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USMLE – Psoriasis

Psoriasis is a non-infectious, inflammatory disease of the skin, characterized by well-defined erythematous plaques with large, adherent, silvery scales.

The main abnormality in psoriasis is increased epidermal proliferation due to excessive division of cells in the basal layers. The transit time of keratinocytes through the epidermis is shortened and the epidermal turnover time falls from 28 to 5 or 6 days.

Between 1% and 3% of most populations has psoriasis. It is most common in Europe and North America. It may start at any age but is rare under 10 years and often seen between 15 and 40 years. The course of disease is unpredictable but is usually chronic with exacerbations and remissions.

Etiology

Basic defect
This remains unknown but the following factors are involved.

Genetic. There is frequently a genetic predisposition. A child with one affected parent has a 15% chance of developing the disease and this rises to 50% if both parents are affected. If non-psoriatic parents have a child with psoriasis, the risk for subsequent children is about 10%. Psoriasis is a genetically complex disease trait. There is wide clinical and genetic heterogeneity. Linkages have been demonstrated to different loci, including chromosomes 6p (Cw6 region), 17q, 4q and 2q.

Biochemical. It is not known if biochemical abnormalities are the cause or result of increased epidermal proliferation. There are increased levels of prostaglandins, leukotrienes and hydroxyeicosatetrenoic (HETE) acids in the epidermis. These may cause both the increased cellular proliferation seen in psoriasis and the inflammatory changes. Increased activity of phospholipase A2 appears to be primarily responsible for these changes.

Decreased cyclic adenosine monophosphate (cAMP) and increased cyclic guanosine monophosphate (cGMP) are found in lesions and beta-adrenoceptor antagonist drugs may exacerbate psoriasis by inhibiting cAMP formation. Polyamines are elevated in lesional skin, due to increased activity of ornithine decarboxylase and may be intimately associated with cellular proliferation. Plasminogen activator is greatly increased in the lesions of psoriasis and its level parallels the epidermal mitotic rate.

The level of calmodulin, a calcium-binding protein, is also raised in lesions and falls with successful treatment. The calcium-calmodulin complex may regulate epidermal cell proliferation by influencing phospholipase A2 and cAMP phosphodiesterase (catalyses cAMP conversion to AMP) activity.

Immunopathological. The inflammatory reaction may be part of an immunological response to as yet unknown antigens. Immune complexes to epidermal antigens have been detected in damaged skin and may activate complement, thereby attracting neutrophils to the area. Certain interleukins (IL-1, IL-2, IL-6 and IL-8), interferon gamma and growth factors (TNF-alpha and TGF-alpha) are elevated and adhesion molecules are expressed or upregulated in lesions of psoriasis. The mononuclear infiltrate is mainly of T lymphocytes, most of which are of the helper type (Th-1) in the dermis and of the cytotoxic type in the epidermis. The beneficial effect of cyclosporin A in psoriasis may be due to its anti-T helper cell effect. Streptococcal superantigens, from the throat, appear to be responsible for T-cell activation in guttate psoriasis.

Dermal. There is substantial evidence to suggest that the increased epidermal cell proliferation of psoriasis is also related to the increased replication and metabolism of dermal fibroblasts. Both dermal and epidermal abnormalities appear to be necessary for the sustenance of psoriasis.

Given the basic defect, an individual may not inevitably develop psoriasis but certain precipitating factors make this more likely.

Precipitating factors
Although there appears to be no obvious precipitating factor in about 70% of exacerbations of psoriasis, many factors are responsible for the minority of flare-ups.

Clinical features

Stable plaque psoriasis
This is the most common type. Individual lesions are well demarcated and range from a few millimeters to several centimeters in diameter. The lesions are red with dry, silvery-white scaling, which may be obvious only after scraping the surface. The elbows, knees and lower back are commonly involved.

Other sites of predilection include:

Scalp. This site is often involved, presumably due to repeated trauma from brushing and combing. Areas of marked scaling are interspersed with normal skin, producing a lumpiness which is more easily felt than seen. Significant hair loss occurs only if there is gross involvement.

Nails. Involvement of the nails is common, with ‘thimble pitting‘, onycholysis (separation of the nail from the nail bed) and subungual hyperkeratosis. It often reflects the severity of the psoriasis elsewhere.

Flexures. Psoriasis involving the natal cleft, submammary and axillary folds is not scaly but red, glistening and symmetrical.

Palms. Psoriasis here is often difficult to recognize, as individual plaques may be poorly demarcated and barely erythematous.

Napkin area. This may give the first hint of a psoriatic tendency in an infant.

Guttate psoriasis
This is usually seen in children and adolescents and may be the first sign of psoriasis. The rash often appears rapidly and individual lesions are droplet-shaped, small (seldom greater than 1 cm in diameter) and scaly. Bouts of guttate psoriasis usually clear in a few months, but patients may develop the plaque pattern later.

Erythrodermic psoriasis
The skin becomes universally red and scaly. Shivering compensates for the considerable heat loss. This unpleasant variant may be initiated by the irritant effect of tar or dithranol or the withdrawal of systemic or potent topical corticosteroids.

Pustular psoriasis
The generalized form is a rare but serious type of psoriasis. The onset is sudden, with myriads of small sterile pustules erupting on an erythematous base. The patient is ill with a swinging pyrexia, coinciding with the appearance of new pustules, and requires hospital admission.

The localized form is more common. It most often involves the palms and soles. The eruption consists of numerous small sterile pustules lying on an erythematous base, which leave brown macules or scaling in their wake. Some regard this as a separate disease entity.

Complications
Psoriatic arthropathy is a possible complication, occurring in about 5% of psoriatics. Distal arthritis involves the terminal interphalangeal joints of the toes and fingers, especially those with marked nail changes. Other patterns include: involvement of a single large joint, a variety which mimics rheumatoid arthritis and which may be destructive; and one involving the sacroiliac joints and lumbar spine (associated with HLA-B27). Tests for rheumatoid factor are usually negative in true psoriatic arthropathy and rheumatoid nodules are absent.

Investigations
Few are indicated. Biopsy is seldom necessary because the clinical picture is usually characteristic. Throat swabbing for beta-hemolytic streptococci should be performed in guttate psoriasis and an ASO titer or DNAase B may be helpful. Skin scrapings and nail clippings may have to be examined to exclude tinea. Radiology and tests for rheumatoid factor are important in assessing arthritis.

Management

General measures
Explanation, reassurance and instruction are vital and must relate to the patient’s or parent’s intelligence. Both doctor and patient must keep the disease in perspective, so that treatment does not become more troublesome than the disease itself.

Physical and mental rest help to support the specific management of acute flare-ups of psoriasis. Concomitant depression and anxiety should be treated.

Local measures
Coal tar preparations. Crude coal tar and its distillation products have been used to treat psoriasis for many years. Their main mode of action is probably by inhibiting DNA synthesis.

Many products are available; in general the messier, less refined preparations (e.g. 10% strong coal tar solution and 4% tar paste) are more effective than the more refined and cleaner proprietary ointments. They are applied to the patches of psoriasis once or twice daily. Salicylic acid (1-2%), sometimes added to tar preparations to remove scaling, is useful in the management of scalp psoriasis.

Dithranol. This also inhibits DNA synthesis. Although it is irritant and more tricky to use than coal tar, its use has become widespread. The most popular regimen is short contact therapy in which the cream is applied to lesions for no longer than 30 minutes and then washed off. Initially 0.1% dithranol cream is used but, depending on the response, the strength may be increased stepwise to 2% over a few weeks. Dithranol stains normal skin purple-brown but the discoloration peels off after a few days.

Eruptive and unstable patches of psoriasis are unsuitable for treatment with coal tar or dithranol and those with limited experience of their use should select test patches of psoriasis for initial treatment. Coal tar preparations and dithranol are best avoided on the face, genitalia and body folds because they are irritating.

Calcipotriol. This recently introduced vitamin D analogue reduces epidermal proliferation and restores a normal horny layer. It is applied twice daily and providing no more than 100 g is used each week, it does not cause hypercalcemia and hypercalciuria. Patients like calcipotriol because it is odor less, color less and does not stain. Irritation, which is usually transient, is the main side-effect.

Retinoids. Topical preparations have become available recently. They are most useful for localized plaques. Significant systemic absorption is avoided by limiting the amount applied.

Corticosteroids. These are liked by patients and some doctors because they are clean and effective initially. However, there are few indications for their long-term use as, on their withdrawal, psoriasis may relapse rapidly or even change to an unstable phase which is more difficult to manage than previously.

Only mild steroids should be used on the face but moderately potent ones are suitable for elsewhere. Tarsteroid combinations are a useful stepping stone to pure tar preparations, while steroid-antifungal combinations are helpful for flexural psoriasis.

Ultraviolet radiation. Most patients improve with natural sunlight and many clear their psoriasis by sunbathing during holiday periods. During the winter 6-week courses of medium wave or narrow-band ultraviolet radiation (UVB) given in specialist centers 2-3 times weekly are often helpful. In the majority of patients sun beds (emitting long-wave ultraviolet waves-UVA) are not beneficial. Combination therapies with UVB, coal tar preparations and dithranol are used to clear psoriasis more quickly than can be achieved by monotherapies.

Systemic treatment
This will be considered by a dermatologist if extensive psoriasis fails to respond to the local measures outlined above. The most commonly used systemic treatments are photochemotherapy with PUVA (psoralen + UVA). retinoids (acitretin), methotrexate and cyclosporin A. All of these treatments have potential side-effects and patients receiving them require regular, specialist supervision.

Lillian Thompson By Lillian Thompson

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