Depigmentation Following Diphenylcyclopropenone Immunotherapy Leading to Discontinuation of Treatment.

Sir,

Alopecia areata (AA) is an autoimmune disorder involving hair follicle, usually presenting as sudden onset, nonscarring patchy hair loss. Topical immunotherapy is one of the recommended therapies for the treatment of AA with extensive hair loss having promising results.[1] Herein, we report a case of AA who developed vitiligo-like depigmentation postdiphenylcyclopropenone acetate (DPCP) application.

A 20-year-old male student, diagnosed case of alopecia universalis past 2½ years, was initiated on topical immunotherapy with DPCP 0.001% after sensitization as per standard recommendations.[1] There was no personal or family history of vitiligo or other autoimmune diseases. He responded to treatment after 3 months (SALT score 32) with DPCP 0.1% [Figure 1]. The patient complained of white-colored patches over the scalp and hands post 6 months of DPCP therapy. Clinical examination revealed multiple depigmented patches on scalp, neck, and dorsum of hands [Figure 2]. Seventy-five percent of regrown hairs were still present on the scalp, with SALT score 49. The treatment with DPCP was interrupted as the patient was very anxious and started on oral mini pulse with dexamethasone 2.5 mg twice a week along with topical mometasone 0.1% cream. This was followed by repigmentation of patches by 8 weeks but was associated with loss of regrown hair [Figure 3]. The patient did not want immunotherapy again.

Figure 1

Regrowth of hair on the whole scalp after few months of topical immunotherapy with diphenylcyclopropenone

Figure 2

Vitiligo-like depigmented patches after few weeks of diphenylcyclopropenone immunotherapy treated areas on the scalp

Figure 3

Repigmentation at the site of diphenylcyclopropenone induced vitiligo after 8 weeks of oral and topical steroid treatment

As per recommendation, in cases of AA of universalis, subtype immunotherapy is the treatment of choice.[1] DPCP, most effective topical immunotherapy for AA, has been in use since decades showing variable response rates.[2] DPCP is most preferable agent among other topical immunotherapies in AA due to its low cost, stability, and no mutagenicity.[3] Exact mechanism of action is not yet understood, but several hypotheses have been established such as antigen competition, perifollicular lymphocyte apoptosis,[3] inhibiting production of antifollicular antibodies.[4] Adverse effects include erythema, eczematous reactions, blistering, lymphadenopathy, scalp and facial edema, contact urticaria, flu-like symptoms, erythema multiforme-like reactions, and pigment changes such as hyperpigmentation, hypopigmentation, and vitiligo-like depigmentation which sometimes warrants withdrawal of therapy if severe.[1]

DPCP-induced depigmentation is a rare unpredictable side effect documented in patients of AA during its treatment. Clear pathomechanism underlying it is not yet established. Various hypothesis postulated includes koebnerization if the patient had associated vitiligo or other autoimmune diseases and direct cytotoxic effect on melanocytes through systemic absorption.[5] Management includes discontinuation of DPCP, initiation of topical or systemic corticosteroids, phototherapy with psoralen ultraviolet A (PUVA) or narrowband UV-B,[6] though with fewer success rates. DPCP-induced vitiligo has also been reported in patient with verruca plana[6] which was treated with topical tacrolimus 0.1% and excimer laser with repigmentation. Table 1 summarizes previously reported cases of vitiligo-like depigmentation postimmunotherapy.

Table 1

Summary of reports of vitiligo-like depigmentation with contact immunotherapy

Author	Contact immunotherapy used (%)	Duration of adverse effect after starting contact immunotherapy	Mechanism proposed	Treatment offered	Response
Pires et al., 2010[5]	DPCP 0.02	4 weeks	Direct cytotoxicity on melanocytes	Desonide lotion	No repigmentation
oh et al., 2012[6]	DPCP 0.001	4 months	Direct cytotoxicity	Narrowband UVB	Good response
Nilforoushzadeh et al., 2012 (2 cases)[7]	DPCP 0.5	4-6 weeks	Induction of Allergic contact dermatitis, ?postinflammatory	DPCP stopped No treatment offered	No repigmentation
Ganzetti et al., 2010[8]	DPCP 0.5	9 months (vitiligo over preceding contact dermatitis)	Induction of Allergic contact dermatitis, ?postinflammatory	Narrowband UVB	Good response, repigmentation occurred

DPCP – Diphenylcyclopropenone; UVB – Ultraviolet B

In this patient, he did not have either personal or family history of vitiligo, atopy, or any other autoimmune disease. The patient developed vitiligo-like depigmentation on scalp, neck, dorsum of hands at post 6 months therapy with DPCP. His lesions repigmented with oral corticosteroid minipulse and stopping of DPCP after 8 weeks. The distant involvement like on the dorsum of hands in this patient may be due to cytotoxic effect on melanocytes after systemic absorption and neck involvement could be due to gravitational flowing of DPCP.

Appearance of vitiligo-like patches in types IV and V skin leads to significant psychological implications as vitiligo carries social stigma and patients regard it as a dreaded complication. Although DPCP-induced vitiligo-like depigmentation is a rare, undesirable side effect, the patients need to be counseled and informed before the onset of this side effect.[8]

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Conflicts of interest

There are no conflicts of interest.