Dermatological Treatments

The outcome of topical dermatological therapy depends on drug potency, topical bioavailability and patient adherence to treatment regimen. A basic understanding of the physicochemical (drug and vehicle) and physiological (skin at treatment site, anatomic site variation in permeability, age and metabolic activity) parameters that govern skin absorption is critical to topical dermatological therapy. An understanding of these parameters can enhance efficacy and reduce or eliminate side effects due to local and/or systemic exposure to drug or vehicle components (excipients). Studies have shown that patients do not prefer the use of an inconvenient and messy topical preparation even if justified by the drug’s effectiveness since the treatment may adversely affect patients’ quality of life. For topical therapy to be successful, it is imperative that healthcare practitioners discuss with patients the advantages and limitations associated with the different vehicle options available for a topical dermatological drug. Such an approach ensures that patients’ desires and preferences are central to the treatment regimen and are therefore expected to improve patient adherence to treatment and treatment outcome. This chapter provides a summary of the physiological and physicochemical aspects of topical drug absorption and methods of optimizing topical dermatological therapy (including the use of microspheres, occlusion by dressings, spray and foam vehicles).

Due to drastic environmental changes and more so, changes in life style, the frequent showers, bath, use of soaps, and cleansing wash make skin lose its natural oils. It causes dryness and more easily formation of subclinical fissures which can be followed of inflammation, itch and irritation. Emollient agents are used to combat all these effects. They operate to restore the cutaneous barrier. Numerous cutaneous dermatosis manifest with an abnormal thickening of the corneum stratum. It results in the appearance of scales on the skin. Keratolytic agents can help to favor elimination of scale and to reduce the thickness of corneum stratum.

Topical corticosteroids are useful to treat inflammatory dermatoses due to their anti-inflammatory, antiproliferative, immunosuppressive, and vasoconstrictive effects. Scientific research has tried to develop high potency topical corticosteroids with minimum adverse effects. Nowadays, there are a growing list of these drugs, with different potency and activity. Some of the inflammatory diseases that usually respond to topical corticosteroids are atopic dermatitis, psoriasis, seborrheic dermatitis, nummular eczema, contact dermatitis, papular urticaria, or lichen simplex chronicus. To select a topical corticosteroid that is indicated in certain inflammatory diseases, it is also important to take into account the skin area, the vehicle, the conditions that potentiate the risk for systemic absorption, or the patient’s compliance. One application daily of topical corticosteroids may be preferable, because there is no difference with once or twice daily application. Local side effects occur more frequently than systemic ones, but both are equally uncommon. Children and elderly patients have a greater risk of side effects. Appropriate human studies in pregnancy or breastfeeding have never been undertaken, so topical corticosteroids may be applied in this case only when benefits justify the possible risk to the fetus. Patient education about the application of topical corticosteroids is essential in optimizing therapy.

Topical antimicrobials agents are an attractive therapeutic option due to the high drug concentration achieved in the site of infection with minimal systemic absorption. When used properly, they allow good cure rates with minimal systemic adverse effects conferring great popularity to topical therapy. However the success of topically used drugs entails its main disadvantage: antimicrobial resistance. Indiscriminate use leads to the emergence of antimicrobial resistance hindering the response to treatment and, at community level, risking potential serious systemic infections by resistant germens. These risks prompt us to a judicious use of topical drugs.

In this chapter, topical antimicrobials are addressed focusing on microbiologic coverage and clinical uses. Antibacterials are summarized including the recently appeared nadifloxacin and retapamulin increasing the therapeutic arsenal against methicillinresistant Staphilococcus aureus (MRSA) and mupirocin-resistant MRSA. Antivirals are summarized including off-label uses for recalcitrant conditions. Antifungals are summarized including the topical lacquer options for the combined therapy of onychomycoses. Antiparasitic agents are summarized for the treatment of scabies and pediculosis.

Topical retinoids are drugs specifically employed in determined disorders of the skin. For instance, tretinoin, isotretinoin and adapalene are employed mainly in acne. Moreover, tazarotene is also indicated for the treatment of stable plaque psoriasis. On the other hand, alitretinoin is indicated for the treatment of AIDs-related Kaposi sarcoma and bexarotene for mycosis fungoides. New indications for topical retinoids might be emerging, such as the use of bexarotene gel for chronic hand eczema or for alopecia areata. In contrast to systemic retinoids, topical retinoids have a safe toxicity profile. Local effects are the main adverse events, such as erythema, dryness, stinging and itching are frequent at the beginning of the treatment.

In the last decade, new molecules with the ability to change the local immune response of skin have appeared. The topical application of these medications enhance (imiquimod) or reduce (tacrolimus, pimecrolimus) the inflammatory response of skin. Imiquimod is a synthetic compound that is a member of the imidazoquinolone family of drugs. This class of drugs has the properties of topical immune response modifiers and stimulators. The mechanism of action of imiquimod involves cytokine induction in the skin, which then triggers the host's immune system to recognize the presence of a viral infection or tumor, ultimately to eradicate the associated lesion. Topical calcineurin inhibitors (TCI), tacrolimus and pimecrolimus are immunomodulator macrolides that block T cell activation in the skin. The therapeutic effects of calcineurin inhibitors are mainly attributed to these effects on T cells. Tacrolimus and pimecrolimus belong to the group of ascomycin derivates obtained from the fungus-like bacteria Streptomyces. Tacrolimus was isolated from Streptomyces tsukubaensis and pimecrolimus is produced by Streptomyces hygroscopicus. TCI are used for the management of atopic dermatitis (AD) and have proven to be of benefit in the treatment of other dermatosis.

Glucocorticoids are among the most frequently prescribed anti-inflammatory drugs not only in dermatology but all of medicine because of their anti-inflammatory and immunosuppressive properties, and are prescribed by a wide variety of physicians, both specialists and generalists. We described the mechanism of action of GCs, the pharmacokinetics, the indications and dosage, adverse events, risks and precautions, particularly in pregnancy.

Infectious skin diseases caused either by bacteria, fungi or viruses, account for an important burden in dermatology practice. The number is increasing due to higher percentage of immunocompromised patients. Although in many instances they can be successfully treated with topical agents, sometimes systemic antimicrobial agents are indicated. This occurs in extensive or complicated skin and soft tissue infections, tinea capitis, onychomycosis, genital herpes or herpes zoster. Besides, some antibacterial agents have been shown to have antiinflammatory properties and they have been successfully used for the treatment of noninfectious skin diseases.

New drugs are continuously developing due to increasing multi-drugs resistant microorganisms, especially in the context of immunocompromised patients. Appropriate antimicrobial selection requires the consideration of multiple factors, including conditions of the host, the disease and the drug. Clinicians should know the properties, indications and adverse events related to the old and new antimicrobial agents in order to choose the correct option.This chapter summarizes the characteristics of systemic antimicrobial agents commonly used in dermatology.

Systemic retinoids are drugs specifically employed in dermatology, with only isolated indications in other specialties. Nevertheless, they have effects on different organs different from skin, and dermatologists should be aware of these effects. In this chapter four drugs are reviewed: isotretinoin, acitretin, alitretinoin and bexarotene. There is a wide spectrum of conditions responsive to systemic retinoids: acne, psoriasis, eczema, cutaneous lymphoma… etc. and they are important instruments in their therapy, once adverse effects have been controlled. An individualized assessment has been performed, mainly on the indications and adverse events, due to the differences among them.

Fumaric Acid Esters (FAEs) have been used in north European countries for more than thirty years to treat moderate-severe psoriasis. In 1994 a defined mixture of FAEs was registered in Germany under the brand name of Fumaderm®. The main ingredient of this mixture is dimethylfumarate (DMF). This and its main metabolite, monomethylfumarate, have proven to possess potent immunomodulatory functions. Several studies have demonstrated the efficacy of FAEs therapy for chronic plaque type psoriasis, exanthematic guttate type, pustular type and psoriatic erythroderma. The most common adverse effects under FAEs therapy were gastrointestinal complains and flushing and no severe secondary effects have been described. By reason of that, FAEs therapy are now considered an effective and save treatment option on moderate or severe psoriasis patients.

Dermatologists are often required to prescribe immunosuppressive agents for the treatment of serious and recalcitrant dematoses. Azathioprine, cyclophosphamide, methotrexate, and cyclosporine are the immunosuppressive agents most commonly used by dermatologists. The immunosuppressive drugs act by a variety of mechanisms. In general, the precise mechanisms responsible for most therapeutic benefits observed with these agents are understood only partially. Unlike biologic agents that selectively inhibit a proinflammatory cytokine and/or block its receptor, the immunosuppressive drugs interfere with combinations of critical pathways in the inflammatory cascade. Among the immunosuppressive drugs, several are "cytotoxic", causing either cell death or impaired proliferation; such drugs include cyclophosphamide, chlorambucil, methotrexate, and azathioprine. Other drugs suppress the immune system by inhibiting the proliferation or function of lymphocytes. This class includes drugs such as cyclosporine and tacrolimus, which specifically target calcineurin and thereby inhibit the production of interleukin-2 by activated T-lymphocytes. Others prevent lymphocyte proliferation by inhibiting nucleotide synthesis, for example, mycophenolate mofetil blocks the synthesis of purine. Finally glucocorticoids have many effects upon innate and acquired immunity. Familiarity with disease-specific clinical efficacy, side-effect profile, and dosage allows the successful and judicious use of these drugs in dermatologic disorders. This chapter summarizes the characteristics of systemic immunosuppressive agents commonly used in dermatology.

In the past two decades an explosion in the use of biological treatments has occurred in dermatology. These drugs target cytokines and cells involved in chronic inflammatory and autoimmune diseases, changing the classical approach to different conditions. Biological drugs are synthesized by different cell types and produce their effects by binding to specific cell surface receptors. The inhibition of the inflammatory cascade at different points (TNF blockade, B or T lymphocyte inhibition) obtained with these medications showed to be helpful in numerous dermatological conditions (psoriasis, psoriatic arthritis, pemphigus, hydradenitis supurativa… etc.) and new indications are continuously reported in the literature. In this chapter, tumor necrosis factor inhibitors (infliximab, etanercept, adalimumab), alefacept, ustekinumab and rituximab are reviewed. Licensed and off-label indications are considered, as well as dosage, contraindications and adverse events.

In this chapter, three different drugs are resumed. Antihistamines are widely used in dermatological conditions to ameliorate pruritus and to inhibit the histamine release. Dapsone has been used for almost 50 years in the treatment of several infectious diseases including, leprosy and malaria and recently in the treatment of pneumocystic carinii pneumonia in patients with AIDS. Dapsone also has anti-inflammatory properties and has been used in dermatology and rheumatology. The development of the synthetic antimalarials and their use in the treatment of cutaneous diseases have been well described. Chloroquine is a 4-aminoquinoline antimalarial used in the treatment and prophylaxis of malaria. It has also been used in the treatment of hepatic amoebiasis, lupus erythematosus, light-sensitive skin eruptions, and rheumatoid arthritis.

Radiation has been used to treat cutaneous conditions since ancient times. Despite all the recent advances in the field of dermatological therapy that have taken place in the last years, phototherapy and photochemotherapy still represent a useful alternative to control prevalent dermatoses such as psoriasis and atopic dermatitis. Moreover, it is a useful tool to manage less frequent skin diseases like cutaneous T-cell lymphomas. Classical phototherapeutic modalities (broadband UVB, PUVA, bath- PUVA, etc.), its indications and side effects are revised in this chapter, as well as relatively new options such as narrowband UVB therapy and UVA-1.

The basic principles of photodynamic therapy include the use of a photosensitizing agent and the subsequent irradiation with a light source. Because of the skin accessibility to light sources, a great deal of research has been focused on the various light sources and lasers used to get an improvement in different skin diseases. In Europe, the most used combination in photodynamic therapy is the utilization of methyl ester of 5-aminolevulinic acid (commercialized as Metvix®) and best utilized with a red light source at 630 nm. In most European countries, New Zealand and Australia, Metvix® cream is approved for the treatment of basal cell carcinoma, non-hyperkeratotic actinic keratosis (Aks) of the face and scalp and Bowen disease in combination with red light. Photodynamic therapy is being used more and more in a huge number of dermatological and non-dermatological diseases, apart from its approved indications. One of the most promising indications in the future is its use in the management of viral warts with a reasonable cosmetic result due to the fact that this is an entity very difficult to treat. Other current targets of photodynamic therapy are acne, psoriasis, squamous cell carcinoma or even melanoma or mycosis fungoides. A very promising indication in the future could be the prevention of the onset of pre-malignant (actinic keratosis) or malignant (squamous cell carcinoma) lesions, as photodynamic therapy has an action in non-visible lesions. Photodynamic therapy has been used as well, occasionally with good results, in cutaneous photorejuvenation because this technique usually improves characteristics as hyperpigmentation, fine lines or roughness.

Extracorporeal photochemotherapy (ECP) is a complex therapy in which cells collected from patients are exposed to the effects of photosensitizing agents (specifically 8-methoxypsolaren) and ultraviolet Light-A. Its most common indication is advanced stage cutaneous T-cell lymphoma. However, this therapy has yielded successful results in other cutaneous and metabolic diseases like phemphigus vulgaris and autoimmune diabetes mellitus [1]. Although the cost represents a significant limitation, extracorporeal photochemotherapy should be considered in the aforementioned diseases in patients where other conventional therapies have failed or are contraindicated.

The term laser is an acronym for light amplification by the stimulated emission of radiation. The origins of this technique are in the postulates of Einstein in 1917. In the 80´s the theory of selective thermolysis showed that specific destruction of a target in the skin could be achieved with minimal unwanted thermal injury. The number of indications has increased continuosly, with the improvement in the knowledge of the interaction between light and skin. Vascular and pigmented lesions, tattoos, unwanted hair to be removed, cutaneous aging etc are only examples of the wide spectrum of conditions that can be boarded through LASERs.