Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA

Background

For many years, clinicians have expressed ongoing concerns about treatment adherence by patients, especially pertaining
to those with chronic skin disorders. Although crucial to effective therapeutic outcomes, the issue of patient adherence has
been largely ignored in dermatologic disease management until recently. Two types of nonadherence have been defined:

• Unintentional nonadherence, i.e., a patient’s intention to use medication is defeated by barriers, such as forgetfulness.
• Deliberate nonadherence, i.e., a patient arrives at a decision (usually planned) not to use the treatment as directed.¹
• More common in chronic diseases, such as psoriasis, when the treatment regimen interferes with daily routines.

Studies have demonstrated that up to 40% of patients with psoriasis do not comply with the recommended treatment
regimen. Moreover, experts have suggested that many psoriatic patients do not seek help because they believe that no
suitable treatment exists for their condition.1 Furthermore, in a study by Krueger, et al., more than half of the psoriasis
patients who were surveyed were unhappy with their treatment.²

Contributing Factors

Although numerous variables affecting patient adherence
have been identified, some important factors that engender
nonadherence include:

• sociodemographic factors such as gender, marital status and employment status.
• treatment-related factors, i.e.,
  • the type of treatment, i.e., systemic, light, or topical:
    • A survey of psoriasis patients reported a greater preference for systemic treatments over topical or light therapies.³
    • In a later study, patients using topical therapy were more compliant than those on systemic or phototherapy, despite having less favorable perceptions of the medical care received and treatment outcomes.⁴
    • In another study, patients receiving topical treatments adhered to their therapy in 51% of cases due to the frequency of application and in 71% of cases because of the duration of treatment.⁵
  • the duration of the treatment:
    • Adherence with a treatment decreases if the duration of a treatment is long.⁶
  • the time point, e.g., starting a new treatment
  • the delivery mechanism, i.e., cream, ointment, foam, gel
  • the frequency of the treatment:
    • Treatment adherence rates for a once daily regimen were significantly higher than twice daily dosing (82% vs. 44%, respectively).⁷
    • Once daily treatments include fluticasone propionate or betamethasone dipropionate plus calcipotriol.
  • the side-effects:
    • Adherence is significantly higher for treatment regimens without adverse-effects.⁷
  • the time taken to use treatments
  • disease distribution factors, e.g., age of onset, severity.
  • the patient’s perceptions of the care provided, i.e.,
    • satisfaction with the consultation
    • opinion about the clinician’s interpersonal skills
    • optimism about the treatment process
    • knowledge about psoriasis and the adopted therapeutic approach
    • beliefs about the safety of their treatment, which may conflict with the clinician’s views.
    • recognition that the patient’s active participation is essential to treatment success.

Adherence has also been reported to be higher for patients who are being treated for the first time7 and for those who are
facing a shorter treatment duration.^8,9 It appears that initiating a new therapy may present a unique opportunity to establish
an effective working relationship and improve patient adherence.

Strategies for Improvement

A number of strategies have been suggested to address the issue of nonadherence:

• Simplify the regimen, i.e., minimize the number of medications and frequency of use.
• Devote time to patient education. Patients armed with adequate and accurate information will enable them to understand the objectives of the therapy and the impact of nonadherence.
• Ensure that patients understand both written and verbal instructions for using the medications.
• Provide clarity regarding patients’ concerns on the safety and efficacy of long-term therapy.
• Encourage behavioral methods, such as reminders and environmental cues (e.g., apply immediately after showering).

Topical Therapies

Conclusion

Maintaining a partnership with patients should involve³:

• a continuous assessment of their quality of life.
• a continuous assessment of their implicit standards of regimen acceptability.
• a move toward a more collaborative model of self-management behavior.

Planning the treatment together with the patient, and allowing him or her to play a central role in its establishment, will likely
foster treatment adherence.

References

1. Richards HL, et al. J Eur Acad Dermatol Venereol 20(4):370-9 (2006 Apr).
2. Krueger G, et al. Arch Dermatol 137(3):280-4 (2001 Mar).
3. Richards HL, et al. J Am Acad Dermatol 41(4):581-3 (1999 Oct).
4. Richards HL, et al. Br J Dermatol 147(5):1070 (2002 Nov).
5. Fogh K, et al. Vitamin D3 analogues. In: van de Kerkhof PCM, ed. The Management of Psoriasis: Clinics in Dermatology. New York: Elsevier. 15:705-14 (1997).
6. Rosenstock IM. Diabetes Care 8(6):610-6 (1985 Nov-Dec).
7. Zaghloul SS, et al. Arch Dermatol 140(4):408-14 (2004 Apr).
8. van de Kerkhof PC, et al. Dermatology 200(4):292-8 (2000).
9. Bell RA, et al. J Gen Intern Med 17(11):817-24 (2002 Nov).
10. Toole JWP, Skin Therapy Lett 12(4):1-3 (2007 May).
11. Kircik L, et al. Skin Therapy Lett FP 3(3):4-5 (2007 Aug).

Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA

ABSTRACT

Hand and foot psoriasis is a chronic and debilitating disease that manifests as plaque-type or pustular-type lesions. Although the palms and soles represent only 2% of the total body surface area, psoriasis of these regions may lead to physical dysfunctions that can greatly impair dexterity, mobility, and the quality of life of affected individuals. Deregulation of T-lymphocyte-mediated immune response is important in the pathophysiology of psoriasis. Efalizumab (Raptiva®, Genentech) is an anti-CD11a monoclonal antibody that disrupts the interaction between T cells and antigen-presenting cells, thereby inhibiting various T-cell-mediated immune processes that include activation and trafficking. Recent evidence indicates that efalizumab may be beneficial for patients with hand and foot psoriasis.

Key Words:
Hand and foot, psoriasis, efalizumab, monoclonal antibody

Pathophysiology and Prevalence

Psoriasis is a chronic, inflammatory, autoimmune skin disease that affects approximately 2% of the US population. The cutaneous lesions characteristic of psoriasis can cause physical, psychological, and social dysfunctions in affected individuals.1 The pathophysiology of psoriasis consists of an abnormal immune response. T cells in the dermis and epidermis are overactivated, which triggers the release of proinflammatory cytokines and hyperproliferation of keratinocytes. This, in turn, manifests as the skin lesions that are the hallmark of psoriasis.

Hand and Foot Psoriasis

For hand and foot psoriasis, lesions may occur on:

• the palms of the hands
• the soles of the feet
• the dorsal surface of the hands and feet.

In addition to exhibiting plaque-type lesions, this variant of psoriasis can also include fissuring, crusting, erythema, and recurrent painful pustules. Hand and foot psoriasis occurs in approximately one-third of the psoriatic population, and interestingly, many patients with this disease do not have psoriasis on other parts of their body. The biological basis for the differences in affected body area is not known.^2,3

Hand and foot psoriasis may make routine tasks, such as writing, hand shaking, and walking very difficult for affected individuals. Not only can this profoundly affect their quality of life, it can also greatly affect their family members and caregivers. To better understand these impacts, investigators conducted a survey of patients with and without hand and foot involvement to compare disease severity.² The results indicated that patients with hand and foot psoriasis reported significantly greater functional disability and physical discomfort, such as burning and soreness, as compared with those who did not have hand and foot involvement.

Interestingly, the survey revealed that the added disabilities were related to physical activities in general and not to social issues, which dispels the assumption that psoriasis on the hands and feet can lead to greater psychosocial dysfunction than psoriasis on other parts of the body. Furthermore, the survey found that for patients who experienced associated pain and discomfort from hand and foot psoriasis, complete clearing of the lesions was not as important to them as pain reduction.

Limitations of Conventional Treatment

Hand and foot psoriasis is often refractory to treatment, and the lack of effective therapeutic options creates an unmet medical need. (See Table 1 for a summary of treatment modalities.) Topical therapies elicit insufficient response rates, in part because it is more
difficult for drugs to penetrate the thicker skin of the palms and soles, as compared with skin absorption on other regions of the body. The biological basis for the difficulty in treating with conventional systemic agents remains unclear. At present, a combination of topical psoralen photochemotherapy and systemic retinoids is frequently used. Other treatment options include cyclosporine and methotrexate; each has proven to be beneficial for some patients. However, several of these systemic treatments must be administered at high doses in order to be effective for the hands and feet. This can lead to significant side-effects, such as a higher risk of skin cancer, infections, teratogenicity, and hyperlipidemia.^4-6

Efalizumab

Efalizumab is a recombinant, humanized anti-CD11a monoclonal IgG1 antibody that has been approved for the treatment of moderate-to-severe chronic plaque psoriasis in adult patients.⁷ The biological basis for the therapeutic benefits of efalizumab is its inhibition of T-cell-mediated immune responses. Efalizumab targets the T-cell adhesion molecule, leukocyte functionassociated antigen 1 (LFA-1), which is present on the surface of T cells and is made up of a heterodimer of CD11a and CD18 proteins. Interaction between LFA-1 and intracellular adhesion molecule 1 (ICAM-1), a cell surface protein of the antigen-presenting cell (APC), serves as the predominant adhesion interface between T cells and their APCs. LFA-1/ICAM-1 interaction is critical for T-cell activation and trafficking. By binding to the CD11a subunit of LFA-1 with high affinity and specificity, efalizumab prevents CD11a interaction with ICAM-1, thereby inhibiting the initiation of an immune response and the release of inflammatory cytokines involved in keratinocyte proliferation and the development of psoriatic lesions.²¹

Efalizumab for the Treatment of Moderate-to-Severe
Plaque Psoriasis

The safety and efficacy of efalizumab for the treatment of moderate-to-severe plaque psoriasis have been well documented in multiple, phase III, randomized, placebocontrolled, multicenter studies.^22-25 In these studies, 27%-33% of efalizumab-treated patients achieved 75% improvement on the Psoriasis Area and Severity Index (PASI-75) after 12 weeks of treatment. Furthermore, after 24 weeks of continuous efalizumab treatment, 44% of treated patients achieved PASI-75.^24,26 Leonardi, et al. found that response can be maintained with long-term treatment, i.e., 45% of patients achieved PASI-75 after 144 weeks of continuous efalizumab treatment.²⁷

Efalizumab for the Treatment of Hand and Foot
Psoriasis

A recently published case report series suggested benefits for efalizumab in the treatment of patients with hand and foot psoriasis.⁴ The report presents cases of 17 patients: four men and 13 women with plaque-type (n=11) or pustular-type (n=5) hand and foot psoriasis, and one patient with both plaque- and pustular-type. The age range of the patients was 29-33 years and the range of their disease duration was 3-30 years. Hand and foot psoriasis in these patients was refractory to various treatments, including topicals, methotrexate, cyclosporine, prednisone, acitretin, psoralen UVA phototherapy, and the tumor necrosis factor inhibitor etanercept. Each of these patients received subcutaneous injections of efalizumab (1mg/kg/wk), and the treatment outcome was measured by PASI, the Physician’s Global Assessment (PGA), or the affected body surface area. With efalizumab treatment, the patients achieved 50%-100% clearance of their hand and foot psoriasis as early as 2 weeks following the start of treatment. For two of the patients, it took approximately 1 year to achieve 85% and 100% clearance of their disease. One patient had additional psoriasis in the fingernails and toenails with pitting and onycholysis, which also cleared with efalizumab treatment. Efalizumab was generally well tolerated by all of the patients in this case series, with one occurrence each of hemolytic anemia and mild myalgia; three patients developed mild flu-like symptoms, which were determined to be reversible drug-related adverse events.

A 12-week, phase IV, randomized, double-blind, placebo-controlled study was recently completed to assess the efficacy and safety of efalizumab in 75 enrolled patients with chronic moderate-to-severe hand and foot psoriasis. The study population included patients with or without pustules, and with or without psoriasis at locations other than the hands and feet, who had a PGA rating of moderate (3) or severe (4) for hand and/or foot psoriasis and no previous exposure to the study drug. Patients were administered efalizumab 1mg/kg/wk (n=52) or placebo (n=28). In a preliminary report of the data collected, 46.2% of efalizumab-treated patients achieved a PGA rating of clear (0), almost clear (1) or mild (2) after 12 weeks of treatment versus 17.9% of placebo-treated patients.^12,28 The incidence of adverse events in patients treated with efalizumab was similar to those treated with placebo, which was consistent with the safety profile observed in previous phase III studies.

Conclusion

Physicians and caregivers may sometimes underestimate the impact of hand and foot psoriasis on affected individuals; simple routine and important functions can become physically and psychosocially challenging for these patients. Efforts to find effective long-term therapeutic options with favorable safety profiles remain an elusive achievement. As a prerequisite to fulfilling this unmet medical need, basic research must be conducted to gain a thorough understanding of the pathophysiology of hand and foot psoriasis and to further determine whether there are distinct disease pathways that lead to the plaque versus pustular forms of this disease. To date, the options available for treatment have been limited by inadequate response to therapy and/or toxicity related to increased dosage and long-term use. As noted above, recently published case studies and preliminary results from a phase IV study have shown potential benefits of efalizumab in the treatment of hand and foot psoriasis. It would be of great interest to evaluate the effects of efalizumab in the long-term treatment of hand and foot psoriasis.

^References

1. Fortune DG, Main CJ, O’Sullivan TM, et al. Quality of life in patients with psoriasis: the contribution of clinical variables and psoriasis-specific stress. Br J Dermatol 137(5):755-60 (1997 Nov).
2. Pettey AA, Balkrishnan R, Rapp SR, et al. Patients with palmoplantar psoriasis have more physical disability and discomfort than patients with other forms of psoriasis: implications for clinical practice. J Am Acad Dermatol 49(2):271-5 (2003 Aug).
3. Enfors W, Molin L. Pustulosis palmaris et plantaris. A follow-up study of a ten-year material. Acta Derm Venereol 51(4):289-94 (1971).
4. Fretzin S, Crowley J, Jones L, et al. Successful treatment of hand and foot psoriasis with efalizumab therapy. J Drugs Dermatol 5(9):838-46 (2006 Oct).
5. Marsland AM, Griffiths CE. Treatments for chronic palmoplantar pustular psoriasis. Skin Therapy Lett 6(12):3-5 (2001 Nov).
6. Marsland AM, Chalmers RJ, Hollis S, et al. Interventions for chronic palmoplantar pustulosis. Cochrane Database Syst Rev (1):CD001433 (2006).
7. Raptiva® [efalizumab] (package insert). South San Francisco, Calif: Genentech, Inc. (2005 Jun).
8. Lassus A, Geiger JM. Acitretin and etretinate in the treatment of palmoplantar pustulosis: a double-blind comparative trial. Br J Dermatol 119(6):755-9 (1988 Dec).
9. Myers W, Christiansen L, Gottlieb AB. Treatment of palmoplantar psoriasis with intramuscular alefacept. J Am Acad Dermatol 53(2 Suppl 1):S127-9 (2005 Aug).
10. Prossick TA, Belsito DV. Alefacept in the treatment of recalcitrant palmoplantar and erythrodermic psoriasis. Cutis 78(3):178-80 (2006 Sep).
11. Erkko P, Granlund H, Remitz A, et al. Doubleblind placebo-controlled study of long-term lowdose cyclosporin in the treatment of palmoplantar pustulosis. Br J Dermatol 139(6):997-1004 (1998 Dec).
12. Leonardi CL, Sobell JM, Sofen H, et al. Phase IV study to evaluate the safety and efficacy of efalizumab for treatment of hand and foot psoriasis. J Am Acad Dermatol 56(2):AB48 (2007 Feb).
13. Weinberg JM. Successful treatment of recalcitrant palmoplantar psoriasis with etanercept. Cutis 72(5):396-8 (2003 Nov).
14. Mihara M, Hagari Y, Morimura T, et al. Itraconazole as a new treatment for pustulosis palmaris et plantaris. Arch Dermatol 134(5):639-40 (1998 May).
15. Bhushan M, Burden AD, McElhone K, et al. Oral liarozole in the treatment of palmoplantar pustular psoriasis: a randomized, double-blind, placebo controlled study. Br J Dermatol 145(4):546-53 (2001 Oct).
16. Duweb GA, Abuzariba O, Rahim M, et al. Occlusive versus nonocclusive calcipotriol ointment treatment for palmoplantar psoriasis. Int J Tissue React 23(2):59-62 (2001).
17. Kragballe K, Larsen FG. A hydrocolloid occlusive dressing plus triamcinolone acetonide cream is superior to clobetasol cream in palmo-plantar pustulosis. Acta Derm Venereol 71(6):540-2 (1991).
18. Kumar B, Sandhu K, Kaur I. Topical 0.25% methotrexate gel in a hydrogel base for palmoplantar psoriasis. J Dermatol 31(10):798-801 (2004 Oct).
19. Kumar B, Kumar R, Kaur I. Coal tar therapy in palmoplantar psoriasis: old wine in an old bottle? Int J Dermatol 36(4):309-12 (1997 Apr).
20. De Rie MA, Van Eendenburg JP, Versnick AC, et al. A new psoralen-containing gel for topical PUVA therapy: development and treatment results in patients with palmoplantar and plaquetype psoriasis, and hyperkeratotic eczema. Br J Dermatol 132(6):964-9 (1995 Jun).
21. Werther WA, Gonzalez TN, O’Connor SJ, et al. Humanization of an anti-lymphocyte functionassociated antigen (LFA)-1 monoclonal antibody and re-engineering of the humanized antibody for binding to rhesus LFA-1. J Immunol 157(11):4986-95 (1996 Dec).
22. Lebwohl M, Tyring SK, Hamilton TK, et al. A novel targeted T-cell modulator, efalizumab, for plaque psoriasis. N Engl J Med 349(21):2004-13 (2003 Nov).
23. Gordon KB, Papp KA, Hamilton TK, et al. Efalizumab for patients with moderate to severe plaque psoriasis: a randomized controlled trial. JAMA 290(23):3073-80 (2003 Dec).
24. Menter A, Gordon K, Carey W, et al. Efficacy and safety observed during 24 weeks of efalizumab therapy in patients with moderate to severe plaque psoriasis. Arch Dermatol 141(1):31-8 (2005 Jan).
25. Leonardi CL, Papp KA, Gordon KB, et al. Extended efalizumab therapy improves chronic plaque psoriasis: results from a randomized phase III trial. J Am Acad Dermatol 52(3 Pt 1):425-33 (2005 Mar).
26. Gottlieb AB, Hamilton T, Caro I, et al. Longterm continuous efalizumab therapy in patients with moderate to severe chronic plaque psoriasis: updated results from an ongoing trial. J Am Acad Dermatol 54(4 Suppl 1):S154-63 (2006 Apr).
27. Leonardi C, Menter A, Hamilton T, et al. Efalizumab: results of a 3 year continuous dosing study for the long-term control of psoriasis. Br J Dermatol, submitted June 2007.
28. Genentech. Genentech announces positive results from a phase IV study of Raptiva in patients with moderate-to-severe hand and foot psoriasis [press release]. February 2, 2007. http://www.gene.com/gene/news/press-releases/display.do?method=detail&id=10447, last accessed August 13, 2007.

1. Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA
2. Division of Dermatology, University of Western Ontario, London, ON, Canada
3. Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada

Background

The number of patients with psoriasis is increasing, while the number of medical dermatologists is shrinking. There are more than 1 million psoriasis patients in Canada, with 620,000 visits to a health care professional in 2006 for treatment of this condition. Approximately 35% of these visits were with dermatologists; the remainder was handled primarily by family practitioners.

Disease Severity

There are a wide range of definitions of disease severity for psoriasis. In light of the various measures that are currently available, patients can be separated into two categories: those treated with local (topical) therapy and those treated with systemic therapy. This article will deal with topical therapy.

Topical Treatment Options and the Treatment Triangle

Topical medications, either as monotherapy or in combination, are the most commonly prescribed treatments by both dermatologists and family practitioners. The treatment triangle brings together evidence-based medicine, patient preference, and the physician’s expertise in order to determine the most appropriate treatment approach. Given the increasingly limited access to dermatologists, adequate education on all available treatment options must be provided to family practitioners in order for them to adequately manage the psoriatic population in Canada.

Commonly Used Topical Antipsoriatic Therapies

• Emollients/ Keratolytics
• Topical Steroids
• Tars
• Anthralin
• Tazarotene
• Calcipotriol
• Calcipotriol + Betamethasone Dipropionate
• Calcineurin inhibitors

Emollients

The use of emollients improves the skin barrier function by restoring hydration and forming a protective layer that guards against infection and other irritants. Additional benefits include:

• improvement of itching
• removal of superficial scales, resulting in a smoother appearance to the skin
• improvement of penetration of other topical medications.

Topical Corticosteroids

Corticosteroids are potent compounds widely used for their
anti-inflammatory, immunosuppressive and antiproliferative
effects.

• Efficacy and safety have been confirmed when used as monotherapy in short-term courses and when given intermittently for more lengthy periods.
• Studies have shown improved efficacy when applied in the late afternoon or evening.

Tar

Tar slows the proliferation of skin cells and reduces inflammation, itching and scaling. While tar compounds are very effective for treating scalp psoriasis, they have several limitations:

• They are odiferous.
• They can irritate and stain.
• They can cause folliculitis.
• There is concern that they may be carcinogenic.

Anthralin

Anthralin reduces the rapid acceleration of skin growth, as seen in psoriasis.

• An effective treatment for mild-to-moderate disease, however, patients are slow to respond.
• Skin irritation and staining are common side-effects.
• Its availability is limited and is rarely used by outpatients.

Tazarotene

• It is a retinoid with the ability to mediate skin cell proliferation and differentiation
• It is mostly used in non-psoriasis indications
• It may cause irritation to psoriatic lesions
• Its effects can be enhanced when used in combination with topical corticosteroids, calcipotriol and phototherapy.

Calcipotriol

• A vitamin D analogue that acts to modulate both epidermal proliferation and differentiation.
• Twice daily application has been shown to be more effective than tar, short contact anthralin, and some corticosteroids.

Compounding

Use of calcipotriol in combination with steroids enhances efficacy. However, compounding should be used with caution. Ad hoc mixtures of calcipotriol plus steroids (including betamethasone dipropionate and betamethasone valerate) have been shown to be unstable. The valerate steroid activity disappeared within 24 hours, while the dipropionate steroid activity was more than one-third depleted after only 4 weeks.

Calcipotriol plus Betamethasone Dipropionate

• Available as a stable commercial preparation.
• Phase III trials involving more than 6,000 psoriasis patients have demonstrated clear or almost clear responses in 50% of those treated after 4 weeks of therapy.
• Reduction in Psoriasis Area and Severity Index (PASI) score was consistent throughout the study population: approximately 40% after 1 week and 70% after 4 weeks. The PASI is a visual rating system that is determined by assessing the amount of body surface area affected by psoriasis, redness, thickness, and degree of scaling.
• Response rates were uniform across patients of differing age, sex, races, and baseline disease severity.
• Combination therapy with calcipotriol and betamethasone dipropionate can enhance the rate and degree of improvement for patients undergoing treatment with UVB, PUVA, methotrexate, cyclosporine, retinoids, or alefacept.
• The addition of calcipotriol and betamethasone dipropionate can have a dose sparing effect, reducing some of the side-effects produced by many antipsoriatic treatments.
• Many dermatologists agree that including calcipotriol and betamethasone dipropionate in combination therapy produces synergistic effects.
• Can be considered as first-line topical therapy due to once daily application, quick onset of action, and favorable safety and efficacy profiles over 52 weeks of “as needed” use.

Topical Calcineurin Inhibitors

• Calcineurin inhibitors are immunosuppressive agents that interfere with T-cell signaling and affect the body’s inflammatory responses.
• Studies have indicated therapeutic benefits for psoriasis, especially on the face, and in the groin and skin folds.

Noncompliance and Nonadherence

Noncompliance or nonadherence to treatment can influence outcomes in all disease states. They unquestionably lower response to treatment, and this is of particular concern with topical medications. When the illness has the severity potential of psoriasis, physicians need to find treatment options that best suit each patient.

There is no reliable method to ensure or improve compliance in patients with psoriasis. Some clinical strategies to promote compliance include:

• encouraging patient feedback and input surrounding their treatment.
• selecting fast-acting topical therapies.
• selecting treatments that facilitate ease of use, i.e., once-daily dosing.
• referring patients to national organizations for support.

Conclusion

Advancements in topical antipsoriatic therapies have provided safer and more effective treatment options, especially when used in combination. Consequently, much research is underway to investigate novel treatment combinations for psoriasis in the hope that it will provide further enhancements in efficacy that will lead to improved patient compliance.

Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN

Acne Vulgaris

Acne vulgaris is a disorder of the pilosebaceous units located on the face, chest, and back. It affects up to 45 million Americans, mostly in the 15–24 year age group, and can cause a
poor self image, withdrawal, and even depression and suicidal ideation. More than $100 million per year is spent on OTC acne products. Scarring and postinflammatory hyperpigmentation are the most important sequelae.

Pathophysiology of Acne Vulgaris

The microcomedone is the precursor of all lesions.

Classification of Acne

1. Noninflammatory
   a. Open comedones and closed comedones
   b. Treated with topical agents
2. Inflammatory
   a. Papules: erythematous small bumps less than 1.0cm
   b. Pustules: pus filled erythematous small bumps less than 1.0cm
   c. May not respond to topical agents alone. Topicals can be combined with oral agents.
3. Nodulocystic Acne
   a. Nodules (more than 1.0 cm tender lesions)
   b. Cysts (more than 1.0 cm tender lesions)
   c. Treated with oral agents

Treatment

The most important treatment goal is to minimize scarring by preventing further acne development. Patient compliance is also very important in acne treatment. Minimizing adverse events and ease of treatment will maximize patient compliance.

Topical Retionoids

• Tretinoin (Retin-A®, Retin-A® Micro and Stieva-A®)
• Tazarotene (Tazorac®)
• Adapalene (Differin®)

Topical retinoids are most efficacious at preventing microcomedone formation. They should be applied sparingly to all affected areas, usually at night. Irritation and dryness make topical retinoid application challenging. It is advisable to avoid nasolabial and melolabial folds. Some retinoids, such as tazarotene, can be used as a short-contact treatment to avoid irritation. Use of gentle cleansers, noncomedogenic moisturizers, and avoidance of alcohol-based products and astringents will help to increase the compliance.

Topical Antibiotics

• Erythromycin (Aknemycin®, ATS®)
• Clindamycin (Cleocin T®, Clindagel®, Evoclin® Foam)

Both agents have anti-inflammatory and anti-infective action; however, due to reports of bacterial resistance, use as monotherapy is not recommended. Combinations of different
agents (e.g., in combination products) should be the first-line treatment for inflammatory lesions.

Combination Therapy

• Topical Clindamycin 1% + 5% BPO in moisturizing base (Duac®)
• Topial Clindamycin 1% + 5% BPO (Benzaclin®)
• Topical Erthromycin 3% + 5% BPO (Benzamycin®)

These combination products will fight both inflammatory and noninflammatory lesions (comedones). They will also help to prevent bacterial resistance. They may result in fabric
bleaching.

Combination Therapy

• All patients with acne can benefit from topical therapy, except those receiving isotretinoin.
• Topical retinoids should be applied to the whole acne prone area. They should be thought of as preventing new lesions rather than treating those that have already formed.
• For inflammatory acne, it is reasonable to use a combination topical therapy early on, such as a BPO/antibiotic combination. One can be used in the morning and the other in the evening.
• An adequate response to treatment can be measured in a few months, not weeks.
• Systemic therapy can be used if response is still poor after at least 3 months.

Importance of Vehicle in Topical Treatment

The role of vehicle in topical acne treatment is also very important.

• Glycerin – humectant
• Dimethicone – occlusive emollient

Combining these two products contributes to barrier restoration and will reduce adverse events such as dryness, peeling and irritation. Therefore, products containing these vehicles may be more tolerable for patients, in particular if they develop irritation with topical retinoids. The use of combination products will prevent emergence of antibiotic resistance.

Acne Surgery

Removal of noninflammatory lesions with a comedone extractor is helpful, but time consuming.

Cryotherapy

A spray of liquid nitrogen in moderate amounts or the application of slushed dry ice can be considered in the treatment of acne vulgaris. Periodic glycolic or salicylic acid peels also have benefits.

The Number One Reason for the Failure of Acne Treatment is Compliance

Management of the patients’ expectations and compliance are crucial aspects of acne treatment. Disease chronicity and long-term treatment should be discussed at length during the initial consultation. A skin care regimen with gentle cleansers and moisturizers will ease these patients into their treatment program and increase compliance by decreasing dryness and irritation from topical medications.

Editor’s Comment:

As Dr. Kircik notes, the microbe P. acnes remains central to the etiology of inflammatory acne lesions. Elucidation of the entire genome of this commensal organism has led to new insights into pathogenesis and to a new understanding of why certain therapeutic interventions are successful.¹ For example, the genome discloses that P. acnes is capable of producing glycocalyx material necessary to form a biofilm.

In turn, this explains the relative resistance of the putative causative bacterium to topical antibiotics when given as monotherapy. The addition of benzoyl peroxide, which disrupts the biofilm-rich microenvironment, allows better penetration of a concomitant antibiotic. Disruption of the biofilm also increases the local oxygen tension, thereby creating a less satisfactory situation for P. acnes, a commensal anaerobe.

Development of antimicrobial resistance when acne is treated with topical antibiotic monotherapy is a real phenomenon. Even more importantly, the genome discloses that P. acnes possesses the necessary intracellular mechanisms to pass on resistance to other bacteria.

A recent study demonstrated that this may, indeed, happen under normal clinical conditions.²
Thus, use of synergistic therapy (such as benzoyl peroxide along with antibiotic) is truly appropriate. A recent innovative therapy, the use of high intensity visible blue light, is also justified by the genome-directed synthesis and secretion by P. acnes of a photo-target (porphyrin).^3,4

The treatment of acne may expand even further as modern technology, such as genetic sequencing, is brought to bear on this common and distressing disorder.

References

1. Bruggemann H. Insights in the pathogenic potential of Propionibacterium acnes from its complete genome. Semin Cutan Med Surg. 2005 ;24:67-72.
2. Levy RM, Huang EY, Roling D, Leyden JJ, Margolis DJ. Effect of antibiotics on the oropharyngeal flora in patients with acne. Arch Dermatol 2003;139:467-71
3. Morton CA, Scholefield RD, Whitehurst C. Birch J. An open study to determine the efficacy of blue light in the treatment of mild to moderate acne. J Dermatol Treat 2005;16:219-23.
4. Tremblay JF, Sire DJ, Lowe NJ, Moy RL. Light-emitting diode 415 nm in the treatment of inflammatory acne: an open-label, multicentric, pilot investigation. J Cosmet Laser Ther. 2006 8:31-3.