The increased rate of production of epidermal cells outweighs the rate of exfoliation of the skin, causing thick scaling plaques. Psoriasis was previously thought to be a skin disease only. However, more and more evidence suggests that it has several systemic implications, including depression, myocardial infarctions and arthritis.
There are a number of factors implicated in the aetiology of psoriasis, with autosomal dominant patterns of inheritance being the most significant of all. HLA-B13,-B17, and -Cw6 are all associated with plaque psoriasis.
Several putative genetic susceptibility loci have also been identified, including psoriasis susceptibility 1 (PSOR1) on chromosome 6, which is associated with up to 50% of cases.
Other factors that precipitate or aggravate the disease include trauma, sun burns, infections, HIV infection, and psychological stress. All types of trauma have been associated with the development of plaque psoriasis. Even excessive scratching can aggravate or precipitate localised psoriasis by a process called Koebner reaction.
Even severe sunburn can lead to an exacerbation of the disease by the same reaction.
Pharyngeal streptococcal infections have been shown to produce a clinically distinctive disease flare known as guttate psoriasis. Furthermore, there is an increase in psoriasis activity in patients who are infected or become infected with HIV. At first, the extent and severity of the skin disease appears to parallel that of the HIV stage with the psoriasis becoming less active in advanced HIV. A number of medications have been shown to cause an exacerbation of psoriasis.
Lithium and withdrawal from systemic corticosteroids are well known to cause flares of the disease. Beta-blockers, antimalarials, and non-steroidal anti-inflammatory drugs (NSAIDs) have also been implicated. Moreover, most patients report an increase in psoriasis severity with psychological stress.
The pathogenesis of psoriasis is complex and involves an interplay of the immune cells with the keratinocytes in the skin. Activation of T cells in the dermis and the epidermis and the local effects of cytokines such as tumour necrosis factor lead to inflammation, cell-mediated immune responses and epidermal hyperproliferation observed in persons with psoriasis. An interleukin (IL)-12-related cytokine, IL-23, is involved in the establishment of chronic inflammation and in the development of a T-helper (Th)-cell subset producing IL-17. These cells which are designated Th-17 are the T-effector cell subset together with IL-23/IL-17 are implicated in the induction and progression of a number of inflammatory diseases, including psoriasis.
The plaque type of psoriasis is the most common, although several other distinctive clinical variants are recognised (e.g. Guttate psoriasis, psoriasis of the nails, pustular psoriasis, and psoriatic arthritis). Plaque psoriasis is characterised by raised and easily palpable lesions, owing to the thickened epidermis, expanded vascular compartment as well as infiltrate of neutrophils and lymphocytes. The plaques are well defined with sharply demarcated boundaries. The scales tend to be silvery-white, which when removed lead to some capillary bleeding. The lesions are more commonly found on the scalp, trunk, intergluteal cleft, and limbs with a predilection for the extensor surfaces such as the elbows and knees. Pruritus can be severe in some of the cases.
Guttate psoriasis is described as a raindrop-type rash of multiple psoriasis areas appearing on the trunk of patients, usually some 2-3 weeks after an upper respiratory tract infection.
It occurs in people younger than 30 years of age and often resolves within 20 weeks, but a significant number will progress to plaque psoriasis. Most studies have found evidence of recent streptococcal infection in the majority (up to 93%) of patients with acute guttate psoriasis.
Patients with these lesions may sometimes need to be treated with antibiotics to eliminate carrier states.
Pustular psoriasis is an uncommon form of psoriasis consisting of widespread pustules on an erythematous background. It may affect the palms and soles or rarely lead to a generalised erythroderma.
Cutaneous lesions characteristic of psoriasis vulgaris may be present before, during, or after an acute pustular episode. Pruritus, intense burning, fever, erythroderma, hypocalcaemia and cachexia are usually observed. Other systemic complications may include acute respiratory distress syndrome, pneumonia, congestive heart failure, and hepatitis. Episodes of pustular psoriasis can be evoked by withdrawal of systemic corticosteroids as well the use of certain drugs, like iodides, coal tar, minocycline, and salicylates. The treatment of choice is oral retinoids which can result in quick relief. Other oral treatments are also very effective.
Nail psoriasis can be easily mistaken for onychomycosis. The nails may exhibit pitting, onycholysis, subungual hyperkeratosis, or the oil drop sign.
The disease tends to affect most nails and is usually associated with plaque psoriasis elsewhere. Thus a good history and examination are necessary to distinguish it from a fungal infection.
The treatment mainly entails the use of oral medications as topical creams cannot be applied to the nail bed. Some authorities also advocate the use of scalp preparations of corticosteroids to be applied around the nails, which can be effective in very mild cases.
Psoriatic arthritis can occur in up to 30% of patients with skin disease.
It affects any age and typically starts around a decade after the onset of skin lesions. The symptoms can range from mild to severe and there is no correlation between the severity of skin lesions and that of the joints.
The patients complain of morning stiffness, pain, swelling of joints, pain in ligaments and tendons that is variable and unpredictable with flares and remissions.
There is a definite association between HLA-B27 and radiological evidence of sacroiliitis. However, there are probably other genes that are associated with psoriatic arthropathy.
When these symptoms are present, patients need to be treated aggressively and referred to a rheumatologist to stabilise their condition, before the onset of permanent joint damage.
As the understanding of the disease evolved over the years, research has produced various medications that target different pathways of the disease.
Up till the 1980s, it was known to be a disease of keratinocyte dysfunction. Thus various treatments targeting keratinocyte differentiation were used: methotrexate, retinoids, UVB and PUVA. The immunologic component of the disease was identified in the 1980s whereby the use of ciclosporin was introduced for the treatment. In the following decade, the targeted approach to IL12, led to the development of various biologics, including tumour necrosis factor alpha blockers. Finally, as from 2005, new medications that target even more specific pathways, the IL-23 and Th17, have found their place in the treatment of severe skin and joint disease. These include ustekinumab and secukinumab.
It must be added that even though we have many new therapies for psoriasis, the older medications are still widely and safely used with great success.
AUTHOR: Dr Rakesh Newaj, Specialist Dermatologist, Arwyp Medical Centre and Glynwood Hospital.