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The Ocular Manifestations of Atopic Dermatitis

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The Ocular Manifestations of
Atopic Dermatitis and Rosacea
Andrew S. Eiseman, MD
Corresponding author
Andrew S. Eiseman, MD
Eye Clinic, Walter Reed Army Medical Center,
Washington, DC 20307, USA.
E-mail: Andrew.Eiseman@na.amedd.army.mil
are discussed, and the importance of including an ocular
assessment in their evaluation, even if the dermatologic
abnormality appears to be well-controlled, is illustrated.
Current Allergy and Asthma Reports 2006, 6:292 –298
Current Science Inc. ISSN 1529-7322
Copyright © 2006 by Current Science Inc.
Atopic Dermatitis and Keratoconjunctivitis
Atopic dermatitis and rosacea are chronic diseases that
have both dermatologic and ocular manifestations. The
occurence of ocular disease is often proportionately
higher than that of dermatologic disease. Even if the
skin abnormalities appear well controlled, these patients
require ophthalmic evaluation as well. Optimal management usually requires a team approach that includes
internists, dermatologists, and ophthalmologists. Both
disorders are characterized by acute exacerbations and
require maintenance therapy for control. Exacerbations need aggressive treatment to limit ocular signs and
symptoms and to reduce ocular inflammation that can
lead to permanent visual loss. Topical corticosteroid use,
although at times needed, should be minimized for both
disorders. Future research will continue to emphasize
the use of steroid-sparing and immune-modulating agents
that have the potential to provide long-lasting anti-inflammatory control with a more favorable side-effect profile.
Introduction
Many eyelid abnormalities associated with dermatologic
diseases are easy to identify because they are quite similar
to the skin changes found on other parts of the body.
However, several dermatologic diseases not only have
eyelid abnormalities but ocular abnormalities as well.
These ocular manifestations can be significant, and they
may be out of proportion to the skin changes observed.
If not identified early and managed appropriately, they
can lead to severe signs and symptoms and even loss of
vision that can be permanent. Two of the most common
dermatologic diseases that have the potential for significant ocular findings that are often out of proportion to
the skin changes are atopic dermatitis and rosacea. In
this article, the ocular manifestations of these disorders
Eczematous dermatitis, hay fever, allergic asthma, and
perennial allergic rhinitis make up the “major” atopies.
Atopy is quite common, affecting up to 20% of the population [1]. Approximately 2% of the population is affected
by atopic dermatitis, with most initial manifestations
beginning in childhood [2]. Atopic dermatitis affecting
the eyelids is one of the most common causes of chronic
eyelid dermatitis. Svensson and Moller [3] found that
39% of their population affected with eyelid dermatitis
had atopic disease. Nethercott et al. [4] found that of the
79 patients in their study who were affected with eyelid
dermatitis, 23% had atopic dermatitis. Although the eyelid
manifestations of those affected with atopic disease are
common, they are not particularly distinguishing. Care
must be taken when evaluating these patients to ensure
that the correct diagnosis is determined.
Differential diagnosis
Pruritic and inflamed eyelids with edema, erythema,
and scaling are common presenting signs and symptoms
and must be differentiated from the more common conditions of contact and irritant dermatitis. Patients with
contact and irritant dermatitis can also present with the
ocular symptoms of itching and burning. However, the
intense signs of ocular inflammation and scarring are
usually absent. A careful history, including a family history, and patch testing can be very helpful in separating
those patients with allergic contact dermatitis from those
with atopic disease. A familial predisposition to atopic
disease is found in more than 50% of these patients [1]. It
may be difficult to find the underlying causative agent in
allergic contact disease. Therefore, it is also important to
carefully evaluate the patient for other signs of atopic disease. Patients with atopic dermatitis have a second atopic
disease 75% to 80% of the time [5].
Some patients present with more ocular signs and
symptoms than skin findings. Ocular swelling, itch,
and irritation can be due to atopic keratoconjunctivitis,
The Ocular Manifestations of Atopic Dermatitis and Rosacea
Eiseman
293
Figure 1. Patient with
atopic dermatitis
affecting the eyelids
shows thickened skin
with mild scaling.
The eyelid margins
are erythematous,
and multiple eyelashes are missing
(madarosis). The
conjunctival vessels
show mild engorgement as well.
Table 1. Ocular manifestations of atopic dermatitis
Eyelid findings
Swelling, erythema, scaling, and fissures
Lichenification and thickening
Ectropion
Blepharitis
Madarosis (lash loss), trichiasis (lash misdirection)
Bacterial colonization and viral infections
Ocular findings
Eyelid and periocular findings
Conjunctival erythema and swelling
Atopic dermatitis that affects the eyelids can present with
a host of symptoms, usually including bilateral itching,
burning, tearing, photophobia, and thick, stringy, ropy
discharge. The signs of the disease include eyelid swelling with erythema and a scaly, thickened, and wrinkled
appearance of the skin (Table 1). With chronicity, lichenification can occur, which is thickening and accentuation
of the normal skin lines [2,6]. The lids may become indurated, and eyelid malpositions, such as ectropion, can
occur. A chronic cycle of rubbing and scratching can also
lead to changes such as fissures, especially near the lateral
canthus [6]. Several periorbital markers of atopy have also
been described. The Dennie-Morgan fold is a crease from
the inner canthus extending laterally to the midpupillary
line of the lower eyelid [2,6]. Periorbital darkening, known
as the “allergic shiner,” is also commonly encountered [2].
Hertoghe’s sign is seen in severe forms of atopic lid disease
and is identified by the absence of lateral eyebrows [6].
Eyelid margin inflammation, known as blepharitis, is also
commonly seen. It presents with morning crusting, eyelid
hyperemia, and eyelash abnormalities [2]. Madarosis is
loss of eyelashes and trichiasis is misdirection of eyelashes
(Fig. 1). Trichiasis can be very annoying to the patient,
especially when the lashes are in contact with the surface
of the eye (Fig. 1).
Chronic colonization with bacteria is another problem
commonly associated with the skin abnormalities of atopic
disease. Staphylococcus aureus is found on the skin of only
5% to 10% of healthy persons and is usually confined to
the vestibulum nasi, axilla, perineum, and the interdigital
spaces of the feet [7,8•]. In patients with atopic dermatitis,
S. aureus colonizes 40% to 90% of the patients, and it is
found on even normal-appearing skin [7,8•]. It is postulated that the organism comes from the fingernails and is
spread by frequent rubbing and itching. More than 90%
of the S. aureus phagotypes derived from the skin match
those from the fingernails [7,8•]. Such bacterial colonization must be taken into account when ocular surgeries are
planned. Thorough preoperative disinfection with a povidone iodine preparation is mandatory. Some even suggest
that bacterial isolation should be performed preoperatively
so that antibiotic sensitivities can be determined for use
during the perioperative period [7,8•].
Symblepharon
Limbal papillae
Corneal erosions, ulcers, neovascularization, and scarring
Keratoconus
Anterior and posterior subcapsular cataracts
but they can also be due to seasonal or perennial allergic
conjunctivitis, giant papillary conjunctivitis, and vernal keratoconjunctivitis. Allergic conjunctivitis is a
commonly encountered entity that occurs seasonally
in response to a wide variety of airborne allergens. It
is characterized by itching, burning, redness, tearing,
chemosis (conjunctival swelling), and lid edema, and
is often found with concomitant allergic rhinitis and/or
sinusitis [1]. Perennial allergic conjunctivitis presents in
a similar fashion but is less common and occurs without
seasonal dependence. Perennial allergens, such as house
dust mites, animal danders, and mold, may be the underlying provoking agents [1]. Giant papillary conjunctivitis
is an inflammatory reaction of the upper tarsal conjunctiva usually thought to be due to a reaction to a foreign
body on the external ocular surface [1]. The most common offending agents are contact lenses and products
associated with their use. Although the symptoms may
be severe and troublesome to the patient, these disorders
are not usually accompanied by the sight-threatening,
severe ocular inflammation that is the hallmark of atopic
disease. The other disorder that can mimic atopic disease
and potentially has sight-threatening findings is vernal
keratoconjunctivitis. It is sometimes difficult to distinguish between the two, but vernal keratoconjunctivitis
is more likely to have seasonal variation, is more likely
to resolve spontaneously, and is more likely to present
at an earlier age, typically in the second decade of life
[5,6]. Atopic keratoconjunctivitis can begin in the teenage years, but occurs more often in the third or fourth
decades of life [5,6]. Finally, vernal disease more commonly affects the superior conjunctiva with papillae as
compared to the more common inferior eyelid disease of
atopic keratoconjunctivitis [6].
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Ocular Allergy
Atopic dermatitis patients are also prone to severe
herpes simplex infections that can include eczema herpeticum or Kaposi’s varicelliform eruption. This disorder
is a generalized vesicular eruption that can be seen in the
dermatitic skin of the atopic individual and can be lifethreatening. In the periorbital area, it can present with
umbilicated vesicles, reddened conjunctiva, and keratitis
(corneal infection) [2,8•]. Atopic individuals seem to be
particularly prone to herpes simplex keratitis, and it is
commonly bilateral with frequent recurrences and slow
healing, even with appropriate antiviral therapy [2,6,8•].
The slow healing also makes these patients prone to
secondary bacterial infections because of the previously
mentioned bacterial colonization. Atopic dermatitis
patients are also prone to infections with viral warts and
molluscum contagiosum [2,8•].
Ocular manifestations
The ocular findings of atopic keratoconjunctivitis can
be significant and can lead to visual loss if not managed
appropriately (Table 1). Severe ocular surface inflammation is the rule, and this can lead to erythematous
and chemotic conjunctiva. Tarsal conjunctival papillary
hypertrophy is common as are limbal papillae that give
the appearance of gelatinous nodules adjacent to the
cornea [2,6]. Chronic disease can lead to conjunctival
scarring with shortening of the inferior fornix and symblepharon formation [2,6].
Corneal findings mostly affect the inferior third of
the cornea, with punctuate erosions and neovascularization [2,6]. However, visual acuity can be reduced by
corneal haze, microcysts, thinning, and extension of the
new blood vessels into the central cornea. Corneal ulceration can also occur, and these ulcers can be infectious or
noninfectious [2,6]. The noninfectious ulcers present as
persistent epithelial defects with corneal thinning and can
occur in up to 37.8% of the patients [1]. Corneal ectasias
such as keratoconus have also been shown to occur frequently in patients with atopic disease. A study by Foster
and Calonge [1] found a 6.7% rate of keratoconus in 45
patients. Tuft et al. [5] found that six of their 37 patients
had keratoconus, for a rate of 18%. Harrison et al. [9]
also found an increased rate of kerataconus among atopic
patients. They also found that patients with atopy and
keratoconus did not differ in regard to sex, age of onset, or
rate of keratoplasty. However, patients with very high levels of
systemic IgE did appear to be more prone to corneal transplant rejections [9]. It is unclear why atopic individuals have
a greater rate of keratoconus but it may be due to excessive
eye rubbing or a genetic predisposition.
Lenticular abnormalities are also commonly identified in atopic individuals. Whether cataracts are truly a
manifestation of atopy or a complication of corticosteroid treatment is still under debate. Some believe that
atopic individuals are predisposed to cataract formation,
whereas others believe that cataract progression is has-
tened by the concomitant use of steroids. Cataracts in
atopic individuals tend to be subcapsular with posterior
subcapsular cataracts being more common than anterior
subcapsular cataracts [2,6]. The appearance of cataracts
from atopy is indistinguishable from those induced by
steroids, making the cause and effect relationship even
harder to prove.
When a patient presents with significant eyelid or
ocular disease, it is important to remember that atopic
dermatitis is a systemic disorder. The skin disease usually presents before the ocular disease. The infantile
stage begins between 6 months and 2 years of age and
usually affects the extensor surfaces, such as the tops of
the feet, the backs of the hands, the knees, and the face.
When the patients are older, usually the flexural sites are
affected—for example, the antecubital fossae and behind
the knees [2,6]. Cutaneous infections can complicate the
skin disease, and the constant scratching and rubbing can
lead to permanent scarring. Many of these patients also
suffer from psychoneurotic behavior, such as poor compliance and medication abuse. Foster and Cologne [1] found
psychoneurotic problems in 33% of their study population.
Pathogenesis
The exact underlying pathogenesis of atopic dermatitis
and atopic keratoconjunctivitis is unknown. However,
both type I and type IV hypersensitivity reactions appear
to be involved [1,6]. Elevated serum and tear levels of IgE
are characteristic of exacerbations of atopic keratoconjunctivitis, and during remissions, these levels decline
[6]. Cell-mediated immunity defects have been found in
the skin, but there is still no clear evidence of a systemic
defect in cell-mediated immunity [2]. Recent research
efforts have concentrated on the basis for the increased IgE
synthesis and how it is related to defects in T-cell regulation. Interleukin (IL)-4 from T cells acts as a switch factor
to commit B cells to the IgE pathway [10]. In contrast,
interferon (IFN)-γ inhibits IgE synthesis and IL-4–induced
IgE synthesis [10]. Thus, the finding that atopic dermatitis
patients have decreased levels of IFN-γ from a post-transcriptional defect and that they have increased levels of
IL-4 is important in planning future immune-modulating
therapies [10,11]. It also gives a rationale for the use of IFNγ as a therapeutic agent. A recent study showed that the
administration of IFN-γ not only decreased the production
of IgE but it also improved the skin disease in patients with
atopic dermatitis [10].
Treatment
The treatment of eyelid atopic dermatitis and atopic keratoconjunctivitis can be very challenging and requires
a compliant patient and a dedicated physician. The
underlying goal is the preservation of vision and the
reduction of symptoms while carefully managing the
side-effect profile of the therapeutic agents used. Usually, a chronic regimen of agents that can be used on
The Ocular Manifestations of Atopic Dermatitis and Rosacea
a long-term basis is used, and then exacerbations are
treated aggressively to prevent damage. The mainstay of
treatment is designed to break the “itch-scratch” cycle
that can cause mechanical degranulation of mast cells,
further traumatize the inflamed skin, and increase the
risk for secondary infection [2,6]. It is also important
to remember that atopic dermatitis is a systemic disease
and that it may be helpful to manage the patient with
a team that includes dermatologists, ophthalmologists,
and allergists.
Patients should be instructed to avoid known inciting allergens and to use cool compresses and bland
emollients to help with itching of the eyelid skin. Bland
emollients include ointment-based agents without preservatives or fragrances, such as white petrolatum and
Aquaphor (Beiersdorf, Norwalk, CT) [2]. These agents
also help restore the epidermal barrier function of the
skin by decreasing xerosis [2]. Antihistamines can also be
prescribed to diminish skin itch. The nonsedating agents
can be used during the day, and the more sedating ones
can be used before bed.
Periodic exacerbations of skin disease can be treated
with short courses of low-dose topical corticosteroid.
Fluorometholone 0.1% ophthalmic ointment can be
used two to three times a day on the eyelid skin and
then tapered over a week or two. Because it is an ophthalmic ointment, it is much less irritating (if some gets
in the eye) than skin preparations used on the eyelid
skin. When using steroids, the philosophy of using the
lowest dose possible for the shortest time possible is
important to prevent the complications of long-term
steroid use around the eye, such as glaucoma, cataract,
skin atrophy, telangiectasia, and infection. If frequent
topical steroid application is necessary, one should
consider starting the immune-modulating agent tacrolimus. Tacrolimus 0.1% ointment twice a day has been
shown in several studies to be a safe and effective treatment option for patients with moderate-to-severe eyelid
dermatitis [12•,13]. Tacrolimus works by blocking Tlymphocyte activation and by inhibiting the production
of proinflammatory cytokines. Side effects appear to be
minimal and include itching and burning at the site of
application with a decrease in these symptoms as skin
inflammation improves [12•]. Systemic absorption of
the topical agent has been shown to be minimal without associated adverse sequelae [12•].
The treatment philosophy for atopic keratoconjunctivitis is similar to the treatment of the eyelid dermatitis. A
regimen of agents that are safe for long-term use should
be instituted to include a preservative-free artificial tear
preparation and a mast-cell stabilizer antihistamine
combination. There are several of these combination eye
drops available, including olopatadine 0.1% and ketotifen 0.025%, and they can be used two to three times a
day. Topical vasoconstrictors should be avoided because
they can cause rebound hyperemia with long-term use.
Eiseman
295
Topical nonsteroidal agents may also have a role in treating both ocular inflammation and pruritis. Ketorolac
tromethamine 0.5% can be used up to four times a day
and works by inhibiting prostaglandin synthetase [6].
Topical nonsteroidal agents may sting upon instillation,
and there has been some evidence to suggest that they
can cause corneal abnormalities, including corneal
melting, that can result in ocular perforation. Although
the evidence for corneal melts is anecdotal, it may be best
to only prescribe these agents when the patient is being
carefully followed by an ophthalmologist.
Severe exacerbations can be treated with topical
corticosteroids. They block the formation of arachidonic acid metabolites by inhibiting phospholipase
A 2, which in turn prevents leukocyte immigration [6].
As with the treatment of the skin disease, the lowest
dose of topical steroid should be used for the shortest
amount of time. This will reduce the ocular inflammation while minimizing the complications of steroid use
that include infections, glaucoma, cataracts, and the
possibility of corneal melts. Topical corticosteroids
should only be administered by ophthalmologists.
New agents are currently under investigation that can
reduce the ocular inflammation while minimizing the
risks of steroid administration. One such item is topical
cyclosporine 0.05%. Cyclosporine acts specifically and
reversibly on T lymphocytes and inhibits the release
of lymphokines by activated T cells. A recent study
showed that topical cyclosporine appears safe and
has some effect in alleviating the signs and symptoms
of severe atopic keratoconjunctivitis that is refractory to topical steroid treatment [14•]. Additional research using
immune-modulating agents may give hope to patients
with severe resistant disease or to those who are suffering
from the side effects of topical steroids.
Rosacea
Rosacea is a chronic disorder affecting the sebaceous
glands of the face. It is characterized by inflammatory
papules and pustules, facial flushing, erythema and
telangiectasia, ocular lesions, and occasionally by connective tissue hypertrophy resulting in rhinophyma
[2,15]. Rosacea may be found in up to 10% of the general population and mostly affects adult white women
at a rate two to three times greater than that for men
[15]. Disease severity may be worse in men, and ocular
complications may be worse in men as well. Rosacea
typically affects patients who are between the ages of 40
and 50, whereas ocular rosacea appears more common
between the ages of 50 and 60 [2,15,16]. Ocular rosacea
occurs in patients with rosacea from 3% to 58% of the
time, depending on the series studied [2,15,16]. Ocular
disease is independent of the severity of the skin disease
and seems to occur with equal frequency in men and
women [2,15,16].
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Ocular Allergy
Table 2. Ocular manifestations of rosacea
Periorbital lymphedema
Eyelid margin erythema and telangiectasia
Blepharitis, and inspissated meibomian gland orifices
Hordeola (styes) and chalazia
Bacterial colonization
Dry eye
Corneal erosions, vascularization, and thinning
Episcleritis, scleritis, iritis, and vitritis
Dermatologic findings
Rosacea is a clinical diagnosis, and in patients with skin
and ocular disease, 53% develop their skin lesions first,
20% develop their ocular disease first, and 27% develop
them simultaneously [15]. There are four stages of rosacea.
The first is characterized by recurrent flushing of the
face, which may extend to the neck, presternal area, and
shoulders. Flushing is often triggered by hot beverages,
tobacco, alcohol, spicy foods, and emotional stress [15].
The second stage is vascular. After recurrent episodes
of flushing, the forehead, cheeks, nose, and neck show
persistent erythema from an increased number of erythrocytes in a mildly inflamed superficial vasculature [15].
The third stage is inflammatory. It is characterized by
papules and pustules. Rosacea can be distinguished from
acne vulgaris by the absence of comedones and by confinement of the lesions to the flush areas [16]. The last
stage, rhinophyma, is the least common. It is seen almost
exclusively in men after decades of chronic disease [16].
Ocular manifestations
Ocular rosacea can be severe even if the dermatologic
involvement is minor (Table 2). Symptoms can be out of
proportion to the findings and include burning, redness,
itching, foreign-body sensation, tearing, dryness, photophobia, and lid fullness and swelling [2,15]. The primary
defect in ocular rosacea is related to meibomian gland
dysfunction and includes inflammation of the glands with
dilation and plugging of the gland orifices [2]. Pressure on
the eyelids below the gland openings will often produce a
thick toothpaste-like secretion. Chronic inflammation can
result in complete loss of secretion and gland drop-out with
hyperkeratinization of the ductal epithelium [2,15]. These
gland abnormalities lead to eyelid disease that includes
blepharitis, hordeola, chalazia, and telangiectasias [15].
The eyelids often become thickened with prominent vascularization, keratinization, and inspissated meibomian
gland orifices that may be reduced in number [2]. Signs of
blepharitis include collarettes around lashes, loss of lashes,
whitening of lashes, misdirected lashes, and erythema of
the lid margin (Fig. 2). Telangiectatic vessels can be seen
crossing the eyelid margin [2]. Internal hordeola often
develop and represent individual inflamed meibomian
glands. Chalazia, or sterile lipogranulomas, also occur due
Figure 2. Patient with rosacea shows significant eyelid inflammation
with débris in lashes (blepharitis), conjunctival injection, and
medial corneal infiltration (keratitis). Note the nasal changes as
well (rhinophyma).
to extravasation of the meibomian gland secretions into
the lid [15]. Recurrent chalazia are twice as common in
patients with rosacea, and 57% of the patients presenting
with chalazia have signs of rosacea [2,17]. Staphylococcal
colonization is also quite common and can contribute to
ocular complications as well [15,16].
Conjunctival hyperemia is one of the more common
findings in ocular rosacea, and it is usually found widely
dispersed in the interpalpebral zone, although it can also
be found more focally with conjunctival induration (Fig. 2).
These conjunctival signs can be worsened by decreased
tear production that is found in more than one third of
the patients with ocular rosacea [2,15]. However, tear
abnormalities are not only due to decreases in the aqueous
component of the tear film. Qualitative abnormalities also
occur and are due to the abnormal lipid secretions from
the meibomian glands. The lipid layer of the tear film usually stabilizes the tear film and prevents rapid evaporation.
Abnormalities of this function can be seen by abnormally
fast tear break-up times. A dry spot occurring in the tear
film in less than 10 seconds after a blink to redistribute
fluorescein dye is considered abnormal [2].
Corneal findings in ocular rosacea are also common
and include inferior punctuate keratopathy and superficial vascularization of the peripheral cornea with a
wedge-shaped subepithelial infiltrate [2,15,16]. Vascularization can encroach on the visual axis and lead to
decreased vision, as can inflammatory episodes that can
lead to deeper corneal scarring, ulceration, thinning,
and, rarely, perforations [2,15,16]. Secondary bacterial
infections can also be seen, especially with the incidence
of bacterial colonization previously discussed. Other
ocular manifestations of rosacea have been reported, but
The Ocular Manifestations of Atopic Dermatitis and Rosacea
with much lower frequency. These include chronic periorbital lymphedema, also known as blepharophyma, and
episcleritis, scleritis, iritis, and vitritis [2,15,16,18,19].
Pathogenesis
The cause of rosacea is unknown, but there are many
hypotheses, and several associations exist. Some believe
it is primarily a vascular disease, as facial blood flow in
affected patients is three to five times that of normal controls [15]. Sunlight-induced damage also seems to play a
role, as increased levels of solar elastosis are evident in
histopathologic specimens of skin involved with rosacea.
Further evidence for this comes from the occurrence of
rosacea in sun-exposed skin, its prevalence in older,
fair-skinned individuals, and its increase in frequency
during the springtime months [15,16]. A cell-mediated
immune hypersensitivity may play a role because histopathologic specimens show inflammatory cell infiltration
with granuloma formation, and rosacea patients have
a higher incidence of autoimmune disease [15]. Associations also exist between rosacea and gastrointestinal
disorders, especially gastric disease. Studies have identified achlorhydria in some and increases in Helicobacter
pylori in others [15,16]. Whether H. pylori colonization is
truly a cause or just an associated finding is still unclear.
Demodex mites have also been proposed as a possible
inflammatory agent because increased numbers of mites
have been found on rosacea-affected skin when compared
to controls [15]. Antibodies to Demodex have also been
found in affected skin and in conjunctival epithelium of
inflamed eyes [15,16]. The role of these antibodies is not
known, but they may play a proinflammatory role or be a
causative agent in a subset of patients [15,16].
The sebaceous and meibomian glands of rosacea
patients exhibit abnormalities to include keratinization
of epithelial cells that leads to thickened secretions and
plugging of the orifices with subsequent trapping of secretions as well [15]. The meibomian glands also produce an
increased amount of free fatty acids that may cause tearfilm instability and irritation to the ocular tissues [15,16].
Whether this increase in free fatty acids is due to a primary
biochemical abnormality or due to bacterial lypolytic
exoenzymes that split neutral lipids into free fatty acids
or a combination of both is not known [15,16,20]. Bacterial colonization, especially with Propionibacterium acnes
and S. aureus, is quite common in rosacea patients, and
these bacteria are known to contain the lipases discussed
earlier [15,16,20]. No one theory adequately explains the
development of all of the signs and symptoms of rosacea.
Rosacea is probably a combination of several factors that
act together to produce the clinical entity observed.
Treatment
Rosacea is a chronic disease with intermittent exacerbations that cannot be cured. However, the disease can be
controlled with maintenance therapy and more aggres-
Eiseman
297
sive treatment to control exacerbations. The flushing and
erythema stage is difficult to treat, and there is currently
no satisfactory treatment [2]. Patients should be advised
to avoid exposure factors, such as sunlight, heat, hot
drinks, spicy food, and other known triggers, to minimize flushing. Broad-brim hats and sunscreen can also
be helpful. The mainstay of treatment is oral antibiotic
therapy, and tetracycline and its derivatives, such as
doxycycline, are most effective. These drugs are incorporated into the sebum and alter the interaction of sebum
and bacteria by decreasing the concentration of free fatty
acids [15,16]. They also decrease the production of microbial inflammatory mediators and can produce significant
positive effects on ocular disease even without decreasing the number of bacteria on the lids [15,16]. Side effects
include gastrointestinal upset, vaginal yeast infections,
photosensitivity, and decreased effectiveness of oral contraceptives [2,15]. Tetracycline 250 mg four times a day
for 6 to 8 weeks followed by 250 mg a day for a total of
3 months has shown to be effective in all ocular lesions
[2,16]. An alternative that minimizes the gastrointestinal
upset and increases compliance is doxycycline 100 mg
twice a day for 6 to 8 weeks followed by 100 mg a day for
a total of 3 months.
Moderate-to-severe skin involvement can be treated
with metronidazole gel 0.75% twice a day. It has been
shown to decrease papules and pustules and can help
somewhat with erythema as well [21]. It is well-tolerated
but may increase the number of visible telangiectasias
[21]. An ocular preparation is not available, and, therefore, eyelid application should be done with care. Other
topical agents that have shown effectiveness for the
treatment of papules and pustules include topical 0.1%
tretinoin cream twice a day [2,15]. These agents can cause
skin irritation and erythema and should be used with
care on the eyelids.
The treatment of eyelid disease revolves around
treating the blepharitis. Warm compresses are effective
at melting and unplugging the meibomian glands, and
this may speed the resolution of hordeola and chalazia as well. Gentle massage of the tarsal plate can help
express secretions from the glands [2]. Eyelid-margin
scrubs with a dilute solution of baby shampoo can
remove oil and débris, and the application of an ophthalmic antibiotic such as erythromycin or bacitracin
once or twice a day can decrease bacterial lipases that
can produce free fatty acids [2,15]. Dry eye should be
aggressively treated with preservative-free artificial
tears at least four times a day. If this is not effective
enough, temporary or permanent punctal occlusion
can be used. Steroids should only be used for more
severe inflammation that is refractory to other treatments or if iritis is encountered. The lowest dose for the
shortest time should be used under the direct supervision of an ophthalmologist to reduce the complications
of cataract, glaucoma, and infection.
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Ocular Allergy
Conclusions
Atopic dermatitis and rosacea are two chronic diseases
that have both dermatologic and ocular manifestations.
The ocular disease can be proportionately higher than the
dermatologic disease, and, even if the skin abnormalities
appear well-controlled, these patients require ophthalmic
evaluation as well. Optimal management usually requires
a team approach that includes internists, dermatologists,
and ophthalmologists. Both disorders require maintenance
therapy for control, but even with adequate maintenance
therapy, acute exacerbations are common. Exacerbations
need aggressive treatment to limit ocular signs and symptoms and to reduce ocular inflammation that can lead to
permanent visual loss. Topical corticosteroid use should
be minimized for both disorders. If they are required, the
lowest dose should be used for the shortest time to reduce
ocular inflammation and complications. Future research
will probably continue to emphasize the use of steroidsparing and immune-modulating agents that have the
potential to provide long-lasting anti-inflammatory treatment with a better side-effect profile.
Acknowledgments
The views expressed in this manuscript are those of the
author and do not reflect the official policy of the Department of the Army, the Department of Defense, or the
United States Government.
References and Recommended Reading
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