MTA W2 Flashcards
Asthma, rhinosinusitis and middle ear disease are accompanied by…
Chronic nasal inflammation
Factors that increase the development of allergic rhinitis
- Female sex
- Particulate air pollution
- Maternal smoking
Factors that decrease the risk of developing allergic rhinitis
- Increased number of siblings
- Grass pollen exposure
- Farm environment
- Mediterranean diet
Intermittent allergic rhinitis duration
- Less than 4 days per week or less than 4 weeks
Persistent allergic rhinitis
- More than four days a week AND more than 4 weeks
This type of allergic rhinitis allows normal sleep, school and work, and does not cause impairment of daily activities, sports, leisure.
It also does not present with troublesome symptoms.
Mild allergic rhinitis
Moderate/severe allergic rhinitis is characterized by the presence of one or more of these items:
- Abnormal sleep
- Impairment of daily activities, sports or leisure
- Abnormal school and work
- Troublesome symptoms
40% of px. With chronic rhinitis also present ________
80% of px. With asthma symptoms have persistent __________
- Asthma
- Nasal symptoms
Rhinosinusitis is common in patients with ______, which is most commonly presented as _______ chronic sinusitis
- asthma
- bilateral
How does nasal allergy lead to bacterial proliferation?
Nasal allergy progresses to acute sinusitis by sinus ostial edema —> results in sinus drainage + shift to anaerobic conditions suitable for bacterial proliferation
How are allergy and chronic sinus disease related?
Both involve anti-staphylococcal IgE and present persistent type 2 inflammation of the sinus
Ear complications derived from allergic rhinitis
- Concomitant otitis media with effusion
- Eustachian tube dysfunction when exposed to pollen
Nasal obstruction associated with allergic rhinitis and sleep problems may lead to…
- Microarousal
- Hypopneas
- Apnea
Alterations developed by children with persistent severe rhinitis:
- Mouth breathing
- Palatal anatomy
- Dental malocclusion
First event in the pathogenesis of allergic rhinitis
Sensitization of nasal mucosa to airborne allergens, leading to interactions between APC, LTh2 and LB
LB begins production of IgE
In allergic rhinitis pathogenesis, what happens after IgE antibodies bind to mast cells and basophils
Degranulation with the release of preformed histamine and newly generated Leukotriene C4 and PGD2
Other mediators produced by mast cells and Th2 in allergic rhinitis pathogenesis
Eosinophil cationic protein, IL-4, IL-3 and IL-13
Why are nasal turbinates enlarged in allergic rhinitis?
Due to cytokine release + inflammatory cells’ (lymphocytes, eosinophils and basophils) constant migration
Why do patients with allergic rhinitis are more responsive to everyday stimuli?
Inflammatory changes lower the tress hold of responsiveness to specific and non-specific stimuli
What’s the role of eotaxin 1 and 2, RANTES and MCP-1, 3- and 4?
They are cytokines that attract eosinophils and induce inflammation in allergic responses
Family history of atopy, male sex, maternal exposure to smoking during the first year of life, firstborn status, early use of antibiotics, exposure to allergens and IgE over a 100 UI are risk factors in the development of
Allergic rhinitis
Name the typical symptoms of allergic rhinitis (either with or without conjunctivitis) (6)
- Congestión
- Sneezing
- Rhinorrhea
- Pruritus
- Watering and redness
How can a person with allergic salute be identified?
If he/she presents any of the following:
- Transverse nasal crease
- Dennis-Morgan folds
- Allergic shiners
Usually, nasal congestion __________ in allergic rhinitis. Nevertheless, if unilateral obstruction is persistent, the patient may have _____, ______ or ________
- Alternates between both sides
- Anatomical defect, inflammatory mass, tumor
Describe rhinorrea in allergic rhinitis and what its opposite may indicate…
- Clear to white
- If it’s purulent, it may indicate chronic sinusitis or atopic rhinitis
What symptoms may change the diagnostic and treatment of allergic rhinitis?
Headache, feeling of facial fullness, anosmia, cough and halitosis
What symptom may be associated to a possible NS lesion if presented more prominently than nasal and ocular symptoms?
Anosmia
Temporal patterns and triggers of allergic rhinitis
- More severe symptoms during early morning (circadian rhythms)
- Aggravation while or after exposure to allergens
- Clear-cut worsening in the outside (outdoor allergens)
- Well demarcated seasonal allergic rhinitis indicate reaction to an outdoor allergen
Mention the allergens related to the seasonality
- Spring = tree pollen exposure
- Summer = grass and mold
- Fall = weeds and mold
Triggers of allergic rhinitis that act as irritants instead of allergens and provoke nasal symptoms
- Volatile organic compounds (perfumes, paints, cleaning fluids)
- Pollution particles
Most important factor in non-allergic rhinitis response
Change in climatic factors
Red flags in children that raise suspicion of allergic rhinitis
- Malocclusion or facial deformities due to chronic, severe nasal obstruction
- Transverse crease over the lower portion of the nose due to repetitive pushing forward
What are the signs of allergic rhinitis found during nasal and nostrils inspection?
- Asymmetry of the nostrils
- Swelling of the mucosa
- Pale mucosa
- Clear to white discharge
Atrophic rhinitis presents with…
Crusting inside the nostrils, especially with dried blood
Discolored discharge or erythematous mucous membranes are signs of
- Chronic rhinosinusitis
- Idiopathic rhinosinusitis
Besides conjunctival injection due to frequent rubbing, what is other sign of allergic rhinitis found in eye examinations?
Venous stasis caused by cyanosis of intraorbital tissues (pathognomonic)
Provides enhanced view of superior and posterior structures of the nose
Fiber optic rhinoscopy
This dx. Method allows for the differentiation between allergic and non allergic rhinitis and has to be accompanied with a nasal allergen challenge to confirm the diagnosis
Testing for specific IgE
Local allergy rhinitis or entropy is diagnosed when…
Specific IgE can only be found in the nose
This dx. Method should be considered when there is presence of atypical symptoms or unresponsiveness to therapy.
CT/radiographic images
Inflammation of paranasal sinuses, seen as mucoperiosteal thickening in px. With uncomplicated allergic rhinitis is detected with…
CT scans
This type of retinitis is presented by bakers, laboratory workers and furriers; it worsens during the week and improves over weekends and vacations but may persist due to _______. The dx. Is done by skin or blood testing for SPECIFIC IgE.
Work-related rhinitis
Chronic rhinosinusitis with or without nasal polyps is an inflammatory disease of the paranasal sinuses that lasts 12 weeks or longer.
Name its 4 cardinal symptoms
- Mucopurulent drainage
- Nasal obstruction
- Facial discomfort
- Decreased sense of smell
Dx. Of Chronic rhinosinusitis with or without nasal polyps
At least 2 of the cardinal symptoms + CT or endoscopic evidence of sinus mucosal inflammation
Name the 6 types of non-allergic rhinitis
- Idiopathic non-allergic rhinitis (vasomotor rhinitis)
- Non-allergy rhinitis with eosinophilia
- Atrophic rhinitis
- Rhinitis associated with drugs
- Hormonal rhinitis
- Rhinitis related to systemic disease
Non-allergic rhinitis that presents with chronic or intermittent nasal congestion and/or watery rinorrhea, may include gustatory rhinitis (eating) and the symptoms worsen acutely in response to non-specific triggers:
Idiopathic (vasomotor)
It’s true about skin tests on patients with idiopathic non-allergic vasomotor rhinitis
Specific IgE is negative, including food allergens
Most common symptoms in NARES caused by local allergic rhinitis with local IgE to an unknown allergen
Nasal congestion and discharge
**Often undiagnosed
This type of rhinitis is a chronic condition with symptoms of nasal crusting, purulent discharge, nasal obstruction and halitosis
Atrophic rhinitis
Prevalence and association of primary Atrophic rhinitis
- Women
- Warm climates like the South Asia and the Middle East
- Associated with chronic bacterial infections —> most commonly Klebsiella ozaenae
This type of Atrophic rhinitis occurs mostly in developed countries. Name it and the px. That are more susceptible to it.
Secondary Atrophic rhinitis
- Older patients
- Multiple/aggressive nasal surgeries (empty nose syndrome)
- Nasal trauma
- Nasal irradiation
Rhinitis medicamentosa is a chronic rhinitis caused by _______
Prolonged use of topical a-adrenergic descongestants like oxymetazoline and phenylephrine
Mechanism of drug-associated rhinitis development
Rebound nasal congestion due to downregulation of a-agonist receptors
Symptoms and physical exam findings of rhinitis associated with drugs
- Severe nasal congestion
- Occasional nasal discomfort
- Minimal discharge
- Swollen, red nasal mucous membranes
Symptoms of cocaine-use rhinitis medicamentosa
- Crusting
- Bleeding
- Septal perforation
Medications that can act as causative agents of rhinitis associated with drugs
- a-adrenergic descongestants
- antihypertensives
- erectile dysfunction drugs
- psychiatric medications
- NSAIDs
New-onset nasal symptoms (congestion and/or rhinorrhea) lasting 6 or more weeks and resolving within 2 weeks postpartum
Hormonal rhinitis in pregnancy
____________ complication in uncontrolled rhinitis may lead to:
- Severe snoring
- Gestational hypertension
- Preeclampsia
- Intrauterine growth retardation
Systemic diseases that can cause rhinitis symptoms, affecting both the nose and sinus cavities, and leading to lung involvement, fatigue and poor appetite
- Granulomatous disease
- Cystic fibrosis
- Cilliary dyskinesia syndromes
- Immunodeficiencies
Besides mechanisms of rhinitis, what factors can cause chronic nasal blockage without other major symptoms?
- Anatomic abnormalities
Name the 3 most common abnormalities in the nose
- Concha bullosa
- Nasal septal deviation
- Adenoidal enlargement that causes nasal obstruction
Name the treatments indicated for allergic rhinitis
- Allergen avoidance
- Intranasal descongestants if less than 10 days
- Oral descongestants
- Oral or topical antihystamine
- Antileukotrienes
- Chromones
- Intranasal corticosteroid
- Specific immunotherapy
These targets of allergen avoidance measures should be based on positive allergy testing:
- Dust mites
- Animal dander
- Molds
Effective strategies for avoidance of large, heavy dust mites
- Pillow and mattress encasings
- Acaricidal sprays and powders for carpets
- Frequent washing of bed linens in hot water
Most common animal allergen and related strategies for avoidance
- Cats
- Best —> remove the cat from home
Oooor
- Remove carpets
- Wash bedding frequently
- Clean upholstered furniture and washing the cat
Outdoor allergies avoidance strategies and management
Limit outdoor activity duren peak pollen hours (11 am - 3 pm)
Best managed with pharmacotherapy and/or immunotherapy
Antihistamines are the main pharmacotherapy for allergic rhinitis. What is their mechanism of action?
Competitive, reversible antagonism or inverse agonism of histamine H1 receptors (Gq protein-coupled receptor)
PERENNIAL allergic rhinitis refers to
Chronic allergic rhinitis
Out of all allergic rhinitis symptoms, what are oral h1-antihistamines not effective for?
Nasal congestion
Because of effects such as sedation and anticholinergic symptoms, these generation of oral antihistamines is preferred over the 1st one.
2nd gen antihistamines for allergic rhinitis
Azelastine hydrochloride and olopatadine hydrochloride are ___________ H1-antihistamines that show faster results (15-30 min) and reduce nasal congestion, itching, sneezing and runny nose. They also have the following side effects:
Intranasal H1 antihistamines
- Taste sensation and somnolence
Diphenydramine, clorpheniramine and hydroxyzine are…
First generation antihistamines
Fexofenadine, loratadine, desloratadine and cetirizine are examples of…
Second generation antihistamines
How do decongestants work, and what symptom do they treat?
They act via α-adrenergic stimulation, causing vascular constriction and reducing nasal blood supply. They only reduce nasal congestion, not other symptoms.
• Can be catecholamines or imidazoline derivatives.
• Faster onset & stronger effect than systemic decongestants.
• No systemic side effects but may cause seizures in children.
• Rebound congestion if used >5 days.
• Recommended for acutely severe rhinitis.
• Help penetration of intranasal corticosteroids/antihistamines.
Topical descongestants
How do oral decongestants compare to topical ones?
Less effective but don’t cause rebound congestion.
• Often combined with antihistamines for acute/chronic rhinitis.
What are the side effects and contraindications of oral decongestants?
• Side effects: Insomnia & irritability
• Normal doses: May worsen hypertension & arrhythmias.
• Overdose risks: Renal failure, psychosis, strokes, seizures.
Avoid in:
• Hypertension, heart disease, seizure disorders, hyperthyroidism, prostatic hypertrophy.
• Those taking MAOIs (risk of hypertensive crisis) —> opt for topical admin.
Most potent drug available against all nasal symptoms, it is used in non-allergic rhinitis, has an effect within 7-8 h
Intranasal corticosteroids (INS)
Intranasal corticosteroids side effects
- Local nasal irritation
- Epistaxis
- Systemic side effects
- Rare septal perforations and Candida overgrowth
This drugs are only used in patients with any type of rhinitis who initially have severe nasal obstruction to decrease nasal edema and allow use of INS (also mention the reason of its limited use)
- Systemic corticosteroids
- Limited because of adverse side effects and limited morbidity of disease
Systemic corticosteroids contraindications and adverse side effects
- Avoid IM injections because of side effects —> aseptic necrosis
- Prolonged use is a risk factor for the development of cataracts and osteoporosis
Montelukast is a ___________ with similar effects to oral antihistamines, it is less effective than INS but relieves all ocular and nasal symptoms such as…
Leukotriene inhibitor
- Congestion, rhinorrhea and sneezing
Although useful in asthma, Montelukast is reserved for patients that are unresponsive or intolerant to other treatments. What is the reason for it?
May produce drug-induced neuropsychiatric events and they are not as effective as intranasal steroids
The intranasal 4% solution of ___________ is effective, and summed to an antihistamine it may be a great reliever of sneezing, itching and rhinorrea
Cromolyn sodium
Children and pregnancy-safe drug dosed 4 times a day in the treatment of allergic rhinitis; it is more effective when dosage starts before onset of symptoms.
Cromolyn sodium
Cromolyn sodium is less effective for the treatment of:
Nasal congestion
This type of drugs (…), which includes Ipratropium, has no systemic effects via intranasal, therefore it is a good option of ________________, while having NO effect on other symptoms
- Anticholinergics
- Perennial rhinitis
What systemic medications help reduce redness, tearing, and itching in allergic eye symptoms?
Oral H1-antihistamines and leukotriene receptor antagonists
When are topical ocular antihistamines used?
• As adjunctive treatment in rhinoconjunctivitis.
• As primary treatment for isolated allergic conjunctivitis.
What is the onset and duration of effect for topical ocular antihistamines?
• Onset: A few minutes.
• Duration: 12–24 hours.
How do intranasal steroids (INSs) help with allergic eye symptoms?
• They reduce intranasal inflammation.
• Inhibit the nasal-ocular reflex triggered by allergens in the nasal mucosa.
• As effective as antihistamines for ocular symptom control.
Allergic rhinitis usual treatment scheme
Oral antihistamines + oral descongestants
This combination of meds is more effective together than given alone in the treatment of allergic rhinitis
INS + intranasal antihistamine
In the treatment of allergic rhinitis, _________ are given to those that don’t respond to the 1st one alone or present severe ocular symptoms
Oral antihistamines + INS
2 years of treatment with this therapy leads to complete tolerance and is effective in seasonal and perennial allergic rhinitis
Allergen immunotherapy
A 28-year-old woman with a 5-year history of allergic rhinitis reports worsening nasal congestion, sneezing, and itchy eyes despite using oral antihistamines and intranasal corticosteroids. Allergen avoidance hasn’t helped. She recently developed mild asthma and experiences insomnia from antihistamines. She asks for a long-term solution. What is the next best step?
Allergen immunotherapy (Subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT))
A patient with chronic nasal obstruction reports poor quality of life due to constant congestion. Exam reveals a significant septal deviation and persistent turbinate swelling unresponsive to meds and immunotherapy. What is the next step?
Surgical intervention
• Septal deviation: Surgery indicated if it affects quality of life
• Turbinate reduction: Consider only if mucosal edema is refractory to pharmacotherapy and immunotherapy
Bilateral, self-limiting conjunctival inflammatory process that occurs in sensitized individuals with no gender difference
Allergic conjunctivitis
How does allergic conjunctivitis begin?
Initiates by allergen binding to IgE on resident mast cells
What’s the difference between seasonal and perennial allergic conjunctivitis?
• Seasonal (hay fever conjunctivitis): More common; linked to pollen exposure during specific seasons.
• Perennial: Related to year-round allergens like animal dander and dust mites.
How common is allergic conjunctivitis and what symptoms are typical?
• Affects 20% of the population.
• 35% of people have allergies; of those, 50% report eye symptoms like itching, redness, and tearing.
Signs and symptoms of SAC
- Ocular itching
- Tearing (watery discharge)
- Chemosis, redness
- Often associated with rhinitis
- Not sight threatening
Differential diagnoses of SAC
- Infective conjunctivitis
- Preservative toxicity
- Medicamentosa
- Dry eye
- PAC, AKC, VKC
Histopathology of SAC
- Mast cell/eosinophil infiltration in conjunctival epithelium and substantial propia
- Mast cell activation
- Upregulation of ICAM-1 on epithelial cells
Laboratory manifestations in seasonal/perennial allergic conjunctivitis
Increased in tears:
- Specific IgE antibody
- Histamine
- Tryptase
- TNF-a
What triggers mast cell degranulation in allergic conjunctivitis?
Antigen cross-linking of IgE bound to FcεRI receptors on mast cells → Degranulation.
What are the two types of mediators released by mast cells?
• Preformed (seconds–minutes): Histamine, tryptase
• Newly synthesized (hours): Arachidonic acid metabolites
What mast cell subtypes are found in the conjunctiva?
• MCt (tryptase only) is the main type in conjunctiva
• MCtc (tryptase + chymase) also exists
• Normally rare, but increased in allergic conjunctivitis
What mediators are found in the tear film of allergic conjunctivitis patients?
IgE, tryptase, histamine, eotaxin, eosinophil cationic protein (ECP)
What does histamine do in allergic conjunctivitis?
• Increases vascular permeability
• Causes smooth muscle contraction, mucus secretion
• Promotes inflammation and leukocyte migration
What cytokines are involved and what do they do?
• IL-4, 5, 6, 13, TNF-α, IL-10, IFN-γ
• Promote eosinophil recruitment, inflammation, and cell activation
How do histamine and cytokines affect conjunctival epithelial cells?
• Activate H1 receptors → calcium mobilization
• TNF-α increases ICAM-1 expression → leukocyte adhesion
Dominant symptom of allergic conjunctivitis
Mild to severe ocular itching
Symptoms like watery discharge, redness, swelling, burning, sensation of fullness in eyes or eyelids, urge to rub eyes, sensitivity to light and blurred vision may be present in…
Allergic conjunctivitis
Periorbital pigmentation due to decreased venous return in skin and subcutaneous tissue
Allergic shiners (periorbital darkening)
Typical findings in allergic conjunctivitis
Conjunctival hyperemia and chemosis with parpebral edema
How is dry eye different from allergic conjunctivitis?
There isn’t presence of itching
Dry eye is mostly caused by foreign objects or anticholinergic meds
How is bacterial conjunctivitis different from allergic conjunctivitis?
Bacterial conjunctivitis
- One-eye presentation
- Palpable preauricular nodes
- Mucoid or purulent discharge
- Morning crusting + difficulty opening eyes
Non-specific ocular symptoms
Tearing, irritation, stinging and burning
Treatment of allergic conjunctivitis is aimed at
Preventing and alleviating symptoms
Interventions that alleviate conjunctival allergy discomfort:
- Avoidance of scratching or rubbing
- Application of cool compresses
- Artificial tears and refrigeration of topical ocular meds
Oral antihistamines considerations when used for eye itch
- 1st generation should be avoided because of reduced tear production
- Topical treatments are more effective together than relieve itching and may be additive to oral
Best treatment for mild to moderate allergic conjunctivitis
Dual-acting topical meds
- Mast cells stabilizing component
- Rapid relieve because of high affinity to H1 receptor
Treatment for severe allergic conjunctivitis
Combination therapy: oral antihistamines + topical meds
Low potency steroids, along with measurement of intra-ocular pressure every 3 months + anual evaluation for cataracts, are used to treat:
Extreme cases of allergic conjunctivitis
Chronically relapsing inflammatory skin disease associated with respiratory allergies
Atopic dermatitis
Name the 2 presentations of atopic dermatitis
- Weeping eczema of early childhood
- Chronic xerosis and lichenified lesions in older people
______ and ______ are typically related to atopic dermatitis, meaning 65% of px with AD present the symptoms of the others
- Allergic rhinitis
- Asthma
Increased prevalence of atopic dermatitis might be due to… (3)
- Increased exposure to pollutants and indoor allergens
- Decline in breastfeeding
- Greater awareness of AD
Risk factors for the development of atopic dermatitis
- Metropolis, black race and higher educational level (eczema)
- Cities with temperate climate
Age of atopic dermatitis symptom onset
3-6 months
Main gene and type of mutation involved in the pathogenesis of atopic dermatitis; it encodes for filaggrin, an essential protein of the epidermal barrier
FGL gene (loss of function)
How does loss-of-function mutations on FGL influence the development of atopic dermatitis?
It allows for increased trans-epidermal loss and entry of allergens, antigens and chemicals, producing a skin inflammatory response
What are the environmental triggers in atopic disease pathogenesis and how do they enter the body?
Triggers include allergens, microbes, pollutants, and irritants.
They penetrate through a damaged epidermal barrier, especially the **stratum corneum and stratum **, which may be compromised by mutations in barrier-related genes
Which disorder involves defects on these genes, and what happens when they are dysfunctional?
• EDC genes: FLG, LOR, LCEs, S100s, SPRRs • Tight junction gene: CLDN1 • Proteases: KLK5, KLK7 • Antiprotease: LEKTI-1
- Atopic dermatitis
- If defective, the skin barrier weakens → increased permeability to allergens and microbes → immune activation.
Which immune cells and mediators are involved in the adaptive response of atopic disease?
• Th2 cells release IL-4 and IL-13 → drive allergic inflammation.
• Chemokines: RANTES and eotaxin → attract eosinophils (Eos).
This leads to chronic allergic inflammation characteristic of atopic diseases.
What role does TSLP play in atopic inflammation?
Damaged skin triggers dendritic cells to release TSLP (thymic stromal lymphopoietin) → promotes Th2 polarization of the immune system and activates mast cells, leading to allergic inflammation.
What is the role of innate immunity in atopic disease?
Innate immunity is activated through pattern recognition receptors like TLRs, CD14, NOD1, NOD2, and genes like DEFB1, IRF2.
These recognize microbes and danger signals, contributing to the dysregulated immune response.
What genetic and immunologic traits are patients with atopic dermatitis predisposed to?
Patients with atopic dermatitis (AD) have a genetic predisposition to develop IgE antibodies to environmental allergens and show overproduction of Th2 cytokines, contributing to eosinophilia.
How does early-onset atopic dermatitis (AD) affect the risk of respiratory allergies?
Onset before 3 months of age increases the risk of developing asthma and rhinoconjunctivitis.
It is linked to a higher incidence and severity of respiratory allergic diseases.
What factors increase the risk of respiratory allergies in patients with AD?
Respiratory allergy risk increases when:
• AD begins before 3 months of age
• Patient has ≥1 atopic family member
How does AD influence asthma severity?
Children with atopic dermatitis tend to have more severe asthma than children without AD, due to systemic immune activation and sensitization through the skin.
How does allergen sensitization through the skin affect respiratory allergies?
Epidermal allergen sensitization can trigger a systemic allergic response, predisposing patients to severe and persistent respiratory allergies.
How does atopic dermatitis progress regarding age?
- Many px. Outgrow the disease by adolescence, in others it becomes less severe
- Some adults present relapses characterized by hand dermatitis (especially if daily activities require repeated hand wetting)
AD associated skin barrier abnormalities
- Increased transepidermal water loss
- Increased levels of endogenous proteolytic enzymes
- Reduced ceramides levels
How does soap use contribute to skin barrier breakdown in atopic dermatitis?
Soap increases skin pH, enhancing endogenous protease activity, which breaks down the skin barrier and increases allergen/microbial penetration.
What external and genetic factors worsen skin barrier damage in AD?
• Exogenous proteases from house dust mites and Staphy aureus
• Lack of protease inhibitors
• Mutation of the FLG gene (Chr 1q21) → ↓ Filaggrin, essential for barrier function
What is the role of filaggrin in atopic dermatitis?
Filaggrin is crucial for epidermal barrier formation. Its deficiency (due to FLG mutation) increases risk for eczema-associated asthma and allergen sensitization.
How does skin allergen exposure in AD affect future allergic disease risk?
Skin allergen sensitization increases the risk of developing respiratory allergies like asthma later in life due to systemic allergic response.
Which cytokines contribute to barrier dysfunction in AD?
• IL-4, IL-13: Downregulate FLG expression
• **IL-22 from Th22 and CD8⁺ T cells**: Regulates genes like FLG, loricrin, and involucrin, worsening barrier abnormalities.
The reduced expression of these tight junctions proteins is observed in atopic dermatitis patients:
- Claudin-1 and 23
Reduced CLDN-1 expression leads to barrier and immune dysfunction
Which barrier-related proteins are decreased in atopic dermatitis?
Filaggrin-2, corneodesmosin, desmoglein-1, desmocollin-1, and transglutaminase-3
↓ Expression = weaker skin barrier
Which enzymes are decreased in AD and what is their effect?
Arginase-1, caspase-14, and γ-glutamylcyclotransferase
↓ Expression leads to reduced natural moisturizing factors → increased water loss
How does increased fatty-acid binding protein expression affect AD?
↑ Expression triggers inflammatory response through eicosanoid signaling, perpetuating skin inflammation.
T/F: AD is diagnosed based on pathognomonic lesions and laboratory parameters
F. Dx is based on presence of major and associated clinical features.
How is the severity of atopic dermatitis assessed?
Using standardized scoring systems like SCORAD (Severity Scoring of AD) and EASI (Eczema Area and Severity Index).
Principal features of AD
- Severe pruritus
- Chronically relapsing course
- Typical morphology and distribution of skin lesions
- History of atopic disease
This symptom is critical for the diagnosis of atopic dermatitis:
Pruritus
(Usually accompanied by dry skin)
What are the 3 types of lesions in atopic dermatitis?
- Acute – erythema, edema, PRURITIC vesicles, serous exudate
- Subacute – scaling, crusting, erythematous and excoriated dry patches
- Chronic – thickened skin, lichenification, excoriated fibrotic papules
This type of AD may present with the 3 types of lesions:
Chronic AD
Body areas involved in infant AD
Face, scalp, extensor surfaces of extremities and infragluteal areas
In cases of infant AD, the diaper area is spared; what should you suspect if you see lesions in that area?
Secondary Candida infection
Where are AD lesions located in older patients?
Flexural folds of extremities
Major features of AD
- Pruritus
- Facial and extensor involvement in infants and children
- Flexural lichenification in adults
- Chronic or relapsing dermatitis
- Personal or family history of atopic disease
Minor features
- Xerosis
- Cutaneous infections
- Nonspecific dermatitis of hands or feet
- Pytiriasis alba
- Nipple eczema
- White dermatographism and delayed blanch response
- Anterior subcapsular cataracts
- Elevated serum IgE levels
T/F. Positive immediate-type allergy skin tests are a major feature of atopic dermatitis.
False, they are a minor feature of AD.
Complicating features of atopic dermatitis:
- Ocular problems
- Hand dermatitis
- Infections
What ocular problems are associated with atopic dermatitis?
• IgE-bearing Langerhans cells (LCs) in conjunctiva → inflammation
• Atopic keratoconjunctivitis (always bilateral): itching, burning, tearing, mucoid discharge
• Associated with eyelid dermatitis & chronic blepharitis → risk of corneal scarring
• May lead to keratoconus (from eye rubbing) and anterior subcapsular cataracts
What are features of hand dermatitis in atopic dermatitis?
• Non-specific, aggravated by repeated wetting
• AD history doubles effect of irritant exposure
• Increases risk in occupations with frequent hand washing
Which infections are AD patients more susceptible to?
• HSV, molluscum contagiosum, HPV
• Risk of eczema herpeticum and eczema vaccinatum
• Often due to defective antimicrobial peptide response
• Dermatophytes and Pityrosporum ovale may worsen AD
What are features of AD with eczema herpeticum (EH)?
• More severe disease & widespread lesions
• Increased eosinophils, IgE, chemokines (TARC, CTACK)
• More likely asthma/inhalant allergies
• Reduced IFN-γ → poor HSV response
• Frequent co-infections with S. aureus or molluscum contagiosum
What is the role of S. aureus in atopic dermatitis?
• Colonizes 90% of AD patients
• Adheres better to inflamed skin via adhesins (e.g. fibronectin, fibrinogen)
• Worsens inflammation and barrier dysfunction
Psychosocial implications of atopic dermatitis
Stimulation of CNS intensify cutaneous vasomotor
Stress-related emotions may exacerbate AD, leading to itching and scratching
Food Ag can exacerbate AD in some patients, resulting in ___________. How can this be avoided?
- Eczematous lesions
- Elimination of certain foods to ameliorate skin disease and decrease basophil histamine release
T/F. Triggers of AD cannot be predicted by allergy testing
T
Relationship btwn aeroallergens and atopic dermatitis
- Exposure to pollen, house-dust mite and animal danders may exacerbate AD
- Intranasally absorbed allergens may produce eczematous skin lesion
- Inhalation or contact may be involved in pathogenesis of AD
- Reducing exposure may improve AD
Which fungi are linked to increased IgE in AD, especially in head and neck? What does improvement with antifungal therapy suggest?
- M. Sympodialis and Trychophyton rubrum
- Improvement indicates a role of fungi in pathogenesis
Almost 50% of AD patients have IgE antibodies against ________ toxins, linking superantigen exposure to histamine release and skin inflammation
Staphylococcal (specifically S. Aureus)
___________ correlate with AD severity and amplify cutaneous inflammation by enhancing allergen-specific IgE synthesis
They also disrupt Treg cell function and induce corticosteroid resistance, worsening AD symptoms.
Superantigens
Autoantigens play a role in chronic AD. What protein in skin keratinocytes has been identified as an IgE-reactive autoantigen?
HOM S 1
Damage in skin induces the release of intracellular antigens, what effect does this have on AD?
It sustains IgE and T cell responses in AD
_________ might act as an auto allergen in some AD patients. How does this relate with M. Sympodialis infection?
Manganese superoxide dismutase
Molecular mimicry with MnSOD from the moo’ yeast could induce cross-reactive sensitization in AD
Abnormal increases in atopic dermatitis (7)
- Synthesis of IgE
- Levels of specific IgE
- Expression of CD23 on B cells and monocytes
- Surface expression of FceRI on antigen-presenting cells in the skin
- Cutaneous T cell attracting chemokine (CTACK and TARCK)
- Levels of monocyte cyclic adenosine monophosphate phosphodiesterase
- IL-10 and PGE2
The secretion of these interleukins and cells plays a major role in AD pathogenesis:
IL4, IL5 and IL13 by T helper type 2 (Th2) cells
Immunoregulatory decreases in AD
- Secretion of IFN-y by Th1 cells
- CD4 and CD25 Tregs after superantigen stimulation
- Secretion of antimicrobial peptides by keratinocytes
What histological findings are seen in normal-appearing AD skin?
Mild epidermal hyperplasia and sparse lymphocytic infiltrate in dermis
What is characteristic of acute eczematous lesions in AD?
Spongiosis (intercellular edema)
Sparse lymphocytes in epidermis
Perivenular lymphocytic infiltrate
Some monocytes in dermis (Eos, basophils and NT may be present)
What defines chronic lichenfield lesions in AD?
Hyperkeratosis in epidermis
Increased number of epidermal cutaneous lymphocytes (Langherhans)
Dermal infiltrate of monocytes/macrophages
What immune markers are identified via immunohistochemistry in AD lesions?
• CD3, CD4 T cells
• CD45RO (memory T cells)
• CD25, HLA-DR (activation markers)
• CLA (cutaneous lymphocyte antigen)
What is the role of keratinocytes in AD pathogenesis?
Produce TSLP —> Activates DC to prime LTh2 differentiation
The production of these antimicrobial peptides is reduced in atopic dermatitis:
Defensins and cathelicidines
What helps restore keratinocyte function?
Vitamin D → supports antimicrobial peptide production (preventive role)
Cytokine expression in acute vs chronic lesions in AD
Acute: high IL4, IL5 and IL13
Chronic: IL5 and eosinophil infiltration, low IL4 and increased IL12 and IFN-y
IL-31 overexpression and its production by superantigens is linked to…
Pruritus
Role of TSLP in AD
TLSP-driven Th2 cytokines contribute to skin barrier dysfunction and microbial colonization
What type of immune response is primarily involved in AD: Th1 or Th2?
Th2. AD is driven by allergen-induced, IgE-mediated, Th2-dominant responses.
What are the two phases of IgE-dependent reactions in AD?
• Immediate-type reaction: Mast cells release mediators → pruritus & erythema.
• Late-phase reaction: Persistent symptoms and chronic inflammation.
What cytokines are expressed by T lymphocytes during the late-phase reaction in AD?
A: IL-3, IL-4, IL-5, GM-CSF (but not IFN-γ).
How do Langerhans cells (LCs) contribute to sustained inflammation in AD?
• LCs in AD skin express IgE
• They are more efficient at presenting allergens, promoting persistent local T cell activation
What is the initial maintenance treatment for atopic dermatitis?
Twice-daily emollient application and once-daily bathing in lukewarm water (5–10 min) using a soap-free cleanser.
What should be done if there is no flare-up in a patient with atopic dermatitis?
Continue with maintenance treatment only
What are the treatment steps for a mild flare-up of atopic dermatitis?
• Continue maintenance treatment
• Add twice-daily low to medium potency topical steroid
What is the next step if a mild flare-up does not respond to treatment?
Start treatment for a moderate flare-up.
What is the treatment approach for a moderate flare-up of atopic dermatitis?
• Continue maintenance
• Twice-daily medium to high potency topical steroid
• Twice-daily topical calcineurin inhibitor
• Optional: Crisaborole (Eucrisa), dilute bleach baths (2x/week), wet wrap therapy
Q: What should be done if a moderate flare-up responds to AD treatment?
Q: What is the next step if a moderate flare-up does not respond to AD treatment?
- Switch to treatment for a mild flare-up.
- Start treatment for a severe flare-up.
What is the treatment for a severe flare-up of atopic dermatitis?
• Continue maintenance
• Twice-daily high potency topical steroid
• Twice-daily topical calcineurin inhibitor
• Twice-weekly dilute bleach baths
• Wet wrap therapy
• Consider specialist referral
What clinical tool is recommended to assess severity of atopic dermatitis flare-ups?
The Scoring Atopic Dermatitis (SCORAD) index, which evaluates body area affected, lesion intensity, and symptoms.
What are the core treatments if AD is not severe?
Eliminate exacerbating factors
• Address psychosocial/QOL issues
• Education and hydration
• Moisturizers
• Low to mid potency topical corticosteroids
• Topical calcineurin inhibitors
• Topical PDE4 inhibitor
• Anti-infective and anti-pruritic therapy
• Written care plan
What advanced treatments are considered in severe or resistant AD?
• Culture & sensitivity (r/o MRSA)
• Wet wrap therapy
• Dupilumab
• Hospitalization
• UV light therapy
• Systemic immunosuppressives
What therapy is suggested for maintenance in responsive cases?
Topical immunomodulators
What condition should be ruled out with persistent skin lesions in AD?
MRSA (via culture and sensitivity)
Why is skin hydration essential in atopic dermatitis?
Because AD has increased transepidermal water loss and reduced water-binding capacity due to decreased ceramide levels
What is the recommended bathing technique for hydrating AD skin?
Soak in warm water for 10 minutes and immediately after apply an occlusive agent to prevent evaporation
How does frequent bathing affect AD during flares?
Múltiple daily baths are more effective than infrequent bathing technique
Affordable and effective moisturizers for AD
Vegetable oil and petroleum jelly
What type of moisturizer is the most occlusive and effective?
Ointments - better delivery and less water content
What is the role of alpha-hydroxy acids in moisturizers?
Improve skin barrier, increase dermal collagen and help reverse the atrophy from topical corticosteroids
What is required for optimal skin barrier repair in AD?
Equivocar ratio of ceramides, colesterol and fatty acids
What is the recommended principle for choosing TCS?
Use the lowest effective potency for the shortest duration
Common side effects of topical corticosteroids use in the long term?
Skin thinning, telangiectasias, hypopigmentation, acne, striae and infections
Why must low-potency TCS be used on the face or folds?
These areas are more sensitive and prone to side effects like perioral dermatitis or steroid addiction
This treatment is effective for AD cases and has advantages such as: no skin atrophy, safe for face and folds, good for steroid insensitive px, and can reduce flare frequency
Topical calcineurin inhibitors (TCIs)
Overactive enzyme in AD that contributes to ceramide deficiency
M deacyclase, which competes with ceramide-producing enzymes
Why are systemic corticosteroids avoided in AD?
They cause rebound flares after discontinuation
What are side effects of topical calcineurin inhibitors?
Transient burning, especially on inflamed skin
What strength of tacrolimus is used in adults vs children with AD?
- Adults 0.1%
- Children 0.03%
