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Atopic Dermatitis (Eczema)

Atopic dermatitis, also known as eczema, is a chronic, relapsing, pruritic, inflammatory skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions disease that occurs more frequently in children, although adults can also be affected. The condition is often associated with elevated serum levels of IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions and a personal or family history Family History Adult Health Maintenance of atopy. Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions dryness, erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion, oozing, crusting, and lichenification are present. Pruritus is a cardinal symptom. Diagnosis is established clinically. The mainstays of management are avoidance of triggers Triggers Hereditary Angioedema (C1 Esterase Inhibitor Deficiency), emollients Emollients Oleaginous substances used topically to soothe, soften or protect skin or mucous membranes. They are used also as vehicles for other dermatologic agents. Pityriasis Rosea, and topical corticosteroids Corticosteroids Chorioretinitis.

Last updated: 29 Nov, 2021

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Atopic dermatitis (also known as eczema) is a disorder of altered skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions barrier integrity and immune dysregulation that presents as a chronic relapsing inflammatory skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions disease.

Epidemiology

  • Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency:
    • School-aged children: approximately 17%
    • Adults: 2%–10%
  • Atopic triad (present in 30%–50% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship):
    • Atopic dermatitis
    • Allergic rhinitis Rhinitis Inflammation of the nasal mucosa, the mucous membrane lining the nasal cavities. Rhinitis
    • Asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma
  • 30% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship develop asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma.
  • Vast majority of cases in children; linked with family history Family History Adult Health Maintenance of atopy
  • Most cases occur prior to age 5.
  • Slight female preponderance
  • Previous history of atopy is an important risk factor.
  • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency higher in:
    • Urban areas
    • Developed countries

Etiology

  • Multifactorial and not completely understood
  • Genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics:
    • Family history Family History Adult Health Maintenance of atopy
    • Filaggrin gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics mutations (loss-of-function mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations):
      • Strongest known genetic risk factor
      • Keratinocyte Keratinocyte Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Erythema Multiforme barrier dysfunction
      • Increased susceptibility to potential antigens
  • Immune defects: Th2 Th2 A subset of helper-inducer T-lymphocytes which synthesize and secrete the interleukins il-4; il-5; il-6; and il-10. These cytokines influence b-cell development and antibody production as well as augmenting humoral responses. T cells: Types and Functions disease (T helper cells)
  • Prenatal factors: elevated cord blood IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions
  • Infection:
    • Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus aureus colonization Colonization Bacteriology:
      • Often causes flares
      • Acts as a superantigen Superantigen Microbial antigens that have in common an extremely potent activating effect on T-cells that bear a specific variable region. Superantigens cross-link the variable region with class II mhc proteins regardless of the peptide binding in the t-cell receptor’s pocket. The result is a transient expansion and subsequent death and anergy of the T-cells with the appropriate variable regions. Toxic Shock Syndrome
    • HSV HSV Herpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals. Herpes Simplex Virus 1 and 2
  • Hygiene hypothesis Hypothesis A hypothesis is a preliminary answer to a research question (i.e., a “guess” about what the results will be). There are 2 types of hypotheses: the null hypothesis and the alternative hypothesis. Statistical Tests and Data Representation: Early childhood exposure Exposure ABCDE Assessment to microbes and allergens prevents atopy.

Pathophysiology and Clinical Presentation

Pathophysiology

  • Pathogenesis is poorly defined.
  • Characterized by spongiosis (epidermal edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema)
  • Edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema leads to breaking of intercellular attachments → vesicle Vesicle Primary Skin Lesions formation
  • Lymphocytic dermal infiltrates are present.
  • Acanthosis and hyperkeratosis Hyperkeratosis Ichthyosis Vulgaris may be present.
  •  2 interrelated pathways have been implicated:
    •  Primary epithelial barrier disruption (outside-in hypothesis Hypothesis A hypothesis is a preliminary answer to a research question (i.e., a “guess” about what the results will be). There are 2 types of hypotheses: the null hypothesis and the alternative hypothesis. Statistical Tests and Data Representation):
      • Disruption of tight junctions Tight junctions Cell-cell junctions that seal adjacent epithelial cells together, preventing the passage of most dissolved molecules from one side of the epithelial sheet to the other. The Cell: Cell Junctions and increased permeability of stratum corneum Stratum corneum Skin: Structure and Functions
      • Increased transepidermal water loss
      • Can be associated with defects in structural proteins Structural proteins Proteins and Peptides (filaggrin is the major one implicated)
      • Barrier disruption can also be caused by microbial colonization Colonization Bacteriology and release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology of inflammatory cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response.
    • Immune-response defect (inside-out hypothesis Hypothesis A hypothesis is a preliminary answer to a research question (i.e., a “guess” about what the results will be). There are 2 types of hypotheses: the null hypothesis and the alternative hypothesis. Statistical Tests and Data Representation):
      • Secondary immunologic dysregulation
      • Defect in toll-like receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors has been implicated in the loss of epidermal innate immunity Innate immunity The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring anti-infective agents, constitutional factors such as body temperature and immediate acting immune cells such as natural killer cells. Innate Immunity: Phagocytes and Antigen Presentation ( colonization Colonization Bacteriology with S. aureus S. aureus Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. Staphylococcus leads to severe inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation).
      • IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions–mediated allergic sensitization → increased susceptibility to irritants/allergens secondary to structural epidermal defects
Histological findings atopic dermatitis

Atopic dermatitis:
Histological image of the epidermal layer with a mild lymphohistiocytic and granulocytic infiltrate, predominantly eosinophilic

Image: “Atopic dermatitis, short stature, skeletal malformations, hyperimmunoglobulin E syndrome, hypereosinophilia Hypereosinophilia Absolute eosinophil count of ≥ 1.5 X 10⁹/L. Chronic Eosinophilic Leukemia and recurrent infections Recurrent infections Common Variable Immunodeficiency (CVID)” by Leonardi S, Filippelli M, Costanzo V, Rotolo N, La Rosa M. License: CC BY 2.0

Clinical presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor

  • Chronic course with periods of remission Remission A spontaneous diminution or abatement of a disease over time, without formal treatment. Cluster Headaches and exacerbation
  • Intense pruritus: cardinal symptom
  • Cutaneous hyperreactivity to environmental stimuli
  • Age:
    • Infants and younger children:
      • Papulovesicular lesions
      • Intense pruritis
      • Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion
      • Edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
      • Excoriations Excoriations Excoriation is a linear abrasion produced by mechanical means (scratching, rubbing, or picking) that usually involves only the epidermis but can reach the papillary dermis. Secondary Skin Lesions: result of itching
      • Location: face, scalp, extensor surfaces, with sparing of the diaper area
    • Older children and young adults:
      • Chronic lesions with lichenification
      • Flexor surfaces of elbows, knees and sides of the neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess, wrists, and ankles
      • Improves with age with remission Remission A spontaneous diminution or abatement of a disease over time, without formal treatment. Cluster Headaches seen by 13 years of age in approximately 50% of cases
  • Severity:
    • Mild:
      • Areas of dry skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions
      • Pruritus: infrequent
      • Minimal impact on activities, sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep, and psychosocial well-being
    • Moderate:
      • Areas of dry skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions
      • Pruritus: frequent
      • Redness Redness Inflammation
      • Localized skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions thickening with or without excoriation Excoriation Mastitis
      • Moderate impact on activities and psychosocial well-being
      • Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep frequently disturbed
    • Severe:
      • Widespread dry skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions
      • Pruritus: incessant
      • Redness Redness Inflammation
      • Extensive skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions thickening, bleeding, oozing, cracking, and pigmentation alteration
      • Severe impact on activities, psychosocial functioning, and sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep

Diagnosis

History

  • Pruritus
  • 3 or more of the following (in addition to pruritus):
    • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions creases involved:
    • Asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma or hay fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever history (or 1st-degree relative if child < 4 years of age)
    • Dry skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions in the past year
    • Symptoms beginning prior to age 2 (not used if child is < 4 years old)
    • Dermatitis of flexural surfaces (if child < 4 years old, cheeks Cheeks The part of the face that is below the eye and to the side of the nose and mouth. Melasma, forehead Forehead The part of the face above the eyes. Melasma, or outer aspects of extremities)
  • Chronic or relapsing history
  • Environmental stimuli (certain foods, allergens, medications)

Physical exam ( skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions)

  • Young children/infants:
    • Face
    • Scalp
    • Neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess
    • Extensor surfaces
    • Papulovesicular lesions
    • Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion
    • Edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
    • Excoriations Excoriations Excoriation is a linear abrasion produced by mechanical means (scratching, rubbing, or picking) that usually involves only the epidermis but can reach the papillary dermis. Secondary Skin Lesions
  • Older children and adults:
    • Lichenification
    • Flexor surfaces:
      • Elbows
      • Knees
      • Sides of neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess, wrists, ankles
  • Dry skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions

Laboratory studies

  • Only to rule out other skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions conditions
  • Serum IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions: elevated in 80% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma
  • Potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia hydroxide preparation of skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions scrapings to rule out Tinea corporis Tinea corporis Dermatophytes/Tinea Infections
  • Patch Patch Nonpalpable lesion > 1 cm in diameter Generalized and Localized Rashes testing to rule out contact dermatitis Contact dermatitis A type of acute or chronic skin reaction in which sensitivity is manifested by reactivity to materials or substances coming in contact with the skin. It may involve allergic or non-allergic mechanisms. Male Genitourinary Examination
  • Genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies

Management

Supportive/prophylactic measures

Patient education:

  • Children
  • Parents

Elimination Elimination The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy of exacerbating factors:

  • Avoid triggers Triggers Hereditary Angioedema (C1 Esterase Inhibitor Deficiency):
    • Heat Heat Inflammation
    • Low humidity
    • Excessive bathing (without moisturization)
    • Stress and anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder
    • Exposure Exposure ABCDE Assessment to solvents and detergents
    • Xerosis Xerosis Sjögren’s Syndrome (dry skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions)
    • Overheating of skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions
    • Harsh detergents
  • Treat associated skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
    • S. aureus S. aureus Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. Staphylococcus
    • Herpes simplex Herpes Simplex A group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. Congenital TORCH Infections

Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions hydration (mainstay of treatment to reduce itching and episodes of inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation):

  • Emollients Emollients Oleaginous substances used topically to soothe, soften or protect skin or mucous membranes. They are used also as vehicles for other dermatologic agents. Pityriasis Rosea:
    • Apply at least twice a day
    • Immediately after bathing or handwashing
  • Moisturizers containing:
    • Glycyrrhetinic acid
    • Urea Urea A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. Urea Cycle
    • Glycerol

Medications/interventions

Topical treatments:

  • Corticosteroids Corticosteroids Chorioretinitis: Prolonged use may cause skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation or other adverse effects.
  • Calcineurin inhibitors Calcineurin Inhibitors Compounds that inhibit or block the phosphatase activity of calcineurin. Immunosuppressants: 2nd-line treatment
  • Phosphodiesterase 4 (PDE4) inhibitors ( crisaborole Crisaborole Phosphodiesterase Inhibitors)

Oral antihistamines Antihistamines Antihistamines are drugs that target histamine receptors, particularly H1 and H2 receptors. H1 antagonists are competitive and reversible inhibitors of H1 receptors. First-generation antihistamines cross the blood-brain barrier and can cause sedation. Antihistamines:

  • H1 agents
  • Beneficial when sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep disturbed by pruritus
  • Diphenhydramine Diphenhydramine A histamine h1 antagonist used as an antiemetic, antitussive, for dermatoses and pruritus, for hypersensitivity reactions, as a hypnotic, an antiparkinson, and as an ingredient in common cold preparations. It has some undesired antimuscarinic and sedative effects. Antihistamines
  • Hydroxyzine Hydroxyzine A histamine h1 receptor antagonist that is effective in the treatment of chronic urticaria, dermatitis, and histamine-mediated pruritus. Unlike its major metabolite cetirizine, it does cause drowsiness. It is also effective as an antiemetic, for relief of anxiety and tension, and as a sedative. Antihistamines
  • Cyproheptadine Cyproheptadine A serotonin antagonist and a histamine h1 blocker used as antipruritic, appetite stimulant, antiallergic, and for the post-gastrectomy dumping syndrome, etc. Serotonin Syndrome

Oral immunosuppressants Immunosuppressants Immunosuppressants are a class of drugs widely used in the management of autoimmune conditions and organ transplant rejection. The general effect is dampening of the immune response. Immunosuppressants:

  • Cyclosporin
  • Recurrence common upon discontinuation of treatment

Human monoclonal antibody:

Phototherapy Phototherapy Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. Hyperbilirubinemia of the Newborn:

  • Used in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with diffuse pruritus not controlled with topical therapy alone
  • Reduced production of histamine from mast cells Mast cells Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Innate Immunity: Phagocytes and Antigen Presentation and basophils Basophils Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. Innate Immunity: Phagocytes and Antigen Presentation
  • Narrowband ultraviolet B (NBUVB)
  • Ultraviolet A1 (UVA1)

Differential Diagnosis

  • Contact dermatitis Contact dermatitis A type of acute or chronic skin reaction in which sensitivity is manifested by reactivity to materials or substances coming in contact with the skin. It may involve allergic or non-allergic mechanisms. Male Genitourinary Examination: an erythematous, papular dermatitis, often with areas of vesiculation. Occurs due to direct skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions exposure Exposure ABCDE Assessment to an offending irritant with a direct cytotoxic Cytotoxic Parvovirus B19 effect. Diagnosis is made by history and physical exam findings. Treatment is with avoidance of offending irritants and adoption of protective measures as well as emollients Emollients Oleaginous substances used topically to soothe, soften or protect skin or mucous membranes. They are used also as vehicles for other dermatologic agents. Pityriasis Rosea and moisturizers. Topical steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors are the 1st-line intervention.
  • Seborrheic dermatitis Seborrheic dermatitis Seborrheic dermatitis is a common chronic, relapsing skin disorder that presents as erythematous plaques with greasy, yellow scales in susceptible areas (scalp, face, and trunk). Seborrheic dermatitis has a biphasic incidence, occurring in two peaks: first in infants, then in adolescence and early adulthood. Seborrheic Dermatitis: a chronic, relapsing, and usually mild form of dermatitis with a biphasic incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in infants and adults. The condition is characterized by well-demarcated, erythematous plaques with greasy-appearing, yellow-like scales Scales Dry or greasy masses of keratin that represent thickened stratum corneum. Secondary Skin Lesions in sebaceous gland Sebaceous Gland Small, sacculated organs found within the dermis. Each gland has a single duct that emerges from a cluster of oval alveoli. Each alveolus consists of a transparent basement membrane enclosing epithelial cells. The ducts from most sebaceous glands open into a hair follicle, but some open on the general surface of the skin. Sebaceous glands secrete sebum. Hordeolum (Stye) rich areas. The cause is unknown, but sebaceous glands appear to be necessary for the development of the disorder. The diagnosis is made clinically. Treatment is with topical antifungal Antifungal Azoles, anti-inflammatory, and over-the-counter agents.
  • Diaper dermatitis: a form of irritant dermatitis most common in infants and children. Excessive moisture, friction, increased pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance, and high enzymatic activity contribute to local disruption of the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions barrier. The condition is limited to the groin Groin The external junctural region between the lower part of the abdomen and the thigh. Male Genitourinary Examination area and often spares folds where urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat/feces do not contact the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions. The diagnosis is made clinically. Treatment involves general skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions care measures (frequent diaper changes, exposure Exposure ABCDE Assessment to air, and cleaning), topical steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors, and antifungals (in severe cases of superinfection by Candida Candida Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis).
  • Mycosis Mycosis Fungi belong to the eukaryote domain and, like plants, have cell walls and vacuoles, exhibit cytoplasmic streaming, and are immobile. Mycosis is an infection caused by fungi. Mycology fungoides: a type of cutaneous T cell lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum. The disease presents in the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions but also can involve the lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy, blook, and viscera. Mycosis Mycosis Fungi belong to the eukaryote domain and, like plants, have cell walls and vacuoles, exhibit cytoplasmic streaming, and are immobile. Mycosis is an infection caused by fungi. Mycology fungoides often involves sites beneath undergarments and is uncommon in children. The disease presents with persistent progressive skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions lesions of varying shapes and sizes and can be localized or widespread plaques or tumors, or generalized erythroderma. Pruritus is common. Diagnosis is clinical along with skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma with routine histology. Treatment involves topical agents, including steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors, chemotherapy Chemotherapy Osteosarcoma, retinoids Retinoids Retinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of carotenoids found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products. Fat-soluble Vitamins and their Deficiencies, imiquimod Imiquimod A topically-applied aminoquinoline immune modulator that induces interferon production. It is used in the treatment of external genital and perianal warts, superficial carcinoma, basal cell; and actinic keratosis. Hypertrophic and Keloid Scars, local radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma, and phototherapy Phototherapy Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. Hyperbilirubinemia of the Newborn
  • Psoriasis Psoriasis Psoriasis is a common T-cell-mediated inflammatory skin condition. The etiology is unknown, but is thought to be due to genetic inheritance and environmental triggers. There are 4 major subtypes, with the most common form being chronic plaque psoriasis. Psoriasis: a common chronic inflammatory skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions disorder characterized by erythematous papules and plaques with a silver scale Scale Dermatologic Examination. Psoriasis Psoriasis Psoriasis is a common T-cell-mediated inflammatory skin condition. The etiology is unknown, but is thought to be due to genetic inheritance and environmental triggers. There are 4 major subtypes, with the most common form being chronic plaque psoriasis. Psoriasis is a complex immune-mediated disease whereby T lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes: Histology, cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response, dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions, and tumor Tumor Inflammation necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage factor play a predominant role. Previously, it was viewed as a disease of hyperproliferation. Diagnosis is made by physical exam. Management is with topical corticosteroids Corticosteroids Chorioretinitis, phototherapy Phototherapy Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. Hyperbilirubinemia of the Newborn, retinoids Retinoids Retinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of carotenoids found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products. Fat-soluble Vitamins and their Deficiencies, methotrexate Methotrexate An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of tetrahydrofolate dehydrogenase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. Antimetabolite Chemotherapy, cyclosporin, or biologic immune modifying agents.
  • Scabies Scabies Scabies is an infestation of the skin by the Sarcoptes scabiei mite, which presents most commonly with intense pruritus, characteristic linear burrows, and erythematous papules, particularly in the interdigital folds and the flexor aspects of the wrists. Scabies: a cutaneous infestation caused by the mite Sarcoptes scabiei Sarcoptes scabiei A species of mite that causes scabies in humans and sarcoptic mange in other animals. Specific variants of s. Scabiei exist for humans and animals, but many have the ability to cross species and cause disease. Scabies. Scabies Scabies Scabies is an infestation of the skin by the Sarcoptes scabiei mite, which presents most commonly with intense pruritus, characteristic linear burrows, and erythematous papules, particularly in the interdigital folds and the flexor aspects of the wrists. Scabies is an intensely pruritic eruption with small erythematous papules on the fingers, wrists, axillae, areolae, waist, genitalia, and buttocks areas. Diagnosis is by history and physical exam along with detection of mites Mites Any arthropod of the subclass acari except the ticks. They are minute animals related to the spiders, usually having transparent or semitransparent bodies. They may be parasitic on humans and domestic animals, producing various irritations of the skin (mite infestations). Many mite species are important to human and veterinary medicine as both parasite and vector. Mites also infest plants. Scabies, eggs, or fecal pellets under microscopic evaluation. Treatment is aimed at both the patient and close contacts. Topical permethrin Permethrin A pyrethroid insecticide commonly used in the treatment of lice infestations and scabies. Scabies and oral ivermectin Ivermectin A mixture of mostly avermectin h2b1a (rn 71827-03-7) with some avermectin h2b1b (rn 70209-81-3), which are macrolides from streptomyces avermitilis. It binds glutamate-gated chloride channel to cause increased permeability and hyperpolarization of nerve and muscle cells. It also interacts with other chloride channels. It is a broad spectrum antiparasitic that is active against microfilariae of onchocerca volvulus but not the adult form. Anthelmintic Drugs are the mainstays of therapy.

References

  1. Weston, W., Howe, W. (2021). Atopic dermatitis (eczema): Pathogenesis, clinical manifestations, and diagnosis. In Corona, R. (Ed.). UpToDate. Retrieved March 15, 2021, from https://www.uptodate.com/contents/atopic-dermatitis-eczema-pathogenesis-clinical-manifestations-and-diagnosis
  2. Weston, W., Howe, W. (2021). Treatment of atopic dermatitis (eczema). In Corona, R. (Ed.). UpToDate. Retrieved March 15, 2021, from https://www.uptodate.com/contents/treatment-of-atopic-dermatitis-eczema
  3. Spergel, J., Lio, P. (2021). Management of severe atopic dermatitis (eczema) in children. In Corona, R. (Ed.). UpToDate. Retrieved March 15, 2021, from https://www.uptodate.com/contents/management-of-severe-atopic-dermatitis-eczema-in-children
  4. Kim, B. (2020). Atopic Dermatitis. In James, W. (Ed). Medscape. Retrieved March 15, 2021, from https://reference.medscape.com/article/1049085-overview
  5. Eichenfield, L.F., et al. (2014). Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 71(1), 116–132. https://pubmed.ncbi.nlm.nih.gov/24813302/
  6. Weidinger, S., Novak, N. (2016). Atopic dermatitis. Lancet. 387(10023), 1109–1122. https://pubmed.ncbi.nlm.nih.gov/26377142/

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