The impact of isotretinoin on the pituitary-ovarian axis: An interpretative review of the literature.

Isotretinoin (13-cis-retinoic acid), a derivative of vitamin A, is used in the treatment of severe acne resulting in sebum suppression induced by sebocyte apoptosis. Isotretinoin treatment is associated with several adverse effects including teratogenicity, hepatotoxicity, and dyslipidemia. Isotretinoin's effects on endocrine systems and its potential role as an endocrine disruptor are not yet adequately investigated. This review presents clinical, endocrine, and molecular evidence showing that isotretinoin treatment adversely affects the pituitary-ovarian axis and enhances the risk of granulosa cell apoptosis reducing follicular reserve. Isotretinoin is associated with pro-apoptotic signaling in sebaceous glands through upregulated expression of p53, forkhead box O transcription factors (FOXO1, FOXO3), and tumor necrosis factor-related apoptosis inducing ligand (TRAIL). Two literature searches including clinical and experimental studies respectively support the hypothesis that isotretinoin's toxicological mode of action on the pituitary-ovarian axis might be caused by over-expressed p53/FOXO1 signaling resulting in gonadotropin suppression and granulosa cell apoptosis. The reduction of follicular reserve by isotretinoin treatment should be especially considered when this drug will be administered for the treatment of acne in post-adolescent women, in whom fertility may be adversely affected. In contrast, isotretinoin treatment may exert beneficial effects in states of hyperandrogenism, especially in patients with polycystic ovary syndrome.

Evaluation of biophysical skin parameters and hair changes in patients with acne vulgaris treated with isotretinoin, and the effect of biotin use on these parameters.

AIM: Impairment of biotin metabolism with the use of isotretinoin and the mucocutaneous side effects observed in patients using isotretinoin suggests that they are a result of decreased enzyme activity. We aimed to determine the pattern of skin and hair changes in patients with acne receiving isotretinoin and how these changes were affected by biotin added to the treatment. MATERIALS AND METHODS: Sixty patients were divided into two groups. Each group contained 30 patients. Groups A and B received 0.5 mg/kg/day isotretinoin, and 10 mg/day biotin supplement was added to Group B. Both groups were evaluated using a digital dermoscope for hair changes and with a DermaLab® Combo device for transepidermal water loss (TEWL), skin retraction, skin hydration, and skin sebum levels at the beginning and end of the fourth month. RESULTS: In group B, the anagen hair ratio increased (P = 0.034) and the telogen hair ratio decreased significantly (P = 0.003). Skin sebum and the skin retraction values decreased in both groups. Skin hydration decreased significantly in group A (P = 0.001), but there was no significant decrease in group B (P = 0.43). CONCLUSION: Biotin (10 mg/day) given in addition to isotretinoin treatment decreased telogen and increased anagen hair rates and helped to maintain skin hydration. The use of 10 mg/day biotin can prevent the mucocutaneous adverse effects of isotretinoin treatment.

Correlation study between clinical classification and disability index in a holistic evaluation of acne severity and impact in Turkey.

BACKGROUND: This study provides a comparison between disease severity observed by inspectors and the disease burden assessed by patients is scanty in acne study. METHODS: In a multicenter prospective hospital-based study, modified Comprehensive Acne Severity Scale (mCASS) and Cardiff Acne Disability Index (CADI) were employed to grade disease severity and to determine the quality of life, respectively. The average of the mCASS and CADI scores, with range at 0-25, was termed as Acne Severity and Impact Grading System (ASIG). RESULTS: In 1331 evaluated patients (mean: 21,51±4,93 years), including 306 men and 1025 women, an overall significant, positive correlation was found between ASIG and mCASS (r=0.862), or CADI (r=0.686), respectively (P=0.001 each). Adult women with back acne and adolescent with décolleté expressed greater concern (higher CADI) than the clinical severity (lower mCASS). The overall prevalence of acne in décolleté area, including neck, was 32.3%. CONCLUSIONS: Discrepancies in the acne severity between self-perception and objective evaluation exist in certain subgroups of patients. Décolleté acne deserves special attention in clinical assessment.

The effect of personal, familial, and environmental characteristics on acne vulgaris: a prospective, multicenter, case controlled study.

BACKGROUND: There are only a few studies about epidemiological features of acne vulgaris in the literature. The aim of this study was to analyze demographic, clinical, familial and environmental characteristics of acne, the role of diet and aggravating factors and association of these factors with acne severity. METHODS: Patients with a diagnosis of mild-moderate to severe acne were consecutively interviewed at the participating centers during the study period. RESULTS: A total of 3826 patients and 759 control patients were involved in this study. Mild acne was the most common type of acne, and most of the lesions were localized on face followed by the trunk. The severity of acne was worse in patients who had a positive family history of acne. The most common triggering factor was psychological stress. We found a positive correlation with chocolate, bread, green tea, milk, white sugar, ripe banana, ice cream, apple, orange, and red meat consumption. As we compare the acne severity according to geographical features we detected mild- moderate acne was more common in Mediterranean region and severe acne was more common in East Anatolian region. Family history positivity was more common in Aegean region and least common in Central Anatolian region. There was statistically significant relationship as we compare acne severity and dietary factors such as chocolate, dairy products such as milk, sunflower seed consumption within the geographical regions. CONCLUSIONS: This study presents the demographic and clinical characteristics of acne patients in Asian and the European parts of Turkey. We believe that this study will provide a useful overview of acne in Turkey.

Systemic comorbidities associated with rosacea: a multicentric retrospective observational study.

BACKGROUND: Once considered a disorder limited to the skin, rosacea is now known to be associated with systemic disorders. The aim of this study was to determine what systemic comorbidities accompany rosacea and to determine the relationship between the type, severity, and duration of rosacea, and the presence of and type of systemic comorbidities. METHODS: This retrospective multicenter study was conducted by the Turkish Society of Dermatology Acne Study Group. Thirteen dermatology clinics throughout Turkey participated in the study. A structured physician-administered questionnaire was used to collect patient demographics, clinical findings, and lifestyle data. The principal rosacea subtype, physician global assessment of severity, and duration of rosacea were recorded. Physicians recorded each participant's medical history, including current and past comorbidities, duration of any such comorbidity, and the use of medications to treat any comorbidities. RESULTS: The study included 1,195 rosacea patients and 621 controls without rosacea aged 18-85 years. As compared to the controls, more of the rosacea patients had respiratory tract, gastrointestinal system, and metabolic and hepatobiliary system disorders in a rosacea's severity- and duration-dependent manner. CONCLUSION: Clinicians must be aware of the potential for systemic comorbidities in rosacea patients, which becomes more likely as disease duration and severity increase.

Primary myxoid melanoma with dermoscopic findings.

Myxoid melanoma is a rare variant of melanoma, which is characterized by atypical spindle cells and dense mucin deposition in dermis. This tumor is usually seen in elderly people with a similar progress in other variants of melanoma. A 28-year-old male presented to our outpatient clinic with a 6-month history of a slowly growing asymptomatic pink lesion on his arm. Dermoscopic examination revealed pink-white cristalline structures and blue-grayish ovoid globules. The lesion was totally excised with initial diagnosis of basosquamous carcinoma, amelanotic melanoma and basal cell carcinoma. Histopathological examination was consistent with myxoid melanoma. We present this case due to the rarity of myxoid melanoma and occurrence at such a young age.

Primary cutaneous CD 30 (+) ALK (-) anaplastic large cell lymphoma with dermoscopic findings: a case report.

Primary cutaneous CD 30 (+) anaplastic large cell lymphoma (PCALCL) is a rare and indolent type of cutaneous T cell lymphoma, which usually presents as an asymptomatic solitary firm nodule that rapidly grows and often ulcerates without any systemic involvement. A 64-year-old female presented to our outpatient clinic with a one-year history of multiple pink nodular lesions on the chest, back and gluteal regions. Dermoscopic examination of the nodular lesions revealed pink-to-yellow structureless areas and arborizing-to-polymorphous vessels. Histopathologic examination was consistent with CD30 (+) anaplastic large cell lymphoma. Systemic involvement was not detected. Local radiotherapy for large nodules and surgical excision for small nodules were performed. The large nodules had totally regressed after 10 sessions of radiotherapy.

An investigation of cytochrome p450 (CYP) and glutathione S-transferase (GST) isoenzyme protein expression and related interactions with phototherapy in patients with psoriasis vulgaris.

Oxidative stress may play an important role in the pathogenesis of psoriasis. Glutathione S-transferases (GSTs) make up a group of antioxidant enzymes. Cytochrome p450 (CYP) enzymes can influence oxidation and reduction reactions. We investigated the potential effects of GST and CYP enzymes in the pathogenesis of psoriasis. The study included 32 psoriasis patients and 22 healthy subjects. Psoriasis patients were administered 20 sessions of narrowband ultraviolet B phototherapy. Expressions of GST and CYP enzymes were assessed by immunohistochemical staining. Expression levels of GSTK1, GSTM1, and GSTT1 were significantly higher in psoriasis than in control tissues (P = 0.022, P = 0.001, and P = 0.006, respectively). Pre- and post-treatment expression was similar. Expression of CYP1A1 and CYP2E1 was significantly higher in pre- (P = 0.003 and P = 0.001, respectively) and post-treatment (P = 0.003 and P = 0.001, respectively) psoriatic tissues than in control tissues. No significant differences in CYP1B1 levels between the study and control groups were detected before treatment (P > 0.05). However, CYP1B1 levels were higher in post-treatment psoriatic tissue than in control tissue (P = 0.045). The significant increases in expression of GSTK1, GSTM1, and GSTT1 in psoriasis may reflect the increased activation of GST in response to excessive free radical formation from activated neutrophils or ultraviolet exposure to maintain antioxidant capacity in psoriasis. Furthermore, expressions of CYP1A1 and CYP2E1 represent important enzymatic systems in psoriasis. These findings suggest that psoriasis is an oxidative stress condition, although phototherapy does not affect these enzymatic systems. Further investigation is required.

Ocular findings in patients with alopecia areata.

OBJECTIVES: This study investigated ocular findings in patients with alopecia. METHODS: A total of 42 patients with alopecia (31 male, 11 female; 84 eyes) and 45 healthy individuals (28 male, 17 female; 90 eyes) were enrolled in the study. Of the patients with alopecia, 34 had alopecia areata, seven had alopecia universalis, and one had ophiasis alopecia. Seven patients had eyebrow involvement and seven had eyelash involvement. Autorefractometry, keratometry, visual acuity, central corneal thickness and intraocular pressure (IOP) measurements, bilateral anterior and posterior segment examinations, Schirmer's tests, and visual field examinations were performed in both groups. RESULTS: The mean ± standard deviation age of the subjects was 25.21 ± 10.88 years in the alopecia group and 28.24 ± 9.31 years in the control group. Lens abnormalities were observed in 35 eyes in the alopecia group and in 11 eyes in the control group (P < 0.05). Posterior segment abnormalities were seen in 29 eyes in the alopecia group and four eyes in the control group (P < 0.05). There were no statistically significant differences in age, sex, visual acuity, refractive error, keratometric findings, IOP, central corneal thickness, perimetry, or Schirmer's test results between the alopecia and control groups (P > 0.05). CONCLUSIONS: Patients with alopecia may have more lenticular and retinal findings than normal individuals, but those findings do not interfere with visual acuity. Close surveillance for the early onset of cataract formation is important in patients with alopecia.

Does Lichen Planus Cause Increased Carotid Intima-Media Thickness and Impaired Endothelial Function?

BACKGROUND: Lichen planus (LP) has been associated with cardiovascular disease (CVD) risk factors, but there are no studies on the association between LP and subclinical atherosclerosis. We investigated the presence of subclinical atherosclerosis in patients with LP not known to have CVD using carotid intima-media thickness (CIMT) and flow-mediated dilatation (FMD). METHODS: The study included 30 patients with LP and 30 controls. High-resolution ultrasonography was used to assess CIMT and FMD. Participants' biochemical parameters, body mass index (BMI), and waist circumference were recorded in both groups. RESULTS: FMD was significantly lower (7.45% ± 3.63% vs 11.01% ± 5.34%; P = 0.004) and CIMT was higher (0.8 mm [range, 0.7-0.9 mm] vs 0.6 mm [0.4-0.6 mm]; P < 0.001) in the LP group compared with the control group. After adjustment for age, sex, BMI, high-density lipoprotein cholesterol levels, and C-reactive protein levels, the presence of LP was associated with impairment of FMD (ß = -0.441; 95% CI, -9.336 to -0.321; P = 0.037) and an increase in CIMT (ß = 0.459; 95% CI, 0.057 to -0.351; P = 0.008). CONCLUSIONS: Reduced FMD and increased CIMT levels are sensitive indicators of target-organ damage and display increased risk for cardiovascular morbidity and mortality. Our study found that patients with LP showed a tendency toward impaired levels of FMD and increased CIMT. LP may be a novel predictor of early vascular dysfunction and structural changes.

Evaluation of ocular findings in patients with vitiligo.

In this study, we aimed to investigate ocular manifestations in patients with vitiligo. Sixty-one patients with vitiligo were included in the study. From the patients who referred for examination to the dermatology and ophthalmology clinic, 57 patients without any systemic disease were taken as the control group. In both groups, otorefractometry, keratometry, visual acuity test, intraocular pressure measurement, anterior segment, and fundus examinations of the eye with slit lamp, Schirmer test, and perimetry were carried out. The mean age was 24.54 ± 11.90 years and 23.03 ± 8.72 years in the patients and control group, respectively. The mean Schirmer test results were as follows: 16.74 ± 9.11 mm and 17.64 ± 9.41 mm for the right and left eyes of the patients, and 21.96 ± 12.51 mm and 23.42 ± 12.51 mm for the right and left eyes of controls, respectively. Of the patients, 36 eyes showed lenticular findings. However, only 12 eyes of the controls have some lenticular findings. Twenty-nine eyes in the vitiligo group and four in the controls showed some fundus findings. When the two groups were compared with each other, there was a statistically significant difference between them in terms of Schirmer test results, lens, and fundus findings (P < 0.05 for all). However, there was no significant difference in terms of age, gender, visual acuity, refraction, keratometry, intraocular pressure, perimetry, and corneal findings (P > 0.05 for all). Patients with vitiligo may have more lenticular and retinal findings than normal. They can be more prone to dry eye syndrome as well.

General psychiatric symptoms, quality of sleep, and coping strategies in patients with psoriasis vulgaris.

BACKGROUND: Psoriasis is a common dermatological disorder with psychiatric comorbidity. Psoriasis is associated with a variety of psychological problems, including poor self-esteem, sexual dysfunction, sleep disturbances, anxiety, depression, and suicidal ideation. OBJECTIVES: We aimed to investigate general psychiatric symptoms, quality of sleep, and coping strategies in patients with psoriasis vulgaris. METHODS: A total of 79 subjects (37 patients with psoriasis vulgaris and 42 control subjects) were enrolled in the study. Coping strategies were measured using the Coping Orientations to Problems Experienced (COPE) Scale. General psychopathological status was assessed using the Symptom Checklist-90-R (SCL90R), and sleep quality and disturbances were assessed using the Pittsburgh Sleep Quality Index (PSQI). RESULTS: The mean age of the patients was 39.18 ± 16.85 years. The mean age of control subjects was 39.33 ± 11.61 years. The mean score on the Psoriasis Area and Severity Index (PASI) was 7.56 ± 3.66. There were no significant differences in scores on the SCL90R and COPE subscales between the patient and control groups. However, significant differences between the groups emerged on the PSQI subscales for subjective sleep quality and habitual sleep efficiency (Z = -1.964, P = 0.049, and Z = -2.452, P = 0.014, respectively). CONCLUSIONS: The present study found no significant differences in general psychiatric symptoms and coping strategies between the psoriasis patients and the control group, by contrast with findings reported elsewhere in the literature. We think that the low PASI scores of our patients, which indicate the low severity of disease in the present group, is the main reason for this finding. However, sleep quality is lower in psoriasis vulgaris patients than in healthy controls. This may be associated with the itch and pain caused by lesions. Further experimental studies are required to explain these findings.