Plaque and scales on the skin. ( Psoriasis)
Psoriasis is a common inflammatory dermatosis, most frequently characterized by red scaly plaques on extensor aspects of limbs and scalp.
Psoriasis has a worldwide prevalence of up to 3000 per 100 000. It is estimated to affect 2% of the UK population. It is uncommon in Native Americans and the Inuit population (500 per 100 000).
There is a genetic predisposition to psoriasis. Approximately 30% of those with chronic plaque psoriasis have a family member with the disease and twin studies indicate a 70% concordance in monozygotic twins and 30% in dizygotic twins. Current research groups are attempting to identify the gene(s) linked to psoriasis. Independent genome-wide scans have identified at least nine disease susceptibility loci (PSORS1-9, psoriasis susceptibility 1-9) . Of these, the PSORS1 region on chromosome 6p21 may account for up to 50% of psoriasis familial clustering. Within this region reside at least three potential candidate genes for psoriasis susceptibility: human leukocyte antigen C (HLA-C), α-helical coiled coil rod (HCR) and corneodesmosin (CDSN) genes. The relatively low concordance rate in monozygotic twins together with the heterogeneity of chromosomal loci indicate that psoriasis is probably a polygenic disease expressed only in the presence of certain stimuli (such as streptococcal infection).
Psoriasis is most commonly characterized by well-defined, salmon pink plaques with silvery white scales on the extensor aspects of limbs, scalp, navel and natal cleft. Psoriasis does not scar the skin but may be itchy. The severity and duration of the disease are variable and a wide variety of clinical patterns are recognized. Different forms of the disease may occur in the same patient at different time.
Sunshine can exacerbate psoriasis in a few patients, but in the majority natural sunshine is beneficial. Psoriasis exhibits the Köbner phenomenon-psoriasis appears at sites of trauma. Other precipitating or exacerbating factors are listed as following - drugs such as beta blocker, ACE inhibitors, lithium, antimalarial, NSAIDS and alcohol.Infection , HIV or beta hemolytic streptococci.Injury to the skin such as mechanical injury or sunburn.
Chronic plaque psoriasis is also known as psoriasis vulgaris. It is the most common form, accounting for 80% of disease, and is equally common in both sexes. It is characterized by well-demarcated, thickened, red plaques, covered by silvery scales). 'Auspitz sign' is a characteristic diagnostic feature where light scraping of the scale with a wooden spatula produces multiple bleeding points. Although the plaques may be distributed anywhere, the most common sites are the extensor aspects of limbs (particularly knees and elbows), the lumbosacral region and scalp. The disease may be localized or widespread, covering most of the body). When psoriasis involves flexures or the genitalia, it is frequently atypical in that there is no scaling as a result of the moist environment.
Guttate psoriasis is the acute onset of small droplets of psoriasis, generally on the trunk . It classically occurs 2-3 weeks after a streptococcal throat infection in children and young adults. On examination, there are numerous red, oval or round, scaly plaques up to 1 cm in diameter. These rapidly appear on the trunk and proximal limbs, and may coalesce. Guttate psoriasis is usually self-limiting and responds readily to treatment. A short course of an antistreptococcal antibiotic in those with a proven streptococcal throat infection may also be beneficial.
Pustular psoriasis is rare and may be localized or generalized. Chronic, localized pustular psoriasis (also called palmoplantar pustulosis) occurs predominantly in adults and is 9 times more common in women. There is an association with tobacco use: over 90% of patients are smokers. It manifests as recurrent crops of sterile yellow pustules, 0.1-0.5 cm in diameter, on palms and soles. The pustules involute to leave red-brown stained macules which may scale before disappearing.Generalized pustular psoriasis is a serious, unstable form of psoriasis associated with a significant mortality. Erythematous plaques studded with sterile pustules rapidly appear at any site and may become confluent. Fever and malaise are common. This pustular form may occur in patients with chronic plaque psoriasis after withdrawal of oral or potent topical steroids.
Active psoriasis can progress to sub-erythroderma (70% body surface area involved) or erythroderma (over 90% of body surface area affected), which can be life threatening as skin fluid loss, temperature dysregulation and potential sepsis can occur. Patients need urgent admission to hospital and may require systemic therapy.
Scalp psoriasis describes areas of well-demarcated erythema and lumpy scaling interspersed with normal skin . An unusual form of thick psoriasis on the scalp is pityriasis amiantacea in which the scales are adherent to the hair shaft (the same clinical appearance may also be seen in seborrhoeic dermatitis
Nail abnormalities are present in up to 50% of patients with psoriasis, especially in those with associated psoriatic arthritis. The most common findings are pitting, onycholysis (separation of the nail plate from the nail bed), 'salmon patches' or oil spots (subungual yellow-brown areas of discolouration), and subungual hyperkeratosis. Severe nail dystrophy can occur and may need to be differentiated from onychomycosis.
The diagnosis of psoriasis is made clinically and laboratory investigations are rarely helpful.
A skin biopsy may be required when the diagnosis is unclear or if the patient fails to respond to treatment .
ASO titres may be performed to screen for streptococcal infection in patients with guttate psoriasis.
Psoriasis in the context of a modified immune response is commonly atypical, severe and refractory to treatment. An HIV test should be performed in such clinical cases.
In the case of guttate psoriasis, the differential diagnosis includes secondary syphilis. This can be ruled out by appropriate serological tests.
Nail clippings for microscopy and fungal culture are performed to rule out onychomycosis (dermatophyte nail infection) in patients with severe nail dystrophy.
There is no cure for psoriasis. Treatment is suppressive and aimed at inducing remission or at least reducing the extent and severity, so that the disease has as minimal an impact as possible on the patient's daily routine. Response to treatment will be influenced by compliance, and so regimens should be adapted to suit each patient's circumstances. The need for treatment will often be dictated by the patient's own perception of his or her disability, and management should take these views into account. Tolerance and understanding are required in helping patients overcome the social stigma that may be associated with their disease.
Patients with psoriasis should be encouraged to use emollients regularly to moisturize the skin and prevent fissuring.
Occasionally psoriasis may be itchy, and in these cases a sedating antihistamine can be useful at night when pruritus is usually most troublesome.
Chronic plaque psoriasis is classified as mild if less than 10% of the body surface area (BSA) is affected. Mild disease is usually treated with first-line topical treatment. Depending on the ease with which these treatments can be applied, patients may be managed in the primary care setting or in hospital. More severe disease (>15% of BSA affected) requires second-line treatments that are predominantly hospital based and supervised by a dermatologist.
Keratolytics, such as salicylic acid, may be used in combination with one of the other first-line treatments to descale plaques.
The mechanism of action of coal tar is poorly understood; however, it is a keratolytic and probably possesses anti-inflammatory and antiproliferative effects. Inpatient treatment is usually started with 1% coal tar and can be gradually increased to 30%, depending on efficacy and local irritation. Crude extracts of coal tar can be made up in emulsifying ointment to be used by patients at home. There are also shampoos which contain coal tar for scalp psoriasis. The most common side effects are irritation of uninvolved skin, folliculitis, odour and staining of clothing, so compliance is often a problem. Coal tar treatments act synergistically with ultraviolet B radiation in the traditional Goeckerman regimen. There is at present no epidemiological evidence that topical tar products cause cutaneous or internal cancers when used to treat psoriasis.
This is one of the oldest treatments available for psoriasis, and when used together with ultraviolet B radiation (Ingram regimen) it is an important management option for inpatients or those treated at day treatment centres. Dithranol has a direct antiproliferative effect on epidermal keratinocytes. It is probably the most effective and safest topical treatment available but, as with coal tar, its use is limited by cosmetic acceptability. Treatment, usually in hospital, is started at 0.1% in non-smudging zinc oxide (Lassar's) paste and gradually increased. Paste is applied to each plaque and left in place under stockinette gauze for up to 24 hours. There are also short-contact preparations of dithranol, such as Dithrocream, which can be used at home under the supervision of the general practitioner. The main side effects are irritation, burning and purple-brown discolouration of uninvolved skin, clothes and baths.
Topical corticosteroids have a high patient compliance because of their efficacy and cosmetic acceptability. However, patients should be warned of their potential side effects. They can be used all over but are particularly reserved for sites such as hands, feet, flexures, genitalia and scalp. Recalcitrant psoriasis, particularly on the hands and feet, usually requires treatment with potent corticosteroids, sometimes under occlusion. In areas where the skin is much thinner, such as flexural sites, the face and genitalia, only mild potency steroids should be used. Topical corticosteroids should not be used regularly for more than 4 weeks without review. Rapid relapse may occur after stopping therapy. Corticosteroids can be used as monotherapy or in conjunction with other topical agents including tar, dithranol and vitamin D3 analogues.
Vitamin D3 analogues
Vitamin D3 analogues (calcipotriol and tacalcitol) directly normalize the abnormal epidermal keratinocyte proliferation and differentiation in psoriasis, and may be anti-inflammatory. They have the advantage of being cosmetically acceptable, effective and relatively safe. They are usually used once daily, in the evening, in combination with a moderate-potent corticosteroid in the mornings, for a few weeks. Their use in extensive psoriasis is limited by irritation and the potential for hypercalcaemia.
Tazarotene, a third-generation acetylenated retinoid, has been shown to have some effect in psoriasis, possibly by normalization of epidermal keratinocyte proliferation and differentiation.
UVB (wavelength 290-320 nm) plays an important role in the management of psoriasis. It is effective in the treatment of guttate and thin plaque psoriasis but has little efficacy in thick chronic plaque psoriasis. The main side effects are burning and potential carcinogenicity. UVB-induced erythema is predominantly caused at wave-lengths of 290-300 nm, however recent studies have shown that the therapeutic wavelengths in psoriasis are in the order of 311-315 nm. This led to the development of the TL-01 lamp which emits a wavelength of 311-313 nm, so-called 'narrowband UVB', allowing a higher dose of UVB to be delivered with less burning. TL-01 has been shown to be more effective than traditional broadband UVB. Clearance rates of 80-85% have been achieved in some studies of TL-01 therapy, and these are compatible to rates achieved with PUVA. Current human use suggests that TL-01 has a similar long-term risk to the older broadband tubes and a reduced risk of carcinogenicity when compared to PUVA.
Photochemotherapy is extremely effective with clearance rates of up to 90%. It combines a photosensitizing agent (psoralen) with long-wave UVA (wavelength 320-400 nm) and is known as PUVA. Patients take psoralen tablets 2-3 hours before UVA. If nausea occurs, bath PUVA can be considered. Patients are advised to wear UVA protective glasses for 12 hours after taking psoralen. Long-term PUVA causes photoageing and non-melanoma skin cancers, especially squamous cell carcinoma, and may possibly be related to the development of melanoma. In view of these long-term effects, PUVA is now only used twice a week when attempting to clear psoriasis, and maintenance treatments are now avoided.
Methotrexate is effective treatment for all forms of psoriasis. It is given as a once-weekly dose, but its use is limited by potential side effects of bone marrow toxicity and hepatic fibrosis. Patients are advised to abstain from alcohol while on the drug. Hepatic fibrosis can occur despite normal liver function tests. Recently, it has been shown that serum levels of the amino-propeptide of procollagen III, a marker of fibrosis, correlate with the results of liver biopsy in patients taking methotrexate.This marker is now used instead of regular liver biopsiesin patients on methotrexate to monitor hepatic fibrosis; only if the procollagen levels are repeatedly high is a liver biopsy recommended.
Ciclosporin has a known suppressive effect on T-lymphocyte function. It is a highly effective and rapidly acting systemic treatment for psoriasis. Before initiation of treatment patients should be normotensive with normal renal and hepatic function. The most common side effects are dysaesthesia, hypertrichosis, malaise and gingival hypertrophy. The main risks of prolonged treatment are hypertension and renal dysfunction, which is dose related. Ciclosporin should not be used in combination with phototherapy because of an increased risk of skin cancer.
Acitretin is a polyaromatic retinoid. It is an antiproliferative agent that acts on keratinocytes. Although not as effective as methotrexate or ciclosporin, it is relatively safe in the long term as it is not immunosuppressive. Before treatment, liver function and fasting lipids should be measured as acitretin is occasionally hepatotoxic and may increase serum levels of cholesterol and triglycerides. It is teratogen with a long half-life and therefore should be avoided in women of child-bearing age. Women should be advised not to become pregnant during and for at least 2 years after treatment with acitretin. Generalized pustular psoriasis and palmoplantar pustular psoriasis are particularly responsive to acitretin.
Other immunomodulation agents
Other systemic agents include hydroxyurea, azathioprine and mycophenolate mofetil.
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