Pityriasis roseaPityriasis rosea

Cause:Cause:-The cause of pityriasis rosea is not known. -The cause of pityriasis rosea is not known. -An infectious agent may be the cause, but has not yet been -An infectious agent may be the cause, but has not yet been proven: human herpesvirus 7 is the latest suspect.proven: human herpesvirus 7 is the latest suspect.-The disorder seems not to be contagious.-The disorder seems not to be contagious.

Presentation:Presentation:-It is common, particularly during the winter. -It is common, particularly during the winter. -Mainly affects children and young adults. -Mainly affects children and young adults. -Most patients develop one plaque -Most patients develop one plaque (the ‘herald’ or ‘mother’ plaque)(the ‘herald’ or ‘mother’ plaque) before the others. It is larger (2–5 cm in diameter) than later before the others. It is larger (2–5 cm in diameter) than later lesions, and is rounder, redder and more scaly. lesions, and is rounder, redder and more scaly. -After several days many smaller plaques appear, mainly on the -After several days many smaller plaques appear, mainly on the trunk, but some also on the neck and extremities. trunk, but some also on the neck and extremities. -An individual plaque is oval, salmon pink and shows a delicate -An individual plaque is oval, salmon pink and shows a delicate scaling, adherent peripherally as a scaling, adherent peripherally as a collarettecollarette. . -The configuration of such plaques is often characteristic, their -The configuration of such plaques is often characteristic, their longitudinal axes run down and out from the spine, along the lines longitudinal axes run down and out from the spine, along the lines of the ribs.of the ribs.-About half of the patients complain of itching.-About half of the patients complain of itching.-A minority of patients have systemic symptoms such as aching -A minority of patients have systemic symptoms such as aching and tiredness.and tiredness.

Course:Course:-The herald plaque precedes the generalized eruption by several -The herald plaque precedes the generalized eruption by several days. days. -Subsequent lesions enlarge over the first week or two. -Subsequent lesions enlarge over the first week or two. -The eruption lasts between 2 and 10 weeks and then resolves-The eruption lasts between 2 and 10 weeks and then resolvesspontaneously, sometimes leaving hyperpigmented patches that spontaneously, sometimes leaving hyperpigmented patches that fade more slowly.fade more slowly.

Treatment:Treatment:-No treatment is curative, and active treatment is seldom needed. -No treatment is curative, and active treatment is seldom needed. -A moderately potent topical steroid or calamine lotion will help the -A moderately potent topical steroid or calamine lotion will help the itching. itching. -One per cent salicylic acid in soft white paraffin or emulsifying -One per cent salicylic acid in soft white paraffin or emulsifying ointment reduces scaling. ointment reduces scaling. -Sunlight or artificial UVB often relieves pruritus and may hasten -Sunlight or artificial UVB often relieves pruritus and may hasten resolution.resolution.

PsoriasisPsoriasis

-One to three per cent of most populations have psoriasis. -One to three per cent of most populations have psoriasis. -It is a chronic inflammatory skin disorder, characterized by well--It is a chronic inflammatory skin disorder, characterized by well-defined erythematous plaques covered by large adherent silvery defined erythematous plaques covered by large adherent silvery scales. scales. -It can start at any age but is rare under 10 years, and appears-It can start at any age but is rare under 10 years, and appearsmost often between 15 and 40 years. most often between 15 and 40 years. -Its course is unpredictable but is usually chronic with -Its course is unpredictable but is usually chronic with exacerbations and remissions.exacerbations and remissions.

Cause and pathogenesis:Cause and pathogenesis:-The precise cause of psoriasis is still unknown.-The precise cause of psoriasis is still unknown.-However, there is often a genetic predisposition, and sometimes -However, there is often a genetic predisposition, and sometimes an obvious environmental trigger.an obvious environmental trigger.-There are two key abnormalities in a psoriatic plaque: -There are two key abnormalities in a psoriatic plaque: 1-hyperproliferation of keratinocytes; 1-hyperproliferation of keratinocytes; 2-inflammatory cell infiltrate in which neutrophils and TH-1 2-inflammatory cell infiltrate in which neutrophils and TH-1 lymphocytes predominate.lymphocytes predominate. -Each of these abnormalities can induce the other, leading to a -Each of these abnormalities can induce the other, leading to a vicious cycle of keratinocyte proliferation and inflammatory vicious cycle of keratinocyte proliferation and inflammatory reaction; but it is still not clear which is the primary defect. reaction; but it is still not clear which is the primary defect.

Genetics:Genetics:-A child with one affected parent has a 16% chance of developing -A child with one affected parent has a 16% chance of developing the disease, rises to 50% if both parents are affected. the disease, rises to 50% if both parents are affected. -Psoriatic fathers are more likely to pass the disease to their -Psoriatic fathers are more likely to pass the disease to their children than are psoriatic mothers. children than are psoriatic mothers. -If non-psoriatic parents have a child with psoriasis, the risk for -If non-psoriatic parents have a child with psoriasis, the risk for subsequent children is about 10%. subsequent children is about 10%. -In one study, the disorder was concordant in 70% of monozygotic -In one study, the disorder was concordant in 70% of monozygotic twins but in only 20% of dizygotic ones. twins but in only 20% of dizygotic ones. -The mode of inheritance categorized as genetically complex, -The mode of inheritance categorized as genetically complex, implying a polygenic inheritance.implying a polygenic inheritance.

Psoriasis is also genetically heterogeneous.Psoriasis is also genetically heterogeneous. *Early onset psoriasis shows an obvious hereditary element*Early onset psoriasis shows an obvious hereditary elementand linkage analysis revealed the first psoriasis susceptibility and linkage analysis revealed the first psoriasis susceptibility locus (S1), close to the major histocompatibility complex Class I locus (S1), close to the major histocompatibility complex Class I (MHC-I) region. (MHC-I) region. *The hereditary element and the HLA associations are much *The hereditary element and the HLA associations are much weaker in late-onset psoriasis.weaker in late-onset psoriasis.*In 1994, a second psoriasis susceptibility locus (S2) was *In 1994, a second psoriasis susceptibility locus (S2) was discovered on 17q, incidentally next to a Crohn’s disease discovered on 17q, incidentally next to a Crohn’s disease susceptibility gene. susceptibility gene. *Since then three more susceptibility loci have been confirmed (on *Since then three more susceptibility loci have been confirmed (on 4q, 1q and 3q).4q, 1q and 3q).

Epidermal cell kinetics:Epidermal cell kinetics:The increased epidermal proliferation of psoriasis is caused by: The increased epidermal proliferation of psoriasis is caused by: 1.Excessive number of germinative cells entering the cell cycle 1.Excessive number of germinative cells entering the cell cycle The growth fraction approaches 100%, compared with 30% in The growth fraction approaches 100%, compared with 30% in normal skin. normal skin. 2.The epidermal turnover time is greatly shortened, to less than 10 2.The epidermal turnover time is greatly shortened, to less than 10 days as compared with 60 days in normal skin. days as compared with 60 days in normal skin.

Others think that psoriasis is caused by a genetic defect of Others think that psoriasis is caused by a genetic defect of retinoid signallingretinoid signalling and that is why it improves with retinoid and that is why it improves with retinoid treatment. treatment.

Inflammation:Inflammation: Certain interleukins and growth factors are elevated, and adhesion Certain interleukins and growth factors are elevated, and adhesion molecules are expressed or up-regulated in the lesions. molecules are expressed or up-regulated in the lesions. Immune events may well have a primary role in the pathogenesis Immune events may well have a primary role in the pathogenesis as follows:as follows:

1. 1. Keratinocytes are stimulated by various insults (e.g. trauma, Keratinocytes are stimulated by various insults (e.g. trauma, infections, drugs, ultraviolet radiation) to release IL-1, IL-8 and infections, drugs, ultraviolet radiation) to release IL-1, IL-8 and IL-18.IL-18.2. 2. IL-1 up-regulates the expression of intercellular adhesion IL-1 up-regulates the expression of intercellular adhesion molecule-1 (ICAM-1) on keratinocytes and E selectin on vascular molecule-1 (ICAM-1) on keratinocytes and E selectin on vascular endothelium in the dermal papillae.endothelium in the dermal papillae.Memory T lymphocytes accumulate in these papillary vessels Memory T lymphocytes accumulate in these papillary vessels because their lymphocyte function-associated antigen (LFA-1) because their lymphocyte function-associated antigen (LFA-1) sticks to adhesion molecules that are expressed on the vascular sticks to adhesion molecules that are expressed on the vascular endotheliumendothelium3. 3. IL-8 from keratinocytes attracts T lymphocytes and neutrophils IL-8 from keratinocytes attracts T lymphocytes and neutrophils to migrate from papillary vessels into the epidermis where the T to migrate from papillary vessels into the epidermis where the T cells are held by adhesion of their LFA-1 with ICAM-1 on cells are held by adhesion of their LFA-1 with ICAM-1 on keratinocytes.keratinocytes.

4. 4. T cells accumulating in the epidermis are activated as a result T cells accumulating in the epidermis are activated as a result of their interactions with Langerhans cells and keratinocytes.of their interactions with Langerhans cells and keratinocytes.Activated T cells release IL-2, IFN-alpha and tumour necrosis Activated T cells release IL-2, IFN-alpha and tumour necrosis factor-alpha (TNF-á).factor-alpha (TNF-á).5. 5. IL-2 ensures proliferation of the local T cells.IL-2 ensures proliferation of the local T cells.6. 6. IFN-alpha and TNF-alpha induce keratinocytes to to up-regulate IFN-alpha and TNF-alpha induce keratinocytes to to up-regulate their ICAM-1 expression and to produce further IL-6, IL-8 and their ICAM-1 expression and to produce further IL-6, IL-8 and TGF-alpha. TGF-alpha.

Bacterial exotoxins produced by Staphylococcus aureus and Bacterial exotoxins produced by Staphylococcus aureus and certain streptococci can act as superantigens and promote certain streptococci can act as superantigens and promote marked T-cell proliferation. marked T-cell proliferation. This appears to be a key mechanism in the pathogenesis ofThis appears to be a key mechanism in the pathogenesis ofguttate psoriasis.guttate psoriasis.

The dermis:The dermis:The dermal capillary loops in psoriatic plaques are abnormally The dermal capillary loops in psoriatic plaques are abnormally dilated and tortuous, and these changes come before epidermal dilated and tortuous, and these changes come before epidermal hyperplasia in the development of a new plaque. hyperplasia in the development of a new plaque. Fibroblasts from psoriatics replicate more rapidly in vitro.Fibroblasts from psoriatics replicate more rapidly in vitro.

Precipitating factors:Precipitating factors:1. 1. Trauma; if the psoriasis is active, lesions can appear in skin Trauma; if the psoriasis is active, lesions can appear in skin damaged by scratches or surgical wounds (the Kobner damaged by scratches or surgical wounds (the Kobner phenomenon).phenomenon).2. 2. Infection; tonsillitis caused by alpha-haemolytic streptococciInfection; tonsillitis caused by alpha-haemolytic streptococcioften triggers guttate psoriasis. AIDS often worsens it, or often triggers guttate psoriasis. AIDS often worsens it, or precipitates explosive forms.precipitates explosive forms.3. 3. Hormonal; psoriasis frequently improves in pregnancy only to Hormonal; psoriasis frequently improves in pregnancy only to relapse postpartum. relapse postpartum. 4.4. Hypocalcaemia secondary to hypoparathyroidism is a rare Hypocalcaemia secondary to hypoparathyroidism is a rare precipitating cause. precipitating cause. 5.5. after withdrawal of treatment with systemic steroids or potent after withdrawal of treatment with systemic steroids or potent topical steroids. topical steroids. 6. 6. Cigarette smoking and alcohol; both have an independent effect Cigarette smoking and alcohol; both have an independent effect in precipitating or maintaining psoriasis.in precipitating or maintaining psoriasis.7. 7. Emotion; emotional upsets seem to cause some exacerbations.Emotion; emotional upsets seem to cause some exacerbations.

Presentation:Presentation:Common patternsCommon patternsPlaque patternPlaque pattern Lesions are well demarcated and range from a few millimetres to Lesions are well demarcated and range from a few millimetres to several centimetres in diameter. The lesions are pink or red with several centimetres in diameter. The lesions are pink or red with large dry silvery-white scales. large dry silvery-white scales. The elbows, knees, lower back and scalp are sites of predilection.The elbows, knees, lower back and scalp are sites of predilection.

Guttate patternGuttate patternThis is seen in children and adolescents, often triggered by This is seen in children and adolescents, often triggered by streptococcal tonsillitis. Numerous small round red macules come streptococcal tonsillitis. Numerous small round red macules come up suddenly on the trunk and soon become scaly. up suddenly on the trunk and soon become scaly. The rash often clears in a few months but plaque psoriasis may The rash often clears in a few months but plaque psoriasis may develop later.develop later.

ScalpScalpAreas of scaling are interspersed with normal skin; their lumpiness Areas of scaling are interspersed with normal skin; their lumpiness is more easily felt than seen. Frequently, the psoriasis overflows is more easily felt than seen. Frequently, the psoriasis overflows just beyond the scalp margin. Significant hair loss is rare.just beyond the scalp margin. Significant hair loss is rare.

NailsNails pitting, onycholysis (separation of the nail from the nail bed and pitting, onycholysis (separation of the nail from the nail bed and sometimes subungual hyperkeratosis.sometimes subungual hyperkeratosis.

FlexuresFlexuresPsoriasis of the submammary, axillary and anogenital folds is not Psoriasis of the submammary, axillary and anogenital folds is not scaly although the glistening sharply demarcated red plaques, scaly although the glistening sharply demarcated red plaques, often with fissuring in the depth of the fold, are still readily often with fissuring in the depth of the fold, are still readily recognizable.recognizable.Flexural psoriasis is most common in women and in the elderly. Flexural psoriasis is most common in women and in the elderly.

Palms and solesPalms and solesPalmar psoriasis may be hard to recognize as its lesions are often Palmar psoriasis may be hard to recognize as its lesions are often poorly demarcated and barely erythematous.poorly demarcated and barely erythematous.The fingers may develop painful fissures.The fingers may develop painful fissures.

Less common patternsLess common patternsNapkin psoriasisNapkin psoriasisA psoriasiform spread outside the napkin area may give the first A psoriasiform spread outside the napkin area may give the first clue to a psoriatic tendency in an infant. Usually it clears quickly clue to a psoriatic tendency in an infant. Usually it clears quickly but there is an increased risk of ordinary psoriasis developing in but there is an increased risk of ordinary psoriasis developing in later life.later life.

Localized pustular psoriasis (palmo-plantarLocalized pustular psoriasis (palmo-plantar pustulosis)pustulosis)This is a recalcitrant, often painful condition. This is a recalcitrant, often painful condition. It affects the palms and soles, which become studded with It affects the palms and soles, which become studded with numerous sterile pustules, 3–10 mm in diameter, lying on annumerous sterile pustules, 3–10 mm in diameter, lying on anerythematous base. erythematous base. The pustules change to brown macules or scales. The pustules change to brown macules or scales. Generalized pustular psoriasis is a rare but serious condition, with Generalized pustular psoriasis is a rare but serious condition, with fever and recurrent episodes of pustulation within areas of fever and recurrent episodes of pustulation within areas of erythema.erythema.

Erythrodermic psoriasisErythrodermic psoriasisThis is also rare and can be sparked off by the irritant effect of tar This is also rare and can be sparked off by the irritant effect of tar or dithranol, by a drug eruption or by the withdrawal of potent or dithranol, by a drug eruption or by the withdrawal of potent topical or systemic steroids.topical or systemic steroids.The skin becomes universally and uniformly red with variable The skin becomes universally and uniformly red with variable scaling. scaling. Malaise is accompanied by shivering and the skin feels hot and Malaise is accompanied by shivering and the skin feels hot and uncomfortable.uncomfortable.

Psoriatic arthritis:Psoriatic arthritis:Arthritis occurs in about 5% of psoriatics. Several patterns are Arthritis occurs in about 5% of psoriatics. Several patterns are recognized: recognized: -Distal arthritis involves the terminal interphalangeal joints of the -Distal arthritis involves the terminal interphalangeal joints of the toes and fingers, especially those with marked nail changes.toes and fingers, especially those with marked nail changes.-Involvement of a single large joint.-Involvement of a single large joint.-One which mimics rheumatoid arthritis and may become -One which mimics rheumatoid arthritis and may become mutilating.mutilating.-One where the brunt is borne by the sacro-iliac joints and spine, -One where the brunt is borne by the sacro-iliac joints and spine, rheumatoid factor are negative and nodules are absent.rheumatoid factor are negative and nodules are absent.In patients with spondylitis and sacroiliitis there is a strong In patients with spondylitis and sacroiliitis there is a strong correlation with the presence of HLA-B27.correlation with the presence of HLA-B27.

Treatment:Treatment: At present there is no cure for psoriasis; all treatments are At present there is no cure for psoriasis; all treatments are suppressive and aimed at either inducing a remission or making suppressive and aimed at either inducing a remission or making the condition more tolerable. the condition more tolerable. However, spontaneous remissions will occur in 50% of patients. However, spontaneous remissions will occur in 50% of patients. No treatment, at present, alters the overall course of the disease.No treatment, at present, alters the overall course of the disease.

Main types of treatmentMain types of treatmentThese can be divided into four main categories: local, ultraviolet These can be divided into four main categories: local, ultraviolet radiation, systemic and combined.radiation, systemic and combined.

Local treatments:Local treatments:Vitamin D analogues:Vitamin D analogues: Calcipotriol and tacacitol are analogues of chlolecalciferol. Calcipotriol and tacacitol are analogues of chlolecalciferol. Both can be used for psoriasis affecting less than 40% of the Both can be used for psoriasis affecting less than 40% of the skin. skin. They work by influencing vitamin D receptors in keratinocytes, They work by influencing vitamin D receptors in keratinocytes, reducing epidermal proliferation and restoring a normal horny reducing epidermal proliferation and restoring a normal horny layer.layer. Local and usually transient irritation may occur, one way of Local and usually transient irritation may occur, one way of lessening this is to combine the use of calcipotriol with a lessening this is to combine the use of calcipotriol with a moderately potent steroid. moderately potent steroid. Calcipotriol should not be used on the face. Calcipotriol should not be used on the face.

Local retinoids:Local retinoids:Tazarotene is a topically active retinoid. It improves psoriasis by Tazarotene is a topically active retinoid. It improves psoriasis by reducing keratinocyte proliferation, normalizing the disturbed reducing keratinocyte proliferation, normalizing the disturbed differentiation and lessening the infiltrate of dermal inflammatory differentiation and lessening the infiltrate of dermal inflammatory cells. cells. It is applied once a day, in the evening, and can be used for It is applied once a day, in the evening, and can be used for courses of up to 12 weeks. courses of up to 12 weeks. It is available as either a 0.05% or 0.1% gel. It is available as either a 0.05% or 0.1% gel. Its main side effect is irritation, if this occurs, the strength should Its main side effect is irritation, if this occurs, the strength should be reduced to 0.05%; if irritation persists, applications should be be reduced to 0.05%; if irritation persists, applications should be cut to alternate days and a combination treatment with a local cut to alternate days and a combination treatment with a local steroid considered.steroid considered.The drug should not be used in pregnancy or during lactation.The drug should not be used in pregnancy or during lactation.

Topical corticosteroid:Topical corticosteroid:It is safe, but only under proper supervision by doctors well aware It is safe, but only under proper supervision by doctors well aware of problems such as dermal atrophy, tachyphylaxis, early of problems such as dermal atrophy, tachyphylaxis, early relapses, the occasional precipitation of unstable psoriasis and, relapses, the occasional precipitation of unstable psoriasis and, rarely, in extensive cases, of adrenal suppression caused by rarely, in extensive cases, of adrenal suppression caused by systemic absorption. systemic absorption.

The regular use of topical corticosteroids is less controversial The regular use of topical corticosteroids is less controversial under the following circumstances.under the following circumstances.1. 1. In ‘limited choice’ areas such as the ears, genitals and flexures In ‘limited choice’ areas such as the ears, genitals and flexures where tar and dithranol are seldom tolerated (mildly potent steroid where tar and dithranol are seldom tolerated (mildly potent steroid preparations should be used if possible).preparations should be used if possible).2. 2. For patients who cannot use vitamin D analogues, tar or For patients who cannot use vitamin D analogues, tar or dithranol because of allergic or irritant reactions (moderately dithranol because of allergic or irritant reactions (moderately potent preparations, except for ‘no choice’ areas where mildly potent preparations, except for ‘no choice’ areas where mildly potent ones should be used if possible).potent ones should be used if possible).3. 3. For unresponsive psoriasis on the scalp, palms and soles For unresponsive psoriasis on the scalp, palms and soles (moderately potent, potent and very potent but only in the short (moderately potent, potent and very potent but only in the short term preparations).term preparations).4. 4. For patients with minor localized psoriasis (moderately potent or For patients with minor localized psoriasis (moderately potent or potent preparations).potent preparations).

Dithranol (anthralin):Dithranol (anthralin):Inhibits DNA synthesis, but some of its benefits may be brought Inhibits DNA synthesis, but some of its benefits may be brought about by the formation of free radicals of oxygen. about by the formation of free radicals of oxygen. It has to be applied to the plaques only; and, if left on for more than It has to be applied to the plaques only; and, if left on for more than 30 min, must be covered with gauze dressings. 30 min, must be covered with gauze dressings. It is irritant, so treatment should start with a weak (0.1%) It is irritant, so treatment should start with a weak (0.1%) preparation, thereafter the strength can be stepped up at weekly preparation, thereafter the strength can be stepped up at weekly intervals.intervals.

Short contact therapy, in which dithranol is applied for no longer Short contact therapy, in which dithranol is applied for no longer than 30 min, is also effective. Initially a test patch of psoriasis is than 30 min, is also effective. Initially a test patch of psoriasis is treated with a 0.1% dithranol cream, left on for 20 min and then treated with a 0.1% dithranol cream, left on for 20 min and then washed off. If there is no undue reaction, the application can be washed off. If there is no undue reaction, the application can be extended the next day and, if tolerated, can be left on for 30 min.extended the next day and, if tolerated, can be left on for 30 min.After the cream is washed off, a bland application such as soft After the cream is washed off, a bland application such as soft white paraffin or emulsifying ointment is applied.white paraffin or emulsifying ointment is applied.

Dithranol is too irritant to apply to the face, the inner thighs, genital Dithranol is too irritant to apply to the face, the inner thighs, genital region or skin folds. Special care must be taken to avoid contact region or skin folds. Special care must be taken to avoid contact with the eyes.with the eyes.

Coal tar preparations:Coal tar preparations:Their mode of action is uncertain but tar inhibit DNA synthesis.Their mode of action is uncertain but tar inhibit DNA synthesis.The less refined tars are smelly, messy and stain clothes, but are The less refined tars are smelly, messy and stain clothes, but are more effective than the cleaner refined preparations. more effective than the cleaner refined preparations. Tar emulsions can also be added to the bath. Tar emulsions can also be added to the bath. Surprisingly, no increase in skin cancer has been found in patients Surprisingly, no increase in skin cancer has been found in patients treated for long periods with tar preparations; it has even been treated for long periods with tar preparations; it has even been suggested that psoriatics are less likely than normal to develop suggested that psoriatics are less likely than normal to develop skin cancer.skin cancer.

Ultraviolet radiation:Ultraviolet radiation:Most patients improve with natural sunlight. Most patients improve with natural sunlight. During the winter, courses of artificial ultraviolet radiation (UVB), During the winter, courses of artificial ultraviolet radiation (UVB), may help. may help. Both broadband UVB and narrow band UVB (311 nm) can be Both broadband UVB and narrow band UVB (311 nm) can be used. used. Treatments should be given twice to three times weekly for 8 Treatments should be given twice to three times weekly for 8 weeks. weeks. Goggles should be worn. Goggles should be worn. The main risk of UVB therapies in the short term is acute The main risk of UVB therapies in the short term is acute phototoxicity (sunburn-like reaction) and, in the long term, the phototoxicity (sunburn-like reaction) and, in the long term, the induction of skin cancer.induction of skin cancer.

Systemic treatmentSystemic treatmentA systemic approach should be considered if extensive psoriasis A systemic approach should be considered if extensive psoriasis (more than 20% of the body surface) fails to improve with (more than 20% of the body surface) fails to improve with prolonged courses of tar or dithranol.prolonged courses of tar or dithranol.The most commonly used systemic treatments are The most commonly used systemic treatments are photochemotherapy with psoralen and ultraviolet A (PUVA) photochemotherapy with psoralen and ultraviolet A (PUVA) treatment, retinoids, methotrexate, hydroxyurea treatment, retinoids, methotrexate, hydroxyurea (hydroxycarbamide), sulfasalazine, mycophenolate mofetil, (hydroxycarbamide), sulfasalazine, mycophenolate mofetil, cyclosporin and biological agents.cyclosporin and biological agents.

Photochemotherapy (PUVA)Photochemotherapy (PUVA)An oral dose of 8-methoxypsoralen (8-MOP) or 5 An oral dose of 8-methoxypsoralen (8-MOP) or 5 methoxypsoralen (5-MOP) is followed by exposure to long-wave methoxypsoralen (5-MOP) is followed by exposure to long-wave ultraviolet radiation (UVA: 320–400 nm). ultraviolet radiation (UVA: 320–400 nm).

The psoralen reaches the skin and, in the presence of UVA, forms The psoralen reaches the skin and, in the presence of UVA, forms photo-adducts with DNA pyrimidine bases; this inhibits DNA photo-adducts with DNA pyrimidine bases; this inhibits DNA synthesis and epidermal cell division.synthesis and epidermal cell division.

The drug is taken 1–2 h before exposure to a bank of UVA tubes.The drug is taken 1–2 h before exposure to a bank of UVA tubes. The initial exposure is calculated either by determining the The initial exposure is calculated either by determining the patient’s minimal phototoxic dose (the least dose of UVA that after patient’s minimal phototoxic dose (the least dose of UVA that after ingestion of 8-MOP produces a barely perceptible erythema 72 h ingestion of 8-MOP produces a barely perceptible erythema 72 h after testing) or by assessing skin color and ability to tan.after testing) or by assessing skin color and ability to tan.

The usual starting dose is from 0.5 J/cm2 (skin type I: always The usual starting dose is from 0.5 J/cm2 (skin type I: always burns and never tans) to 2.0 J/cm2 (skin type IV: never burns and burns and never tans) to 2.0 J/cm2 (skin type IV: never burns and always tans). always tans). Treatment is given two or three times a week with increasing Treatment is given two or three times a week with increasing doses of UVA, depending on erythema production and the doses of UVA, depending on erythema production and the therapeutic response. therapeutic response. Protective goggles are worn during radiation.Protective goggles are worn during radiation.

Clearance takes 5–10 weeks. Thereafter it is often possible to Clearance takes 5–10 weeks. Thereafter it is often possible to keep the skin clear by PUVA once a fortnight or every 3 weeks. keep the skin clear by PUVA once a fortnight or every 3 weeks. However, as the side-effects of PUVA relate to its cumulative However, as the side-effects of PUVA relate to its cumulative dose, maintenance therapy should not be used unless alternative dose, maintenance therapy should not be used unless alternative treatments prove to be unsatisfactory. treatments prove to be unsatisfactory.

Side effects: Side effects: Painful erythema, itching during and immediately after radiation, Painful erythema, itching during and immediately after radiation, nausea. nausea. Long-term side-effects include premature ageing of the skin, Long-term side-effects include premature ageing of the skin, cutaneous malignancies and cataract.cutaneous malignancies and cataract.

Retinoids Acitretin (10–25 mg daily) is an analogue of vitamin A, and is one of the few drugs helpful in pustular psoriasis. Minor side-effects are frequent and dose-related, include dry lips, mouth, vagina and eyes, peeling of the skin, pruritus, thinning of the hair, and unpleasant paronychia. All settle on stopping or reducing the dosage of the drug.

Acitretin can be used for long periods, but: Acitretin can be used for long periods, but: -regular blood tests are needed to exclude abnormal liver function -regular blood tests are needed to exclude abnormal liver function and the elevation of serum lipids. and the elevation of serum lipids. -yearly X-rays should detect bone spurs and ossification of -yearly X-rays should detect bone spurs and ossification of ligaments, especially the paraspinal ones (disseminated interstitial ligaments, especially the paraspinal ones (disseminated interstitial skeletal hyperostosis (DISH) syndrome).skeletal hyperostosis (DISH) syndrome). The most important side-effect is teratogenicity and acitretin The most important side-effect is teratogenicity and acitretin should not normally be prescribed to women of childbearing age.should not normally be prescribed to women of childbearing age.

Blood donation should be avoided for a similar period.Blood donation should be avoided for a similar period.

Retinoids and PUVA act synergistically and are often used Retinoids and PUVA act synergistically and are often used together in the so-called Re-PUVA regimen.together in the so-called Re-PUVA regimen.

MethotrexateMethotrexateThis folic acid antagonist inhibits DNA synthesis.This folic acid antagonist inhibits DNA synthesis. After an initial trial dose of 2.5 mg, in an adult of average weight, After an initial trial dose of 2.5 mg, in an adult of average weight, the drug is given orally once a week and the dose increased the drug is given orally once a week and the dose increased gradually to a maintenance one of 7.5–15 mg/week. gradually to a maintenance one of 7.5–15 mg/week.

The drug is eliminated largely by the kidneys and so the dose The drug is eliminated largely by the kidneys and so the dose must be reduced if renal function is poor.must be reduced if renal function is poor.

Minor and temporary side-effects, such as nausea and malaise, Minor and temporary side-effects, such as nausea and malaise, are common in the 48 h after administration.are common in the 48 h after administration.

The most serious drawback to this treatment isThe most serious drawback to this treatment ishepatic fibrosis, the risk of which is greatly increased in those who hepatic fibrosis, the risk of which is greatly increased in those who drink an excessive amount of alcohol, and a liver biopsy to drink an excessive amount of alcohol, and a liver biopsy to exclude active liver disease is advised for those with risk factors exclude active liver disease is advised for those with risk factors and should be repeated after every cumulative dose of 1.5–2 g, and should be repeated after every cumulative dose of 1.5–2 g, especially in less than perfectly healthy drinking adults.especially in less than perfectly healthy drinking adults.

Blood checks to exclude marrow suppression, and to monitor Blood checks to exclude marrow suppression, and to monitor renal and liver function, should also be performed regularly.renal and liver function, should also be performed regularly.

The drug is teratogenic and should not be given to females in their The drug is teratogenic and should not be given to females in their reproductive years.reproductive years. Oligospermia has been noted in men and fertility may be lowered; Oligospermia has been noted in men and fertility may be lowered; however, a child fathered by a man on methotrexate can be however, a child fathered by a man on methotrexate can be expected to be normal.expected to be normal. Folic acid, 5 mg daily, taken on days when the patient does not Folic acid, 5 mg daily, taken on days when the patient does not have methotrexate, can lessen nausea and reduce marrow have methotrexate, can lessen nausea and reduce marrow suppression. suppression.

Methotrexate should not be taken at the same time as systemic Methotrexate should not be taken at the same time as systemic steroids or cyclosporin.steroids or cyclosporin.

CyclosporinCyclosporinCyclosporin inhibits cell-mediated immune reactions.Cyclosporin inhibits cell-mediated immune reactions.It blocks resting lymphocytes in the G0 or early G1 phase of the It blocks resting lymphocytes in the G0 or early G1 phase of the cell cycle and inhibits lymphokine release, especially that of IL-2.cell cycle and inhibits lymphokine release, especially that of IL-2.

The initial daily dose is 3–5 mg/kg/day. With improvement the The initial daily dose is 3–5 mg/kg/day. With improvement the dose can often be reduced.dose can often be reduced.

Side-effects of long-term treatment include hypertension, kidney Side-effects of long-term treatment include hypertension, kidney damage and persistent viral warts with a risk of skin cancer. damage and persistent viral warts with a risk of skin cancer.

Blood pressure and renal function should be assessed carefully Blood pressure and renal function should be assessed carefully before starting treatment.before starting treatment.

The serum creatinine should be measured two or three times The serum creatinine should be measured two or three times before starting therapy to be sure of the baseline and then every before starting therapy to be sure of the baseline and then every other week for the first 3 months of therapy. Thereafter, if the other week for the first 3 months of therapy. Thereafter, if the results are stable, the frequency of testing will depend on the results are stable, the frequency of testing will depend on the dosage (monthly for > 2.5 mg/kg/day or every other month for < dosage (monthly for > 2.5 mg/kg/day or every other month for < 2.5 mg/kg/day).2.5 mg/kg/day). The dosage should be reduced if the serum creatinine The dosage should be reduced if the serum creatinine concentration rises to 30% above the baseline level on two concentration rises to 30% above the baseline level on two occasions within 2 weeks. occasions within 2 weeks.

If these changes do not reverse themselves when the dosage has If these changes do not reverse themselves when the dosage has been reduced for 1 month, then the drug should be stopped.been reduced for 1 month, then the drug should be stopped.

Hypertension is a common side-effect of cyclosporin:Hypertension is a common side-effect of cyclosporin:nearly 50% of patients develop a systolic blood pressure over 160 nearly 50% of patients develop a systolic blood pressure over 160 mmHg and/or a diastolic blood pressure over 95 mmHg. Usually mmHg and/or a diastolic blood pressure over 95 mmHg. Usually these rises are mild or moderate, and respond to concomitant these rises are mild or moderate, and respond to concomitant treatment with a calcium channel blocker or angiotensin-treatment with a calcium channel blocker or angiotensin-converting enzyme inhibiter.converting enzyme inhibiter.Diuretics, which may themselves worsen renal function, and Diuretics, which may themselves worsen renal function, and alpha blockers, which may themselves worsen psoriasis, should alpha blockers, which may themselves worsen psoriasis, should be avoided.be avoided.

Biologic therapyBiologic therapythese are new drugs, include:these are new drugs, include:infleximabinfleximabadalimumabadalimumabetanerceptetanerceptalefacept….etcalefacept….etc

Other systemic drugsOther systemic drugs Antimetabolites such as mycophenolate mofetil, 6-Antimetabolites such as mycophenolate mofetil, 6-thioguanine, azathioprine and hydroxyurea help psoriasis, but less thioguanine, azathioprine and hydroxyurea help psoriasis, but less than methotrexate; they tend to damage the marrow rather than than methotrexate; they tend to damage the marrow rather than the liver. Regular blood monitoring is again essential. the liver. Regular blood monitoring is again essential. Sulfasalazine occasionally helps psoriasis.Sulfasalazine occasionally helps psoriasis.

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