PATHOLOGY

The pathology of psoriasis reflects the underlying immune-mediated inflammation and cellular hyperproliferation.

·         Hyperkeratosis with parakeratosis (presence of nucleated keratinocytes in the stratum corneum due lack of maturation of cells since rapid transit time do not permit normal maturation of cells).
·         Reduced or absent granular layer.
·         Acanthosis with elongation of rete ridges and a corresponding upward elongation of dermal papillae.

·         Infiltrate: Mononuclear in dermis and polymorphs in the upper epidermis forming collections called ‘microabscess of Munro’.

·         Upper dermal vasculature shows dilatation and tortuosity.

CLINICAL FEATURES

·        Family history is frequently elicited.

·        First manifestation at any age but two peaks are observed: the first peak in the second decade , the second in the sixth decade.

·        Onset may follow trauma, infection, sunburn or psychological stress.

·        Patients complain of prominent itchy, elevated red areas with increased scaling.

·        Patients may recognize that new lesions appear at sites of injury to the skin.

(This isomorphic phenomenon (Koebner reaction) typically occurs 7-14 days after the skin has been injured and has been found in 40-80% of patients with psoriasis.

In some patients, so-called reverse-Koebner reactions may be noted in which preexisting psoriatic plaques will clear after injury or trauma to the skin.

Koebner reaction may also be found in other dermatoses like, lichen planus, lichen nitidus, verruca plana and vitiligo  )

·        Joint pain, stiffness, and deformity are complaints in about10% of patients who have psoriatic arthritis.

Types of presentations: the patients may present in a variety of ways with overlapping features being not uncommon.

·        Chronic plaque psoriasis. The commonest type, presenting with typical plaques of psoriasis of the extensors and scalp.

·        Guttate psoriasis. Is commoner in childhood. Acute eruption of drop-shaped lesions distributed widely over the body. Usually follows an upper respiratory infection.

·        Flexural psoriasis: lesions are present over the flexors and intertriginous areas( axilla, groin, umbilical region, inframammary folds) the lesions may be moist and lack the typical scaling.

·        Pustular psoriasis. may be localized or generalized. Localized pustular psoriasis usually presents with persistent pustular eruptions of the hands and feet.
Generalized pustular psoriasis may occur as an explosive eruption of generalized pustules with systemic disturbances. This may follow withdrawal of systemic steroid therapy or application of irritants.

·        Arthropathic psoriasis . Arthritis may accompany any variety of psoriasis in about ten per cent of patients . Psoriatic arthritis may take several forms.  The commonest type is asymmetrical oligoarthritis, other types are: symmetrical seronegative rheumatoid-like disease , distal interphalangeal involvement( most characteristic, but relatively rare), axial skeletal involvement, and a destructive mutilating form (arthritis mutilans)

·        Erythrodermic psoriasis. Psoriasis may present with erythroderma (exfoliative dermatitis) There is generalized inflammatory erythema with profuse scaling.

Physical Exam:

The typical lesions of psoriasis have the following features;

·        The lesions are very well marginated with distinct border.

·        The lesions are raised above the surface.

·        The plaques usually have a diameter of one to several centimeters and have a round or oval shape. The lesions may merge together to give rise to geographic patterns.

·        The plaques typically have a rich red color and may be surrounded by a pale halo ( the halo of Woronoff).

·        The lesions are covered with a silvery white, mica-like, loosely adherent scales which, on removal may reveal  punctate bleeding points (Auspitz sign)

·        Symmetry:: the lesions are symmetrically disposed on extensor surfaces of the body. Typical sites of affection are the elbows, knees, shin, knuckles, sacral areas and scalp.

·        Uniformity: the psoriatic plaques tend to have the same features irrespective of site except for certain locations like the palms and soles, and the flexors.

Variations of lesions:

Variations by morphology or shape:

Apart from the typical plaque lesions, guttate lesions and pustules, lesions may take on a variety of morphological forms and shapes. Verrucous, lichenoid, follicular, linear, annular, figurate, gyrate are some of the terms used to describe these variants.

Variations by site:

Scalp: Diffusely involved. Thick scaling, no hair loss.

Penis:. Well-circumscribed reddish plaque without scales.

Hands and feet: Diffuse hyperkeratosis, Thick scales, fissures.

Sacral regions: thick fissures plaques, scaling may be absent.

Nails: involved in 25 to 50% of cases.

Nail pitting.
Discoloration.
Subungual hyperkeratosis.
Onycholysis (separation of nail-plate from the nail bed) giving rise to oil-drop sign.
Thickened friable nail plate.

Seborrhoeic dermatitis                                   Lichen simplex

Pityriasis rubra pilaris                                     Secondary syphilis

Leprosy                                                           Lichen planus

Candidiasis                                                     Tinea corporis and cruris

Discoid lupus erythematosus                         Bowen’s disease

Cutaneous T-cell lymphoma                          Hyperkeratotic eczema of hands and  feet         

Pityriasis rosea                                               Parapsoriasis

Three main modalities of therapy are used: topical, phototherapy and systemic agents. These are used either alone or in combinations.

TOPICAL THERAPY - Outpatient topical therapy is the first-line approach in the treatment of plaque psoriasis.

      Topical steroid :Potent topical steroids, applied twice a day is effective in controlling limited plaque psoriasis. Intralesional injection of triamcinolone acetonide into isolated chronic plaques may also be used/

      Anthralin (Dithranol): Derived from chrysarobin (active ingredient of Goa powder, derived from the bark of South American Araroba tree), it has antiproliferative and immunosuppressive action. It is best applied as short-contact therapy (washing off the medicine after a contact period of 10 to 30 minutes). Dithranol is irritant and can stain cloth , it  causes a reversible brownish pigmentation of the treated skin.

      Vitamin D3 analogues: Calcitriol and Calcipotriol are as effective as topical steroids and anthralin. Act by regulating keratinocyte proliferation and maturation. Side effects include irritation and hypercalcemia and kidney stones with high dose.

      Retinoids:  The synthetic retinoid Tazarotene when used topically, can regulate keratinocyte proliferation and maturation. Main side effect is irritation. Special precaution: women of child-bearing age.

      Coal tar: Tars have antiproliferative effect. May be combined with steoid therapy. Coal tar solution may be used for scalp psoriasis.

      Salicylic acid: As a two to ten per cent ointment, often combined with topical steroids, helps remove scales and also helps in penetration of steroids.

PHOTOTHERAPY - Phototherapy is used in the cases  of extensive, widespread disease resistant to topical treatment Proper facilities are required for the two main forms of phototherapy.

• UVB - Ultraviolet B (UVB) irradiation utilizes ultraviolet radiation with  wavelengths 290-320 nm (visible light range is 400-700 nm). It is used alone or combined with one or more topical treatments. The Goeckerman regimen uses coal tar followed by UVB exposure  and the Ingram method is based on anthralin application following a tar bath and UVB treatment. UVB more commonly is now combined with topical corticosteroids, calcipotriene, tazarotene, or simply bland emollients. UVB phototherapy is extremely effective for treating moderate-to-severe plaque psoriasis. Narrow-band UVB (UVB of 311 nm wave length) is now increasingly used for its effectiveness and low potential for photodamage.

• PUVA photochemotherapy -  In this  therapy (also known as PUVA),  a photosensitizing drug methoxsalen (8-methoxypsoralens) is given orally, followed by  ultraviolet A (UVA) irradiation to treat patients with more extensive disease. UVA irradiation utilizes light with wavelengths 320-400 nm. PUVA, decreases cellular proliferation by interfering with DNA synthesis, and also induces a localized immunosuppression by its action on T lymphocytes... Therapy usually is given 2-3 times per week on an outpatient basis, with maintenance treatments every 2-4 weeks until remission. Adverse effects of PUVA therapy include nausea, pruritus, and burning. Long-term complications include increased risks of photo damage and skin cancer. PUVA has been combined with oral retinoid derivatives to decrease the cumulative dose of UVA radiation to the skin.

SYSTEMIC THERAPY - Systemic treatments are used  when both topical treatments and phototherapy have failed. Also used for patients with very active psoriatic arthritis, erythrodermic psoriasis and generalized pustular psoriasis. Patients who have disabling disease through physical, psychological, social, or economic means also are considered candidates for systemic treatment.

 .     Antimetabolites: Methotrexate is the most popular agent used. A weekly oral or intramuscular dose of 15 to 25 mg is used. Started with low dose and gradually increased to the desired dosage. 5mg 12 hourly X 3 doses per week is the usual oral regimen. CBC, platelets, LFT, urinalysis, and creatinine. must be normal before starting therapy. These tests are repeated at regular intervals to monitor toxicity. Main side effects are nausea, vomiting, hepatic dysfunction (even fibrosis on long term therapy), and microcytic anemia. Hydroxyurea is the alternative antimetabolite. It is more toxic than methotrexate and rarely used.

Acitretin: A synthetic vitamin A derivative. Is used in a dose of 10 to 20 mg/day gradually increased to the maximum dose of 50mg/day. Main side effects are : teratogenicity (the drug should not be used in women of child-bearing potential) , hypertriglyceridemia, xerosis of skin, chelitis and alopecia. It may be used in combination with phototherapy, methotrexate or cyclosporine.

Cyclosporine: this drug selectively inhibits T-helper cell production of IL-2 and thus exerts an immunosuppressive effects. The usual dosage is 3 to 6mg/kg per day. A new microemulsion formulation may be used in a lower dosage. The commonest side effects are hypertension and nephrotoxicity.

Mycophenolate mofetil:  still under evaluation, this newly introduced drug inhibits synthesis of the nucleotide guanosine. The recommended dosage is500mg four times a day with a maximum dose of 4 gm . side effects are: teratogenicity, neutropenia, GI symptoms, and opportunistic infections.

Sulphasalazine may be used to treat psoriasis either alone or combined with methotrexate, particularly in psoriatic arthropathy.

• Complications are relatively uncommon.
• Many of the complications (pustular psoriasis, erythroderma) are commonly due to inappropriate and aggressive therapy.
• Psoriatic arthritis.
• Pustular psoriasis.
• Erythroderma and its metabolic complications.
• Infection, particularly Staph. infections of the patches.
• Eczematization due to topical agents.
• Amyloidosis , rare sequel to arthropathic of pustular psoriasis.
• Psychological consequences : depression, anxiety, lack of self-esteem.
• Potential complications of systemic therapy should not be overlooked.

• The course of plaque psoriasis is unpredictable. The duration of active disease, the time or the frequency of relapses, or the duration of a remission are unpredictable.. The disease rarely is life threatening, but often is intractable to treatment with relapses occurring in the majority of patients.

• Both early onset and family history of disease are considered poor prognostic indicators.

• Some suggest that stress also is associated with an unfavorable prognosis.