Eosinophilic esophagitis is characterized by eosinophil-predominant inflammation in the esophagus. Potential etiologies include food and aeroallergen sensitization, genetics involving genes like TSLP, and cytokines/chemokines such as IL-5 and eotaxin-3. The pathogenesis involves activation of epithelial inflammatory pathways producing eotaxin-3, impaired barrier function mediated by loss of desmoglein-1, and increased TGF-β. Clinical features commonly include dysphagia, abdominal pain, failure to thrive, and food impactions. Diagnosis is based on symptoms and histological evidence of ≥15 eosinophils per hpf. Treatment
Autoimmune pancreatitis is the pancreatic manifestation of a systemic disorder that affects various organs, including the bile duct, retroperitoneum, kidney, and parotid and lacrimal glands. It represents a recently described subset of chronic pancreatitis that is immune mediated and has unique histologic, morphologic, and clinical characteristics. A hallmark of the disease is its rapid response to corticosteroid treatment. Although still a rare disease, autoimmune pancreatitis is increasingly becoming recognized clinically, leading to evolution in the understanding of its prognosis, clinical characteristics, and treatment.
Diagnosis of Inflammatory bowel disease have challenges including differentiating from Irritable bowel disease using noninvasive biomarkers. Fecal calprotectin is a novel fecal marker which meets the diagnostic & monitoring requirements for IBD.
gutCARE IBS Talk on 20/5/2020.
In this talk, we update Singapore local epidemiology about increasing trend of IBS locally since 1998. There is also challenges in diagnosing IBS confidently in primary care due to patient presentation and symptoms.
We also update audience about latest diagnostic criteria for IBS.
New treatment for IBS, relationship between Small intestine bacterial overgrowth and IBS and the role of hydrogen breath testing in managing IBS.
We hope you enjoy the slides.
Presentation by DR. MISHAL on the topic of NON CIRRHOTIC PORTAL HYPERTENSION. Its a grey area but very important topic particularly for FCPS residents .
Autoimmune pancreatitis is the pancreatic manifestation of a systemic disorder that affects various organs, including the bile duct, retroperitoneum, kidney, and parotid and lacrimal glands. It represents a recently described subset of chronic pancreatitis that is immune mediated and has unique histologic, morphologic, and clinical characteristics. A hallmark of the disease is its rapid response to corticosteroid treatment. Although still a rare disease, autoimmune pancreatitis is increasingly becoming recognized clinically, leading to evolution in the understanding of its prognosis, clinical characteristics, and treatment.
Diagnosis of Inflammatory bowel disease have challenges including differentiating from Irritable bowel disease using noninvasive biomarkers. Fecal calprotectin is a novel fecal marker which meets the diagnostic & monitoring requirements for IBD.
gutCARE IBS Talk on 20/5/2020.
In this talk, we update Singapore local epidemiology about increasing trend of IBS locally since 1998. There is also challenges in diagnosing IBS confidently in primary care due to patient presentation and symptoms.
We also update audience about latest diagnostic criteria for IBS.
New treatment for IBS, relationship between Small intestine bacterial overgrowth and IBS and the role of hydrogen breath testing in managing IBS.
We hope you enjoy the slides.
Presentation by DR. MISHAL on the topic of NON CIRRHOTIC PORTAL HYPERTENSION. Its a grey area but very important topic particularly for FCPS residents .
Eosinophilic GI disorders are rare disorders. Manifestation depends on its location. Treatment is dietetic therapy, pharmacological and endoscopic therapy.
Food allergy has been long recognized and well documented. Other adverse reactions to foods first referred to as “toxic idiopathies” by John Freeman, co inventor of immunotherapy, at the early part of the 1900s can be mediated by and have their impact on the nervous and endocrine systems. It can also be mediated by pharmacologic mechanisms and can also affect any part of the body. There’s a great clinical need to accurately identify triggers of adverse reactivity as they have now been linked with even the most serious of modern maladies and diseases. In fact, inflammation is the hallmark of metabolic syndrome. Given the multitude of pathogenic mechanisms underlying adverse reactions to foods and other environmental exposures it is necessary that a utilizable and cost effective technology be understood so that its application be utilized under the appropriate circumstances.
KEY LEARNING POINTS
• The natural ability of certain foods to initiate an inflammatory response and induce metabolic disruptions and counterbalancing mechanisms to prevent that
• How foods can trigger “danger signals” for the immune system
Pharmacologic vs. immunologic reactions to foods
• Is there a common final pathway of all these mechanisms that can reliably indicate triggers of clinical pathology?
• Cellular testing vs. serologic testing: The advantages of cellular testing
Acute Leukemia Initial Presentation as Acute Appendicitis - Case Reportasclepiuspdfs
Appendicitis represents a real, everyday working problem for the primary physician and those who care for children. Acute appendicitis can be initial manifestation of leukemia or relapse. However, such cases have only been reported in adults. Very few cases are reported in pediatric population. Here, we report a 5-year-old girl who presented with clinical features suggestive of acute appendicitis. The clinical findings were supported with radiological findings. On further investigations, found to have acute leukemia. Acute appendicitis was treated conservatively. The parents were reluctant to accept the clinical diagnosis. The parents were keen to get more and more second opinion in this regard before accepting final diagnosis.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
4. Introduction
• Disorders that selectively affect GI tract
• Eosinophil-rich inflammation in the absence of
known causes for eosinophilia
Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
6. Epidemiology(1)
• EoE is a global health problem now reported
in
- Australia - Japan
- Brazil - Spain
- England - Switzerland
- Italy - Israel
Shitrit AB, Reinus C, Zeides S, et al. Eosinophilic esophagitis. Isr Med Assoc J 2006;8:587.
7. Epidemiology(4)
Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis. The New England journal of medicine. 2004;351(9):940-1.
8. Epidemiology(3)
• 0.4% (~4 : 1000) prevalence of EoE in a
random sample of Swedish adults.
• EoE occurred in about 1 : 1000 children in the
Cincinnati metropolitan area over a 10-year
period.
Ronkainen J, Talley NJ, Aro P, et al. Prevalence of eosinophilia and eosinophilic esophagitis in
adults in the community: a random population based study (Kalixanda). Gastroenterology 2006;130:A575
Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis. N Engl J Med 2004;351:940-1.
10. Gastrointestinal Eosinophils Under Homeostatic
Healthy States
• Eosinophils are present at low levels in
numerous tissues
• In biopsy and autopsy specimens, organs that
normally demonstrate tissue eosinophils at
substantial levels are
- GI tract - Lymph nodes
- Spleen - Thymus
DeBrosse CW, Case JW, Putnam PE, Collins MH, Rothenberg ME. Quantity and distribution of eosinophils in
the gastrointestinal tract of children. Pediatric and developmental pathology : the official journal of the
Society for Pediatric Pathology and the Paediatric Pathology Society. 2006;9(3):210-8.
11. Gastrointestinal Eosinophils Under Homeostatic
Healthy States
• Eosinophils throughout the GI tract of
conventional healthy mice : normally present
in the lamina propria of the stomach, small
intestine, cecum, and colon.
• Eosinophils are not normally present in Peyer
patches or intraepithelial locations.
• Eosinophils are frequently infiltrate in Peyer
patches regions in EGID.
Mishra A, Hogan SP, Lee JJ, et al. Fundamental signals that regulate eosinophil homing to the gastrointestinal tract. J Clin
Invest 1999;103: 1719-27
Rothenberg ME, Mishra A, Collins MH, et al. Pathogenesis and clinical features of eosinophilic esophagitis. J Allergy Clin
Immunol 2001;108:891-4.
13. DeBrosse CW, Case JW, Putnam PE, Collins MH, Rothenberg ME. Quantity and distribution of eosinophils in
the gastrointestinal tract of children. Pediatric and developmental pathology : the official journal of the
Society for Pediatric Pathology and the Paediatric Pathology Society. 2006;9(3):210-8.
14. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-279
PROINFLAMMATORY ROLE OF EOSINOPHILS
16. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-279
17. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-279
18. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-279
MBP, EPX, and ECP have
cytotoxic effects on
epithelium at concentrations
similar to those in biologic
fluids from patients with
eosinophilia
19. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-279
MBP triggers
degranulation of mast cells
and basophils.
20. Kita H. et al.Middleton's Allergy ; 8th edition. 2014. p. 265-279
Eosinophil-mediated
damage is caused by
• Toxic hydrogen
peroxide and halide acids
generated by EPX
• Superoxide generated
by the respiratory burst
oxidase enzyme pathway
in eosinophils
21. Proinflammatory Role of Eosinophils
• Triggering of eosinophils by engagement of
receptors for cytokines, immunoglobulins, and
complement can lead to the generation of a
wide range of inflammatory cytokines
Yousefi S, Gold JA, Andina N, Lee JJ, Kelly AM, Kozlowski E, et al. Catapult-like release of mitochondrial DNA
by eosinophils contributes to antibacterial defense. Nature medicine. 2008;14(9):949-53.
22. Proinflammatory Role of Eosinophils
• TGF-β is linked with epithelial growth, fibrosis,
and tissue remodeling.
• Eosinophils express MHC class II molecules
and relevant costimulatory molecules (CD28,
CD40, CD80 [B7-1], CD86
• Eosinophils secrete cytokines capable of
promoting lymphocyte proliferation ,
activation &Th1 or Th2 polarization (IL-2, -4, -
6, -12, -10).
Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
23. Clinical Evaluation
• Pts with EGID present with a variety of clinical
problems, most often
-Failure to Thrive -Abdominal pain
-Irritability -Gastric dysmotility
-Vomiting -Diarrhea
-Dysphagia -Microcytic anemia
-Hypoproteinemia
Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
26. Clinical Evaluation
Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
•Blood eosinophil
counts are generally
in the normal range
in most pts
• Above-normal
levels can distinguish
pts with active
versus inactive EoE
27. Evaluation for Hypereosinophilic syndrome
Diagnostic criteria for HES established by Chusid and
colleagues,1975
1.Peripheral blood eosinophilia (>1,500 cells/microliter)
for longer than 6 months
2.Evidence of eosinophil-related target organ damage
3.Exclusion of all other etiologies for eosinophilia
Chusid MJ, Dale DC, West BC, Wolff SM. The hypereosinophilic syndrome: analysis of fourteen cases with
review of the literature. Medicine. 1975;54(1):1-27.
28. Evaluation for Hypereosinophilic syndrome
Contemporary consensus proposal on criteria and
classification of eosinophilic disorders and related
syndromes
1. Hypereosinophilia-absolute eosinophil count >1,500
cells/microlitr for 1 mo,checked on 2 occasions*
2. Evidence of eosinophil-mediated target organ
damage
3. Exclusion of all other potential causes of
hypereosinophilia
Valent P, et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and
related syndromes. The Journal of allergy and clinical immunology. 2012;130(3):607-12.e9.
29. Evaluation for Hypereosinophilic syndrome
*Tissue hypereosinophilia can be identified in
addition to an elevated absolute eosinophil count
with tissue hypereosinophilia, defined as:
1. Eosinophils >20% of nucleated cells in bone
marrow
2. Extensive tissue infiltration of target organ by
histologic analysis
3. Histologic evidence of eosinophil degranulation
in a target tissue in the absence of eosinophils in
that target tissue
Valent P, et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and
related syndromes. The Journal of allergy and clinical immunology. 2012;130(3):607-12.e9.
30. HE-related organ damage
Organ dysfunction
With
Marked tissue eosinophil
infiltrates
And/Or
Extensive deposition of
eosinophil-derived proteins
In the presence or absence
of marked tissue eosinophils
(1) Fibrosis (lung, heart,
digestive tract, skin, and others)
(2) Thrombosis with or without
thromboembolism
(3) Cutaneous (including
mucosal) erythema,
edema/angioedema, ulceration,
pruritus, and eczema
(4) Peripheral or central
neuropathy with chronic or
recurrent neurologic deficit
And 1 or
more of
the
following
Valent P, et al. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and
related syndromes. The Journal of allergy and clinical immunology. 2012;130(3):607-12.e9.
31. Evaluation for Hypereosinophilic syndrome
• Pts with EGID, the diagnosis of HES should
always be considered, especially if they develop
extra-GI manifestations .
• Thus, additional diagnostic testing for HES
should be considered.
Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
32. Evaluation for Hypereosinophilic syndrome
• Pts with marked eosinophilia are at risk for the
development of cardiac disease.
• Routine surveillance of the cardiorespiratory
system is warranted.
Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
35. Definition
• “Eosinophilic esophagitis represents a chronic,
immune/antigen mediated, esophageal
disease characterized clinically by symptoms
related to esophageal dysfunction and
histologically by eosinophil-predominant
inflammation”
Liacouras CA, Furuta GT, Hirano I, Atkins D, Attwood SE, Bonis PA, et al. Eosinophilic esophagitis: updated
consensus recommendations for children and adults. The Journal of allergy and clinical immunology.
2011;128(1):3-20.e6; quiz 1-2.
40. Esophageal eosinophilic inflammation is
mechanistically linked to pulmonary
inflammation, on the basis of the induction of
experimental EoE by repeated delivery of
specific allergens to the lung of mice.
Mishra A, Hogan SP, Brandt EB, et al. An etiological role for aeroallergens and eosinophils in experimental esophagitis. J Clin
Invest 2001; 107:83-90.
41. Fogg MI, Ruchelli E, Spergel JM. Pollen and eosinophilic esophagitis. The Journal of allergy and clinical immunology.
2003;112(4):796-7.
43. Genetics
• 3 Basic approach
1) Mendelian disorder
2) Candidate gene identification
3) Genome wide association study
44.
45.
46. Thymic stromal lymphopoeitin (TSLP)
protein
• GWAS, genotyping 351 patients with EoE and
3104 healthy controls and evaluating 550,000
common variants.
• On chromosome 5q22, a single locus spanning
the TSLP and WD repeat domain 36 (WDR36)
genes showed a significant association with
EoE.
Rothenberg ME, Spergel JM, Sherrill JD, Annaiah K, Martin LJ, Cianferoni A, et al. Common variants at 5q22 associate with
pediatric eosinophilic esophagitis. Nature genetics. 2010;42(4):289-91.
47. Thymic stromal lymphopoeitin (TSLP)
protein
• TSLP has a known role in processes germane
to EoE
1. Polarization of Th2 immunity
2. Induction of eotaxins
Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
49. Blanchard C, Wang N, Stringer KF, et al. Eotaxin-3 and a uniquely conserved gene expression profile in eosinophilic
esophagitis. J Clin Invest 2006;116:536-47.
50.
51.
52.
53. Pathogenesis
• Activation of epithelial inflammatory
pathways (production of eotaxin-3 [encoded
by CCL26]).
Rothenberg ME. Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis. Gastroenterology. 2015.
54. Pathogenesis
• Activation of epithelial inflammatory
pathways (production of eotaxin-3 [encoded
by CCL26]).
• Impaired barrier function (mediated by loss of
desmoglein-1).
Rothenberg ME. Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis. Gastroenterology. 2015.
55. Pathogenesis
• Activation of epithelial inflammatory
pathways (production of eotaxin-3 [encoded
by CCL26]).
• Impaired barrier function (mediated by loss of
desmoglein-1).
• Increased production and/or activity of
transforming growth factor-b.
Rothenberg ME. Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis. Gastroenterology. 2015.
56. Pathogenesis
• Activation of epithelial inflammatory
pathways (production of eotaxin-3 [encoded
by CCL26]).
• Impaired barrier function (mediated by loss of
desmoglein-1).
• Increased production and/or activity of
transforming growth factor-b.
• Induction of allergic inflammation by
eosinophils and mast cells.
Rothenberg ME. Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis. Gastroenterology. 2015.
57.
58. Rothenberg ME. Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis. Gastroenterology. 2015.
59. Clinical feature(1)
Yan BM, Shaffer EA. Eosinophilic esophagitis: a newly established cause of dysphagia. World journal of gastroenterology :
WJG. 2006;12(15):2328-34.
61. Clinical feature(2)
Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis. The New England journal of medicine. 2004;351(9):940-1.
62. Remedios M, Campbell C, Jones DM, Kerlin P. Eosinophilic esophagitis in adults: clinical, endoscopic, histologic findings, and response to
treatment with fluticasone propionate. Gastrointestinal endoscopy. 2006;63(1):3-12.
63. Remedios M, Campbell C, Jones DM, Kerlin P. Eosinophilic esophagitis in adults: clinical, endoscopic, histologic findings, and response to
treatment with fluticasone propionate. Gastrointestinal endoscopy. 2006;63(1):3-12.
Study of 26 adult patients with EoE, all had dysphagia, 11 had
food impaction.
68. Radiographic studies
Figure 2. Radiographic and endoscopic
studies from an 18-year-old female with
history of asthma, eczema, and long-
standing obstructive dysphagia beginning
in early childhood.
A.Barium esophagram showing a small
caliber esophagus
Fox VL, Nurko S, Furuta GT. Eosinophilic esophagitis: it's not just kid's stuff. Gastrointestinal endoscopy. 2002;56(2):260-70.
69. Endoscopic Studies
Fox VL, Nurko S, Furuta GT. Eosinophilic esophagitis: it's not just kid's stuff. Gastrointestinal endoscopy. 2002;56(2):260-70.
70. Endoscopic Studies
Fox VL. Eosinophilic esophagitis: endoscopic findings. Gastrointestinal endoscopy clinics of North America.
2008;18(1):45-57; viii.
71. Endoscopic Studies
Fox VL. Eosinophilic esophagitis: endoscopic findings. Gastrointestinal endoscopy clinics of North America.
2008;18(1):45-57; viii.
72. Endoscopic Studies
Fox VL. Eosinophilic esophagitis: endoscopic findings. Gastrointestinal endoscopy clinics of North America.
2008;18(1):45-57; viii.
73. Endoscopic Studies
A) mucosal edema, concentric ring, linear furrow B) linear furrow, white exudates
C) corrugated appearance, linear shearing
Fox VL. Eosinophilic esophagitis: endoscopic findings. Gastrointestinal endoscopy clinics of North America.
2008;18(1):45-57; viii.
75. Histology
Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointestinal endoscopy clinics of North
America. 2008;18(1):59-71; viii-ix.
76. Histology
Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointestinal endoscopy clinics of North
America. 2008;18(1):59-71; viii-ix.
77. Histology
Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointestinal endoscopy clinics of North
America. 2008;18(1):59-71; viii-ix.
78. Histology
Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, et al. Eosinophilic esophagitis in children and adults:
a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007;133(4):1342-63.
79. Histology
Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, et al. Eosinophilic esophagitis in children and adults:
a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007;133(4):1342-63.
80. Histology
Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointestinal endoscopy clinics of North
America. 2008;18(1):59-71; viii-ix.
81. Histology
Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointestinal endoscopy clinics of North
America. 2008;18(1):59-71; viii-ix.
82. Histology
Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointestinal endoscopy clinics of North
America. 2008;18(1):59-71; viii-ix.
83. Histology
Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointestinal endoscopy clinics of North
America. 2008;18(1):59-71; viii-ix.
84. Histology
Collins MH. Histopathologic features of eosinophilic esophagitis. Gastrointestinal endoscopy clinics of North
America. 2008;18(1):59-71; viii-ix.
87. Allergy Evaluation
• Peripheral blood eosinophil count
- There was a significant amount of variability
in the defining level for “peripheral
eosinophilia”
-Range of eosinophils reported as abnormal
ranged from greater than 350 eosinophils
per mm3 to greater than 800 eosinophils per
mm3).
Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, et al. Eosinophilic esophagitis in children and adults:
a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007;133(4):1342-63.
88. Allergy Evaluation
• Peripheral blood eosinophil count
• One study demonstrated that persistent blood
eosinophilia correlated with persistent
dysphagia.
• In another study, the degree of elevation of
serum eosinophils correlated with the severity
of Eosinophilic esophagitis
Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, et al. Eosinophilic esophagitis in children and adults:
a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007;133(4):1342-63.
91. 26 Pts with EoE
Identify by BX
SPT+ Milk&Egg
Patch+Wheat
SPT &
Patch test
Avoid
food
Resolution
18 Pts
Partial
improve
6 Pts
Loss F/U
2 Pts
Overall, after intervention, esophageal eosinophil
counts improved from 55.8 to 8.4 eosinophils/HPF
Spergel JM, Beausoleil JL, Mascarenhas M, Liacouras CA. The use of skin prick tests and patch tests to identify causative foods in eosinophilic
92. Treatment
• A trial of specific food allergen and
aeroallergen avoidance
• Systemic or topical glucocorticoids
• Anti–IL-5 monoclonal antibody
• Anti– human IL-13 antibody
• Siglec-F
• PPI
Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
93. Specific food allergen and aeroallergen
avoidance
• Indicated for patients with atopic EoE
• If results are unsatisfactory or avoidance is
difficult for practical reasons
- A diet consisting of an elemental (amino
acid–based) formula
- Avoidance of the most common allergic
foods (cow’s milk, soy, wheat, egg,
peanut/tree nuts, seafood/shellfish)
Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
94. Kagalwalla AF, Sentongo TA, Ritz S, Hess T, Nelson SP, Emerick KM, et al. Effect of six-food elimination diet on clinical and
histologic outcomes in eosinophilic esophagitis. Clinical gastroenterology and hepatology : the official clinical practice
journal of the American Gastroenterological Association. 2006;4(9):1097-102.
95. 60 Pts with EoE
ELED
25 Pts
SFED
35 Pts
6 weeks later Esophageal
Bx Specimen was
obtained
SFED gr. Improve
Esophageal inflammation
26 Pts(74%)
ELED gr improve
Esophageal inflammation
22 Pts (88%)
Kagalwalla AF, Sentongo TA, Ritz S, Hess T, Nelson SP, Emerick KM, et al. Effect of six-food elimination diet on clinical and
histologic outcomes in eosinophilic esophagitis. Clinical gastroenterology and hepatology : the official clinical practice
journal of the American Gastroenterological Association. 2006;4(9):1097-102.
96. Kagalwalla AF, Sentongo TA, Ritz S, Hess T, Nelson SP, Emerick KM, et al. Effect of six-food elimination diet on clinical and
histologic outcomes in eosinophilic esophagitis. Clinical gastroenterology and hepatology : the official clinical practice
journal of the American Gastroenterological Association. 2006;4(9):1097-102.
97. Systemic or topical glucocorticoids
• Systemic glucocorticoids are used for acute
exacerbations
• Topical glucocorticoids are used to provide
long-term control
Rothenberg ME. Middleton's Allergy ; 8th edition. 2014. p. 1095-1106
98. Systemic or topical glucocorticoids
Liacouras CA, Furuta GT, Hirano I, Atkins D, Attwood SE, Bonis PA, et al. Eosinophilic esophagitis: updated
consensus recommendations for children and adults. The Journal of allergy and clinical immunology.
2011;128(1):3-20.e6; quiz 1-2.
99. Konikoff MR, Noel RJ, Blanchard C, Kirby C, Jameson SC, Buckmeier BK, et al. A randomized, double-blind,
placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology.
2006;131(5):1381-91.
100. Konikoff MR, Noel RJ, Blanchard C, Kirby C, Jameson SC, Buckmeier BK, et al. A randomized, double-blind,
placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology.
2006;131(5):1381-91.
101. 36 Pts with EoE
880 g of FP
21 Pts
Placebo
15 Pts
3 mnths later Esophageal
Bx Specimen was
obtained
50% of FP Pts
Improve
9% of Placebo Pts
Improve
Konikoff MR, Noel RJ, Blanchard C, Kirby C, Jameson SC, Buckmeier BK, et al. A randomized, double-blind,
placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology.
2006;131(5):1381-91.
102. Result
• FP decreased esophageal eosinophil levels,
with a more pronounced effect in nonallergic individuals
Konikoff MR, Noel RJ, Blanchard C, Kirby C, Jameson SC, Buckmeier BK, et al. A randomized, double-blind,
placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology.
2006;131(5):1381-91.
Eo/HPF
In Proximal
Esophagus
Eo/HPF
In Distal
Esophagus
P (Value)
FP 65.9 +/- 25.3 84.6+/-19.7 .03
Placebo 1.4+/-1.1 19.6+/- 12.9 .04
103. Anti–IL-5 monoclonal antibody
Spergel JM, Rothenberg ME, Collins MH, Furuta GT, Markowitz JE, Fuchs G, 3rd, et al. Reslizumab in children and
adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. The Journal of
allergy and clinical immunology. 2012;129(2):456-63, 63.e1-3.
105. Spergel JM, Rothenberg ME, Collins MH, Furuta GT, Markowitz JE, Fuchs G, 3rd, et al. Reslizumab in children and
adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. The Journal of
allergy and clinical immunology. 2012;129(2):456-63, 63.e1-3.
106. Spergel JM, Rothenberg ME, Collins MH, Furuta GT, Markowitz JE, Fuchs G, 3rd, et al. Reslizumab in children and
adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. The Journal of
allergy and clinical immunology. 2012;129(2):456-63, 63.e1-3.
107. Spergel JM, Rothenberg ME, Collins MH, Furuta GT, Markowitz JE, Fuchs G, 3rd, et al. Reslizumab in children and
adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. The Journal of
allergy and clinical immunology. 2012;129(2):456-63, 63.e1-3.
227 Pts with EoE
Reslizumab 1
mg/kg
56 Pts
Reslizumab 3
mg/kg
57 Pts
Reslizumab 2
mg/kg
57 Pts
Placebo
% Reduction Eo
59 %
% Reduction Eo
67 %
% Reduction Eo
64 %
% Reduction Eo
24 %
108. Siglec-F
Rubinstein E, Cho JY, Rosenthal P, Chao J, Miller M, Pham A, et al. Siglec-F inhibition reduces esophageal eosinophilia and
angiogenesis in a mouse model of eosinophilic esophagitis. Journal of pediatric gastroenterology and nutrition.
2011;53(4):409-16.
• New approach is to target the sialic acid–binding
immunoglobulin-like lectin F (Siglec-F)
• An inhibitory receptor expressed on eosinophils
• Siglec-F inhibition was useful in a mouse model of
EoE.
109. Proton Pump Inhihitor
• PPI are useful
1. Eliminate GERD as a cause of esophageal
eosinophilia.
2. GERD is a comorbid disease
3. PPI-responsive esophageal eosinophilia
• Mechanism of PPI
1. Primarily involve acid blockade
2. Other mechanisms
Liacouras CA, Furuta GT, Hirano I, Atkins D, Attwood SE, Bonis PA, et al. Eosinophilic esophagitis: updated
consensus recommendations for children and adults. The Journal of allergy and clinical immunology.
2011;128(1):3-20.e6; quiz 1-2.
110. Proton Pump Inhihitor
• Recommended PPI dose that should be used to
eliminate PPI-responsive esophageal eosinophilia
- Adults
20-40 mg, once or twice daily for 8 to 12 weeks
- Children
1 mg/kg per dose, twice daily for 8 to 12 weeks
Liacouras CA, Furuta GT, Hirano I, Atkins D, Attwood SE, Bonis PA, et al. Eosinophilic esophagitis: updated
consensus recommendations for children and adults. The Journal of allergy and clinical immunology.
2011;128(1):3-20.e6; quiz 1-2.
111. Prognosis
• EoE requires prolonged treatment, similar to
allergic asthma.
• Natural history of EoE has not been fully
delineated.
• Results of a 15-year follow up study of
esophageal eosinophilia indicate that
Vast majority of patients have ongoing
symptoms from childhood into adulthood.
DeBrosse CW, Franciosi JP, King EC, Butz BK, Greenberg AB, Collins MH, et al. Long-term outcomes in pediatric-onset
esophageal eosinophilia. The Journal of allergy and clinical immunology. 2011;128(1):132-8.
112. Prognosis
• If left untreated, chronic EoE will likely develop
into progressive esophageal scarring &
dysfunction -> consideration of esophageal
dilation
• The risk for developing Barrett esophagitis,
especially in pts with coexisting EoE and GERD
• Pts with EoE are at increased risk for developing
other forms of EGID -> routine surveillance of the
entire GI tract by endoscopy
Rothenberg ME. Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis. Gastroenterology. 2015.
113. Rothenberg ME. Molecular, Genetic, and Cellular Bases for Treating Eosinophilic Esophagitis. Gastroenterology. 2015.