Squaric acid dibutylester or SADBE is a contact sensitizing agent used to treat alopecia areata

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  Squaric Acid Dibutylester (SADBE) for Alopecia Areata

Contact sensitization is one of the therapies, which have been used for treating alopecia. In this mode of treatment, topical sensitizers are applied to the affected scalp area to promote hair growth. A typical treatment begins with the application of a predetermined concentration of the medication on the scalp to get an allergic response such as itching and scaling, which eventually leads to hair growth. A successful response is usually obtained in 3 to 12 months.

It is important to note that contact sensitizers do not work by suppressing or slowing down hair growth but by promoting, cosmetically acceptable hair growth. Contact sensitization is a type of immunotherapy, directed at hair regrowth.

Squaric Acid Dibutylester

Squaric acid dibutylester or SADBE is one of the three major contact sensitizers, which have been used for alopecia areata therapy. The other two are dinitrochlorobenzene or DNCB and diphencyprone or DPCP. Although efficacy of DNCB ranges from 25% to 89%, it was found to be mutagenic in the Ames test and is therefore rarely used now. SADBE is used in those patients who become tolerant to DPCP.

How these contact sensitizers work is not clear but it is speculated that it could be antigen competion. The contact sensitizers divert the attention of the inflammatory cells to themselves, thus making them move away from the hair follicles. This results in either removal of the supposed offending antigen or inhibition of the immune action on hair follicle antigens. Studies showing a relative increase of OKT8+ cells in the peribular infiltrate follicles of patients, treated with contact sensitizers, support such views.

One view holds that the contact sensitizers work by altering the T-helper/T-suppressor ratio. However, in one study no specific changes were found in the lymphocyte subsets of patients treated with SADBE, but an increase in the number of infiltrating T-helper cells was observed.

Squaric acid dibutylester has been found to be effective in both humans and mice. In a clinical trial on mice, with alopecia areata, a contact dermatitis was established by treating them with SADBE. In nine of the twelve mice under trial, there was hair growth on the treated area. In another clinical trial, squaric acid dibutylester was dissolved in acetone and applied weekly to one side of the head of patients with extensive alopecia areata. 46 or 86% of the patients had hair growth on the treated side. The growth was exclusive, denser and quicker on the treated side in comparison to the growth on the untreated side. A persistent response was noted in 70% of the cases.

A study was done on 28 children, under 13 years of age, who had extensive and long-standing alopecia areata, and did not respond to conventional treatment. These children were sensitized to 2% SADBE in acetone and treated weekly for twelve months. Nine patients or 32% achieved complete or cosmetically acceptable hair growth.

In a more recent study, the effects of long-term topical immuno therapy on children, with extensive alopecia areata was examined. In this study, 33 children with alopecia totalis or universalis were treated for one year. Complete hair growth was seen in 10 children. During the follow up period, of a mean time of five to nine years, 7 of these 10 children suffered a severe relapse.

Patients are usually sensitized to SADBE by an application of a 2% solution in acetone to an area on the scalp or the upper arm. After a 2-week delay to limit unnecessary irritation caused by the addition of the elicitation dose to the persistent sensitization one, a dilute concentration of 0.0001% to 0.001% SADBE is applied. The dose is adjusted weekly to find a reaction of minimal erythema without discomfort.

Hair growth is usually observed, 8 to 10 weeks after commencement of treatment. The frequency of treatment can be reduced later until complete hair growth is observed and eventually treatment may be stopped. In case of a relapse, after discontinuation of treatment, the treatment should be restarted immediately to arrest growth of alopecia areata and induce hair regrowth.

Generally, in the initial phase, topical sensitizers are applied to one half of the affected area, the other half being left untreated. Such a step allows the untreated half to be used as a control, enabling better interpretations of the treatment outcome. Once there is regrowth in the treated half, treatment can be extended to the entire affected area. There is a likelihood of spontaneous remission, if hair growth occurs on the treated as well as the untreated side. But the chances of the observed growth, being a genuine hair regrowth, cannot be ruled out.

Success Rate

With a median response rate of 43%, the success rate of SADBE compares well with other therapies. The variation in the success rate reported could be due to different parameters used to measure success in different studies. In the treatment of alopecia areata by contact sensitizers there are three factors which indicate negative prognosis. These are degree of scalp involvement before treatment, duration of the disease before commencement of treatment and nail abnormalities.

Side Effects

According to some reports, apart from mild acute or sub acute effects, which are given below, no long term side effects have been reported after 21 years of treatment with SADBE.

However, using contact sensitizers like SADBE has an inherent disadvantage. They are likely to produce a vigorous allergic response. Some of the side effects include:

  • Pruritis or severe itching
  • Severe contact dermatitis
  • Abnormal enlargement of the lymph nodes
  • Erythema or redness of the skin
  • Vitiligo or leukoderma


Finally, it must be noted, that none of the three contact sensitizers, SADBE included, have been subjected to rigorous test for stability, purity, absorption, metabolism, excretion and toxic effects. They have not received FDA approval. SADBE, though, found non-mutagenic in the Ames test and clinically seemingly effective, is not as commonly used as DPCP, as it is reportedly unstable in acetone. Although, SADBE has shown a good response rate of 43%, its long-term efficacy is still to be properly evaluated.

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