Psoriasis is skin disease with unknown etiology. There is no cure for psoriasis, but there are many treatments that can decrease the symptoms and appearance of the disease.
In general, there are three treatment options for patients with psoriasis: Phototherapy, topical and systemic. A combination of therapies is often recommended. Combining various topical, systemic and light treatments often allows lower doses of each and can result in increased effectiveness.
4.2. Light therapy (phototherapy)
Solar ultraviolet (UV) radiation has been used since ancient times to treat various diseases. This has a scientific background in the fact that a large number of molecules (chromophores) in different layers of the skin interact with and absorb UV. These interactions may have both positive and negative biological implications. Most of the positive effects of solar radiation are mediated via ultraviolet-B (UVB) induced production of vitamin D in skin . In our day’s phototherapy is a valuable option in the treatment of many psoriatic and nonpsoriatic conditions, including atopic dermatitis, sclerosing skin conditions such as morphea, scleroderma, vitiligo, and mycosis fungoides . UVB radiation reaches the epidermis and the upper dermis where it is absorbed by DNA, trans-urocanic acid (trans-UCA), and cell membranes . Absorption of UVB by nucleotides leads to the formation of DNA photoproducts, primarily pyrimidine dimers. UVB exposure reduces the rate of DNA synthesis. In addition, UVB radiation causes photoisomerization of trans-UCA to cis-UCA which has immunosuppressive effects. Furthermore, UV radiation can affect extranuclear molecular targets (cell surface receptors, kinases, phosphatases, and transcription factors) located in the cytoplasm and in the cell membanes . Keratinocytes, circulating and cutaneous T lymphocytes, monocytes, Langerhans cell, mast cells and fibroblasts are all targeted by narrowband UVB . Narrowband UVB induces also local and systemic immunosuppressive effects which may particularly contribute to the beneficial effects of this light source. UVA radiation penetrates more deeply into the skin than UVB, and reaches not only epidermis, but also dermis with blood vessels affecting dermal dendritic cells, dermal fibroblasts, endothelial cells, mast cells, and granulocytes . UVA radiation is absorbed by pyridine nucleotides (NAD and NADP), riboflavins, porphyrins, pteridines, cobalamins and bilirubin  Porphyrins and riboflavins are photosensitizers. UVA effects are dominated by indirect DNA damage caused by reactive oxygen species such as singlet oxygen. The ability of UVA radiation to cause skin erythema is approximately 103 to 104 times lower than that of UVB. As UVA-1 is even less erythematogenic than broadband UVA much higher doses of UVA-1 can be tolerated by the patients. UVA-1 phototherapy works mainly through induction of apoptosis of skin infiltrating T cells, T-cell depletion and induction of collagenase-1 expression in human dermal fibroblast  .
Sunlight: Already several thousands of years ago sunlight (heliotherapy) was used to treat a variety of skin conditions in Egypt, Greece and Rome . Ultraviolet (UV) light is a wavelength of light in a range too short for the human eye to see.
UVB phototherapy: Controlled doses of UVB light from an artificial light source may improve mild to moderate psoriasis symptoms. UVB phototherapy, also called broadband UVB, can be used to treat single patches, widespread psoriasis and psoriasis that resist topical treatments.
Narrowband UVB therapy: A newer type of psoriasis treatment, narrowband UVB therapy may be more effective than broadband UVB treatment. It's usually administered two or three times a week until the skin improves, then maintenance may require only weekly sessions.
Goeckerman therapy: The combination of UVB treatment and coal tar treatment is known as Goeckerman treatment. The two therapies together are more effective than either alone because coal tar makes skin more receptive to UVB light.
Photochemotherapy: Photochemotherapy involves taking a light-sensitizing medication (psoralen) before exposure to UVA light. UVA light penetrates deeper into the skin than does UVB light and psoralen makes the skin more responsive to UVA exposure.
Excimer laser: This form of light therapy, used for mild to moderate psoriasis, treats only the involved skin. A controlled beam of UVB light of a specific wavelength is directed to the psoriasis plaques to control scaling and inflammation. Healthy skin surrounding the patches isn't harmed.
Pulsed dye laser: Similar to the excimer laser, the pulsed dye laser uses a different form of light to destroy the tiny blood vessels that contribute to psoriasis plaques.
Systemic treatment: Oral or injected medications
Patients with moderate to severe disease generally require systemic agents (e.g. cyclosporin, methotrexate, oral retinoids, fumaric acid esters) to control their disease adequately. The severity of psoriasis traditionally has been evaluated by objective measurement of the extent of the body surface affected and consideration of the subtype of psoriasis, degree of disability, and feasibility of topical therapy .
Retinoids: Several systemic retinoids (derivatives of vitamin A) have been developed for the treatment of psoriasis. Systemic retinoids are known to have immunosuppressive and anti-inflammatory activity and to modulate epidermal proliferation and differentiation . As mentioned previously, clinical data suggest that combination retinoid–PUVA therapy may be more effective than either treatment alone, and may minimize the toxicities associated with each modality through dose-sparing or independent chemopreventive effects  .
Methotrexate (MTX): It was introduced as a therapy for psoriasis in 1958 (Edmomudson et al., 1958). Taken orally, methotrexate helps psoriasis by decreasing the production of skin cells and suppressing inflammation. It may also slow the progression of psoriatic arthritis in some people. Methotrexate is generally well tolerated in low doses. Hepatic fibrosis typically occurs after total cumulative MTX doses of at least1.5 g. . The risk of hepatotoxicity may decrease if MTX is given in short courses and rapidly discontinued after clinical improvement .
Cyclosporine: It was first used (inadvertently) for the treatment of psoriasis in 1979 . Cyclosporine suppresses the immune system and is similar to methotrexate in effectiveness. Major toxicities associated with cyclosporin therapy include nephrotoxicity, hypertension and immunosuppression
Fumaric acid esters (FAE): Oral FAE therapy for psoriasis was first reported in 1959. Dimethylfumarate, and its metabolite monomethylfumarate, appear to be the principal active components of Fumaderm®. Treatment with dimethylfumarate and/or monomethylfumarate produces a beneficial shift towards Th2-like cytokine secretion associated with a reduction in peripheral lymphocytes (primarily T cells)  and inhibits the proliferation of epidermal keratinocytes in patients with psoriasis. Haematological changes, notably leucopenia, lymphopenia and eosinophilia, are frequently observed during FAE therapy .
Tumour necrosis factor alpha (TNFα) inhibitors: It is known that TNF alpha is elevated in both the skin and synovium of psoriatic patients and the effectiveness of its blockade by these two agents in psoriasis and Psoriatic arthritis (PsA) confirms its role in their pathogenesis. TNFi (infliximab, etanercept and adalimumab) revolutionised the treatment of autoimmune diseases such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD) and plaque psoriasis. Anti-TNF alpha therapy has proved to have disease-reducing activity in PsA and psoriasis and appears to be well tolerated . The widespread use of TNFalpha antagonists in recent years has led to the recognition of paradoxical adverse effects, defined as the onset or exacerbation of disorders that are usually improved by TNFalpha antagonists . During these treatments, cutaneous adverse effects may occur like eczema, lupus, alopecia areata or psoriasis, which represents a paradoxical adverse effect.Then, therapy with TNF α inhibitors can be associated with paradoxical reactions. They are considered a class effect of these drugs, and their incidence ranges from 1 to 5%, with paradoxical psoriasis (psoriasis vulgaris, palmoplantar pustulosis, scalp psoriasis and their combinations) being most frequently reported .
Phosphodiestrase inhibitors: Phosphodiesterases play a pivotal role in degrading cyclic nucleotides (cGMP, cAMP), key second messengers in all cells. Particularly cAMP plays an important regulatory role in virtually all the cell types involved in the pathophysiology of allergic and inflammatory diseases including asthma and chronic obstructive pulmonary disease, but also skin diseases including atopic dermatitis and psoriasis. Of the cAMP-degrading PDEs, PDE4 is the one that has been studied most extensively in recent years. PDE4 is abundant, and is the major cAMP-degrading isoenzyme in almost all inflammatory and immune cells. In spite of varied structurallasses, highly selective PDE4 inhibitors have the same quality in suppressing several pro-inflammatory mechanisms likecytokine generation and secretion, superoxide generation, degranulation, IgE production, proliferation, histamine generation and chemotaxis  . The PDE4 family comprises four genetically distinct subtypes (PDE4 A-D). These subtypes differ with respect to their regulatory behaviour and tissue expression patterns. The search for selective inhibitors of PDE4 as novel anti-inflammatory drugs has continued for more than 30 years and almost two decades have passed since targeting PDE4 became a focus in the development of novel therapeutics for pulmonary inflammatory diseases. The development of PDE4 inhibitors with PDE4B selectivity has been considered a promising approach because much evidence demonstrates that ablation or inhibition of PDE4B produces a broad spectrum of anti-inflammatory effects while minimizing unwanted side effects  . Nazarian et al.’s studies in 2009 showed that AN-2728 (PDE4) is well tolerated and demonstrates significant effects on markers of efficacy, with results that were comparable to positive controls. AN-2728 appears to have good therapeutic potential, although further and larger trials are required to assess the long-term safety and characterize the broad utility of this drug . Nevertheless, the impact of PDE4B-selective inhibitors on inflammatory diseases awaits further clinical trials. Several PDE4B and PDE4D selective inhibitors have been designed and synthesized, and their effects on inflammation are under investigation. Although several compounds have demonstrated therapeutic effects in diseases such as asthma, COPD, atopic dermatitis and psoriasis, none have reached the market. A persistent challenge in the development of PDE4 inhibitors has been drug-induced gastrointestinal adverse effects, such as nausea. Despite the challenges and complications that have been encountered during the development of PDE4 inhibitors, these drugs may provide a genuinely novel class of anti-inflammatory agents, and there are several compounds in development that could fulfill that promise . McCann et al., in 2012 showed oral Apremilast targets PDE4 inhibitor, modulates a wide array of inflammatory mediators involved in psoriasis and psoriatic arthritis, including decreases in the expression of inducible nitric oxide synthase, TNF-α, and interleukin (IL)-23 and increases IL-10. In phase II studies of subjects with psoriasis and psoriatic arthritis, apremilast reversed features of the inflammatory pathophysiology in skin and joints and significantly reduces clinical symptoms. The use of an oral targeted PDE4 inhibitor for chronic inflammatory diseases, like psoriasis and psoriatic arthritis, represents a novel treatment approach that does not target any single mediator, but rather focuses on restoring a balance of pro-inflammatory and anti-inflammatory signals . Now, several PDE4B and PDE4D selective inhibitors have been designed and synthesized, and their effects on inflammation are under investigation.
In summary: Managing psoriasis
Currently, there is no universal standard of care for patients with moderate to severe psoriasis, and the benefits and risks of systemic therapy must be weighed carefully for each patient to ensure optimal management of psoriasis symptoms and minimization of acute and cumulative toxicities . Whether the symptoms are mild, moderate, or severe, the optimal treatment plan is the one the patient is most likely to follow. For those with localized disease, topical therapy is a suitable first choice. Phototherapy is generally the first-line treatment for patients with extensive psoriasis or disabling symptoms. When phototherapy is not feasible or is ineffective, systemic treatments with conventional oral agents or biologics are indicated . Psoriasis is a common skin disorder that needs long-term management, not only because of its prevalence but also because of the profound impact it can have on quality of life.