Australian Doctor Australian Doctor 12 May 2017 | Page 20

How to Treat – Psoriasis
Pathophysiology
FUNDAMENTALLY,
psoriasis
is considered to be a problem of
immune dysregulation, involving
changes in both innate and adap-
tive immunity. 1
This results in hyperprolifera-
tion of the epidermis, with pro-
duction of thickened but inflexible
and fragile stratum corneum with
underlying erythema secondary
to vascular proliferation. Though
mechanisms are not yet fully under-
stood, recent developments offer a
RECENT DEVELOPMENTS
OFFER A GOOD
INDICATION OF
POSSIBLE MOLECULAR
PATHWAYS.
good indication of possible molecu-
lar pathways.
Mechanisms involving tumour
necrosis factor alpha (TNF-alpha)
and the Th17/IL23 axis have
recently been the area of focus of
research because of their seemingly
pivotal roles in the development of
this disease.
Genetic susceptibility coupled
with a triggering event initially acti-
vate dendritic antigen-presenting
cells in the skin. Signalling between
the innate and adaptive immune
system is carried out by TNF-alpha
(amongst other cytokines), and
once activated along with IL-23
(and subsequently Th17), induce a
plethora of proinflammatory medi-
ators implicated in the psoriatic dis-
ease process. 1
In addition to the IL-23/Th17
axis, cytotoxic T-cells, neutro-
phils, lymphocytes and a myriad
of cytokines are implicated in
inducing an environment of high
keratinocyte turnover and angio-
genesis.
An overview of one commonly
accepted mechanism is illustrated
in figure 4. In psoriatic patients,
due to the disturbance of the fine
immunological balance usually
maintained in the skin, triggering
events such as local trauma can
lead to the development of pso-
riatic plaques. This is known as
‘Koebnerisation’ or Koebner phe-
nomenon’. 1
Figure 4. Possible mechanisms playing a role in the pathogenesis of psoriasis.
A dendritic cell perspective on psoriasis pathogenesis. A combination of environmental triggers and genetic factors leads to disease onset. In the initial phase, plasmacytoid dendritic cells are recruited
to pre-psoriatic skin through chemerin and activated by self DNA and/or RNA that is released by keratinocytes and forms complexes with LL-37. IFN- released by activated pDCs, self-RNA-LL-37
complexes, as well as keratinocyte-derived pro-inflammatory cytokines, TNF, IL-6, and IL-1, leads to activation of dermal dendritic cells. Activated DDCs migrate to the skin-draining lymph nodes
where they promote the differentiation of naïve T cells into Th1 and/or Th17 cells. In psoriatic lesions, DDCs and inflammatory DCs produce IL-12, TNF, IL-20, nitric oxide (NO) radicals and IL-23 which
activate skin resident T cells to produce pro-inflammatory cytokines. Pro-inflammatory Th1 and Th17 cytokines then act on keratinocytes and feedback on DDCs, leading to a sustained and amplified
inflammatory status which ultimately leads to the formation of a psoriatic plaque.
Source: Chu CC, et al. Harnessing dendritic cells in inflammatory skin diseases. Seminars in Immunology 2011; 23:28-41. https://creativecommons.org/licenses/by/3.0/
Diagnosis
THE diagnosis of psoriasis is
often made clinically. If there is
ambiguity or possible differential
diagnoses such as tinea infections,
eczema, seborrhoeic dermatitis,
and lichen planus, then a skin
biopsy, culture, or investigations
such as an FBC may be of use. 2
Family history, history of trig-
gering factors, and age may all
provide clues that strengthen the
likelihood of this diagnosis. If a
biopsy is taken, features typically
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| Australian Doctor | 12 May 2017
seen include: acanthosis, hyperker-
atosis, hyperparakeratosis, dilata-
tion of dermal vasculature, dermal
and epidermal inflammatory infil-
trate, and epidermal subcorneal
microabscess formation. 2
One important task to consider
after a diagnosis of psoriasis is
established is grading the psoriasis
using a tool such as the Psoriasis
Area and Severity Index (PASI).
Using the index is helpful for
several reasons.
First, it can produce a score that
helps convey the severity of the dis-
ease among healthcare profession-
als managing psoriatic patients.
Second, the score can be used to
monitor response to treatment.
And finally, though other site-
specific scores (such as palmo-
plantar, scalp, and nail scores)
can also be helpful, the PASI is
specifically needed to show treat-
ment responses in applications to
the PBS for biologic therapies (see
www.australiandoctor.com.au
online resources for an example of
how an index can be calculated).
Many randomised control tri-
als present ‘PASI-75’ or ‘PASI-90’
data as endpoints, referring to the
percentage of patients who have
achieved a 75% or 90% reduction
in their PASI score from baseline.
In addition, determining severity
and the need for referral should be
based on the psychological burden
of disease.
For example, similar to the
index, a measurement of greater
than 10 points on the Daily Life
Quality Index is indicative of
severe psoriasis. 6
If there is evidence on history,
examination, or investigation of
known comorbid associations
(listed above), further investiga-
tion may also be warranted. 2
Information on Psoriasis Area
and Severity Index forms and
applications is provided under
Online resources.