http://www.ncbi.nlm.nih.gov/pubmed/15102088

I took accutane 5 years ago and have permanent damage: Now my face has skin fragility and thinness, extreme dryness and wrinkling, inflammation and irritation, dyshesion and diminished waterproofing, as the skin barrier homeostasis has been disrupted, etc. etc.

about 1 year ago i started taking adderall for adhd. and this has made my skin condition worse.

i'm wondering if anyone knows anything about PPAR stimulators ...which stimulate seb glands and other relevant mechanisms. i did not realize that there are TOPICAL ppar stims. i have posted about internal treatments for diabetes, but a topical option seems more pragmatic and less risky, especially since my damage is mostly localized in the face.

the specific one i read about is called GW1514....







Peroxisome proliferator-activated receptor (PPAR)-beta/delta stimulates differentiation and lipid accumulation in keratinocytes.
Schmuth M, Haqq CM, Cairns WJ, Holder JC, Dorsam S, Chang S, Lau P, Fowler AJ, Chuang G, Moser AH, Brown BE, Mao-Qiang M, Uchida Y, Schoonjans K, Auwerx J, Chambon P, Willson TM, Elias PM, Feingold KR.

Department of Medicine, University of California, San Francisco, California, USA.
Erratum in:

J Invest Dermatol. 2004 Oct;123(4):806.
Peroxisome proliferator-activated receptor (PPAR) are nuclear hormone receptors that are activated by endogenous lipid metabolites. Previous studies have demonstrated that PPAR-alpha activation stimulates keratinocyte differentiation in vitro and in vivo, is anti-inflammatory, and improves barrier homeostasis. Recent studies have shown that PPAR-beta/delta activation induces keratinocyte differentiation in vitro. This study demonstrated that topical treatment of mice with a selective PPAR-beta/delta agonist (GW1514) in vivo had pro-differentiating effects, was anti-inflammatory, improved barrier homeostasis, and stimulated differentiation in a disease model of epidermal hyperproliferation [corrected]. In contrast to PPAR-alpha activation, PPAR-beta/deltain vivo did not display anti-proliferative or pro-apoptotic effects. The pro-differentiating effects persisted in mice lacking PPAR-alpha, but were decreased in mice deficient in retinoid X receptor-alpha, the major heterodimerization partner of PPAR. Furthermore, in vitro PPAR-beta/delta activation, aside from stimulating differentiation-related genes, additionally induced adipose differentiation-related protein (ADRP) and fasting induced adipose factor (FIAF) mRNA in cultures keratinocytes, which was paralleled by increased oil red O staining indicative of lipid accumulation, the bulk of which were triglycerides (TG). Comparison of differentially expressed genes between PPAR-beta/delta and PPAR-alpha activation revealed distinct profiles. Together, these studies indicate that PPAR-beta/delta activation stimulates keratinocyte differentiation, is anti-inflammatory, improves barrier homeostasis, and stimulates TG accumulation in keratinocytes.

Hi there,
Does anyone out there live in the Los Angeles area and if so have you ever thought of participating in an Acne Clinical Trial Study where you get to use products free of charge to see if they work for you? If you have what was the experience like? I'm thinking of participating in a clinical trial with a local company and just wanted some feedback as to what it was like? Was the experience positive did you get resutls?
Thanks
Annette

http://www.egowoon.com/sub_06_11.htm

It won't tell me how much it costs though, but damn I would do it in a heartbeat!

Does anyone know where they do it and how much it would cost??

Production of Superoxide Anions by Keratinocytes Initiates P. acnes-Induced Inflammation of the Skin

Since most (all?) normal people without acne have P. acnes on their skin, the question is always: where exactly in the chain of events leading to lesions is the difference between having and not having acne. This test tube study implies you need the superoxide anion production combined with P. acnes to get the inflammation and acne lesions.

This makes me happy because my current model of acne is that it is caused by a failure to produce enough zinc superoxide dismutase (ZSOD). This study is consistent with that model, since ZSOD (as the name implies) can dispatch the superoxide anions and prevent this possibly crucial step in the formation of inflammation and lesions.

"NanoBio's NanoStat™ acne treatment, NB-003, uniquely penetrates the skin and enters epidermal tissues targeting the pilosebaceous units (an oil producing gland connected to a hair follicle) resulting in effective delivery of the nanoemulsion droplets to the site of infection. These droplets disrupt the P. acnes and are cidal on contact"

http://www.nanobio.com/Dermatology/Acne.html
There some nice pix/illustrations on the site demontrating the purported effect of this new "wonder" acne killer.

I'll be interested in the results when they finish the clinical trials. Their site suggests that this treatment can be used with other anti acne medications to increase the effectiveness. I guess if you used NanoStat with the Isolaz Profusion system http://ultimaskin.com/skincare/site/articl...n-rejuvenation/ you could suck out the gunk from the sebaceous gland, zap it with light and deliver an ultra potent topical. The combination might be overkill, but is there ever such a thing when it comes to acne?

acne vaccine?
http://www.ncbi.nlm.nih.gov/pubmed/1846368...Pubmed_RVDocSum

Thought this was really interesting. Heat-killed p. acnes can still induce inflammation in the skin (so, I wonder if p. acnes killed by other means does too?). This may explain why people often don't get great results from heat treatment devices like Zeno - some people say they get more inflammation after using it or that it doesn't really help the inflammation. Maybe you also need to be using products that are anti-inflammatory along with the heat treatment devices? Makes me wonder about laser treatments too.


1: Exp Dermatol. 2009 Jul 14. [Epub ahead of print] Links
Heat-killed Propionibacterium acnes is capable of inducing inflammatory responses in skin.
Lyte P, Sur R, Nigam A, Southall MD.
Preclinical Pharmacology, Skin Research Center, Johnson and Johnson Consumer Products, Skillman, NJ, USA.

Please cite this paper as: Heat-killed Propionibacterium acnes is capable of inducing inflammatory responses in skin. Experimental Dermatology 2009.

Abstract: The etiology of acne is a complex process, and acne is one of the most common skin disorders affecting millions of people. The pathogenesis of acne is closely associated with the bacterium, Propionibacterium acnes which was previously known as Corynebacterium parvum. Both viable and non-viable P. acnes/C. parvum have been shown to induce an immunostimulatory effect in vivo, suggesting that even dead bacteria continue to activate an inflammatory response. Acne treatments with lasers or devices, induce a bactericidal effect through heat generation which may not address the immunogenic activity of P. acnes and the resulting acne inflammation. Therefore, we sought to determine whether killed P. acnes is capable of inducing an inflammatory response and therefore could be a contributing factor in acne. Direct heat treatment of P. acnes cultures with temperatures ranging from 50 degrees C to 80 degrees C reduced P. acnes viability. Both viable and heat-killed P. acnes activated the p38 MAP kinase and its downstream substrate Hsp27. Stimulating keratinocytes with normal and heat-inactivated P. acnes resulted in an induction of proinflammatory nitric oxide and IL-8 production. Thus killed P. acnes is capable of inducing inflammation in skin suggesting that therapies that have both bactericidal and anti-inflammatory effects may result in a more effective treatment of patients with acne than treatments that are bactericidal alone.

What do you think? It makes more sense to me than how acne severity is currently classified. In this new system you can be graded mild to severe for any form of acne lesions. So, a person could have severe comedonal acne or mild nodular acne (an example would be a person with just one nodule. Right now, that is still classified as a severe form of acne).


Making the grade: New acne severity index helps doctors assess lesions

Oct 1, 2008
By: Ilya Petrou, M.D.
Dermatology Times



A new acne grading system, known as the Bikowski Acne Severity Index (BASI), is assisting physicians to better grade these lesions.

"This innovative acne grading system not only allows a more precise grading of acne lesions, but also allows the practitioner to more accurately document the changes seen in patients for study purposes, as well as keep more exact medical records," says Joseph Bikowski M.D., F.A.A.D., director of the Bikowski Skin Care Center in Sewickley, Pa.


The BASI follows suit with the PASI (Psoriasis Area and Severity Index) and the EASI (Eczema Area and Severity Index), known for their clarity and international uniformity.

The BASI system determines acne severity based upon the type, number and location of acne lesions.

Type

Lesions are classified by type as grade I (comedone — open or closed), grade II (papule), Grade III (pustule) and grade IV (nodule).

If the nodule is present long enough, it can become an enclosed and encapsulated cyst, and the goal is to treat the nodule before it becomes a cyst.

Number

The number of lesions is classified as mild (1-10 lesions), moderate (11-20 lesions) and severe (greater than 20 lesions).

Dr. Bikowski says that these numbers are based on his clinical experience and observation of acne patients over the last 30 years.

Location

When addressing the location of acne lesions, Dr. Bikowski divides anatomical areas into units.

When speaking of facial acne, for example, he divides the face into five separate anatomical units — forehead, left and right cheek, nose, and chin — because in acne, sometimes certain anatomical units are not affected.

Once separated into units, types of lesions are assessed and counted in each anatomical area.

"For example, severe grade I acne of the forehead would be greater than 20 open and/or closed comedones of the forehead unit. A moderate grade II or III acne of the chin would be 11 to 20 papules and pustules. A mild grade IV acne of the cheek is one nodule.

"This is actually mild acne if only one nodule and nothing else is present," Dr. Bikowski tells Dermatology Times.

Effectiveness

According to Dr. Bikowski, there are four reasons to better document the severity of acne lesions in patients:

1. The quality of medical charting and, hence, the quality of medical care is better due to the more precise system the BASI uses. Dr. Bikowski says that most physicians do not take photographs of the patients' acne and, therefore, have no before-and-after images to compare. The BASI system can better quantify and qualify the acne lesions from visit to visit, yielding a much more precise medical record.

2. As with all diseases and conditions, physicians need to better document acne at each visit for legal reasons.

3. Insurance companies usually will reimburse physicians only if there is accurate documentation, so the more documentation and the more accurate the detail of the documentation, the better the chance for problem-free reimbursement for services rendered.

4. According to Dr. Bikowski, the systems currently used in documenting acne are insufficient. A universal standardized objective system when documenting the number, distribution and types of acne lesions is needed and crucial when evaluating the efficacy of drugs in medical trials.

Dr. Bikowski also says the older grading systems that are still being used — the Pillsbury, Shelly, Kligman, the Cook, and the Burke & Cunliffe grading systems — lack objectivity, are less accurate and, therefore, can be open to interpretation.

The BASI system will have all physicians "on the same page" when defining the severity of acne lesions in patients, he adds.

"I think that this system is simple and easy to do, and it makes better sense out of all the terminology we have been using in the past with other grading systems.

"The BASI helps you manage each individual patient objectively and more effectively," Dr. Bikowski says.
------------

http://www.lifescript.com/channels/beauty/...r_mild_acne.asp

"People suffering from mild cases of acne can benefit significantly from small doses of Accutane and other tretinoin-based acne treatments, a new study finds. Conducted by researchers at Israel's Soroka University, the study found that low-dose Accutane was also an effective means of reducing the side effects of inflammation and dryness that have been associated with Accutane in past research. For the purposes of the study, "low-dose" was defined as 20 milligrams of Accutane daily over the course of six months. At that dosage, researchers found that a remarkable 95% of patients experienced either complete remission of their acne or significant improvement at minimum."

I've got mild yet extremely persistant acne, so I'm definately considering this

INTRODUCTION

The effects of hormones in acne are most notable in women. Androgens such as
dihydrotestosterone (DHT) and testosterone, the adrenal precursor dehydroepiandrosterone
sulfate (DHEAS), estrogen, and other hormones, including growth
hormone or insulin-like growth factors (IGFs), may each be important. It is likely
that the hormones affecting the sebaceous gland are both taken up from the
serum in addition to being made locally within the gland.
Hormonal therapy is an option in women whose acne is not responding to
conventional treatment or if signs of endocrine abnormalities are present. The greatest
therapeutic benefit from hormonal therapy is achieved in combination with
other effective anti-acne medications. This chapter focuses on the role of hormones
in acne, the clinical presentation of adult female acne, the work-up of a suspected endocrine abnormality, and the available options for hormonal therapy.




ANDROGENS IN ACNE

Both clinical observation and experimental evidence confirm the importance of
androgens in the pathophysiology of acne. The majority of circulating androgens
are produced by the gonads and the adrenal gland. Androgens can also be produced
locally within the sebaceous gland from the adrenal precursor hormone, DHEAS.
The main androgens that interact with the androgen receptor are testosterone
and DHT. Androgen receptors are found in the basal layer of the sebaceous gland
and the outer root sheath keratinocytes of the hair follicle (1,2).DHTis approximately
five to 10 times more potent than testosterone in its interaction with the androgen
receptor.
An essential role for androgens in stimulating sebum production is supported
by several lines of evidence. For example, the development of acne in the prepubertal
period has been associated with elevated serum levels of DHEAS, a precursor for
testosterone (3,4). Androgen-insensitive subjects who lack functional androgen
receptors do not produce sebum and do not develop acne (5). Tumors of the
ovary or the adrenal that produce androgens are often associated with the
development of acne. Systemic administration of testosterone and dehydroepiandrosterone
increases the size and secretion of sebaceous glands (6), and we know
that severe acne is often associated with elevated serum androgens (7,8).

Androgen Metabolism Within the Skin

Acne may be mediated by serum androgens, locally produced androgens, or a combination
of both. Insights have been gained regarding the local metabolism of
androgens within sebaceous glands (9). Such insights may be of benefit in the
design of new acne therapies. The skin and sebaceous gland are capable of
producing and metabolizing androgens (9). DHEAS is the major adrenal androgen
precursor. It circulates in the blood stream in relatively high levels compared with
other hormones with the exception of cortisol. In fact, in for review, see
Ref. postmenopausal women, all sex steroids made in the skin are from adrenal
steroid precursors, especially DHEA. Secretion of this precursor steroid by the
adrenals decreases progressively from age 30 to less than 50% of its maximal
value at age 60 (10). The enzyme 3b -hydroxysteroid dehydrogenase (3b -HSD)
acts on DHEA to convert it to androstenedione (Fig. 1). This conversion may take
place in the adrenal gland and tissues such as the sebaceous gland, where activity
of the 3b -HSD enzyme has been identified by several investigators (11–13). The
reversible conversion of androstenedione into testosterone is then catalyzed in
the human skin by 17b -HSD, a member of the short chain alcohol dehydrogenases
that are related to retinol metabolizing enzymes (14–18). This is a reversible
enzyme that can oxidize and reduce both androgens and estrogens. It is responsible
for converting the weak androgen androstenedione into the more potent androgen
testosterone. It can also interconvert weak and potent estrogens such as estrone
and estradiol. The 17b -HSD enzyme may represent a regulatory point in androgen
and estrogen metabolism within the skin.
DHT is produced from testosterone within peripheral tissues such as the skin
by the action of the 5a -reductase enzyme. Two isozymes of 5a -reductase have been
identified (19). The type 1 isozyme is active within the sebaceous gland (20,21). The
type 2 isozyme is most active in the prostate gland, where it can be inhibited by
drugs such as finasteride. Activity of 5a-reductase and 17b -HSD exhibits regional
differences depending upon the source of the sebaceous glands (9). In skin that is
prone to acne, such as facial skin, activity of the type 1 5a-reductase in sebaceous
glands is greater than in sebaceous glands obtained from nonacne-prone skin
(20). This implies that more DHT is being produced in sebaceous glands from
facial skin compared with other areas of the body that are not prone to develop
acne. The net effect of the activity of these two enzymes is the greater production
of potent androgens such as testosterone and DHT within sebaceous glands of
facial areas, which may in part account for the development of acne in these areas.


The Sebaceous Gland Is a Steroidogenic Tissue

The skin and sebaceous glands are capable of synthesizing cholesterol de novo from
acetate (22–24). Although this cholesterol is utilized in cell membranes, in the formation
of the epidermal barrier, and is secreted in sebum, its use as a substrate for
steroid hormone synthesis had not been established until recently. In order for
steroid synthesis to occur, cholesterol needs to be translocated from the outer to
the inner mitochondrial membrane. This process is regulated by the steroidogenic
acute regulatory protein (25). Additional enzymes and cofactors needed to convert
cholesterol into a steroid include P450 cholesterol side chain cleavage, adrenodoxin
reductase, cytochrome P450c17, and steroidogenic factor-1. Expression of each of
these proteins was found in human facial skin, sebocytes, and in a recently developed
simian virus (SV) 40-immortalized human sebocyte cell line (SEB-1) (26).
These data demonstrate that the skin is in fact a steroidogenic tissue. The clinical
significance of this finding in mediating androgenic skin disorders such as acne,
hirsutism, or androgenetic alopecia remains to be established.

ESTROGENS IN ACNE

Very little is known about the role of estrogens in modulating sebumproduction. Any
estrogen given systemically in sufficient amounts will decrease sebum production.
The dose of estrogen required to suppress sebum production, however, is greater
than the dose required to suppress ovulation (27). The major active estrogen is estradiol,
which is produced from testosterone by the action of the enzyme aromatase.
Aromatase is active in the ovary, adipose tissue, and other peripheral tissues. Estradiol
can be converted to the less potent estrogen, estrone, by the action of the 17b -HSD
enzyme. Both aromatase and 17b -HSD are present in the skin (17,28). Estrogens
may act by severalmechanisms; theymay: (i) directly oppose the effects of androgens
locallywithin the sebaceous gland, (ii) inhibit the production of androgens by gonadal
tissue via a negative feedback loop on pituitary gonadotrophin release, and (iii)
regulate genes that negatively influence sebaceous gland growth or lipid production.
GROWTH HORMONE AND INSULIN-LIKE GROWTH FACTORS IN ACNE
Growth hormone is secreted by the pituitary gland. It acts on the liver and peripheral
tissues to stimulate the production of IGFs, formerly known as somatomedians.
There are two forms of IGF, termed IGF-1 and IGF-2. IGF-1 is the more prevalent
growth factor. It has been hypothesized that growth hormone may be involved in
the development of acne (29). Acne is most prevalent in adolescents during a
time when growth hormone is maximally secreted and serum levels of IGF-1 are
highest. In addition, IGF-1 can be produced locally within the skin, where it can
interact with receptors on the sebaceous gland to stimulate its growth. Furthermore,
conditions of growth hormone excess such as acromegaly are associated with seborrhea
and the development of acne. In some tissues, the actions of IGF-1 can be
mediated by androgens. It is possible that androgens may influence IGF-1 action
in the sebaceous gland as well.

CLINICAL PRESENTATION OF ADULT FEMALE ACNE

For reasons that are not understood, the distribution of facial acne in many adult
females differs from that seen in adolescents and in males. Many adult women
Hormonal Influences in Acne 85
note that acne localizes to the lateral face, chin, and neck (Fig. 2). Oftentimes, acne
in these women is not necessarily widespread or severe, but rather it may be
low-grade, persistent, and consist of a few isolated deep-seated tender nodules.
Many women note flares of their acne just prior to their menstrual period with
reports ranging from 27–60% to 70% of women (30–32). One study has been published
that provides quantitative documentation of acne lesion counts over the
menstrual period (33). In this study of women, who were followed over two menstrual
cycles, 63% showed a 25% increase in inflammatory acne lesions prior to the
menstrual period. Some women may feel that intermittent acne therapy prior to
their menstrual period may be beneficial. There is no evidence for this approach.
Since most acne therapy is designed to prevent the formation of lesions and since
this process often takes several weeks, it seems unlikely that intermittent therapy
would be beneficial. For this reason, it is important to have patients use their medications
consistently and to avoid spot treatment.

WHEN TO SUSPECT AN ENDOCRINE DISORDER IN ACNE PATIENTS


Although hormones influence acne, most acne patients do not have an endocrine
disorder. Hyperandrogenism should be considered in female patients whose acne
is severe, sudden in its onset, or is associated with hirsutism, or irregular menstrual
periods. Additional clinical signs of hyperandrogenism include Cushinoid features,
increased libido, clitoromegaly, deepening of the voice, acanthosis nigricans, or
androgenetic alopecia. Women with hyperandrogenism may also have insulin
resistance. They are at risk for the development of diabetes and cardiovascular
disease. It is therefore important for the long-term health of these patients to identify
hyperandrogenism so that they can receive appropriate therapy from an endocrinologist
or gynecologist.

SCREENING FOR AN ENDOCRINE DISORDER

A medical history and physical examination should be performed that is directed
toward eliciting any symptoms or signs of hyperandrogenism. Screening laboratory
tests for hyperandrogenism include a serum DHEAS, total testosterone, free testosterone,
and luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio.
These tests should be obtained apart from the time of ovulation in order to avoid
the surge of hormones associated with ovulation. From a practical standpoint, it
may be easiest to suggest that women have these tests performed either just prior
to or during the menstrual period. It is important to note that if a patient is on
oral contraceptives at the time of hormonal testing, an underlying hyperandrogenemia
may be masked. This does not occur with antiandrogens such as cyproterone
or spironolactone. Therefore, it is best that patients discontinue oral contraceptives
four to six weeks prior to the endocrine evaluation.
Excess androgens may be produced by either the adrenal gland or the ovary.
Serumlevels ofDHEAS can be used to screen for an adrenal source of excess androgen
production. Patientswith a serumDHEAS greater than 8000 ng/mL (units may differ
depending upon the laboratory)may have an adrenal tumor and should be referred to
an endocrinologist for further evaluation. Some adrenal tumorsmay also produce testosterone.
Values ofDHEAS in the range of 4000 ng/mLto 8000 ng/mLmay be associated
with congenital adrenal hyperplasia, which is most commonly due to a partial
deficiency in the 21-hydroxylase or 11-hydroxylase enzyme in the adrenal gland.

Such an enzyme deficiency results in the shunting of steroids fromthe cortisol biosynthetic
pathway into the androgen biosynthetic pathway.
An ovarian source of excess androgens can be suspected in cases where the
serum total testosterone is elevated. Serum total testosterone in the range of
150 ng/dL to 200 ng/dL or an increased LH/FSH ratio (greater than 2 to 3) can
be found in cases of polycystic ovary disease. This condition is a spectrum and is
often, but not always, associated with irregular menstrual periods, reduced fertility,
obesity, insulin resistance, or hirsutism. Greater elevations in serum testosterone
may indicate an ovarian tumor and appropriate referral should be made. In some
cases, there can be modest elevations in both DHEAS and testosterone. A serum
level of 17-hydroxypregneneolone can be obtained to discern between an ovarian
or adrenal source of androgens. If 17-hydroxypregneneolone is elevated, it indicates
an adrenal source of excess androgens, most often secondary to late onset congenital
adrenal hyperplasia. Of note is that there is a significant amount of variation in
an individual’s serum androgen levels. In cases where abnormal results are
obtained, it is recommended to repeat the test before proceeding with therapy or
a more extensive work-up.
Questions arise as to the importance of a pelvic ultrasound in the diagnosis of
polycystic ovarian syndrome. This test can be nonspecific, in that women with
normal androgens may have ovarian cysts and conversely, women with hyperandrogenism
and other findings associated with polycystic ovarian syndrome
may not have ovarian cysts at the time of pelvic ultrasound. For this reason, the
diagnosis of polycystic ovarian syndrome is more heavily based upon the serum
hormonal profile and associated clinical findings.
In the majority of women with acne, serum androgens are completely normal,
yet these women will in fact respond if treated with hormonal therapy. Studies have
shown that, as a group, women with acne may have higher levels of serum DHEAS,
testosterone, and DHT than those without acne (7,34). However, although higher,
these laboratory values may still be within the normal range. Serum levels of
DHEAS, DHT, and IGF-1 are reported to correlate positively with acne lesion
counts in women, whereas androstenedione and DHEAS correlate with lesion
counts in men (35). Reduction of serum androgens or inhibition of their action, as
obtained with oral contraceptives or antiandrogens, respectively, can lead to
improvement in acne in women with normal serum androgen levels.

OPTIONS FOR THE HORMONAL THERAPY OF ACNE IN WOMEN


Once the decision has been made to initiate hormonal therapy, the various options
to choose from include: (i) androgen receptor blockers, or antiandrogens (this class
of drugs block the effect of androgens on the sebaceous gland); (ii) inhibitors of
androgen production by the ovary or adrenal gland such as oral contraceptives
or glucocorticosteroids, respectively; or (iii) in the future, it may be possible to
inhibit the activity of androgen metabolizing enzymes in the skin or sebaceous
gland itself.

Agents that Block the Androgen Receptor

Within the class of androgen receptor blockers, therapeutic options include spironolactone,
cyproterone acetate, and flutamide. In the United States, spironolactone is
the most commonly used drug, although flutamide is also available.
Hormonal Influences in Acne 87

Spironolactone

Oral spironolactone decreases sebum excretion rate by 30% to 50%. Recommended
doses are 50 to 100 mg taken with meals (36,37). However, many women with
sporadic outbreaks of inflammatory lesions or isolated cysts respond well to
25 mg twice daily and some even respond to just 25 mg a day. These low doses
in healthy young women are generally well-tolerated. However, if this drug is
used in older women who may have other medical problems, or if higher doses
are used for conditions such as hirsutism or androgenetic alopecia, serum electrolytes
should be monitored. Side effects of spironolactone include breast tenderness
and menstrual irregularities. Additionally, it is important that pregnancy be
avoided during treatment with spironolactone due to the potential for abnormalities
of the male fetal genitalia such as hypospadias.

Cyproterone Acetate

Cyproterone acetate is available in many parts of the world, but not in the United
States. It possesses dual activity in that it serves as a progestogen in oral contraceptives
in addition to its direct inhibition of the androgen receptor. It can be given in
doses of 2 to 100 mg per day as a single agent, in which case there can be improvement
in 75% to 90% of women with acne. Cyproterone acetate, however, is most
commonly used in the form of an oral contraceptive combined with ethinyl estradiol
in varying doses (38). Numerous clinical studies support the efficacy of these
oral contraceptive preparations in women with acne.

Flutamide

Flutamide is apotent nonsteroidal antagonist of the androgenreceptor. Althoughmost
commonly used to treat prostate cancer, flutamide has been reported to be efficacious
in the treatment of acne, hirsutism, and androgenic alopecia (39). It can be given in
doses of 250 mg twice daily in combinationwith an oral contraceptive. Fatal hepatitis
has been reportedwith this drug. Liver function tests should bemonitoredand serious
consideration should be given to the risk/benefit ratio of its use in acne (40). Additionally,
because it is an antiandrogen, pregnancy issues are a concern.
Inhibitors of Adrenal Androgen Production
Another option in hormone therapy is to block the production of androgens either
by the adrenal gland or ovary, which can be accomplished through the use of lowdose
glucocorticoids or oral contraceptives, respectively.

Glucocorticoids

Low-dose glucocorticoids are most commonly used to treat patients with late onset
congenital adrenal hyperplasia, which is an inherent defect in the 21-hydroxylase
or the 11-hydroxylase enzyme. This defect causes a block in the cortisol biosynthetic
pathway, which results in a buildup of steroid precursors that are shunted into the
androgen biosynthetic pathway. Low-dose prednisone (2.5 to 5 mg a day, at bedtime)
can be used. Low doses of dexamethasone can also be used, but the risk of adrenal
suppression is higher. To ascertain if therapy with glucocorticoids is having the
desired effect, serum DHEAS can be monitored for a decrease or normalization of
the level of DHEAS. To check for adrenal suppression, an adrenocorticotrophin
hormone (ACTH) simulation test can be performed. This consists of injecting
88 Thiboutot
ACTH and assessing the plasma cortisol 30 minutes later. If plasma cortisol has risen
by an appropriate amount, the adrenal gland is not suppressed.

Inhibition of Ovarian Androgen Production

Gonadotropin-Releasing Agonists

Androgen production in the ovary can also be blocked by gonadotropin-releasing
hormone agonists such as buserelin, nafarelin, or leuprolide. These gonadotropinreleasing
agonists block ovulation by interrupting the cyclic release of FSH and LH
fromthe pituitary. These drugs are efficacious in acne and hirsutism, and are available
as injectable drugs or nasal spray. However, in addition to suppressing the production
of ovarian androgens, these drugs also suppress the ovarian production of estrogens,
thereby eliminating the function of the ovary. Thus, the patient could develop menopausal
symptoms and suffer from hypoestrogenism. Headaches can also develop, as
well as the occurrence of bone loss, due to the reduction in estrogen.

Oral Contraceptives

Oral contraceptives generally contain an estrogen (most commonly ethinyl estradiol)
and a progestin. In their early formulations, oral contraceptives contained
over 100 mg of estrogen. In these and higher doses, estrogens themselves can suppress
sebum production. Estrogens also act on the liver to increase the synthesis of
sex hormone-binding globulin that binds testosterone and lowers the circulating
levels of free testosterone. In addition, oral contraceptives inhibit the ovarian production
of androgens by suppressing ovulation. This, in turn, decreases serum
androgen levels and reduces sebum production. The concentrations of estrogen
in oral contraceptives have decreased over the years from 150 to 35 mg, and in
the most recent forms, to 20 mg, in order to reduce the side effects associated
with estrogen (41). Oral contraceptives containing low doses of estrogen are
listed in Table 1.

Progestins

The progestins contained in oral contraceptives include estranges and gonanes,
which are derivatives of 19-nortestosterone, cyprotereone acetate, and a novel progestin,
drosperinone. Members of the estrane and gonane class of progestins
(Table 2) can cross-react with the androgen receptor, which can lead to increased
androgenic effects and could aggravate acne, hirsutism, or androgenic alopecia.
These progestins can also cause changes in lipid metabolism and can increase
serum glucose, leading to glucose intolerance, as well as possibly interfering with
the beneficial effect of estrogen on the sex hormone-binding globulin. However,
the third generation progestins, including norgestimate, desogestrel, and gestodene,
are more selective for the progesterone receptor rather than the androgen
receptor. The biological relevance of these differences, however, is uncertain. For
TABLE 1 Oral Contraceptives Containing Low Doses of Estrogen
Ethinyl estradiol 20 mg/Levonorgestrel 0.1 mg (AlesseTM)
Ethinyl estradiol 20, 10 mg/Desogestrel 0.15 mg (MircetteTM)
Ethinyl estradiol 20, 30, 35 mg/norethindrone 1.0 mg (Estrostepw)
Ethinyl estradiol 20 mg/norethindrone acetate 1.0 mg (Lo-Estrinw 1/20)
Ethinyl estradiol 20 mg/drospirenone 3.0 mg (YazTM)

Hormonal Influences in Acne


For years, it has been known that almost all oral contraceptives are beneficial in the
treatment of acne (42). It is possible that some women are more sensitive to the
androgenic effects of a progestin, but it is more likely that the effect of progestin
may be offset by estrogen. All oral contraceptives, regardless of the type of progestin,
will inhibit serum androgen levels. Moreover, although some progestins might
be more androgenic than others, there is an increase in sex hormone-binding globulin
with the use of any oral contraceptives and an improvement of the acne in
women who are treated with them.
Drospirenone is a novel progestin that is derived from 17a-spironolactone. It
possesses antiandrogenic and antimineralocorticoid activity, which can be of
benefit in androgenic-related conditions such as acne and hirsutism and in the
estrogen-related fluid retention associated with some oral contraceptives (43).

ORAL CONTRACEPTIVES STUDIED IN ACNE


Many oral contraceptives have been studied in the treatment of acne (Table 3).
These include those containing ethinyl estradiol in combination with cyproterone
acetate (Diane, Dianette), ethynodiol diacetate (Demulen), levonorgestrel
(TriPhasil, Alesse), norgestimate (Ortho Tri-Cyclenw), desogesterel (Desogen),
and drosperinone (Yasmin, Yaz). Numerous studies point to the efficacy of
ethinyl estradiol/cyproterone acetate oral contraceptives (Diane and Dianette) in
the treatment of acne. Reductions in inflammatory lesion count on the order of
50% to 75% have been reported (44,45). Two large studies involving a total of
approximately 500 women with moderate acne were conducted with ethinyl
estradiol 35 mg/norgestimate (Ortho Tri-Cyclen). Improvement in inflammatory
lesions, total lesions, and global assessment was noted with this oral contraceptive
after six months of treatment (46,47). There was a 50% to 60% improvement in
inflammatory lesions. Decreases in serum free testosterone and an increase in sex
hormone-binding globulin were noted in the active group. Two large, six-month,
placebo-controlled trials (350 and 371 women, respectively) were conducted

TABLE 2 Progestins: 19-Nortestosterone Derivatives
Estranes Gonanes
Norethindrone Norgestrel
Norethindrone acetate Levonorgestrel
Ethynodiol diacetate Desogestrel
Gestodene
Norgestimate

TABLE 3 Oral Contraceptives Studied in Acne
Demulen (ethinyl estradiol 35 mg/ethynodiol diacetate)
Diane, Dianette (ethinyl estradiol 50, 35 mg/cyproterone acetate)
Estrostep (ethinyl estradiol 20, 25, 30 mg/norethindrone)
Alesse (ethinyl estradiol 20 mg/levonorgestrel)
Ortho Tri-Cyclen (ethinyl estradiol 35 mg/norgestimate)
Desogen (ethinyl estradiol 30 mg/desogestrel)
Yasmin (ethinyl estradiol 30 mg/drospirenone)
Yaz (ethinyl estradiol 20 mg/drospirenone)
Triphasil (ethinyl estradiol 30 mg, 40 mg/levonorgestrel)
90 Thiboutot
using ethinyl estradiol 20 mg/levonorgestrel (Alesse) in the treatment of acne
(48,49).

In each study, the oral contraceptive demonstrated significantly greater
reduction in acne lesion counts and improvement in global assessment scores compared
with placebo. The reduction in inflammatory lesion count was on the order of
47%. A study of 128 women with mild-to-moderate acne compared the efficacy of
ethinyl estradiol 30 mg/drospirenone (Yasmin) and ethinyl estradiol 35 mg/cyproterone
acetate (Diane-35) in the treatment of acne for nine cycles (50). Both treatments
produced comparable reductions in acne lesion counts, with an
approximate 60% reduction in inflammatory lesion count. Both treatments also
reduced sebum production and yielded comparable increases in sex hormonebinding
globulin. Two large placebo-controlled studies involving a total of approximately
593 women with moderate acne, found improvement in inflammatory
lesions, total lesions, global assessment, and quality of life in women who were
treated for six months with a triphasic oral contraceptive that contains doses of
20 to 35 mg of ethinyl estradiol in combination with 1.0 mg norethindrone acetate
(Estrostep) (51). In these studies, inflammatory lesion counts were reduced by
approximately 47% (51).
Oral contraceptives that have been approved for the treatment of acne in the
United States include ethinyl estradiol 35 mg/norgestimate (Ortho Tri-Cyclen)
ethinyl estradiol 20 to 35 mg/norethindrone acetate (Estrostep), and ethinyl estradiol
20 mg/drospirenone (Yaz).

ORAL CONTRACEPTIVES AND ANTIBIOTICS

The concern regarding oral contraceptives and antibiotics is essentially theoretical,
owing to the action of broad-spectrum antibiotics, which reduce the gut flora bacteria
and thus may result in decreased absorption of estrogen. This could lead to a
possible reduction in the efficacy of oral contraceptives, although pharmacokinetic
studies suggest that serum levels of estrogen are unaffected by antibiotics such as
tetracycline, doxycycline, and others (52,53). Nevertheless, there have been very
few reports in the literature of pregnancies associated with the use of antibiotics
in conjunction with oral contraceptives (54,55). Existing reports have focused on
tetracycline, and the incidence was 1.2 to 1.4 pregnancies/100 woman years of
use of the oral contraceptive. These data are no greater than the background
failure rate of oral contraceptives (54,55).

NEWER FORMS OF CONTRACEPTIVES

Recently, newer forms of contraceptives have been developed, such as contraceptive
patches, vaginal rings, and injectable combination hormones. Each of these is
designed to suppress ovulation and in this regard will lower the ovarian production
of androgens. As of yet, these formulations have not been studied in the treatment
of acne. The contraceptive patch (Ortho Evra) contains 20 mg of ethinyl estradiol
and 150 mg of the progestin, norelgestromin. The patch is worn for three weeks
and removed for one week, during which time menstrual bleeding will occur.
The advantages of this formulation are better patient compliance, dosing that is
not affected by gastrointestinal disturbances, and more consistent serum levels of
estrogen serum levels compared to oral dosing (56). The vaginal ring (NuvaRing)
is a contraceptive vaginal ring that releases 15 mg of ethinyl estradiol and 120 mg
of the progestin, etonogestrel. It is placed within the vagina for three weeks and
removed for one week. In one study, the incidence of irregular bleeding was less
compared with an oral combination contraceptive (57). An injectable combination
of estradiol cypionate and medroxyprogesterone acetate (Lunelle) has been developed.
This is given as a monthly contraceptive injection. Contraceptive efficacy was
shown to be comparable to a triphasic oral contraceptive containing ethinyl estradiol
and norethindrone (Ortho 7/7/7) (58).

APPROACH TO HORMONAL THERAPY IN FEMALE ACNE

Hormonal therapy is an excellent option for treatment of women whose acne is not
responding to conventional therapy. If there are signs of hyperandrogenism, an
endocrine evaluation is indicated, consisting of tests such as DHEAS, total- and
free-testosterone, and an LH/FSH ratio. Although hyperandrogenism is an indication
for hormonal therapy, women with normal serum androgen levels also
respond well to treatment. The mainstays of hormonal therapy include oral contraceptives
and spironolactone. Other agents to choose from include cyproterone
acetate, flutamide, and glucocorticoids. Hormonal agents work best as part of a
combination regimen including topical retinoids or topical or oral antibiotics
depending upon the severity of the acne. In some women, the additional of hormonal
therapy has improved acne to the point where subsequent treatment with isotretinoin
was no longer necessary. As more is learned about the hormones involved
in acne, their source of production and the mechanisms by which they influence
sebaceous gland growth and sebum production, new opportunities will arise for
the development of novel therapies aimed at the hormonal aspects of acne.

ABSTRACT TAKEN FROM:ACNE AND ITS THERAPY,EDITED BY GUY F. WEBSTER,ANTHONY V. RAWLINGS

I was reading this dudes thread about using bactine to clear acne and decided to look into it

http://www.acne.org/messageboard/POST-READ-t75810.html

Benzalkonium Cl 0.13% is the active ingredient

Benzalkonium Cl is a family of benzyldimethylalkylammonium compounds which are selective inhibitors of histamine release induced by 48/80 and many other polyamines, but do not inhibit histamine release caused by antigen-antibody reactions, ionophores, enzymes or detergents.

so i did a search on histamine acne in pubmed

Identification of histamine receptors and reduction of squalene levels by an antihistamine in sebocytes.

Pelle E, McCarthy J, Seltmann H, Huang X, Mammone T, Zouboulis CC, Maes D.
Estee Lauder Research Laboratories, Melville, New York 11747, USA. epelle@estee.com
Overproduction of sebum, especially during adolescence, is causally related to acne and inflammation. As a way to reduce sebum and its interference with the process of follicular keratinization in the pilosebaceous unit leading to inflammatory acne lesions, antihistamines were investigated for their effect on sebocytes, the major cell of the sebaceous gland responsible for producing sebum. Reverse transcriptase-PCR analysis and immunofluorescence of an immortalized sebocyte cell line (SZ95) revealed the presence of histamine-1 receptor (H-1 receptor), and thus indicated that histamines and, conversely, antihistamines could potentially modulate sebocyte function directly. When sebocytes were incubated with an H-1 receptor antagonist, diphenhydramine (DPH), at non-cytotoxic doses, a significant decrease in squalene levels, a biomarker for sebum, was observed. As determined by high-performance liquid chromatography, untreated sebocytes contained 6.27 (+/-0.73) nmol squalene per 10(6) cells, whereas for DPH-treated cells, the levels were 2.37 (+/-0.24) and 2.03 (+/-0.97) nmol squalene per 10(6) cells at 50 and 100 microM, respectively. These data were further substantiated by the identification of histamine receptors in human sebaceous glands. In conclusion, our data show the presence of histamine receptors on sebocytes, demonstrate how an antagonist to these receptors modulated cellular function, and may indicate a new paradigm for acne therapy involving an H-1 receptor-mediated pathway.

so theoretically anthistamines could lower or somehow modulate characteristics of sebum although im not sure how spraying bactine on your face could antagonize the receptors. But then again i was surprised to find that bp works as well at least for some people.

anyway i will now be spraying bactine on my face everyday and will post the results, if any, in a month.

http://www.ncbi.nlm.nih.gov/pubmed/1871623...Pubmed_RVDocSum

Acne is not associated with yet-uncultured bacteria.
Bek-Thomsen M, Lomholt HB, Kilian M.

Institute of Medical Microbiology and Immunology, The Bartholin Building, Wilhelm Meyer's Allé 1240, Aarhus University, Aarhus C DK-8000, Denmark.

Current clinical and microbiological information on acne fails to demonstrate a clear association between particular species, including Propionibacterium acnes, and disease, and the disease continues to be a considerable problem. To test if acne is associated with hitherto uncultured bacteria residing in diseased skin follicles, sequencing and phylogenetic analysis of approximately 5,700 amplified and cloned 16S rRNA genes were used to determine the microbial diversity in follicles from acne patients and healthy individuals and from the superficial skin of acne patients. Follicles from healthy skin were exclusively colonized by P. acnes, whereas the follicular microbiota of acne patients included, in addition, Staphylococcus epidermidis and minor proportions of other species. In comparison, samples from superficial skin showed a complex microbiota represented by 12 to 16 bacterial species. The findings of the study exclude the possibility that acne is associated with yet-uncultured bacteria and shows that healthy skin follicles constitute a remarkably exclusive habitat allowing colonization only by P. acnes.

i was doing my regular survery of acne related articles on pubmed, and this one caught my eye. i generally don't pay much attention to laser/light therapy articles, but what i thought was interesting here was that the researchers noted a "a significant decrease of skin sebum excretion" as a result of this red light therapy. i've read about the anti-microbial properties of blue/red/UV light, but i wasnt familiar with any effects on sebum outside of things like IPL/ALA treatments. is anyone here better read on this/tried it in the past?

in futurederm.com there is an article that describes how botox is being used for acne. by reducing sebum.

there is also a clinical trial listed for it on clincialtrial.gov

while watching a news interview on culture in china (on NBC, and due to the olympic games this summer), i saw a segment on accupuncture treatments. i googled it a bit, and found a site combining ancient chinese medicinal practices with current dermatalogical ones. intruiged, i searched remedies for acne. as i read through the current cures section, i came across a paragraph breifly mentioning topical isotretinoin. i was confused. at least in the americas, there is no such thing as topically applied accutane, or at least nothing of the sort that i had ever heard of. i researched this further, and found the two easiest-to-read-while-still-relatively-medical reports to be:
http://www.ncbi.nlm.nih.gov/pubmed/9522243
http://www.acnetreatmentlab.com/medicine-p...sotretinoin.htm

i'm so excited! of course, my excitement wont last too long if the topical accutane turns out to be just as destructive as the oral kind. i understand that dryness, peeling, and redness may still occur, and that using it while pregnant is still not a good idea, but what about the possible blurry vision and hearing loss, muscle pain, hair loss, issues with the liver, brain, and bones, and depression? and does topical accutane sport the same long-term treatment as the oral kind does? does the redness and peeling, as well as the hypersensitivity and erythema, subside eventually like it does when taken orally? also, does applying accutane externally really blast the pores, possibly exposing them to a whole new set of problems?

ANY INFO on this would be VERY MUCH APPRECIATED
thanks guys

anyone know?

http://www.ncbi.nlm.nih.gov/pubmed/18692613?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportP
anel.Pubmed_RVDocSum ://http://www.ncbi.nlm.nih.gov/pubmed/...ubmed_RVDocSum

Exp Dermatol. 2004
Neuroendocrine regulation of sebocytes -- a pathogenetic link between stress and acne

A causative link between emotional stress and acne has long been postulated. There is mounting evidence that the molecular mechanism underlying this observation is related to the expression of receptors for several neuroendocrine mediators by the sebaceous gland. Recent and ongoing studies have indicated that human sebocytes express functional receptors for corticotropin-releasing hormone, melanocortins, beta-endorphin, vasoactive intestinal polypeptide, neuropeptide Y and calcitonin gene-related peptide. After ligand binding, these receptors modulate the production of inflammatory cytokines, proliferation, differentiation, lipogenesis and androgen metabolism in sebocytes. By means of their autocrine, paracrine and endocrine actions, these neuroendocrine factors appear to mediate centrally and topically induced stress towards the sebaceous gland, ultimately affecting the clinical course of acne.

Proc Natl Acad Sci U S A. 2002 May 14;99(10):7148-53. Links
Corticotropin-releasing hormone: an autocrine hormone that promotes lipogenesis in human sebocytes

Sebaceous glands may be involved in a pathway conceptually similar to that of the hypothalamic-pituitary-adrenal (HPA) axis. Such a pathway has been described and may occur in human skin and lately in the sebaceous glands because they express neuropeptide receptors. Corticotropin-releasing hormone (CRH) is the most proximal element of the HPA axis, and it acts as central coordinator for neuroendocrine and behavioral responses to stress. To further examine the probability of an HPA equivalent pathway, we investigated the expression of CRH, CRH-binding protein (CRH-BP), and CRH receptors (CRH-R) in SZ95 sebocytes in vitro and their regulation by CRH and several other hormones. CRH, CRH-BP, CRH-R1, and CRH-R2 were detectable in SZ95 sebocytes at the mRNA and protein levels: CRH-R1 was the predominant type (CRH-R1/CRH-R2 = 2). CRH was biologically active on human sebocytes: it induced biphasic increase in synthesis of sebaceous lipids with a maximum stimulation at 10(-7) M and up-regulated mRNA levels of 3 beta- hydroxysteroid dehydrogenase/Delta(5-4) isomerase, although it did not affect cell viability, cell proliferation, or IL-1 beta-induced IL-8 release. CRH, dehydroepiandrosterone, and 17 beta-estradiol did not modulate CRH-R expression, whereas testosterone at 10(-7) M down-regulated CRH-R1 and CRH-R2 mRNA expression at 6 to 24 h, and growth hormone (GH) switched CRH-R1 mRNA expression to CRH-R2 at 24 h. Based on these findings, CRH may be an autocrine hormone for human sebocytes that exerts homeostatic lipogenic activity, whereas testosterone and growth hormone induce CRH negative feedback. The findings implicate CRH in the clinical development of acne, seborrhea, androgenetic alopecia, skin aging, xerosis, and other skin disorders associated with alterations in lipid formation of sebaceous origin.[/b]




Horm Res. 2000;54(5-6):281-6. Links
Neuroimmunoregulation of androgens in the adrenal gland and the skin
Human adrenals produce large quantities of androgens, especially DHEA which is the most abundant circulating hormone in the human body. Adrenal androgens are regulated by several factors, including pituitary ACTH and an intricate intraadrenal network involving immune cells, cytokines and neuroendocrine factors. The skin is a major target of androgens and androgen receptors are expressed in the epidermis, dermis, sebaceous glands and hair. In addition, the skin has the capacity to metabolize androgens into more powerful compounds. Similar to the adrenal gland, there is an intradermal neuro-immune network involving the local expression of cytokines and neuropeptides. Dysregulation of androgens in the adrenals and/or the skin is associated with acne, hirsutism and androgenic alopecia. Therefore, understanding the mechanisms of these intricate networks is of both basic and clinical relevance and may help to develop new strategies for the treatment of androgen-dependent skin disorders. [/b]Copyright 2001 S. Karger AG, Basel


Horm Metab Res. 2007 Feb;39(2):166-70. Links
Corticotropin-releasing hormone skin signaling is receptor-mediated and is predominant in the sebaceous glands

There is increasing evidence that the sebaceous gland expresses receptors for several neuropeptides and is involved in responses to stress. Among them, corticotropin-releasing hormone (CRH) was currently found to be produced also in the skin. In this study, the distribution of CRH, CRH receptors 1 and 2 (CRH-R1 and CRH-R2), and CRH binding protein (CRH-BP) in cultured human (SZ95) sebocytes was further characterized. Moreover, the effects of CRH and CRH-like peptides on proliferation and inflammatory signaling of CRH receptor-expressing SZ95 sebocytes IN VITRO were investigated. Urocortin (Uct), urotensin and sauvagine are recently described members of the family of structurally related CRH-like peptides, whereas Uct shares a 45% homology with CRH. CRH and Uct inhibited SZ95 sebocyte proliferation with CRH also stimulating interleukin-6 (IL-6) and interleukin-8 (IL-8) release from SZ95 sebocytes. However, CRH had no effect on interleukin-1alpha and interleukin-1beta production in these cells. alpha-Helical-CRF, a CRH antagonistic peptide, annulled the CRH effect on SZ95 sebocyte proliferation and interleukin secretion, while the non-peptidic CRH-R1 selective antagonist antalarmin inhibited the increased production of neutral lipids caused by CRH. In conclusion, CRH, and to a lesser extent Uct, may be involved in signaling of stress pathophysiology in the skin. However, further investigations into the downstream effects of CRH and Uct are required to elucidate the mechanism by which these neuropeptides could establish a stress-related pathophysiological condition in the skin.


also read this
http://www.pubmedcentral.nih.gov/articlere...p;artid=2232898


over the past few months if been considering this a real possibility. my first experiance was with with meditation and practicing relaxation, then my recent friendship that was going really well which helped ease my stress, and my acne has improved drastically, or its just coincidence but i can tell you that i dont ever think ive been able to deal with my emotions effectively, also my famly is in shambles but we deny it, and i also noticed that when i was clear it was when i was most satisfied with my life, but when trouble came acne usually returned.

I suspect that life satisfaction as defined by experiancing joy and pleasure on a consistent basis could be the cure for most. Learning to stomp out negative stressful feelings by either altering your life our altering your perception of life, im sure a combination of the two, and also good healthy relationships that make you feel so good and not sick to your stomach.

There is an new area of psychology that is called emotional intelligence and it studies peoples ability and skill in dealing with emotions, such as learning to sense the subtle emotions and discomforting feelings and finding healthy solutions to dealing with them as opposed to denying that you feel them, becoming emotionally numb or dealing with them the wrong way like indulging in your anger towards someone or taking drugs but you get the jist of it.