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Comorbidities newly associated with psoriasis: correlation versus causality.

A few decades ago, Psoriasis was considered an exclusively dermatological disease, affecting only the skin (1). Today, Psoriasis is condidered a multisystemic disease, more complex and associated with numerous comorbidities, more so than was once thought.

The etiopathology of this disease is linked to psychological and psychiatric apects in 30% of cases of patients with Psoriasis that eventually develop depression that may lead to suicide. There are multiple comorbidities associated with Psoriasis that can lead to psychological problems but the comorbidity most frequently responsible for psychiatric perturbations is acne associated with Psoriasis (2).

The clinical aspects linked to the "classical" comorbidities which are associated with Psoriasis, already well known, such as, Psoriaticlike Arthritis and Irritable Bowel Syndrome, are now used to better understand how complex this disease really is. Biological therapy is a new treatment and has been found to be beneficial in the treatment of Psoriasis. Even though there is no cure for Psoriasis, targeted therapy can help. The etiopathology of the disease is being used to explain why certain comorbidities are associated with Psoriasis and what type of treatment can lead to a possible cure. It is important to understand the etiopathology of the disease because its complexity, like genetic modifications, exposure to environmental factors and infections, can prose a problem in treatment.

Psoriasis is known to be a genetic disease that affects members of the same family having autosomal dominant transmission. It was found that 65% to 72% of monozygotic twins and 15% to 20% of dizygotic twins suffer from this disease. Studies have shown that MHC 1 is most implicated in the acquisition of genetic predisposition to express the HLA Cw6 gene on the 6p21.33 gene locus, named PSORS1. This gene is responsible for the premature manifestation of plaques and Guttate psoriasis. Alongside the PSORS1 locus, there have been another 15 loci discovered which have been found to play a role in T cell regulation. The genes responsible for the host's immune response by macrophage activation and NF-kB signaling are RUNX3, TAGAP and STAT3. Another gene locus implicated in immune system regulation is PSORS2, i.e. 17q25.3. This is important to note due to the genetic implications in an immune system modulated inflammatory response. Thus, Psoriasis can be classified into the HLA system:

Type 1 (familial): associated with HLA-CW6, B13 and BW57

Type 2 (sporadic): not associated with HLA DNA methylation plays a role in genomic instability and cellular differentiation. Also, depression can be determined by a genetic variations (3). However, it is important to note that environmental factors play a significant role in cutaneous eruption manifestation and continuity.

It is essential to mention possible environmental factors associated with Psoriasis:

* Stress: Psoriasis is a disease with no cure. The prolonged treatment, necessary to help keep symptomes at bay, may be stressful. Furthermore, the cutaneous eruptions can be caused by stress factors. This is a vicious cycle that Psoriasis suffers are susceptible to. A study conducted in Europe, in which 13 EU member states partcipated, monitored the association between dermatological diseases and the presence of depression or suicide risk. The study concluded that patients with Psoriasis developed depression and were at greater risk of committing suicide (4). Also, predisposition of suicide based on sex was also monitored and no correlations could be made between Psoriasis, risk of suicide and sex. It must be noted that while females are predisposed to think about suicide, males actually act upon their thoughts and end up actually committing suicide (5).

* Smoking: Psoriasis is present when the P450 gene is not functioning properly. Smoking can lead to this phenomenon by reducing P450's activity.

* Alcohol Consumption: The consumption of alcohol increases the risk of developing Psoriasis. The mechanism by which this is possible is still unknown, but it is thought that by suppressing the immune system by increasing proinflammatory cytokines, the disease may become manifest. However, the presence of Psoriasis may lead to alcohol consumption; linked to the depression felt by the patient. The patients that conusme alcohol may be less therapeutically compliant and the effect of the medications given may be modified, increasing toxicity or inhibiting the medicine's efficacity completely (6).

In the study by Kirby et al, the importance between alcohol consumption and the onset of Psoriasis is underlined. This study also mentions that further studies and investigations into upholding this correlation are necessary in order to improve the patients' quality of life (7).

However, there are factors that may lead to the manifestaion of Psoriasis but that can be changed by the patient, like obesity.

* Obesity: The risk of developing Psoriasis is twice as great in patients that are obese. Adipose tissue is comprised of adipocytes that secrete cytokines; in this case, the cytokines secreted are named adipokines. They are proinflammatory cells with a powerful inflammatory response. The main proinflammatory cytokines are leptin, resistin and IL-6. Studies have shown that obesity may lead to excessive alcohol consumption, anxiety and personality disorders. Furthermore, antidepressant and antipsychotic medication are known to have weight gain as a primary side effect (8,9). From here, the question, "What is the correlation between obesity and the onset of other diseases," arises. Is weight gain the cause of certain symptomes or is it a clinical manifestion that transpasses multiple medical domaines and is actually much more complex?

* Pruritus and Pain: These are two symptomes that are clinical manifestations of Psoriasis and can bring on discomfort to the patient. This prolonged discomfort can be one of the reasons for why the patient may end up suffering from depression (10,11).

* Hormonal Factors: The skin, the central nervous system and the endocrine system have the same embryologic origins.

The comorbidities associated with the etiopathogenesis of Psoriasis are linked to inflammatory processes. The most frequent associated comorbidities are: obesity, hypertension, hyperlipidemia and diabetes. All these comorbidities are also linked to cardiovascular disease and excess stress. Thus, depression is considered as a factor that is frequently present in patients with Psoriasis (12,13). For exemple, it has been proven that antiinflammatory drugs taken by Psoriasis suffers reduced the severity of the depression felt by the patient, independent of the deramtological symptomology (14). Studies found in the literature have noted that 15% of cases of patients suffering from different forms of Psoriasis were also diagnosed with depression. The greatest percentage of patients that had Psoriasis and suffered from depression were found among children (15,16).

A Danish study in 2014 highlighted that the incidence of Psoriasis is two times greater among patients with Schizophrenia in com parison to the general population. This is due to the patient's compromised immune system and modified HLA in both Psoriasis and Schizophrenia sufferers (17). Another recent study by Dowlati et al in 2010, demonstrated that patients with major depression have elevated plasma levels of inflammatory proteins such as TNF-[alpha]. This is significant because increased plasma levels of pro-inflammatory factors has a positive correlation with the onset of cardiovascular disease and Psoriasis. Moreover, the presence of infammation is a risk factor for developing various comorbidities that have a similar underlying etiopathology.

In patients with Psoriasis and depression, higher plasmatic levels of pro-inflammatory cytokines, modified calcium homeostasis, (3-adrenergic receptor malfunction and increased melatonin secretion, are found (18, 19, 20,21).

It is important to mention that the correlation between a primary disease and other secondary diseases or "comorbidities" is difficult to asses because the extent to which such a correlation can be made hinges on the degree of severity of the primary disease, in this case Psoriasis, etiopathology and the succession of clinical manifestations.

ACKNOWLEDGEMENTS AND DISCLOSURES

Article in the project "Cardiovascular risk assessment protocol in patients with psoriasis" (PSOCARDIO), funded by SRD.Conflict of interest--NONE DECLARED.

REFERENCES

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(2.) Gupta, M.A., Gupta A.K. Psychiatric and psychological co-morbidity in patients with dermatologic disorders: epidemiology and management. Am J Clin Dermatol 2003; 4(12):833-842.

(3.) Brummett, B.H. Krystal, A.D. Siegler, I.C. et al. Associations of a regulatory polymorphism of monoamine oxidase-A gene promoter (MAOA-uVNTR) with symptoms of depression and sleep quality. Psychosom Med 2007, pp. 396-401.

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(6.) Farkas, A, Kemeny, L. Psoriasis and alcohol: is cutaneous ethanol one of the missing links? Br J Dermatol 2010; 162(4):711-716.

(7.) Kirby, B, Richards, H.L, Mason, D.L. et al.: Alcohol consumption and psychological distress in patients with psoriasis. Br J Dermatol 2008; 158:138-40.

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(9.) Dent, R, Blackmore, A, Peterson, J., et al: Changes in body weight and psychotropic drugs: a systematic synthesis of the literature. PLoS One, 7 (6) (2012), p. e36889.

(10.) Rieder E, Tausk F. Psoriasis, a model of dermatologic psychosomatic disease: psychiatric implications and treatments. Int J Dermatol 2012; 51:12-26.

(11.) Palijan, T.Z., Kovacevic, D., Koic E., et al. The impact of psoriasis on the quality of life and psychological characteristics of persons suffering from psoriasis. Coll Antropol 2011; 35:81-85.

(12.) Lee, M.-S., Lin, R.Y., Lai, M.S. Increased risk of diabetes mellitus in relation to the severity of psoriasis, concomitant medication, and comorbidity: A nationwide population-based cohort study. J Am Acad Dermatol 2014; 70: 691-698.

(13.) Setty, A.R., Curhan, G., Choi, H.K. Obesity, waist circumference, weight change, and the risk of psoriasis in women: Nurses' health study II. Arch Int Med 2007; 167: 1670-1675.

(14.) Tyring, S., Gottlieb, A., Papp, K. Gordon, C. Leonardi, A. Wang, D. Lalla, M. Woolley, A. Jahreis, R. Zitnik, D. Cella. Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial. Lancet 2006; 367 (9504): 29-35.

(15.) Altobelli, E., Maccarone, M., Petrocelli, R., et al. Analysis of health care and actual needs of patients with psoriasis: a survey on the Italian population. BMC Public Health 2007:, 7: 59.

(16.) Kimball, A.B., Wu, E.Q., Guerin, A. et al. Risks of developing psychiatric disorders in pediatric patients with psoriasis. J Am Acad Dermatol 2012:, 67: 651-657.

(17.) Benros, M.E., Pedersen, M.G., Rasmussen. H., et al. A nationwide study on the risk of autoimmune diseases in individuals with a personal or a family history of schizophrenia and related psychosis. Am J Psychiatry 2014; 171:218-226.

(18.) Dowlati, Y., Herrmann, N., Swardfager, W., et al. A meta-analysis of cytokines in major depression. Biol Psychiatry 2010:, 67: 446-457.

(19.) Devrimci-Ozguven, H., Kundakci, T.N., Kumbasar, H., et al. The depression, anxiety, life satisfaction and affective expression levels in psoriasis patients. J Eur Acad Dermatol Venereol 2000; 14:267-271.

(20.) Hagforsen, E., Michaelsson, K., Lundgren, E., et al. Women with palmoplantar pustulosis have disturbed calcium homeostasis and a high prevalence of diabetes mellitus and psychiatric disorders: a case-control study. Acta Derm Venereol 2005; 85:225-232.

(21.) Sandyk, R., Pardeshi, R. Mood-dependent fluctuations in the severity of tardive dyskinesia and psoriasis vulgaris in a patient with schizoaffective disorder: possible role of melatonin. Int J Neurosci 1990; 50:215-221.

Elena Porumb-Andrese--M.D., Ph. D., Assistant Professor, Department of Dermatology "Grigore T. Popa" University of Medicine and Pharmacy Iasi, Romania

Dan Vaja--M.D., Ph. D., Lecturer, Department of Dermatology "Grigore T. Popa" University of Medicine and Pharmacy Iasi, Romania

Laura Statescu--M.D., Ph. D., Lecturer, Department of Dermatology "Grigore T. Popa" University of Medicine and Pharmacy Iasi, Romania

Alina Ioana Grajdeanu--M.D., Ph. D., Assistant Professor, Department of Dermatology "Grigore T. Popa" University of Medicine and Pharmacy Iasi, Romania

Adriana Patrascu--M.D. Dermatology Clinic County Emergency Hospital "St. Spiridon" Iasi

Laura Gheuca-Solovastru--M.D., Ph. D., Associated Professor, Department of Dermatology "Grigore T. Popa" University of Medicine and Pharmacy Iasi, Romania

Correspondence:

Dan Vaja,

M.D., Ph. D., Lecturer, Department of Dermatology "University of Medicine and Pharmacy "Gr. T. Popa" Iasi, Faculty of Medicine, Department of Medical Specialties, danvata@yahoo.com

E-mail: alexandra.mastaleru@gmail.com

Submission: 03 apr 2018

Acceptance: 15 may 2018
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Article Details
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Author:Porumb-Andrese, Elena; Vaja, Dan; Statescu, Laura; Grajdeanu, Alina; Patrascu, Adriana; Gheuca-Solov
Publication:Bulletin of Integrative Psychiatry
Article Type:Report
Date:Jun 1, 2018
Words:2074
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