Atopic dermatitis is a chronic inflammatory skin disease associated with respiratory allergies and other atopic disorders. It is characterized by recurrent eczematous lesions and intense itch. Genetic factors like filaggrin mutations contribute to skin barrier defects allowing entry of allergens and microbes. Type 2 immunity cytokines and colonization with Staphylococcus aureus drive inflammation. Clinical features include erythematous patches, scaling, and lichenification. Management involves patient education, avoidance of triggers, topical anti-inflammatory treatments, and bleach baths to reduce S. aureus burden.
The document provides an overview of atopic dermatitis (AD). It discusses the epidemiology, pathophysiology, clinical features, diagnosis, and management of AD. Some key points:
- AD is a chronic inflammatory skin disease associated with respiratory allergy and other atopic disorders. It is characterized by recurrent eczematous lesions and intense itch.
- The global prevalence of AD symptoms is estimated to be 10-20% in children and 1-3% in adults. Most cases begin within the first year of life.
- The pathophysiology of AD involves genetic predisposition, skin barrier defects, immune dysregulation, and environmental factors like allergens and microbes. Fil
This document discusses the pathogenesis and treatment of atopic dermatitis (AD). It notes that AD is a common inflammatory skin condition characterized by pruritus and chronic relapsing inflammation. The disease involves defects in the epidermal barrier that allow penetration of allergens and activation of dendritic cells and Th2 cells. This leads to epidermal dysfunction, skin inflammation, and IgE class switching. Biologic therapies that have been or are being tested for AD target components of the adaptive immune response such as IgE, B cells, T cells, Th2 cytokines, and their receptors. Drugs targeting the IL-4/IL-13 pathway like dupilumab have shown promising results in clinical trials for treating moderate
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by dry, itchy skin lesions. It is associated with elevated IgE levels and a family history of atopic diseases. The causes involve genetic susceptibility and environmental triggers that disrupt the skin barrier and promote a TH2-mediated immune response. Treatment focuses on identifying and avoiding triggers while improving the skin barrier with emollients and controlling inflammation with topical corticosteroids and calcineurin inhibitors. New targeted therapies that block cytokines and immune cells involved in AD pathogenesis are under investigation.
Atopic dermatitis is a chronic inflammatory skin condition that often starts in early childhood. It is caused by complex interactions between genetic, immune, and environmental risk factors. A defective skin barrier is a consistent feature of atopic dermatitis. Filaggrin gene mutations contribute to impaired skin barrier function. Diagnosis is based on clinical features like itchy skin rashes and personal or family history of atopy. Treatment focuses on managing symptoms and avoiding triggers while working to strengthen the skin barrier.
The document discusses mast cell disorders and their classification. It describes localized mastocytosis, which includes cutaneous mastocytosis subtypes like urticaria pigmentosa and diffuse cutaneous mastocytosis. Systemic mastocytosis is classified into several subtypes based on severity from indolent to aggressive forms. The pathogenesis involves mutations in the KIT gene in most cases that lead to mast cell proliferation. Clinical features can include systemic symptoms from mast cell mediators as well as dermatologic findings like the rash of urticaria pigmentosa.
This document provides information on atopic dermatitis (AD), including its definition, epidemiology, pathophysiology, clinical manifestations, and treatment. Some key points:
1. AD is a chronic inflammatory skin disease associated with other atopic disorders like asthma. It is characterized by dry skin and sensitization to allergens.
2. The prevalence of AD has increased in recent decades, commonly starting early in life. Genetic factors like mutations in the filaggrin gene contribute to impaired skin barrier function which increases allergen sensitization risk.
3. Clinical features include severe pruritus, chronic relapsing course, and characteristic rash typically located in flexural areas. Complications can include
Atopic dermatitis is a common inflammatory skin condition characterized by itchy, red lesions. It has a complex pathogenesis involving skin barrier dysfunction, immune dysregulation with Type 2 inflammation, and microbial dysbiosis. Genetic factors like filaggrin mutations contribute to impaired skin barrier function. Colonization by Staphylococcus aureus and Malassezia yeasts further damages the skin and promotes inflammation. Pruritus (itching) activates scratch responses that sustain the condition through additional skin damage and inflammation. Treatment involves managing symptoms, restoring skin barrier function, and controlling inflammation and infection.
This document provides an overview of atopic dermatitis (AD), including its pathogenesis, phenotypes, and approaches to management and treatment. It discusses the role of skin barrier dysfunction and genetic and environmental factors. Key points include:
- AD results from a complex interplay between skin barrier defects and immune dysregulation. Filaggrin gene mutations contribute to barrier defects but are absent in many AD cases.
- Both innate and adaptive immune responses are involved, with dysregulation of cytokines like IL-4, IL-13 and IL-31 contributing to barrier defects.
- Microbes like Staphylococcus aureus can both exacerbate skin inflammation and be exacerbated by skin barrier defects in AD patients.
The document provides an overview of atopic dermatitis (AD). It discusses the epidemiology, pathophysiology, clinical features, diagnosis, and management of AD. Some key points:
- AD is a chronic inflammatory skin disease associated with respiratory allergy and other atopic disorders. It is characterized by recurrent eczematous lesions and intense itch.
- The global prevalence of AD symptoms is estimated to be 10-20% in children and 1-3% in adults. Most cases begin within the first year of life.
- The pathophysiology of AD involves genetic predisposition, skin barrier defects, immune dysregulation, and environmental factors like allergens and microbes. Fil
This document discusses the pathogenesis and treatment of atopic dermatitis (AD). It notes that AD is a common inflammatory skin condition characterized by pruritus and chronic relapsing inflammation. The disease involves defects in the epidermal barrier that allow penetration of allergens and activation of dendritic cells and Th2 cells. This leads to epidermal dysfunction, skin inflammation, and IgE class switching. Biologic therapies that have been or are being tested for AD target components of the adaptive immune response such as IgE, B cells, T cells, Th2 cytokines, and their receptors. Drugs targeting the IL-4/IL-13 pathway like dupilumab have shown promising results in clinical trials for treating moderate
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by dry, itchy skin lesions. It is associated with elevated IgE levels and a family history of atopic diseases. The causes involve genetic susceptibility and environmental triggers that disrupt the skin barrier and promote a TH2-mediated immune response. Treatment focuses on identifying and avoiding triggers while improving the skin barrier with emollients and controlling inflammation with topical corticosteroids and calcineurin inhibitors. New targeted therapies that block cytokines and immune cells involved in AD pathogenesis are under investigation.
Atopic dermatitis is a chronic inflammatory skin condition that often starts in early childhood. It is caused by complex interactions between genetic, immune, and environmental risk factors. A defective skin barrier is a consistent feature of atopic dermatitis. Filaggrin gene mutations contribute to impaired skin barrier function. Diagnosis is based on clinical features like itchy skin rashes and personal or family history of atopy. Treatment focuses on managing symptoms and avoiding triggers while working to strengthen the skin barrier.
The document discusses mast cell disorders and their classification. It describes localized mastocytosis, which includes cutaneous mastocytosis subtypes like urticaria pigmentosa and diffuse cutaneous mastocytosis. Systemic mastocytosis is classified into several subtypes based on severity from indolent to aggressive forms. The pathogenesis involves mutations in the KIT gene in most cases that lead to mast cell proliferation. Clinical features can include systemic symptoms from mast cell mediators as well as dermatologic findings like the rash of urticaria pigmentosa.
This document provides information on atopic dermatitis (AD), including its definition, epidemiology, pathophysiology, clinical manifestations, and treatment. Some key points:
1. AD is a chronic inflammatory skin disease associated with other atopic disorders like asthma. It is characterized by dry skin and sensitization to allergens.
2. The prevalence of AD has increased in recent decades, commonly starting early in life. Genetic factors like mutations in the filaggrin gene contribute to impaired skin barrier function which increases allergen sensitization risk.
3. Clinical features include severe pruritus, chronic relapsing course, and characteristic rash typically located in flexural areas. Complications can include
Atopic dermatitis is a common inflammatory skin condition characterized by itchy, red lesions. It has a complex pathogenesis involving skin barrier dysfunction, immune dysregulation with Type 2 inflammation, and microbial dysbiosis. Genetic factors like filaggrin mutations contribute to impaired skin barrier function. Colonization by Staphylococcus aureus and Malassezia yeasts further damages the skin and promotes inflammation. Pruritus (itching) activates scratch responses that sustain the condition through additional skin damage and inflammation. Treatment involves managing symptoms, restoring skin barrier function, and controlling inflammation and infection.
This document provides an overview of atopic dermatitis (AD), including its pathogenesis, phenotypes, and approaches to management and treatment. It discusses the role of skin barrier dysfunction and genetic and environmental factors. Key points include:
- AD results from a complex interplay between skin barrier defects and immune dysregulation. Filaggrin gene mutations contribute to barrier defects but are absent in many AD cases.
- Both innate and adaptive immune responses are involved, with dysregulation of cytokines like IL-4, IL-13 and IL-31 contributing to barrier defects.
- Microbes like Staphylococcus aureus can both exacerbate skin inflammation and be exacerbated by skin barrier defects in AD patients.
1. Atopic dermatitis (AD), also known as eczema, is a chronic inflammatory skin disorder characterized by pruritus and skin lesions that varies by age.
2. The pathogenesis of AD is complex, involving both genetic and environmental factors that contribute to skin barrier dysfunction and immune dysregulation. Defects in filaggrin play an important role.
3. Clinically, AD presents differently in infants/children (extensor involvement), children (flexural involvement), and adults (persistent flexural involvement). The distribution and features change over time.
This document discusses the etiology and pathogenesis of atopic dermatitis (AD). It notes that AD is a chronic, relapsing eczematous skin condition typically diagnosed based on a recurring itchy rash. Genetic factors like filaggrin gene defects that cause skin barrier dysfunction play an important role in AD development. Immune dysregulation also contributes, with increased Th2 cytokines and IgE levels. Environmental factors like allergens, microbes, and lack of early childhood infections may also influence AD risk and severity. The diagnosis of AD is based on clinical features and criteria from Hanifin and Rajka which involve characteristic rash appearance and distribution.
Allergic conjunctivitis is a common bilateral inflammatory condition of the conjunctiva caused by an IgE-mediated allergic response. It can be seasonal due to pollen allergens or perennial due to indoor allergens like dust mites. Symptoms include itching, redness, tearing and blurred vision. Treatment involves avoidance of allergens, artificial tears, oral antihistamines and topical mast cell stabilizers and antihistamines. Atopic keratoconjunctivitis is a chronic inflammation of the conjunctiva and eyelids associated with atopic dermatitis. It presents with itching, mucus discharge, and papillae on the tarsal conjunctiva.
The document provides an in-depth overview of atopic dermatitis (AD), including its pathogenesis, clinical presentation, systemic immune response, and treatment approaches. It discusses several theories for its pathogenesis, including abnormalities in cyclic adenosine monophosphate signaling, the allergy hypothesis involving TH2 cell responses, and genetic factors like filaggrin gene mutations. Diagnosis involves characteristic clinical features along with personal or family history of atopy. Management focuses on emollients, topical corticosteroids, antibiotics, phototherapy, immunomodulators, and avoidance of triggers.
Atopic dermatitis is a recurring inflammatory skin disease that usually develops in childhood. It is associated with respiratory allergies and a family history of atopic diseases. Theories of its pathogenesis include abnormalities in cyclic AMP levels that lead to increased inflammatory cell activity and cytokine production, as well as early antigen exposures that cause Th2-dominant immune responses. Skin lesions show inflammatory infiltrates including lymphocytes, mast cells, eosinophils, and increased expression of adhesion molecules. Systemic features include elevated IgE, eosinophils, and Th2 cytokines. Chronic lesions have increased expression of Th1 cytokines and eosinophils compared to acute lesions. Factors influencing T cell differentiation include cytokines, genetics, pharmac
The document provides an in-depth overview of atopic dermatitis (AD), including its pathogenesis, clinical presentation, systemic immune response, and treatment approaches. It discusses several theories for its pathogenesis, including abnormalities in cyclic adenosine monophosphate signaling, the allergy hypothesis involving TH2 cell responses, and genetic factors like filaggrin gene mutations. Diagnosis involves characteristic clinical features along with personal or family history of atopy. Management focuses on emollients, topical corticosteroids, antibiotics, phototherapy, immunomodulators, and avoidance of triggers.
Atopic dermatitis is a recurring inflammatory skin disease that usually develops in childhood. It is associated with respiratory allergies and a family history of atopic diseases. Theories of its pathogenesis include abnormalities in cyclic AMP levels that lead to increased inflammatory cell activity and cytokine production, as well as early antigen exposures that cause Th2-dominant immune responses. Skin lesions show inflammatory infiltrates including lymphocytes, mast cells, eosinophils, and increased expression of adhesion molecules. Systemic features include elevated IgE, eosinophils, and Th2 cytokines. Chronic lesions have increased expression of Th1 cytokines and eosinophils compared to acute lesions. Factors influencing T cell differentiation include cytokines, genetics, pharmac
The document discusses the role of anti-DNA IgG in the pathogenesis of cutaneous lupus erythematosus (CLE). It first provides background on lupus being an autoimmune disease caused by abnormal immune responses. The objective is then stated as elucidating the role of anti-DNA IgG in CLE. Materials and methods describe collecting tissue samples from CLE patients and healthy controls, using murine anti-DNA IgG, and techniques like flow cytometry, ELISA, and western blot to analyze interactions. Results show that anti-DNA IgG binds to antigens in collagen III and SOCS1 in keratinocytes, inducing apoptosis. It concludes that anti-DNA IgG may contribute to CLE lesions by amplifying TWEA
The document discusses the role of anti-DNA IgG in the pathogenesis of cutaneous lupus erythematosus (CLE). It describes experiments examining the interaction of anti-DNA IgG with keratinocytes and its effects. Skin tissue samples from CLE patients and healthy controls were obtained and anti-DNA IgG clones were cultured. Experiments found that anti-DNA IgG binds to keratinocytes and induces apoptosis. It also binds to novel antigens like collagen III and SOCS1. This binding may amplify TWEAK/Fn14 signals and modulate SOCS1, contributing to macrophage chemoattraction and skin lesions in CLE. The document aims to better understand the pathogenic effects of anti-DNA IgG in C
Allergic rhinitis is a type I hypersensitivity reaction mediated by IgE antibodies. It has a prevalence of 10-20% in the US and is characterized by symptoms like sneezing, rhinorrhea, nasal congestion and pruritus. Risk factors include family history of atopy, environmental exposures, and lifestyle factors. Treatment involves allergen avoidance, pharmacotherapy with antihistamines, intranasal corticosteroids, leukotriene receptor antagonists and immunotherapy for selected patients.
This document provides information on the bacteriology, immunology, and pathogenesis of Mycobacterium leprae, which causes leprosy. It describes the taxonomy and characteristics of M. leprae, how it is transmitted and the animal models used to study it. The mechanisms of nerve damage, immune responses in leprosy including cytokine profiles in tuberculoid and lepromatous states, and the genetic factors involved in susceptibility are summarized. Immunological events leading to reactions are also outlined.
The document discusses host defense mechanisms against pathogens. It describes three lines of defense: 1) physical barriers like skin and mucous membranes, 2) inflammatory response and defensive cells, and 3) the immune system. The immune system has both innate and acquired branches. Innate immunity provides non-specific protection using physical and chemical barriers while acquired immunity involves adaptive, antigen-specific responses. Key cells of the immune system that provide defense include macrophages, neutrophils, lymphocytes and natural killer cells. Antibodies and the complement system are important components that help eliminate pathogens.
Immune System Update in dermatology - Dr. Oki Suwarsa, dr. M.Kes., Sp.KK(K), ...AdiSutriwantoPasarib1
This document summarizes recent findings about the immune system and its role in acne pathogenesis. It discusses how the skin has both innate and adaptive immune systems. In acne, Propionibacterium acnes triggers an inflammatory response by activating innate immunity through pattern recognition receptors and releasing proinflammatory factors. This leads to the development of an adaptive immune response against P. acnes, with dendritic cell maturation presenting P. acnes antigens and stimulating B and T cell responses. Genetic factors also influence the immune response. Together, the immune activation and release of proinflammatory mediators from keratinocytes and sebocytes results in follicular hyperkeratinization and inflammation, key drivers of the acne lesions.
This presentation deals with the role of the intestinal microbiome in the causation of various disorders like psoriasis, Acne and Atopic dermatitis. Helpful for students preparing for MD Dermatology exit examinations.
Immune responses in periodontal disease final.pptxmalti19
This document discusses the immune responses involved in periodontal disease. It begins by defining periodontitis as an infectious disease caused by anaerobic bacteria. Both bacteria and a susceptible host are required to cause disease. It then describes the pathogenesis which involves environmental and genetic risk factors interacting with the microbial challenge to activate the host immune response, resulting in inflammation and bone/tissue destruction. The document discusses the types of immunity, including innate and adaptive immunity. It covers topics such as dendritic cells, T-cell and B-cell roles, the roles of cytokines and RANKL in linking the immune response to bone loss, and hypotheses about the roles of the Th1 and Th2 responses in periodontitis.
This document summarizes the mechanisms of atopic dermatitis (AD). It discusses the epidemiology of AD and notes that it commonly affects children under 5 years old. The pathophysiology involves genetic, environmental, immunological, and epidermal factors. Key aspects of the pathophysiology discussed include the role of skin barrier dysfunction and genes involved in barrier function like filaggrin. It also examines the role of the immune system in AD, focusing on the predominance of TH2 cytokines and immune cells like dendritic cells, T lymphocytes, mast cells, and eosinophils that perpetuate the inflammatory response in AD.
This document provides an overview of epicutaneous immunotherapy (EPIT). It discusses the history of EPIT, mechanisms of EPIT, comparisons of EPIT to other forms of immunotherapy like oral immunotherapy and sublingual immunotherapy, clinical trials of EPIT for food allergies and environmental allergies. In particular, EPIT generates gut-homing regulatory T-cells that suppress systemic anaphylaxis without modifying humoral or cellular immunity. Clinical trials demonstrate EPIT's potential as a safe and effective treatment for food allergies that can provide sustained immune tolerance.
This document provides an overview of atopic dermatitis (AD), including its epidemiology, pathophysiology, natural history, diagnosis, and treatment. AD is a common inflammatory skin disorder characterized by intense itching and eczematous lesions. Its causes are complex and multifactorial, involving genetic predispositions, epidermal barrier dysfunction, immunological dysregulation, and environmental factors. The pathophysiology involves interactions between these elements that result in chronic inflammation. AD follows a heterogeneous natural history and can range from early transient disease to chronic persistent forms.
The JAK-STAT signaling pathway mediates important cellular processes such as immune response, carcinogenesis, cell differentiation, division and death. Therefore, drugs that interfere with different JAK-STAT signaling patterns have potential indications for various medical conditions. The main dermatological targets of JAK-STAT pathway inhibitors are inflammatory or autoimmune diseases such as psoriasis, vitiligo, atopic dermatitis and alopecia areata; however, several dermatoses are under investigation to expand this list of indications. As JAK-STAT pathway inhibitors should gradually occupy a relevant space in dermatological prescriptions
1. The document discusses conditions other than cirrhosis that can result in diffuse surface nodularity of the liver or portal hypertension such as chronic Budd-Chiari syndrome, chronic portal vein thrombosis, sarcoidosis, and pseudocirrhosis of treated breast cancer metastases or fulminant hepatic failure.
2. It provides imaging examples and characteristics of these non-cirrhotic conditions that can mimic cirrhosis on imaging. For example, pseudocirrhosis of treated breast cancer metastases shows diffuse hepatic nodularity and signs of portal hypertension but the history of breast cancer and prior imaging helps identify the correct diagnosis.
3. Nodular regenerative hyperplasia, congenital hepatic fibrosis, and
This document summarizes ultrasound findings for cirrhosis of the liver. Key findings include coarse echotexture and nodular surface of the liver. Regenerating nodules appear isoechoic or hypoechoic. Portal hypertension is a complication and is evidenced by dilated portal veins, low portal flow, and portosystemic collaterals visible on ultrasound. Doppler ultrasound can detect changes in portal flow from normal hepatopetal to reversed hepatofugal flow in advanced cases.
1. Atopic dermatitis (AD), also known as eczema, is a chronic inflammatory skin disorder characterized by pruritus and skin lesions that varies by age.
2. The pathogenesis of AD is complex, involving both genetic and environmental factors that contribute to skin barrier dysfunction and immune dysregulation. Defects in filaggrin play an important role.
3. Clinically, AD presents differently in infants/children (extensor involvement), children (flexural involvement), and adults (persistent flexural involvement). The distribution and features change over time.
This document discusses the etiology and pathogenesis of atopic dermatitis (AD). It notes that AD is a chronic, relapsing eczematous skin condition typically diagnosed based on a recurring itchy rash. Genetic factors like filaggrin gene defects that cause skin barrier dysfunction play an important role in AD development. Immune dysregulation also contributes, with increased Th2 cytokines and IgE levels. Environmental factors like allergens, microbes, and lack of early childhood infections may also influence AD risk and severity. The diagnosis of AD is based on clinical features and criteria from Hanifin and Rajka which involve characteristic rash appearance and distribution.
Allergic conjunctivitis is a common bilateral inflammatory condition of the conjunctiva caused by an IgE-mediated allergic response. It can be seasonal due to pollen allergens or perennial due to indoor allergens like dust mites. Symptoms include itching, redness, tearing and blurred vision. Treatment involves avoidance of allergens, artificial tears, oral antihistamines and topical mast cell stabilizers and antihistamines. Atopic keratoconjunctivitis is a chronic inflammation of the conjunctiva and eyelids associated with atopic dermatitis. It presents with itching, mucus discharge, and papillae on the tarsal conjunctiva.
The document provides an in-depth overview of atopic dermatitis (AD), including its pathogenesis, clinical presentation, systemic immune response, and treatment approaches. It discusses several theories for its pathogenesis, including abnormalities in cyclic adenosine monophosphate signaling, the allergy hypothesis involving TH2 cell responses, and genetic factors like filaggrin gene mutations. Diagnosis involves characteristic clinical features along with personal or family history of atopy. Management focuses on emollients, topical corticosteroids, antibiotics, phototherapy, immunomodulators, and avoidance of triggers.
Atopic dermatitis is a recurring inflammatory skin disease that usually develops in childhood. It is associated with respiratory allergies and a family history of atopic diseases. Theories of its pathogenesis include abnormalities in cyclic AMP levels that lead to increased inflammatory cell activity and cytokine production, as well as early antigen exposures that cause Th2-dominant immune responses. Skin lesions show inflammatory infiltrates including lymphocytes, mast cells, eosinophils, and increased expression of adhesion molecules. Systemic features include elevated IgE, eosinophils, and Th2 cytokines. Chronic lesions have increased expression of Th1 cytokines and eosinophils compared to acute lesions. Factors influencing T cell differentiation include cytokines, genetics, pharmac
The document provides an in-depth overview of atopic dermatitis (AD), including its pathogenesis, clinical presentation, systemic immune response, and treatment approaches. It discusses several theories for its pathogenesis, including abnormalities in cyclic adenosine monophosphate signaling, the allergy hypothesis involving TH2 cell responses, and genetic factors like filaggrin gene mutations. Diagnosis involves characteristic clinical features along with personal or family history of atopy. Management focuses on emollients, topical corticosteroids, antibiotics, phototherapy, immunomodulators, and avoidance of triggers.
Atopic dermatitis is a recurring inflammatory skin disease that usually develops in childhood. It is associated with respiratory allergies and a family history of atopic diseases. Theories of its pathogenesis include abnormalities in cyclic AMP levels that lead to increased inflammatory cell activity and cytokine production, as well as early antigen exposures that cause Th2-dominant immune responses. Skin lesions show inflammatory infiltrates including lymphocytes, mast cells, eosinophils, and increased expression of adhesion molecules. Systemic features include elevated IgE, eosinophils, and Th2 cytokines. Chronic lesions have increased expression of Th1 cytokines and eosinophils compared to acute lesions. Factors influencing T cell differentiation include cytokines, genetics, pharmac
The document discusses the role of anti-DNA IgG in the pathogenesis of cutaneous lupus erythematosus (CLE). It first provides background on lupus being an autoimmune disease caused by abnormal immune responses. The objective is then stated as elucidating the role of anti-DNA IgG in CLE. Materials and methods describe collecting tissue samples from CLE patients and healthy controls, using murine anti-DNA IgG, and techniques like flow cytometry, ELISA, and western blot to analyze interactions. Results show that anti-DNA IgG binds to antigens in collagen III and SOCS1 in keratinocytes, inducing apoptosis. It concludes that anti-DNA IgG may contribute to CLE lesions by amplifying TWEA
The document discusses the role of anti-DNA IgG in the pathogenesis of cutaneous lupus erythematosus (CLE). It describes experiments examining the interaction of anti-DNA IgG with keratinocytes and its effects. Skin tissue samples from CLE patients and healthy controls were obtained and anti-DNA IgG clones were cultured. Experiments found that anti-DNA IgG binds to keratinocytes and induces apoptosis. It also binds to novel antigens like collagen III and SOCS1. This binding may amplify TWEAK/Fn14 signals and modulate SOCS1, contributing to macrophage chemoattraction and skin lesions in CLE. The document aims to better understand the pathogenic effects of anti-DNA IgG in C
Allergic rhinitis is a type I hypersensitivity reaction mediated by IgE antibodies. It has a prevalence of 10-20% in the US and is characterized by symptoms like sneezing, rhinorrhea, nasal congestion and pruritus. Risk factors include family history of atopy, environmental exposures, and lifestyle factors. Treatment involves allergen avoidance, pharmacotherapy with antihistamines, intranasal corticosteroids, leukotriene receptor antagonists and immunotherapy for selected patients.
This document provides information on the bacteriology, immunology, and pathogenesis of Mycobacterium leprae, which causes leprosy. It describes the taxonomy and characteristics of M. leprae, how it is transmitted and the animal models used to study it. The mechanisms of nerve damage, immune responses in leprosy including cytokine profiles in tuberculoid and lepromatous states, and the genetic factors involved in susceptibility are summarized. Immunological events leading to reactions are also outlined.
The document discusses host defense mechanisms against pathogens. It describes three lines of defense: 1) physical barriers like skin and mucous membranes, 2) inflammatory response and defensive cells, and 3) the immune system. The immune system has both innate and acquired branches. Innate immunity provides non-specific protection using physical and chemical barriers while acquired immunity involves adaptive, antigen-specific responses. Key cells of the immune system that provide defense include macrophages, neutrophils, lymphocytes and natural killer cells. Antibodies and the complement system are important components that help eliminate pathogens.
Immune System Update in dermatology - Dr. Oki Suwarsa, dr. M.Kes., Sp.KK(K), ...AdiSutriwantoPasarib1
This document summarizes recent findings about the immune system and its role in acne pathogenesis. It discusses how the skin has both innate and adaptive immune systems. In acne, Propionibacterium acnes triggers an inflammatory response by activating innate immunity through pattern recognition receptors and releasing proinflammatory factors. This leads to the development of an adaptive immune response against P. acnes, with dendritic cell maturation presenting P. acnes antigens and stimulating B and T cell responses. Genetic factors also influence the immune response. Together, the immune activation and release of proinflammatory mediators from keratinocytes and sebocytes results in follicular hyperkeratinization and inflammation, key drivers of the acne lesions.
This presentation deals with the role of the intestinal microbiome in the causation of various disorders like psoriasis, Acne and Atopic dermatitis. Helpful for students preparing for MD Dermatology exit examinations.
Immune responses in periodontal disease final.pptxmalti19
This document discusses the immune responses involved in periodontal disease. It begins by defining periodontitis as an infectious disease caused by anaerobic bacteria. Both bacteria and a susceptible host are required to cause disease. It then describes the pathogenesis which involves environmental and genetic risk factors interacting with the microbial challenge to activate the host immune response, resulting in inflammation and bone/tissue destruction. The document discusses the types of immunity, including innate and adaptive immunity. It covers topics such as dendritic cells, T-cell and B-cell roles, the roles of cytokines and RANKL in linking the immune response to bone loss, and hypotheses about the roles of the Th1 and Th2 responses in periodontitis.
This document summarizes the mechanisms of atopic dermatitis (AD). It discusses the epidemiology of AD and notes that it commonly affects children under 5 years old. The pathophysiology involves genetic, environmental, immunological, and epidermal factors. Key aspects of the pathophysiology discussed include the role of skin barrier dysfunction and genes involved in barrier function like filaggrin. It also examines the role of the immune system in AD, focusing on the predominance of TH2 cytokines and immune cells like dendritic cells, T lymphocytes, mast cells, and eosinophils that perpetuate the inflammatory response in AD.
This document provides an overview of epicutaneous immunotherapy (EPIT). It discusses the history of EPIT, mechanisms of EPIT, comparisons of EPIT to other forms of immunotherapy like oral immunotherapy and sublingual immunotherapy, clinical trials of EPIT for food allergies and environmental allergies. In particular, EPIT generates gut-homing regulatory T-cells that suppress systemic anaphylaxis without modifying humoral or cellular immunity. Clinical trials demonstrate EPIT's potential as a safe and effective treatment for food allergies that can provide sustained immune tolerance.
This document provides an overview of atopic dermatitis (AD), including its epidemiology, pathophysiology, natural history, diagnosis, and treatment. AD is a common inflammatory skin disorder characterized by intense itching and eczematous lesions. Its causes are complex and multifactorial, involving genetic predispositions, epidermal barrier dysfunction, immunological dysregulation, and environmental factors. The pathophysiology involves interactions between these elements that result in chronic inflammation. AD follows a heterogeneous natural history and can range from early transient disease to chronic persistent forms.
The JAK-STAT signaling pathway mediates important cellular processes such as immune response, carcinogenesis, cell differentiation, division and death. Therefore, drugs that interfere with different JAK-STAT signaling patterns have potential indications for various medical conditions. The main dermatological targets of JAK-STAT pathway inhibitors are inflammatory or autoimmune diseases such as psoriasis, vitiligo, atopic dermatitis and alopecia areata; however, several dermatoses are under investigation to expand this list of indications. As JAK-STAT pathway inhibitors should gradually occupy a relevant space in dermatological prescriptions
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1. The document discusses conditions other than cirrhosis that can result in diffuse surface nodularity of the liver or portal hypertension such as chronic Budd-Chiari syndrome, chronic portal vein thrombosis, sarcoidosis, and pseudocirrhosis of treated breast cancer metastases or fulminant hepatic failure.
2. It provides imaging examples and characteristics of these non-cirrhotic conditions that can mimic cirrhosis on imaging. For example, pseudocirrhosis of treated breast cancer metastases shows diffuse hepatic nodularity and signs of portal hypertension but the history of breast cancer and prior imaging helps identify the correct diagnosis.
3. Nodular regenerative hyperplasia, congenital hepatic fibrosis, and
This document summarizes ultrasound findings for cirrhosis of the liver. Key findings include coarse echotexture and nodular surface of the liver. Regenerating nodules appear isoechoic or hypoechoic. Portal hypertension is a complication and is evidenced by dilated portal veins, low portal flow, and portosystemic collaterals visible on ultrasound. Doppler ultrasound can detect changes in portal flow from normal hepatopetal to reversed hepatofugal flow in advanced cases.
1. The document discusses the diagnosis and treatment of acute ischemic stroke. It outlines the time windows for treatment with intravenous thrombolysis, which is most effective within 4.5 hours of symptom onset.
2. Early diagnosis is critical in stroke care due to the concept of "time is brain". Delays in treatment can lead to further neuronal damage and worse outcomes. The goals are to perform a CT scan within 20 minutes of arrival and initiate thrombolysis within 60 minutes.
3. Post-thrombolytic management focuses on monitoring for hemorrhagic complications and providing supportive care to reduce disability from the stroke.
hepaticcoma.pdf is important for medical studentsDrYaqoobBahar
Hepatic coma is an advanced complication of liver failure characterized by reversible decreased neurologic function and loss of consciousness due to the liver's failure to detoxify toxic substances. It is caused by chronic liver disease, fulminant hepatic failure, or portosystemic shunts. Patients experience disturbances in consciousness, neurological signs, and mental changes. Treatment focuses on treating the underlying cause, decreasing ammonia production, and controlling risk factors through supportive care, lactulose, rifaximin, and L-ornithine/L-aspartate supplementation. Complications can include brain herniation, organ failure, and brain edema.
1) Abdominal tuberculosis poses a diagnostic challenge due to its nonspecific symptoms. It is increasingly common and can involve the gastrointestinal tract, peritoneum, lymph nodes or solid organs.
2) Tubercle bacilli typically spread from the lungs or ingested materials to the abdominal cavity via the bloodstream or lymphatics. This can cause caseating granulomas and lesions in the abdomen.
3) Common presentations include abdominal pain, fever, weight loss, and ascites or abdominal masses. Imaging shows lymphadenopathy, bowel thickening or strictures, and ascites. Diagnosis relies on clinical suspicion plus histology, microbiology or response to antitubercular treatment.
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A pulmonary embolism is a sudden blockage in a lung artery, usually caused by a blood clot breaking off and traveling to the lungs. PE is a common cause of death in hospitalized patients. Risk factors include genetic mutations, cancer, obesity, smoking, and surgery. Symptoms may include dyspnea, chest pain, and cough. Diagnosis involves assessing risk factors, blood tests, imaging like CT scans, and echocardiograms. Treatment involves immediate anticoagulation with blood thinners, potentially thrombolytic therapy for severe cases, and inferior vena cava filters for high-risk patients. Anticoagulation may continue for several months depending on the underlying cause of clotting.
This document discusses peripartum cardiomyopathy, which is a type of dilated cardiomyopathy of unknown origin that presents with left ventricular systolic dysfunction. It can occur in 1 in 4,000 live births in the United States. The precise causes are unclear but may involve viral infection, immune response abnormalities, or prolonged use of tocolytics. Symptoms include dyspnea, chest pain, and edema. Diagnosis involves excluding other potential causes through ECG, echocardiogram, biomarkers and imaging. Treatment focuses on heart failure medications, anticoagulants if needed, and assisted devices. Prognosis is generally good with 50% fully recovering but risks include persistent symptoms or progression to heart failure.
Heart failure is a clinical syndrome where the heart is unable to pump sufficiently to maintain blood flow to meet the body's needs. It can be caused by structural or functional defects in the heart. The most common causes are coronary artery disease, high blood pressure, and diabetes. While it affects about 2% of adults globally, the risk increases to 6-10% for those over age 65. Treatment involves controlling underlying causes, removing precipitating factors, and managing symptoms through diuretics, ACE inhibitors, beta blockers, and other medications.
Pulmonary edema refers to excess fluid accumulation in the lungs. It can be caused by increased hydrostatic pressure, permeability changes, or a mix of both. Common causes include heart failure, fluid overload, near drowning, trauma, and certain drugs. Symptoms include shortness of breath, cough, wheezing, and anxiety. Diagnosis involves physical exam, imaging like chest x-rays, and tests to check for underlying conditions. Treatment focuses on addressing the underlying cause, giving oxygen, diuretics, and other medications to reduce fluid buildup. Ventilatory support may be needed in severe cases.
Pulmonary edema refers to excess fluid accumulation in the lungs. It has four main categories based on pathophysiology: increased hydrostatic pressure, interstitial edema, alveolar flooding, and permeability edema. Causes include heart failure, mitral regurgitation, near-drowning, and renal failure. Symptoms include difficulty breathing, cough, and anxiety. Diagnosis involves clinical exam, BNP levels, chest x-ray, and echocardiogram. Treatment focuses on addressing the underlying cause with oxygen, diuretics, nitrates, and sometimes ventilation support.
1. Acute variceal hemorrhage refers to bleeding from enlarged veins (varices) in the esophagus or stomach that is caused by portal hypertension from liver cirrhosis. Variceal bleeding is a severe complication and is the cause of bleeding in 70% of upper GI bleeds in cirrhotic patients.
2. Varices develop due to increased pressure in the portal vein system from cirrhosis. Once varices form, there is a risk of 15% annual bleeding for large varices. Bleeding can often be controlled with medical and endoscopic therapy but there is a high risk (60%) of rebleeding without intervention.
3. Varices are classified based on location
Hypertension emergencies require rapid reduction of blood pressure to prevent end organ damage. Hypertensive urgency can be managed as an outpatient but emergencies require hospitalization. Initial evaluation assesses for signs of damage to heart, kidneys, brain, or vasculature. Parenteral drugs like nicardipine, labetalol, and esmolol are used to lower blood pressure 10-15% within 1 hour and further to 160/100 mmHg in 2-6 hours, with goals tailored to specific conditions like stroke, heart failure, or aortic dissection. Oral agents like clonidine or nifedipine may be used after initial parenteral treatment to control blood pressure before discharge
Hypertension emergencies require rapid reduction of blood pressure to prevent end organ damage. Hypertensive urgency can be managed as an outpatient with oral medications, while emergencies require hospitalization and intravenous drugs. Initial evaluation assesses for signs of heart, brain, kidney and vascular damage. Parenteral drugs like nicardipine, labetalol and esmolol are used but sodium nitroprusside is no longer first-line due to risks. Treatment goals depend on the specific organ involved and reduce pressure by 10-25% within 1-2 hours.
1) Myxedema coma is a rare life-threatening condition that occurs when a patient with severe, long-standing hypothyroidism experiences physiological decompensation, usually brought on by an external precipitating event like infection.
2) It is characterized by hypothermia, unconsciousness, decreased metabolism and oxygen consumption. Patients often present with symptoms of both the underlying hypothyroidism and the precipitating condition.
3) Treatment involves supportive care, thyroid hormone replacement, glucocorticoids, and treating any underlying infections or precipitating conditions. Patients require intensive monitoring and care due to involvement of multiple organ systems.
This document discusses portal hypertension and variceal bleeding. It covers the pathophysiology of variceal formation, causes of portal hypertension, detection of varices via endoscopy and other imaging modalities, management of variceal bleeding, and medical therapies to decrease portal pressure including vasopressin analogs, somatostatin analogs, beta-blockers, and other agents. Key points are that variceal bleeding has high mortality, endoscopy is the primary method to detect varices, and drugs like terlipressin and beta-blockers aim to decrease portal pressure and prevent rebleeding.
This document discusses gastroesophageal varices, which develop in 55% of cirrhotic patients. It covers the risk factors, signs, diagnosis, and treatment of variceal bleeding, including endoscopic band ligation, TIPS procedure, pharmacologic therapies like beta-blockers, and balloon tamponade. The priority in treatment is stabilizing the patient hemodynamically before diagnostic or therapeutic endoscopy. Recurrence of bleeding remains high, so long-term management is also addressed.
This document summarizes adrenal gland function and adrenal insufficiency. It describes:
1) The adrenal glands produce cortisol, aldosterone, and androgens which regulate stress response, electrolyte balance, and sex characteristics.
2) Primary adrenal insufficiency results from adrenal gland dysfunction and causes deficiencies in cortisol, aldosterone, and sex hormones. Secondary adrenal insufficiency is caused by pituitary or hypothalamic disease and causes cortisol deficiency alone.
3) Adrenal crisis is a life-threatening emergency characterized by refractory hypotension that requires aggressive treatment with glucocorticoid replacement such as hydrocortisone.
This document defines hypertensive emergencies and discusses their management. It begins by classifying hypertension and defining hypertensive crises. Hypertensive emergencies are acute severe hypertension with signs of target organ damage, while hypertensive urgencies have severe hypertension without organ damage. The document then covers the epidemiology, etiology, pathophysiology, presentation, investigations, and management of hypertensive emergencies. It discusses treating different organ-specific emergencies like stroke, heart failure, and kidney injury. The management involves rapid blood pressure reduction while monitoring for complications. Various intravenous medications are outlined for treating hypertensive emergencies based on the target organ involved.
This document discusses diffuse parenchymal lung diseases (DPLDs), also called interstitial lung diseases (ILDs). It classifies DPLDs into four main groups and describes some of the most common diseases within each group, including their symptoms, radiologic appearances, and differential diagnoses. Major diseases discussed include sarcoidosis, idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, pneumoconiosis like silicosis, and interstitial lung diseases associated with connective tissue diseases. HRCT is highlighted as a sensitive tool for detecting and characterizing different interstitial lung disease patterns.
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The temple and the sanctuary around were dedicated to Asklepios Zmidrenus. This name has been known since 1875 when an inscription dedicated to him was discovered in Rome. The inscription is dated in 227 AD and was left by soldiers originating from the city of Philippopolis (modern Plovdiv).
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3. Introduction
• Atopic dermatitis (AD) - chronically relapsing inflammatory skin disease usually associated with
respiratory allergy
• Associated with other atopic disorders
• 50% Asthma
• 75% AR
• Characterized by recurrent eczematous lesions: poorly defined, erythematous patches with
exudation, blistering and crusting and scaling, fissuring and lichenification at later stages and
intense itch and discomfort
• Extremely heterogenous disease with wide spectrum of clinical features ranging from minimal
flexural eczema to erythroderma to eczema limited to the hands
• Complex interrelationship of genetic, environmental, immunologic, and epidermal factors
Middleton’s 8th Ed.
Weidinger et al. NATURE REVIEWS 2018
4. Epidemiology
• 15 – 30% in children
• 45% of all cases begin within the first 6 months of life
• 60% during the first year
• 85% before 5 years of age
• Up to 70% of children with AD will go into clinical remission before adolescence
• 7–10% in adult
Weidinger et al. NATURE REVIEWS 2018
Kapur et al. Allergy Asthma Clin Immunol 2018
5. Global Prevalence of Atopic Dermatitis Symptoms
Weidinger et al. NATURE REVIEWS 2018
9. Genetics
• Skin barrier/epidermal differentiation genes and immune response/host defense genes - key role
• Skin barrier abnormalities - loss-of-function mutations of the gene encoding epidermal barrier protein filaggrin (major
predisposing factor for AD)
•FLG gene mutations - early-onset, severe, and persistent AD, outgrow slowly than those without FLG mutations, increased
risk for development of asthma, as well as food and inhalant allergies
• Loricrin and involucrin both were significantly decreased in involved and uninvolved skin of AD patients
• Variants in SPINK5 gene - expressed in the uppermost epidermis where its product LEKTI-1 inhibits two serine proteases
(stratum corneum tryptic and chymotryptic enzymes) involved in desquamation and inflammation
• Imbalance of protease versus protease inhibitor activity → skin barrier breakdown and staphylococcal colonization in AD
Middleton’s 8th Ed.
10. Filaggrin Mutation
• FLG located in the
epidermal differentiation
complex, cluster of
approximately 60 genes
involved in epithelial
differentiation, on
chromosome 1q21
• Loss-of-function mutation
Alan D. Irvine et al. NEJM 2011.
11. Genetics
• Impaired skin barrier function in AD
pathogenesis
• ↑ transepidermal water loss
• ↑ entry of allergens, antigens, and
chemicals from the environment
• Causes skin inflammatory responses
Middleton’s 8th Ed.
12. Role of Epidermal Barrier
• Abnormalities in skin barrier: ↑ transepidermal water loss,
↑ levels of endogenous proteolytic enzymes, and ↓ three
key lipids at stratum corneum (cholesterol, free fatty acid
and ceramide)
• Use of soaps → ↑ skin pH, ↑ activity of endogenous
proteases → breakdown of epidermal barrier function
Middleton’s 8th Ed.
M. Janssens et al. J Lipid Res. 2012. 53: 2755
13. Role of Epidermal Barrier
•Exogenous proteases from house-dust mites and S. aureus
• Lack of endogenous protease inhibitors
• Mutations in FLG gene (located in the epidermal differentiation complex on chromosome 1q21)
→ complete or partial ↓ expression of epidermal protein, filament-aggregating protein
(filaggrin)
• Upregulated Th2 cytokines such as IL-4 and IL-13 in AD → downregulate FLG expression
• IL-22–producing “Th22” CD4+ and CD8+ cells reported in AD skin of AD patients
Middleton’s 8th Ed.
14. Role of Epidermal Barrier
• Tight junctions (TJs) located below the stratum
corneum regulate the selective permeability of the
paracellular pathway
• ↓ expression of the tight-junction (TJ) proteins claudin-
1 and claudin-23
• Impairment in TJs → barrier dysfunction and immune
dysregulation - mediated by ↓ claudin-1
Middleton’s 8th Ed.
15. Modified from Donald Y. M. Leung and DE BENEDETTO et al. J Allergy Clin Immunol 2011.
Stratum Corneum
• ↓ FLG, Loricrin, Involucrin
• Lipid defects
• ↓ Protease inhibitors & ↑ Proteases
• More alkaline pH
• Itch-scratch cycle
Tight Junctions
• ↓ CLDN proteins (CLDN1,4,8,23)
• ↓ Electrical resistance & ↑ Permeability
• Altered activation and location of APCs
Basal Cells
• Hyperproloferative
• ↑ Keratins 5,14,16
• Altered Na absorption
(ENaC)
16. Role of Allergen
FOOD
• 33% of infants and young children with AD - clinically relevant reactivity to food allergen
• Repeated challenges → eczematous lesions
AEROALLERGEN
• Respiratory route OR direct contact with inhalant allergens → induction and exacerbation of
AD
• Severity of AD correlated with degree of sensitization to aeroallergens
• Environmental control reducing dust mite allergen → clinical improvement in AD patients
Middleton’s 8th Ed.
17. Role of Allergen
MICROBIAL AGENTS
• Both lipophilic yeast Malassezia sympodialis and superficial dermatophyte Trichophyton
rubrum associated ↑ specific-IgE levels
• Malassezia sympodialis - patients with AD predominantly at head and neck
• S. aureus exotoxins (enterotoxins A and B and toxic shock syndrome toxin-1) = superantigens
→ persistent inflammation or exacerbations of AD
• Superantigens - augment allergen-specific IgE synthesis, subvert T regulatory (Treg) cell
function, and induce corticosteroid resistance
Middleton’s 8th Ed.
18. KENNEDY et al. J Allergy Clin Immunol 2017
• Comparing patients and control subjects, infants who had
affected skin at month 12 had statistically significant
differences in bacterial communities on the antecubital fossa
at month 2 compared with infants who were unaffected at
month 12
• Commensal staphylococci were significantly less abundant in
infants affected at month 12, suggesting that this genus
might protect against the later development of AD
• Conclusions: This study suggests that 12-month-old infants
with AD were not colonized with S aureus before having AD
19. PALLER et al. J Allergy Clin Immunol 2019
• Crosstalk between commensals and the immune system is
now recognized because microorganisms can modulate both
innate and adaptive immune responses
• In patients with AD, a decrease in microbiome diversity
correlates with disease severity and increased colonization
with pathogenic bacteria, such as S aureus
• Early clinical studies suggest that topical application of
commensal organisms (eg, Staphylococcus hominis or
Roseomonas mucosa) reduces AD severity, which supports
an important role for commensals in decreasing S aureus
colonization in patients with AD
20. Role of Allergen
AUTOANTIGENS
• Roles for autoantigens in chronic AD - patients with severe AD contain IgE antibodies directed
against human proteins
• Mainly intracellular protein, released from damaged tissues by infectious organisms or
scratchingtrigger IgE or T cell–mediated responses
• Hom s 1 - IgE-reactive autoantigens, 55-kD cytoplasmic protein in skin keratinocytes
• Dense fine speckles 70 kD (DFS70) – both IgG and IgE autoantibodies
• Human manganese superoxide dismutase (MnSOD) - induced primarily by exposure to MnSOD
of skin-colonizing yeast M. sympodialis
Middleton’s 8th Ed.
21. • Expression of structural proteins
• Expression of tight junction proteins
• Water Retention
• Altered lipids
• Altered microbiota
• Altered
proteolysis
• Irritability
• Permeability
• ↑ pH
• Susceptibility
to infections
Weidinger et al.
NATURE REVIEWS 2018
23. Weidinger et al. NATURE REVIEWS 2018
Itch Pathways
Histamine-dependent and Histamine-independent Itch Signalling Pathways
• Sensory neurons expressing histamine H1 receptor (H1R) and H4R respond to histamine
release
• Histamine-independent pathway: type 2 immunity cytokines and thymic stromal lymphopoietin
(TSLP) activate neurons expressing transient receptor potential cation channels
• C fibres relay the signal to spinal dorsal horn, where signal transducer and activator of
transcription 3 (STAT3)-dependent reactive astrocytes produce lipocalin 2 (LCN2, neutrophil
gelatinase-associated lipocalin)
• LCN2 sensitizes pruritic processing neuronal network involving neurons expressing gastrin-
releasing peptide receptor (GRPR)
24. Weidinger et al. NATURE REVIEWS 2018
Type 2 Immunity Cytokine
Signalling
25. Weidinger et al. NATURE REVIEWS 2018
Type 2 Immunity Cytokine
Signalling
• IL-4 and IL-13 produced mainly by T helper 2 (TH2) cells, basophils and group 2 innate lymphoid cells
• IL-4 binds cytokine receptor common subunit γC → activates Janus kinase 3 (JAK3)
• Both IL-4 and IL-13 bind IL-4 receptor subunit-α (IL-4Rα) → activates JAK1
• IL-13 binds IL-13 receptor subunit-α1 (IL-13Rα1) → activates non-receptor tyrosine-protein kinase TYK2 and JAK2
• JAK1, JAK2, JAK3 and TYK2 → phosphorylate STAT6 → dimerizes and migrates to nucleus
• STAT6 binds to promoters of IL-4-responsive and IL-13–responsive → promotes various effect
• IL-31 produced mainly by TH2 cells binds to IL-31 receptor subunit-α (IL-31Rα) → activates JAK1 and/or JAK2 →
phosphorylate STAT1, STAT3 and STAT5
• Dimers of these signal transducers translocate to the nucleus and activate IL-31-responsive genes
28. Diagnostic Features
Hanifin, J.M. and Rajka, G. Acta Derm Venereol Suppl (Stockh) 1980
3 Major + 3 Minor
Ichthyosis Keratosis Pilaris Cheilitis
Denny-Morgan Line White Dermatographism
29. Phenotypes of AD (1)
• Acute VS Chronic Eczema
• Associated with ichthyosis, keratosis pilaris,
palmar hyperlinearity, early onset, severe and
persistent eczema (FLG null genotype)
• Intrinsic VS Extrinsic Atopic Eczema
• Adult VS Early Onset Eczema
Thomas Bieber et al. NEJM 2008
Silvia Pugliarello et al. JDDG 2011
Acute Lesion Chronic Lesion
30. Phenotypes of AD (2)
• Morphological variants:
- Nummular eczema - Atopic prurigo
- Lichen planus-like - Pityriasis alba
• Localized variants:
- Hand eczema - Cheilitis
- Juvenile palmar and plantar dermatitis
- Eyelid dermatitis - Nipple dermatitis
- Periorificial dermatitis
Silvia Pugliarello et al. JDDG 2011
33. Complicating Features
OCULAR PROBLEMS
• ↑ Numbers of IgE-bearing Langerhans found in conjunctival epithelium can capture
aeroallergens and present them to infiltrating T cells → ocular inflammation
Atopic keratoconjunctivitis
• Bilateral, itching, burning, tearing, and copious mucoid discharge
• Associated with eyelid dermatitis, chronic blepharitis
→ corneal scarring
Keratoconus - conical deformity of the cornea from persistent rubbing of the eyes
Anterior subcapsular cataracts - adolescence or early adult life
Middleton’s 8th Ed.
34. HAND DERMATITIS
• Irritating and aggravated by repeated wetting
INFECTIONS
• Virus: HSV, Molluscum Contagiosum, HPV
• Unique susceptibility that AD patients have to eczema herpeticum (EH) and eczema vaccinatum
(smallpox vaccine)
- acquired defect in the cutaneous antimicrobial
peptide response
• Superimposed dermatophytosis → AD flare
(opportunistic yeast Malassezia sympodialis)
Complicating Features
Middleton’s 8th Ed.
35. INFECTIONS
• Adherence of S. aureus may be related to expression of adhesins such as fibronectin and
fibrinogen in inflamed skin
• Higher rate of S. aureus colonization in AD lesions compared with lesions from other skin
disorders - associated with colonization of the nares
• Recurrent pustulosis - methicillin-resistant S. aureus (MRSA) as important pathogen in AD
Complicating Features
Middleton’s 8th Ed.
41. IRRITANTS AVOIDANCE
• Patients with AD - lowered threshold of irritant responsiveness
• Detergents, soaps, chemicals, pollutants, and abrasive materials, extremes of temperature and
humidity
ALLERGENS AVOIDANCE
• Negative skin tests - high predictive value
• Positive skin tests - lower correlation with clinical symptoms
• Environmental control of dust mite may improve AD in patients who demonstrate specific IgE
to dust mite allergen
Management
Middleton’s 8th Ed.
42. Bathing
Thai CPG 2014 Middleton’s 2014 Practice Parameter
2012
European 2018 AAD 2014
•
• 5 -10
•
• (emollient)
• (anti-septic)
• Soak affected area
or bathe ∼10
minutes
• Warm (not
lukewarm) water
• Apply an occlusive
agent within a few
minutes after
hydrating the skin
• Warm soaking baths
for at least 10
minutes
• Followed by the
application of a
moisturizer
• Cleansing followed
by rapid rinse
• 27–30°C
• 5 min + use of bath
oils (2 last minutes
of bathing)
• Topical emollients
directly after bath
• 5-10 minutes
• Warm water
• Soaking in plain
water for 20 minutes
• Immediate
application of anti-
inflammatory
therapies
43. Bleach Bathing
Thai CPG 2014 Middleton’s 2014 Practice Parameter
2012
European 2018 AAD 2014
• N/A • Dilute sodium
hypochlorite (¼ to ½
cup per full tub)
• Nasal mupirocin
• Reduce skin
infections
• May lead to skin
irritation
• 0.5 cup of bleach in
40 gallons of water
twice weekly
• Plus intranasal
mupirocin (5
days/month)
• Decreased severity
of AD
• 0.005% sodium
hypochlorite bleach
• Did not show
superiority to water
baths
• Maybe helpful in
cases of moderate to
severe disease with
frequent bacterial
infections
44. Wet Wrap Therapy + Topical
Steroids
Thai CPG 2014 Middleton’s 2014 Practice Parameter
2012
European 2018 AAD 2014
• ,
• 6
• 1, 2, 3
• 2-14 (7 )
• Reduce pruritus and
inflammation
• Not with TCIs
• Refractory AD
• Not with TCIs
• Acute oozing,
erosive skin
• Up to 14 days (up to
3 days)
• Significant flares
and/or recalcitrant
disease
• Several hours to 24
hours
• Several days up to 2
weeks
46. Moisturizers
Thai CPG 2014 Middleton’s 2014 Practice Parameter
2012
European 2018 AAD 2014
• 250 /500 /
• 2
•
• Amount N/A
• Applied several
times daily
• Alpha-hydroxy acids
• Amount N/A • up to 100 g/week in
young children, and
up to 500 g/week in
adults
• Amount N/A
• 2 or 3 times daily
47. 1. OCCLUSIVES
• Forming a hydrophobic layer on surface of skin providing exogenous barrier to water loss
• Prevent evaporation from the skin, effective when applied to already dampened skin
• E.g. Petrolatum, Dimethicone, Silicone
2. HUMECTANTS
• ↑ Water content of skin by enhancing water absorption from dermis into epidermis
• Hydrate stratum corneum by absorbing water from external environment
• E.g. Glycerin, Propylene Glycol, α-Hydroxy Acids, Urea, Hyarulonic acid
Types of Moisturizers
Nolan et al. Dermatologic Therapy 2012
48. 3. EMOLLIENT
• Filling in the crevices between corneocytes ↑ softness and smoothness of the skin and
improves overall appearance
• Lipid-containing substance
• E.g. Stearic, Linoleic, Linolenic, Oleic and Lauric acids from palm oil, coconut oil and wool fat
Types of Moisturizers
Nolan et al. Dermatologic Therapy 2012
51. Topical Corticosteroids
Thai CPG 2014 Middleton’s 2014 Practice Parameter
2012
European 2018 AAD 2014
• 2
• 1 FTU = 0.5 gm
•
• 1 FTU hand or groin
• 2 FTUs face or foot
• 3 FTUs an arm
• 6 FTUs leg
• 14 FTUs trunk
• 30 g for entire body
adult
• Amount N/A
• Ultra high potency 1-
2 weeks and not on
facial or skinfold
areas
• High potency up to 3
weeks for
exacerbations
• Twice to thrice
weekly
• Monthly amounts:
15 g in infants,
30 g in children
up to 60– 90 g in
adolescents and
adults
• 1 FTU = 0.5 g, 2 adult
palms
• Rule of 9’s
• Once daily
52. Relative Potencies of Topical Corticosteroids
Eichenfield et al. J AM ACAD DERMATOL JULY 2014
53. • Suppression of inflammatory genes → ↓ inflammation and pruritus
• Age-appropriate indications:
• Fluticasone 0.05% cream - up to 28 days in children age ≥3 months
• Fluticasone lotion - ≥12 months of age
• Mometasone cream/ointment - ≥2 years of age
• Local side effects: Thinning of the skin with telangiectasias, bruising, hypopigmentation, acne, striae, secondary
infections, perioral dermatitis, atrophic change
• Systemic side effects: cataract, glaucoma, suppress HPA axis, suppress growth, iatrogenic Cushing’s syndrome
• “Steroid Addiction” = adverse effect primarily of face of adult women with burning sensation which improve with
total discontinuation
• Proactive Therapy: twice-weekly applications of topical corticosteroid to areas that previously been involved but
now normal (↓ relapses and less need for topical corticosteroids)
Topical Corticosteroids
Middleton’s 8th Ed.
55. • Inhibit pro-inflammatory cytokine production from T cells
• Anti-inflammatory potency of 0.1% Tacrolimus = Intermediate TCS
• Anti-pruritic (inhibit mast cell degranulation)
• Second-line Therapy approved for age > 2 years
• Steroid-sparing, safe for face and intertriginous area
• Avoid sunlight
• NOT recommended in pregnant or immunocompromised patients
• Side effect: transient burning sensation, but NOT cause atrophy
• Proactive Therapy: twice-weekly → ↓ Relapse, need for TCS
Topical Calcineurin Inhibitors
Thai CPG 2014
Middleton’s 8th Ed.
56. Topical Calcineurin Inhibitors
TACROLIMUS
• Tacrolimus 0.03% age 2-16 years
• Tacrolimus 0.1% age > 16 years
• For all AD severity
• Safe as monotherapy use of 4 years
PIMECROLIMUS
• 1% Pimecrolimus age > 2 years
• Moderate to severe AD
• Safe as monotherapy use of 2 years
Thai CPG 2014
Middleton’s 8th Ed.
57. Coal Tar
• Similar to topical corticosteroid = ability to inhibit the influx of proinflammatory cells and in the
expression of CAMs in response to epicutaneous allergen challenge
• Tar preparations + topical corticosteroids → may ↓ need for more potent TCS
• Tar shampoos beneficial for scalp involvement
• Avoid use on acutely inflamed skin
• Side Effects: (rare) dryness, irritation, photosensitivity reactions, pustular folliculitis
Thai CPG 2014
Middleton’s 8th Ed.
58. Anti-infective Therapy
• Secondary infection with S. aureus is present
• Systemic therapy with semisynthetic penicillins or first- or second-generation cephalosporins
for 7 - 10 days
• Maintenance antibiotic therapy should be avoided → colonization by methicillin-resistant
organisms
• Topical anti-staphylococcal antibiotic mupirocin (Bactroban) 3 three times daily to affected
areas for 7 - 10 days
• Topical anti-staphylococcal antibiotic twice daily treatment for 5 days with a nasal preparation
of mupirocin may reduce nasal carriage of S. aureus
Middleton’s 8th Ed.
60. Anti-pruritus
• Systemic antihistamine and anxiolytics maybe most useful
• Pruritus often worsen at night → sedative antihistamine at bedtime
• 2nd generation antihistamine → modest clinical benefit
• Topical antihistamines and topical anesthetics should be avoided because of potential
sensitization
Middleton’s 8th Ed.
61. Treatment for Recalcitrant Disease
• Cyclosporin A
• Mycophenolate Mofetil
• Azathioprine
• Methotrexate
• Phototherapy
Middleton’s 8th Ed.
62. Cyclosporin A
• Children: 2.5 mg/kg/day
• Rapid and highly significant improvements in all indices of disease activity: signs and symptoms,
body surface area, pruritus, and sleep disturbance
• Remain remission after treatment stop
• Decreased disease severity in all studies
• Side effects: ↑ serum urea, creatinine, and bilirubin concentrations, irreversible nephrotoxicity
Middleton’s 8th Ed.
63. Mycophenolate Mofetil
• Purine biosynthesis inhibitor
• Initial responses occurred within 8 weeks (mean 4 weeks) with maximal effects attained after 8
to 12 weeks (mean 9 weeks)
• 40 to 50 mg/kg/day in younger children
• 30 to 40 mg/kg/day in adolescents
• Well tolerated in all patients, with no infectious complications or laboratory abnormalities
• Reported herpes retinitis
Middleton’s 8th Ed.
64. Azathioprine
• Immunosuppressive agent affecting purine nucleotide synthesis
• Decrease in disease severity after active treatment
• Side effects: myelosuppression, hepatotoxicity, gastrointestinal disturbances, increased
susceptibility to infections, and risk of skin cancer.
• 1 to 3 mg/kg daily but should be adjusted based on TPMT levels, and routine screening blood
tests
• Onset of action is usually slow, and benefit may not be apparent for several months after
starting treatment
Middleton’s 8th Ed.
65. Methotrexate
• Folic acid antagonist that interferes with purine and pyrimidine synthesis
• Methotrexate (10 to 22.5 mg/week) comparable clinical efficacy to azathioprine (1.5 to 2.5
mg/kg/ day) after 12 weeks of treatment
• Symptom improvement in 2 weeks and up to 3 months
• Side effects: nausea and liver enzyme elevation
Middleton’s 8th Ed.
66. Phototherapy
• Narrowband UVB, broadband UVB, and UVA1
• Age > 12 years
• Well tolerated
• Median length of remission 3 months
• Short-term adverse effects: erythema, skin pain, pruritus, and pigmentation
• Long-term adverse effects: premature skin aging and cutaneous malignancies
Middleton’s 8th Ed.
67. Biologic Treatment: Dupilumab
Dupilumab - interleukin 4 (IL-4) receptor a-antagonist → reducing Th2 response
• Approved in the United States and Europe for the treatment of adult patients with moderate-
to-severe AD
• Adults with moderate-to-severe AD who receive weekly or biweekly dupilumab injections →
improved clinical and patient-reported outcomes: EASI, SCORAD, DLQI, itch Numeric Rating
Scale scores
• Greater outcome with concomitant use of topical corticosteroids
• Common adverse events: nasopharyngitis, upper respiratory tract infection, injection site
reactions, skin infections, and conjunctivitis
Gooderham et al. J AM ACAD DERMATOL 2018
71. Immunotherapy
• Can be effective for patients with AD when it is associated with aeroallergen sensitivity
Middleton’s 8th Ed.
72. Linda Cox et al. J ALLERGY CLIN IMMUNOL PRACT 2016
73. Linda Cox et al. J ALLERGY CLIN IMMUNOL PRACT 2016
74. Linda Cox et al. J ALLERGY CLIN IMMUNOL PRACT 2016
75. Prevention
• No established primary prevention strategies for AD
• Effectiveness of early, consistent application of emollients for infants at increased risk
→ 30–50% reduction in AD at 6 months
• Reducing AD → potential to prevent food allergy
Kapur et al. Allergy Asthma Clin Immunol 2018