**5.2 Imiquimod**

Imiquimod is usually used for topical treatment of anogenital warts and basal cell carcinomas [20]. It is an imidazoquinoline and is an immune response modifier. It acts by stimulating the monocytes/macrophages and plasmacytoid dendritic cells in dermis and epidermis of the immune system to produce pro-inflammatory cytokines, mainly interferon α and other signals that activate T-cell-mediated response leading to apoptosis of tumor cells. Prolonged use of imiquimod has shown to result in depigmentation [1]. Imiquimod also stimulates CD8 cells to become cytotoxic and enhances antigen presentation [21]. Recently, it was reported that human melanocytes express toll-like receptor 7 (TLR7). When applied topically, imiquimod binds to TLR7 followed by stimulation of various cytokines, which induce the abovementioned T-lymphocytic response [22]. Imiquimod also has a direct action on melanocytes via

**63**

**7. Conclusion**

*Depigmentation Therapies in Vitiligo*

**5.3 Diphencyprone (DPCP)**

crusting.

**6. Limitations**

these doubts:

*DOI: http://dx.doi.org/10.5772/intechopen.84271*

apoptosis of melanocytes. This action is related to reduction of expression of Bcl-2 and/or an increase in the proapoptotic stimulus (cytotoxic T lymphocytes, natural

Thus, there is a strong possibility that imiquimod may cause elimination of melanocytes by direct influence on cells as well as inducing acquired immunity indirectly, which eventually induces vitiligo-like hypopigmented lesions [28]. Some common side effects include itching, pain, burning, erosions, erythema, and

DPCP is used traditionally as a treatment modality for alopecia areata. Depigmentation was found to be one of the side effects due to the use of DPCP. It has an immunomodulatory mechanism of action. As reported by Duhra and Foulds [12], in a case of alopecia totalis where topical DPCP was used, there a was marked reaction with erythema and edema on the forearm after 3 days, but the scalp manifested only slight macular erythema. The reaction on the forearm subsided after 2 weeks and was replaced by a depigmented patch over a period of 6 weeks. Upon incubating the affected skin with dopa followed by electron microscopy, an absence of melanosomes and melanocytes was revealed. It has been observed that vitiligo

can develop even with DPCP concentrations as low as 0.0001% [12].

nopathy, blistering, and eczematous reactions [20].

1.Aspects that cannot be controlled

b.End result (color matching or same color).

d.Repigmentation during pregnancy (at times extensive).

repigmentation is possible, are candidates for depigmentation?

3.Whether depigmentation in children is a safe and viable alternative?

Vitiligo has a huge psychological impact and is also socially stigmatizing, particularly for patients with darker skin types in whom the contrast between the

a.Remote depigmentation.

e.Resistance to MBEH.

Some of the adverse effects include hyperpigmentation, regional lymphade-

The science of depigmentation is still not a perfected one and that does leave many questions unanswered. Further research in this arena can help shed light on

c.Hairs do not lose pigment (can give repigmentation especially follicular).

2.Can patients with less than 50% involvement, willing to accept that no more

cytotoxic T cells/killer cells, granzymes B, Fas, TNF, Bax, etc.) [23].

#### *Depigmentation Therapies in Vitiligo DOI: http://dx.doi.org/10.5772/intechopen.84271*

*Depigmentation*

*4.2.1 Points to ponder*

relapse [16].

**5.1 Imatinib**

**5.2 Imiquimod**

• Treatment is expensive.

Some other potential Q-switched lasers that can selectively destruct melanocytes include neodymium:yttrium aluminum garnet (Nd:YAG) laser (1064 nm) and the frequency-doubled Q-switched Nd:YAG laser (532 nm) [1]. In a study by Boen et al., Q-switched ruby laser (QSRL) 694 nm, Q-switched alexandrite laser (QSAL) 755 nm, and picosecond 755-nm alexandrite lasers provided the most significant pigment reduction when different recalcitrant pigmented areas of the body were treated by the abovementioned lasers over different areas in the same patient. In all the patients treated with this laser therapy, no adverse reactions apart from mild postprocedure erythema and crusting were noticed. The picosecond laser poses more advantages over the traditional Q-switch laser as it has increased photochemical action due to shorter pulse duration, requires lesser treatment sessions, and has reduced specific photothermal damage. This results in an increase in the safety profile of the laser and

improves the effectiveness of this therapeutic modality [19, 24–26].

• Procedure is slightly painful and may require local anesthesia.

ments because of Koebner's phenomenon.

**5. Emerging therapies for depigmentation**

• Possibility of failure in removing pigmented patches even after several treat-

• Patients with active vitiligo respond better to laser treatments compared to those with stable vitiligo. Hence, patients who are Koebner negative may often

Also known as imatinib mesylate, it is used to treat conditions like leukemia and gastrointestinal stromal tumors. It was observed that patients treated with imatinib were reported to develop generalized depigmentation as a side effect. Imatinib is a tyrosinase kinase inhibitor, thus inhibiting the activity of the enzyme, resulting in decreased pigmentation of the skin. The side effects of imatinib include fluid retention, periorbital edema, diarrhea, and myelosuppression. Some of the dermatological side effects include erythroderma, follicular mucinosis, and lichenoid eruption [27].

Imiquimod is usually used for topical treatment of anogenital warts and basal cell carcinomas [20]. It is an imidazoquinoline and is an immune response modifier. It acts by stimulating the monocytes/macrophages and plasmacytoid dendritic cells in dermis and epidermis of the immune system to produce pro-inflammatory cytokines, mainly interferon α and other signals that activate T-cell-mediated response leading to apoptosis of tumor cells. Prolonged use of imiquimod has shown to result in depigmentation [1]. Imiquimod also stimulates CD8 cells to become cytotoxic and enhances antigen presentation [21]. Recently, it was reported that human melanocytes express toll-like receptor 7 (TLR7). When applied topically, imiquimod binds to TLR7 followed by stimulation of various cytokines, which induce the abovementioned T-lymphocytic response [22]. Imiquimod also has a direct action on melanocytes via

**62**

apoptosis of melanocytes. This action is related to reduction of expression of Bcl-2 and/or an increase in the proapoptotic stimulus (cytotoxic T lymphocytes, natural cytotoxic T cells/killer cells, granzymes B, Fas, TNF, Bax, etc.) [23].

Thus, there is a strong possibility that imiquimod may cause elimination of melanocytes by direct influence on cells as well as inducing acquired immunity indirectly, which eventually induces vitiligo-like hypopigmented lesions [28]. Some common side effects include itching, pain, burning, erosions, erythema, and crusting.

### **5.3 Diphencyprone (DPCP)**

DPCP is used traditionally as a treatment modality for alopecia areata. Depigmentation was found to be one of the side effects due to the use of DPCP. It has an immunomodulatory mechanism of action. As reported by Duhra and Foulds [12], in a case of alopecia totalis where topical DPCP was used, there a was marked reaction with erythema and edema on the forearm after 3 days, but the scalp manifested only slight macular erythema. The reaction on the forearm subsided after 2 weeks and was replaced by a depigmented patch over a period of 6 weeks. Upon incubating the affected skin with dopa followed by electron microscopy, an absence of melanosomes and melanocytes was revealed. It has been observed that vitiligo can develop even with DPCP concentrations as low as 0.0001% [12].

Some of the adverse effects include hyperpigmentation, regional lymphadenopathy, blistering, and eczematous reactions [20].

### **6. Limitations**

The science of depigmentation is still not a perfected one and that does leave many questions unanswered. Further research in this arena can help shed light on these doubts:

	- a.Remote depigmentation.
	- b.End result (color matching or same color).
	- c.Hairs do not lose pigment (can give repigmentation especially follicular).
	- d.Repigmentation during pregnancy (at times extensive).
	- e.Resistance to MBEH.

#### **7. Conclusion**

Vitiligo has a huge psychological impact and is also socially stigmatizing, particularly for patients with darker skin types in whom the contrast between the

#### *Depigmentation*

vitiliginous lesions and uninvolved skin can be especially apparent and disfiguring. In patients with widespread involvement covering more than 50% of their body and in cases where medical modalities including phototherapy have proved ineffective, depigmentation therapy should be considered. Patient selection, adequate counseling, and patient education are extremely important for a positive long-term outcome.
