Discussion
Recent studies on the pathogenesis of psoriasis have shown that the
disease occurs as a result of complex relationships between
T-lymphocytes, dendritic cells, macrophages, mast cells, neutrophils,
and keratinocytes 1. Macrophages are potent phagocytic
cells, capable of antigen presentation and secretion of a wide range of
chemical mediators. They are thought to play a key role in psoriasis by
releasing important inflammatory products such as TNFα and IL-1716. Along with genetic predisposition, chronic
inflammation is responsible for comorbidities, especially in severe form
psoriasis 3, 17.
ChT, a member of the mammalian chitinase family (GH18), hydrolyzes
chitin in lysosomes. There is growing evidence that ChT can be a marker
of inflammation. Although studies have shown high activities of ChT in a
wide range of diseases including cardiovascular disease diabetes
mellitus, and cancer, there is no data on the role of ChT activity in
patients with cutaneous disorders 5-12, 18. To the
best of our knowledge, this is the first study investigating the
possible role of ChT activity in patients with psoriasis and related
comorbidities. Our study showed a relationship between ChT activity and
psoriasis, especially in patients with accompanying comorbidity. ChT
activity, CRP and ESR levels were statistically significant higher in
patients with comorbidity compared to controls. However, only ChT levels
were statistically significant higher in patients with comorbidity
compared to patients without comorbidity. This outcome suggests that ChT
may be a better marker in predicting the development of comorbid
conditions compared to other parameters of systemic inflammation such as
ESR and CRP.
Psoriasis Area and Severity Index (PASI) is a scoring system used to
measure the severity and extent of psoriasis. To calculate a PASI score,
a representative area of psoriasis is chosen for each body area. The
intensity of redness, thickness, and scaling of the lesion is evaluated
as none, mild, moderate, severe, or very severe. The three intensity
scores are added up for each of the four body areas to give subtotals.
To calculate PASI score each subtotal is multiplied by the body surface
area represented by that region 19. Our study revealed
no correlation between the PASI scores and ChT activity. The majority of
the cases included in our study were mild cases and severe cases
remained in the minority. This limitation may explain the absence of a
statistical correlation between the PASI scores and ChT activity.
Dyslipidemia is not uncommon in psoriasis 20, 21. In
our study, only HDL cholesterol was low in patients without comorbidity
compared to the healthy control group. In patients with comorbidity,
total cholesterol, triglyceride, and LDL-cholesterol levels were higher
compared to the controls. There was no correlation between lipid
parameters and ChT activity. No lipid parameters showed statistically
significant differences between patients with and without comorbidity.
This indicates that the atherogenic lipid profile can occur in psoriasis
patients regardless of the presence of comorbidity.
In our study, 16 (30.1%) patients had PsA. The frequency of
inflammatory arthritis has been reported to be 6-42% in patients with
psoriasis 3. The incidence of arthritis increases in
proportion to the severity and duration of psoriasis. Early diagnosis of
PsA can prevent joint damage and improve quality of life22. In our study, ChT activity and other inflammatory
parameters showed no statistically significant differences in patients
with psoriatic arthritis (Table 4).
Psoriasis is associated with an increased risk of diabetes and insulin
resistance, independent of traditional risk factors 3.
Inflammatory mediators secreted by macrophages such as IL-6 and TNF-α
have been reported to cause insulin resistance in psoriasis23. Two different studies found high ChT activity in
diabetic patients 9, 24. In our study, the ChT
activity was also higher in diabetic psoriasis patients compared to
healthy subjects, but there was no significant difference compared to
patients without comorbidity. The low number of patients with diabetes
may explain this situation (Table 4).
Another common comorbidity in psoriasis is hypertension. Various
proinflammatory cytokines released from macrophages such as TNF-α and
IL-1β, and increased reactive oxygen species have been suggested to play
critical roles in the pathogenesis of hypertension 23,
25. In our study, ChT activity was found to be quite high in patients
with hypertension compared to other comorbidities (30.9 ± 15.6) (Table
4). The higher activity of ChT in hypertension suggests that macrophages
may have a greater role in the pathogenesis of hypertension. Apparently,
there is no study investigating the relationship between hypertension
and ChT activity in the relevant literature. However, the levels of
YKL-40, an inflammatory protein in the same family as ChT, has been
shown to be high in essential hypertension 26.
Early diagnosis and treatment of psoriasis-related comorbidities can
improve the quality of life and reduce mortality. Currently, there is no
specific laboratory test for the prediction of psoriasis-related
comorbidities. In our study, we found a high activity of ChT in patients
with comorbidity compared to patients without comorbidity and healthy
individuals. The high ChT activity was especially remarkable in patients
with hypertension.
To conclude, our data support the pathogenetic role of inflammatory
processes induced by macrophage activation in psoriasis and related
comorbidities. We believe that high ChT activity in patients with
psoriasis may serve as a clue for the early prediction of possible
related comorbidities.
The main limitation of our study was relatively small number size of the
patients having high PASI scores. However, ChT seems as a promising
marker to predict comorbid complications of psoriasis. It is obvious
that this clue needs to be evidenced with large sample series.
Data availability: The data associated with the paper are not
publicly available but are available from the corresponding author on
reasonable request.