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    psoriasis introduction psoriasis introduction Document Transcript

    • Special Feature Introduction to psoriasis By OLIVIA STEVENSON, MBBS, MRCP and IRSHAD ZAKI, MBBS, MRCP , In the first part of our special feature on psoriasis, the authors outline the aetiology, pathogenesis, and clinical features of the condition Svartsengi, Iceland: The waste water from the geothermal power station has properties P which benefit sufferers from psoriasis who come to bathe there soriasis is one of the commonest skin disorders seen by general practition- rapid turnover of the skin cells. The turnover over the mode of inheritance. The history of ers. It is a chronic skin disease that of cells can rise to seven times the normal psoriasis in some families seem to suggest a affects 2–3 per cent of the population rate, leading to thickening of the superficial simple autosomal inheritance with reduced in Western Europe. Worldwide, there are layers of the skin. The most characteristic penetrance, although evidence has been pre- estimated to be 80 million people suffering lesions consist of sharply demarcated, dull- sented for multifactorial genetic components. from psoriasis. red or salmon-pink thickened patches with (Penetrance is the frequency with which a The prevalence of psoriasis is identical silvery scales. mutant gene produces its characteristic effect in men and women, and across all socio- The extensor surfaces of the limbs (espe- in those individual possessing it.) Examination economic groups. Certain areas, such as cially the elbows, knees and shins), scalp, and of large numbers of family pedigrees suggests South America, China, and Nigeria, have a lower back/buttocks are particularly affected, that no single pattern predominates, and the particularly low prevalence. but psoriasis may involve any part of the body. absence of 100 per cent concordance among Psoriasis can develop at any age, When psoriasis involves the groins, armpits, monozygotic twins does indicate that environ- although it commonly appears between the perineum and the area under the breasts, the mental factors contribute to the aetiology. ages of 15 and 22. A second peak appears lesions tend to be less scaly and rather shiny. There is also evidence of a link with during the 60–69 age range. Females tend The disease is highly variable in duration human leucocyte antigen (HLA) phenotypes. to develop psoriasis slightly earlier than and extent, and there are several common Specifically, there is a strong association of males, and those with a family history also morphological variants. Contrary to popular psoriasis with the phenotype, HLA-CW6, have an earlier age of onset. The disease belief, up to 50 per cent of affected patients with the relative risk of developing the dis- may last for just a few weeks or for a lifetime, experience significant itch, especially on the ease being increased 10-fold. The with alternating periods of relapses and scalp and lower legs. phenotypes, HLA-B13 and HLA-B17 have remissions. It is difficult to predict the course In some cases, psoriasis is associated with also been linked with psoriasis.1,2 of the disease. psoriatic arthritis, a condition similar to The precise cause of psoriasis is not clear, rheumatoid arthritis, that causes inflamma- but the enhanced keratinocyte proliferation DESCRIPTION tion and stiffness in and around joints. About results in thickening of the epidermis. Initially, 15 per cent of people with psoriasis will the rapid keratinocyte proliferation seen in P soriasis is an inflammatory and prolifera- tive disease of the skin that results in a develop psoriatic arthritis, and psoriatic arthritis can also be present without psoriasis. psoriasis was thought to be at least partly due to reduced cell cycle time. Recent evidence suggests that the augmented growth rate of AETIOLOGY the epidermis is a result of an increased pro- Dr Stevenson is specialist registrar in dermatology portion of cycling cells recruited from the at Walsgrave Hospital, Coventry and Dr Zaki is consultant dermatologist at Solihull Hospital T here is evidence that psoriasis can be inherited, but there is much controversy basal epidermis rather than a change in the cell cycle time.3,4 J U L Y /A U G U S T 2002 V O L.9 H O S P I TA L P H A R M A C I S T 187
    • PATHOGENESIS or without a previous history of psoriasis. The amount of scaling is highly variable, However, there is also evidence that contin- the most characteristic being the silvery T lymphocytes have been implicated in the pathogenesis of psoriasis. The evidence for this includes the following: uing, subclinical streptococcal infection may be a contributory factor in refractory psoriasis. scale, which varies considerably in thickness. The top scales lift away easily but deeper scales stick together, and when removed, the exposed skin leaves punctate bleeding l Infiltration of psoriatic lesions with acti- Sunlight Although sunlight generally benefits points. This is known as Auspitz sign and vated T cells psoriasis patients, a small minority of occurs because there are dilated tortuous l The efficacy of treatments that target T patients experience a worsening of their con- capillaries within the papillary dermis. It can cells, such as, ciclosporin, anti-CD4 dition when exposed to strong sunlight. be a useful clinical sign to aid diagnosis but monoclonal antibodies, and a lympho- is not exclusive to psoriasis. When scaling is cyte selective toxin Drugs There are over 200 drugs that have a not evident, it may be induced by lightly l Raised serum levels of interleukin-2 tendency to exacerbate psoriasis, the most scratching the surface of the plaque. receptor protein during active phases of prominent being beta-blockers, lithium and Plaques may be few or many and they disease, signifying T cell activation antimalarials. Recent reports suggest that the tend to be symmetrical. Thickened plaques l The demonstration that T cell clones smoking cessation drug bupropion may trig- can fissure, especially those that overlie propagated from lesional biopsies ger acute pustular psoriasis in susceptible areas of joint movement. release growth factors that induce ker- individuals. atinocyte proliferation Scalp The scalp is often affected in psoriasis. Alcohol/smoking Excessive consumption of Well-defined pale red plaques with a thick One of the immunocyte-derived factors alcohol at a level detrimental to general surface of silvery scales are seen (see Figure that is believed to alter keratinocyte pheno- health has been associated with severe pso- 2, p189). These may become confluent and type is tumour necrosis factor (TNF). This riasis in men. It is likely, however, that the entire scalp can be involved. The scaling cytokine induces pro-inflammatory effects by alcohol is not a direct exacerbating factor tends to be quite adherent and rarely, can binding to specific TNF receptors and acti- but is associated with poor treatment com- cause local alopecia. A specific form of vating a signal transduction pathway. pliance and is a symptom of the stress scalp psoriasis seen mainly in younger Although its role in psoriasis is not complete- associated with severe skin disease. patients is pityriasis amiantacea, where large ly understood, TNF may be involved in many Smokers are at an increased risk of chron- scales of skin become stuck to the hair of the steps that lead to the induction and ic plaque psoriasis and almost all patients shafts. The term is derived from amiante, the progression of the disease. TNF can stimu- with palmar-plantar pustular psoriasis are French word for asbestos because the scales late all the processes required to produce smokers. are said to resemble the layers seen when immunocyte infiltration in tissues, including raw asbestos is mined. the upregulation of cell adhesion molecule HIV infection Psoriasis has been shown to expression and the induction of secondary flare significantly and to appear de novo as Flexures Lesions of psoriasis in flexures, cytokines and chemokines. HIV infection progresses. especially under the breasts, and in the natal TNF-alpha has been shown to be over- cleft and perineum can appear different expressed in psoriatic skin lesions and CLINICAL FEATURES from plaques elsewhere. The scale is usually increased concentrations have been found reduced or absent, leaving shiny deep pink in the serum in generalised pustular psoria- sis. The inhibition of TNF-alpha using drugs such as etanercept and infliximab has been P soriasis has several clinical variants. These differ in severity, location, longevi- ty, and shape and pattern of the scaling. The plaques, which may fissure in the depth of the skin crease. These lesions may follow intertrigo in the area and are generally more shown to be a useful therapeutic modality.5,6 commonest of these clinical variants are: common in older patients, as well as in those The involvement of T lymphocytes may be who are overweight. the result of a specific cellular immune l Plaque psoriasis response in psoriatic lesions, due either to l Guttate psoriasis Hands and feet Psoriasis can affect the putative autoantigen or perhaps related to l Pustular psoriasis hands and feet and can be difficult to distin- beta-haemolytic streptococci. It has there- l Erythrodermic psoriasis guish from contact dermatitis or endogenous fore been suggested that psoriasis is a T eczema when it involves the palms and cell-mediated autoimmune disease. Plaque psoriasis Plaque psoriasis is also soles. A history of psoriasis elsewhere can known as chronic stable plaque psoriasis or aid diagnosis. Again, the well-defined edge EXACERBATING FACTORS psoriasis vulgaris (see Figure 1, p189). is characteristic and significant nail dystro- Chronic plaque is the most common form of phy is more suggestive of psoriasis. There C ertain conditions can provoke or exac- erbate psoriasis. These include trauma, infection, sunlight, drugs, alcohol, smoking psoriasis. The lesions are of a deeper pink colour than those seen in eczema or sebor- rhoeic dermatitis, although they can look may be significant itch. The skin of the palms and soles may become quite thick. However, the most troublesome symptom is and AIDS. rather bluish on the legs. The distinctive often painful splitting. Splitting occurs over nature of this hue of pink is lost in individu- the fingertips and heels, leaving painful fis- Trauma It is a well-known fact that psoriasis als who are dark-skinned. sures which may be slow to heal. There may tends to appear at sites of injury (Köebner The classical sites of involvement are the be cyclical thickening, splitting and peeling, phenomenon). A variety of stimuli have been knees, elbows, buttocks, scalp and the anteri- leaving the fingertips raw and tender. Psoria- demonstrated to elicit this response and pso- or shins and forearms. sis of the dorsal aspect of the hands tends to riasis may also show a predilection for scars The plaques usually begin as small red present as well-defined areas of dull-red that have been present for several years. papules that subsequently scale as they grow thickening, with variable scaling, especially Psoriasis can also develop on tattoos. larger. As the plaques grow in size, they can over the knuckles. merge to form annular (ring-shaped) and Infection Streptococcal infection, especially gyrate (coiled) forms. These plaques usually Nails The fingernails and toenails may show of the throat, has long been known to pro- have a clearly defined edge in contrast to the dystrophic changes of psoriasis that may be voke acute guttate psoriasis in patients with rather vague outline seen in eczema. marked, and can aid diagnosis. Nail 188 H O S P I TA L P H A R M A C I S T J U L Y /A U G U S T 2002 V O L.9
    • Figure 1: Chronic plaque ps r a i oiss Figure 2: Scalp psoriasis Figure 3: Onycholysis (lift n o t e n i p a e ig f h al lt) Figure 4: Severe psoriatic nail dystrophy with destruction of the nail plate Figure 5: Guttate psoriasis on the trunk Figure 6: Palmar plantar pustular ps r a i oiss J U L Y /A U G U S T 2002 V O L.9 H O S P I TA L P H A R M A C I S T 189
    • changes may occur with significant disease, usually on a background of erythroderma scratching. Palmar and plantar eczema can or herald the development of psoriasis else- (total skin involvement, see below). There be hyperkeratotic and differentiating it from where. In some patients, nail dystrophy may be areas of classical psoriasis to aid psoriasis can be quite difficult. remains the only manifestation of psoriasis diagnosis but often patients are just extreme- for many years. Pitting is the commonest nail ly red with little or no scaling. Oral steroids Candidiasis Candidiasis can also coexist in change. It is manifested as small discrete pits can trigger this condition and should never the flexures. Small satellite pustules and in the nail plate (often referred to as “thimble be used routinely for the treatment of psoria- papules are suggestive of candidiasis. pitting”, because of its similarity to the sur- sis. Patients are usually systemically unwell face of a thimble). However, the whole of the and have to be admitted to hospital as a Athlete’s foot Trycophyton rubrum is a fun- nail may loosen and become raised from the matter of urgency. gus that commonly causes athlete’s foot. nail bed. This is known as onycholysis (see When it infects the nails it can look similar to Figure 3, p189). Patches of psoriasis under Erythrodermic psoriasis Erythroderma is the the onycholysis seen in psoriasis. Evidence of the nail can give a distinctive appearance term that is used when more than 95 per athlete’s foot elsewhere is suggestive of the known as “oil spots” or “salmon patches”. cent of the skin is involved in a rash of any infection. This fungus may also infect the In severe onycholysis, marked thickening kind. palm or sole. However, the pattern tends to of the nail plate, along with a build-up of Erythrodermic psoriasis can arise in two be assymetric, which is unusual for psoriasis keratotic material under the free edge of the ways: at this site. nail plate (known as sub-ungual keratosis) is also commonly seen. Psoriatic nail dystro- l Chronic lesions may gradually evolve SUMMARY phy, especially in the absence of classical into an exfoliative phase, resulting in psoriasis elsewhere, may be mistaken for a fungal infection (see Figure 4, p189). extensive plaques covering most of the body. This condition is less likely to cause systemic upset and usually P soriasis is a common skin condition with a genetic predisposition. The typical lesions of chronic plaque psoriasis are char- Guttate psoriasis This form of psoriasis more responds well to mild to moderate treat- acteristically well defined, salmon-pink, and commonly affects children and young adults ments with a variable silvery scale over the extensor and often follows a streptococcal sore l Unstable psoriasis can develop sudden- surfaces. Many patients will also have nail throat. It classically appears as many small, ly or follow a period of increasing and scalp involvement. The course is vari- red, drop-like, scaly spots (the term guttate is instability and intolerance to topical able but could be lifelong. derived from the Latin word for “raindrop”). therapy. This is a medical emergency Guttate psoriasis tends to have a better Each lesion is usually 0.2–1cm in diameter and patients should be admitted to hos- prognosis, and may occur with or without a and round to oval in shape (see Figure 5, pital for intensive therapy and previous history of psoriasis. There is a p189). monitoring. It is often associated with strong association with beta-haemolytic Guttate psoriasis may develop into the significant systemic upset and can result streptococci. more common chronic plaque form of the in loss of temperature control and fluid Some patients will not have a classical disease. The percentage of patients who go imbalance. The condition may be trig- rash, but factors that may suggest the diag- on to develop plaque psoriasis is unclear, gered by hypocalcaemia, antimalarials, nosis of psoriasis include a positive family but may be as high as 40–50 per cent. coal tar, or withdrawal of systemic ther- history, scaling in the scalp and prominent Patients with chronic plaque psoriasis may apy, especially systemic steroids nail changes. also develop a guttate flare following upper respiratory tract infections. DIAGNOSIS REFERENCES Pustular psoriasis There are two forms of pustular psoriasis: palmar-plantar and gen- eralised. D iagnosis of psoriasis is usually made on clinical examination, although a family history usually leads to suspicion of the dis- 1. Elder JT, Henseler T, Christophers E, Voorhees JJ, Nair RP Of genes and antigens: the inheritance . of psoriasis. J Invest Dermatol ease. The classical clinical picture once seen 1994;103:150S–153S. Palmar-plantar pustulosis Palmar-plantar is readily recognisable. For guttate psoriasis, 2. Nickoloff BJ.The immunologic and genetic basis pustulosis is also known as palmar-plantar there is often a history of a preceding upper of psoriasis. Arch Dermatol pustular psoriasis. It is a localised form of respiratory tract infection. 1999;135:1104–10. psoriasis presenting as sterile pustules of the The following are conditions that may 3. van Erp PEJ, Boezeman JBM, Brons PPT. Cell palms and soles, usually arranged symmetri- cause some diagnostic confusion. cycle kinetics in normal human skin by in vitro cally. This form of psoriasis is extremely rare administration of iododeoxuridine and before adulthood, and may appear de novo Seborrhoeic dermatitis Seborrhoeic dermati- application of a differentiation marker –— or in patients already known to have psoria- tis is quite common and there is no reason implications for cell cycle kinetics in psoriatic sis. There is usually well demarcated why it should not coexist with psoriasis. The skin. Anal Cell Pathol 1996;11:43–54. erythema and scaling, with areas of pustula- lesions in seborrhoeic dermatitis are paler 4. van Ruissen F, de Jongh GJ, van Erp PEJ, tion (see Figure 6, p189). Early pustules are and less well-defined than psoriasis, with a Boezeman JB, Schalkwijk J. Cell kinetic classically creamy-white on an erythematous scale that is rather dull and loose and often characterization of cultured human keratinocytes base. They usually mature to a mid-brown quite greasy. from normal and psoriatic individuals. J Cell colour. The skin of the hands and feet can Physiol 1996;168:684–94. become very thick and crack painfully. Both Eczema In eczema, the pink colour is not as 5. Mease PJ, Goffe BS, Metz J, Vanderstoep A, conditions may be intensely itchy. There deep as in psoriasis, and there is generally a Finck B, Burge DJ. Etanercept in the treatment of appears to be a strong association of pustu- less well-defined edge to lesions and scaling psoriatic arthritis and psoriasis: a randomised lar psoriasis with smoking; up to 95 per cent tends to be much finer. Nail ridges and trial.The Lancet 2000;356:3853–90. of those affected are smokers. occasionally pitting can be seen in severe 6. Terajima S, Higaki M, Igarashi Y, Nogita T, eczema involving the hands, but severe nail Kawashima M. An important role of tumor Generalised pustular psoriasis Generalised dystrophy is unusual. Eczema can be rather necrosis factor-alpha in the induction of pustular psoriasis is a dermatological emer- “psoriasiform” on the legs where it becomes adhesion molecules in psoriasis. Arch Dermatol gency. Sheets of sterile pustules appear, thickened and lichenified secondary to Res 1998;290:246–52. 190 H O S P I TA L P H A R M A C I S T J U L Y /A U G U S T 2002 V O L.9