79: Rosacea Flashcards
What is the hallmark symptom of rosacea?
The hallmark of rosacea is flushing.
How does the prevalence of rosacea differ between genders?
Rosacea affects women more than men at a ratio of 3:1.
What are the common clinical findings associated with rosacea?
Common clinical findings include:
- Flushing
- Transient erythema
- Persistent erythema
- Telangiectasia
- Papules and pustules
- Phymatous changes
- Edema
- Pain, stinging or burning, pruritus (rarely)
What is the typical age of onset for rosacea in women and men?
The normal age of onset for rosacea is 35 to 45 years in women and 45 to 55 years in men.
What is persistent erythema and how long does it last?
Persistent erythema is characterized by erythema that lasts for at least 3 months and is caused by vasodilation of arterioles or capillaries, leading to increased perfusion and redness.
What are the characteristics of rhinophyma in rosacea?
Rhinophyma is characterized by:
- Persistent, firm, nonpainful, nonpitting swelling of the tissue of the nose.
- Occurs almost 20 times more often in male patients.
- Initially appears in the skin of the alae nasi and at the distal end of the nose as dilated patulous follicles.
- Resembles a “peau d’orange” appearance of the nose.
What is the likely diagnosis for a patient with persistent erythema lasting over 3 months?
The likely diagnosis is persistent erythema associated with rosacea. It is caused by vasodilation of arterioles or capillaries, leading to increased perfusion and redness.
What are the key clinical findings associated with rosacea, and how do they vary by age and gender?
Key clinical findings of rosacea include:
- Flushing
- Transient erythema
- Persistent erythema
- Telangiectasia
- Papules and pustules
- Phymatous changes
- Edema
- Pain, stinging, or burning (rarely)
Variations by age and gender:
- Younger patients: Flushing and erythema are often the first symptoms.
- Older adults: Telangiectasia is more common.
- Male patients: More likely to develop rhinophyma.
How does the progression of rosacea manifest, and what triggers can exacerbate the condition?
The progression of rosacea is described as a ‘crescendo’ manifestation, characterized by:
- Increased numbers of flushes after exposure to trigger factors.
Common triggers include:
- Temperature changes
- Spicy foods
- Alcohol consumption
- Stress
- Sun exposure
What is rhinophyma, and how does it differ in presentation between male and female patients?
Rhinophyma is a form of phymata characterized by:
- Persistent, firm, nonpainful swelling of the tissue of the nose.
- Occurs almost 20 times more often in male patients than in female patients.
- Initially appears in the skin of the alae nasi and at the distal end of the nose as dilated patulous follicles.
- The appearance resembles a ‘peau d’orange’ due to prominent humps and grooves.
In contrast, female patients are less likely to develop this condition, and when they do, it may present less severely.
What are the characteristics of the fibrous form of rhinophyma?
- Asymmetry of nasal swelling due to diffuse hyperplasia of connective tissue and sebaceous hyperplasia.
- Large actinic comedones can be prominent, referred to as “potato nose.”
What is flushing in rosacea and what are its common triggers?
Flushing in rosacea is a pathophysiological neurovascular process experienced for more than 5-10 minutes due to neuropeptide release. Common triggers include:
- Heat
- Hot steam (kitchen, beverages)
- Red wine and certain alcoholic beverages
- Medications (e.g., Niacin, topical glucocorticoids)
- Noxious cold
- Hormonal changes (menopause)
How does blushing differ from flushing in rosacea?
Blushing is almost exclusively induced by emotionally stressful situations and is not triggered by spicy food or other rosacea factors. It has a pinkish appearance and is characterized by:
- Sudden transient redness (mostly <5 mins)
- Involuntary redness of the peripheral cheeks, ears, neck, and chest
- Often starts in early adulthood
- “Pale islands” in between salmon-like redness are characteristic of blushing.
What is telangiectasia and its significance in rosacea?
Telangiectasia is a permanent visible dilated blood vessel on the skin or mucosal surface. It is classified as a primary feature of rosacea and can coexist with or without other rosacea features.
What are papules and pustules in the context of rosacea?
Papules can occur with or without pustules and can develop into cysts and nodules, referred to as rosacea conglobata.
What subtype of rosacea is characterized by asymmetric nasal swelling with a ‘potato nose’ appearance?
This is fibrous rhinophyma, a subtype of phymatous rosacea. It is characterized by diffuse hyperplasia of connective tissue and sebaceous hyperplasia, often with large actinic comedones.
What physiological mechanism underlies flushing triggered by hot beverages and red wine?
Flushing in rosacea is a neurovascular process caused by neuropeptide release, leading to prolonged vasodilation and erythema.
What are the key differences between flushing and blushing in rosacea, and how do their triggers differ?
Flushing:
- Pathophysiological neurovascular process lasting more than 5-10 minutes.
- Associated with stinging, burning pain.
- Can occur with persistent erythema, papules, pustules, or phymata.
- Common triggers include heat, hot steam, red wine, certain medications, noxious cold, and hormonal changes.
Blushing:
- Induced by emotionally stressful situations, not by food or other triggers.
- Characterized by sudden transient pinkish redness, mostly lasting <5 minutes.
- Occurs on rosacea-atypical sites and often starts in early adulthood.
What are the clinical implications of the different forms of rhinophyma in rosacea?
Fibrous Form:
- Asymmetry of nasal swelling due to connective tissue and sebaceous hyperplasia.
- Prominent large actinic comedones, known as “potato nose.”
Fibroangiomatous Form:
- Nose appears copper to dark red, grossly enlarged with ectatic veins and pustules.
Gnathophyma:
- Involves the central chin.
Otophyma:
- Involves lower half of the ears and lobes.
Clinical Implications:
- Higher incidence of basal and squamous cell carcinomas in rhinophyma-affected skin compared to nonlesional skin.
What systemic symptoms may accompany flushing in rosacea, and what is their clinical significance?
Flushing in rosacea may be accompanied by:
- Wheezing
- Diarrhea
- Headache
Clinical Significance:
- These symptoms indicate a potential role of nerves and mast cells in the flushing process.
- The release of gastrin hormonal mediators from the GI tract can lead to frequent facial flushing, persistent vasodilation, and telangiectasias, highlighting the systemic nature of rosacea.
How does the presence of telangiectasia relate to the diagnosis of rosacea?
Telangiectasia is characterized by:
- Permanent visible dilated blood vessels on the skin or mucosal surface.
- Classified as a primary feature of rosacea.
- Can coexist with or without other rosacea features, aiding in the diagnosis of the condition.
What are the potential complications associated with papules and pustules in rosacea?
Papules and Pustules:
- Can occur with or without pustules.
- May develop into cysts and nodules, known as rosacea conglobata.
Potential Complications:
- Risk of secondary infections due to pustule formation.
- Cosmetic concerns and psychological impact due to visible lesions.
- Possible scarring if cysts or nodules develop.
What is the typical distribution and characteristics of papules in rosacea?
Papules in rosacea typically have a centrofacial distribution and are characterized by a lack of comedones and scales. They are mostly small, low pain, dome-shaped, and red in color, often appearing as multiples. Lesions tend to occur symmetrically on centrofacial skin but can extend to the neck, chest, and forehead.
What are the ocular manifestations associated with rosacea?
Ocular rosacea involves the eyelids, eyelashes, or eyes and can lead to blindness if left untreated. It occurs in 25% of patients with rosacea and 50% of those with papules and pustules. Patients may experience a ‘foreign body’ sensation, itching, burning, stinging in the eyes, and grittiness around the eyes, along with red, swollen, crusty, or scaly margins. Telangiectasia of the conjunctiva may also occur.
What are the characteristics of Lupoide or Granulomatous rosacea?
Lupoide or Granulomatous rosacea is characterized by:
- Chronic, therapy-resistant lesions, 0.2 to 0.3 cm in size, often follicular, brown-red or red papules.
- Development of granulomatous plaques and nodules on the cheek, forehead, or chin.
- Skin appears thickened and erythematous.
- Involvement of centrofacial and perioral regions of the face.
- Possible involvement of upper and lower eyelids.
- Rare cases observed after treatment with infliximab or etanercept.
What are the clinical findings associated with Rosacea fulminans?
Rosacea fulminans (Pyoderma faciale-O’Leary) is characterized by:
- Predilection for postadolescent women (20-30 years old), particularly pregnant women.
- Associations with seborrheic dermatitis and Crohn’s disease.
- Clinical findings develop within days to weeks, affecting the complete face, particularly the chin, cheeks, forehead, and nose.
- Lesions present as papulopustules and coalescent purplish nodules, with associated abscesses forming confluent fistulae.
- Reddish to violaceous firm swelling of the face.
- Patients report an oiliness of the skin before the outbreak.
- Systemic symptoms such as fatigue, fever, arthralgia, and anemia are usually absent.
- When controlled, the disease does not recur.
What triggers Halogen rosacea and what are its symptoms?
Halogen rosacea is triggered by the ingestion of iodides or bromides. Symptoms can include:
- Development of erythematous pustules.
- Formation of vegetative nodules.
- In extreme cases, fungating nodules, small to large blisters, exudative plaques, ulcers, and circumscribed panniculitis.
What differentiates rosacea papules from acne?
Rosacea papules lack comedones and scales, which are characteristic of acne.
What subtype of rosacea involves the eyelids, eyelashes, or eyes, and what is the risk if untreated?
This is ocular rosacea, which involves the eyelids, eyelashes, or eyes. If untreated, it bears the risk of blindness.
What rare subtype of rosacea is indicated by therapy-resistant, brown-red papules on the cheeks and forehead?
This indicates lupoid or granulomatous rosacea, characterized by chronic, therapy-resistant papules that can develop into granulomatous plaques.
What are the clinical features of papules in rosacea and their typical distribution on the face?
- Papules in rosacea are mostly small, low pain, dome-shaped, and red in color, appearing as multiples.
- They tend to occur symmetrically on centrofacial skin but can extend to the neck, chest, and forehead.
- There is a lack of comedones and scales associated with these lesions.
What is the significance of forehead rosacea in relation to male pattern baldness and UV radiation?
- Forehead rosacea almost exclusively develops in patients with male pattern baldness.
- This supports the concept that UV radiation is a trigger factor for rosacea.
What are the symptoms and potential complications of ocular rosacea if left untreated?
- Ocular rosacea involves the eyelids, eyelashes, or eyes, and can lead to blindness if left untreated.
- Symptoms include a ‘foreign body’ sensation, itching, burning, stinging in the eyes, and grittiness around the eyes.
- There may be red, swollen, crusty, or scaly margins, and telangiectasia of the conjunctiva may occur.
Describe the characteristics and clinical implications of granulomatous rosacea. What are the potential treatment challenges?
- Granulomatous rosacea presents as chronic, therapy-resistant, 0.2 to 0.3 cm sized, often follicular, brown-red or red papules that can develop into epithelioid (lupoid) plaques and nodules on the face.
- The skin appears thickened and erythematous, affecting centrofacial and perioral regions.
- Treatment challenges include its resistance to therapy and the potential involvement of eyelids in some cases.
What are the clinical findings and systemic symptoms associated with rosacea fulminans, and how does it differ from other forms of rosacea?
- Rosacea fulminans is characterized by papulopustules, coalescent purplish nodules, and associated abscesses that can drain serous or mucoid discharge.
- It typically affects postadolescent women, particularly pregnant women, and is associated with seborrheic dermatitis and Crohn’s disease.
- Systemic symptoms such as fatigue, fever, arthralgia, and anemia are usually absent, and when controlled, the disease does not recur.
What are the potential sources that can lead to persistent edema in rosacea?
Potential sources include:
- Citrus-flavored soft drinks
- Seafood
- Diagnostic radiocontrast media
- Pool disinfectants
- Certain topical antiseptics
- Permanent hair wave formulations
- Vitamin preparations and medications (e.g., Thyroid medication, chemotherapeutics)
What distinguishes steroid rosacea from other forms of rosacea?
Steroid rosacea is characterized by:
- Complexion changes to a deep flaming red.
What are the potential sources that can lead to persistent edema in rosacea?
Potential sources include:
- Citrus-flavored soft drinks
- Seafood
- Diagnostic radiocontrast media
- Pool disinfectants
- Certain topical antiseptics
- Permanent hair wave formulations
- Vitamin preparations and medications (e.g., Thyroid medication, chemotherapeutics)
What distinguishes steroid rosacea from other forms of rosacea?
Steroid rosacea is characterized by:
- Complexion changes to a deep flaming red or copper-red covered by a network of telangiectases.
- Atrophic skin with patches of scales, follicular papulopustules, nodules, and secondary comedones.
- Symptoms are restricted to the area of corticosteroid application.
- Patients report severe discomfort and nagging pain sensation.
How does gram-negative rosacea differ from papulopustular rosacea?
Gram-negative rosacea is differentiated from papulopustular rosacea by:
- Prolonged treatment with topical or systemic antibiotics that covered gram-positive bacteria, leading to the selection of gram-negative pathogens.
- Presence of minuscule yellow pustules on a preexisting or newly formed erythema background.
- Requires different therapeutic approaches due to the underlying pathogen.
What genetic factors are associated with an increased risk of developing rosacea?
Genetic factors associated with rosacea include:
- Positive family history increases chances of developing rosacea.
- Null mutation polymorphisms in the glutathione S-transferase (GST) gene indicating increased oxidative stress.
- Two single nucleotide polymorphisms (SNPs) related to butyrophilin-like 2 (BTN2L) and human leukocyte antigen (HLA)-DRA loci.
What is the clinical significance of the TACR3 gene in rosacea?
The TACR3 gene encodes a tachykinin receptor subtype that responds to substance P family members, which is significant because:
- Substance P is a neuropeptide involved in neurogenic inflammation, flare, and edema in rosacea.
What are the characteristics of persistent edema in rosacea?
Persistent edema in rosacea is characterized by:
- Hard, nonpitting swellings mainly in the caudal half of the face (forehead, eyelids, cheeks, nose, and glabella).
- Absence of systemic reactions.
- Tendency to become chronic, with flare-ups and periods of partial regression.
A patient develops erythematous pustules and vegetative nodules after ingesting iodides. What is the likely diagnosis?
The likely diagnosis is halogen rosacea, caused by ingestion of iodides or bromides.
A patient with rosacea reports severe discomfort and nagging pain in areas of corticosteroid application. What subtype of rosacea is this?
This is steroid rosacea, characterized by deep red complexion, telangiectases, and atrophic skin with follicular papulopustules.
A patient with rosacea develops minuscule yellow pustules on a newly formed erythema background after prolonged antibiotic use. What is the likely condition?
The condition is gram-negative rosacea, caused by prolonged antibiotic treatment selecting gram-negative pathogens.
A patient with rosacea has hard, nonpitting swellings on the cheeks and glabella. What is this condition, and how does it differ from Morbihan disease?
This is persistent edema of rosacea, characterized by chronic, nonpitting swellings. Unlike Morbihan disease, systemic reactions are absent.
A patient with rosacea has a family history of the condition. What genetic polymorphisms are associated with increased risk?
Polymorphisms in the glutathione S-transferase (GST) gene, BTN L2, and HLA-DRA loci are associated with increased risk of rosacea.
A patient with rosacea has increased oxidative stress. What genetic mutation might explain this?
A null mutation polymorphism in the glutathione S-transferase (GST) gene is associated with increased oxidative stress in rosacea.
A patient with rosacea has elevated levels of substance P. What role does this neuropeptide play in the disease?
Substance P is involved in neurogenic inflammation, flare, and edema in rosacea.
What are the potential sources that can lead to persistent edema in rosacea, and how does the condition typically respond after elimination of exposure?
Potential sources include:
- Citrus-flavored soft drinks
- Seafood
- Diagnostic radiocontrast media
- Pool disinfectants
- Certain topical antiseptics
- Permanent hair wave formulations
- Vitamin preparations and medications (e.g., Thyroid medication, chemotherapeutics)
The condition typically improves in 4-6 weeks after elimination of the exposure.
How does steroid rosacea present, and what are the common symptoms reported by patients?
Steroid rosacea presents with:
- Complexion changes to a deep flaming red or copper-red covered by a network of telangiectases.
- Atrophic skin develops patches of scales, follicular papulopustules, nodules, and secondary comedones.
- Symptoms include severe discomfort and nagging pain sensation, and it is restricted to the area of corticosteroid application.
What distinguishes gram-negative rosacea from papulopustular rosacea, and what are the key characteristics of gram-negative rosacea?
Gram-negative rosacea is distinguished from papulopustular rosacea by:
- Prolonged treatment with a topical or systemic antibiotic that covered gram-positive bacteria, which selects for gram-negative pathogens.
- Key characteristics include:
- Miniscule yellow pustules on a preexisting or newly formed erythema background.
- Requires differentiation from papulopustular rosacea due to differences in therapy.
What genetic factors are associated with an increased risk of developing rosacea, and what role does oxidative stress play?
Genetic factors associated with an increased risk of developing rosacea include:
- Positive family history.
- Null mutation polymorphisms in the glutathione S-transferase (GST) gene, indicating increased oxidative stress.
- Two single nucleotide polymorphisms (SNPs) found in patients with rosacea encode for butyrophilin-like 2 (BTNL2) and human leukocyte antigen (HLA)-DRA loci, which are involved in inflammatory responses.
What is the clinical significance of the TACR3 gene in relation to rosacea, and how does it relate to neurogenic inflammation?
The TACR3 gene encodes a tachykinin receptor subtype that responds to substance P family members. Substance P is a neuropeptide involved in neurogenic inflammation, flare, and edema in rosacea. This suggests that variations in the TACR3 gene may contribute to the inflammatory processes observed in rosacea patients.
What are some common environmental trigger factors associated with rosacea?
Common environmental trigger factors for rosacea include:
- Heat (rarely, noxious cold)
- UV radiation
- Spicy food
- Certain alcoholic beverages (red wine more than white wine)
- Stress
- Microbial infestation (e.g., Demodex mites)
How do microorganisms, particularly Demodex folliculorum, relate to rosacea?
Demodex folliculorum is a commensal microorganism found on human and animal skin, predominantly in oily skin near the pilosebaceous glands. It is increased in some patients with rosacea, especially those with:
- Phymata
- Papules and pustules
The exact role of Demodex mites in rosacea pathophysiology is still unclear, with potential candidates for involvement including Bacillus oleronius, proteases, or chitins.
What is the role of ultraviolet radiation in the pathophysiology of rosacea?
Ultraviolet (UV) radiation is a significant trigger for rosacea, with the following implications:
- Patients behind glass shields develop asymmetric rosacea erythema and flushing, indicating a role for UVA.
- UVB triggers TRP vanilloid type 4 (TRPV4) activation on keratinocytes, which is increased in patients with chronic photodermatitis and rosacea.
- UV radiation can induce neuroinflammation, endoplasmic reticulum stress, and innate immune responses, contributing to skin fibrosis or solar elastosis, characteristics of rosacea.
What are the reported incidences of various triggers for rosacea according to the table provided?
The reported incidences of various triggers for rosacea are as follows:
| Trigger | Reported Incidence (%) | Putative Receptor or Pathway |
|—————————-|————————|—————————————|
| Sun exposure | 81 | NALP3, TLR-2, TRPV4 |
| Emotional stress | 79 | NALP3, TLR-2, TRPV1 |
| Hot weather | 75 | TRPV1, TRPV2 |
| Wind | 57 | NALP3, TLR-2, TRPV(?) |
| Heavy exercise | 56 | NALP3, TLR-2, TRPV1 |
| Alcohol consumption | 52 | NALP3, TLR-2, TRPV1 |
| Hot baths | 51 | TRPV1 |
| Cold weather | 46 | TRPA1 |
| Spicy foods | 45 | TRPV1 |
| Humidity or osmotic changes | 44 | TRPV4 |
| Indoor heat | 41 | TRPV1 |
| Certain skin-care products | 41 | NALP3, TLR-2, TRPA1 |
| Heated beverages (steam) | 36 | TRPV1 |
| Certain cosmetics | 27 | NALP3, TLR-2, TRPA1 |
| Medications | 15 | NALP3, TLR-2, TRPV(?) |
| Microorganisms | NR | NALP3, TLR-2 |
| Garlic, mustard oil | NR | TRPA1 |
| Noxious heat (52 °C) | NR | TRPA1 |
A patient with rosacea has comorbid Crohn’s disease. What shared genetic susceptibility might explain this association?
The shared susceptibility to the HLA-DRA locus may explain the association between rosacea and Crohn’s disease.
A patient with rosacea has increased cathelicidin levels. What metabolic diseases might this patient also be at risk for?
The patient may be at risk for diabetes, hypertension, dyslipidemia, and coronary artery disease.
A patient with rosacea reports frequent flushing after sun exposure. What molecular pathway is likely involved?
UV radiation triggers TRPV4 activation on keratinocytes, leading to neuroinflammation and innate immune responses.
A patient with rosacea has increased Demodex folliculorum density. What lesions are commonly associated with this microorganism?
Demodex folliculorum is commonly associated with papulopustular lesions in rosacea.
A patient with rosacea reports increased erythema after using certain skin-care products. What receptor might be involved?
NALP3 and TLR-2 receptors may be involved in the inflammatory response triggered by certain skin-care products.
What are the common environmental trigger factors associated with rosacea and their potential mechanisms of action?
Common environmental trigger factors for rosacea include:
1. Heat (rarely, noxious cold)
2. UV radiation
3. Spicy food
4. Certain alcoholic beverages (red wine more than white wine)
5. Stress
6. Microbial infestation (e.g., Demodex mites)
These triggers can activate transient receptor potential (TRP) ion channels, such as TRPV1 and TRPA1, which are involved in the sensation of temperature changes and may contribute to the pathophysiology of rosacea.
How do microorganisms, particularly Demodex folliculorum, relate to the pathophysiology of rosacea?
Demodex folliculorum is a commensal organism found predominantly in oily skin near the pilosebaceous glands. Its increased presence in some rosacea patients, especially those with papules and pustules, suggests a potential role in the disease’s pathophysiology. The exact mechanisms by which Demodex mites contribute to rosacea are still unclear, but candidates for involvement include substances they produce, such as Bacillus oleronius, proteases, or chitins.
What is the significance of UV radiation in the context of rosacea triggers?
UV radiation is a well-accepted trigger for rosacea, with both UVA and UVB playing roles in symptom induction. Patients exposed to UV radiation may develop asymmetric rosacea erythema and flushing. UVB specifically triggers TRP vanilloid type 4 (TRPV4) activation in keratinocytes, which is increased in patients with chronic photodermatitis and rosacea, indicating a molecular pathway through which UVB may induce rosacea symptoms.
What are the primary sources of proinflammatory mediators in the mechanisms of rosacea disease?
The primary sources of proinflammatory mediators include:
- Keratinocytes: Release cathelicidin, VEGF, and endothelin-1.
- Endothelial cells: Produce nitric oxide and pituitary adenylate cyclase activating peptide (PACAP).
- Mast cells: Release cathelicidin, MMP, and TNF-alpha.
- Macrophages: Secrete interferon-gamma, TNF, MMP, IL-25, TH1 cells, and TH17 cells.
How do environmental triggers contribute to the mechanisms of rosacea?
Environmental triggers such as heat, noxious cold, spicy food, ethanol, and pH changes can activate sensory nerves, leading to the release of vasoactive and proinflammatory neuromediators. This process contributes to neurogenic inflammation and the symptoms of rosacea.
What role do neuropeptides play in the pathophysiology of rosacea?
Neuropeptides, such as Substance P and PACAP, are potent inducers of edema and vasodilation, which are fundamental to the flushing and erythema observed in rosacea. They are released from sensory nerves activated by various trigger factors.
What is the significance of Toll-Like receptors (TLRs) in rosacea?
Toll-Like receptors (TLRs), particularly TLR-2, are involved in the upregulation and activation of the innate immune peptide cathelicidin via KLK-5. This process contributes to erythema, immune response, and angiogenesis through the release of serine proteases, MMPs, cytokines, chemokines, and the proliferation of endothelial cells.
How does skin barrier dysfunction relate to rosacea symptoms?
Skin barrier dysfunction in rosacea is characterized by increased transepidermal water loss (TEWL) and a rise in facial skin pH. This dysfunction leads to enhanced epidermal ‘leakage’, allowing access for microbes, and an alkaline pH that enhances enzyme activity, contributing to the inflammatory processes in rosacea.
A patient with rosacea has upregulated TLR-2 expression. What downstream effects does this have?
TLR-2 upregulates cathelicidin via KLK-5, leading to erythema, immune response, and angiogenesis.
A patient with rosacea has increased transepidermal water loss (TEWL). How does this contribute to the disease?
Increased TEWL leads to enhanced epidermal ‘leakage,’ allowing microbial access and contributing to skin barrier dysfunction.
A patient with rosacea has elevated kallikrein (KLK) activity. What inflammatory responses are mediated by KLK-5?
KLK-5 activates LL-37, leading to erythema, cytokine release, and angiogenesis.
What role do keratinocytes play in the mechanisms of rosacea disease progression?
Keratinocytes release proinflammatory mediators such as cathelicidin, VEGF, and endothelin-1, which contribute to the inflammatory processes in rosacea.
What leads to enhanced epidermal ‘leakage’ in rosacea?
Increased transepidermal water loss (TEWL) allows microbial access and contributes to skin barrier dysfunction.
What inflammatory responses are mediated by KLK-5 in rosacea?
KLK-5 activates LL-37, leading to erythema, cytokine release, and angiogenesis.
What role do keratinocytes play in rosacea disease progression?
Keratinocytes release proinflammatory mediators such as cathelicidin, VEGF, and endothelin-1, contributing to the inflammatory response.
How do sensory nerves contribute to the inflammatory response in rosacea?
Sensory nerves release vasoactive and proinflammatory neuromediators in response to triggers like heat and spicy food, leading to neurogenic inflammation.
What is the significance of Toll-Like Receptors (TLRs) in rosacea?
TLRs, particularly TLR-2, are involved in the upregulation of innate immune responses, including the release of cathelicidin and other inflammatory mediators.
What are the effects of increased transepidermal water loss (TEWL) in rosacea?
Increased TEWL leads to enhanced epidermal ‘leakage’, allowing microbial access and contributing to skin barrier dysfunction.
How do neuropeptides influence the symptoms of rosacea?
Neuropeptides like Substance P and PACAP induce edema and vasodilation, key mechanisms underlying flushing and erythema.
What are the components of the inflammasome involved in rosacea?
The inflammasome consists of NALP3, Caspase-1, and ASC.
What are the effects of inflammasome activation in rosacea?
Inflammasome activation results in neutrophil chemotaxis, IL-1 & TNF-mediated inflammation amplification, and Prostaglandin E2 synthesis.
How do T and B lymphocytes contribute to adaptive immunity in rosacea?
CD4+ T cells are more prevalent than CD8+ T cells, with dominance of CD4+ TH1 and TH17 cells, and elevated TH1 and TH17 cytokines.
What role do TH17 cells play in rosacea?
TH17 cells induce VEGF, promoting angiogenesis, and are associated with T-cell immunosuppression after infections or therapies.
What is the significance of immunologic tolerance in rosacea?
Immunologic tolerance is preserved in rosacea, indicated by high numbers of tolerogenic T cells, influencing disease pathophysiology.
What other molecules are involved in the pathophysiology of rosacea?
Other important molecules include Endr1 and IL-18, supporting the role of TH1 immune responses, ROS molecules, and angiogenesis.
What inflammasome component mediates IL-1β release in rosacea?
The NALP3 inflammasome mediates IL-1β release.
What role do TH17 cells play in rosacea?
TH17 cells induce VEGF, promoting angiogenesis.
What immune cells are likely involved in VEGF-mediated angiogenesis in rosacea?
TH17 cells and neutrophils are involved in VEGF-mediated angiogenesis.
What is the role of the inflammasome in rosacea?
The inflammasome orchestrates IL-1 cleavage and activation, leading to neutrophil chemotaxis and inflammation amplification.
What are the clinical implications of cytokine profiles in rosacea?
Elevated TH1 and TH17 cytokines indicate a strong inflammatory response, guiding therapeutic strategies.
What role does Protease-Activated Receptor-2 (PAR-2) play in rosacea?
PAR-2 induces neuroinflammation and cytokine release, recruiting immune cells to inflammation sites.
How does TLR-2 influence the immune response in rosacea?
TLR-2 increases KLK-5 expression, activating cathelicidin and contributing to inflammation and angiogenesis.
What is the significance of matrix metalloproteinases (MMPs) in rosacea?
Increased MMP-2 and MMP-9 contribute to skin degeneration and inflammation by activating KLK-5.
What environmental triggers activate sensory nerves in rosacea?
Triggers include heat, noxious cold, exercise, spicy food, and alcohol.
How does immune system dysregulation contribute to rosacea symptoms?
Dysregulation leads to increased inflammation and vascular permeability, causing flushing and skin irritation.
What role does MMP-9 play in rosacea?
MMP-9 activates KLK-5, leading to LL-37 activation and contributing to inflammation and angiogenesis.
What receptor is likely activated when a rosacea patient flushes after spicy food?
TRPV1 is likely activated, leading to neurogenic inflammation.
What inflammatory mediators are released due to increased PAR-2 expression?
PAR-2 activation leads to the release of IL-1, TNF, and MMPs.
What symptoms might elevated Substance P cause in rosacea?
Substance P can cause vasodilation, edema, and painful burning sensations.
What microbial products might activate TLR-2 in rosacea?
Microbial products from Bacillus oleronius may activate TLR-2.
What symptoms might elevated endothelin-1 (ET-1) contribute to in rosacea?
Elevated ET-1 levels contribute to vasodilation, flushing, and erythema.
What role does IL-6 play in rosacea?
IL-6 contributes to inflammation, angiogenesis, and immune cell recruitment.
What environmental triggers might activate TRPA1 channels in rosacea?
TRPA1 channels can be activated by noxious cold, irritants, and certain chemicals.
What symptoms might elevated CGRP cause in rosacea?
CGRP can cause vasodilation, flushing, and pain.
What pathological changes might increased TGF-β induce in rosacea?
TGF-β contributes to fibrosis and angiogenesis.
What mediators are released by increased mast cell activity in rosacea?
Mast cells release VEGF, TNF-α, and MMPs, contributing to angiogenesis and inflammation.
What cellular damage might elevated ROS cause in rosacea?
Elevated ROS levels can cause oxidative stress, leading to inflammation and tissue damage.
What symptoms might increased TRPV1 expression cause in rosacea?
Increased TRPV1 expression can lead to painful burning sensations and vasodilation.
What triggers might exacerbate elevated LL-37 levels in rosacea?
Triggers such as heat, UVB, and irritants can exacerbate rosacea.
What role does PAR-2 play in the immune response in rosacea?
PAR-2 induces neuroinflammation and cytokine release, recruiting immune cells to inflammation sites.
How does TLR-2 affect the immune response in rosacea?
TLR-2 induces proinflammatory cytokine release and activates cathelicidin, contributing to inflammation.
What is the significance of MMPs in rosacea skin?
Increased MMP-2 and MMP-9 contribute to skin degeneration and inflammation.
Describe the connection between TRP channels and inflammation in rosacea.
TRP channels are activated by environmental triggers, leading to neurogenic inflammation through neuropeptide release.
What is the role of the inflammasome in rosacea?
The inflammasome mediates IL-1β release, leading to neutrophil chemotaxis and inflammation amplification.
What physiological factors control blood vessel diameter in the face related to rosacea?
Blood vessel diameter is modulated by sympathetic nerves, parasympathetic nerves, and sensory nerves. These factors influence the state of the blood vessel diameter through neurotransmitters such as (nor)epinephrine, acetylcholine, and neuropeptides.
What are the key pathophysiological processes involved in flushing associated with rosacea?
The key pathophysiological processes involved in flushing with rosacea include neurogenic inflammation, autonomic dysregulation, and neuro-inflammatory responses.
What role do transient receptor potential (TRP) channels play in rosacea?
TRP channels, specifically TRPA1 and TRPV1, are involved in cross-talk with neuropeptide receptors, rendering thermal, chemical, and mechanical stimuli into clinical manifestations of rosacea, and establishing neuroimmune and neurovascular communication.
What is the significance of mast cells and B cells in the pathophysiology of phymatous changes in rosacea?
Mast cells and B cells contribute to skin fibrosis through the release of matrix metalloproteinases (MMPs), considered a plausible pathway for the development of phymata through chronic inflammation.
What are the potential triggers for rosacea?
Common triggers for rosacea include sun exposure, emotional stress, hot weather, alcohol consumption, spicy foods, humidity or osmotic factors, and certain skin-care products.
What are the histopathological features of erythematous skin and telangiectasia in rosacea?
Features include perivascular inflammatory infiltrate, dilated blood and lymphatic vessels, microscopically visible dermal edema, prominent upper dermal blood vessels, mild perivascular infiltrate, and solar elastosis.
What are the characteristics of papules in rosacea?
Papules are composed of CD4+ T H 1 and T H 17 cells, macrophages, mast cells, and plasma cells.
What are the histopathological features of phymatous rosacea lesions?
Features include infiltrate of T H 1 and T H 17 cells, macrophages, mast cells, glandular hyperplasia, follicular plugging, fibrosis, and presence of Demodex folliculorum.
What distinguishes ocular rosacea from other forms of rosacea?
Ocular rosacea is characterized by dilation of blood and lymphatic vessels and obstruction of the meibomian gland.
What are the diagnostic features of granulomatous rosacea?
Features include dermal edema, dermal granulomas of the tuberculoid type, and marked upper dermal vasodilation.
What are the two classification systems for rosacea?
The two classification systems are the Syndrome or Typology Classification (2002) and the Modified Classification or Grading System (2016-2017).
What is the minimum diagnostic sign of rosacea?
Persistent centrofacial erythema associated with periodic intensification by potential trigger factors.
What are the major features that are not diagnostic of rosacea?
Major features that are not diagnostic include flushing, telangiectasia, and inflammatory papules or pustules.
What are the essential features for diagnosing rosacea?
Essential features include centrofacial location of diagnostic and major features and bilateral facial location.
What are the secondary symptoms of rosacea?
Secondary symptoms include stinging sensation, edema, dry sensation, and burning sensation.
What are the key elements of general skin care for managing rosacea?
Key elements include avoidance of trigger factors, usage of sunscreen SPF 30+, frequent use of moisturizers, and gentle cleansers.
What is the grading scale for the severity of rosacea?
The grading scale includes mild, moderate, and severe.
What are the first-line therapies for rosacea based on?
First-line therapies are based on the pathophysiology of the condition and clinical severity of the symptoms.
What should be done if erythema is associated with pain in rosacea patients?
Consider topical or systemic analgesic therapy, nonsteroidal anti-inflammatory drugs, or antidepressants.
What is the importance of trigger avoidance in managing rosacea?
Trigger avoidance is important as it protects from relapses and is as important as therapy in improving the condition.
What are the therapeutic strategies for persistent erythema with pain in rosacea?
Strategies include topical/systemic analgesics, antidepressants, and neuroleptics.
What is the role of adrenergic receptor blockers in rosacea?
Adrenergic receptor blockers like brimonidine and oxymetazoline reduce erythema by vasoconstriction.
What are the essential elements of general skin care advice for rosacea patients?
Essential elements include avoiding trigger factors, using sunscreen SPF 30+, and gentle cleansers.
How should the severity of papules and pustules in rosacea be graded?
Severity should be graded based on the number of papules and pustules and whether plaques are present.
What is the recommended first-line therapy for persistent erythema in rosacea?
Approved first-line therapies include topical brimonidine gel (1%) and oxymetazoline cream (1%).
What is the role of trigger avoidance in rosacea management?
Trigger avoidance is important to improve the condition and protect from relapses.
What are the common treatments for flushing and transient erythema in rosacea?
Common treatments include laser therapy, topical adrenergic receptor modulators, and avoidance of triggers.
How can telangiectasia be treated in rosacea patients?
Telangiectasia can be treated with laser therapy or aethoxysclerol injections.
What is the recommended basic therapy for papules and pustules in rosacea?
Basic therapy includes avoiding triggers, applying photoprotective agents, and stress management.
What are the treatment options for severe or resistant cases of papules and pustules in rosacea?
Treatment options include systemic metronidazole, clarithromycin, and azithromycin.
What is the role of low-dose isotretinoin in the treatment of rosacea?
Low-dose isotretinoin has beneficial effects in early and established rosacea and can be used before procedures.
What are the management strategies for ocular rosacea?
Management includes eyelid hygiene, artificial tear substitutes, and UV-blocking sunglasses.
What is the significance of maintenance therapy in rosacea management?
Maintenance therapy is important for managing symptoms and is superior to sudden discontinuation of treatment.
What is the significance of Demodex mites in rosacea?
Increased Demodex mite numbers can contribute to folliculitis and perifolliculitis.
What are the therapeutic options for flushing in rosacea?
Options include laser therapy, topical adrenergic receptor modulators, and trigger avoidance.
What are the therapeutic options for telangiectasia in rosacea?
Options include laser therapy and aethoxysclerol injections.
What are the therapeutic options for ocular rosacea?
Options include eyelid hygiene, artificial tear substitutes, and UV-blocking sunglasses.
What are the therapeutic options for papules and pustules in rosacea?
Options include topical ivermectin, metronidazole, azelaic acid, and systemic antibiotics.
What systemic therapies are used for severe or resistant cases of papules and pustules in rosacea?
Systemic therapies include metronidazole, clarithromycin, and azithromycin.
What is the role of isotretinoin in treating phymata in rosacea?
Low-dose isotretinoin has anti-inflammatory effects and reduces sebaceous gland activity.
What therapies are recommended for flushing and transient erythema in rosacea?
Recommended therapies include laser therapy, topical adrenergic receptor modulators, and trigger avoidance.
What are the treatment options for telangiectasia in rosacea?
Telangiectasia can be treated with laser therapy or aethoxysclerol injections.
What is the basic therapy for papules and pustules in rosacea?
Basic therapy includes avoiding triggers, applying photoprotective agents, and stress management.
What is the role of multimodal therapy in the treatment of ocular rosacea?
Multimodal therapy combines topical vasoconstrictors with light or laser therapy.
What is the basic therapy for rosacea?
Basic therapy includes avoiding triggers, applying photoprotective agents, stress management, and optimized skin cleansing and moisturizing routines.
What is the role of multimodal therapy in the treatment of ocular rosacea?
Multimodal therapy combines topical vasoconstrictors with light or laser therapy, addressing features that coexist in many patients.
What are the types of laser systems used in the treatment of erythema and telangiectasia in ocular rosacea?
The types of laser systems include:
Laser System | Wavelength (nm) | Function |
|————–|—————-|———-|
| Potassium-titanyl-phosphate (PTP) | 532 | Blood vessel destruction |
| Neodymium-doped yttrium aluminum garnet (Nd:YAG) | 1,064 | Blood vessel destruction |
| Pulsed-dye laser | 585-595 | Absorbed by hemoglobin for blood vessel destruction |
What are the surgical interventions available for treating phymata in ocular rosacea?
Surgical interventions include:
Intervention Type | Description |
|——————-|————-|
| Scalpel excisions | Direct surgical removal |
| Dermabrasion | Used for mild and severe phymata |
| Electrosurgery | Minimally invasive option |
| CO2 laser | Relatively lower risk of bleeding |
| Erbium:YAG laser | Another laser option for treatment |
What are the risks associated with classical surgical excision and resection for large phymata?
Classical surgical excision has a relatively high bleeding rate and lower risk of bleeding with electrosurgery, but electrosurgery has a higher risk of deeper tissue destruction.
What role does the TAC3 gene play in neurovascular communication in rosacea?
The TAC3 gene encodes for neurokinin receptor-3, which induces neuroinflammation, pain, and immune responses in various tissues.
How do TRP channels contribute to the pathophysiology of rosacea?
TRP channels, particularly TRPA1 and TRPV1, sustain neurovascular responses and inflammation in rosacea by releasing vasoactive neuropeptides.
What is the significance of neuropeptides like PACAP and CGRP in rosacea?
Neuropeptides such as PACAP and CGRP are involved in vasodilation, plasma extravasation, and leukocyte recruitment.
What is the function of PAR-2 in the context of rosacea?
PAR-2 induces the release of neuropeptides and cytokines from nerves, contributing to vasoregulation, pain, and inflammation.
How do TLRs contribute to the immune response in rosacea?
TLRs, particularly TLR-2, are pattern recognition receptors that sense pathogen-associated molecular patterns and induce the release of neuropeptides and proinflammatory cytokines.
What triggers the immediate vascular response in facial flushing associated with rosacea?
Facial flushing is triggered by irritative stimuli that activate TRP ion channels on keratinocytes and sensory nerves.
What is the role of transient receptor potential (TRP) ion channels in rosacea?
TRP channels mediate neurogenic inflammation and vasodilation by releasing neuropeptides.
What is the role of protease-activated receptor-2 (PAR-2) in rosacea?
PAR-2 induces neuropeptide release, cytokines, and chemokines, contributing to vasoregulation and immune activation.
What is the role of neuropeptides in rosacea?
Neuropeptides like substance P and CGRP mediate vasodilation, plasma extravasation, and leukocyte recruitment.
What is the role of kallikreins (KLKs) in rosacea?
KLKs activate PAR-2, leading to neuropeptide release and immune activation.
What is the role of UV exposure in rosacea?
UV exposure can activate TLR2 and TRP channels, leading to neuroinflammation and vasodilation.
What is the role of stress in rosacea pathophysiology?
Stress activates the autonomic nervous system, leading to neuropeptide release and vasodilation.
What is the role of nitric oxide (NO) in rosacea?
NO is a potent vasodilator involved in neurovascular dysregulation and erythema.
What is the role of Toll-like receptor 2 (TLR2) in rosacea?
TLR2 activates the innate immune system, leading to neuropeptide release and immune modulation.
What are the potential triggers for facial flushing in rosacea?
Triggers include spicy food, alcohol, UVB, heat, noxious cold, exercise, and emotional stress.
What are the main factors contributing to fibrosis and glandular hyperplasia in rosacea?
Factors include exogenous irritants, endogenous cytokines, immune response activation, and barrier disruption.
How do Toll-like receptors (TLRs) contribute to the pathomechanism of rosacea?
TLRs recognize irritants, activate the immune system, and trigger inflammation, contributing to fibrosis and glandular hyperplasia.
What role do proteases play in the development of fibrosis in rosacea?
Proteases activate skin cells and immune cells, promoting inflammation and fibrosis.
What is the significance of the corticotropin-releasing hormone (CRH) in the context of rosacea?
CRH modulates stress response and influences sebaceous gland activity, contributing to glandular hyperplasia.
What is the pathophysiological mechanism of phymata in rosacea?
Phymata develop due to chronic inflammation, sebaceous gland hyperplasia, and fibrosis.
What is the role of mast cells in rosacea pathophysiology?
Mast cells release vasoactive mediators, contributing to neurovascular dysregulation and inflammation.
What is the role of matrix metalloproteinases (MMPs) in rosacea?
MMPs contribute to extracellular matrix destruction, vasodilation, and fibrosis.
What is the role of platelet-derived growth factor (PDGF) in rosacea?
PDGF remodels and activates dermal fibroblasts, contributing to fibrosis.
What are the key investigations for diagnosing Systemic Lupus Erythematosus (SLE) in the context of differential diagnosis for Rosacea?
Key investigations include skin biopsy, direct immunofluorescence, ANA and anti-DNA tests, and patient history.
What investigations are used to differentiate between Chronic Discoid Lupus Erythematosus (CDLE) and Rosacea?
Investigations include skin biopsy, direct immunofluorescence, and assessment of photosensitivity.
What features are associated with the differential diagnosis of Rhinophyma?
Features include shiny brown, red, or violaceous swelling, rapid growth, and possible association with other conditions.
What are the common causes and differential diagnoses of persistent erythema?
Common causes include rosacea, demodicosis, drug-induced erythema, contact dermatitis, and seborrheic dermatitis.
What are the helpful observations to differentiate various forms of flushing?
Observations include duration, associated symptoms, and triggers of flushing.
What are the differential diagnoses of flushing?
Differential diagnoses include benign causes, systemic diseases, neurologic causes, tumors, and idiopathic flushing.
What are the differential diagnoses of telangiectasias?
Differential diagnoses include chronic discoid lupus erythematosus, drug-induced erythema, and basal cell carcinoma.
What are the differential diagnoses of papules and pustules in rosacea?
Differential diagnoses include rosaceiform dermatitis, acne vulgaris, and perioral dermatitis.
What are the differential diagnoses of halogen rosacea?
Differential diagnoses include acne conglobata and acne fulminans.
What is ic dermatitis?
A common skin condition that can cause red, scaly patches.
What is Tinea faciei?
A fungal infection that can cause red patches on the face.
What is Ulytherma?
A condition that can cause skin eruptions.
What are the differential diagnoses of halogen rosacea?
- Acne conglobata: A severe form of acne characterized by inflamed nodules.
- Acne fulminans: A rare and severe form of acne with systemic symptoms.
- Halogen rosacea: Flushing and erythema associated with halogen exposure.
- Gram-negative folliculitis: Infection of hair follicles that can mimic rosacea.
What are the recommended cosmetic practices for individuals with rosacea?
Allowed Practices:
- Use powder cosmetics with a matte finish; green is the best color.
- Try cosmetics before purchasing.
- Wear light earth tones for eye shadow.
- Apply a separate sunblock after topical medication.
- Use moisturizer on dry skin with at least SPF 20.
- Avoid cosmetics with formaldehyde, alcohol, and other irritants.
- Use a flat or soft brush applicator without rubbing.
- Use facial forms of powder or cream with a matte finish.
- Wear only black mascara.
- Use pencil forms of eyeliner.
- Start new medications or cosmetics on weekends to monitor reactions.
What are the contraindicated cosmetic practices for individuals with rosacea?
Not Allowed Practices:
- Use cream or liquid cosmetics.
- Use old cosmetics.
- Wear deep eye shadows in blue, purple, red, or pink.
- Use cosmetics containing perfume.
- Purchase cosmetics with more than 10 ingredients.
- Apply with a sponge or fingers.
- Massage creams into the skin.
- Use peeling ‘rejuvenating’ agents.
- Use light-reflective powders containing mica.
- Use nail polish.
- Avoid waterproof eye cosmetics.
What are the different laser therapies used in rosacea treatment and their indications?
- PDL laser: Treats erythema, telangiectasia; more effective than Nd:YAG; purpura induction possible.
- PTP laser: Treats telangiectasia (erythema); short healing process, well tolerated.
- Nd:YAG laser: Treats erythema, telangiectasia; minor pain sensation; good safety profile.
- IPL: Treats erythema, telangiectasia, papules or pustules; good safety and tolerability profile.
What surgical interventions are available for treating phymata in rosacea?
- Dermabrasion: Risk of bleeding.
- Electrocautery: Rapid procedure; potential cartilage damage.
- Laser (CO₂ or Er:YAG): Low risk for bleeding; Er:YAG has low scarring risk.
- Scalpel excision: Risk of intraoperative bleeding; deep tissue excisions or resections.
What are the general measures recommended for managing rosacea symptoms?
- Patient education
- Avoidance of triggers
- Sun protection
- Skin care
- Doctor-patient relationship
What topical therapies are recommended for flushing/transient erythema in rosacea?
- Brimonidine 3 mg/g (high efficacy)
- Oxymetazoline cream 1% (high efficacy)
What systemic therapy options are available for severe or treatment-resistant rosacea?
- Low-dose isotretinoin
- Combination of topical and systemic anti-inflammatory therapy
What is the role of physical interventions in the management of rosacea?
- Intense Pulsed Light (IPL)
- Laser treatments
What topical therapies are suggested for papules and pustules in rosacea?
- Topical therapies include:
- Permethrin
- Benzoyl peroxide
- Retinoids
- Calcineurin inhibitors
What are the therapeutic strategies targeting TLR-2 in rosacea?
The therapeutic strategies targeting TLR-2 in rosacea include:
1. Isotretinoin
2. Ivermectin (IVM)
These treatments aim to modulate cytokines, chemokines, and MMPs, addressing glandular hyperplasia and fibrosis.
How do serine proteases/PARs contribute to the treatment of rosacea?
Serine proteases/PARs contribute to the treatment of rosacea through:
- Azelaic acid (AZA)
- Doxycycline
- eACA (ε-aminocaproic acid)
These agents help in reducing cytokines, chemokines, and growth factors, promoting vasodilation and addressing fibrosis.
What role do cathelicidins (AMP) play in the management of rosacea?
Cathelicidins (AMP) play a role in the management of rosacea by:
- Utilizing eACA and protease inhibitors
- Applying IVM (topical)
These strategies target cytokines, chemokines, and oxidative burst, contributing to the overall therapeutic approach.
What are the therapeutic options for mast cell mediators in rosacea?
Therapeutic options for mast cell mediators in rosacea include:
- Cromolyn sodium
- Doxycycline
- Laser Tx
- IVM
These treatments aim to reduce the effects of MMPs, cytokines, and other inflammatory mediators.
What is the significance of targeting vascular SMCs/ECs in rosacea treatment?
Targeting vascular SMCs/ECs in rosacea treatment is significant as it involves:
- Minocycline (MNZ)
- Doxycycline
- Na sulfa
- IVM
- AA
These treatments promote vasodilation and address the underlying vascular components of rosacea.
