This concept has encouragedus to highlight this habit as lethal in our community also. That is why we havehighlighted hazards of tobacco smoking in our 'Fact File'. 'News from Internet'has also brought the latest ongoing research news with their outcomes.

We thank again for your support and wish you ‘Shuvo Noboborsho’.

With regards,

Prof. Farida HuqMBBS, M.Phil, FCPS, Ph.D.(London)Medical DirectorBeximco Pharmaceuticals Ltd.

Dr. Selina AkhtarSenior ManagerMedical DepartmentBeximco Pharmaceuticals Ltd.

3

CRITICAL CARE

The primary function of the skin is to serve as aprotective barrier against the environment.Loss of integrity of large portions of the skin as

a result of injury or illness may lead to major disabilityor even death. Every year, in the United States morethan 1.25 million people have burns and 6.5 millionhave chronic skin ulcers caused by pressure, venousstasis or diabetes mellitus. In 2005, 11.8 millionwounds were treated in emergency departments in theUnited States. More than half a million burns and 7.3million lacerations are treated annually and woundscaused by cutting or piercing instruments areresponsible for an additional 2 million outpatientvisits each year.

The primary goals of treatment of wounds are rapidwound closure and a functional and aestheticallysatisfactory scar. Recent advances in cellular andmolecular biology have greatly expanded theunderstanding of the biological processes involved inwound repair and tissue regeneration. At the sametime several technological improvements in acutewound healing give the physicians a promisingoutcome not only in successful wound closure withsatisfactory scar but also in preventing infection andfurther trauma as well as by providing an environmentthat optimizes healing of the wound. This articledescribes the various recent approaches in themanagement of acute cutaneous wound.

General Principles of Care

All wounds should be thoroughly cleansed with tapwater or normal saline. For heavily contaminatedwounds, high-pressure irrigation can be achieved withthe use of a 10 to 50 ml syringe and splatter shield.The patient's tetanus-immunization status should beascertained, and standard recommendations followedto ensure that the patient is protected against tetanus.

A moist environment for the wound accelerateshealing by preventing cellular dehydration andstimulating collagen synthesis and angiogenesis, thusimproving cosmesis and reducing pain, the risk ofinfection, and the costs of care. A moist environmentmay be created by covering the wound with a topicalantimicrobial agent or by applying an occlusivedressing that reduces the loss of fluid through

evaporation. Topical antimicrobial agents have beenshown to reduce rates of infection of traumaticlacerations but not in cases of wounds caused byelective surgery.

Occlusive dressings have also shown to reduce ratesof infection. Cyanoacrylate liquid bandages areeffective for clean, simple wounds. The choice ofdressing depends on the cause, size, depth, location,degree of exudation, and level of contamination of thewound, as well as on cost. There is no clinicallydirective evidence to support the choice of onedressing over another. Occlusive dressings are lesspainful and more convenient for patients and mayspeed healing, although they are more expensive thantopical antibiotics and gauze dressings. Wet dressingsthat promote maceration of the tissue and proliferationof bacteria should be avoided. Prophylactic systemicantibiotics should not be used routinely.

Abrasions

Abrasions are skin scrapes that do not fully penetratethe epidermis. These are evaluated, cleansed, anddebrided like it is done in case of lacerations.Abrasions are harder to anesthetize, which isparticularly problematic when large amount of dirt,stones, or glass are embedded as this occursfrequently. Regional block or intravenous sedationmay therefore be needed. After the wound has beenirrigated and foreign bodies have been removed,abrasions that are limited to the superficial dermisshould be treated with a topical antibiotic or anocclusive dressing.

Deep abrasions that extend below the dermis(especially if they have a surface area larger than 1cm2

or involve underlying structures) and those that havenot healed in 2 weeks may require more advanced carelike grafting, and consultation with a plastic surgeonshould be considered.

Current Management of AcuteCutaneous Wounds

Position of hand for splinting burns and frostbites

4

CRITICAL CARE

Natural Biological Process of Wound Healing

Wound healing is a dynamic, interactive process involving soluble mediators, blood cells, extracellularmatrix, and parenchymal cells. The complete healing of a wound has three phases- inflammation, tissueformation, and tissue remodeling which overlap in time.

5

CRITICAL CARE

Post-traumatic Tattooing : Post-traumatic tattooing isabnormal skin pigmentation due to embedded foreignparticles. If particles embedded in the injured skin arenot removed, post-traumatic tattooing develops. Thiscondition is most commonly seen with injuries fromexplosions or fire works and also in 'road rash'- anabrasion of the skin from contact with a surfacecontaining asphalt, tar or dirt, with embedding of theseparticles. Initial treatment consists of the meticulousremoval of all particles with standard surgical scrub-brushes.

During this procedure, a topical lidocaine, localinfiltrative anesthetics, or regional anesthetics shouldbe used for abrasions of small to moderate size, andsystemic opioids or procedural sedation for extensiveabrasions. Removal of particles within 24 hours afterinjury has been shown to have the best cosmeticresults. Treatment of established post-traumatictattooing has had disappointing results, and requiresreferral to a plastic surgeon.

Lacerations

Skin Tears : Skin tears are particularly commonamong patients who are receiving long-termcorticosteroid therapy and among the elderly, whotend to have fragile skin. Frail skin presents a clinicalchallenge for the practitioner, as even the simplestmovement can result in damage of the skin. Accordingto a retrospective study, skin tears occur most often inthe upper extremities. Although nearly 80% of suchlaceration occur on hand and arms, this maysometimes appear on the back and buttocks oftenmistaken as pressure ulcer.

For category I tears (without tissue loss), the woundedges can be approximated with surgical tapes, andthe area covered with a non-adherent dressing. In onestudy, the healing rate of skin tears with the use of thistreatment was 66%, as compared with 33% with theuse of a thin-film dressing. Category II skin tears(partial tissue loss) and category III skin tears(complete tissue loss) can be managed with one of anumber of absorbent dressings such as petroleum-based gauzes, hydrogels, foams, hydrocolloids, nylon-impregnated gauzes, and silicone-coated dressings.These dressings usually remain in place for 5-7 daysand are covered with a secondary absorbent gauzedressing that can be changed daily as needed. Elastictubular nets should be used to support the underlyingdressings. Skin tears of all types that are treated within8 hours after injury can also be closed withcyanoacrylate-based topical adhesive.

Plantar Puncture Wounds : The rate of superficialinfection (cellulitis) ranges from 2-10% amongpatients who present to the emergency departmentwith planter puncture wounds. Most of the infectionsare caused by Staphylococcus aureus or Streptococcuspyogenes. The incidence of osteomyelitis, chondritis,and septic arthritis is considerably lower. Puncturewounds in patients who were wearing tennis shoesthat were saturated with sweat at the time of injurymay be associated with pseudomonas osteomyelitis. Aprospective observational study of 63 adults whopresented to the emergency department within 24hours after receiving a plantar puncture woundsuggests that cleansing alone may be adequatetherapy. If this approach is used, close follow-up isrecommended, and antibiotics should be administeredimmediately in patients who have signs and symptomsof infection.

If the presence of a foreign body is suspected,computed tomographic imaging or ultrasonographyshould be used to detect non-radiopaque objects.Some studies suggest that deep wounds, especiallythose occurring over the forefoot, have an increasedlikelihood of infection, and patients with such woundsshould receive prophylactic antibiotics. Since mostinfections are caused by streptococcus orstaphylococcus, or occasionally pseudomonas species,antibacterial agents that target these species should beused. (e.g. dicloxacillin and ciprofloxacin). Frequentcleansing of the puncture wound and application of atopical antibiotic are also indicated.

Mammalian Bites : The risk of infection after dog, cat,and human bites ranges from 3-18% for dog bites to28-80% for cat bites. Whereas most cat bites are deeppuncture wounds, many dog bites cause openlacerations. Large observational studies and limitedclinical trials suggest that after high-pressureirrigation of the wound, it is safe to close most bitewounds (even on the extremities) up to 12 hours afterinjury (healing by primary intention). Puncturewounds and scratches should be allowed to heal bysecondary intention. These wounds should be coveredwith a topical antimicrobial agent and an absorbentdressing. Close follow-up and daily changes of thedressings are required.

For large, heavily contaminated lacerations, delayedprimary closure, after an observation period of 3-5days healing by tertiary intention may be considered.Human bites that are sustained over themetacarpophalangeal joints (clenched-fist bites) are

6

CRITICAL CARE

particularly prone to infection. These bites requireaggressive irrigation and treatment with antibiotics(e.g. amoxicillin-clavulanate) and should not beclosed. This commonly occurs as a result of a personpunching another person in the mouth and hitting atooth. The tooth may lacerate the extensor tendon andjoint capsule in the hand, inoculating the joint withsaliva. As patients may be reluctant to disclose thecircumstances resulting in such injury, it shouldalways be suspected when patients present withlacerations that are located over themetacarpophalangeal joints. These injuries generallyrequire specialized consultation. Althoughprophylactic antibiotics are widely used for

mammalian bites, a systemic review has demonstratedsignificant reductions in the rates of infection only incases of bites to the hands and in human bites.

Subungual Hematomas : A subungual hematoma is apainful condition that results from a collection ofblood under the fingernail. Previously, hematomasinvolving more than 50% of the nail bed wererecommended for removal of the nail by thephysicians. This is because the incidence ofunderlying lacerations was found to be quite highespecially in association with underlying tuftfractures. However, in a study involving 45 patientswho presented to the emergency room with subungual

7

CRITICAL CARE

hematomas, simple nail trephination resulted inhealing without any nail deformities or othercomplications in all the patients. Thus, simple nailtrephination with the use of a handheld portablecautery is recommended for most subungualhematomas. Nail removal should probably be reservedfor subungual hematomas that are associated withdisruption of the nail or surrounding nail folds.

Burns

Burns are dynamic injuries that may progress over thefirst 2-3 days. Therefore, frequent reassessment of thewound is required to ensure optimal management.

Managing Burns According to Their Classifications :First-degree burns are limited to the epidermis and areerythematous and painful. They generally heal withinseveral days. Second-degree burns involve all of theepidermis and part of the underlying dermis and are

classified according to the depth of dermalinvolvement. Superficial second-degree burns usuallyheal within 2 weeks, with minimal scarring. Deepsecond-degree burns are often difficult to distinguishfrom third-degree, or full-thickness burns.

Deep burns are characterized by hemorrhagic blistersand are covered with layer of white or red injureddermis that does not blanch. These burns usually doesnot heal for at least 3 weeks and often result inhypertrophic scarring and contractures, especially inchildren. It is very important to distinguish betweensuperficial second-degree burns and deep burns (deeppartial-thickness and full-thickness burns).

Full-thickness burns may be dark brown or tan andhave a leathery texture that is insensitive to touch.Circumferential burns (burns that completely encirclea limb, the neck or the torso) can compromiseperfusion, and it may be necessary to relieve thepressure by means of an escharotomy, in which anincision is made over the lateral and medial aspect ofthe involved areas down to the subcutaneous tissue.The depth of the burn is often difficult to assessimmediately after injury and is often underestimated.The true depth becomes more obvious with time,therefore, careful surveillance of the wound andreassessment of the treatment are necessary.

The size of a burn is described by an estimation of thepercentage of the total body-surface area that hassustained second- or third-degree burns. Errors inestimating the size of the burn, often results inoverestimation.

Cooling of Burns : Cooling of burns with the use ofcold (15-250C) tap water within 30 minutes afterinjury has been shown to reduce the pain, the depthand extent of the injury, the need for surgical excisionof the burn, scarring and mortality. Cooling of burnsshould continue until the pain is substantially reducedor resolved. The use of ice or ice water may increasetissue injury and should be avoided. Concern thatcooling of large burns may result in hypothermia hasbeen based on a single study in small animals withextensive burns.

Management of Blisters : The debate regarding theremoval of burn blisters has been confusing due toconflicting data regarding the in vitro effects of blisterfluid. Two clinical trials involving patients andvolunteers with superficial burns demonstrated thatintact blisters healed faster and were less likely to

Treatment of category I skin tear of the dorsal forearm

8

CRITICAL CARE

become infected than blisters that were ruptured. Blisterlarger than 3 cm in diameter and those over mobileareas usually rupture spontaneously and also they maybe aspirated under sterile conditions. When blistersrupture, they should be washed with soap and water, andthe non-adherent necrotic epidermis carefully removed.In order to relieve pain while the burn is beingthoroughly cleansed, the patient often requires analgesiawith oral or perenteral opioids.

Local Therapy for Burns : Although first-degree burnsdo not require any specific therapy, topicalnonsteroidal anti-inflammatory drugs or aloe veramay be used to reduce the pain. Superficial second-degree burns should be treated with a topicalantimicrobial agent or an absorptive occlusivedressing. Studies suggest that occlusive dressings aremore convenient and less painful than treatment withtopical antimicrobials and also result in more rapidhealing. Deep second-degree burns and third-degreeburns should be covered with a topical antimicrobialagent, and the patient should be referred to a burnspecialist for consultation regarding the need forexcision and grafting. Routine use of systemicantibiotics is not supported by the evidences.

The optimal treatment for heavily contaminated orinfected burns and those with a large amount ofexudates is application of topical antimicrobial agentsand absorbent gauze dressings.

Traditional topical antimicrobial agents that containsilver, such as silver sulfadiazine, confer wideantimicrobial coverage and are most useful for deepsecond-degree burns and third-degree burns.However, the use of these antimicrobial agents isassociated with cellular toxicity and delayed healing.Synthetic dressings that reduce the cytotoxic effects ofsilver by slowly releasing it in small amounts are nowavailable. They are more effective than silversulfadiazine in reducing pain and improving healingand are also cost effective.

A large number of synthetic and biological occlusivedressings have been evaluated for the localmanagement of burns. Absorptive hydrocolloiddressings can be used for weeping burns, althoughthey tend to become malodorous. As compared withsilver sulfadiazine, these dressings have been shownto result in less pain, better acceptance andcompliance, and more pleasing cosmetic results inpatients with superficial partial-thickness burns. Theyare also as effective as and less expensive thancollagen based dressings.

The polyurethane films are not recommended sincethey do not absorb exudates. A silicone mesh dressingthat adheres gently to the wound bed and allowswound exudates to escape onto a secondary dressing isalso available and results in faster healing thantreatment with silver sulfadiazine. Biologicaldressings based on collagen or skin cells should bereserved for deep burns and should be applied by burnspecialists.

Chemical Burns : Chemical burns cause tissue injurythrough the interaction of the chemical agent with thetissue. Initial treatment consists of copious waterlavage commencing at the scene and removal of anyparticles. The important exception to the treatment ofa chemical burn with water lavege involves injuryfrom elemental metals (lithium, sodium, magnesium,and potassium), which spontaneously ignite withwater. Exposure to hydrofluoric acid, which is used inetching and rust removal, leads to intense pain andtissue damage.

Method of performing an escharotomy

Treatment includes copious irrigation followed by theapplication of calcium gluconate gel or subcutaneousinjection of calcium gluconate, with the goal ofrelieving the pain. A burn from hydrofluoric acid thatinvolves more than 5% of total body-surface area, ormore than 1% of total body surface area if theconcentration of hydrofluoric acid is greater than50%, requires hospital admission forelectrocardiographic monitoring and serialmeasurements of calcium levels since life-threateningarrhythmias and hypocalcemia can occur. The patientshould be referred to a burn specialist becauseimmediate excision of the wound may be necessary incases of hypocalcemia that is unresponsive to intra-arterial or intravenous calcium gluconate.

Frostbite : Frostbite occurs when exposure to coldresults in the freezing of tissue. It usually affects themost exposed appendages. Fingers, toes, nose and earsare among those most affected parts. Initial treatmentconsists of rapid rewarming over a period of 20minutes in water that is at a temperature of 40 to 420C.The appearance of the skin after rewarming and overthe next 24-48 hours is the main clinical factor that isused to determine the level and extent of the injury.The use of radio-imaging with technetium-99m at 1week is helpful in predicting the ultimate level oftissue injury and the extent of amputation that may berequired. Opioids are used to control pain. Massagingthe area is not recommended, since it may increasetissue damage.

Frostbite is classified in the same way as burns - thatis according to the size and depth of the injury within24-48 hours after rewarming. Other than rapidrewarming, there are no unified treatment protocal forfrostbite. General principle for treatment includesplinting and elevation of the injured area. Treatmentwith ibuprofen, 400mg twice daily, is recommended todecrease the levels of prostaglandin and thromboxane,

since elevated levels of these lead to vasoconstrictionand platelet aggregation, resulting in progressivetissue injury. Although some recommends routinedebridement and application of aloe vera because ofthe high concentration of prostaglandin F2α andthromboxane B2, there is a risk of desiccation. Sosterile aspiration of tense blisters is recommendedthat are larger than 3 cm in diameter.

Recently, it has been shown that tissue plasminogenactivator given intravenously or intra-arterially within24 hours after injury and within 6 hours afterrewarming significantly decreases the extent and levelof amputation. Other treatment includessympathectomies, hyperbaric oxygen, andpetoxifylline. In general, the treatment remainsconservative until the wound is completely healed orclearly demarcated. This process usually takes morethan 3 weeks, at which time, final debridement andgrafting, flap coverage, or amputation is performed asneeded basis.

Conclusion

Many types of cutaneous wounds are managed bydifferent specialities of health care practitioners inmultiple clinical settings. However, wound irrigations,debridement, protection from further trauma andbacterial contamination, creation of a moist woundenvironment, and juditious use of antibiotics (whenindicated) will often help achieve optimal outcomes.

References

1. The New England Journal of Medicine, 2008; 359:1037-1045

2. Advances in skin and wound care, 2008; byBaranoski, Sharon

3. http://www.merk.com4. The New England Journal of Medicine, 1999; 341:

738-746

9

CRITICAL CARE

Determination of Burn DepthA. A superficial second-degree burn B. A deep second-degree burn C. A third-degree burn

A B C

10

3

2

10 Facts About Smoking

Tobacco is the leading preventablecause of death in the world. It causes 1in 10 deaths among adults worldwide.In 2005, tobacco caused 5.4 milliondeaths, or an average of one deathevery 6 seconds. The death toll isprojected to reach more than 8 millionby 2030 if current trends continue.

Tobacco kills up to half of its regularusers. On average 29% of peoplearound the world are smokingtobaccos. Smoking is more commonamong men- 47.5% of all men smokecompared to 10.3% of women.

More than 80% of the world's,more than one billion smokers livein low- and middle-incomecountries. Unless urgent action istaken, by 2030, more than 80% oftobacco related deaths will occurin the developing world.

1

11

6

5

10 Facts About Smoking

The smoke produced by burningtobacco products is known as second-hand tobacco smoke or environmentaltobacco smoke. Tobacco smoke inenclosed spaces is breathed byeveryone, exposing both smokers andnon-smokers to its harmful effects. Thisis commonly referred to as involuntarysmoking or passive smoking.

Second-hand tobacco smoke isdangerous to health. There are about4000 known chemicals in tobaccosmoke. Second-hand smoke alsocauses heart disease and manyserious respiratory andcardiovascular diseases in adultswhich can lead to death.

4Tobacco caused 100 million deathsin the 20th century. If currenttrends continue, there could be upto one billion deaths in the 21st

century.

12

8

9

10

10 Facts About Smoking

Source : World Health Organization

There is no safe level of exposure tosecond-hand tobacco smoke. Neitherventilation nor filtration, even incombination, can reduce the exposureindoors to levels that are consideredacceptable. Only 100% smoke-freeenvironments provide effectiveprotection.

Exposure to second-hand smoke alsoimposes economic costs onindividuals, businesses and society asa whole, in the form of direct andindirect medical costs and productivitylosses.

The International Labor Organizationestimates that at least 20,000 workers dieevery year due to exposure to smoke atwork. The United States EnvironmentalProtection Agency estimates that second-hand smoke is responsible for about 3000lung cancer deaths annually among non-smokers in the country.

7An estimated 700 million children, oralmost half of the world's children,breathe air polluted by tobaccosmoke, particularly at home.Second-hand smoke causes manyserious diseases in children andworsens conditions such as asthma.

13

UROLOGY

Presence of blood in the urine can originate atany point along the urinary tract and both grossand microscopic hematuria may represent

serious underlying disease. Microscopic or non-visible hematuria, unlike gross hematuria is often anincidental finding during evaluation of urinary tractinfection or during routine health screening. Althoughremaining asymptomatic, it may be associated withurologic malignancy in up to 10% of adults. Despitethis risk, results of a recent study revealed that 39-90% of persons with microscopic hematuria onscreening urinalysis received no follow-up testing.Non-visible or microscopic hematuria thus presents achallenging clinical scenario for general practitioners.

Prevalence

Non-visible hematuria is present in about 2.5% of thegeneral population, although it can be as high as 20%,depending on features of the study population, such asage, sex, the presence of risk factors for disease, andthe definition used. Within patients withasymptomatic non-visible hematuria detected byscreening, the overall incidence of serious conditionssuch as urological malignancy is <1.5%, so theconsensus is that populations screening is notwarranted. In contrast, a cause for non-visiblehematuria is found in about 15% of cases selected forreferral from primary care towards specific health careauthorities. But there is currently no evidence tosupport opportunistic testing for hematuria without aclinical reason.

Causes

The etiologies of microscopic hematuria are numerousand range from clinically insignificant causes topotentially life-threatening neoplastic lesions. In one

study of 1930 patients who had completed urologicalevaluation for hematuria, 982 had microscopichematuria. Nearly 1 in 5 patients with microscopichematuria had significant disease compared withabout 1 in 3 patients with gross hematuria. In thisstudy, 92 (9.4%) of the patients with microscopichematuria had cancer. Evaluation of the upper urinarytract followed by cystoscopy fails to identify thesource of microscopic hematuria in 19-68% ofpatients. Finally the younger the patient, the less likelyit is the etiology to be identified.

Investigation of Non-Visible Hematuria inPrimary Care

Urine Dipstick : Chemical dipsticks detect intact redcells (RBC), free hemoglobin, or free myoglobin.

Evaluation of Non-Visible Hematuriain Primary Care

Non-visible hematuria under microscope

Medications That Can Cause Hematuria

• Aminoglycosides• Amitriptyline• Analgesics• Anticonvulsants• Aspirin• Busulfan• Chlorpromazine

• Cyclophosphamide • Diuretics• Oral contraceptives• Penicillins• Quinine• Vincristine• Warfarin

A B C

A. Urinary sediment showing red-cell cast and red cells B. Urinary sediment showing normal red cells and crenated red cellforms with spicules (arrowhead) C. Doughnut-like cells with membrane blebs attached (arrowhead)

14

UROLOGY

15

UROLOGY

They provide an instant result. Although the efficiencyof this test is difficult to estimate, analysis of data setsindicates that it is a reasonable way to detect non-visible hematuria in primary care.

Urine Microscopy : Red blood cell counts have beenused to define microscopic hematuria, and cut-offpoints have varied (including >2 cells per high powerfield and >5 cells per power field). Microscopyprovides an accurate measure of red blood cells whenassessed by an expert in fresh voided early morningmidstream specimens of urine. However, time toanalysis affects the integrity of RBC. In a prospective

multicenter study, RBC counts dropped by 5-9% atfive hours, 11-28% at 24 hours, and 29-35% at 72hours. Because immediate microscopy is not feasiblein primary care, the accuracy of quantitative RBCmicroscopy is questionable.

References

1. British Medical Journal, 2009; 338: 227-2322. American Family Physicians, 2006; 73: 1748-17543. http://www.clevelandclinicmeded.com4. The New England Journal of Medicine, 2003; 348:

2330-2338

17

GASTROENTEROLOGY

Until recently, the cause of intermittent orprogressive difficulty in swallowing solidswas thought to be a mechanical problem such

as a stricture, ring, or cancer of the uppergastrointestinal tract (GIT). Also motility disorderssuch as achalasia or diffuse esophageal spasm wereimplicated in difficulty in swallowing of both solidsand liquids. But now health professionals arebecoming aware of a relatively new disease,eosinophilic esophagitis (EE), as a cause of dysphagiain both adults and children.

Over the last several years, EE has emerged as thetopic of an ever-increasing number of articles in theadult and pediatric gastrointestinal as well as allergyjournals. EE is an increasingly recognized cause of avariety of esophageal symptoms, including dysphagia,food impaction, atypical chest pain, and heartburn thatdoes not respond to medical therapy. Although theexact cause is still not well known, allergic andimmune-mediated mechanisms similar to those ofasthma and other atopic diseases are implicated.

When and how was Eosinophilic EsophagitisDetected?

Abundant eosinophils in the esophagus were firstdescribed in 1977 in a 51-year-old man withdysphagia, chest pain, and a personal history of severeasthma and marked peripheral eosinophilia. In 1983, asimilar case was reported in an adolescent withdysphagia. In both patients, large numbers ofeosinophils were also noted in the duodenum,suggesting that these findings were part of a systemichypereosinophilic syndrome. Increased numbers ofeosinophils in the GIT have also been described in anumber of diseases, including Crohn’s disease,connective tissue disorders, malignancy, variousinfections, and drug hypersensitivity reactions.

However, not until 1993, EE was described as adistinct clinical entity, consisting of isolatedesophageal eosinophilia (typically more than 15eosinophils per high-power field) in patients withdysphagia. What was originally a case reportabledisease ten years ago is now one that is appearing innumerous gastrointestinal and allergy journals on aregular highlight.

Epidemiology

Eosinophilic esophagitis predominantly affects menbetween the ages of 20 and 40, but cases in womenand in younger and older patients have also beenreported. Recent systemic reviews found male-to-female ratio of approximately 3:1. Epidemiologicstudies suggest that EE may be as common asinflammatory bowel disease. In a study of children inCincinnati, Ohio, the incidence was estimated at 10per 100,000 children per year, and the prevalence wasestimated at 43 per 100,000. Of interest, 97% of caseswere diagnosed after the year 2000. EE may occur inisolation or in conjunction with eosinophilicgastroenteritis. While isolated EE was previouslythought to be a rare condition, in the last several years,numerous case series have been reported from Northand South America, Europe, Asia and Australia. Thecause of this dramatic rise is likely a combination ofan increasing incidence of EE as well as a growingawareness of the condition.

Eosinophilic Esophagitis: Asthmaof the Esophagus!

• Clinical symptoms of esophageal dysfunctionsuch as dysphagia, food impaction

• At least 15 eosinophils per high-power field

• Either no response to a high-dose proton pumpinhibitor or normal results on pH monitoring of thedistal esophagus and

• Other features such as basal zone hyperplasia,edema, and papillary elongation are seen to agreater extent in patients with EE than in patientswith gastro-esophageal reflux disease (GERD)

The Current Consensus Definition for EE

Child with EE being treated in hospital

18

GASTROENTEROLOGY

Pathophysiology

The growing incidence of EE is quite similar withasthma, eczema, allergic rhinitis, and other atopicdiseases, raising the possibility that these disordersshare common environmental exposures and similarinflammatory pathways. The pathologicalmechanisms of EE are unknown, but emergingevidence suggests that like other allergic diseases, itis an immune response mediated by type 2 T helpercells. Recently, eotaxin-3, a potent attractant foreosinophils, was shown to be markedly overexpressed in children with EE compared withcontrols. Acid reflux does not appear to be acausative factor in most patients. However, refluxmay play a secondary role, as some patients haveexperienced symptomatic, endoscopic, andhistological resolution of EE after treatment with aproton pump inhibitor.

The role of environmental allergens contributing toEE has also been suggested in humans. There may beseasonal variation of EE, as suggested by a case reportof a 21-year-old woman when had EE that worsenedsymptomatically and histologically during the pollenseason but resolved during winter. This is anotherexample of aeroallergens that may play a role in thisdisease. Biopsies obtained during non-pollen monthswere normal, suggesting that tissue eosinophilia wastriggered by pollen exposure. Studies focusing onchildren suggest that food allergies are a majorcontributor to EE. In children, a strict amino-acidelemental diet has led to complete resolution ofsymptoms and a marked decrease in EE. However,symptoms tend to recur once patients resume a regulardiet. It is unclear if dietary modification is effective inadults. In six adults with EE and a history of wheatand rye allergies, symptoms did not improve whenthese foods were eliminated and did not worsen whenthey were reintroduced.The most commonly identifiedfood allergens include milk, soy, egg, wheat, peanuts,and shellfish. Evidence of a genetic predisposition tothis disease is also growing with a number of casereports describing multiple affected family membersspanning generations.

Diagnosis

The diagnosis of EE has often been overlooked withmany patients having had endoscopies withalternative diagnoses that included Schatzki's rings orgastroesophageal reflux disease. In many cases,misdiagnosis led to repeated endoscopies, esophageal

dilations and delay in the institution of appropriatemedical interventions.

Clinical Presentation : More than 90% of adults withEE present with intermittent difficulty in swallowingsolids, while food impaction occurs in more than 60%.Heartburn is the only manifestation in 24% ofpatients. Non-cardiac chest pain, vomiting, andabdominal pain have also been seen, but lessfrequently. In children, presenting symptoms varywith age and include feeding disorders, vomiting,abdominal pain, and dysphagia. Up to 80% of patientswith EE have a history of atopic diseases such asasthma, allergic rhinitis, or allergies to food ormedicine. One-third to one-half of patients hasperipheral eosinophilia, and up to 55% have increasedserum levels of immunoglobulin E (IgE). Childrenwith EE have a higher frequency of atopic symptomsand peripheral eosinophilia than does in adults.

Endoscopic Findings : Although no single endoscopicfeature of EE is pathognomonic, the esophagus showsmucosal fragility in 59% of cases, a corrugated orringed appearance in 49%, strictures in 40%, whitishpapules in 16%, and a narrow caliber in 5%. Many ofthese features, including longitudinal furrows, aresubtile and can be missed. Between 9% and 32% ofpatients with symptoms suggesting EE have normalendoscopic findings. In large clinical series of 381children, the most common endoscopic features were

A. Concentric mucosal rings throughout the length of theesophagus in a patient with a food impaction

B. Linear furrows or creases in the esophageal mucosaC. White exudates/plaques which corresponds to areas ofeosinophilic abscess eruption through esophageal mucosaD. Concentric mucosal rings and small caliber esophagus

A B

C D

19

GASTROENTEROLOGY

linear furrows (41%), normal appearance (32%),esophageal rings (12%), and white plaques (15%).

Histological Findings: While certain endoscopicfeatures are characteristic of EE, this condition isultimately diagnosed by obtaining biopsy specimens,which demonstrate histological findings of increasedintramucosal eosinophils in the esophagus.Eosinophilic infiltration in the stomach or duodenumis typically absent. Another histological feature of EEis superficial layering of the eosinophils. Eosinophilicmicroabscess, intercellular edema, degranulation ofeosinophils, and the presence of other inflammatorycells such as lymphocytes may be seen. Studies havealso shown evidence of subepithelial fibrosis in EEpatients. Another histological finding in EE isepithelial hyperplasia, defined by papillary heightelongation and basal zone proliferation. Epithelialhyperplasia is also a cardinal feature of thehistopathology of reflux esophagitis.

Additional Diagnostic Testing : Radiographically, EEcan appear as a series of concentric rings on bariumstudy- hence the term 'ringed esophagus' appeared. Ina study of 14 patients with EE, 10 (70%) had stricturesof various length with rings within the strictures.

These findings support the theory that inflammationcan lead to submucosal fibrosis, remodeling,narrowing, and eventually symptoms. Furthermore,two recent studies found that children with EE hadincreased subepithelial collagen deposition in theirbiopsy specimens suggesting increased potential forfibrosis.

GERD and EE: What is the Relationship?

Given the high prevalence of GERD in the generalpopulation, much time and effort have been spent oncomparing EE with GERD. Both diseases sharevarying degrees of esophageal eosinophilia, leading tospeculation on the relationship of EE and GERD. Arecent review article suggested that the mucosal injurycaused by acid reflux may allow swallowed allergensto penetrate an esophageal layer that is otherwiseimpermeable to most proteins, thereby causing mildeosinophilia. Conversely, the intense degranulation ofactivated eosinophils seen in EE can trigger changesin the lower esophageal sphincter that couldpredispose to acid reflux. Although the clinical andpathological features may overlap, GERD and EEappear to have different genetic profiles. In a recentpediatric study, it was found that the genes up-regulated in EE were markedly different that those inchronic esophagitis. This suggests that while the twodiseases share a constellation of symptoms, they havedifferent pathogenesis. Nevertheless, because of thispossible overlap, the diagnosis of EE should be madeafter acid reflux has been either treated or excludedwith pH testing.

Treatment

Dietary Therapy : Treatment approaches for EE varybetween children and adult patients. In children, themost common approach is to embark on elimination ofsome diet and introduction of elemental diet. Strictelemental amino-acid diets have resulted in completesymptomatic and histological resolution of EE inchildren. However, these elemental diets often have tobe given by nasogastric tube because they areunpalatable, and the disease tends to return once thediet is discontinued. Elimination diets, based either onavoiding the six foods most commonly associatedwith allergy (egg, wheat, soy, cow's milk protein,seafood, peanuts) or on allergy testing such as skinprick testing or atopy patch testing, have shownpromise in children. Similar large-scale studies ofelimination diets in adults have not been so farconducted.

A. Microscopic picture of GERDB. Microscopic picture of EE

A

B

20

GASTROENTEROLOGY

Allergy Evaluation : The recent recommendationsdevoted considerable attention to the role of allergyevaluation. Between 50-80% of patients with EE havea coexisting atopic disease such as atopic dermatitis,eczema, allergic rhinitis, or asthma, with a higherprevalence in children than in adults. Evidencesuggests that allergy testing may predict response totherapy. Therefore, the current recommendation for allpatients with EE is to undergo a complete evaluationby an experienced allergist. Checking the peripheralblood eosinophil count before and after treatment isreasonable, as many patients have elevated eosinophilcounts that decreases after treatment. Similarly, manypatients with EE have elevated serum total IgE levelssuggesting a concomitant atopic disease. So IgE levelshould also be evaluated and treated. Data on atopypatch testing in EE are currently limited butpromising.

Medical Therapy : Swallowed fluticasone is themainstay of therapy for both children and adults. Inone case series, 21 adult patients with EE received a 6-week course of swallowed fluticasone two to fourpuffs (220 μgm/puff) twice daily. Symptomscompletely resolved in all patients for at least 4months, and no patient needed endoscopic dilation. Inanother study, 19 patients treated with fluticasone for4 weeks showed dramatic improvement bothsymptomatically and histologically. However, after 3months, 14 (74%) of them had a recurrence ofsymptoms pointing to the chronic relapsing nature ofthe disease. Swallowed fluticasone is generally welltolerated, although cases of esophageal candidiasishave been reported.

Acid suppression still has an unclear role in thetreatment of EE. Most patients referred for furtherevaluation of EE have tried twice-daily proton pump

inhibitor therapy without success. The impact ofconcomitant therapy with a proton pump inhibitor hasnot yet been determined, but the recent guidelinessuggest that these drugs are reasonable as co-therapyin patients who also have GERD symptoms. Systemiccorticosteroids have been used with success in bothadults and children with hypereosinophilic syndromesas well as in patients with refractory EE, but adverseeffects limit their routine and long-term use.Cromolyn sodium, a mast cell stabilizer, andmontelukast, a leukotriene inhibitor, have been usedwith limited success. Mepolizumab, a humanizedmonoclonal antibody to human interleukin 5,decreased the number of eosinophils in the esophagusand peripheral blood and improved clinical symptomsin patients with refractory EE in a recent open-labeltrial. Further studies with mepolizumab and otherbiological agents are expected.

Invasive Procedure : Endoscopic dilation with either aguide wire or a balloon technique is often used to treatstrictures and a diffusely narrowed esophagus inpatients with EE. A common endoscopic feature ismucosal fragility. Although this procedure is safe; therisk of perforation appears to be greater than in thosewith other indications for dilation. Nevertheless,immediate symptomatic improvement has beenreported in 83% of patients after dilation, withsymptoms recurring in 20% within 3-8 months. Currentrecommendations suggest that dilation should be donecautiously in patients who have documented esophagealnarrowing for which drug therapy has failed.

Conclusion

Although during the past few years, increasedawareness of the prevalence and presentations of EEhas developed, the upcoming researches will behelpful in enhancing the understanding of its naturalhistory, pathophysiology and treatment modalities.Further studies delineating the molecular mechanismsbehind EE should lead to the development of targetedtherapeutic agents. Therefore the results of theseongoing researches and other studies are eagerlyawaited.

References

1. Cleveland Clinic Journal of Medicine, 2008; 9:623-633

2. Northwestern University Feinberg School ofMedicine, USA

3. http://www.medicinenet.com4. http://www.medscape.com

Endoscopic appearence of EE

21

PROCEDURE IN PRACTICE

The insertion of a femoral venous catheter maybe necessary when peripheral access to thecirculatory system is compromised and no

other sites for placement of a central catheter areavailable.

Indications

Such catheter are used to administer large fluidvolumes or potentially irritating medicines, to providetemporary access for emergency dialysis, forimmediate central access during emergencyresuscitation, to facilitate cardiac catheterization, or,in rare instances, for drawing blood, if a patientrequires frequent blood sampling and no other accesssite is available.

Contraindications

There are few absolute contraindications to placementof a central catheter, other than the patient's notagreeing to the procedure. As compared withsubclavian or jugular catheters, femoral catheters areassociated with higher risk of infection, thrombosis,and in the absence of ultrasound guidance, arterialpuncture may also be a possibility. Considering thesefactors, a safer option if exists, then that should bechosen. Uncooperative patients place both theoperator and themselves at risk of injury, thus itshould be considered with importance. Evidentinfection at the site where the needle will enter shouldprompt the operator to seek another site. In addition,complications are more likely to occur if the site is

Ultrasonography to detect femoral artery Visualization of femoral artery directly through USG

Placement of A Femoral Venous Catheter

General Preparations

• Appropriate selection of patients suitable forfemoral venous catheterization should beconfirmed as well as selecting the correctanatomical location.

• The procedure should be explained to thepatient and a written informed consent shouldbe taken when possible.

• An assistant should be present with theauthorization to halt the procedure ifinappropriate technique is applied.

• For optimal exposure of the femoral region,external rotation and abduction of the patient'sleg away from midline should be obtained.

• The vein should be localized by palpating thefemoral artery or by using ultrasonography(USG) as the femoral vein lies medial to thefemoral artery while running distal to inguinalligament.

• The skin should be prepared withchlorhexidine, and the sterile area should becovered with a sterile drape. Full sterile dressshould be used.

• Then the central-catheter kit is prepared andthe catheter ports are flushed with sterilesaline. If ultrasound guidance is used, then theultrasound probe should be prepared for sterileuse.

• The selected area should be anesthetized withlong-acting anesthetic such as lidocaine withepinephrine or bupivicaine. Adequateanalgesia will increase the patient's comfortand the operator's likelihood of successfulcatheter placement.

22

PROCEDURE IN PRACTICE

distorted by trauma or is obscured. In patients withuncorrected bleeding disorders, a central cathetershould be placed with caution and only if necessary.Central catheters should not be placed byinexperienced hands.

Equipments

Materials required for this procedure include personalprotective equipment, a bag of sterile saline forinfusion, intravenous tubing, local anestheticmedications, a central-catheter kit, and blood-drawingequipment. The central-catheter kit typically includes asterile drape, skin preparation solution, sterile gauze, anintroducer needle, a guide wire, a scalpel, a dilator, andintravenous catheter, a mechanism for securing thecatheter to the skin, and a sterile, transparent dressing.

Procedure of Placing the Catheter

After ensuring proper anesthetization, the position ofthe femoral vein is reconfirmed by palpating femoralartery or by visualizing directly with ultrasonography.The introducer needle is then inserted at 450 anglefrom the skin, directed along the course of the artery,while pulling back the plunger. In order to prevent thefemoral-artery cannulation, palpation of the arteryshould be maintained while advancing the needle.Once a flash of blood is seen, the needle is carefullyanchored to avoid dislodging it from an intraluminallocation. The syringe is detached and the guidewire isto be thread through the needle. It should pass easilywithout resistance into the lumen of the vessel. Whilemaintaining the grasp of the wire, the introducerneedle is removed. The skin is then incised at the wire-entry site with a scalpel keeping the sharp edge awayfrom the wire.

The dilator is advanced over the wire to make a tractthrough the tissues into the vessel. Larger cathetersmay have dilators that fit inside them and must beadvanced together with the catheter. But unless that isthe case, the dilator is to be removed and the catheteris stranded over the wire. Before advancing thecatheter past the skin, the guidwire is firmly graspedwhich is protruding from the proximal end of thecatheter. It is often necessary to feed the wire backthrough the catheter to accomplish this. After thecatheter has been threaded into the vessel, the wire isremoved. The intravenous location of the catheter isconfirmed, the sterile saline is flushed through theport, and the catheter is secured with sutures or staple.A sterile dressing is placed over the site beforeremoving the drapes.

Complications and Their Remedies

Potential complications include infection,thromboembolism, arterial puncture, and hematoma.It is important to be aware of these possible problemsand to keep them in mind when monitoring thepatient. Most of these complications can be preventedby following proper sterile technique, usingultrasonography for placing the catheter, limiting thenumber of attempts at placing the catheter, andremoving it as soon as possible. If the femoral arteryhas been punctured, pressure is applied to the site forat least 10 minutes. Small hematomas may bemanaged conservatively, but continuing hemorrhagemay require surgical intervention.

Source: The New England Journal of Medicine, 2008;358: 26

A

B C

D E

A. Equipments for Femoral venous catheterization B. Inserting the introducer needle C. Attaching the cannula

D. Inserting the needle at the centre of the probe E. Anchoringthe needle F. Advancing the dialater to make a tract

G. Completion with a transparent dressing

F G

23

Clindamycin Phosphate, Benzoyl PeroxideCombination Improves Severe Acne

O ral antibiotics for severe acne have limitationsbecause of side effect concerns and mountingevidence of antibiotic resistance to

Propionibacterium acnes. A topical combination ofclindamycin phosphate 1.2% and low-concentrationbenzoyl peroxide (BPO) 2.5% aqueous gel is effectivefor severe inflammatory and noninflammatory acne,according to a study. The analysis included 531patients with severe acne who participated in 2 largermulticenter, double-blind studies which involvedpatients with both moderate and severe acne. Patientswere randomized in a 2:2:2:1 ratio to receiveclindamycin phosphate 1.2% plus low-concentrationBPO 2.5%, each active ingredient, or vehicle, oncedaily for 12 weeks. At weeks 4, 8 and 12, thecombination showed statistically significant efficacyover vehicle for all lesion types. The median percentchange from baseline with the topical combinationwas 49% in inflammatory lesions and 45% innoninflammatory lesions. The overall medianreduction in total lesion counts with the study drugwas 44% at week 12. In both treatment arms, meancutaneous tolerability scores (each for burning,stinging, scaling, erythema, and itching) at weeks 4, 8,and 12 were less than 1 in a scale of 0 (none) to 3(severe). No patient in either arm dropped out becauseof burning, stinging, scaling, erythema, or itching.

Desonide Hydrogel in Dermatitis

U se of desonide hydrogel in patients withmild to moderate atopic dermatitis resultedin significant reductions in symptom

severity and high patient satisfaction. The surveysincluded questions about prior medication use foratopic dermatitis, assessments of symptom severity,satisfaction, intent to continue, and recommendationof desonide hydrogel to other patients. A total of 1,025patients completed the surveys (60% female; meanage, 35 years), with approximately two-thirds having

used at least 1 prior medication for atopic dermatitis.Results showed desonide hydrogel reduced redness by58%, scaling/flaking by 59%, and itching severity wasreduced by 60% (P < 0.05). Of the patients (n = 692)who had used other medications for their condition,satisfaction with desonide hydrogel was nearly twiceas high, on average, than satisfaction with their priormedications (P < 0.05). Satisfaction with desonidehydrogel for all respondents averaged 7.7 to 9 on ascale of 1 (not at all satisfied) to 9 (very satisfied),with 83% of respondents rating their satisfactionbetween 7 and 9. Most patients said they wouldcontinue using desonide hydrogel if necessary, andmost said they would recommend the medication toother patients. The researchers emphasized for furtherstudies to confirm that the effectiveness of desonidehydrogel plus high patient satisfaction may enhancetreatment compliance.

Calcipotriol Plus Betamethasone DipropionateFormulation Effective in Scalp Psoriasis

A ccording to the researchers, a scalpformulation combining calcipotriol plusbetamethasone dipropionate markedly

decreases itching related to scalp psoriasis.Participants in the trial were aged 18 years or moreand had scalp psoriasis of at least moderate severitythat covered at least 10% of the scalp with at least 1clinical sign (redness, thickness, or scaliness) that wasconsidered at least moderate and the other 2 signs atleast slight by the investigator. Three hundred andtwelve patients were randomized to treatment with ascalp solution containing calcipotriol 50 μg/g plusbetamethasone dipropionate 0.5 mg/g once daily or ascalp solution containing calcipotriol alone twicedaily to the affected psoriatic lesions on the scalp forup to 8 weeks. Patients assessed the extent of itchingat weeks 0, 2, 4, and 8. Results showed that thenumber of patients reporting itching on the Skindex-16 scale was significantly lower in the 2-compoundgroup compared with the calcipotriol-alone group atall time points (week 2: P < 0.001; week 4: P < 0.001;week 8: P = 0.044). This was also true for scalpburning (week 2: P < 0.001; week 4: P < 0.001; week8: P = 0.002) and hurting at weeks 2 and 4 (week 2: P= 0.003; week 4: P < 0.001). After 2 weeks oftreatment, a significant effect on itching was achievedin the 2-compound group compared with baseline (P <0.001), and this reduced level of itching remainedconstant throughout the treatment period. This effectwas also true for symptoms of burning and hurting.After 8 weeks, a complete absence of itching wasmore than twice (57.5% vs. 26.7%, P < 0.001) aslikely in the 2-compound group.

Source : http://www.pslgroup.com

NEWS

FROM

INTERNET

NEWS

FROM

INTERNET

American Academy of Dermatology’s 67th Annual Meeting Report