1. Treatment of
hyperpigmentation
Hyperpigmentation is treated
with products containing hydroquinone that produce reversible depigmentation of
the skin by inhibiting the enzymatic oxidation of tyrosine to
3,4-dihydroxyphenyalanine and also
inhibiting other melanocyte metabolic processes.
It is indicated for the
gradual bleaching of hyperpigmented skin in conditions such as melasma and freckles.
Concomitant application of SPF
15–30 sunscreens and meticulous photoprotection are essential to minimize
sun-induced exacerbation of hyperpigmentation.
Photoprotection from the acute
and chronic effects of sun exposure is readily available with sunscreens that
include :
Chemical agents that absorb
incident solar radiation in the UVB and/or UVA ranges
Physical agents that contain particulate materials
that can block or reflect incident energy and reduce its transmission to the
skin.
Ideal properties of Sunscreens
Many of the sunscreens
available are mixtures of organic chemical absorbers and particulate physical
substances.
Ideal sunscreens provide a
broad spectrum of protection and are formulations that are:
photostable
remain intact for sustained periods on the skin.
They should also be
nonirritating, invisible, and nonstaining to clothing.
No single sunscreen ingredient
possesses all these desirable properties, but many are quite effective
nonetheless.
UVA sunscreens
UVA filters include:
avobenzone,
oxybenzone
(2-hydroxy-4-methoxy-benzophenone);
titanium dioxide;
zinc oxide.
Other UVA sunscreens include:
ecamsule,
bisethylhexyloxyphenol methoxyphenyl triazine,
methylene bisbenzotriazolyl
tetramethylbutylphenol.
UVB Sunscreen Agents
There are numerous UVB
filters, including PABA esters (e.g., padimate O); cinnamates (octinoxate); octocrylene
(2-ethylhexyl-2-cyano-3,3 diphenylacrylate); and salicylates (octisalate).
Sunscreens: Sun protection
factor(SPF)
The major measurement of
sunscreen photoprotection is the sun protection factor (SPF)
SPF defines a ratio of:
The minimal dose of incident
sunlight that will produce erythema or redness (sunburn) on skin with the
sunscreen in place (protected) and
The dose that evokes the same
reaction on skin without the sunscreen (unprotected).
Sunscreens:
SPF
The SPF provides valuable
information regarding UVB protection but is not useful in documenting UVA
efficacy because no standard systems have been developed to measure UVA
protection.
Such protocols are needed
because more than 85% of solar ultraviolet radiation reaching earth’s surface
is UVA, which penetrates more deeply into human skin than does UVB and appears
to play an important role in photoaging and photocarcinogenesis.
Regular use of sunscreens has been found to reduce the risk of actinic keratoses and
squamous cell carcinomas of the skin.
3. Antimalarial drugs
used in dermatology
The major antimalarials used
commonly in dermatology include :
chloroquine ,
hydroxychloroquine and
to a lesser extent, quinacrine.
All the three drugs are useful because of their
anti-inflammatory effects especially in connective tissue disorders and
photosensitivity diseases.
Mechanisms of action
The mechanism of action of the
immunological and anti-inflammatory effects of antimalarials include:
Inhibition of phospholipase A2
(hydrolyzes phospholipids leading to formation of arachdonic acid) ,
A range of lysosomal effects
(e.g., an increase in pH, membrane stabilization, and inhibition of release and
activity of lysosomal enzymes),
Inhibition of phagocytosis,
An increase in intracellular pH
in cytoplasmic vacuoles leading to decreased stimulation of autoimmune CD4+ T
cells,
Decreased cytokine release from lymphocytes and
stimulated monocytes,
Inhibition of immune complex formation, and antioxidant
activity.
In patients with porphyria cutanea tarda,
chloroquine and hydroxychloroquine bind to porphyrins and/or iron to facilitate
their hepatic clearance.
The ability to bind to melanin and other pigments may contribute to the
retinal toxicity seen occasionally when antimalarial agents are used.
Therapeutic uses
Hydroxychloroquine is used in
treatment of discoid and systemic lupus erythematosus.
It is also a first-line drug in the treatment
of dermatomyositis, porphyria cutanea tarda and sarcoidosis.
Usual doses of antimalarials are
hydroxychloroquine, 200 mg twice a day; chloroquine, 250–500 mg/day; and
quinacrine, 100–200 mg/day.
Therapeutic uses
Usually, hydroxychloroquine is
started first, and if no improvement is noted in 3 months, quinacrine is added.
Alternatively, chloroquine is
used as a single agent.
Dosing should be adjusted for
low-weight individuals so that chloroquine dosing is 2.5 mg/kg/day and
hydroxychloroquine is 6.5 mg/kg/day.
Antimalarial agents are the
treatment of choice for widespread forms of cutaneous lupus that do not respond
to topical glucocorticoids and sunscreens.
Clinical improvement may be
delayed for several months.
Therapeutic uses
Porphyria cutanea tarda,
characterized by fluid-filled vesicles and bullae on sun-exposed areas, can be
either genetic or associated with alcohol abuse or hepatitis C.
Although the associated iron
overload is treated with phlebotomy, the dermatologic manifestations sometimes
are treated with antimalarial agents.
These patients require reduced
doses because of the potential for hepatotoxicity, as manifested by elevated
transaminase levels, and the rapid excretion of large amounts of uroporphyrins
in the urine that can occur with usual doses.
Low-dose twice-weekly
administration is effective and avoids these side effects.
Toxicity and monitoring
The incidence of retinopathy
from chloroquine and hydroxychloroquine is low, as long as the doses are as
described above and the medication is used for less than 10 years in patients
with normal renal function.
Quinacrine does not cause
retinopathy. Eye examinations every 6 months or even yearly after a baseline
examination probably are sufficient, provided dosing guidelines are followed.
Toxicity and
monitoring
Although caution is required,
there is evidence that antimalarial agents probably are safe in pregnancy and
in children.
Rare hematological side
effects include agranulocytosis, aplastic anemia, and hemolysis in patients
with glucose-6-phosphatase deficiency.
Liver function tests and
complete blood counts should be performed monthly at the start of therapy and
at least every 4–6 months throughout treatment.
4. Glucocorticoids:
General principles
Glucocorticoids are prescribed
frequently for their immunosuppressive and anti-inflammatory properties.
They are administered locally,
through topical and intralesional routes, and systemically, through
intramuscular, intravenous, and oral routes.
Therapeutic uses
Glucocorticoids are used in
treatment of many inflammatory skin diseases.
The administration is either
topical or intralesional.
Selection of the steroid is
based on:
Potency ,
The site of involvement,
The severity of the skin disease.
Administration of
glucocorticoids
Usually, a more potent steroid
is used initially, followed by a less potent agent.
Twice-daily application is sufficient,and more
frequent application does not improve response.
In general, only nonfluorinated
glucocorticoids should be used on the face or in occluded areas such as the
axillae or groin.
Intralesional preparations of
glucocorticoids include insoluble preparations of triamcinolone acetonide and
triamcinolone hexacetonide, which solubilize gradually and therefore have a
prolonged duration of action.
Glucocorticoids: Potency
Low potency steroids are the
safest agents
For long term use
On large surface areas
On the face and other areas of the body with thinner skin
On children
Glucocorticoids: Potency
More potent agents are
beneficial for:
Severe diseases
Areas of the body where the
skin is thicker e.g. palms and soles
Toxicity and monitoring
Chronic use of potent topical
glucocorticoids (e.g., diflorasone diacetate 0.05%, betamethasone dipropionate
0.05%) can cause skin atrophy, striae, telangiectasias, and acneiform eruptions.
Because perioral dermatitis
and rosacea can develop after the use of fluorinated compounds on the face,
they should not be used in this site.
Systemic
glucocorticoids
Systemic glucocorticoid
therapy is used for severe dermatological illnesses.
In general, it is best to
reserve this method for allergic contact dermatitis to plants (e.g., poison
ivy) and for life-threatening vesiculobullous dermatoses such as pemphigus
vulgaris and bullous pemphigoid.
Chronic administration of oral
glucocorticoids is problematic, given the side effects associated with their
long-term use.
Systemic glucocorticoids:
Administration
Daily morning dosing with
prednisone generally is preferred, although divided doses are used occasionally
to enhance efficacy.
Fewer side effects are seen
with alternate-day dosing, and if required for chronic therapy, prednisone is
tapered to every other day as soon as it is practical.
Systemic glucocorticoids:
Administration
Pulse therapy using large
intravenous doses of methylprednisolone sodium succinate (SOLU-MEDROL) is an
option for severe resistant pyoderma gangrenosum, pemphigus vulgaris, systemic
lupus erythematosus with multisystem disease, and dermatomyositis.
The dose usually is 0.5–1 g
given over 2–3 hours.
More rapid infusion has been
associated with increased rates of hypotension, electrolyte shifts, and cardiac
arrhythmias.
Toxicity and monitoring
Most side effects are
dose-dependent.
Long-term use is associated
with a number of complications, including psychiatric problems, cataracts,
myopathy, osteoporosis, avascular bone necrosis, glucose intolerance or overt
diabetes mellitus, and hypertension.
In addition, psoriatic
patients treated with parenteral or topical glucocorticoids may have a pustular
flare, particularly if the steroid is tapered rapidly.
5. Capsaicin
Capsaicin is a naturally
occurring substance derived from hot chili peppers of the genus Capsicum.
Capsaicin interacts with the
vanilloid receptor (VR1) on sensory afferents.
Capsaicin
VR1 is a gated cation channel
of the TRP family, modulated by a variety of noxious stimuli.
Chronic exposure to capsaicin
stimulates and desensitizes this channel.
Capsaicin also causes local
depletion of substance P, an endogenous neuropeptide involved in sensory
perception and pain transmission.
Capsaicin: Therapeutic uses
Capsaicin is available as a
0.025% cream and a 0.075% cream to be applied 3–4 times daily.
Capsaicin is FDA-approved for
the treatment of postherpetic neuralgia and painful diabetic neuropathy.
6. Masoprocol
Masoprocol, a dicatechol
compound with an aliphatic spacer, is derived from the plant Larrea divaricata;
It is a potent 5-lipoxygenase
inhibitor with antitumor activity.
It is effective for the
topical therapy of actinic keratoses.
Masoprocol is available as a
cream (ACTINEX) and is applied twice daily for approximately 1 month.
Common side effects include
redness, scaling, and pruritus.
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