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.

Diagnostic and therapeutic guidelines for plaque psoriasis - Brazilian Society of Dermatology

Abstract: Psoriasis is a chronic inflammatory disease that affects 1.3% of the Brazilian population. The most common clinical manifestations are erythematous, scaling lesions that affect both genders and can occur on any anatomical site, preferentially involving the knees, elbows, scalp and genitals. Besides the impact on the quality of life, the systemic nature of the disease makes psoriasis an independent risk factor for cardiovascular disease, especially in young patients with severe disease. By an initiative of the Brazilian Society of Dermatology, dermatologists with renowned clinical experience in the management of psoriasis were invited to form a work group that, in a partnership with the Brazilian Medical Association, dedicated themselves to create the Plaque Psoriasis Diagnostic and Treatment Guidelines. The relevant issues for the diagnosis (evaluation of severity and comorbidities) and treatment of plaque psoriasis were defined. The issues generated a search strategy in the Medline-PubMed database up to July 2018. Subsequently, the answers to the questions of the recommendations were devised, and each reference selected presented the respective level of recommendation and strength of scientific evidence. The final recommendations for making up the final text were worded by the coordinators.

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.

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.

The efficacy and safety of etanercept when used with as-needed adjunctive topical therapy in a randomised, double-blind study in subjects with moderate-to-severe psoriasis (the PRISTINE trial).

OBJECTIVE: To assess the efficacy and safety of two etanercept dose regimens for psoriasis treatment. METHODS: Subjects were ≥18 years old with stable moderate-to-severe plaque psoriasis. Subjects were randomised to etanercept 50 mg once weekly (QW) or 50 mg twice weekly (BIW) double-blind for 12 weeks, followed by 50 mg QW open label in all subjects through week 24. Only mild topical corticosteroids were permitted on scalp, axillae and groin for first 12 weeks; topical medications (corticosteroids of all potencies, vitamin D analogues and combination products) were allowed as needed for second 12 weeks at physicians' discretion, consistent with "real-world" therapeutic practice. An independent ethics committee reviewed and approved the study protocol. RESULTS: At week 24, 59.9% and 78.2% in the QW/QW and BIW/QW groups achieved PASI 75 improvement. Mean percentage PASI improvement in these groups was 58.5% and 74.1% at week 12 and 70.7% and 81.3% at week 24. Although permitted from weeks 12 to 24, topical agents were used in only 27.7% and 22.6% in the QW/QW and BIW/QW groups by week 24. CONCLUSION: Both etanercept regimens were efficacious in moderate-to-severe psoriasis, although the BIW/QW regimen consistently provided higher response rates than the QW/QW regimen. More potent topical medications were used electively in <25% of subjects in each group.

[Treatment of disseminated granuloma annulare with anthralin]. / Therapie des Granuloma anulare disseminatum mit Anthralin.

Granuloma annulare is a benign, often asymptomatic and self-limiting granulomatous skin disease. In cases of disseminated granuloma annulare, spontaneous regression is considerably less frequent than in localized forms so that therapy is often desired. Systemic treatments should always be assessed critically and reserved for patients who are severely affected and in whom treatment approaches with few side effects such as local application of anthralin do not suffice to achieve a satisfactory effect.

Dithranol therapy in childhood psoriasis: unjustifiably on the verge of falling into oblivion.

BACKGROUND: In childhood psoriasis, physicians aim for an effective and safe treatment such as with dithranol. This study presents the largest study of dithranol-treated patients described in the literature. OBJECTIVE: The aim of the study was to determine the position of dithranol in the treatment strategy for psoriasis. METHODS: All juvenile patients receiving dithranol treatment at our center were evaluated retrospectively. RESULTS: Sixty patients (with 82 treatment episodes in total) were included. The mean age at the start of dithranol treatment was 11.1 years (range: 3.7-17.9 years). The result of the treatment was: excellent (3.7%), good (69.5%), moderate (8.5%), reasonable (13.4%) or disappointing (4.9%). Mild irritation was seen in 39%, and severe irritation in 63% of the patients. CONCLUSIONS: Dithranol can be regarded as an efficacious and safe topical therapy for the treatment of childhood psoriasis. It is a valuable alternative topical treatment which should not be disregarded in the treatment regimen for childhood psoriasis and should be commenced before ultraviolet or systemic treatments are initiated.

Childhood psoriasis: often favorable outcome.

(1) Plaque psoriasis is the most common form of psoriasis in children. Topical agents should be tried first, especially well-tolerated products such as emollients. Topical corticosteroids are sometimes useful during exacerbations but, given adverse effects, they should only be used for short periods; (2) UVB phototherapy is an option for extensive psoriasis refractory to local treatments, but it carries a long-term risk of skin cancer. Immunosuppressants have not been well assessed in this setting, but methotrexate has been better evaluated than the others.

The cutaneous epidermal growth factor network: Can it be translated clinically to stimulate hair growth?

The influences exerted by the epidermal growth factor receptor (EGFR) on the skin act at multiple levels, which involve compartments that normally express EGFR. These include the basal and suprabasal layers of the epidermis, sebaceous glands, and the outer root sheath of the hair follicles. The physiological roles of EGFR ensure epidermal renewal and integrity, along with a gatekeeping and function and hair growth stimulation functions. Important cellular functions that are altered during EGF receptor blocking therapy consist of epidermal differentiation, proliferation, apoptosis, and migration, with an overall dominating effect of inducing growth arrest and terminal differentiation of the keratinocytes in the basal layers. The effects of EGFR blockage on the hair cycle include terminal differentiation of the hair follicle, which in certain cases may be associated with trichomegaly. Trichomegaly of the eyelashes may occur as an isolated occurrence or, frequently, as part of a generalized phenomenon that may be associated with the use of the EGFR inhibitors. Molecular changes associated with EGFR blockage are discussed, relevant to their association with hair growth. Modulation of Akt, AP2alpha, CDK4, Notch-1, p27KIP1, and Hedgehog expression are involved in the initiation of the hair cycle and inducement of the anagen phase, followed by proliferation and differentiation of the hair follicles. Epidermal growth factor receptor inhibitors have been developed as therapeutic molecules directed against cancer; in these regimens the knowledge of EGF receptor signaling functions has been translated into significant clinical results. However, among their various collateral effects on the skin, hair growth is observed to occur in certain patients. A particular "wavy" hair phenotype is observed during the pharmacological EGFR receptor blockade, just as in murine transgenic models that carry loss of function of TGF-alpha or EGFR genes. A better characterization of the individual roles pertaining to the EGF family ligands and receptors, has the potential provide new strategies for the management of hair loss.

Psoriasis of the nail: anatomy, pathology, clinical presentation, and a review of the literature on therapy.

Psoriasis is a chronic skin disease that affects millions of people throughout the world. Even though cutaneous signs and symptoms are the most common clinical manifestations, the nails can be involved in up to 50% of cases, and their involvement remains an important yet often overlooked aspect of the disease. There is a broad spectrum of nail dystrophies associated with psoriasis, ranging from the common pitting and loosening of the nail plate to the less frequent discoloration and splinter hemorrhages seen in the nail bed. This article discusses the normal anatomy and embryology of the nail unit as well as the current understanding of the pathogenesis of the disease. It also provides an extensive review of the existing literature with respect to psoriatic nail therapy. Although there have been many recent advances in the treatment of the cutaneous form of the disease-most notably in the field of immunotherapies-the options for nail psoriasis are far more limited. While a number of treatment alternatives currently exist for nail disease, the general paucity of clear evidence regarding these choices often makes it difficult to select the most efficient, safe, and optimal treatment for the patient. Even though the current literature has shown some support for the use of topical, intralesional, radiation, systemic, and combination therapies for nail psoriasis, the available studies lack sufficient power to extrapolate a standardized therapeutic regimen. Therefore, until better-documented evidence validating the treatment options emerges within the literature, clinicians and patients are left with a vague and relatively unproven approach to psoriatic nail disease.

In search for new antipsoriatic agents: NAD topical composition.

The aim of the study was to examine the effectiveness of the oxidized form of nicotinamide adenine dinucleotide (NAD(+)), adenosine precursor, in 37 patients suffering from psoriasis. As NAD(+) is known to be relatively unstable, the second goal was to establish the proper conditions for the satisfactory stability of topical NAD(+) composition. In each patient, two matching plaques were selected for the study. Topical treatment with 1 or 0.3% NAD(+) in Vaseline ointment administered twice daily was compared with overnight therapy with 0.1% anthralin applied for 12 h and placebo. The enzymatic method was applied to determine the stability of NAD(+) in Vaseline ointment. After a 4-week application, the reduction in erythema, infiltration and desquamation caused by 1 or 0.3% topical NAD(+) composition was similar to the reduction caused by 0.1% anthralin. It was demonstrated that NAD(+) underwent a considerable decomposition at room temperature, while it was sufficiently stable at 5 degrees C; thus, for a longer use the agent should be stored at fridge temperature. NAD(+) therapy combines good efficacy, cosmetic acceptability and convenient twice-daily application.

[The immunology of psoriasis: from basic research to the bedside]. / A pikkelysömör immunológiája: az alapkutatástó1 a betegágyig.

Psoriasis is a frequent, chronic, clinically variable inflammatory disease of unknown etiology, affecting primarily the skin and the joints. A cure for the disease is still missing, and due to the chronic course of the disease, currently available treatments are associated with serious morbidity. Psoriasis is considered to be an (auto)immune disorder, probably initiated by the overactive skin innate immune system, and maintained by immigrating activated type 1 T cells and abnormally proliferating and differentiating keratinocytes. A complex network of cytokines and chemokines mediates the pathological reaction, whereas the abnormal function of psoriatic regulatory T cells is likely responsible for the chronic nature of psoriasis. The most important clinical, histological, and pathogenic characteristics of psoriasis are discussed, and an overview of traditional and novel therapeutic modalities is provided. Based on recently obtained evidence from animal disease models and clinical studies using biological drugs with selective immunological action, a complex model for the immunopathogenesis of psoriasis is outlined. Advances in understanding the immunology of psoriasis have not only provided more insights into the cause and development of the disease, but gave new therapeutic tools into the hands of clinicians to more selectively and (possibly) more effectively treat psoriasis.

The effect of treatment on quality of life in psoriasis patients.

Psoriasis is a chronic skin disease with substantial impact on patients' social and relational ways of living and subsequently on their quality of life. The aim of this study was to evaluate the health-related quality of life (HRQoL) of patients with moderate to severe psoriasis treated with short contact dithranol treatment, UVB phototherapy or inpatient dithranol treatment. HRQoL was evaluated in an open randomized multicentre study by appliance of the Dutch short form of the Sickness Impact Profile and the Psoriasis Disability Index; 250 patients were included. Successful short contact dithranol treatment and UVB phototherapy both led to a comparable improvement in HRQoL immediately after treatment until the end of the follow-up (maximum 1 year). Inpatients experienced a more impaired HRQoL and showed no significant improvement in HRQoL directly following treatment. At the end of the study HRQoL became comparable for all treatment groups. All three treatments led to substantial improvement in HRQoL; however, patients treated by short contact treatment or UVB showed a better HRQoL than inpatients.

Linear naevoid psoriasis along lines of Blaschko.

Congenital linear naevoid psoriasis along Blaschko's lines on the thigh of a 3-year-old girl is reported. The history of asymptomatic, erythematous scaly lesions since birth, the peculiar distribution and the histopathology confirmed the diagnosis.

Restoration of hair growth in mice with an alopecia areata-like disease using topical anthralin.

Anthralin is a widely used topical anti-psoriatic drug that may have an immunomodulating effect on alopecia areata (AA) as it does in psoriasis. The aims of the present study were to investigate the effects of anthralin on hair growth in balding C3H/HeJ mice affected by an AA-like disease and to study the underlying mechanisms. Affected C3H/HeJ mice were treated daily for 10 weeks on half of the dorsal skin with 0.2% anthralin and the contra-lateral side was treated with the vehicle ointment. The percentage of surface hair coverage and hair density was graded weekly for both sides and hair growth indices were calculated using these two variables. Hair regrowth was observed in 9/14 mice on the treated sides. Four mice displayed near complete replacement of normal density and length hairs. All the vehicle-treated sides showed either no change or continued hair loss. An RNase protection assay (RPA) showed that expression of tumor necrosis factor-alpha (TNF-alpha) and -beta were inhibited by anthralin upon successful treatment. It appears that anthralin may be an effective therapy for C3H/HeJ mice with AA and certain cytokines may be involved in the therapeutic effects of anthralin on restoring hair regrowth in AA-affected C3H/HeJ mice.

Dithranol in an emulsifying oil base (bio-wash-oil) for the treatment of psoriasis of the scalp.

On the scalp, dithranol has been studied in only a few trials. The dithranol molecule that contains both hydrophilic and lipophilic centers can be incorporated into detergents and allows easy removal from hair. This property has led to the incorporation of dithranol in an emulsifying oil base (bio-wash-oil). The formulation has been used routinely for more than two decades in East Germany. We reexamined the efficacy and safety of dithranol in bio-wash-oil and compared it to dithranol embedded in crystalline monoglycerides (Micanol) in patients with psoriasis of the scalp. In a prospective, parallel group study, 64 patients attending a day-care clinic were randomly allocated to 3 treatment groups: (1) dithranol in bio-wash-oil; (2) Micanol cream, and (3) Micanol cream in bio-wash-oil. Treatment was carried out for 3 weeks and results assessed using a modified Psoriasis Area and Severity Index score. Dithranol in bio-wash-oil resulted in a reduction in the score of 34% on day 7 and 57% on day 14. This was significantly better than in groups 2 and 3, as were the overall response and patients' assessment at the end of treatment (p < 0.05). Dithranol in a bio-wash-oil is an effective, well-tolerated and low-priced treatment in psoriasis of the scalp.

Optimizing the frequency of outpatient short-contact dithranol treatment used in combination with broadband ultraviolet B for psoriasis: a randomized, within-patient controlled trial.

BACKGROUND: Recent concerns over the side-effects of psoralen plus ultraviolet (UV) A, immunosuppressive and cytotoxic treatments have led to increased interest in dithranol for treatment of psoriasis. Few studies have investigated how frequently dithranol should be applied. Dithranol-induced inflammation is maximal at 48-72 h, suggesting that daily application of dithranol may not be optimal. OBJECTIVES: To investigate the effectiveness of five times weekly application of short-contact dithranol (SCD) compared with three times weekly application in a dedicated hospital outpatient treatment unit. METHODS: A randomized, within-patient, controlled study was performed. Patients had SCD applied five times weekly to one half of the body, and three times weekly to the other side. Whole-body UVB irradiation was given 5 days a week. Patients were assessed weekly for 8 weeks. Principal outcome measures were percentage reduction in modified Psoriasis Area and Severity Index (mPASI) at the end of study and time to 50% improvement in mPASI score. RESULTS: Twenty-nine patients were recruited; four were excluded from analysis. Mean percentage reduction in mPASI score at the end of study for five times weekly application was 57.3% (95% confidence interval, CI 39.6-75.0%) and for three times weekly application was 55.4% (95% CI 37.8-73.1%; P = 0.34). Mean time to 50% improvement in mPASI for five times weekly treatment was 4.1 weeks and for three times weekly treatment was 4.0 weeks (P = 0.50). There was no difference in the frequency or severity of burning episodes for each side. CONCLUSIONS: This study suggests that three times weekly application of SCD may be as effective as five times weekly when used in conjunction with UVB administered five times weekly. Large studies of whole-body comparisons are warranted to assess further the optimal frequency of SCD and UVB therapy for psoriasis.

Soluble tumor necrosis factor-alpha receptor type 1 during selenium supplementation in psoriasis patients.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) and its receptors play important roles in the induction and maintenance of psoriatic lesions. Selenium (Se), a trace element with immunomodulatory properties, is usually decreased in psoriasis patients. We examined the influence of Se supplementation on soluble TNF-alpha receptor type 1 (sTNF-R1) and topical treatment in psoriasis patients. METHODS: The study was conducted in between January and June 2002. Twenty-two inpatients with active plaque psoriasis received topical treatment with 5% salicylic acid ointment, 0.1% to 0.3% dithranol ointment, and 200 microg daily of Se as selenomethionine (SeMet; n = 11, group 1) or placebo (n = 11, group 2) for 4 wk. Psoriasis Area and Severity Index (PASI) score and Se and sTNF-R1 concentrations were assessed at baseline and every 2 wk. Control sera were obtained from 10 healthy subjects. For statistical analysis, parametric tests were used, and the level of significance was set at P = 0.05. RESULTS: The baseline sTNF-R1 levels were 1.87 +/- 0.58 ng/mL (1.98 +/- 0.44 ng/mL in group 1 and 1.75 +/- 0.69 ng/mL in group 2, P = 0.34) in psoriasis patients and 1.65 +/- 0.25 ng/mL in control subjects (P = 0.17); baseline Se concentrations were 48.31 +/- 13.20 microg/L (48.31 +/- 13.20 microg/L in group 1 and 50.35 +/- 13.49 microg/L in group 2, P = 0.41) in psoriasis patients and 58.30 +/- 17.21 microg/L in control subjects (P = 0.05). A positive correlation between PASI and sTNF-R1 was noticed (r = 0.36, P = 0.04; r = 0.51 in group 1 and r = 0.18 in group 2). After 4 wk, almost complete remission of skin lesions was achieved in both groups, but the PASI score was higher in group 1 than in group 2 (4.30 +/- 3.92 and 1.67 +/- 1.17, respectively; P < 0.05). TNF-R1 levels were 1.81 +/- 0.42 ng/mL in group 1 and 1.33 +/- 0.40 ng/mL in group 2 (P = 0.01), and the correlation between PASI score and TNF-R1 level became inverse (r = -0.24 in group 1 and r = -0.59 in group 2). Se concentrations were 107.51 +/- 18.08 microg/L in group 1 and 56.83 +/- 15.32 microg/L in group 2 (P < 0.01). CONCLUSIONS: Increased level of sTNF-R1 may be an indicator of active psoriasis. Supplementation with selenomethionine was ineffective as adjuvant treatment in plaque psoriasis and may contribute to the maintenance of elevated TNF-R1 concentration in psoriasis patients despite the remission of skin lesions.