The Lancet, when not retracting bogus MMR research papers or trying to ‘out-woke’ the NEJM, still produces comprehensive and reasonable updates of interest to the general reader. This is a personal commentary on Psoriasis (Griffiths, Christopher E M et al. The Lancet, Volume 397, Issue 10281, 1301 – 1315, April 03, 2021). I once worked for one of the authors in what a medical geologist might call the Pre-Biologic era.
Psoriasis affects 2-3% of the world population with the majority developing the condition before 40. The genetic basis continues to be discovered. From each psoriasis linked gene an immune pathway flows opening the possibility of targeted therapeutic intervention.
External factors linked to the development of psoriasis remain largely limited to a small number of drugs and streptococcal pharyngitis precipitating widespread small plaque pattern termed ‘guttate’. It seems that around 40% of guttate cases progress to chronic plaque psoriasis.
Classification includes acute small plaque, chronic large plaque, pustular and erythrodermic. Some quaint terms still exist for rarer variants, which can be safely filed by the general reader. Of interest though is that 90% of cases are chronic overall, most will have scalp involvement, with 50% having nail involvement.
Looking at a section of psoriatic skin, we would see too much of everything. Too many keratinocytes, too many lymphocytes and other workers of the skin immune system. If one delved into the key immune pathway’s cytokines such as TNF-α, IL-17 and IL-23 would emerge as key players revolving around a manager: the Th17 lymphocyte subset of skin bound memory cells.
Fascinating as all this is, it remains that a biopsy of psoriasis is not required for diagnosis.
Associated non-skin pathologies are dominated by arthritis. Around 30% of patients will suffer this, sometimes before the onset of a rash. The patterns vary from oligoarthritic, asymmetric small joint and spondyloarthropathy. In severe psoriasis a modestly increased risk (x 1.3) of cardiovascular disease and NIDDM are noted. While this may relate to a genetic linkage for the conditions it remains at present an association not causation.
The potential for psoriasis to be linked with depression is now emphasised within the literature.
Treatments have significantly changed over the past 20 years. Inpatient treatment with tar, dithranol and Psoralens UVA phototherapy are gone, with topical corticosteroid being the mainstay for most patients. UVB phototherapy has a strong track record of safety only limited by the ability of patients to access a brief treatment two to three times per week for at least 8-12 weeks. Conventional oral treatment has consolidated around ciclosporin, methotrexate and acitretinoin with 40-60% of patients being controlled by these interventions over a three-month period.
However, what has really changed are the options for a patient with severe psoriasis – an extensive area of body involvement and failure to respond to conventional oral treatment. These patients now have access to biologic therapies through a closely controlled PBS eligibility system.
These agents are in general engineered monoclonal antibodies to key receptors or cytokines involved in the psoriatic immune cascade. Given by injection at regular intervals and with a high degree of patient tolerance, it is not an overstatement to say this has revolutionised the treatment of patients who had life-ruining disease.
They are often now totally clear of the condition. The costs of these drugs run into the tens of thousands. With some biologics now off patent in Australia, it will be interesting to see if accessibility alters. However, compared with other drugs, biologics are high cost to produce and the savings from generics may be constrained.
Despite considerable improvements to our knowledge of the immunology of psoriasis, basic answers to questions such as the distribution of plaques remain. One hypothesis is proposed by this paper: the distribution reflects the distribution of memory T cells within the skin.
Key messages
- Psoriasis is a major world health issue
- Joint involvement can occur without skin lesions
- Biologic therapies are often successful in clearing severe disease.
Author competing interests – nil