Psoriasis and steatotic liver disease: Are PNPLA3 and TM6SF2 polymorphisms suitable for the hepato-dermal axis hypothesis?

INTRODUCTION AND OBJECTIVES: A high prevalence of steatotic liver disease has been described in psoriasis. However, the influence of genetic polymorphisms has yet to be investigated in this scenario. This study aims to determine the frequency of steatosis, advanced liver fibrosis and PNPLA3/TM6SF2 genotypes in individuals with psoriasis and to evaluate the impact of genetic polymorphisms, metabolic parameters and cumulative methotrexate dose on steatosis and fibrosis. MATERIALS AND METHODS: Cross-sectional study that prospectively included psoriasis outpatients, submitted to clinical and laboratory analysis, transient elastography (FibroScan®, Fr) and PNPLA3/TM6SF2 genotyping. Steatosis was defined by CAP ≥275 dB/m and advanced liver fibrosis as transient elastography ≥10 kPa. Logistic regression analysis evaluated the independent variables related to steatosis and fibrosis; p-value< 0.05 was considered significant. RESULTS: One hundred and ninety-nine patients were enrolled (age 54.6 ± 12.6 years, 57.3% female). Metabolic syndrome (MetS), steatosis and advanced liver fibrosis prevalence were 55.8%, 54.8% and 9%, respectively. PNPLA3 and TM6SF2 genotypes frequencies were CC 42.3%/CG 49.5%/GG 8.2% and CC 88.7%/ CT 11.3%/ TT 0%. MetS (OR3.01 95%CI 1.51-5.98; p = 0.002) and body mass index (OR1.17 95%CI 1.08-1.26; p < 0.01) were independently associated with steatosis. Diabetes Mellitus (T2DM) (OR10.76 95%CI 2.42-47.87; p = 0.002) and harboring at least one PNPLA3 G allele (OR5.66 95%CI 1.08-29.52; p = 0.039) were associated with advanced fibrosis, but not TM6SF2 polymorphism or cumulative MTX dose. CONCLUSIONS: MetS and T2DM confer higher odds for steatosis and advanced fibrosis in individuals with psoriasis. PNPLA3 G allele, but not TM6SF2 polymorphism, impacts a 5-fold odds of advanced liver fibrosis.

Evaluation of cardiovascular risk in patients with psoriatic disease in a multiracial population: a cross-sectional study.

BACKGROUND: Psoriatic disease (PD) is a chronic inflammatory disorder often associated with cardiovascular risk (CVR) factors such as obesity, hypertension, diabetes, dyslipidaemia and smoking. It is estimated that 2%-4% of the population worldwide has PD. Cutaneous lesions of psoriasis (PsO) may be associated with psoriatic arthritis (PsA) in up to 40% of patients. Studies have been carried out around the world with the aim of evaluating CVR in such patients. AIM: To determine CVR in a multiracial population with PsA or PsO from southeastern Brazil, which has a predominantly tropical climate, compared with controls. METHODS: A cross-sectional study was carried out in outpatients with PsO or PsA followed up at a quaternary referral hospital in Rio de Janeiro. The Framingham Risk Score (FRS) was used to predict cardiovascular events (CVEs) over 10 years in patients with PsO and PsA compared with controls. RESULTS: FRS was significantly higher at 10 years in patients with PsO (mean ± SD 16.3 ± 14) and PsA (18.0 ± 15) compared with controls (10.6 ± 9.5) (P = 0.01) and also increased with age. The chance of having a high FRS in the PsO and PsA groups increased by 0.30 and 0.23 times per year, respectively, compared with controls (PsO vs. controls 95% CI 0.090-1.00; PsA vs. controls 95% CI 0.08-0.75). CONCLUSION: In this multiethnic Brazilian population, both PsO and PsA were associated with higher CVR compared with controls. The frequency of high FRS was highest in the sixth decade of life for all three groups of participants. Annual assessment of patients with PD is necessary in order to prevent CVEs.

Coexistence of onychomycosis and nail psoriasis and its correlation with systemic treatment.

BACKGROUND: Epidemiological studies indicate that onychomycosis may affect up to 79% of psoriatic patients. Onychomycosis in psoriatic patients is more commonly caused by yeasts comparing with non-psoriatic. OBJECTIVES: Evaluate the prevalence of fungi in nail psoriasis. Evaluate the association between direct mycological examination (DME) and mycological culture, Nail Psoriasis Severity Index (NAPSI) and systemic treatment for psoriasis. METHODS: Of 133 nails from 20 patients with nail psoriasis were evaluated as follows: 9 patients were using topical treatment and 11 were on systemic treatment. The assessment of psoriasis severity using NAPSI was performed in all psoriatic nails. The presence of fungi was confirmed in DME and culture. RESULTS: DME showed the presence of fungal elements in 45 nails (33.83%) with a predominance of blastoconidia (95.5%) No septate hyphae were seen. Mycological culture was positive in 36 (27.06%) samples. Among them, Candida grew in 31 (86.1%): Candida parapsilosis in 15 (48.38%), Candida spp in 14 (45.16%). No growth of dermatophytes was observed. Patients with systemic treatment showed a higher frequency of positive test (DME and culture) for fungi when compared to topic treatment (p:.006). There was a positive correlation between NAPSI, mycological culture and systemic treatment (p:.0063); the risk was four times higher (OR:4.0). LIMITATION OF THE STUDY: Sample size. CONCLUSION: These results are consistent with some previous reports, Candida was the fungus with higher frequency on the psoriatic nails, however, the role of these fungi is controversial (contamination x colonisation x infection). The fact that the immunosuppressive treatment increases the chance of fungal infection leads us to a greater attention to this patient profile, to prevent the intensification of nail psoriasis (Köbner phenomenon).

The Importance of the Biopsy Technique in the Diagnosis of Histoid Leprosy.

Histoid leprosy (HL) was originally described by Wade in 1963 and is regarded as a rare variant of lepromatous leprosy (LL). These characteristic clinical lesions are firm, deeply adhered nodules with features reminiscent of dermatofibromas or keloids in a background of apparently healthy skin. The main histopathological findings described are the presence of spindle cell histiocytes immersed in a richly collagenized background, usually forming a nodular pattern of infiltration with sharply delimitation and positive staining for acid-fast bacilli. The classical form of HL lesions should be devoid of foam histiocytes and globi. However, we and other authors noticed that in most of the cases, despite characteristic clinical features, histopathology depicts a mixture of LL and HL patterns. Therefore, we present a case with clinical features similar to HL in which an excisional scalpel biopsy of a nodule demonstrated features of classical LL in the center of the lesion and features of HL in the periphery, highlighting that a proper biopsy technique could enhance the ability of the dermatopathologist to histopathologically diagnose cases of HL. In cases in which HL is clinically suspected, we advocate replacing the usual 4-mm incisional punch biopsy by a broader elliptical scalpel biopsy, encompassing the totality of the lesion whenever possible to achieve a reliable representation of the pathologic process.

Quantification of histopathological changes in patients with psoriasis before and after phototherapy.

BACKGROUND: One of the most used resources for the treatment of psoriasis is ultraviolet radiation (UV) with psoralens (PUVA) and narrow-band UV (UVB-NB 311-312 nm). Although many researchers have assessed the histopathological effects of this therapy modality, none used a morphological classification system specific to psoriasis. PURPOSE: To assess the clinical and histopathological response in the phototherapy treatment of plaque psoriasis with PUVA and UVB-NB with use of PASI and TROZAK. METHODS: Histopathological changes of plaque psoriasis were quantified with help of the grading system for psoriasis-Trozak in 20 patients of both sexes, before and after 32 PUVA phototherapy sessions (10 patients-GPUVA) and UVB-NB (10 patients-GUVB-NB). The severity and extension of psoriasis was evaluated through PASI. The slides stained with hematoxylin and eosin were scanned in an Aperio CS2 scanner (Leica Biosystems) and evaluated through the software ImageScopeTM (Aperio Technologies). Statistical analysis was performed with the use of the program SPSS 22.0, with application of the Wilcoxon and Mann-Whitney tests. RESULTS: All patients presented improvement in psoriatic plaques with decrease in PASI after treatment (P < 0.01) and significant reduction in histopathological changes in psoriasis from 15.4 ± 1.7 to 3.7 ± 3.2 (P < 0.01) in group GPUVA and from 13.2 ± 1.7 to 4.9 ± 5.2 (P < 0,01) in group GUVB-NB. CONCLUSIONS: Phototherapy, regardless of type, is an effective treatment for moderate and severe psoriasis, with possibility of being quantified clinically by PASI and histopathologically by Trozak.

History of Seborrheic Dermatitis: Conceptual and Clinico-Pathologic Evolution.

Seborrheic dermatitis is an inflammatory and chronic disease with a high incidence and prevalence (1% to 3% in the general population, 3% to 5% in young adults, and 40% to 80% in HIV-positive individuals). Although the condition was first described in 1887, its clinical aspects and clinical forms have still not been well individualized, nor has its etiopathogenesis been fully elucidated. The disease, despite having clinical features similar to dermatitis, does not have the same histopathologic features or the same progressive clinical behavior. This contribution reviews the history of seborrheic dermatitis.

Carboxymethyl Cellulose, Trichloroacetic Acid, and Unna Boot for Healing Venous Ulcers: A Comparative Study of Their Efficacy and Socioeconomic Impact.

Chronic ulcers are defined as a breakdown of the long-term cutaneous barrier or frequent recurrence of breakdowns. Dressings are a form of treatment and, in view of the variety and high cost of the products on the market, three agents were selected for this investigation, regarding their efficacy and cost/benefit ratio. The objective of the investigation was to evaluate and compare the efficacy, costs, and benefits of carboxymethylcellulose in paste at 20% (CMC 20%), trichloroacetic acid at 90% (TCA 90%), and Unna boot for treatment of chronic venous ulcers. Three groups of 30 patients each were chosen randomly for ambulatory treatment with TCA 90% (G1), CMC 20% (G2), and Unna boot (G3). The evolution of the cicatricial process of each group separately and between groups was analyzed with measurement of the lesion areas in square centimeters (cm2) and observation of the amount of exudate from observation of the photographic record, until their healing, in the maximum period of 20 weeks. A significant reduction of lesion areas in all groups was observed (P=.0001), with a median reduction of 7.6 cm2 (38.1%) for G1, 3.9 cm2 (38.8%) for G2, and 16.2 cm2 (77.8%) for G3. There was a significant difference in the absolute delta of the lesion areas (P=.0001) of the groups. The three types of treatments promoted effective improvement, with acquisition and utilization of all three products in the public health services being recommended.

Dermatomyositis--Part 1: Definition, Epidemiology, Etiology and Pathogenesis, and Clinics.

Dermatomyositis is an inflammatory autoimmune disorder that affects the skin, muscles, and blood vessels. The prevailing clinical manifestations are intense erythema, typically around the eyes and dorsum of the hands, accompanied by proximal muscle weakness. There is one clinical form, called amyopathic dermatomyositis, which lacks muscular symptoms and laboratory evidence of muscle damage.

Dermatomyositis-Part 2: Diagnosis, Association With Malignancy, and Treatment.

In this second part of the series on dermatomyositis, the diagnosis and its criteria with review of autoantibodies, capillaroscopy, imaging exams, histopathology, muscle biopsy, electroneuromyography, and muscular enzymes will be assessed. The association with malignancy, since it is described as paraneoplasic, will be discussed. The different therapeutic options for this disease will also be reported, including for dystrophic calcification, a rare and late complication of dermatomyositis.

Correlation Between Severity Index and Quality of Life Index in Patients With Psoriasis Assessed Before and After Phototherapy.

Psoriasis is a common disease whose impact on the life of patients is well documented. The authors investigated the correlation between clinical severity and quality of life in patients with psoriasis before and after phototherapy. Twenty men and women were assessed before and after 32 phototherapy sessions, employing the Dermatology Life Quality Index (DLQI) questionnaire and the Psoriasis Area Severity Index (PASI). A positive and moderate correlation was found between PASI and DLQI after phototherapy (r=0.48, P=.03). This result was not observed before treatment (r=0.13, P=.57). The clinical signs reduction obtained with phototherapy was associated with clinical improvement in patient quality of life. The negative findings for the pretreatment phase suggest a possible acceptance by patients through strategies establishment to improve the handling of the disease, which has a chronic character, and change in the disease's perception after therapy.

Geographic tongue and fissured tongue in 348 patients with psoriasis: correlation with disease severity.

Geographic tongue (GT) and fissured tongue (FT) are the more frequent oral lesions in patients with psoriasis. The aims of this study were to compare the prevalence of GT/FT between psoriasis group (PG) and healthy controls (HC) and investigate the correlation between GT/FT and psoriasis severity using the PASI and age of psoriasis onset. Three hundred and forty-eight PG and 348 HC were selected. According to the age of psoriasis onset, the individuals were classified as having early psoriasis and late psoriasis. The severity of vulgaris psoriasis was determined according to PASI. A follow-up was conducted in patients with psoriasis vulgaris (PV) with GT to evaluate the progression of oral and cutaneous lesions. The FT and GT were more frequent in PG than in HC. The incidence of GT was higher in patients with early psoriasis and that of FT in late-psoriasis. There is association between psoriasis intensity and GT; and a higher monthly decrease of PASI score in patients without GT. The presence of GT and FT is higher in PG than in the HC. GT is associated with disease severity and may be a marker of the psoriasis severity.

Assessment of fatigue in a large series of 1492 Brazilian patients with Spondyloarthritis.

BACKGROUND: The aim of the present study was to analyze the score of fatigue in a large cohort of Brazilian patients with SpA, comparing different disease patterns and its association with demographic and disease-specific variables. METHODS: A common protocol of investigation was prospectively applied to 1492 Brazilian patients classified as SpA according to the European Spondyloarthropathies Study Group (ESSG) criteria, attended at 29 reference centers. Clinical and demographic variables were recorded. Fatigue was evaluated using the first item of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questionnaire. RESULTS: The mean BASDAI fatigue score was 4.20 ± 2.99. There was no significant difference in the fatigue score between the different SpA. Fatigue was higher in female patients (p < 0.001), with mixed (axial + peripheral) involvement (p < 0.001) and in those who did not practice exercises (p < 0.001). Higher scores of fatigue were significantly associated with inflammatory low back pain (p = 0.013), alternating buttock pain (p = 0.001), cervical pain (p = 0.001), and hip involvement (p = 0.005). Fatigue presented a moderate positive statistical correlation with Bath Ankylosing Spondylitis Functional Index (BASFI) (0.469; p < 0.001) and Ankylosing Spondylitis Quality of Life (0.462; p < 0.001). CONCLUSION: In this large series of Brazilian SpA patients, higher fatigue scores were associated with female gender, sedentary, worse functionality, and quality of life.

Split-scalp pilot study to evaluate effectiveness of Minoxidil 0,5% MMP® versus Topical Minoxidil 5% in the treatment of Female Pattern Hair Loss.

Female Pattern Hair Loss (FPHL) is a common form of non-scaring hair loss that occurs in adult women. Although several treatments have already been proposed for FPHL, only Topical Minoxidil accumulated an adequate level of evidence. This study aimed to evaluate the therapeutic response of MMP® (intradermal infiltration) of Minoxidil formulation in the frontal-parietal-vertex regions compared with the gold-standard home administration of Minoxidil 5% Capillary Solution. This self-controlled comparative study evaluated 16 FPHL patients, without treatment for at least 6 months, confirmed by trichoscopy with TrichoLAB® software. They received 4 monthly sessions of MMP® with Minoxidil 0,5% on the right side of the scalp (frontal-parietal-vertex areas), followed by occlusion with plastic film for 12 h and prescription of Minoxidil 5% Solution for home use once a day, on both scalp sides, starting 72 h after the procedure. The reassessment trichoscopy was 6 weeks after the last session and they answered a "self-assessment" questionnaire. Treated scalp areas were compared and showed both treatments, in general, were effective, with no difference between them. If they were analyzed separately by treated areas, there were signs of better response in the parietal-vertex regions with treatment by MMP® with Minoxidil, while clinical treatment indicated a better response in the other regions. When patients were divided into more and less advanced cases, a better response in parietal-vertex regions treated by MMP® with Minoxidil in less advanced patients was confirmed. MMP® with Minoxidil showed a better response in the parietal-vertex regions in less advanced FPHL patients. It represents yet another resource to improve quality of life of these suffering patients.

The development of candidate composite disease activity and responder indices for psoriatic arthritis (GRACE project).

OBJECTIVE: To develop new composite disease activity indices for psoriatic arthritis (PsA). METHODS: Data from routine clinic visits at multiple centres were collected in a systematic manner. Data included all domains identified as important in randomised controlled trials in PsA. Decisions to change treatment were used as surrogates for high disease activity. New indices were developed by multiple linear regression (psoriatic arthritis disease activity score: PASDAS) and empirically, utilising physician-defined cut-offs for disease activity (arithmetic mean of desirability functions: AMDF). These were compared with existing composite measures: Composite Psoriatic arthritis Disease Activity Index (CPDAI), Disease Activity for PSoriatic Arthritis (DAPSA), and Disease Activity Score for rheumatoid arthritis (DAS28). RESULTS: 161/503 (32%) subjects had treatment changes. Although all measures performed well, compared with existing indices, PASDAS was better able to discriminate between high and low disease activity (area under receiver operating curves (ROC)) curve with 95% CI: PASDAS 0.773 (0.723, 0.822); AMDF 0.730 (0.680, 0.780); CPDAI 0.719 (0.668, 0.770); DAPSA 0.710 (0.654, 0.766); DAS28 0.736 (0.680, 0.792). All measures were able to discriminate between disease activity states in patients with oligoarthritis, although area under the receiver operating curves (AUC) were generally smaller. In patients with severe skin disease (psoriasis area and severity index>10) both nonparametric and AUC curve statistics were nonsignificant for all measures. CONCLUSIONS: Two new composite measures to assess disease activity in PsA have been developed. Further testing in other datasets, including comparison with existing measures, is required to validate these instruments.

Oral candidiasis in patients with psoriasis: correlation of oral examination and cytopathological evaluation with psoriasis disease severity and treatment.

BACKGROUND: Infections are known to trigger and exacerbate psoriasis. Although oral candidiasis is often clinically diagnosed, it is not always confirmed by laboratory tests such as oral cytopathology. OBJECTIVES: The aims of this study were to determine the prevalence of oral candidiasis in patients with psoriasis through clinical and cytopathological diagnosis and to investigate the association between oral candidiasis and psoriasis with regards to the severity of the clinical presentation and the type of treatment for psoriasis. METHODS: A total of 140 patients with psoriasis and 140 healthy control subjects received an oral examination. Scrapings of the tongue were also obtained for a cytopathological examination. RESULTS: The oral examination and the results of the cytopathological smear revealed 37 (26%) cases of candidiasis in the patients with psoriasis and no cases of candidiasis in the healthy control subjects. There was no correlation between the type of psoriasis treatment and the presence of oral candidiasis (P = .616). There was a statistically significant association (P = .033) between the clinical severity of psoriasis and the presence of Candida. LIMITATIONS: This study was limited by the small number of subjects and the lack of follow-up to determine the development of psoriasis after treatment for oral candidiasis. CONCLUSIONS: The presence of oral candidiasis is higher in patients with psoriasis and it is associated with disease severity. This increased presence of oral candidiasis was apparent despite any type of treatment for the psoriasis. Cytopathology to rule out oral candidiasis should be used in the routine medical workup of patients with psoriasis.

Dermal dendritic cell population and blood vessels are diminished in the skin of systemic sclerosis patients: relationship with fibrosis degree and disease duration.

Recent studies have suggested that the number of dermal dendritic cells is altered in the skin of patients with scleroderma and that these cells may have an important role in the pathogenesis of this disease. There is also a belief that insufficient blood flow to the affected organs may also be responsible for the disease. Our aim was to quantify CD34+ cells, factor XIIIa cells, and blood vessels in the skin of patients with systemic sclerosis and to correlate these data with fibrosis degree and duration of disease. Paraffin-embedded skin sections from patients with systemic sclerosis and from healthy subjects were immunolabelled with antibodies against CD34+ and factor XIIIa. Cells and blood vessels were quantified in the papillary and reticular dermis. Both, the number of CD34+ cells and factor XIIIa cells in the skin of patients with systemic sclerosis were reduced. The reduction of these cell types preceded the appearance of intense fibrosis, suggesting that fibrosis is not responsible of this phenomenon. Blood vessel volume and surface density were also reduced in the skin of systemic sclerosis patients. This reduction was also noted early in the evolution of the disease. Our results suggest that CD34+ cells and factor XIIIa cells may contribute to normal regulation of extracellular matrix assembly. We confirmed the observation that capillary density is diminished in scleroderma skin.

Management of Nail Disease in Patients With Psoriatic Arthritis: An Updated Literature Review Informing the 2021 GRAPPA Treatment Recommendations.

OBJECTIVE: Nail psoriasis is common, impairs fine motor finger functioning, affects cosmesis, and is associated with a lower quality of life. This review updates the previous Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for nail psoriasis. METHODS: This systematic literature review of the PubMed, MEDLINE, Embase, and Cochrane databases examined the updated evidence since the last GRAPPA nail psoriasis treatment recommendations published in 2014. Recommendations are based on preformed PICO (Patient/Population - Intervention - Comparison/Comparator - Outcome) questions formulated by an international group of dermatologists, rheumatologists, and patient panel members. Data from this literature review were evaluated in line with Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. RESULTS: Overall, there is insufficient evidence to make any recommendation for the use of topical corticosteroids, topical calcipotriol, topical tazarotene, topical cyclosporine, dimethyl fumarates/fumaric acid esters, phototherapy, and alitretinoin. There is a low strength of evidence to support the use of calcipotriol and corticosteroid preparations, topical tacrolimus, oral cyclosporine, oral methotrexate, intralesional corticosteroids, pulsed dye laser, acitretin, Janus kinase inhibitors, and apremilast. CONCLUSION: The highest strength of supporting evidence is for the recommendation of biologic agents including tumor necrosis factor inhibitors, and interleukin 12/23, 17, and 23 inhibitors.

Paget's disease of the breast.

The initial presentation of Paget's disease of the breast is an eczematous lesion, similar to contact dermatitis, in the skin of the breast at the areola and/or nipple and is refractory to usual topical treatments. It is frequent among women, especially those in their 50s and 60s. Most cases are associated with an in situ or underlying invasive breast neoplasia. The histopathology is usually diagnostic, with immunohistochemistry useful for its differentiation from melanoma and other types of tumors. Treatment should always be surgical with invasive procedures for the effective and complete removal of the breast tumor.

Primary adenoid cystic carcinoma of the skin.

We report a case of primary adenoid cystic carcinoma of the skin in a 44-year-old Brazilian man that was present for 6 years with no metastasis. It is a rare malignant neoplasm of the eccrine gland. Metastases have been found in a few cases, usually to the lungs or lymph nodes. This neoplasm microscopically presents with large nests of cells with adenoid or cribriform features and many epithelial small solid islands. Histopathologic analysis is necessary for diagnosis.