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Al ternati ve Therapi es

for Common
Dermatol ogi c
Di sorders, Part 1
Vincent Morelli, MD*, Erick Calmet, MD,
Varalakshmi Jhingade, MD
ROSACEA
Rosacea, a common inflammatory/infectious condition, is frustrating for afflicted
patients and treating physicians. Although its clinical manifestations of facial flushing,
erythema, papules, pustules, ocular manifestations (conjunctivitis/blepharitis in 50%
of patients), and rhinophyma are well recognized, the cause remains unknown.
Current theories lean toward a genetic predisposition coupled with environmental
exposures leading to the inflammatory clinical manifestations. Vascular degradation
and inflammation are thought to play a key role.
1
Exacerbations of the disease have
been reported with the ingestion of various foods, under various environmental condi-
tions (sun, wind, cold) and in stressful emotional states.
2
Although the association of
rosacea with Helicobacter pylori and follicular mite infection has been postulated, no
definite conclusions in this regard have emerged nor have any more efficacious treat-
ments resulted from this line of inquiry.
35
Despite ongoing research, the cause and cure remain elusive. This leads many
patients to seek alternative therapies. The most frequently used herbal compounds
include licorice, feverfew, green tea, oatmeal, lavender, chamomile, tea tree oil, and
camphor oil. The usefulness of most of these herbs is based on their topical anti-
inflammatory properties.
Department of Family and Community Medicine, Meharry Medical College, School of Medi-
cine, 1005 Dr DB Todd Jr Boulevard, Nashville, TN 37208, USA
* Corresponding author.
E-mail address: morellivincent@yahoo.com
KEYWORDS

Dermatology

Alternative medicine

Rosacea

Seborrheic dermatitis

Urticaria

Herpes simplex

Apthous stomatitis

Psoriases
Prim Care Clin Office Pract 37 (2010) 269283
doi:10.1016/j.pop.2010.02.004 primarycare.theclinics.com
0095-4543/10/$ see front matter 2010 Elsevier Inc. All rights reserved.
Biologic-Based Therapies
Chrysanthellum indicum
Chrysanthellum indicum is a plant-based extract from the mothers daisy or golden
chamomile flower. This compound contains phenylpropanoic acid, flavonoids, and
saponoids and has been found in vitro to have a salutary effect on vascular wall
stability and permeability.
6
One recent randomized trial of 246 patients
7
evaluated chrysanthellum indicum
cream versus placebo in the treatment of moderate rosacea. Investigators found
that twice-daily application of the cream resulted in statistically significant improve-
ments in most study metrics (erethema surface and erethema severity); however,
this probably results in little, if any, practical usefulness in the clinical setting.
Chibixiao recipe
This herbal compound, Chibixiao recipe, is the aqueous extract of several herbs used
in Chinese medicine (made from loquat leaf, mulberry bark, scutellaria root, imperata
rhizome, red peony root, safflower, red sage root, chuanxiong, dahurian angelica root,
motherwort, and Chinese trumpet creeper flower). It was given twice daily to 68
women with rosacea in a recent randomized trial. All women were put on antiandro-
genic spironolactone and then randomized to a treatment arm or placebo arm.
Women were evaluated over an 8-week period. In the treated group, the cure rate
was 87.5% and the recurrence rate was 6.5%. The control group showed only
a 45% cure rate with a 41.2% recurrence rate. This initial study seems promising
and may merit further studies with larger numbers of patients and further standardiza-
tion of the therapeutic compounds.
8
Azelaic acid
Azelaic acid, a naturally occurring 9-carbon acid found in whole grain cereals and
animal products, has beenshowntonormalizekeratinization anddecreaseproliferation
of bacteria that contribute to acne. Although it is Food and Drug Administration (FDA)
approved as a topical preparation to treat acne vulgaris, it is also used by some as an
off-label treatment of rosacea. Although the product is commercially available, it is dis-
cussed in this article because it is based in naturally occurring plant compounds.
Two recent trials evaluated the efficacy of azelaic acid in the treatment of rosacea.
The first, a 3-month randomized trial of 116 patients, found that a twice-daily applica-
tion of azelaic acid (20% cream) was more effective than placebo in the treatment of
papulopustular rosacea. There was a greater reduction in total inflammatory lesions,
73.4% reduction with azelaic acid and 50.6% reduction placebo (P 5 .011), and in
erythema severity score, 47.9% reduction with azelaic acid and 37.9% reduction
with placebo (P 5 .031). Physician and patient satisfaction ratings were higher in
the azelic acid group. Local adverse reactions were mild and transient, and there
was no difference between azelaic acid and placebo.
9
The second study compared the efficacy of topical azelaic acid 20% cream and
topical metronidazole 0.75% cream in 40 patients with rosacea. After 15 weeks of
treatment, both treatment groups showed equal reductions in the number of inflam-
matory lesions (pustules and papules) and equal reductions of signs and symptoms
of dryness, burning, telangiectasia, and itching. A trace amount of stinging on applica-
tion was reported with azelaic acid; however, such discomfort did not seem to
concern patients because their overall impression of azelaic acid was superior to
that of metronidazole. The study concludes, azelaic acid (20%) cream is an effective
and safe alternative to metronidazole (0.75%) cream with the added benefit of
increased patient satisfaction.
10
Morelli et al 270
Alternative Systems
Although a true cure for rosacea has been elusive, a summary of the useful alternative
treatments is listed:
1. Apply zelaic acid (20%) cream twice daily.
2. Although controversial, consider evaluation for and treatment of H pylori.
3. The Textbook of Natural Medicine
11
recommends dietary avoidance of coffee,
caffeine, alcohol, hot or spicy foods, refined sugar, transfatty acids, milk, and
hydrogenated oils in patients with rosacea. Similar recommendations can be found
at http://www.rosacea.org and in other sources but the authors could find no clin-
ical studies or dietary surveys in MEDLINE supporting these claims. In conclusion,
dietary manipulation may be beneficial, but it is not evidence based.
SEBORRHEIC DERMATITIS
Seborrheic dermatitis is an inflammatory papulosquamous dermatosis that principally
affects sebaceous areas. The exact cause of this condition is unknown but genetics,
stress, diet, and infection with yeast-like organisms (Plasmodium ovale) are thought to
contribute. The affliction is present in 83% of AIDS patients, which seems to support
an immune/infectious contribution as well.
Biologic-Based Therapies
Pyridoxine
Although studies conducted in Italy and Germany in the 1970s and 1980s suggested
a role for pyridoxine in the treatment of seborrheic dermatitis, no rigid English-
language studies have been performed to confirm this.
Tea tree oil
Tea tree oil, an essential oil distilled from the Melaleuca alternifolia tree native to
Australia, has been shown to have antibacterial and antifungal properties.
12
With
this activity in mind, tea tree oil was recently tested in patients with dandruff, a mani-
festation of seborrheic dermatitis. In this randomized trial of 126 patients, 5% tea tree
oil shampoo was tested against placebo in mild to moderate dandruff. Patients
receiving tea tree oil showed a 41% improvement whereas patients receiving placebo
showed only 11% improvement (P<.001).
13
No MEDLINE studies could be found comparing the efficacy of tea tree oil with
conventional treatments of seborrheic dermatitis nor could the authors find evidence
for any other alternative treatments of this condition.
Lithium
At least 3 significant studies with lithium have been performed. All have found topical
lithium effective in the treatment of seborrheic dermatitis.
The first multicentered study of 227 patients using 8% lithium succinate ointment in
the treatment of seborrheic dermatitis found lithium significantly more effective than
placebo. No adverse side effects were observed and relapse was slow when treat-
ment was stopped.
14
The area of involvement improved 12% in the treatment arm
and only 6% in the placebo arm. When a global composite of redness, scaling, greas-
iness, itching, subjective impression, and percent of area involved was calculated, the
treatment arm reported an overall 20% improvement whereas the placebo group only
an 8% improvement. It may be concluded that the 8% lithium preparation used in the
study may be somewhat effective in the treatment of seborrheic dermatitis, but
because it was not compared with conventional treatments, the authors cannot
Therapies for Common Dermatologic Disorders 271
make comparative recommendations. Also, if the investigators had reported dramatic
clinical response, further corroborating studies might have been done and more wide-
spread clinical use seen.
14
The second randomized trial of 129 patients used lithium gluconate ointment and
found more impressive positive results. The active treatment arm experienced
a complete remission of 29.1% whereas only 3.8% of patients in the placebo group
experienced remission after 8 weeks.
15
The final corroborating study found twice-a-day topical lithium gluconate 8% oint-
ment application 22% more effective than ketoconizole in the treatment of seborrheic
dermatitis with no difference in side effects.
16
Thus, topical lithium seems an effective alternative treatment of seborrheic
dermatitis.
Alternative Systems
Effective treatment of seborrheic dermatitis using a low-dose, oral homeopathic medi-
cation consisting of potassium bromide, sodium bromide, nickel sulfate, and sodium
chloride has been shown effective in 1 study.
17
In a double-blind placebo-controlled
study, 41 patients with seborrheic dermatitis were randomized to receive the
homeopathic treatment (4 mL of solution containing potassium bromide [3.5 mg/
mL], sodium bromide [3 mg/mL], nickel sulfate [0.6 mg/ml], and sodium chloride
[0.06 mg/mL] daily) or a placebo. At the end of 10 weeks, the placebo group worsened
by 10% whereas the treatment arm improved 38% (using the seborrhea area and
severity index scale, which evaluates erythema and area of involvement). These
results were further substantiated by a crossover phase of the study that showed
similar reduction in symptoms in those switched to the active arm. No difference in
side effects between placebo groups and active groups was observed. The mecha-
nism of action of the remedy is unknown. Further research is needed to substantiate
this initial study, because the data presented were incomplete and the statistical
methods flawed.
CHRONIC URTICARIA
Urticaria, the final common manifestation of many different inciting insults, affects
15% to 20% of the population at least once in a lifetime. It has been estimated that
up to 25% of patients with acute urticaria progress to chronic urticaria,
18
which is
defined by the occurrence of frequent, recurrent eruptions for at least 6 weeks in
the absence of any causative physical or environmental trigger. Fifty percent of
patients with chronic urticaria can expect symptoms to resolve in 1 year, but 20%
experience episodes for more than 20 years.
19
When dealing with chronic urticaria, the usual questions about contacts, ingestions,
inhalations, and prescription medicines should be asked. Drugs are a common cause
of chronic urticaria in adults and have been reported as causative agents in up to 9%
of patients seen in dermatology outpatient departments. Although some studies have
reported that the cause of chronic urticaria remains a mystery in more than 75% of
cases,
18,20
more recent investigations find that 30% to 50% of patients with idiopathic
disease actually have histamine-releasing autoantibodies in their blood, highlighting
an autoimmune role in the affliction.
21,22
Other investigators insist that food additives,
preservatives, and pseudoallergens are the most common offenders.
23
The lack of
knowledge regarding cause and the fact that no definitive treatment exists make
the condition seemingly ripe for further scientific investigation and alternative treat-
ments. No herbal and few alternative therapies for chronic urticaria, however, were
Morelli et al 272
revealed in MEDLINE searches. An overview is presented of some findings that may
prove useful in the clinical setting.
Double Filtration Plasmapheresis
The theory behind this therapy is that double filtration plasmapheresis removes
medium to large molecular substances, such as IgG and IgE, from circulation, thus
decreasing the presence of histamine-releasing antibodies. There is an isolated
case report of resolution of chronic urticaria after double filtration plasmapheresis
was performed. More research is needed in this realm.
24
Narrowband Ultraviolet B Phototherapy
Ultraviolet B phototherapy (UVB) is known to induce several immunosuppressive and
anti-inflammatory processes at the cellular level; however, the exact mechanismof the
action of narrowband UVB (NB-UVB) in chronic urticaria remains unclear.
25,26
An early, open study of 43 patients administered UVB daily for 2 to 3 weeks in
patients with chronic urticaria. Results were promising in that 25 of the 43 had resolu-
tion of symptoms at the end of the treatment cycle. The lack of a control group and the
bias of this early publication, however, precluded drawing any real conclusions.
27
More recently, a retrospective review published in 2004 reviewed 94 patients with
chronic urticaria resistant to antihistamines and dietary modifications (see discussion
on food additives later) The study reported that 70% were helped by NB-UVB
treatment (3 times/wk for 8 weeks) and 80% maintained some improvement at
a 12-week follow-up, with 30% remaining in complete resolution. The investigators
concluded that proper randomized trials were warranted.
28
Even more recently, a randomized single-blind study
29
was done at Selc uk Univer-
sity in Turkey. This study of 81 patients compared NB-UVB plus antihistamines to anti-
histamines alone. NB-UVB was administered 3 times per week for 20 exposures. To
assess the treatment response, an urticaria activity score and a visual analog score
were used. Results showed a 50% improvement in the NB-UVBantihistamine group
at 7 weeks that was maintained at a 12-week follow-up. The antihistamine group
demonstrated only a 33% improvement at 7 weeks and showed a worsening of symp-
toms at the 12-week follow-up. Whether or not the investigators thought NB-UVB was
a clinically useful modality was not fully discussed.
As with full-spectrum sunlight, NB-UVB exposure can result in burning; however,
the risks of UVB causing skin aging or skin cancers are unknown.
NB-UVB lights for use in phototherapy are available from a variety of vendors on the
Internet.
A Note on Food Additives
Food additives and certain food pseudoallergens are a common cause of chronic urti-
caria. In 1 recent study, 64 patients hospitalized for chronic urticaria were put on a diet
avoiding preservatives, dyes, and natural pseudoallergens. In 73% of patients, symp-
toms ceased or were greatly reduced within 2 weeks. Follow-up at 6 months after
hospitalization showed complete remission in 46% of participants on the diet and
lasting improvement in all but 1. The investigators state that such a response rate
was clearly higher than the reported 24% spontaneous remission rate over the
same time period and that an additive-free, stringently controlled diet was clearly
the way to help the majority of patients with chronic urticaria.
23
In another study, 158 patients with chronic urticaria were put on a diet free of salic-
ylates, benzoates, and azo dyes. Fifty participants responded to dietary manipulation
and were recognized as sensitive to food additives.
30
Therapies for Common Dermatologic Disorders 273
Tartrazine is a widely used food colorant in packaged foods and in many commonly
used drugs (including antihistamines and steroids). During the 1970s, it was found to
be a frequent causative agent in chronic urticaria. This finding led to its ban in Sweden
and to current US regulations requiring the listing of all azo dyes on food labels and
drug package inserts. It is estimated that approximately 0.1%of the population is sen-
sitive.Twenty percent to 50% of aspirin-sensitive individuals are also sensitive to tar-
trazinethus, it is something specific to ask about in a dietary history.
31
Salicylates are another widely known allergen and cause of urticaria.
32
What is less
commonly known is their widespread use as food flavoring in gum, ice cream, cake
mixes, and soft drinks. They also occur naturally in foods, such as dried fruit, nuts,
and seeds. The average US diet contains 10 to 200 mg of salicylates per day, making
it a suspect in any case of chronic urticaria.
33
Alternative Systems
In 1 pilot study of 15 patients with chronic urticaria (average duration of 8 years) inves-
tigators found 6 patients cured and 8 patients improved with 14 months of hypno-
therapy and relaxation techniques.
34
As with all uncontrolled studies, conclusions
about true efficacy are difficult to make.
In conclusion, although the authors could find little substantial research regarding
alternative treatments of idiopathic chronic urticaria, they thought it important to
emphasize the role that diet and possibly UVB may play in controlling this disturbing
condition.
HERPES SIMPLEX
The herpes family of viruses contains more than 70 distinct members, including herpes
simplex virus (HSV) type 1 (HSV-1) and type 2 (HSV-2), varicella-zoster virus, Epstein-
Barr virus, and cytomegalovirus. Serologic testing has estimated that as many 73% of
US adults have evidence of past HSV-1 or HSV-2 exposure and that 20% of sexually
active adults in the United States are serologically positive for HSV-2.
35,36
Despite this,
only 26% to 34% of those who are serologically positive experience clinical manifes-
tations.
3538
Because conventional oral antiviral medication taken during prodromal
symptoms results in only minimal shortening of the duration of lesions and reduction
in symptoms,
39
this may be an area ripe for alternative intervention.
Oral Labial Herpes
Oral and perioral herpes are the result of infection with HSV-1. In the United States,
between 60% and 80% of adults are seropositive for the virus. Primary infections
are generally more severe than recurrences and may be accompanied by more
widespread eruptions as well as constitutional symptoms. Recurrences are charac-
terized by 1- to 2-mm vesicular eruptions at the vermillion of the lip, which progress
from ulceration to crusting to healingthe whole course lasts between 10 and 14
days.
Treatment of primary infections
Primary labial herpes is generally not treated in otherwise healthy patients, but
moderate to severe cases often require conventional antiviral therapy. In these more
extensively affected patients, a small randomized trial of 72 children showed a signif-
icant reduction in the duration of oral lesions (4 vs 9 days) and the duration of related
constitutional symptoms in those treated with oral antivirals. Topical antivirals are
generally ineffective.
40
Morelli et al 274
Treatment of recurrent oral labial herpes
Approximately one-third of persons with primary HSV-1 infection experience recurrent
episodes. The mean duration of untreated recurrent herpes labialis is between 5 and 6
days, but this duration can be highly variable, ranging from 2 to 20 days. Although
most episodes are mild and self-limiting, patients report significant irritation, pain,
discomfort, and loss of self-esteem. A randomized controlled trial using famciclovir
(1500 mg single dose or 750 mg twice a day for 1 day) versus placebo showed reduc-
tion of time to healing by approximately 2 days if the treatment is started within 1 hour
of onset of the prodromal symptoms.
41
Two studies with valacyclovir (which has greater bioavailability than acyclovir) have
also been performed. The first (N 51524) initiated treatment (2 g twice a day for 1 day)
at the time of prodromal symptoms and the second (N 5 1627) treated on day 1 (2 g
twice a day) and on day 2 (1 g twice a day). Use of valcycolvir showed a reduction in
the duration of symptoms by 1 day and 0.5 days, respectively.
42
Alternative Treatments of Oral Labial Herpes
Topical zinc
The most recent randomized, placebo-controlled, double-blind trial was published in
2002. In this study of 46 patients with oral herpes, treatment armsubjects were treated
with a zinc oxide/glycine cream every 2 hours within 24 hours of onset of signs and
symptoms. Those treated experienced a significantly shorter duration of cold sore
lesions (mean, 5 days) than did the placebo group (mean, 6.5 days),
43
thus making
zinc equally as effective or slightly better than conventional antiviral creams. With
the minimal degree of improvement, however, the clinical efficacy of either method
must be questioned.
44
A more recent, small (N 5 20), nonblinded trial in 2005 suggested that that oral zinc
sulfate (22.5 mg twice daily) could also be helpful in the treatment of herpes labialis.
This open study found zinc to reduce the duration of episodes to an average time to
healing of 5.7 days.
45
At this time, studies are too small and methodologically weak to recommend that
topical or oral zinc be used in the treatment of herpes labialis.
Vitamin C
One randomized, placebo-controlled, double-blind study of 32 patients evaluated the
effect of a vitamin C solution (Ascoxal) on labial HSV. It was applied to lesions 3 times
on the first day of symptoms. Each application lasted 2 minutes with 30-minute inter-
vals between treatments. Results showed that the persistence of lesions was signifi-
cantly shorter in the active treatment group (means 3.4 vs 5.9 days).
46
Rhubarb and sage extracts
A recent, randomized, double-blind study of 145 participants compared the use of
sage-rhubarb extract cream (23 mg/g) with Zovirax cream. The mean time to healing
was 6.7 days with the sage-rhubarb extract cream and 6.5 days with Zovirax cream.
Although the study concluded, the combined topical sage-rhubarb preparation
proved as effective as topical acyclovir cream, the usual time to healing for placebo
groups is 5.5 to 7 days, highlighting that the product was helpful.
47,48
L-Lysine
In vitro studies have shown that HSV replication requires the synthesis of arginine rich
proteins and that lysine, by competitive inhibition, acts to limit synthesis of these
proteins. Although it has long been claimed that the amino acid lysine is effective in
the treatment and prevention of recurrent herpes labialis, the data are controversial
Therapies for Common Dermatologic Disorders 275
with only 2 small studies of sufficient quality to weigh in on the subject. The most
recent (1987) randomized trial of 52 patients reported that those treated with L-lysine
(N 5 27; 1000 mg 3 times daily for 6 months) had fewer recurrent episodes of HSV
infection than the placebo group (N 5 25). The lysine group experienced an average
of 3.1 recurrent attacks whereas the placebo arm experienced an average of 4.2
attacks over the study period. The investigators failed to state whether or not this
objective difference was statistically significant. In patients subjective evaluation of
their treatment, however, 74% of participants in the lysine group rated their treatment
as effective or very effective whereas only 28% of the placebo arm had similar subjec-
tive ratings. This subjective difference was noted by the investigators as statistically
significant.
49
A more rigorous crossover trial performed in 1984 also found that high-dose lysine
(1248 mg/d) was effective in reducing the recurrence of herpes manifestations. Using
41 participants, researchers found that lysine-treated patients experienced an
average of 1.56 recurrences over the 6-month study period whereas the placebo
group experienced an average of 2.5 recurrences (unchanged from the prestudy
number of outbreaks). The investigators caution, however, that consideration must
be given to the small sample size and that larger series may not support their find-
ings.
50
Other earlier trials using lower doses of lysine showed no improvement.
5153
The paucity of data and less than efficacious results must lead to the conclusion that
lysine is not a clinically useful method of prevention or treatment.
Lemon balm
Melissa officinalis, a lemon-scented member of the mint family native to the eastern
Mediterranean, has been widely used for years in the treatment of herpes labialis.
Leaves are distilled to produce an essential oil containing many active ingredients,
including polyphenols, citronella, citral, and terpenes. It has been shown to have in
vitro viricidal effects against HSV-1.
54
In a 1994 placebo-controlled study of 115 participants, the application of a 1%
extract of lemon balm 5 times daily resulted in complete healing of lesions in 5 days
whereas those in the control group took 10 days to heal.
55
A follow-up randomized trial
of 60 patients in 1999 failed to measure complete healing times as a primary endpoint,
seeming to indicate a less than dramatic effect in that study.
56
Larger studies need be
done to validate earlier findings.
Licorice gel
Also known as Glycyrrhiza glabra, this botanic has also been shown to inhibit HSV in
vitro
57
and has been reported as effective in the topical treatment of herpes labialis.
58
No clinical trials in the MEDLINE database substantiating these claims, however,
could be located. Black currant (Ribes nigrum), Echinacea, Bupleurum rigidum, and
others may have in vitro action against HSV, but no clinical trials have yet been
conducted.
Sunscreen
Sunscreen is an effective prophylactic measure in patients afflicted with herpes labi-
alis. A randomized trial of 38 patients found no outbreaks in those using a sunscreen
whereas 71% of those in the placebo arm experienced lesions during the study
period.
59
Creatine
Lastly, a 2001 article deserves mention,
60
not because it necessarily establishes effi-
cacy of a nutritional supplement but because of the investigators insight and
Morelli et al 276
conscientious follow-up of their patients with herpes. The investigators, working at
a general military clinic at Camp Pendleton, California, found that several patients
with recurrent genital herpes failed to return for periodic acyclovir therapy. Their field
follow-up revealed that these patients had begun creatine supplementation (for
athletic enhancement) and experienced no further herpes outbreaks. They postulate
that cyclocreatine, a proved inhibitor of HSV-1 and -2 and other viruses in vitro, was
structurally similar to creatine and may have similar effects. Pilot studies to assess
the impact of creatine recurrence of oral and genital herpes seem warranted.
Genital Herpes
Genital herpes affects approximately 22% of the US population, with approximately
38% of symptomatic individuals experiencing 6 or more recurrences per year. Genital
herpes can result from infection with HSV-2 or -1. In the US, HSV-2, which causes
more recurrences and more severe disease, predominates.
Although the classic picture of clinical infection in women is one of vaginal and
vulvar lesions, infection of the cervix, often subclinical, is the actual main site of
involvement. Men typically develop lesions on the glans, prepuce, or shaft of the penis.
The natural course of disease progression is decreased frequency and severity of
recurrences over time. Approximately one-third of patients do not experience this
time-dependent regression, however. The clinical courses of untreated genital herpes
is characterized by a 2- to 21-day incubation period followed by typical viral eruptions
lasting 2 to 4 weeks in primary episodes and 7 to 12 days in recurrent episodes.
Treatment of recurrent genital herpes
Recurrent genital herpes is a major problem for patients worldwide. Treatment is
divided into 2 groups: episodic and suppressive.
Early episodic treatment, started at the first prodromal symptoms with short-course
antiviral therapy, is effective, often stopping progression of outbreaks. Such episodic
therapy is a common management approach for recurrent genital herpes and has
evolved in recent years from traditional 5-day regimens to shorter course schedules
that are equally effective and more convenient. Three-day therapy with valaciclovir
(1000 mg once daily),
61
2-day regimens with high-dose acyclovir (800 mg 3 times
a day)
62
and famciclovir (a 500-mg initial dose, followed by 250 mg twice a day),
63
and single-day famciclovir therapy (1000 mg administered twice)
64
all have been
shown effective, with approximately one-third of the patients remaining free from
lesions, and, in those whose lesions were not aborted, episodic treatment reduces
the time to healing approximately from 6 days to 4 days.
Antivirals may also be used in continuous suppressive therapy and have been
shown to decrease recurrence rates (although not the duration of symptoms) in
patients with genital herpes. One international randomized trial (N 5 384) found that
valacyclovir (1 g daily) prolonged the time to first recurrence in newly diagnosed
HSV-2 subjects compared with placebo. Seventy-one percent of subjects on valacy-
clovir remained recurrence-free at 24 weeks whereas only 43%of subjects on placebo
did so. This study, sponsored by pharmaceutical company, SKG-Pharma Ltd, did not
report on time to healing, leading an astute reader to conclude that the duration of the
subsequent outbreaks were not shortened by the treatment.
61
Alternative treatment of recurrent genital herpes
Using conventional antiviral treatment (discussed previously) as a comparative stan-
dard, the authors had intended to compare the effectiveness of alternative therapies
against these drugs. Despite case reports, in vitro studies, and some low-quality early
Therapies for Common Dermatologic Disorders 277
pilot studies, there was no reliable work found in this area. Perhaps the most inter-
esting study, which claims effectiveness in decreasing the duration of genital herpes
by half (5 days vs 10 days with placebo), is one using Ganoderma lucidum (reishi
mushroom), in Japan. This small study (N 5 15) seemed to indicate effectiveness of
an herbal concoction containing the mushroom, Ganoderma lucidum. These results
should lead investigators to further study this compound.
65
Herpes Zoster
Herpes zoster (shingles) is a painful rash resulting fromthe reactivation of the varicella-
zoster virus in the dorsal root ganglia. Approximately 30% of people are afflicted with
zoster in their lifetime, making this a significant public health issue.
66
The risk factors
for developing herpes zoster are increasing age, immunosuppression, intrauterine
exposure to varicella, and outbreak of varicella at age younger than 18 months.
67
Herpes zoster is contagious to those who have not had varicella or have not received
the varicella vaccine.
Natural course of untreated disease
A typical outbreak of acute herpes zoster vesicles lasts approximately 2 to 4 weeks.
The painful symptoms of postherpetic neuralgia (PHN), pain that does not resolve after
120 days, last months to years. PHN occurs in less than 2% of patients under age 60,
7.5% of patients between 60 and 69, and 18% in patients ages 70 and older.
68
Course of conventionally treated disease
Acyclovir (800 mg orally 5 times/d), famciclovir (500 mg 3 times/d), or valacyclovir
(1000 mg 3 times/d), all initiated within 72 hours of the emergence of lesions and
administered for 7 days, have been shown to minimally improve time to healing of
cutaneous lesions. Conventional treatment, however, significantly shortens the dura-
tion of acute herpes-associated pain (from approximately 60 to 30 days).
69
Corticosteroids have also been shown to minimally shorten the time to healing of
acute zoster skin lesions and to significantly decrease acute painful symptoms. The
use of these drugs in conjunction with antivirals is common but must be weighed
against the potential harmful side effects of steroids. Neither antivirals nor corticoste-
roids, however, have been proved to decrease the incidence or shorten the duration of
PHN.
70
Postherpetic Neuralgia
Painful symptoms of PHN
As discussed previously, neither antivirals nor steroids, when used in the acute setting,
improve the pain associated with PHN.
71
Treatment then, is limited to alleviating late
symptoms. Several conventional therapies are used to control painful symptoms,
including opioids, tricyclics, lidocaine patch, and nonsteroidal anti-inflammatory
drugs.
71
In addition, gabapentin and pregabalin have been shown to reduce painful
symptoms by 30%.
72
Capsaicin cream
Capsaicin, an extract from hot chili peppers, is currently the only alternative drug
labeled by the FDA for the treatment of PHN. In 1 study,
73
capsaicin cream, (applied
4 times/d) resulted in a 21%reduction in the pain score versus a 6%reduction in those
receiving placebo. Capsaicin, however, can cause burning, stinging, and erythema,
making it difficult to achieve true blinding in clinical studies, and in the clinical setting,
capsaicin is intolerable in up to one-third of patients.
Morelli et al 278
A comment on the zoster vaccine
The incidence of zoster outbreaks in patients over 60 years old who have received the
vaccine is 50% lower than those not receiving it. In addition, the intensity of acute pain
is decreased slightly by the vaccine and the incidence of PHN is decreased by 67% in
those receiving it.
74
SUMMARY
Despite purported as effective on herbal Web sites, Hypericum, Euphorbia, chamo-
mile, alfalfa, mugwort, and vervain along with the Bach flowers rescue remedy, walnut,
Mimulus, and aspen, have not been properly studied or proved useful in the treatment
of herpes zoster. The authors searches revealed no alternative treatments that have
been proved effective in decreasing the intensity or shortening the duration of symp-
toms of PHN.
In conclusion, herpes zoster and PHN are common conditions in elderly and immu-
nocompromised patients. Although the diagnosis is generally straightforward, treat-
ment can be frustrating for patients and physicians. Acute treatment modalities
include antiviral agents and possibly corticosteroids. The treatment of PHN is more
difficult and varied. The use of herbals and alternative treatments of zoster, despite
their use by herbalists and their purported efficacy on popular Web sites, are unsub-
stantiated in the medical literature.
REFERENCES
1. Bamford JT. Rosacea: current thoughts on origin. Semin Cutan Med Surg 2001;
20:199206.
2. Blount BW, Pelletier AL. Rosacea: a common, yet commonly overlooked, condi-
tion. Am Fam Physician 2002;66:43540.
3. Bamford JT, Tilden RL, Blankush JL, et al. Effect of treatment of Helicobacter
pylori infection on rosacea. Arch Dermatol 1999;135:65963.
4. Roihu T, Kariniemi AL. Demodex mites in acne rosacea. J Cutan Pathol 1998;25:
5502.
5. Szlachcic A, Sliwowski Z, Karczewska E, et al. Helicobacter pylori and its eradi-
cation in rosacea. J Physiol Pharmacol 1999;50:77786.
6. Honore-Thorez D. [Description, identification and therapeutic use of Chrysanthel-
lum americanum: Chrysanthellum indicum DC. subsp. afroamericanum
B.L.Turner]. J Pharm Belg 1985;40(5):32331 [in French].
7. Rigopoulos D, Kalogeromitros D, Gregoriou S, et al. Randomized placebo-
controlled trial of a flavonoid-rich plant extract-based cream in the treatment of
rosacea. J Eur Acad Dermatol Venereol 2005;19(5):5648.
8. Yu TG, Zheng YZ, Zhu JT, et al. Effect of treatment of rosacea in females by Chi-
bixiao Recipe in combination with minocycline and spironolactone. Integr Med
2006;12(4):27780.
9. Bjerke R, Fyrand O, Graupe K. Double-blind comparison of azelaic acid 20%
cream and its vehicle in treatment of papulo-pustular rosacea. Acta Derm Vene-
reol 1999;79:4569.
10. Maddin S. A comparison of topical azelaic acid 20% cream and topical metroni-
dazole 0.75% cream in the treatment of patients with papulopustular rosacea.
J Am Acad Dermatol 1999;40(6 Pt 1):9615.
11. Pizzorno JE, Murray MT. Rosacea. In: Pizzorno JE, Murray MT, editors. Textbook
of natural medicine, vol. 2. 2nd edition. New York: Churchill Livingstone; 1999. p.
1538.
Therapies for Common Dermatologic Disorders 279
12. DAuria FD, Laino L, Strippoli V, et al. In vitro activity of tea tree oil against
Candida albicans mycelial conversion and other pathogenic fungi. J Chemother
2001;13:37783.
13. Satchell AC, Saurajen A, Bell C, et al. Treatment of dandruff with 5% tea tree oil
shampoo. J Am Acad Dermatol 2002;47:8525.
14. Efalith Multicenter Trial Group. A double-blind, placebo-controlled, multicenter
trial of lithium succinate ointment in the treatment of seborrheic dermatitis.
J Am Acad Dermatol 1992;26(3 Pt 2):4527.
15. Dreno B, Moyse D. Lithium gluconate in the treatment of seborrhoeic dermatitis:
a multicenter, randomised, double-blind study versus placebo. Eur J Dermatol
2002;12:54952.
16. Dreno B, Chosidow O, Revuz J, et al. Lithium gluconate 8% vs ketoconazole 2%
in the treatment of seborrhoeic dermatitis: a multicentre, randomized study.
Br J Dermatol 2003;148:12306.
17. Smith SA, Baker AE, Williams JH. Effective treatment of seborrheic dermatitis
using a low dose, oral homeopathic medication consisting of potassium bromide,
sodium bromide, nickel sulfate, and sodium chloride in a double-blind, placebo-
controlled study. Altern Med Rev 2002;7(1):5967.
18. Negro-Alvarez JM, Miralles-Lopez JC. Chronic idiopathic urticaria treatment.
Allergol Immunopathol (Madr) 2001;29:12932.
19. Soter NA. Acute and chronic urticaria and angioedema. J Am Acad Dermatol
1991;25(1 Pt 2):14654.
20. Burrall BA, Halpern GM, Huntley AC. Chronic urticaria. West J Med 1990;152:
26876.
21. Grattan CE, Sabroe RA, Greaves MW. Chronic urticaria. J Am Acad Dermatol
2002;46:64557 [quiz: 65760].
22. Greaves MW. Pathophysiology of chronic urticaria. Int Arch Allergy Immunol
2002;127:39.
23. Zuberbier T, Chantraine-Hess S, Hartmann K, et al. Pseudoallergen-free diet in
the treatment of chronic urticaria. A prospective study. Acta Derm Venereol
1995;75:4847.
24. Jiang X, Lu M, Ying Y, et al. A case report of double-filtration plasmapheresis
for the resolution of refractory chronic urticaria. Ther Apher Dial 2008;12(6):
5058.
25. Walters IB, Ozawa M, Cardinale I, et al. Narrowband (312 nm) uv-B suppresses
interferon gamma and interleukin (iL) 12 and increases iL-4 transcripts: differen-
tial regulation of cytokines at the single-cell level. Arch Dermatol 2003;139:
15561.
26. Ibbotson SH, Bilsland D, Cox NH, et al. An update and guidance on narrowband
ultraviolet B phototherapy: a British Photodermatology group Workshop Report.
Br J Dermatol 2004;151:28397.
27. Johnsson M, Falk ES, Volden G. UVB treatment of factitious urticaria. Photoder-
matol 1987;4:3024.
28. Berroeta L, Clark C, Ibbotson SH, et al. Narrow-band (TL-01) ultraviolet B photo-
therapy for chronic urticaria. Clin Exp Dermatol 2004;29(1):978.
29. Engin B, O

zdemir M, Balevi A, et al. Treatment of chronic urticaria with narrow-


band ultraviolet b phototherapy: a randomized controlled trial. Acta Derm
Venereol 2008;88:24751.
30. Rudzki E, Czubalski K, Grzywa Z. Detection of urticaria with food additives
intolerance by means of diet. Dermatologica 1980;161:5762.
Morelli et al 280
31. Collins-Williams C. Clinical spectrum of adverse reactions to tartrazine. J Asthma
1985;22:13943.
32. Wright AL, Minford A. Urticaria and hidden salicylates. Pediatr Dermatol 1999;16:
4634.
33. Roberts-Thomson PJ, Chan A, Kupa A, et al. Urticaria and angio-oedema.
Med J Aust 1984;141(Suppl 5):S347.
34. Shertzer CL, Lookingbill DP. Effects of relaxation therapy and hypnotizability in
chronic urticaria. Arch Dermatol 1987;123:9136.
35. Xu F, Schillinger JA, Sternberg MR, et al. Seroprevalence and coinfection with
herpes simplex virus type 1 and type 2 in the United States, 19881994. J Infect
Dis 2002;185:101924.
36. Corey L. Challenges in genital herpes simplex virus management. J Infect Dis
2002;186(Suppl 1):S2933.
37. Oliver L, Wald A, Kim M, et al. Seroprevalence of herpes simplex virus infections
in a family medicine clinic. Arch Fam Med 1995;4:22832.
38. Koutsky LA, Ashley RL, Holmes KK, et al. The frequency of unrecognized type 2
herpes simplex virus infection among women. Implications for the control of
genital herpes. Sex Transm Dis 1990;17:904.
39. Opstelten W, Neven AK, Eekhof J. Treatment and prevention of herpes labialis.
Can Fam Physician 2008;54(12):16837.
40. Amir J, Harel L, Smetana Z, et al. Treatment of herpes simplex gingivostomatitis
with aciclovir in children: a randomised double blind placebo controlled study.
BMJ 1997;314(7097):18003.
41. Spruance SL, Bodsworth N, Resnick H, et al. Single-dose, patient-initiated famci-
clovir: a randomized, double-blind, placebo-controlled trial for episodic treatment
of herpes labialis. J Am Acad Dermatol 2006;55(1):4753.
42. Spruance SL, Jones TM, Blatter MM, et al. High dose, short-duration, early vala-
cyclovir therapy for episodic treatment of cold sores: results of two randomized,
placebo controlled, multicenter studies. Antimicrobial Agents Chemother 2003;
47(3):107280.
43. Godfrey HR, Godfrey NJ, Godfrey JC, et al. A randomized clinical trial on the
treatment of oral herpes with topical zinc oxide/glycine. Altern Ther Health Med
2001;7:4956.
44. Lin L, Chen XS, Cui PG, et al. Topical application of penciclovir cream for the
treatment of herpes simplex facialis/labialis: a randomized, double-blind, multi-
centre, aciclovir-controlled trial. J Dermatolog Treat 2002;13(2):6772.
45. Femiano F, Gombos F, Scully C. Recurrent herpes labialis: a pilot study of the effi-
cacy of zinc therapy. J Oral Pathol Med 2005;34(7):4235.
46. Hovi T, Hirvimies A, Stenvik M, et al. Topical treatment of recurrent mucocutaneous
herpes with ascorbic acid-containing solution. Antiviral Res 1995;27:26370.
47. Saller R, Buechi S, Meyrat R, et al. Combined herbal preparation for topical treat-
ment of Herpes labialis. Forsch Komplementarmed Klass Naturheilkd 2001;8:
37382.
48. Spruance SL, Rea TL, Thoming C, et al. Penciclovir cream for the treatment of
herpes simplex labialis. A randomized, multicenter, double-blind, placebo-
controlled trial. Topical Penciclovir Collaborative Study Group. JAMA 1997;277:
13749.
49. Griffith RS, Walsh DE, Myrmel KH, et al. Success of L-lysine therapy in frequently
recurrent herpes simplex infection. Treatment and prophylaxis. Dermatologica
1987;175:18390.
Therapies for Common Dermatologic Disorders 281
50. McCune MA, Perry HO, Muller SA, et al. Treatment of recurrent herpes simplex
infections with L-lysine monohydrochloride. Cutis 1984;34(4):36673.
51. Simon CA, Van Melle GD, Ramelet AA. Failure of lysine in frequently recurrent
herpes simplex infection. Arch Dermatol 1985;121:1678.
52. DiGiovanna JJ, Blank H. Failure of lysine in frequently recurrent herpes simplex
infection. Treatment and prophylaxis. Arch Dermatol 1984;120:4851.
53. Milman N, Scheibel J, Jessen O. Lysine prophylaxis in recurrent herpes simplex
labialis: a double-blind, controlled crossover study. Acta Derm Venereol 1980;60:
857.
54. Dimitrova Z, Dimov B, Manolova N, et al. Antiherpes effect of Melissa officinalis L.
extracts. Acta Microbiol Bulg 1993;29:6572.
55. Wolbling RH, Leonhardt K. Local therapy of herpes simplex with dried extract
from Melissa Officinalis. Phytomedicine 1994;1:2431.
56. Koytchev R, Alken RG, Dundarov S. Balm mint extract (Lo-701) for topical treat-
ment of recurring herpes labialis. Phytomedicine 1999;6:22530.
57. Pompei R, Flore O, Marccialis MA, et al. Glycyrrhizic acid inhibits virus growth
and inactivates virus particles. Nature 1979;281:68990.
58. Murray MT, Pizzorno JE Jr. Herpes simplex. In: Fontanarosa PB, editor. Alternative
medicine: an objective assessment. Chicago (IL): American Medical Association;
2000. p. 1275.
59. Rooney JF, Bryson Y, Mannix ML, et al. Prevention of ultraviolet-light-induced
herpes labialis by sunscreen. Lancet 1991;338(8780):141922.
60. Ness SR, McCarty MF. Does supplemental creatine prevent herpes recurrences?
Med Hypotheses 2001;57:3102.
61. Fife KH, Warren TJ, Justus SE, et al. An international, randomized, double-blind,
placebo-controlled, study of valacyclovir for the suppression of herpes simplex
virus type 2 genital herpes in newly diagnosed patients. Sex Transm Dis 2008;
35(7):66873.
62. Wald A, Carrell D, Remington M, et al. Two-day regimen of acyclovir for treatment
of recurrent genital herpes simplex virus type 2 infection. Clin Infect Dis 2002;
34(7):9448.
63. Bodsworth N, Bloch M, McNulty A, et al. 2-day versus 5-day famciclovir as treat-
ment of recurrences of genital herpes: results of the FASTstudy. Sex Health 2008;
5(3):21925 [Erratum in: Sex Health. 2008 Dec;5(4):379].
64. Aoki FY, Tyring S, Diaz-Mitoma F, et al. Single-day, patient-initiated famciclovir
therapy for recurrent genital herpes: a randomized, double-blind, placebo-
controlled trial. Clin Infect Dis 2006;42(1):813 [Erratum in: Clin Infect Dis
2006;42(4):588].
65. Hijikata Y, Yamada S, Yasuhara A. Herbal mixtures containing the mushroom
Ganoderma lucidum improve recovery time in patients with herpes genitalis
and labialis. J Altern Complement Med 2007;13(9):9857.
66. Brisson M, Edmunds WJ, Law B, et al. Epidemiology of varicella zoster virus infec-
tion in Canada and the United Kingdom. Epidemiol Infect 2001;127(2):30514.
67. Helgason S, Petursson G, Gudmundsson S, et al. Prevalence of postherpetic
neuralgia after a first episode of herpes zoster: prospective study with long
term follow up. BMJ 2000;321(7264):7946.
68. Galil K, Choo PW, Donahue JG, et al. The sequelae of herpes zoster. Arch Intern
Med 1997;157(11):120913.
69. Wood MJ, Kay R, Dworkin RH, et al. Oral acyclovir therapy accelerates pain reso-
lution in patients with herpes zoster: a meta-analysis of placebo-controlled trials.
Clin Infect Dis 1996;22(2):3417.
Morelli et al 282
70. Li Q, Chen N, Yang J, et al. Antiviral treatment for preventing postherpetic
neuralgia. Cochrane Database Syst Rev 2009;(2):CD006866.
71. Dubinsky RM, Kabbani H, El-Chami Z, et al. Practice parameter: treatment of
postherpetic neuralgia: an evidence-based report of the Quality Standards
Subcommittee of the American Academy of Neurology. Neurology 2004;63(6):
95965.
72. Dworkin RH, Corbin AE, Young JP Jr, et al. Pregabalin for the treatment of post-
herpetic neuralgia: a randomized, placebo-controlled trial. Neurology 2003;60(8):
127483.
73. Watson CP, Tyler KL, Bickers DR, et al. A randomized vehicle-controlled trial of
topical capsaicin in the treatment of postherpetic neuralgia. Clin Ther 1993;
15(3):51026.
74. Oxman MN, Levin MJ, Johnson GR, et al. A vaccine to prevent herpes zoster and
postherpetic neuralgia in older adults. N Engl J Med 2005;352(22):227184.
Therapies for Common Dermatologic Disorders 283

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