in affected BSA and signs of psoriasis at the target lesion were also observed early following treatment with HP/TAZ lotion and maintained up to 4 weeks posttreatment. The patient had substantial improvements in QoL during the study, with DLQI score decreasing from 9 (“moderate effect†on life) at baseline to 1 (“no effect†on life) at weeks 4 and 8.
No adverse events were reported. Dryness was the only local skin reaction present at baseline (assessed as moderate by the investigator), which subsided at weeks 2–6 and returned to mild dryness by study end (Table 1). No itching was reported during HP/TAZ treatment until posttreatment follow-up, where it was assessed as moderate. The patient did not report burning/ stinging at any study visit. Further, there were no instances of skin atrophy, striae, telangiectasias, or folliculitis—other known drug-related skin reactions.
No adverse events were reported. Dryness was the only local skin reaction present at baseline (assessed as moderate by the investigator), which subsided at weeks 2–6 and returned to mild dryness by study end (Table 1). No itching was reported during HP/TAZ treatment until posttreatment follow-up, where it was assessed as moderate. The patient did not report burning/ stinging at any study visit. Further, there were no instances of skin atrophy, striae, telangiectasias, or folliculitis—other known drug-related skin reactions.
DISCUSSION
Racial and ethnic differences in epidemiology, clinical features, genetic predisposition, and response to treatment of psoriasis are important to address given our increasingly diverse patient population.7 Here we report the management of psoriasis in a Black male enrolled in a clinical trial who was randomized to treatment with HP 0.01%/TAZ 0.045% lotion once daily for 8 weeks, with a 4-week posttreatment follow-up at week 12.
HP/TAZ was efficacious in this patient, who achieved an IGA score of 1 (almost clear) within 4 weeks and maintained treatment success at weeks 8 and 12. Affected BSA decreased 50% from baseline to week 8. Quality of life was improved in this patient, whose DLQI score by week 8 indicated “no effect†of psoriasis on the patient’s QoL, a substantial and clinically meaningful16 improvement from the “moderate effect†observed at baseline. A clinical feature of this patient was the presence of prominent keloid scars, which are benign fibrous growths resulting from an abnormal connective tissue response.17 While the cause of the keloids in this patient is not known, the presence of keloids is not unexpected, as there are racial differences in prevalence, with Black individuals forming keloids more often than White individuals.17
The patient experienced dyspigmentation of the affected skin during the trial, which is also not unexpected, given that resolution of psoriasis in darker skin is associated with both hypo- and hyper-pigmentation.18 Dyspigmentation is of particular concern, as it can have significant psychosocial impacts, contribute to greater negative emotions, and even be more bothersome than the psoriasis itself in patients with skin of color.2,4,7 Hypopigmentation was primarily experienced from weeks 2-8, with the greatest degree at week 4. By week 12 the affected skin area had returned to normal, with only small regions of hyperpigmentation, primarily around the periphery of the lesion. This relatively fast time to resolution is notable given that dyspigmented patches can take between 3 and 12 months to resolve.2
Skin color is primarily due to the presence of melanin, a pigment formed by immune cells called melanocytes. Melanin formation, or melanogenesis, is a complex process of melanin synthesis, transport, and release to keratinocytes, which occurs within organelles of melanocytes called melanosomes.19 The mechanisms and pathogenesis of postinflammatory hypo- and hyperpigmentation in psoriasis are not fully elucidated, though multiple hypotheses have been suggested. Inflammationassociated hypopigmentation may be a result of rapid turnover of keratinocytes during hyperplasia, which can interfere with melanosome transfer.18 Cutaneous inflammation, through signaling of growth factors and pro-inflammatory cytokines such as IL-17 and TNF-α, can also lead to hypopigmentation through inhibition of melanogenesis,18,20 with more severe inflammation potentially leading to permanent pigmentary changes through loss or death of melanocytes.20 Interestingly, it has been observed that while hypopigmentation often accompanies active inflammation, patients are at risk of developing hyperpigmentation once the inflammation has resolved, potentially due to increased numbers and activity of melanocytes.18,21 This too may be the result of cytokine signaling during inflammation. For example, IL-17 and TNF-α can simultaneously suppress melanogenesis while also stimulating the proliferation of melanocytes; as such, upon resolution of inflammation, the increased number of melanocytes in lesional skin (without concurrent suppression of melanogenesis) will produce excess melanin, leading to postinflammatory hyperpigmentation.18
The fixed combination of HP and TAZ used to treat psoriasis in the patient from this case report resulted in psoriasis lesion clearance with self-limited postinflammatory hypopigmentation and low levels of hyperpigmentation observed by week 12. Topical corticosteroids, a mainstay of treatment for psoriasis,8 are used as first-line therapy for hyperpigmentation when combined with hydroquinone and topical retinoids.5,22 Corticosteroids are thought to be effective by decreasing cellular metabolism, thereby inhibiting melanin synthesis.22 Corticosteroids have also been shown to minimize the risk of postinflammatory hyperpigmentation after laser resurfacing.23 Topical retinoids are effective in treating postinflammatory hyperpigmentation with other agents as described above or as monotherapy.22 For example, TAZ 0.1% gel and cream have demonstrated efficacy in acne-related postinflammatory hyperpigmentation, significantly improving pigmentation intensity versus vehicle24,25; TAZ was also more effective than adapalene 0.3% gel in reducing hyperpigmentation.25 Tazarotene 0.1% cream is approved as an adjunctive treatment in the mitigation of facial mottled hyper- and hypopigmentation. Retinoids are thought to reduce hyperpigmentation through multiple mechanisms, including:
HP/TAZ was efficacious in this patient, who achieved an IGA score of 1 (almost clear) within 4 weeks and maintained treatment success at weeks 8 and 12. Affected BSA decreased 50% from baseline to week 8. Quality of life was improved in this patient, whose DLQI score by week 8 indicated “no effect†of psoriasis on the patient’s QoL, a substantial and clinically meaningful16 improvement from the “moderate effect†observed at baseline. A clinical feature of this patient was the presence of prominent keloid scars, which are benign fibrous growths resulting from an abnormal connective tissue response.17 While the cause of the keloids in this patient is not known, the presence of keloids is not unexpected, as there are racial differences in prevalence, with Black individuals forming keloids more often than White individuals.17
The patient experienced dyspigmentation of the affected skin during the trial, which is also not unexpected, given that resolution of psoriasis in darker skin is associated with both hypo- and hyper-pigmentation.18 Dyspigmentation is of particular concern, as it can have significant psychosocial impacts, contribute to greater negative emotions, and even be more bothersome than the psoriasis itself in patients with skin of color.2,4,7 Hypopigmentation was primarily experienced from weeks 2-8, with the greatest degree at week 4. By week 12 the affected skin area had returned to normal, with only small regions of hyperpigmentation, primarily around the periphery of the lesion. This relatively fast time to resolution is notable given that dyspigmented patches can take between 3 and 12 months to resolve.2
Skin color is primarily due to the presence of melanin, a pigment formed by immune cells called melanocytes. Melanin formation, or melanogenesis, is a complex process of melanin synthesis, transport, and release to keratinocytes, which occurs within organelles of melanocytes called melanosomes.19 The mechanisms and pathogenesis of postinflammatory hypo- and hyperpigmentation in psoriasis are not fully elucidated, though multiple hypotheses have been suggested. Inflammationassociated hypopigmentation may be a result of rapid turnover of keratinocytes during hyperplasia, which can interfere with melanosome transfer.18 Cutaneous inflammation, through signaling of growth factors and pro-inflammatory cytokines such as IL-17 and TNF-α, can also lead to hypopigmentation through inhibition of melanogenesis,18,20 with more severe inflammation potentially leading to permanent pigmentary changes through loss or death of melanocytes.20 Interestingly, it has been observed that while hypopigmentation often accompanies active inflammation, patients are at risk of developing hyperpigmentation once the inflammation has resolved, potentially due to increased numbers and activity of melanocytes.18,21 This too may be the result of cytokine signaling during inflammation. For example, IL-17 and TNF-α can simultaneously suppress melanogenesis while also stimulating the proliferation of melanocytes; as such, upon resolution of inflammation, the increased number of melanocytes in lesional skin (without concurrent suppression of melanogenesis) will produce excess melanin, leading to postinflammatory hyperpigmentation.18
The fixed combination of HP and TAZ used to treat psoriasis in the patient from this case report resulted in psoriasis lesion clearance with self-limited postinflammatory hypopigmentation and low levels of hyperpigmentation observed by week 12. Topical corticosteroids, a mainstay of treatment for psoriasis,8 are used as first-line therapy for hyperpigmentation when combined with hydroquinone and topical retinoids.5,22 Corticosteroids are thought to be effective by decreasing cellular metabolism, thereby inhibiting melanin synthesis.22 Corticosteroids have also been shown to minimize the risk of postinflammatory hyperpigmentation after laser resurfacing.23 Topical retinoids are effective in treating postinflammatory hyperpigmentation with other agents as described above or as monotherapy.22 For example, TAZ 0.1% gel and cream have demonstrated efficacy in acne-related postinflammatory hyperpigmentation, significantly improving pigmentation intensity versus vehicle24,25; TAZ was also more effective than adapalene 0.3% gel in reducing hyperpigmentation.25 Tazarotene 0.1% cream is approved as an adjunctive treatment in the mitigation of facial mottled hyper- and hypopigmentation. Retinoids are thought to reduce hyperpigmentation through multiple mechanisms, including:
