The estimated prevalence of psoriasis in Brazil is 1.3%, with higher frequencies in the Southern and Southeastern regions.1 The association with a wide range of comorbidities is recognized, particularly psoriatic arthritis (PA), metabolic syndrome, cardiovascular disease, diabetes mellitus, psychiatric disorders, asthma, and inflammatory bowel disease.2,3 Immune-mediated or autoimmune diseases such as rheumatoid arthritis, celiac disease, and vitiligo are also well-known associations.4

Although the association between psoriasis and thyroid abnormality has been investigated by several authors (Table 1), case-control and population-based studies have been published without definitive conclusions.5–12 The correlation with psoriasis severity13,14 and the frequency (incidence or prevalence) of thyroid abnormality in patients with psoriatic disease15–19 have also been previously investigated.

Considering the importance of the association for clinical management and the scarcity of these data in the Brazilian population, this study aimed to evaluate the prevalence of thyroid abnormality in patients with psoriasis and to analyze its association with three factors: severity (measured by the Psoriasis Area and Severity Index – PASI); the presence of psoriatic arthritis; and treatment with immunobiologicals. Additionally, the study assessed publications of interest, identifying the study design and inclusion of a control group in the studies, and according to the adopted criteria, compared by meta-analysis the group of cases in this study with the control group from the selected publications.

After approval by the local Research Ethics Committee, a cross-sectional observational study was conducted in the Dermatology department. Data from 250 patients were analyzed.

All patients followed at the Dermatology Outpatient Clinic of Psoriasis and Immunobiologicals from January 2018 to December 2019 were considered eligible, constituting a convenience sample. The inclusion criteria were: diagnosis of psoriasis vulgaris and duration of treatment – considering the use of topical treatments, phototherapy, conventional systemic drugs (acitretin, methotrexate and cyclosporine), or immunobiological agents (infliximab, etanercept, adalimumab, ustekinumab, secukinumab). The exclusion criteria were: diagnosis of other forms of psoriasis other than vulgaris, patients who did not agree to participate in the study, those younger than 12 years, previous thyroidectomy, current treatment with medications that could affect thyroid function (lithium, amiodarone, anticonvulsants and interferon) and absence of records in the medical file regarding thyroid hormones or antibodies.

Initially, 250 patients were considered eligible, but 15 were not included because they had a diagnosis of exclusive palmoplantar psoriasis or generalized pustular psoriasis. Of the total of 235 patients included in the study, 74 were excluded (64 due to incomplete information in the medical records, three due to the use of medications that alter thyroid function and seven due to loss of follow-up). Therefore, the final sample consisted of 161 patients, whose data were analyzed.

Among the sample patients, 64.60% were male, with a mean age of 55 years. The prevalence of thyroid abnormality was 28.57% and of hypothyroidism, 14.91%. The following autoimmune diseases were detected in the sample: Sjögren's syndrome, vitiligo and type I diabetes (in one, two and one patients, respectively). With regard to treatment, 44.09% of the patients were using immunobiological therapy, 37.88% were using non-immunobiological systemic treatment, 3.72% were using phototherapy and 14.28% were using exclusive topical therapy. Considering the PASI, 15.55% (21 patients) were considered to have moderate/severe disease (Tables 2 and 3).

Quantitative variables (age, BMI, disease duration and PASI) were compared with gender and the presence or absence of comorbidities (hypertension, dyslipidemia, diabetes, hypothyroidism and PA). There was no difference in PA frequency between the male and female sex. Hypertension, dyslipidemia and hypothyroidism were more prevalent at older ages (OR=1.066 [95% CI 1.038–1.094] p<0.0001; OR=1.039 [95% CI 1.014–1.064] p=0.0025 and OR=1.048 [95% CI 1.009–1.077] p=0.0125, respectively). In parallel, diabetes was more frequent in older patients (OR=1.048 [95% CI 1.020–1.076] p=0.0006) and those with higher BMI (OR=1.083 [95% CI 1.007–1.164] p=0, 0314). No statistically significant difference was found considering hypothyroidism and PASI.

Patients allocated considering PASI (mild or moderate/severe), PA (presence or absence) and current treatment (immunobiologicals or non-immunobiologicals) were compared regarding thyroid abnormality. As depicted in Tables 4, 5 and 6, no statistically significant difference was found between these groups.

Patients on non-immunobiological therapy were divided into groups according to the type of treatment: exclusively topical, phototherapy and systemic medication. There was, however, no statistically significant difference between the groups for the hypothyroidism (p=0.10) and thyroid abnormality (p=0.17) variables.

The association between psoriasis and several comorbidities has been an important topic of research and current evidence suggests a multifactorial aspect of the disease, expanding its spectrum and its impact beyond the dermatological and rheumatological areas. Therefore, knowing the possible associations with other comorbidities, such as thyroid disease, is a key element in improving care.

The activation of the inflammatory pathway by tumor necrosis factor-alpha, interleukin 23, and interleukin 17 (TNF-α, IL-23, IL-17) is involved in the pathophysiology of psoriasis.22 The role of this pathophysiological pathway has been studied in thyroid diseases.

Previous studies have shown that the status of epidermal proliferation changes with thyroid disease,23 and thyroid hormones are able to induce the production of epidermal growth factor (EGF), whose persistence could be associated with the hyperproliferative state of psoriasis.24,25

It is currently known that psoriasis has a high frequency of Treg/IL17+ lymphocytes and recent studies have demonstrated high levels of T-helper 17 (Th17) lymphocytes, both in the peripheral tissue and in the thyroid tissue of patients with autoimmune thyroid disease, as well as Th17 expression in patients with Hashimoto thyroiditis (HT).26,27 This pathway may be related not only to the pathophysiology of psoriasis but to that of immune-mediated thyroid diseases, suggesting a connection between them.

Cytokine CXCL10 plays an important role in Th1 lymphocyte chemoattraction and is found at high levels in patients with PA and HT when compared to patients with isolated PA,13,28 representing another point in common in the pathophysiological pathway.

Although already hypothesized and demonstrated in previous studies,7,8,18 this is one of the first studies with Brazilian data to assess the prevalence of thyroid abnormality in patients with psoriasis vulgaris.

The prevalence of hypothyroidism of 7.4% and of chronic autoimmune thyroid disease of 16.9% in the Brazilian population has been previously estimated.29,30 The prevalence of HT in the study by Valduga et al., which analyzed 60 Brazilian patients and 60 controls, was 21.6% for the case group.21 The sample evaluated herein, which had a more substantial number of participants, found prevalence rates of 28.57% for thyroid abnormality and 14.91% for hypothyroidism. Additionally, 10.29% of the patients had altered TSH levels and positive anti-TPO and anti-TG were demonstrated in 8.55% and 4.83% of the patients, respectively. However, it should be noted that the present study was conducted in a specialized outpatient clinic and, therefore, is not comparable to the general Brazilian population.

Similar results were demonstrated by other authors. Mallick et al. found a frequency of 15.2% for thyroid disorders in a sample of 112 patients with psoriasis vulgaris;16 Namiki et al. studied thyroid dysfunction in 85 patients and found a prevalence of 8% in patients with psoriasis without PA, 13% in patients with PA, and 45% in patients with generalized pustular psoriasis (GPP).17 In contrast, patients with GPP were excluded from this study, although they may be included in future evaluations.

It has been demonstrated a high frequency of thyroid autoimmunity in females, who are up to eight times more frequently affected than males.31 In the assessed sample, 64.6% of the patients were men, which should imply a lower frequency of thyroid abnormality, suggesting that the high frequency found should be valued and discussed in future studies.

The available systemic medications for psoriasis vulgaris are mainly reserved for patients with moderate to severe clinical conditions during the course of disease evolution. In this carried-out study, 83.84% of the patients used systemic drug therapy. However, 15.55% had PASI>10, with mean and median values corresponding to 5.62 and 2.2 (0–57), respectively. Most patients were, therefore, undergoing adequate treatment and under disease control during the study. There was no association between PASI and thyroid abnormality. However, the score is dynamic, being impacted by treatment and changing during the follow-up, so it does not reflect disease severity when assessed at intervals.

In line with other studies, Arican et al. established an association between thyroid disease and PASI, demonstrating higher index values in patients with thyroid abnormality.14,17 Treatment withdrawal for at least one month, as adopted by the authors, made the PASI a more reliable score for assessing disease severity.

Immunobiological therapy, when compared to conventional therapy, was not associated with thyroid abnormality (p=0.13). Similarly, no statistically significant difference was found between patients when divided into the three groups of non-immunobiological treatment: systemic, phototherapy, and topical treatments, considering the variables of hypothyroidism (p=0.10) and thyroid abnormality (p=0, 17).

PA, prevalent in up to 30% of the patients, has a significant impact on quality of life and is associated with the occurrence of other comorbidities.2 The association with hypothyroidism, positive anti-TPO, and ultrasonographic findings (thyroid hypoechogenicity) has been previously demonstrated.18,19 There was no association of PA in the assessed sample, considering hypothyroidism (p=0.65), anti-TPO (p=0.76), or thyroid abnormality (p=0.87). Ultrasonography for thyroid assessment was not performed in this study, which constitutes a limitation.

Historical control and literature control are most frequently used in clinical trials, with benefits regarding the reduction of costs and study duration.32,33 The literature review and use of the control group from the selected articles for comparison complement the study.

The prevalence of hypothyroidism among patients with psoriatic disease when compared to literature control data was higher, with a statistically significant difference. These data, corroborated by those observed in the Brazilian study by Valduga et al.,21 justifiy that greater attention be paid to thyroid function in patients with psoriasis.

However, some considerations must be made related to the study design. The composition of the control group of the articles included in the meta-analysis varied, consisting of patients with other dermatological diseases in the studies by Arican et al.14 and Gul et al.,6 while in the study by Valduga et al.21 it consisted of patients from the gynecology and ophthalmology clinic. Meanwhile, in the article by Hansen et al.11 patients belonged to the Danish General Suburban Population Study database. Therefore, the control group obtained from the literature review was not restricted to a single population, reducing the risk of choosing a control group that was very different from the cases and improving the analysis. However, the fact that the control group did not come from the same center or the same geographic area is a limiting factor.

The way hypothyroidism was diagnosed also varied between the studies. The article by Hansen et al.11 used self-reported hypothyroidism information, while the others made the diagnosis based on laboratory data obtained during the study. In the present study, the patients with a previous diagnosis of hypothyroidism and those who had altered laboratory data, including the diagnosis of thyroid abnormality, were included.

Although many studies have investigated the association or frequency of thyroid abnormality in patients with psoriasis, this was one of the first studies carried out with Brazilian data. The prevalence of thyroid abnormality was 28.57% and that of hypothyroidism was 14.91%. Moreover, the prevalence of hypothyroidism when compared to the literature control was positive. This analysis complements the current study, allowing a more complete comparison and assessment of the data obtained in the present series.

The analyzed results allow future studies to be conducted aiming at evaluating the existence of an association or the screening for thyroid autoimmunity in this population group.

None declared.

Luiza de Castro Fernandes: Design and planning of the study; data collection, or data analysis and interpretation; statistical analysis; drafting and editing of the manuscript or critical review of important intellectual content; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; approval of the final version of the manuscript.

Ana Carolina Belini Bazan Arruda: Design and planning of the study; data analysis and interpretation; drafting and editing of the manuscript or critical review of important intellectual content; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; approval of the final version of the manuscript.

Lisa Gava Baeninger: Design and planning of the study; data collection, drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; critical review of the literature; approval of the final version of the manuscript.

Debora Pedroso Almeida: Design and planning of the study; data collection, drafting and editing of the manuscript; collection, analysis, and interpretation of data; effective participation in research orientation; critical review of the literature; approval of the final version of the manuscript.

Danilo Villagelin: Design and planning of the study; data collection, or data analysis and interpretation; statistical analysis; drafting and editing of the manuscript or critical review of important intellectual content; collection, analysis, and interpretation of data; effective participation in research orientation; intellectual participation in the propaedeutic and/or therapeutic conduct of the studied cases; critical review of the literature; approval of the final version of the manuscript.

None declared.