Atopic Dermatitis <-> Asthma

Comorbidity A_BEFORE_B CURATED
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.
A

Disease A

Atopic Dermatitis
Slug:Atopic_Dermatitis
B

Disease B

Asthma
Slug:Asthma
G

Causal Mechanism Graphs

Atopic Dermatitis

graph LR
    Microbial_Dysbiosis["Microbial Dysbiosis"]
    IL13["IL13"]
    Epidermal_Barrier_Dysfunction["Epidermal Barrier Dysfunction"]
    FLG["FLG"]
    TOPK_Inhibitors["TOPK Inhibitors"]
    Pruritogen_Induced_Neuronal_Activation["Pruritogen-Induced Neuronal Activation"]
    TOPK_STAT3_Signaling_Axis["TOPK-STAT3 Signaling Axis"]
    Eczematoid_Dermatitis["Eczematoid Dermatitis"]
    Elevated_Serum_IgE["Elevated Serum IgE"]
    Flexural_Lichenification["Flexural Lichenification"]
    Type_2_Immune_Response["Type 2 Immune Response"]
    Scratching_Induced_Barrier_Injury["Scratching-Induced Barrier Injury"]
    Food_Allergy["Food Allergy"]
    Asthma["Asthma"]
    Pruritus["Pruritus"]
    Recurrent_Skin_Infections["Recurrent Skin Infections"]
    STAT6["STAT6"]
    Allergic_Rhinitis["Allergic Rhinitis"]
    STAT6_Degrader_SAR448272_NX_3911["STAT6 Degrader (SAR448272/NX-3911)"]
    Secondary_Inflammatory_Amplification["Secondary Inflammatory Amplification"]
    Erythema["Erythema"]
    Xerosis["Xerosis"]
    Sleep_Disturbance["Sleep Disturbance"]

    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
    Microbial_Dysbiosis --> Type_2_Immune_Response
    Microbial_Dysbiosis --> Secondary_Inflammatory_Amplification
    STAT6_Degrader_SAR448272_NX_3911 --> Type_2_Immune_Response
    TOPK_Inhibitors --> TOPK_STAT3_Signaling_Axis
    FLG --> Epidermal_Barrier_Dysfunction
    IL13 --> Type_2_Immune_Response
    STAT6 --> Type_2_Immune_Response

    style Microbial_Dysbiosis fill:#dcfce7
    style IL13 fill:#f3e8ff
    style Epidermal_Barrier_Dysfunction fill:#dbeafe
    style FLG fill:#f3e8ff
    style TOPK_Inhibitors fill:#fce7f3
    style Pruritogen_Induced_Neuronal_Activation fill:#dbeafe
    style TOPK_STAT3_Signaling_Axis fill:#dbeafe
    style Eczematoid_Dermatitis fill:#fef3c7
    style Elevated_Serum_IgE fill:#fef3c7
    style Flexural_Lichenification fill:#fef3c7
    style Type_2_Immune_Response fill:#dbeafe
    style Scratching_Induced_Barrier_Injury fill:#dbeafe
    style Food_Allergy fill:#fef3c7
    style Asthma fill:#fef3c7
    style Pruritus fill:#fef3c7
    style Recurrent_Skin_Infections fill:#fef3c7
    style STAT6 fill:#f3e8ff
    style Allergic_Rhinitis fill:#fef3c7
    style STAT6_Degrader_SAR448272_NX_3911 fill:#fce7f3
    style Secondary_Inflammatory_Amplification fill:#dbeafe
    style Erythema fill:#fef3c7
    style Xerosis fill:#fef3c7
    style Sleep_Disturbance fill:#fef3c7

Asthma

graph LR
    Rapid_Breathing["Rapid Breathing"]
    Prenatal_Acid_Suppressive_Medication_Exposure["Prenatal Acid-Suppressive Medication Exposure"]
    IL13["IL13"]
    SIRT1_Mediated_NAD+_Signaling_and_Protective_Deacetylation["SIRT1-Mediated NAD+ Signaling and Protective Deacetylation"]
    Type_2_Immune_Response___Th2_Signaling["Type 2 Immune Response / Th2 Signaling"]
    ADAM33["ADAM33"]
    Fatigue["Fatigue"]
    Allergens["Allergens"]
    Occupational_Exposures["Occupational Exposures"]
    Respiratory_Distress["Respiratory Distress"]
    CDHR3["CDHR3"]
    Wheezing["Wheezing"]
    Chest_Tightness["Chest Tightness"]
    Airway_Remodeling["Airway Remodeling"]
    Sleep_Disturbance["Sleep Disturbance"]
    Bronchoconstriction["Bronchoconstriction"]
    Cyanosis["Cyanosis"]
    Anxiety["Anxiety"]
    Hill_mechanochemical_morphoelastic_model_of_asthmatic_airway_remodelling["Hill mechanochemical morphoelastic model of asthmatic airway remodelling"]
    Airway_Inflammation["Airway Inflammation"]
    IL4["IL4"]
    STAT3["STAT3"]
    Winkler_integrative_bronchial_tree_model_of_asthmatic_bronchoconstriction["Winkler integrative bronchial-tree model of asthmatic bronchoconstriction"]
    Exercise_Intolerance["Exercise Intolerance"]
    STAT6_Degrader_SAR448272_NX_3911["STAT6 Degrader (SAR448272/NX-3911)"]
    Mucus_Overproduction["Mucus Overproduction"]
    Coughing["Coughing"]
    Air_Pollution["Air Pollution"]
    Reduced_Exercise_Tolerance["Reduced Exercise Tolerance"]
    Tobacco_Smoke["Tobacco Smoke"]
    House_Dust_Mite_Allergen_Protease_Induced_Epithelial_Oxidant_Signaling["House Dust Mite Allergen Protease-Induced Epithelial Oxidant Signaling"]
    Early_Life_Rhinovirus_Wheezing_Illness_and_Asthma_Inception["Early-Life Rhinovirus Wheezing Illness and Asthma Inception"]

    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
    Allergens --> Type_2_Immune_Response___Th2_Signaling
    Air_Pollution --> Airway_Inflammation
    Tobacco_Smoke --> Airway_Inflammation
    Occupational_Exposures --> Airway_Inflammation
    Prenatal_Acid_Suppressive_Medication_Exposure --> Type_2_Immune_Response___Th2_Signaling
    STAT6_Degrader_SAR448272_NX_3911 --> Type_2_Immune_Response___Th2_Signaling
    Hill_mechanochemical_morphoelastic_model_of_asthmatic_airway_remodelling --> Airway_Remodeling
    Hill_mechanochemical_morphoelastic_model_of_asthmatic_airway_remodelling --> Bronchoconstriction
    Hill_mechanochemical_morphoelastic_model_of_asthmatic_airway_remodelling --> Airway_Inflammation
    Winkler_integrative_bronchial_tree_model_of_asthmatic_bronchoconstriction --> Bronchoconstriction
    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 Rapid_Breathing fill:#fef3c7
    style Prenatal_Acid_Suppressive_Medication_Exposure fill:#dcfce7
    style IL13 fill:#f3e8ff
    style SIRT1_Mediated_NAD+_Signaling_and_Protective_Deacetylation fill:#dbeafe
    style Type_2_Immune_Response___Th2_Signaling fill:#dbeafe
    style ADAM33 fill:#f3e8ff
    style Fatigue fill:#fef3c7
    style Allergens fill:#dcfce7
    style Occupational_Exposures fill:#dcfce7
    style Respiratory_Distress fill:#fef3c7
    style CDHR3 fill:#f3e8ff
    style Wheezing fill:#fef3c7
    style Chest_Tightness fill:#fef3c7
    style Airway_Remodeling fill:#dbeafe
    style Sleep_Disturbance fill:#fef3c7
    style Bronchoconstriction fill:#dbeafe
    style Cyanosis fill:#fef3c7
    style Anxiety fill:#fef3c7
    style Hill_mechanochemical_morphoelastic_model_of_asthmatic_airway_remodelling fill:#ecfccb
    style Airway_Inflammation fill:#dbeafe
    style IL4 fill:#f3e8ff
    style STAT3 fill:#f3e8ff
    style Winkler_integrative_bronchial_tree_model_of_asthmatic_bronchoconstriction fill:#ecfccb
    style Exercise_Intolerance fill:#fef3c7
    style STAT6_Degrader_SAR448272_NX_3911 fill:#fce7f3
    style Mucus_Overproduction fill:#dbeafe
    style Coughing fill:#fef3c7
    style Air_Pollution fill:#dcfce7
    style Reduced_Exercise_Tolerance fill:#fef3c7
    style Tobacco_Smoke fill:#dcfce7
    style House_Dust_Mite_Allergen_Protease_Induced_Epithelial_Oxidant_Signaling fill:#dbeafe
    style Early_Life_Rhinovirus_Wheezing_Illness_and_Asthma_Inception fill:#dbeafe
S

Association Signals

Signal 1
LITERATURE LITERATURE_ASSOCIATION A_BEFORE_B
Population:Pooled birth-cohort studies (systematic review) of children with atopic eczema in the first 4 years of life, asthma assessed at >=6 years.
Temporal: A before B: , B before A: , Same time:
OR: 2.14
CI: 1.67 - 2.75
p:
FDR:
Pooled OR for asthma after early-childhood eczema vs children without eczema (birth cohorts).
PMID:17655920 (SUPPORT)
Source: HUMAN_CLINICAL
"The pooled odds ratio for the risk of asthma after eczema, compared with children without eczema, in birth cohort studies was 2.14 (95% CI, 1.67-2.75)."
Systematic review of prospective birth cohorts quantifies the increased risk of subsequent asthma in children with atopic eczema.
H

Hypotheses

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.
PMID:30479073 (SUPPORT)
Source: HUMAN_CLINICAL
"The Atopic march denotes the progression from atopic dermatitis (AD) to the development of other allergic disorders such as immunoglobulin (Ig) E-mediated food allergy, allergic rhinitis and asthma in later childhood."
Defines the atopic march as progression from AD to other allergic disorders including asthma.
PMID:28583447 (SUPPORT)
Source: OTHER
"Importantly, epithelial dysfunction characterized by these traits appears to pre-date atopy and development of allergic disease."
Supports barrier dysfunction as an upstream trait preceding atopy, consistent with AD barrier dysfunction preceding asthma.
Pathophysiology:
Epicutaneous Sensitization Driving Allergic Airway Disease: Allergen penetration through the AD-compromised skin barrier primes type 2 sensitization that, via the atopic march, manifests later as asthma.
Cell types:
T-helper 2 cell Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves T-helper 2 cell (CL:0000546). CL:0000546 is a cell type from the Cell Ontology.
Biological processes:
type 2 immune response Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased type 2 immune response (GO:0042092). GO:0042092 is a biological process from the Gene Ontology. immunoglobulin production Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased immunoglobulin production (GO:0002377). GO:0002377 is a biological process from the Gene Ontology.
PMID:30479073 (SUPPORT)
Source: HUMAN_CLINICAL
"the pathways that may be responsible for triggering the progression from the skin barrier dysfunction seen in AD to epicutaneous sensitization, food allergy and allergic airway disorders."
Review of atopic-march mechanism identifies skin barrier dysfunction in AD progressing through epicutaneous sensitization to allergic airway disease (asthma).
PMID:28583445 (SUPPORT)
Source: OTHER
"spreads beyond the skin to initiate the atopic march, which includes food allergy, asthma, and allergic rhinitis"
Describes AD-initiated immune activation spreading beyond skin to initiate the atopic march including asthma.
Y

Raw YAML

Show YAML 
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
      reference_title: "Mechanisms by Which Atopic Dermatitis Predisposes to Food Allergy and the Atopic March."
      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
      reference_title: "Novel concepts of prevention and treatment of atopic dermatitis through barrier and immune manipulations with implications for the atopic march."
      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
    reference_title: "Mechanisms by Which Atopic Dermatitis Predisposes to Food Allergy and the Atopic March."
    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
    reference_title: "Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases."
    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
      reference_title: "Risk of developing asthma in young children with atopic eczema: a systematic review."
      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.
Source:GitHub