Synergistic therapeutic effect of systemic steroids and dithranol in a patient of alopecia totalis—A case report

INTRODUCTION

Alopecia areata (AA) is an autoimmune disorder marked by non-scarring patchy hair loss. It can appear as localized patches of hair loss or more widespread thinning, and in some cases, it may progress to affect the entire scalp or even the whole body. There are various topical therapies available, like high-potency steroids, minoxidil, contact immunotherapy like squaric acid dibutylester (SADBE), and 2,3-diphenylcyclopropenone (DPCP) and contact irritants like dithranol, trichloroacetic acid, and phenol. Anthralin (dithranol) is a topical irritant used in short-contact therapy that has been found to treat AA effectively. While its exact mechanism of action is not fully understood, it is thought to work through immunosuppressive and anti-inflammatory effects, potentially involving the generation of free radicals.

Studies in mouse models of AA have shown that anthralin inhibits the expression of tumor necrosis factor (TNF)-α and TNF-β, contributing to its therapeutic efficacy.^[1] Most clinicians prefer combining systemic therapy with topical therapy in severe cases like totalis and universalis but are hesitant to combine steroids with irritants like dithranol as there is a belief that steroids will decrease the efficacy of dithranol. We present this case of alopecia totalis in which both systemic steroids and dithranol were prescribed, and a synergistic therapeutic effect was noted.

CASE REPORT

A 12-year-old boy presented to our outpatient department in the year 2020 with complete loss of hair on the scalp for 6 months. The patient was apparently alright 6 months ago when the parents started noticing two patches of alopecia. The patches were initially coin-sized; over the next 2 months, there was an increase in size as well as the number of patches, and by the next 4 months, there was a complete loss of all hair on the entire scalp. On examination, there was a complete loss of hair on the scalp [Figure 1], and trichoscopy showed the presence of multiple yellow dots. The patient started on an oral betamethasone pulse of 2 mg each on two consecutive days of a week. The patient was given Derobin^TM ointment (a combination of 5.3% coal tar, 1.15% salicylic acid, and 1.15% dithranol) to be applied on one half of the scalp for 5 minutes for the first week and then on the other half of the scalp for 5 minutes for the next week. To avoid severe irritant contact dermatitis, the patient was instructed to increase the time of contact slowly every week by 5 minutes till a maximum of 30 minutes or till there is a tolerable erythema and apply on both halves of the scalp on a weekly rotational basis. However, the patient misunderstood the instructions and continued to apply the ointment to only one-half of the scalp (the right half) while taking systemic steroids. The patient followed up in the outpatient department (OPD) after 2 months, and to our surprise, we could see hair growth only on the right half of the scalp [Figure 2]. On enquiry patient admitted he was applying the ointment only on the right side. Seeing the synergistic effect of systemic steroids and topical dithranol, we advised the patient to continue application only on the right side. There was almost a complete regrowth of scalp hair after 4 months on the side where dithranol was being applied, i.e., the right side [Figure 3], with some regrowth on the contralateral side possibly due to the castling phenomenon and systemic steroid action.

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Figure 1:

A 12-year-old boy with complete loss of hair on the scalp for 6 months duration.

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Figure 2:

Post two months of oral betamethasone pulse and Derobin^TM application. Note that there is hair regrowth only on the right side of the scalp as the patient was applying the medication only on the right side.

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Figure 3:

Post four months of taking medication, there was complete regrowth of hair on the right side of the scalp.

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DISCUSSION

Anthralin (also called dithranol) is an immunomodulator drug that induces hair growth by inhibiting pro-inflammatory cytokines that cause perifollicular inflammation, such as tumor necrosis factor-α and interferon-γ.^[1,2] Since steroids also reduce these pro-inflammatory cytokines, a combination of dithranol and steroids should have a synergistic effect. In a retrospective study, 68% of patients achieved at least 50% maximal scalp regrowth using topical anthralin.^[3] The most common concurrent treatments were topical corticosteroids (78), minoxidil (57%), and intralesional corticosteroids (16%). Thus, in this study, topical/intralesional steroids showed a synergistic effect; however, oral steroids were not used in this study along with dithranol. Therapy with dithranol has a drawback of dermatitis, which can prompt many patients to stop therapy. Combining dithranol with steroids can reduce this dermatitis and improve compliance. In a randomized trial, Ozdemir and colleagues employed brief cessation of anthralin, wet wraps, and topical steroids to manage severe dermatitis cases before resuming anthralin treatment.^[4] A retrospective study indicated that mild (<25%), moderate (25%–75%), and severe (>75%) AA may all show improvement with dithranol therapy. However, patients with severe AA tend to take significantly longer time to respond.^[5] In our case, the response was seen as early as 2 months, probably because of the synergistic effects of dithranol and systemic steroids. Hence, combining dithranol with steroids can reduce its irritating potential without reducing its efficacy and can show synergistic effects, improving hair regrowth.

CONCLUSION

In this case of alopecia totalis, the combination of systemic steroids and topical dithranol demonstrated a synergistic effect, promoting significant hair regrowth. The steroids enhanced the efficacy of dithranol while reducing its irritant potential, offering a promising approach for treating severe cases of alopecia areata. This suggests that combining both therapies could improve both the speed and extent of hair regrowth.