graph LR
Sleep_Disturbance["Sleep Disturbance"]
STAT6["STAT6"]
Erythema["Erythema"]
Scratching_Induced_Barrier_Injury["Scratching-Induced Barrier Injury"]
IL13["IL13"]
TOPK_Inhibitors["TOPK Inhibitors"]
Epidermal_Barrier_Dysfunction["Epidermal Barrier Dysfunction"]
Asthma["Asthma"]
Allergic_Rhinitis["Allergic Rhinitis"]
Elevated_Serum_IgE["Elevated Serum IgE"]
Xerosis["Xerosis"]
Flexural_Lichenification["Flexural Lichenification"]
TOPK_STAT3_Signaling_Axis["TOPK-STAT3 Signaling Axis"]
FLG["FLG"]
Secondary_Inflammatory_Amplification["Secondary Inflammatory Amplification"]
Type_2_Immune_Response["Type 2 Immune Response"]
Pruritogen_Induced_Neuronal_Activation["Pruritogen-Induced Neuronal Activation"]
Pruritus["Pruritus"]
Recurrent_Skin_Infections["Recurrent Skin Infections"]
Eczematoid_Dermatitis["Eczematoid Dermatitis"]
Food_Allergy["Food Allergy"]
Epidermal_Barrier_Dysfunction --> Xerosis
Epidermal_Barrier_Dysfunction --> Eczematoid_Dermatitis
Epidermal_Barrier_Dysfunction --> Recurrent_Skin_Infections
Type_2_Immune_Response --> Epidermal_Barrier_Dysfunction
Type_2_Immune_Response --> Pruritogen_Induced_Neuronal_Activation
Type_2_Immune_Response --> Elevated_Serum_IgE
Type_2_Immune_Response --> Food_Allergy
Type_2_Immune_Response --> Allergic_Rhinitis
Type_2_Immune_Response --> Asthma
TOPK_STAT3_Signaling_Axis --> Type_2_Immune_Response
TOPK_STAT3_Signaling_Axis --> Secondary_Inflammatory_Amplification
Pruritogen_Induced_Neuronal_Activation --> Scratching_Induced_Barrier_Injury
Pruritogen_Induced_Neuronal_Activation --> Pruritus
Pruritogen_Induced_Neuronal_Activation --> Sleep_Disturbance
Scratching_Induced_Barrier_Injury --> Secondary_Inflammatory_Amplification
Scratching_Induced_Barrier_Injury --> Flexural_Lichenification
Secondary_Inflammatory_Amplification --> Erythema
TOPK_Inhibitors --> TOPK_STAT3_Signaling_Axis
FLG --> Epidermal_Barrier_Dysfunction
IL13 --> Type_2_Immune_Response
STAT6 --> Type_2_Immune_Response
style Sleep_Disturbance fill:#fef3c7
style STAT6 fill:#f3e8ff
style Erythema fill:#fef3c7
style Scratching_Induced_Barrier_Injury fill:#dbeafe
style IL13 fill:#f3e8ff
style TOPK_Inhibitors fill:#fce7f3
style Epidermal_Barrier_Dysfunction fill:#dbeafe
style Asthma fill:#fef3c7
style Allergic_Rhinitis fill:#fef3c7
style Elevated_Serum_IgE fill:#fef3c7
style Xerosis fill:#fef3c7
style Flexural_Lichenification fill:#fef3c7
style TOPK_STAT3_Signaling_Axis fill:#dbeafe
style FLG fill:#f3e8ff
style Secondary_Inflammatory_Amplification fill:#dbeafe
style Type_2_Immune_Response fill:#dbeafe
style Pruritogen_Induced_Neuronal_Activation fill:#dbeafe
style Pruritus fill:#fef3c7
style Recurrent_Skin_Infections fill:#fef3c7
style Eczematoid_Dermatitis fill:#fef3c7
style Food_Allergy fill:#fef3c7
graph LR
Chest_Tightness["Chest Tightness"]
Exercise_Intolerance["Exercise Intolerance"]
Sleep_Disturbance["Sleep Disturbance"]
Type_2_Immune_Response___Th2_Signaling["Type 2 Immune Response / Th2 Signaling"]
IL4["IL4"]
Wheezing["Wheezing"]
IL13["IL13"]
Airway_Inflammation["Airway Inflammation"]
Early_Life_Rhinovirus_Wheezing_Illness_and_Asthma_Inception["Early-Life Rhinovirus Wheezing Illness and Asthma Inception"]
Rapid_Breathing["Rapid Breathing"]
Respiratory_Distress["Respiratory Distress"]
STAT3["STAT3"]
Coughing["Coughing"]
Bronchoconstriction["Bronchoconstriction"]
Reduced_Exercise_Tolerance["Reduced Exercise Tolerance"]
CDHR3["CDHR3"]
Anxiety["Anxiety"]
Airway_Remodeling["Airway Remodeling"]
Mucus_Overproduction["Mucus Overproduction"]
ADAM33["ADAM33"]
House_Dust_Mite_Allergen_Protease_Induced_Epithelial_Oxidant_Signaling["House Dust Mite Allergen Protease-Induced Epithelial Oxidant Signaling"]
Fatigue["Fatigue"]
Cyanosis["Cyanosis"]
SIRT1_Mediated_NAD+_Signaling_and_Protective_Deacetylation["SIRT1-Mediated NAD+ Signaling and Protective Deacetylation"]
Airway_Inflammation --> Bronchoconstriction
Type_2_Immune_Response___Th2_Signaling --> Airway_Inflammation
Type_2_Immune_Response___Th2_Signaling --> Mucus_Overproduction
Bronchoconstriction --> Wheezing
Bronchoconstriction --> Chest_Tightness
Bronchoconstriction --> Rapid_Breathing
Bronchoconstriction --> Respiratory_Distress
Bronchoconstriction --> Cyanosis
Bronchoconstriction --> Exercise_Intolerance
Bronchoconstriction --> Reduced_Exercise_Tolerance
Bronchoconstriction --> Fatigue
Bronchoconstriction --> Anxiety
Mucus_Overproduction --> Coughing
Mucus_Overproduction --> Sleep_Disturbance
SIRT1_Mediated_NAD+_Signaling_and_Protective_Deacetylation --> Type_2_Immune_Response___Th2_Signaling
SIRT1_Mediated_NAD+_Signaling_and_Protective_Deacetylation --> Mucus_Overproduction
SIRT1_Mediated_NAD+_Signaling_and_Protective_Deacetylation --> Airway_Remodeling
SIRT1_Mediated_NAD+_Signaling_and_Protective_Deacetylation --> Bronchoconstriction
Early_Life_Rhinovirus_Wheezing_Illness_and_Asthma_Inception --> Type_2_Immune_Response___Th2_Signaling
House_Dust_Mite_Allergen_Protease_Induced_Epithelial_Oxidant_Signaling --> Airway_Inflammation
Wheezing --> Respiratory_Distress
Wheezing --> Reduced_Exercise_Tolerance
IL4 --> Type_2_Immune_Response___Th2_Signaling
IL13 --> Type_2_Immune_Response___Th2_Signaling
ADAM33 --> Airway_Remodeling
STAT3 --> SIRT1_Mediated_NAD+_Signaling_and_Protective_Deacetylation
CDHR3 --> Early_Life_Rhinovirus_Wheezing_Illness_and_Asthma_Inception
style Chest_Tightness fill:#fef3c7
style Exercise_Intolerance fill:#fef3c7
style Sleep_Disturbance fill:#fef3c7
style Type_2_Immune_Response___Th2_Signaling fill:#dbeafe
style IL4 fill:#f3e8ff
style Wheezing fill:#fef3c7
style IL13 fill:#f3e8ff
style Airway_Inflammation fill:#dbeafe
style Early_Life_Rhinovirus_Wheezing_Illness_and_Asthma_Inception fill:#dbeafe
style Rapid_Breathing fill:#fef3c7
style Respiratory_Distress fill:#fef3c7
style STAT3 fill:#f3e8ff
style Coughing fill:#fef3c7
style Bronchoconstriction fill:#dbeafe
style Reduced_Exercise_Tolerance fill:#fef3c7
style CDHR3 fill:#f3e8ff
style Anxiety fill:#fef3c7
style Airway_Remodeling fill:#dbeafe
style Mucus_Overproduction fill:#dbeafe
style ADAM33 fill:#f3e8ff
style House_Dust_Mite_Allergen_Protease_Induced_Epithelial_Oxidant_Signaling fill:#dbeafe
style Fatigue fill:#fef3c7
style Cyanosis fill:#fef3c7
style SIRT1_Mediated_NAD+_Signaling_and_Protective_Deacetylation fill:#dbeafe
name: com_Atopic_Dermatitis__Asthma
creation_date: "2026-06-30T00:00:00Z"
curation_status: CURATED
notes: >-
The "atopic march": early-onset atopic dermatitis (AD) is a well-established
antecedent and risk factor for later childhood asthma. The leading mechanistic
account is barrier-first — skin barrier dysfunction in AD permits epicutaneous
allergen sensitization that progresses to allergic airway disease — which is
the same conserved sequence captured by the epithelial_barrier_dysfunction
module that both AD and asthma conform to. This entry is directed (A_BEFORE_B:
AD precedes asthma); the broader march also includes IgE-mediated food allergy
and allergic rhinitis, which are not yet separate dismech entries.
disease_a:
slug: Atopic_Dermatitis
disease_b:
slug: Asthma
directionality: A_BEFORE_B
hypotheses:
- description: >-
Barrier-first atopic march: skin barrier dysfunction in AD enables
epicutaneous allergen sensitization and a type 2 immune response that
spreads beyond the skin to drive allergic airway disease (asthma). This is
the cross-tissue epithelial-barrier mechanism shared by both diseases.
pathophysiology:
- name: Epicutaneous Sensitization Driving Allergic Airway Disease
conforms_to: "epithelial_barrier_dysfunction#Increased Transepithelial Allergen Penetration and Innate Immune Activation"
description: >-
Allergen penetration through the AD-compromised skin barrier primes type 2
sensitization that, via the atopic march, manifests later as asthma.
biological_processes:
- preferred_term: type 2 immune response
term:
id: GO:0042092
label: type 2 immune response
modifier: INCREASED
- preferred_term: immunoglobulin production
term:
id: GO:0002377
label: immunoglobulin production
modifier: INCREASED
cell_types:
- preferred_term: T-helper 2 cell
term:
id: CL:0000546
label: T-helper 2 cell
evidence:
- reference: PMID:30479073
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "the pathways that may \nbe responsible for triggering the progression from the skin barrier dysfunction \nseen in AD to epicutaneous sensitization, food allergy and allergic airway \ndisorders."
explanation: >-
Review of atopic-march mechanism identifies skin barrier dysfunction in
AD progressing through epicutaneous sensitization to allergic airway
disease (asthma).
- reference: PMID:28583445
supports: SUPPORT
evidence_source: OTHER
snippet: "spreads beyond the skin to initiate the atopic march, \nwhich includes food allergy, asthma, and allergic rhinitis"
explanation: >-
Describes AD-initiated immune activation spreading beyond skin to
initiate the atopic march including asthma.
evidence:
- reference: PMID:30479073
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The Atopic march denotes the progression from atopic dermatitis (AD) to the \ndevelopment of other allergic disorders such as immunoglobulin (Ig) E-mediated \nfood allergy, allergic rhinitis and asthma in later childhood."
explanation: >-
Defines the atopic march as progression from AD to other allergic
disorders including asthma.
- reference: PMID:28583447
supports: SUPPORT
evidence_source: OTHER
snippet: "Importantly, epithelial dysfunction characterized by these traits appears to \npre-date atopy and development of allergic disease."
explanation: >-
Supports barrier dysfunction as an upstream trait preceding atopy,
consistent with AD barrier dysfunction preceding asthma.
association_signals:
- source: LITERATURE
method: LITERATURE_ASSOCIATION
population: >-
Pooled birth-cohort studies (systematic review) of children with atopic
eczema in the first 4 years of life, asthma assessed at >=6 years.
directionality: A_BEFORE_B
statistics:
metrics:
- metric_type: OR
metric_value: 2.14
metric_ci_lower: 1.67
metric_ci_upper: 2.75
notes: Pooled OR for asthma after early-childhood eczema vs children without eczema (birth cohorts).
evidence:
- reference: PMID:17655920
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "The pooled odds \nratio for the risk of asthma after eczema, compared with children without \neczema, in birth cohort studies was 2.14 (95% CI, 1.67-2.75)."
explanation: >-
Systematic review of prospective birth cohorts quantifies the increased
risk of subsequent asthma in children with atopic eczema.