dermatology.Psoriasis.(dr.darseem)

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dermatology.Psoriasis.(dr.darseem)

  1. 1. Pityriasis rosea
  2. 2. Cause: -The cause of pityriasis rosea is not known. -An infectious agent may be the cause, but has not yet been proven: human herpesvirus 7 is the latest suspect. -The disorder seems not to be contagious.
  3. 3. Presentation: -It is common, particularly during the winter. -Mainly affects children and young adults. -Most patients develop one plaque (the ‘herald’ or ‘mother’ plaque) before the others. It is larger (2–5 cm in diameter) than later lesions, and is rounder, redder and more scaly. -After several days many smaller plaques appear, mainly on the trunk, but some also on the neck and extremities. -An individual plaque is oval, salmon pink and shows a delicate scaling, adherent peripherally as a collarette . -The configuration of such plaques is often characteristic, their longitudinal axes run down and out from the spine, along the lines of the ribs. -About half of the patients complain of itching. -A minority of patients have systemic symptoms such as aching and tiredness.
  4. 5. Course: -The herald plaque precedes the generalized eruption by several days. -Subsequent lesions enlarge over the first week or two. -The eruption lasts between 2 and 10 weeks and then resolves spontaneously, sometimes leaving hyperpigmented patches that fade more slowly.
  5. 6. Treatment: -No treatment is curative, and active treatment is seldom needed. -A moderately potent topical steroid or calamine lotion will help the itching. -One per cent salicylic acid in soft white paraffin or emulsifying ointment reduces scaling. -Sunlight or artificial UVB often relieves pruritus and may hasten resolution.
  6. 7. Psoriasis
  7. 9. -One to three per cent of most populations have psoriasis. -It is a chronic inflammatory skin disorder, characterized by well-defined erythematous plaques covered by large adherent silvery scales. -It can start at any age but is rare under 10 years, and appears most often between 15 and 40 years. -Its course is unpredictable but is usually chronic with exacerbations and remissions.
  8. 10. Cause and pathogenesis: -The precise cause of psoriasis is still unknown. -However, there is often a genetic predisposition, and sometimes an obvious environmental trigger. -There are two key abnormalities in a psoriatic plaque: 1-hyperproliferation of keratinocytes; 2-inflammatory cell infiltrate in which neutrophils and TH-1 lymphocytes predominate. -Each of these abnormalities can induce the other, leading to a vicious cycle of keratinocyte proliferation and inflammatory reaction; but it is still not clear which is the primary defect.
  9. 11. Genetics: -A child with one affected parent has a 16% chance of developing the disease, rises to 50% if both parents are affected. -Psoriatic fathers are more likely to pass the disease to their children than are psoriatic mothers. -If non-psoriatic parents have a child with psoriasis, the risk for subsequent children is about 10%. -In one study, the disorder was concordant in 70% of monozygotic twins but in only 20% of dizygotic ones. -The mode of inheritance categorized as genetically complex, implying a polygenic inheritance.
  10. 12. Psoriasis is also genetically heterogeneous. *Early onset psoriasis shows an obvious hereditary element and linkage analysis revealed the first psoriasis susceptibility locus (S1), close to the major histocompatibility complex Class I (MHC-I) region. *The hereditary element and the HLA associations are much weaker in late-onset psoriasis. *In 1994, a second psoriasis susceptibility locus (S2) was discovered on 17q, incidentally next to a Crohn’s disease susceptibility gene. *Since then three more susceptibility loci have been confirmed (on 4q, 1q and 3q).
  11. 13. Epidermal cell kinetics: The increased epidermal proliferation of psoriasis is caused by: 1.Excessive number of germinative cells entering the cell cycle The growth fraction approaches 100%, compared with 30% in normal skin. 2.The epidermal turnover time is greatly shortened, to less than 10 days as compared with 60 days in normal skin. Others think that psoriasis is caused by a genetic defect of retinoid signalling and that is why it improves with retinoid treatment.
  12. 14. Inflammation: Certain interleukins and growth factors are elevated, and adhesion molecules are expressed or up-regulated in the lesions. Immune events may well have a primary role in the pathogenesis as follows:
  13. 15. 1. Keratinocytes are stimulated by various insults (e.g. trauma, infections, drugs, ultraviolet radiation) to release IL-1, IL-8 and IL-18. 2. IL-1 up-regulates the expression of intercellular adhesion molecule-1 (ICAM-1) on keratinocytes and E selectin on vascular endothelium in the dermal papillae. Memory T lymphocytes accumulate in these papillary vessels because their lymphocyte function-associated antigen (LFA-1) sticks to adhesion molecules that are expressed on the vascular endothelium 3. IL-8 from keratinocytes attracts T lymphocytes and neutrophils to migrate from papillary vessels into the epidermis where the T cells are held by adhesion of their LFA-1 with ICAM-1 on keratinocytes.
  14. 16. 4. T cells accumulating in the epidermis are activated as a result of their interactions with Langerhans cells and keratinocytes. Activated T cells release IL-2, IFN-alpha and tumour necrosis factor-alpha (TNF-á). 5. IL-2 ensures proliferation of the local T cells. 6. IFN-alpha and TNF-alpha induce keratinocytes to to up-regulate their ICAM-1 expression and to produce further IL-6, IL-8 and TGF-alpha. Bacterial exotoxins produced by Staphylococcus aureus and certain streptococci can act as superantigens and promote marked T-cell proliferation. This appears to be a key mechanism in the pathogenesis of guttate psoriasis.
  15. 17. The dermis: The dermal capillary loops in psoriatic plaques are abnormally dilated and tortuous, and these changes come before epidermal hyperplasia in the development of a new plaque. Fibroblasts from psoriatics replicate more rapidly in vitro.
  16. 18. Precipitating factors: 1. Trauma; if the psoriasis is active, lesions can appear in skin damaged by scratches or surgical wounds (the Kobner phenomenon). 2. Infection; tonsillitis caused by alpha-haemolytic streptococci often triggers guttate psoriasis. AIDS often worsens it, or precipitates explosive forms. 3. Hormonal; psoriasis frequently improves in pregnancy only to relapse postpartum. 4. Hypocalcaemia secondary to hypoparathyroidism is a rare precipitating cause. 5. after withdrawal of treatment with systemic steroids or potent topical steroids. 6. Cigarette smoking and alcohol; both have an independent effect in precipitating or maintaining psoriasis. 7. Emotion; emotional upsets seem to cause some exacerbations.
  17. 19. Presentation: Common patterns Plaque pattern Lesions are well demarcated and range from a few millimetres to several centimetres in diameter. The lesions are pink or red with large dry silvery-white scales. The elbows, knees, lower back and scalp are sites of predilection. Guttate pattern This is seen in children and adolescents, often triggered by streptococcal tonsillitis. Numerous small round red macules come up suddenly on the trunk and soon become scaly. The rash often clears in a few months but plaque psoriasis may develop later.
  18. 22. Scalp Areas of scaling are interspersed with normal skin; their lumpiness is more easily felt than seen. Frequently, the psoriasis overflows just beyond the scalp margin. Significant hair loss is rare. Nails pitting, onycholysis (separation of the nail from the nail bed and sometimes subungual hyperkeratosis. Flexures Psoriasis of the submammary, axillary and anogenital folds is not scaly although the glistening sharply demarcated red plaques, often with fissuring in the depth of the fold, are still readily recognizable. Flexural psoriasis is most common in women and in the elderly.
  19. 26. Palms and soles Palmar psoriasis may be hard to recognize as its lesions are often poorly demarcated and barely erythematous. The fingers may develop painful fissures. Less common patterns Napkin psoriasis A psoriasiform spread outside the napkin area may give the first clue to a psoriatic tendency in an infant. Usually it clears quickly but there is an increased risk of ordinary psoriasis developing in later life.
  20. 28. Localized pustular psoriasis (palmo-plantar pustulosis) This is a recalcitrant, often painful condition. It affects the palms and soles, which become studded with numerous sterile pustules, 3–10 mm in diameter, lying on an erythematous base. The pustules change to brown macules or scales. Generalized pustular psoriasis is a rare but serious condition, with fever and recurrent episodes of pustulation within areas of erythema.
  21. 31. Erythrodermic psoriasis 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 topical or systemic steroids. The skin becomes universally and uniformly red with variable scaling. Malaise is accompanied by shivering and the skin feels hot and uncomfortable.
  22. 33. Psoriatic arthritis: Arthritis occurs in about 5% of psoriatics. Several patterns are recognized: -Distal arthritis involves the terminal interphalangeal joints of the toes and fingers, especially those with marked nail changes. -Involvement of a single large joint. -One which mimics rheumatoid arthritis and may become mutilating. -One where the brunt is borne by the sacro-iliac joints and spine, rheumatoid factor are negative and nodules are absent. In patients with spondylitis and sacroiliitis there is a strong correlation with the presence of HLA-B27.
  23. 34. Treatment: At present there is no cure for psoriasis; all treatments are suppressive and aimed at either inducing a remission or making the condition more tolerable. However, spontaneous remissions will occur in 50% of patients. No treatment, at present, alters the overall course of the disease. Main types of treatment These can be divided into four main categories: local, ultraviolet radiation, systemic and combined.
  24. 35. Local treatments: Vitamin D analogues: Calcipotriol and tacacitol are analogues of chlolecalciferol. Both can be used for psoriasis affecting less than 40% of the skin. They work by influencing vitamin D receptors in keratinocytes, reducing epidermal proliferation and restoring a normal horny layer. Local and usually transient irritation may occur, one way of lessening this is to combine the use of calcipotriol with a moderately potent steroid. Calcipotriol should not be used on the face.
  25. 36. Local retinoids: Tazarotene is a topically active retinoid. It improves psoriasis by reducing keratinocyte proliferation, normalizing the disturbed differentiation and lessening the infiltrate of dermal inflammatory cells. It is applied once a day, in the evening, and can be used for courses of up to 12 weeks. It is available as either a 0.05% or 0.1% gel. Its main side effect is irritation, if this occurs, the strength should be reduced to 0.05%; if irritation persists, applications should be cut to alternate days and a combination treatment with a local steroid considered. The drug should not be used in pregnancy or during lactation.
  26. 37. Topical corticosteroid: It is safe, but only under proper supervision by doctors well aware of problems such as dermal atrophy, tachyphylaxis, early relapses, the occasional precipitation of unstable psoriasis and, rarely, in extensive cases, of adrenal suppression caused by systemic absorption.
  27. 38. The regular use of topical corticosteroids is less controversial under the following circumstances. 1. In ‘limited choice’ areas such as the ears, genitals and flexures where tar and dithranol are seldom tolerated (mildly potent steroid preparations should be used if possible). 2. For patients who cannot use vitamin D analogues, tar or dithranol because of allergic or irritant reactions (moderately potent preparations, except for ‘no choice’ areas where mildly potent ones should be used if possible). 3. For unresponsive psoriasis on the scalp, palms and soles (moderately potent, potent and very potent but only in the short term preparations). 4. For patients with minor localized psoriasis (moderately potent or potent preparations).
  28. 39. Dithranol (anthralin): Inhibits DNA synthesis, but some of its benefits may be brought 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 30 min, must be covered with gauze dressings. It is irritant, so treatment should start with a weak (0.1%) preparation, thereafter the strength can be stepped up at weekly intervals.
  29. 40. Short contact therapy, in which dithranol is applied for no longer 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 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. After the cream is washed off, a bland application such as soft white paraffin or emulsifying ointment is applied. 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 with the eyes.
  30. 41. Coal tar preparations: Their mode of action is uncertain but tar inhibit DNA synthesis. The less refined tars are smelly, messy and stain clothes, but are more effective than the cleaner refined preparations. Tar emulsions can also be added to the bath. Surprisingly, no increase in skin cancer has been found in patients treated for long periods with tar preparations; it has even been suggested that psoriatics are less likely than normal to develop skin cancer.
  31. 42. Ultraviolet radiation: Most patients improve with natural sunlight. During the winter, courses of artificial ultraviolet radiation (UVB), may help. Both broadband UVB and narrow band UVB (311 nm) can be used. Treatments should be given twice to three times weekly for 8 weeks. Goggles should be worn. The main risk of UVB therapies in the short term is acute phototoxicity (sunburn-like reaction) and, in the long term, the induction of skin cancer.
  32. 43. Systemic treatment A systemic approach should be considered if extensive psoriasis (more than 20% of the body surface) fails to improve with prolonged courses of tar or dithranol. The most commonly used systemic treatments are photochemotherapy with psoralen and ultraviolet A (PUVA) treatment, retinoids, methotrexate, hydroxyurea (hydroxycarbamide), sulfasalazine, mycophenolate mofetil, cyclosporin and biological agents.
  33. 44. Photochemotherapy (PUVA) An oral dose of 8-methoxypsoralen (8-MOP) or 5 methoxypsoralen (5-MOP) is followed by exposure to long-wave ultraviolet radiation (UVA: 320–400 nm). The psoralen reaches the skin and, in the presence of UVA, forms photo-adducts with DNA pyrimidine bases; this inhibits DNA synthesis and epidermal cell division. The drug is taken 1–2 h before exposure to a bank of UVA tubes. The initial exposure is calculated either by determining the patient’s minimal phototoxic dose (the least dose of UVA that after ingestion of 8-MOP produces a barely perceptible erythema 72 h after testing) or by assessing skin color and ability to tan.
  34. 45. 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 always tans). Treatment is given two or three times a week with increasing doses of UVA, depending on erythema production and the therapeutic response. Protective goggles are worn during radiation.
  35. 46. Clearance takes 5–10 weeks. Thereafter it is often possible to keep the skin clear by PUVA once a fortnight or every 3 weeks. However, as the side-effects of PUVA relate to its cumulative dose, maintenance therapy should not be used unless alternative treatments prove to be unsatisfactory. Side effects: Painful erythema, itching during and immediately after radiation, nausea. Long-term side-effects include premature ageing of the skin, cutaneous malignancies and cataract.
  36. 47. 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.
  37. 48. Acitretin can be used for long periods, but: -regular blood tests are needed to exclude abnormal liver function and the elevation of serum lipids. -yearly X-rays should detect bone spurs and ossification of ligaments, especially the paraspinal ones (disseminated interstitial skeletal hyperostosis (DISH) syndrome). The most important side-effect is teratogenicity and acitretin should not normally be prescribed to women of childbearing age. Blood donation should be avoided for a similar period. Retinoids and PUVA act synergistically and are often used together in the so-called Re-PUVA regimen.
  38. 49. Methotrexate This folic acid antagonist inhibits DNA synthesis. 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 gradually to a maintenance one of 7.5–15 mg/week. The drug is eliminated largely by the kidneys and so the dose must be reduced if renal function is poor. Minor and temporary side-effects, such as nausea and malaise, are common in the 48 h after administration.
  39. 50. The most serious drawback to this treatment is hepatic fibrosis, the risk of which is greatly increased in those who drink an excessive amount of alcohol, and a liver biopsy to exclude active liver disease is advised for those with risk factors and should be repeated after every cumulative dose of 1.5–2 g, especially in less than perfectly healthy drinking adults.
  40. 51. Blood checks to exclude marrow suppression, and to monitor renal and liver function, should also be performed regularly. The drug is teratogenic and should not be given to females in their reproductive years. Oligospermia has been noted in men and fertility may be lowered; however, a child fathered by a man on methotrexate can be expected to be normal. Folic acid, 5 mg daily, taken on days when the patient does not have methotrexate, can lessen nausea and reduce marrow suppression. Methotrexate should not be taken at the same time as systemic steroids or cyclosporin.
  41. 52. Cyclosporin Cyclosporin inhibits cell-mediated immune reactions. It blocks resting lymphocytes in the G0 or early G1 phase of the cell cycle and inhibits lymphokine release, especially that of IL-2. The initial daily dose is 3–5 mg/kg/day. With improvement the dose can often be reduced. Side-effects of long-term treatment include hypertension, kidney damage and persistent viral warts with a risk of skin cancer. Blood pressure and renal function should be assessed carefully before starting treatment.
  42. 53. The serum creatinine should be measured two or three times before starting therapy to be sure of the baseline and then every other week for the first 3 months of therapy. Thereafter, if 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 < 2.5 mg/kg/day). The dosage should be reduced if the serum creatinine concentration rises to 30% above the baseline level on two occasions within 2 weeks. If these changes do not reverse themselves when the dosage has been reduced for 1 month, then the drug should be stopped.
  43. 54. Hypertension is a common side-effect of cyclosporin: nearly 50% of patients develop a systolic blood pressure over 160 mmHg and/or a diastolic blood pressure over 95 mmHg. Usually these rises are mild or moderate, and respond to concomitant treatment with a calcium channel blocker or angiotensin-converting enzyme inhibiter. Diuretics, which may themselves worsen renal function, and alpha blockers, which may themselves worsen psoriasis, should be avoided.
  44. 55. Biologic therapy these are new drugs, include: infleximab adalimumab etanercept alefacept….etc
  45. 56. Other systemic drugs Antimetabolites such as mycophenolate mofetil, 6- thioguanine, azathioprine and hydroxyurea help psoriasis, but less than methotrexate; they tend to damage the marrow rather than the liver. Regular blood monitoring is again essential. Sulfasalazine occasionally helps psoriasis.
  46. 57. Thanks

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