Anthralin Therapy Research Articles

Evolution of Topical Therapy in the Treatment of Psoriasis: A Review

Major developments in topical therapy for psoriasis have taken place since 1500 B.C. Older methods such as coal tar and anthralin therapy are effective but less popular given difficulty of use. Topical steroids were a revolutionary development for psoriasis. However, they are limited in use due to local and systemic side effects. Non-steroidal topical agents are less efficacious than super-potent topical steroids but have a more favorable side effect profile. Combination medications, such as betamethasone/calcipotriene agents, allow the agents to act synergistically for psoriasis management, while maintaining a safe side effect profile. We recommend a sequential strategy when using a newer combination agent to maximize efficacy and safety, and increase patient compliance.

Fluorescence remission spectroscopy of psoriatic lesions and the effect of topical anthralin therapy

Psoriatic lesions are characterized by induration, scaling and erythema. Erythema is a result of inflammation and increased microvascular blood flow. Anthralin is the strongest topical antipsoriatic drug that causes clearing of psoriatic lesions and temporary remission. The objective evaluation of skin perfusion might be a suitable way to gain a better insight in the pathophysiological process of this disease and to evaluate the response to antipsoriatic anthralin therapy. We evaluated 21 psoriatic lesions (plaques, patches and pinpoint lesions) including 4 lesions in remission with anthralin induced erythema and 4 controls of healthy, uninvolved skin. We performed the measurements with a combined fluorescence and remission imaging (FRIS). The FRIS sensor is coupled with a touch screen industrial computer. The equipment consists of a white-light halogen lamp (20 W), two VIS-spectrometer modules (Zeiss) for remission detection and references. Imaging is realized by CCD-colour camera module and white light ring-lighting. Fluorescence emission was realized using an ultraviolet LED with a wavelength of 370 nm. The fluorescence detector is a highly sensitive MCS CCD (Zeiss) with an integration time of 2.5 sec. Spectral remission of psoriatic skin is characterized by a pronounced decrease (60-80%) of the haemoglobin double-peak compared to uninvolved skin. The NADH-fluorescence is diminished in lesional psoriatic skin including anthralin-treated areas with clinical remission. Vascular perfusion is increased in psoriatic lesions as demonstrated by remission spectroscopy. NADH-fluorescence is reduced in lesional psoriatic skin and in anthralin-induced erythema. FRIS is a suitable tool for objective evaluation of the cutaneous response to antipsoriatic treatment.

Alteration of the Expression of Bcl-2, Bcl-x, Bax, Fas, and Fas Ligand in the Involved Skin of Psoriasis vulgaris following Topical Anthralin Therapy

Anthralin (dithranol) is frequently used for the treatment of psoriasis. However, the mode of action of anthralin has not been completely elucidated as yet. Recent findings suggest that psoriatic keratinocytes are resistant to the apoptotic process. In this study, we examined the immunohistochemical expression of apoptosis-regulated protein in the involved psoriatic skin following topical anthralin therapy. Biopsy specimens were obtained from back skins treated with topical anthralin or white petrolatum (control) in 4 patients with psoriasis vulgaris. Immunohistochemical examination revealed that psoriatic keratinocytes expressed high levels of Bcl-x, which was significantly reduced after anthralin treatment. Bax was not detected in the epidermal keratinocytes in the petrolatum-treated skin, while it was present in the upper keratinocytes after anthralin therapy. Bcl-2 was detected only in basal layers of psoriatic epidermis following both petrolatum and anthralin application. Psoriatic keratinocytes expressed higher levels of Fas in the lower epidermis, while only weak expression was detected in anthralin-treated plaques. On the other hand, hyperproliferative keratinocytes strongly expressed Fas ligand (FasL) on their plasma membranes as well as infiltrating lymphocytes in the upper dermis. Furthermore, anthralin-treated psoriatic epidermis did not express FasL. In normal skin, keratinocytes expressed low to absent levels of Bcl-x and Bax, while Bcl-2 was detected only in melanocytes in basal layers. Neither Fas nor FasL were detected in the epidermis of normal skin. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) staining revealed positive labeling on the majority of psoriatic keratinocytes through the epidermis in petrolatum-treated skin, whereas anthralin treatment markedly reduced TUNEL-positive keratinocytes. These in vivo results may reflect improvement of the psoriatic skin following effective anthralin therapy.

Topical anthralin for psoriasis vulgaris: evaluation of 70 Japanese patients.

In order to determine the usefulness of anthralin in the treatment of psoriasis, we evaluated the effectiveness of topical anthralin therapy in patients with psoriasis vulgaris in our hospital. Seventy patients with plaque-type psoriasis (58 men and 12 women), aged 17-79 years-old (mean; 47.6 years-old), who were treated at the Department of Dermatology, Tokyo Medical and Dental University, between 1992 and 1999, were retrospectively evaluated. Mean psoriasis activity and severity index (PASI) score before therapy was 24.6. Patients were treated with 0.1-2.0% topical anthralin. Responses were determined by clinical examination. The mean PASI score decreased to 8.7 after three months. The most effective anthralin concentration was 0.4-0.5%. The overall response rate was 85.7%, complete remission was obtained in 21.4%, and partial remission in 64.3%. Ten patients (14.3%) were anthralin-resistant. In all patients who entered complete remission, recurrence was noted within six months after stopping anthralin. Minor skin irritation and pigmentation occurred in most of the patients; however, no severe side effects were noted during the treatment. Our study indicated that anthralin is effective for chronic plaque-type psoriasis.

Current status and recent developments in anthracenone antipsoriatics.

Treatment of psoriasis is rapidly changing, and there have been dramatic additions such as topical vitamin D analogs and a topical retinoid to the therapeutic armamentarium in recent years. Even though drug therapy is often inadequate and serves only to abate the skin disorder, anthralin of the anthracenone antipsoriatics clears the rash totally. Of all antipsoriatic agents, anthralin has proven to be the most remarkably consistent and time-honored drug for treating the disease. However, anthralin therapy is accompanied by inflammation and staining of the nonaffected skin surrounding a psoriatic lesion. A large body of evidence has shown that the biochemical basis for its mechanism of action at the molecular level is related to its redox chemistry leading to the production of oxygen radicals. These can react with all classes of biological macromolecules and are involved in the principal cellular effects of the anthracenones. This article will focus on current strategies to minimize the potential of skin inflammation by anthralin and the underlying concepts of controlling and manipulating oxygen-radical generation which are essential for the rational design of novel anthracenones. Various studies have shown that by altering the structure of anthralin the in vitro profile can be markedly altered from an only moderate 5-lipoxygenase inhibitor to a more potent inhibitor of this enzyme, which may reflect improved activity against the inflammatory component of psoriasis while the antiproliferative activity is retained. The structural change is also accompanied by significantly diminished oxygen-radical generation and proinflammatory action on the skin. In particular, derivatives bearing a phenylacyl substituent in the critical 10-position of the anthracenone molecule have a favorable overall profile for achieving improved topical therapy of psoriasis.

Detection of human papillomavirus DNA in keratoacanthomas by polymerase chain reaction.

The etiology of keratoacanthomas is unknown, but human papillomavirus (HPV) has been suspected to be involved in the pathogenesis of this lesion because koilocytic changes may be observed and because HPV has been found in cutaneous squamous-cell carcinomas and premalignant keratoses in immunosuppressed patients. We analyzed DNA extracted from 39 keratoacanthomas from 22 "at-risk" patients (nine patients undergoing UV light and/or anthralin therapy for psoriasis, 10 solid organ transplant recipients, one patient with xeroderma pigmentosa, one patient with acquired immunodeficiency syndrome, and one patient undergoing therapy for non-Hodgkin's lymphoma) for the presence of HPV. The results were compared with analyses of DNA extracted from 30 keratoacanthomas from 28 patients at no known increased risk for these lesions. Using polymerase chain reaction (PCR) primers designed to detect multiple HPV types (including 6, 11, 16, 18, 31, and 33), HPV was detected in seven keratoacanthomas from six of the at-risk patients and in eight sporadic keratoacanthomas from eight patients without risk factors. HPV was also present in one of 26 nonlesional skin controls. Statistical analysis showed a significant difference in the prevalence of HPV DNA sequences found in keratoacanthomas compared to normal control skin (p = 0.038). The presence of virus by PCR could not be predicted by histologic evaluation. Sequence analysis showed the presence of HPV types 11, 13, 24, 33, and 57. Although these results confirm the frequent presence of HPV in keratoacanthomas, the role of this virus in the etiology and pathogenesis of these lesions remains to be elucidated.

UVABA therapy for psoriasis: Efficacy with shortened treatment times with the combined use of coal tar, anthralin, and metal halide ultraviolet machines

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.

The effect of triethanolamine application on anthralin-induced inflammation and therapeutic effect in psoriasis

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.

Reduction of anthralin-induced inflammation by application of amines

Twenty-two primary, secondary, and tertiary amines were studied to determine whether they could reduce anthralin-induced inflammation. Amine solutions of 0.18 mol/L were applied after anthralin application to normal forearm skin. Inflammation was measured with the use of Harpenden calipers by the increase in skin thickness at 48 hours. Inflammation was reduced by 66% to 95% with the use of nine different amines. There was no overall correlation between the inhibiting effect and either amine basicity or octanol/water partition coefficient. However, within each of the series of primary, secondary, and tertiary alkylamines there appeared to be some correlation between inhibitory effect and alkyl chain size, which may reflect differences in transdermal flux. Some of these amines are used in cosmetics and skin cleansers and could help reduce the inflammation that accompanies anthralin therapy for psoriasis.

Combined tar-anthralin versus anthralin treatment lowers irritancy with unchanged antipsoriatic efficacy: Modifications of short-contact therapy and Ingram therapy

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.

The enhanced monocyte and neutrophil chemotaxis in psoriasis is normalized after treatment with psoralens plus ultraviolet A and anthralin

The chemotactic activity of purified monocytes and neutrophils was studied in twenty-two psoriatic patients prior to the initiation of psoralens plus ultraviolet A (PUVA) or anthralin therapy and during the treatment. Patients with untreated, active psoriasis had increased chemotactic response of their monocytes and neutrophils to N-formyl-methionyl-leucyl-phenylalanine. Plasma from untreated psoriasis patients had an enhanced chemotactic activity toward neutrophils from persons without psoriasis. Treatment with PUVA or anthralin resulted in a progressive clearing of psoriatic lesions and in a significant depression of leukocyte chemotaxis 2 weeks after the start of the respective therapy. The chemotactic activity of both monocytes and neutrophils was normalized after 4 weeks of anthralin therapy and after 6 weeks of PUVA treatment. The chemotaxis-enhancing properties of plasma from psoriasis patients returned to normal values already after 2 weeks of treatment.

The release and percutaneous permeation of anthralin products, using clinically involved and uninvolved psoriatic skin

The release and permeation of 1% Westragel and 1% Westrastick and three commercial 1% anthralin products were investigated in vitro with the use of a Franz diffusion cell unit. An inert Teflon membrane with a mesh opening of 74 mu was used for measuring the rate of release. Involved psoriatic and uninvolved human skin collected from the same subjects were used for the permeation study. The permeation of danthron and dianthrone, the major degradation products of anthralin, was also studied with the use of microemulsion gels of 1% danthron and 1% dianthrone, which were prepared in the same way as 1% Westragel. The penetrating anthralin, danthron, and dianthrone were stabilized by a modified receptor fluid, and sample solutions were analyzed by a high-power liquid chromatography method. Involved psoriatic skin was found to be much more permeable to anthralin than was uninvolved psoriatic skin. The slow permeation rate of anthralin, danthron, and dianthrone through normal skin and uninvolved skin indicates that the stratum corneum is the rate-limiting barrier. In involved psoriatic skin, the release rate of anthralin from the topical product becomes the rate-determining step. Large individual variations were found in the permeation of anthralin through involved psoriatic skin, suggesting that the permeation rate of anthralin also may depend on the disease state of psoriatic patients. The anthralin molecule, possessing both hydrophilic and lipophilic centers, diffused significantly faster than did danthron and dianthrone. Westragel, 1%, showed the highest diffusion rate as well as the highest driving force when compared to other commercial 1% anthralin products. This suggests that 1% Westragel may be an optimal design, especially for short-contact anthralin therapy.

Reduction of anthralin inflammation by potassium hydroxide and Teepol.

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.

Effect of short-contact anthralin therapy on ultraviolet B irradiation of psoriasis

The influence of short-contact anthralin on the therapeutic effect of ultraviolet B irradiation (Sylvania UV-21 tubes) was investigated with the half-body comparison method in fifteen outpatients with plaque-type psoriasis. The lesions on the right or left half of the body were exposed to one of the topically applied compounds (either anthralin and 2% salicylic acid in petrolatum or 2% salicylic acid in petrolatum alone) for 10 to 30 minutes daily. Of the fifteen patients, five (Group I) were given 0.3% anthralin and five (Group II) received increasing concentrations of anthralin (0.3, 1, 3%); the other five (Group III) were patients who had failed to respond to ultraviolet B therapy alone, and for them a new clearing treatment was started with the addition of anthralin in increasing concentrations (0.3%, 1%, 3%). Only two patients in Group I, one patient in Group II, and one in Group III showed a moderately better clearance of psoriasis on the short-contact anthralin side. Irritation of nonaffected skin by anthralin was common only during the first week of the treatment. Staining of clothes and bedding occurred.

Woronoff ring during anthralin therapy for psoriasis

Woronoff ring during anthralin therapy for psoriasis

Anthralin therapy for psoriasis. A new look at an old compound

Anthralin therapy for psoriasis. A new look at an old compound

Addition of short-contact anthralin therapy to an ultraviolet B phototherapy regimen: Assessment of efficacy

The purpose of this study was to determine whether the addition of short-contact anthralin therapy to an ultraviolet B phototherapy regimen would result in more rapid resolution of psoriatic plaques. A bilateral paired comparison between an ultraviolet B phototherapy regimen with and without short-contact anthralin was completed in eleven patients. Only two of the patients responded faster on the anthralin-treated side. Our results do not support the routine addition of short-contact anthralin therapy to ultraviolet B phototherapy regimens, but this combination may be more effective in a minority of patients.

Short contact anthralin therapy of psoriasis with and without UV-irradiation and maintenance schedule to prevent relapses

A short term anthralin application schedule was used at home in 42 patients with severe psoriasis. In another group of 21 patients treated at our day care center, UV-B irradiation was added when the surplus of anthralin had been washed off. Good healing results within 3-8 weeks were noted in most patients. To prevent relapses 31 patients continued the anthralin treatment once or twice a week after healing. In 15 cases this was combined with UV irradiation. One patient relapsed after a severe infection, but 16 others were observed for 6-9 months and 14 for 3-5 months without relapses. Irritation of non-affected skin is common especially at the beginning of the treatment and some staining of clothes and linen can occur. With proper information about this, the treatment is well accepted by the patient who generally finds it reasonably simple without the need of special protective dressings.

Anthralin for psoriasis: Short-contact anthralin therapy compared with topical steroid and conventional anthralin

Anthralin is an effective topical drug for psoriasis therapy. Recent studies have suggested that anthralin may be effective in high concentrations for short periods of skin contact. The purpose of these studies was to compare psoriasis improvement rates in patients treated with 0.3% anthralin ointment for 10 minutes' skin contact daily with patients treated with a topical steroid, difluorosone diacetate. A further study conducted was a bilateral paired comparison between conventional strength (0.1%–0.5%) anthralin ointment overnight with high concentration anthralin (0.5%–3%) for short contact periods of 10 minutes daily. The results showed good responses in all treatment groups. Short-contact anthralin is confirmed as a practical means of outpatient therapy for psoriasis.

Anthralin Toxicity

A group of 40 patients was collected to study the possible existence of systemic toxicity secondary to the use of topically administered anthralin. Creatinine clearance, chemistry profile, complete blood cell count, and urinalysis performed on all patients before treatment and after one and three months of continuous topical anthralin therapy indicated no evidence of systemic toxicity in any patient. No change in renal function studies in two anthralin-treated patients with renal disease suggests that even renal disease is not necessarily a contraindication to the use of topically administered anthralin in low concentrations for treatment of psoriasis.