Skin Tag Orgins and Removal Treatments

What are skin tags?

Skin tags are small, benign growths that are composed of a core of fibers and ducts, nerve cells, fat cells, and a covering or epidermis. Additional names for skin tags include acrochordon, cutaneous papilloma, cutaneous tag, fibroepithelial polyp, fibroma molluscum, fibroma pendulum, papilloma colli, soft fibroma, and Templeton skin tag. They are often seen raised from the skin on a stalk called a peduncle.

Who gets skin tags?
Both men and women tend to get skin tags as they age. Skin tags are also more common in pregnant women, obese people, and people with type 2 diabetes mellitus. About 46% of people develop skin tags at some point in their lives.

Where do skin tags appear?
Skin tags often form in areas where the skin creases, such as the neckline, the groin, the underside of the arms, the area beneath the breasts, and the eyelids. The most common location is the armpit. It is common for skin tags to appear in groups. They often become stuck on jewelry, are shaved in error, and are agitated by clothing. Women who shave their armpits should be careful not to shave or cut skin tags that are located there.

Are skin tags harmful?
Although skin tags are technically tumors, they are benign and normally harmless. They can, however, become damaged and become inflamed and sore. If shaved off or rubbed hard, they may bleed.

What causes skin tags?
Although we do not know the exact cause of skin tags, the following are thought to be associated with their appearance:

* Chaffing and irritation from the skin rubbing together
* Hormones secreted during pregnancy or in cases of acromegaly (gigantism)
* Insulin resistance caused by diabetes
* Human papilloma virus
* Illegal steroid use that interferes with the body and muscles, causing the collagen fibers in the skin to bond so that skin tags are formed

How are skin tags removed?
Since skin tags are generally harmless, they are usually removed for aesthetic or cosmetic reasons. Physicians usually remove skin tags using one of the following methods:

* Cauterizatio - the skin tag is burned off using electrolysis
* Cryosurgery - the skin tag is frozen off using liquid nitrogen
* Ligation - the blood supply to the skin tag is interrupted
* Excision - the skin tag is removed with a scalpel

Squamous Cell Carcinoma Treatments

Most squamous cell carcinomas may be treated by one of the following methods. More healthy tissue around the lesion is removed
than for basal cell carcinomas because of the potential of squamous cell carcinomas to spread. Nearby lymph nodes are also examined
carefully. The choice of treatment is influenced by:

* size, location, grade, and type of tumour
* whether the tumour is primary or is recurring
* person’s age and health
* people with organ transplants are at a high risk of aggressive squamous cell carcinoma, which is considered in their treatment plan
* availability of the treatment

Surgery (Wide Excision)

# used for:
- most small lesions that are less than 2 cm
- superficial or SCC that has not spread
- verrucous carcinomas (slow growing and less aggressive)
- tumours that have previously been treated with radiation therapy
- lesions on the eyelid, forehead, scalp, lip, penis, vulva and anus

Mohs Micrographic Surgery

* used for all types of squamous cell cancer
* commonly used for:
- areas that are at high risk of recurrence (eyelids, nose, ears, forehead, scalp), as well as areas that have - already recurred
- areas where it is important to keep function and appearance
- lesions that are larger than 2 cm, and lesions with poorly defined borders
- aggressive tumours, and invasive lesions that have spread to nerves, cartilage or bone
- tumours that have been left untreated for a long time
- lesions that had not been completely removed with prior surgery it involves a meticulous study of tissues removed by a  pathologist at the time of surgery

Radiation Therapy

* used after surgery for:
- elderly individuals
- ensuring cancer free margins
- treatment of involved lymph nodes
- squamous cell carcinoma that has recurred after surgery
- to relieve or control the symptoms of very large tumours
- for people who are unwilling or unable to undergo surgery
- tumours on the eyelid, cheek, earlobe and nose not used for verrucous carcinomas (slow growing and less aggressive)

Chemotherapy

* systemic chemotherapy is used for squamous cell cancer that has spread to other parts of the body
* drugs used most often in chemotherapy:
- cisplatin
- doxorubicin
- bleomycin

Curettage And Electrodesiccation (C & E)

used for
- small areas that are less than 2 cm
- lesions that haven’t spread
- squamous cell carcinoma with distinct margins in Actinic Keratosis should not be used for:

- larger lesions that are greater than 2 cm
- recurrent tumours
- aggressive squamous cell carcinoma
- lesions with poorly defined borders
- hairy areas like the underarms, scalp, and the pubic area
- areas where it is important to keep function and appearance uncommonly used

Skin Tags and Seborrheic Keratoses

Nuisances You don’t have to put up with. As time goes on, we all acquire tiny bits of extra skin called skin tags. These can range in size from 1-10 mm, and are flesh colored or brown.

Skin tags can be found on any part of the body, but are most common on the eyelids and neck, and in the armpits and groin, and under the breasts.  While skin tags are benign they can be annoying if they become irritating or rub on sporting equipment, and skin tags can interfere with shaving and can detract from one’s appearance and self-image.

Fortunately, we don’t have to put up with skin tags. These little annoyances can be easily removed in an office visit with little or no discomfort. Skin tags can almost always be removed without needing stitches, and the treated areas usually have healed completely in a week or two.

The cost of removing skin tags is quite reasonable - ranging from about $80 for a few tiny ones to about $200 for a larger number scattered over several areas.

Seborrheic keratoses are firm flat or raised, sometimes scaly or crusty flesh-colored, brown or black “barnacles” which accumulate (usually on the face and trunk) as time goes on. Some people start to develop seborrheic keratoses in their thirties, and most people have at least a few by the time they are sixty. To look at pictures of different types of moles, click on www.SkinCancerGuide.ca .

Seborrheic keratoses are usually just a nuisance, but - like skin tags — they can rub on clothing and equipment, and their appearance can sometimes be so distressing that they interfere with choice of clothing, sports like swimming, and intimacy.  Because seborrheic keratoses grow above the skin (but not down into the skin) they can be easily scraped off, and the treated areas heal up nicely within a few weeks. Sometimes the healed area remains pink for a few months after the seborrheic keratosis is removed.

The cost of removing seborrheic keratoses is similar to that for removal of skin tags: about $80 for one or two, with the cost gradually increasing depending on the number and size of seborrheic keratoses to be removed.

The cost of removing skin tags and seborrheic keratoses is a tax-deductible medical expense, just like things like dental bills.  So, if you are annoyed by skin tags or seborrheic keratoses you can be confident that it is simple and inexpensive to rid yourself of these nuisances.

By Kevin C. Smith MD FACP FRCPC

Using Lasers and IPL for Pigmentary Lesions

Lasers and intense pulsed light sources are frequently used for the treatment of pigmented lesions, and the appropriate selection of devices for different lesions is vital to achieving satisfactory clinical outcomes. In dark-skinned patients, the risk of post-inflammatory hyperpigmentation is of particular importance. In general, long-pulse laser and intense pulsed light sources can be effective with a low risk of post-inflammatory hyperpigmentation (PIH) when used for the treatment of lentigines. However, for dermal pigmentation and tattoo, Q-switched lasers are effective, with a lower risk of complications. In the removal of melanocytic nevi, a combined approach with a long-pulse pigmented laser and a Q-switched laser is particularly applicable.
Key Words: pigmented lesions, hyperpigmentation, lasers, intense pulsed light sources

The cutaneous application of lasers and intense pulsed light sources for the treatment of pigmented lesions can be divided into the following categories:

• a)  Tattoos
• b)  Epidermal pigmentation such as lentigines and café au lait patches
• c)  Dermal pigmentation such as nevus of Ota, acquired bilateral nevus of Ota, and melanocytic nevi

Tattoos

The use of lasers has been effective in the removal of some,  but not all, tattoos. Q-switched lasers have been found to be safe and effective in the treatment of tattoos. The response to laser treatment can vary greatly due to the wide range of tattoo ink. Previous in vitro quantitative chemical analysis of tattoo pigments found that the most common elements were aluminium, titanium, and carbon. Titanium overrepresentation was identified as the main reason for a poor response to laser treatment. Picosecond lasers were found to be more effective in achieving a greater degree of clearing. To improve the clinical outcome, more recent developments have included the external application of magnets to improve the removal of magnetite skin tattoos after Q-switched laser treatment, and the use of intradermal focusing of the Q-switched laser. In terms of complications, tattoos can darken after laser treatment due to the reduction of ferric oxide to ferrous oxide. This can be rectified with repeated Q-switched laser treatment and the use of a resurfacing laser. Less common complications include the development of allergic dermatitis or even anaphylactic shock after the laser surgery. Such reactions are thought to occur due to the release of allergic pigment into the extracellular space after laser exposure.

Epidermal Lesions

Lentigines

Lasers have been used for the treatment of lentigines, and although this is often effective for light-skinned patients with limited complications, for dark-skinned patients with a higher epidermal melanin content it can be associated with complications such as hyperpigmentation. Two years ago, our group performed an in vivo study of 34 patients and compared a Q-switched 532nm Neodymium:Yttrium-Aluminum-Garnet (QS 532nm Nd:YAG) laser to a long-pulse 532nm Nd:YAG laser. We found that the long pulse 532nm Nd:YAG laser (2msec pulse duration, 6.5-8J/cm2 fluence, 2mm spot size, with slate gray appearance as the clinical end-point) can result in a lower risk of PIH when used in the treatment of lentigines in Asians. We created controversy when we suggested that the photomechanical effect of QS lasers might not be desirable when used in such treatment. Intense pulsed light sources (IPL), which emit a broad band of visible light from a non-coherent filtered flashlamp, produce only photothermal effects. Recent studies that investigated the use of IPL to remove lentigines in Asians confirmed their effectiveness. Interestingly, no case of PIH was observed in two independent studies.

These observations confirm our hypothesis that the photomechanical effect of Q-switched laser for the treatment of lentigines in Asians is not desirable. The main concern regarding the use of the long-pulse laser for the treatment of cutaneous pigmented lesions is the potential of thermal diffusion from the epidermis to the dermis, which increases the risk of scar formation. To prevent such an occurrence, the pulse duration should be shorter than the thermal relaxation time of the epidermis basal layer, which was estimated to be in the range of 1.6-2.8ms if the epidermal basal layer thickness was 20mm.

It is now our routine approach to test patients with a long pulse 532nm Nd:YAG laser (2ms pulse duration, 6.5J/cm2 fluence, 2mm spot size), and if they respond well, we offer them full treatment. Those who do not wish to have down time, or those who develop post-inflammatory hyperpigmentation after the test, are offered IPL treatment, which requires several more treatment sessions to achieve the desired clinical outcome.

Café au Lait Patch

The use of lasers in the treatment of the café au lait patch has yielded variable results, and although some early studies indicated complete removal without recurrence, such findings have not always been repeated. Previous studies showed that 510nm pulsed dye lasers and copper vapor lasers can be used successfully, with no recurrence, at least one year after treatment. These reports were confirmed by others. Grossman, et al. used a QS Ruby laser and a frequency double Q-switched Nd:YAG laser, and found that the degree of clearance varied across lesions. Moreover, the categorization of the patches into the two histological sub-types that they identified did not help to predict the extent of the clinical response. We looked at the use of normal-mode ruby laser (NMRL) and compared it to QS Ruby laser in the clearing of café au lait patches in 33 patients. Our preliminary data indicated that there was a lower risk of recurrence when the NMRL was used (42.4% of recurrence, as compared to 81.8% recrrence in those who were treated with QS Ruby laser) 3 months after a single treatment. By affecting the follicular melanocytes, the long-pulse laser may reduce the recurrence rate. Further histological study is necessary to confirm this hypothesis.

Dermal Lesions

Nevus of Ota

Q-switched Alexandrite (QS Alex), QS Ruby, and QS 1064nm Nd:YAG have been used for the treatment of nevus of Ota with excellent results and minimal risk of complications. The clinical efficacy of the QS Ruby was confirmed when Watanabe and Takahashi⁶ studied 114 nevus of Ota patients and found that a good-to-excellent degree of lightening was achieved after three or more treatment sessions. The side-effects were few, with transient hyperpigmentation after the first treatment being the most common. Studies comparing the use of QS Alex and QS Nd:YAG lasers found that most patients better tolerated the former. However, QS Nd:YAG laser appeared to be more effective than QS Alex in the lightening of nevus of Ota after three or more laser treatment sessions. In terms of complications, hypopigmentation was common, especially among those treated with QS Ruby. The original pigmentation could also recur in patients after complete laser-induced clearing, which is an important issue, especially for pediatric patients. The risk of such recurrence is estimated to be between 0.6% and 1.2%. However, the use of QS Ruby laser for the treatment of nevus of Ota in children can achieve an excellent result in fewer sessions and at a lower complication rate than later treatment.  Hence, the advantages and disadvantages of treating nevus of Ota early in childhood should be thoroughly discussed with the patient’s relatives.

Acquired Bilateral Nevus of Ota-like Macules (ABNOM) or Hori’s Macules

Acquired bilateral nevus of Ota-like macules (ABNOM), or Hori’s macules, are a pigmentary disorder that is clinically characterized by speckled or confluent brownish-blue or slate gray pigmentation over the face, and histologically characterized by diffuse upper dermal melanocytosis. Unlike nevus of Ota, the pigmentation occurs in a symmetrical bilateral fashion, has a late onset in adulthood, and does not involve the mucosa.

One hundred forty patients with ABNOM were treated with a Q-switched Ruby laser (7-10J/cm2 fluence at a repetition rate of 1Hz, 2-4mm spot size). Complete clearance was obtained in 131 patients, and hyperpigmentation was observed in 7%. Hypopigmentation persisted in 2.1% of the patients, and there was no recurrence after 6 months to 4.3 years of follow up (mean was 2.5 years). QS Nd:YAG laser was also used to treat ABNOM, and the rate of PIH was estimated to be between 50% and 73%.⁸ Our group showed that QS Alex laser is effective in the treatment of ABNOM. Post-operative pigmentary changes were frequent, and the use of topical bleaching agents was necessary to achieve a satisfactory result. The risk of transient hypopigmentation was high, and it affected up to 50% of the patients. More recently, a combination approach with a scanned carbon dioxide laser followed by a Q-switched Ruby laser has been found to be effective.

Melanocytic nevi are common, and often removed for cosmetic reasons. Various pigmented lasers have been used in their removal. A previous study using a QS Ruby laser found that an average clearance of 76% occurred after eight treatment sessions.10 However, recurrence can be a problem depending upon the depth of the nests of melanocytes. The use of a normal mode ruby laser (NMRL) for the treatment of melanocytic nevi is based upon the principle that with longer pulse durations, a greater degree of clearance is achieved when nests of cells are destroyed. A combined approach with a QS Ruby laser followed immediately, or 2 weeks later, with an NMRL has more recently been used with the intention of removing the superficial pigment first with the QS Ruby laser, thereby enhancing the penetration of the NMRL. A previous study found that although 52% of the nevi showed a visible reduction in pigment, no lesion had complete histological clearance. The short- and long-term histological findings of congenital nevi that have been treated with the NMRL indicated that subtle microscopic scars of up to 1mm in diameter are frequent. It has been proposed that such scars cover the underlying nevus cells, which leads to cosmetic improvement. Better cosmetic results were produced by first using an NMRL to remove the epidermis, immediately followed by multiple passes of a QS Ruby laser.¹¹ This approach effectively removes the epidermis, and in doing so enables a greater degree of penetration by the QS Ruby, of which multiple passes further enhance the clinical efficacy. A similar approach using a long-pulse pigmented laser immediately followed by multiple passes of a Q-switched pigmented laser can obtain similar results.

Conclusion

For epidermal pigmented lesions, long-pulse pigmented laser or IPL can be effective with a lower risk of post-inflammatory hyperpigmentation, especially when used on dark-skinned patients. Q-switched laser is necessary to remove dermal pigment and tattoo in order to avoid the risk of scarring. A combination approach can be used for the removal of melanocytic nevi.

H.H.L. Chan, MD, FRCP¹, and T. Kono, MD^2
1Division of Dermatology, Department of Medicine, the University of Hong Kong, China
²Department of Plastic and Reconstructive Surgery, Tokyo Women’s Medical University, Tokyo, Japan

Methyl Aminolevulinate Cream + Benzyl Alcohol

Update on Drugs and Drug News

Name/Company	Approval Dates and Comments
Benzyl Alcohol Lotion 5% Sciele Pharma	The US FDA approved this prescription medication in April 2009 for the treatment of head lice infestation for use in patients 6 months of age and older.
Red Light Technology Device + Methyl Aminolevulinate Cream Aktilite® CL 128 + Metvix® Photocure/ Galderma	Health Canada approved this LED-based narrow band red light technology device in combination with methyl aminolevulinate in April 2009 for the treatment of actinic keratosis and superficial basal cell carcinoma.

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Drug News

Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals, Inc. announced in April 2009 that a Phase III trial evaluating sorafenib tablets (Nexavar®) in patients with unresectable Stage III or Stage IV melanoma was stopped early following a planned interim analysis by the independent Data Monitoring Committee (DMC). The trial was sponsored by the National Cancer Institute (NCI) and led by the Eastern Cooperative Oncology Group (ECOG) under a Clinical Trials Agreement between NCI and Bayer and Onyx. The DMC concluded that the study would not meet the primary endpoint of improved overall survival among patients receiving sorafenib in combination with the chemotherapeutic agents carboplatin and paclitaxel vs. patients receiving placebo plus the chemotherapeutic agents. The treatment effect was comparable in each arm. There were no unexpected serious side-effects, though the final analysis of the data will occur per protocol and statistical analysis plan. Bayer and Onyx will further review the findings of this analysis to determine what, if any, impact these data might have on other ongoing sorafenib melanoma trials. Data from this study are expected to be presented at an upcoming scientific meeting.

In a study presented at the 2009 Annual Meeting of the American Academy of Allergy, Asthma & Immunology*, researchers at Mount Sinai Hospital in New York studied 14 patients with persistent atopic dermatitis who received traditional Chinese medicine at Ming Qi Natural Health Center in Manhattan between August 2006 and May 2008. The treatments consisted of Erka Shizheng Herbal Tea, a bath additive, creams, and acupuncture. The study authors utilized 2 measures: the SCORAD index to gauge atopic dermatitis severity and the Dermatology Life Quality Index (DLQI) to calculate impairment to life quality. Baseline median scores for SCORAD and DLQI were 89 and 17, respectively. After a median 8 months of treatment, the median scores fell to 11 for SCORAD and 1 for DLQI. In all but 1 patient, SCORAD measures decreased between 60% to 90% after 3.3 months of treatment. More than 50% improvement in DLQI scores was documented in all but 1 patient after 2.4 months. Patients also reported a reduction in the use of steroids, antibiotics, and antihistamines within 3 months of being treated with traditional Chinese medicine. There were no abnormalities of liver and kidney function observed. While the researchers concluded that the use of traditional Chinese medicine is safe and effective for patients with persistent atopic dermatitis, especially those with a severe case and significant life quality impairment, it is still recommended to speak with a physician before taking any complementary or alternative medicines. * Wisniewski J, Nowak-Wegrzyn A, Steenburgh-Thanik H, et al. Efficacy and safety of traditional Chinese medicine for treatment of atopic dermatitis (AD). J Allergy Clin Immunol 123(Suppl 2):Abstract #131 (2009 Feb).

Treating Actinic Keratoses and Nonmelanoma Skin Cancers

Methyl Aminolevulinate-PDT for Actinic Keratoses and Superficial Nonmelanoma Skin Cancers

Methyl aminolevulinate-hydrochloride cream (Metvix® [in Canada] and Metvixia® [in the US], Galderma) in combination with photodynamic therapy (PDT) provides an effective treatment option for actinic keratoses (AKs), superficial basal cell carcinoma (sBCC), and Bowen’s disease (BD). Good clinical outcomes have been reported in the literature. Complete responses (CRs) in AK range from 69% to 93% at 3 months. In sBCC, reported CR rates were from 85% to 93% at 3 months and almost on par with cryosurgery at 60 months (75% vs. 74%). In BD, CR rates were 93% at 3 months and 68% at 2 years. Current evidence has shown that this noninvasive treatment is superior in terms of cosmetic outcome to other management strategies such as surgery. It also offers the advantages of relative simplicity, low risk of side-effects and decreased complications due to scar formation.

Topical Methyl Aminolevulinate (MAL)-PDT

Photodynamic therapy (PDT) treats superficial skin cancers and pre-cancerous lesions through photosensitized reactions requiring oxygen. Over the past several decades, PDT has been extensively investigated as an experimental therapy for human cancers. There is now growing interest in the use of PDT not only for nonmelanoma skin cancer (NMSC), but also for other skin tumors such as lymphoma, as well as for nononcological indications, such as psoriasis, localized scleroderma, acne, and skin rejuvenation.^1-4 In Europe, as well as in the US, porphyrin-inducing precursors, such as 5-aminolevulinic-acid (ALA) and MAL have been proven effective for the treatment of actinic keratoses (AKs) and basal cell carcinomas.^5-7 Both ALA and MAL induce protoporphyrin IX (PpIX) locally in the skin. Photodynamic therapy combines the simultaneous presence of a photosensitizer activated by an appropriate wavelength of light. For topical PDT, upon illumination, PpIX is transformed to the excited state and then returns to its ground state through a type-II photo-oxidative reaction.5 In this reaction, these molecules transfer energy to oxygen producing highly reactive oxygen species (ROS), singlet oxygen in particular. ROS accumulates locally within the affected tissue leading to direct cellular damage by apoptosis or necrosis, and indirect stimulation of inflammatory cell mediators.⁶

Previous studies have shown that MAL in combination with red light (570-670nm) has provided good clinical outcomes in the treatment of NMSC (both sBCC and Bowen’s disease) and AKs.⁷ MAL, the methylated ester of ALA, is a new topical photosensitizer that may offer advantages over ALA in terms of its deeper skin penetration (up to 2mm in depth) due to potentially enhanced lipophilicity and greater specificity for neoplastic cells.⁸ In a typical PDT session, the lesion surface is prepared by light curettage of any surface crusts and scales. The 3 hour application of 160mg/g MAL prior to irradiation with 37J/cm2 from a light-emitting diode system (emission peak of 632nm) corresponds to the time point of the highest ratio of fluorescence depth to tumor depth2 under occlusion. Two treatments 1 week apart for AKs, sBCC, and BD have been recommended; however, a single treatment session is possible and may be potentially sufficient for very thin AKs. For partially cleared responses, a second treatment course (consisting of two weekly PDT sessions) at 3 months may be considered.⁹ This article reviews key published trials of topical MAL-PDT for AK, sBCC, and BD.

AKs

A US randomized, multicenter, double-blind, placebo controlled study was performed in 80 patients with mild-to-moderate AKs on the face and scalp. Forty-two patients (260 lesions) were treated with MAL-PDT and 38 patients (242 lesions) received the placebo cream. MAL was applied for 3 hours followed by illumination with noncoherent red light (75J/cm2). Treatment was repeated after 1 week. A complete response rate of 89% with MAL-PDT and 38% with placebo was assessed after 3 months follow-up. An excellent or good cosmetic outcome was reported in more than 90% of patients treated with MAL.¹⁰

Tarstedt et al.11 reported response rates in an open label, prospective study that compared 2 regimens:

1. A single treatment session 2. 2 MAL-PDT sessions 1 week apart.

One hundred six patients received the single treatment and 105 patients received the second regimen. For thin lesions, clearance rates showed no significant difference (93% with single session vs. 89% with double sessions) For thicker lesions, clearance rates were higher for double sessions (84%) when compared with single treatment (70%). The authors concluded that single treatment is effective for thin AKs. Repeated treatments were needed for thicker or resistant lesions.

In another randomized, multicenter study, MAL-PDT (n=360 lesions) was compared with a single-thaw cycle of cryotherapy (n=421 lesions) or placebo (n=74 lesions). The PDT treatment arm consisted of 2 treatment sessions 1 week apart using 75J/cm2 with a noncoherent red light (570-670nm). After 3 months, clearance rates for MAL-PDT were significantly higher (91%) compared with cryosurgery (68%) and placebo (30%). Of the MAL-PDT treated patients, 83% were rated as having an excellent cosmetic outcome by an investigator vs. 51% of those treated with cryotherapy; the corresponding patient assessments were 76% and 56% respectively.¹²

A large randomized, intraindividual, right-left comparative study of 119 patients with face/scalp AKs was performed.14 The aim of the study was to compare 1 MAL PDT session to double freeze-thaw cryotherapy. After a 3-hour application of MAL using 37J/cm2 with double treatment 7 days apart, cure rates were seen when using MAL-PDT (87%) compared with cryotherapy (76%). Of patients treated with MAL-PDT, 10% required re-treatment after 3 months vs. 21% for cryotherapy. Cosmetic outcome significantly favored MAL-PDT (i.e., 77% vs. 50%).13 A recent study, however, showed lower efficacy with MAL-PDT (78% clearance) on the extremities compared with cryotherapy (88% clearance).¹⁴

In a recent multicenter, double-blind, randomized study by Pariser,15 the efficacy of MAL-PDT using a red light-emitting diode (n=363 lesions) was evaluated vs. placebo (n=360 lesions) for grade 1 (slightly palpable) and grade 2 (moderately thick) AKs on the face and scalp. Lesion complete response rates were significantly superior for MAL-PDT (86.2%) vs. placebo (52.5%). The patient complete response rate was 59.2% for MAL-PDT subjects, and lower for those who had vehicle PDT alone (14.9%). Scalp lesions responded better with MAL-PDT (93%) than did facial lesions (87%). Grade 1 lesions had slightly higher complete response rates than grade 2 lesions (89% vs. 80%). Furthermore, larger lesions with diameters of >20mm had poorer response rates compared with smaller lesions (74% vs. 86%).

When treating AKs, biopsies should be considered for thick, keratotic lesions to rule out squamous cell carcinoma. Calzavara-Pinton et al.¹⁶ have shown that even if squamous cell carcinoma is limited to microinvasive involvement, the treatment outcome is poor.

Superficial BCCs

The recent British Photodermatology Group guidelines for topical PDT concluded MAL-PDT to be effective for sBCC.⁹ In an attempt to compare clearance rates and cosmetic outcomes between MAL-PDT (n=60) and double freeze-thaw cryotherapy (n=58) in sBCC, a 5-year European randomized trial was performed in 118 patients. This protocol used MAL applied for 3 hours at 75J/cm2 with noncoherent red light (570-670nm) for 1 session. Partially treated patients at 3 months were given 2 further MAL-PDT sessions (n=20) or repeat cryotherapy (n=16). Complete clinical response rates after 3 months’ follow-up for MAL-PDT were 97% of 102 lesions, while that of cryotherapy was 95% of 98 lesions; the difference between these 2 treatments was not statistically significant. At 5 years’ follow-up, clearance rates were similar for the MAL-PDT group (75%) and cryotherapy (74%). Of the lesions initially cleared with MAL-PDT, 22% had recurred vs. 20% after cryotherapy. Cosmetic outcome was judged superior following PDT (87% vs. 49%).¹⁷ Double MAL-PDT treatment cycles for ‘difficult-to-treat’ sBCC (and nBCC) were reported by 2 prospective multicenter studies. This included recurrent, large-sized lesions and/or those occurring on the mid-face or ears. In the first study, 87% of patients (n=94) had ‘difficult-to-treat’ lesions occurring on the face or scalp. The protocol was a single cycle of MAL-PDT (MAL 3h, 75J/cm2, 570-670nm or 580-740nm, 50-200mW/cm2) involving 2 treatment sessions 1 week apart. For partially treated lesions after 3 months’ follow-up, a second cycle was repeated. Complete clearance at 3 months was 85% for sBCC after histological review (75% for nBCC). After 2 years, the recurrence rate was 22% for sBCC (14% for nBCC). Ninety-four percent of patients were assessed to have a good to excellent cosmetic outcome.¹⁸ In the second study, efficacy, safety, and cosmetic outcomes were examined in 95 patients with BCCs that were ‘difficult-to-treat’ and at high risk for surgical complications. A total of 148 BCCs (sBCC and nBCC) were treated with the same PDT protocol (MAL 3h, 75J/cm2, 570-670nm, 50-200mW/cm2) with re-treatment for non-complete response lesions at 3 months. Overall, histologically-confirmed lesion complete response rate was 89% (93% sBCC and 82% nBCC) after 3 months’ follow-up. Fifteen percent of lesions had histologically confirmed recurrence within 2 years increasing to 20% within 4 years. Ninety-seven percent of patients rated their cosmetic outcome as good to excellent at 3 months.¹⁹

Bowen’s Disease

A large randomized, controlled, multicenter study reported similar clearance response rates following MAL-PDT (86%), single freeze-thaw cryotherapy (82%), and 1 month application of 5-fluorouracil (83%) in 225 patients with histologically confirmed Bowen’s disease. MAL-PDT (MAL 3h, 75J/cm2, 570-670nm, 70-200mW/cm2) was given as a single cycle 1 week apart. Lesions with a partial response at 3 months were re-treated. Cosmetic outcome was superior for MAL-PDT in 94% of patients vs. 66% with cryotherapy, and 76% with fluorouracil.²⁰ Clearance rates after 2 years for MAL-PDT was 68% vs. 60% with cryotherapy and 59% with fluorouracil.⁷

Conclusion

MAL is an effective low molecular weight topical porphyrin-inducer that is typically used in combination with a red light-emitting diode for PDT. It offers therapeutic benefit for thin and moderate thickness AKs. It should be considered as a treatment option for superficial BCCs and Bowen’s disease, particularly in situations where surgery may be problematic or where patients have multiple lesions. However, long-term cure rates, as mentioned above for Bowen’s disease and sBCC, are only 68% and 75% respectively. Because of the appreciable nonresponse and recurrence rates, patients treated with PDT for either disease should be monitored closely during the first 2-3 years after PDT, which is when most lesion recurrences occur. According to studies, patients’ high preference for MAL-PDT may be mainly due to its good to excellent cosmetic outcome and general tolerability of side-effects. No direct comparative studies have yet been reported with MAL and ALA. Important parameters, such as the depth of penetration of MAL-PDT, tumor thickness, location, and careful patient selection are key elements for efficacy. In the US, MAL-PDT is currently FDA-approved for the treatment of AKs only, whereas in Canada, MAL-PDT is officially indicated for the treatment of both AKs and sBCCs.

B. Ortiz-Policarpio, MD and H. Lui, MD, FRCPC

Photomedicine Institute, Department of Dermatology and Skin Science, Vancouver Coastal Health Research Institute, BC Cancer Agency, and University of British Columbia, Vancouver, BC, Canada

Skin Tags and Impaired Carbohydrate Metabolism

Following up with a previous report on the correlation between high numbers of achrocordons (skin tags) and a possible role of insulin-resistance, a 2007 case-controlled study was published on PubMed, (a service of the U.S. National Library of Medicine and the National Institutes of Health), examining skin tags as a cutaneous marker for impaired carbohydrate metabolism.

Excerpts from the team’s findings are published below.

Department of Dermatology, Hazrat-e Rasool Akram University Hospital, Iran University of Medical Sciences, Tehran, Iran. Rasi A, Soltani-Arabshahi R, Shahbazi N.

BACKGROUND: Skin tags are common benign skin tumors usually occurring on the neck and major flexors of older people. A possible association with impaired carbohydrate metabolism has been suggested in previous studies, but the results are not conclusive.

OBJECTIVE: To investigate and compare the prevalence of diabetes and impaired glucose tolerance (IGT) in patients with skin tag and a control group.

PATIENTS AND METHODS: A case-control study was conducted in individuals over 15 years old, comparing cases (n = 104) with at least three skin tags and age-, sex-, and body mass index (BMI)-matched controls (n = 94) without skin tag. Cases and controls were recruited from patients consecutively seen at an academic outpatient dermatology clinic. All patients underwent a standard 2-h oral glucose tolerance test with 75 g glucose.

RESULTS: Patients with skin tag had higher frequency of diabetes than the control group (23.07% vs. 8.51%, chi(2)-test, P = 0.005). The difference in the frequency of IGT was not significant (13.46% vs. 10.63%, chi(2)-test, P = 0.543). There was a positive correlation between the total number of skin tags and the mean fasting plasma glucose (Pearson correlation, r = 0.260, P = 0.031); patients with more than 30 skin tags were particularly at an increased risk of diabetes (52.0%). No correlation was found between the number of skin tags and BMI. We did not find any correlation between the anatomical localization of skin tags and impaired carbohydrate metabolism, except for skin tags under the breast in women.

CONCLUSION: These results show an increased risk of diabetes mellitus in patients with multiple skin tags. With regard to the importance of early diagnosis of diabetes, we recommend a high level of suspicion for impaired carbohydrate metabolism in patients with skin tag.

Source: PMID: 17988334 [PubMed - indexed for MEDLINE

Staph Wound Infections and Staphylococcus aureus

Staph Wound Infections and Methicillin Resistant Staphylococcus aureus

Staphylococcus aureus, also called S. aureus or “staph,” is a bacterium that frequently colonizes the human skin and is present in the nose of about 25-30% of U.S. adults. S. aureus can exist in this form without harming its host or causing symptoms. However, if there is a break in the patient’s skin from a wound or surgery, or if there is a depression in the person’s immune system, then colonizing S. aureus can cause an infection. Staph frequently causes localized skin infections, such as folliculitis, furuncles, and impetigo. It can also cause abscesses and spread into the bones (osteomyelitis), lungs (staphylococcal pneumonia), blood (bacteremia or sepsis), heart (endocarditis – which can damage the heart valves), and other organs. Staph may also infect others as it can be passed from both infected and colonized people to other people through skin contact or through sharing contaminated objects, such as towels or razors.

Hospital-acquired infections
Staph infections acquired while a patient is in a hospital, long-term care facility, or other health care setting have been a challenge for many years. The confined population and the widespread use of antibiotics have led to the development of antibiotic-resistant strains of S. aureus. These strains are called methicillin resistant staphylococcus aureus (MRSA), named after the antibiotic treatment that was developed in 1960 to treat penicillin-resistant strains. Infections caused by MRSA are frequently resistant to a wide variety of antibiotics and are associated with ignificantly higher rates of morbidity and mortality, higher health care costs, and longer hospital stays than infections caused by methicillin susceptible S. aureus. Risk factors for MRSA infection in the hospital include surgery, prior antibiotic therapy, admission to intensive care, exposure to a MRSA-colonized patient or health care worker, being in the hospital more than 48 hours, and having an indwelling catheter or other medical device that goes through the skin.

One strategy that may be used in an effort to control the spread of infection includes active surveillance for the detection of MRSA in patients admitted to intensive care units (ICUs) and other high risk areas. Another approach is to screen all patients admitted to a health care facility. Community-acquired infections
MRSA infections have increased in importance in the community in recent years because they have been associated with a growing number of outbreaks and deaths in non-medical settings where individuals are in close contact such as prisons, day care facilities, military units, and contact sports. These infections are occurring in people who do not have classic MRSA risk factors as described above. A significant number of those affected have had to be hospitalized for what appears to be a simple but persistent skin infection or for pneumonia that develops after a bout of influenza.

Until recently, part of the problem with community-acquired MRSA (CA-MRSA) has been a lack of awareness in the medical community and the community at large. Historically, physicians have treated staph infections, based on their severity, with either over-the-counter triple-antibiotic ointments or with a standard course of antibiotics. They did not routinely order cultures to identify the organism and its antibiotic susceptibility profile unless the infection appeared extensive or the initial treatment was unsuccessful. With CA-MRSA, however, these conventional therapy options have frequently failed. A significant number of those affected have been hospitalized and a few previously healthy patients have died.

Investigations of these outbreaks have revealed that the CA-MRSA was spread from infected or colonized patients to those around them through skin contact (such as sports-related cuts and abrasions), through droplets from the respiratory tract, or through exposure to contaminated objects, such as shared sports equipment, towels, toys, or playground equipment. Investigations have also revealed that the S. aureus strains involved in CA-MRSA are genetically distinct from those that have been causing hospital-acquired MRSA. The CA-MRSA are resistant to methicillin and related antibiotics (oxacillin, dicloxacillin, nafcillin) and erythromycin but remain susceptible to many other antibiotics.

Laboratory Tests

The purpose of culturing wound infections is to identify the bacteria causing the infection and to determine the susceptibility of the microorganism to available antibiotics. If an infection is due to MRSA, it should be investigated to determine the source of the infection. This is especially important in CA-MRSA to prevent further cases from occurring.

The primary laboratory tests performed are:

* Cultures of the affected areas. Fluid or pus from a wound, sputum, blood, joint fluid, or even breast milk (in the case of an infected breast) is collected and spread onto a thin layer of nutrient gel and/or grown in a nutrient broth. Sometimes, multiple samples are collected to evaluate different body sites or to attempt to detect bacteria that may be present in small numbers.
* Nasal cultures (collected by inserting a swab inside the nose) used to screen healthy people may also be ordered to determine whether someone has been colonized with MRSA and is a carrier. The cultured samples are incubated and examined for the growth of characteristic S. aureus colonies. If they are present, susceptibility testing is performed to determine whether the strain is MRSA.
* Nasal swabs may be collected to detect MRSA colonization based on rapid molecular tests, which do not grow the bacteria but detect their presence and antibiotic resistance by detecting the genes responsible for the methicillin resistance.

Identifying MRSA can sometimes be challenging. The population of staph that a person has tends to be mixed. This means that even if a patient has CA-MRSA or hospital-acquired MRSA, not all of the staph present will be equally resistant. Since resistant strains may grow more slowly than susceptible strains, there is the potential for missing them.

A variety of methods may be used to track different strains of MRSA. These are used in the investigation of the spread of MRSA within a community or region but are not used in the treatment of an individual patient.

Oil Production in the skin

The skin has many oil (sebaceous) glands, which secrete oil that contains wax esters, triglycerides, and squalene - a hydrocarbon that is an intermediate in the formation of cholesterol. These fats (or lipids) form a film that helps keep moisture in the skin. While increased sebum production results in oily skin, the opposite is not always the case, as dry skin can also arise from an impaired skin barrier. Oil production can be affected by diet, stress, and hormones-as well as genetics. In a study of twenty pairs each of identical and nonidentical same-sex twins, identical twins had virtually identical amounts of oil production, while the nonidentical twins had significantly different amounts.

No amount of blotting and scrubbing will “remove” the skin’s oil production, and many of us unknowingly destroy the natural beauty of the skin in pursuit of clarity. The skin’s own sebum mechanism is there to regulate own moisture. Drying your skin profusely with oil-stripping, foaming cleansers, detergents and de-greasers like soap and sulfates, or alcohol-based toners that leave the skin feeling tight (always a sign it’s been stripped), will only cause the skin to “rebound” with excess oiliness and destroy its protective and anti-bacterial “matrix,” leaving it sensitized. By stripping the natural acid mantle of the skin, these deep cleaning products actually make skin more vulnerable to bacteria and inflammation. Dabbing benzoyl peroxide often destroys the beauty of the skin by causing flaking, while more aggressive treatments, such as antibiotics or Accutane can cause a cascade of side-effects.

Alternative Acne Treatments and Prevention

Several surgical or medical treatments may be used to reduce acne or the scars caused by the disease.
•    Chemical peel. A chemical known as glycolic acid is first applied to the skin. When it dries, it is peeled off, taking the top layer of skin with it. This treatment helps reduce scarring.

•    Collagen injection. Shallow scars are filled in by injecting collagen, a skin protein, beneath the scars.
•    Comedo extraction. A special tool is used to remove a comedo from a pore.
•    Dermabrasion. The affected skin is first frozen with a chemical spray. Then it is removed with a brush or sandpaper-like instrument.

•    Intralesional injection. Anti-inflammatory drugs are injected directly into inflamed pimples.
•    Punch grafting. Deep scars are removed and the area repaired with small skin grafts.

Alternative treatments for acne focus on proper hygiene and diet. Patients are advised to keep their skin clean and oil-free. They are also encouraged to eat a well-balanced diet high in fiber, zinc, and raw fruits and vegetables. They should also avoid alcohol, dairy products, caffeine, sugar, smoking, processed foods, and foods high in iodine, such as table salt.

Some doctors recommend the use of herbs to supplement the diet. Some herbs that have been used in the treatment of acne include burdock root, red clover, and milk thistle. Additional nutrients that may help to control acne include B-complex vitamins and chromium. Chinese herbal treatments that are recommended include cnidium seed and honeysuckle flower. Another herbal treatment is tea tree oil. The proper dose of these substances can be recommended by physicians or nutritionists.

Acne cannot be cured. However, it can be controlled in about 60 percent of patients with the drug isotretinoin. Improvement usually takes at least two months, and the problem may recur after treatment has been stopped. Inflammatory acne that results in the formation of scars may require one of the more aggressive treatments already described.

PREVENTION

There are no sure ways to prevent acne. However, the following steps tend to reduce flare-ups ofthe condition:
•    Gently wash—do not scrub—the affected areas once or twice every day.
•    Avoid rough cleansers.
•    Use makeup and skin moisturizers that do not produce comedos.
•    Shampoo often and wear hair away from the face.
•    Eat a well-balanced diet and avoid foods that trigger flare-ups.
•    Give dry pimples a limited amount of sun exposure unless otherwise directed by your doctor.
•    Do not pick or squeeze pimples.
•    Reduce stress.

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