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Anthralin/dithranol in dermatology
Abstract
Anthralin (1,8-dihydroxy-9anthrone, dithranol) was first synthesized as a derivative of chrysarobin, prepared from the araroba tree in Brazil over a century ago. Drawbacks to the use of anthralin include irritation and discoloration of the skin. This property of the molecule prompted workers to investigate details of its pharmacology, mode of action, and indications. The major point of this article is to highlight and revisit these aspects for pertinent future use. Therefore, it is worthwhile to consider that the drug is relatively innocuous, yet effective, and is devoid of any systemic side effects in contrast to a wide variety of systemic and topical therapies available for psoriasis and other dermatoses.
... Another mechanism by which anthralin exerts its effect is by inhibiting keratinocyte proliferation, which makes it an effective antipsoriatic agent. [28] ...
... Anthralin is an effective treatment option for limited plaque psoriasis, scalp and nail psoriasis, juvenile psoriasis, and localized psoriasis in pregnancy. [28] e Ingram regimen consisting of a coal tar bath and ultraviolet light exposure followed by treatment with anthralin in Lassar's paste was used to treat psoriatic plaques. Later, in 1985, modified Ingram regimen was developed to maximize the efficacy and patient compliance. ...
... Based on these trials, it is recommended to use anthralin once in 24 hours, thrice weekly for optimal results. [28] Children: Safety and efficacy in children are not established. ...
Immunosuppressive drugs are the main stay of treatment for autoimmune dermatoses. The main disadvantage of these drugs is the increased susceptibility to life-threatening infections. Hence, in recent years, there has been an enthusiastic search for newer groups of drugs that can reduce this risk. Immune enhancing agents are considered as the key players of future. Immune enhancers function by activating various elements of the immune system and thereby amplifying the immune responses. They can be specific or non-specific in action. The main autoimmune dermatoses where the benefits of these drugs have so far been utilized include alopecia areata, vitiligo, psoriasis, lichen planus, and discoid lupus erythematosus. Immunostimulants are available in both topical and systemic forms. Topical immune- enhancing agents include contact sensitizers (diphenylcyclopropenone, dinitrochlorobenzene, and squaric acid dibutyl ester), anthralin, topical zinc, and interferons. Systemic agents include levamisole, zinc, probiotics, and so on. The exact mechanism of action of some of these drugs and other autoimmune conditions where they can be benefited is not completely understood. Another therapeutic agent that may come up in the future is individualized vaccines. Let us look forward to the days when individualized vaccines work wonders in the management of autoimmune diseases.
... Steroids, vitamin D3 and vitamin A analogues are most commonly used as topical agents in such patients, but besides changes in their pharmaceutical formulation, they have not been developed further in recent years (de Korte et al., 2008;Krueger et al., 2001;Langley et al., 2011;Schaarschmidt et al., 2015). Short courses of dithranol (1,8-dihydroxy-9-anthracenone or anthralin) have been successfully used as intermittent topical treatment of psoriasis since 1916 (Nast et al., 2012;Sehgal et al., 2014;Vleuten et al., 1996). Despite its numerous disadvantages like brown staining and irritation of perilesional skin, dithranol has remained one of the most effective topical treatment modalities in psoriasis. ...
... Despite its numerous disadvantages like brown staining and irritation of perilesional skin, dithranol has remained one of the most effective topical treatment modalities in psoriasis. Analogous to the most recent generation of biologics (including anti-IL-17 and anti-IL-23 antibodies), dithranol delivers PASI75 rates in 66-82.5% of patients with fast action and clearance of skin lesion within very few weeks (Kemény et al., 1990;Painsi et al., 2015b;Sehgal et al., 2014;van de Kerkhof, 2015). Although dithranol has been used for many years, its exact mechanism of action has remained largely unknown (Holstein et al., 2017;Kemény et al., 1990;Kucharekova et al., 2006;Sehgal et al., 2014). ...
... Analogous to the most recent generation of biologics (including anti-IL-17 and anti-IL-23 antibodies), dithranol delivers PASI75 rates in 66-82.5% of patients with fast action and clearance of skin lesion within very few weeks (Kemény et al., 1990;Painsi et al., 2015b;Sehgal et al., 2014;van de Kerkhof, 2015). Although dithranol has been used for many years, its exact mechanism of action has remained largely unknown (Holstein et al., 2017;Kemény et al., 1990;Kucharekova et al., 2006;Sehgal et al., 2014). ...
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.
... Steroids, vitamin D3 and vitamin A analogues are most commonly used as topical agents in such patients, but besides changes in their pharmaceutical formulation, they have not been developed further in recent years (de Korte et al., 2008;Krueger et al., 2001;Langley et al., 2011;Schaarschmidt et al., 2015). Short courses of dithranol (1,8-dihydroxy-9-anthracenone or anthralin) have been successfully used as intermittent topical treatment of psoriasis since 1916 (Nast et al., 2012;Sehgal et al., 2014;Vleuten et al., 1996). Despite its numerous disadvantages like brown staining and irritation of perilesional skin, dithranol has remained one of the most effective topical treatment modalities in psoriasis. ...
... Despite its numerous disadvantages like brown staining and irritation of perilesional skin, dithranol has remained one of the most effective topical treatment modalities in psoriasis. Analogous to the most recent generation of biologics (including anti-IL-17 and anti-IL-23 antibodies), dithranol delivers PASI75 rates in 66-82.5% of patients with fast action and clearance of skin lesion within very few weeks (Kemény et al., 1990;Painsi et al., 2015b;Sehgal et al., 2014;van de Kerkhof, 2015). Although dithranol has been used for many years, its exact mechanism of action has remained largely unknown (Holstein et al., 2017;Kemény et al., 1990;Kucharekova et al., 2006;Sehgal et al., 2014). ...
... Analogous to the most recent generation of biologics (including anti-IL-17 and anti-IL-23 antibodies), dithranol delivers PASI75 rates in 66-82.5% of patients with fast action and clearance of skin lesion within very few weeks (Kemény et al., 1990;Painsi et al., 2015b;Sehgal et al., 2014;van de Kerkhof, 2015). Although dithranol has been used for many years, its exact mechanism of action has remained largely unknown (Holstein et al., 2017;Kemény et al., 1990;Kucharekova et al., 2006;Sehgal et al., 2014). ...
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.
... Steroids, vitamin D3 and vitamin A analogues are most commonly used as topical agents in such patients, but besides changes in their pharmaceutical formulation, they have not been developed further in recent years (de Korte et al., 2008;Krueger et al., 2001;Langley et al., 2011;Schaarschmidt et al., 2015). Short courses of dithranol (1,8-dihydroxy-9-anthracenone or anthralin) have been successfully used as intermittent topical treatment of psoriasis since 1916 (Nast et al., 2012;Sehgal et al., 2014;Vleuten et al., 1996). Despite its numerous disadvantages like brown staining and irritation of perilesional skin, dithranol has remained one of the most effective topical treatment modalities in psoriasis. ...
... Despite its numerous disadvantages like brown staining and irritation of perilesional skin, dithranol has remained one of the most effective topical treatment modalities in psoriasis. Analogous to the most recent generation of biologics (including anti-IL-17 and anti-IL-23 antibodies), dithranol delivers PASI75 rates in 66-82.5% of patients with fast action and clearance of skin lesion within very few weeks (Kemény et al., 1990;Painsi et al., 2015b;Sehgal et al., 2014;van de Kerkhof, 2015). Although dithranol has been used for many years, its exact mechanism of action has remained largely unknown (Holstein et al., 2017;Kemény et al., 1990;Kucharekova et al., 2006;Sehgal et al., 2014). ...
... Analogous to the most recent generation of biologics (including anti-IL-17 and anti-IL-23 antibodies), dithranol delivers PASI75 rates in 66-82.5% of patients with fast action and clearance of skin lesion within very few weeks (Kemény et al., 1990;Painsi et al., 2015b;Sehgal et al., 2014;van de Kerkhof, 2015). Although dithranol has been used for many years, its exact mechanism of action has remained largely unknown (Holstein et al., 2017;Kemény et al., 1990;Kucharekova et al., 2006;Sehgal et al., 2014). ...
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.
... It is a yellow-colored active moiety, first synthesized from chrysarobin (belongs to family Leguminose), and formerly derived from South American Araroba tree [1]. Also, named as anthralin and cignolin, it was first synthesized in 1916 as a substitute of chrysarobin, and EugenGalewsky from Dresden/Saxony represented DTH as a potential therapeutic agent [2,3]. In recent studies, it has been shown that DTH exhibits a wide range of pharmacological activities against many dermal disorders including psoriasis, alopecia areata, warts, inflammatory linear verrucous epidermal nevus and seborrheic dermatitis. ...
... In recent studies, it has been shown that DTH exhibits a wide range of pharmacological activities against many dermal disorders including psoriasis, alopecia areata, warts, inflammatory linear verrucous epidermal nevus and seborrheic dermatitis. It inhibits human monocytes, downregulates epidermal growth factor receptor, keratinocyte transforming growth factor α, 12hydroxyeicosatetreneoate receptor and leucotriene production [3]. At the molecular level, DTH inhibits cell proliferation and PMN leucocyte function, modulates the arachidonic acid metabolism and is observed to inflect surface receptors of epidermal cells [4]. ...
... It has been the most promising and extensively investigated pharmacological activity of DTH . This moiety has been marked as a potential agent for both prevention and treatment of a variety of psoriasis, including plaque, scalp, nail and juvenile/childhood psoriasis [3]. Psoriasis is chronic, distressing and T cell-mediated multifactorial autoimmune disorder affecting joints and skin [32]. ...
Objective
Dithranol (DTH) is a promising well known moiety that has long been used to impede and treat skin disorders, particularly psoriasis. Now a days, a rekindled interest in the use of DTH for this disorder has been observed. Side effects associated with conventional topical formulations of this moiety have aroused interest of scientific community in novel cargos for psoriasis management.
Keyfinding
Dithranol is a frequently prescribed active molecule in the management of alopecia areata, warts, seborrheic dermatitis and psoriasis. Previous research have evidenced anti inflammatory and anti-proliferating potential of DTH. Numerous studies have indicated that DTH inhibits polymorphonuclear (PMN) leucocyte, modulate epidermal cell receptors and promotes anti-psoriatic action. However, some deterrent factors like poor solubility, stability, toxicity, staining and skin irritation hampers its use as a potential therapeutic agent. With the adoption of novel drug delivery technologies, the above mentioned inherent limitations of DTH have been compensated to reestablish this drug moiety.
Conclusion
This article reviews novel drug delivery aspects, safety concerns, clinical evidences, current status, and future opportunities of DTH in the management of psoriasis. Further, it will update researchers on this promising drug moiety, which is free from systemic adverse responses in comparison to other therapeutic molecules like steroids for psoriasis treatment.
... In order to investigate the antiproliferative activity of FM, the inflammatory keratinocytes were established using HaCaT stimulated with M5. Anthralin, an effective inhibitor of keratinocyte proliferation [54][55][56], was used as a positive control. After treatment with anthralin or FM for 72 h, FM showed more significant inhibitory effects on the growth of keratinocytes compared with anthralin (IC 50 : ...
... In order to investigate the external antipsoriatic effects of FM, the immortal human keratinocyte cell line (HaCaT) was used to establish inflammatory keratinocyte model by M5 stimulation. Anthralin, which has been reported to inhibit keratinocyte proliferation [54][55][56], was used as a positive control. According to the results, FM showed more significant inhibitory effects on the growth of keratinocytes as compared with anthralin (IC 50 : 0.182 ± 0.004 μM, 7.418 ± 0.275 μM, respectively) ( Fig. 2A). ...
Psoriasis is a chronic, inflammatory autoimmune disease mediated by T cells, and characterized with abnormal proliferation and differentiation of keratinocytes, and inflammatory infiltration. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway has been identified to play essential roles in mediating various of biological processes, and is closely related to autoimmune diseases. Dendritic cells (DCs) are important antigen presenting cells and play an important regulatory role in T cells. The proliferation, differentiation and function of DCs are regulated by JAK and FMS-like tyrosine kinase 3 (FLT3) signal pathways. Flonoltinib maleate (FM), a high selectivity dual JAK2/FLT3 inhibitor with IC50 values of 0.8 nM and 15 nM for JAK2 and FLT3, respectively, was developed by our laboratory. Moreover, FM was a potent JAK2 inhibitor with 863-fold and 696-fold selectivity over JAK1 and JAK3, respectively. In this study, the anti-psoriasis activity of FM was evaluated both in vitro and in vivo. FM effectively inhibited the proliferation of HaCaT, the inflammatory keratinocyte induced by M5 and markedly suppressed the generation and differentiation of DCs from bone marrow (BM), and inhibited the expression of FLT3 in DCs in vitro. FM effectively inhibited the ear thickening and improved the pathological changes of the ear in interleukin (IL)-23-induced psoriasis-like acanthosis mouse model. Further in keratin 14-vascular endothelial growth factor (K14-VEGF) transgenic homozygous mice model, FM could obviously improve the psoriatic symptom and pathological changes, significantly inhibit the generations of Th1 and Th17 cells in the spleen, and the accumulations of DCs in the ears. FM could also significantly reduce the expression of various inflammatory factors both in C57BL/6 and K14-VEGF mice ears, and the serum of K14-VEGF mice. Mechanism revealed that FM effectively suppressed the phosphorylation of JAK2, STAT3 and STAT5 in inflammatory keratinocytes and the mice ears of C57BL/6 and K14-VEGF, as well as the phosphorylation of FLT3 in K14-VEGF mice ears. In conclusion, FM plays an excellent anti-psoriasis activity, including inhibiting keratinocyte proliferation and regulating inflammatory response through inhibiting JAK2 and FLT3 signaling pathway.
... Further, accumulation of anthralin inside the mitochondria impairs energy supply to the cell, probably due to the free radicals resulting from oxidation of the drug [17]. Anthralin also interferes with the replication of DNA and slows down the extreme cell division that occurs in psoriatic plaques [18]. Although anthralin is remarkably effective in the management of psoriasis, its side effects are equally disturbing. ...
... This confirms that the prepared nanocarriers were able to abate the notorious anthralin side effects [74]. Anthralin staining is a commonly reported limitation [18,75]. ...
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.
... (4) Applied 1-3 times a day [13], especially after warm baths [14]. (5) Zinc oxide paste should not be combined with topical salicylic acid [15] or anthralin [16] to avoid inactivation of both drugs. (6) Safe in pregnant and lactating women and in pediatric patients [13]. ...
... (3) When used in combination with topical corticosteroids, α-hydroxyl acids exert a synergistic effect and reduce steroid-induced skin atrophy [8,17]. (4) Applied 1-3 times a day in concentrations from 15 to 20% [18]. (5) Might cause irritant dermatitis [18]. ...
Psoriasis is a chronic multisystem inflammatory disease affecting primarily the skin and joints and also involves several comorbidities. The disease affects between 0.2 and 4% of the population worldwide. The approach to the patient and its proper management needs a holistic approach, where the physician treats the patient and not just the plaques of psoriasis. The Kasr Al-Ainy Psoriasis Unit developed a protocol of therapy for psoriasis, based on the best available scientific evidence and the expert opinion of the team, taking into consideration the regional characteristics of our patients (factors such as cultural, socioeconomic, and epidemiologic specificities). The protocol offers an algorithm for the choice of adequate therapy for patients with psoriasis, both for initiation and for maintenance, according to the severity and the course of the disease. Topical and systemic therapies available in the Egyptian market are highlighted for their efficacy and safety data. An algorithm for screening of cardiovascular comorbidities is also presented. This protocol is the backbone of our daily practice in Kasr Al-Ainy Psoriasis Unit and we beleive physicians dealing with psoriasis in primary-care centers or in their clinics can find it useful to deliver a better service to their patients.
... Alternativ kann in Abhängigkeit von der zu erwartenden Patientenakzeptanz auch eine Therapie mit Dithranol (Cignolin) erwogen werden. Es zeigt insgesamt eine hohe Ansprechrate und kaum Therapieversager [29]. In einer österreichischen Untersuchung bei 63 Patienten wurde ein PASI75 bei 82.5 % und ein PASI90 bei 81 % der Patienten erreicht, die durchschnittliche Behandlung betrug hierbei 12.5 Tage [55]. ...
... Die Durchführung der Therapie ist vorzugsweise stationär zu empfehlen. [11,29] Bei gut geschulten Patienten ist in Ausnahmefällen auch eine ambulante Anwendung möglich. Der Patient sollte darauf hingewiesen werden, dass es bei einer Therapie mit Dithranol zur Verfärbung der Kleidung wie auch der Badkeramik kommen kann. ...
Zusammenfassung
Die topische Behandlung der Psoriasis und ihrer Sonderformen hat einen hohen Stellenwert im Praxisalltag. Sie ist Therapiestandard bei leichter Psoriasis und wird unterstützend auch bei mittelschwerer bis schwerer Psoriasis eingesetzt. Bei der Optimierung der Behandlung der Psoriasis spielt neben den geeigneten Wirkstoffen auch die Wahl der Galenik eine entscheidende Rolle. Die Weiterentwicklungen in diesem Bereich wurden in der 2017 publizierten Aktualisierung der S3‐Leitlinie nicht berücksichtigt. Der vorliegende Behandlungspfad wurde im Rahmen der PsoNet‐Sprecherkonferenz erarbeitet und durch die nationale Versorgungskonferenz Psoriasis bestätigt. Er stellt eine Illustration der aktuellen Optionen dar. Die Fachinformationen der genannten Präparate sind dabei stets zu berücksichtigen.
Die Festlegung von Therapiezielen mit dem Patienten ist obligat und adhärenzsteigernd. Dabei sollten die persönlichen Präferenzen und Vorerfahrungen des Patienten berücksichtigt werden. Goldstandard in der Initialphase ist die Fixkombination aus Calcipotriol (Cal) 50 μg/g und Betamethason‐Dipropionat (Bet) 0,5 mg/g 1x täglich über vier bis acht Wochen. Als Darreichungsform ist der Schaum am effektivsten, wobei die individuelle Wahl der Grundlage auch nach Patientenpräferenz erfolgen sollte.
In der Erhaltungsphase hat sich die 1–2x wöchentliche (proaktive) Anwendung dieser Fixkombination bewährt. In zweiter Linie können auch Vitamin D3 Analoga (Calcipotriol, Tacalcitol) und topische Corticosteroide als Monotherapie zur Anwendung kommen. Eine begleitende wirkstofffreie topische Basistherapie sollte regelhaft empfohlen werden. Bei besonderen Therapiesituationen werden spezifische Empfehlungen gegeben. Reicht eine alleinige Lokaltherapie nicht aus, sollte eine Therapieeskalation analog der S3‐Leitlinie zur Therapie der Psoriasis erfolgen.
... Simatupang and colleagues [29] identified three anthrone compounds in the benzene extract of the heartwood of V. guianensis for the first time, namely chrysophanic acid-9-anthrone, physcion-9-anthrone, and physcion-10anthrone (Table 1). Some anthrone derivatives have been shown to cause skin irritation [32]. ...
The Vatairea genus (Fabaceae family) is widespread in the Amazon rainforest. Some species of this genus are known for their ethnobotanical significance and biological potential. The present study explores the pharmacological and promising therapeutic activities, ethnobotanical profile, and phytochemical prospection of Vatairea sp., a monophyletic group of flowering plants, which includes economically and culturally important genera due to their diverse uses, including medicinal applications. V. lundellii, V. guianensis, V. erythrocarpa, V. fusca, V. heteroptera, V. paraensis, V. sericea, and V. macrocarpa are included in the Vatairea sp., also recognized for its high wood quality and potential medicinal properties. Studies show significant antibacterial activity in V. guianensis extracts against Gram-positive and Gram-negative bacteria, whereas V. macrocarpa lectin exhibits broad-spectrum antibacterial effects, including modulation of antibiotic resistance. Additionally, V. macrocarpa and V. guianensis have demonstrated antifungal properties, with compounds like Vatacarpan exhibiting potent activity against Candida sp. In vivo studies highlight the neurotoxic effects of V. macrocarpa lectin, suggesting a dual role in the central nervous system. Despite these findings, research on Vatairea’s toxicological aspects is limited, with only a few studies on V. macrocarpa and V. guianensis extracts indicating a need for further exploration of this genus’ pharmacological and therapeutic potential.
... One of the most successful drugs used in treatment of psoriasis is dithranol ( Figure 1), also called anthralin [12][13][14][15][16][17][18][19], routinely used since 1916 [18], but the antipsoriatic effect of chrysarobin, the precursor of dithranol, a substance of plant origin, was described as early as 1876 by Squire. Dithranol (DIT) inhibits the synthesis of DNA that hyperproliferates the epidermis, adjusts the cycle of epidermal renewal, suppresses the production of products of the arachidonic acid cascade, suppresses the penetration of neutrophils into the epidermis, limits the activation of lymphocytes and the function of dendritic cells in target cells, acts at the level of mitochondria, and thus has several desired effects precisely in the psoriatic process [20]. ...
Psoriasis is a chronic autoimmune skin disorder characterized by the rapid overproduction of skin cells, resulting in the formation of red, inflamed, and scaly patches or plaques on the skin. Dithranol, also known as anthralin, is a very effective topical medication used in the treatment of psoriasis, with several shortcomings like photo-instability; staining skin, clothing, and bedding; and causing skin irritation. Antiproliferative dithranol is frequently used in combination therapy with keratolytic salicylic acid. We have therefore proposed a novel topical antipsoriatic prodrug comprising dithranol and salicylic acid joined together with an ester bond, specifically 8-hydroxy-9-oxo-9,10-dihydroanthracen-1-yl-2-hydroxybenzoate. An ester bond is cleavable by endogenous esterase hydrolyzing this bond and releasing dithranol and salicylic acid in a 1:1 stoichiometric ratio. We performed an exhaustive theoretical analysis of this molecule using the reliable computational methods of quantum chemistry and ADME in silico studies to investigate its biological and pharmacokinetic activities. We found its molecular structure, vibrational spectra, molecular orbitals, MEP (molecular electric potential), UV-VIS spectra, and TDOS (total density of states), and we performed an RDG (reduced density gradient) analysis. The obtained results may be useful for the understanding of its properties, which may assist in the synthesis and further experimental study of this possible antipsoriatic dual-action prodrug with reduced adverse effects and enhanced therapeutic efficacy.
... Dithranol (Figure 1a), known also as cignoline or anthralin (1,8-Dihydroxy-9(10H)anthracenone), is a synthetic derivative of chrysarobin (Figure 1b), a natural product from the bark of the South American araroba tree, used since 1916 [19] as a topical treatment for psoriasis. Dithranol reduces the proliferation of keratinocytes and the activation of T lymphocytes and regulates cell differentiation, probably by its accumulation in mitochondria and the production of reactive oxygen species (ROS), inducing apoptosis [20][21][22][23][24][25][26]. While dithranol's lipophilic nature and ability to penetrate the skin quickly are advantageous for its therapeutic use, they can also lead to some of its unwanted side effects; for example, skin irritation and skin and laundry staining [27]. ...
Dithranol is one of the oldest and most efficient drugs used in the treatment of psoriasis. One of the challenges with using dithranol is its photostability, because it easily degrades when exposed to light. This study investigated the potential of coaxial core-sheath PCL/PVA nanofibers as a dual-functional system for enhancing dithranol photostability and remote-controlled drug delivery for psoriasis therapy. We have shown that coaxial nanofibers with titanium oxide nanoparticles (reflecting and absorbing ultra-violet light) in the PVA-based sheath part of the nanofibers can increase dithranol photostability. Incorporation of dithranol and magnetic nanoparticles into a PCL-based core of the nanofibers enables dithranol release control via an external radio-frequency field. The application of a radio-frequency field generates heat that can be used to control the release rate of drugs. Our approach therefore offers a non-invasive and remotely controlled drug release system that hold promise for the development of new topical formulations for psoriasis treatment using dithranol.
... Anthralin, also called dithranol, is the generic form of a topical medicine used to treat psoriasis and has been used for more than 100 years. It is an effective treatment of skin lesions in psoriasis by inhibiting keratinocyte hyperproliferation [114,115]. The use of anthralin may be limited by reversible pigmentation of the nail plate and irritation. ...
Nail psoriasis is a refractory disease that affects 50–79% skin psoriasis patients and up to 80% of patients with psoriatic arthritis (PsA). The pathogenesis of nail psoriasis is still not fully illuminated, although some peculiar inflammatory cytokines and chemokines seems to be the same as described in psoriatic skin lesions. Psoriatic nail involving matrix can cause pitting, leukonychia, red spots in lunula, and nail plate crumbling, while nail bed involvement can result in onycholysis, oil-drop discoloration, nail bed hyperkeratosis, and splinter hemorrhages. The common assessment methods of evaluating nail psoriasis includes Nail Psoriasis Severity Index (NAPSI), Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA), Nail Psoriasis Quality of life 10 (NPQ10), and so on. Treatment of nail psoriasis should be individualized according to the number of involving nail, the affected site of nail and presence of skin and/or joint involvement. Generally, topical therapies are used for mild nail psoriasis, while biologic agents such as etanercept are considered for severe nail disease and refractory nail psoriasis. Even though the current literature has shown some support for the pathogenesis, clinical presentation, or therapies of nail psoriasis, systemic review of this multifaceted disease is still rare to date. We elaborate recent developments in nail psoriasis epidemiology, pathogenesis, anatomy, clinical manifestation, diagnosis, differential diagnosis, and therapies to raise better awareness of the complexity of nail psoriasis and the need for early diagnosis or intervention.
... It was originally obtained from the bark of the araroba tree that grows in the rain forest of the Amazon. Dithranol inhibits the release of proinflammatory cytokines and the proliferation of keratinocytes [46,81] and was used as a positive control in our settings. However, dithranol can cause severe skin irritations in vivo such as redness, itching and a burning sensation, and might stain the skin and clothes brown. ...
Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferation of keratinocytes and expression of pro-inflammatory cytokines in the epidermis. New biological drugs were developed for the systemic treatment of moderate to severe psoriasis. However, products for the topical treatment of mild psoriasis are still required. Here, we examined the effect of natural compounds on psoriasis-like keratinocytes in vitro and ex vivo. Psoriasis-like keratinocytes were generated by treating human primary keratinocytes with the psoriasis-associated cytokines IL-17A, TNF-α and IL-22. Initially, 10 botanical extracts from Ayurvedic Medicine, Traditional Chinese Medicine, Northern American traditional medicine and Occidental Monastic Medicine were investigated using BrdU assays and IL-6 and IL-8 ELISAs. Curcuma amada, Humulus lupulus and Hypericum perforatum turned out to be the most effective plant extracts. In vitro, the plant extracts inhibited the expression of anti-microbial peptides (β-defensin 2), the hyperproliferation marker keratin 17, the glucose transporter 1 and downregulated the nuclear translocation of NF-κB and pSTAT3. In an ex vivo psoriasis model, Humulus lupulus displayed the most prominent anti-proliferative and anti-inflammatory effect. In conclusion, among the plant extracts investigated, Humulus lupulus showed the most promising anti-psoriatic effect. It is an interesting candidate for topical psoriasis treatment that should be further studied in clinical trials.
... Dithranol (anthralin; 1,8-dihydroxy-9(10H)-anthracenone) is widely used as an effective topical treatment for patients with psoriasis (Hendriks et al. 2012). The precise molecular basis for dithranol's actions is believed to be related to the production of free radicals and the keratinization of the epidermis, along with its strong irritative and pro-inflammatory properties (Sehgal et al. 2014). However, orofacial tissue inflammation can result in prolonged neuronal activation in trigeminal nociceptive pathways. ...
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.
... Topical medicines for psoriasis include some of the drugs used for systemic treatment, such as calcineurin inhibitors (TAC, CsA), vitamin A and its derivatives ("Small-Drug Therapy"), and also corticosteroids, vitamins D and D 3 and analogs, and dithranol (1,8-dihydroxy-9-anthrone; DIT), a synthetic substitute of chrysarobin which is found in the bark of the Brazilian araroba trees [36]. Over-the-counter medicines include salicylic acid and coal tar ( Table 2). ...
Psoriasis is a chronic immune-mediated skin disease, with a pathogenesis resulting from a combination of genetic and environmental factors. The pathogenesis of psoriasis is driven by the interaction between innate and adaptive immune cells and keratinocytes, in a complex process mediated by cytokines and other signaling molecules. This leads to an inflammatory process with increased proliferation of epidermal cells, neo-angiogenesis, and infiltration of white cells in the skin, which cause the characteristic psoriasis plaques. Several studies have suggested that the neurotransmitter serotonin, a key mediator between the skin and the neuroendocrine system, also plays an important role in the pathogenesis of psoriasis. Psoriasis often needs long-term treatment, which can be a burden. Thus, the choice of the treatment is crucial to increase the patients’ adherence and quality of life. This review addresses the currently available systemic and topical treatments for psoriasis, used by themselves or combined with phototherapy. It particularly focuses on the importance of advanced drug delivery systems as a way to increase the drug penetration and retention in the skin, while also enhancing its solubility and stability. Finally, we discuss the role of the serotonin system in psoriasis, and summarize what is known about the effects of antidepressants, in particular specific serotonin reuptake inhibitors, on the physical symptoms of this disease.
... For more than 100 years anthralin (A), also known as dithranol and cignolin, has been applied as an effective topical agent for the treatment of the skin disease psoriasis ( Ashton et al., 1983;Van de Kerkhof, 1991;Sehgal, Verma & Khurana, 2014;Körber et al., 2019). The compound was for many years believed to be anthracene-1,8,9-triol, but spectroscopic and crystallographic analyses indicated that the prevailing constitution is that of the tautomer 1,8-dihydroxy-9(10H )-anthracenone (Hellier & Whitefield, 1967;Avdovich & Neville, 1980;Ahmed, 1980), see Fig. 1. ...
Anthralin (1,8-dihydroxyanthrone, 1,8-dihydroxy-9(10H)-anthracenone), also known as dithranol and cignolin, is one of the most efficient drugs in the treatment of psoriasis and other skin diseases. The precise mode of biochemical action is not fully understood, but the activity of the drug is increased by the influence of UV radiation. In the present investigation, the UV absorption of anthralin is studied by synchrotron radiation linear dichroism (SRLD) spectroscopy on molecular samples partially aligned in stretched polyethylene, covering the near and vacuum UV regions with wavenumbers ranging from 23,000 to 58,000 cm-1 (430-170 nm). The observed polarization spectra are well predicted by quantum chemical calculations using time-dependent density functional theory (TD-DFT). About a dozen spectral features are assigned to computed electronic transitions. The calculations support interpretation of the anomalous fluorescence of anthralin as a result of barrier-less excited state intramolecular proton transfer (ESIPT) to the tautomer 8,9-dihydroxy-1(10H)-anthracenone.
... The mechanism of anthralin in AA is unclear. Certain proinflammatory cytokines might be implicated in its pathogenesis (Sehgal, Verma, & Khurana, 2014). Anthralin with 0.2-1% concentrations induces irritant dermatitis and discoloration of the skin. ...
Background:
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 (SADBE) and diphenylcyclopropenone (DPCP) in contact immunotherapy is by far the best chemotherapy for AA.
The aim of work:
To evaluate the efficacy and safety of combination therapy with diphenylcyclopropenone (DPCP) and anthralin in chronic extensive AA.
Patients and method:
A total of 24 patients (12 were treated only with DPCP and 12 with DPCP and anthralin for at least 24 weeks) were evaluated.
Results:
Complete hair regrowth was observed in 62.5% and 18.2% of the patients who received DPCP and combination therapy, respectively (P = 0.04). Hair regrowth duration was different in both groups.
Conclusion:
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 to complete hair regrowth, Moreover, the increasing side effects in combination therapy group. This article is protected by copyright. All rights reserved.
... Por más de un siglo se había empleado en Brasil e India el extracto de la leguminosa Vataireopsis araroba, anteriormente nombrada Andira araroba, como remedio tradicional contra enfermedades de la piel; este extracto se conoce comúnmente como polvo de Goa, polvo de Aroba o polvo de Brasil. En En la actualidad, el uso de este fármaco es limitado ya que sus productos de degradación son nocivos para la piel.[40][41][42][43][44][45][46] Adicionalmente, los derivados 9-antrona tiene propiedades biológicas interesantes, y están siendo usadas como laxantes, antimicrobianos y antitumorales.35 ...
... Anthralin (dithranol) was first synthesized as a derivative of chrysarobin, prepared from the araroba tree in Brazil over a century ago. It is an effective treatment of skin lesions in psoriasis by inhibiting keratinocyte hyperproliferation and interfering with several relevant steps of the immune system [65]. In one uncontrolled study, 20 psoriasis patients with nail involvement were treated with topical anthralin therapy [66]. ...
Nail involvement affects 80-90 % of patients with plaque psoriasis, and is even more prevalent in patients with psoriatic arthritis. This review is the result of a systemic approach to the literature and covers topical, intralesional, conventional systemic, and biologic systemic treatments, as well as non-pharmacological treatment options for nail psoriasis. The available evidence suggests that all anti-tumor necrosis factor-α, anti-interleukin (IL)-17, and anti-IL-12/23 antibodies which are available for plaque psoriasis and psoriatic arthritis are highly effective treatments for nail psoriasis. Conventional systemic treatments, including methotrexate, cyclosporine, acitretin, and apremilast, as well as intralesional corticosteroids, can also be effective treatments for nail psoriasis. Topical treatments, including corticosteroids, calcipotriol, tacrolimus, and tazarotene, have also been shown to have a position in the treatment of nail psoriasis, particularly in mild cases. Finally, non-pharmacological treatment options, including phototherapy, photodynamic therapy, laser therapy, and several radiotherapeutic options, are also reviewed but cannot be advised as first-line treatment options. Another conclusion of this review is that the lack of a reliable core set of outcomes measures for trials in nail psoriasis hinders the interpretation of results, and is urgently needed.
... As mentioned above, regulation of the pathological changes initiated or perpetuated by keratinocytes may be effective in psoriasis management [20]. Given their capability to attenuate inflammatory responses and bring homeostasis to the epidermis, drugs such as dithranol and vitamin D analogs are currently used in clinical settings to treat psoriasis with satisfactory results [21,22]. Laboratory studies have demonstrated the immunosuppressive effects of ART on T cells both in vitro and in vivo [7]. ...
Artemether exhibits diverse pharmacological effects and has multiple applications. This study aimed to investigate its antiproliferative and apoptogenic effects on HaCaT cells and keratinocyte differentiation-inducing activity in vivo. WST-8 analysis demonstrated that Artemether can inhibit the proliferation of cultured HaCaT cells in a time- and dose-dependent manner. Annexin V/PI dual staining and JC-1 staining further revealed that Artemether can dose-dependently augment HaCaT apoptosis. To investigate the keratinocyte differentiation-inducing activity of Artemether, it was prepared as topical creams at concentrations of 1%, 3%, and 5%. During the 4 weeks of topical treatment, no evidence of irritation was observed in the mouse tail test. Artemether cream dose-dependently increased the degree of orthokeratosis and the relative epidermal thickness of mouse tail skin, indicative of the keratinocyte differentiation-inducing activity. Taking the in vitro and in vivo findings together, the present study suggests that Artemether may be a promising antipsoriatic agent worthy of further investigation.
... Due to a high likelihood of no exposure potential, it was designated as "low priority." Anthralin is a topical medication approved for treating psoriasis; it is sequestered in the mitochondria of keratinocytes, where it triggers apoptosis and promotes the growth of new skin tissue (Sehgal et al. 2014). Due to its lipophilicity and sequestration in dermal tissues, anthralin is unlikely to enter the systemic circulation to a significant extent and is also predicted to have low BBB permeability, resulting in it being a "low priority" chemical. ...
Adverse outcome pathways (AOPs) link adverse effects in individuals or populations to a molecular initiating event (MIE) that can be quantified using in vitro methods. Practical application of AOPs in chemical-specific risk assessment requires incorporation of knowledge on exposure, along with absorption, distribution, metabolism, and excretion (ADME) properties of chemicals.
A conceptual workflow was developed to consider exposure and ADME properties in relation to an MIE. The utility of this workflow was demonstrated using a previously established AOP, acetylcholinesterase (AChE) inhibition.
Thirty chemicals found to inhibit human AChE in the ToxCast(TM) assay were examined with respect to their exposure, absorption potential, and ability to cross the blood-brain barrier (BBB). Structures of active chemicals were compared against structures of 1,029 inactive chemicals to detect possible parent compounds that might have active metabolites.
Application of the workflow screened ten "low priority" chemicals out of the thirty active chemicals. Fifty-two of the 1,029 inactive chemicals exhibited a similarity threshold above 75% with their nearest active neighbors. Out of these 52 compounds, 30 were excluded due to poor absorption or distribution. The remaining 22 compounds may inhibit AChE in vivo either directly or following metabolism.
The incorporation of exposure and ADME properties into the conceptual workflow eliminated 10 "low priority" chemicals that may otherwise have undergone additional, resource-consuming analyses. Our workflow also increased confidence in interpretation of in vitro results by identifying possible "false negatives."
... These disorders can further exacerbate the inflammatory reaction and drive angiogenesis in psoriasis [20,21]. Therefore, drugs that can block the pathological changes of keratinocytes, such as clinically used dithranol and vitamin D analogues, will be of benefit for patients with psoriasis [22,23]. As far as the baicalin cream is concerned, the keratinocyte differentiationinducing activity thus becomes another key to its antipsoriatic mechanism. ...
Scutellaria baicalensis is a Chinese herbal medicine that has been used for centuries to treat psoriasis. Baicalin is one of the major flavonoids and bioactive components of S. baicalensis and is responsible for the pharmacologic actions of the plant.
This study aimed to investigate the anti-inflammatory effect and keratinocyte differentiation-inducing activity of baicalin in vivo.
Baicalin was formulated into topical creams at concentrations of 1%, 3%, and 5%. The anti-inflammatory effect of baicalin cream was evaluated in 2,4-dinitrofluorobenzene (DNFB)-induced contact hypersensitivity (CHS) mice, and its keratinocyte-modulating action was assessed using the mouse tail model for psoriasis.
During the topical application of baicalin cream, no evidence of irritant effect was observed in both tests. In the inflammation model, mice exposed to baicalin cream displayed a reduction in DNFB-induced CHS responses compared with vehicle-treated animals, showing that the topical application of baicalin cream exerted an anti-inflammatory effect. In the second model, baicalin cream dose-dependently increased the orthokeratosis of granular layers and the relative epidermal thickness of mouse tail skin, indicative of the keratinocyte differentiation-inducing activity of this topical preparation.
Taking the in vivo findings together, the present study indicated that baicalin cream may be a promising antipsoriatic agent worthy of further investigation for psoriasis treatment.
Psoriasis is a noncontagious, autoimmune chronic inflammatory disease with an unknown root cause. It is classified as a multifactorial and chronic skin disorder that also affects the immune system and is genetic. Environmental factors such as stress, infections, and injuries all play an important role in the disease's development. Although there is no cure for this disease, topical, oral, and systemic whole‐body treatments are available to relieve symptoms. Several plants and phytochemicals which have been found effective in the management of the psoriasis experimentally (preclinical and clinical). These plants/phytochemicals have applications in topical, oral, and systemic treatments. Traditionally, some of the plants have been utilized as the primary treatment, including their extracts and/or phytochemicals, for individuals with moderate to severe psoriasis (due to fewer side effects), while phototherapy is generally reserved for more advanced cases. This report describes various plants and phytochemicals that have been found to be effective against psoriasis in in vitro, preclinical, and clinical studies. This review summarizes the key findings from experimental studies on various pathological aspects of psoriasis and may be useful, effective, and informative for future research.
Aim: Alopecia areata (AA) is a chronic inflammatory disease characterized by non-scarring hair loss. In this study, we aimed to investigate the effects and side effects of topical anthralin and topical clobetasol propionate treatment in patients with AA using phototrichogram. Materials and Methods: The study included 40 patients with AA that were randomly divided into two groups: topical anthralin (n=20) and clobetasol 17-propionate 0.05% (n=20). Phototrichogram values were assessed before and after treatment. Results: An evaluation of treatment response at the end of three months indicated inadequate response in 7 (35%), partial response in 8 (40%), and cosmetic response in 5 (25%) of the patients in the clobetasol 17-propionate 0.05% group as opposed to inadequate response in 4 (20%), partial response in 8 (40%), and cosmetic response in 8 (40%) of the patients in the local anthralin group. Although the cosmetic response rate was higher in the local anthralin group, there was no significant difference (p=0.470). The rate of patients unresponsive to treatment was lower in the topical anthralin group, while no significant difference was established (p
Psoriasis (Pso) is an autoimmune inflammatory skin disease characterized by red plaques covered in silver scales. The existing treatments provide limited benefits and are associated with certain drawbacks which limit their use. Thus, there is a need to explore more options that are highly target-specific and associated with minimal side effects. Researchers have thoroughly investigated the use of herbal drugs for their therapeutic potential. Preclinical studies demonstrate that phytochemicals such as curcumin, psoralen, and dithranol have antipsoriatic effects. These phytoconstituents inhibit the signalling pathways, such as the interleukin (IL) 23/Th17 axis and IL36 inflammatory loop involved in the pathogenesis of Pso. These phytoconstituents downregulate the pro-inflammatory cytokines like IL17 and tumor necrosis factor (TNF)-α. However, their application in clinical settings is limited due to poor bioavailability and access to target sites. Combining phytoconstituents with modern delivery platforms like nanocarriers can address these shortcomings and improve therapeutic efficacy. This review explores the potential of herbal remedies as a substitute for conventional therapies, emphasizing the clinical trials conducted with these herbal medicines. The paper is supported by the discussion on nanocarriers like liposomes, niosomes, emulsomes, ethosomes, nanostructured lipid carriers, nanoemulsions, and dendrimers that are used to deliver herbal medicines.
Psoriasis (PSO) is a chronic autoimmune skin condition characterized by the rapid and excessive growth of skin cells, which leads to the formation of thick, red, and scaly patches on the surface of the skin. These patches can be itchy and painful, and they may cause discomfort for patients affected by this condition. Therapies for psoriasis aim to alleviate symptoms, reduce inflammation, and slow down the excessive skin cell growth. Conventional topical treatment options are non-specific, have low efficacy and are associated with adverse effects, which is why researchers are investigating different delivery mechanisms. A novel approach to drug delivery using nanoparticles (NPs) shows promise in reducing toxicity and improving therapeutic efficacy. The unique properties of NPs, such as their small size and large surface area, make them attractive for targeted drug delivery, enhanced drug stability, and controlled release. In the context of PSO, NPs can be designed to deliver active ingredients with anti-inflammatory effect, immunosuppressants, or other therapeutic compounds directly to affected skin areas. These novel formulations offer improved access to the epidermis and facilitate better absorption, thus enhancing the therapeutic efficacy of conventional anti-psoriatic drugs. NPs increase the surface-to-volume ratio, resulting in enhanced penetration through the skin, including intracellular, intercellular, and trans-appendage routes. The present review aims to discuss the latest approaches for the topical therapy of PSO using NPs. It is intended to summarize the results of the in vitro and in vivo examinations carried out in the last few years regarding the effectiveness and safety of nanoparticles.
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.
Psoriasis is a life-threatening autoimmune inflammatory skin disease, triggered by T lymphocyte. Recently, the drugs most commonly used for the treatment of psoriasis include methotrexate (MTX), cyclosporine (CsA), acitretin, dexamethasone, and salicylic acid. However, conventional formulations due to poor absorptive capacity, inconsistent drug release characteristics, poor capability of selective targeting, poor retention of drug molecules in target tissue, and unintended skin reactions restrict the clinical efficacy of drugs. Advances in topical nanocarriers allow the development of prominent drug delivery platforms can be employed to address the critical issues associated with conventional formulations. Advances in nanocarriers design, nano-dimensional configuration, and surface functionalization allow formulation scientists to develop formulations for a more effective treatment of psoriasis. Moreover, interventions in the size distribution, shape, agglomeration/aggregation potential, and surface chemistry are the significant aspects need to be critically evaluated for better therapeutic results. This review attempted to explore the opportunities and challenges of current revelations in the nano carrier-based topical drug delivery approach used for the treatment of psoriasis.
Background
Drug loaded β-cyclodextrin based nanosponges (CDNS) are of special interest for the entrapment of moieties with the view to address their physicochemical challenges, and to improve their delivery characteristics and utility. Dithranol (DTH), the standard drug for psoriasis, has poor stability and solubility, which limits its pharmaceutical applications.
Objective
The objective of the current study was to entrap DTH in CDNS in order to alleviate the above-mentioned challenges.
Methods
To synthesize CDNS, β-cyclodextrin was treated with diphenyl carbonate in various molar ratios. The obtained placebo CDNS were loaded with DTH by lyophilisation. The particle size of the DTH loaded CDNS was found to lie between 150 and 450 nm, with narrow polydispersity index range. Fourier transform infrared spectroscopy, thermal analysis, X-ray diffraction, zeta potential and electron microscopy with energy dispersive spectroscopy (EDS) were conducted for characterization of DTH-CDNS.
Results
Findings from spectral examinations confirmed the formation of inclusion complexes. Solubilisation efficiency of DTH (in distilled water), was found augmented 4.54 folds with optimized CDNS. The cytocompatibility study was performed by the MTT assay employing THP1 cell lines. A remarkable amelioration in stability and photostability of DTH was also observed, by its inclusion in nanosponges.
Conclusion
In nutshell, we report the rational engineering and characterization of DTH loaded cyclodextrin-based nanosponges, and subsequently, their stepwise screening for photostability, in vitro release, in vitro cytocompatibility, in vitro antioxidant and in vitro inflammatory activity in a top-down manner, yielding the best carrier for this drug.
This study was to develop a combination of zedoary turmeric oil (ZTO) and tretinoin (TRE)-loaded liposomal gel as a topical drug delivery system. We used a combination of single factor experiment and orthogonal experiment to systematically optimize encapsulation process of the compound liposomes. The optimized liposome vesicles were incorporated into Carbopol gel matrix and studied by continuous in vitro (skin penetration and retention) and in vivo (anti-psoriatic activity using mouse vaginal model and mouse tail model) experiments. The optimized liposomes had an entrapment efficiency (EE) of ZTO was (64.63 ± 1.00)%, EE of TRE was (90.33 ± 0.72)%, drug loading (DL) of ZTO was (9.09 ± 0.14)%, DL of TRE was (1.43 ± 0.02)%, particle size of 257.41 ± 7.58 nm, polydispersity index (PDI) of 0.10 ± 0.04 and zeta potential of −38.77 ± 0.81 mV. Transmission electron microscopy showed liposomes had a regular spherical surface. After 1 month storage at (4 ± 2) °C, the optimized liposome preparations maintained its stability. In vitro study indicated that liposome formulations could significantly prolong the penetration of drugs into the hair follicles of mice and keep more drugs in the skin compared with conventional gel formulations. In vivo study showed that liposomal gel was more effective than conventional gel in treating psoriasis and had a significant dose-dependent effect on psoriasis. In summary, liposomal gel is expected to be an ideal carrier for topical drug delivery systems of ZTO and TRE.
Background/Objectives
Data on treatment options in pediatric alopecia areata are limited. Topical anthralin has been demonstrated to be an effective treatment option in adults and has minimal systemic toxicity. Prior results on its efficacy in children with alopecia areata have been mixed.
Methods
Medical records of 37 patients with alopecia areata who were started on topical anthralin before age 17 were reviewed for efficacy and safety data. Scalp regrowth was quantified by serial photography if available or by medical record documentation if photographs were unavailable. Mean duration of clinical follow‐up was 2.5 years.
Results
Most patients were started on anthralin while continued on prior therapies, including topical corticosteroids, minoxidil, and/or intralesional corticosteroids. Twelve patients (32%) experienced complete scalp regrowth, while 25 patients (68%) experienced at least 50% maximal scalp regrowth with using anthralin. Of the patients with at least 50% scalp regrowth, mean time to first clinically observed response was 3.4 months. Mean time to maximal response was 15 months. Four patients stopped anthralin due to skin irritation. Relapses affected 64% of those with at least 50% maximal scalp regrowth.
Conclusions
Topical anthralin provides children with alopecia areata an additional option that offers potential for significant scalp regrowth with minimal systemic effects. Treatment course may need to be continued for at least 1 year in order to achieve maximal efficacy. The efficacy of anthralin may be limited by high rate of recurrence and local adverse effects.
The network approaches of systems pharmacology and toxicology serve as early predictors of the most relevant screening approach to pursue both in drug discovery and development and ecotoxicological assessments. Computational approaches have the potential to improve toxicological experimental design, enable more rapid drug efficacy and safety testing and also reduce the number of animals used in experimentation. Rapid advances in availability of computing technology hold tremendous promise for advancing applied and basic science and increasing the efficiency of risk assessment.
This book provides an understanding of the basic principles of computational toxicology and the current methods of predictive toxicology using chemical structures, toxicity-related databases, in silico chemical-protein docking, and biological pathway tools. The book begins with an introduction to systems pharmacology and toxicology and computational tools followed by a section exploring modelling adverse outcomes and events. The second part of the book covers the discovery of protein targets and the characterisation of toxicant-protein interactions. Final chapters include case studies and additionally discuss interactions between phytochemicals and Western therapeutics.
This book will be useful for scientists involved in environmental research and risk assessment. It will be a valuable resource for postgraduate students and researchers wishing to learn about key methods used in studying biological targets both from a toxicity and pharmacological activity standpoint.
Various topical agents can be used to augment the effectiveness of phototherapy for psoriasis, especially when the lesions are thick and light cannot penetrate. Topical retinoids (tazoratene) and keratolytics (salicylic acid and lactic acid) can help reduce scale. Coal tar and anthralin, although messy and more difficult to use, can also increase the effectiveness of phototherapy as demonstrated in the Goeckerman regimen and Ingram regimen, respectively.
Psoriasis is one of the most common skin diseases, affecting 2–5% of the world's population. It is a skin autoimmune disorder, resulting in an excessive growth and aberrant differentiation of keratinocytes. Psoriasis is an incurable lifetime disease which can only be controlled and relieved through medication. Various approaches have been explored to treat the disease. Treatment of psoriasis includes topical therapy, systemic therapy and phototherapy. Topical therapy is the first line treatment and it is the most practical medication method for psoriasis patients. However, the conventional topical treatments such as gel and cream have low efficiency, poor cosmetic and aesthetic appeal, leading to poor patient compliance or adherence, while systemic and photo therapy produce significant adverse side effects. Nanoemulsion is defined as an emulsion system consisting of oil, surfactant, and water with an isotropic, transparent (or translucent) appearance. The emulsion droplet size is defined to be less than 200 nm. Nonetheless, if the emulsion has low surfactant content and is kinetically stable, a size of less than 500 nm can be accepted as nanoemulsion. A small droplet size would enhance the delivery and penetration of a drug through the psoriasis skin layer. There has been a growing interest in using nanoemulsions in topical applications, due to their high stability and their optical transparency or translucency, which make them good and very dermatologically attractive. A good selection of oils and surfactants would enhance the transdermal treatment efficacy. This review highlights the potential of drug-loaded nanoemulsions for the treatment of psoriasis towards achieving better efficacy and eliminating side effects.
Background:
Evidence of the efficacy of dithranol and patient perspectives on the treatment is scant.
Patients and methods:
Using a telephone interview survey, we collected retrospective data from 63 patients (41 men [65.1 %] and 22 women [34.9 %]) who had been treated with classic inpatient dithranol (CID). PsoRA (www.psoriasisregistry.at) was used to obtain clinical data and treatment responses, which were then correlated with the interview responses.
Results:
Fifty-two (82.5 %) patients achieved a PASI75 and 51 (81 %) a PASI90 response within a median of 12.5 (range: 3 to 25) days. Ten out of twelve (83 %) patients showed a satisfactory response to CID (PASI75 or greater reduction) despite the fact that they had previously failed to adequately respond to methotrexate, oral retinoids, cyclosporine, or ustekinumab. Overall, patients recalled a median recurrence-free interval of four (95 % CI: 3-9) months after responding to CID, which was positively correlated with the patients' recommendation of (p = 0.018) and their overall high satisfaction with the treatment (p = 0.012).
Conclusions:
Despite the known limitations of CID, this survey indicates that dithranol remains a highly efficacious and valuable treatment option as induction therapy in psoriasis. CID can be effective in patients who have failed to respond to systemic therapy, including traditional agents and biologics.
Background:
Evidence of the efficacy of dithranol and patient perspectives on the treatment is scant.
Patients and methods:
Using a telephone interview survey, we collected retrospective data from 63 patients (41 men [65.1 %] and 22 women [34.9 %]) who had been treated with classic inpatient dithranol (CID). PsoRA (www.psoriasisregistry.at) was used to obtain clinical data and treatment responses, which were then correlated with the interview responses.
Results:
Fifty-two (82.5 %) patients achieved a PASI75 and 51 (81 %) a PASI90 response within a median of 12.5 (range: 3 to 25) days. Ten out of twelve (83 %) patients showed a satisfactory response to CID (PASI75 or greater reduction) despite the fact that they had previously failed to adequately respond to methotrexate, oral retinoids, cyclosporine, or ustekinumab. Overall, patients recalled a median recurrence-free interval of four (95 % CI: 3-9) months after responding to CID, which was positively correlated with the patients' recommendation of (p = 0.018) and their overall high satisfaction with the treatment (p = 0.012).
Conclusions:
Despite the known limitations of CID, this survey indicates that dithranol remains a highly efficacious and valuable treatment option as induction therapy in psoriasis. CID can be effective in patients who have failed to respond to systemic therapy, including traditional agents and biologics.
Dithranol (known in the US as anthralin and in Germany as cignolin) is one of the oldest and safest long-term topical antipsoriatic treatments. However, established evidence for dithranol's therapeutic efficacy is scant; and data regarding the extent to which dithranol may reduce the Psoriasis Area and Severity Index (PASI), the current standard parameter for assessing therapeutic efficacy in treated psoriasis patients, are minimal. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Efficacy of intralesional triamcinolone acetonide (10mg/ml) and topical anthralin 1.15% cream was compared in the treatment of alopecia areata. Study groups consisted of 37 patients for injection and 32 patients for cream. All of them belonged to Type I of Ikeda's classification. The study showed that triamcinolone induces more adequate response in terms of regrowth of hairs than anthralin. However, the relapse rate was higher with triamcinolone. No difference was noted in terms of complete regrowth of hairs on the lesional skin and side effects of drugs.
Background
Women comprise half of all psoriasis patients and because the majority of psoriasis cases present before age 40 the disease affects women who may become pregnant. Information regarding the heritability of psoriasis can be used in counseling patients who inquire about the potential risk to their children. Patients with psoriasis who become pregnant will likely notice an associated improvement of their symptoms if any change is noted at all.
Objective
Because of potential fetal effects, the treatment of chronic psoriasis in pregnancy involves prudent consideration of whether the severity of the disease warrants treatment and selection of the safest treatments available.
Conclusion
Topical corticosteroids and topical calcipotriene as well as topical anthralin and topical tacrolimus appear to be safe choices for control of localized psoriasis in pregnancy. UVB is the safest treatment for extensive psoriasis during pregnancy, particularly when topical application of other agents is not practical. Short-term use of cyclosporine during pregnancy is probably the safest option for management of severe psoriasis that has not responded to topical or UVB treatment.
• Membrane-associated thioredoxin reductase (TR) activity has been measured in 3-mm punch biopsy specimens from psoriatic and uninvolved skin in eight patients with chronic plaque-type psoriasis vulgaris. The mean specific activity for this free radical reducing enzyme in psoriatic vs uninvolved skin was 28.5 ± 8.0 U vs 16.8 ± 4.25 U. Because TR contains two reactive thiolate groups at its active site, this enzyme reacts with anthralin to form a covalent anthralin-TR complex causing irreversible enzyme deactivation. This mode of action for anthralin was confirmed by using pure TR from Escherichia coli. Keratinocyte cell cultures, grown from normal and psoriatic skin of one donor, revealed 24% and 42% inhibition of cell surface TR activity, respectively, in the presence of 2×10-5M anthralin. Time-dependent topical application of anthralin on guinea pig skin gave 70% inhibition of TR with concentrations of 0.25% to 1.0% after 24 hours in open and occlusive applications of the drug. Short contact with 1% anthralin showed 70% inhibition after 120 minutes.
(Arch Dermatol 1987;123:1494-1498)
• Anthralin minute entire skin treatment (AMEST) was developed to improve the efficacy and cosmetic results of anthralin short-contact therapy. In a split comparison study to determine the optimal period of anthralin application, ten minutes of anthralin contact time gave maximum antipsoriatic activity with minimal side effects. Dosimetry variables for AMEST were determined based on the patient's pigmentation type, the erythematous response, the therapeutic effect, and so on. Such treatment of 43 patients resulted in complete clearing in 31 patients (72%), with 90% improvement in two patients (5%) and less than 90% clearing in seven patients (16%). Psoriatic lesions disappeared, leaving no spotty pigmentation that is known to occur following conventional anthralin therapy. The dosimetry variables employed in our study allowed AMEST with minimal skin irritation. Laboratory values did not change significantly during therapy. In addition, AMEST does not involve systemic medication and is easy to perform without special equipment; therefore, it is economic and can be used for outpatients and probably for home treatment.(Arch Dermatol 1985;121:1512-1515)
This preliminary study suggests that a 1 h application of dithranol may be effective in the treatment of psoriasis. It is conceivable that short application periods for other topically applied agents, e. g. corticosteroids, may reduce the side-effects in non-affected skin, while maintaining the therapeutic benefit in diseased areas.
Anthralin cream 0.5% to 1.0% was used to treat 68 patients with severe alopecia areata. Therapy was relatively well tolerated, although all patients experienced pruritus and local erythema and scaling. Cosmetic response was seen in 17 (25%) of the patients, and was maintained during therapy in 12 (71%) of the 17 cosmetic responders. For the patients treated with 0.5% anthralin, the mean time to response (44 of 66 patients) was 11 weeks; the mean time to cosmetic response (13 of 66 patients) was 23 weeks. Duration of the current episode of hair loss did not correlate with cosmetic response. Compared with other currently available topical treatments, anthralin appears to be a reasonable therapeutic option for severe alopecia areata.
A single blind comparison of 0·1% dithranol in a 17% urea cream base (Psoradrate®) with a coal tar and salicyclic acid pomade in the treatment of scalp psoriasis is described. Roth treatments were equally effective, though Psoradrate caused significantly more side-effects. We concluded that Psoradrate is effective in the treatment of scalp psoriasis.
The results reported in connection with previously published data suggest the importance of increased lipid peroxidation in the epidermis after Dithranol treatment. Malonaldehyde, one of the main products of lipid peroxidation, reacts with epidermal phosphofructokinase and glucose-6-phosphate dehydrogenase to cause enzyme inactivation by cross-linking of the enzyme protein demonstrated by dodecyl sulphate electrophoresis. Enzyme inactivation leads to an inhibition of hexose monophosphate shunt and glycolysis. The effect on energy donating metabolism in psoriatic lesions is discussed.Copyright © 1975 S. Karger AG, Basel
Anthralin is a most widely used compound for topical treatment of psoriasis. Whereas numerous studies have ascertained anthralin as a safe and effective drug its mode of action still remains unclear. Previous studies demonstrated dose-dependent inhibition of a number of pro-inflammatory functions in human enutrophils and monocytes (MO). The aim of the present study was to investigate in stimulated MO the effect of anthralin on the secretion of cytokines which are of known importance for the psoriatic tissue reaction.
Highly purifies MO were incubated with anthralin (0·01–1·0μg/ml), its clinically inactive derivative danthrone (0·1 and 10 μg/ml), the solvent acetone, or medium alone. Culture supernatants were analysed for immunoreactivity for interleuking-1β, and -8 (IL-1β, IL-8), and tumour necrosis factor β (TNF-β) by specific ILISA. IL-6 bioactivity was determined using the B9-bioassay. Additionally, IL-1 bioactivity was measured by the D10[N4]M-bioassay.
The results show a dose-dependent inhibition of MO IL-6, IL-8, and TNF-α release with a half- maximal inhibitory concentration of 0.25–0.6μ/ml of anthralin. There was no effect of danthrone or acetone on the secretion of these cytokines from MO. Secretion of IL-1β immunoreactivity measured by ELISA as determination of biological activity of IL-1 using the D10[N4]M- bioassay revealed a slight increase in IL-1 secretion with a maximum at an anthralin concentration of 0.1 μg/ml. Danthrone at a concentration of 10μg/ml and acetone (0.1%) similarly enhanced IL-1 secretion from human MO measured by both methods.
Our results demonstrate a differential, dose-dependent inhibition of cytokine secretion from human MO by anthralin. The present data provide evidence that the anti-inflammatory and anti- proliferative activity of anthralin may at least in part be due to its inhibitory effect on pro-inflammatory cytokine secretion by MO.
The effect of anthralin and its oxidation products danthrone and anthralin-dimer on the production of 5-lipoxygeanse products (5-HETE, leukotriene B4 ω-oxidized LTB4 by Ca-ionaphore A 23187-stiumulated human neutrophils has been studied in vitro. Anthralin exhibited dose-dependent inhibitory activity showing 50% inhibition at 7 μM with 10⁷ neutrophils. Inhibitory effects strongly depended upon cell densities and maximal inhibition occured at low cell concentrations, whereas inhibitory rates of anthralin were low at high cell densities.
Inhibition of leukotriene production persisted after washing of anthralin-treated neutrophils. Also, with increasing amounts of arachidonic acid as substrate only slight changes of inhibitory activity were detected, indicating a noncompetitive way of action. In addition to the inhibition of leukotriene-production, the formation of ω-OH-LTB4 from LTB4 as well as ω-COOH-LTB4 from ω-OH-LTB4 was inhibited with IC50 (half maximum inhibition concentration) near 4.4 μM and 2.2 μM, respectively. In contrast to anthralin, both metabolites–danthrone as well as anthralin-dimer–did not show any effect on leukotriene production and ω-oxidation even at high concentrations (up to 70 μM and 44 μM, respectively).
SummaryA stiff dithranol 0.5% ointment showed colour changes, degradation and loss of potency after adverse storage. Varying strengths of salicylic acid were added in an attempt to protect the dithranol. A new method was employed to quantify the colour changes using a Colour Chart and to express the results as percentage reflectance values. Spectrophotometric analysis was undertaken for degradation products. Clinical assessment was carried out on a double blind basis. All three methods of assessment confirmed that the optimum strength of salicylic acid was 0.5% to ensure a good shelf life, provided the ointment was stored in well-filled containers protected from light.
This article reviews the different treatments of alopecia areata (AA). The information includes both a review of the literature as well as practical aspects regarding the use of the most commonly used therapies for AA. These modalties are summarized in a practical algorithm that can be used as a guide. For patients less than 10 years of age, the options are topical corsticosteroids, topical minoxidil, and anthralin. For adults with less than 50% scalp involvement, the first option is usually the use of intralesional corticosteroids, followed by topical corticosteroid creams, minoxidil solution, or anthralin cream. For adults with more than 50% scalp involvement, topical immunotherapy and phototherapy are added to the other options. Other modalities such as cyclosporine, tacrolimus, interferon, dapsone, and cosmetic coverups are also discussed.
Wir untersuchten an unserem stationären Patientenkollektiv, in wieweit die antipsoriatische Wirkung des Dithranols durch Kombination
mit einem externen Retinoidpräparat (Tazaroten) verstärkt werden kann. In einer randomisierten, offenen, prospektiven Studie
untersuchten wir an 50 Psoriatikern (22 Frauen, 28 Männer, PASI>10) die antipsoriatische Effizienz einer externen Dithranol/Retinoid-Kombination
im Vergleich zu einer Dithranol-Monotherapie. Hierbei zeigte sich nach 4 Wochen die Dithranol/Retinoid-Kombination (Kollektiv
2, Rückgang des PASI von 17,2 auf 2,8) der Dithranol Monotherapie (Kollektiv 1, Rückgang des PASI von 18,5 auf 4,8) als signifikant
überlegen. Dieser Unterschied ist bereits nach 1 Woche nachweisbar und läßt sich sonometrisch quantifizieren. Das Irritationspotential
der Kombination (gemessen an einem klinischen Score und an der periläsionalen Hautperfusion mittels Laser Doppler Imaging)
war gegenüber dem monotherapeutischen Dithranolansatz gesteigert. Die antipsoriatische Wirkung von Dithranol läßt sich durch
Kombination mit einem externen Retinoidpräparat (Tazaroten) steigern.
We examined wether it is possible to increase the antipsoriatic action by combining dithranol with a retinoid (tazarotene).
In a randomized, open, prospective study with 50 psoriatic patients (22 females, 28 males, PASI>10) the antipsoriatic effectiveness
of dithranol monotherapy to was compared combined therapy with dithranol and retinoid. The combination dithranol/retinoid
(collective 2, reduction of the PASI from 17,2 to 2,8) revealed a significantly faster healing than the dithranol monotherapy
(collective 1, reduction of the PASI from 18,5 to 4,8). The irritation of the combination therapy as evaluated with clinical
score and laser doppler imaging was increased. Anti-psoriatic effectiveness of dithranol can be increased by combining it
with tazarotene.
Das seborrhoische Ekzem ist eine pathogenetisch ungeklärte erythematosquamöse Hauterkrankung mit einer Prävalenz von etwa
2,5%. Die häufig schwierig zu behandelnden Hautveränderungen sprechen gelegentlich gut auf die topische Applikation niedriger
Dosen von Dithranol an, einer Substanz, die jedoch als unerwünschte Wirkung abhängig von verwendeter Konzentration und individueller
Empfindlichkeit eine pustulöse Dermatitis auslösen kann. Wir berichten über das Auftreten einer pustulösen Dermatitis nach
Anwendung eines fälschlich 50fach zu hoch konzentrierten Dithranolpräparates der magistralen Rezeptur bei einem 30jährigen
Patienten mit seborrhoischem Ekzem.
Seborrhoic dermatitis is an erythemato-squamous condition of unknown etiology with a prevalence of approximately 2.5%. Frequently
difficult to treat, it may respond to the application of low doses of dithranol, a substance which can induce a pustular dermatitis
as an adverse side effect depending on the applied concentration and individual susceptibility. We describe a pustular dermatitis
after the application of a preparation containing dithranol at an erroneously high concentration in a 30-year-old patient
with seborrhoic dermatitis.
A 4-year-old, otherwise healthy white girl was referred for a 15-month history of alopecia areata. Anthralin 0.1% cream was prescribed for the left side of the scalp, while corticosteroids for the right side. After 4 months, only the right side of the scalp showed hair regrowth. Half-side strategy, that is, treating one side and managing the other--divided by the mid sagittal suture--as an internal control for no treatment, placebo or other treatment, has been commonly used in clinical studies for decades. In everyday practice, bilateral treatment is useful to evaluate the responsiveness to two topically delivered interventions and diminishes the time necessary to identify an effective one.
There have been various controversial reports regarding the efficacy of topical agents in topical therapy of alopecia areata.
The study aims to find out the effective ones among the readily available ones for a dermatologist.
Eighty patients were chosen from the skin OPD of Bankura Sammilani Medical College, Bankura, West Bengal, after evaluating the exclusion criterions. Treatments were continued for 3 month period and a follow up after further 3 months. After dividing them into four groups-group-I (topical steroids), group-II (topical tretinoin 0.05%) group-III (dithranol paste 0.25%), and group-IV (white soft petrolatum jelly)-patients were evaluated.
Seventy percent of group-I, 55% of group-II, 35% of group-III, and 20% of the control group (white soft petrolatum jelly) responded favorably. Side effects in the form of dermatitis and hyperpigmentation were seen in group-III. However, no patient discontinued from the study.
We conclude that both topical steroids and tretinoin were fairly effective in limited variant of alopecia areata.
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.
The aim of the study was to determine the position of dithranol in the treatment strategy for psoriasis.
All juvenile patients receiving dithranol treatment at our center were evaluated retrospectively.
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.
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.
Evidence-based recommendations for therapeutic decision making in childhood psoriasis are lacking.
We sought to systematically review all available literature concerning treatment efficacy and safety in childhood psoriasis and to propose a recommendation for topical and systemic treatment of childhood psoriasis.
Databases searched were PubMed, EMBASE, and the Cochrane Controlled Clinical Trial Register. All studies reporting on efficacy and safety of all treatment options in childhood psoriasis were obtained and a level of evidence was determined.
Literature search revealed 2649 studies, of which 64 studies met the inclusion criteria. The majority of topical and systemic therapies given in childhood psoriasis are efficacious. Short-term side effects were usually mild; long-term side effects were not described.
Most conclusions formulated are not based on randomized controlled trials.
A rough summary of the proposed algorithm is as follows: first, calcipotriene with/without topical corticosteroids, followed by dithranol. Methotrexate is considered to be the systemic treatment of choice.
The results reported in connection with previously published data suggest the importance of increased lipid peroxidation in the epidermis after Dithranol treatment. Malonaldehyde, one of the main products of lipid peroxidation, reacts with epidermal phosphofructokinase and glucose-6-phosphate dehydrogenase to cause enzyme inactivation by cross-linking of the enzyme protein demonstrated by dodecyl sulphate electrophoresis. Enzyme inactivation leads to an inhibition of hexose monophosphate shunt and glycolysis. The effect on energy donating metabolism in psoriatic lesions is discussed.
We attempted to induce hair growth in patients with alopecia areata by producing an inflammatory nonallergic dermatitis. Anthralin (dithranol) in 0.2% to 0.8% concentrations is known to induce irritant dermatitis without serious side effect. This report concerns 32 patients with alopecia areata who were advised to apply anthralin as often as necessary in order to induce a visible but tolerable dermatitis. The positive and cosmetically good results have encouraged us to continue anthralin treatment, as it is well tolerated by patients and free of serious side effects. It appears to be more effective than topical corticosteroids, as some of our patients were unsuccessfully treated with these preparations before anthralin therapy. However, marked erythema with mild itching is necessary for effective therapy. Our results suggest that anthralin treatment may be useful in cases of alopecia areata with patchy hair loss and cases of alopecia totalis with recent hair loss.
The rate of relapse after dithranol therapy is significantly less that when betamethasone valerate under occlusion is combined with ditrhanol in the treatment of psoriasis. It is also argued that local steroids are inferior to deithranol in the management of psoriasis.
Anthralin is an effective topical treatment for active psoriasis; however, its mechanism of action is unknown. Both TGF-alpha and its receptor, the EGF receptor, are overexpressed in active psoriatic plaques and might, therefore, play a role in psoriatic epidermal hyperplasia. In order to assess whether anthralin might act via alteration of this growth factor pathway, we examined the in vitro effects of pharmacologic concentrations of anthralin on cultured normal human keratinocytes. Keratinocyte proliferation was inhibited by 98% at an anthralin concentration of 10 ng/ml. In contrast, lymphocyte proliferation was inhibited by only 50% at an anthralin concentration of 10 micrograms/ml. Anthralin treatment did not induce cell-cycle-specific growth arrest as assessed by flow-cytometric analysis of acridine-orange-stained keratinocytes. Northern analysis of anthralin-treated keratinocytes demonstrated a marked decrease in TGF-alpha mRNA expression. Anthralin-treated keratinocytes showed decreased binding of 125I-EGF and 125I-IGF-I to their respective receptors, but EGF receptor binding was inhibited to a greater extent. Anthralin decreased ligand-binding affinity and cell-surface numbers of EGF receptors as assessed by Scatchard analysis of 125I-EGF binding to anthralin-treated keratinocytes. These results indicate that anthralin alters components of the EGF receptor pathway in cultured keratinocytes and that these effects might contribute to the clinical efficacy of anthralin in the treatment of active psoriasis.
Anthralin is a well-established and widely used compound for topical treatment of psoriasis. In recent years attention has been focused on the anti-inflammatory properties of anthralin, with particular reference to psoriasis. In this study the effect of anthralin on human monocyte chemotaxis, superoxide-anion generation, and enzyme degranulation, were investigated. For comparison, the effect of the clinically inactive anthralin derivative danthrone and the solvent (acetone) were also studied. The results show that anthralin potently inhibits stimulated human monocyte superoxide-anion generation and enzyme degranulation, with a half-maximal inhibitory concentration (IC50) of as low as 0.02 micrograms/ml. Chemotactic migration of monocytes, however, was only affected when very high doses of anthralin (10 micrograms/ml) were used for pretreatment of the cells. Danthrone, up to a concentration of 10 micrograms/ml, or acetone alone (0.1%, v/v), did not inhibit the monocyte functions tested. Our results indicate that anthralin at pharmacological concentrations is a potent and selective inhibitor of human monocyte pro-inflammatory activities, by inhibiting respiratory burst activity (e.g. superoxide-anion generation) and enzyme degranulation, without affecting chemotactic migration.
An assessment was made in healthy skin of dithranol erythema caused by a 10-min occlusive application of 0.5% dithranol (CAS 1143-38-0) in liposomal gel (Natipide II) with and without the addition of 3% salicylic acid, and of 0.5% dithranol in vaseline and in a removable standard ointment base, both with 3% salicylic acid. Both liposomal preparations led to a significant potentiation of the dithranol erythema. The results indicate a strong promotion of the penetration of dithranol by the liposomal gel.
The effects of dithranol and its therapeutically inactive oxidation product, danthrone, on 12(S)-HETE binding to the human epidermal cell line SCL-II were studied. Dithranol (0.25-1 microgram/ml), in contrast to danthrone, induced a substantial decrease in 12(S)-HETE binding in a dose-dependent manner. The inhibition occurred after a latency period of 6 h, reached its maximum at 18-24 h and slowly declined thereafter. At a concentration of 1 microgram/ml, the drug led to an approximately 50% decrease in the number of specific high-affinity 12(S)-HEFE receptors (Bmax), whereas receptor affinity (Kd) showed no change. The down-regulation of 12(S)-HETE receptors on epidermal cells by dithranol may contribute to its antipsoriatic action.
Eugen Galewsky (1864-1935), dermatologist in Dresden, introduced 1,8-dihydroxyanthrone (Cignolin, Dithranol) for therapy of psoriasis. He intended to substitute Chrysarobin, a synthetic product, which causes strong discolouring and irritation of skin. In 1916 the firm Farbenfabrik Bayer, Leverkusen, obtained a patent for synthesis of 1.8-dihydroxyanthrone by an inexpensive method. There is a reason to believe that the brother of Eugen Galewsky, the chemist Paul Galewsky, was a co-worker to the Farbenfabrik Bayer and that he recommended his brother Eugen testing Cignolin. Even now Cignolin is still used in the treatment of psoriasis.
Clobetasol-17-propionate (CP) and crude coal tar (CT) have an anti-inflammatory potential. Both agents have been advocated to suppress irritation of the skin during dithranol treatment. The effect of CP and CT on dithranol-induced irritation was studied by the assessment of erythema and measurement of alkaline phosphatase (ALP) as a direct reflection of the metabolic activity of the endothelial cells. Dithranol was applied for 2 h in the relatively high concentration of 10%, which resulted in a marked inflammation of the skin in all volunteers. Neither CP nor CT influenced the erythema. In contrast, CP and CT had a synergistic effect on the dithranol-induced induction of ALP. In conclusion, the present study indicates that CP and CT are not indicated for the treatment of dithranol-induced irritation.
Rapid clearing of psoriasis in a psoriasis treatment center setting has been obtained with a combination of short-contact coal tar, phototherapy from high-pressure metal halide lamps (consisting of UVA and UVB), and short-contact high-potency anthralin therapy. These intensive 1 1/2- to 2-hour treatment sessions done three or four times weekly were as efficacious as reported responses to PUVA therapy or conventional psoriasis day care therapy. The treatment schedule allows minimal time away from work, decreased hours per week in contact with crude coal tar, shortened UV treatment times, decreased cost, and a low risk of side effects. It is suggested that the use of UVA and UVB combined with anthralin (UVABA) is effective for many patients with moderate to severe psoriasis.
Inflammatory linear verrucous epidermal nevus (ILVEN) is a rare and chronic skin disorder, which may trouble the patient considerably. The condition is generally believed to be resistant to therapy, although some authors have reported success with several treatments. including dithranol and etretinate. The present case, a classical presentation of ILVEN, again illustrates the refractoriness to various treatments, including an experimental treatment with topical 13-cis-retinoic acid. A review of the literature on therapeutic possibilities of ILVEN is presented. Based on our own observations and literature data, it is attractive to hypothesize that a positive result with treatments such as dithranol and retinoids should be interpreted as an antipsoriatic effect in ILVEN with superimposed psoriasis.
Combination therapy with 5% minoxidil plus 0.5% anthralin was used to treat 51 patients with severe treatment-resistant alopecia areata. History of a cosmetically inadequate response to one or both drugs used as a single agent was present in 50 of the 51 patients. Therapy was relatively well tolerated except by 1 patient who developed a severe irritant reaction and was dropped from the study. Mild to moderate irritant dermatitis was seen in all remaining patients. Cosmetic response was seen in 5 (11%) of 45 patients who completed the 6-month study. Cosmetic response was maintained in 4 (80%) of 5 patients who continued treatment for as long as 84 weeks. All responders had evidence of hair regrowth by week 12. The rapidity and extent of hair regrowth were greater with combination therapy than with either drug used as a single agent. Serum and 24-hour urinary minoxidil determinations showed enhanced systemic minoxidil absorption, which was probably secondary to the irritant dermatitis in some patients; however, no clinical evidence of a systemic minoxidil effect was found. These data suggest that combination therapy using drugs with probable different mechanisms of action may provide a synergistic effect in alopecia areata.
Twenty patients with chronic plaque psoriasis were treated with short-contact anthralin followed by 10% triethanolamine application to one side of the body and aqueous cream to the other. Anthralin-induced inflammation was inhibited on the triethanolamine-treated side whereas anthralin therapy had to be temporarily stopped in 18 patients on the aqueous cream side because of anthralin-induced inflammation. Therapeutic response was not different in the two sides. This study shows that anthralin-induced inflammation and its therapeutic effect can be dissociated.
Thirty patients having mosaic warts of the soles for 2 years (range 3 months-6 years) were treated daily with a wax-based anthralin stick supplemented by weekly paring. Six patients dropped out, because they failed to appear for follow-up. Of the remaining patients 17/24 cleared, whereas the warts persisted in 7/24. Although the trial was an open study, this result can hardly be explained by placebo effect since mosaic warts are notoriously resistant to treatment.
Results of an anthralin stain removal study on white 65% polyester/35% cotton, white 100% polyester, white 100% cotton, a white shower curtain, white tile with crevice, and white ceramic shower tile are reported. An optimum stain removal technic was developed by using a 10-minute soak in full-strength chlorine bleach (Good Measure or Clorox) followed by a water rinse and air drying. This technic completely removed all stains of 24-hour duration from the test fabrics. The stain removal test on shower curtains, floor tiles, and ceramic shower tiles was also discussed.
Membrane-associated thioredoxin reductase (TR) activity has been measured in 3-mm punch biopsy specimens from psoriatic and uninvolved skin in eight patients with chronic plaque-type psoriasis vulgaris. The mean specific activity for this free radical reducing enzyme in psoriatic vs uninvolved skin was 28.5 +/- 8.0 U vs 16.8 +/- 4.25 U. Because TR contains two reactive thiolate groups at its active site, this enzyme reacts with anthralin to form a covalent anthralin-TR complex causing irreversible enzyme deactivation. This mode of action for anthralin was confirmed by using pure TR from Escherichia coli. Keratinocyte cell cultures, grown from normal and psoriatic skin of one donor, revealed 24% and 42% inhibition of cell surface TR activity, respectively, in the presence of 2 X 10(-5)M anthralin. Time-dependent topical application of anthralin on guinea pig skin gave 70% inhibition of TR with concentrations of 0.25% to 1.0% after 24 hours in open and occlusive applications of the drug. Short contact with 1% anthralin showed 70% inhibition after 120 minutes.
A case of inflammatory linear verrucous epidermal nevus (ILVEN) is reported. Short contact treatment with dithranol resulted in complete relief from itching and a remarkable clearing of all linear lesions except from a small verrucous band on the shin. In patients with ILVEN it is advisable to try dithranol therapy before carrying out surgical procedures such as excision, cryotherapy, electrocautery. The prompt response to dithranol is best explained by the assumption that most of the lesions in this case of ILVEN represented true linear psoriasis.
Dithranol (anthralin) is one of the basic compounds used in the treatment of psoriasis vulgaris. However, in outpatients its use is largely restricted as it may cause discoloration of skin, clothes, and bedding as well as significant skin irritation. The combination of dithranol with urea results in a better benefit/side-effect ratio. Even at relatively low dithranol concentrations (0.1%/0.2%) combined preparations have been found to be effective over several weeks of application. The therapeutic results of such treatment are comparable to those of topical glucocorticosteroid preparations.
This report describes the successful treatment of facial seborrheic dermatitis with a low-dose dithranol preparation. The results of a pilot study involving 18 outpatients are presented.
The effect of anthralin and its oxidation products danthrone and anthralin-dimer on the production of 5-lipoxygenase products (5-HETE, leukotriene B4, omega-oxidized LTB4) by Ca-ionophore A 23187-stimulated human neutrophils has been studied in vitro. Anthralin exhibited dose-dependent inhibitory activity showing 50% inhibition at 7 microM with 10(7) neutrophils. Inhibitory effects strongly depended upon cell densities and maximal inhibition occurred at low cell concentrations, whereas inhibitory rates of anthralin were low at high cell densities. Inhibition of leukotriene production persisted after washing of anthralin-treated neutrophils. Also, with increasing amounts of arachidonic acid as substrate only slight changes of inhibitory activity were detected, indicating a noncompetitive way of action. In addition to the inhibition of leukotriene-production, the formation of omega-OH-LTB4 from LTB4 as well as omega-COOH-LTB4 from omega-OH-LTB4 was inhibited with IC50 (half maximum inhibition concentration) near 4.4 microM and 2.2 microM, respectively. In contrast to anthralin, both metabolites--danthrone as well as anthralin-dimer--did not show any effect on leukotriene production and omega-oxidation even at high concentrations (up to 70 microM and 44 microM, respectively).
This study reports the results of the Ingram dithranol regimen for the treatment of psoriasis in 275 inpatients. The median duration of hospitalization until clearance was 25 days and the medians of the interval until a next treatment or hospitalization was needed were 11 and 8.5 months, respectively.
Anthralin cream 0.5% to 1.0% was used to treat 68 patients with severe alopecia areata. Therapy was relatively well tolerated, although all patients experienced pruritus and local erythema and scaling. Cosmetic response was seen in 17 (25%) of the patients, and was maintained during therapy in 12 (71%) of the 17 cosmetic responders. For the patients treated with 0.5% anthralin, the mean time to response (44 of 66 patients) was 11 weeks; the mean time to cosmetic response (13 of 66 patients) was 23 weeks. Duration of the current episode of hair loss did not correlate with cosmetic response. Compared with other currently available topical treatments, anthralin appears to be a reasonable therapeutic option for severe alopecia areata.
In 44 patients with chronic plaque psoriasis anthralin therapy was used as high-strength short-contact therapy in a bilateral comparison of anthralin versus 5% crude coal tar-anthralin combination. These two trials were undertaken with and without ultraviolet (UV) irradiation immediately after anthralin therapy. The combined tar-anthralin therapy was significantly less of an irritant during the first 3 weeks of treatment than anthralin alone, and it did not decrease the antipsoriatic efficacy. The use of UV irradiation, either with anthralin or tar-anthralin combination, did not produce an additional therapeutic effect. These findings lead us to prefer combined tar-anthralin therapy because of its lower irritancy in comparison with anthralin alone and they show the ineffectiveness of additional UV irradiation under the conditions of this study.
Application of 1% potassium hydroxide (KOH) reduced subsequent development of anthralin inflammation without loss of its therapeutic effect on psoriasis. Teepol had a similar but smaller effect on subsequent development of inflammation. The action of KOH appears to have resulted from enhanced oxidation of anthralin to inactive products and the action of Teepol to have increased anthralin solubility and removal. The effect of KOH and Teepol decreased with time after anthralin application and both were ineffective by 24 h, indicating that anthralin persists on the skin in an active form for up to 24 h after a single application. The reduction of anthralin inflammation without loss of therapeutic effect is potentially useful in short contact anthralin therapy.
Topical anthralin application producing a brisk irritant contact dermatitis has been reported to have therapeutic benefit in alopecia areata. A pilot clinical study was undertaken to determine whether topical anthralin application in doses low enough to produce only minimal contact dermatitis would produce a similar therapeutic response. None of the patients in the study received any benefit from this low-dose regimen. If anthralin is of benefit in the therapy of alopecia areata, a significant irritant contact dermatitis is apparently required.
The inflammatory dose-response to anthralin was measured in human skin 24 h after pretreatment with topical corticosteroids and anthralin, and 48 h after removal of the stratum corneum with adhesive tape. Anthralin inflammation was increased after 1% hydrocortisone application and decreased by 0.1% betamethasone valerate and 0.05% clobetasol propionate; although the difference between these effects was not significant, the difference between the effect of hydrocortisone and clobetasol propionate was. Anthralin inflammation was not significantly affected by pretreatment with anthralin and was reduced, although not significantly by removal of the stratum corneum. The finding that anthralin inflammation is not altered in skin in which aryl hydrocarbon hydroxylase (AHH) activity is increased and that anthralin inflammation may be altered in situations in which AHH activity is unchanged, excludes a direct relationship between anthralin inflammation and AHH activity.
The effect of topical clobetasol propionate and a 1% topical indomethacin gel which could inhibit UV erythema was measured on anthralin inflammation by change in skin-fold thickness and erythema. The time course of the inflammatory oedema and erythema were different, as was their response to the drugs studied. The oedema of anthralin inflammation was completely inhibited by clobetasol propionate but the erythemal response showed a small and non-significant reduction. Indomethacin had no effect on anthralin oedema but produced a small but significant reduction in erythema in the first 24 h after anthralin application. These results suggest that either anthralin inflammation is not due to production of prostenoids, or that if it is, it occurs by other than the classical enzymic pathway.