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

Treatment of Anogenital Warts

Safety, Efficacy & Recurrence Rates of Imiquimod Cream 5% for Treatment of Anogenital Warts

Imiquimod 5% cream (Aldara™, Graceway Pharmaceuticals) is an immune response modifier used for the topical treatment of anogenital warts in non-HIV-infected patients. Several randomized controlled trials have demonstrated that imiquimod 5% cream is a safe and efficacious treatment. Current data regarding efficacy shows that complete clearance of warts occurred in up to 50% of patients treated with imiquimod 5% cream applied once-daily, 3 times per week for up to 16 weeks. Recurrence rates ranged from up to 19% at 3 months to 23% at 6 months. Imiquimod 5% cream showed an acceptable safety profile; local inflammatory reactions were the most frequent adverse effects, with local erythema being the most common.

Imiquimod is an immune response modifier that was approved by the US FDA in 1997 for the topical treatment of anogenital warts in individuals 12 years old and older. An estimated 30%-50% of sexually active adults in the US are infected with human papillomavirus (HPV), and approximately 1%-2% of this same population have clinically evident genital warts.¹ This review will focus on studies that evaluate the safety, efficacy, and recurrence rates of imiquimod 5% cream in the treatment of anogenital warts in non-HIV-infected men and women. Local inflammatory reactions were the most frequent adverse effects, with local erythema being the most common. Overall, imiquimod 5% cream is a safe and efficacious treatment for anogenital warts.

Using Imiquimod

Imiquimod cream is supplied in individual packets. Each gram of the 5% cream contains 50mg of imiquimod in an off-white oil-in-water vanishing cream base.² The US Center for Disease Control recommends that imiquimod 5% cream be applied once daily at bedtime, 3 times per week for up to 16 weeks. The product should be washed off with mild soap and water 6-10 hours following application.^2-4 Many considerations exist when using imiquimod. Some of these are listed in Box 1. The US FDA provides a full list of considerations.³

Mechanism of Action

Imiquimod is a Toll-like receptor agonist that induces the production of local cytokines from predominantly T helper (Th) 1-type cells, thus stimulating both acquired and cellular immunity, which is important for fighting virus-infected and tumor cells.^5-7 Cytokines such as interferon (INF)-á, tumor necrosis factor (TNF)-á, interleukin (IL)-1, -6, -8, -10, and -12 stimulate tissue-specific apoptosis of virus-infected keratinocytes, thus leading to a viral load reduction of HPV types 6 and 11 with subsequent wart regression and normalization of keratinocyte proliferation.^5,6,8 Regression of warts after treatment with imiquimod is strongly associated with evidence of tissue production of INF-á, -â, and -ã and TNF-á as well as a decrease in the presence of HPV DNA and in the expression of mRNA for both early and late viral proteins.⁹

Points to consider when using imiquimod:

It is common for patients to experience local skin reactions and treatment can be resumed after the skin reaction has subsided. Sexual (genital, anal, oral) contact should be avoided while the cream is on the skin. Imiquimod may weaken condoms and vaginal diaphragms, therefore concurrent use is not recommended. Imiquimod is pregnancy category C and it is not known whether topically applied imiquimod is excreted in breast milk. New warts may develop during therapy, as imiquimod is not considered a cure.

Box 1: Information for patients being treated for external genital warts3

Safety

In all the randomized controlled trials (RCTs) examined, topical imiquimod 5% cream showed an acceptable safety profile. Local skin reactions are associated with a local inflammatory reaction including itching, erythema, burning, irritation, tenderness, ulceration, erosion, and pain.¹⁰ In several studies, local erythema was the most common reaction.^11-13 There were no differences in adverse systemic reactions or flu-like symptoms among treatment groups.^10,12,13 The optimal dosing regimen is 3 times per week. With more frequent applications (up to 3 times daily), wart clearance does not improve significantly and is associated with an increase in local adverse events, such as erythema, vesicle formation, ulceration, and excoriation.¹⁴ Imiquimod 5% cream is effective for up to 16 weeks of treatment for external anogenital warts and is well-tolerated for up to 32 weeks.¹¹ Imiquimod is contraindicated in individuals with a history of sensitivity reactions to any of its components and should be discontinued if hypersensitivity to any of its ingredients is noted. Overall, patient-applied imiquimod 5% cream is an effective treatment for external genital warts and has a favorable safety profile.

Efficacy and Recurrence

Several randomized controlled trials demonstrated that imiquimod 5% cream is an efficacious treatment for external anogenital warts when applied 3 times per week for up to 16 weeks. Complete clearance of warts occurred in up to 50% of patients treated with imiquimod 5% cream applied 3 times daily. At the end of 16 weeks, recurrence rates ranged from up to 19% after 3 months and 23% after 6 months.11 See Table 1 for comparisons. The recurrence rates of external genital warts were found to be similar at both 3- and 6-month follow-up, suggesting that after 3 months, the risk of developing recurrence is low.¹⁵

The studies that follow were chosen to evaluate imiquimod 5% cream for the treatment of anogenital warts because of sufficient data on efficacy, recurrence rates, and safety.^10-13 Studies that did not include this data were excluded. Several other studies focused on the treatment of anogenital or vulvar warts in the female population; however, the efficacy rates are generally higher for this population, ranging from 71%-77%.^12,16-18 To maintain continuity, this review focuses on comparing studies that include treatment of anogenital warts with imiquimod 5% cream in non-HIV-infected men and women.

Detailed Findings of This Study Can be Found Indexed by the US National Library of Medicine and PubMed

Monotherapy Compared with Combination Therapy: Imiquimod + Surgery

Carrasco et al.¹⁹ showed that treatment with imiquimod 5% cream followed by excision of remaining warts resulted in a lower recurrence rate compared with surgery alone. This strategy represents a viable option for those with residual lesions and may provide long-term clearance of anogenital warts in patients for whom imiquimod monotherapy is insufficient.¹⁹

Conclusion

Patient-applied imiquimod 5% cream is a first-line topical treatment for anogenital warts that is both safe and efficacious, and yields complete and partial responses in the majority of patients. Various studies demonstrate complete clearance rates of up to 50% and partial responses manifest as a 50%-90% reduction in baseline wart area.^12-14 Recurrence rates range up to 19% at 3 months and 23% at 6 months. More studies are needed to compare the efficacy of combination therapies vs. monotherapy vs. other treatment modalities. Longer follow-up is also needed to evaluate recurrence rates after monotherapy, as well as in combination with other treatments for anogenital warts.

M.L. Diamantis, BS¹; B.L. Bartlett, MD²; S.K. Tyring, MD, PhD³

1. The University of Texas Medical School at Houston, Houston, TX
2. Center for Clinical Studies, Houston, TX
3. The University of Texas Health Science Center at Houston and Center for Clinical Studies, Houston, TX

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

Identifying Skin Lesions - Warts, Moles and SebKs

By Van Le |  While freckles can add to a person’s beauty and uniqueness, other skin lesions such as large moles, skin tags, warts, and seborrheic keratoses can be unsightly and embarrassing. Most lesions are malignant (non-cancerous), however, it is important to be aware of and track any skin abnormalities on your body as a preventative measure.

Freckles

Freckles are irritating for some and embraced by others. They are pigment cells that retain within the skin to form light brown spots, and individuals with lighter complexions are more susceptible to freckles since their skin contains less melanin. Freckles, also known as ephelides, can appear on the face, arms and other sun-exposed areas. Excessive and continued exposure to harmful UV rays can cause more freckles and cause them to appear darker. While they are harmless, it is important to distinguish between freckles and symptoms of melanoma, a type of skin cancer that can grow from an existing freckle. Consult your doctor if you notice any change in freckle size, shape and color.

Skin tags

Skin tags are pieces of skin that hang from the surface of a surrounding area. Like freckles, they are benign, but can cause irritation if located on an area that is exposed to constant contact, such as the eyelids or areas where they can be snagged by jewelry or clothing. Skin tags can vary from a small pin-point size to a large grape size. While some can fall off on their own, there are several ways to medically remove skin tags, including freezing and burning. There are home remedies as well as creams available on the market to remove unwanted and embarrassing skin tags.

Seborrheic keratoses

Seborrheic keratoses, another benign skin lesion, can form anywhere on the body, but is commonly found on the chest and back. They can be distinguished from other types of lesions due to their waxy, stuck-on-the-skin appearance and often described as brown candle wax stuck on the skin. While the cause is still unknown, scientists have found that they can be hereditary and not affected by sun exposure.

Warts

Most warts are skin infections caused by viruses of the human papillomavirus (HPV) family. Basically, warts are benign tumors of the epidermis (outer layer of skin), and can occur in people of all ages, but are most commonly found on children and teenagers. There are different types, including flat and plantar warts. Flat warts are small in size but can be high in quantity, can spread to other areas of the body by shaving or scratching, and can be transferred person-to-person by physical contact. Plantar warts grow on the heel, ball or sole of the foot, and pressure from standing or walking pushes them into the deeper layers of skin.

Skin lesions like warts, seborrheic keratoses and skin tags are often harmless, but they can be embarrassing. While they can be surgically removed, there are creams and ointments available on the market to remove and reduce their appearance. If you have further questions about a particular skin lesion, consult your doctor or pharmacist for proper diagnosis and treatment.

Van Le is a staff writer for the CSU Daily Titan and writing intern for Vivoderm Laboratories in Los Angeles, California. She is currently pursuing a Journalism degree at California State University, Fullerton.

For the latest findings on skin lesions and treatments, you can also link to http://www.dermatosispapulosanigra.net

Skin Tags and Thyroid Nodules Connected?

According to recent findings published on PubMed, a service of the U.S. National Library of Medicine and the National Institutes of Health, high prevalence of thyroid nodules have been found in patients with achrocordons (skin tags) and can indicate a possible role of insulin-resistance.

Excerpts from various published articles and comments follow below. From the Centro Privado de Endocrinología, Mendoza:

“Due to the observation of a great number of patients having achrocordons, when they underwent fine needle biopsies for thyroid nodules, we decided to perform a prospective study to investigate the relationship between this finding and the presence of insulin resistance (IR), since achrocordons are commonly seen in hyperinsulinemic subjects.

A total of 120 consecutive women, aged 18-35 yrs were studied. All subjects were also evaluated by thyroid ultrasound (US) for measuring thyroid volume and the presence of non-palpable nodules. Basal and post-prandial serum insulin was measured in all of them, as well as the Homeostasis Model Assessment (HOMA).

Subjects were divided in two groups: Group A, with achrocordons (n = 44) and Group B, without achrocordons (n = 76). Group A showed 24 patients (54.5%) with thyroid nodules, whereas Group B only 13 subjects (17.1%); p = 0.0087. When we considered, as having high normal thyroid volume, the glands weighting more than 16 grams by US, without nodules, it was found that 8/44 cases from Group A (18.6%) and 3/76 from Group B (3.9%) fitted in such category, p = 0.0076.

In patients with nodules and/or bigger thyroids, IR was observed in 36/44 (81.8%) of Group A and 14/76 (18.4%) of Group B, p = 0.0069, while the overall prevalence of IR was 0.47 in Group A and 0.05 in Group B, p = 0.00094. It is concluded that patients with achrocordons have a higher prevalence of US-detected thyroid nodules and larger thyroid glands. Then, it may be beneficial to search for thyroid abnormalities in those subjects with skin tags.”

A question followed from the Dermatology Department, Shiraz University of Medical Science, Shiraz, Iran.

“Is there any relation between serum insulin and insulin-like growth factor-I in non-diabetic patients with skin tag?”

Answer: Jowkar F, Fallahi A, Namazi MR.

Abstract Background Skin tags are common benign lesion occurring mainly on the neck and major flexures as a small soft pedunculated protrusion. This study evaluate insulin and insulin-like growth factor-I (IGF-I) in non-diabetic ones. Methods and materials A case-control study was conducted in non-diabetic persons. Comparing insulin and IGF-I between matched cases (n= 40) and controls (n= 40) by radioimmunoassay test.

Cases and controls were recruited from patients consecutively seen at an academic outpatient dermatology clinic. Results The insulin level in patients with skin tags was significantly higher than controls (P = 0.00) but IGF-I level was not significantly different (P = 0.43). Conclusion These results show an increased insulin level in non-diabetics ones and overall importance of insulin effect in pathogenesis of skin tags.

Conflicts of interest None declared.

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

Taking Elidel Top To Treat Atopic Dermatitis

PIMECROLIMUS - TOPICAL : Pronunciation: (pim-eck-row-LEE-muss) , Brand Name(s): Elidel

Elidel Top is used to treat the following:  Atopic Dermatitis, Eczema Skin Condition Resisting Treatment

Pimecrolimus is used to treat certain skin conditions such as eczema (atopic dermatitis) in people who should not use or have not responded to other eczema medications (e.g., topical steroids). Eczema is an allergic-type condition that causes red, irritated, and itchy skin. This drug works by changing the skin’s defense (immune) system, thereby decreasing the allergic reaction that causes eczema. Pimecrolimus belongs to a class of drugs known as topical calcineurin inhibitors (TCIs).

This medication is not recommended if you have a history of a certain rare genetic disorder (Netherton’s syndrome). Also, this medication should not be used by anyone who has a weakened immune system (e.g., following an organ transplant).

How to use Elidel Top

Read the Medication Guide provided by your pharmacist before you start using pimecrolimus and each time you get a refill. If you have any questions regarding the information, consult your doctor or pharmacist.

Wash your hands with soap and water before using this medication. Apply a thin layer to the affected areas of skin, usually twice daily or as directed by your doctor. Rub the medication into the skin gently and completely. Wash your hands after using this product unless your hands are being treated. If your doctor recommends a moisturizer, apply it after this medication.

Pimecrolimus is for use on the skin only. Avoid getting this medication in your eyes or on the inside of your nose or mouth. Do not apply this medication to open wounds or infected areas. Do not cover the treated area with plastic or waterproof bandages unless directed to do so by your doctor. Do not bathe, shower or swim right after applying this medication.

Use this medication exactly as directed. Your doctor may instruct you to stop using it once your eczema has cleared up and to start using it again if signs or symptoms reappear. Consult your doctor for details.

Inform your doctor if your condition does not improve after 6 weeks of using this medication or if your condition worsens at any time.

WARNINGS

Patients have benefited from use of pimecrolimus when it is used correctly. Long-term safety for this drug is not known at this time. There have been rare reports of cancers (e.g., skin cancer, lymphoma) in patients using pimecrolimus. It is not known whether pimecrolimus caused these cancers when used on the skin. Further studies to determine the long-term safety of this product are ongoing. In the unlikely event that unusual lumps, swollen glands, or growths (especially on the skin) occur, contact your doctor immediately.

The FDA recommends the following: This drug should be used only if other drugs have failed or if other medications are not considered appropriate by your doctor. Pimecrolimus should be used on the skin for short treatment periods only. If needed, treatment may be repeated with breaks in between. Use the smallest amount that will treat your condition properly, and apply only on the affected skin. Also, this medication should not be used in children younger than 2 years. As with all medications, discuss the risks, benefits, and proper use of this medication with your doctor.

Milia and Keratin Cysts

Milia are very common, benign, keratin-filled cysts. Primary milia are typically seen in infants but also may occur in children and adults. Secondary milia are observed in a number of blistering disorders and following dermabrasion. Milia en plaque and multiple eruptive milia are distinct entities.

The eMedicine Pediatrics article Milia may be of interest, as may the Medscape Dermatologic Surgery Resource Center.

Pathophysiology: Milia are tiny epidermoid cysts. The cysts may be derived from the pilosebaceous follicle. Primary milia arise on facial skin bearing vellus hair follicles.  Secondary milia result from damage to the pilosebaceous unit.

Frequency in the United States:
Primary milia in newborns are so common that they can be considered normal (occurring in approximately half of all infants). Multiple eruptive milia and milia en plaque are rare entities.

Race : No racial predilection is recognized.
Sex : Sexual prevalence is equal for primary and secondary milia. Eruptive milia and milia en plaque occur more frequently in women.
Age : Milia occur in persons of all ages but are typically found in infants.

Clinical History
Milia are asymptomatic. In children and adults, they usually arise around the eye. Eruptive milia, as the name suggests, have a rapid onset, often within a few weeks.

Physical
* Skin lesions
o Milia are superficial, uniform, pearly white to yellowish, domed lesions measuring 1-2 mm in diameter.
o In milia en plaque, multiple milia arise on an erythematous plaque.
* Skin distribution
o Primary milia, in term infants, occur on the face, especially the nose. They also may be found on the mucosa (Epstein pearls) and palate (Bohn nodules).
o Primary milia in older children and adults develop on the face, particularly around the eyes.
o Milia have been observed to occur in a transverse, linear distribution along the nasal groove in some children.
o Secondary milia are found anywhere on the body at the sites affected by the predisposing condition.
o Eruptive milia occur on the head, neck, and upper body.
o Milia en plaque manifests as distinct plaques on the head and neck. Plaques have been described in the postauricular area, unilaterally or bilaterally, the cheeks, the submandibular plaques, and on the pinna.

Causes
* Primary milia are believed to arise in sebaceous glands that are not fully developed, explaining the high prevalence in newborn infants.
* Secondary lesions arise following blistering or trauma due to disruption of the sweat ducts. Milia have been described in association with many disorders, including bullous pemphigoid, inherited and acquired epidermolysis bullosa, bullous lichen planus, porphyria cutanea tarda, and burns. Skin trauma from dermabrasion or radiotherapy can result in milia formation.
* Secondary milia have arisen from a bullous contact dermatitis and a photocontact allergy to sunscreen.

They have also arisen following treatment of cutaneous leishmaniasis and after topical nitrogen mustard ointment for plaque stage mycosis fungoides.
* Secondary milia have been described following potent topical corticosteroid use.
* Milia are a feature of a number of very rare genodermatoses (eg, Bazex-Dupré -Christol syndrome).  Both primary milia and multiple eruptive milia have been reported as familial disorders with autosomal dominant inheritance.
* The etiology of milia en plaque is unknown.

Medical Care
No topical or systemic medications are effective on primary and secondary milia. Single case reports have demonstrated the success of topical isotretinoin, oral etretinate and minocycline in treating patients with milia en plaque.

Surgical Care
Milia can be safely left alone, but if the patient requests treatment, then incision with a cutting-edge needle and manual expression of the contents are effective. This can be performed without local anesthetic. A paper clip has been successfully used to express the contents of the cyst. Milia en plaque has been treated effectively with electrodesiccation, carbon dioxide laser, dermabrasion, and cryosurgery.

« Previous Page — Next Page »