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Study Letter
88 (
); 845-848

Switching immune sensitizer agents in refractory alopecia areata as a valuable therapeutic strategy a retrospective case series

Department of Dermatology, University Hospital Dr. José Eleuterio González, Madero y Gonzalitos S/N Col. Mitras Centro, Monterrey, Nuevo León, Mexico
Corresponding Author: Dr. Maira Elizabeth Herz-Ruelas, Department of Dermatology, University Hospital Dr. José Eleuterio González, Madero y Gonzalitos S/N Col. Mitras Centro, Monterrey, Nuevo León, Mexico.
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Herz-Ruelas ME, Ocampo-Candiani J, Gómez-Flores M, Martínez-Rico JC, Chávez-Alvarez S, Rivera-Izaguirre BC. Switching immune sensitizer agents in refractory alopecia areata as a valuable therapeutic strategy a retrospective case series. Indian J Dermatol Venereol Leprol 2022;88:845-8.


Alopecia areata is an autoimmune hair disorder that can affect any hair-bearing region of the body. Treatments include topical, intralesional, and systemic medications.1 When considering immunotherapy, guidelines suggest using diphenylcyclopropenone, with subsequent consideration of squaric acid dibutylester in nonresponders.2

After approval by the local research and ethical committee (DE21-00004), a retrospective analysis of cases from the immunotherapy clinic database of the dermatology department at the Dr. José Eleuterio González University Hospital of the U.A.N.L., in Monterrey, Mexico was conducted. Patients who had been treated with both diphenylcyclopropenone and squaric acid dibutylester were identified. Medical records were examined and several variables were evaluated [Table 1]. Informed consent had been obtained prior to treatment. Patients were sensitized with 2% diphenylcyclopropenone or squaric acid dibutylester in a 5 cm2 alopecic patch. After eight hours the immune sensitizer was removed and the patient returned to the clinic three weeks later for treatment starting with a low concentration such as 0.001% and gradual increments according to the patient’s response and tolerance.

Table 1:: Clinical characteristics of the 10 patients from the immunotherapy clinic database
Patient # 1 2 3 4 5 6 7 8 9 10
Gender F M F F M F F F M F
Age (years) 8 10 20 17 16 35 17 8 10 47
Personal medical history Allergic rhinitis, generalised anxiety disorder - Vitiligo Allergic rhinitis - - Obesity, separation anxiety disorder, hypertriglyceridemia, hypothyroidism Atopic dermatitis Major depression Syphilis
Duration (years) 4 5 19 3 11 20 15 2 4 7
# Episodes 1 1 2 1 1 1 2 1 1 2
Clinical variant of AA AU AU AT AT AU AT AU AS AV AT
# Application treatments 72 80 41 47 44 45 18 35 49 26
# Application treatments 23 70 120 32 35 83 30 37 39 35
SALT score prior to primary sensitizer S5 S5 S4 S4 S5 S5 S5 S4 S2 S4
SALT score prior to secondary sensitizer S5 S5 S3 S4 S4 S4 S3 S3 S2 S3
Reason to switch to secondary contact sensitizer Tolerance, relapse with first sensitizer Tolerance, relapse with first sensitizer Minimal response, lack of cosmetically acceptable outcome Lack of response with first sensitizer Tolerance, relapse with first sensitizer Lack of response with first sensitizer Development of urticaria Minimal response, lack of cosmetically acceptable outcome Lack of response with first sensitizer Minimal response, lack of cosmetically acceptable outcome
Final SALT score S5 S5 S1 S4 S4 S1 S1 S1 S1 S1
Response category after switch Non responder Non responder Partial Non responder Non responder Excellent Partial Partial Partial Partial

SALT: Severity of Alopecia Tool, S: SALT score, AA: Alopecia areata, AU: Alopecia universalis, AT: Alopecia totalis, AS: Sisaipho, AV: Alopecia vulgaris, SADBE: Squaric acid dibutyl ester, DPCP: Diphenylcyclopropenone

Assessment of therapeutic regrowth was based on the Severity of Alopecia Tool (SALT): S0 = no hair loss, S1 = <25% hair loss, S2 = 25-49%, S3 = 50-74%, S4 = 75-99% and S5 = 100% hair loss. Clinical response was classified as excellent (>75% reduction in SALT score), partial (reduction 25-74%), and minimal response (reduction of <25%). Patients were classified as non-responders when the SALT score remained unchanged.3,4 If there was no hair regrowth, nor a cosmetically acceptable outcome, patients were switched to a second sensitizer, depending on which one they received initially. Ten patients treated with both agents were identified from a total of 54 patients treated at the immunotherapy clinic from September 2009 to November 2020, seven females and three males, ages ranging from 8 to 47 years. The alopecia areata pattern was universalis in 5 (50%), totalis in 3 (30%), sisaipho in 1 (10%) and vulgaris in 1 (10%).

The SALT score before squaric acid dibutylester as initial treatment was S5 in two patients and S4 in three. The SALT score at the time of switching, was S5 in two, S4 in one and S3 in two. Two initially responded to the primary sensitizer but developed tolerance, two had a minimal response and one had no improvement. When switched to secondary agent, three continued to be unresponsive and two improved from S3 to S1 achieving a partial response.

Before treatment with diphenylcyclopropenone as the first sensitizer, the SALT score was S5 in three, S4 in one and S2 in one. The SALT score at the time of switching to squaric acid dibutylester was S4 in two, S3 in two and S2 in one. One patient developed tolerance to diphenylcyclopropenone, one had minimal improvement, two had lack of response and one was switched to squaric acid dibutylester because of urticaria. Four improved to S1, including the latter achieving an excellent response in one and a partial response in the other three, thus one continued to be unresponsive.

Switching was done after 18-80 treatments corresponding to 5-20 months. Side effects were observed in all patients, the most common being pruritus and erythema. Patients showing benefit with the second sensitizer, continue to have adequate disease control and are scheduled every 2-3 months for immunotherapy of limited affected areas.

Alopecia areata is a chronic relapsing disease with an unpredictable course. Patients with <40-50% patchy scalp involvement may present spontaneous regrowth within one year from onset without treatment. In more severe cases, topical immunotherapy has been used with encouraging results.

Information is lacking regarding the real benefit and expectations when treating with a secondary agent when unresponsive to a first sensitizer.1 Van der Steen et al. reported the use of squaric acid dibutylester in 15 patients who developed tolerance to diphenylcyclopropenone showing total regrowth in three and cosmetically acceptable regrowth in four, helping almost half of re-treated patients.5

In our study, six patients had excellent outcomes achieving a final S1 score and remarkable cosmetic results [Figures 1a-e]. Although an S0 score was not achieved, and limited lesions remained, the quality of life was strikingly improved. While more studies are required to reach definitive conclusions, it seems that trying a second sensitizing agent after an initial failure to respond, might help nearly half of re-treated patients according to our experience and the Van DerSteen report.5

Figure 1a:: 35-year-old woman with alopecia areata universalis. Baseline after four treatment applications with primary contact sensitizer diphenylcyclopropenone, SALT score S5
Figure 1b:: Same patient, SALT S4 after 40 treatments with diphenylcyclopropenone, prior to switching to squaric acid dibutyl ester as secondary contact sensitizer
Figure 1c:: Patient after switching to squaric acid dibutyl ester as secondary contact sensitizer. SALT S1 after receiving 20 treatments
Figure 1d:: Patient after receiving 36 treatments with squaric acid dibutyl ester, still SALT S1, thought with better cosmetic results
Figure 1e:: Follow-up of same patient after 80 treatments with secondary contact sensitizer (squaric acid dibutyl ester), SALT score S1. Minimal lesions remained. Excellent cosmetic results

Immunotherapy continues to be a first-line therapeutic alternative due to its excellent safety profile and adequacy for long-term use. It seems that there is a potential value in re-treatment with a second contact sensitizer in non-responders or in those who have developed tolerance. Based on our small study, we could suggest that switching to squaric acid dibutylester might provide better results than switching to diphenylcyclopropenone.


We thank Sergio Lozano-Rodriguez, M. D. for his help in editing the manuscript.

Declaration of patients consent

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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