DERM 09: Rosacea Flashcards
1
Q
What is rosacea?
A
chronic cutaneous vascular disorder of central face (cheeks, chin, nose, and forehead)
- non-contagious
- relapsing and remitting
2
Q
What are the signs and symptoms of rosacea?
A
- persistent centrofacial erythema
- flushing (transient erythema/blushing)
- telangiectasias (spider-like blood vessels)
- papules and pustules
- ocular lesions (rare)
- rhinophyma – hypertrophy of sebaceous glands of nose, resulting in fibrosis
- stinging, burning, edema, and dry appearance
3
Q
Describe the epidemiology of rosacea.
A
- onset typically between 30-50 years old
- most observed in fair-skinned individuals (Fitzpatrick Skin Types I-III), but observed in all skin types
- redness less likely to be detected in Fitzpatrick Skin Types V or VI – can appear as dusky brown or purple
- patients often report sensitive skin, and history of blushing is common
4
Q
Describe the pathophysiology of rosacea.
A
(unclear cause and pathogenesis – likely multifactorial)
- genetic predisposition
- environmental triggers (ie. UV radiation, temperature extremes)
- vascular hyperreactivity and neurovascular dysregulation
- immune dysfunction
- microorganisms (ie. demodex mites)
- inflammatory cascade
5
Q
Genetic Predisposition
A
- positive family history = ↑ chance of developing rosacea
- 3 HLA alleles, two single-nucleotide polymorphisms (SNPs) identified/associated with rosacea
6
Q
Environmental Triggers
A
ie. UV radiation, temperature extremes
- damage tissue
- trigger abnormal or exaggerated neurovascular and immune reaction
- role of UV is unclear
7
Q
Vascular Hyperreactivity and Neurovascular Dysregulation
A
activated nervous system and abnormal vascular response
- possibly result of upregulation of pro-inflammatory genes involved in nervous (ie. adrenergic receptors) and neural inflammation (ie. TRPV1), and subsequent ↑ in inflammatory infiltrate
- ie. TRPs (transient receptor potential channels) are activated and release substance P and CGRP → pain, edema, and vasodilation
- may result in ↑ blood flow, vessel density
- vasoactive peptide release → flushing
8
Q
Immune Dysfunction
A
innate immune response
- upregulation of toll-like receptor 2 (TLR2) = pro-inflammation
- increased production of abnormal cathelicidin (LL-37) peptides and kallikrein 5 (KLK5), which promote leukocyte chemotaxis and angiogenesis
- cathelicidin (LL-37): antimicrobial peptide
- kallikrein 5 (KLK5): protease that cleaves/activates LL-37
adaptive immune response
- involvement of T and B lymphocytes – dominating activated cells include CD4+ Th1 cells, macrophages, and mast cells
9
Q
Microorganisms
A
- linked to demodex (demodex folliculorum) mite infestation of skin – increased prevalence of mites and increased density
- demodex brevis may be associated with ocular pathology
- mites may be associated with bacteria which can initiate immune response – staph epidermidis, bacilllus oleronius, and heliobacter pylori
10
Q
What are the clinical features of rosacea?
A
- persistent erythema (centrofacial erythema)
- flushing
- telangiectasia
- papules and pustules
- phymatous changes
- ocular manifestations
11
Q
Describe the distribution of rosacea.
A
‘flush areas’ of face
- nose, cheeks > brows, chin, and eyes
12
Q
What is required to diagnose rosacea?
A
at least 1 diagnostic or 2 major phenotypes required
13
Q
What are the 2 diagnostic phenotypes of rosacea?
A
- centrofacial erythema
- phymatous changes
14
Q
What is the centrofacial erythema phenotype?
A
- fixed or persistent – may occasionally intensify
- difficult to detect on darker skin tones
15
Q
What is the phymatous changes phenotype?
A
- rhinophyma is most common form
- characterized by distended follicles, skin thickening, glandular hyperplasia, and bulbous appearance of nose
- more common in men
- erroneous association with alcoholism (‘rum nose’ or ‘whisky nose’)
16
Q
What are the 4 major phenotypes of rosacea?
A
- papules and pustules
- flushing
- telangiectasia
- ocular features
17
Q
What is the papules and pustules phenotype?
A
no comedones
18
Q
What is the flushing phenotype?
A
- frequent, prolonged flushing
- can occur within seconds to minutes
19
Q
What is the telangiectasia phenotype?
A
prominent small linear blood vessels
20
Q
What is the ocular features phenotype?
A
- watery, bloodshot eyes, dry eyes, foreign body sensation, irritation, photophobia
- can cause blepharitis, conjunctivitis, scleritis, keratitis, eyelid irregularities, inflammation
- vision loss possible
21
Q
What are the differential diagnoses for rosacea?
A
- acne vulgaris: comedo formation, no ocular symptoms
- contact dermatitis: itching, improves over time with removal of causative agent
- photodermatitis: rash appears on multiple body sites after sun exposure
- seborrheic dermatitis: distinct distribution pattern involving scalp, eyebrows, nasolabial folds
- systematic lupus erythematosus (SLE): rarely has pustules (butterfly rash)
- carcinoid syndrome, systemic mastocytosis, benign cutaneous flushing, perimenopause, medullary carcinoma of thyroid, pancreatic and renal cell tumors: common symptom is flushing
22
Q
What are the goals of therapy for rosacea?
A
- increase awareness of avoiding triggers in rosacea
- reduce signs and symptoms (erythema, flushing, papules, pusutules)
- reduce recurrences and severity of cutaneous and ocular rosacea
- improve appearance of skin when it affects patient’s overall quality of life (QoL)
- prevent rhinophyma (nose enlargement) with aggressive early treatment
- reduce or obliterate broken small-diameter linear blood vessels (telangiectasia)
23
Q
What are the common triggers of rosacea?
A
- sun exposure
- emotional stress
- hot weather
- wind
- heavy exercise
- alcohol consumption
- hot baths
- cold weather
- spicy foods
- humidity
- indoor heat
- certain skin-care products
- heated beverages
- certain cosmetics
- medications
- medical conditions
- certain fruits
- marinated meats
- certain vegetables
- dairy products
24
Q
What medications can aggravate rosacea?
A
- niacin
- amyl nitrate
- calcium channel blockers
- opioid analgesics
- topical steroids, nasal steroids
- amiodarone
- high doses of vitamins B6 and B12
25
What are some preventative measures for rosacea?
sunscreen and skin care
- daily broad-spectrum (UVA and UVB) sunscreen (SPF30)
- physical blockers (ie. titanium dioxide, zinc oxide) are well tolerated
- sunscreen should contain protective silicones (dimethicone or cyclomethicone)
- green-tinted creams can provide coverage of erythema
- use non-soap cleansers and fragrance-free moisturizers
- avoid: astringents, toners, menthols, camphor, waterproof cosmetics requiring solvents for removal, or products containing sodium lauryl sulfate or chemical exfoliating agents (ie. alpha hydroxy acids)
26
What is the treatment for rosacea?
- avoid triggers
- use sunscreens, general skin care (soap-free cleansers, fragrance-free moisturizers), camouflage make-up
- drug treatment based on presenting phenotype
27
What is the treatment for flushing and persistent erythema rosacea?
topical brimonidine
28
What are some other treatments for flushing and persistent erythema rosacea?
- oxymetazoline (US only)
- oral agents
29
Brimonidine
MOA
alpha-2 adrenergic receptor agonist
30
Brimonidine
Use
- potent vasoconstrictor – effective for erythema
- may flare after discontinuation
- lack of quality evidence for flushing – used on based consensus
- does not impact telangiectasias b/c lacks vasomotor tone (venules)
- not effective for papulopustular lesions
onset is 30 min, max effect at 3 hr, lasts 10 hr
31
Brimonidine
Products and Administration
Onreltea 0.33% gel once daily
32
Brimonidine
Safety
mild and transient ADR (ie. well-tolerated) – pruritis, irritation, worsened erythema
33
Oxymetazoline
MOA
alpha-2 adrenergic receptor agonist
34
Oxymetazoline
Use
- effective for moderate to severe erythema (similar to brimonidine)
- not effective for papules/pustules
- less rebound effect than brimonidine
- effective within 1 hour, and lasts 12 hours
35
Oxymetazoline
Products and Administration
- Dristan 0.05% nasal spray
- US only, expensive
36
Oxymetazoline
Safety
- well-tolerated
- may cause inflammation (worsening of pustules), erythema, pruritis
37
What oral agents are used for flushing rosacea?
- propanolol 20-40 mg
- clonidine 0.3 mg daily
- carvedilol
- methodologic limitations with all evidence
- used where flushing is predominant feature in refractory rosacea
38
What is the treatment for inflammatory papules and pustules rosacea?
- topical azelaic acid
- topical metronidazole
- topical ivermectin
- if inadequate response after 8-12 weeks, try alternate topical or combination of topicals
- can also use antibiotics for papules and pustules after, or in addition to, topicals
- if inadequate response after 8-12 weeks again, consider low dose isotretinoin (refer to dermatologist)
39
Metronidazole
MOA
antibacterial, antiprotozoal, anti-inflammatory, and antioxidant
40
Metronidazole
Use
- effective for papulopustular lesions (1st line)
- effective for erythema (seen in patients with papulopustular lesions)
- improvement in 3-6 weeks
- relapse occurs – long-term treatment needed
- no difference in efficacy of 0.75% vs. 1%
41
Metronidazole
Products and Administration
- MetroGel 0.75% and 1%
- Noritate 1% cream
42
Metronidazole
Safety
- ADR: well-tolerated, local skin irritations such as facial burning, stinging, and pruritis
- less stinging and irritation with cream
- better tolerated than azelaic acid
- safe in pregnancy
43
Azelaic Acid
MOA
antibacterial, anti-inflammatory, and keratolytic
44
Azelaic Acid
Use
- effective for papulopustular lesions (1st line)
- as effective as metronidazole
- limited effectiveness for erythema
- improvement in 3-6 weeks
- relapse occurs – long-term treatment needed
45
Azelaic Acid
Products and Administration
Finacea 15% gel once daily
46
Azelaic Acid
Safety
- ADR: local skin irritations such as facial burning, stinging, and pruritis
- safe in pregnancy
47
Ivermectin
MOA
anti-inflammatory and acaricide – decreases number of demodex mites present
48
Ivermectin
Use
- effective for papulopustular lesions (1st line)
- symptoms continue to improve with prolonged treatment (40 weeks) and extended time to first relapse upon D/C
49
Ivermectin
Products and Administration
- Ivermectin 1% cream (Rosiver) once daily
- expensive (compared to metronidazole and azelaic acid)
50
Ivermectin
Safety
- ADR: well-tolerated, skin irritation and burning, dry skin, hypersensitivity
- long-term safety with up to 1 year of therapy
51
What is the treatment for inflammatory phyma rosacea?
- oral antibiotics – doxycycline or tetracycline
- consider topical retinoids or low-dose oral isotretinoin (refer to dermatologist)
52
Doxycycline and Tetracycline
Use
- effective for papules and pustules, but low confidence for use in inflammed phyma
- can be used for moderate to severe papules and pustules, or when response is inadequate to topicals
53
What must be considered when selecting oral antibiotics for rosacea treatment?
- bacterial resistance (limit to 3 months)
- ↑ ADR
- improved adherence
- inexpensive
54
Tetracycline
MOA
anti-inflammatory – inhibits matrix metalloproteinase enzyme involved in cathelicidin pathway
55
Tetracycline
Dose
250-1000 mg daily
56
Doxycycline
Dose
100 mg daily
57
Doxycycline
Alternative
Apprilon MR 40 mg once daily x 4 months (sub-antimicrobial low dose)
- similar efficacy for papules/pustules
- fewer GI effects
- less concern about resistance
- more expensive
58
Minocycline
Products
minocycline 1.5% foam (US) – effective and well-tolerated for moderate-severe papulopustular rosacea
59
Minocycline
Safety
2nd line due to adverse effects
- hyperpigmentation
- hepatotoxicity
- drug-induced lupus
60
What are some options for oral antibiotics that have no high-quality evidence to support use?
- erythromycin/azithromycin
- metronidazole
- trimethoprim
61
Retinoids
MOA
minimizes progression (low confidence)
62
Isotretinoin
- low dose 0.25-0.3mg/kg for persistent and severe papules and pustules – may be beneficial for patients with early phymatous changes (low confidence)
- treat for 12-28 weeks
- many adverse effects, careful monitoring required
- contraindicated in pregnancy
63
What is the treatment for non-inflammatory phyma rosacea?
laser resurfacing or electrosurgery – cosmetic repair (tissue excision)
64
What is the treatment for ocular rosacea?
refer to ophthalmologist
- minimize exposure to aggravating factors – ie. AC, central heating, smoky atmosphere, periocular cosmetic
- lid care and artificial tears – cleanse eyelashes twice daily with baby shampoo on wet washcloth
- oral doxycycline, minocycline or tetracycline for several weeks
- cyclosporine 0.05% eye drops – inhibit T-lymphocyte activation, ↓ activated lymphocytes in conjunctiva
- cyclosporine ADR: stinging, ocular infections due to suppressed immune system
- may see ophthalmic antibiotic ointment (ie. fusidic acid) prescribed and applied to lid margins/eyelash
65
Describe maintenance treatment for rosacea.
- rosacea is chronic condition requiring ongoing care
- if inadequate improvement after 8-12 weeks, escalate frequency or dose, or use alternate treatment
- once improvement is seen, taper treatment by dose and frequency to treatments recommended for mild rosacea as long-term – topical brimonidine/laser/IPL, topical metronidazole/ivermectin/azelaic acid, lid care/artificial tear drops
66
Rosacea vs. Acne
Comedones
- rosacea: no
- acne: yes
67
Rosacea vs. Acne
Telangiectasias
- rosacea: yes
- acne: no
68
Rosacea vs. Acne
Deep Diffuse Erythema
- rosacea: yes
- acne: no
69
Rosacea vs. Acne
Age of Onset
- rosacea: peak 40-50 years old
- acne: peak adolescence
70
Rosacea vs. Acne
Areas of Involvement
- rosacea: usually central face
- acne: face, back, and chest
71
Rosacea vs. Acne
Androgen Stimulation
- rosacea: no
- acne: yes
