Dithranol

Uses

Dithranol is used for subacute and chronic psoriasis.

Dithranol is also used to associated treatment for these conditions: Psoriasis Chronic, Quiescent Psoriasis

How Dithranol works

Dithranol inhibits the proliferation of keratinocytes (epidermal skin cells), prevents the action of T-cells, and promotes cell differentiation, likely through mitochondrial dysfunction. In addition, the production of free radicals may contribute to its anti-psoriatic effect . In vitro studies demonstrate that anthralin prolongs the prophase component of mitosis for keratinocytes and leukocytes . Prophase is the first step of mitosis, the process separating the duplicated genetic material carried in the nucleus of a parent cell into two identical daughter cells . In vivo studies demonstrate that anthralin blocks DNA synthesis and can increase the release of reactive oxygen species .

Dithranol is believed to normalize the rate of epidermal cell proliferation and keratinization by reducing the mitotic activity of the epidermal hyperplasia in psoriasis .

Anti-proliferative and anti-inflammatory effects of anthralin have been demonstrated on both psoriatic and healthy skin. The anti-proliferative effects of anthralin are thought to be due to a combination of inhibition of DNA synthesis and its strong reducing properties. The effectiveness of anthralin as an anti-psoriatic agent is partly owed to its ability to promote lipid peroxidation and reduce the concentration of endothelial adhesion molecules, which are found to be elevated in psoriatic patients , .

Recent studies suggest that its ability to prevent T-lymphocyte activation and normalize keratinocyte differentiation may occur by a direct effect on mitochondria .

Dosage

Dithranol dosage

Short-contact therapy: As cream: Apply into lesions for up to 60 min/day before washing off. May increase strength gradually from 0.1-2%.

Side Effects

Burning sensation esp on perilesional skin, temporary staining of skin and hair; skin irritation and/or warmth feeling on application site.

Toxicity

Some mild adverse effects include alterations in nail coloring, hair coloring, increase in photosensitivity, and skin irritation .

The most common side effects of anthralin are skin irritation and staining of nearby skin, nails, clothing, and other objects that come in contact with the treated patient. The incidence of irritation of psoriatic/surrounding healthy skin is higher in patients who leave anthralin on the skin without rinsing than in those who use short-contact therapy of 2 hours or less, followed by rinsing .

If the psoriatic plaques are well circumscribed, the surrounding normal skin may be protected by the use of a coating agent such as zinc oxide ointment. Dithranol should be applied cautiously to the face and intertriginous areas due to the risk of severe skin irritation .

There is no current evidence of any long-term anthralin toxicity related either to skin exposure or to systemic issues . Some long-term studies in mice have demonstrated anthralin to be tumorigenic in mouse skin. This carcinogenic potential has not been thoroughly evaluated. Tumorigenic and carcinogenic effects of anthralin have not been observed in humans at this time . Dithranol is classified as FDA pregnancy risk category C drug . It is not known if anthralin can cause fetal harm when administered during gestation. Because of the lack of evidential human data, anthralin should be used during pregnancy only when clearly required .

Precaution

Patient with fair skin. Children. Pregnancy and lactation.

Interaction

May enhance the effect of photosensitising drugs. Propylene glycol-containing drugs may oxidise or inactivate dithranol. Withdrawal of long term steroids in psoriasis may cause rebound phenomenon.

Food Interaction

Elimination Route

Dithranol penetrates damaged skin and psoriatic lesions faster and to a greater extent than normal skin, likely due to increased vascularity of psoriatic lesions .

Pregnancy & Breastfeeding use

Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Contraindication

Acute pustular psoriasis or inflamed skin.

Acute Overdose

Symptoms: Burning and deep staining of the skin.

Management: Rinse first with water only and then wash at a temp not exceeding 30° C.

Storage Condition

Store between 15-30°C. Protect from excessive heat.

Innovators Monograph

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