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Skin lesions in psoriasis
4 Skin lesions in psoriasis MARK
GOODFIELD
Psoriasis is a chronic, relapsing inflammatory disease of the skin and joints (K6bner, 1878). Psoriasis of the skin is a common disorder affecting between 1% and 3% of the population at any time (Hellgren, 1967; R e a e t al, 1976). It is equally common in men and women, occurs at any age (although it is rare before puberty) (Holgate, 1975; Farber and Nail, 1985) and shows certain unexplained geographical variations in prevalence. It is common in all Caucasian races, but is unusual in Africans, where the prevalence is 0.8% (Obasi, 1986) and populations derived from this ethnic group, e.g. American Blacks (Kenney, 1971). It is also uncommon in the indigenous populations of the Far East (Rajan et al, 1982; Yui Yip, 1984) and is almost completely absent from Eskimos (Kavli et al, 1985b) and American Indian populations (Convit, 1962). Some of this variability is determined by genetic factors, with HLA-Cw6, B13 and B17 being strongly associated with early onset of the disease (Batchelor and Morris, 1978; Henseler and Christophers, 1985), and HLACw2 and B27 with late onset of the disease in Caucasian populations. The pattern of inheritance is varied; it is autosomal dominant with variable penetrance in some families (Abele et al, 1963), but almost certainly polygenic in others. Expression is influenced by a number of extraneous and environmental factors. The most important of these are infection, particularly streptococcal throat infection (Whyte and Baugham, 1964) and human immunodeficiencyvirus (HIV) infection (Duvic et al, 1987); drugs, particularly lithium and the antimalarials (Abel et al, 1986); and cutaneous injury due to trauma or another skin disease (Koebner's phenomenon).
HISTOPATHOLOGY (Lever and Lever, 1983) The epidermis is thickened (acanthosis; Figure l(b)), except in the area overlying the dermal papilla, where it may be only one or two cells thick. This alternating thinning and thickening gives a characteristic saw-toothed appearance to the epidermis. There is also patchy parakeratosis of the epidermis, where the abnormally proliferating keratinocytes retain their nuclei. This becomes more prominent with longer established lesions. At the sites of the dermal papillae, neutrophils invade the epidermis (the Bailli&e's Clinical Rheumatology--
Vol. 8, No. 2, May 1994 ISBN 0-70207-1820-1
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squirting papilla), producing small clusters of inflammatory cells and ultimately small 'abscesses' (Munro microabscesses) within the epidermis. There may also be a degree of epidermal oedema (spongiosis) and, in the absence of Munro abscesses, differentiation from seborrhoeic eczema may sometimes be difficult (Pinkus and Mehregan, 1966). The dermis is also invaded by inflammatory cells, but these are usually T cells, at least in the early stages of the lesion. Later, the inflammatory infiltrate is more mixed, mainly neutrophilic, but mast cells increase in number. The early infiltrate is also perivascular in site. The vessels themselves are elongated into the lengthened dermal papillae, and are tortuous and dilated.
(a)
(b) Figure 1. (a) Typicalpsoriatic plaque. (b) Photomicrographof an established psoriatic lesion showing acanthosis, with epidermal thinning above the papillary dermis (H&E, original magnification x 40).
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PATHOGENESIS
Abnormalities are detectable in many of the cell types and structures of the skin. The epidermis is hyperproliferative and differentiation is reduced (Patterson et al, 1984), and this is reflected by keratin profiles (Bowden et al, 1983). A number of biochemical changes have been reported in keratinocytes and dermal fibroblasts, (as reviewed by Fry, 1988), but it still remains likely that these are secondary changes induced by the hyperproliferative state. There is vascular proliferation in and around psoriatic plaques and also, according to Ross (1964), occurring as a prelesional phenomenon in those with the psoriatic tendency. The lesional vascular proliferation is accompanied by an overgrowth of venous endothelial cells (Braverman and Sibley, 1982). With treatment, the epidermal changes reverse first, and the vascular abnormalities regress last (Ragaz and Ackerman, 1979). There is evidence that vascular dilatation and proliferation are very early events in the enlargement of psoriatic plaques, and that this enlargement is directional in the majority of lesions, i.e. plaques increase in size in a particular direction, not by general enlargement in all directions (Macdonald Hull et al, 1989). There has been great interest in the products of arachidonic acid metabolism as leukocyte attractants in psoriasis. Neutrophils are the main cell type in established psoriatic lesions (Lever and Lever, 1983), and their attraction to the site of inflammation was seen as a possible site for therapeutic intervention. Encouraged by the success of benoxaprofen as a treatment for psoriasis (Allen and Littlewood, 1982), research focused on the leukotrienes and, in particular, the product of the enzyme 5-1ipoxygenase (inhibited by benoxaprofen), leukotriene B4 and other related compounds (Brain et al, 1984b; Camp et al, 1985). These are found in psoriatic plaques in biologically active amounts (Brain et al, 1984a) and are probably important in this phase of inflammation. However, it seems clear that neutrophil invasion occurs relatively late in the development of a psoriatic lesion, and interest is focused on the role of T lymphocytes (Baker et al, 1984) and the cytokines involved in their attraction and activation (Nickoloff, 1988). This area of investigation has been greatly stimulated by the finding that cyclosporin A is an effective treatment for the disease (Ellis et al, 1986). Cyclosporin has a number of potent actions on the immune system, including inhibition of T lymphocyte activation and expansion (Bos et al, 1989). Activated T lymphocytes are found in both the dermis and epidermis in plaque lesions (Morhenn et al, 1982). They express HLA-DR antigens on the cell surface, as do plaque keratinocytes (but not normal keratinocytes). HLA-DR expression is induced by interferon ,/, which is produced by activated T cells. Intercellular adhesion molecule 1 is also induced on the keratinocyte surface membrane by interferon, and facilitates the binding of attracted T cells (Bos, 1988). Induction of other adhesion molecules on endothelial cells, and the increased production of cytokines such as transforming growth factor oLby a number of cell types, have been discovered in the psoriatic plaque (Elder et al, 1989). These discoveries slowly piece together the evolution of a psoriatic lesion, but the first change remains elusive, as do the genetic abnormalities that lead to disease susceptibility.
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MORPHOLOGY OF SKIN LESIONS
The typical skin lesion (Figure l(a)) is a well-defined erythematous plaque with a well-marked silvery scale. The colour, often described as 'salmon pink', is characteristic, and it is this, together with the sudden change from normal to abnormal skin, that makes psoriasis easy to recognize in the classical case. The rapid change discernible at a clinical level does not represent the events at a microscopic and microvascular level, where cellular events are graded and often directional. The erythema is quite different from that seen in eczematous conditions, lichenoid reactions or 'erythemas' of other origin. The colour presumably represents the influence of the acanthotic epidermis and the effect of inflammatory cells in the dermis and epidermis on the transmission of light, although this remains speculative. The erythema is lost in coloured skins, where the colour is often more purple.
Figure 2. Flexural psoriasis in the perineum.
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The morphology of the skin lesion is modified by its site. Thus, lesions in flexures lack the silvery scale that is seen at less occluded sites (Figure 2). This is also often true of lesions on the penis. Lesions on the palms and soles are much more hyperkeratotic and thickened (Samitz and Albom, 1951) (Figure 3). As well as this regional variation, there is considerable variability in the appearance of lesions in different patients. The reason for this is unknown. Individual lesions may be apparently non-scaly, although it is usually possible to produce scaling by gentle scratching of the plaque with a fingernail. Similar gentle scraping may produce pin-point bleeding (Auspitz's sign) from the dilated and proliferating blood vessels in the papillary dermis, where there is little protection by the overlying atrophic epidermis. Other lesions (although rarely in the same patient) may be thickly covered in scale--rupioid psoriasis. Similar hyperkeratosis is common in the scalp, where the affected areas may be very closely confined to the hair-bearing skin (Figure 4). In extreme cases the excess keratin may adhere closely to the hair, and 'grow' out with the hair, producing the clinical appearance known as pityriasis amiantacea (Knight, 1977). The clinical picture is not unique to psoriatic scalp disease, but can occur, for example, in seborrhoeic dermatitis of the scalp. Commonly, scalp disease is more minor, with patchy plaque-like disease, although scaling is normally greater here than elsewhere on the body, with the exception of the palms and soles. Very occasionally, scalp disease may be accompanied by hair loss, often at the sites of maximum scaling, and
Figure 3. Hyperkeratoticpsoriasis of the soles of the feet.
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Figure 4. Psoriasisof the scalp affectingthe hair line. often occurring as treatment removes the scale. The scalp underlying these areas of hair loss may be boggy and oedematous, with secondary infection being marked and follicular pustulation occurring. This pustulation may be bacterial in origin, but may also be sterile and a manifestation of the severity of the psoriatic process. Even more rarely, the hair loss may be followed by scarring, with permanent loss of hair follicles and the development of tufted alopecia more commonly seen in skin diseases such as lichen planus (Shuster, 1972). Skin lesions are commonly found on the elbows and knees and in the scalp, but can occur anywhere on the body. Other typical sites are the lower back and at the hair line. Occasionally, lesions may be predominantly flexural in situation (inverse psoriasis) or may be found only on the perineum or genitalia, where the diagnosis is often not made for many years. The size of individual lesions is very variable, ranging from less than 1 mm in early acute psoriasis and in rapidly extending disease, up to 10 cm or more in established plaque-type disease. Small lesional psoriasis is common, and one variant of this clinical picture, guttate psoriasis in which small lesions develop rapidly all over the body, is well known to follow streptococcal infection of the upper respiratory tract (Figure 5). It can rarely be associated with streptococcal glomerulonephritis (Chalmers and Ive, 1982). This explosive type of psoriasis probably occurs as a consequence of crossreaction between streptococcal antigen and certain keratinocyte antigens,
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Figure 5. Guttate psoriasis.
leading to an immunological attack on the skin (Swerlick et al, 1986). Despite the dramatic clinical appearance, the response to treatment of this variety of psoriasis is usually very good. PSORIASIS IN CHILDHOOD
Although psoriasis is uncommon in childhood, all of the typical patterns can occur. Scalp disease and disease of the extremities (nail or fingers) is well recognized (Nyfors, 1981). Napkin psoriasis may be true psoriasis (Rasmussen et al, 1986), but is more often a psoriasiform type of seborrhoeic eczema (Warin and Faulkner, 1961). Follicular psoriasis can occur and must be distinguished from localized pityriasis rubra pilaris. Distinction of psoriasis from a psoriasiform inflammatory linear naevus is made on clinical grounds.
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DIFFERENTIAL DIAGNOSIS
Psoriasis is normally easy to recognise and to distinguish from the main alternatives: discoid eczema for plaque lesions, seborrhoeic eczema for scalp lesions and flexural psoriasis where candidal intertrigo also needs to be considered. In most of these alternatives, the lesions are less well defined and the erythema less striking. Lichen simplex may mimic localized psoriasis, as may the localized plaques of Bowen's disease (intraepidermal squamous carcinoma). Hyperkeratotic eczema of the palms and soles may be impossible to distinguish from psoriasis. Less commonly, lichen planus and pityriasis lichenoides chronica may have certain psoriasiform features, but the rather shiny purple erythema of lichen planus and the characteristics of pityriasiform scale (centrally placed) usually allow the correct diagnosis to be made. PROGNOSIS OF CHRONIC PLAQUE PSORIASIS
There is no cure for psoriasis of the skin (Church, 1958). As many as 40% of affected individuals may achieve complete remission (Farber and Nall, 1974), although this seems high for a hospital population. The majority of patients respond to simple therapies, and clearance of the skin is often achieved. Remission is variable in duration, but can last for years after a single episode of treatment, although it is more often short lived (Durham and Morgan, 1974). The use of systemic therapy (cytotoxic drugs or photochemotherapy) can keep patients clear of cutaneous psoriasis, but at the risk of drug-related side-effects. ERYTHRODERMIC AND PUSTULAR PSORIASIS
In any type of psoriasis, severe attacks may occur in which generalized plaque lesions rapidly extend, become more inflammatory and lead to erythrodermic psoriasis. The majority of the skin surface becomes inflamed and unstable. Such severe psoriasis can occur as the initial manifestation of the disease, and then diagnosis can be impossible either clinically or histopathologically until the skin begins to settle and more typical lesions appear. Patients with this variety of psoriasis are severely unwell, and have considerable problems with thermoregulation (Grice et al, 1968) and occasionally malabsorption (Marks, 1982). They require in-patient care and great expertise in management. If uncontrolled, such skin may become pustular due to the severity of the inflammatory process, and in the past patients died from this rare complication of this common disease. In the most severe forms of psoriasis, generalized pustular psoriasis (von Zumbusch) may occur. Sheets of sterile micropustules occur on a background of very inflammatory or erythrodermic psoriasis (Figure 6) in a very ill patient. Micropustules amalgamate to form 'lakes of pus', a very dramatic physical sign. This is most often encountered after the inappropriate use of topical steroids for worsening disease following the withdrawal of systemic
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Figure 6. Generalized pustular psoriasis.
steroids, or after the use of irritant therapies on inflamed psoriasis (Baker and Ryan, 1968). Infection and severe fluid loss due to hypoalbuminuria are the main complications of this type of psoriasis, and fatal complications of acute hypovolaemia may occur (Baker and Ryan, 1968). Treatment needs to be supportive and intense, as well as aiming at the underlying psoriasis. PUSTULAR PSORIASIS OF THE PALMS AND SOLES (Figure 7) More localized pustular lesions occur in the well-defined clinical entity of pustulosis of the palms of the hands and soles of the feet (Baker, 1984). This occurs in about 1% of the population, is more common in women of middle age, and is very unusual in non-smokers (O'Docherty, 1984). There may be an association with HLA-B8 (Thomsen and Osterbye, 1973). The condition
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is usually bilateral in presentation, but may be unilateral at onset, and can affect the palms of the hand, the soles of the feet, or both. It is characterized by a degree of hyperkeratosis and scaling, within which small (1-2 mm) pustules occur. These are sterile and resolve spontaneously, leaving brown papules that are slowly shed, only to be replaced by a new crop of lesions. The affected areas are itchy, tend to enlarge, and rarely settle spontaneously. The onset of the disease, and its progression, are largely uninfluenced by stress, infection or climate, and differ from typical psoriasis in this respect. The role of cigarette smoking is unclear, but there does appear to be a genuine relationship between the occurrence of the disease and smoking behaviour. Acrodermatitis continua is a form of localized pustular psoriasis affecting the fingertips and nails, and is particularly debilitating and difficult to treat. The differential diagnosis of pustular psoriasis includes infective pustulation usually due to staphylococci, often on a background of eczema,
Figure 7. Pustularpsoriasis of the sole of the foot.
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pustular variants of drug eruptions and Reiter's disease, although this distinction is semantic (Wright and Reed, 1964). Again, there is no cure for this variety of psoriasis, but control is normally possible with combinations of topical and systemic therapy, including photochemotherapy with psoralen and ultraviolet (UV) A (PUVA). NAIL DISEASE IN PSORIASIS The nail apparatus is commonly involved in psoriasis. Indeed, at least 25% of psoriatic patients have some involvement of the nails (Zaias, 1969). Nail matrix involvement produces the characteristic pitting of the nail, while nail-bed involvement produces onycholysis (in which the nail separates from the underlying nail bed) or subungual hyperkeratosis (Robbins et al, 1983). Localized nail-bed disease can also produce the 'oil drop sign' where a patch of browny yellow discoloration is seen in the central portion of the nail (Kouskoukis et al, 1983). Nail disruption can be the only manifestation of psoriatic skin disease, and should be sought in all patients suspected of having the condition. It can also be very severe, with gross thickening and destruction of the nail. This has considerable functional importance to affected patients, since nails are essential for the protection of the fingers and toes, and also for the fine function of the fingers. Involvement of the nail in pustular psoriasis can be particularly severe (Figure 8). It is important to exclude fungal nail disease in patients with nail dystrophy. This can occur as a primary infection, but any mould infection can occur as a secondary problem in nails made abnormal by psoriasis.
Figure 8. Acrodermatitis continua with nail involvement.
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Alternative causes of nail pathology include traumatic nail dystrophies and lichen planus, but, in the absence of typical cutaneous psoriasis, diagnosis may be impossible without nail matrix biopsy. THE INTER-RELATIONSHIP OF SKIN AND JOINT DISEASE
While there is no evidence that the pathogenesis of skin and joint disease in psoriasis is the same, it is clear that there is a relationship between the severity of skin disease and the occurrence or severity of joint disease in patients with psoriasis. Reported prevalence rates for joint disease in those with cutaneous disease have been between 6% for hospitalized psoriatic patients (Leczinsky, 1948) and 20% for patients having PUVA for their skin disease (Stern, 1985). It is recognized that the more severe the cutaneous disease, the greater the risk of associated arthropathy (Little et al, 1975), so these prevalence rates are likely to be overestimates. Of course, it is possible to have severe skin disease with no element of arthropathy, and equally to have severe joint disease without any skin disease, although, in the latter case, the diagnosis of psoriasis is unlikely to be definite since it is usually the skin pathology that is diagnostic. It is certainly possible to have even mutilating joint disease with only minimal skin involvement. Apart from a striking association with pustular and erythrodermic psoriasis of the skin (Baker et al, 1963), the type of skin involvement is unrelated to the incidence and type of joint disease. In the case of pustular skin disease, the relationship appears to hold true for both generalized (Baker and Ryan, 1968) and localized disease (Baker et al, 1963). It is generally accepted that the skin lesions of pustular psoriasis and those of keratoderma blenorrhagica are identical (Camp, 1992). NAIL DISEASE AND JOINT DISEASE Nail disease may be more common in patients with joint disease than in those without. Approximately twice as many patients with joint disease due to psoriasis may have nail disease than patients with skin disease alone (Baker et al, 1964; Scarpa et al, 1984). This is disputed, however, and some authors believe that as many as 90% of patients with psoriatic skin disease have nail involvement at some time in the course of their disease, regardless of whether they have had arthropathy (Samman, 1978). The type of nail disease reflects the site of inflammation within the nail apparatus, with pits reflecting dorsal matrix disease (Baran and Dawber, 1984). There does not appear to be any association between joint disease and the severity of nail disease. There is also dispute about the relationship between the type of arthropathy and nail involvement. Baker and Ryan (1968) found that patients with more severe joint disease had a greater incidence of nail disease, regardless of the site of joint involvement, whereas Wright (1979) found that those with distal joint disease inevitably had nail involvement.
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It is possible that nail disease produces the ragged appearance of the distal phalanx seen in some patients through a deep Koebner phenomenon (Mahowald and Parrish, 1982). It seems more likely that distal joint disease influences nail behaviour through a shared blood supply (Abel and Farber, 1979). It is well described that abnormalities of the peripheral circulation can disturb nail growth and structure, e.g. in acrocyanosis or Raynaud's phenomenon (Fenton and Wilkinson, 1984). Such a relationship would also require the existence of Koebner's phenomenon to explain the morphology of the nail lesions, since those seen in other abnormalities of the circulation are not psoriatic in nature. Acro-osteolysis is a severe example of such distal bone disease, but this tuft osteolysis has been described without nail disease (Cheesbrough, 1979), raising the possibility that only those two thirds of patients able to produce a Koebner reaction develop nail problems in this way. In summary, severity of skin disease does relate to the frequency of arthritis, although not to its severity. Only pustular and erythrodermic psoriasis are specifically related to joint problems. Nail disease is Very common in all patients with psoriasis, but does seem to be specifically related to those with distal joint disease. The cause of this relationship is unclear. MANAGEMENT General measures
Although therapy for psoriasis has improved markedly in recent times, the general approach has not changed for many years (Ingrain, 1954). The majority of patients with psoriasis can be managed at home. Their general health should be attended to, and the effect of the disease on their health, life-style and emotional state should be documented. The psoriasis disability index is one simple way of measuring this. A full discussion of the disease and its implications should help the patient to understand and comply with treatment, and to be positive about the outlook. Anxiety and stress should be minimized. In severe disease, when out-patient management has failed, in-patient care is appropriate, preferably in a dedicated dermatology unit with specialist nursing. Topical therapy
For straightforward plaque-type psoriasis, treatment consists of topical agents applied directly to the affected areas of skin. For limited or very inflamed disease, simple emollients are valuable, but these have no particular antipsoriatic effect. However, several other topical agents are useful, being more or less specific for the disease. Anthralin (dithranol) is the only truly specific antipsoriatic therapy, and is applied to the affected skin as precisely as possible. It is left in place for periods varying for 15 rain to 24 h; short-term application is very effective and much more convenient than longer applications (Macdonald and Marks, 1986). The active agent can be delivered to
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the skin in a number of bases, although Lassar's paste (a combination of zinc oxide and salicylic acid which helps to stabilize the anthralin) and a cream base are the most commonly used (Whitefield, 1981). The concentration of anthralin is gradually increased, depending on the patient's response and the degree of irritation produced; irritation is the major side-effect of anthralin treatment. Staining of the skin occurs, but is temporary. Staining of clothes and baths also occurs and is permanent. Used in combination with tar baths and graded UVB exposure (the Ingram regimen), anthralin will clear the majority of patients in about 6 weeks of treatment as an out-patient, and in about half that time as an in-patient. The mode of action of anthralin is unclear.
Tar preparations Coal tar preparations are less specific treatments for psoriasis, but in many units are the first line of treatment, giving clearance rates similar to those of anthralin. Again, there is a choice of base for delivery of the drug, but an ointment containing tar and salicylic acid in various combinations is commonly used, particularly on the scalp. Increasing concentrations of coal tar in Lassar's paste are a useful remedy, traditionally in conjunction with UVB exposure (the Goekermann regimen). There is some doubt about the additional benefit of the UVB exposure (Comaish, 1981). Tar preparations are messy to use, but attempts to make them more acceptable by using a cream base also result in considerable loss of efficacy. Tar shampoos are the first-line treatment for mild scalp disease, while paste preparations are particularly successful for localized pustular psoriasis. Tar preparations are probably antimitotic, but it is not clear whether this is the mode of action in psoriasis (Fisher and Maibach, 1973). Fish tar (ichthamol) is also effective in psoriasis, although less so than coal tar. It is often used on patients with inflammatory psoriasis in combination with eosin, an old-fashioned, but none the less effective, combination that can be used as an intermediate between simple emollients and more active treatment in those with very inflamed skin.
Topical steroids Topical steroids have a role in psoriasis of the flexures, face and hands where other treatments are too irritating or a rapid response is needed. Prolonged or widespread use of topical steroids, particularly powerful fluorinated ones (e.g. Betnovate), is to be avoided because of the problems of tachyphylaxis and the production of unstable and pustular psoriasis (Baker, 1976). A steroid cream application under occlusion provided by a swimming cap is useful for severely affected and crusty scalps as a rapid way of descaling the area.
Calcipotriol The latest addition to the topical remedies for psoriasis is the vitamin D
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analogue, calcipotriol. This compound was designed after it was reported that vitamin D compounds used orally (Morimoto et al, 1986) were of value in plaque psoriasis. Used topically (Van der Kerkhof et al, 1989), the naturally occurring vitamin produced little benefit. Calcipotriol is much more potent in its cutaneous effects, and has already proved of great benefit in patients with stable plaque psoriasis (Kragballe et al, 1988). It has a number of effects on keratinocytes, fibroblasts and as an immunomodulator, and it is not clear which, if any, is its major action in psoriasis (Kragballe, 1988). About 70% of patients respond to it satisfactorily, without gaining complete clearance of their disease in the majority of cases.
Ultraviolet therapy Exposure to UVB forms a part of all of the major out-patient regimens for the treatment of psoriasis, and is effective when used alone (LeVine and Parrish, 1980). It is not as effective as natural sunlight in the majority of patients, and some question its value when used as combination therapy (Comaish, 1981). UVA is much less powerful in its effects than UVB. When used alone, long exposures of UVA are necessary to produce any significant effect.
Photochemotherapy (PUVA) The combination of a photosensitizing agent (psoralen) with short exposures of UVA (PUVA) is a very effective therapy for those patients resistant to simple topical measures (Melski et al, 1977). This form of treatment has been in wide use around the world since the mid 1970s and has been a great help to many sufferers. The psoralen is usually given by mouth (8- or 5-methoxypsoralen), but can also be used topically to small areas of psoriasis, or in a bath as an alternative to oral treatment. To reduce the danger of cataract, the eyes must be protected by wearing appropriately filtering sunglasses for 24 h after taking psoralen tablets. Acute toxicity consists of burning due to overexposure to UV, or nausea due to the tablets (Farber et al, 1983). In the long term there is a definite risk of non-melanoma skin cancer, particularly squamous cell lesions, which has to be balanced against the benefit of treatment to the patient. Previous exposure to cytotoxic therapies increases the level of this risk considerably. The incidence of melanoma may also be increased (Henseler et al, 1987).
Systemic therapy Patients with extensive psoriasis resistant to both topical treatments and phototherapy need systemic treatment, and there are a number of agents that may be of value. Retinoids
Derivatives of vitamin A have been available for the treatment of psoriasis,
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amongst other conditions, since the 1970s. Until the present time, etretinate has been the retinoid most widely studied and used in psoriasis. It may be of value in chronic plaque, erythrodermic or pustular psoriasis when used in doses of around 1 mg per kg body-weight and, in the latter two conditions, the response is often rapid (Lowe et al, 1988). Side-effects are common, with dryness of skin and mucous membranes being almost inevitable and dose related. Abnormalities of serum lipids are common, while hepatotoxicity is rare. More significantly, skeletal abnormalities may occur, with hyperostosis, ossification of interosseous membranes and premature fusion of epiphyses in children, and should be screened for (Gerber et al, 1984). Retinoids are also teratogenic and, since the compounds are strongly lipid soluble, traces persist in the body for up to 2 years after discontinuing therapy. Pregnancy must therefore be avoided for this time after stopping therapy. Etretinate has been used in conjunction with PUVA in an attempt to reduce the amount of UV exposure needed to clear the disease. This may occur, but is still disputed (Parker et al, 1984). The immediate metabolite of etretinate, acetretin, is as active as the parent compound and is now available in the UK and elsewhere in the world (Gollnik et al, 1988). It is intended that it will replace etretinate in the treatment of psoriasis during 1994. Methotrexate
The dihydrofolate reductase inhibitor, methotrexate, has an established role in the management of severe psoriasis (Baker, 1970). It is given as a weekly dose, either by mouth or by intramuscular or intravenous injection, after an initial test dose of 2.5 mg. Dosages range from 2.5 to 25 mg weekly, depending on age, size, renal function and response. Care must be taken with concomitant medication which may enhance blood levels of the drug, either by displacement from protein binding (Roenigk et al, 1988) or by reduced excretion (Nierenberg and Mamelok, 1983). Maximal response occurs over about 4 weeks, and therapy may need to be continued permanently, although some patients are able to stop the drug once their psoriasis is controlled. Immediate toxicity consists of gastrointestinal upset and bone marrow suppression; in the longer term, hepatic fibrosis, cirrhosis and liver failure can occur (Roenigk et al, 1988). Hepatic toxicity is commoner in the obese, diabetics and consumers of alcohol, and caution should be exercised in all such patients (Miller et al, 1985). High alcohol intake is relatively common amongst psoriatics, although whether this precedes or follows the onset of the disease is unclear (Monk and Neill, 1986). The incidence of liver problems appears to be higher in psoriatics than in other groups of patients treated with methotrexate. The need for regular liver biopsy in patients treated with this drug continues to be debated, although the accuracy of other diagnostic techniques such as radio-isotope scanning or ultrasonography is not generally believed to be sufficient to replace liver biopsy in those thought to be at risk (Coulson et al, 1987). The American Association of Dermatology has specific guidelines dealing with the timing of liver
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biopsy, and recommends investigation after stabilization on the drug, after the first 1.5 g, and at intervals of i g thereafter (Roenigk et al, 1988). Pulmonary fibrosis can also occur in psoriatic patients on methotrexate, and regular chest radiography is advisable (Verdich and Christensen, 1979).
Hydroxyurea (Layton et al, 1989) Hydroxyurea interferes with the enzyme ribonucleoside diphosphate reductase, and it is possible that this cytotoxic action is responsible for the success of the drug in psoriasis. Oral doses up to 1.5 g daily are given, and are helpful in patients with difficult psoriasis. Response is slow and marrow toxicity is more common than with methotrexate, but recovery always occurs provided the drug is stopped promptly. Compared with methotrexate, gastrointestinal upset or liver damage is much less common, but hyperpigmentation, actinic psoriasis and a drug-induced autoimmune diathesesis with the lupus anticoagulant have all been described (Layton et al, 1989).
Cyclosporin A This immunosuppressive agent has been increasingly used in psoriasis since 1984. It is effective and relatively safe in therapy-resistant disease in the majority of patients when used in doses up to 5 mg per kg body-weight (Van Joost et al, 1988). Above this dose, the incidence of renal toxicity and hypertension becomes unacceptably high, and high dosages should be avoided (Mihatsch and Wolff, 1990). Guidelines for use of cyclosporin A in psoriasis have recently been produced. As with all cytotoxic agents, relapse after stopping treatment is inevitable but, with cyclosporin at least, the rate of relapse is no higher than after topical treatment with dithranol (Higgins et al, 1992).
Systemic steroids For cutaneous disease in psoriasis, the only role for systemic, as opposed to topical, steroid therapy is in patients with life-threatening erythrodermic or pustular psoriasis. In this situation, other treatments may take some time to work, and the patient may require the rapid effect of oral steroid, whilst the slower-acting drugs protect from the problem of rebound or exacerbation of pustulation that can be induced by steroid therapy. In all other situations, oral steroids are best avoided (Champion, 1966). The potential danger of steroid exacerbation of psoriasis needs to be considered when steroids are used to treat joint disease. Relatively minor cutaneous disease can rapidly become unstable and difficult to treat, and this complication must be anticipated and dealt with quickly when it occurs. Other treatments
A number of other agents, including occlusive therapy with various occlusive
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agents e.g. hydrocolloid dressings (Friedman, 1987), sulphasalazine (Gupta et al, 1989a), topical and oral vitamin D (Morimoto et al, 1986), fish oils (Gupta et al, 1989b), antibiotics (Rosenberg et al, 1986), benoxaprofen (Allen and Littlewood, 1982) and razoxane (Horton and Wells, 1983)--the latter two are now unavailable--have all been reported to have a role in the management of psoriasis. Those still available may be useful when all the above measures have failed. SUMMARY
Psoriatic skin disease is common; it occurs at all ages and co-exists with joint disease in approximately 10% of cases. All areas of skin, scalp and nails may be involved. In the typical case, the skin lesions are easy to recognize. Atypical forms of skin involvement and lesions at unusual sites are less easily diagnosed by non-specialists. The cause is unknown, but there is a clear genetic element, with external factors being important in precipitation and exacerbations of the condition. Topical treatment is successful in most patients, hut in resistant cases combinations of systemic therapy and ultraviolet radiation usually give good control. Although there is no cure, the majority of sufferers live normal lives and, with the exception of severe erythrodermic or generalized pustular psoriasis, there is no mortality. Morbidity, particularly social and occupational, is more of a problem than is often acknowledged. REFERENCES Abel E & Farber EM (1979) Psoriasis. In Dennis DJ, Dobson RL & McGuire J (eds) Clinical Dermatology, vol. 1, pp 150-155. Philadelphia: Harper Medical. Abel EA, DiCicco LM, Orenberg EK et al (1986) Drugs in exacerbation of psoriasis. Journalof the American Academy of Dermatology 15: 1007-1022. Abele DC, Dobson RL & Graham JB (1963) Heredity and psoriasis. Archives of Dermatology 88: 38-47. Allen BR & Littlewood SM (1982) Benoxaprofen: effect on cutaneous lesions in psoriasis. British Medical Journal 285: 1241. Baker BS, Swain AF, Fry Let al (1984) Epidermal T lymphocytes and HLA-DR expression in psoriasis. British Journal of Dermatology 110: 555-564. Baker H (1970) Intermittent high dose oral methotrexate therapy in psoriasis. British Journal of Dermatology 82: 65-69. Baker H (1976) Corticosteroids and pustular psoriasis. British Journal of Dermatology 94 (supplement 12): 83-88. Baker H & Ryan TJ (1968) Generalised pustular psoriasis. British Journal of Dermatology 80: 771-793. Baker H, Golding DN & Thompson M (1963) Psoriasis and arthritis. Annals of Internal Medicine 58: 909-925. Baker H, Golding DN & Thompson M (1964) The nails in psoriatic arthritis. British Journal of Dermatology 76: 549-554. Baran R & Dawber RPR (1984) The nail in dermatological diseases. In Baran R & Dawber RPR (eds) Diseases of the Nails and their Management, pp 157-203. Oxford: Blackwell Scientific Publications. Barker H (1984) Pustular psoriasis. Dermatology Clinics 2" 455-470. Batchelor JR & Morris PJ (1978) HLA and disease--joint report. In Bodmer WF, Batchelor
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JR, Bodmer JG et al (eds) Histocompatibility Testing 1977, pp 205-258. Copenhagen: Munksgaard. Bos JD (1988) The pathomechanisms of psoriasis; the skin immune system and cyclosporin. British Journal of Dermatology 118: 141-155. Bos JD, Meinardi MMHM, van Joost T et al (1989) Use of cyclosporin in psoriasis. Lancet ii: 1500-1502. Bowden PE, Wood EJ & Cunliffe WJ (1983) Comparison of prekeratin and keratin polypeptides in normal and psoriatic human epidermis. Biochemica et Biophysica Acta 743: 172-179. Brain S, Camp R, Dowd P e t al (1984a) The release of leukotriene B4 like material in biologically active amounts from the skin lesions of patients with psoriasis. Journal of Investigative Dermatology 83: 70-73. Brain SD, Camp RDR, Cunningham FM et al (1984b) Leukotriene B4-1ike material in scale of psoriatic lesions. British Journal of Pharmacology 83: 313-317. Braverman IM & Sibley J (1982) Role of the microcirculation in the treatment and pathogenesis of psoriasis. Journal oflnvestigative Dermatology 78: 12-17. Camp RDR (1992) Psoriasis. In Champion RH, Burton JL & Ebling FJG (eds) Textbook of Dermatology, vol. 5, pp 1391-1457. Oxford: Blackwell Scientific Publications. Camp RDR, Mallett AI, Cunningham FM et al (1985) The role of chemoattractant lipoxygenase products in the pathogenesis of psoriasis. British Journal of Dermatology 113 (supplement 28): 98-103. Chalmers RJG &Ive FA (1982) Is acute guttate psoriasis with renal disease a rarity? Archives of Dermatology 118:141 (letter). Champion RH (1966) Treatment of psoriasis. British Medical Journal ii: 993-996. Cheesbrough MJ (1979) Osteolysis and psoriasis. Clinical and Experimental Dermatology 4: 341-344. Church R (1958) The prospect of psoriasis. British Journal of Dermatology 70: 139-145. Comaish JS (1981) Tar and related compounds in the therapy of psoriasis. Clinical and Experimental Dermatology 6: 639-645. Convit J (1962) Investigation of the incidence of psoriasis among Latin American Indians. In Proceedings of the XII Congress of Dermatology, p 196. Amsterdam: Exerpta Medica Foundation. Coulson IH, McKenzie J, Neild VS et al (1987) A comparison of liver ultrasound with liver biopsy histology in patients receiving long-term methotrexate therapy. British Journal of Dermatology 116: 491-495. Durham GA & Morgan JK (1974) A 7-year follow-up study of ninety patients with psoriasis. British Journal of Dermatology 91: 7-11. Duvic M, Johnson TM, Rapini RP et al (1987) Acquired immunodeficiency syndromeassociated psoriasis and Reiter's syndrome. Archives of Dermatology 123: 1622-1632. Elder JT, Fisher GJ, Lindquist PB et al (1989) Overexpression of transforming growth factor alpha in psoriatic epidermis. Science 243: 811-814. Ellis CN, Gorsulowski DC & Hamilton TA (1986) Cyclosporin improves psoriasis in a double blind study. Journal of the American Medical Association 256: 3110-3116. Farber EM & Nall ML (1974) The natural history of psoriasis in 5600 patients. Dermatologica 148: 1-18. Farber EM & Nail ML (1985) Epidemiology: natural history and genetics. In Roenigk HH & Maibach HI (eds) Psoriasis, pp 141-186. New York: Marcel Dekker. Farber EM, Abel EA & Cox AJ (1983) Long term risks of psoralen and UV-A therapy for psoriasis. Archives of Dermatology 119: 421-431. Fenton DA & Wilkinson JD (1984) The nail in systemic diseases and drug induced changes. In Baran R & Dawber RPR (eds) Diseases of the Nails and their Management, pp 205-265. Oxford: Blackwell Scientific Publications. Finlay AY, Khan GK, Luscombe DK & Salek MS (1990) Validation of sickness impact profiles and psoriasis disability index in psoriasis. British Journal of Dermatology 123: 751-756. Fisher LB & Maibach HI (1973) Topical antipsoriatic agents and epidermal mitoses in man. Archives of Dermatology 108: 374-377. Friedman SJ (1987) Management of psoriasis vulgaris with a hydrocolloid occlusion dressing. Archives of Dermatology 123: 1046-1052.
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Fry L (1988) Psoriasis. British Journal of Dermatology 119: 445-461. Gerber LH, Helfgott RK, Gross EG et al (1984) Vertebral abnormalities associated with synthetic retinoid use. Journal of the American Academy of Dermatology 10: 817-823. Gollnik H, Bauer R, Brindley C et al (1988) Acitretin versus etretinate in psoriasis. Journal of the American Academy of Dermatology 19: 458-469. Grice K, Blendis LM, Keir MI et al (1968) Accidental hypothermia in erythroderma from generalized psoriasis. Archives of Dermatology 98: 263-267. Gupta AK, Ellis CN, Siegel MT et al (1989a) Sulfasalazine: a potential psoriasis therapy? Journal of the American Academy of Dermatology 20: 79%800. Gupta AK, Ellis CN, Tellner DC et al (1989b) Double blind placebo controlled study to evaluate the efficacy of fish oil and low dose UVB in the treatment of psoriasis. British Journal of Dermatology 120: 801-807. Hellgren L (ed.) (1967) Psoriasis. The Prevalence in Sex, Age and Occupational Groups in Total
Populations in Sweden. Morphology, Inheritance and Association with other Skin and Rheumatic Diseases. pp 55-63. Stockholm: Almqvist & Wiksell. Henseler T & Christophers E (1985) Psoriasis of early and late onset: characterisation of two types of psoriasis vulgaris. Journal of the American Academy of Dermatology 13: 450-456. Henseler T, Christophers E, Honigsmann H et al (1987) Skin tumours in the European PUVA study. Journal of the American Academy of Dermatology 16: 108-116. Higgins E, Munro C, Marks J e t al (1992) Relapse rates in moderately severe chronic psoriasis treated with Cyclosporin A. British Journal of Dermatology 121: 71-74. Holgate MC (1975) The age-of-onset of psoriasis and the relationship to parental psoriasis. British Journal of Dermatology 92: 443-448. Horton JJ & Wells RS (1983) Razoxane: a review of 6 years' therapy in psoriasis. British Journal of Dermatology 109: 669-673. Ingram JT (1954) The significance and management of psoriasis. British Medical Journal ii: 823-828. Kavli G, Stenvold SE & Vandbakk O (1985) Low prevalence of psoriasis in Norwegian Lapps. Acta Dermato-Venereologica 65: 262-263. Kenney JA (1971) Psoriasis in the American black. In Farber EM & Cox AJ (eds) Psoriasis. Proceedings of the 1st International Symposium, pp 49-52. Stanford: Stanford University Press. Knight AG (1977) Pityriasis amiantacea: a clinical and histopathological investigation. Clinical and Experimental Dermatology 2: 137-143. K6bner H (1878) Klinische, experimentelle und therapeutische Mitteilungen uber Psoriasis. Berlin Klin Wochenschr 21: 631-632. Kouskoukis CE, Scher RK & Ackerman AB (1983) The 'oil drops' sign of psoriatic nails. A clinical finding specific for psoriasis. American Journal of Dermatopathology 5: 259-262. Kragballe K, Beck HI & Sogaard H (1988) Improvement of psoriasis by a topical vitamin D3 analogue (MC903) in a double blind study. British Journal of Dermatology 119: 223-230. Layton AM, Sheehan-Dare RA, Goodfield MJD et al (1989) Hydroxyurea in the management of therapy resistant psoriasis. British Journal of Dermatology 121: 647-653. Leczinsky CG (1948) The incidence of arthropathy in a ten year series of psoriasis cases. Acta Dermato-Venereologica 28: 483-487. Lever WF & Lever GS (eds) (1983) Histopathology of the skin, 6th edn. Philadelphia: Lippincott. LeVine MJ & Parrish JA (1980) Outpatient phototherapy of psoriasis. Archives of Dermatology 116: 552-554. Little M, Harvie JN & Lester RS (1975) Psoriatic arthritis in severe psoriasis. Canadian Medical Association Journal 112: 317-319. Lowe NJ, Lazarus V & Matt L (1988) Systemic retinoid therapy for psoriasis. Journal of the American Academy of Dermatology 19: 186-191. Macdonald ICIS & Marks J (1986) Short contact anthralin in the treatment of psoriasis: a study of different contact times. British Journal of Dermatology 114: 235-239. Macdonald Hull S, Goodfield M, Wood EJ & Cunliffe WJ (1989) Active and inactive edges of psoriatic plaques: identification by tracing and investigation by laser-Doppler flowmetry and immunocytochemical techniques. Journal oflnvestigative Dermatology 92: 782-785. Mahowald WL & Parrish RM (1982) Severe osteolytic arthritis in pustular psoriasis. Archives of Dermatology 118: 434-438.
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Marks J (1982) Erythroderma and its management. Clinical and Experimental Dermatology 7: 415-422. Melski JW, Tanenbaum L, Parrish JA et al (1977) Oral methoxsalen photochemotherapy for the treatment of psoriasis. Journal oflnvestigative Dermatology 68: 328-335. Mihatsch MJ & Wolff K (1990) Risk benefit ratios of cyclosporin A in psoriasis. British Journal of Dermatology 122 (supplement 36): 1-30. Miller JA, Dodd H, Rustin MHA et al (1985) Ultrasound as a screening procedure for methotrexate induced hepatic damage in severe psoriasis. British Journal of Dermatology 113: 699-705. Monk BE & Neill SM (1986) Alcohol consumption and psoriasis. Dermatologica 173: 57-60. Morhenn VB, Abel E A & Mahrle G (1982) Expression of HLA-DR antigen in skin from patients with psoriasis. Journal of Investigative Dermatology 78: 165-168. Morimoto S, Yoshikawa K, Kozuka T et al (1986) An open study of vitamin D3 treatment in psoriasis vulgaris. British Journal of Dermatology 115: 421-429. Nickoloff BJ (1988) Role of interferon-gamma in cutaneous trafficking of lymphocytes with emphasis on molecular and cellular adhesion events. Archives of Dermatology 124: 18351843. Nierenberg DW & Mamelok RD (1983) Toxic reaction to methotrexate in a patient receiving penicillin and frusemide. Archives of Dermatology 119: 449-450. Nyfors A (1981) Psoriasis in children. Acta Dermato-Venereologica 61 (supplement 95): 47-53. Obasi OE (1986) Psoriasis vulgaris in the Guinea Savannah region of Nigeria. International Journal of Dermatology 25: 181-183. O'Doherty CJ & Macintyre C (1985) Palmoplantar pustulosis and smoking. British Medical Journal 291: 861-864. Parker S, Coburn P, Lawrence C et al (1984) A randomised double blind comparison of PUVA-etretinate and PUVA-placebo in the treatment of chronic plaque psoriasis. British Journal of Dermatology 110: 215-220. Patterson JAK, Eisinger M, Haynes BF, Berger CL & Edelson RL (1984) Monoclonal antibody 4F2 reactive with basal layer keratinocytes: studies in the normal and a hyperproliferative state. Journal oflnvestigative Dermatology 83: 210-213. Pinkus H & Mehregan AH (1966) The primary histologie lesion of seborrhoeic dermatitis and psoriasis. Journal of lnvestigative Dermatology 46: 109-115. Ragaz A & Ackerman AB (1979) Evolution, maturation and regression of lesions of psoriasis. American Journal of Dermatopathology 1: 199-214. Rajan VS, Thiru Moorthy T, Giam YC et al (1982) Psoriasis: the Singapore experience. In Farber FM, Cox AJ, Nail L & Jaeobs PH (eds) Psoriasis, Proceedings of the 3rd International Symposium, pp 407-408. New York: Grnne and Stratton. Rasmussen HB, Haydrup H & Schmidt H (1986) Psoriasiform napkin dermatitis. Acta Dermato-Venereologica 66: 534-536. Rea JN, Newhouse ML & Halil T (1976) Skin disease in Lambeth. British Journal of Preventive and Social Medicine 30: 107-114. Robbins TO, Kouskoukis CE & Ackerman AB (1983) Onycholysis in psoriatic nails. American Journal of Dermatopathology 5: 39-41. Roenigk HH, Auerbach R, Maibaeh H et al (1988) Methotrexate in psoriasis: revised guidelines. Journal of the American Academy of Derrnatology 19: 145-146. Rosenberg EW, Noah PW, Zanolli MD et al (1986) Use of rifampiein with penicillin and erythromycin in the treatment of psoriasis. Journal of the American Academy of Dermatology 14: 761-764. Ross JB (1964) The psoriatic capillary. Its nature and value in the identification of the unaffected psoriatic. British Journal of Dermatology 76: 511-518. Samitz MH & Albom JJ (1951) Palmar psoriasis. Archives of Dermatology and Syphilology 64: 199-204. Samman PD (1978) (ed.) The Nails in Disease, 3rd edn. London: Heinemann. Scarpa R, Oriente P, Pueino A et al (1984) Psoriatic arthritis in psoriatic patients. British Journal of Rheumatology 23: 246-250. Shuster S (1972) Psoriatic alopecia. British Journal of Dermatology 87: 73-77. Stern RS (1985) The epidemiology of joint complaints in patients with psoriasis. Journal of Rheumatology 12: 315-320. Swerlick RA, Cunningham MW & Hall NK (1986) Monoclonal antibodies cross-reactive with
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group A streptococci and normal and psoriatic human skin. Journal of Investigative Dermatology 87: 367-371. Thornsen K & Osterbye P (1973) Pustulosis palmaris et plantaris. British Journal of Dermatology 89: 293-296. Van Joost T, Bos JD, Heule F et al (1988) Low dose cyclosporin A in severe psoriasis: a double blind study. British Journal of Dermatology 118: 183-190. Van de Kerkhof PCM, Van Bokhaven M, Zultak Met al (1989) A double blind study of topical 1 ct 25-dihydroxyvitamin D3 in psoriasis. British Journal of Dermatology 120: 661-664. Verdich J & Christensen AL (1979) Pulmonary disease complicating intermittent methotrexate therapy of psoriasis. Acta Dermato-Venereologica 59: 471-473. Warin RP & Faulkner KE (1961) Napkin psoriasis. British Journal of Dermatology 773: 445-447. Whitefield M (1981) Pharmaceutical formulations of anthralin. British Journal of Dermatology 105 (supplement 20): 28-32. Whyte HJ & Baugham RD (1964) Acute guttate psoriasis and streptococcal infection. Archives of Dermatology 89: 350-356. Wright V & Reed WB (1964) The link between Reiter's syndrome and psoriatic arthritis. Annals of the Rheumatic Diseases 23: 12-21. Wright V, Roberts MC & Hill AGS (1979) Dermatological manifestations in psoriatic arthritis. A follow up study. Acta Dermato-Venereologica 59: 235-240. Yui Yip S (1984) The prevalence of psoriasis in the mongoloid race. Journal of the American Academy of Dermatology 10: 965-968. Zaias N (1969) Psoriasis of the nail. Archives of Dermatology 99: 567-579.
GOODFIELD
Psoriasis is a chronic, relapsing inflammatory disease of the skin and joints (K6bner, 1878). Psoriasis of the skin is a common disorder affecting between 1% and 3% of the population at any time (Hellgren, 1967; R e a e t al, 1976). It is equally common in men and women, occurs at any age (although it is rare before puberty) (Holgate, 1975; Farber and Nail, 1985) and shows certain unexplained geographical variations in prevalence. It is common in all Caucasian races, but is unusual in Africans, where the prevalence is 0.8% (Obasi, 1986) and populations derived from this ethnic group, e.g. American Blacks (Kenney, 1971). It is also uncommon in the indigenous populations of the Far East (Rajan et al, 1982; Yui Yip, 1984) and is almost completely absent from Eskimos (Kavli et al, 1985b) and American Indian populations (Convit, 1962). Some of this variability is determined by genetic factors, with HLA-Cw6, B13 and B17 being strongly associated with early onset of the disease (Batchelor and Morris, 1978; Henseler and Christophers, 1985), and HLACw2 and B27 with late onset of the disease in Caucasian populations. The pattern of inheritance is varied; it is autosomal dominant with variable penetrance in some families (Abele et al, 1963), but almost certainly polygenic in others. Expression is influenced by a number of extraneous and environmental factors. The most important of these are infection, particularly streptococcal throat infection (Whyte and Baugham, 1964) and human immunodeficiencyvirus (HIV) infection (Duvic et al, 1987); drugs, particularly lithium and the antimalarials (Abel et al, 1986); and cutaneous injury due to trauma or another skin disease (Koebner's phenomenon).
HISTOPATHOLOGY (Lever and Lever, 1983) The epidermis is thickened (acanthosis; Figure l(b)), except in the area overlying the dermal papilla, where it may be only one or two cells thick. This alternating thinning and thickening gives a characteristic saw-toothed appearance to the epidermis. There is also patchy parakeratosis of the epidermis, where the abnormally proliferating keratinocytes retain their nuclei. This becomes more prominent with longer established lesions. At the sites of the dermal papillae, neutrophils invade the epidermis (the Bailli&e's Clinical Rheumatology--
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squirting papilla), producing small clusters of inflammatory cells and ultimately small 'abscesses' (Munro microabscesses) within the epidermis. There may also be a degree of epidermal oedema (spongiosis) and, in the absence of Munro abscesses, differentiation from seborrhoeic eczema may sometimes be difficult (Pinkus and Mehregan, 1966). The dermis is also invaded by inflammatory cells, but these are usually T cells, at least in the early stages of the lesion. Later, the inflammatory infiltrate is more mixed, mainly neutrophilic, but mast cells increase in number. The early infiltrate is also perivascular in site. The vessels themselves are elongated into the lengthened dermal papillae, and are tortuous and dilated.
(a)
(b) Figure 1. (a) Typicalpsoriatic plaque. (b) Photomicrographof an established psoriatic lesion showing acanthosis, with epidermal thinning above the papillary dermis (H&E, original magnification x 40).
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PATHOGENESIS
Abnormalities are detectable in many of the cell types and structures of the skin. The epidermis is hyperproliferative and differentiation is reduced (Patterson et al, 1984), and this is reflected by keratin profiles (Bowden et al, 1983). A number of biochemical changes have been reported in keratinocytes and dermal fibroblasts, (as reviewed by Fry, 1988), but it still remains likely that these are secondary changes induced by the hyperproliferative state. There is vascular proliferation in and around psoriatic plaques and also, according to Ross (1964), occurring as a prelesional phenomenon in those with the psoriatic tendency. The lesional vascular proliferation is accompanied by an overgrowth of venous endothelial cells (Braverman and Sibley, 1982). With treatment, the epidermal changes reverse first, and the vascular abnormalities regress last (Ragaz and Ackerman, 1979). There is evidence that vascular dilatation and proliferation are very early events in the enlargement of psoriatic plaques, and that this enlargement is directional in the majority of lesions, i.e. plaques increase in size in a particular direction, not by general enlargement in all directions (Macdonald Hull et al, 1989). There has been great interest in the products of arachidonic acid metabolism as leukocyte attractants in psoriasis. Neutrophils are the main cell type in established psoriatic lesions (Lever and Lever, 1983), and their attraction to the site of inflammation was seen as a possible site for therapeutic intervention. Encouraged by the success of benoxaprofen as a treatment for psoriasis (Allen and Littlewood, 1982), research focused on the leukotrienes and, in particular, the product of the enzyme 5-1ipoxygenase (inhibited by benoxaprofen), leukotriene B4 and other related compounds (Brain et al, 1984b; Camp et al, 1985). These are found in psoriatic plaques in biologically active amounts (Brain et al, 1984a) and are probably important in this phase of inflammation. However, it seems clear that neutrophil invasion occurs relatively late in the development of a psoriatic lesion, and interest is focused on the role of T lymphocytes (Baker et al, 1984) and the cytokines involved in their attraction and activation (Nickoloff, 1988). This area of investigation has been greatly stimulated by the finding that cyclosporin A is an effective treatment for the disease (Ellis et al, 1986). Cyclosporin has a number of potent actions on the immune system, including inhibition of T lymphocyte activation and expansion (Bos et al, 1989). Activated T lymphocytes are found in both the dermis and epidermis in plaque lesions (Morhenn et al, 1982). They express HLA-DR antigens on the cell surface, as do plaque keratinocytes (but not normal keratinocytes). HLA-DR expression is induced by interferon ,/, which is produced by activated T cells. Intercellular adhesion molecule 1 is also induced on the keratinocyte surface membrane by interferon, and facilitates the binding of attracted T cells (Bos, 1988). Induction of other adhesion molecules on endothelial cells, and the increased production of cytokines such as transforming growth factor oLby a number of cell types, have been discovered in the psoriatic plaque (Elder et al, 1989). These discoveries slowly piece together the evolution of a psoriatic lesion, but the first change remains elusive, as do the genetic abnormalities that lead to disease susceptibility.
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MORPHOLOGY OF SKIN LESIONS
The typical skin lesion (Figure l(a)) is a well-defined erythematous plaque with a well-marked silvery scale. The colour, often described as 'salmon pink', is characteristic, and it is this, together with the sudden change from normal to abnormal skin, that makes psoriasis easy to recognize in the classical case. The rapid change discernible at a clinical level does not represent the events at a microscopic and microvascular level, where cellular events are graded and often directional. The erythema is quite different from that seen in eczematous conditions, lichenoid reactions or 'erythemas' of other origin. The colour presumably represents the influence of the acanthotic epidermis and the effect of inflammatory cells in the dermis and epidermis on the transmission of light, although this remains speculative. The erythema is lost in coloured skins, where the colour is often more purple.
Figure 2. Flexural psoriasis in the perineum.
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The morphology of the skin lesion is modified by its site. Thus, lesions in flexures lack the silvery scale that is seen at less occluded sites (Figure 2). This is also often true of lesions on the penis. Lesions on the palms and soles are much more hyperkeratotic and thickened (Samitz and Albom, 1951) (Figure 3). As well as this regional variation, there is considerable variability in the appearance of lesions in different patients. The reason for this is unknown. Individual lesions may be apparently non-scaly, although it is usually possible to produce scaling by gentle scratching of the plaque with a fingernail. Similar gentle scraping may produce pin-point bleeding (Auspitz's sign) from the dilated and proliferating blood vessels in the papillary dermis, where there is little protection by the overlying atrophic epidermis. Other lesions (although rarely in the same patient) may be thickly covered in scale--rupioid psoriasis. Similar hyperkeratosis is common in the scalp, where the affected areas may be very closely confined to the hair-bearing skin (Figure 4). In extreme cases the excess keratin may adhere closely to the hair, and 'grow' out with the hair, producing the clinical appearance known as pityriasis amiantacea (Knight, 1977). The clinical picture is not unique to psoriatic scalp disease, but can occur, for example, in seborrhoeic dermatitis of the scalp. Commonly, scalp disease is more minor, with patchy plaque-like disease, although scaling is normally greater here than elsewhere on the body, with the exception of the palms and soles. Very occasionally, scalp disease may be accompanied by hair loss, often at the sites of maximum scaling, and
Figure 3. Hyperkeratoticpsoriasis of the soles of the feet.
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Figure 4. Psoriasisof the scalp affectingthe hair line. often occurring as treatment removes the scale. The scalp underlying these areas of hair loss may be boggy and oedematous, with secondary infection being marked and follicular pustulation occurring. This pustulation may be bacterial in origin, but may also be sterile and a manifestation of the severity of the psoriatic process. Even more rarely, the hair loss may be followed by scarring, with permanent loss of hair follicles and the development of tufted alopecia more commonly seen in skin diseases such as lichen planus (Shuster, 1972). Skin lesions are commonly found on the elbows and knees and in the scalp, but can occur anywhere on the body. Other typical sites are the lower back and at the hair line. Occasionally, lesions may be predominantly flexural in situation (inverse psoriasis) or may be found only on the perineum or genitalia, where the diagnosis is often not made for many years. The size of individual lesions is very variable, ranging from less than 1 mm in early acute psoriasis and in rapidly extending disease, up to 10 cm or more in established plaque-type disease. Small lesional psoriasis is common, and one variant of this clinical picture, guttate psoriasis in which small lesions develop rapidly all over the body, is well known to follow streptococcal infection of the upper respiratory tract (Figure 5). It can rarely be associated with streptococcal glomerulonephritis (Chalmers and Ive, 1982). This explosive type of psoriasis probably occurs as a consequence of crossreaction between streptococcal antigen and certain keratinocyte antigens,
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Figure 5. Guttate psoriasis.
leading to an immunological attack on the skin (Swerlick et al, 1986). Despite the dramatic clinical appearance, the response to treatment of this variety of psoriasis is usually very good. PSORIASIS IN CHILDHOOD
Although psoriasis is uncommon in childhood, all of the typical patterns can occur. Scalp disease and disease of the extremities (nail or fingers) is well recognized (Nyfors, 1981). Napkin psoriasis may be true psoriasis (Rasmussen et al, 1986), but is more often a psoriasiform type of seborrhoeic eczema (Warin and Faulkner, 1961). Follicular psoriasis can occur and must be distinguished from localized pityriasis rubra pilaris. Distinction of psoriasis from a psoriasiform inflammatory linear naevus is made on clinical grounds.
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DIFFERENTIAL DIAGNOSIS
Psoriasis is normally easy to recognise and to distinguish from the main alternatives: discoid eczema for plaque lesions, seborrhoeic eczema for scalp lesions and flexural psoriasis where candidal intertrigo also needs to be considered. In most of these alternatives, the lesions are less well defined and the erythema less striking. Lichen simplex may mimic localized psoriasis, as may the localized plaques of Bowen's disease (intraepidermal squamous carcinoma). Hyperkeratotic eczema of the palms and soles may be impossible to distinguish from psoriasis. Less commonly, lichen planus and pityriasis lichenoides chronica may have certain psoriasiform features, but the rather shiny purple erythema of lichen planus and the characteristics of pityriasiform scale (centrally placed) usually allow the correct diagnosis to be made. PROGNOSIS OF CHRONIC PLAQUE PSORIASIS
There is no cure for psoriasis of the skin (Church, 1958). As many as 40% of affected individuals may achieve complete remission (Farber and Nall, 1974), although this seems high for a hospital population. The majority of patients respond to simple therapies, and clearance of the skin is often achieved. Remission is variable in duration, but can last for years after a single episode of treatment, although it is more often short lived (Durham and Morgan, 1974). The use of systemic therapy (cytotoxic drugs or photochemotherapy) can keep patients clear of cutaneous psoriasis, but at the risk of drug-related side-effects. ERYTHRODERMIC AND PUSTULAR PSORIASIS
In any type of psoriasis, severe attacks may occur in which generalized plaque lesions rapidly extend, become more inflammatory and lead to erythrodermic psoriasis. The majority of the skin surface becomes inflamed and unstable. Such severe psoriasis can occur as the initial manifestation of the disease, and then diagnosis can be impossible either clinically or histopathologically until the skin begins to settle and more typical lesions appear. Patients with this variety of psoriasis are severely unwell, and have considerable problems with thermoregulation (Grice et al, 1968) and occasionally malabsorption (Marks, 1982). They require in-patient care and great expertise in management. If uncontrolled, such skin may become pustular due to the severity of the inflammatory process, and in the past patients died from this rare complication of this common disease. In the most severe forms of psoriasis, generalized pustular psoriasis (von Zumbusch) may occur. Sheets of sterile micropustules occur on a background of very inflammatory or erythrodermic psoriasis (Figure 6) in a very ill patient. Micropustules amalgamate to form 'lakes of pus', a very dramatic physical sign. This is most often encountered after the inappropriate use of topical steroids for worsening disease following the withdrawal of systemic
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Figure 6. Generalized pustular psoriasis.
steroids, or after the use of irritant therapies on inflamed psoriasis (Baker and Ryan, 1968). Infection and severe fluid loss due to hypoalbuminuria are the main complications of this type of psoriasis, and fatal complications of acute hypovolaemia may occur (Baker and Ryan, 1968). Treatment needs to be supportive and intense, as well as aiming at the underlying psoriasis. PUSTULAR PSORIASIS OF THE PALMS AND SOLES (Figure 7) More localized pustular lesions occur in the well-defined clinical entity of pustulosis of the palms of the hands and soles of the feet (Baker, 1984). This occurs in about 1% of the population, is more common in women of middle age, and is very unusual in non-smokers (O'Docherty, 1984). There may be an association with HLA-B8 (Thomsen and Osterbye, 1973). The condition
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is usually bilateral in presentation, but may be unilateral at onset, and can affect the palms of the hand, the soles of the feet, or both. It is characterized by a degree of hyperkeratosis and scaling, within which small (1-2 mm) pustules occur. These are sterile and resolve spontaneously, leaving brown papules that are slowly shed, only to be replaced by a new crop of lesions. The affected areas are itchy, tend to enlarge, and rarely settle spontaneously. The onset of the disease, and its progression, are largely uninfluenced by stress, infection or climate, and differ from typical psoriasis in this respect. The role of cigarette smoking is unclear, but there does appear to be a genuine relationship between the occurrence of the disease and smoking behaviour. Acrodermatitis continua is a form of localized pustular psoriasis affecting the fingertips and nails, and is particularly debilitating and difficult to treat. The differential diagnosis of pustular psoriasis includes infective pustulation usually due to staphylococci, often on a background of eczema,
Figure 7. Pustularpsoriasis of the sole of the foot.
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pustular variants of drug eruptions and Reiter's disease, although this distinction is semantic (Wright and Reed, 1964). Again, there is no cure for this variety of psoriasis, but control is normally possible with combinations of topical and systemic therapy, including photochemotherapy with psoralen and ultraviolet (UV) A (PUVA). NAIL DISEASE IN PSORIASIS The nail apparatus is commonly involved in psoriasis. Indeed, at least 25% of psoriatic patients have some involvement of the nails (Zaias, 1969). Nail matrix involvement produces the characteristic pitting of the nail, while nail-bed involvement produces onycholysis (in which the nail separates from the underlying nail bed) or subungual hyperkeratosis (Robbins et al, 1983). Localized nail-bed disease can also produce the 'oil drop sign' where a patch of browny yellow discoloration is seen in the central portion of the nail (Kouskoukis et al, 1983). Nail disruption can be the only manifestation of psoriatic skin disease, and should be sought in all patients suspected of having the condition. It can also be very severe, with gross thickening and destruction of the nail. This has considerable functional importance to affected patients, since nails are essential for the protection of the fingers and toes, and also for the fine function of the fingers. Involvement of the nail in pustular psoriasis can be particularly severe (Figure 8). It is important to exclude fungal nail disease in patients with nail dystrophy. This can occur as a primary infection, but any mould infection can occur as a secondary problem in nails made abnormal by psoriasis.
Figure 8. Acrodermatitis continua with nail involvement.
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Alternative causes of nail pathology include traumatic nail dystrophies and lichen planus, but, in the absence of typical cutaneous psoriasis, diagnosis may be impossible without nail matrix biopsy. THE INTER-RELATIONSHIP OF SKIN AND JOINT DISEASE
While there is no evidence that the pathogenesis of skin and joint disease in psoriasis is the same, it is clear that there is a relationship between the severity of skin disease and the occurrence or severity of joint disease in patients with psoriasis. Reported prevalence rates for joint disease in those with cutaneous disease have been between 6% for hospitalized psoriatic patients (Leczinsky, 1948) and 20% for patients having PUVA for their skin disease (Stern, 1985). It is recognized that the more severe the cutaneous disease, the greater the risk of associated arthropathy (Little et al, 1975), so these prevalence rates are likely to be overestimates. Of course, it is possible to have severe skin disease with no element of arthropathy, and equally to have severe joint disease without any skin disease, although, in the latter case, the diagnosis of psoriasis is unlikely to be definite since it is usually the skin pathology that is diagnostic. It is certainly possible to have even mutilating joint disease with only minimal skin involvement. Apart from a striking association with pustular and erythrodermic psoriasis of the skin (Baker et al, 1963), the type of skin involvement is unrelated to the incidence and type of joint disease. In the case of pustular skin disease, the relationship appears to hold true for both generalized (Baker and Ryan, 1968) and localized disease (Baker et al, 1963). It is generally accepted that the skin lesions of pustular psoriasis and those of keratoderma blenorrhagica are identical (Camp, 1992). NAIL DISEASE AND JOINT DISEASE Nail disease may be more common in patients with joint disease than in those without. Approximately twice as many patients with joint disease due to psoriasis may have nail disease than patients with skin disease alone (Baker et al, 1964; Scarpa et al, 1984). This is disputed, however, and some authors believe that as many as 90% of patients with psoriatic skin disease have nail involvement at some time in the course of their disease, regardless of whether they have had arthropathy (Samman, 1978). The type of nail disease reflects the site of inflammation within the nail apparatus, with pits reflecting dorsal matrix disease (Baran and Dawber, 1984). There does not appear to be any association between joint disease and the severity of nail disease. There is also dispute about the relationship between the type of arthropathy and nail involvement. Baker and Ryan (1968) found that patients with more severe joint disease had a greater incidence of nail disease, regardless of the site of joint involvement, whereas Wright (1979) found that those with distal joint disease inevitably had nail involvement.
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It is possible that nail disease produces the ragged appearance of the distal phalanx seen in some patients through a deep Koebner phenomenon (Mahowald and Parrish, 1982). It seems more likely that distal joint disease influences nail behaviour through a shared blood supply (Abel and Farber, 1979). It is well described that abnormalities of the peripheral circulation can disturb nail growth and structure, e.g. in acrocyanosis or Raynaud's phenomenon (Fenton and Wilkinson, 1984). Such a relationship would also require the existence of Koebner's phenomenon to explain the morphology of the nail lesions, since those seen in other abnormalities of the circulation are not psoriatic in nature. Acro-osteolysis is a severe example of such distal bone disease, but this tuft osteolysis has been described without nail disease (Cheesbrough, 1979), raising the possibility that only those two thirds of patients able to produce a Koebner reaction develop nail problems in this way. In summary, severity of skin disease does relate to the frequency of arthritis, although not to its severity. Only pustular and erythrodermic psoriasis are specifically related to joint problems. Nail disease is Very common in all patients with psoriasis, but does seem to be specifically related to those with distal joint disease. The cause of this relationship is unclear. MANAGEMENT General measures
Although therapy for psoriasis has improved markedly in recent times, the general approach has not changed for many years (Ingrain, 1954). The majority of patients with psoriasis can be managed at home. Their general health should be attended to, and the effect of the disease on their health, life-style and emotional state should be documented. The psoriasis disability index is one simple way of measuring this. A full discussion of the disease and its implications should help the patient to understand and comply with treatment, and to be positive about the outlook. Anxiety and stress should be minimized. In severe disease, when out-patient management has failed, in-patient care is appropriate, preferably in a dedicated dermatology unit with specialist nursing. Topical therapy
For straightforward plaque-type psoriasis, treatment consists of topical agents applied directly to the affected areas of skin. For limited or very inflamed disease, simple emollients are valuable, but these have no particular antipsoriatic effect. However, several other topical agents are useful, being more or less specific for the disease. Anthralin (dithranol) is the only truly specific antipsoriatic therapy, and is applied to the affected skin as precisely as possible. It is left in place for periods varying for 15 rain to 24 h; short-term application is very effective and much more convenient than longer applications (Macdonald and Marks, 1986). The active agent can be delivered to
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the skin in a number of bases, although Lassar's paste (a combination of zinc oxide and salicylic acid which helps to stabilize the anthralin) and a cream base are the most commonly used (Whitefield, 1981). The concentration of anthralin is gradually increased, depending on the patient's response and the degree of irritation produced; irritation is the major side-effect of anthralin treatment. Staining of the skin occurs, but is temporary. Staining of clothes and baths also occurs and is permanent. Used in combination with tar baths and graded UVB exposure (the Ingram regimen), anthralin will clear the majority of patients in about 6 weeks of treatment as an out-patient, and in about half that time as an in-patient. The mode of action of anthralin is unclear.
Tar preparations Coal tar preparations are less specific treatments for psoriasis, but in many units are the first line of treatment, giving clearance rates similar to those of anthralin. Again, there is a choice of base for delivery of the drug, but an ointment containing tar and salicylic acid in various combinations is commonly used, particularly on the scalp. Increasing concentrations of coal tar in Lassar's paste are a useful remedy, traditionally in conjunction with UVB exposure (the Goekermann regimen). There is some doubt about the additional benefit of the UVB exposure (Comaish, 1981). Tar preparations are messy to use, but attempts to make them more acceptable by using a cream base also result in considerable loss of efficacy. Tar shampoos are the first-line treatment for mild scalp disease, while paste preparations are particularly successful for localized pustular psoriasis. Tar preparations are probably antimitotic, but it is not clear whether this is the mode of action in psoriasis (Fisher and Maibach, 1973). Fish tar (ichthamol) is also effective in psoriasis, although less so than coal tar. It is often used on patients with inflammatory psoriasis in combination with eosin, an old-fashioned, but none the less effective, combination that can be used as an intermediate between simple emollients and more active treatment in those with very inflamed skin.
Topical steroids Topical steroids have a role in psoriasis of the flexures, face and hands where other treatments are too irritating or a rapid response is needed. Prolonged or widespread use of topical steroids, particularly powerful fluorinated ones (e.g. Betnovate), is to be avoided because of the problems of tachyphylaxis and the production of unstable and pustular psoriasis (Baker, 1976). A steroid cream application under occlusion provided by a swimming cap is useful for severely affected and crusty scalps as a rapid way of descaling the area.
Calcipotriol The latest addition to the topical remedies for psoriasis is the vitamin D
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analogue, calcipotriol. This compound was designed after it was reported that vitamin D compounds used orally (Morimoto et al, 1986) were of value in plaque psoriasis. Used topically (Van der Kerkhof et al, 1989), the naturally occurring vitamin produced little benefit. Calcipotriol is much more potent in its cutaneous effects, and has already proved of great benefit in patients with stable plaque psoriasis (Kragballe et al, 1988). It has a number of effects on keratinocytes, fibroblasts and as an immunomodulator, and it is not clear which, if any, is its major action in psoriasis (Kragballe, 1988). About 70% of patients respond to it satisfactorily, without gaining complete clearance of their disease in the majority of cases.
Ultraviolet therapy Exposure to UVB forms a part of all of the major out-patient regimens for the treatment of psoriasis, and is effective when used alone (LeVine and Parrish, 1980). It is not as effective as natural sunlight in the majority of patients, and some question its value when used as combination therapy (Comaish, 1981). UVA is much less powerful in its effects than UVB. When used alone, long exposures of UVA are necessary to produce any significant effect.
Photochemotherapy (PUVA) The combination of a photosensitizing agent (psoralen) with short exposures of UVA (PUVA) is a very effective therapy for those patients resistant to simple topical measures (Melski et al, 1977). This form of treatment has been in wide use around the world since the mid 1970s and has been a great help to many sufferers. The psoralen is usually given by mouth (8- or 5-methoxypsoralen), but can also be used topically to small areas of psoriasis, or in a bath as an alternative to oral treatment. To reduce the danger of cataract, the eyes must be protected by wearing appropriately filtering sunglasses for 24 h after taking psoralen tablets. Acute toxicity consists of burning due to overexposure to UV, or nausea due to the tablets (Farber et al, 1983). In the long term there is a definite risk of non-melanoma skin cancer, particularly squamous cell lesions, which has to be balanced against the benefit of treatment to the patient. Previous exposure to cytotoxic therapies increases the level of this risk considerably. The incidence of melanoma may also be increased (Henseler et al, 1987).
Systemic therapy Patients with extensive psoriasis resistant to both topical treatments and phototherapy need systemic treatment, and there are a number of agents that may be of value. Retinoids
Derivatives of vitamin A have been available for the treatment of psoriasis,
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amongst other conditions, since the 1970s. Until the present time, etretinate has been the retinoid most widely studied and used in psoriasis. It may be of value in chronic plaque, erythrodermic or pustular psoriasis when used in doses of around 1 mg per kg body-weight and, in the latter two conditions, the response is often rapid (Lowe et al, 1988). Side-effects are common, with dryness of skin and mucous membranes being almost inevitable and dose related. Abnormalities of serum lipids are common, while hepatotoxicity is rare. More significantly, skeletal abnormalities may occur, with hyperostosis, ossification of interosseous membranes and premature fusion of epiphyses in children, and should be screened for (Gerber et al, 1984). Retinoids are also teratogenic and, since the compounds are strongly lipid soluble, traces persist in the body for up to 2 years after discontinuing therapy. Pregnancy must therefore be avoided for this time after stopping therapy. Etretinate has been used in conjunction with PUVA in an attempt to reduce the amount of UV exposure needed to clear the disease. This may occur, but is still disputed (Parker et al, 1984). The immediate metabolite of etretinate, acetretin, is as active as the parent compound and is now available in the UK and elsewhere in the world (Gollnik et al, 1988). It is intended that it will replace etretinate in the treatment of psoriasis during 1994. Methotrexate
The dihydrofolate reductase inhibitor, methotrexate, has an established role in the management of severe psoriasis (Baker, 1970). It is given as a weekly dose, either by mouth or by intramuscular or intravenous injection, after an initial test dose of 2.5 mg. Dosages range from 2.5 to 25 mg weekly, depending on age, size, renal function and response. Care must be taken with concomitant medication which may enhance blood levels of the drug, either by displacement from protein binding (Roenigk et al, 1988) or by reduced excretion (Nierenberg and Mamelok, 1983). Maximal response occurs over about 4 weeks, and therapy may need to be continued permanently, although some patients are able to stop the drug once their psoriasis is controlled. Immediate toxicity consists of gastrointestinal upset and bone marrow suppression; in the longer term, hepatic fibrosis, cirrhosis and liver failure can occur (Roenigk et al, 1988). Hepatic toxicity is commoner in the obese, diabetics and consumers of alcohol, and caution should be exercised in all such patients (Miller et al, 1985). High alcohol intake is relatively common amongst psoriatics, although whether this precedes or follows the onset of the disease is unclear (Monk and Neill, 1986). The incidence of liver problems appears to be higher in psoriatics than in other groups of patients treated with methotrexate. The need for regular liver biopsy in patients treated with this drug continues to be debated, although the accuracy of other diagnostic techniques such as radio-isotope scanning or ultrasonography is not generally believed to be sufficient to replace liver biopsy in those thought to be at risk (Coulson et al, 1987). The American Association of Dermatology has specific guidelines dealing with the timing of liver
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biopsy, and recommends investigation after stabilization on the drug, after the first 1.5 g, and at intervals of i g thereafter (Roenigk et al, 1988). Pulmonary fibrosis can also occur in psoriatic patients on methotrexate, and regular chest radiography is advisable (Verdich and Christensen, 1979).
Hydroxyurea (Layton et al, 1989) Hydroxyurea interferes with the enzyme ribonucleoside diphosphate reductase, and it is possible that this cytotoxic action is responsible for the success of the drug in psoriasis. Oral doses up to 1.5 g daily are given, and are helpful in patients with difficult psoriasis. Response is slow and marrow toxicity is more common than with methotrexate, but recovery always occurs provided the drug is stopped promptly. Compared with methotrexate, gastrointestinal upset or liver damage is much less common, but hyperpigmentation, actinic psoriasis and a drug-induced autoimmune diathesesis with the lupus anticoagulant have all been described (Layton et al, 1989).
Cyclosporin A This immunosuppressive agent has been increasingly used in psoriasis since 1984. It is effective and relatively safe in therapy-resistant disease in the majority of patients when used in doses up to 5 mg per kg body-weight (Van Joost et al, 1988). Above this dose, the incidence of renal toxicity and hypertension becomes unacceptably high, and high dosages should be avoided (Mihatsch and Wolff, 1990). Guidelines for use of cyclosporin A in psoriasis have recently been produced. As with all cytotoxic agents, relapse after stopping treatment is inevitable but, with cyclosporin at least, the rate of relapse is no higher than after topical treatment with dithranol (Higgins et al, 1992).
Systemic steroids For cutaneous disease in psoriasis, the only role for systemic, as opposed to topical, steroid therapy is in patients with life-threatening erythrodermic or pustular psoriasis. In this situation, other treatments may take some time to work, and the patient may require the rapid effect of oral steroid, whilst the slower-acting drugs protect from the problem of rebound or exacerbation of pustulation that can be induced by steroid therapy. In all other situations, oral steroids are best avoided (Champion, 1966). The potential danger of steroid exacerbation of psoriasis needs to be considered when steroids are used to treat joint disease. Relatively minor cutaneous disease can rapidly become unstable and difficult to treat, and this complication must be anticipated and dealt with quickly when it occurs. Other treatments
A number of other agents, including occlusive therapy with various occlusive
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agents e.g. hydrocolloid dressings (Friedman, 1987), sulphasalazine (Gupta et al, 1989a), topical and oral vitamin D (Morimoto et al, 1986), fish oils (Gupta et al, 1989b), antibiotics (Rosenberg et al, 1986), benoxaprofen (Allen and Littlewood, 1982) and razoxane (Horton and Wells, 1983)--the latter two are now unavailable--have all been reported to have a role in the management of psoriasis. Those still available may be useful when all the above measures have failed. SUMMARY
Psoriatic skin disease is common; it occurs at all ages and co-exists with joint disease in approximately 10% of cases. All areas of skin, scalp and nails may be involved. In the typical case, the skin lesions are easy to recognize. Atypical forms of skin involvement and lesions at unusual sites are less easily diagnosed by non-specialists. The cause is unknown, but there is a clear genetic element, with external factors being important in precipitation and exacerbations of the condition. Topical treatment is successful in most patients, hut in resistant cases combinations of systemic therapy and ultraviolet radiation usually give good control. Although there is no cure, the majority of sufferers live normal lives and, with the exception of severe erythrodermic or generalized pustular psoriasis, there is no mortality. Morbidity, particularly social and occupational, is more of a problem than is often acknowledged. REFERENCES Abel E & Farber EM (1979) Psoriasis. In Dennis DJ, Dobson RL & McGuire J (eds) Clinical Dermatology, vol. 1, pp 150-155. Philadelphia: Harper Medical. Abel EA, DiCicco LM, Orenberg EK et al (1986) Drugs in exacerbation of psoriasis. Journalof the American Academy of Dermatology 15: 1007-1022. Abele DC, Dobson RL & Graham JB (1963) Heredity and psoriasis. Archives of Dermatology 88: 38-47. Allen BR & Littlewood SM (1982) Benoxaprofen: effect on cutaneous lesions in psoriasis. British Medical Journal 285: 1241. Baker BS, Swain AF, Fry Let al (1984) Epidermal T lymphocytes and HLA-DR expression in psoriasis. British Journal of Dermatology 110: 555-564. Baker H (1970) Intermittent high dose oral methotrexate therapy in psoriasis. British Journal of Dermatology 82: 65-69. Baker H (1976) Corticosteroids and pustular psoriasis. British Journal of Dermatology 94 (supplement 12): 83-88. Baker H & Ryan TJ (1968) Generalised pustular psoriasis. British Journal of Dermatology 80: 771-793. Baker H, Golding DN & Thompson M (1963) Psoriasis and arthritis. Annals of Internal Medicine 58: 909-925. Baker H, Golding DN & Thompson M (1964) The nails in psoriatic arthritis. British Journal of Dermatology 76: 549-554. Baran R & Dawber RPR (1984) The nail in dermatological diseases. In Baran R & Dawber RPR (eds) Diseases of the Nails and their Management, pp 157-203. Oxford: Blackwell Scientific Publications. Barker H (1984) Pustular psoriasis. Dermatology Clinics 2" 455-470. Batchelor JR & Morris PJ (1978) HLA and disease--joint report. In Bodmer WF, Batchelor
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JR, Bodmer JG et al (eds) Histocompatibility Testing 1977, pp 205-258. Copenhagen: Munksgaard. Bos JD (1988) The pathomechanisms of psoriasis; the skin immune system and cyclosporin. British Journal of Dermatology 118: 141-155. Bos JD, Meinardi MMHM, van Joost T et al (1989) Use of cyclosporin in psoriasis. Lancet ii: 1500-1502. Bowden PE, Wood EJ & Cunliffe WJ (1983) Comparison of prekeratin and keratin polypeptides in normal and psoriatic human epidermis. Biochemica et Biophysica Acta 743: 172-179. Brain S, Camp R, Dowd P e t al (1984a) The release of leukotriene B4 like material in biologically active amounts from the skin lesions of patients with psoriasis. Journal of Investigative Dermatology 83: 70-73. Brain SD, Camp RDR, Cunningham FM et al (1984b) Leukotriene B4-1ike material in scale of psoriatic lesions. British Journal of Pharmacology 83: 313-317. Braverman IM & Sibley J (1982) Role of the microcirculation in the treatment and pathogenesis of psoriasis. Journal oflnvestigative Dermatology 78: 12-17. Camp RDR (1992) Psoriasis. In Champion RH, Burton JL & Ebling FJG (eds) Textbook of Dermatology, vol. 5, pp 1391-1457. Oxford: Blackwell Scientific Publications. Camp RDR, Mallett AI, Cunningham FM et al (1985) The role of chemoattractant lipoxygenase products in the pathogenesis of psoriasis. British Journal of Dermatology 113 (supplement 28): 98-103. Chalmers RJG &Ive FA (1982) Is acute guttate psoriasis with renal disease a rarity? Archives of Dermatology 118:141 (letter). Champion RH (1966) Treatment of psoriasis. British Medical Journal ii: 993-996. Cheesbrough MJ (1979) Osteolysis and psoriasis. Clinical and Experimental Dermatology 4: 341-344. Church R (1958) The prospect of psoriasis. British Journal of Dermatology 70: 139-145. Comaish JS (1981) Tar and related compounds in the therapy of psoriasis. Clinical and Experimental Dermatology 6: 639-645. Convit J (1962) Investigation of the incidence of psoriasis among Latin American Indians. In Proceedings of the XII Congress of Dermatology, p 196. Amsterdam: Exerpta Medica Foundation. Coulson IH, McKenzie J, Neild VS et al (1987) A comparison of liver ultrasound with liver biopsy histology in patients receiving long-term methotrexate therapy. British Journal of Dermatology 116: 491-495. Durham GA & Morgan JK (1974) A 7-year follow-up study of ninety patients with psoriasis. British Journal of Dermatology 91: 7-11. Duvic M, Johnson TM, Rapini RP et al (1987) Acquired immunodeficiency syndromeassociated psoriasis and Reiter's syndrome. Archives of Dermatology 123: 1622-1632. Elder JT, Fisher GJ, Lindquist PB et al (1989) Overexpression of transforming growth factor alpha in psoriatic epidermis. Science 243: 811-814. Ellis CN, Gorsulowski DC & Hamilton TA (1986) Cyclosporin improves psoriasis in a double blind study. Journal of the American Medical Association 256: 3110-3116. Farber EM & Nall ML (1974) The natural history of psoriasis in 5600 patients. Dermatologica 148: 1-18. Farber EM & Nail ML (1985) Epidemiology: natural history and genetics. In Roenigk HH & Maibach HI (eds) Psoriasis, pp 141-186. New York: Marcel Dekker. Farber EM, Abel EA & Cox AJ (1983) Long term risks of psoralen and UV-A therapy for psoriasis. Archives of Dermatology 119: 421-431. Fenton DA & Wilkinson JD (1984) The nail in systemic diseases and drug induced changes. In Baran R & Dawber RPR (eds) Diseases of the Nails and their Management, pp 205-265. Oxford: Blackwell Scientific Publications. Finlay AY, Khan GK, Luscombe DK & Salek MS (1990) Validation of sickness impact profiles and psoriasis disability index in psoriasis. British Journal of Dermatology 123: 751-756. Fisher LB & Maibach HI (1973) Topical antipsoriatic agents and epidermal mitoses in man. Archives of Dermatology 108: 374-377. Friedman SJ (1987) Management of psoriasis vulgaris with a hydrocolloid occlusion dressing. Archives of Dermatology 123: 1046-1052.
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Fry L (1988) Psoriasis. British Journal of Dermatology 119: 445-461. Gerber LH, Helfgott RK, Gross EG et al (1984) Vertebral abnormalities associated with synthetic retinoid use. Journal of the American Academy of Dermatology 10: 817-823. Gollnik H, Bauer R, Brindley C et al (1988) Acitretin versus etretinate in psoriasis. Journal of the American Academy of Dermatology 19: 458-469. Grice K, Blendis LM, Keir MI et al (1968) Accidental hypothermia in erythroderma from generalized psoriasis. Archives of Dermatology 98: 263-267. Gupta AK, Ellis CN, Siegel MT et al (1989a) Sulfasalazine: a potential psoriasis therapy? Journal of the American Academy of Dermatology 20: 79%800. Gupta AK, Ellis CN, Tellner DC et al (1989b) Double blind placebo controlled study to evaluate the efficacy of fish oil and low dose UVB in the treatment of psoriasis. British Journal of Dermatology 120: 801-807. Hellgren L (ed.) (1967) Psoriasis. The Prevalence in Sex, Age and Occupational Groups in Total
Populations in Sweden. Morphology, Inheritance and Association with other Skin and Rheumatic Diseases. pp 55-63. Stockholm: Almqvist & Wiksell. Henseler T & Christophers E (1985) Psoriasis of early and late onset: characterisation of two types of psoriasis vulgaris. Journal of the American Academy of Dermatology 13: 450-456. Henseler T, Christophers E, Honigsmann H et al (1987) Skin tumours in the European PUVA study. Journal of the American Academy of Dermatology 16: 108-116. Higgins E, Munro C, Marks J e t al (1992) Relapse rates in moderately severe chronic psoriasis treated with Cyclosporin A. British Journal of Dermatology 121: 71-74. Holgate MC (1975) The age-of-onset of psoriasis and the relationship to parental psoriasis. British Journal of Dermatology 92: 443-448. Horton JJ & Wells RS (1983) Razoxane: a review of 6 years' therapy in psoriasis. British Journal of Dermatology 109: 669-673. Ingram JT (1954) The significance and management of psoriasis. British Medical Journal ii: 823-828. Kavli G, Stenvold SE & Vandbakk O (1985) Low prevalence of psoriasis in Norwegian Lapps. Acta Dermato-Venereologica 65: 262-263. Kenney JA (1971) Psoriasis in the American black. In Farber EM & Cox AJ (eds) Psoriasis. Proceedings of the 1st International Symposium, pp 49-52. Stanford: Stanford University Press. Knight AG (1977) Pityriasis amiantacea: a clinical and histopathological investigation. Clinical and Experimental Dermatology 2: 137-143. K6bner H (1878) Klinische, experimentelle und therapeutische Mitteilungen uber Psoriasis. Berlin Klin Wochenschr 21: 631-632. Kouskoukis CE, Scher RK & Ackerman AB (1983) The 'oil drops' sign of psoriatic nails. A clinical finding specific for psoriasis. American Journal of Dermatopathology 5: 259-262. Kragballe K, Beck HI & Sogaard H (1988) Improvement of psoriasis by a topical vitamin D3 analogue (MC903) in a double blind study. British Journal of Dermatology 119: 223-230. Layton AM, Sheehan-Dare RA, Goodfield MJD et al (1989) Hydroxyurea in the management of therapy resistant psoriasis. British Journal of Dermatology 121: 647-653. Leczinsky CG (1948) The incidence of arthropathy in a ten year series of psoriasis cases. Acta Dermato-Venereologica 28: 483-487. Lever WF & Lever GS (eds) (1983) Histopathology of the skin, 6th edn. Philadelphia: Lippincott. LeVine MJ & Parrish JA (1980) Outpatient phototherapy of psoriasis. Archives of Dermatology 116: 552-554. Little M, Harvie JN & Lester RS (1975) Psoriatic arthritis in severe psoriasis. Canadian Medical Association Journal 112: 317-319. Lowe NJ, Lazarus V & Matt L (1988) Systemic retinoid therapy for psoriasis. Journal of the American Academy of Dermatology 19: 186-191. Macdonald ICIS & Marks J (1986) Short contact anthralin in the treatment of psoriasis: a study of different contact times. British Journal of Dermatology 114: 235-239. Macdonald Hull S, Goodfield M, Wood EJ & Cunliffe WJ (1989) Active and inactive edges of psoriatic plaques: identification by tracing and investigation by laser-Doppler flowmetry and immunocytochemical techniques. Journal oflnvestigative Dermatology 92: 782-785. Mahowald WL & Parrish RM (1982) Severe osteolytic arthritis in pustular psoriasis. Archives of Dermatology 118: 434-438.
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