A Retrospective Review of Anthralin in Petrolatum in the Treatment of Alopecia Areata in the Pediatric Population.

BACKGROUND/OBJECTIVES: Alopecia areata (AA) is a T-cell driven autoimmune disease, which results in hair loss. This study aims to determine the efficacy, tolerability and safety of different concentrations of anthralin in the treatment of pediatric AA. METHODS: A retrospective cohort study of patients < 18 yo diagnosed with AA treated with anthralin at SickKids Hospital, Toronto dermatology outpatient clinic in 2016 - 2018. Anthralin used at 0.1%, 0.2%, 0.5% and 1% in petrolatum at short contact, at increments of 15 minutes every week until a 1 hr maximum contact achieved. No other treatment was used in conjunction. Severity of Alopecia Tool (SALT) scores (SS) were determined using photographs and descriptions to assess severity of alopecia at baseline and post anthralin treatment. RESULTS: A total of 11 charts were reviewed in this retrospective cohort. Hair loss pattern; 3 patients with patchy, 6 had mixed (patchy and ophiasis), and 2 were totalis. All except for 1 patient had failed traditional treatments. One patient had complete hair regrowth, 3 showed more than 85% hair re-growth and 7 patients showed more than 75% hair regrowth, the average time for this to occur was 6.5 months. None of the patients experience serious side effects. CONCLUSIONS: Our study demonstrated the efficacy and tolerability of topical anthralin 0.1% to 1% in pediatric alopecia areata. In our study, anthralin 0.2% appears to offer the best performance and tolerability profile among the different concentrations used, with treatment course of at least 6 months in order to achieve more than 75% hair regrowth.

Induction of IL-1ß and antimicrobial peptides as a potential mechanism for topical dithranol.

Topical dithranol is effective in autoimmune conditions like alopecia areata, inducing hair regrowth in a high percentage of cases. Exact mechanisms of dithranol in alopecia areata, with seemingly healthy epidermis besides altered hair follicles, are not well understood. To better understand dithranol's mechanisms on healthy skin, we analysed its effect on normal murine as well as xenografted human skin. We found a strong increase in mRNA expression of anti-microbial peptides (AMPs) (eg Lcn2, Defb1, Defb3, S100a8, S100a9), keratinocyte differentiation markers (eg Serpinb3a, Flg, Krt16, Lce3e) and inflammatory cytokines (eg Il1b and Il17) in healthy murine skin. This effect was paralleled by inflammation and disturbed skin barrier, as well as an injury response resulting in epidermal hyperproliferation, as observed in murine and xenografted adult human skin. This contact response and disturbed barrier induced by dithranol might lead via a vicious loop between AMPs such as S100a8/a9 (that led to skin swelling itself after topical application) and cytokines such as IL-1ß to an immune suppressive environment in the skin. A better understanding of the skin's physiologic response to dithranol may open up new avenues for the establishment of novel therapeutics (including AMP-related/interfering molecules) for certain skin conditions, such as alopecia areata.

Orofacial skin inflammation increases the number of macrophages in the maxillary subregion of the rat trigeminal ganglion in a corticosteroid-reversible manner.

Inflammation of the cutaneous orofacial tissue can lead to a prolonged alteration of neuronal and nonneuronal cellular functions in trigeminal nociceptive pathways. In this study, we investigated the effects of experimentally induced skin inflammation by dithranol (anthralin) on macrophage activation in the rat trigeminal ganglion. Tissue localization and protein expression levels of ionized calcium-binding adaptor molecule 1 (Iba1), a macrophage/microglia-specific marker, and proliferation/mitotic marker antigen identified by the monoclonal antibody Ki67 (Ki67), were quantitatively analyzed using immunohistochemistry and western blots in control, dithranol-treated, dithranol- and corticosteroid-treated, and corticosteroid-treated trigeminal ganglia. Chronic orofacial dithranol treatment elicited a strong pro-inflammatory effect in the ipsilateral trigeminal ganglion. Indeed, daily dithranol treatment of the orofacial skin for 3-5 days increased the number of macrophages and Iba1 protein expression in the maxillary subregion of the ipsilateral ganglion. In the affected ganglia, none of the Iba1-positive cells expressed Ki67. This absence of mitotically active cells suggested that the accumulation of macrophages in the ganglion was not the result of resident microglia proliferation but rather the extravasation of hematogenous monocytes from the periphery. Subsequently, when a 5-day-long anti-inflammatory corticosteroid therapy was employed on the previously dithranol-treated orofacial skin, Iba1 immunoreactivity was substantially reduced in the ipsilateral ganglion. Collectively, our findings indicate that both peripheral inflammation and subsequent anti-inflammatory therapy affect macrophage activity and thus interfere with the functioning of the affected sensory ganglion neurons.

Treatment of chronic extensive alopecia areata by diphenylcyclopropenone alone versus in combination with anthralin.

Alopecia areata (AA) is a chronic inflammatory, recurrent, tissue-specific autoimmune disease, mediated by autoreactive CD8+ T cells, occurring in genetically predisposed individuals. Targeting intrabulbar and peribulbar lymphocytic infiltrate by using squaric acid dibutyl ester and diphenylcyclopropenone (DPCP) in contact immunotherapy is by far the best chemotherapy for AA. The aim of this work was to evaluate the efficacy and safety of combination therapy with DPCP and anthralin in chronic extensive AA. A total of 24 patients (12 were treated only with DPCP and 12 with DPCP and anthralin for at least 24 weeks) were evaluated. Complete hair regrowth was observed in 62.5 and 18.2% of the patients who received DPCP and combination therapy, respectively (p = .04). Hair regrowth duration was different in both groups. The DPCP therapy is superior to the combination therapy with DPCP and anthralin in terms of efficacy, the time of onset of hair regrowth, and the time of completion of hair regrowth, Moreover, combination therapy has more side effects in combination therapy group have been discussed in this work.

Recalcitrant alopecia areata responsive to leflunomide and anthralin-Potentially undiscovered JAK/STAT inhibitors?

Several treatment modalities are available for the management of alopecia areata (AA); however, no therapy is universally effective and treatment can be frustrating in severe cases, with low response and high recurrence rates. Recent studies show that the JAK/STAT pathway plays a central role in the pathogenesis of this disease by determining the crosstalk between the infiltrating CD8+ T cells and the hair follicles, suggesting a role of JAK inhibitors in the treatment of AA. However, reports on the off-label use of these more expensive targeted agents have shown variable results. We present a case of a child with recalcitrant ophiasis-pattern AA who had failed steroid therapy and was treated successfully with leflunomide and anthralin, possibly by the synergistic effect on the JAK/STAT pathway inhibition, and we propose this combination could be a cost-effective therapeutic option for recalcitrant AA.

Higher concentrations of dithranol appear to induce hair growth even in severe alopecia areata.

Alopecia areata (AA) is the commonest autoimmune cause of non-scarring alopecia. Topical treatments including corticosteroids and irritants maybe beneficial. Studies report variable hair regrowth with dithranol (anthralin) but all used low concentrations (0.1-1.25%) and inconsistent measurements of AA severity. We report retrospective data (2005-2014) of 102 patients who had failed ultra-potent topical steroids and were referred to a specialist hair clinic for treatment with dithranol up to 3%. The severity of alopecia areata tool was used and participants graded as mild (<25%), moderate (>25 to 75%), and severe (>75%) hair loss. Compared with baseline any and at-least 50% hair regrowth [72%, 68%, 50% and 61.5%, 48.4%, 37.5%, in mild, moderate and severe AA respectively] occurred in all groups (median treatment duration 12 months). Twenty-nine patients (28.4%) were discharged with complete regrowth; with no difference in proportions in severity groups (33.3%, 29%, and 21.9%) but in the period to discharge [7.9, 6.3, and 29.4 months (p-values <.05)] for mild, moderate, and severe AA. Treatment trials of 12 months with dithranol at higher concentrations may be an option in patients who failed potent topical or intra-lesional steroids) regardless of AA severity. Randomized trials (of less staining formulations) of dithranol are warranted.

Efficacy and safety of diphenylcyclopropenone alone or in combination with anthralin in the treatment of chronic extensive alopecia areata: a retrospective case series.

BACKGROUND: Some patients with chronic extensive alopecia areata (AA) may be refractory to topical immunotherapy. Combination therapy is recommended for such patients. Efficacy and safety of a combination therapy with diphenylcyclopropenone (DPCP) and anthralin in chronic extensive AA is unknown. OBJECTIVE: We sought to determine whether the combination therapy of DPCP and anthralin is superior to DPCP alone in chronic extensive AA. METHODS: We retrospectively analyzed the efficacy, side effects, and relapse rates of DPCP (alone or with anthralin) in chronic extensive AA. RESULTS: A total of 47 patients (22 were treated only with DPCP, and 25 with DPCP and anthralin for at least 30 weeks) were evaluated. Complete hair regrowth was observed in 36.4% and 72% of the patients who received DPCP and combination therapy, respectively (P = .01). Hair regrowth duration was shorter with combination therapy (P = .01). Regrowth rates of the eyebrows, eyelashes, and beard in patients on combination therapy were higher than those in patients on DPCP (P = .01). Side effects such as folliculitis, hyperpigmentation, and staining of skin, hair, and clothes were more common in combination therapy group. LIMITATIONS: The retrospective design and small number of patients are limitations. CONCLUSION: Combination therapy with DPCP and anthralin is superior to DPCP alone in chronic extensive AA.

Optimized dithranol-imiquimod-based transcutaneous immunization enables tumor rejection.

Introduction: Transcutaneous immunization (TCI) is a non-invasive vaccination method promoting strong cellular immune responses, crucial for the immunological rejection of cancer. Previously, we reported on the combined application of the TLR7 agonist imiquimod (IMQ) together with the anti-psoriatic drug dithranol as novel TCI platform DIVA (dithranol/IMQ based vaccination). In extension of this work, we further optimized DIVA in terms of drug dose, application pattern and established a new IMQ formulation. Methods: C57BL/6 mice were treated on the ear skin with dithranol and IMQ-containing ointments together with ovalbumin-derived peptides. T cell responses were determined by flow cytometry and IFN-ɤ ELISpot assay, local skin inflammation was characterized by ear swelling. Results: Applying the adjuvants on separate skin sites, a reduced number of specific CD8+ T cells with effector function was detectable, indicating that the local concurrence of adjuvants and peptide antigens is required for optimal vaccination. Likewise, changing the order of dithranol and IMQ resulted in an increased skin inflammatory reaction, but lower frequencies of antigen-specific CD8+ T cells indicating that dithranol is essential for superior T cell priming upon DIVA. Dispersing nanocrystalline IMQ in a spreadable formulation (IMI-Sol+) facilitated storage and application rendering comparable immune responses. DIVA applied one or two weeks after the first immunization resulted in a massive increase in antigen-specific T cells and up to a ten-fold increased memory response. Finally, in a prophylactic tumor setting, double but no single DIVA treatment enabled complete control of tumor growth, resulting in full tumor protection. Discussion: Taken together, the described optimized transcutaneous vaccination method leads to the generation of a strong cellular immune response enabling the effective control of tumor growth and has the potential for clinical development as a novel non-invasive vaccination method for peptide-based cancer vaccines in humans.

Topical diphenylcyclopropenone plus topical 0.5% anthralin versus topical diphenylcyclopropenone alone for the treatment of chronic extensive alopecia areata: A split-scalp, double-blind, controlled study.

Background: The combination of diphenylcyclopropenone (DCP) and anthralin may demonstrate synergistic effects in the treatment of chronic extensive alopecia areata (AA). Objective: The objective of the study was to compare the efficacy of the combination therapy of topical DCP and topical 0.5% anthralin versus topical DCP alone for the treatment of chronic extensive AA. Materials and Methods: Ten patients were included in the study. Of these, 1, 2, and 7 patients were diagnosed with alopecia totalis, severe AA (>50% hair loss), and alopecia universalis, respectively. For each patient, one side of the scalp was treated with a DCP solution and 0.5% anthralin for 6 months, while the other side was treated with DCP and a cream base for the same duration. The clinical responses were assessed at baseline and then monthly until the end of the 6-month study period using the Severity of Alopecia Tool score. The side effects were evaluated at each follow-up visit. Results: The difference in the efficacies of the combination treatment and DCP alone was not statistically significant (P = 0.59). Regarding the side effects, DCP plus 0.5% anthralin caused significantly more excessive dermatitis than DCP alone (7 patients vs. 2 patients; P = 0.02). Eight patients reported temporary hyperpigmentation at the combination-treatment site, whereas no hyperpigmentation was reported at the DCP-alone site of any patient (P < 0.001). Conclusions: The combination of DCP and 0.5% anthralin was not superior to DCP alone for the treatment of chronic extensive AA. An increase in side effects - excessive dermatitis and hyperpigmentation - was observed in the combination-treatment group.

A randomized trial of diphenylcyclopropenone (DPCP) combined with anthralin versus DPCP alone for treating moderate to severe alopecia areata.

BACKGROUND: Alopecia areata (AA) is a chronic autoimmune disorder. Finding the best treatment regimen for it remains a challenge. Currently, one of the best documented treatment modalities for AA is topical immunotherapy. AIM: To evaluate the safety and efficacy of combined DPCP and anthralin versus standard protocol (DPCP alone). METHODS: A prospective randomized clinical trial was conducted on 50 patients with Alopecia areata who received DPCP alone (group D) or in combination with anthralin (group D/A). Percentage of hair regrowth after 6 months of treatment and the incidence of drug-related adverse effects were evaluated and compared between the two groups. RESULTS: Complete hair regrowth was observed among three patients in each group (18.75% in Group D and 15.79% in Group D/A) after 6 months. Moreover, 25% and 31% of patients in group D and 21% and 47% of patients in group D/A had > 75% and > 50% hair regrowth respectively at the end of the study (P-value: 0.696). In addition, earlier age of onset, chronicity of lesions, nail involvement, facial hair loss and extensive lesions at baseline were associated with poor clinical outcome. CONCLUSION: DPCP and anthralin was as effective as DPCP alone and anthralin did not add to the effect of DPCP in treating AA.

Liposomal and Ethosomal Gels for the Topical Delivery of Anthralin: Preparation, Comparative Evaluation and Clinical Assessment in Psoriatic Patients.

To enhance anthralin efficacy against psoriasis and reduce its notorious side effects, it was loaded into various liposomal and ethosomal preparations. The nanocarriers were characterized for drug encapsulation efficiency, size, morphology and compatibility between various components. Optimum formulations were dispersed in various gel bases and drug release kinetics were studied. Clinical efficacy and safety of liposomal and ethosomal Pluronic®F-127 gels were evaluated in patients having psoriasis (clinicaltrials.gov identifier is NCT03348462). Safety was assessed by recording various adverse events. Drug encapsulation efficiency ≥97.2% and ≥77% were obtained for liposomes and ethosomes, respectively. Particle sizes of 116 to 199 nm and 146 to 381 nm were observed for liposomes and ethosomes, respectively. Fourier-Transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC) studies confirmed the absence of interaction between anthralin and various nanocarrier components. Tested gel bases showed excellent ability to sustain drug release. At baseline, the patients had a median Psoriasis Area and Severity Index (PASI) of 3.4 for liposomes and 3.6 for ethosomes without significant difference. After treatment, mean PASI change was -68.66% and -81.84% for liposomes and ethosomes, respectively with a significant difference in favor of ethosomes. No adverse effects were detected in both groups. Anthralin ethosomes could be considered as a potential treatment of psoriasis.

Anthralin Suppresses the Proliferation of Influenza Virus by Inhibiting the Cap-Binding and Endonuclease Activity of Viral RNA Polymerase.

Influenza virus RNA-dependent RNA polymerase (vRdRp) does not have capping activity and relies on the capped RNAs produced by the host RNA polymerase II (RNAPII). The viral polymerases process the capped RNAs to produce short capped RNA fragments that are used as primers to initiate the transcription of viral mRNAs. This process, known as cap-snatching, can be targeted by antiviral therapeutics. Here, anthralin was identified as an inhibitor against influenza a virus (IAV) infection by targeting the cap-snatching activity of the viral polymerase. Anthralin, an FDA-approved drug used in the treatment of psoriasis, shows antiviral activity against IAV infection in vitro and in vivo. Importantly, anthralin significantly reduces weight loss, lung injury, and mortality caused by IAV infection in mice. The mechanism of action study revealed that anthralin inhibits the cap-binding function of PB2 subunit and endonuclease activity of PA. As a result, viral mRNA transcription is blocked, leading to the decreases in viral RNA replication and viral protein expression. In conclusion, anthralin has been demonstrated to have the potential of an alternative antiviral against influenza virus infection. Also, targeting the captive pocket structure that includes the N-terminus of PA endonuclease domain and the C-terminal of PB2 cap-binding domain of IAV RdRp may be an excellent strategy for developing anti-influenza drugs.

Dithranol targets keratinocytes, their crosstalk with neutrophils and inhibits the IL-36 inflammatory loop in psoriasis.

Despite the introduction of biologics, topical dithranol (anthralin) has remained one of the most effective anti-psoriatic agents. Serial biopsies from human psoriatic lesions and both the c-Jun/JunB and imiquimod psoriasis mouse model allowed us to study the therapeutic mechanism of this drug. Top differentially expressed genes in the early response to dithranol belonged to keratinocyte and epidermal differentiation pathways and IL-1 family members (i.e. IL36RN) but not elements of the IL-17/IL-23 axis. In human psoriatic response to dithranol, rapid decrease in expression of keratinocyte differentiation regulators (e.g. involucrin, SERPINB7 and SERPINB13), antimicrobial peptides (e.g. ß-defensins like DEFB4A, DEFB4B, DEFB103A, S100 proteins like S100A7, S100A12), chemotactic factors for neutrophils (e.g. CXCL5, CXCL8) and neutrophilic infiltration was followed with much delay by reduction in T cell infiltration. Targeting keratinocytes rather than immune cells may be an alternative approach in particular for topical anti-psoriatic treatment, an area with high need for new drugs.

Efficacy and safety of anthralin in combination with diphenylcyclopropenone in the treatment of alopecia areata: a retrospective case series.

Contact immunotherapy with diphenylcyclopropenone (DPCP) and anthralin is considered the treatment option for extensive alopecia areata (AA) unresponsive to DPCP immunotherapy alone. Only one study has described the efficacy of combination therapy; therefore, we investigated whether topical DPCP and anthralin can promote hair regrowth in DPCP-non responders. In this retrospective case-series we analyzed the efficacy and side effects of DPCP with anthralin in AA patients who did not respond to several months of treatment with DPCP alone. Thirty-two DPCP-nonresponsive AA patients were treated with DPCP and anthralin for the average of 8.3 ± 3.8 (3-17) months. During the treatment, 40.62% of patients (13 patients out of 32) had terminal hair regrowth. The mean of hair regrowth rate was 41%; it was mainly as partial hair regrowth (˂ 50%) and 27.27% of cases achieved > 50% terminal hair regrowth. Treatment response strongly related to the duration of combination therapy (p value ˂ 0.001), but we did not find any relation with other demographic characteristics. The first signs of response to treatment were noticed 2-12 months (5.5 ± 3.4) after initiation of combination therapy while there was a positive correlation among the duration of treatment and percentage of hair regrowth (p < 0.001). The most common complication was bullae (25%), and the least frequent side effect was generalized pruritus (3.1%). The combination therapy with DPCP and anthralin could be effective to treat DPCP non-responder AA patients. Additionally, the higher treatment response could be achieved by longer treatment duration.

Serum YKL-40 as a potential biomarker of inflammation in psoriasis.

OBJECTIVE: YKL-40 is an inflammatory glycoprotein associated with atherosclerosis, cardiovascular disease, diabetes or metabolic syndrome which are common comorbidities in psoriasis. The aim of the study was to assess serum YKL-40 level in psoriasis and elucidate possible associations with disease activity, inflammatory or metabolic parameters and treatment. METHODS: A total of 37 individuals with active plaque-type psoriasis and 15 healthy controls were enrolled. Blood samples were collected before and after 2 weeks of therapy. Serum YKL-40 concentrations were evaluated by enzyme-linked immunosorbent assay (ELISA). The results were correlated with Psoriasis Area and Severity Index (PASI), body mass index (BMI), inflammatory and biochemical markers, lipid profile and topical therapy. RESULTS: Median YKL-40 serum levels were significantly increased in psoriatic patients in comparison to the controls (p < .0001). No significant correlations between investigated protein and metabolic parameters as BMI (p = .19), glucose (p = .32) nor lipids levels were found. Significant positive relation with CRP (p = .003) or alanine aminotransferase (p = .04) and no correlation with PASI (p = .2) were noted. Serum YKL-40 level remained unchanged (p = .5) after topical treatment, despite clinical improvement. CONCLUSIONS: YKL-40 might be a biomarker of psoriasis and inflammation in psoriatic patients, but not a reliable indicator of metabolic conditions, severity of psoriasis nor efficacy of the treatment.

Serum irisin levels in patients with psoriasis.

BACKGROUND: Irisin has been proposed to regulate metabolic diseases such as obesity, diabetes or metabolic syndrome which are common comorbidities in psoriasis. OBJECTIVES: The aim of this study was to evaluate the serum irisin level in psoriasis and elucidate possible associations with disease activity, inflammatory or metabolic parameters and topical treatment. METHODS: Thirty-seven individuals with active plaque-type psoriasis and 15 healthy controls were enrolled. Blood samples were collected before and after two weeks of therapy. Serum irisin concentrations were examined by enzyme-linked immunosorbent assay (ELISA). The results were correlated with psoriasis area and severity index (PASI), body mass index (BMI), inflammatory and biochemical markers, lipid profile and effectiveness of topical treatment. RESULTS: Irisin serum levels were insignificantly increased in psoriatic patients in comparison to the controls (p = 0.38). No significant correlations between investigated adipokine and several indicators of metabolic disorders, nor BMI (p = 0.37) or PASI (p = 0.5) were found. Significant positive correlations with C-reactive protein (CRP) (0.009), lipocalin-2 (p = 0.02), age (p = 0.02) and disease duration (p = 0.008) were noted. After topical treatment, serum irisin level did not significantly change (p = 0.31), despite clinical improvement. CONCLUSIONS: Irisin might be a marker of inflammation in psoriatic patients, but may not be a reliable indicator of metabolic conditions, severity of psoriasis nor efficacy of antipsoriatic treatment.

Effect of psoriasis activity and topical treatment on serum lipocalin-2 levels.

OBJECTIVE: Psoriasis has been considered as systemic disorder. Lipocalin-2 might be a link between psoriasis and its comorbidities. Aim of the study was to investigate the associations between serum lipocalin-2 levels and the disease activity, markers of inflammation or metabolic disturbances and changes after topical treatment in psoriatic patients. METHODS: Thirty-seven individuals with active plaque-type psoriasis and 15 healthy controls were recruited. Blood samples were collected before and after 14 days of therapy. Serum lipocalin-2 concentrations were examined by enzyme-linked immunosorbent assay. The results were correlated with Psoriasis Area and Severity Index (PASI), body mass index (BMI), inflammatory and biochemical markers, lipid profile and with effectiveness of topical treatment. RESULTS: Lipocalin-2 serum levels were significantly increased in psoriatic patients in comparison to the controls (p = 0.023). No significant correlations with indicators of inflammation, nor BMI or PASI were noted. A statistical association between lipocalin-2 and low-density lipoprotein-cholesterol was shown. After topical treatment serum lipocalin-2 level did not significantly change (p = 0.9), still remaining higher than in the controls, despite clinical improvement. CONCLUSIONS: Lipocalin-2 might be a marker of psoriasis and convey cardiovascular or metabolic risk in psoriatic patients, but may not be a reliable indicator of inflammation, severity of psoriasis nor efficacy of antipsoriatic treatment.

Anthralin modulates the expression pattern of cytokeratins and antimicrobial peptides by psoriatic keratinocytes.

BACKGROUND: Psoriasis is an inflammatory skin disease with aberrant keratinocyte proliferation, presumably as a result of immune cell activation. Th17 cytokines like IL-17A and IL-22 are critically implicated in epidermal thickening, altered keratinocyte differentiation and production of innate factors such as antimicrobial peptides. Psoriasis treatment options include modern targeted therapies using anti-cytokine antibodies and traditional non-targeted treatments like anthralin (dithranol). While the mode of action of anti-cytokine antibodies is defined, the effects of topical anthralin on psoriatic skin are not fully understood. OBJECTIVE: This study aims to unravel the direct effects of anthralin on keratinocyte proliferation, differentiation and production of psoriasis-associated factors. METHODS: We tested the effects of anthralin on cell proliferation, cytokeratin expression and changes in the expression of antimicrobial peptides using primary keratinocytes and 3D psoriasis tissue models with and without stimulation of the psoriasis-promoting cytokines IL-17A and IL-22. Moreover, we compared the findings derived from monolayer and multilayer cultures to data derived from lesional skin of patients with psoriasis before and under treatment with anthralin. RESULTS: Our study shows that anthralin directly induces cell apoptosis in vitro in monolayer cultures but not in 3D psoriasis tissue models treated with IL-17A and IL-22. Yet, keratinocyte proliferation as determined by Ki-67 staining is impaired by anthralin in vivo. In lesional skin but not in 3D psoriasis tissue models anthralin rapidly normalizes cytokeratin (CK)16 expression. Furthermore, anthralin directly inhibits DEFB4 expression in vitro and in vivo, while other antimicrobial peptides and cytokines studied like IL-6 and IL-8 are regulated differently in vitro and in vivo. CONCLUSIONS: Our results show that anthralin directly regulates DEFB4A expression. However, its beneficial effects on psoriasis cannot be explained by direct effects on keratinocyte differentiation or cytokine expression.

Serum Fatty Acid-Binding Protein 4 is Increased in Patients with Psoriasis.

Psoriasis is associated with metabolic syndrome and cardiovascular disease. Fatty acid-binding proteins (FABP) have been recognized as predictors of these systemic disorders. The aim of this study was to assess correlations between levels of serum heart and adipocyte fatty acid-binding proteins (FABP3, FABP4) and disease severity, indicators of inflammation or metabolic disturbances, and topical treatment in psoriatic patients. Thirty-seven patients with relapse of plaque-type psoriasis and 16 healthy volunteers were recruited. Blood samples were collected before and after 14 days of therapy. Serum FABP concentrations were examined by enzyme-linked immunosorbent assay for correlation with Psoriasis Area and Severity Index (PASI), body mass index (BMI), inflammatory or metabolic parameters, and treatment used. The median FABP4 serum levels were significantly increased (p = 0.038) in psoriatic patients, while FABP3 levels did not differ (p = 0.47) compared to the controls. No significant correlations were noted between the proteins and PASI, C-reactive protein (CRP), BMI, or levels of glucose or lipids. FABP3 significantly correlated with white blood count (p = 0.03) and aspartate aminotransferase (p = 0.04). After topical treatment, there was no significant change in serum FABP3 [11.5 (4.9-30.3) vs. 12.9 (3.5-30.3) ng/ml] (p = 0.96), whereas FABP4 was decreased [27,286 (20,344-32,257) vs. 23,034 (18,320-29,874) pg/ml] (p = 0.12), losing its basal significance. FABP4 may be a marker of psoriasis, and FABP3 may be associated with inflammation or liver disorders in psoriatic patients. FABP do not appear to be useful for determining disease severity or the effectiveness of antipsoriatic treatment.

Dithranol treatment of plaque-type psoriasis increases serum TNF-like weak inducer of apoptosis (TWEAK).

PURPOSE: TNF-like weak inducer of apoptosis (TWEAK) mediates not only apoptosis, but also inflammation, cell growth and angiogenesis. The role of TWEAK in psoriasis remains unknown. The aim of the study was to assess serum levels of TWEAK in psoriatic patients before and after topical treatment with dithranol in relation to the clinical activity of the disease. MATERIAL AND METHODS: Serum samples were collected from 40 patients with plaque type psoriasis before and after topical treatment with dithranol. The concentrations of serum TWEAK were measured by ELISA and next compared with 16 healthy controls. The data were analyzed with respect to Psoriasis Area and Severity Index (PASI). RESULTS: Baseline serum TWEAK concentrations of psoriatic patients (685±166pg/ml) were significantly greater compared to healthy controls (565±110pg/ml). Topical treatment resulted in further increase in serum TWEAK (749±179pg/ml; p<0.01). In case of patients with initial serum TWEAK concentrations above the median, PASI after topical treatment was lower compared to the individuals with initial TWEAK below the median. CONCLUSION: According to the study, serum Tweak was increased in psoriasis patients compared with controls. Moreover, dithranol topical treatment caused further increase in serum TWEAK. Also, a higher effectiveness of topical treatment was observed in case of patients with higher initial TWEAK concentrations. The results suggest a potential role of TWEAK in psoriasis therapy.