Psoriasis Arthritis

Autoantibodies against nuclear antigens, cytokeratins, epidermal

keratins, and heat-shock proteins have been reported in persons with
psoriatic arthritis, indicating that the disease has a humoral immune
component.
The pathologic process of skin and joint lesions in psoriatic arthritis is
an inflammatory reaction, and evidence also indicates autoimmunity,
perhaps mediated by complement activation. The inflammatory nature
of the skin and joint lesions in psoriatic arthritis is demonstrated by
synovial-lining cell hyperplasia and mononuclear infiltration, resembling
the histopathologic changes of RA. However, synovial-lining hyperplasia
is less, macrophages are fewer, and vascularity is greater in psoriatic
arthritis than in RA synovium.
The cytokine profile for psoriatic arthritis reflects a complex interplay
between T cells and monocyte macrophages. Type 1 helper Tcell
cytokines (eg, TNF-alpha, IL-1 beta, IL-10) are more prevalent in
psoriatic arthritis than in RA, suggesting that these 2 disorders may
result from a different underlying mechanism.
Several studies have shown a significant reduction in the number and
percentage of CD4
+
T cells in the peripheral blood, whereas they are
found throughout the skin lesions and synovium.
Dendritic cells have been found in the synovial fluid of patients with
psoriatic arthritis and are reactive in the mixed leukocyte reaction; the
inference is that the dendritic cells present an unknown antigen to CD4
+

cells within the joints and skin of patients with psoriatic arthritis, leading
to T-cell activation.[21]
Fibroblasts from the skin and synovia of patients with psoriatic arthritis
have an increased proliferative activity and the capability to secrete
increased amounts of IL-1, IL-6, and platelet-derived growth factors.
Several studies suggest that cytokines secreted from activated T cells
and other mononuclear proinflammatory cells induce proliferation and
activation of synovial and epidermal fibroblasts.
Psoriatic plaques in skin have increased levels of leukotriene B4.
Injections of leukotriene B4 cause intraepidermal microabscesses,
suggesting a role for this compound in the development of psoriasis.
Infections
The temporal relationship between certain viral and bacterial infections
and the development or exacerbation of psoriasis and psoriatic arthritis
suggests a possible pathogenetic role for viruses and bacteria.
Pustular psoriasis is a well-described sequela of streptococcal
infections. However, the response to streptococcal antigens by cells
from patients with psoriatic arthritis is not different from that of cells from
patients with RA, making the role of Streptococcus species in psoriatic
arthritis doubtful.
Psoriasis and psoriatic arthritis have been reported to be associated
with HIV infection and to be prevalent in some HIV-endemic areas.
Although the prevalence of psoriasis in patients infected with HIV is
similar to that in the general population, patients with HIV infection
usually have more extensive erythrodermic psoriasis, and patients with
psoriasis may present with exacerbation of their skin disease after being
infected with HIV.
Trauma
A few studies have reported the occurrence of arthritis and acro-
osteolysis after physical trauma in patients with psoriasis.
Environmental factors
The theory of environmental factors playing a role in the etiology of
psoriatic arthritis involves a process of superantigens reacting with
autoantigens


Psoriasis Plaque
Etiology
Genetic factors
HLA-B13, -B17, and -Cw6 are all associated with plaque psoriasis.
Multifactorial inheritance mechanisms and etiologies without any
genetic component have not yet been excluded, although many families
appear to exhibit autosomal dominant patterns of inheritance with
decreased penetrance. Studies of twin siblings have shown concordant
disease in 73% of monozygotic twins compared with 20% in dizygotic
twins.
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. Six other psoriasis susceptibility
loci (PSOR2, PSOR3, PSOR4, PSOR5, PSOR6, PSOR7) have been
discovered, as well as the transcription factor RUNX1. While this
certainly points to genetic mechanisms, the absence of 100%
concordance among monozygotes suggests that environmental factors
must play a role in the pathophysiology of this disease.
Trauma
All types of trauma have been associated with the development of
plaque psoriasis (eg, physical, chemical, electrical, surgical, infective,
and inflammatory injury). Even excessive scratching can aggravate or
precipitate localized psoriasis. The development of psoriatic plaques at
a site of injury is known as the Koebner reaction.
Sunlight
Most patients consider sunlight to be beneficial for their psoriasis; they
report a decrease in illness severity during the summer months or
periods of increased sun exposure. However, a small minority of
patients find that their symptoms are aggravated by strong sunlight, and
these individuals actually experience a worsening of their disease in the
summer. A severe sunburn can lead to an exacerbation of plaque
psoriasis via the Koebner reaction.
Infection
Pharyngeal streptococcal infections have been shown to produce a
clinically distinctive disease flare known as guttate psoriasis. Some
evidence suggests that subclinical streptococcal colonization or
overgrowth could be responsible for refractory plaque psoriasis.
HIV infection
An increase in psoriasis activity has been observed in patients who are
infected, or become infected, with HIV. The extent and severity of skin
disease initially appears to parallel the disease stage. Psoriasis often
becomes less active in advanced HIV infection.
Drugs
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 disease. Beta-blockers, antimalarials, and
nonsteroidal anti-inflammatory drugs (NSAIDs) have also been
implicated.
Psychogenic/emotional factors
Many patients report an increase in psoriasis severity with psychological
stress. A clear cause-and-effect relationship between disease
exacerbation and stress unfortunately has not been proven. Patients
may show a decreased capacity to cope with their treatment regimen
with higher levels of stress. Pruritus in the setting of increased anxiety
or depression may promote scratching and a Koebner reaction.
Smoking
An increased risk of chronic plaque psoriasis exists in persons who
smoke cigarettes.
Alcohol consumption
Alcohol consumption is considered a risk factor for psoriasis, particularly
in young to middle-aged men.
Endocrinologic factors
Psoriasis severity has been noted to fluctuate with hormonal changes.
Disease incidence peaks at puberty and during menopause. During
pregnancy, symptoms are more likely to improve than worsen, if any
changes occur at all. In contrast, the disease is more likely to flare in the
postpartum period, again if any changes occur at all.

Pathophysiology
The pathophysiology of psoriasis must be understood in terms of the
prominent pathologies occurring in both major components of the skin
the epidermis and the dermis.
Psoriasis is fundamentally an inflammatory skin condition with reactive
abnormal epidermal differentiation and hyperproliferation. Current
research suggests that the inflammatory mechanisms are immune
based and most likely initiated and maintained primarily by T cells in the
dermis.[9]
In this model, antigen-presenting cells in the skin, such as Langerhans
cells, are believed to migrate from the skin to regional lymph nodes,
where they interact with T cells. Presentation of an as yet unidentified
antigen to the T cells, as well as a number of co-stimulatory signals,
triggers an immune response, leading to T-cell activation and the
release of cytokines.
Co-stimulatory signals are initiated via the interaction of adhesion
molecules on the antigen-presenting cells, such as lymphocyte
functionassociated antigen (LFA)3 and intercellular adhesion
molecule-1, with their respective receptors CD2 and LFA-1 on T cells.
These T cells are released into the circulation and traffic back into the
skin.
Reactivation of T cells in the dermis and epidermis and the local effects
of cytokines such as tumor necrosis factor lead to the inflammation, cell-
mediated immune responses, and epidermal hyperproliferation
observed in persons with psoriasis.
An interleukin (IL)-12related 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 Th17, are distinct from Th1 and Th2 populations. Th17 cells
are now recognized as a third T-effector cell subset, and the IL-23/IL-17
pathway has been implicated in the induction and progression of a
number of inflammatory diseases, including psoriasis.[10]
Environmental factors
Infection and a number of physical agents (eg, HIV infection,
alcoholism, smoking, UV light) all can affect the course, duration, and
clinical appearance of plaque psoriasis. See Etiology of Plaque
Psoriasis, below, for more details on the role of environmental factors.
Tx.
Systemic Agents
Initiate systemic treatment only after both topical treatments and
phototherapy have proved unsuccessful. Consider systemic therapy for
patients with very active psoriatic arthritis. Patients who have disease
that is physically, psychologically, socially, or economically disabling are
also considered candidates for systemic treatment. All patients must be
informed of the risks and adverse effects of systemic therapy before
treatment is initiated.[2, 3, 4]
Plaque psoriasis appears to respond better to combination
topical/systemic therapy than to systemic treatment alone. In a
randomized study, adding a topical corticosteroid to etanercept therapy
in patients with moderate to severe plaque psoriasis proved to be a
more effective treatment than etanercept alone.[17] In the study, which
involved 592 adult patients with a psoriasis area and severity index
(PASI) score of 10 or higher and with 10% or more of their body surface
area affected by psoriasis, treatment consisted of either etanercept
alone or etanercept plus topical clobetasol propionate foam. Significant
differences favoring combination therapy were seen at week 12,
including percentage of improvement in the PASI score (76.5% for
combination therapy vs 68.2% for etanercept alone)
Topical Therapy
Outpatient topical therapy is the first-line treatment of plaque psoriasis.
A number of topical treatments are available (eg, corticosteroids, coal
tar, anthralin, calcipotriene, tazarotene).[15]
No single topical agent is ideal for plaque psoriasis, and many are often
used concurrently in a combined approach. With the different adverse
effect profiles for the various agents, using a rotational therapeutic
approach in which different topical agents are used sequentially over
time in the same patient is common.
In general, the effects of topical therapy should become evident within
the first 2-3 weeks of use. Clearing of scale is usually observed first,
followed by flattening of the treated plaques. Resolution of erythema
may take 6-8 weeks.
Auxiliary agents such as keratolytics can often be added to these
preparations. However, some auxiliary agents are incompatible with the
active ingredients of these preparations. For example, salicylic acid
inactivates calcipotriene. On the other hand, agents such as anthralin
require the auxiliary agent salicylic acid for chemical stability.