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clinical practice
Rosacea
Frank C. Powell, F.R.C.P.I.
This Journal feature begins with a case vignette highlighting a common clinical problem.
Evidence supporting various strategies is then presented, followed by a review of formal guidelines,
when they exist. The article ends with the authors clinical recommendations.
A 47-year-old white woman reports facial redness and flushing. Her eyes are itchy and
irritated. She thinks she may have rosacea and is worried that she will have a whiskey
nose. On examination, multiple erythematous papules, pustules, and telangiectasias
are observed on a background of erythema of the central portion of her face. How
should her case be managed?
Grade Features
Erythematotel- Persistent erythema of the central face. 1 Occasional mild flushing; faint persistent Reduce flushing and redness and mini- Difficult to treat satis-
angiectatic Flushing; telangiectasias often present; erythema; occasional telangiectasias. mize skin irritation. Topical medi- factorily.
(subtype 1) easily irritated facial skin. Patient may 2 Frequent troublesome flushing; moderate cations recommended for papulo-
The
report stinging or burning of the face persistent erythema; several distinct tel- pustular rosacea are not indicated
and have symptoms of ocular rosacea. angiectasias. and may cause irritation. Systemic
Rhinophyma occasionally coexists. 3 Frequent severe flushing; pronounced persis- treatments used for papulopustu-
tent erythema; possible edema; many lar rosacea may reduce erythema if
prominent telangiectasias. significant inflammation is present.
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inflammation, and phymatous skin 3 Many or extensive papules or pustules; pro- quired to maintain
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head (metophyma), ears (otophyma), hypertrophy of connective tissue or seba- are very difficult to treat but may form (rhinophyma)
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tour due to hypertrophy of the sebaceous
glands or connective tissue, with nodular
component.
clinical practice
of severity should be assessed in each of these. Patients should also be asked to grade the psychological, social, and occupational effects of their disease on a similar scale. For example,
In general, 1 denotes mild disease, 2 moderate disease, and 3 severe disease, but grades of severity are not always clearly defined. Patients may have more than one subtype, and the grade
rosacea during social situations and it regularly causes embarrassment; in grade 3 (severe), the patient is constantly thinking about the condition and avoids social interaction because of
in grade 1 (mild), the patient is conscious of the condition, but it does not cause embarrassment or inhibit social functioning; in grade 2 (moderate), the patient is constantly aware of the
threatening ocular
sociated with rosacea are due to excessive alcohol
agnosed. Vision-
but often not di-
inflammation is
consumption makes rosacea a socially stigmatizing
condition for many patients.
rare.
strategies and evidence
The diagnosis of rosacea is a clinical one. There is
it. Such grading on the part of the patient facilitates evaluation of the overall effect of the disease on him or her and guides assessment of the efficacy of therapy.
Topical medication for grade 1; system-
subtype 1
hordeolum. Keratitis, episcleritis or
Management
Systemic or topical antibiotics, or both, are the
mainstays of therapy for subtype 2 rosacea (Table 3),
and the response is often satisfactory (Fig. 4A and
4B). Moderate-to-severe (i.e., grade 2 or 3) papulo-
pustular rosacea may require systemic therapy to
achieve clearance of inflammatory skin lesions,
whereas milder (grade 1 and some cases of grade 2)
disease can often be treated with topical medica-
tions alone.25 Although data are lacking to support
the combined use of topical and systemic therapies,
many clinicians recommend such a combination for
the treatment of moderate-to-severe disease.20,25
On the basis of an analysis that pooled data from
two randomized trials, van Zuuren and colleagues
concluded that there was strong evidence of the ef-
ficacy of topical metronidazole and azelaic acid
cream.26 Sixty-eight of 90 patients (76 percent)
treated with topical metronidazole for eight or nine
weeks considered their rosacea to be improved, as
compared with 32 of 84 patients (38 percent) in the
placebo group.26 Significant reductions in the num-
ber of inflammatory lesions and in erythema were Figure 3. Severe Papulopustular Rosacea with Moderate
reported in two large placebo-controlled, double- Ocular Involvement.
blind studies of a 15 percent azelaic acid gel applied In this patient with grade 3 papulopustular disease, in-
flammatory lesions have coalesced into an erythema-
twice daily.27 A double-blind, randomized, parallel- tous plaque below the eye. Note the multiple small,
group trial involving 251 patients with papulopus- studded pustules on the surface of the plaque and the
tular rosacea28 demonstrated the superiority of 15 inflammatory lesions on the lower eyelid (grade 2 ocular
percent azelaic acid gel over 0.75 percent metroni- rosacea).
dazole gel applied twice daily for 15 weeks. In a dou-
Contraindications
Medication Properties and Actions Dosage and Duration and Side Effects Comments
Topical
Metronidazole (0.75% gel Antibacterial; antiinflam- Applied once or twice dai- Contraindications: women of Gel and cream and
or cream; 1% cream) matory. ly. Can be used as ini- childbearing age not on both concentra-
tial treatment to clear oral contraception should tions appear to be
inflammatory lesions use with caution because equally effective.
or as indefinite main- of possibility of absorption
tenance therapy after and mutagenic effects.
clearance with sys- Side effects: gel preparation
temic therapy. may be irritating to skin.
Transient watering of eyes
may occur when applied to
periocular skin.
Azelaic acid Antibacterial; anti- Applied twice daily. Can Side effects: may cause mild May be used in wom-
(20% cream; 15% gel) inflammatory. be used as initial or burning or stinging sensa- en of childbearing
indefinite mainte- tion when applied initially. age and during
nance therapy. Pruritus, dryness, or scal- pregnancy.
ing can occur. Rarely, con-
tact dermatitis or facial
edema may occur.
10% Sodium sulfaceta- Antibacterial; keratolytic Applied twice daily. Can Contraindications: hypersensi- Sulfur component
mide and 5% sulfur in (sulfur); hydrating be used as initial or tivity to sulphonamide or may help accom-
cream or lotion. Prep- (urea). indefinite mainte- sulfur. panying seborrhe-
arations may include nance therapy. Side effects: rarely, systemic ic dermatitis. Sun-
10% urea; sunscreen; Cleanser preparation hypersensitivity reactions. screen or tinted
green tint. available. May cause redness, peel- preparations may
ing, and dryness of skin. reduce number of
topical prepara-
tions needed.
Erythromycin Antibacterial; anti- Applied twice daily. Can Side effects: local irritation or May be used in preg-
(2% solution) inflammatory. be used as initial or dryness. nancy. Alcohol in
indefinite mainte- solution may re-
nance therapy. duce tolerance.
Tretinoin (0.025% cream Alters epidermal keratini- Applied at night. Can be Contraindications: teratogenic; Theoretically useful
or lotion; 0.01% gel) zation. May improve used as initial or in- women of childbearing age for actinically
photoaging changes. definite maintenance not on oral contraceptives damaged skin
therapy. should use with caution. (common in
Side effects: Irritating and rosacea).
poorly tolerated by some
patients. May cause photo-
sensitivity. Use on dam-
aged skin and contact with
eyes should be avoided.
Systemic
Oxytetracycline Antibacterial; antiinflam- 250 to 500 mg twice daily Contraindications: should be
matory. for 6 to 12 weeks to avoided by women who are
achieve remission. In- pregnant, contemplating
termittent low-dose pregnancy, or lactating and
therapy may prevent by persons with impaired
relapse. renal or hepatic function.
Side effects: gastrointestinal
upset; candida; photosen-
sitivity; benign intracranial
hypertension. May reduce
effectiveness of oral contra-
ceptives. May cause tooth
discoloration or enamel hy-
poplasia.
Poor absorption if taken with
food, milk, or some medi-
cations.
Table 3. (Continued.)*
Contraindications
Medication Properties and Actions Dosage and Duration and Side Effects Comments
Doxycycline Antibacterial; antiinflam- 50 to 100 mg once or Same as for oxytetracycline. May be taken with
matory. twice daily for 6 to 12 food.
weeks.
Minocycline Antibacterial; antiinflam- 50 to 100 mg twice daily Contraindications: pregnancy Randomized, clinical
matory. or sustained-action or lactation. Persons with trials to support
formulation once dai- hepatic impairment should its use in rosacea
ly for 6 to 12 weeks. use with caution. are lacking, but
Side effects: gastrointestinal clinical impres-
upset (but less than with sion is of equal
tetracycline); allergic reac- efficacy to oxytet-
tions. Hyperpigmentation racycline. Unlike
of the skin may occur. oxytetracycline,
Long-term use should be can be taken with
avoided (hepatic damage food.
or systemic-lupus-erythe-
matosuslike syndrome
may be induced). Drug in-
teractions with antacids,
mineral supplements, anti-
coagulants.
Erythromycin Antibacterial; antiinflam- 250 to 500 mg once or Contraindications: severe Alternative to oxy-
matory. twice daily for 6 to 12 hepatic impairment. tetracycline or
weeks. Side effects: gastrointestinal minocycline as
upset; headache or rash. first-line systemic
Drug interactions (many). treatment. Useful
if systemic thera-
py necessary in
oxytetracycline-
intolerant or preg-
nant or lactating
patients.
Metronidazole Antibacterial; antiinflam- 200 mg once or twice dai- Contraindications: pregnant Side-effect profile lim-
matory. ly for 4 to 6 weeks. or lactating women should its its use to resis-
use with caution. tant cases for
Side effects: gastrointestinal short periods.
upset; leukopenia; neuro-
logic effect (seizures or pe-
ripheral neuropathy). Drug
interactions with alcohol,
anticoagulants, or pheno-
barbital.
* Topical treatment alone is usually effective for mild-to-moderate (grade-1-to-2) papulopustular rosacea. Topical metronidazole, combination
10 percent sodium sulfacetamide and 5 percent sulfur, and 15 percent azelaic acid have been approved by the Food and Drug Administration
for the treatment of rosacea; however, several other topical medications are used off label. For patients with moderate-to-severe papulopus-
tular rosacea (grade 2 to 3), oral medication is usually indicated. These patients may not tolerate topical medications initially, owing to in-
flamed skin, but topical therapy may be added as the inflammation subsides and is used to maintain remission after cessation of oral therapy.
Dosage ranges relate to published reports and reflect the lack of uniformity in the approach to the treatment of papulopustular rosacea.
Contraindications and side effects are selected examples rather than a comprehensive summary.
ble-blind study of 103 patients, a lotion containing fur lotion with 0.75 percent metronidazole showed
10 percent sodium sulfacetamide and 5 percent sul- a significantly greater clearance of lesions among
fur reduced inflammatory lesions by 78 percent, as the patients treated with sodium sulfacetamide and
compared with a reduction of 36 percent in the pla- sulfur.30 An uncontrolled study showed a reduction
cebo group.29 An investigator-blinded study involv- in erythema, papules, and pustules in 13 of 15 pa-
ing 63 patients that compared the combination of tients (87 percent) who were treated with topical
10 percent sodium sulfacetamide and 5 percent sul- erythromycin applied twice daily for four weeks.31
The woman described in the vignette should be facetamidesulfur preparation applied twice daily
reassured that inflammatory papules and pustules for six months and then gradually discontinued,
usually respond to therapy and resolve without scar- as outlined above. Laser therapy should be consid-
ring and that rhinophyma rarely develops in wom- ered for residual, prominent telangiectatic vessels.
en. She should be advised to apply a sunscreen daily The oral antibiotic is likely to help the patients oc-
that provides protection against both ultraviolet A ular symptoms, and she should also be advised to
and ultraviolet B irradiation and to avoid using irri- clean her eyelids with warm water twice daily and
tating topical products. Treatment should be initi- to use artificial tears. Referral to an ophthalmolo-
ated with 100 mg of doxycycline or 100 mg of mi- gist should be considered if her ocular symptoms
nocycline daily for a period of 6 to 12 weeks. This persist.
should be followed by maintenance therapy with Dr. Powell reports having received speaking fees from Galderma
Laboratories, Bradley Pharmaceuticals, and Dermik Laboratories.
azelaic acid, topical metronidazole, or a sodium sul-
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