الفهرس 
AcknowledgementsOnly 14 pages are availabe for public view
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Abstract
Acne vulgaris is a common skin disease of young females usually starting at adolescence and recently discovered to can extend beyond the third decade. It is resulting from a complex interaction of various pathogenic factors (Sobhan et al., 2020). These factors include sebaceous gland activity with hyperseborrhea, abnormal follicular differentiation and increased cornification, bacterial hypercolonization and inflammation with immunological host reaction. On the other hand, the causes of adult acne have not been completely clarified up to now (Vergou et al., 2012).
Literature brings out quite clearly the controversies that exist as far as TSH status of patient with acne vulgaris is concerned. Studies on the association of TSH level dysfunction changes in acne vulgaris patients is hardly available. This generated our interest in this direction and so this study aimed to assess the thyroid function in acne vulgaris female patients to minimize its subsequent complications. The present study is a cross-sectional, case–control, observational study aimed to assess the thyroid function in relation to age, BMI and acne severity in acne female patients attended outpatient clinics of the Dermatology, Venerology and Andrology (Assiut University Hospital), and Assiut General Hospital between August 2019 and January 2021. The study included 112 female subjects (59 acne cases and 53 matched controls). The mean age of studied cases was 27.76 ± 8.2 and the mean age of the control group was 29.19 ± 4.3, with no statistically significant difference between both studied groups. Similarly, the BMI in our population was matched between the two study groups (28.55 ± 6.2 vs 29.65 ± 5.5, P=0.327) respectively. These data are relevant to the Turkish case control study of Ekiz which aimed to investigate the status of thyroid functions and lipid levels in patients with postadolescent acne and found that the mean age of patients was 30.4 ± 4.9 years, with no significant difference (Ekiz et al., 2015). While the case control study of Stewart and Bazergy which aimed to confirm the association between thyroid autoimmunity and post-adolescent acne in adult women, they found that the median age of studied cases was 26 and ranged from 21 to 36 year (Stewart and Bazergy., 2017). Also Kaur study aimed to compare the severity of acne vulgaris with TSH levels according to age reported that the majority of female patients with acne are between 21 and 30 years with a mean age of 24.52 ± 6.54 years (Kaur et al., 2021). The difference in the age of prevalence and peak age from the present study could be attributed to the older ages incriminated into the study and the associated natural prevalence of thyroid dysfunction at these ages, the more stressful life events that occurs then, and the more prevalence of hormonal and androgens dysregulation at the older ages. Regarding disease severity, The global acne grading system (GAGS) gives a weight to each region (face and back) with a severity score, in the current study, the mean of GAG score was 19.07± 8.2 whereas 57.6% had mild acne, 30.5% showed moderate and about 11.9% reported severe degree of acne. Similarly; Ozuguz reported that most of the studied patients had moderate acne vulgaris (GAGS 19–30) (Ozuguz et al., 2017).
On the contrary, the recent study of Barrea reported that the clinical severity of acne evaluated by GAGS was 22.08 ± 9.12, according to GAGS categories, where 33.3% had mild acne, 51.0% showed moderate acne, and 15.7% presented severe acne (Barrea et al., 2021). This difference could be explained by the difference in the eligibility criteria between our study and the study of Barrea as the author exclude acne female patients with a diagnosis of acne lasting > 6 months or were receiving any systemic treatment for acne including acitretin, ciclosporin, methotrexate, phototherapy or biologics for at least 3 months, and also the author exclude patients with any endocrine disorders including thyroid dysfunction. Regarding the acne site distribution, the current study reported that 27 (45.8%) of studied cases were suffered from facial acne, 2 (3.4%) had truncal acne and 30 (50.8%) with mixed (facial and truncal) acne. This finding is consistent with the finding of Abo El-Fetoh et al. who found that the acne site distribution was 46.2% in the face, 3.6% in the back and 50.2% in multiple sites (Abo El-Fetoh et al., 2016). Meanwhile the Brazilian study of Bagatin reported that the face was affected in 97.5% of acne patients (Bagatin et al., 2014), Al- Riyadh study NM found that the face was affected in 96.4% of cases (NM et al., 2016), and also another study of Alanazi reported that the face was affected by acne in almost all patients of his study (Alanazi et al., 2018). This difference could be attributed to different inclusion criteria, as different age, sex, diet, and different socio-demographic data. Treatment of acne is dependent on acne morphology and severity of disease. Options range from topical agents for mild acne to oral isotretinoin for the more severe acne. Current guidelines recommend combination therapy, with a topical retinoid plus an antibacterial agent considered first-line therapy (Sandoval et al., 2014). Among our studied cases 69.5% received either topical antibiotic, tretinoin, intervention or mixed, and 55.9% received systemic treatment, either systemic antibiotic, isotretinoin, hormonal therapy or mixed. While 13.56% of cases didn’t received any topical or systemic treatment. In contrast to our study the Egyptian study of Tayel reported that facial cleansers were the most frequently self-administered treatments (59.42%) followed by facial masks (31.71%) and medicated soap (23.44%) as topical applications. This difference could be explained by that Tayel study included only adolescent patients in his study (Tayel et al., 2020). In the current study no significant difference was found between acne patients and controls for all thyroid function and dysfunction level (P>0.05), except that TSH (µIU/ml) level which was significantly higher among the acne patients compared to control group (P=0.004). Also we found that 15 (25.4%) cases versus 9 (17.0%) controls, with significant statistical difference (P= 0.042) had abnormal TSH level with Global acne grading system (GAGS) score showed no significant difference according to thyroid dysfunction levels. Thus we did not found relation between thyroid dysfunction levels and different acne severity groups (P=0.470). This could be attributed to the limited sample size, the natural increased prevalence with age of thyroid dysfunction in the included age groups, and presence of undiagnosed controls with thyroid dysfunction. Our finding is supported by the previous case control study of Vergou who concluded that no differences in thyroid functions namely (TSH, fT3 and fT4) were found between acne and control groups. But they reported a relationship between acne and thyroid autoimmunity through the cytokines (Vergou et al., 2012), Ekiz study didn’t find any significant differences in thyroid function, thyroid autoantibodies, and thyroid ultrasound findings between acne and control groups (Ekiz et al., 2015), Stewart and Bazergy reported similar finding whereas the differences in TSH, FT3 and FT4 between the case and control groups were not statistically significant (Stewart and Bazergy., 2017). The elevated TSH level in cases in our study compared to matched control was the only reported difference between our study and all above mentioned studies which address thyroid function in adult acne patients, this could be explained by different gender (as our study included women only, while the others included both genders), in addition to different racial, environmental, and genetic factors, and dietary habits that may affect thyroid functions. No significant relation was found between TFT and disease severity “by GAG score” among acne cases, except for a significantly higher free T3 in moderate compared to mild GAG score groups (P=0.038). Unfortunately the previous studies which address this issue of thyroid dysfunction in acne cases; dose not measure the severity of acne by GAG score, so we can’t compare our results to them. Patients’ age and BMI showed significant positive correlation with TSH level and significant negative correlation with both T3 and T4. Our study is supported by the study of Kaur who reported positive correlation between age and TSH (Kaur et al., 2021). Bensenor explained this by demonstrating that aging promotes a natural decrease in the pituitary TSH secretion and deiodination of T4, while increases the occurrence of antithyroglobulin and antithyroperoxidase antibodies (Bensenor et al., 2012). Although literature studies reporting thyroid function in the pathophysiology in acne vulgaris patients are very few, this could be explained by that; TSH can cause stimulation of sebaceous gland cell activity. Also it has been described that Thyroxine decrease mitotic activity and to increase lipid synthesis, while TSH stimulates sebaceous gland cell activity (Zouboulis et al., 1998). Also involvement of cytokines can explain the above observed association. Cytokines such as IL-1, IFN-c, IFN-a, IL-2, and macrophage colony-stimulating factor may play a role in the disease manifestation and acne severity (Kaur et al., 2021). Thyroid hormone axis plays an important role in body weight balance, with hypothyroidism being associated with weight gain and hyperthyroidism promoting weight loss (Biondi., 2010; Mullur et al., 2014). Even within the normal range, variations of thyroid function have been associated with significant weight variation (Bjergved et al., 2014). On the other hand, obesity, particularly morbid obesity, has been associated with significant alterations of thyroid function. Most studies reported increased serum thyroid-stimulating hormone (TSH) concentrations in patients with morbid obesity (Neves et al., 2018). Despite the conflicting data available, several cross-sectional studies have shown a significant positive association between body mass index (BMI) and serum thyrotropin (TSH) ( Sakurai et al., 2014; Kitahara et al., 2012). Also there are controversial data regarding association between BMI and serum free thyroid hormones, most documenting negative association (Ortega et al., 2007; Ambrosi et al., 2010). GAG score showed significant positive correlation with both T3 and T4 p =(0.043 and 0.013) respectively. The current study reported that fT4 was significantly higher among acne patients with mixed acne site (both facial and truncal) than in patients with only one site either facial or truncal (P=0.048) i.e in mixed-site versus mono-acne-site. There was no previous studies addressed the same issue to compare our results with, fortunately. Study Strengths and LimitationsStrengthsUp-to-our knowledge, limited number of studies assessing Thyroid Dysfunction in female patients with acne vulgaris. LimitationsLimited sample size. The effect of different lines of treatment received by the studied participants on the thyroid function level need further evaluation. Autoimmune thyroid antibodies (anti-TPO, anti-TG) aren’t frequently assessed despite of their major implications in the clinical presentation of thyroid dysfunction patients. The present study is a cross-sectional, case–control, observational study aimed to assess the thyroid function in relation to age, BMI and acne severity in acne female patients. The study included 112 patients (59 cases and 53 matched controls). Both studied groups were comparable as regard to age and BMI with no statistically significant difference between them (P>0.05). The global acne grading system (GAGS) gives a weight to each region (face and back) with a severity score with a mean of 19.1± 8.2 and ranged from 4 up to 42 (58% had mild severity, 31% had moderate and 12% had severe acne). The majority of studied cases have received topical and/or systemic treatment. Facial acne was reported in 27 (45.8%) of studied cases, truncal acne was observed in 2 (3.4%) and 30 (50.8%) suffered from mixed (facial and truncal) acne. No significant difference was found between acne patients and controls for all thyroid function and dysfunction level (P>0.05), except the TSH (µIU/ml) level which was significantly higher among the acne patients. However; thyroid dysfunction levels showed no significant difference with either GAGS score or with different acne severity groups. No significant relation was found between TFT and disease severity “by GAG score” among acne cases, except for a significant difference between GAG score mild and moderate degree and free T3 where moderate GAG cases had higher fT3 in mild and moderate GAG score groups. Patients’ age and BMI show significant positive correlation with TSH level and significant negative correlation with both T3 and T4, while GAG score show significant positive correlation with both T3 and T4. Patients with mixed acne site have significantly higher fT4 than patients with only one site either facial or truncal. The present results report possible role of thyroid function test in the pathophysiology of acne vulgaris in adult female patients. We need larger multi-center studies to confirm our finding in order to help in the management of acne vulgaris in adult female patients for better outcomes and better quality of life among them. Acne vulgaris among female patients especially adults and late onset acne was positively affected by higher TSH levels among studied cases, while no clear or apparent impact of other thyroid function parameters (T3, T4) on acne incidence and severity. Both age and BMI have a great impact on thyroid stimulating hormone, but they have a negative impact on fT3 and fT4. GAGS scale was positively affected by thyroid stimulating hormone, but did not have a clear affection by fT3 and fT4. Based on the finding of the current study we recommended that: Thyroid function tests are considered to be assessed in middle aged female patients with acne before starting treatment. Further assessment of autoimmune thyroid antibodies (anti-TPO, anti-TG) are recommended. The effect of different lines of treatment (especially retinoids) received by the patients on the thyroid function level should be measured. Analyzing serum TSH, fT3 and fT4 level in all female acne patients with additional phenotypic manifestations such as premenstrual flare, hirsutism, adult-onset acne and persistent acne irrespective of its severity. Other contributing factors as hormonal profile and androgens could be included. Further studies with wider scale are recommended.