Common Bacterial Infections of the Skin

Our skin is host to a number of bacteria, most of which are beneficial. Including the friendly flora in our gut, more than 200 species of bacteria reside within the tissues exposed to the external environment. Skin infections result from these bacteria when the integrity of the skin breaks down or when the immune defense system is weak.

Skin infections can occur on the skin surface or deeper within the skin tissue. The most common bacteria that infect the skin are Staphylococcus aureus and Streptococcus pyogenes. Read more about bacterial infections on www.skincareguide.ca/conditions/bacterial_infections

TYPES OF BACTERIAL INFECTIONS:

Impetigo and Ecthyma

Impetigo begins with a redness of the skin and progresses to blisters that fill with fluid and itch, and then produce honey-colored crusts. Lesions usually form around the nose and face. Ecthyma is a deeper version of impetigo that usually forms on the legs. It causes large boils, crusts, and deep sores that leave scars.

Folliculitis

Folliculitis is an infection of the hair follicles. It produces pimplelike skin bumps and small blisters with pus. Folliculitis occurs on the face, upper trunk, arms, and buttocks. When the infection goes deeper, feels tender, and produces more pus, it is furunculosis. Carbuncles are furuncles that have fused.

Abscess

An abscess is a deep infection that appears like a closed blister or an open hole with pus. It is usually tender and becomes sore and painful as the infection progresses.

Erysipelas and Cellulitis

Erysipelas is a superficial infection that tends to occur in young children and the elderly. It is also seen in those who have chronic swelling of the limbs, are addicted to alcohol, have diabetes mellitus, or have experienced trauma. Erysipelas mostly occurs on the face or legs. A fever occurs abruptly, the cheeks become red, and the skin feels hot, tense, and swollen. Cellulitis is a deeper form of this infection.

TREATMENTS:

Bacterial skin infections are treated according to their severity. Your physician may incise and drain deeper infections and abscesses, and recommend that you apply warm compresses. Creams such as Fucidin® or Bactroban® are prescribed for mild stages of:

* impetigo
* ecthyma
* folliculitis
* abscess

If the infection is more extensive, oral antibiotics such as Cloxacillin or Cephalexin are used as well as those in the erythromycin family. Penicillin is often used to treat for strep.

Antibiotic resistance is an increasing problem so it is best to have early adequate proper treatment to minimize risk of exposure to antibiotics and lower the risk of transmission to others.

During treatment, remember to wash your hands daily with an antibacterial solution such as Trisan®, Tersaseptic® or Hibitane®, or use a product like Safe4Hours® (www.invisicare.com) which kills bacteria for four hours. Hand washing is the most important thing you can do to minimize the spread of infection.

If you suspect a bacterial skin infection, see your doctor before it becomes severe. Due to the increase of bacterial resistance to drugs in general, it is important to take the full course of your prescribed medicines.

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).

Management and Treatment of Pruritus

Pruritus, or itch, is a common sensation that causes a person to want to scratch. It is a complex process that may negatively impact quality of life and commonly occurs with skin disorders such as atopic dermatitis and urticaria. It could also be a symptom related to an underlying disease process such as cholestasis or hyperthyroidism, or simply be caused by dry skin, especially in the cold, winter months. Therapy is often aimed at eliminating the underlying cause first, followed by the management of the itchy sensation. Treatment may include prescription and over-the-counter (OTC) medications, herbal remedies, hydrotherapy, phototherapy, and ultraviolet therapy. This overview provides information regarding the various management and treatment options for pruritus.

Pathophysiology of Pruritus

Pruritus is a complex process that involves the stimulation of free nerve endings found superficially in the skin. The sensation of pruritus is transmitted through the C-fibers in the skin to the dorsal horn of the spinal cord, and then, via the spinothalamic tract to the cerebral cortex for processing. Many chemicals have been found to be pruritogenic, therefore causing the itch sensation, including histamine, serotonin, cytokines, and opioids. There are six categories of pruritus: dermatologic, systemic, neurogenic, psychogenic, mixed, and other. Various treatment and management options exist depending on the category or cause.¹

Treatment

Treatment of pruritus can be categorized in several ways. A common method of grouping the various options is causative vs. symptomatic treatment. Causative treatment involves finding the underlying disorder and then correcting it, thereby eliminating the itch sensation. Symptomatic treatment involves substituting another sensation for the itch, using methods such as cooling, heating, or counter irritation (e.g., scratching). Symptomatic treatment can be used in addition to treating the underlying disease process in order to provide earlier relief. Most of the available treatment options are categorized under symptomatic therapy and management.

Prescription Medications

Prescription medications include topical and systemic antihistamines, corticosteroids, local anesthetics, and topical immunomodulators, among others. Some lower concentration preparations of these medications are available OTC.

Antihistamines

Itching occurs when histamine is released, causing redness, swelling, warmth, and consequently itchiness. Antihistamines, or H1 antagonists, act by blocking the histamines, and are the most widely used medications for this condition. They take approximately 15–30 minutes to be effective and can be short- or long-acting.²

Topical antihistamines are available in prescription as well as nonprescription forms. Camphor (Caladryl^®, Pfizer) is a common diphenhydramine preparation that has both antipruritic and anesthetic properties. This traditional therapy carries with it a small risk of contact dermatitis and allergic sensitization.³

Corticosteroids

Local Anesthetics

Calcineurin Inhibitors

Cholestyramine

Rifampicin

Naltrexone

Ultraviolet (UV) Light Therapy

UV phototherapy is used to treat various pruritic conditions including chronic renal failure; AD; HIV; aquagenic pruritus; solar, chronic, and idiopathic urticaria; urticaria pigmentosa; polycythemia vera; pruritic folliculitis of pregnancy; breast carcinoma skin infiltration; Hodgkin’s lymphoma; chronic liver disease; and acquired perforating dermatoses, among others. It is often undertaken after multiple attempts to treat stubborn itch, and can offer relief without many of the side-effects and risks of systemic medications. UV-based therapy utilizes UVB and UVA in both broadband and narrowband, as well as PUVA (psoralen UVA). Cost and side-effects can be a prohibitive factor for patients. Erythema is common in UVB, as is premature aging and photocarcinogenesis with both UVA and UVB. Side-effects associated with PUVA include redness, burning, headache, and nausea.^16,19

UVA, UVB, and PUVA light therapies have been especially useful in the treatment of pruritus in HIV patients, as well as in those patients with systemic mastocytosis and cutaneous T-cell lymphoma. It localizes the effect on the superficial nerve endings, sparing the remaining helper cells, and relieving the pruritus. Because of its more superficial penetration, UVB is believed to be safer than UVA. UVB also spares the remaining helper cells in HIV patients and may localize the effect on the superficial nerve endings, thus relieving pruritus. Systemic mastocytosis and cutaneous T-cell lymphoma also respond to UV therapy and because destruction of the proliferating CD4 clone is desirable, UVA is usually the preferred modality over UVB, although Millikan suggests that the relief of pruritus is more predictable with UVB than with UVA.3

Cutaneous Field Stimulation (CFS)

CFS, which electrically stimulates thin afferent fibers, including nocireceptive C-fibers, was reported to inhibit histamine-induced itching. The reduction in itching is accompanied by degeneration of the epidermal nerve fibers. In one open trial, localized itching responded to CFS treatment, and pruritus was reduced by 49% at the end of 5 weeks. Itch relapsed gradually after the discontinuation of CFS, which led the researchers to conclude that nerve fibers regenerated into the epidermis.20

Over-the-Counter Treatments

In addition to the nonprescription medications mentioned above, there are other OTC treatments that can be helpful for treating and managing pruritus. Moisturizing after a bath is extremely important, and emollients such as white petrolatum, or petrolatum depositing moisturizing body washes, and in-shower moisturizers (e.g., Olay^® Ribbons^®, Procter & Gamble; emulsifying ointment USP) can be helpful when applied while the skin is still wet.²¹

There is new evidence to show that moisturizers containing niacinamide and glycerin (e.g., Olay^® Quench^®, Procter & Gamble) not only hydrate the skin, but improve the skin’s resistance to external factors and improve the barrier function. Glycerin is required for moisturizers to work quickly and add moisture to the skin, but the niacinamide helps to sustain that benefit over a longer period of time.²¹

Alternative Therapies

Several alternatives to traditional treatment of pruritus have been proposed. Often these therapies can be used in conjunction with prescribed or OTC medications to relieve symptoms quickly. Compounds that have been found to be effective for pruritus by depressing cutaneous sensory receptors include menthol, camphor, and phenol.⁷ Some other alternative therapies that have been suggested include herbal remedies, nutritional therapy, reflex therapy, and hydrotherapy.³

Herbal Remedies

Several herbs have been proposed as corticosteroid-sparing agents and may provide a viable alternative to topical steroids and their side-effects. Oatmeal baths appear to be most useful because of its colloidal protein and high mucilaginous content. Other herbs have been suggested because of their high mucilage content as well, including flax, fenugreek, English plantain, hearts ease, marshmallow, mulberry, mullein, and slippery elm.3 More extensive research needs to be conducted regarding their possible use and effectiveness for the treatment of pruritus.

Tannins, also derived from herbs, may be helpful as well. The exact mechanism of action is unclear, but may perhaps be related to the coagulation of proteins in the skin. The most common tannin-containing herb is witch hazel, but others include oak bar, English walnut leaf, goldenrod, Labrador tea, lady’s mantel, lavender, and St. John’s wort.

Other possible herbs that may be advantageous include chamomile, which has shown to be equivalent to low concentrations of hydrocortisone, aloe vera, and capsaicin.3 Some side-effects may include irritant or allergic contact dermatitis. Some herbals can be toxic if ingested as well. Some of the oldest group of medications used to soothe and cool pruritic skin is menthol and camphor, which are both considered low risk and safe to use topically. ^3,4

Nutritional Therapy

Nutritional therapy, despite not being sufficiently researched as a monotherapy for pruritus, may be helpful in combination with other anti-itch treatments. Vitamins D and E, and linolenic acid have shown some efficacy in the treatment of psoriasis and atopic eczema.³

Reflex Therapy, Acupuncture, and Hydrotherapy

While they are not traditionally used, reflex therapy, acupuncture, and hydrotherapy are three treatments that may be beneficial as adjunctive therapy, however further research is needed. There is little research available regarding the effectiveness of reflex therapy and hydrotherapy. These options may be considered in difficult-to-treat patients where traditional approaches have been unsuccessful. Acupuncture is based on the gate theory of neurotransmission, however it is infrequently used in the Western world, and therefore has insufficient evidence to fully support its use. ³

Management

The management of symptoms is paramount in the treatment of pruritus. Patients should be educated regarding the self-care aspects of this condition. Eliminating the use of irritating or tight clothing is recommended, as well as maintaining a cool environment. Patients should avoid the frequent use of soap, topical irritants in clothing, dry environments, and vasodilators such as caffeine, alcohol, and hot water. Patients should be advised to take brief, tepid or lukewarm baths using mild cleansers with a low pH. Soap film should be rinsed off completely and skin should be patted lightly, followed by the generous application of a moisturizing lotion or cream.^4,7,22

Conclusion

Pruritus is a common complaint, but one that can often be a challenge to treat. It can be a major quality of life issue for patients, so it is important that both the underlying disease and associated symptoms are treated as quickly and effectively as possible. Health teaching regarding the prevention and management of pruritus should be included in the overall treatment of the cause and symptoms.

P. Lovell, RN, BScN1; R. B. Vender, MD, FRCPC²
1. Michael DeGroote School of Medicine McMaster University
2. Dermatrials Research, Hamilton, ON, Canada

Wart Treatment by Type of Wart

Treatment will depend in part on the location, the age of the patient, as well as the size and immune status of the individual. The treatment choice will depend in part on previous experience of the patient and the patient’s preference. Many of the treatments can be uncomfortable and therefore difficult to use in children.

Treatments can be either destructive as in the use of liquid nitrogen or most recently there is an immunological approach to boost the patient’s own immune system.

Common Warts

Liquid nitrogen cryotherapy is most commonly used in those who can tolerate the pain. Repeat treatments are frequently required. Excising or scraping off these warts is less desirable as it will scar. The use of pulse dye laser or very occasionally the Co2 laser can be used in resistant lesions. Cantharone can be used particularly in children as it is more easily tolerated. Other treatments involve the use of immune therapy. Substances such as DNCB involve painting the substance on the warts in order to develop an allergic reaction. This immune allergic reaction will be useful for destroying the wart.

Flat Warts

Flat warts frequently occur on the face and on the legs. Care needs to be taken not to use a treatment that will have a high risk of scarring. Very light liquid nitrogen cryotherapy can be used.

It is important that shaving is done very carefully or is stopped for a while as this is known to spread these warts. Treatments such as Aldara have been used. Topical treatments such as vitamin A acids (Tretinoin) can sometimes be of benefit. Efudex cream has also been used.

Plantar Warts

Plantar warts can be stubborn. Because of their location aggressive use of liquid nitrogen cryotherapy is difficult in that it can not only be painful but swelling and soreness can prevent walking for a number of days. Often paring the warts by thinning them down can be helpful. The use of salicylic acid preparations that are applied daily and cover the affected area will eat away at the surface of the wart allowing it to be pared down. This may make it more responsive to liquid nitrogen. The use of duct tape to soften the lesions in some individuals can be in itself curative. It appears that changing the water content and making the skin mushy enhances the patient’s ability to eradicate these warts. Treatments such as surgery and scraping of these warts is discouraged as scars can sometimes be painful on the weight-bearing parts of the foot. The pulse dye laser can be used once the wart has been thinned as it does not produce scarring. Occlusion combining these therapies with Aldara cream in some individuals is helpful.

Genital Warts

Genital warts are usually sexually transmitted. It is important that woman be checked to rule out any atypical changes on the cervix. Small warts can be treated with liquid nitrogen although this is uncomfortable. Podophyllin or podophyllotoxin can be applied every few days and this can be helpful.

A Novel Combination for Treatment of Acne Vulgaris

Adapalene 0.1% and Benzoyl Peroxide 2.5%: A Novel Combination for Treatment of Acne Vulgaris

Topical products commonly used to treat acne include retinoids and antimicrobials, due to their effects on different components of pathogenesis. Accordingly, a fixed combination of adapalene 0.1% and benzoyl peroxide (BPO) 2.5% was developed (Epiduo™, Galderma) and was approved by the US FDA in December 2008 for the treatment of acne. The superior efficacy of this combination was demonstrated in 2 large randomized controlled trials. This paper reviews the evidence for efficacy and tolerability of the combination of the retinoid adapalene 0.1% and BPO 2.5%, a once-daily gel formulation for the treatment of acne.

Adapalene, a receptor-selective naphthoic acid derivative with retinoid-like properties, has comedolytic, anticomedogenic, and anti-inflammatory effects. Benzoyl peroxide (BPO) is a highly lipophilic oxidizing agent with bacteriocidal and keratolytic effects. The addition of adapalene with BPO does not result in chemical or photo-instability of the combined product. Retinoids are considered first line therapy for mild comedonal and inflammatory acne.¹ In dermatological practice, topical retinoids are the class of agents most commonly used as topical monotherapy for acne. When 2 topical agents are used, the agents most frequently selected are retinoids and BPO, either alone or with antibiotics.² In view of the primary role of these 2 classes of topical agents, a single formulation comprising both is rational and may increase adherence and improve overall efficacy.

Review of Clinical Studies

Dose-ranging Studies

Individually, topical retinoids and BPO are potentially irritating agents and a combination product may increase this potential. In an irritancy study³ comparing adapalene 0.1% gel, tazarotene cream 0.05%, and tretinoin microsphere gel 0.04% used in combination with 2 different clindamycin/BPO products under occlusion, the adapalene 0.1% gel was reported to be the least irritating. This 3-week randomized, controlled intraindividual study involved test site applications at the back under occlusion. The tolerability of 2 different combination clindamycin/BPO topical products followed 8 hrs later by adapalene 0.1% gel, tazarotene cream 0.05%, and tretinoin microsphere gel 0.04% was evaluated. Regardless of the type of clindamycin/BPO combination, the mean cumulative irritancy index and erythema scores were significantly lower for sites involving adapalene gel. The combination of adapalene 0.1% and BPO 2.5% was selected for further development based on a cutaneous tolerability study⁴ evaluating adapalene 0.1% combined with either BPO 2.5% or 5%. In that study, 60 healthy subjects were randomized into a 3 week split-face trial with daily application of adapalene 0.1% + BPO 2.5%, adapalene 0.1% + BPO 5%, BPO 2.5% or 5%. This study showed that irritation scores (total sum score comprising erythema, dryness, pruritus, and stinging/burning) for adapalene 0.1% + BPO 2.5% were lower than for the combination product containing BPO 5%, and similar to BPO 5% alone.

Randomized-Controlled Trials (See Table 1)

A Phase II/III randomized, double-blind, parallel group study5 of adapalene 0.1% + BPO 2.5% gel, adapalene 0.1% gel, BPO 2.5% gel, or vehicle gel used nightly for 12 weeks involved 517 acne patients enrolled in a 2:2:2:1 ratio, respectively. The combination arm was significantly more effective in achieving a facial acne global grade of clear/almost clear (i.e., 28% vs. 16% vs. 15% vs. 10%, respectively). The differences were significant against the BPO (P=0.003) and vehicle (P=0.02) arms, and borderline for adapalene itself (P=0.08). Significant improvements in the lesion counts were observed for the combination compared with monotherapy and vehicle arms. Total acne lesions were reduced by 51% (median 78 at baseline to 40 at end of study), inflammatory lesions by 63% (27 to 17), and noninflammatory lesions by 51% (44 to 22). Overall local tolerability of the combination was similar to that for adapalene alone, with a somewhat higher percentage of subjects in the combination group having erythema, dryness, and/or stinging/burning. Mean tolerability scores, based on erythema, scaling, dryness, and stinging/burning, peaked at the first week and declined thereafter. Mean symptom scores were mild or less for all treatment arms.

A subsequent larger Phase III double-blind, randomized-controlled trial⁶ (RCT) with similar trial design involving 1668 patients randomized into the same 4 treatment arms in a 1:1:1:1 ratio was performed. Results demonstrated that the combination was more effective in achieving clear/almost clear global scores (30% vs. 20% for adapalene 0.1% gel , 22% for BPO 2.5% gel and 10% for vehicle gel), and in reducing acne counts. Total acne counts were reduced by 56% (median 76 at baseline to 35 at end of study), inflammatory lesions by 62% (27 to 11), and noninflammatory lesions by 54% (44 to 20). A significant reduction in all lesion counts were noted within the first week of treatment compared with vehicle. Local intolerability adverse events were mild-to-moderate in all treatment arms and peaked during the first week. However, more patients in the adapalene + BPO combination group experienced signs and symptoms of local intolerability compared with the other treatment groups. The number of patients with adverse events leading to discontinuation was slightly higher with the combination compared with adapalene monotherapy, BPO monotherapy, and vehicle groups: 11 (2.7%) vs. 4 (1.0%), 5 (1.2%), and 2 (0.5%), respectively. The most frequent treatment-related adverse event was dry skin, which was higher in the combination and adapalene groups than in the BPO monotherapy and vehicle groups (i.e., 6.0%, 4.3%, 1.9%, and 2.2% respectively).

Study	Summary	Epiduo™	Adapalene 0.1% in Vehicle Gel	BPO 2.5% in Vehicle Gel	Vehicle Gel
Thiboutot, et al.5	number of patients	149	148	149	71
	success rate (%)	28	16	15	10
	P-value (vs. Epiduo™)		0.008	0.003	0.002
	total lesions (median % change)	-51	-35*	-36*	-31*
	inflammatory lesions	-63	-46*	-44*	-38*
	noninflammatory lesions	-51	-33*	-36*	-38*
Stein-Gold et al.6	number of patients	415	420	415	418
	success rate (%)	30	20	22	11
	P-value (vs. Epiduo™)		<0.001	0.006	<0.001
	total lesions (median % change)	-56	-47**	-48**	-28**
	inflammatory lesions	-62	-50**	-56**	-34**
	noninflammatory lesions	-54	-49**	-44**	-29**
Pooled outcomes	number of patients	564	568	564	489
	success rate (%)	28	18	19	10
Table 1: Efficacy of Epiduo™ and its components on success rate and lesion reduction in acne (success defined as investigator global scores of clear or almost clear). * P <0.001; ** P < 0.017

Long-term Safety and Efficacy

The long-term tolerability and safety of adapalene 0.1% + BPO 2.5% gel was evaluated in 452 acne subjects over 12 months.⁷ Of these, 327 completed the study (72%). No subjects discontinued due to lack of efficacy, while discontinuation due to adverse events was 2%. Overall, treatment was well tolerated with mean scores for local intolerance (comprising erythema, dryness, scaling, and burning/stinging) reported as mild or less in all study visits. The mean worst scores of subjects were consistent with mild irritation. The highest irritation scores were recorded at the first week and subsequently declined thereafter. The most common adverse event was dry skin (17%). Efficacy, based on the intent to treat population with last observation carried forward, was 65% reduction in total, 70% in inflammatory, and 66% in noninflammatory lesion counts.

Conclusion

The combination of adapalene 0.1% + BPO 2.5% gel in a single formulation is a novel topical agent for the treatment of mild-to-moderate inflammatory acne. The clinical efficacy and tolerability of this fixed dose combination over 12 weeks has been shown in 2 large high quality RCTs. Furthermore, long-term tolerability and ongoing efficacy has been demonstrated in a 12-month study.

J. K. L. Tan, MD, FRCPC
Department of Medicine, University of Western Ontario, London, ON, Canada